Beijing, China

Peking Union Medical College is among the most selective medical colleges in the People's Republic of China, located in Beijing. It is a relatively independent institution affiliated with Tsinghua University which is one of the top two universities in China. Peking Union Medical College graduates receive Peking Union Medical College diploma signed by both the Peking Union Medical College and Tsinghua presidents. The Hospital and College is located at No.9 Dongdan 3rd Alley, Dongcheng, Beijing, next to the Wangfujing shopping area. Wikipedia.


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Gao W.,Yunnan Normal University | Farahani M.R.,Iran University of Science and Technology | Shi L.,Peking Union Medical College
Acta Medica Mediterranea | Year: 2016

A large number of previous drug experiments revealed that there are strong inherent connections between the drug's molecular structures and the bio-medical and pharmacology characteristics. The forgotten topological index is introduced to be applied into chemical compound and drug molecular structures, which is quite helpful for medical and pharmaceutical workers to test the biological features of new drugs. Such approaches are widely applied in developing areas which are not rich enough to afford the relevant equipment and chemical reagents. In this paper, using drug structure analysis and edge dividing technique, we determine the forgotten topological index of some molecular structures which appear widely in various classes of drugs.


PURPOSE:: To evaluate the effect of intravitreal injection of bevacizumab in vitrectomy for patients with proliferative vitreoretinopathy (PVR)-related retinal detachment. METHODS:: The PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from their earliest entries through October, 2016, to identify the studies that had evaluated the effects of intravitreal injection of bevacizumab in vitrectomy for eyes with PVR-related retinal detachment. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. The relevant data were analyzed using Stata 12.0 software. The weighted mean difference, relative risk, and their 95% confidence intervals were used to assess the strength of the association. RESULTS:: The authorsʼ search yielded 133 records from which 3 studies that have examined the effects of intravitreal injection of bevacizumab (120 eyes with PVR-related retinal detachment) were included for review and analysis. Their meta-analyses showed that neither the best-corrected visual acuity nor retinal redetachment rate showed any clinically or statistically important difference between the nonbevacizumab and bevacizumab groups (P > 0.05). In addition, bevacizumab did not influence the interval between vitrectomy and retinal redetachment (P > 0.05). CONCLUSION:: Based on the available evidence, intravitreal injection of bevacizumab in vitrectomy for patients with PVR-related retinal detachment did not decrease retinal redetachment rate or improve visual acuity. Better-designed studies with larger simple sizes and longer follow-up periods are required to reach valid conclusions regarding benefits and harms. Moreover, evaluation of anti–vascular endothelial growth factor therapy on surgical outcomes in eyes with milder subtypes of PVR or no PVR, but deemed at high risk of PVR, may be worthy of future consideration. © 2017 by Ophthalmic Communications Society, Inc.


Li S.,Peking Union Medical College
Clinical Nuclear Medicine | Year: 2017

ABSTRACT: A 57-year-old man with a history of hypertrophic cardiomyopathy diagnosed by echocardiography experienced atypical chest pain and dyspnea for 6 months. A rest Tc-MIBI myocardial SPECT imaging and a F-FDG myocardial PET/CT imaging were performed, which showed multiple matched myocardial perfusion/metabolism defects in the left ventricle, indicating scar tissue. Surprisingly, subsequent contrast coronary angiography revealed no significant coronary artery stenosis. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.


OBJECTIVES:: The relationship between respiratory mechanical parameters and hemodynamic variables remains unclear. This study was performed to determine whether mean airway pressure and central venous pressure in the first day of mechanical ventilation are associated with patient outcomes. DESIGN:: Retrospective first 24-hour comparison during ICU stay. SETTING:: The Department of Critical Care Medicine of Peking Union Medical College Hospital. PATIENTS:: Patients with mechanical ventilation. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: The clinical data of patients who received mechanical ventilation, especially respiratory and hemodynamic data, were collected and analyzed. In terms of the hemodynamic and perfusion data, the nonsurvivors group (177/2,208) had higher heart rate, respiratory rate, central venous pressure, and lactates and a lower perfusion index and P(v-a)CO2 (p < 0.05). In terms of respiratory condition, mean airway pressure, peak airway pressure, positive end-expiratory pressure, driving pressure, and inspiratory time/total respiration time of nonsurvivors were significantly higher, and arterial oxygen pressure and dynamic compliance worsened and were lower than the survivors (p < 0.05). Increased central venous pressure (odds ratio, 1.125; 95% CI, 1.069–1.184; p < 0.001) and elevated mean airway pressure (odds ratio, 1.125; 95% CI, 1.069–1.184; p < 0.001) were independently associated with 28-day mortality. The area under receiver operating characteristic demonstrated that central venous pressure and mean airway pressure were measured at 0.795 (95% CI, 0.654–0.757) and 0.833 (95% CI, 0.608–0.699), respectively. Based on the cutoff of central venous pressure and mean airway pressure, all of the participants were divided into the following groups: low central venous pressure and mean airway pressure, only high central venous pressure or mean airway pressure, or high central venous pressure and mean airway pressure. Post hoc tests showed significant differences among these three groups based on 28-day survival (log rank [Mantel-Cox], 131.931; p < 0.001). CONCLUSIONS:: During the first 24 hours of mechanical ventilation, patients with elevated mean airway pressure and elevated central venous pressure had worse outcomes. Copyright © by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.


Yang M.,Peking Union Medical College
Journal of Computer Assisted Tomography | Year: 2017

OBJECTIVE: The objectives of this study were to evaluate sternal development and variations in patients with microtia and to identify the incidence of congenital sternal anomalies and then to investigate the interaction between microtia and sternal anomalies. METHODS: A total of 212 consecutive patients received a preoperative 3-dimensional chest computed tomography. A retrospective study was performed with the clinical and imaging data from November 2014 to July 2015. Descriptive statistics, analysis of variance, Spearman analysis, χ test, and Fisher χ test were performed for statistics analysis. RESULTS: We evaluated the ossification centers and developmental variations in the manubrium and body, as well as the xiphoid process, manubriosternal and sternoxiphoidal fusion, and sternal anomalies. Significant variations were observed from person to person. Sternal foramen was detected in 6 male patients (2.8%). All foramina were located in the inferior part of the body. Sternal cleft was observed in 4 cases (1.9%), of which 2 were accompanied by a foramen in the distal part of the sternum. CONCLUSIONS: The development of the different components of the sternum is a process with wide variation among patients with microtia. A different distribution of mesosternal types I to II among our population age range was found, and the incidence of sternal foramina was lower in patients with microtia. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.


Qi D.,Capital Medical University | Nie X.-L.,Capital Medical University | Wu S.,University of Science and Technology of China | Cai J.,Peking Union Medical College
PLoS ONE | Year: 2017

Objectives The study sought to determine the link between Vitamin D concentrations and incident hypertension in prospective study and meta-Analysis. Methods The study was embedded in the Kailuan Study, a population-based cohort of adults that contains underground miners. In 2012, we studied 2,456 men and women free of prevalent hypertension, age 21 to 67 at baseline. Serum 25-hydroxyVitamin D was measured from previously frozen baseline samples using ELISA (Enzyme-Linked ImmunoadSorbent Assay). We use the logistic regression analysis to estimate the odd radio (ORs) 95% confidence intervals (CIs) for 25-hydroxyVitamin D [25(OH)D] concentrations with incident hypertension. To help place our new data in context, we conducted a systemic review and metaanalysis of previous prospective reports of Vitamin D and hypertension. Results During a median follow-up of 2 years, 42.6% of the cohort (n = 1047) developed hypertension. Compared with the 25-hydroxyVitamin D >30ng/ml, 25-hydroxyVitamin D <20 ng/ml was associated with a greater hypertension risk (OR: 1.225 [95% CI: 1.010 to 1.485] p = 0.04), although the association was attenuated and not statistically significant after adjusting for potential confounders (OR: 1.092 [95% CI: 0.866 to 1.377] p = 0.456). This meta-Analysis included seven prospective studies for 53,375 participants using adjusted HR founded a significant association between Vitamin D deficiencies and incident hypertension (HRs = 1.235 (95% CI: 1.083 to 1.409, p = 0.002))., , Conclusion Lower serum 25-hydroxyVitamin D concentrations were not associated with a greater risk of incident hypertension. More research is needed to further determine the role of 25-hydroxyVitamin D in hypertension prevention and therapy. © 2017 Qi et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Zhao X.,Peking Union Medical College | Xia S.,Peking Union Medical College | Wang E.,Peking Union Medical College | Chen Y.,Peking Union Medical College
PLoS ONE | Year: 2017

As a new ophthalmic non-steroidal anti-inflammatory drug (NSAID) with prodrug structure, Nepafenac was supposed to have a better efficacy than conventional NSAIDs both in patients' tolerability and ocular inflammation associated with cataract surgery. However, many current studies reached contradictory conclusions on the superiority of Nepafenac over Ketorolac. The objective of our study is to evaluate the efficacy and patients' tolerability of Nepafenac and Ketorolac following cataract surgery. To clarify this, we conducted a meta-analysis of randomized controlled trials. Eleven articles were included in this study. The dataset consisted of 1165 patients, including 1175 cataract surgeries. Among them, 574 patients were in the Nepafenac group and 591 in the Ketorolac group. Our analysis indicated that these two drugs were equally effective in controlling post cataract surgery ocular inflammation, reducing macular edema, achieving a better visual ability and maintaining intraoperative mydriasis during cataract surgery. However, Nepafenac was more effective than Ketorolac in reducing the incidence of postoperative conjunctival hyperemia and ocular discomfort. This meta-analysis indicated that topical Nepafenac is superior to Ketorolac in patients' tolerability following cataract surgery. However, these two drugs are equally desirable in the management of anterior chamber inflammation, visual rehabilitation and intraoperative mydriasis. Given the limitations in our study, more researches with larger sample sizes and focused on more specific indicators such as peak aqueous concentrations of drugs or PEG2 levels are required to reach a firmer conclusion. © 2017 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


BACKGROUND: To determine the influence of right ventricular function in patients with constrictive pericarditis (CP) undergoing surgery and to compare the outcomes of patients who received surgery with those managed medically.METHODS: Patients with the diagnosis of CP and healthy volunteers were recruited from January 2006 to November 2011. Patients with CP chose to either receive pericardiectomy or medical management. Echocardiographic measurements were performed to evaluate heart function, and survival was recorded.RESULTS: A total of 58 patients with CP (36 received pericardiectomy, 22 managed medically), and 43 healthy volunteers were included. CP patients who received surgery had a higher survival rate than those managed medically (P = 0.003), and higher survival was also seen in the subgroup of CP patients with severely impaired right systolic function. Albumin level, left ventricular end-diastolic dimension, and tricuspid regurgitation velocity were associated with survival in CP patients who received surgery.CONCLUSIONS: Preoperative right heart function does not affect surgical outcomes. Patients with severely impaired preoperative right systolic function obtain a greater survival advantage with surgery than with medical treatment.


Su Y.C.,Peking Union Medical College
Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology | Year: 2016

It is a digital age today. Exposed to all kinds of digital products in many fields. Certainly, implant dentistry is not exception. Digitalization could improve the outcomes and could decrease the complications of implant dentistry. This paper introduces the concepts, definitions, advantages, disadvantages, limitations and errors of digital implant dentistry.


Xu W.-H.,Peking Union Medical College
Annals of Translational Medicine | Year: 2014

Large arteries are the upstream vessels of cerebral small vessels, through which blood flow is transported. Since structurally and functionally connected, large arteries and cerebral small vessels are physiologically correlated. However, large vessel diseases and small vessel diseases are investigated separately in old era. More and more evidence suggested they are inter-mingled and should be considered together. When a deep brain lacunar infarct occurs, it is of necessity to perform high-resolution magnetic resonance imaging to screen intracranial large artery atherosclerosis, which requires more intensified treatment. It may be the appropriate strategy to keep longitudinal monitoring of the trend of large artery stiffness and give intervention such as aggressive blood pressure control to prevent cerebral white matter lesions (WMLs) occurrence or progression. More data from cohort studies are required, especially the biomarkers of "diseased" artery stiffness. In the future, when randomized clinical trials are performed, the end points should take both large artery and small vessel damages into consideration. The two diseases are in the same "boat", i.e., the pan-vessel diseases. In order to save one, we have to save both. © Annals of Translational Medicine. All rights reserved.


Li B.,Peking Union Medical College | Li X.,Peking Union Medical College
Chinese Journal of Interventional Imaging and Therapy | Year: 2016

Cystic lesions and cystic-solid tumors are the common diseases in clinic, but the effective treatment methods and curative effect is limited currently. Using of thermal ablation technique in the treatment of cystic lesions and cystic-solid tumors is of great significance. The clinical application and research progress of thermal ablation therapy in cystic lesions and cystic-solid tumors were reviewed in this article. Copyright © 2016 by the Press of Chinese Journal of Medical Imaging and Technology.


Cui Y.,Central University of Costa Rica | Sun J.-L.,Peking Union Medical College | Yu L.,Yancheng Health Vocational & Technical College
Entomologia Experimentalis et Applicata | Year: 2017

The clustered regularly interspaced short palindromic repeats (CRISPR) structural family form an acquired immune system in bacteria that is able to degrade invading virus or phage DNA. The CRISPR/Cas system has been co-opted as an RNA-mediated nuclease for use in targeted genome engineering. The CRISPR/Cas system provides a novel tool for manipulating genomic DNA using an approach that is simple, convenient, and easy to learn. Since its first description as a genome editor in 2012, it has been widely applied to bacteria, yeast, nematodes, flies, zebrafish, mice, rats, and human cells. This review describes the basic principles of the system and its application. In particular, we focus on CRISPR as a tool to manipulate and study the functional genomes of the planet's most abundant organisms, insects, which have diverse impacts on humans and the environment. © 2017 The Netherlands Entomological Society


Zhong S.,Peking Union Medical College
Zhonghua yi xue za zhi | Year: 2016

OBJECTIVE: To study the clinical features of multiple myeloma (MM) patients with 1q21 amplification and the detection and biological characteristics of 1q21 copy number variation among different stages of plasma cell dyscrasias.METHODS: We analyzed the amplification and copy number variation of 1q21 in a cohort of 397 MM patients (290 newly diagnosed patients and 107 relapsed/refractory patients) in Institute of Hematology and Blood Diseases Hospital in the period between January 2009 and December 2012, using fluorescence in situ hybridization (FISH). We compared the incidence and biological characteristics of 1q21 gains among different stages of MM.RESULTS: Among the newly diagnosed MM patients, the cases without 1q21 gains (148 cases) had difference prevalence of q13 deletion (38.3% (56/146) vs 57.7% (82/142), P=0.001), t(4; 14) translocation (17.4% (25/144) vs 30.7% (42/137), P=0.009), and high-risk cytogenetic abnormalities (28.3% (39/138) vs 41.9% (57/136), P=0.018), and International Staging System (ISS) stage (P=0.010) compared to those with 1q21 gains (142 cases); however, there were no significant differences in age(P=0.448), Durie-Salmon clinical stage (P=0.352) and β2-microglobulin level (P=0.414). In the newly diagnosed patients, the incidence of this 1q21 aberration with the percentages of plasma cells involved being ≥10%, ≥20%, and ≥30% was 52.4% (152/290), 49.0% (142/290), and 46.2% (134/290), respectively, lower than that in the relapsed/refractory patients (71.0% (76/107), P=0.001; 68.2% (73/107), P=0.001; 63.6% (68/107), P=0.002). Differences were found between the newly diagnosed MM patients and the relapsed/refractory ones in terms of the incidence of 1q21 copy number gains being 2 (52.2% (145/278) vs 33.3% (34/102), P=0.001), but not in the incidence of 1q21 copy number gains being 3, 4, and >5 (all P>0.05).CONCLUSIONS: Amplification of chromosome 1q21 is a common genetic abnormality in MM patients. The copy number varies in patients carrying 1q21 gains, mainly with two or more copies of 1q21. It may therefore be recommended to include testing for 1q21 gains in routine genetic testing of MM patients.


OBJECTIVE: To explore the relationship between early adulthood weight status and body weight changes from early adulthood to middle age and high-density lipoprotein cholesterol (HDL-C) level.METHODS: Data were obtained from China Multicenter Collaborative Study of Cardiovascular Epidemiology Study, which was conducted in 1998, 15 participants population samples aged from 35-59 years old from 12 provinces were selected by random cluster sampling. Approximately 1 000 men and women in each sample population were surveyed for cardiovascular disease risk factors, body weight at age 25 from all participants were also obtained. Body mass index (BMI) at the age of 25 years was calculated with the weight at 25 years and the height measured during the survey, participants were divided into underweight (BMI<18.5 kg/m(2), n=1 331), normal-weight (18.5 kg/m(2)≤BMI <24 kg/m(2), n=10 400), overweight (24 kg/m(2)≤BMI<28 kg/m(2), n=2 019) and obesity (BMI≥28 kg/m(2), n=133) groups. Weight change was defined as the difference between the body weight at the age of 25 and at the survey and was grouped into<-7.5 kg (n=903), -7.5--2.6 kg (n=1 883), -2.5-2.5 kg (n=2 573), 2.6-7.5 kg (n=2 786), 7.6-12.5 kg (n=2 674) and>12.5 kg (n=3 064). The association of body weight status in early adulthood and body weight change from early adulthood to middle age with HDL-C level was examined by logistic regression model.RESULTS: The prevalence of low HDL-C in underweight, normal weight, overweight and obesity groups at age of 25 years were 10.7%(143/1 331), 15.5%(1 612/10 400), 16.3%(330/2 019) and 24.8%(33/133), respectively(P for trend <0.01). The prevalence of low HDL-C for adult weight change were 8.8%(79/903), 8.0%(151/1 883), 10.5%(269/2 573), 13.4%(373/2 786), 19.1%(511/2 674), and 24.0%(735/3 064)(P for trend <0.01)for weight change of <-7.5 kg, -7.5--2.6 kg, -2.5-2.5 kg, 2.6-7.5 kg, 7.6-12.5 kg and>12.5 kg, respectively. Multivariate logistic regression showed that overweight and obesity at age of 25 years and subsequent weight gain till middle age were positively correlated with low HDL-C after adjusted other risk factors(all P for trend <0.01).CONCLUSION: Overweight and obesity in early adulthood and significant adult weight gain from early adulthood to middle age were both independently associated with marked increases in the risk of low HDL-C in middle-aged Chinese men and women. Thus, body weight control at early adulthood could be a key strategy to reduce the incidence of low HDL-C at middle-aged population.


Feng M.,Peking Union Medical College
Zhonghua yi xue za zhi | Year: 2016

OBJECTIVE: To predict the therapeutic effect of Cushing's disease after transsphenoidal surgery by using morning serum cortisol level.METHODS: The clinical data of 275 cases that had transsphenoidal surgery in Peking Union Medical College Hospital from 2010 to 2014 were analyzed retrospectively.Early morning serum cortisol level less than 140 nmol/L 3 days postoperation was usedto predict endocrinological remission. And long-term efficacy was evaluated by follow-up.RESULTS: Of the 275 patients, there were 49 males and 226 females; average age was 36.5 years old.Remission wasconfirmed in 201 cases, the remission rate was 73.1%, and 8 cases recurrent duringfollow-up.There were 17 macroadenomas, theremission rate was 47.1%; 258 microadenomas and MRI negative adenomas, the remission rate was 74.8%.And 43 recurrent cases had reoperations; the remission rate was 46.5%.CONCLUSION: Early morningserum cortisol 3 days post operation can evaluate the effectof transsphenoidal surgery, but even if the level of cortisol is less than 140 nmol/L, there is still tumor recurrence.Patients should be follow-up for a lifetime.


OBJECTIVE: To investigate the bowel symptoms and psychological status of patients with irritable bowel syndrome (IBS) with diarrhea (IBS-D), and to verify whether sigmoid colon mucosal mast cells (MCs) and their activation have effect on the symptoms and psychological status of IBS-D patients.METHODS: Patients meeting Rome Ⅲ diagnostic and subtyping criteria of IBS-D who visited the outpatient clinic of gastroenterology of Peking Union Medical College Hospital were consecutively enrolled between July 2009 and June 2012. IBS symptoms questionnaire was completed using face-to-face interview, and Hamilton Anxiety Scale (HAMA)/ Hamilton Depression Scale (HAMD) were administrated to evaluate psychological status, both by well-trained investigators. Mast cell tryptase monoclonal antibody was used for immunohistochemical staining to detect MCs and degranulated MCs in mucosal biopsy of sigmoid colon. MCs and degranulated MCs were blindly counted by a senior pathologist, and presented as number of cells in high power field (HPF) and percentage of activated MCs. Correlation analysis was performed using Spearman rank correlation analysis.RESULTS: Ninety-seven patients with IBS-D were enrolled in this study, with mean age of (44±11) years. 70.10%(68 cases) of the IBS-D patients had comorbid anxiety and/or depression. The median total numbers of MCs, activated MCs, and percentage of activated MCs in sigmoid mucosa were 11.60 (7.09)/HPF, 2.00 (1.40) /HPF, and 17.50% (10.90%), respectively. Patients having abdominal pain/discomfort before bowel movement "every day with intermediate to high severity" had significantly larger numbers of total MCs in sigmoid colon compared with those with pain or discomfort "not every day and mild" [13.80(4.85)vs 7.60(5.90)/HPF, P=0.019]; the patient having "frequent" urge to have a bowel movement and mushy stools showed significantly higher percentage of activated MCs in sigmoid colon mucosa compared to those having the symptoms "some of the time" [18.75%(9.12%) vs 14.50%(13.14%), P=0.031; 21.33%(7.43%)vs 11.51%(10.65%)vs 18.42%(8.61%), P=0.030]. There was a positive correlation between the bowel movement during IBS-D onset and the percentage of activated MCs (r=0.221, P=0.030). There were no statistically significant differences in the total number of MCs and percentage of activated MCs between the patients with anxiety/depression and those without anxiety/depression (P=0.255, P=0.315). Scores of HAMA and HAMD were found not correlated with either total MCs number or percentage of activated MCs in sigmoid colon mucosa(all P>0.05).CONCLUSIONS: The majority of IBS-D patients had comorbid anxiety and/or depression. The total number and activation status of MCs in sigmoid colon mucosa might be related with some intestinal symptoms in IBS-D patients. Psychological disorders might influence the pathogenesis and regression of IBS-D through brain-gut axis other than MCs in sigmoid colon mucosa.


Li L.,Peking Union Medical College
Zhonghua yi xue za zhi | Year: 2016

OBJECTIVE: To investigate the impact of placement in the procedures of gynecological laparoscopies or routine placement on the effects of levonorgestrel-releasing intrauterine system (LNG-IUS) for symptomatic adenomyosis in a prospective cohort study.METHODS: From December, 2006 to December, 2014, patients with adenomyosis diagnosed by transvaginal ultrasound in outpatient or inpatient clinics of Peking Union Medical College Hospital received the treatment of LNG-IUS.Before and after placement of LNG-IUS all the parameters were recorded including carrying status of IUS, symptoms and scores of dysmenorrhea, menstruation scores, biochemical indicators, physical parameters, menstruation patterns and adverse effects.Impact of placement timing (in the procedures of laparoscopies vesus routine placement) on the treatment effects, menstruation patterns and adverse effects of LNG-IUS were analyzed.RESULTS: 1 100 patients meet the inclusion criteria, with median age 36 years (20-44 years), median follow-up 35 months (1-108 months), of which 385 cases (35.0%) received LNG-IUS in the procedures of gynecological laparoscopies. Most common indications and pathology outcomes were endometriosis, major of which had deep infiltrating endometriosis. The accumulative carrying ratio of LNG-IUS were 73% and 63% on 60 months for operative patients and non-operative patients respectively (P<0.001), and accumulative take-out ratio were 7.8% and 10.3% (P=0.044). Placement timing of LNG-IUS was the only significant factor related with loss to follow-up (P<0.001) and take-out ratio (P<0.001). Operations and pathological outcome had no significant impact on patients' treatment effects, changes of menstruation patterns, adverse effects in total or in subclass.CONCLUSION: Placement of LNG-IUS in the procedures of gynecological laparoscopies for symptomatic adenomyosis increased carrying ratio and reduce take-out ratio at patients'request, but didn't influence treatment effects or adverse effects.


Cao Z.,Peking Union Medical College
Zhonghua wai ke za zhi [Chinese journal of surgery] | Year: 2016

Solid pseudopapillary neoplasm of the pancreas (SPN) is a rare neoplasm which primarily affects young women without specific clinical manifestation. Computed tomography and magnetic resonance imaging contribute to the preoperative diagnosis of SPN. Surgery is the main treatment approach for SPN and more research of radiation and chemotherapy is needed. Tumor diameter larger than 5 cm, tumor infiltrating nerve, vessel or adipose tissue can increase the risk of recurrence. However, these patients can still get good prognosis after surgical resection.


Zhang Y.S.,Peking Union Medical College
Zhonghua wai ke za zhi [Chinese journal of surgery] | Year: 2016

OBJECTIVE: To explore how clinical features of renal cell carcinoma (RCC) relate to cancer patients' prognosis and survival.METHODS: A total of 1 497 renal cell carcinoma patients received surgical treatments in Department of Urology, Peking Union Medical College were admitted between January 2002 and December 2012. Telephone interviews and complimentary medical records review were carried out to acquire follow-up data, including post-surgery adjuvant therapy, disease progression and survival.RESULTS: There were 1 326 of all 1 497 RCC cases successfully followed up, including 899 male and 427 female cases. The median age was 54(18) years (M(QR)). There were 1 049 T1 cases (79.11%), 139 T2 cases (10.48%), 125 T3 cases (9.43%), and 13 T4 cases (0.98%). As for types of surgery, there were 584 (44.04%) nephron-sparing surgery cases, and 742 (55.96%) radical nephrectomy cases. As for pathological subtypes, it included 1 153 (86.95%) clear cell renal cell carcinoma cases, and 173 (13.05%) non-clear cell renal cell carcinoma cases. Median length of follow-up was 43.6 months. During follow-up, 147 patients developed RCC related progression, with a median progression free survival of 18.2 months.Sixty-four patients died from RCC related progression, with a median cancer specific survival (CSS) of 27.7 months. RESULTS of data analysis showed that CSS rates of 1-, 5-, 10-year of T1 stage post-surgical RCC were 99.61%, 97.24%, 92.08%, respectively; CSS rates of 1-, 5-, 10-year of T2 stage were 98.51%, 92.01%, 85.08%, respectively; and CSS rates of 1-, 5-, 10-year of T3-4 stage were 92.40%, 77.99%, 42.56%, respectively. Multivariable Cox regression analysis showed that signs of lung metastasis, signs of bone metastasis, tumor N stage, pathological subtype, microscopic sarcomatoid changing, and types of progression were major risk factors for RCC cancer specific survival (P<0.05).CONCLUSIONS: Surgery is the primary choice of treatment in RCC. The survival is not same with different T stage. T stage affects the progression of renal cell carcinoma. N stage, lung and bone symptoms, pathological type, sarcomatoid changes and postoperative metastasis of renal cell carcinoma will affect the mortality of patients.


Guo J.C.,Peking Union Medical College
Zhonghua wai ke za zhi [Chinese journal of surgery] | Year: 2016

With United States starting"precision medical plan", it is widespread all over the world and opens a new direction to the development of medicine. Our country also starts the plan, trying to take the opportunity. At present, tumor threats human health with high incidence and mortality. In China, the incidence and mortality of tumor has been on the rise.So the tumor has become one of the most important fields of precision medicine.Precision medicine, hoping to reveal the Chinese characteristics of precision medicine, and getting the personal and social maximize health benefits are discussed in the paper.


OBJECTIVE: To explore the clinical characteristics and impact of diabetes mellitus (DM) on prognosis in patients with nonvalvular atrial fibrillation (AF).METHODS: Data of nonvalvular AF patients in the Chinese Emergency Atrial Fibrillation Registry Study were retrospectively analyzed. The eligible patients were divided into the DM group and the non-DM group. Uni- and multi-variate Cox regression analysis were used to explore risk factors of 1-year outcomes.RESULTS: A total of 1 644 patients were enrolled in the study with 227 patients combined with DM (16.8%). Compared with non-DM group, patients with DM were older and had higher body weight, had higher prevalence of myocardial infarction, coronary heart disease, hypertension and stroke, and were at higher risk of thromboembolism. The proportion of anticoagulant treatment was low in both groups (10.1% vs 7.4%, P=0.141). Compared with patients without DM, patients with DM had higher all-cause mortality (19.5% vs 12.7%, P=0.004), cardiovascular death (10.8% vs 7.02%, P=0.047) and combined end events (CEE, 26.4% vs 2.4%, P=0.023), while with comparable incidence of stroke (10.1% vs 7.4%, P=0.141). Multi-variate Cox regression analysis showed that DM was an independent risk factor for 1-year all-cause mortality (HR=1.558, 95% CI 1.126-2.156), cardiovascular death (HR=1.615, 95% CI 1.052-2.479) and CEE (HR=1.523, 95% CI 1.098-2.112), while not for stroke (HR=1.523, 95% CI 1.098-2.112).CONCLUSION: DM is the independent risk factor for all-cause mortality, cardiovascular death and combined end events in patients with nonvalvular AF, while not a predictor for the occurrence of stroke.


Zhang S.,Peking Union Medical College
Zhonghua yi xue za zhi | Year: 2016

OBJECTIVE: To explore the method of cheek blood sampling in mice in continuous blood test.METHODS: Cheek blood sampling was carried out in 10 9-week-old mice once every 2-3 days. The volumes of blood samples were recorded. Reactions of the mice were observed.RESULTS: Cheek blood sampling collected 0.3-0.6 ml of blood every time, and did not affect the normal activities of the mice. The blood sampling could be repeated every 2-3 days.CONCLUSIONS: Cheek blood sampling has several advantages including being capable to draw adequate blood, simple and easy to operate, well tolerated, and ethical in treating laboratory animals.


Zou Y.,Peking Union Medical College
Zhonghua er ke za zhi = Chinese journal of pediatrics | Year: 2016

OBJECTIVE: To evaluate the copy number variations (CNVs) in pediatric ETV6/RUNX1 gene positive acute lymphoblastic leukemia(ALL) and its correlation with clinical features and prognosis.METHOD: Totally 141 children (<14 years of age) with newly diagnosed ETV6/RUNX1 positive ALL in Institute of Hematology and Blood Diseases Hospital, were included from January 2006 to November 2012. The CNVs were analyzed by multiplex ligation-dependent probe amplification (MLPA). The survival rate between the patients with CNVs were explored. Overall survival (OS) and event-free survival (EFS) were estimated by the Kaplan-Meier method and compared with the log-rank test.RESULT: Among the 141 cases, 55.3% (n=78) were boys and 44.7% (n=63) were girls and the median age was 4 (1-13) years. The estimated 5-year DFS rate for the patients was (84±4)%. The estimated 5-year OS rate for the patients was (85±4)%. Ninety-five patients were tested MLPA. CNVs were detected in 73 cases (76.8%). CNVs of genes EBF1(15.8%), CDKN2A/2B(18.9%), PAX5(21.1%), ETV6(54.8%), BTG1(10.5%) were detected in more than 10% of the patients. Among the 95 patients, EBF1 deletions were found in 9 patients and EBF1 amplifications were found in 6 patients; 5-year recurrence-free survival (RFS) was statistically significant among 3 groups (χ(2)=9.809, P=0.007) . PAX5 deletions were found in 13 patients and PAX5 amplifications were found in 7 patients; the difference in 5-year RFS was statistically significant between 3 groups(χ(2)=7.622, P=0.022). ETV6 deletions were found in 39 patients and ETV6 amplifications were found in 13 patients; the difference in 5-year RFS was statistically significant among the 3 groups (χ(2)=11.045, P=0.004).CONCLUSION: The CNVs had prognostic relevance in ETV6/RUNX1 positive ALL.


Sun H.,Peking Union Medical College
Zhonghua xin xue guan bing za zhi | Year: 2016

OBJECTIVE: To investigate the medical care resources of acute myocardial infarction (AMI) in Chinese hospitals of different regions and levels.METHODS: We selected 115 hospitals in China, including 61 northern hospitals, 54 southern hospitals, 52 eastern hospitals, 26 central hospitals, 37 western hospitals, 79 tertiary hospitals, 36 secondary hospitals, 34 pro vincial-level hospitals, 46 prefectural-level hospitals and 35 county hospitals. From November 2012 to August 2013, we sent questionnaire to the cardiologists in each hospital, to collect related information.RESULTS: (1) The number of AMI admitted each year of northern hospital was more than the number of southern hospital (220 (120, 400) cases vs. 220 (80, 350) cases, P=0.033), while number of coronary care unit (CCU), thrombolytic therapy, percutaneous coronary intervention (PCI), primary PCI and coronary artery bypass grafting (CABG) were similar (all P> 0.05). (2) The number of AMI admitted each year of eastern, central and western hospital was 295(150, 501) cases, 175(75, 300) cases and 170(50, 250) cases respectively(P=0.007), with no significant difference among them for setting CCU, carrying out thrombolytic therapy, PCI, primary PCI and CABG (all P>0.05). (3) The total number of the in-patient beds and AMI admitted each year of tertiary hospitals were significantly higher than that in the secondary hospitals(104(70, 152)vs. 47(30, 52), P<0.001) and (300(200, 460)cases vs.80(47, 135)cases, P<0.001) respectively. There was a significant difference between tertiary and secondary hospitals for the number of CCU (97.5% (77/79)and 75.0%(27/36)), PCI (98.7%(78/79)and 27.8%(10/36)), primary PCI (96.2%(76/79)and 22.2%(8/36)), CABG (81.0%(64/79)and 11.1%(4/36)), intra-aortic balloon pump (IABP) (91.1%(72/79) and 13.9%(5/36)) respectively (all P<0.001). (4) There were obvious differences among provincial-level, prefectural-level and country-level hospitals for the admitted AMI patient numbers annually which was 400(250, 600), 232(100, 380)and 80(50, 162)cases, CCU proportion which was 100 %(34/34), 95.7%(44/46) and 74.3%(26/35), thrombolytic therapy proportion which was 88.2%(30/34), 100%(46/46)and 91.4%(32/35), PCI proportion which was 100%(34/34), 89.1%(41/46)and 37.1%(13/35), primary PCI proportion which was 100%(34/34), 84.8%(39/46)and 31.4%(11/35), CABG proportion which was 97.1%(33/34), 67.4%(31/46) and 11.4%(4/35)respectively (P<0.01 or 0.05) .CONCLUSIONS: Different regional hospitals have no significant difference in number of CCU and reperfusion therapies, while there is a big difference on medical care resources of AMI between different-level hospitals, which may affect the diagnosis and treatment effect of patients with AMI. Clinical Trail Registry: National Institutes of Health, NCT01874691.


OBJECTIVE: To explore the effects of five different therapy in women at early stage of menopause on menopausal symptoms, quality of Life and cardiovascular risk factors.METHODS: A total of 140 women at early stage of menopause were randomly divided into five groups. Thirty women took Conjugated estrogen and medroxyprogesterone acetate(CEE+ MPA) sequential therapy, 27 women took estradiol valerate and medroxyprogesterone acetate(E2V+ MPA) sequential therapy, 26 women took estradiol valerate and Progesterone Soft Capsules(E2V+ P) sequential therapy, 30 women took Kuntai capsule, and 27 took Cohosh extract.Patients in the Menopausal Hormone Therapy(MHT) groups took twelve cycles of treatment course, in the botanical drug and Chinese patent drug groups took twelve months. The KMI scalewas used to measure the level of menopausal symptoms. MENQOL scale was used to measure the health-related quality of life before and at the 3(rd) month, 6(th) month, 9(rd) month and 12(th) month after the treatment. Some serological indicators which related to cardiovascular risk factors were collected before and at the 12(th) month after the treatment.RESULTS: (1) KMI: It showed that the KMI in five groups after the treatment were significantly different(P<0.01), the group of CEE+ MPA decreased most(13±1). The KMI after the treatment were all significantly lower than that before. (2)MENQOL: It showed that the MENQOL in five groups were significantly different(P<0.01), the group of CEE+ MPA decreased most (84±3), then the group of Kuntai(85±3). The MENQOL after the treatment were all significantly lower than that before. (3)The change of cardiovascular risk factors: it showed that the serological indicators FBGin group of CEE+ MPA after the treatment were significantly lower than that before(P<0.05); the TC, LDL, FI in group of E2V+ MPA after the treatment were significantly lower than that before(P<0.05); the FBG, FI in group of E2V+ P after the treatment were significantly lower than that before(P<0.05).CONCLUSION: The MHT, botanical drug and Chinese patent drug have great clinical curative effects in treating perimenopause syndrome, improving the health-related quality of life and decreasing risk factors of cardiovascular disease.With rare adverse events and good clinical medication safety, they could be widely applied to clinic to women at early stage of menopause who was suffering menopausal symptoms.


Zhang H.,Peking Union Medical College
Zhonghua yi xue za zhi | Year: 2016

OBJECTIVE: To analyze the effect of preoperative factors on the clinical outcome in patients receiving total knee replacement.METHODS: From January 2011 to September 2013, 145 patients (206 knees; 22 males, 31 knees; 123 females, 175 knees)receiving total knee arthroplasty were successfully included in this study and followed up. The average ages was (66.5±7.6) years old(range, 51-83 years old). The data of preoperative factorsincludedgender, age, body mass index (BMI), preoperative range of motion (ROM), the knee varus angle, flexion deformity and preoperative the hospital for special surgery (HSS) scorewere collected. The correlation between preoperative factors and the clinical outcome (postoperative HSS score, postoperative ROM)after total knee replacement was evaluated statistically.RESULTS: The average follow-up time was 35 months (range, 24-56 months). The HSS score was increased from (55.1±7.6) preoperativelyto (89.3±5.1) postoperatively. ROM elevated from (95.6±10.0)°preoperatively to (115.1±7.8)° postoperatively.The correlation analysis showed that the postoperative ROM was positively correlated with the preoperative ROM, and was negatively correlated with the BMI, the knee varus angle(r=-0.864, -0.353, all P<0.01). The postoperative HSS score was positively correlated with preoperative ROM, preoperative HSS score(r=0.101, 0.244, P=0.033, P<0.01), and was negatively correlated with the BMI (r=-0.277, P=0.039).CONCLUSIONS: Total knee arthroplasty can definitely improve the function of knee joint. The BMI, the preoperative ROM, the knee varus angle and preoperative HSS score have influence on postoperative function of patients receiving total knee arthroplasty.


Xiao Y.,Peking Union Medical College
Zhonghua wai ke za zhi [Chinese journal of surgery] | Year: 2016

Considering radical surgeries of right colon cancer, the reasonable extent of lymphadenectomy has always been argued. The concept of complete mesocolic excision (CME) has recently been established and optimized, which follows similar oncological principles as total mesorectal excision (TME) does for rectal cancer and is recommended by more and more surgeons. Studies published so far in the literature have been comprehensively reviewed, they do not, however, provide convincing evidence that demonstrate the standardized operation indications. Moreover, the existence of potential surgical risk and discernible oncological benefit has not been determined. Thus future studies are needed to further investigate the safety and efficacy of CME surgery, as has been demonstrated with TME such that it should become the procedure of choice in surgical practice.


Zheng X.,Peking Union Medical College
Zhonghua yi xue za zhi | Year: 2016

OBJECTIVE: We aimed to assess trends in clinical characteristics, treatment, and outcomes for hospitalized patients undergoing percutaneous coronary intervention (PCI) in eastern urban China from 2001 to 2011.METHOD: We analyzed a Chinese eastern representative sample of hospital admissions for PCI identified in China PEACE-retrospective CathPCI study using a two-stage random sampling design and calculated the weighted data of clinical information in each year.RESULTS: We included 3 308 admissions for PCI in 29 urban hospitals.Between 2001 and 2011, rates of hospitalizations for PCI increased by 15 fold.Compared with 2001, the patients undergoing PCI were more likely to be female, older than 70 years, and to have history of diabetes, hypertension, dyslipidemia and PCI in 2011.The proportion of trans radial PCIs was increased from 3.5% in 2001 to 72.6% in 2011 (Statistic=-28.95, Ptrend<0.000 1); the proportion of drug eluting stents (DES) among all the implanted stents was increased from 18.2%in 2001 to 98.4% in 2011(Statistic=-40.82, Ptrend<0.000 1), largely due to increased use of domestic DES.Less than 10% of medical records of patients undergoing primary PCI documented door time and balloon time.The median length of stay decreased from 13 days in 2001 to 10 days in 2011 (Statistic=-0.11, Ptrend<0.001). In-hospital mortality did not change significantly, but both any bleeding (Statistic= 2.66, Ptrend< 0.01) and access bleeding were decreased significantly (Statistic= 5.55, Ptrend< 0.000 1).CONCLUSIONS: During 2001 and 2011 in eastern urban China, there has been a rapid increase in the number and significant change in treatment patterns of PCI.Quality gaps are identified that represent opportunities to improve care.


Guo Z.-R.,Peking Union Medical College
Yaoxue Xuebao | Year: 2017

Precision medicine (PM) involves the application of "omics" analysis and system biology to analyze the cause of disease at the molecular level for targeted treatments of individual patient. Based on the targeted treatment PM is closely related to pharmaceuticals, which, as a therapeutic means and supply front, mainly embody the two aspects: drug discovery/development, and clinical administration. Innovation of new molecular entities with safety and specific efficacy is the prerequisite and guarantee for the PM practice; on the other hand, the outcome and clues in clinical PM feedback to new drug research. PM and drug research/application are interdependent and promote each other. Aimed at precision medicine, drug discovery and development involve well-known contents: the discovery and validation of targets, the association between target functions and indications (proof of concept), lead discovery and optimization, the association between preclinical investigations and clinical trials, the lean of industrialization and pharmacoeconomics. At the molecular level the therapeutic efficacy originates from the interactive binding between specific atoms or groups of the drug molecule and the complementary atoms or groups of the macromolecular target in three-dimensional space. The strict arrangement of such critical atoms, groups, or fragments reflect specific features for a precise binding to the corresponding target. An alteration of amino acid residues in mutational targets leads to the change in conformation of the target protein, and an accurate structure of drug is necessary for binding to the mutant species and avoiding off-targeting effect. For the tailoring of clinical treatment to the individual patient design and development of various new molecular entities are critical for treatment choice according to the molecular features of biological markers of patients. This article provides some examples and methods of drug design and development in the new period.


Yang J.,Peking Union Medical College | Zheng R.,Peking Union Medical College
Chinese Journal of Medical Imaging Technology | Year: 2016

131I therapy has proven effective in treatment of differentiated thyroid cancer (DTC) patients with pulmonary metastases.131I therapy can enhance the cure rate, efficiency, long-term efficacy and survival rate of DTC patients with lung metastases. Factors that affect the efficacy of 131I therapy on DTC patients with lung metastases include dose and frequency of treatment, patients' age, 131I uptake capacity and effective half-life, whether combined with other distant metastases, the size of pulmonary metastases, histological type, serum thyroid stimulating hormone level and thyroglobulin level for the first time before treatment. 131I therapy has proven to be of high security to DTC patients with lung metastases. The main adverse reactions are lung function damage, gastrointestinal irritation, neck swell and ache, salivary glands dysfunction. Curative effect and influencing factors of 131I in treatment of DTC patients with pulmonary metastases were reviewed in this paper. Copyright © 2016 by the Press of Chinese Journal of Medical Imaging and Technology.


Wang D.,Peking Union Medical College | Li H.,Peking Union Medical College | Ji Z.,Peking Union Medical College
International Journal of Clinical and Experimental Medicine | Year: 2017

This study aimed to evaluate the effect of nephron-sparing surgery (NSS) along with preoperative selective arterial embolization (SAE) on the treatment of giant renal angiomyolipomas (AML). Between July 2010 and October 2014, 3 men and 8 women with 11 sporadic giant renal AMLs were treated by NSS along with preoperative SAE in our center. The tumor size ranged from 10.4 to 24.2 cm. The medical data were collected. Of the 11 giant AMLs, 8 were completely devascularized by SAE, and the other 3 were mostly devascularized. The rate of post-embolization syndrome was 27.2% (3/11). NSS was successfully performed after SAE in all patients. The operating time was 70-155 min (mean, 115 min). Blood loss was 50-150 ml (mean, 70 ml). The warm ischemia time was 8-25 min (mean, 15 min). The incidence of perioperative complications was 18.2% (2/11), and no severe complications occurred after NSS. The hospitalization time after NSS was 5-10 d (mean, 6.6 d). There was no statistical difference in kidney function pre- and post-surgery. No evidence of recurrence was found during the follow-up period. NSS with preoperative SAE can be considered a viable and effective treatment option for giant renal AMLs, for it avoids excess blood loss and shortens warm ischemia time during NSS. © 2017, E-Century Publishing Corporation. All rights reserved.


Chen W.,Peking Union Medical College | Yan W.,Peking Union Medical College | Cai J.,Peking Union Medical College
International Journal of Clinical and Experimental Medicine | Year: 2017

The associations between nephrotic syndrome and prostate cancer are less reported. We herein describe an instructive case in a 64-year-old male. He was admitted in our hospital because of nephrotic syndrome. The result of renal biopsy was membranous nephropathy stage II. Although steroid and cytotoxic drug were given, the control of proteinuria was poor. One year later, the patient was hospitalized again, accepted transrectal prostatic biopsy because of a 3-month history of dysuria and the high level of PSA (6.86 ng/ml). The pathological result was poorly differentiated prostatic adenocarcinoma (T1aN0M0). Subsequently he underwent radical prostatectomy. After operation the patient went into complete remission of nephrotic syndrome, no proteinuria was subsequently detected. The immuofluoresence and electron microscopy found the decrease of staining of IgG and C3, and absorption of immune-complex by the glomerular basement membrane. No relapse of nephrotic syndrome or prostate cancer was observed during nearly 3 years of follow-up. The observation of clinical remission after radical prostatectomy and pathological findings before and after operation in our study indicate that there is a relationship between prostatic cancer and nephrotic syndrome. This case reminds clinicians that for elder patients with nephrotic syndrome, a diagnosis of prostate cancer should be considered. © 2017, E-Century Publishing Corporation. All rights reserved.


OBJECTIVES: Radioactive iodine (RAI) therapy is recommended for differentiated thyroid cancer (DTC) patients with microscopic extrathyroid extension (ETE). Patients with a low preablative stimulated thyroglobulin (ps-Tg) level have a more favorable prognosis. It remains uncertain whether low-activity RAI could have the same efficacy in patients with low ps-Tg. This study aimed to evaluate the effectiveness of low-activity RAI therapy in low-level ps-Tg DTC with ETE. PATIENTS AND METHODS: The inclusion criteria for this retrospective study were as follows: (a) age 18 years or older, (b) DTC after total or near-total thyroidectomy of DTC, (c) no distant metastasis after thyroidectomy and before RAI therapy, (d) American Joint Committee on Cancer pT3 stage (with microscopic ETE) with any American Joint Committee on Cancer N stage, (e) ps-Tg level of 5 ng/ml or less, and (f) after the first time of RAI therapy. The response of patients was assessed at 20–24 months after RAI therapy and considered an excellent response (ER) or non-ER. RESULTS: A total of 132 patients were included, 69 patients in low activity (1100 MBq) and 63 in high activity (≥3700 MBq). ER was observed in 86.9% of patients in the low-activity group (60/69), which did not differ from the high-activity group (P=0.165) at 20–24 months’ assessment. For patients with different N statuses (N0, N1a, N1b), a noninferior response could also be achieved under low-activity RAI therapy compared with the high-activity group (P=1.000, 0.286, 0.722, respectively). CONCLUSION: Low-activity RAI therapy is not inferior to high-activity therapy in achieving an ER in microscopic ETE DTC with ps-Tg less than 5 ng/ml irrespective of the lymph node metastases. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.


Wang H.,Capital Medical University | Cai J.,Peking Union Medical College
Biochimica et Biophysica Acta - Molecular Basis of Disease | Year: 2016

MicroRNAs are small non-coding RNA molecules that regulate gene expression by inhibiting mRNA translation and/or inducing mRNA degradation. In the past decade, many in vitro and in vivo studies have explored the involvement of microRNAs in various cardiovascular diseases. In this paper, studies focused upon the target genes and functionality of miRNAs in the pathophysiological processes of heart failure are reviewed. The selected miRNAs are categorized according to the biological relevance of their target genes in relation to four cardiovascular pathologies, namely angiogenesis, cardiac hypertrophy, fibrosis and apoptosis. This review illustrates the involvement of miRNAs in different biological signaling pathways and provides an overview of current understanding of the roles of miRNAs in cardiovascular health and diseases. This article is part of a Special Issue entitled: Genetic and epigenetic control of heart failure - edited by Jun Ren & Megan Yingmei Zhang. © 2016.


Chen W.,Peking Union Medical College | Zheng R.,Peking Union Medical College | Zeng H.,Peking Union Medical College | Zhang S.,Peking Union Medical College
Chinese journal of cancer | Year: 2016

BACKGROUND: The National Central Cancer Registry (NCCR) collected population-based cancer registration data in 2012 from local registries and estimated the cancer incidence and mortality in China.METHODS: In the middle of 2015, 261 cancer registries submitted reports on new cancer cases and deaths occurred in 2012. Qualified data from 193 registries were used for analysis after evaluation. Crude rates, number of cases, and age-standardized rates stratified by area (urban/rural), sex, age group, and cancer type were calculated according to the national population in 2012.RESULTS: The covered population were 198,060,406 from 193 qualified cancer registries (74 urban and 119 rural registries). The major indicators of quality control, percentage of cases morphologically verified (MV%), death certificate-only cases (DCO%), and the mortality to incidence (M/I) ratio, were 69.13%, 2.38%, and 0.62, respectively. It was estimated that there were 3,586,200 new cancer cases and 2,186,600 cancer deaths in 2012 in China with an incidence of 264.85/100,000 [age-standardized rate of incidence by the Chinese standard population (ASRIC) of 191.89/100,000] and a mortality of 161.49/100,000 [age-standardized rate of mortality by the Chinese standard population (ASRMC) of 112.34/100,000]. The ten most common cancer sites were the lung, stomach, liver, colorectum, esophagus, female breast, thyroid, cervix, brain, and pancreas, accounting for approximately 77.4% of all new cancer cases. The ten leading causes of cancer death were lung cancer, liver cancer, gastric cancer, esophageal cancer, colorectal cancer, pancreatic cancer, female breast cancer, brain tumor, leukemia, and lymphoma, accounting for 84.5% of all cancer deaths.CONCLUSIONS: Continuous cancer registry data provides basic information in cancer control programs. The cancer burden in China is gradually increasing, both in urban and rural areas, in males and females. Efficient cancer prevention and control, such as health education, tobacco control, and cancer screening, should be paid attention by the health sector and the whole society of China.


Deng T.,Chinese Institute of Clinical Medical Sciences | Chen Q.,Peking Union Medical College | Han D.,Peking Union Medical College
Frontiers in Bioscience - Landmark | Year: 2016

Three members of a receptor tyrosine kinase family, including Tyro3, Axl, and Mer, are collectively called as TAM receptors. TAM receptors have two common ligands, namely, growth arrest specific gene 6 (Gas6) and protein S (ProS). The TAM-Gas6/ProS system is essential for phagocytic removal of apoptotic cells, and plays critical roles in regulating immune response. Genetic studies have shown that TAM receptors are essential regulators of the tissue homeostasis in immunoprivileged sites, including the testis, retina and brain. The mechanisms by which the TAM-Gas6/ProS system regulates the tissue homeostasis in immunoprivileged sites are emerging. The roles of the TAM-Gas6/ProS system in regulating the immune privilege were intensively investigated in the mouse testis, and several studies were performed in the eye and brain. This review summarizes our current understanding of TAM signaling in the testis and other immunoprivileged tissues, as well as highlights topics that are worthy of further investigation. © 1996-2016.


Li Z.-H.,Peking Union Medical College | Liao G.-Y.,Peking Union Medical College
Chinese Journal of Biologicals | Year: 2016

The mortality of acute respiratory infections is only below those of cardiovascular diseases, which has become a serious public health problem. There are several kinds of vaccines against the pneumonia associated pathogens in market or in development. However, effective vaccines against Mycoplasma pneumonia are rarely reported. The special structure of M. pneumoniae makes it is difficult to be treated effectively by conventional drugs, resulting in that the incidence increased year by year. Hie research on the related mechanism as well as methods for prevention and treatment of pneumouiais caused by M. pneumonia has become a hot spot, and it is more and more important to decrease the risk of disease by development of the relevant vaccines.


Li X.,Peking Union Medical College
Pediatric Critical Care Medicine | Year: 2017

OBJECTIVES:: Assess the diagnostic value of serial monitoring of procalcitonin levels on early postoperative infection after pediatric cardiac surgery with cardiopulmonary bypass. DESIGN:: Prospective, observational study. SETTING:: A pediatric cardiac surgical ICU (PICU) and pediatric cardiac surgery department at Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College. PATIENTS:: Patients were 3 years old and below, underwent cardiac surgery involving cardiopulmonary bypass, the Aristotle Comprehensive Complexity score was 8 or higher and free from active preoperative infection or inflammatory disease. INTERVENTIONS:: Blood samples for measurement of procalcitonin, C-reactive protein, and WBC were taken before surgery and daily for 7 days in postoperative period. Clinical, laboratory, and imaging data were collected on enrollment. Procalcitonin, C-reactive protein, WBC levels, and procalcitonin variation were calculated and compared between those with and without infection. MEASUREMENTS AND MAIN RESULTS:: Two hundred and thirty-eight children were enrolled. Presence of infection within 7 days of surgery, length of intubation, and ICU stay were documented. Two independent experts in regard to the complete medical chart determined the final diagnosis of postoperative infection. Infection was diagnosed in 45 patients. Procalcitonin peaked on the first postoperative day. No differences were found on procalcitonin within 3 days after operation between the infected and the noninfected patients, and significant correlation was found between procalcitonin on postoperative days 1–3 and cardiopulmonary bypass duration. Serum procalcitonin concentration was always higher than 1.0 ng/mL within 7 days after surgery and/or procalcitonin variation between postoperative days 4 and 7 was positive in the infected patients. Best receiver operating characteristics curves area under the curve were obtained for procalcitonin and procalcitonin variation from postoperative days 5 to 7. WBC- and C-reactive protein–related receiver operating characteristics curves area under the curve revealed a very poor ability to predict infection. Logistic regression found that only procalcitonin on postoperative day 7 and PICU stay was independently correlated to the infection status. There was no significant correlation between the absolute value of procalcitonin and timing of infection. CONCLUSIONS:: Procalcitonin was more accurate than C-reactive protein and WBC to predict early postoperative infection, but the diagnostic properties of procalcitonin could not be observed during the first 3 postoperative days due to the inflammatory process related to cardiopulmonary bypass. The dynamic change of procalcitonin is more important than the absolute value to predict postoperative infection. The maintenance of a high level (procalcitonin > 1.0 ng/mL) within 7 days after surgery and/or a second increase in procalcitonin between the fourth and the seventh postoperative day could be used as an indicator of postoperative infection. Continuous procalcitonin monitoring might help to discover infection earlier. ©2017The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies


Li Y.,Peking Union Medical College | Zhu C.Y.,Peking Union Medical College
International Journal of Nanomedicine | Year: 2017

In oral administration, gastrointestinal physiological environment, gastrointestinal epithelial cell membranes, and blood circulation are typical biological barriers to hepatic delivery of ligand-modified nanoparticle drug delivery systems. To elucidate the mechanism of oral hepatic targeting of cholic acid receptor-mediated nanoliposomes (LPs) (distearoyl phosphatidylethanolamine-polyethylene glycol-cholic acid-modified LPs, CA-LPs), evaluations were performed on colon cancer Caco-2 cell monolayers, liver cancer HepG2 cells, and a rat intestinal perfusion model. CA-LPs, ~100 nm in diameter, exhibited sustained-release behavior and had the greatest stability in rat gastrointestinal fluid and serum for both size and entrapment efficiency. CA-LPs demonstrated highest transport across Caco-2 cells and highest cellular uptake by HepG2 cells. The enhanced endocytosis of CA-LPs was found to be mediated by Na+/taurocholate cotransporting polypeptide and involved the caveolin-mediated endocytosis pathway. Further, we used fluorescence resonance energy transfer (FRET) technology to show that the CA-LPs maintained their structural integrity in part during the transport across the Caco-2 cell monolayer and uptake by HepG2 cells. © 2017 Li and Zhu.


Geng X.-L.,Peking Union Medical College | Liao G.-Y.,Peking Union Medical College
Chinese Journal of Biologicals | Year: 2017

At present, vaccination is still the most effective measure to prevent influenza. Influanza vaccines are mainly trivalent inactivated vaccine and live attenuated vaccine. Although the inactivated vaccine is safe and effective, it needs a large amount of antigen, complicate production process and long production cycle, while induces low mucosal immunity. However, live attenuated influenza vaccine can induce antibody as well as a series of adaptive immune responses including mucosal and cellular immunities, thus is considered more effective than inactivated vaccine. This article reviews the history and current situation, screening of candidate vaccine virus strain and development of cell-based live attenuated influenza vaccine.


Li B.,Peking Union Medical College | Ye J.,Peking Union Medical College
Zhonghua Shiyan Yanke Zazhi/Chinese Journal of Experimental Ophthalmology | Year: 2017

Proliferative diabetic retinopathy (PDR) is one of the serious ocular complications of patients with diabetes mellitus and also the leading cause of blindness. Pars plana vitrectomy (PPV) is an effective treatment for severe vitreous hemorrhage and PDR. The intraocular concentration of vascular endothelial growth factor (VEGF) of patients with PDR usually increase abnormally, which promote growth of neovessels and make it early to leak and bleed. Numerous neovessels in vitreous cavity and retinal surface can lead to intraoperative bleeding and may affect the definition and precision of operation and prolong surgical time. If we conduct gas/fluid exchange regardless of severe active bleeding, proliferate membrane may reoccur at a high rate postoperatively due to the residual platelet and impair the success rate of surgery seriously. In addition, with the high activity of neovessels, anterior chamber, vitreous and retinal hemorrhage may appear as well as other postoperative complications like postoperative high intraocular pressure caused by inflammation or hemorrhage and traction retinal detachment because of reoccurrence of fibro membrane, which directly affect the postoperative visual function recovery and long-term prognosis. As wide clinical application of anti-VEGF agents in recent years, studies found that preoperative intravitreal injection of anti-VEGF drugs assisted PPV can limit the activity of neovessels and significantly reduce the incidence of intraoperative and postoperative bleeding, facilitate operation, shorten surgical time and improve the success rate of surgery. In this paper, the mechanism, effectiveness, clinical utility and safety of anti-VEGF therapy assisted vitrectomy for the treatment of PDR are reviewed. Copyright © 2017 by the Chinese Medical Association.


Li L.,Peking Union Medical College | Bai H.,Peking Union Medical College | Yang J.,Peking Union Medical College | Cao D.,Peking Union Medical College | Shen K.,Peking Union Medical College
Oncotarget | Year: 2017

Ovarian cancer has the worst prognosis of any gynecological malignancy, and generally presents with metastasis at advanced stages. Copy number variation (CNV) frequently contributes to the alteration of oncogenic drivers. In this study, we sought to identify genetic targets in heterogeneous clones from human ovarian cancers cells. We used array-based technology to systematically assess all the genes with CNVs in cell models clonally expanded from A2780 and SKOV3 ovarian cancer cell lines with distinct highly and minimally invasive/migratory capacities. We found that copy number alterations differed between matched highly and minimally invasive/migratory subclones, differentially affecting specific functional processes including immune response processes, DNA damage repair, cell cycle and cell proliferation. We also identified seven genes as strong candidates, including DDB1, ERCC1, ERCC2, PRPF19, BCAT1, CDKN1B and MARK4, by integrating the above data with gene expression and clinical outcome data. Thus, by determining the molecular signatures of heterogeneous invasive/migratory ovarian cancer cells, we identified genes that could be specifically targeted for the treatment and prognosis of advanced ovarian cancers.


Li W.,Peking Union Medical College | Zhang J.,Peking Union Medical College | Guo L.,Peking Union Medical College | Chuai S.,Burning Rock Biotech | And 2 more authors.
Journal of Thoracic Oncology | Year: 2017

Introduction The purpose of this study was to explore the complicated rearrangement mechanisms underlying cases with atypical and negative anaplastic lymphoma receptor tyrosine kinase gene (ALK) fluorescence hybridization (FISH) and positive immunohistochemistry (IHC) results and to stress the importance of combinational assay of these two methods in current pathological diagnosis. Methods A total of 3128 NSCLCs were screened for ALK fusions through both FISH analysis and IHC assays with Ventana-D5F3 antibody. Fourteen cases with atypical and negative FISH results with the current criteria and positive IHC results were analyzed with targeted next-generation sequencing (NGS). Results Of the 3128 cases tested, 228 (7.3%) and 214 (6.8%) were ALK positive by IHC and FISH, respectively. Fourteen cases with negative and atypical FISH results all demonstrated IHC positivity. Of 2991 cases, eight (0.27%) with negative FISH results demonstrated echinoderm microtubule associated protein like 4 gene (EML4)-ALK fusions revealed by targeted NGS, and the relative abundance of fusion ranged from 0.9% to 46.8%. Three of 2991 cases (0.1%) did not exhibit any type of ALK fusions. In addition, two patients showed an isolated 5′ side signal and targeted NGS revealed two novel ALK partner genes, baculoviral IAP repeat containing 6 gene (BIRC6) and phosphatidylinositol binding clathrin assembly protein gene (PICALM). One patient showed an isolated and attenuated 3′ red signal and demonstrated a novel translocation partner with CCAAT/enhancer binding protein zeta gene (CEBPZ). Of all the patients, four received crizotinib treatment and demonstrated partial responses at the end of follow-up. Conclusions Our study showed that patients with negative and atypical ALK FISH patterns may have positive results for IHC testing and harbor the translocation partners of EML4 or other genes. Therefore, additional testing with NGS should be conducted to explore the molecular mechanisms underlying the complicated gene rearrangement events. © 2016 International Association for the Study of Lung Cancer


Tian C.,Peking Union Medical College | Pan S.,Peking Union Medical College
Interactive Cardiovascular and Thoracic Surgery | Year: 2017

We report the case of a 26-year old woman who underwent successful tricuspid valve repair for the absence of the anterior papillary of the tricuspid valve. Preoperative echocardiography revealed grade IV tricuspid valve regurgitation, caused by congenital absence of the anterior papillary muscle and prolapse of the anterior leaflet. Tricuspid valve repair was performed using artificial chords consisting of two polytetrafluoroethylene sutures and a concomitant ring annuloplasty. Postoperative echocardiography revealed mild tricuspid valve regurgitation. This approach represented a safe and effective technique for tricuspid valve repair in congenital absence of papillary muscle. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.


Kong X.,Peking Union Medical College | Kong X.,Massachusetts General Hospital | Kong Y.,Peking Union Medical College
OncoTargets and Therapy | Year: 2017

The aim of this study was to summarize the findings of previous studies focusing on whether the risks of certain neurotoxicities are correlated to the programmed death 1 (PD-1) inhibitor nivolumab versus other chemotherapy or immunotherapy drugs. Six eligible studies, including 3,023 patients, were considered in the meta-analysis. The risk ratios (RRs) of fatigue, headache, dysgeusia, vertigo, paresthesia, anxiety or malaise and peripheral neuropathy were 0.908 (95% confidence interval [95% CI]: 0.724, 1.138; P=0.402), 0.841 (95% CI: 0.606, 1.168; P=0.302), 0.423 (95% CI: 0.132, 1.357; P=0.148), 0.762 (95% CI: 0.475, 1.223; P=0.261), 0.411 (95% CI: 0.232, 0.730; P=0.002), 1.049 (95% CI: 0.094, 11.752; P=0.969) and 0.192 (95% CI: 0.039, 0.935; P=0.041), respectively. Our analysis supported that the PD-1 inhibitor nivolumab did not cause increased or decreased risks of fatigue, headache, dysgeusia, vertigo and anxiety or malaise and was associated with decreased risks of paresthesia and peripheral neuropathy as compared with controls. These outcomes indicated that although clinicians should be attentive of the side effects of nivolumab, in terms of nervous system side effects, nivolumab is generally safe. © 2017 Kong and Kong.


Dong H.-J.,Peking Union Medical College
Journal of Craniofacial Surgery | Year: 2017

ABSTRACT: The author aim to track the distribution of human umbilical cord mesenchymal stem cells (MSCs) in large blood vessel of traumatic brain injury -rats through immunohistochemical method and small animal imaging system. After green fluorescent protein (GFP) gene was transfected into 293T cell, virus was packaged and MSCs were transfected. Mesenchymal stem cells containing GFP were transplanted into brain ventricle of rats when the infection rate reaches 95%. The immunohistochemical and small animal imaging system was used to detect the distribution of MSCs in large blood vessels of rats. Mesenchymal stem cells could be observed in large vessels with positive GFP expression 10 days after transplantation, while control groups (normal group and traumatic brain injury group) have negative GFP expression. The vascular endothelial growth factor in transplantation group was higher than that in control groups. The in vivo imaging showed obvious distribution of MSCs in the blood vessels of rats, while no MSCs could be seen in control groups. The intravascular migration and homing of MSCs could be seen in rats received MSCs transplantation, and new angiogenesis could be seen in MSCs-transplanted blood vessels. © 2017 by Mutaz B. Habal, MD.


Zhong Y.,Peking Union Medical College
Chinese Journal of Ophthalmology | Year: 2016

Secondary optic neuropathy of optic nerve abnormalities is the leading cause of persistent visual impairment. Previous ocular neuroprotection studies have proved that the nerve growth factor and other agents are of significant in the preservation of optic nerve axon and retinal ganglion cells. However, finding novel safe and effective approach as well as the appropriate applications of optic neuroprotection should be highly emphasized and would be very helpful in the treatment of optic neuropathy. Copyright © 2016 by the Chinese Medical Association.


Chen B.,Peking Union Medical College | Sun L.,Peking Union Medical College | Sun L.,Tsinghua University | Zhang X.,Peking Union Medical College
Journal of Autoimmunity | Year: 2017

The interaction between genetic predisposition and environmental factors are of great significance in the pathogenesis and development of autoimmune diseases (AIDs). The human mucosa is the most frequent site that interacts with the exterior environment, and commensal microbiota at the gut and other human mucosal cavities play a crucial role in the regulation of immune system. Growing evidence has shown that the compositional and functional changes of mucosal microbiota are closely related to AIDs. Gut dysbiosis not only influence the expression level of Toll-like receptors (TLRs) of antigen presenting cells, but also contribute to Th17/Treg imbalance. Epigenetic modifications triggered by environmental factors is an important mechanism that leads to altered gene expression. Researches addressing the role of DNA methylation, histone modification and non-coding RNA in AIDs have been increasing in recent years. Furthermore, studies showed that human microbiota and their metabolites can regulate immune cells and cytokines via epigenomic modifications. For example, short-chain fatty acids (SCFAs) produced by gut microbiota promote the differentiation of naïve T cell into Treg by suppressing histone deacetylases (HDACs). Therefore, we propose that dysbiosis and resulting metabolites may cause aberrant immune responses via epigenetic modifications, and lead to AIDs.With the development of high-throughput sequencing, metagenome analysis has been applied to investigate the dysbiosis in AIDs patients. We have tested the fecal, dental and salivary samples from treatment-naïve rheumatoid arthritis (RA) individuals by metagenomic shotgun sequencing and a metagenome-wide association study. Dysbiosis was detected in the gut and oral microbiomes of RA patients, but it was partially restored after treatment. We also found functional changes of microbiota and molecular mimicry of human antigens in RA individuals.By integrating the analysis of multi-omics of microbiome and epigenome, we could explore the interaction between human immune system and microbiota, and thereby unmasking specific and more sensitive biomarkers as well as potential therapeutic targets. Future studies aiming at the crosstalk between human dysbiosis and epigenetic modifications and their influences on AIDs will facilitate our understanding and better managing of these debilitating AIDs. © 2017 Elsevier Ltd.


Zhou A.-P.,Peking Union Medical College
Chinese Journal of New Drugs | Year: 2017

Biopharmaceuticals has been widely used in the treatment of various diseases. As the expiration of patents and data protection of the original biologic products, there is a international research and development tide of biosimilars. Biosimilars has high comparability or similarity with the original biologic products, so it was usually approved for the same indications with the original biologic products. Usage of biosimilars can reduce the cost of clinical application, but it can not replace the original biologic products because of the complexity and uniqueness. The approval principles and regulations of clinical generic drugs are not suitable for the biopharmaceuticals. More than 20 countries around the world had established the guidelines of biosimilars in order to describe how the biosimilars approval process will work. The guidelines can ensure the affordable and quality of biological products which can meet the clinical needs on efficacy and safety.The research and development property of biologic products and the advances in biopharmaceuticals and biosimilars were reviewed in this paper. © 2017, Chinese Journal of New Drugs Co. Ltd. All right reserved.


Wang L.,Peking Union Medical College | Wan X.-H.,Peking Union Medical College
Chinese Journal of Contemporary Neurology and Neurosurgery | Year: 2017

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Botulinum toxin (BTX) has been recommended as the first-line treatment choice for the most common subtype, i.e. cervical dystonia. But some patients respond poor to BTX injection. In the new "collum-caput (COL-CAP)" concept, which is generated based on cervical functional anatomy, the abnormal postures of cervical dystonia are divided into 8 basic types instead of previous 4. The concept is helpful for clinicians to analyze the abnormal posture precisely, and improve the efficacy of BTX injection thereafter. Copyright © 2017 by the Editorial Board of Chinese Journal of Contemporary Neurology and Neurosurgery


Yuan D.,Peking Union Medical College | Yang X.,Peking Union Medical College | Yuan Z.,Peking Union Medical College | Zhao Y.,Peking Union Medical College | Guo J.,Peking Union Medical College
Oncotarget | Year: 2017

Groucho (Gro)/Transducin-like enhancer of split (TLE) family proteins act as corepressors of many transcription factors, and are involved in key signaling pathways. TLE1 negatively regulates inflammation and has potential roles in various diseases, including cancer. Previous studies suggest TLE1 could be used as a diagnostic marker and is a possible therapeutic target in various malignancies. It is therefore important to elucidate the mechanisms underlying TLE1 function during cancer initiation and metastasis. In this review, we highlight the functions of TLE1 in cancer and explore targeted approaches for cancer diagnosis and treatment. In particular, we discuss the TLE1 function in pancreatic cancer.


Xu W.,Peking Union Medical College | Li C.,Peking Union Medical College | Zhang W.,Peking Union Medical College
Medicine (United States) | Year: 2017

Rational: SAPHO (Synovitis-Acne-Pustulosis-Hyperstosis-Osteitis) syndrome is a rare disease featured by its dermatological and 'osteoarthritic disorders, the latter of which mainly affecting the anterior chest wall, spine, and sacroiliac joint. However, rheumatoid arthritis (RA) is a chronic autoimmune disease, mainly affecting the synovial tissue of small joints in hands and feet. Here, we present an extremely rare case diagnosed with both SAPHO syndrome and RA, with an onset interval of 10 years. So far, only 1 similar case has been reported in the English literature. Patient Concerns: In Sep 2015, a 59-year-old female patient presented to our hospital, complaining of refractory low back pain, left sternoclavicular joint pain, and palmoplanar pustulosis (PPP). In addition, RA had been diagnosed 10 years earlier in the patient, manifested as pain and swelling in bilateral hands and wrists, accompanied by morning stiffness, as well as positive serologic tests. Interventions: In our hospital, laboratory tests revealed elevated inflammatory markers, and imaging examinations of relevant sites showed specific osteoarthritic lesions for SAPHO syndrome. Diagnoses: These findings lead us to make an easy diagnosis of the coexistence of SAPHO syndrome and RA in this petient. Outcomes: Treatment with tripterygium wilfordii polyglycosidium and prednisone was introduced. Both dermatological and osteoarthritic symptoms improved during a 3-month follow-up. Symptoms of RA were successfully controlled with prednisone and leflunomide since 2005. Lessons: We present an extremely rare case diagnosed with both SAPHO syndrome and RA, with an onset interval of 10 years. With this case report, we want to draw attention to the diverse features of SAPHO syndrome.


News Article | May 5, 2017
Site: www.scientificcomputing.com

A collaboration between stroke neurologists at the Medical University of South Carolina (MUSC) and bioengineers at the University of Massachusetts has led to the creation of a realistic, 3D-printed phantom of a stenotic intracranial artery that is being used to standardize protocols for high-resolution MRI, also known as vessel-wall MRI, at a network of U.S. and Chinese institutions, according to an article published online March 9, 2017 by the Journal of NeuroInterventional Surgery. High-resolution or vessel-wall MRI has been used to study the plaque components in vessels in the brain for more than ten years and has the potential to elucidate the underlying pathology of intracranial atherosclerotic disease (ICAD), the leading cause of stroke worldwide, as well as to gauge patient risk and inform clinical trials of new therapies. However, progress has been stymied by the lack of standardization in high-resolution MRI protocols, which poses an obstacle to multicenter trials. "There is a lot of exciting research that is possible with high-resolution MRI techniques, but it has much less opportunity to affect patient care if it can't be systematically distributed to multiple sites and multiple populations," says Tanya N. Turan, M.D., director of the MUSC Stroke Division and senior author of the article. To overcome this obstacle, Turan worked with bioengineers at the University of Massachusetts to produce a phantom of a stenotic intracranial vessel using imaging sequences obtained from a single patient with ICAD at MUSC. The 3-D printed ICAD phantom mimics both the stenotic vessel and its plaque components, including the fibrous cap and the lipid core. The phantom is being shared with collaborating institutions so that it can be used to standardize high-resolution MRI protocols. The imaging data presented in the Journal of NeuroInterventional Surgery article demonstrate the feasibility of using the phantom for standardization and were obtained from six U.S. and two Chinese sites. Producing the phantom was a major step in the right direction for standardizing high-resolution MRI ICAD protocols. However, several more years may be necessary to complete the process. The next major challenge for these investigators will be establishing parameters for MRI machines from a variety of manufacturers. So far, MRI parameters have been established for Siemens and GE systems but work is still under way on Philips systems. The phantom is also being shared with sites in China, where the burden of intracranial stenosis is especially high. Turan is collaborating with Weihai Xu, M.D., of Peking Union Medical College, the lead Chinese site, to collect additional data to assess interrater reliability among the participating institutions. Once high-resolution MRI protocols have been standardized and good interrater reliability demonstrated, the international team plans to conduct a prospective observational trial to examine risk prediction at participating centers, which would more quickly meet the required patient enrollment than would a trial conducted in the U.S. alone. "We're only going to be able to advance the field more quickly if we work together," says Turan. "The phantom gives us the tool to be able to work together."


News Article | May 5, 2017
Site: www.scientificcomputing.com

A collaboration between stroke neurologists at the Medical University of South Carolina (MUSC) and bioengineers at the University of Massachusetts has led to the creation of a realistic, 3D-printed phantom of a stenotic intracranial artery that is being used to standardize protocols for high-resolution MRI, also known as vessel-wall MRI, at a network of U.S. and Chinese institutions, according to an article published online March 9, 2017 by the Journal of NeuroInterventional Surgery. High-resolution or vessel-wall MRI has been used to study the plaque components in vessels in the brain for more than ten years and has the potential to elucidate the underlying pathology of intracranial atherosclerotic disease (ICAD), the leading cause of stroke worldwide, as well as to gauge patient risk and inform clinical trials of new therapies. However, progress has been stymied by the lack of standardization in high-resolution MRI protocols, which poses an obstacle to multicenter trials. "There is a lot of exciting research that is possible with high-resolution MRI techniques, but it has much less opportunity to affect patient care if it can't be systematically distributed to multiple sites and multiple populations," says Tanya N. Turan, M.D., director of the MUSC Stroke Division and senior author of the article. To overcome this obstacle, Turan worked with bioengineers at the University of Massachusetts to produce a phantom of a stenotic intracranial vessel using imaging sequences obtained from a single patient with ICAD at MUSC. The 3-D printed ICAD phantom mimics both the stenotic vessel and its plaque components, including the fibrous cap and the lipid core. The phantom is being shared with collaborating institutions so that it can be used to standardize high-resolution MRI protocols. The imaging data presented in the Journal of NeuroInterventional Surgery article demonstrate the feasibility of using the phantom for standardization and were obtained from six U.S. and two Chinese sites. Producing the phantom was a major step in the right direction for standardizing high-resolution MRI ICAD protocols. However, several more years may be necessary to complete the process. The next major challenge for these investigators will be establishing parameters for MRI machines from a variety of manufacturers. So far, MRI parameters have been established for Siemens and GE systems but work is still under way on Philips systems. The phantom is also being shared with sites in China, where the burden of intracranial stenosis is especially high. Turan is collaborating with Weihai Xu, M.D., of Peking Union Medical College, the lead Chinese site, to collect additional data to assess interrater reliability among the participating institutions. Once high-resolution MRI protocols have been standardized and good interrater reliability demonstrated, the international team plans to conduct a prospective observational trial to examine risk prediction at participating centers, which would more quickly meet the required patient enrollment than would a trial conducted in the U.S. alone. "We're only going to be able to advance the field more quickly if we work together," says Turan. "The phantom gives us the tool to be able to work together."


HONG KONG, April 28, 2017 /PRNewswire/ -- Digital China Holdings Limited ("DC Holdings" or the "Group"; stock code: 00861.HK, 910861.TW), China's largest integrated IT service provider, is pleased to announce that the signing ceremony of China Healthcare Big Data Development Co., Ltd. (CHBDDC) was held in Beijing. DC Holdings initiated the establishment of CHBDDC. Guo Wei, Chairman of DC Holdings, and Jin Xiaotao, Deputy Director of National Health and Family Planning Commission, delivered speech at the ceremony. Lu Jiang, Vice Mayor of Xia'men, representatives of Changzhou Municipal Government, China Population and Development Research Center, Peking Union Medical College Hospital, Peking University, and Philips (China) Investment Co., Ltd attended the signing ceremony. Under the guidance of National Health and Family Planning Commission, CHBDDC was initiated by DC Holdings, and cosponsored by Industrial and Commercial Bank of China Limited, Bank of China Limited, Chinese Academy of Sciences Holding Co., Ltd.,China Telecom Corporation Limited, China Cinda Asset Management Co., Ltd., Shougang Corporation, Guangzhou Urban Construction Investment Group Co., Ltd., Wonders Information Co., Ltd., Neusoft Corporation, Inspur and Ylz Information Technology, Bringspring Science and Technology Co., Ltd. and many other central enterprises, state-owned enterprises and well-known listed companies. The new company will respond to the country's policy guidelines to promote the "Interconnection, Open Sharing" of Big Data in healthcare and promote the supply-side structural reform on healthcare and fulfill the mission of "Digitalised China" for the benefit of the people. Based on the top-level design for industrial parks of healthcare Big Data and combined with the development plan of "Healthy China", CHBDDC will be undertaking the construction of national and local industrial parks of healthcare Big Data. CHBDDC will put effort in the construction of Big Data center, Big Data platform, medical services, healthcare services, integrated management, precision medicine, delicacy insurance, insurance audit, medical payment and other key areas, to promote a full layout and construction of industrial parks of healthcare Big Data, and to become a new support for medical reform and a new driver of local economy. The new company will serve as a platform to integrate the relevant advantages of state-owned enterprises and listed enterprises: to invest and operate the National Healthcare Big Data Center and industrial parks so as to build a service system of healthcare Big Data under the principles of "Government-led, Commercial Operation and Joint Innovation for Win-win"; to open up the data of the whole industry chain to build a Sm@rt Big Data ecology; to utilize financial means for the promotion of incubation and cultivation of health industry and to build a large healthcare data ecosystem and develop the construction of healthcare Big Data. DC Holdings upholds its mission to drive the "Digitalised China". Combined with technology and capital, DC Holdings has formed cloud computing and Big Data as core capabilities. The Company is working towards the transformation to cloud computing and Big Data based on the ecological circle created through internal bottom-up innovation system and external investment for M&As and with Sm@rt City, modern agriculture, precision medicine and intelligent manufacturing as core business areas. The integration of healthcare resources and building up the integration platform by DC Holdings will fully demonstrate the benefit of health Big Data. As one of the key parts in DC Holdings' core business areas, Digital China Health is determined to build the top brand of healthcare Big Data in China by providing comprehensive and accurate information services and cancer-related data services. About Digital China Holdings Limited Digital China Holdings Limited ("DC Holdings", Stock Code: 0861.HK) was listed on the Main Board of The Stock Exchange of Hong Kong in 2001 following a successful spin-off from the then Legend Group in 2000. It has developed its capital platforms across Mainland China, Hong Kong and Taiwan through the following four listed companies – DC Holdings, Digital China Information Service Company Ltd., Digiwin Software Company Ltd., and HC International, Inc. Their combined market capitalization reaches nearly HK$50 billion. Since its listing 16 years ago, DC Holdings has adhered to the mission of driving the "Digitalization in China". With the corporate value of "Commitment, Passion and Innovation", the Company evolved from China's largest IT product distributor into the largest integrated IT services provider and then the most influential Sm@rt City solutions provider in China. According to its latest development strategy, DC Holdings will capture the opportunities arising from the "Internet +" strategy and leverage on its technological strengths and capital resources to drive breakthroughs in Sm@rt City, precision healthcare, modern agriculture and Sm@rt manufacturing based on the Cloud computing and Big Data technology. With comprehensive innovation mechanism and multi-layer incubation system, the Company is determined to become a genuine innovative enterprise. For additional information about DC Holdings, please visit the Group's website at www.dcholdings.com.hk. For investor and media inquiries: Charles Chan Emma Liang PRChina Limited PRChina Limited Tel: 852-2522-1838 Tel: 852-2522-1838 Email: ckchan@prchina.com.hk Email: eliang@prchina.com.hk Digital China Holdings Limited Tel: 852-3416-8000 Email: ir@digitalchina.com   To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/dc-holdings-initiates-the-establishment-of-china-healthcare-big-data-development-co-ltd-to-construct-the-healthcare-big-data-ecosystem-300447914.html


Deep Learning Platform from Startup Infervision Acts as Second Pair of Eyes to Find Suspicious Lesions and is World's First to Reshape the Workflow of Radiologists SAN JOSE, CA / ACCESSWIRE / May 8, 2017 / (GPU Tech Conference) Infervision, a tech company using big data and artificial intelligence to assist and improve medical diagnoses, is introducing its innovative, deep learning solution to help radiologists identify suspicious lesions and nodules in lung cancer patients faster than ever before. The Infervision AI platform is the world's first to reshape the workflow of radiologists and it is already showing dramatic results at several top hospitals in China. The company founder, Chen Kuan, will present a talk on the company and its use of AI for medical diagnoses at the NVIDIA GPU Tech Conference in San Jose (Monday, May 8, 9-9:50AM PT). Infervision's AI-aided CT diagnosis, with its high-performance parallel computing power, effectively learns the core characteristics of lung cancer and efficiently detects suspected cancer features in different CT image sequences, helping with early diagnosis and, consequently, early treatment. The technology is also used to assist in X-ray diagnosis and has achieved extremely high accuracy so that it is close to that of a deputy chief physician in the diagnosis of cardiothoracic diseases at one of the top Chinese hospitals where the software is now in use. For the past six months, the technology has been in use at several top hospitals in China, a country experiencing hundreds of thousands of new lung cancer patients annually, while it has too few radiologists. After rigorous testing and integrating the software with the standard PACS (Picture Archiving and Communication System), Infervision's technology is proving to be extremely effective and is enhancing the work of Chinese doctors by acting as a second pair of eyes. The Infervision solution improves the workflow of radiologists, delivering a faster reading of hundreds of images for each patient, and bringing to the doctor's attention those scans that may have malignant lesions or nodules so radiologists will thoroughly review them. "Our goal at Infervision is to build a stronger medical industry and help accelerate diagnoses, which is so important for patients," said Chen Kuan, founder and CEO of Infervision. "In China, we have a severe shortage of radiologists, particularly in lower-level hospitals all over the country. There are 80,000 radiologists who must diagnose 1.4 billion radiology scans a year. By using artificial intelligence and deep learning, the Infervision platform augments the work of these doctors so they can get through scans quickly. A process that used to take 15 minutes can be dramatically reduced so detection and treatment of lung cancer is faster. This could be life changing for many." Additionally, Infervision's technology and a group of radiologists recently went head-to-head in a report reading experiment with different types and sizes of nodules. Infervision's AI-CT predicted more accurately than radiologists in every category. "In no way will this technology ever replace doctors. It is intended to eliminate much of the highly repetitive work. Infervision empowers doctors and helps them deliver more accurate reports and do it much faster," continued Kuan. The Infervision artificial intelligence continues to learn as more data becomes available and also as it analyzes past results. Lung cancer is particularly rampant in China, due to both air pollution and smoking, with between 600,000 and 700,000 new lung cancer cases are diagnosed annually. While this is an unfortunate statistic, it provides a huge trove of medical data that can make the Infervision technology stronger and even more effective. Infervision specializes in assisted medical image diagnosis, using artificial intelligence and deep learning to help improve the workflow and efficiency of radiologists for diagnosing various types of cancer and other diseases. The company has raised a Series A round of 50M RMB ($7.2M USD) led by Sequoia Capital and established cooperative business partnerships with close to 20 Tertiary Grade A hospitals, including Peking Union Medical College Hospital and Shanghai Changzheng Hospital. It also has relationships with online and offline medical image platforms, including Ali Cloud Computing, and has entered into strategic partnerships with GE Healthcare, Cisco, and NVIDIA. Founders and scientists with Infervision studied at top universities and research institutions around the world. For more information, visit www.infervision.com.


Since its inception, MMAAP foundation has awarded over 40 Fellowship and Project grants to support the work of exceptional physician scientists and investigators with the vision, drive and dedication to find new and innovative ways towards advancements in the targeted medical fields. These outstanding award recipients represent more than 20 prestigious Chinese medical institutions including Peking Union Medical College Hospital, Xijing Hospital, the Fourth Military Medical University, Peking University Institute of Hematology, West China Hospital, Sichuan University, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, and others. "The visionary leadership of MMAAP Foundation Chairman and Founder, Howard P. Milstein, has brought together and funded exchanges between outstanding researchers, medical talent, and institutions in these regions," said Sean X. Leng, MD, PhD, President of MMAAP Foundation. "The 2017 recipients are among the most talented investigators in their fields and our support of their work is vital to both furthering medical research and strengthening relations between the U.S. and China." Grant applications were evaluated through a two-step peer review process according to the National Institute of Health standard. Panels of Chinese and U.S. experts in their respective fields jointly reviewed all proposals, and finalists were submitted for approval by MMAAP Foundation. The U.S. panels in Geriatrics, Skin Disease, Hematology, Reproductive Medicine, and Translational Medicine include members of the American Geriatrics Society, Medical Advisory Committee of American Skin Association, New York Blood Center, Jones Foundation for Reproductive Medicine, as well as members of other leading U.S. institutions in each field. The mission of Milstein Medical Asian American Partnership Foundation (MMAAP Foundation) is to improve world health by developing mutually beneficial partnerships between the U.S. and China, as well as greater Asia. Working with some of the premier health organizations in the world, MMAAP Foundation brings together and funds exchanges among the best research, medical talent, and institutions in the regions. This strategy is a high priority for MMAAP Foundation's founder Howard P. Milstein. MMAAP Foundation is a 501(c) (3) non-profit organization. For more than 50 years, the Milstein family has been actively involved in health-related and medical philanthropy. MMAAP Foundation builds upon this distinguished history in five areas: Senior Healthcare, Skin Disease and Melanoma, Reproductive Biology, Blood Research, and Translational Medicine. MMAAP Foundation works in close collaboration with other medical organizations supported by the Milstein family, including American Skin Association, Milstein Melanoma Research Program at The Rockefeller University, Howard and Georgeanna Jones Foundation for Reproductive Medicine, New York Blood Center, and the Program for Translational Chemical Biology at New York-Presbyterian Hospital/Weill Cornell Medical Center. For more information, please visit MMAAP Foundation's website at www.mmaapf.org. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/milstein-medical-asian-american-partnership-foundation-announces-2017-fellowship-and-project-awards-300447740.html


Li X.,Peking University | Zeng H.,Peking Union Medical College | Teng L.,Peking Union Medical College | Chen H.,Peking University
Materials Letters | Year: 2014

Terbium (Tb) doped fluorapatite (FA:Tb) and hydroxyapatite (HA:Tb) crystals are hydrothermally synthesized. Their composition, crystal structure, fluorescence and biological properties are investigated. The Tb-doped crystals are in nanoscale and present a uniform slender morphology. The doping of Tb 3+ ions can promote the preferential growth of apatite nanocrystals along the c-axis (002) direction, and cause the binding energy to increase for FA:Tb3+ crystals or decrease for HA:Tb3+ crystals. The FA crystal structure tends to combine more Tb3+ ions than the HA crystal structure, and shows a stronger green fluorescence. Four Tb-doping lattice models along the apatite hexagonal structure are proposed, revealing a necessity for coexistent substitution mechanism of (Ca7Tb2©) (PO4)6(OH)2, (Ca6Tb 2Na2)(PO4)6(OH)2, (Ca9Tb)(PO4)6(OH)O, and (Ca8TbNa) (PO4)6(OH)2. The Tb-doped apatite nanocrystals exhibit bright fluorescence, good cytocompatibility and excellent cell imaging capacity, providing feasibility for imaging and tracking of cells with multilineage differentiation. © 2014 Elsevier B.V. All rights reserved.


Miller V.A.,Sloan Kettering Cancer Center | Miller V.A.,City College of New York | Hirsh V.,McGill University | Cadranel J.,Hopital Tenon | And 15 more authors.
The Lancet Oncology | Year: 2012

Background: Afatinib, an irreversible ErbB-family blocker, has shown preclinical activity when tested in EGFR mutant models with mutations that confer resistance to EGFR tyrosine-kinase inhibitors. We aimed to assess its efficacy in patients with advanced lung adenocarcinoma with previous treatment failure on EGFR tyrosine-kinase inhibitors. Methods: In this phase 2b/3 trial, we enrolled patients with stage IIIB or IV adenocarcinoma and an Eastern Cooperative Oncology Group performance (ECOG) performance score of 0-2 who had received one or two previous chemotherapy regimens and had disease progression after at least 12 weeks of treatment with erlotinib or gefitinib. We used a computer-generated sequence to randomly allocate patients (2:1) to either afatinib (50 mg per day) or placebo; all patients received best supportive care. Randomisation was done in blocks of three and was stratified by sex and baseline ECOG performance status (0-1 vs 2). Investigators, patients, and the trial sponsor were masked to treatment assignment. The primary endpoint was overall survival (from date of randomisation to death), analysed on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT00656136. Findings: Between May 26, 2008, and Sept 21, 2009, we identified 697 patients, 585 of whom were randomly allocated to treatment (390 to afatinib, 195 to placebo). Median overall survival was 10·8 months (95% CI 10·0-12·0) in the afatinib group and 12·0 months (10·2-14·3) in the placebo group (hazard ratio 1·08, 95% CI 0·86-1·35; p=0·74). Median progression-free survival was longer in the afatinib group (3·3 months, 95% CI 2·79-4·40) than it was in the placebo group (1·1 months, 0·95-1·68; hazard ratio 0·38, 95% CI 0·31-0·48; p<0·0001). No complete responses to treatment were noted; 29 (7%) patients had a partial response in the afatinib group, as did one patient in the placebo group. Subsequent cancer treatment was given to 257 (68%) patients in the afatinib group and 153 (79%) patients in the placebo group. The most common adverse events in the afatinib group were diarrhoea (339 [87%] of 390 patients; 66 [17%] were grade 3) and rash or acne (305 [78%] patients; 56 [14%] were grade 3). These events occurred less often in the placebo group (18 [9%] of 195 patients had diarrhoea; 31 [16%] had rash or acne), all being grade 1 or 2. Drug-related serious adverse events occurred in 39 (10%) patients in the afatinib group and one (<1%) patient in the placebo group. We recorded two possibly treatment-related deaths in the afatinib group. Interpretation: Although we recorded no benefit in terms of overall survival with afatinib (which might have been affected by cancer treatments given after progression in both groups), our findings for progression-free survival and response to treatment suggest that afatinib could be of some benefit to patients with advanced lung adenocarcinoma who have failed at least 12 weeks of previous EGFR tyrosine-kinase inhibitor treatment. Funding: Boehringer Ingelheim Inc. © 2012 Elsevier Ltd.


Li X.,Nanjing Medical University | Zhang J.,Peking Union Medical College | Huang J.,Nanjing Medical University | Ma A.,Xi'an Jiaotong University | And 8 more authors.
Journal of the American College of Cardiology | Year: 2013

Objectives The purpose of this study was to assess the effects of qili qiangxin capsules in patients with chronic heart failure (CHF). Background Qili qiangxin capsules are a traditional Chinese medicine that has been approved in China for the treatment of CHF, but the evidence supporting its efficacy remains unclear. Methods A total of 512 patients with CHF were enrolled and randomly assigned to receive the placebo or qili qiangxin capsules in addition to their standard medications for the treatment of CHF. The primary endpoint was the reduction or percent change in the plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) level during 12 weeks of treatment. Results At the 12-week follow-up, a significant reduction in the NT-proBNP level from baseline was observed in both groups, but the qili qiangxin capsule group demonstrated a significantly greater reduction than the placebo group (p = 0.002); 47.95% of patients in the qili qiangxin capsule group demonstrated reductions in NT-proBNP levels of at least 30% compared with 31.98% of patients in the placebo group (p < 0.001). Treatment with qili qiangxin capsules also demonstrated superior performance in comparison to the placebo with respect to New York Heart Association functional classification, left ventricular ejection fraction, 6-min walking distance, and quality of life. Conclusions On a background of standard treatment, qili qiangxin capsules further reduced the levels of NT-proBNP. Together, our data suggest that qili qiangxin capsules could be used in combination therapy for CHF. © 2013 by the American College of Cardiology Foundation Published by Elsevier Inc.


Zhang X.,Peking Union Medical College | Liu L.,Peking Union Medical College | Zhang Y.,Peking Union Medical College | Dai G.,Beijing Tuberculosis and Thoracic Tumor Research Institute | And 2 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2015

p-Aminosalicylic acid (PAS) is an important compound for treating multidrug-resistant tuberculosis (TB). Previous studies showed that thyA mutations are often related to PAS resistance in clinical isolates. We performed a systematic analysis of isolate genotypes and detected mutations in three folate pathway genes (folC, thyA, and ribD) in 61.1% (127/208) of PAS-resistant isolates, including 11 double mutants. This result expands our knowledge about the distribution and frequency of mutations related to PAS resistance in mycobacterial clinical isolates. Copyright © 2015 American Society for Microbiology. All Rights Reserved. All the mycobacterial strains used in this project were acquired from the Beijing Bio-Bank of Clinical Resources on Tuberculosis.


Cheng J.,Nanjing Forestry University | Cheng J.,Peking Union Medical College | Cao F.,Nanjing Forestry University | Liu Z.,Nanjing Forestry University | Liu Z.,Peking Union Medical College
Molecular Biology and Evolution | Year: 2013

Phylogenetic analysis based on alignment method meets huge challenges when dealing with whole-genome sequences, for example, recombination, shuffling, and rearrangement of sequences. Thus, various alignment-free methods for phylogeny construction have been proposed. However, most of these methods have not been implemented as tools or web servers. Researchers cannot use these methods easily with their data sets. To facilitate the usage of various alignment-free methods, we implemented most of the popular alignment-free methods and constructed a user-friendly web server for alignment-free genome phylogeny (AGP). AGP integrated the phylogenetic tree construction, visualization, and comparison functions together. Both AGP and all source code of the methods are available at http://www.herbbol.org:8000/agp (last accessed February 26, 2013). AGP will facilitate research in the field of whole-genome phylogeny and comparison. © 2013 The Author.


Lou S.,Royal Melbourne Hospital | Lou S.,Peking Union Medical College | MacLaren G.,Royal Melbourne Hospital | MacLaren G.,National University of Singapore | And 6 more authors.
Critical Care Medicine | Year: 2014

Objectives: To explore the prevalence and risk factors for hemolysis in children receiving extracorporeal membrane oxygenation and examine the relationship between hemolysis and adverse outcomes. Design: Retrospective, single-center study. Setting: Tertiary PICU. Patients: Two hundred seven children receiving extracorporeal membrane oxygenation. Interventions: None. Measurements and Main Results: Plasma-free hemoglobin was tested daily and hemolysis was diagnosed based on peak plasma-free hemoglobin as mild (< 0.5 g/L), moderate (0.5-1.0 g/L), or severe (> 1.0 g/L). Gender, age, weight, diagnosis, oxygenator type, cannulation site, mean venous inlet pressure, mean pump speed, mean flow, and visible clots in the extracorporeal membrane oxygenation circuit were entered into the ordered logistic regression model to identify risk factors of hemolysis. Complications and clinical outcomes were compared across four hemolysis groups. Of the 207 patients, 69 patients (33.3%; 95% CI, 27.0-40.2%) did not have hemolysis, 98 patients (47.3%; 95% CI, 40.4-54.4%) had mild hemolysis, 26 patients (12.5%; 95% CI, 8.4-17.9%) had moderate hemolysis, and 14 patients (6.8%; 95% CI, 3.7-11.1%) had severe hemolysis with a median peak plasma-free hemoglobin of 1.51 g/L (1.18-2.05 g/L). The independent risk factors for hemolysis during extracorporeal membrane oxygenation were use of Quadrox D (odds ratio, 7.25; 95% CI, 3.10-16.95; p < 0.001) or Lilliput (odds ratio, 37.32; 95% CI, 8.95-155.56; p < 0.001) oxygenators, mean venous inlet pressure (odds ratio, 0.95; 95% CI, 0.91-0.98; p = 0.002), and mean pump speed (odds ratio, 2.89; 95% CI, 1.36-6.14; p = 0.006). Patients with hemolysis were more likely to experience a longer extracorporeal membrane oxygenation run and require more blood products. After controlling for age, weight, pediatric index of mortality 2, and diagnosis, patients with severe hemolysis were more likely to die in the ICU (odds ratio, 5.93; 95% CI, 1.64-21.43; p = 0.007) and in hospital (odds ratio, 6.34; 95% CI, 1.71-23.54; p = 0.006). Conclusions: Hemolysis during extracorporeal membrane oxygenation with centrifugal pumps was common and associated with a number of adverse outcomes. Risk factors for hemolysis included oxygenator types, mean venous inlet pressure, and mean pump speed. Further studies are warranted comparing pump types while controlling both physical and nonphysical confounders. Copyright © 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.


Pang X.,Peking Union Medical College | Song J.,Peking Union Medical College | Zhu Y.,Peking Union Medical College | Xu H.,Hong Kong Jockey Club Institute of Chinese Medicine | And 2 more authors.
Cladistics | Year: 2011

The Consortium for the Barcode of Life (CBOL) Plant Working Group (PWG) established the use of matK+rbcL as core barcodes and ITS2 as one of the supplementary loci for differentiating plants at the Third International Barcoding Conference. Here, we tested the applicability of four DNA regions (rbcL, matK, rpoC1 and ITS2) as the barcodes for identifying species within Rosaceae. Based on assessments of the success rates of PCR amplifications, the sequence quality, extent of specific genetic divergence, DNA barcoding gap and ability for species discrimination, our results suggest that ITS2 is the best of the four loci tested for barcoding Rosaceae. We further evaluated the effectiveness of ITS2 for identifying a wide range of species within Rosaceae. Of the 1410 plant samples collected from 893 species in 96 diverse genera, ITS2 successfully identified 78 and 100% of them at the species and genus levels, respectively. Therefore, our research indicated that the ITS2 region is a powerful, though not perfect, barcode for Rosaceae identification that also contributes valuable information for identifying closely related species in other plant taxonomic groups. © The Willi Hennig Society 2010.


Lee M.K.,Hospital Drive | Tong W.M.,Peking Union Medical College | Wang Z.Q.,Leibniz Institute for Age Research | Wang Z.Q.,Friedrich - Schiller University of Jena | And 2 more authors.
Cell Death and Differentiation | Year: 2011

Cellular stimulation results in phosphorylation of the tumor suppressor p53 on multiple residues, though the functional relevance is not always clear. It is noteworthy that the serine (S) 315 residue is unique, as it has been suggested to be phosphorylated not only by genotoxic signals, but also during cell-cycle progression and by endoplasmic-reticulum stress. However, in vitro data have been conflicting as phosphorylation at this site was shown to both positively and negatively regulate p53 functions. We have thus generated knock-in mice expressing an unphosphorylable S312 (equivalent to human S315), by substitution with an alanine (A) residue, to clarify the conflicting observations and to evaluate its functional relevance in vivo. Born at Mendelian ratios, the p53 S312A/S312Amice show no anomalies during development and adulthood. p53 activation, stability, localization and ability to induce apoptosis, cell-cycle arrest and prevent centrosome amplification are not compromised in p53 S312A/S312Acells. p53 S312A/S312A mice are unable to rescue mdm2 / lethality, and tumorigenesis- both spontaneous and irradiation/oncogene-induced- is not accentuated. Taken together, the results show that the S312 phosphorylation site is not in itself necessary for efficient p53 function, and advocates the possibility that it is neither relevant in the mouse context nor important for p53 functions in vivo. © 2011 Macmillan Publishers Limited All rights reserved.


Zhang L.,Sun Yat Sen University | Ma S.,Zhejiang Cancer Hospital | Song X.,Guangxi Zhuang Autonomous Region Tumour Hospital | Han B.,Shanghai Chest Hospital | And 11 more authors.
The Lancet Oncology | Year: 2012

Background: Maintenance treatment of patients with advanced non-small-cell lung cancer (NSCLC) without disease progression after first-line chemotherapy is a subject of ongoing research. The aim of the randomised, double-blind, placebo-controlled, INFORM study was to investigate the efficacy, safety, and tolerability of the EGFR-tyrosine-kinase inhibitor gefitinib in the maintenance setting. Methods: Patients were aged 18 years or older, were of east Asian ethnic origin, had a life expectancy of more than 12 weeks, histologically or cytologically confirmed stage IIIb or IV NSCLC, a WHO performance status of 0-2, and had completed four cycles of first-line platinum-based doublet chemotherapy without disease progression or unacceptable toxic effects. Between Sept 28, 2008 and Aug 11, 2009, 296 patients were randomly assigned 1:1 to receive either gefitinib (250 mg per day orally) or placebo (orally) within 3-6 weeks after chemotherapy until progression or unacceptable toxic effects. Randomisation was done via an interactive web response system with computer-generated randomisation codes. Our primary endpoint was progression-free survival assessed in the intention-to-treat population. This completed study is registered with Clinicaltrials.gov, number NCT00770588. Findings: Progression-free survival was significantly longer with gefitinib (n=148) than with placebo (148) (median progression-free survival 4·8 months [95% CI 3·2-8·5] vs 2·6 months [1·6-2·8]; hazard ratio [HR] 0·42, 95% CI 0·33-0·55; p<0·0001). Adverse events occurred more frequently with gefitinib than with placebo; the most common adverse events of any grade were rash (73 [50%] of 147 in the gefitinib group vs 14 [9%] of 148 in the placebo group), diarrhoea (37 [25%] vs 13 [9%]), and alanine aminotransferase increase (31 [21%] vs 12 [8%]). The most commonly reported grade 3 or 4 adverse event was alanine aminotransferase increase (3 [2%] of 147 in the gefitinib group, none of 148 in the placebo group). Ten of 147 (7%) patients given gefitinib and five of 148 (3%) patients given placebo had serious adverse events. Three deaths were thought to be related to treatment with gefitinib: one from interstitial lung disease; one from lung infection; and one from pneumonia. Interpretation: Maintenance treatment with gefitinib significantly prolonged progression-free survival compared with placebo in patients from east Asia with advanced NSCLC who achieved disease control after first-line chemotherapy. Clinicians should consider these data when making decisions about maintenance treatment in such patients. Funding: AstraZeneca. © 2012 Elsevier Ltd.


Zhang H.,Peking Union Medical College | Plutzky J.,Harvard University | Skentzos S.,160 North Frances Street | Morrison F.,Tulane University | And 3 more authors.
Annals of Internal Medicine | Year: 2013

Background: Systematic data on discontinuation of statins in rou-tine practice of medicine are limited. Objective: To investigate the reasons for statin discontinuation and the role of statin-related events (clinical events or symptoms be-lieved to have been caused by statins) in routine care settings. Design: A retrospective cohort study. Setting: Practices affiliated with Brigham and Women's Hospital and Massachusetts General Hospital in Boston. Patients: Adults who received a statin prescription between 1 Jan-uary 2000 and 31 December 2008. Measurements: Information on reasons for statin discontinuations was obtained from a combination of structured electronic medical record entries and analysis of electronic provider notes by validated software. Results: Statins were discontinued at least temporarily for 57 292 of 107 835 patients. Statin-related events were documented for 18 778 (17.4%) patients. Of these, 11 124 had statins discontinued at least temporarily; 6579 were rechallenged with a statin over the subsequent 12 months. Most patients who were rechallenged (92.2%) were still taking a statin 12 months after the statin-related event. Among the 2721 patients who were rechallenged with the same statin to which they had a statin-related event, 1295 were receiving the same statin 12 months later, and 996 of them were receiving the same or a higher dose. Limitations: Statin discontinuations and statin-related events were assessed in practices affiliated with 2 academic medical centers. Utilization of secondary data could have led to missing or misinter-preted data. Natural-language-processing tools used to compensate for the low (30%) proportion of reasons for statin discontinuation documented in structured electronic medical record fields are not perfectly accurate. Conclusion: Statin-related events are commonly reported and of-ten lead to statin discontinuation. However, most patients who are rechallenged can tolerate statins long-term. This suggests that many of the statin-related events may have other causes, are tolerable, or may be specific to individual statins rather than the entire drug class. Primary Funding Source: National Library of Medicine, Diabetes Action Research and Education Foundation, and Chinese National Key Program of Clinical Science. © 2013 American College of Physicians.


Gao L.,Peking Union Medical College | Tao Y.,Peking University | Zhang L.,Beijing Centers for Diseases Control and Prevention | Jin Q.,Peking Union Medical College
International Journal of Tuberculosis and Lung Disease | Year: 2010

BACKGROUND: Host genetic susceptibility has been suggested as one of the most important explanations for inter-individual differences in tuberculosis (TB) risk. The vitamin D receptor (VDR) gene has been studied as a candidate locus due to genetic polymorphisms that affects the activity of the receptor and subsequent down-stream vitamin D-mediated effects. METHODS: We reviewed published studies on VDR polymorphisms and TB susceptibility up to 15 April 2009 and quantitatively summarised associations of the most widely studied polymorphisms (FokI, TaqI, ApaI and BsmI) using meta-analysis. RESULTS: A total of 23 eligible studies were included in this review. Heterogeneous results were observed, which may be partly explained by the differences between populations. Among Asians, the FokI ff genotype showed a pronounced positive association (OR 2.0, 95%CI 1.3-3.2), a significant inverse association was observed for the BsmI bb genotype (OR 0.5, 95%CI 0.4-0.8), and marginal significant associations were found for TaqI and ApaI polymorphisms. However, none of the polymorphisms was significantly related to TB among Africans or South Americans. CONCLUSIONS: The association of VDR polymorphisms with risk of TB observed in our analyses supports the hypothesis that vitamin D deficiency might play a role as risk factor during the development of TB. © 2010 The Union.


Wu X.,Beijing Normal University | Shi Y.,China National Institute of Biological Sciences | Shi Y.,Peking Union Medical College | Li J.,China National Institute of Biological Sciences | And 6 more authors.
Cell Research | Year: 2013

microRNAs (miRNAs) play important roles in the regulation of gene expression. In Arabidopsis, mature miRNAs are processed from primary miRNA transcripts (pri-miRNAs) by nuclear HYL1/SE/DCL1 complexes that form Dicing bodies (D-bodies). Here we report that an RNA-binding protein MOS2 binds to pri-miRNAs and is involved in efficient processing of pri-miRNAs. MOS2 does not interact with HYL1, SE, and DCL1 and is not localized in D-bodies. Interestingly, in the absence of MOS2, the recruitment of pri-miRNAs by HYL1 is greatly reduced and the localization of HYL1 in D-bodies is compromised. These data suggest that MOS2 promotes pri-miRNA processing through facilitating the recruitment of pri-miRNAs by the Dicing complexes. © 2013 IBCB, SIBS, CAS. All rights reserved.


Li Y.,Massachusetts Institute of Technology | Jiang Y.,Tsinghua National Laboratory for Information Sciences and Technology | Chen H.,Tsinghua National Laboratory for Information Sciences and Technology | Liao W.,Tsinghua National Laboratory for Information Sciences and Technology | And 5 more authors.
Nature Chemical Biology | Year: 2015

An important goal of synthetic biology is the rational design and predictable implementation of synthetic gene circuits using standardized and interchangeable parts. However, engineering of complex circuits in mammalian cells is currently limited by the availability of well-characterized and orthogonal transcriptional repressors. Here, we introduce a library of 26 reversible transcription activator-like effector repressors (TALERs) that bind newly designed hybrid promoters and exert transcriptional repression through steric hindrance of key transcriptional initiation elements. We demonstrate that using the input-output transfer curves of our TALERs enables accurate prediction of the behavior of modularly assembled TALER cascade and switch circuits. We also show that TALER switches using feedback regulation exhibit improved accuracy for microRNA-based HeLa cancer cell classification versus HEK293 cells. Our TALER library is a valuable toolkit for modular engineering of synthetic circuits, enabling programmable manipulation of mammalian cells and helping elucidate design principles of coupled transcriptional and microRNA-mediated post-transcriptional regulation. © 2015 Nature America, Inc. All rights reserved.


Liu Y.,Peking University | Dai W.,Ministry of Health | Dai X.,Peking Union Medical College | Li Z.,Peking University
Archives of Gynecology and Obstetrics | Year: 2012

Purpose We aimed to investigate the combined associations of prepregnancy body mass index (BMI) and gestational weight gain (GWG) with pregnancy outcomes in Chinese women. Methods Data for 292,568 singleton term pregnancies were selected from 1993 to 2005 based on the Perinatal Health Care Surveillance System, with anthropometric measurements being collected prospectively. Prepregnancy BMI was categorized according to the definitions of the World Health Organization (WHO). Total GWG was categorized into four groups. Adjusted associations of prepregnancy BMI and GWG with outcomes of interest were estimated using logistic regression analyses. GWG was categorized as below, within and above the Institute of Medicine (IOM) (2009) recommendations. Results Maternal overweight and high GWG or GWG above the IOM recommendation were associated with hypertensive disorders complicating pregnancy, cesarean delivery, macrosomia and large-for-gestational-age (LGA) infants. Maternal underweight and low GWG or GWG below the IOM recommendation were risk factors for lowbirth- weight (LBW) and small-for-gestational-age (SGA) infants. Moreover, being overweight [odds ratio (OR) 1.2, 95 % confidence interval (CI) 1.0–1.3) and having a low weight gain (OR 1.1, 95 % CI 1.0–1.1) increased the risk of newborn asphyxia. Conclusion Being overweight/obese and having a high weight gain, as well as being underweight and having a low weight gain, were associated with increased risks for adverse pregnancy outcomes in Chinese women. © Springer-Verlag 2012.


Zhou J.,Fudan University | Yu M.,Fudan University | Sun Y.,Fudan University | Zhang X.,Beijing Normal University | And 4 more authors.
Biomaterials | Year: 2011

Molecular imaging modalities provide a wealth of information that is highly complementary and rarely redundant. To combine the advantages of molecular imaging techniques, 18F-labeled Gd3+/Yb3+/Er3+ co-doped NaYF4 nanophosphors (NPs) simultaneously possessing with radioactivity, magnetic, and upconversion luminescent properties have been fabricated for multimodality positron emission tomography (PET), magnetic resonance imaging (MRI), and laser scanning upconversion luminescence (UCL) imaging. Hydrophilic citrate-capped NaY0.2Gd0.6Yb0.18Er0.02F4 nanophosphors (cit-NPs) were obtained from hydrophobic oleic acid (OA)-coated nanoparticles (OA-NPs) through a process of ligand exchange of OA with citrate, and were found to be monodisperse with an average size of 22 × 19 nm. The obtained hexagonal cit-NPs show intense UCL emission in the visible region and paramagnetic longitudinal relaxivity (r1 = 0.405 s-1·(mM)-1). Through a facile inorganic reaction based on the strong binding between Y3+ and F-, 18F-labeled NPs have been fabricated in high yield. The use of cit-NPs as a multimodal probe has been further explored for T1-weighted MR and PET imaging in vivo and UCL imaging of living cells and tissue slides. The results indicate that 18F-labeled NaY0.2Gd0.6Yb0.18Er0.02 is a potential candidate as a multimodal nanoprobe for ultra-sensitive molecular imaging from the cellular scale to whole-body evaluation. © 2010 Elsevier Ltd.


Xu M.,Peking Union Medical College | Xu M.,China National Institute of Biological Sciences | Long C.,China National Institute of Biological Sciences | Chen X.,China National Institute of Biological Sciences | And 5 more authors.
Science | Year: 2010

Semiconservative DNA replication ensures the faithful duplication of genetic information during cell divisions. However, how epigenetic information carried by historie modifications propagates through mitotic divisions remains elusive. To address this question, the DNA replication-dependent nucleosome partition pattern must be clarified. Here, we report significant amounts of H3.3-H4 tetramers split in vivo, whereas most H3.1-H4 tetramers remained intact. Inhibiting DNA replication-dependent deposition greatly reduced the level of splitting events, which suggests that (i) the replication-independent H3.3 deposition pathway proceeds largely by cooperatively incorporating two new H3.3-H4 dimers and (ii) the majority of splitting events occurred during replication-dependent deposition. Our results support the idea that "silent" histone modifications within Large heterochromatic regions are maintained by copying modifications from neighboring preexisting histones without the need for H3-H4 splitting events.


Mu X.,Peking Union Medical College | He G.-R.,Peking Union Medical College | Yuan X.,Peking University | Li X.-X.,Peking Union Medical College | Du G.-H.,Peking Union Medical College
Pharmacology Biochemistry and Behavior | Year: 2011

Many studies of Parkinsons disease suggest that oxidative stress is involved in the neurodegenerative process. Baicalein has been shown to have antioxidant effects. The present study examines the effect of baicalein on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in C57BL/6 mice. MPTP treatment impaired spontaneous motor activity and rotarod performance, but baicalein improved this deficit. Moreover, baicalein at 280 and 560 mg/kg exhibited a protective effect against the MPTP-induced decrease in tyrosine hydroxylase (TH)-positive fibers in the substantia nigra, demonstrated by the immunohistological, morphological and behavioral outcomes. MPTP treatment also decreased dopamine levels in the striatum. However, treatment with baicalein attenuated these decreases in dopamine levels by changing dopamine catabolism and inhibiting dopamine turnover. The neuroprotective effect of baicalein on dopaminergic neurons may partly be due to its antioxidant properties. Therefore, we speculate that baicalein might be a promising candidate for prevention or treatment of oxidative stress-related neurodegenerative disorders such as Parkinsons disease. © 2011 Elsevier Inc. All rights reserved.


Gan W.,Peking University | Gan W.,China National Institute of Biological Sciences | Guan Z.,China National Institute of Biological Sciences | Liu J.,China National Institute of Biological Sciences | And 4 more authors.
Genes and Development | Year: 2011

Transcriptional R loops are anomalous RNA:DNA hybrids that have been detected in organisms from bacteria to humans. These structures have been shown in eukaryotes to result in DNA damage and rearrangements; however, the mechanisms underlying these effects have remained largely unknown. To investigate this, we first show that R-loop formation induces chromosomal DNA rearrangements and recombination in Escherichia coli, just as it does in eukaryotes. More importantly, we then show that R-loop formation causes DNA replication fork stalling, and that this in fact underlies the effects of R loops on genomic stability. Strikingly, we found that attenuation of replication strongly suppresses R-loop-mediated DNA rearrangements in both E. coli and HeLa cells. Our findings thus provide a direct demonstration that R-loop formation impairs DNA replication and that this is responsible for the deleterious effects of R loops on genome stability from bacteria to humans. © 2011 by Cold Spring Harbor Laboratory Press.


Pulido T.,Ignacio Chavez National Heart Institute | Adzerikho I.,Republican Scientific Practical Center Cardiology | Channick R.N.,Massachusetts General Hospital | Delcroix M.,Gasthuisberg University Hospital | And 19 more authors.
New England Journal of Medicine | Year: 2013

BACKGROUND: Current therapies for pulmonary arterial hypertension have been adopted on the basis of short-term trials with exercise capacity as the primary end point. We assessed the efficacy of macitentan, a new dual endothelin-receptor antagonist, using a primary end point of morbidity and mortality in a long-term trial. METHODS: We randomly assigned patients with symptomatic pulmonary arterial hypertension to receive placebo once daily, macitentan at a once-daily dose of 3 mg, or macitentan at a once-daily dose of 10 mg. Stable use of oral or inhaled therapy for pulmonary arterial hypertension, other than endothelin-receptor antagonists, was allowed at study entry. The primary end point was the time from the initiation of treatment to the first occurrence of a composite end point of death, atrial septostomy, lung transplantation, initiation of treatment with intravenous or subcutaneous prostanoids, or worsening of pulmonary arterial hypertension. RESULTS: A total of 250 patients were randomly assigned to placebo, 250 to the 3-mg macitentan dose, and 242 to the 10-mg macitentan dose. The primary end point occurred in 46.4%, 38.0%, and 31.4% of the patients in these groups, respectively. The hazard ratio for the 3-mg macitentan dose as compared with placebo was 0.70 (97.5% confidence interval [CI], 0.52 to 0.96; P = 0.01), and the hazard ratio for the 10-mg macitentan dose as compared with placebo was 0.55 (97.5% CI, 0.39 to 0.76; P<0.001). Worsening of pulmonary arterial hypertension was the most frequent primary end-point event. The effect of macitentan on this end point was observed regardless of whether the patient was receiving therapy for pulmonary arterial hypertension at baseline. Adverse events more frequently associated with macitentan than with placebo were headache, nasopharyngitis, and anemia. CONCLUSIONS: Macitentan significantly reduced morbidity and mortality among patients with pulmonary arterial hypertension in this event-driven study. Copyright © 2013 Massachusetts Medical Society.


Shao N.,CAS Beijing National Laboratory for Molecular | Shao N.,Beijing Normal University | Jin J.,CAS Beijing National Laboratory for Molecular | Jin J.,Hunan University | And 6 more authors.
Journal of the American Chemical Society | Year: 2010

Despite considerable efforts toward the development of various sophisticated spiropyrans for metal ion sensing, less attention has been paid to organic molecule sensing. One of the major difficulties for detection of organic molecules using a spiropyran is the weak and nonspecific interaction between the spiropyran and the target. Here, we report the synthesis and molecular recognition characterization of two bis-spiropyrans for dipolar molecules and their application to in vivo glutathione (GSH) fluorescent probes. Unlike the mono-spiropyrans, the newly designed bis-spiropyran molecules feature a rigidly maintained molecular cleft and two spiropyran units as binding modules. The molecular recognition is based on multipoint electrostatic interactions and structure complementarity between the opened merocyanine form of the spiropyran and the analyte. It was observed that the spiropyran 1a binds GSH in aqueous solution with high affinity (K = (7.52 ± 1.83) × 104 M-1) and shows strong fluorescence emission upon binding. Remarkably, fluorescence output of 1a is not significantly affected by other amino acids and peptides, especially, structurally similar compounds, such as cysteine and homocysteine. Furthermore, fluorescence anisotropy and confocal fluorescent microscopy confirmed that spiropyran 1a is a comparatively good candidate for intracellular delivery and can be accumulated intensively into cells. Thus, 1a can be utilized in vivo as a GSH probe or as a marker to show the level of intracellular GSH. © 2010 American Chemical Society.


Liu M.S.,Peking Union Medical College | Cui L.Y.,Peking Union Medical College | Fan D.S.,Peking University
Acta Neurologica Scandinavica | Year: 2014

Background: For patients with amyotrophic lateral sclerosis (ALS), age at onset is not only a key factor for diagnosis and prognosis, but also a clue for exploring pathogenesis. Reports based on results from a single medical center suggested that the mean age at onset of ALS in China was earlier than in other developed countries. A larger, multicenter-based study is needed to confirm this finding. Methods: A registry-based study of ALS was conducted at 10 ALS centers of the Chinese ALS Association from March 1, 2009 to August 31, 2009. The demographical and clinical features of patients with ALS were collected. Results: Data from a total of 455 patients with ALS were available for analysis. The mean age at onset for the entire cohort was 52.4 ± 12.1 years. The peak age at onset was in the 45- to 49-year-old age group for women and the 55- to 59-year-old age group for men. The age at onset for patients from Guangzhou (a southern region) was significantly earlier than it was for patients from Shanghai (an eastern region) (t = 2.270, P = 0.025). Conclusions: This investigation confirmed the earlier age at onset of ALS in China as compared with other countries. Further population-based case-control investigations of genetic and environmental factors are needed to identify the potential risk factors for Chinese ALS patients. © 2013 John Wiley & Sons A/S.


Jing Z.-C.,Tongji University | Parikh K.,Care Institute of Medical Science | Pulido T.,Instituto Nacional Of Cardiologia | White R.J.,University of Rochester | And 6 more authors.
Circulation | Year: 2013

BACKGROUND-: Pulmonary arterial hypertension (PAH) is a progressive, fatal disease with no cure. Parenteral and inhaled prostacyclin analogue therapies are effective for the treatment of PAH, but complicated administration requirements can limit the use of these therapies in patients with less severe disease. This study was designed to evaluate the safety and efficacy of the oral prostacyclin analogue treprostinil diolamine as initial treatment for de novo PAH. METHODS AND RESULTS-: Three hundred forty-nine patients (intent-to-treat population) not receiving endothelin receptor antagonist or phosphodiesterase type-5 inhibitor background therapy were randomized (treprostinil, n=233; placebo, n=116). The primary analysis population (modified intent-to-treat) included 228 patients (treprostinil, n=151; placebo, n=77) with access to 0.25-mg treprostinil tablets at randomization. The primary end point was change from baseline in 6-minute walk distance at week 12. Secondary end points included Borg dyspnea index, clinical worsening, and symptoms of PAH. The week 12 treatment effect for 6-minute walk distance (modified intent-to-treat population) was 23.0 m (P=0.0125). For the intent-to-treat population, 6-minute walk distance improvements were observed at peak (26.0 m; P=0.0001) and trough (17.0 m; P=0.0025) plasma study drug concentrations. Other than an improvement in the combined 6-minute walk distance/Borg dyspnea score, there were no significant changes in secondary end points. Oral treprostinil therapy was generally well tolerated; the most common adverse events (intent-to-treat) were headache (69%), nausea (39%), diarrhea (37%), and pain in jaw (25%). CONCLUSIONS-: Oral treprostinil improves exercise capacity in PAH patients not receiving other treatment. Oral treprostinil could provide a convenient, first-line prostacyclin treatment option for PAH patients not requiring more intensive therapy. CLINICAL TRIAL REGISTRATION:-: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00325403. © 2012 American Heart Association, Inc.


Motzer R.J.,Sloan Kettering Cancer Center | Hutson T.E.,Baylor Sammons Cancer Center Texas Oncology | Cella D.,Northwestern University | Reeves J.,Florida Cancer Specialists | And 21 more authors.
New England Journal of Medicine | Year: 2013

BACKGROUND: Pazopanib and sunitinib provided a progression-free survival benefit, as compared with placebo or interferon, in previous phase 3 studies involving patients with metastatic renal-cell carcinoma. This phase 3, randomized trial compared the efficacy and safety of pazopanib and sunitinib as first-line therapy. METHODS: We randomly assigned 1110 patients with clear-cell, metastatic renal-cell carcinoma, in a 1:1 ratio, to receive a continuous dose of pazopanib (800 mg once daily; 557 patients) or sunitinib in 6-week cycles (50 mg once daily for 4 weeks, followed by 2 weeks without treatment; 553 patients). The primary end point was progression-free survival as assessed by independent review, and the study was powered to show the noninferiority of pazopanib versus sunitinib. Secondary end points included overall survival, safety, and quality of life. RESULTS: Pazopanib was noninferior to sunitinib with respect to progression-free survival (hazard ratio for progression of disease or death from any cause, 1.05; 95% confidence interval [CI], 0.90 to 1.22), meeting the predefined noninferiority margin (upper bound of the 95% confidence interval, <1.25). Overall survival was similar (hazard ratio for death with pazopanib, 0.91; 95% CI, 0.76 to 1.08). Patients treated with sunitinib, as compared with those treated with pazopanib, had a higher incidence of fatigue (63% vs. 55%), the hand-foot syndrome (50% vs. 29%), and thrombocytopenia (78% vs. 41%); patients treated with pazopanib had a higher incidence of increased levels of alanine aminotransferase (60%, vs. 43% with sunitinib). The mean change from baseline in 11 of 14 health-related quality-of-life domains, particularly those related to fatigue or soreness in the mouth, throat, hands, or feet, during the first 6 months of treatment favored pazopanib (P<0.05 for all 11 comparisons). CONCLUSIONS: Pazopanib and sunitinib have similar efficacy, but the safety and quality-of-life profiles favor pazopanib. Copyright © 2013 Massachusetts Medical Society.


Lai C.-C.,Tulane Center for Cardiovascular Health | Lai C.-C.,Peking Union Medical College | Sun D.,Tulane Center for Cardiovascular Health | Sun D.,Peking University | And 7 more authors.
Journal of the American College of Cardiology | Year: 2014

Background Cardiovascular risk factors are associated with left ventricular hypertrophy (LVH), but little is known regarding related impact of longitudinal measures of childhood adiposity and LV hemodynamic variables.Objectives The aim of this study was to examine the impact of cumulative long-term burden and trends of excessive adiposity and elevated blood pressure (BP) during childhood on adulthood LVH and LV geometric remodeling patterns.Methods This longitudinal study consisted of 1,061 adults, age 24 to 46 years, who had been examined 4 or more times for body mass index (BMI) and BP starting in childhood, with a mean follow-up of 28.0 years. The area under the curve (AUC) was calculated as a measure of long-term burden (total AUC) and trends (incremental AUC) of BMI and BP from childhood to adulthood. Four LV geometric types were defined - normal, concentric remodeling (CR), eccentric hypertrophy (EH), and concentric hypertrophy (CH) - all on the basis of LV mass indexed for body height (m2.7) and relative wall thickness.Results Higher values of BMI and systolic and diastolic BP in childhood and adulthood, as well as total AUC and incremental AUC, were all significantly associated with higher LV mass index and LVH, adjusted for race, sex, and age. In addition, higher values of BMI and BP in childhood and adulthood, total AUC, and incremental AUC were significantly associated with EH and CH but not with CR. Importantly, all of these measures of BMI had a consistently and significantly greater influence on EH than did measures of BP.Conclusions These findings indicate that the adverse influence of excessive adiposity and elevated BP levels on LVH begins in childhood. © 2014 American College of Cardiology Foundation.


Zhang X.-D.,Peking Union Medical College | Luo Z.,National University of Singapore | Chen J.,Peking Union Medical College | Shen X.,Peking Union Medical College | And 6 more authors.
Advanced Materials | Year: 2014

Radiosensitizers can increase local treatment efficacy under a relatively low and safe radiation dose, thereby facilitating tumor eradication and minimizing side effects. Here, a new class of radiosensitizers is reported, which contain several gold (Au) atoms embedded inside a peptide shell (e.g., Au10-12 (SG)10-12) and can achieve ultrahigh tumor uptake (10.86 SUV at 24 h post injection) and targeting specificity, efficient renal clearance, and high radiotherapy enhancement. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Liu L.,First Affiliated Hospital | Wang L.,Peking Union Medical College | Tang G.,First Affiliated Hospital
European Journal of Obstetrics Gynecology and Reproductive Biology | Year: 2013

Objective Leptin, a multifunctional peptide hormone encoded by the obese (ob) gene, plays an important role in modulating lipid metabolism and energy equilibrium. Leptin reportedly acts as a cell growth factor and enhances the proliferation of various tumors. We investigated the effect of leptin on aromatase (P450arom) expression and estradiol (E2) formation in a model of endometrial carcinoma. Study design We established a co-culture model of endometrial fibroblasts and the Ishikawa endometrial carcinoma cell line. P450arom mRNA and protein expression were measured with RT-PCR and immunoblotting, respectively, before and after leptin treatment. The effect of leptin on estradiol formation in endometrial carcinoma cells was also detected with a radioimmunological method. Results P450arom mRNA expression was increased in co-cultures treated with 100 ng/ml leptin (P < 0.01). Estradiol synthesis was induced when androstenedione was added to the culture medium, and significantly higher estradiol concentration was observed in co-cultures treated with 100 ng/ml leptin, Conclusions Leptin is an important component of the microenvironment and stimulates endometrial carcinoma cell proliferation via enhancing P450arom expression and estradiol synthesis. © 2013 Elsevier Ireland Ltd. All rights reserved.


Li H.,Peking Union Medical College | Zhao H.,Tianjin Medical University | Wang D.,Peking University | Yang R.,Peking Union Medical College
British Journal of Haematology | Year: 2011

Megakaryocytopoiesis is governed by a complex network of haematopoietic growth factors that regulate the different stages of the process, in which haematopoietic stem cells undergo megakaryocytic lineage commitment, proliferation, maturation, and functional activation to produce platelets. MicroRNAs (miRNA) are a class of about 22-nucleotide noncoding RNAs that have been highly conserved during evolution and play a significant role in haematopoiesis, including differentiation and lineage commitment of megakaryocyte. This review summarizes the miRNAs which have changed expression during megakaryocytopoiesis, and their positive and negative functions on megakaryocytic differentiation. In addition, the abnormal miRNA expression profiles in megakaryocytic disorders are reviewed. © 2011 Blackwell Publishing Ltd.


Li T.,Peking Union Medical College | Li T.,Peking University | Wu R.,Peking Union Medical College | Zhang Y.,Peking Union Medical College | Zhu D.,Peking Union Medical College
BMC Genomics | Year: 2011

Background: Functional studies have demonstrated that microRNAs (miRNAs or miRs) play critical roles in a wide spectrum of biological processes including development and disease pathogenesis. To investigate the functional roles that miRNAs play during chicken skeletal muscle development, the miRNA transcriptomes of skeletal muscles from broiler and layer chickens were profiled using Solexa deep sequencing.Results: Some miRNAs have multiple isoforms and several miRNAs* are present at higher levels than their corresponding miRNAs. Thirty three novel and 189 known chicken miRNAs were identified using computational approaches. Subsequent miRNA transcriptome comparisons and real-time PCR validation experiments revealed 17 miRNAs that were differentially expressed between broilers and layers, and a number of targets of these miRNAs have been implicated in myogenesis regulation. Using integrative miRNA target-prediction and network-analysis approaches an interaction network of differentially expressed and muscle-related miRNAs and their putative targets was constructed, and miRNAs that could contribute to the divergent muscle growth of broiler and layer chickens by targeting the ACVR2B gene were identified, which can causes dramatic increases in muscle mass.Conclusions: The present study provides the first transcriptome profiling-based evaluation of miRNA function during skeletal muscle development in chicken. Systematic predictions aided the identification of potential miRNAs and their targets, which could contribute to divergent muscle growth in broiler and layer chickens. Furthermore, these predictions generated information that can be utilized in further research investigating the involvement of interaction networks, containing miRNAs and their targets, in the regulation of muscle development. © 2011 Li et al; licensee BioMed Central Ltd.


Cheng Z.,Peking Union Medical College | Sun X.,Yunnan Institute of Parasitic Diseases | Yang Y.,Peking Union Medical College | Wang H.,Peking Union Medical College | Zheng Z.,Peking Union Medical College
Journal of Clinical Microbiology | Year: 2013

Although malaria remains one of the leading infectious diseases in the world, the decline in malaria transmission in some area makes it possible to consider elimination of the disease. As countries approach elimination, malaria diagnosis needs to change from diagnosing ill patients to actively detecting infections in all carriers, including asymptomatic and low-parasite-load patients. However, few of the current diagnostic methods have both the throughput and the sensitivity required. We adopted a sandwich RNA hybridization assay to detect genus Plasmodium 18S rRNA directly from whole-blood samples from Plasmodium falciparum and Plasmodium vivax patients without RNA isolation. We tested the assay with 202 febrile patients from areas where malaria is endemic, using 20 μl of each blood sample in a 96-well plate format with a 2-day enzyme-linked immunosorbent assay (ELISA)-like work flow. The results were compared with diagnoses obtained using microscopy, a rapid diagnostic test (RDT), and genus-specific real-time PCR. Our assay identified all 66 positive samples diagnosed by microscopy, including 49 poorly stored samples that underwent multiple freeze-thaw cycles due to resource limitation. The assay uncovered three false-negative samples by microscopy and four false-negative samples by RDT and agreed completely with real-time PCR diagnosis. There was no negative sample by our assay that would show a positive result when tested with other methods. The detection limit of our assay for P. falciparum was 0.04 parasite/μl. The assay's simple work flow, high throughput, and sensitivity make it suitable for active malaria screening. Copyright © 2013, American Society for Microbiology. All Rights Reserved.


Fan J.,Peking Union Medical College | Song Y.,Peking University | Song Y.,Harvard University | Wang Y.,Peking Union Medical College | And 2 more authors.
PLoS ONE | Year: 2012

Background: The relationship between dietary glycemic index, glycemic load and risk of coronary heart disease (CHD), stroke, and stroke-related mortality is inconsistent. Methods: We systematically searched the MEDLINE, EMBASE, and Science Citation Index Expanded databases using glycemic index, glycemic load, and cardiovascular disease and reference lists of retrieved articles up to April 30, 2012. We included prospective studies with glycemic index and glycemic load as the exposure and incidence of fatal and nonfatal CHD, stroke, and stroke-related mortality as the outcome variable. Pooled relative risks (RR) and 95% confidence intervals (CI) were calculated using random-effects models. Results: Fifteen prospective studies with a total of 438,073 participants and 9,424 CHD cases, 2,123 stroke cases, and 342 deaths from stroke were included in the meta-analysis. Gender significantly modified the effects of glycemic index and glycemic load on CHD risk, and high glycemic load level was associated with higher risk of CHD in women (RR = 1.49, 95%CI 1.27-1.73), but not in men (RR = 1.08, 95%CI 0.91-1.27). Stratified meta-analysis by body mass index indicated that among overweight and obese subjects, dietary glycemic load level were associated with increased risk of CHD (RR = 1.49, 95%CI 1.27-1.76; P for interaction = 0.003). Higher dietary glycemic load, but not glycemic index, was positively associated with stroke (RR = 1.19, 95% CI 1.00-1.43). There is a linear dose-response relationship between dietary glycemic load and increased risk of CHD, with pooled RR of 1.05 (95%CI 1.02-1.08) per 50-unit increment in glycemic load level. Conclusion: High dietary glycemic load is associated with a higher risk of CHD and stroke, and there is a linear dose-response relationship between glycemic load and CHD risk. Dietary glycemic index is slightly associated with risk of CHD, but not with stroke and stroke-related death. Further studies are needed to verify the effects of gender and body weight on cardiovascular diseases. © 2012 Fan et al.


Yan X.,Peking Union Medical College | Yan X.,Peking University | Yin J.,Peking Union Medical College | Yao H.,Chinese Institute of Basic Medical Sciences | And 3 more authors.
Cancer Research | Year: 2010

Resistance to platinum drugs has emerged as a major obstacle in the treatment of ovarian cancers. Through proteomic analysis, we have found that the expression of annexin A3, a member of the Ca2+ and phospholipidbinding annexin family, is significantly increased in platinum-resistant ovarian cell lines. Anti-annexin A3 immunostaining indicated that cancers from platinum-resistant patients also possess higher levels of annexin A3 than those from platinum-sensitive patients. Although expression of annexin A3 made susceptible ovarian cancer cells more resistant to platinum, expression of antisense annexin A3 downregulated its expression and rendered the resistant cells more sensitive to platinum. In athymic mice, the growth of tumors from inoculated SKOV3 cells was inhibited by the administration of platinum, whereas tumors from annexin A3-expressing SKOV3/Ann were resistant to platinum treatment. Interestingly, the intracellular platinum concentration and platinum-DNA binding are significantly lower in annexin A3-overexpressing cells than those in parental cells. The lower cisplatin concentration was also accompanied by reduced induction of p53, which could be restored by downregulation of annexin A3. These results indicate that increased expression of annexin A3 is a mechanism of platinum resistance in ovarian cancer. It seems to act by preventing uptake or accumulation of platinum in cells. Therefore, it is conceivable that annexin A3 could be a target for therapeutic intervention and may also serve as a biomarker for drug resistance in ovarian cancer patients. ©2010 AACR.


Wang L.,Peking Union Medical College | Yin J.,Peking Union Medical College | Fadel R.,Stallergenes S.A. | Montagut A.,Stallergenes S.A. | And 2 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2014

Background The efficacy and safety of sublingual immunotherapy in house dust mite-induced asthma have yet to be firmly established. We report the results of a double-blind, placebo-controlled, randomized clinical trial performed in mainland China. Methods After a three-month baseline period, 484 asthmatic adults were randomized 2: 1 to 12 months of daily treatment with either an aqueous, standardized, 300 index of reactivity mixture of Dermatophagoides pteronyssinus and Dermatophagoides farinae extracts or a placebo. The primary efficacy criterion was well-controlled asthma for at least 16 of the last 20 weeks of treatment. Results In the active (n = 308) and placebo (n = 157) groups, well-controlled asthma was achieved by 85.4% and 81.5% of the patients, respectively (P = 0.244). A subsequent post hoc analysis by asthma severity revealed significant clinical benefits in actively treated subjects with moderate, persistent asthma at baseline [401-800 μg budesonide/day (n = 175)], with greater achievement of well-controlled asthma (80.5% and 66.1% for the active treatment and placebo groups, respectively; P = 0.021) and totally controlled asthma (54.0% and 33.9%, respectively, P = 0.008), a higher percentage of patients with an asthma control questionnaire score < 0.75 (56.6% and 40.0%, respectively; P = 0.039) and a greater mean reduction in inhaled corticosteroid use (218.5 μg and 126.2 μg, respectively; P = 0.004). The active vs placebo differences in disease control and corticosteroid use were not significant for mild, persistent asthma. No treatment-related serious adverse events were reported. Conclusions Sublingual mite allergen immunotherapy was well tolerated in adult asthmatics and effectively controlled disease in patients with moderate (but not mild) persistent asthma (ClinicalTrials.gov: NCT00660452). © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Shi Y.,Peking Union Medical College | Au J.S.-K.,Queen Elizabeth Hospital | Thongprasert S.,Chiang Mai University | Srinivasan S.,Apollo Speciality Hospital | And 6 more authors.
Journal of Thoracic Oncology | Year: 2014

INTRODUCTION:: PIONEER (NCT01185314) was a prospective, multinational, epidemiological study of epidermal growth factor receptor (EGFR) mutations in patients from Asia with newly diagnosed advanced lung adenocarcinoma. METHODS:: Eligible patients (aged ≥20 years) had untreated stage IIIB/IV adenocarcinoma. The EGFR mutation status (primary end point: positive, negative, or undetermined) of tumor samples (biopsy, surgical specimen, or cytology) was determined (Scorpion amplification refractory mutation system). EGFR mutation frequency was calculated and compared between demographic and clinical subgroups. RESULTS:: Of 1482 patients from seven Asian regions, 43.4% of patients were female, median age was 60 years (range, 17-94), and 52.6% of patients were never-smokers. EGFR mutation status was evaluable in tumors from 1450 patients (97.8%) (746 [51.4%] positive; 704 [48.6%] negative). Country, sex, ethnicity, smoking status, pack-years (all p < 0.001), disease stage (p = 0.009), and histology type (p = 0.016) correlated significantly with EGFR mutation frequency. Mutation frequency was 61.1% in females, 44.0% in males; lower in patients from India (22.2%) compared with other areas (47.2%-64.2%); highest among never-smokers (60.7%); and decreased as pack-year number increased (>0-10 pack-years, 57.9%; >50 pack-years, 31.4%) (similar trend by sex). Ethnic group (p < 0.001) and pack-years (p < 0.001) had statistically significant associations with mutation frequency (multivariate analysis); sex was not significant when adjusted for smoking status. CONCLUSION:: PIONEER is the first prospective study to confirm high EGFR mutation frequency (51.4% overall) in tumors from Asian patients with adenocarcinoma. The observed high mutation frequency in demographic/clinical subgroups compared with white populations suggests that mutation testing should be considered for all patients with stage IIIB/IV adenocarcinoma, even males and regular smokers, among Asian populations. © 2013 by the International Association for the Study of Lung Cancer.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-3.2-4 | Award Amount: 3.83M | Year: 2009

Current human resources planning models in nursing are unreliable and ineffective as they consider volumes, but ignore effects on quality in patient care. The project RN4CAST aims innovative forecasting methods by addressing not only volumes, but quality of nursing staff as well as quality of patient care. RN4CAST is a consortium of 15 partners that will quantify in 11 European countries-Belgium, Finland, Germany, Greece, Ireland, Poland, Spain, Sweden, Switzerland, Netherlands, UK - important unmeasured factors in forecasting models including how features of hospital work environments and qualifications of the nurse workforce impact on nurse recruitment, retention, productivity and patient outcomes. Three partners outside Europe - China, South Africa, and Botswana- provide additional perspectives. Innovative elements of the project include unique measures of workplace dynamics and patient outcomes. Nurse workforce planning initiatives at national and European levels will be reviewed and newly collected data added to enhance accuracy for nurse workforce management. Data collection focuses on general hospitals, which employ the majority of nurses, account for the largest number of medical errors and comprise the largest share of national health expenditures. Each European partner will conduct a study of 20 to 50 hospitals depending on country size yielding information on more than 350 hospitals including surveys from over 50,000 nurses and outcomes of tens of thousands of patients. European partners were selected by geographic distribution, membership duration in the EU, research expertise and availability of patient discharge data. University of Pennsylvania, USA, will contribute specialized research expertise derived from previous international research. RN4CAST will be the largest nurse workforce study ever conducted in Europe, will add to accuracy of forecasting models and generate new approaches to more effective management of nursing resources in Europe.


Lee M.,Hospital Drive | Teoh W.,Hospital Drive | Phang B.,Hospital Drive | Tong W.,Peking Union Medical College | And 4 more authors.
Cancer Cell | Year: 2012

The specific roles of mutant p53's dominant-negative (DN) or gain-of-function (GOF) properties in regulating acute response and long-term tumorigenesis is unclear. Using "knockin" mouse strains expressing varying R246S mutant levels, we show that the DN effect on transactivation is universally observed after acute p53 activation, whereas the effect on cellular outcome is cell-type specific. Reducing mutant p53 levels abrogated the DN effect. Mutant p53's DN effect protected against radiation-induced death but did not accentuate tumorigenesis. Furthermore, the R246S mutant did not promote tumorigenesis compared to p53-/- mice in various models, even when MDM2 is absent, unlike the R172H mutant. Together, these data demonstrate that mutant p53's DN property only affects acute responses, whereas GOF is not universal, being mutation-type specific. © 2012 Elsevier Inc.


Qian H.,Peking Union Medical College | Wang H.,Peking Union Medical College | Ma F.,Peking Union Medical College
BMC Cancer | Year: 2014

Background: Crizotinib was granted accelerated approval by the Food and Drug Administration in 2011 for the treatment of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). To evaluate the efficacy and safety of crizotinib, we performed a meta-analysis of published clinical trials using the random effect model.Methods: The efficacy and safety of crizotinib was evaluated based on 1-year overall survival (OS), progression-free survival (PFS), overall response rate (ORR), partial response, complete response, stable disease, and dose reduction or cessation because of crizotinib toxicity.Results: Six clinical trials were included in the meta-analysis. Crizotinib treatment demonstrated a 1-year OS of 66.8% (95% CI, 52.2-78.8%) and a PFS of 8.6 months (95% CI, 7.3-9.9 months). The aggregate ORR, partial response and complete response rates were 61.2%, 59.8% and 1.5%, respectively. The proportion of patients achieving stable disease was 42.6% (95% CI, 17.3-72.5%). The most frequently reported adverse effects of crizotinib were mild visual disturbances, nausea, vomiting, diarrhea, constipation, edema, reduction in glomerular filtration rate, and generally reversible but sometimes severe elevations in aspartate aminotransferase and alanine aminotransferase. The proportion of patients who required dose reduction or cessation because of crizotinib toxicity was 6.5% (95% CI, 4.1-10.1%).Conclusions: This meta-analysis revealed extended survival and improved response rates in patients treated with crizotinib. As a novel, targeted anticancer agent, crizotinib appears to be a favorable treatment option for patients with locally advanced or metastatic ALK-positive NSCLC. © 2014 Qian et al.; licensee BioMed Central Ltd.


Wang Y.-H.,Peking University | Wang Y.-H.,Peking Union Medical College | Yu H.-T.,Jiangsu Kanon Pharmaceutical Co. | Pu X.-P.,Peking University | Du G.-H.,Peking Union Medical College
Journal of Molecular Neuroscience | Year: 2014

Advanced glycation end products (AGEs) have been identified in age-related intracellular protein deposits of neurodegenerative diseases. Methylglyoxal (MGO), a dicarbonyl metabolite, is a major precursor of AGEs which have been linked to the development of neurodegenerative diseases. Myricitrin, a flavanoid isolated from the root bark of Myrica cerifera, attenuated 6-OHDA-induced mitochondrial dysfunction and had a potential anti-Parkinson's disease in our previous investigation. The aims of this study were to investigate the protective effects of myricitrin against MGO-induced injury in SH-SY5Y cells and also to look for the possible mechanisms. The results showed that exposure of SH-SY5Y cells to MGO caused decreases of cell viability, intracellular ATP, mitochondrial redox activity, and mitochondrial membrane potential and an increase in reactive oxygen species generation. However, these mitochondrial dysfunctions were alleviated by co-treatment with myricitrin. Additionally, myricitrin was capable of inhibiting AGEs formation, blocking RAGE expression, and inhibiting NF-κB activation and translocation triggered by MGO in SH-SY5Y cells. Our results suggest that myricitrin alleviates MGO-induced mitochondrial dysfunction, and the possible mechanism is through modulating the AGEs/RAGE/NF-κB pathway. In summary, myricitrin might offer a promising therapeutic strategy to reduce the neurotoxicity of reactive dicarbonyl compounds, providing a potential benefit agent with age-related neurodegenerative diseases. © 2014 Springer Science+Business Media.


Sun X.,Peking Union Medical College | Xu Y.,Peking University | Wu J.,Peking University | Zhang Y.,Peking University | Sun K.,Peking Union Medical College
Journal of Surgical Research | Year: 2013

Background: Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy could serve as a diagnostic tool for detecting and discriminating different diseases. The aim of this preliminary study was to distinguish malignant and nonmalignant lung tissues with ATR-FTIR spectroscopy. Methods: Sixty lung tissue samples were obtained from 30 patients who underwent pulmonary lobectomy. Samples were examined with ATR-FTIR spectroscopy before histologic diagnosis. Peak positions, intensities, and full width at half maximum of each absorbent band were measured, and the relative intensity ratios were calculated. Canonical discriminant analysis was performed to discriminate malignant and nonmalignant groups. Results: Twenty-two parameters were significantly different between malignant and nonmalignant groups. Peak intensity at 1546/cm, intensity ratio at 1120/cm, and full width at half maximum at 1303 and 1240/cm were selected as independent factors to form discriminant functions. The sensitivity and specificity of the discriminants were all 96.7%. Conclusions: ATR-FTIR spectroscopy is a promising method for the detection of malignant lung tissue and could be proved useful in lung tumor surgery. © 2013 Elsevier Inc. All rights reserved.


News Article | November 3, 2016
Site: www.24-7pressrelease.com

FAIRPORT, NY, November 03, 2016-- William Y. Chey, MD, DSc, has been included in Marquis Who's Who. As in all Marquis Who's Who biographical volumes, individuals profiled are selected on the basis of current reference value. Factors such as position, noteworthy accomplishments, visibility, and prominence in a field are all taken into account during the selection process.With more than 50 years of experience as a physician, educator and research scientist in gastrointestinal medicine, Dr. Chey is widely recognized for his expertise in the field of gastroenterology and hepatology. Prior to his retirement in 2000, he served as a professor of medicine and director of the Division of Gastroenterology and Hepatology at the University of Rochester Medical Center, and as a consultant gastroenterologist at Canandaigua VA Medical Center. He is a fellow of the American College of Gastroenterology and the American Gastroenterological Association, a member of the AGA Legacy Society, and was a member of the American Association for the Advancement of Science and American Physiological Society, among other medical organizations. In addition, he is the former president of the American Pancreatic Association and the American Society of Acupuncture. He was invited nationally and internationally as a visiting professor by numerous prestigious institutions in the United States, Europe, Asia and Mid-Eastern countries. In particular, he holds the titles of Honorary Professor at the Catholic University College of Medicine, Seoul, Korea and Visiting Professor at Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China and Korea University College of Medicine, Seoul, Korea.After completing his medical education in 1953 through the two top medical schools in Seoul, Korea, Seoul National University and Yonsei University in Seoul, Korea, and serving as a medical officer of the Republic of Korea in the Korean War, Dr. Chey emigrated to the United States in 1954 and had his post-graduate training including internship and residency in internal medicine at City Hospital of New York, fellowship in pathology at Mount Sinai Hospital, New York, and fellowship in hepatology at Jersey City Medical Center, Seton Hall University School of Medicine and Dentistry, Jersey City, NJ. Then he received advanced degrees of Master of Science in Gastroenterology in 1962 and Doctor of Science in Medicine in 1966 from the University of Pennsylvania School of Medicine. At Temple University Medical Center and the Samuel S. Fel's Research Institute, Temple University School of Medicine, Philadelphia, PA, he finished a fellowship in gastroenterology and became a faculty member in 1963. He was an Associate Professor of Medicine and Head of Gastrointestinal Research in 1971 when he was recruited by the University of Rochester School of Medicine and Dentistry, Rochester, NY. He was the Founding Director of the Isaac Gordon Center for Digestive Diseases and Nutrition at the Genesee Hospital and Attending Physician at Strong Memorial Hospital, Rochester, NY. In 1992, he became Director of the Division of Gastroenterology and Hepatology at the University of Rochester Medical Center. He was also the Founding Director of the William and Sheila Konar Center for Digestive and Liver Diseases at Strong Memorial Hospital until his retirement in 2000. During his tenure, he trained numerous clinical and research fellows from the United States and abroad, including Asia, Europe, South America, Mid-East and Africa. The majority of them returned to their native countries and are active in their leadership positions. During the following ten years, he enjoyed practicing gastrointestinal medicine at the Rochester Institute for Digestive Diseases and Sciences and was also actively involved in the American Gastroenterological Association and the American Pancreatic Association. He has been married to Fan K. Tang since 1959. They have 4 children; William D. married to Janine Zwiren, Donna married to Dale Hoellrich, Richard married to Maura Bauman, and Laura married to Richard Warren, and 9 grandchildren; Cameron, Brandon (deceased), Samuel, Megen, Russell, Paris, Wyatt, Josephine and LiLi.He contributed numerous articles to competitive scientific journals, and published many chapters in text-books and two books of his specialty and research. He was a member of the editorial board of the Pancreas and American Journal of Physiology, and has been the Editor-In-Chief of Clinical Endoscopy since 2011. He served as an active member of the National Institute of Health, Surgery and Bioengineering Study Section and a consultant to the Gastrointestinal Drug Advisory Committee, Food and Drug Administration, Department of Health and Human Services.In recognition of his contributions to medicine, Dr. Chey received a wide variety of honors and awards. He was the recipient of the V.L. William and Frisca Go Award for Life Time Achievement from the American Pancreatic Association, the Governor's Award for Excellence in Clinical Research from the American College of Gastroenterology, Distinguished Clinician Award and Mentor's Research Scholar Award from the American Gastroenterological Association, Distinguished Service Award from the Rochester Academy of Medicine and American Top Physicians Award in 2008 from the Consumers' Research Council of America. He has been cited in Marquis Who's Who in America, in Medicine and Health Care, in Science and Engineering, and in the World.About Marquis Who's Who :Since 1899, when A. N. Marquis printed the First Edition of Who's Who in America , Marquis Who's Who has chronicled the lives of the most accomplished individuals and innovators from every significant field of endeavor, including politics, business, medicine, law, education, art, religion and entertainment. Today, Who's Who in America remains an essential biographical source for thousands of researchers, journalists, librarians and executive search firms around the world. Marquis now publishes many Who's Who titles, including Who's Who in America , Who's Who in the World , Who's Who in American Law , Who's Who in Medicine and Healthcare , Who's Who in Science and Engineering , and Who's Who in Asia . Marquis publications may be visited at the official Marquis Who's Who website at www.marquiswhoswho.com


Yang G.,Peking Union Medical College | Waterfield N.R.,University of Warwick
PLoS Pathogens | Year: 2013

The Toxin Complex (TC) is a large multi-subunit toxin encoded by a range of bacterial pathogens. The best-characterized examples are from the insect pathogens Photorhabdus, Xenorhabdus and Yersinia. They consist of three large protein subunits, designated A, B and C that assemble in a 5:1:1 stoichiometry. Oral toxicity to a range of insects means that some have the potential to be developed as pest control technology. The three subunit proteins do not encode any recognisable export sequences and as such little progress has been made in understanding their secretion. We have developed heterologous TC production and secretion models in E. coli and used them to ascribe functions to different domains of the crucial B+C sub-complex. We have determined that the B and C subunits use a secretion mechanism that is either encoded by the proteins themselves or employ an as yet undefined system common to laboratory strains of E. coli. We demonstrate that both the N-terminal domains of the B and C subunits are required for secretion of the whole complex. We propose a model whereby the N-terminus of the C-subunit toxin exports the B+C sub-complex across the inner membrane while that of the B-subunit allows passage across the outer membrane. We also demonstrate that even in the absence of the B-subunit, that the C-subunit can also facilitate secretion of the larger A-subunit. The recognition of this novel export system is likely to be of importance to future protein secretion studies. Finally, the identification of homologues of B and C subunits in diverse bacterial pathogens, including Burkholderia and Pseudomonas, suggests that these toxins are likely to be important in a range of different hosts, including man. © 2013 Yang, Waterfield.


Wang Y.,Capital Medical University | Zhao X.,Capital Medical University | Liu L.,Capital Medical University | Wang D.,Illinois College | And 12 more authors.
New England Journal of Medicine | Year: 2013

BACKGROUND: Stroke is common during the first few weeks after a transient ischemic attack (TIA) or minor ischemic stroke. Combination therapy with clopidogrel and aspirin may provide greater protection against subsequent stroke than aspirin alone. METHODS: In a randomized, double-blind, placebo-controlled trial conducted at 114 centers in China, we randomly assigned 5170 patients within 24 hours after the onset of minor ischemic stroke or high-risk TIA to combination therapy with clopidogrel and aspirin (clopidogrel at an initial dose of 300 mg, followed by 75 mg per day for 90 days, plus aspirin at a dose of 75 mg per day for the first 21 days) or to placebo plus aspirin (75 mg per day for 90 days). All participants received open-label aspirin at a clinician-determined dose of 75 to 300 mg on day 1. The primary outcome was stroke (ischemic or hemorrhagic) during 90 days of follow-up in an intention-to-treat analysis. Treatment differences were assessed with the use of a Cox proportional-hazards model, with study center as a random effect. RESULTS: Stroke occurred in 8.2% of patients in the clopidogrel-aspirin group, as compared with 11.7% of those in the aspirin group (hazard ratio, 0.68; 95% confidence interval, 0.57 to 0.81; P<0.001). Moderate or severe hemorrhage occurred in seven patients (0.3%) in the clopidogrel-aspirin group and in eight (0.3%) in the aspirin group (P = 0.73); the rate of hemorrhagic stroke was 0.3% in each group. CONCLUSIONS: Among patients with TIA or minor stroke who can be treated within 24 hours after the onset of symptoms, the combination of clopidogrel and aspirin is superior to aspirin alone for reducing the risk of stroke in the first 90 days and does not increase the risk of hemorrhage. Copyright © 2013 Massachusetts Medical Society.


Wang Y.,Centers for Diseases Control and Prevention | Banyai K.,Hungarian Academy of Sciences | Tu X.,Peking Union Medical College | Jiang B.,Centers for Diseases Control and Prevention
Journal of Clinical Microbiology | Year: 2012

We previously reported the first detection of simian picobirnaviruses (PBVs) by polyacrylamide gel electrophoresis in fecal specimens of two monkeys with diarrhea in China. We now report the detection of genogroup I PBVs in 48% (44/92) of the fecal specimens by reverse transcriptase PCR (RT-PCR) and amplicon sequencing using primers specific for the RNA-dependent RNA polymerase (RDRP) gene. Molecular characterization of these 44 strains demonstrated both sequence conservation and diversity among simian PBVs and among simian, porcine, and human PBVs. We further determined full-length sequences of segment 2 of the two simian PBV strains, monkey/CHN-14/2002 and monkey/CHN-49/2002, and demonstrated 52.5% to 54.2% nucleotide sequence similarity to the corresponding gene of the bovine strain RUBV and the prototype human strain 1-CHN-97 of geno-group I PBVs and an even lower similarity (38.4%) to segment 2 of the prototype human genogroup II strain 4-GA-91. Further studies are needed to investigate the epidemiology and pathogenesis of PBVs in animals and humans. Copyright © 2012, American Society for Microbiology. All Rights Reserved.


Zhang J.-Y.,Peking Union Medical College | Chan S.S.-C.,University of Hong Kong | Fong D.Y.-T.,University of Hong Kong | Malone R.E.,University of California at San Francisco | Lam T.-H.,University of Hong Kong
Tobacco Control | Year: 2012

Background China has the largest population of smokers in the world. Little previous research has explored the cultural challenges in encouraging smoking cessation in China. This study aimed to explore and generate research questions about culturally distinctive beliefs and barriers to smoking cessation. Methods A convenience sample of 21 smokers and ex-smokers selected from a Guangzhou hospital smoking cessation clinic and medical ward was interviewed about experiences with quitting smoking. Data were analysed to elucidate culturally distinctive obstacles to cessation that may warrant further study. Results Three major obstacles to smoking cessation were identified: family and social influences, the myth that quitting smoking is dangerous to health and misinformation from health professionals. Conclusions This study suggests that smoking cessation in China is made more challenging by a social context in which family, friends and even health professionals may discourage it. However, these identified barriers and beliefs about smoking cessation need to be confirmed in larger, more representative studies in the future.


Fan H.,Shanghai JiaoTong University | Lu S.,Peking Union Medical College
Neoplasma | Year: 2014

Prior studies showed that cell fusion between bone marrow-derived cell (BMDC) and somatic cell might be the origin of cancer stem cell. Our previous study suggested that cell fusion of human bone marrow-derived mesenchymal stem cell (MSC) with esophageal cancer cell did not generate cancer stem cells. But up to now, the origin of cancer stem cell is still ambiguous. In this study, we carried out the cell fusion experiment between hemopoietic stem cells (HSCs) and human esophageal cancer cells, and found that cell fusion slowed the growth speed of esophageal cancer cells and decreased the clone formation ability and tumorigenicity in NOD/SCID mice. In addition, cell fusion did not increase the ratio of side population (SP) cells and the resistance to chemotherapeutic drugs. Collectively, our data indicated that cell fusion between HSCs and esophageal cancer cells has a therapeutic effect rather than generate cells with characteristics of esophageal cancer stem cells. © 2014 Cancer Research Institute Slovak Acad. of Sciences. All right reserved.


Ghofrani H.-A.,Justus Liebig University | Ghofrani H.-A.,Imperial College London | Galie N.,University of Bologna | Grimminger F.,Justus Liebig University | And 9 more authors.
New England Journal of Medicine | Year: 2013

BACKGROUND: Riociguat, a soluble guanylate cyclase stimulator, has been shown in a phase 2 trial to be beneficial in the treatment of pulmonary arterial hypertension. METHODS: In this phase 3, double-blind study, we randomly assigned 443 patients with symptomatic pulmonary arterial hypertension to receive placebo, riociguat in individually adjusted doses of up to 2.5 mg three times daily (2.5 mg-maximum group), or riociguat in individually adjusted doses that were capped at 1.5 mg three times daily (1.5 mg- maximum group). The 1.5 mg-maximum group was included for exploratory purposes, and the data from that group were analyzed descriptively. Patients who were receiving no other treatment for pulmonary arterial hypertension and patients who were receiving endothelin-receptor antagonists or (nonintravenous) prostanoids were eligible. The primary end point was the change from baseline to the end of week 12 in the distance walked in 6 minutes. Secondary end points included the change in pulmonary vascular resistance, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, World Health Organization (WHO) functional class, time to clinical worsening, score on the Borg dyspnea scale, quality-of-life variables, and safety. RESULTS: By week 12, the 6-minute walk distance had increased by a mean of 30 m in the 2.5 mg-maximum group and had decreased by a mean of 6 m in the placebo group (least-squares mean difference, 36 m; 95% confidence interval, 20 to 52; P<0.001). Prespecified subgroup analyses showed that riociguat improved the 6-minute walk distance both in patients who were receiving no other treatment for the disease and in those who were receiving endothelin-receptor antagonists or prostanoids. There were significant improvements in pulmonary vascular resistance (P<0.001), NT-proBNP levels (P<0.001), WHO functional class (P = 0.003), time to clinical worsening (P = 0.005), and Borg dyspnea score (P = 0.002). The most common serious adverse event in the placebo group and the 2.5 mg-maximum group was syncope (4% and 1%, respectively). CONCLUSIONS: Riociguat significantly improved exercise capacity and secondary efficacy end points in patients with pulmonary arterial hypertension. (Funded by Bayer HealthCare; PATENT-1 and PATENT-2 ClinicalTrials.gov numbers, NCT00810693 and NCT00863681, respectively). Copyright © 2013 Massachusetts Medical Society.


Dai M.,Oregon Health And Science University | Shi X.,Oregon Health And Science University | Shi X.,Peking Union Medical College | Shi X.,Shanghai JiaoTong University
PLoS ONE | Year: 2011

Background: Transduction of sound in the cochlea is metabolically demanding. The lateral wall and hair cells are critically vulnerable to hypoxia, especially at high sound levels, and tight control over cochlear blood flow (CBF) is a physiological necessity. Yet despite the importance of CBF for hearing, consensus on what mechanisms are involved has not been obtained. Methodology/Principal Findings: We report on a local control mechanism for regulating inner ear blood flow involving fibrocyte signaling. Fibrocytes in the super-strial region are spatially distributed near pre-capillaries of the spiral ligament of the albino guinea pig cochlear lateral wall, as demonstrably shown in transmission electron microscope and confocal images. Immunohistochemical techniques reveal the inter-connected fibrocytes to be positive for Na+/K+ ATPase β1 and S100. The connected fibrocytes display more Ca2+ signaling than other cells in the cochlear lateral wall as indicated by fluorescence of a Ca2+ sensor, fluo-4. Elevation of Ca2+ in fibrocytes, induced by photolytic uncaging of the divalent ion chelator o-nitrophenyl EGTA, results in propagation of a Ca2+ signal to neighboring vascular cells and vasodilation in capillaries. Of more physiological significance, fibrocyte to vascular cell coupled signaling was found to mediate the sound stimulated increase in cochlear blood flow (CBF). Cyclooxygenase-1 (COX-1) was required for capillary dilation. Conclusions/Significance: The findings provide the first evidence that signaling between fibrocytes and vascular cells modulates CBF and is a key mechanism for meeting the cellular metabolic demand of increased sound activity. © 2011 Dai, Shi.


Katanoda K.,Center for Cancer Control and Information Services | Jiang Y.,U.S. Center for Disease Control and Prevention | Park S.,Yonsei University | Lim M.K.,National Cancer Control Institute | And 2 more authors.
Tobacco Control | Year: 2014

East Asia is one of the world's largest tobacco epidemic regions. Although several international studies have evaluated the status of tobacco control in this region, the findings have not been integrated with knowledge on domestic activities at the national and municipal levels. We analysed the current tobacco control situation in three East Asian countries, Japan, China and the Republic of Korea, using both international and domestic data sources. We collected data between 2008 and 2011 in each country according to the framework of WHO's MPOWER (Monitoring, Protect, Offer, Warn, Enforcement and Raise) approach for guiding implementation of the WHO Framework Convention on Tobacco Control. Analysis revealed that 37-53% of adult men were current smokers and that smoking prevalence among middle-aged men reached 63%. Less than 20% of male smokers plan to quit and the use of nicotine replacement drugs was 14% at maximum. Forty-six percent or more of men and 20% or more of women were exposed to passive smoking at workplaces and at home, respectively. Many tobacco industry activities remain unrestricted and prevalent. Our findings indicate an urgent need for the following set of policies: raise cigarette prices to increase the quit attempt rate, particularly among adult men; develop a multicomponent quitting assistance system to provide adequate assistance for smoking cessation; implement effective smoke-free policies in workplaces and public places to reduce exposure to passive smoking; and rebuild the administrative structure to denormalise tobacco industry activities. The importance of these standard approaches should be reaffirmed by all tobacco control policymakers in East Asia.


News Article | January 6, 2016
Site: www.nature.com

Formidable capacity in genome sequencing, access to millions of patients and the promise of solid governmental support: those are the assets that China hopes to bring to the nascent field of precision medicine, which uses genomic, physiological and other data to tailor treatments to individuals. Almost exactly one year after US President Barack Obama announced the Precision Medicine Initiative, China is finalizing plans for its own, much larger project. But as universities and sequencing companies line up to gather and analyse the data, some observers worry that problems with the nation’s health-care infrastructure — in particular a dearth of doctors — threaten the effort’s ultimate goal of improving patient care. Precision medicine harnesses huge amounts of clinical data, from genome sequences to health records, to determine how drugs affect people in different ways. By enabling physicians to target drugs only to those who will benefit, such knowledge can cut waste, improve health outcomes using existing treatments, and inform drug development. For example, it is now clear that individuals with a certain mutation (which is mostly found in Asian people) respond better to the lung-cancer drug Tarceva (erlotinib; W. Pao et al. Proc. Natl Acad. Sci. USA 101, 13306–13311; 2004), and the discovery of a mutation that causes 4% of US cystic fibrosis cases led to the development of the drug Kalydeco (ivacaftor). The Chinese government is expected to officially announce the initiative after it approves its next five-year plan in March. Just how much the effort will cost is unclear — but it will almost certainly be larger and more expensive than the US$215-million US initiative. Since last spring, Chinese media has been abuzz with estimates of a 60-billion yuan (US$9.2-billion) budget, spread over 15 years. But this figure is not finalized, cautions Zhan Qimin, director of the State Key Laboratory of Molecular Oncology at Peking Union Medical College in Beijing, who is involved in the initiative. He says that the effort will consist of hundreds of separate projects to sequence genomes and gather clinical data, with support for each ranging from tens of millions of yuan to more than 100 million yuan. Anticipating the initiative, leading institutes — including Tsinghua University, Fudan University and the Chinese Academy of Medical Sciences — are scrambling to set up precision-medicine centres. Sichuan University’s West China Hospital, for instance, plans to sequence 1 million human genomes itself — the same goal as the entire US initiative. The hospital will focus on ten diseases, starting with lung cancer. Both the US and the Chinese efforts will focus on genetic links to diseases that are particularly deadly, such as cancer and heart disease. But China will target specific cancers, such as stomach and liver cancer, which are common there. The Chinese initiative is part of a series of research-funding efforts that will replace two major grant programmes, known as 863 and 973, that are due to be phased out by 2017. The new programmes will be “more organized, more efficient”, says Zhan. Genome-sequencing companies are already vying to provide services to deal with the anticipated demand. For several years, China has boasted high genome-sequencing capacity. In 2010, the genomics institute BGI in Shenzhen was estimated to host more sequencing capacity than the entire United States. This was thanks to its equipment, purchased from Illumina of San Diego, California, which at the time represented state-of-the-art technology. But Illumina has since sold upgraded machines to at least three other genomics firms — WuXi PharmaTech and Cloud Health, both in Shanghai, and the Beijing-based firm Novogene. Jason Gang Jin, co-founder and chief executive of Cloud Health, says that this trio, rather than BGI, will be the main sequencing support for China’s precision-medicine initiative — although BGI’s director of research, Xu Xun, disagrees. Xu says that precision medicine is a priority for BGI and that the organization has a diverse portfolio of sequencers that still gives it an edge. “If you are talking about real data output, BGI is still leading in China, maybe even globally,” he says. BGI has already established a collaboration with the Zhongshan Hospital’s Center for Clinical Precision Medicine in Shanghai, which opened in May 2015 with a budget of 100 million yuan and is run by Fudan University. Regardless of the details, Jin thinks that China will be faster than the United States at sequencing genomes and identifying mutations that are relevant to personalized medicine because China’s larger populations of patients for each disease will make it easier to find sufficient numbers to study. Still, it remains to be seen whether China has the resources to apply these insights to the individualized care of patients. “China wants to do it, and everybody is very excited,” says Ta Jen Liu, project director at the MD Anderson Cancer Center in Houston, Texas, who helps to establish collaborations in China and is familiar with the precision-medicine scene there. But there are hurdles. He notes that Chinese researchers and pharmaceutical companies have not had much success in developing drugs so far; that the pathologists needed to diagnose specific diseases are scarce in China; and that physicians there are notoriously overworked. “Doctors are always overwhelmed with patients, seeing 60 or 70 a day,” he says. “They don’t have time to sit down and think about what is best for specific patients.” David Weitz, a physicist at Harvard University who is starting a company in Beijing to develop diagnostic instruments for use in precision medicine, agrees that there will be obstacles, but notes the initiative’s assets. “We need lots of data to validate ideas, to validate tests,” he says. “There’s lots of data here.” He thinks that this, combined with the Chinese government’s determination to succeed, will mean that the effort will ultimately win out. “They really seem devoted to meeting the needs of the society,” he says. “It’s an exciting thing, to try to help that many people.”


News Article | November 4, 2016
Site: www.sciencedaily.com

By removing the protein galectin-3 (Gal3), a team of investigators led by University of California School of Medicine researchers were able to reverse diabetic insulin resistance and glucose intolerance in mouse models of obesity and diabetes. By binding to insulin receptors on cells, Gal3 prevents insulin from attaching to the receptors resulting in cellular insulin resistance. The team led by Jerrold Olefsky, MD, professor of medicine in the Division of Endocrinology and Metabolism at UC San Diego School of Medicine, showed that by genetically removing Gal3 or using pharmaceutical inhibitors to target it, insulin sensitivity and glucose tolerance could be returned to normal, even among older mice. However, obesity remained unchanged. "This study puts Gal3 on the map for insulin resistance and diabetes in mouse model," said Olefsky, associate dean for scientific affairs and senior author of the study. "Our findings suggest that Gal3 inhibition in people could be an effective anti-diabetic approach." Olefsky and other researchers have been studying how chronic tissue inflammation leads to insulin resistance in type 2 diabetes. In the paper, published in the journal Cell on November 3, researchers explain that inflammation requires macrophages -- specialized cells that destroy targeted cells. In obese adipose tissue (fat), for example, 40 percent of cells are macrophages. Macrophages in turn secrete Gal3, which then acts as a signaling protein attracting more macrophages, thus resulting in the production of even more Gal3. Furthermore, investigators identified bone marrow-derived macrophages as the source of Gal3 that leads to insulin resistance. More importantly, researchers found that Gal3 is secreted by macrophages, and can then cause insulin resistance in liver, fat cells, and muscle cells independent of inflammation. Gal3 has previously been connected to other diseases. Olefsky will continue to study Gal3 depletion as a possible therapeutic target for nonalcoholic steatohepatitis as well as heart and liver fibrosis. Study co-authors include: Pingping Li, Chinese Academy of Medical Sciences, Peking Union Medical College and UC San Diego; Shuainan Liu, Zhufang Shen, Bing Cui, Lijuan Kong, Shaocong Hou, Xiao Liang, Chinese Academy of Medical Sciences, Peking Union Medical College; Min Lu, UC San Diego, and Merck Research Laboratories; Gautum Bandyyopadhyay, Dayoung Oh, Andrew M. Johnson, Dorothy Sears, Wei Ying, Olivia Osborn, Joshua Wollam, UC San Diego; Takeshi Imamura, Shiga University of Medical Science; Salvatore Iovino, Martin Brenner, Merck Research Laboratories; Steven M. Watkins, Lipomics Technologies, Inc. This research was funded, in part, by grants from the National Institutes of Health (DK033651, DK074868, DK063491, DK09062) and Merck (LKR159915).


Wolf M.,University of Würzburg | Chen S.,Peking Union Medical College | Song J.,Peking Union Medical College | Ankenbrand M.,University of Würzburg | Muller T.,University of Würzburg
PLoS ONE | Year: 2013

Compensatory base changes (CBCs) in internal transcribed spacer 2 (ITS2) rDNA secondary structures correlate with Ernst Mayr's biological species concept. This hypothesis also referred to as the CBC species concept recently was subjected to large-scale testing, indicating two distinct probabilities. (1) If there is a CBC then there are two different species with a probability of ∼0.93. (2) If there is no CBC then there is the same species with a probability of ∼0.76. In ITS2 research, however, the main problem is the multicopy nature of ITS2 sequences. Most recently, 454 pyrosequencing data have been used to characterize more than 5000 intragenomic variations of ITS2 regions from 178 plant species, demonstrating that mutation of ITS2 is frequent, with a mean of 35 variants per species, respectively per individual organism. In this study, using those 454 data, the CBC criterion is reconsidered in the light of intragenomic variability, a proof of concept, a necessary criterion, expecting no intragenomic CBCs in variant ITS2 copies. In accordance with the CBC species concept, we could demonstrate that the probability that there is no intragenomic CBC is ∼0.99. © 2013 Wolf et al.


BACKGROUND—: The accurate assessment of individual risk can be of great value to guiding and facilitating prevention of atherosclerotic cardiovascular disease (ASCVD). However, prediction models in common use were primarily formulated in white populations. The project is aimed to develop and validate ten-year risk prediction equations for ASCVD from four contemporary Chinese cohorts. METHODS—: Two prospective studies followed up together with a unified protocol were used as the derivation cohort to develop 10-year ASCVD risk equations in 21 320 Chinese participants. The external validation was evaluated in two independent Chinese cohorts with 14 123 and 70 838 participants. Furthermore, the model performance was compared with the Pooled Cohort Equations (PCE) reported in the American College of Cardiology/American Heart Association (ACC/AHA) guideline. RESULTS—: Over 12 years of follow-up in the derivation cohort with 21 320 Chinese participants, 1048 subjects developed a first ASCVD event. Gender-specific equations had C-statistics of 0.794 (95% CI, 0.775-0.814) for men and 0.811 (95% CI, 0.787-0.835) for women, respectively. The predicted rates were similar with the observed rates, as indicated by calibration χ of 13.1 for men (P=0.16) and of 12.8 for women (P=0.17). Good internal and external validations of our equations were achieved in subsequent analyses. Compared with the Chinese equations, the PCE had lower C-statistics and much higher calibration χ in men. CONCLUSIONS—: Our project developed effective tools with good performance for ten-year ASCVD risk prediction among Chinese population, which will help to improve primary prevention and management of cardiovascular disease. © 2016 by the American College of Cardiology Foundation and the American Heart Association, Inc.


Chen L.H.,Peking Union Medical College
Bing du xue bao = Chinese journal of virology / [bian ji, Bing du xue bao bian ji wei yuan hui] | Year: 2012

Adenovirus remains a significant threat to public health. Recent studies showed that bats can harbor diverse adenoviruses. To further investigate the distribution and genetic diversity of bat adenoviruses in China, we collected throat and anal swab samples of 11 bat species from 6 provinces of China, including Beijing, Hunan, Jiangxi, Yunnan, Guizhou and Hainan. Nested PCR was used to identify potential bat adenoviruses from the samples, and positive results were cloned and sequenced for genetic diversity study. In addition, nucleotide sequence alignments based on corresponding amino acid sequence similarities were used for phylogenetic analyses. Our results showed that about 20% of bat species in China are positive to adenoviruses, and Myotis ricketti is likely to be the most important host of bat adenoviruses in all locations. Moreover, we identified two diverse sequences of bat adenoviruses from the same sample of Ia io in Guizhou province of China. In general, the average nucleotide and amino acid sequence similarities of the conserved region of DNA polymerases of bat adenoviruses are 66.6% and 74.7%, respectively. The differences between bat species and their residences environments may have driven the adaptive evolution of the viruses, leading to the genetic diversity of the bat adenoviruses.


Li H.,Shanghai AIER Eye Hospital | Sun T.,Shanghai AIER Eye Hospital | Wang M.,Wang Vision Institute | Zhao J.,Peking Union Medical College
Journal of Refractive Surgery | Year: 2010

PURPOSE: To establish safety and effectiveness of thinflap LASIK using a femtosecond laser and microkeratome in correcting high myopia in Chinese patients. METHODS: Two hundred seventy-four eyes of 148 Chinese patients with high myopia whose spherical equivalent refraction (SE) ranged from -6.12 to -15.75 diopters (D) received thin-flap LASIK with the VISX S4 IR excimer laser system. Corneal flaps were created with a femtosecond laser (15-kHz IntraLase, 134 eyes of 76 patients, target flap thickness 100 μm) and Moria M2 microkeratome (90-μm head, 140 eyes of 72 patients, target flap thickness 110 μm). Clinical outcomes were assessed with uncorrected (UCVA) and best spectacle-corrected visual acuity (BSCVA), manifest refraction, wavefront aberrometry, Schirmer tests, and tear break-up time (TBUT) at 1 day, 1 week, and 1 and 3 months postoperatively. RESULTS: At 3 months, both groups showed comparable clinical outcomes in most parameters assessed, including the percent of postoperative UCVA better than or equal to preoperative BSCVA (P=.642), mean residual spherical equivalent refraction (P=.448), mean Schirmer test (P=.950), and mean TBUT (P=.867). Postoperative coma, trefoil, and spherical aberration were similar in both groups (P=.202, P=.898, and P=.890, respectively). Both groups had a similar percent of eyes with a change of SE of <1.00 D (P=.284). CONCLUSIONS: Thin-flap LASIK with a femtosecond laser and microkeratome are both safe and effective for the correction of high myopia in Chinese patients. Femtosecond laser shows similar predictability, stability, and induction of higher order aberrations to the microkeratome. Copyright ©SLACK Incorporated.


He Y.,Peking Union Medical College | Zhang L.,Peking Union Medical College | Song C.,Peking Union Medical College
International Journal of Nanomedicine | Year: 2010

A sterically stabilized, mitoxantrone-loaded liposome, tailored to target luteinizing hormone-releasing hormone (LHRH) receptor overexpressing cells, was developed to promote the efficiency of intracellular delivery of mitoxantrone through receptor-mediated endocytosis. Liposomes were prepared by lipid film hydration and an ultrasound dispersion process. Thiolated gonadorelin with affinity for the LHRH receptor was chemically coupled to N-[(3-maleimide-1-oxopropyl) aminopropyl polyethylene glycol-carbamyl] distearoyl-lphosphatidyl- ethanolamine via a thioether bond and subsequently inserted into polyethylene glycol-grafted liposomes. The liposome was characterized in terms of its size, ligand density, drug loading, and leakage properties. The targeting nature and antitumor effects of the liposomes were evaluated in vitro using cultured MCF-7 breast cancer cells. A protein assay of ligand coupling to the liposomal surface indicated that more than 60% of the LHRH peptides were inserted into the liposome bilayer. Up to 1.0 mg/mL of stable liposomal mitoxantrone loading was achieved, with approximately 98% of this being entrapped within the liposomes. In vitro cell culture studies revealed that the gonadorelin-modified liposomes bound to their target cells had significantly higher affinity and better antitumor efficiency than generic drug-loaded liposomes. These events were presumed to occur through specific interactions of the LHRH with its cognate receptors on the cell surface. It was concluded that the targeting properties of the delivery system would potentially improve the therapeutic benefits of mitoxantrone, as compared with nontargeted liposomes. © 2010 He et al, publisher and licensee Dove Medical Press Ltd.


Studies have demonstrated that ~60%–80% of emerging infectious diseases (EIDs) in humans originated from wild life. Bats are natural reservoirs of a large variety of viruses, including many important zoonotic viruses that cause severe diseases in humans and domestic animals. However, the understanding of the viral population and the ecological diversity residing in bat populations is unclear, which complicates the determination of the origins of certain EIDs. Here, using bats as a typical wildlife reservoir model, virome analysis was conducted based on pharyngeal and anal swab samples of 4440 bat individuals of 40 major bat species throughout China. The purpose of this study was to survey the ecological and biological diversities of viruses residing in these bat species, to investigate the presence of potential bat-borne zoonotic viruses and to evaluate the impacts of these viruses on public health. The data obtained in this study revealed an overview of the viral community present in these bat samples. Many novel bat viruses were reported for the first time and some bat viruses closely related to known human or animal pathogens were identified. This genetic evidence provides new clues in the search for the origin or evolution pattern of certain viruses, such as coronaviruses and noroviruses. These data offer meaningful ecological information for predicting and tracing wildlife-originated EIDs. © 2015 International Society for Microbial Ecology


Current research performance assessment criteria contribute to some extent to author inflation per publication. Among various indicators for evaluating the quality of research with multiple authors, harmonic counting is relatively superior in terms of calculation, scientific ethics, and application. However, two important factors in harmonic counting are not yet clearly understood. These factors are the perceptions of scientists regarding the (1) corresponding author and (2) equally credited authors (ECAs). We carry out a survey investigation on different perceptions of author position versus contribution among medical researchers with different subfields and professional ranks in China, in order to provide several pieces of evidence on the aforementioned factors. We are surprised to find that researchers with different professional ranks tend to largely acknowledge their own contribution in collaborative research. Next, we conduct an empirical study to measure individual's citation impact using inflated counts versus harmonic counts. The results indicate that harmonic h-index cannot reflect the high peak of harmonic citations. Therefore, we use (1) harmonic R-index to differentiate authors based on the harmonic citations of each paper belonging to their respective h-cores; and (2) Normalization harmonic (h, R) index as a meaningful indicator in ranking scientists. Using a sample of 40 Ph.D. mentors in the field of cardiac and cardiovascular diseases, harmonic counts can distinguish between scientists who are often listed as major contributors and those regularly listed as co-authors. This method may also discourage unethical publication practices such as ghost authorship and gift authorship. © 2012 Akadémiai Kiadó, Budapest, Hungary.


Guan J.,Peking Union Medical College | Guo S.-X.,Peking Union Medical College
Natural Product Communications | Year: 2012

Three new biflavonoids, named (2RγS)-3′-methoxy-8- methylsocotrin-4′-ol (1), (2SγR)-3′-methoxy-8-methylsocotrin- 4′-ol (2), and (2RγR)-8-methylsocotrin-4′- ol (3), were isolated from Chinese Dragon's blood [Dracaena cochinchinensis (Lour.) S. C. Chen], together with two known ones. The structures of these new biflavonoids were elucidated by a combination of HR-ESI-MS, 1H NMR, 13C NMR, HMQC, and HMBC spectra. The absolute configurations of compounds 14 were determined by quantum chemical calculation of the circular dichroism spectrum and comparison with the experimental CD spectrum.


Xiao S.K.,Peking Union Medical College
Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases | Year: 2010

To investigate the serogroups/types distribution and antimicrobial susceptibility of clinical Streptococcus pneumoniae isolates of different serogroups/types in both children and adults in China, and to explore the significance of vaccines in preventing pneumococcal infections and control of epidemic Streptococcus pneumoniae. A total of 580 consecutive and non-repetitive Streptococcus pneumoniae isolates were collected from 13 hospitals between 2005 and 2008. Agar dilution method was used to determine the minimal inhibitory concentrations (MIC) of 11 antibacterial agents. Serotyping was performed by latex agglutination test and the Quellung reaction test. The most prevalent serogroups/types in 362 isolates from adults were 19F (55, 15.2%), 19A (46, 12.7%), 3 (44, 12.2%), 23F (24, 6.6%), 15 (23, 6.4%), and 17 (11, 3.0%), while in the 218 isolates from children, 19F (71, 32.6%), 19A (31, 14.2%), 23F (13, 6.0%), 15 (12, 5.5%), 14 (11, 5.0%), and 6B (10, 4.6%) were the most prevalent. Resistance to β-lactams was related to the serotypes. 19F and 19A were more resistant toβ-lactams than the other serotypes. The prevalence of Penicillin Intermediate Streptococcus pneumoniae increased from 7.4% in 2005 to 24.9% in 2008. The coverage of pneumococcal conjugate vaccine (PCV)-7, PCV-10 and PCV-13 among all age groups was 35.5% (206/580), 38.7% (224/580) and 61.8% (358/580), respectively. The coverage of PCV-7, PCV-10 and PCV-13 among children under 5 years was 55.7% (78/140), 58.6% (82/140), and 77.9% (109/140) respectively. Penicillin intermediate isolates were on the rise with years. PCV-7, PCV-10 and PCV-13 vaccines showed a higher coverage in children than in adults.


Xiao Z.,Chinese University of Hong Kong | Han Li C.,Chinese University of Hong Kong | Chan S.L.,Chinese University of Hong Kong | Xu F.,Chinese University of Hong Kong | And 6 more authors.
Cancer Research | Year: 2014

Small molecules that restore the expression of growth-inhibitory microRNAs (miRNA) downregulated in tumors may have potential as anticancer agents. miR34a functions as a tumor suppressor and is downregulated or silenced commonly in a variety of human cancers, including hepatocellular carcinoma (HCC). In this study, we used an HCC cell-based miR34a luciferase reporter system to screen for miR34a modulators that could exert anticancer activity. One compound identified as a lead candidate, termed Rubone, was identified through its ability to specifically upregulate miR34a inHCC cells. Rubone activated miR34a expression inHCC cells with wildtype or mutated p53 but not in cells with p53 deletions. Notably, Rubone lacked growth-inhibitory effects on nontumorigenic human hepatocytes. In a mouse xenograft model of HCC, Rubone dramatically inhibited tumor growth, exhibiting stronger anti-HCC activity than sorafenib both in vitro and in vivo. Mechanistic investigations showed that Rubone decreased expression of cyclin D1, Bcl-2, and other miR34a target genes and that it enhanced the occupancy of p53 on the miR34a promoter. Taken together, our results offer a preclinical proof of concept for Rubone as a lead candidate for further investigation as a new class of HCC therapeutic based on restoration of miR34a tumor-suppressor function. © 2014 American Association for Cancer Research.


Yu G.,Zhejiang University | Zhang Z.,Zhejiang University | He J.,Peking Union Medical College | Abliz Z.,Peking Union Medical College | Huang F.,Zhejiang University
European Journal of Organic Chemistry | Year: 2012

Cavity-extended pillar[5]arenes containing electron-rich naphthyl groups have been demonstrated to have enhanced binding affinity to linear guests containing electron-deficient pyridinium units. The importance of size effect, charge density, cooperative effect, and C-H···π interactions were investigated, and these factors play significant roles in the complexation of these host-guest systems. Cavity-extended pillar[5]arenes containing electron-rich naphthyl groups have been demonstrated to have enhanced binding affinity to linear guests containing electron-deficient pyridinium units. The importance of size effect, charge density, cooperative effects, and C-H···π interactions were investigated, and these factors play significant roles in the complexation of these host-guest systems. © 2012 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.


Li Y.L.,Peking Union Medical College
Zhonghua nei ke za zhi [Chinese journal of internal medicine] | Year: 2011

To summarize the clinical characteristics of AIDS phobia patients and establish the preliminary clinical diagnostic criteria. The clinical information of 46 AIDS phobia patients was collected and summarized. General demographic data, clinical manifestations and laboratory results were analyzed. The clinical characteristics of AIDS phobia patients include: (1) With or without high-risk behavior of HIV-1 infection; (2) Patients repeatedly demanded HIV/AIDS related laboratory tests, suspected or believed in HIV-1 infection with daily life affected; (3) The main complaints were non-specific including influenza-like symptoms (headache, sore throat and so on), fasciculation, formication, arthrodynia, fatigue and complaint of fever with normal body temperature; physical examination did not reveal any positive physical sign except white coated tongue; (4) Symptoms mainly appeared 0-3 months after the high-risk behavior while HIV-1 antibody kept negative; (5) T lymphocyte subsets test was carried out in 23 patients and showed 19 (82.6%) with CD(4)(+) T lymphocyte count > 500/μl, the remaining 4 were 300 - 500/μl, with the lowest count of 307/μl. Few patients had inversed CD(4)(+)/CD(8)(+) ratio but without excessive CD(8)(+)T lymphocyte activation. AIDS phobia is a complicated physical and mental disease, whose diagnosis and treatment still need further investigation.


To analyze the relationship between electrocardiographic (ECG) features and disease severity in patients with the arrhythmogenic right ventricular cardiomyopathy (ARVC). The study group consisted of 61 subjects with a definite diagnosis of ARVC on the basis of published guideline criteria and patients were divided into 3 subgroups according to the extent of diseased myocardium defined by cardiac magnetic resonance imaging (MRI): Group A: local involvement (n = 19, 31%), Group B: diffuse involvement of whole right ventricle (n = 28, 46%) and Group C: involvement of both right and left ventricles (n = 14, 23%). Normal electrocardiogram was shown in 1 patient in each group. Epsilon wave was detected in 24 (39%) patients, QRS duration was prolonged [≥ 110 ms (V(1)-V(3))] in 21 (34%) patients, S-wave upstroke was prolonged (≥ 55 ms) in 17 (28%) patients, complete right branch bundle block was evidenced in 10 (16%) patients and pathologic Q waves was found in 9 (15%) patients. The incidence of above abnormal ECG changes was increased in proportion to the degree of disease severity (group A < group B < group C). Incidence of Epsilon wave and prolonged QRS duration [ ≥ 110 ms (V(1)-V(3))] were significantly higher in Group C than in Group A. Incidence of prolonged S-wave upstroke (≥ 55 ms) was significantly higher in Group C than in Group A and Group B. T-wave inversion in V(1) leads was often found in Group A. T-wave inversion in inferior leads (V(1)-V(3) leads or beyond V(3)) was often presented in Group B and Group C. Normal ECG does not exclude the possibility of diagnosis of ARVC. The extent of T-wave inversion in the precordial leads and incidence of Epsilon wave, prolonged QRS duration [ ≥ 110 ms (V(1)-V(3))] and prolonged S-wave upstroke (≥ 55 ms) were related to degree of disease severity in patients with ARVC.


Zhu W.,Peking Union Medical College | Xu B.,Peking Union Medical College
PLoS ONE | Year: 2014

Background: Growing evidence from recent studies has revealed the association of microRNA-21 (mir-21) with outcomes in multiple cancers, but inconsistent findings have been reported, which rationalized a summary and analysis of available data to investigate the prognostic role of mir-21. Materials and Methods: Eligible studies were identified through several search strategies and assessed for quality. Data was extracted from studies in terms of baseline characteristics and key statistics such as hazard ratio (HR), 95% confidence interval (CI) and P value, which were utilized to calculate pooled effect size. Results: 25 studies were included in the meta-analysis to evaluate the prognostic role of mir-21 in malignant tumors. Elevated mir-21 level was demonstrated to moderately predict poor overall survival (OS) (HR = 1.903, 95% CI: 1.713-2.113, P = 0.000) and disease-free survival (DFS) (HR = 1.574, 95% CI: 1.139-2.175, P = 0.006) by the fixed and random effect model respectively. Importantly, subgroup analysis disclosed significant association between increased mir-21 level in cancerous tissue and worse survival status. Furthermore, over-expression of mir-21 was an independent prognostic factor for non-small cell lung cancer (NSCLC) and pancreatic cancer patients, with the pooled HR being 2.153 (95% CI: 1.693-2.739, P = 0.000) and 1.976 (95% CI: 1.639-2.384, P = 0.000). Conclusions: Over-expression of mir-21, especially in cancerous tissue, was effectively predictive of worse prognosis in various carcinomas. Non-invasive circulating mir-21, however, exhibited modest ability to discriminate outcomes. Major concerns about mir-21 assay standardization and selection of specimen need to be fully addressed before its practical implementation in management of cancer. © 2014 Zhu, Xu.


Li B.,Peking Union Medical College
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology | Year: 2011

This study was aimed to investigate the expression level of CIAPIN1 mRNA in leukemia patients and explore its significance in leukemias. The fresh bone marrow was collected from 112 newly diagnosed leukemia patients, the total RNA was extracted by means of TRIzoL, the cDNA was synthesized, the expression of CIAPIN1 mRNA was detected by real-time quantitative PCR using β-actin as internal reference; 10 normal healthy persons were selected as controls. The results showed that the expression of CIAPIN1 mRNA was statistically higher in acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and chronic phase chronic myeloid leukemia (CML) patients than that in normal persons (p < 0.05); but there was no statistical difference between chronic lymphocytic leukemia (CLL) and normal persons (p > 0.05). It is concluded that the CIAPIN1 gene higher expresses in MNC of newly diagnosed leukemia patients, up-regulation of CIAPIN1 expression may play an important role in pathogenesis of leukemia.


OBJECTIVE:: Atherosclerosis and arterial stiffness predict cardiovascular morbidity and mortality. We aimed to investigate the influence of BMI and blood pressure (BP) in childhood, and change in BMI and BP, on the development of subclinical atherosclerosis and arterial stiffness in adulthood. METHODS:: The study consisted of 1256 individuals aged 27–42 years who had 2–10 measurements of BMI and BP from childhood. In the final survey (2010–2011), subclinical markers of vascular damage, including carotid intima–media thickness (cIMT), carotid-femoral pulse wave velocity (cfPWV), and brachial-ankle pulse wave velocity (baPWV), were measured. RESULTS:: Pearson correlation analyses showed that BMI and BP in childhood and adulthoood, and also cumulative and incremental values from childhood to adulthood, were all significantly associated with adult cIMT, cfPWV, and baPWV in males and in females (all P?


Sun H.L.,Peking Union Medical College
Zhonghua nei ke za zhi [Chinese journal of internal medicine] | Year: 2010

To investigate antimicrobial resistance among gram-positive cocci in China in 2009. From June to December 2009, 1169 consecutive and non-repetitive gram-positive cocci were collected from 12 teaching hospitals at 9 cities. The minimal inhibitory concentration (MIC) of antibacterial agents was determined by agar dilution method. The prevalences of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococci (MRCoNS) were 45.3% (211/466) and 89.5% (214/239), respectively. The isolation rate of MRSA was 33.3% - 68.1% from different samples. All Staphylococci isolates were susceptible to vancomycin, teicoplanin and linezolid. Five point five percent (7/128) E.faecium strains were resistant to vancomycin. All E. faecalis strains were susceptible to vancomycin. About 99.1% (108/109) of E.faecalis and E.faecium were susceptible to linezolid. The prevalence of penicillin-intermediate Streptococcus pneumoniae (PISP) was 21.6% (48/222). Only 1 (0.5%, 1/222) Streptococcus pneumoniae strain was resistant to penicillin. Teicoplanin, vancomycin, linezolid and tigecycline were the most active agents against Streptococcus pneumoniae (susceptible rate 100%). The high prevalence of methicillin-resistance is among Staphylococcus strains. Different samples show a different MRSA prevalence. Teicoplanin, vancomycin and linezolid show very high activity to Staphylococci, E. faecalis, E. faecium and Streptococcus pneumoniae.


Little is known about the roles of Rictor/mTORC2 in the leukemogenesis of acute myeloid leukemia. Here, we demonstrated that Rictor is essential for the maintenance of mixed lineage leukemia (MLL)-driven leukemia by preventing leukemia stem cells (LSCs) from exhaustion. Rictor depletion led to a reactive activation of mTORC1 signaling by facilitating the assembly of mTORC1. Hyperactivated mTORC1 signaling in turn drove LSCs into cycling, compromised the quiescence of LSCs and eventually exhausted their capacity to generate leukemia. At the same time, loss of Rictor had led to a reactive activation of FoxO3a in leukemia cells, which acts as negative feedback to restrain greater over-reactivation of mTORC1 activity and paradoxically protects leukemia cells from exhaustion. Simultaneous depletion of Rictor and FoxO3a enabled rapid exhaustion of MLL LSCs and a quick eradication of MLL leukemia. As such, our present findings highlighted a pivotal regulatory axis of Rictor-FoxO3a in maintaining quiescence and the stemness of LSCs.Leukemia advance online publication, 9 September 2016; doi:10.1038/leu.2016.223. © 2016 Macmillan Publishers Limited, part of Springer Nature.


To compare the mRNA, protein expression of long leptin receptor (Ob-Rb) in human adrenal tissues and tumors and observe the plasma level of leptin in primary aldosteronism (PA), cortisol-secreting tumors (CS) and pheochromocytomas (PHEO). Total RNA and protein were extracted from 6 normal human adrenal glands, 10 CS, 20 PHEO; and 14 aldosterone-producing adenomas (APA) (RNA), 10 APA (protein); plasma samples were drawn from 20 controls, 15 PHEO, 29 PA and 11 CS. The mRNA and protein of Ob-Rb were widely expressed in human adrenal glands and tumors. The mRNA (0.32±0.12) and protein (1.31±0.26) expressions of Ob-Rb were higher in normal human adrenal cortex (C) than all other tissues (P<0.05) while the mRNA expression of Ob-Rb in APA (0.15±0.10) was higher than CS (0.05±0.02) (P<0.05). The mRNA expression of Ob-Rb in APA was positively correlated with plasma supine aldosterone level (r=0.670, P=0.024). The mRNA expression of Ob-Rb in CS was positively correlated with 24-hour urinary free cortisol level (r=0.870, P=0.005). The plasma level of leptin was higher in CS than in non-CS groups (P=0.001). Ob-Rb is widely expressed in adrenal tissues and tumors. There is a differential expression in various tissues. Further studies are warranted to understand the relationship between leptin and adrenal gland.


Zhou L.,Peking Union Medical College
Journal of Hypertension | Year: 2016

OBJECTIVE:: To evaluate the effects of metformin on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in nondiabetic patients. METHODS:: In this meta-analysis, we systematically searched PubMed, Embase, and the Cochrane Library through March 2016, and randomized controlled trials assessing the effects of metformin treatment compared with placebo were included. Random-effects models were used to estimate pooled mean differences in SBP and DBP. RESULTS:: Twenty-eight studies from 26 articles consisting of 4113 participants were included. Pooled results showed that metformin had a significant effect on SBP (mean difference −1.98?mmHg; 95% confidence interval −3.61, −0.35; P?=?0.02), but not on DBP (mean difference −0.67?mmHg; 95% confidence interval −1.74, 0.41; P?=?0.22). In subgroup analysis, we found that the effect of metformin on SBP was significant in patients with impaired glucose tolerance or obesity (BMI ≥30?kg/m), with a mean reduction of 5.03 and 3.00?mmHg, respectively. Significant heterogeneity was found for both SBP (I?=?60.0%) and DBP (I?=?45.4%). A sensitivity analysis indicated that the pooled effects of metformin on SBP and DBP were robust to systematically dropping each trial. Furthermore, no evidence of significant publication bias from funnel plots or Eggerʼs tests (P?=?0.51 and 0.21 for SBP and DBP, respectively) was found. CONCLUSION:: This meta-analysis suggested that metformin could effectively lower SBP in nondiabetic patients, especially in those with impaired glucose tolerance or obesity. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.


Wang W.B.,Peking Union Medical College
Zhonghua wai ke za zhi [Chinese journal of surgery] | Year: 2010

To verify the obtained immunogenic membrane antigens candidate of pancreatic cancer in the performed research. Pancreatic cancer cell line SW1990 membrane protein underwent immunoblot with serum IgG purified from clinically collected sera of 66 pancreatic cancer patients. Number 3 and number 8 positive dots of immunoblot were identified by MALDI-TOF mass spectrometry and peptide mass fingerprinting matching. The candidate membrane antigens were further validated in cell lines by RT-PCR, real-time PCR and Western blot, and their different expression level of gene and protein in pancreatic cancer cell lines were contrastly studied. Number 3 and number 8 positive dots were identified as: voltage-dependent anion channel (VDAC3) and catechol-o-methyltransferase (COMT). RT-PCR, real-time PCR and Western blot showed that gene and protein of VDAC3 and COMT were expressed in the pancreatic cancer cell line SW1990, AsPc and P3 respectively. VDAC3 and COMT might be the candidate immunogenic membrane antigens of human pancreatic cancer, and their gene and protein are differently expressed in the pancreatic cancer cell line SW1990, AsPc and P3.


Mi S.,Peking Union Medical College
Sheng li ke xue jin zhan [Progress in physiology] | Year: 2010

Abnormal cardiovascular tissue remodeling characterized by myocardial hypertrophy, myocardial cell loss and myocardial fibrosis, are the primary pathological changes for multiple cardiovascular diseases. Targeting tissue remodeling using small molecules (e.g., relaxin, KNK437), biological agents (e.g., BCG, anti-TLR2 antibody), or herb medicine complex CFX and so on, can attenuate tissue fibrosis and improve cardiac functions. Therefore, regulating the property of inflammation and reversing tissue fibrosis should promote the formation of optimal tissue environments for stem cells mobilization and proliferation, which enhances the myocardial regeneration and is potential therapeutic strategy against chronic cardiovascular diseases.


Wang W.J.,Peking Union Medical College
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2010

To construct a recombinant adenovirus for carry tyrosine hydroxylase (TH) gene and expressing bioactive TH protein in the animal model of Parkinson disease. The TH gene was inserted into the shuttle plasmid, which was transformed into E.coli BJ-5183 for homologous recombination with the adenovirus genome. 293 cells were transfected with the recombinant adenovirus genome to obtain the recombinant virus, and the transcription and expression of TH were determined by RT-PCR and immunofluorescence assay, respectively. The production of L-DOPA in the in vitro reaction system was determined using capillary electrophoresis. We have successfully constructed the recombinant adenovirus. The TH mRNA and the corresponding protein were detected by RT-PCR and immunofluoresence assay in 293 cells. L-DOPA was also detected in the reaction system. The adenovirus constructed allows efficient expression of bioactive TH protein in vitro, which provides a basis for future study of gene therapy of Parkinson disease in animal models.


Li J.P.,Peking Union Medical College
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology | Year: 2010

The present study was aimed to investigate the pathways, by which IL-27 regulates the expression of adherent molecule Mac-1, chemotactic factor receptor fMLP-R and pro-inflammatory cytokine IL-1beta in human neutrophils. Highly purified human neutrophils were isolated from peripheral blood using Ficoll-Hypaque gradients centrifugation and erythrocyte lysis. The mRNA expression of IL-27 receptor components (WSX-1/TCCR and gp130) in human neutrophils was detected by reverse transcription polymerase chain reaction (RT-PCR). After incubation with IL-27 and specific inhibitors (p38 MAPK inhibitor SB203580, PI3K inhibitor LY294002 and ERK inhibitor U0126), the mRNA levels of fMLP-R and IL-1beta were determined by real time RT-PCR, and the adherent molecule Mac-1 expression in human neutrophils was determined by flow cytometry. The IL-1beta level in culture supernatant of human neutrophils was assayed by radioimmunoassay. The results showed that IL-27 receptor components (WSX-1/TCCR and gp130) were constitutively expressed in human neutrophils. IL-27 down-regulated Mac-1 expression in human neutrophils (p<0.05). After incubation with specific inhibitors, SB203580, not LY294002 and U0126, inhibited the down-regulation of Mac-1 expression by IL-27. However, IL-27 up-regulated the mRNA expression of fMLP-R and IL-1beta, and increased the release of IL-1beta (p<0.05). Interestingly, LY294002, not SB203580 and U0126, inhibited the up-regulation of fMLP-R and IL-1beta by IL-27. It is concluded that the IL-27 may regulate the expression of Mac-1, fMLP-R and IL-1beta in human neutrophils through p38 MAPK and PI3K signal pathways.


Huang L.,Peking Union Medical College
Lasers in Medical Science | Year: 2013

Since fractional photothermolysis was first introduced in 2004, it has become a very popular procedure, especially with more and more ablative fractional laser systems and treatments. Fractional ablative laser has been shown to be very effective; however, it does not reach the efficacy of conventional ablative laser treatments in most instances. In an attempt order to make the fractional CO2 laser treatment more efficacious and safe, we combined both the conventional CO2 laser and the fractional CO2 laser to treat acne scars. We report our experience with this new modality. A total of 44 Chinese patients with facial acne scars and skin type IV were included in this study. Each patient received a minimum of two treatment sessions. For each laser session, both the conventional CO2 laser treatment and the DeepFX laser treatment were focused on treating the scar areas only. Following this technique, the more superficialf ActiveFX fractional CO2 laser was performed to the entire face. The efficacy of the procedure was evaluated 3 months after the final laser treatment. The improvement in acne scars and the overall skin texture change were assessed by photographic evaluation using the following scales: ≤25 % (mild), 26-50 % (moderate), 51-75 % (marked), and >75 % (excellent). Side effects from this therapy were mild to moderate. Two cases of HSV outbreak were noted; they were treated and resolved without adverse sequelae. Post-laser erythema was resolved within 1 month in one half of the patients. Prolonged erythema (≤3 months) was noted in 12(27 %) cases. Temporary post-inflammatory hyperpigmentation (PIH; ≤1 month) was seen in approximately 50 % of the patients. PIH (≤3 months) was noted in four cases (9 %). Sixty-four percent of the patients (28/44) had an improvement of between 51 and 75 % after more than two sessions of the combination of laser treatments. The average overall improvement was 52.50 % (±12.25 %). Three patients achieved improvement of >75 %. This new modality of ablative conventional CO2 laser therapy with fractional CO2 laser resurfacing was shown to be safe and efficacious in the treatment of acne scars in Asian patients. It did not increase the risk of PIH compared to other reports of laser therapy and PIH. It is the hope that future study with combination therapy will further enhance the clinical results and thus lessen potential adverse events. © 2012 Springer-Verlag London Ltd.


Wang J.,Peking Union Medical College
Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials | Year: 2011

To study the chemical constituents of Ligusticum sinense. The chemical constituents were isolated and purified by column chromatography on silica gel and Sephadex LH-20; Using spectroscopy methods to elucidate their structures. Nine compounds were isolated and identified as levistolide A (1), (Z)-3-butylidene-7-hydroxyphthalide (2), senkyunolide B (3), 3-butylphthalide(4), (Z)-ligustilide (5), riligustilide (6), neocnidilide (7), senkyunolide A (8), beta-sitostesol (9). Compounds 2 and 3 are obtained from this plant for the first time.


Li J.,Peking Union Medical College | Zhan Q.,Peking Union Medical College
British Journal of Cancer | Year: 2011

The human centrosomal ninein-like protein (Nlp) is a new member of the γ-tubulin complexes binding proteins (GTBPs) that is essential for proper execution of various mitotic events. The primary function of Nlp is to promote microtubule nucleation that contributes to centrosome maturation, spindle formation and chromosome segregation. Its subcellular localisation and protein stability are regulated by several crucial mitotic kinases, such as Plk1, Nek2, Cdc2 and Aurora B. Several lines of evidence have linked Nlp to human cancer. Deregulation of Nlp in cell models results in aberrant spindle, chromosomal missegregation and multinulei, and induces chromosomal instability and renders cells tumourigenic. Overexpression of Nlp induces anchorage-independent growth and immortalised primary cell transformation. In addition, we first demonstrate that the expression of Nlp is elevated primarily due to NLP gene amplification in human breast cancer and lung carcinoma. Consistently, transgenic mice overexpressing Nlp display spontaneous tumours in breast, ovary and testicle, and show rapid onset of radiation-induced lymphoma, indicating that Nlp is involved in tumourigenesis. This review summarises our current knowledge of physiological roles of Nlp, with an emphasis on its potentials in tumourigenesis.British Journal of Cancer advance online publication, 19 April 2011; doi:10.1038/bjc.2011.130 www.bjcancer.com.


Lu L.,Peking Union Medical College | Li L.,Peking Union Medical College | Lv X.,Peking Union Medical College | Wu X.-S.,Peking Union Medical College | And 2 more authors.
Cell Research | Year: 2011

A wide variety of nuclear regulators and enzymes are subjected to acetylation of the lysine residue, which regulates different aspects of protein functions. The MYST family histone acetyltransferase, human ortholog of MOF (hMOF), plays critical roles in transcription activation by acetylating nucleosomal H4K16. In this study, we found that hMOF acetylates itself in vitro and in vivo, and the acetylation is restricted to the conserved MYST domain (C2HC zinc finger and HAT), of which the K274 residue is the major autoacetylation site. Furthermore, the class III histone deacetylase SIRT1 was found to interact with the MYST domain of hMOF through the deacetylase catalytic region and deacetylate autoacetylated hMOF. In vitro binding assays showed that non-acetylated hMOF robustly binds to nucleosomes while acetylation decreases the binding ability. In HeLa cells, the recruitment of hMOF to the chromatin increases in response to SIRT1 overexpression and decreases after knockdown of SIRT1. The acetylation mimic mutation K274Q apparently decreases the chromatin recruitment of hMOF as well as the global H4K16Ac level in HeLa cells. Finally, upon SIRT1 knockdown, hMOF recruitment to the gene body region of its target gene HoxA9 decreases, accompanied with decrease of H4K16Ac at the same region and repression of HoxA9 transcription. These results suggest a dynamic interplay between SIRT1 and hMOF in regulating H4K16 acetylation.Cell Research advance online publication 19 April 2011; doi: 10.1038/cr.2011.71.


Zhao J.,Peking Union Medical College | Zhao J.,Qinghai University | Du F.,Peking Union Medical College | Shen G.,Qinghai University | And 2 more authors.
Cell Death and Disease | Year: 2015

Hypoxia is an all but ubiquitous phenomenon in cancers. Two known hypoxia-inducible factors (HIfs), HIf-1α and HIf-2α, primarily mediate the transcriptional response to hypoxia. Despite the high homology between HIf-1α and HIf-2α, emerging evidence suggests differences between both molecules in terms of transcriptional targets as well as impact on multiple physiological pathways and tumorigenesis. To date, much progress has been made toward understanding the roles of HIf-2α in digestive system cancers. Indeed, HIf-2α has been shown to regulate multiple aspects of digestive system cancers, including cell proliferation, angiogenesis and apoptosis, metabolism, metastasis and resistance to chemotherapy. These findings make HIf-2α a critical regulator of this malignant phenotype. Here we summarize the function of HIf-2 during cancer development as well as its contribution to tumorigenesis in digestive system malignancies. © 2015 Macmillan Publishers Limited All rights reserved.


Zhang J.,Peking Union Medical College | Wu W.-M.,Peking Union Medical College | You L.,Peking Union Medical College | Zhao Y.-P.,Peking Union Medical College
Annals of Surgical Oncology | Year: 2013

Background: Robotic surgery is gaining momentum with advantages for minimally invasive management of pancreatic diseases. The objective of this meta-analysis is to compare the clinical and oncologic safety and efficacy of robotic versus open pancreatectomy. Methods: A systematic review of the literature was performed to identify studies comparing robotic pancreatectomy and open pancreatectomy. Postoperative outcomes, intraoperative outcomes, and oncologic safety were evaluated. Meta-analysis was performed using a random-effect model. Results: Seven studies matched the selection criteria, including 137 (40 %) cases of robotic pancreatectomy and 203 (60 %) cases of open pancreatectomy. None of the included studies were randomized. Overall complication rate was significantly lower in robotic group [risk difference (RD) = -0.12, 95 % confidence interval (CI) -0.22 to -0.01, P = 0.03], as well as reoperation rate (RD = -0.12; CI -0.2 to -0.03, P = 0.006) and margin positivity (RD = -0.18; 95 % CI -0.3 to -0.06, P = 0.003). There was no significant difference in postoperative pancreatic fistula (POPF) incidence and mortality. The median (range) conversion rate was 10 % (0-12 %). Conclusions: The results of this meta-analysis suggest that robotic pancreatectomy is as safe and efficient as, if not superior to, open surgery for patients with benign or malignant pancreatic diseases. However, the evidence is limited and more randomized controlled trials are needed to further clearly define this role. © 2013 Society of Surgical Oncology.


Liu H.-H.,Peking Union Medical College | Li J.-J.,Peking Union Medical College
Ageing Research Reviews | Year: 2015

Elderly adults constitute a rapidly growing part of the global population, thus resulting in an increase in morbidity and mortality related to cardiovascular disease (CVD), which remains the major cause of death in elderly population, including men and women. Dyslipidemia is a well-established risk factor for CVD and is estimated to account for more than half of the worldwide cases of coronary artery disease (CAD). Many studies have shown a strong correlation between serum cholesterol levels and risk of developing CAD. In this paper, we review the changes of plasma lipids that occur in men and women during aging and the potential mechanisms of age-related disorders of lipoprotein metabolism covering humans and/or animals, in which changes of the liver sinusoidal endothelium, postprandial lipemia, insulin resistance induced by free fatty acid (FFA), growth hormone (GH), androgen (only for men) and expression and activity of peroxisome proliferator-activated receptor α (PPARα) are mainly focused. © 2014 .


Yang G.,Peking Union Medical College | Zhai X.,411 Hospital of the Peoples Liberation Army | Zhao J.,Peking Union Medical College
Molecular Vision | Year: 2011

Purpose: Congenital cataracts are a clinically and genetically heterogeneous lens disorder. The purpose of this study was to identify the genetic mutation and the molecular phenotype responsible for the presence of an autosomal dominant congenital nuclear cataract disease in a Chinese family. Methods: Patients were given a physical examination and their blood samples were collected for DNA extraction. Genotyping was performed by microsatellite markers, and a logarithm of odds (LOD) score was calculated using the LINKAGE programs. Mutation detection was performed by direct sequencing. Results: Linkage to the crystallin beta A1 (CRYBA1) locus was identified. DNA sequencing of the gene revealed a c.279-281delGAG mutation in exon 4, which resulted in a glycine residue deletion at position 91 (ΔG91). This mutation was identified in all of the affected individuals but was not found in the 100 control chromosomes. Conclusions: Our results identify that the c.279-281delGAG mutation in CRYBA1 is responsible for the autosomal dominant congenital nuclear cataract disease in this Chinese family. © 2011 Molecular Vision.


Huo H.,Peking Union Medical College
Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery | Year: 2011

To develop a simplified Chinese version of the 32-item Quebec sleep questionnaire (QSQ) and to examine the reliability and validity. A cross-sectional sample of 141 patients [22 simple snorers and 119 obstructive sleep apnea hypopnea syndrome (OSAHS)] and a longitudinal sample of 55 patients [35 in uvulopalatopharyngoplasty (UPPP) group and 20 in control group] completed the simplified Chinese version of QSQ for assessment of its feasibility, reliability, validity and responsiveness. QSQ had good feasibility. All internal consistency coefficients exceeded 0.65. Intraclass correlation coefficients of five domains for test-retest reliability ranged from 0.82 - 0.91. There were significant differences in four domains (daytime sleepiness, diurnal symptoms, nocturnal symptoms and social interactions) among patients with different severity of apnea hypopnea index (AHI) and lowest saturation of arterial oxygen (LSaO2, P < 0.01 or < 0.05). Correlations between QSQ scores and five domains and Epworth sleepiness scale (ESS) were statistically significant (P < 0.01). Correlations between QSQ scores and three domains (daytime sleepiness, nocturnal symptoms and social interactions) and polysomnography (PSG) indices (AHI and LSaO2) were statistically significant (P < 0.05). There were significant differences in scores of five domains of patients between at baseline and after UPPP. There were significant differences in change scores of five domains between patients who were treated and those who were not. The simplified Chinese version of QSQ offers good reliability, validity and responsiveness and can be used as a OSAHS-specific instrument to assess impact of illness and treatment effectiveness in OSAHS patients.


Objective: To investigate the mechanism of loss of human esophageal cancer-related gene 4 (ECRG4) expression in esophageal squamous cell carcinoma (ESCC.) Methods: PCR-SSCP and DNA sequencing analysis were used to detect the mutation of ECRG4 exons in esophageal cancer and matched adjacent normal tissues of 80 patients. DNA bisulfite-modifying ssPCR sequencing assay was used to examine the methylation status of ECRG4 promoter in human esophageal squamous cell carcinoma EC9706 cells. The re-expression of ECRG4 mRNA was examined by RT-PCR in EC9706 cells, after treatment with either demethylation drug 5-aza-2′-deoxycytidine or arsenic trioxide. Results: No mutation in the four ECRG4 exons was found in all the ESCC and matched normal adjacent tissues. RT-PCR showed that 11 of 16 CpG islands of ECRG4 promoter were hypermethylated, while ECRG4 mRNA expression level was undetectable in the EC9706 cells. The ECRG4 mRNA was re-expressed after treatment with either demethylation drug 5-aza-2′-deoxycytidine or arsenic trioxide. Conclusion: The epigenetic mechanism of methylation is a reason of loss of ECRG4 gene expression in the ESCC cell line EC9706.


Zhu Y.-C.,Peking Union Medical College | Dufouil C.,French Institute of Health and Medical Research | Dufouil C.,University Pierre and Marie Curie | Tzourio C.,French Institute of Health and Medical Research | And 3 more authors.
Stroke | Year: 2011

Background and Purpose- Silent brain infarcts (SBIs) have been recognized as common lesions in elderly subjects and their diagnosis relies on brain imaging. In this study, we aimed to evaluate the different MRI parameters and criteria used for their evaluation in the literature to better understand the variation across studies and related limitations. Method- Original MRI studies of SBI performed in human populations and reported in the English literature were reviewed. Analyses were restricted to population-based studies or studies in which at least 50 subjects with SBI were detected. The MRI parameters as well as the MRI criteria of SBI (size, signal characteristics, and criteria for differentiation of dilated Virchow-Robin spaces) were described and analyzed. Result- Magnetic field strength, slice thickness, and gap between slices greatly varied among the 45 articles included in this review. The MRI definition of SBI was inconsistent across studies. In half of them, SBI was defined as hypointense on T1 and hyperintense on T2-weighted images. Exclusion criteria for dilated Virchow-Robin spaces were used only in 7 studies. Conclusions- The variation in MRI characteristics and diagnostic criteria for SBI represent a major limitation for interpretation and comparison of data between studies. Efforts are needed to reach unified imaging criteria for SBI. © 2011 American Heart Association. All rights reserved.


Zhu L.,Peking Union Medical College | Zhou H.,Peking Union Medical College | Sun Z.,Peking Union Medical College | Lou W.,Peking Union Medical College | Lang J.,Peking Union Medical College
Journal of Sexual Medicine | Year: 2013

Introduction: Recent years have seen continuous reports about the successful reconstruction of numerous organs with the application of tissue-engineering techniques. Thus, we assess the outcomes for vagina reconstruction using tissue-engineered biological material, which we suggested previously as an ideal graft for vaginoplasty. Aim: To evaluate the anatomic and sexual outcomes in patients undergoing vaginoplasty using tissue-engineered biomaterial mesh. Methods: This prospective study included 53 patients with Mayer-Rokitansky-Küster-Hauser syndrome admitted to our hospital. Patients underwent vaginoplasty with tissue-engineered biological material (acellular dermal matrix). Postoperatively, a silicone vaginal dilator (length: 10cm, diameter: 3.5cm) was advised to be used for the first 3-6 months to prevent contraction of the neovagina. Follow-up was performed at 4 weeks, 12 weeks, 12 months, and then annually. Twenty-four age-matched women who underwent health examinations during the same time period were selected as a health control group and answered Female Sexual Function Index (FSFI) questionnaires for the purpose of comparing sexuality. Main Outcome Measures: Anatomic success was defined by a vaginal length ≥8cm and a width allowing the easy introduction of two fingers. Sexual outcomes were assessed at the 12-month follow-up according to body image perception and FSFI questionnaires validated for the Chinese-speaking population. Results: No severe intra-operative complications occurred. No graft-related infection, rejection, or detachment was recorded. The cost for tissue-engineered biomaterial graft was $1,900 (¥12,000) per person. Postoperatively, granulomatous polyps occurred in 6/53 patients (11.3%) at the vaginal vault and were removed in an outpatient clinic. During a mean follow-up of 21.1 months, the anatomic success rate was 100%, and all of the patients were satisfied with their body image. Postoperatively, 42 patients were followed up for more than 1 year, and 32 of them were sexually active. Among the 24/32 patients (75%) who answered the FSFI questionnaire, the mean total FSFI score was 26.7±3.5, which was similar to that of the control group (25.6±7.4, P=0.46). The similarity was also observed in six separate domains of the functional aspect of female sexuality. Conclusions: Vaginoplasty with tissue-engineered biomaterial graft is a safe, effective, minimally invasive cosmetic procedure that provides near normal sexual function for patients with vaginal aplasia. © 2013 International Society for Sexual Medicine.


Chen X.,Nanjing University of Technology | Guo B.,Nanjing University of Technology | Hu P.,Nanjing University of Technology | Wang Y.,Peking Union Medical College
Electroanalysis | Year: 2014

In this study, a novel non-enzymatic hydrogen peroxide (H2O2) sensor was fabricated based on gold nanoparticles/carbon nanotube/self-doped polyaniline (AuNPs/CNTs/SPAN) hollow spheres modified glassy carbon electrode (GCE). SPAN was in-site polymerized on the surface of SiO2 template, then AuNPs and CNTs were decorated by electrostatic absorption via poly(diallyldimethylammonium chloride). After the SiO2 cores were removed, hollow AuNPs/CNTs/SPAN spheres were obtained and characterized by transmission electron microscopy (TEM), field-emission scanning electron microscopy (FESEM) and Fourier transform infrared spectroscopy (FTIR). The electrochemical catalytic performance of the hollow AuNPs/CNTs/SPAN/GCE for H2O2 detection was evaluated by cyclic voltammetry (CV) and chronoamperometry. Using chronoamperometric method at a constant potential of -0.1V (vs. SCE), the H2O2 sensor displays two linear ranges: one from 5μM to 0.225mM with a sensitivity of 499.82μAmM-1cm-2; another from 0.225mM to 8.825mM with a sensitivity of 152.29μAmM-1cm-2. The detection limit was estimated as 0.4μM (signal-to-noise ratio of 3). The hollow AuNPs/CNTs/SPAN/GCE also demonstrated excellent stability and selectivity against interferences from other electroactive species. The sensor was further applied to determine H2O2 in disinfectant real samples. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Jun L.,Peking Union Medical College | Zheng H.-Y.,Peking Union Medical College
Japanese Journal of Infectious Diseases | Year: 2013

We aimed at determining the characteristics of patients with primary and late latent syphilis who were non-reactive on initial screening by rapid plasma reagin (RPR) but reactive by treponemal tests. We collected the RPR test results of all primary and late latent syphilis patients in our hospital from December 2000 to March 2012. The characteristics of syphilis patients who were non-reactive by RPR testing were compared to those of reactive patients. Multiple logistic regression was used to identify factors associated with non-reactive RPR results. Among primary syphilis patients, 37 (16.5z) were non-reactive on initial RPR and were compared with the 187 reactive cases. Age À35 years was an independent factor associated with a non-reactive result in primary cases (odds ratio [OR], 95z confidence intervals [CI] = 3.55 [1.39-9.07]). Of the late latent patients, 61 (8.8z) were non-reactive by RPR and 636 were reactive. Age À34 years was also an independent factor associated with a non-reactive result in late latent cases (OR [95z CI] = 4.30 [2.28-8.12]). This study suggests that RPR testing alone is insufficient to diagnose primary and late latent infections, especially in middle-aged and elderly individuals. Syphilis detection was lower for patients with primary syphilis than for those with late latent syphilis based on the results of the RPR.


Jiang Q.,Peking Union Medical College | Song P.,Chinese People's Liberation Army | Wang E.,Peking Union Medical College | Li J.,Peking Union Medical College | And 2 more authors.
Journal of Molecular and Cellular Cardiology | Year: 2013

Efficacy of intravenous administration of mesenchymal stromal cells (MSCs) for myocardial infarction (MI) is limited by low cell retention in the damaged myocardium. Previous studies indicated that remote ischemic conditioning could protect against ischemia-reperfusion-induced injury by release of various cytokines including stromal cell derived factor-1 alpha (SDF-1α). However, whether remote ischemic postconditioning (RIPostC) can also enhance the retention of infused cells in the myocardium by activating MSC homing is unclear. In this study, RIPostC was induced with 4cycles of 5min occlusion and reperfusion of the abdominal aorta in female Sprague-Dawley (SD) rats which underwent ligation of the coronary artery 1week previously. Cytokine levels in serum and myocardium were evaluated by enzyme-linked immunosorbent assay (ELISA) at 1, 6, 24 and 48h after RIPostC. Then, a total of 4×106 male MSCs were infused intravenously at 24h after RIPostC. The number of survived cells in the myocardium was evaluated by real-time polymerase chain reaction analysis for Y chromosome and the heart function was evaluated by echocardiography at 1month after cell infusion. Furthermore, 10μg/kg rabbit anti-rat CXCR4 polyclonal antibody was injected intraperitoneally to prove the role of SDF-1α for RIPostC. RIPostC induced an increase in SDF-1α in serum at 1h and enhanced SDF-1α transcription and protein synthesis in the myocardium at 24h after the procedure. 1month after cell transplantation, RIPostC significantly increased MSC myocardial retention by 79.1±12.3% and thereby contributed to enhanced cardiac function in comparison with cell transplantation without RIPostC. Furthermore, blockade with a CXCR4-specific antibody after RIPostC markedly attenuated the enhancement of therapeutic efficacy. We conclude that RIPostC activated SDF-1α expression and enhanced retention of the infused MSCs in the injured myocardium. Priming of the heart with RIPostC might be a novel adjunctive approach for intravenous cell delivery. © 2012 Elsevier Ltd.


Zhang D.,Peking Union Medical College | Wen X.,Peking Union Medical College | Wu W.,Peking Union Medical College | Xu E.,Peking Union Medical College | And 2 more authors.
Atherosclerosis | Year: 2013

Aims: Leukocyte telomere length (LTL) is shortened in patients with clinical atherosclerosis (AS). Here we aimed to explore the contribution of elevated homocysteine (Hcy) level to LTL shortening in AS patients and the underlying mechanism. Methods: Circulating leukocytes were collected from 197 patients with AS and 165 sex- and age-matched healthy subjects for LTL determination. mRNA expression or DNA methylation of human telomerase reverse transcriptase (hTERT) was determined by real-time PCR and methylation-specific PCR assay, respectively. We established a hyperhomocysteinemia (HHcy) mice model to confirm human results. Results: Hcy was negatively correlated with LTL shortening in AS patients (r=-0.179, p=0.015) and controls (r=-0.146, p=0.031). Serum folate and high-sensitivity C-reactive protein levels significantly interacted with Hcy in LTL shortening. Hcy was related to hTERT mRNA downregulation and promoter demethylation, which combined was associated with LTL shortening in AS patients. Hcy-induced LTL shortening did not differ by sites of AS lesions or infarction. Similar to clinical observations, our HHcy mice model suggested that Hcy induced DNA demethylation and downregulation of mouse TERT and further contributed to LTL shortening. Conclusions: Elevated Hcy level induced DNA demethylation of hTERT and was closely related with hTERT downregulation, which led to LTL shortening in AS. These findings provide novel insights into an epigenetic mechanism for Hcy-related AS. © 2013 Elsevier Ireland Ltd.


Zhang Y.X.,Peking Union Medical College
Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials | Year: 2011

To establish HPLC fingerprint of Folium Pyrrosiae for identification. The HPLC method was developed with Diamonsil C18 column (250 mm x 4.6 mm, 5 microm),and a mixture liquid of acetonitrile-0.8% acetic acid solution as mobile phase in a gradient elution. HPLC fingerprints of44 samples were analyzed by similarity, cluster and principal component analysis. The HPLC fingerprint common pattern of Pyrrosia petiolosa, Pyrrosia lingua and common pattern of Pyrrosia sheareri were set up separately. Samples from different species were classified based on the result of cluster and principal component analysis. Fingerprints of Pyrrosia sheareri and Pyrrosia lingua have high degree of similarity, but were different from Pyrrosia petiolosa, while Pyrrosia calvata and Pyrrosia assimlis were classified as adulterants with their dissimilar fingerprints. The method is stable and reliable with a good reproducibility and provides a reference standard for identifying Folium Pyrrosiae from different habitats and species.


Wang J.,Peking Union Medical College | Wu Z.,Peking Union Medical College | Jin Q.,Peking Union Medical College
PLoS ONE | Year: 2012

Enterovirus 71 (EV71), a member of the Picornaviridae family, is found in Asian countries where it causes a wide range of human diseases. No effective therapy is available for the treatment of these infections. Picornaviruses undergo RNA replication in association with membranes of infected cells. COPI and COPII have been shown to be involved in the formation of picornavirus-induced vesicles. Replication of several picornaviruses, including poliovirus and Echovirus 11 (EV11), is dependent on COPI or COPII. Here, we report that COPI, but not COPII, is required for EV71 replication. Replication of EV71 was inhibited by brefeldin A and golgicide A, inhibitors of COPI activity. Furthermore, we found EV71 2C protein interacted with COPI subunits by co-immunoprecipitation and GST pull-down assay, indicating that COPI coatomer might be directed to the viral replication complex through viral 2C protein. Additionally, because the pathway is conserved among different species of enteroviruses, it may represent a novel target for antiviral therapies. © 2012 Wang et al.


Li Y.,Peking Union Medical College | Wang Q.,Capital Medical University | Wang Q.,Beijing Ditan Hospital | Yao X.,Peking Union Medical College
European Journal of Pharmacology | Year: 2010

The herbal products baicalin, baicalein, chlorogenic acid, and ginsenoside Rf have multiple pharmacological effects and are extensively used in alternative and/or complementary therapies. The present study investigated whether baicalin, baicalein, chlorogenic acid, and ginsenoside Rf induced the expression of the cytochrome P450 3A4 (CYP3A4) and multi-drug resistance 1 (MDR1) genes through the pregnane X receptor and constitutive androstane receptor pathways. Real time PCR, western blotting, and a luminescent assay were used to assess the induction of gene expression and activity of CYP3A4 and MDR1 by the test compounds. The interactions of baicalein/chlorogenic acid/ginsenoside Rf with constitutive androstane receptor and pregnane X receptor were evaluated using luciferase reporter and gel shift assays. Baicalein induced the expression of CYP3A4 and MDR1 mRNA by activating pregnane X receptor and constitutive androstane receptor. Chlorogenic acid and ginsenoside Rf showed a relatively weak effect on CYP3A4 promoter activation only in HepG2 cells cotransfected with constitutive androstane receptor and demonstrated no effects on MDR1 via either the constitutive androstane receptor or pregnane X receptor pathway. Baicalin had no effect on either CYP3A4 or MDR1 gene expression. In conclusion, baicalein has the potential to up-regulate CYP3A4 and MDR1 through the direct activation of the constitutive androstane receptor and pregnane X receptor pathways. Chlorogenic acid and ginsenoside Rf only induced constitutive androstane receptor-mediated CYP3A4 expression. © 2010 Elsevier B.V.


Li Z.,Peking Union Medical College | Yu X.,Peking Union Medical College | Shen J.,Peking Union Medical College | Law P.T.Y.,Chinese University of Hong Kong | And 2 more authors.
Oncotarget | Year: 2015

Gallbladder cancer is the most common biliary tract malignancy with poor prognosis. MicroRNAs (miRNAs) are a class of small, endogenous, non-coding RNAs of 19-23 nucleotides in length, which regulate gene expression at post-transcriptional and translational levels. Several studies have demonstrated aberrant expression of miRNAs in gallbladder cancer tissues. Recent evidences also demonstrated that specific miRNAs are functionally involved in gallbladder cancer development through modulating cell proliferation, apoptosis, migration, invasion and metastasis. In this review, we explore the possibilities of using miRNAs as prognostic, diagnostic markers and therapeutic targets in gallbladder cancer.


Shen S.-J.,Peking Union Medical College
Chinese Journal of Oncology | Year: 2012

Objective: Mammography is the principle imaging modality used for early diagnosis of breast cancer in Western countries. It has not been well-established whether this Western diagnostic modality is adoptable for Chinese women. The aim of this study was to evaluate the respective accuracy of the common diagnostic tools for breast cancer including history-taking, physical examination, ultrasound and mammography. Methods: Clinical presentation and investigations for consecutive patients undergoing history-taking, physical examination, ultrasound, mammography and pathological assessment at Peking Union Medical College Hospital were prospectively recorded between April 2010 and September 2011. Breast cancer high-risk factors acquired by history-taking were input into the risk assessment model established previously by Eleventh Five Year Key Programs for Science and Technology Development of China (Grant No. 2006BAI02A09) and classified into low-, medium-, high- and extremely high-risk groups. The low- and medium-risk groups were defined as test negative, while the high- and extremely high-risk groups were defined as test positive. Each mammogram and ultrasound was reported prospectively using a five-point reporting scale of the American College of Radiology (ACR) Breast Imaging Reporting and Data System (BIRADS). Clinical data were compared with pathological findings. Sensitivity, specificity, positive predictive value (PRV), negative predictive value (NPV) and accuracy of respective diagnostic methods were calculated and compared. The patients were divided into two groups, above and below 50 years of age for subgroup analysis. Results: A total of 1468 patients (1475 breast lesions) constituted the study population. The median age was 44 (range 13-92) years. Five hundred and fifty-one patients were diagnosed as breast cancer. The median age at diagnosis was 51 years and breast cancer peaked in the age group of 40-60 years. The sensitivity of risk assessment model, physical examination, ultrasound and mammogram was 47.5%, 86.2%, 89.8% and 79.3%, respectively; specificity was 68.8%, 83.3%, 81.0% and 88.7%, respectively; PRV was 47.6%, 75.5%, 73.8% and 80.8%, respectively; NPV was 68.8%, 91.0%, 93.0% and 87.8%, respectively; and accuracy was 60.9%, 84.4%, 84.3% and 85.2%, respectively. Further subgroup analysis demonstrated that age is an important factor influencing the sensitivity and specificity of physical examination, ultrasound and mammography. Conclusions: Ultrasound is more sensitive than mammography for early diagnosis of breast cancer in Chinese women and should be routinely used as a first-line diagnostic tool. Only a single diagnostic method is not enough sometimes and combined examination is needed for some high-risk populations.


Jiang H.,Nanjing Normal University | Shen Y.,Peking Union Medical College | Liu W.,Peking Union Medical College | Lu L.,Nanjing Normal University
Fungal Genetics and Biology | Year: 2014

Calcium ion is a universal and physiologically important molecule affecting almost every cellular function, while Mid1 (mating induced death) is a stretch-activated ion channel localized in the plasma membrane, which can replenish the fungus with extracellular calcium. Aspergillus fumigatus is one of the most important fungal pathogens but little is known about its calcium channels in the plasma membrane. In this study, a homolog of Saccharomyces cerevisiae Mid1 was identified in A. fumigatus and its encoding gene afmid1 was deleted by replacing it with pyr4 selectable marker, designated as δafmid1. Analysis of the phenotypes demonstrated that δafmid1 had growth defects under solid and liquid cultural conditions. The mutant δafmid1 had delayed germination in minimal medium and abnormal morphogenesis in the medium containing ethylene glycol tetraacetic acid (EGTA), an agent with major affinity for Ca2+ and minor affinity for Mn2+. The sensitivity against cell wall disturbing agents, osmotic stress, alkaline environments, high temperatures or starvation in δafmid1 resembled wild type. However, the mutant δafmid1 demonstrated more sensitivity to oxidative agents (H2O2 and Menadione) than wild type. Most surprisingly, deletion of afmid1 from A. fumigatus led to hypervirulence in the immunosuppressed mice model. © 2013 Elsevier Inc.


Yu X.,Peking Union Medical College | Li Z.,Peking Union Medical College
Oncotarget | Year: 2015

MicroRNAs (miRs, miRs) is a class of small non-coding RNAs, which posttranscriptionally regulate gene expression. Deregulated miRs are frequently obseved in patients with laryngeal cancer. In addition, numerous studies have showed miRs play significant roles in the pathogenesis of laryngeal cancer through regulating tumor cell proliferation, metastasis, invasion and apoptosis. miR can play either an oncogenic or tumor suppressive role in laryngeal cancer. In our review, we summarize the recent researches on laryngeal cancer-associated miRs, focusing on their role in the pathogenesis of laryngeal cancer. As changes in the levels of specific miRs in tissues or serum associate with diagnosis and prognosis of patients, we will also discuss the potential use of miRs in laryngeal cancer diagnosis and prognosis. Furthermore, supplementation of oncomiRs or inhibition of tumor suppressive miRs in vivo may be future therapeutic strategy for laryngeal cancer.


Gong J.-H.,Peking Union Medical College | Liu X.-J.,Peking Union Medical College | Li Y.,Peking Union Medical College | Zhen Y.-S.,Peking Union Medical College
Cancer Chemotherapy and Pharmacology | Year: 2012

Purpose As reported, epidermal growth factor receptor (EGFR) is over expressed in a variety of cancers including esophageal squamous cell carcinoma. Therefore, it becomes one of the potential targets for treating esophageal cancer. Pingyangmycin (PYM), a single A5 component of bleomycin, is currently used for the treatment of different types of cancers of epidermal origin, especially for head and neck cancers. In this report, the effect of PYM on EGFR expression in human esophageal cancer cells and the therapeutic efficacy of the combination of PYM and cetuximab on esophageal cancer xenograft were investigated. Methods The effects of PYM, cetuximab and the combination on EGFR signaling, proliferation, cell cycle, apoptosis were evaluated by using MTT, Western blotting, RT-PCR assays and flow cytometry assays, respectively, in vitro and the therapeutic efficacy by a xenograft model in athymic mice. Results Cell volume and nucleus were enlarged after PYM treatment. PYM showed potent cytotoxicity in both cell lines of Kyse-150 and Eca-109 in time and dosage-depended manner in MTT assay. PYM treatment induced G2/M phase arrest and apoptosis. Notably, the expression of EGFR was down-regulated by PYM in EGFR highly expression esophageal cancer cells. PYM plus cetuximab resulted in a potentiation of antiproliferative activity. PYM combined with cetuximab displayed a much higher therapeutic effect than that of the single agent on esophageal cancer xenograft in athymic mice. Conclusions PYM could down-regulate the expression of EGFR in esophageal cancer cells and potentiate the effects of cetuximab on esophageal cancer xenograft in nude mice. The combination of PYM and cetuximab, the EGFR-targeted combination of a chemotherapeutic agent and an antibody-based drug, might be useful in cancer therapy. © Springer-Verlag 2012.


Xue F.S.,Chinese Academy of Sciences | Ye T.H.,Peking Union Medical College
Anaesthesia | Year: 2010

To assess the effects of midazolam on explicit and implicit memories, 12 volunteers were randomly divided into the two groups: one with an Observer's Assessment of Alertness/Sedation score of 3 (mild sedation) and one with a score of 1 (deep sedation). Blood oxygen-level-dependent functional magnetic resonance imaging was measured before and during an auditory stimulus, then with midazolam sedation, and then during a second auditory stimulus with continuous midazolam sedation. After 4 h, explicit and implicit memories were assessed. There was no evidence of explicit memory at the two levels of midazolam sedation. Implicit memory was retained at a mild level of midazolam sedation but absent at a deep level of midazolam sedation. At a mild level of midazolam sedation, activation of all brain areas by auditory stimulus (as measured by functional magnetic resonance imaging) was uninhibited. However, a deep level of midazolam sedation depressed activation of the superior temporal gyrus by auditory stimulus. We conclude that midazolam does not abolish implicit memory at a mild sedation level, but can abolish both explicit and implicit memories at a deep sedation level. The superior temporal gyrus may be one of the target areas. © 2010 The Association of Anaesthetists of Great Britain and Ireland.


Zhang H.,Peking Union Medical College | Huang B.,Peking Union Medical College
OncoImmunology | Year: 2015

For cancer vaccines, tumor antigen availability is currently not an issue due to technical advances. However, the generation of optimal immune stimulation during vaccination is challenging. We have recently demonstrated that tumor cell-derived microparticles (MP) can function as a new form of potent cancer vaccine by efficiently activating type I interferon pathway in a cGAS/STING dependent manner. © 2015 Taylor & Francis Group, LLC.


Yang M.,Peking Union Medical College | Huang C.-Z.,Peking Union Medical College
World Journal of Gastroenterology | Year: 2015

The mortality rate of gastric cancer worldwide is as high as 70%, despite the development of novel therapeutic strategies. One reason for the high mortality is the rapid and uninhibited spread of the disease, such that the majority of patients are diagnosed at a stage when efficient therapeutic treatment is not available. Therefore, in-depth research is needed to investigate the mechanism of gastric cancer metastasis and invasion to improve outcomes and provide biomarkers for early diagnosis. The mitogen-activated protein kinase (MAPK) signaling pathway is widely expressed in multicellular organisms, with critical roles in multiple biological processes, such as cell proliferation, death, differentiation, migration, and invasion. The MAPK pathway typically responds to extracellular stimulation. However, the MAPK pathway is often involved in the occurrence and progression of cancer when abnormally regulated. Many studies have researched the relationship between the MAPK signaling pathway and cancer metastasis and invasion, but little is known about the important roles that the MAPK signaling pathway plays in gastric cancer. Based on an analysis of published data, this review aims to summarize the important role that the MAP kinases play in the invasion and metastasis of gastric cancer and attempts to provide potential directions for further research and clinical treatment. © 2015 Baishideng Publishing Group Inc. All rights reserved.


Shan Z.,Central South University | Li G.,Central South University | Zhan Q.,Peking Union Medical College | Li D.,Peking Union Medical College
Cancer Biology and Therapy | Year: 2012

Gadd45a, the first well-defined p53 downstream gene, can be induced by multiple DNA-damaging agents, which plays important roles in the control of cell cycle checkpoint, DNA repair process and signaling transduction. Our previous findings suggested that Gadd45a maintains cell-cell adhesion and cell contact inhibition. However, little is known about how Gadd45a participates in the suppression of malignancy in human cancer cells. To examine the functions of Gadd45a in cell invasion and metastasis, we performed the adhesion, wound-healing and transwell assays in Gadd45a+/+ and Gadd45a-/- MEF cell lines. We found the adhesion, migration and invasive abilities were much higher in Gadd45a deficient cells. We furthermore applied high-throughput cDNA microarray analysis and bioinformatics analysis to analyze the mechanisms of Gadd45a gene in invasion and metastasis. Compared with the Gadd45a wild type cells, the Gadd45a deficient cells showed a wide range of transcripts alterations. The altered gene pathways were predicted by the MAS software, which indicated focal adhesion, cell communication, ECM-receptor interaction as the three main pathways. Real-time PCR was employed to validate the differentially expressed genes. Interestingly, we figured out that the deregulations of these genes are caused neither by genomic aberrations nor methylation status. These findings provided a novel insight that Gadd45a may involve in tumor progression by regulating related genes expressions. © 2012 Landes Bioscience.


Dong Y.,Peking Union Medical College | Liu G.,Peking Union Medical College | Liu G.,Tsinghua University
Chemical Communications | Year: 2013

A Rh-catalyzed ortho C-H olefination of arenes directed by a sulfonic acid group was developed with good yields and a broad reaction scope. Efficient performance of the catalyst caused this electron-poor aromatic C-H to be activated effectively and unactivated alkenes are also suitable for this reaction. © 2013 The Royal Society of Chemistry.


Lu S.,Peking Union Medical College
GM crops | Year: 2010

How the abundant tree biomass resources can be efficiently used for future biofuel production has attracted a great deal of interest and discussion in the past few years. Capable technologies are expected to be developed to realize the production of biofuel from wood biomass. A significant effort is put into the field of modifying wood properties of trees and simplifying the process of biomass-to-ethanol conversion, which includes mainly genetic engineering of lignin, cellulose and hemicellulose of woods. Current research in this field has achieved some promising results and opened up new opportunities to utilize wood biomass efficiently. This review will discuss the main developments in genetic modification of lignin, cellulose and hemicellulose biosynthesis in trees as well as other potential genetic technology of biofuel production from wood biomass.


Sunsaneewitayakul B.,Chulalongkorn University | Yao Y.,Peking Union Medical College | Thamaree S.,Naresuan University | Zhang S.,Chulalongkorn University
Journal of Cardiovascular Electrophysiology | Year: 2012

Endocardial Mapping and Ablation of Brugada Syndrome. Introduction: Brugada syndrome (BS) is characterized by ST-segment elevation in the right precordial electrocardiogram (ECG) leads and episodes of ventricular fibrillation (VF). This study aimed to observe the feasibility of substrate modification by radiofrequency catheter ablation and its effects on VF storm. Methods and Results: Ten BS patients (all men; median age 36.5 years) with VF storm (group I, n = 4) and no VF storm (group II, n = 6) were enrolled in the study between August 2007 and December 2008. All patients underwent electrophysiological study using noncontact mapping. The multielectrode array was placed in the right ventricular outflow tract (RVOT). The isopotential map was analyzed during sinus rhythm and the region that had electrical activity occurring during J point to +60 (J+60) milliseconds interval of the V1 or V2 of surface ECG was considered as the late activation zone (LAZ) and also the substrate for ablation. LAZ was found in RVOT with variable distribution in both groups. Endocardial catheter ablation of the LAZ modified Brugada ECG pattern in 3 of 4 patients (75%) and suppressed VF storm in all 4 patients in group I during long-term follow-up (12-30 months). One patient had complete right bundle branch block from the ablation procedure. Conclusions: LAZ on RVOT identified by noncontact mapping may serve as potential VF substrate in BS patients with VF episodes. Radiofrequency ablation on LAZ normalized ECG, suppressed VF storm, and reduced VF recurrence. The procedure is safe and may prevent VF occurrence.


Sun X.H.,Peking Union Medical College
Zhonghua nei ke za zhi [Chinese journal of internal medicine] | Year: 2010

To analyze the clinical features of patients with hemophagocytic syndrome (HPS) in autoimmune diseases (AID). We collected the data of 11 patients with AID complicated with HPS in Peking Union Medical College Hospital from 2004 to 2009. The underlying diseases, clinical features, laboratory findings and treatment outcomes were retrospectively analyzed. Of the 11 patients, 3 were male, 8 were female. Mean age was (30.7 ± 18.3) years. The underlying diseases included Still disease (n = 4), systemic lupus erythematosus(n = 3), and rheumatoid arthritis, primary Sjögren's syndrome, Wegener granulomatosis and Crohn disease in each one case. HPS was associated with the onset of AID (n = 4), active infection alone (n = 1) and both factors (n = 6). HPS was clinically characterized by high fever (100%), hepatosplenomegaly (72.7%), lymphadenopathy (63.3%) and central nervous system involvement (36.3%). 4 patients presented with disseminated intravascular coagulation (DIC) (36.3%). Laboratory data mainly manifested with cytopenia (100%), liver dysfunction (100%), hypofibrinogenemia (62.5%), hypertriglyceridemia (81.8%), serum ferritin > 500 μg/L (100%), low NK-cell activity (80%) and hemophagocytosis in bone marrow (100%). Based on treating underlying infections and use of corticosteroids and immunosuppressive agents in combination with intravenous immunoglobulins (IVIG) therapy, 5 patients recovered, 6 patients died. The mortality rate was 54.5%. DIC were associated with mortality (r = 0.69, P = 0.019). The episode of HPS always occurs simultaneously with multiple system involvement that was often difficult to distinguish from active AID. The present of DIC on HPS related with poor prognosis and high mortality. Corticosteroids and immunodepressant and IVIG may improve the prognosis of HPS, while anti-infection therapy is very important and necessary for the patients accompany with active infection.


Li J.,Peking Union Medical College | Zhang W.,Peking Union Medical College | Jiao L.,Peking Union Medical College | Duan M.-H.,Peking Union Medical College | And 4 more authors.
Blood | Year: 2011

POEMS syndrome is a rare clonal plasma cell disorder without standard treatment. Based on the efficacy and low toxicity of a combination of melphalan and dexamethasone (MDex) for light chain amyloidosis, we conducted a prospective study of MDex treatment for patients with newly diagnosed POEMS syndrome. Thirty-one patients (19 men) were enrolled and the median age at the time of diagnosis was 44 years (range, 32-68 years). All patients received 12 cycles of MDex treatment. Twenty-five patients (80.6%) achieved hematologic response including 12 (38.7%) complete remission and 13 (41.9%) partial remission. Of all 31 patients, the neurologic response rate was 100%, assessed by overall neuropathy limitation scale (ONLS). The initial neurologic response was observed in 24 patients (77.4%) at 3 months after treatment and the median time to maximal neurologic response was 12 months (range, 3-15 months). Moreover, MDex substantially improved the level of serum vascular endothelial growth factor and relieved organomegaly, extravascular volume overload, and pulmonary hypertension. Only 6 patients (19.3%) suffered from grade 3 adverse events during treatment. All patients are alive and free of neurologic relapse after the median follow-up time of 21 months. Therefore, MDex is an effective and well-tolerated treatment option for patients with newly diagnosed POEMS syndrome. © 2011 by The American Society of Hematology.


Zhang C.,Harvard University | Li Y.,Harvard University | Malhotra A.,Harvard University | Ning Y.,Virginia Commonwealth University | And 2 more authors.
Neurology | Year: 2014

Objective: To examine the potential long-term impact of restless legs syndrome (RLS) and other common sleep complaints on subsequent physical function (PF), we conducted a longitudinal analysis of 12,556 men in the Health Professionals Follow-up Study. Methods: We used a set of questions recommended by the International RLS Study Group to assess RLS in 2002. We asked questions regarding other sleep complaints-insomnia, sleep fragmentation, and excessive daytime sleepiness-in 2004. We used the Physical Function (PF-10) survey of the Short Form-36 Health Survey to characterize PF in 1996 and 2008. We examined the 2008 PF-10 scores across categories of baseline RLS (2002), adjusted for age, 1996 PF-10 score, and other potential confounders. Results: The participants with RLS at baseline had significantly lower PF-10 score 6 years later than those without RLS (mean difference = -22.32, p = 0.01), after adjusting for potential confounders. The magnitude of difference in PF-10 score for RLS symptoms ≥15 times/month vs no RLS was more than that of a 5-year increase of age or moderate amount of smoking. Having daily daytime sleepiness and sleep duration ≥9 hours/day were associated with lower mean PF value than not having these symptoms (p < 0.05 for both). Conclusions: RLS and other sleep complaints are associated with lower PF. Our findings need to be replicated by more longitudinal studies including women and populations of other social and cultural backgrounds. It is important to understand whether RLS is an independent risk factor or a marker for other unknown risk factors for disability. © 2014 American Academy of Neurology.


Youn J.-Y.,University of California at Los Angeles | Zhang J.,University of California at Los Angeles | Zhang Y.,University of California at Los Angeles | Chen H.,Peking Union Medical College | And 4 more authors.
Journal of Molecular and Cellular Cardiology | Year: 2013

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Patients with AF have up to seven-fold higher risk of suffering from ischemic stroke. Better understanding of etiologies of AF and its thromboembolic complications are required for improved patient care, as current anti-arrhythmic therapies have limited efficacy and off target effects. Accumulating evidence has implicated a potential role of oxidative stress in the pathogenesis of AF. Excessive production of reactive oxygen species (ROS) is likely involved in the structural and electrical remodeling of the heart, contributing to fibrosis and thrombosis. In particular, NADPH oxidase (NOX) has emerged as a potential enzymatic source for ROS production in AF based on growing evidence from clinical and animal studies. Indeed, NOX can be activated by known upstream triggers of AF such as angiotensin II and atrial stretch. In addition, treatments such as statins, antioxidants, ACEI or AT1RB have been shown to prevent post-operative AF; among which ACEI/AT1RB and statins can attenuate NOX activity. On the other hand, detailed molecular mechanisms by which specific NOX isoform(s) are involved in the pathogenesis of AF and the extent to which activation of NOX plays a causal role in AF development remains to be determined. The current review discusses causes and consequences of oxidative stress in AF with a special focus on the emerging role of NOX pathways. © 2013 Elsevier Ltd.


Li H.-S.,Peking Union Medical College | Liu G.,Peking Union Medical College | Liu G.,Tsinghua University
Journal of Organic Chemistry | Year: 2014

Efficient construction of 2-sulfonylbenzo[b]furans is achieved from readily available trans-2-hydroxycinnamic acids and sodium sulfinates mediated by the CuCl2.2H2O/AgTFA system under mild conditions. This unprecedented synthetic protocol provides expedient access to a series of products in one step via a protodecarboxylation/C-S bond formation/C-O bond formation cascade. © 2013 American Chemical Society.


Qiu H.Z.,Peking Union Medical College
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2011

To report a case of APPEAR performed using a laparoscopic-assisted approach. A laparoscopic-assisted APPEAR was performed with end-to-end anastomosis on October 12, 2010 for a patient with low rectal cancer who received neoadjuvant chemoradiation. After total mesorectal excision was completed laparoscopically, a crescent-shape incision was then made in the middle perineum. The distal part of the rectum was dissected with electrocautery. An double-stapling end-to-end anastomosis was performed after transaction of the rectum. Total operative time was 195 minutes. The perineal approach cost 30 minutes. The estimated blood loss was 50 ml. First stoma output with flatus was on postoperative day 3, and the patient resumed liquid diet. The patient was discharged on postoperative day 7. There were no complications including pelvic sepsis, perineal infection, or anastomotic leak. The APPEAR procedure can be performed safely with the abdominal approach completed laparoscopically.


Li Z.,Zhejiang University | Yang J.,Zhejiang University | Yu G.,Zhejiang University | He J.,Peking Union Medical College | And 2 more authors.
Organic Letters | Year: 2014

By the introduction of 14 anionic carboxylate groups at its two rims, a water-soluble pillar[7]arene (WP7) was synthesized. Its pH-controlled complexation with paraquat G1 in water was investigated. Host WP7 and guest G1 formed a 1:1 [2]pseudorotaxane with a high association constant of (2.96 ± 0.31) × 109 M-1 in water. Furthermore, we took advantage of this novel molecular recognition motif to fabricate a supra-amphiphile based on WP7 and an amphiphilic paraquat derivative G2. The morphologies and sizes of self-assemblies of G2 and WP7⊂G2 were identified by transmission electron microscopy and dynamic light scattering. © 2014 American Chemical Society.


Xu Y.,Peking Union Medical College | Sun Q.,Peking Union Medical College
Journal of Thoracic Disease | Year: 2010

Resistance to endocrine therapy is the major problem for ERα(+) breast cancer patients. Research in endocrine resistance, mainly based on breast cancer cell lines and transplantation animal models, has indicated that phosphorylation of estrogen receptors, high expression of SRC and high activation of ErbB/MAPK pathway are the 3 main mechanisms for occurrence of endocrine resistance. Restoration of ER expression and exploration of inhibitors to various biological targets are the 2 promising ways to solve this problem. Further research is needed to deeply explore relevant mechanisms and resolvents so as to guide clinical practice. © 2010 Journal of Thoracic Disease.


Xie M.Q.,Peking Union Medical College
Zhonghua yi xue za zhi | Year: 2010

To outline the clinical features of Kennedy disease in Chinese patients. The peripheral blood was collected from the male lower motor neuron disease patients of our inpatients and outpatients from July 2005 to September 2008. Then the genome DNA was extracted and the target gene amplified by polymerase chain reaction and sequenced. The clinical data of positive samples were analyzed and summarized. The number of expanded CAG repeats of 12 patients ranged from 43 to 57. And the number of CAG repeats was inversely correlated with the age of onset (r = -0.756, P < 0.005). The first symptom of all of these patients was extremity weakness. The progression of disease was slow. One of the patients died from pneumonia. And the whole disease course lasted for 14 years. As an adult onset degenerative disease with a slower clinical progression, Kennedy disease has its own characteristics of inheritance pattern and natural course. It can be accurately diagnosed by androgen receptor gene analysis.


Beaglehole R.,University of Auckland | Bonita R.,University of Auckland | Alleyne G.,Pan American Health Organization | Horton R.,The Lancet | And 9 more authors.
The Lancet | Year: 2011

Non-communicable diseases (NCDs), principally heart disease, stroke, cancer, diabetes, and chronic respiratory diseases, are a global crisis and require a global response. Despite the threat to human development, and the availability of affordable, cost-effective, and feasible interventions, most countries, development agencies, and foundations neglect the crisis. The UN High-Level Meeting (UN HLM) on NCDs in September, 2011, is an opportunity to stimulate a coordinated global response to NCDs that is commensurate with their health and economic burdens. To achieve the promise of the UN HLM, several questions must be addressed. In this report, we present the realities of the situation by answering four questions: is there really a global crisis of NCDs; how is NCD a development issue; are affordable and cost-effective interventions available; and do we really need high-level leadership and accountability? Action against NCDs will support other global health and development priorities. A successful outcome of the UN HLM depends on the heads of states and governments attending the meeting, and endorsing and implementing the commitments to action. Long-term success requires inspired and committed national and international leadership. © 2011 Elsevier Ltd.


Jing C.,Southern Medical University | Jia-Han W.,Southern Medical University | Hong-Xing Z.,Peking Union Medical College
Wound Repair and Regeneration | Year: 2010

To explore further the role of substance P (SP) in wound healing and scar formation, SP concentrations in wounds of scalded rats were assayed. Expressions of apoptosis-associated genes in fibroblasts cultured with SP were detected. SP concentrations in superficial wounds increased earlier than those in deep wounds. SP was associated with an increased proliferation and a decreased apoptosis of fibroblasts. It had a greater influence on keloid fibroblasts than on hypertrophic scar fibroblasts by elevating the expression of proliferating cell nuclear antigen and BCL-2 in fibroblasts. Spantide completely suppressed the effects of SP on hypertrophic scar fibroblasts, and partly inhibited its effects on keloid scar fibroblasts. SP may play an important role in wound healing by promoting wound fibroblast proliferation and inhibiting apoptosis. It may also participate in pathological scar formation by modulating the expression of apoptosis-associated genes. SP is postulated to play a dual role in wound repair. © 2010 by the Wound Healing Society.


Xing X.,Peking Union Medical College | Guo S.,Peking Union Medical College
Ecological Research | Year: 2011

This study investigated the taxonomic identities and diversity of fungal endophytes isolated from four Rhizophoraceae mangrove plant species, Ceriops tagal, Rhizophoraapiculata, R. stylosa and Bruguiera sexangula var. rhynchopetala, using a combination of morphological and molecular approaches. Two hundred ninety-five isolates were classified into 38 taxa by morphological characteristics. The representative 38 isolates from each taxa were selected for further molecular identification using nuclear ribosomal DNA sequences, including both the internal transcribed spacers (ITS1 and ITS2) and the 5.8S gene region. The 38 representative endophytes were identified to various taxonomic levels. These results suggest that Pestalotiopsis and Phomopsis were the most frequent endophytes in the four host species. Some of the endophytes exhibit host and tissue specificity. The colonization frequencies of endophytic fungi in the stems of the four host plants are evidently higher than in the roots. The four Rhizophoraceae mangrove species have low similarities of endophyte communities. © 2010 The Ecological Society of Japan.


Zhang W.,Peking Union Medical College
Clinical Nuclear Medicine | Year: 2016

ABSTRACT: We presented the serial FDG PET/CT brain scans of a 64-year-old woman with IgLON5 encephalopathy, which is a novel syndrome in association with antibodies to a neuronal cell adhesion protein named IgLON5, and FDG PET findings have not been characterized previously. For our case, the relatively hypermetabolism in primary sensorimotor cortices, basal ganglia, and cerebrum comparing to other cortical regions on the pretreatment FDG PET/CT was partially recovered on the follow-up FDG PET/CT scan after immunotherapy, corresponding with the alleviation of clinical syndromes. The metabolic change pattern was not similar as other types of autoimmune encephalitis. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.


Bao X.-Q.,Peking Union Medical College | Liu G.-T.,Peking Union Medical College
Acta Pharmacologica Sinica | Year: 2010

Aim: To study the inducing effect of bicyclol on heat shock protein 27 (HSP27) and its role on anti-apoptosis in HepG2 cells intoxicated with D-galactosamine (D-GaIN). Methods: HepG2 cells were treated with various concentrations of bicyclol and then subjected to D-GaIN intoxication. Apoptosis was assayed by hoechst 33258 staining and flow cytometry analysis. HSP27, cytochrome c, apoptosis inducing factor (AIF) and c-Jun N-terminal kinase (JNK) were assayed by Western blot. Heat shock factor 1 (HSF1) was determined by electrophoretic mobility shift assay and the interactions of HSP27 with cytochrome c and AIF were detected by co-immunoprecipitation. Results: The results showed that bicyclol induced HSP27 protein and mRNA expression in HepG2 cells in both time- and dose-dependent manners (the maximal response: 1.23 fold increase at 100 mol/L). Bicyclol treatment stimulated HSF1 activation and increased the HSF1-HSE binding activity (the maximal response: 2.1 fold increase at 100 mol/L). This inducing effect of bicyclol on HSP27 and HSF1 was markedly blocked by quercetin. Pretreatment of the cells with bicyclol markedly attenuated D-GaIN-induced apoptosis and the release of cytochrome c and AIF from mitochondria. The induced HSP27 by bicyclol suppressed the activity of caspase-3 and the phosphorylation of JNK caused by D-GaIN in HepG2 cells. All the above effect of bicyclol against D-GaIN-induced hepatocytes apoptosis were significantly reversed by quercetin. Conclusion: HSP27 is involved in the anti-hepatocytes apoptosis of bicyclol, and this effect of bicyclol-induced HSP27 is mainly through inhibition of mitochondria and JNK apoptotic pathways. © 2010 CPS and SIMM All rights reserved.


Zhao H.,Peking Union Medical College | Xi X.,Peking Union Medical College | Cui L.,Peking Union Medical College | He W.,Peking Union Medical College
Cellular and Molecular Immunology | Year: 2012

Adoptive cell-transfer therapy (ACT) has been reported to suppress growing tumors and to overcome tumor escape in animal models. As a candidate ACT effector, δ 9γ2T cells can be activated and expanded in vitro and in vivo and display strong antitumor activity against colorectal, lung, prostate, ovarian and renal cell carcinomas. However, it is difficult to obtain a large enough number of γ δ cells to meet the need for immunotherapy that can overcome the cancer patients' immune suppressive tumor microenvironment. In previous studies, our lab confirmed that δ 9γ 2T cells recognized tumor cells via the CDR3δ region of the γ δ -T-cell receptor (TCR). We constructed full-length human peripheral blood mononuclear cell (PBMC)-derived δ39 and δ 2 chains in which the CDR3 region was replaced by an ovarian epithelial carcinoma (OEC)-derived CDR3. We transferred the CDR3δ-grafted δ 9γ 2TCR into peripheral blood lymphocytes (PBLs) to develop genetically modified γ 9δ 2T cells. In vitro studies have shown that these CDR3δ-grafted γ9δ 2T cells can produce cytokines after stimulation with tumor cell extracts and exhibit cytotoxicity towards tumor cells, including human OEC and cervical adenocarcinoma. CDR3δ -grafted δ 9δ 2T cells adoptively transferred into nude mice bearing a human OEC cell line demonstrated significant antitumor effects. These results indicate that CDR3δ-grafted γ9δ2T cells might be candidates for clinical tumor immunotherapy. © 2012 CSI and USTC. All rights reserved.


Zhuang X.-F.,Peking Union Medical College
Chinese Journal of Oncology | Year: 2012

Objective: To generate an oncolytic herpes simplex virus (oHSV) permissive mouse melanoma cell line B16RHSV, preserving the tumorigenic ability in syngeneic mice. Methods: The herpes simplex virus entry mediator (HVEM) gene was amplified by PCR from human melanoma cell line A375, and cloned into pGEM-T Easy vector for sequencing. The HVEM gene was then cloned into pcDNA3 vector to generate pcDNA3-HVEM for transfection of mouse melanoma cell line B16-F10 cells. After that, the putative transfected cells were selected in full growth medium containing G418. The HVEM-expressing cells were isolated by immunomagnetic bead separation. The mouse melanoma cell line expressing oHSV receptor-HVEM, designated as B16RHSV, was generated. The permissibility of B16R HSV cells to oHSV infection was examined with green fluorescence protein (GFP)-expressing oHSV (oHSVCFP). To investigate the tumorigenic ability of both cells in vivo, 2 × 105 cells in 100 μl were subcutaneously inoculated into the right flanks of C57/BL mice. Results: In vitro, the B16RHSV mouse melanoma cells were shown by fluorescence microscopy capable of being infected by oHSVGFP. In vivo, the B16RHSV cells, like their wild type counterpart, grew to form melanoma in syngeneic mice. Conclusion: A herpes simplex virus-permissive mouse melanoma cell line was established. Its tumorigenicity remained unchanged.


Dong D.,Peking Union Medical College | Li H.,Peking Union Medical College
Journal of Maternal-Fetal and Neonatal Medicine | Year: 2014

Objective: To investigate the diagnosis and treatment of pheochromocytoma during pregnancy. Materials and methods: The data of four cases of pheochromocytoma was analyzed retrospectively. Their ages were 41, 28, 32 and 30 years old, and the four patients were at 32nd week, 12th week, 14th week and 13th week of gestation. All patients had hypertension during pregnancy, accompanied with headache, dizziness, palpitation and sweating. The 24-h urinary catecholamines (24h UCA) increased significantly. Ultrasound and MRI confirmed the diagnosis of pheochromocytoma. Results: One case had Cesarean section at 32 weeks of gestation, and a healthy baby girl was delivered smoothly. Laparoscopic resection of the right adrenal pheochromocytoma was performed at the same time, and an adrenal tumor of 7.0cm was resected successfully. Two cases chose abortion and laparoscopic resection of pheochromocytoma was performed. One case chose abortion and refused further treatment. Histopathology confirmed the diagnosis of pheochromocytoma. Conclusions: For hypertension in pregnant women during pregnancy, typical paroxysmal hypertension accompanied by triad of headache, palpitation and sweating, pheochromocytoma should be considered. Early diagnosis can reduce the maternal and fetal mortality significantly. Second trimester of pregnancy is the ideal time for surgical treatment. Laparoscopic resection of pheochromocytoma during pregnancy is safe and effective. © 2014 Informa UK Ltd. All rights reserved.


Fang X.,Peking Union Medical College
Chinese Journal of Gastroenterology | Year: 2015

The etiology and pathogenesis of functional dyspepsia (FD) are still unknown, recent studies showed that immune responses play a mediation role in the pathogenesis of food allergy, inflammation-related and post-infectious FD. The increased and activated eosinophils in duodenal mucosa, the infiltration of inflammatory immune cells in gastric and duodenal mucosa, and the peripheral immune responses are correlated with delayed gastric emptying, decrease of sensory function of proximal stomach, visceral hypersensitivity and FD symptoms. Strategies that suppress immune response might be prospective for subset of FD patients with evidences of immune dysregulation. Copyright © 2015 by Editorial Office of Chinese Journal of Gastroenterology.


Li Z.,Peking Union Medical College | Yu X.,Peking Union Medical College | Shen J.,Peking Union Medical College | Jiang Y.,Peking Union Medical College
Oncotarget | Year: 2015

Uveal melanoma is the second most common form of melanoma and a predominant intraocular malignant tumor in adults. The development of uveal melanoma is a multistep process involving genetic and epigenetic alteration of proto-oncogenes and tumorsuppressor genes. Recent discoveries have shed a new light on the involvement of a class of noncoding RNA known as microRNAs (miRNAs) in uveal melanoma. A lot of miRNAs show differential expressions in uveal melanoma tissues and cell lines. Genes coding for these miRNAs have been characterized as novel oncogene and tumor-suppressor genes based on findings that these miRNAs control malignant phenotypes of uveal melanoma cells. Several studies have confirmed that dysregulation of miRNAs promotes cell-cycle progression, confers resistance to apoptosis, and enhances invasiveness and metastasis. Moreover, several miRNAs have also been shown to correlate with uveal melanoma initiation and progression, and thus may be used as biomarkers for early diagnosis and prognosis. Elucidating the biological aspects of miRNA dysregulation may help us better understand the pathogenesis of uveal melanoma and promote the development of miRNA directed-therapeutics against this disease.


Chen W.,Yeshiva University | Chen W.,Peking Union Medical College | Frangogiannis N.G.,Yeshiva University
Biochimica et Biophysica Acta - Molecular Cell Research | Year: 2013

Fibroblasts are the predominant cell type in the cardiac interstitium. As the main matrix-producing cells in the adult mammalian heart, fibroblasts maintain the integrity of the extracellular matrix network, thus preserving geometry and function. Following myocardial infarction fibroblasts undergo dynamic phenotypic alterations and direct the reparative response. Due to their strategic location, cardiac fibroblasts serve as sentinel cells that sense injury and activate the inflammasome secreting cytokines and chemokines. During the proliferative phase of healing, infarct fibroblasts undergo myofibroblast transdifferentiation forming stress fibers and expressing contractile proteins (such as α-smooth muscle actin). Mechanical stress, transforming growth factor (TGF)-β/Smad3 signaling and alterations in the composition of the extracellular matrix induce acquisition of the myofibroblast phenotype. In the highly cellular and growth factor-rich environment of the infarct, activated myofibroblasts produce matrix proteins, proteases and their inhibitors regulating matrix metabolism. As the infarct matures, "stress-shielding" of myofibroblasts by the cross-linked matrix and growth factor withdrawal may induce quiescence and ultimately cause apoptotic death. Because of their critical role in post-infarction cardiac remodeling, fibroblasts are promising therapeutic targets following myocardial infarction. However, the complexity of fibroblast functions and the pathophysiologic heterogeneity of post-infarction remodeling in the clinical context discourage oversimplified approaches in clinical translation. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction. © 2012 Elsevier B.V.


Xu H.-Y.,Peking Union Medical College | Gu N.,Nanjing Southeast University
Frontiers of Materials Science | Year: 2014

Increasing evidence shows that magnetic fields and magnetic responsive scaffolds can play unique roles in promoting bone repair and regeneration. This article addresses the synergistic effects of magnetic scaffolds in response to external magnetic fields on the bone regeneration in situ. Additionally, the exploration of using magnetic scaffolds as tools in the bone implant fixation, local drug delivery and mimicking microenvironment of stem cell differentiation are introduced. We also discussed possible underlying mechanisms and perspectives of magnetic responsive scaffolds in the bone repair and regeneration. © 2014 Higher Education Press and Springer-Verlag Berlin Heidelberg.


Xu H.,Peking Union Medical College | Yang Y.-J.,Peking Union Medical College | Yang T.,Peking Union Medical College | Qian H.-Y.,Peking Union Medical College
Ageing Research Reviews | Year: 2013

Stem cell-based therapy is a promising option for the treatment of ischemic heart diseases. As to a successful stem cell-based therapy, one of the most important issues is that the stable engraftment and survival of implanted stem cells in cardiac microenvironment. There are evidences suggest that pharmacological treatment devoted to regulate stem cell function might represent a potential new therapeutic strategy and are drawing nearer to becoming a part of treatment in clinical settings. Statins could exert cholesterol-independent or pleiotropic effects to cardiovascular system. Recent studies have shown that statins could modulate the biological characteristics and function of various stem cells, thus could be an effective method to facilitate stem cell therapy. This review will focus on statins and their modulation effects on various stem cells. © 2012 Elsevier B.V..


Objective: Myocardial edema plays an important role in the development of myocardial no-reflow and reperfusion injury after the revascularization of acute myocardial infarction (AMI). The present study investigated whether the effect of ischemic preconditioning (IPC) against myocardial no-reflow and reperfusion injury was related to the reduction of myocardial edema through the protein kinase A (PKA) pathway. Methods: Twenty-four minipigs were randomized into sham, AMI, IPC, and IPC + H-89 (PKA inhibitor, 1.0 μg · kg-1 · min-1) groups. The area of no-reflow (ANR), area of necrosis (AN), and water content in left ventricle and ischemic-myocardium and non-ischemic area were determined by pathological studies. Microvascular permeability was determined by FITC-labeled dextran staining. Cardiomyocyte cross-sectional area (CSA) and mitochondria cross-sectional area (MSA) were evaluated by histological analysis. Myocardial expression of aquaporins (AQPs) was detected by Western blot. Results: Compared with the MI group, the sizes of no-reflow and infarct were reduced by 31.9% and 46.6% in the IPC group (all P < 0.01), water content was decreased by 5.7% and 4.6% in the reflow and no-reflow myocardium of the IPC group (all P < 0.05), microvascular permeability and cardiomyocytes swelling in the reflow area were inhibited by 29.8% and 21.3% in the IPC group (all P < 0.01), mitochondrial water accumulation in the reflow and no-reflow areas of the IPC group were suppressed by 45.5% and 34.8% respectively (all P < 0.01), and the expression of aquaporin-4, -8, and -9 in the reflow and no-reflow myocardium were blocked in the IPC group. However, these beneficial effects of IPC were partially abolished in the IPC + H-89 group. Conclusions: The cardioprotective effects of IPC against no-reflow and reperfusion injury is partly related to the reduction of myocardial edema by inhibition of microvascular permeability and aquaporins up-regulation via PKA pathway. Copyright © 2012 by the Chinese Medical Association.


Qin W.,Peking Union Medical College
Yi chuan = Hereditas / Zhongguo yi chuan xue hui bian ji | Year: 2012

To further understand the neural toxicity and teratogenicity of antiepileptic drugs in clinic, we established a zebrafish model for antiepileptic toxicity using trimethadione as a probe drug. The results indicated that embryonic malformation occurred under trimethadione treatment in a concentration-dependent manner. The defects included growth retardation, small head, eyes and acoustic capsule, deficient semicircular canals and otolith, and abnormal cardiovascular system. The number of hair cells in neuromast ML2 was obviously reduced in the treated larvae. Whole mount in situ hybridization indicated that the gene expression patterns of brain marker genes, such as zic1 and xb51, and autophagic gene atg5 was changed significantly. The result of RT-PCR showed that the expressions of hearing genes val and hmx2 were also changed in the trimethadione-treated embryos. All these findings suggest that brain tissue and the neural sensors for body balance and hearing are the main targets of trimethadione toxicity, and that zebrafish is able to mimic mammal responses to the teratogenicity and the neural toxicity of trimethadione in the embryonic and larva development.


Zhang Y.H.,Peking Union Medical College | An T.,Peking Union Medical College | Zhang R.C.,Peking Union Medical College | Zhou Q.,Peking Union Medical College | And 2 more authors.
Journal of Nutrition | Year: 2013

Fructose is widely used as a sweetener in the production of many foods, yet the relation between fructose intake and cholesterol remains uncertain. In this study, we performed a systematic review and meta-analysis of human, controlled, feeding trials involving isocaloric fructose exchange for other carbohydrates to quantify the effects of fructose on serumtotal cholesterol (TC), LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C) in adult humans. Weighted mean differences were calculated to determine changes from baseline cholesterol concentrations by means of generic, inverse variance, randomeffect models. The Heyland Methodological Quality was used to assess the quality of the study. Subgroup analyses and meta-regressionwere conducted to explore the possible influences of study characteristics. Twenty-four trials (with a total of 474 participants) were included in the meta-analysis. In an overall pooled estimate, it was shown that fructose exerted no effect on HDL-C. Meta-regression analysis indicated that fructose dose was positively correlated with the effect sizes of TC and LDL-C. Subgroup analyses showed that isocaloric fructose exchange for carbohydrates increased TC by 13.0 mg/dL [(95%CI: 4.7, 21.3); P = 0.002] and LDL-C by 11.6 mg/dL [(95%CI: 4.4, 18.9); P = 0.002] at >100 g fructose/d. However, no effect was shown on TC or LDL-C when the fructose intake was ≤100 g/d. In conclusion, it was shown that very high fructose intake (>100 g/d) increases serum LDL-C and TC concentrations. Larger, longer, and higher-quality human, controlled, feeding trials are needed to confirm these results. © 2013 American Society for Nutrition.


Wang S.,Peking Union Medical College | Tian Y.,Peking Union Medical College
Spine | Year: 2016

Study Design. Prospective study. Objective. The objectives of the study was to (1) seek a relation between motor evoked potential (MEP) and corresponding cervical cord function in cervical compression myelopathy (CCM) and (2) explore a high-sensitive MEP range that can predict the intraoperative monitoring change ahead in cervical spine surgery. Summary of Background Data. There have been lots of controversies concerning the application of transcranial MEP in cervical spine surgery. Methods. We prospectively investigate 86 consecutive patients with CCM who underwent posterior laminoplasty or laminectomy from December 2012 to September 2014. The 18-point modified Japanese Orthopedic Association (mJOA) score and intraoperative MEP were used for neurological and electrophysiological assessment. Statistical correlation analysis and curve fitting were used to definite the relationship between MEP and corresponding cervical cord function. And a novel concept of high-sensitive MEP range was firstly addressed for predicting the intraoperative monitoring change ahead in CCM. Results. Our results showed that the preoperative mJOA score of lower extremity presented a significant correlation with MEP parameters in CCM, and the correlation was expressed in an exponential relationship. The monitoring change in CCM often appeared at a high-sensitive MEP range (amplitude <159mV or latency >36.1 ms). In addition, the high-sensitive MEP ranges not only included MEP degeneration but also a larger number of MEP improvement cases. Conclusion. Intraoperative MEP may imply an exponential correlation with the corresponding cervical cord function in CCM. And we first characterize a high-sensitive MEP range which may indicate high risk for the impending monitoring change during cervical cord decompression and we must watch more closely. © 2016 Wolters Kluwer Health, Inc. All rights reserved.


Zhao J.-C.,Peking Union Medical College | Zhang L.-X.,Peking Union Medical College | Zhang Y.,Peking Union Medical College | Shen Y.-F.,Peking Union Medical College
Journal of Cellular Physiology | Year: 2012

Growth associated protein 43 (Gap43) is a neuron-specific phosphoprotein, which plays critical role in axon growth and synapses functions during neurogenesis. Here we identified two transcription start sites (TSSs) of the mouse Gap43 gene designated as a proximal site at +1, and a distal TSS at -414. RT-qPCR data reveal that the transcripts from +1 increase 10-fold on day-1 post-all-trans retinoic acid (RA) treatment, reached a peak value at day-4 and gradually reduced. By contrast, the distal TSS directs a late, remarkably sharp increase of the transcripts from the day-5 on. An intense signal of Gap43 at the neurites and neural network is determined by the efficient transcription of the distal promoter as shown in Northern blot and RT-qPCR assay. In addition, the targeting of p300 in combination with a differential enrichment of Brm to Brg1 change at the distal promoter region of the gene is induced under RA treatment. The over hundreds of GA rich stretches and the GAGAG elements located between the two TSSs may take parts in the differential transcription of the two TSSs of the Gap43. Our findings provide the first evidence on the identification and differential transcription of the two TSSs of the mouse Gap43 gene, and the preferential distribution of their protein products in the specific stages of RA induced P19 differentiation. These data suggest the efficient transcription of the distal promoter of Gap43 is an important mark for the transition of P19 cells from the progenitor stage into neuronal differentiation. © 2011 Wiley Periodicals, Inc.


Song D.,University of Pennsylvania | Song D.,Peking Union Medical College | Song Y.,University of Pennsylvania | Hadziahmetovic M.,University of Pennsylvania | And 2 more authors.
Free Radical Biology and Medicine | Year: 2012

Oxidative stress plays a key role in a light-damage (LD) model of retinal degeneration as well as in age-related macular degeneration (AMD). Since iron can promote oxidative stress, the iron chelator deferiprone (DFP) was tested for protection against light-induced retinal degeneration. To accomplish this, A/J mice were treated with or without oral DFP and then were placed in constant bright white fluorescent light (10,000 lx) for 20 h. Retinas were evaluated at several time points after light exposure. Photoreceptor apoptosis was assessed using the TUNEL assay. Retinal degeneration was assessed by histology 10 days after exposure to damaging white light. Two genes upregulated by oxidative stress, heme oxygenase 1 (Hmox1) and ceruloplasmin (Cp), as well as complement component 3 (C3) were quantified by RT-qPCR. Cryosections were immunolabeled for an oxidative stress marker (nitrotyrosine), a microglial marker (Iba1), as well as both heavy (H) and light (L) ferritin. Light exposure resulted in substantial photoreceptor-specific cell death. Dosing with DFP protected photoreceptors, decreasing the numbers of TUNEL-positive photoreceptors and increasing the number of surviving photoreceptors. The retinal mRNA levels of oxidative stress-related genes and C3 were upregulated following light exposure and diminished by DFP treatment. Immunostaining for nitrotyrosine indicated that DFP reduced the nitrative stress caused by light exposure. Robust H/L-ferritin-containing microglial activation and migration to the outer retina occurred after light exposure and DFP treatment reduced microglial invasion. DFP is protective against light-induced retinal degeneration and has the potential to diminish oxidative stress in the retina. © 2012 Elsevier Inc.


Kang R.-X.,Peking Union Medical College | Zhang J.-J.,Peking Union Medical College
Biochemical and Biophysical Research Communications | Year: 2012

Hyperhomocysteinemia is believed to induce endothelial dysfunction, which is an independent risk factor for atherosclerosis and vascular diseases. Compound FLZ is a novel synthetic squamosamide cyclic analog with several phenolic hydroxy groups, and exhibits strong anti-oxidative and neuroprotective activities in Alzheimer's and Parkinson's models. In the present study, we examined the actions of FLZ against homocysteine-induced injury to primary cultured rat brain microvascular endothelial cell (rBMECs). Cell survival was measured by MTT assay. Cell nuclei were observed by Hoechst 33342 staining. Senescent cells were detected by senescence-associated β-galactosidase (SA-β-gal) staining. Reactive oxygen species (ROS) were measured by 2',7'-dichlorofluorescein (DCF) fluorescent microscopy. Homocysteine-induced expression of NF-κB, p53, Noxa and Fas, and the release of mitochondrial cytochrome c, were measured by Western blotting. We found that FLZ treatment antagonized homocysteine-induced cell death and apoptosis and increased numbers of senescent cells. These changes were correlated with decreased ROS accumulation. FLZ treatment inhibited activation of NF-κB, the upregulation of p53, Noxa, and Fas, and blocked mitochondrial cytochrome c release. These data suggest that FLZ has a protective action against homocysteine-induced toxicity in rBMECs, suggesting that FLZ may have therapeutic potential for the prevention of cardiovascular diseases. © 2011 Elsevier Inc.


Dong M.,Peking Union Medical College
Zhonghua zhong liu za zhi [Chinese journal of oncology] | Year: 2010

To assess the efficacy of calcium-magnesium (Ca/Mg) infusion and glutathione (GSH) for preventing the neurotoxicity induced by oxaliplatin. This is a randomized, double blind, placebo controlled clinical trail. The patients receiving FOLFOX4 chemotherapy for their solid tumor were randomized to receive Ca/Mg, GSH or normal saline with chemotherapy simultaneously. The incidence and severity of oxaliplatin-induced neurotoxicity were observed. The ECOG performance status was recorded and compared among the 3 groups. Ninety-three patients admitted in our department from Mar 2006 to Dec 2007 were entered into this study, including 29 patients in the Ca/Mg group, 33 in the GSH group and 31 in the chemotherapy alone group. The incidences of acute neurotoxicity were 82.8%, 90.9% and 93.5%, respectively. At the third cycle, the incidences of grade 1-2 chronic neurotoxicity were 37.9%, 48.5% and 42.0%, respectively. No grade 3 neuropathy was observed. After 6 cycles, the incidence of grade 1-2 neuropathy was increased to 68.2%, 88.9% and 85.2%, respectively. A lower percentage was observed in Ca/Mg arm without a statistically significant difference, and grade 3 neuropathy occurred in 5 patients. After 9 cycles, the incidence of grade 1-2 neuropathy was increased to 81.3%, 90.0% and 92.9%, respectively. Grade 3 neuropathy occurred in another 2 patients. No statistically significant difference was observed among the 3 arms. Changes of patient's ECOG score after chemotherapy were similar. This study didn't provide evidence that Ca/Mg infusion and GSH can prevent the oxaliplatin-induced neurotoxicity.


Sankaranarayanan R.,The International Agency for Research on Cancer | Ramadas K.,Regional Cancer Center | Qiao Y.-L.,Peking Union Medical College
BMC Medicine | Year: 2014

Asia accounts for 60% of the world population and half the global burden of cancer. The incidence of cancer cases is estimated to increase from 6.1 million in 2008 to 10.6 million in 2030, due to ageing and growing populations, lifestyle and socioeconomic changes. Striking variations in ethnicity, sociocultural practices, human development index, habits and dietary patterns are reflected in the burden and pattern of cancer in different regions. The existing and emerging cancer patterns and burden in different regions of Asia call for political recognition of cancer as an important public health problem and for balanced investments in public and professional awareness. Prevention as well as early detection of cancers leads to both better health outcomes and considerable savings in treatment costs. Cancer health services are still evolving, and require substantial investment to ensure equitable access to cancer care for all sections of the population. In this review, we discuss the changing burden of cancer in Asia, along with appropriate management strategies. Strategies should promote healthy ageing via healthy lifestyles, tobacco and alcohol control measures, hepatitis B virus (HBV) and human papillomavirus (HPV) vaccination, cancer screening services, and vertical investments in strengthening cancer healthcare infrastructure to improve equitable access to services. © 2014 Sankaranarayanan et al.; licensee BioMed Central Ltd.


Zheng J.,Peking Union Medical College | Liu L.,Peking Union Medical College | Wang J.,Peking Union Medical College | Jin Q.,Peking Union Medical College
BMC Genomics | Year: 2013

Background: Progress in the fields of protein separation and identification technologies has accelerated research into biofluids proteomics for protein biomarker discovery. Urine has become an ideal and rich source of biomarkers in clinical proteomics. Here we performed a proteomic analysis of urine samples from pregnant and non-pregnant patients using gel electrophoresis and high-resolution mass spectrometry. Furthermore, we also apply a non-prefractionation quantitative phosphoproteomic approach using mTRAQ labeling to evaluate the expression of specific phosphoproteins during pregnancy comparison with non-pregnancy. Results: In total, 2579 proteins (10429 unique peptides) were identified, including 1408 from the urine of pregnant volunteers and 1985 from the urine of non-pregnant volunteers. One thousand and twenty-three proteins were not reported in previous studies at the proteome level and were unique to our study. Furthermore, we obtained 237 phosphopeptides, representing 105 phosphoproteins. Among these phosphoproteins, 16 of them were found to be significantly differentially expressed, of which 14 were up-regulated and two were down-regulated in urine samples from women just before vaginal delivery.Conclusion: Taken together, these results offer a comprehensive urinary proteomic profile of healthy women during before and after vaginal delivery and novel information on the phosphoproteins that are differentially regulated during the maintenance of normal pregnancy. Our results may provide a better understanding of the mechanisms of pregnancy maintenance, potentially leading to the development of biomarker-based sensitive assays for understanding pregnancy. © 2013 Zheng et al.; licensee BioMed Central Ltd.


Cheng M.,Peking Union Medical College | Hu Z.,Peking Union Medical College | Lu X.,Peking Union Medical College | Huang J.,Peking Union Medical College | Gu D.,Peking Union Medical College
Canadian Journal of Cardiology | Year: 2014

Background: The association between habitual caffeine intake with incident atrial fibrillation (AF) was unknown. We conducted a meta-analysis to investigate the association between chronic exposure of caffeine and the risk of AF and to evaluate the potential dose-response relation. Methods: We searched PubMed, EMBASE, and the Cochrane Library up to November 2013 and references of relevant retrieved articles. Prospective cohort studies were included with relative risk (RR) or hazard ratio and 95% confidence intervals (CIs) for AF according to coffee/caffeine intake. Results: Six prospective cohort studies with 228,465 participants were included. In the primary meta-analysis, caffeine exposure was weakly associated with a reduced risk of AF (RR, 0.90; 95% CI, 0.81-1.01; P=0.07; I2= 73%). In subgroup analyses, pooled results from studies with adjustment of potential confounders showed an 11% reduction for low doses (RR, 0.89; 95% CI, 0.80-0.99, P= 0.032; I2= 30.9%, P= 0.227) and 16% for high doses (RR, 0.84; 95% CI, 0.75-0.94, P=0.002; I2= 24.1%, P= 0.267) of caffeine consumption in AF risk. An inverse relation was found between habitual caffeine intake and AFrisk (P for overall trend= 0.015; P for nonlinearity= 0.27) in dose-response meta-analysis and the incidence of AF decreased by 6% (RR, 0.94; 95% CI, 0.90-0.99) for every 300 mg/d increment in habitual caffeine intake. Conclusions: It is unlikely that caffeine consumption causes or contributes to AF. Habitual caffeine consumption might reduce AF risk. © 2014 Canadian Cardiovascular Society.


Yu X.,Peking Union Medical College | Li Z.,Peking Union Medical College | Chen G.,Jilin University | Wu W.K.K.,Chinese University of Hong Kong
Current Vascular Pharmacology | Year: 2015

Abnormal proliferation of vascular smooth muscle cells (VSMCs) contributes significantly to the pathogenesis of atherosclerosis. MiR-10b has recently emerged as a critical mediator in regulating cell proliferation in many diseases. In our study, miR-10b expression was up-regulated in VSMCs isolated from atherosclerotic plaques, as well as in PDGF-stimulated VSMCs.Overexpression of miR-10b promoted cell proliferation of VSMCs. Furthermore, we identified the Tat-interacting protein 30 (TIP30) as a direct target gene of miR-10b. TIP30 was down-regulated in VSMCs isolated from atherosclerosis plaques, as well as in proliferative VSMCs. Knockdown of TIP30 promoted VSMCs proliferation. In addition, miR-10b induced TIP30 down-regulation was accompanied by increased Akt phosphorylation. Akt was critical for miR-10b-mediated VSMCs proliferation. Our results demonstrated that miR-10b contributed to abnormal VSMCs proliferation through inhibiting the Akt pathway by targeting TIP30 in atherosclerosis. The modulation of miR-10b in VSMCs provides a potential target for the therapy of atherosclerosis. © 2015 Bentham Science Publishers.


To study the efficacy and safety of estradiol and drospirenone tablets (Angeliq) in treatment of menopausal symptoms among postmenopausal Chinese healthy women. Total 244 postmenopausal Chinese healthy women who had moderate to severe hot flushes were randomly assigned into estradiol and drospirenone (observation group, n = 183) or placebo group (n = 61) by the ratio of 3:1 for 16 weeks in this randomized multi-center double-blind placebo-controlled study. During the trial, the follow-up visits were conducted at week 4, 8, 12, 16 of treatment and 2 weeks after treatment respectively. Height, weight, vital signs, hot flushes, other relevant menopausal symptoms and vaginal bleeding were observed in each follow-up visit, while the clinical global impression scale was assessed at 16 weeks as well. It showed that hot flushes were reduced significantly more in observation group than that in placebo group (P < 0.01), although both treatments were effective. The absolute values of mean severity index of total hot flushes decreased by -0.6 ± 0.5 in observation group and -0.4 ± 0.4 in placebo group from baseline respectively, which reached significant difference (P < 0.05). However, the absolute values of mean severity index of moderate to severe hot flushes decreased by -0.6 ± 0.8 in observation group and -0.3 ± 0.6 in placebo group from baseline respectively, which had no significant difference (P > 0.05). After 16 weeks treatment, it also showed that estradiol and drospirenone had significant better efficacy than placebo on moderate to severe sweating, vaginal dryness and clinical global impression scale (P < 0.01). During the trial, blood pressure in observation group was stable. The rate of vaginal bleeding in observation group was higher than that in the placebo group, especially during the week 4 to week 8 when 48.9% (87/178) in observation group and 10.7% (6/56) in placebo group of patients bled. Although the cumulative amenorrhea rate of observation group was lower than that of placebo group in each cycle (28 days), it increased gradually along with duration of the treatment. The commonest adverse event in observation group was breast tenderness which accounted for 12.0% (22/183). The level of serum potassium was in the normal range in observation group mostly.Meanwhile, the other adverse events rate was low. Serious adverse events reported in this trial were assessed as not study drug related or as unlikely study drug related. Estradiol and drospirenone tablets which could effectively alleviate menopausal symptoms in postmenopausal Chinese healthy women is a novel hormone replacement therapy regimen with high safety and efficacy.


The long term use of Rheum palmatum for the treatment of diseases associated with chronic hepatitis and renal failure can lead to liver and kidney damage. To reduce the toxicity of R. palmatum and alleviate any symptoms of decanta and celialgia, the raw material has been subjected to a specific process prior to its use for hundreds of years. Despite its extensive use in medicine, very little is currently known about the nature of the components present in this material in terms of their efficacy and overall toxicity, and the effect that processing has on the levels of these components in the processed material. The aim of this investigation was to explore potential differences in the chemical markers between batches of raw and processed R. palmatum and to develop a deeper understanding of the underlying mechanisms responsible for the enhanced efficacy and reduced toxicity of the processed material. Raw and processed R. palmatum samples were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) coupled with multivariate statistical analysis using principal component analysis (PCA) and orthogonal partial least square discriminant analysis (OPLS-DA). The emodin-8-O-glucoside, emodin-O-glucoside, catechin-glucopyranoside, gallic acid-3-O-glucoside, torachrysone, and chrysophanol dimethyl ether were rapidly explored as representative markers to distinguish for the first time between the raw and processed R. palmatum material. Among the potential chemical markers, Emodin-8-O-glucoside and gallic acid-3-O-glucoside were determined to be the best markers for the raw and processed R. palmatum. UPLC/Q-TOF-MS with multivariate statistical analysis represents an efficient method for exploring the chemical markers in the raw and processed R. palmatum material, as well as investigating the mechanisms associated with the processing, quality control, and safe application of R. palmatum.


Zinc phthalocyanine labelled polyethylene glycol was prepared to track and monitor the in vivo fate of polyethylene glycol. The chemical structures were characterized by nuclear magnetic resonance and infrared spectroscopy. Their light stability and fluorescence quantum yield were evaluated by UV-Visible and fluorescence spectroscopy methods. The interaction of zinc phthalocyanine labelled polyethylene glycol with bovine serum albumin was evaluated by fluorescence titration and isothermal titration calorimetry methods. Optical imaging in vivo, organ aggregation as well as distribution of fluorescence experiments for tracking polyethylene glycol were performed with zinc phthalocyanine labelled polyethylene glycol as fluorescent agent. Results show that zinc phthalocyanine labelled polyethylene glycol has good optical stability and high emission ability in the near infrared region. Imaging results demonstrate that zinc phthalocyanine labelled polyethylene glycol can track and monitor the in vivo process by near infrared fluorescence imaging, which implies its potential in biomaterials evaluation in vivo by a real-time noninvasive method.


Yu X.,Peking Union Medical College | Li Z.,Peking Union Medical College
Oncology Letters | Year: 2015

The recognition of the biological relevance of long non‑coding RNA (lncRNA) molecules has only recently been recognized as one of the most significant advances in contemporary molecular biology. A growing body of evidence indicates that lncRNAs act not only as the intermediary between DNA and protein but also as significant protagonists of cellular functions. The dysregulation of lncRNAs has increasingly been linked to numerous human diseases, particularly cancers. Recent studies have demonstrated that the lncRNA growth arrest-specific transcript 5 (GAS5) was pervasively downexpressed in most human cancers compared with non‑cancerous adjacent tissues including gastric, breast, lung and prostate cancer. In addition, patients with decreased GAS5 expression have a significantly poorer prognosis than those with higher expression. Furthermore, GAS5 is involved in the control of cell apoptosis, proliferation, metastasis, angiogenesis, DNA repair and tumor cell metabolism. This review provides an overview of the current knowledge concerning the role of GAS5 in tumor expression and biology function. © 2015, Spandidos Publications. All rights reserved.


Zhang W.,Peking Union Medical College | Liu J.,Peking Union Medical College | Tabata Y.,Kyoto University | Meng J.,Peking Union Medical College | Xu H.,Peking Union Medical College
Biomaterials | Year: 2014

Serum in the culture medium is one crucial factor that compromises RNAi efficiency of non-viral vectors. However, mechanistic roles of serum in siRNA delivery remain unknown. In this work, we took one cationic polymer, pullulan chemically modified by spermine (termed as pullulan-spermine, Ps), as a siRNA carrier model to investigate the effects of serum on key steps in siRNA delivery including formation of Ps and siRNA polyplexes (Ps-siRNA), cellular uptake, lysosomal escape, and cytotoxicity. We demonstrate that low serum concentration (1.25% and 2.5%) in culture medium results in large particles of Ps-siRNA, while high serum concentration (10%-40%) leads to small particles of Ps-siRNA. The larger particles initiated the internalization of siRNA more effectively in comparison to the smaller ones. The engulfed Ps-siRNA particles mainly locate in lysosomes. The large particles exhibited stronger abilities of destabilizing lysosomes than that of the small particles as large Ps-siRNA particles contain more amines and subsequently elicit a stronger proton sponge effect which results in more effective lysosomal escape of siRNA. Despite the lower RNAi efficiency, the small particle of Ps-siRNA in the high serum medium generates much lower cytotoxicity. These findings explain why serum significantly affects RNAi and also propose a strategy for improving RNAi efficiency and safety by modulating serum concentration and enhancing lysosomal destabilization. © 2013 Elsevier Ltd.


Wu C.,Peking Union Medical College | Dai R.,Peking Union Medical College | Dong F.,Peking Union Medical College | Wang Q.,Peking Union Medical College
American Journal of Ophthalmology | Year: 2014

PURPOSE: To investigate clinical characteristics of Purtscher-like retinopathy and its clinical implications among patients with systemic lupus erythematosus (SLE).DESIGN: Observational case series.METHODS: SETTING: Tertiary medical center. PATIENT POPULATION: Patients with SLE who were diagnosed with Purtscher-like retinopathy between 2002 and 2013. observation procedures: Assessment and follow-up in the ophthalmology department. main OUTCOME MEASURE: Visual acuity and funduscopic examination at presentation and at 6 month follow-up, with analysis of the association between Purtscher-like retinopathy and other systemic involvement of SLE and overall disease activity.RESULTS: Among 5688 patients with SLE evaluated, 8 cases of Purtscher-like retinopathy were diagnosed. Typical fundus abnormalities included Purtscher flecken, cotton-wool spots, retinal hemorrhages, macular edema, optic disk swelling, and a pseudo-cherry red spot. Fluorescein angiography abnormalities included areas of capillary nonperfusion corresponding to the retinal whitening, late leakage, peripapillary staining, precapillary occlusion, and slower filling of vessels. The prevalence of central nervous system lupus was significantly higher among those with Purtscher-like retinopathy (6/8) than among 240 patients randomly sampled from those without Purtscher-like retinopathy. A very high SLE Disease Activity Index (≥20) was present in all 8 patients with Purtscher-like retinopathy. All patients received corticosteroids combined with immunosuppressants. For the majority of patients, optic atrophy developed during follow-up with persistent low visual acuity. Conclusion As a rare and severe ophthalmic complication of SLE, Purtscher-like retinopathy was associated with central nervous system lupus and highly active disease. Visual acuity recovery was usually poor despite prompt treatment. © 2014 Elsevier Inc. All rights reserved.


To compare the plasma concentrations of N-terminal brain natriuretic peptide precursor (NT-proBNP) in patients with heart failure due to various heart diseases and analyze the influencing factors. We enrolled a total of 804 heart failure patients due to various heart diseases, including valvular heart disease (VHD), dilated cardiomyopathy (DCM), ischemic heart diseases (IHD), restrictive cardiomyopathy (RCM), hypertensive heart disease (HHD), hypertrophic cardiomyopathy (HCM), pulmonary heart disease (PHD) and adult congenital heart disease (CHD). The plasma concentration of NT-proBNP was measured by enzyme-linked immunosorbent assay (ELISA). Multiple linear regression analysis was used to detect the influencing factors for the plasma concentration of NT-proBNP. The plasma concentration of NT-proBNP had no significant difference between patients with VHD, DCM, IHD, RCM, HCM, PHD, HHD and CHD. The median (25 percent, 75 percent) values were 1866 (803 - 3973), 2247 (1087 - 3865), 2400 (1182 - 4242), 2456 (1385 - 5839), 2204 (1053 - 3186), 2285 (1155 - 3424), 2313 (655 - 3850) and 2768 (795 - 4371) pmol/L respectively (P > 0.05). It increased with New York Heart Association (NYHA) class from II through III to IV. The median (25 percent, 75 percent) values were 646 (447 - 1015), 2160 (1118 - 3750) and 3342 (1549 - 5455) pmol/L respectively (P < 0.01). The patients with a body mass index (BMI) of ≥ 25 kg/cm(2) had a lower NT-proBNP concentration than those with a BMI of < 25 kg/cm(2). The median (25 percent, 75 percent) values were 1468 (784 - 3177) and 2424 (1090 - 4213) pmol/L respectively (P < 0.01). Patients with a serum creatinine concentration of ≥ 107 μmol/L had a higher NT-proBNP concentration than those < 107 μmol/L. The median (25 percent, 75 percent) values were 3337 (1470 - 5380) and 1644 (781 - 3375) pmol/L respectively (P < 0.01). Multiple linear regression analysis demonstrated that NYHA class, creatinine, BMI, hepatic damage and diastolic pressure were independently associated with the plasma concentration of NT-proBNP (all P < 0.01). The plasma concentration of NT-proBNP has no significant difference between heart failure patients due to various heart diseases. Its level may be affected by NYHA class, serum creatinine, BMI, hepatic damage and diastolic pressure.


Yang X.O.,Peking Union Medical College
Zhonghua nei ke za zhi [Chinese journal of internal medicine] | Year: 2011

To investigate the value of plasma chromogranin A (CgA) in the diagnosis of neuroendocrine tumors (NETs), and to evaluate the diagnostic efficacy of plasma CgA in different gastrointestinal pancreatic neuroendocrine tumors (GEP NETs). To investigate the role of monitoring plasma CgA in the progress of GEP NETs. ELISA kits were used to measure the CgA plasma level in 56 cases of GEP NETs, 52 cases of pheochromocytoma, and 7 cases of small cell lung cancer (SCLC) and 52 cases of normal controls respectively. The sensitivity and specificity of plasma CgA in diagnosis of gastrointestinal pancreatic endocrine tumor; pheochromocytomas and SCLC were calculated. The group of GEP NETs included 13 cases of gastrointestinal carcinoid tumors, 13 cases of gastrinomas, 12 cases of islet cell tumors and 18 cases of other type tumors of GEP NETs. The differences of plasma CgA levels and various sensitivities were compared in different types tumors of GEP NETs. Meanwhile the value of plasma CgA in the diagnosis of metastatic and nonmetastatic tumors in GEP NETs was determined. The median CgA levels and quartile of the groups of GEP NETs, pheochromocytomas and SCLCs were 84.5 U/L and 38.3 - 175.5 U/L, 154.0 U/L and 53.3 - 243.8 U/L, and 55.0 U/L and 19.0 - 79.0 U/L respectively, which were significantly higher than that of (18.5 U/L and 12.3 - 25.8 U/L) normal controls (P < 0.001). The sensitivities of CgA in diagnosis of GEP NETs, pheochromocytomas and SCLCs were 82.1%, 88.5% and 57.1% respectively, and the specificities were all 96.2%. In the group of GEP NETs, the CgA level of gastrinoma was significant higher than the groups of carcinoid, islet cell tumor, and other type tumors of GEP NETs. The sensitivities of CgA in diagnosis of gastrinoma, carcinoid tumors, and islet cell tumors were 92.3%, 84.6% and 50.0% respectively. In the group of GEP NETs, it showed significant differences in CgA levels in patients with metastatic and non-metastatic tumors. The plasma CgA levels were elevated significantly in the GEP NETs, and showed a high sensitivity and specificity particularly in the diagnosis of gastrinoma. CgA also can be used as a marker in monitoring tumor development and evaluating prognosis during the clinical application.


Bai Y.,Peking Union Medical College
Molecular and cellular biochemistry | Year: 2012

Heart failure (HF) is a complex clinical syndrome and is thought to have a genetic basis. Numerous case-control studies have investigated the association between heart failure and polymorphisms in candidate genes. Most studies focused on the angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphism, however, the results were inconsistent because of small studies and heterogeneous samples. The objective was to assess the association between the ACE I/D polymorphism and HF. We performed a meta-analysis of all case-control studies that evaluated the association between ACE I/D polymorphism and HF in humans. Studies were identified in the PUBMED and EMBASE databases, reviews, and reference lists of relevant articles. Two reviewers independently assessed the studies. Seventeen case-control studies with a total of 5576 participants were included in the meta-analysis, including 2453 cases with HF and 3123 controls. The heterogeneity between studies was significant. No association was found under all the four genetic models (D vs. I, DD vs. ID and II, DD and ID vs. II, DD vs. ID). Subgroup analyses for ischemic HF (IHF) and HF because of dilated cardiomyopathy (DHF) also showed no significant association between ACE I/D polymorphism and HF. No significant association between the ACE I/D polymorphism and risk of HF was found in this meta-analysis. The future studies should focus on large-scale prospective and case-control studies which designed to investigate gene-gene and gene-environment interactions to shed light on the genetics of HF.


Ren G.-X.,Peking Union Medical College | Yan H.-Q.,Peking Union Medical College | Yan H.-Q.,Bengbu Medical College | Zhu H.,Peking Union Medical College | And 2 more authors.
Environmental Microbiology | Year: 2014

Summary: Yersinia pestis, the cause of plague, forms a biofilm in the foregut of its flea vector to enhance transmission. Biofilm formation in Y.pestis is controlled by the intracellular levels of the second messenger molecule cyclic diguanylate (c-di-GMP). HmsT and Y3730, the two diguanylate cyclases (DGC) in Y.pestis, are responsible for the synthesis of c-di-GMP. Y3730, which we name here as HmsD, has little effect on in vitro biofilms, but has a major effect on biofilm formation in the flea. The mechanism by which HmsD plays differential roles in vivo and in vitro is not understood. In this study, we show that hmsD is part of a three-gene operon (y3729-31), which we designate as hmsCDE. Deletion of hmsC resulted in increased, hmsD-dependent biofilm formation, while deletion or overexpression of hmsE did not affect biofilm formation. Localization experiments suggest that HmsC resides in the periplasmic space. In addition, we provide evidence that HmsC might interact directly with the periplasmic domain of HmsD and cause the proteolysis of HmsD. We propose that HmsC senses the environmental signals, which in turn regulates HmsD, and controls the c-di-GMP synthesis and biofilm formation in Y.pestis. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.


Wang B.,Peking Union Medical College | Xi X.,Peking Union Medical College | Lei X.,Peking Union Medical College | Zhang X.,Shanxi Medical University | And 4 more authors.
PLoS Pathogens | Year: 2013

Enterovirus 71 (EV71) is the major causative pathogen of hand, foot, and mouth disease (HFMD). Its pathogenicity is not fully understood, but innate immune evasion is likely a key factor. Strategies to circumvent the initiation and effector phases of anti-viral innate immunity are well known; less well known is whether EV71 evades the signal transduction phase regulated by a sophisticated interplay of cellular and viral proteins. Here, we show that EV71 inhibits anti-viral type I interferon (IFN) responses by targeting the mitochondrial anti-viral signaling (MAVS) protein-a unique adaptor molecule activated upon retinoic acid induced gene-I (RIG-I) and melanoma differentiation associated gene (MDA-5) viral recognition receptor signaling-upstream of type I interferon production. MAVS was cleaved and released from mitochondria during EV71 infection. An in vitro cleavage assay demonstrated that the viral 2A protease (2Apro), but not the mutant 2Apro (2Apro-110) containing an inactivated catalytic site, cleaved MAVS. The Protease-Glo assay revealed that MAVS was cleaved at 3 residues between the proline-rich and transmembrane domains, and the resulting fragmentation effectively inactivated downstream signaling. In addition to MAVS cleavage, we found that EV71 infection also induced morphologic and functional changes to the mitochondria. The EV71 structural protein VP1 was detected on purified mitochondria, suggesting not only a novel role for mitochondria in the EV71 replication cycle but also an explanation of how EV71-derived 2Apro could approach MAVS. Taken together, our findings reveal a novel strategy employed by EV71 to escape host anti-viral innate immunity that complements the known EV71-mediated immune-evasion mechanisms. © 2013 Wang et al.


Liu Z.,Jewish General Hospital | Pan Q.,Jewish General Hospital | Ding S.,Jewish General Hospital | Ding S.,McGill University | And 8 more authors.
Cell Host and Microbe | Year: 2013

The interferon-inducible myxovirus resistance (Mx) proteins play important roles in combating a wide range of virus infections. MxA inhibits many RNA and DNA viruses, whereas the antiviral activity of MxB is less well established. We find that human MxB inhibits HIV-1 infection by reducing the level of integrated viral DNA. Passaging HIV-1 through MxB-expressing cells allowed the evolution of a mutant virus that escapes MxB restriction. HIV-1 escapes MxB restriction by mutating the alanine residue at position 88 in the viral capsid protein (CA), with a consequent loss of CA interaction with the host peptidylprolyl isomerase cyclophilin A (CypA), suggesting a role for CypA in MxB restriction. Consistent with this, MxB associates with CypA, and shRNA-mediated CypA depletion or cyclosporine A treatment resulted in the loss of MxB inhibition of HIV-1. Taken together, we conclude that human MxB protein inhibits HIV-1 DNA integration by a CypA-dependent mechanism. © 2013 Elsevier Inc.


Ma G.-L.,Peking Union Medical College
National Medical Journal of China | Year: 2013

Objective: To analyze the 64-slice computed tomographic (CT) perfusion parameters of hepatocellular carcinoma (HCC) nodule so as to assess the diagnostic value of hemodynamic changes of HCC nodule by this perfusion technique. Methods: Forty volunteers without liver disease (control subjects) and 37 HCC patients (experimental group) were selected. After informed consents, all of them underwent plain, perfusion and contrast CT examinations. Perfusion CT scan was performed at 120 kV, 60 mA and a thickness of up to 40 mm. The injection rate of contrast medium was 4-5 ml/sec at a dose of 1.0 ml/kg body weight. And 50 seconds of continuous scanning time was set at 5 seconds post-injection. The indices were 1 second per 360° revolution, 5 mm slice thickness image reconstruction and a matrix size of 512 × 512 pixels. Perfusion parameters associated with changes in hepatic blood flow included blood flow (HBF), hepatic blood volume (HBV), hepatic arterial perfusion index (HAI), hepatic artery perfusion (HAP) and portal venous perfusion (HPP). Perfusion parameters were measured thrice at each timepoint for each different region of interest (ROI): hepatic parenchyma surrounding HCC nodule, HCC nodule and normal liver parenchyma (control group). Results: For HCC nodule, the increased levels of HBF, HAP and HAI were significantly differentiated from normal liver parenchyma of control group (P < 0.01). Increased HBV and decreased HPP had no difference from control group (P > 0.05). Higher levels of HAP, HPP and HAI in HCC nodules were differentiated from hepatic parenchyma surrounding HCC nodules (P < 0.05). HBV decreased and HBF increased in HCC nodule. But it had no differences from hepatic parenchyma surrounding HCC nodule (P > 0.05). Conclusion: Perfusion CT may visualize the status of liver blood flow caused by HCC nodule so as to serve as a new tool of studying the hemodynamic changes of HCC nodules. Copyright © 2013 by the Chinese Medical Association.


Yang D.,Peking Union Medical College | Liu Z.,Peking Union Medical College | Yang H.,Wenzhou Medical College
Diabetes/Metabolism Research and Reviews | Year: 2012

Previous studies on the effects of continuous positive airway pressure (CPAP) on homeostasis model assessment insulin resistance (HOMA-IR) in obstructive sleep apnea patients have yielded conflicting results. Therefore, we conducted this meta-analysis to evaluate the impact of effective CPAP on HOMA-IR in non-diabetic patients with moderate to severe obstructive sleep apnea. We searched PubMed, HighWire Press, Ovid Medline (R), Cochrane library and EMBASE before December 2011 on original English language studies. The data on HOMA-IR and body mass index (BMI) were extracted from these studies. As compared with baseline values, 8 to 24weeks of effective CPAP (>4h/night) treatment significantly reduced HOMA-IR by an average of 0.75(95% CI, from -0.96 to -0.53; p<0.001). However, in subjects with irregular CPAP (<4h/night), this effect was not observed (-0.22; 95%CI, from -2.24 to 1.80; p=0.83). There were no intervention-related changes in BMI in both regular and irregular CPAP. Our analysis showed that 8 to 24weeks of effective CPAP could significantly improve HOMA-IR in non-diabetic patients with moderate to severe obstructive sleep apnea, while no significant changes in BMI were detected. Further large scale, randomized and controlled trials are needed to evaluate the longer treatment and its possible effects on weight control and cardiovascular disease. © 2012 John Wiley & Sons, Ltd.


To investigate the characteristics of the anatomical distribution of posterior deeply infiltrating endometriosis (PDIE) lesions, pain symptoms and effects of laparoscopic surgery. Clinical data of 176 PDIE patients with laparoscopically diagnosed and histologically confirmed were analyzed and compared with data of 179 cases with non-PDIE. According to the invasion of rectum or vaginal fornix, 176 PDIE cases were divided into three groups: simple (144 cases), fornix (18 cases) or rectum group (14 cases). Compared with the non-PDIE patients, the risk of pain symptoms in PDIE patients were significantly increased, OR for dysmenorrhea, chronic pelvic pain, deep dyspareunia, dyschezia were 6.73 (95%CI, 3.66-12.40), 1.90 (95%CI, 1.17-3.05), 3.09 (95%CI, 1.94-4.92) and 4.90 (95%CI, 2.07-8.11), respectively (all P < 0.05). The highest incidence of dyschezia was observed in rectum group (50.0%, P < 0.05), while deep dyspareunia in fornix group (72.2%, P < 0.05). The longest operative duration (82 +/- 31) minutes and the postoperative hospitalization (7.7 +/- 2.1) days were observed in rectum group (P < 0.01). The median pain relief time was 56 months in the patients with complete excision of PDIE lesions, which was significantly longer than that in patients with incomplete excision (25 months, P < 0.01). Multivariate analysis demonstrated that only incomplete excision of PDIE lesions was the risk factor for shorter pain relief time (P < 0.05). Conservative laparoscopic surgery may effectively relieve pelvic pain symptoms in patients with PDIE, while incomplete excision of PDIE lesions was the only significant predictor of shorter pain relief time.


Liu C.Z.,Peking Union Medical College
Chinese medical sciences journal = Chung-kuo i hsüeh k'o hsüeh tsa chih / Chinese Academy of Medical Sciences | Year: 2012

To investigate the expression profile of microRNA-21 in human cholangiocarcinoma tissues and to validate its bona fide targets in human cholangiocarcinoma cells. The expression profile of microRNA-21 in human cholangiocarcinoma tissues and cholangiocarcinoma cell line, QBC939, was evaluated by using real-time PCR analysis. The bona fide targets of microRNA-21 were analyzed and confirmed by dual luciferase reporter gene assay and western blot, respectively. The expressional correlation of microRNA-21 and its targets was probed in human cholangiocarcinoma tissues by using real-time PCR, locked nucleic acid in situ hybridization (LNA-ISH), and immunohistochemistry analysis. Real-time PCR analysis revealed that microRNA-21 expression depicted a significant up-regulation in human cholangiocarcinoma tissues about 5.6-fold as compared to the matched normal bile duct tissues (P<0.05). The dual luciferase reporter gene assay revealed endogenous microRNA-21 in cholangiocarcinoma cell line, QBC939, inhibited the luciferase reporter activities of wild-type PTEN (P<0.01) and PDCD4 (P<0.05) and had no this effect on mutated PTEN and PDCD4. Moreover, loss of microRNA-21 function led to a significant increase of PTEN and PDCD4 protein levels in QBC939 cells. Elevated microRNA-21 levels were accompanied by marked reductions of PTEN and PDCD4 expression in the same cholangiocarcinoma tissue. microRNA-21 expression is up-regulated in human cholangiocarcinoma and PTEN, PDCD4 are direct effectors of microRNA-21.


She Z.-G.,Peking Union Medical College | Chen H.-Z.,Peking Union Medical College | Yan Y.,Peking Union Medical College | Li H.,Peking Union Medical College | Liu D.-P.,Peking Union Medical College
Antioxidants and Redox Signaling | Year: 2012

The paraoxonase (PON) gene cluster contains three adjacent gene members, PON1, PON2, and PON3. Originating from the same fungus lactonase precursor, all of the three PON genes share high sequence identity and a similar β propeller protein structure. PON1 and PON3 are primarily expressed in the liver and secreted into the serum upon expression, whereas PON2 is ubiquitously expressed and remains inside the cell. Each PON member has high catalytic activity toward corresponding artificial organophosphate, and all exhibit activities to lactones. Therefore, all three members of the family are regarded as lactonases. Under physiological conditions, they act to degrade metabolites of polyunsaturated fatty acids and homocysteine (Hcy) thiolactone, among other compounds. By detoxifying both oxidized low-density lipoprotein and Hcy thiolactone, PONs protect against atherosclerosis and coronary artery diseases, as has been illustrated by many types of in vitro and in vivo experimental evidence. Clinical observations focusing on gene polymorphisms also indicate that PON1, PON2, and PON3 are protective against coronary artery disease. Many other conditions, such as diabetes, metabolic syndrome, and aging, have been shown to relate to PONs. The abundance and/or activity of PONs can be regulated by lipoproteins and their metabolites, biological macromolecules, pharmacological treatments, dietary factors, and lifestyle. In conclusion, both previous results and ongoing studies provide evidence, making the PON cluster a prospective target for the treatment of atherosclerosis. © 2012, Mary Ann Liebert, Inc.


Wu Y.,Tsinghua University | Zhao R.C.H.,Peking Union Medical College
Stem Cell Reviews and Reports | Year: 2012

A growing body of preclinical evidence suggests that mesenchymal stem cells (MSCs) are effective for the structural and functional recovery of the infracted heart. Accordingly, clinical trials are underway to determine the benefit of MSC-based therapies. While systemic administration of MSCs is an attractive strategy, and is the route currently used for the administration of MSCs in clinical studies for myocardial infarction, the majority of infused cells do not appear to localize to infracted myocardium in animal studies. Recently, important progress has been made in identifying chemokine receptors critical for the migration and homing of MSCs. Here, we review recent literature regarding mechanisms of MSC homing and recruitment to the ischemic myocardium, and discuss potential influences of low engraftment rates of systemically administered MSCs to the infracted heart tissue on the effects of MSC-based therapies on myocardial infarction. © 2011 Springer Science+Business Media, LLC.


Bei J.-X.,Sun Yat Sen University | Jia W.-H.,Sun Yat Sen University | Zeng Y.-X.,Sun Yat Sen University | Zeng Y.-X.,Peking Union Medical College
Seminars in Cancer Biology | Year: 2012

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy and has a remarkable geographic distribution, which is highly prevalent in southern China, Southeast Asia, and North Africa. Although most of the NPC are sporadic cases, the familial clustering of NPC has been demonstrated worldwide. Accumulating studies have proposed that the etiology of NPC is multi-stage and multi-factorial, involving genetic lesions, Epstein-Barr virus infection, and environmental exposure. Genetic variations result in differences in gene function, which in turn lead to different susceptibility to disease. Many studies have been carried out to dissect the genetic variants that contribute to NPC susceptibility. This article reviews the current progress of genetic studies to identify genes associated with NPC, focusing on the familial linkage and large-scale case-control study designs. © 2012 Elsevier Ltd.


Yang L.,Peking Union Medical College
Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] | Year: 2013

The aim of the study was to investigate the positivity of human papillomavirus (HPV) and the possible related risk factors for HPV infection in certain district government in Daqing city, Heilongjiang province. A total of 2015 female staffs who participated cervical cancer screening were selected as subjects, in certain district government in Daqing city, Heilongjiang province, from June to October, 2010. First of all, a standardized questionnaire was used for collection of subject's demographic information and possible risk factors. Afterwards, cervical cytological and HPV DNA testing were applied to all participants. Subjects with suspected cervical intraepithelial neoplasia (CIN) or cervical cancer were recalled for taking biopsy under colposcopy for further histopathological diagnosis. Standardized HPV positivity by Segi's world population and compared the difference of HPV positivity of different types. The positivity of HPV between women with and without cervical abnormalities were compared by unconditional logistic regression. And the possible risk factors for HPV infection were also investigated. A total of 1759 out of 2015 subjects had gynecological examination, among which 152 subjects were HPV positive. The positivity of HPV was 8.64% (95%CI: 7.37% - 10.05%), and it was 8.47% (95%CI: 7.93% - 9.03%) after age standardization. Finally, 57 (3.24%) and 1702 (96.76%) subjects had abnormal (≥ CIN1 or low-grade squamous intraepithelial lesion (LSIL)) and normal cervix, respectively. The HPV positivity between women with and without cervical abnormalities were 73.68% (42/57) and 6.46% (110/1702), respectively. There was a significant difference (χ(2) = 307.23, P < 0.05) in HPV positivity between women with and without cervical abnormalities. The risk of cervical abnormalities for women with HPV positivity was 40.52 times (95%CI: 21.79 - 75.36) higher than that for women with HPV negativity. Among women with cervical abnormalities, the most three common HPV types, in descending order, were HPV16 (28.07% (16/57)), HPV52 (14.04% (8/57)) and HPV58 (12.28% (7/57)). While among women with normal cervix, the most three common HPV types were HPV52 (1.23% (21/1702)), HPV16 (1.00% (17/1702)) and HPV58 (0.71% (12/1702)). The positivity of HPV clade A9 among women with and without cervical abnormalities were 59.65% (34/57) and 3.23% (55/1702), which were higher than that of other clades. Analysis for risk factors of HPV infection showed that smoking (OR = 2.71, 95%CI: 1.00 - 7.33), late age (≥ 15 years old) of menarche (OR = 1.44, 95%CI: 1.00 - 2.05), early age (≤ 20 years old) of marriage (OR = 3.09, 95%CI: 1.30 - 7.35), multiple (≥ 2) sexual partners (OR = 2.69, 95%CI: 1.46 - 4.95), husband's extramarital sexual behaviors (OR = 2.77, 95%CI: 1.25 - 6.12) and multiple (≥ 2 times) parity (OR = 1.77, 95%CI: 1.03 - 3.03) would increase the risk of HPV positivity. HPV positivity among women with cervical abnormalities was significantly higher than that among women with normal cervix. HPV16, 52, 58 were the major genotypes among the study population. Smoking, late age of menarche, early age of marriage, multiple sexual partners, husband extramarital sexual behaviors and multiple parity increase the risk of HPV infection.


Liu X.,Peking Union Medical College | Wang S.,Peking Union Medical College | Kao A.A.,University of Miami | Long Q.,Peking Union Medical College
Cornea | Year: 2012

PURPOSE:: To investigate the effect of topical pranoprofen 0.1% on the clinical evaluation and conjunctival human leukocyte antigen II (HLA-DR) expression in dry eyes. METHODS:: Sixty patients with dry eyes were randomized to 2 groups. Patients in group 1 received topical pranoprofen 0.1% plus topical sodium hyaluronate 0.1%; and patients in group 2 received sodium hyaluronate without pranoprofen. Ocular surface disease index (OSDI), tear film break-up time (TBUT), Schirmer I test, ocular surface staining (OSS), and conjunctival HLA-DR expression were evaluated before treatment and at 15 and 30 days after treatment. RESULTS:: On day 15, patients in group 1 had significantly lower OSDI, OSS, and HLA-DR-positive cells compared with patients in group 2 (P < 0.01), and the TBUT was significantly longer in patients in group 1 than that of patients in group 2 (P < 0.01). On day 30, the difference between the 2 groups in OSS lost significance; however, there continued to be significant differences in the OSDI, TBUT, and HLA-DR expression between the 2 groups (P < 0.01). On days 15 and 30, the values in group 1 patients had significant improvement compared with their baseline values in terms of the above-mentioned parameters. The comparisons within group 2 did not reveal any significant differences. There was no significant effect in the Schirmer I test value in eyes of patients in group 1 or group 2 at days 15 or 30 (P > 0.05). CONCLUSIONS:: Topical pranoprofen 0.1% has a beneficial effect in reducing the ocular signs and symptoms of dry eyes and decreasing the inflammatory markers of conjunctival epithelial cells.Copyright © 2012 by Lippincott Williams & Wilkins.


Zheng Z.,Peking Union Medical College
Zhonghua xin xue guan bing za zhi | Year: 2010

To construct a scoring system for the prediction of in-hospital mortality in Chinese patients undergoing coronary artery bypass grafting (CABG). From 2007 to 2008, complete clinical information of 9564 consecutive CABG patients was collected from Chinese coronary artery bypass grafting registry which recruited patients from 43 Chinese centers. This database was randomly divided into developmental and validation subsets (9:1). A risk model was developed using logistic regression. Calibration and discrimination characteristics were assessed in the validation dataset. Thresholds were defined for each model to distinguish different risk groups. The risk model was compared with EuroSCORE system in the validation dataset. In the developmental dataset, calibration by Hosmer-Lemeshow (HL) test was P = 0.44 and discrimination by area under ROC (AUC) was 0.80. In the validation dataset, HL test was P = 0.34, AUC was 0.78. The performance turned out good for all three risk groups. Superiority were found over EuroSCORE (HL P = 0.60; AUC 0.73). The scoring system identified 11 risk factors (with weights in brackets): age over 65 (65 - 69, 3; 70 - 74, 5; over 75, 6), preoperative NYHA stage (NHYA III, 3; NHYA IV, 7), chronic renal failure (6), extracardiac arteriopathy (5), chronic obstructive pulmonary disease (4), Preoperative atrial fibrillation or flutter (within two weeks) (2), left ventricular ejection fraction < 50% (4), other than elective surgery (5), combined valve procedure (4), preoperative critical state (4), BMI (> 24 kg/m(2), -2; < 18 kg/m(2), 5). This study constructs a simple, objective and accurate risk stratification system for Chinese patients undergoing CABG using the most up-to-date data.


The current study comprehensively examined the association between common variants in the Na+-coupled bicarbonate transporter (NCBT) genes and blood pressure (BP) responses to dietary sodium intervention. A 7-day low-sodium followed by a 7-day high-sodium dietary intervention was conducted among 1906 Han participants from rural areas of northern China. Nine BP measurements were obtained at baseline and each intervention using a random-zero sphygmomanometer. A mixed-effect model was used to assess the additive associations of 76 common variants in five NCBT genes, including SLC4A4, SLC4A5, SLC4A7, SLC4A8 and SLC4A10, with salt sensitivity phenotypes. The Bonferroni method was used to adjust for multiple testing. SLC4A4 marker rs4254735 was significantly associated with diastolic BP (DBP) response to low-sodium intervention (P=5.05 × 10-4), with mean (95% confidence interval (CI)) response of −2.91 (−3.21, −2.61) and −0.40 (−1.84, 1.05) mmHg for genotype AA and AG, respectively. In addition, BP responses to high-sodium intervention significantly increased with the number of minor C alleles of SLC4A4 marker rs10022637. Mean systolic BP responses among those with genotypes TT, CT and CC were 4.62 (4.29, 4.99), 5.94 (5.31, 6.58) and 6.00 (3.57, 8.43) mmHg (P=1.14 × 10-4); mean DBP responses were 1.72 (1.41, 2.03), 3.22 (2.52, 3.92) and 3.94 (1.88, 5.99) mmHg (P=2.26 × 10-5) and mean arterial pressure responses were 2.69 (2.40, 2.97), 4.13 (3.57, 4.70) and 4.61 (2.51, 6.71) mmHg (P=2.07 × 10-6), respectively. In brief, the present study indicated that common variants in the SLC4A4 gene might contribute to the variation of BP responses to dietary sodium intake in Han Chinese population.Journal of Human Hypertension advance online publication, 19 November 2015; doi:10.1038/jhh.2015.113. © 2015 Macmillan Publishers Limited


Sun H.N.,Peking Union Medical College
Zhonghua xin xue guan bing za zhi | Year: 2011

To determine the impact of smoking behaviors on long-term outcomes of coronary artery bypass grafting (CABG). We conducted this survey in 2541 consecutive patients who underwent CABG in Fu Wai hospital from January 1, 2004 to December 30, 2005. The preoperative and postoperative smoking habits were obtained. The patients were divided into never smokers and ever smokers. The ever smokers were further divided into the current smokers who smoked before and after CABG and former smokers who stopped smoking before CABG, quitters who stopped smoking after CABG. Death, major adverse cardiovascular or cerebrovascular events and angina pectoris were observed. The relative risk of adverse events in different patients were analyzed by univariate and multivariate Cox analysis. The patients were followed up for 4.27 to 6.41 years (average 5.09 years). After CABG, the percentage of persistent smoking patients was 22.1%. After adjusting baseline characteristics, relative risk for tumor related death (RR: 2.38, 95%CI: 1.06 - 5.36), major adverse cardiovascular or cerebrovascular events (RR: 1.26, 95%CI: 1.01 - 1.57) and angina pectoris (RR: 1.29, 95%CI: 1.04 - 1.59) were significantly higher in ever smokers than in never smokers. Similarly, relative risk of death from all causes (RR: 2.60, 95%CI: 1.53 - 4.46), cardiac death (RR: 2.51, 95%CI: 1.32 - 4.78), tumor cause death (RR: 5.12, 95%CI: 2.08 - 12.59), major adverse cardiovascular or cerebrovascular events (RR: 1.83, 95%CI: 1.42 - 2.34) and angina pectoris (RR: 1.69, 95%CI: 1.33 - 2.16) were also significantly higher in current smokers than in never smokers. Outcome was similar between patients who stopped smoking and never smokers (all P > 0.05). Smoking prevalence is still high in patients after CABG in China. Persistent smoking is associated with higher rates of mortality and morbidity after CABG while smoking cessation is associated with reduction of morbidity and mortality in patients after CABG.


Wang Y.Y.,Peking Union Medical College
Zhonghua fu chan ke za zhi | Year: 2010

To investigate the relationship between the distribution of nerve fibers in multiple endometriosis lesions and pelvic pain. From Sept. 2007 to Sept. 2008, 120 endometriosis patients treated in Peking Union Hospital were enrolled in this study, which including 19 cases with stage I, 29 cases with stage II, 44 cases with stage III and 28 cases with stage IV. The pain symptom was evaluated by visual analogue scales (VAS) score and nerve fibers in multiple endometriosis lesions were detected by immunohistochemical staining. The number of nerve fibers in multiple endometriosis lesions were (29.74+/-17.33)/mm2 in uterosacral ligament, (24.53+/-13.34)/mm2 in vaginal septum, (17.09+/-10.09)/mm2 in uterus rectum crux, (6.77+/-4.21)/mm2 in peritoneal endometriosis lesions, (0.07+/-0.25)/mm2 in endometriosis ovarian cyst wall. The number of nerve fibers in uterosacral ligament was mostly correlated with the degree of pain (r=0.56). The nerve fibers of uterus rectum crux and vaginal septum were correlated with defecation pain (r=0.58 and 0.41) and dyspareunia (r=0.82 and 0.67), which were significantly higher than those in endometriosis leision in peritoneum and ovary. There was no significant different number of nerve fibers among different stage disease (P>0.05). There was significantly different distribution of nerve fibers in multiple endometriosis lesions, which was correlated with dysmenorrhea, anus pain, dyspareunia and chronic pelvic pain, not with clinical staging.


Gui T.,Peking Union Medical College | Shen K.,Peking Union Medical College
Cancer Epidemiology | Year: 2012

A majority of patients with ovarian carcinoma who receive conventional treatment of surgical staging and platinum-based chemotherapy recur and ultimately succumb to their diseases. Novel therapies that target specific pathways involved in ovarian tumorigenesis are rapidly emerging. The epidermal growth factor receptor (EGFR) is overexpressed in 30-98% of epithelial ovarian carcinoma (EOC), and the signaling cascades activated are related with cell proliferation, migration and invasion, and angiogenesis, as well as resistance to cell apoptosis. Various trials are ongoing focusing on EGFR as an attractive target in treatment of EOC. Anti-EGFR monoclonal antibodies (MAbs), cetuximab and panitumumab, and tyrosine kinase inhibitors (TKIs), erlotinib and gefitinib, are the most advanced in clinical development. The available data suggests that MAbs and TKIs only show marginal activity when they are used alone, but combination with platinum-based chemotherapy can induce elevated overall response rate in recurrent EOC patients. Consequently, mechanisms for intrinsic and extrinsic resistance have been explored due to the poor clinical response to EGFR-targeted therapy. Careful consideration of these clinical studies and the possible mechanisms involved in resistance can provide evidence for improvements in subsequent research. Identification of responder profiles and development of rational regimen of combination therapy of EGFR-targeted therapy with other effective treatment modalities may eventually bring about substantial progress in the treatment of epithelial ovarian cancers. © 2012 Elsevier Ltd.


Wang S.,Peking Union Medical College | Qu X.,Peking Union Medical College | Zhao R.C.,Peking Union Medical College
Journal of Hematology and Oncology | Year: 2012

Mesenchymal stem cells (MSC) have generated a great amount of enthusiasm over the past decade as a novel therapeutic paradigm for a variety of diseases. Currently, MSC based clinical trials have been conducted for at least 12 kinds of pathological conditions, with many completed trials demonstrating the safety and efficacy. This review provides an overview of the recent clinical findings related to MSC therapeutic effects. Roles of MSCs in clinical trials conducted to treat graft-versus-host-disease (GVHD) and cardiovascular diseases are highlighted. Clinical application of MSC are mainly attributed to their important four biological properties- the ability to home to sites of inflammation following tissue injury when injected intravenously; to differentiate into various cell types; to secrete multiple bioactive molecules capable of stimulating recovery of injured cells and inhibiting inflammation and to perform immunomodulatory functions. Here, we will discuss these four properties. Moreover, the issues surrounding clinical grade MSCs and principles for MSC therapeutic approaches are also addressed on the transition of MSCs therapy from bench side to bedside. © 2012 Wang et al.; licensee BioMed Central Ltd.


Cui C.-J.,Peking Union Medical College | Li S.,Peking Union Medical College | Li J.-J.,Peking Union Medical College
Clinica Chimica Acta | Year: 2015

Proprotein convertase subtilisin/kexin type 9 (PCSK9), a newly-recognized protein, plays a key role in regulating cholesterol homeostasis. PCSK9 reduces hepatic low-density lipoprotein receptors (LDLRs) thereby increasing LDL-cholesterol (LDL-C). Recently, biologic and genetic research proposed several approaches to inhibit or reduce PCSK9 to improve lipid profile and cardiovascular performance in patients with dyslipidemia, particularly hypercholesterolemia. Of note, PCSK9 is a secreted protein under tight control by multiple modulators. Therefore, elucidating the factors that influence PCSK9 would enhance our understanding of PCSK9 and potentially day-to-day management of these patients at high cardiovascular risk. This review will focus on genetic variants, physiologic processes, pharmacologic agents and pathologic conditions related to PCSK9 in order to assess current and future therapeutic strategies targeting this molecule. © 2014.


Gui T.,Peking Union Medical College | Shen K.,Peking Union Medical College
Cancer Epidemiology | Year: 2012

microRNAs are genomically encoded small non-coding RNAs that regulate genetic information by controlling stability or translation of mRNAs. Down-regulated expression of microRNA-101 (miRNA-101) has been found in a variety of cancers, and associated with the invasion and progression of malignancies. Recent advances in the understanding of miRNA-101 biogenesis, target recognition and participation in regulatory pathways demonstrate a role for miRNA-101 in tumorigenesis. miRNA-101 gene therapy is of great potentiality to be a new modality for treatment of cancers. © 2012 Elsevier Ltd.


Liu Z.-H.,Peking Union Medical College | Sun X.-B.,Peking Union Medical College
Yaoxue Xuebao | Year: 2012

Traditional Chinese medicine (TCM) with the characteristics of holistic view and treatment based on syndrome differentiation, has rich clinical experience thousands of years and demonstrates promising effects to cure complex disease. However, due to the features of multi-component, multi-target and synergistic effect existed in TCM, the effective substances and mechanisms of action are not clear, the qualities of TCM are out of control, and scientific and correct assess system is waiting to be established. The network pharmacology is a novel subject based on the construction of multi-layer networks of disease-phenotype-gene-drug to predict the drug targets in a holistic view, and promote efficiency of drug discovery. Methodologically, network pharmacology integrated the notions of comprehensive research and systematic assessment which agree with the characteristics of holistic view and treatment based on syndrome differentiation in Chinese medicine. Our paper reviewed the challenge and chance within the modernization of TCM, the concept and technology of network pharmacology, and its preliminary application in investigation of TCM. The theoretical system of network pharmacology is emphasized, and the potential prospect of its application in modernization in TCM is focused.


Cheng Z.,Peking Union Medical College | Fang Q.,Peking Union Medical College
Journal of Human Genetics | Year: 2012

Danon disease is a rare X-linked dominant lysosomal disease due to the primary deficiency of lysosome-associated membrane protein 2 (LAMP2) gene. Cardiomyopathy, skeletal myopathy and mental retardation are the typical triad of Danon disease. More than 60 LAMP2 mutations have been reported. The molecular mechanism is defects in LAMP2 protein (due to LAMP2 mutation) which causes insidious glycogen accumulation in cardiac muscle cells and resulting in cardiac hypertrophy and electrophysiological abnormalities. However, there are significant differences between the male and female Danon disease patients with regard to clinical features and cardiac manifestations. The clinical symptoms are variable, from asymptomatic to sudden cardiac death. Wolff-Parkinson-White syndrome is more common in male than female patients. Hypertrophic cardiomyopathy is predominant in male patients, whereas the similar prevalence of hypertrophic and dilated cardiomyopathy in female patients. Male patients are diagnosed usually at teenage, whereas the diagnosis and events occurred approximately 15 years later in female than male patients. Heart transplantation is the reliable treatment once the occurrence of heart failure and should be considered as early as possible due to its rapid progression. © 2012 The Japan Society of Human Genetics. All rights reserved.


Wang L.,Peking Union Medical College
European Journal of Gastroenterology and Hepatology | Year: 2016

Primary biliary cholangitis (PBC, primary biliary cirrhosis) is an autoimmune cholestatic liver disease characterized by chronic nonsuppurative destructive cholangitis and the presence of serum antimitochondrial antibodies. Ursodeoxycholic acid is the only drug approved by the US Food and Drug Administration to treat PBC. However, one-third of patients show incomplete responses to ursodeoxycholic acid and a poor prognosis. A number of old and new medications have been used in these patients, such as fibrates, glucocorticoids, immunosuppressants, obeticholic acid, mesenchymal stem cells, biological agents (anti-interleukin-12, cytotoxic T-lymphocyte antigen 4 immunoglobulin, anti-CD20), and antifibrotic drugs. This article reviews the therapeutic advances of these old and new medications in patients with PBC. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.


Yin Y.-F.,Peking Union Medical College | Zhang X.,Peking Union Medical College
World Journal of Gastroenterology | Year: 2012

Primary biliary cirrhosis (PPBC) is a progressive autoimmune liver disease off unknown etiology that affffects almost exclusively women. Ursodeoxycholic acid (UDDCA) is currently the only approved drug by Food and DDrug Administration ffor patients with PPBC. Although the precise pathogenesis off PPBC remains unclear, it has been postulated that many cell populations, including B cells, are involved in the ongoing inflammatory process, which implicates, not surprisingly, a potential therapeutic target off depleting B cell to treat this disorder. Rituximab is a chimeric anti-CDD20 monoclonal antibody that has been approved ffor the treatment off lymphoma and some autoimmune diseases such as rheumatoid arthritis. Whether it is effffective in the treatment off PPBC has not been evaluated. Recently, Tsuda et al[1] demonstrated that B cell depletion with rituximab significantly reduced the number off anti-mitochondrial antibodies (AMMA)-producing B cells, AMMA titers, the plasma levels off immunoglobulins (IgA, IgMM and IgG) as well as serum alkaline phosphatase, and it was well tolerated by all the treated patients with no serious adverse events. This observation provides a novel treatment option ffor the patients with PPBC who have incomplete response to UDDCA. © 2012 Baishideng.


Yu Y.,Peking Union Medical College | He J.,Peking Union Medical College
Frontiers of Medicine | Year: 2013

Non-small-cell lung cancer (NSCLC) is the most common cause of premature death among the malignant diseases worldwide. The current staging criteria do not fully capture the complexity of this disease. Molecular biology techniques, particularly gene expression microarrays, proteomics, and next-generation sequencing, have recently been developed to facilitate effectively its molecular classification. The underlying etiology, pathogenesis, therapeutics, and prognosis of NSCLC based on an improved molecular classification scheme may promote individualized treatment and improve clinical outcomes. This review focuses on the molecular classification of NSCLC based on gene expression microarray technology reported during the past decade, as well as their applications for improving the diagnosis, staging and treatment of NSCLC, including the discovery of prognostic markers or potential therapeutic targets. We highlight some of the recent studies that may refine the identification of NSCLC subtypes using novel techniques such as epigenetics, proteomics, or deep sequencing. © 2013, Higher Education Press and Springer-Verlag Berlin Heidelberg.


Objective: To evaluate the expression of BRCA1, ERCC1, TUBB3 and PRR13 mRNA and their relationship with clinical chemosensitivity in primary ovarian cancer, and to assess the predictive value of joint detection of both BRCA1 and ERCC1 genes for the treatment of primary ovarian cancer. Methods: Primary epithelial ovarian tumor samples were collected from 46 patients who underwent cytoreductive surgery. Real-time quantitative PCR was used to analyze the relative expression of BRCA1, ERCC1, TUBB3 and PRR13 mRNA in those cases. The correlation of clinical chemosensitivity and the test results was statistically analyzed. The efficacy of the joint prediction of clinical chemosensitivity by combining the two drug resistance gene detection was evaluated. Results: The BRCA1 mRNA relative expression logarithm in the clinical-resistant group was 0.673 ± 2.143, and clinical-sensitive group -1.436 ± 2.594 (P = 0.008). The ERCC1 mRNA relative expression logarithm in the clinical-resistant group was -0.529 ± 1.982 and clinical-sensitive group -3.188 ± 2.601 (P = 0.001). BRCA1 and ERCC1 expression level is negatively correlated with platinum-based chemosensitivity. The PRR13 expressions in the two groups were not significantly different (P = 0.074), and the TUBB3 expressions between the two groups were also not significantly different (P = 0.619). When the intercept point value BRCA1 mRNA expression logarithm was -0.6, the predictive sensitivity, specificity, positive predictive value and negative predictive value were 73.3%, 75.0%, 84.6% and 60.0%, respectively, with the best comprehensive assessment. When the intercept point value of ERCC1 mRNA expression logarithm was -1, the predictive sensitivity, specificity, positive predictive value and negative predictive value were 80.0%, 68.8%, 82.8% and 64.7%, respectively, with the best comprehensive assessment. The combination detection of BRCA1 and ERCC1 can improve the chemotherapeutic sensitivity, specificity, positive predictive value and negative predictive value to 86.7%, 68.8%, 83.9% and 73.3%, respectively. Conclusions: BRCA1 and ERCC1 mRNA expression has a negative correlation with the clinical sensitivity of platinum-based chemotherapy. Combination detection of the two drug-resistance associated genes can improve the predictive efficacy of ovarian cancer chemosensitivity and beneficial to individual treatment of ovarian cancer.


Tong J.L.,Peking Union Medical College
Zhonghua fu chan ke za zhi | Year: 2012

To study the pathologic characteristics of eutopic endometrium in patients with endometriosis. Pathologic characteristics of eutopic endometrium were studied in 176 patients with endometriosis in Peking Union Medical College Hospital from January 2007 to December 2008 retrospectively. About 72.2% (127/176) of eutopic endometrium were in proliferative phase, 19.9% (35/176) of were observed as endometrial polyp, including 32 cases with simple endometrial polyp and 3 cases with abnormal hyperplasia combined with endometrial polyp. And 4.0% (7/176) showed abnormal hyperplasia. The incidence of pathologic changes in eutopic endometrium was 22.2% (39/176). Among 53 endometriosis patients combined with infertility, the incidence of pathologic changes of eutopic endometrium was 35.9% (19/53), which was significantly higher than 16.3% in non-infertile patients (χ(2) = 8.24, P = 0.004). Among 65 cases with irregular menstruation, the incidence of endometrial polypus and endometrial hyperplasia were 20.0% (13/65) and 10.8% (7/65), which were significantly higher than 17.1% (19/111) and 0 in normal menstruation patients (χ(2) = 13.839, P = 0.003). The eutopic endometrium of endometriosis were in proliferative phase state. The pathologic changes of eutopic endometrium were more in patients combined with infertility and irregular menstruation.


Liu C.,Peking Union Medical College | Luan J.,Peking Union Medical College | Ji K.,Peking Union Medical College | Sun J.,Peking Union Medical College
Aesthetic Plastic Surgery | Year: 2012

Background: Measurement of volumetric change after augmentation mammaplasty is of great significance to plastic surgeons. This study aimed to introduce a newmethod using a three-dimensional (3D) scanning technique to measure volumetric change after augmentation mammaplasty. Methods: Preoperative 3D scans of 10 breasts were included in the study. A simulated postoperative breast scan was constructed using software. The true value of volumetric change was calculated. Volumetric change was measured and repeated 10 times by the traditional method and the new method. One investigator used the traditional method, and two investigators used the new method. The difference from the true value between the two methods and the intraclass coefficient (ICC) for each method was evaluated. Comparison of agreement with the true value and comparison of agreement using the new method between the two investigators were made using a Bland-Altman analysis. Results: The mean breast volumetric change was 256.1 ± 61.1 ml for the new method, 281.9 ± 73.7 ml for the traditional method, and 256.0 ± 61.0 ml for the true value. The difference from the true value for the traditional method was significantly greater than for the new method. The ICC was 0.9999 for the new method and 0.993 for the traditional method. Bland-Altman analysis showed a 95 % confidence interval (CI) of -40.9 to 92.7 ml for the traditional method and -0.9 to 1.2 ml for the new method. Comparison of agreement between investigators 1 and 2 showed a 95 % CI of -0.9 to 1.0 ml. The limits of agreement were ±1.0 ml. Conclusions The proposed new method can provide excellent accuracy, repeatability, and reproducibility in measuring volumetric change after augmentation mammaplasty using a 3D scanning technique. Level of Evidence I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266. © Springer Science+Business Media, LLC and International Society of Aesthetic Plastic Surgery 2012.


This study aims to critically evaluate the effects of a walking intervention on bone mineral density (BMD) in perimenopausal and postmenopausal women and to identify the optimal duration of this walking exercise intervention. Two independent reviewers assessed for eligibility randomized and nonrandomized controlled trials evaluating the effects of walking on BMD in perimenopausal and postmenopausal women. Heterogeneity, potential publication bias, and the quality of the included trials were assessed. Ten trials were eligible for inclusion. A meta-analysis of trials assessing lumbar spine BMD showed no significant effects (weighted mean difference [WMD] [fixed effects], 0.01 g/cm(2); 95% CI, -0.00 to 0.02; P = 0.05) regardless of the length of the intervention duration. BMD at the femoral neck increased after long intervention durations (6 mo to 1-2 y), although no significant effect could be seen when all trials assessing femoral neck BMD were taken into account (WMD [fixed effects], 0.01 g/cm(2); 95% CI, -0.00 to 0.01; P = 0.07). The effects of walking on the radius and whole body were not significant (WMD [random effects], -0.01 g/cm; 95% CI, -0.06 to 0.04; P = 0.71; and WMD [fixed effects], 0.04 g/cm(2); 95% CI, -0.00 to 0.08; P = 0.06, respectively). Walking as a singular exercise therapy has no significant effects on BMD at the lumbar spine, at the radius, or for the whole body in perimenopausal and postmenopausal women, although significant and positive effects on femoral neck BMD in this population are evident with interventions more than 6 months in duration.


Feng D.R.,Peking Union Medical College
Zhonghua er ke za zhi. Chinese journal of pediatrics | Year: 2011

Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive disorder characterized by the association of permanent neonatal or early-infancy insulin-dependent diabetes, multiple epiphyseal dysplasia and growth retardation, and other variable multisystem clinical manifestations. Here we describe a Chinese boy affected by WRS. Genetic testing of his EIF2AK3 gene was performed in order to elucidate molecular variations and subsequently to provide credible genetic counseling for prenatal diagnosis in his family. Based on analysis of a nine-year-old boy's clinical symptoms associated with biochemical examination and imaging, the diagnosis of WRS was therefore made. Genomic DNAs were extracted from peripheral blood leukocytes from the boy and his parents with their informed consent for genetic studies. All EIF2AK3 exons and intron-exon boundaries were amplified by Touch-down polymerase chain reaction (Touch-down PCR) and sequenced. Direct sequencing of PCR products revealed the presence of a heterozygous T insertion (c.1408_1409insT) in exon 8 of the EIF2AK3 gene leading to frameshifting and termination, and another heterozygous T to A exchange (c.1596T > A) in exon 9 of the EIF2AK3 gene resulting in nonsense C532X mutation. Combining mutation screening of EIF2AK3 gene with clinical manifestations and effective examination may provide a reliable diagnostic method for patients. In this research, two novel mutations identified in the Chinese boy locate in the catalytic domain of the EIF2AK3 gene, disrupting the ability of autophosphorylation, leading to the truncated proteins that are unable to phosphorylate the natural substrate, which are responsible for the phenotype of Wolcott-Rallison syndrome.


Wang Y.-H.,Peking Union Medical College | Xuan Z.-H.,Shenyang Pharmaceutical University | Tian S.,Peking Union Medical College | He G.-R.,Peking Union Medical College | Du G.-H.,Peking Union Medical College
Journal of Functional Foods | Year: 2013

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic (DA) neurons at the substantia nigra. 6-Hydroxydopamine (6-OHDA) is a dopamine analog, which specifically to damage dopaminergic neurons. Myricitrin, a flavanoid isolated from the root bark of Myrica cerifera, has antinociceptive activity, anti-inflammatory, antioxidant, and immunomodulatory properties. In the present study, the potential protection and mechanism of myricitrin against 6-OHDA-induced damage and apoptosis in PC12 cells was studied. The results showed that myricitrin attenuated 6-OHDA-induced cell damage and mitochondrial dysfunction in a dose-dependent manner, which was correlated with decreased intracellular ATP content and mitochondrial membrane potential. Furthermore, it was found that myricitrin inhibited the apoptosis of PC12 cells induced by 6-OHDA in relation to reduction of cytochrome C release from mitochondria and inhibition of the activity of caspase-3. Finally, the antioxidation of myricitrin in PC12 cells and brain mitochondria was investigated. The results showed that myricitrin decreased the production of reactive oxygen species in PC12 cells and inhibited lipid peroxidation in rat brain mitochondria (IC50=3.19±0.34μM). Thus, myricitrin has the neuroprotective capacity to antagonize 6-OHDA-induced neurotoxicity in PC12 cells and may be useful in treating PD. © 2012 Elsevier Ltd.


Yang J.,Peking Union Medical College | Li X.,Central South University | Morrell N.W.,University of Cambridge
Cardiovascular Research | Year: 2014

The inhibitors of differentiation (Id) proteins belong to the helix-loop-helix group of transcription factors and regulate cell differentiation and proliferation. Recent studies have reported that Id proteins play important roles in cardiogenesis and formation of the vasculature. We have also demonstrated that heritable pulmonary arterial hypertension (HPAH) patients have dysregulated Id gene expression in pulmonary artery smooth muscle cells. The interaction between bone morphogenetic proteins and other growth factors or cytokines regulates Id gene expression, which impacts on pulmonary vascular cell differentiation and proliferation. Exploration of the roles of Id proteins in vascular remodelling that occurs in PAH and atherosclerosis might provide new insights into the molecular basis of these diseases. In addition, current progress in identification of the interactors of Id proteins will further the understanding of the function of Ids in vascular cells and enable the identification of novel targets for therapy in PAH and other cardiovascular diseases. © The Author 2014.


Song N.,Peking Union Medical College
Zhonghua fu chan ke za zhi | Year: 2012

To investigate the expression of transient receptor potential vanilloid subtype 1 (TRPV1) in uterosacral ligament and its correlation with pain in endometriosis. Total of 54 patients undergoing endometriotic lesions excision in uteroscaral ligament by laparoscopy due to pelvic pain were enrolled in this study. According to visual analogue scale (VAS) scores, 27 patients with VAS 5-10 were in group A and 27 patients with VAS 0-4 were in group B. In the mean time, 20 patients with dysmenorrhea without endometriosis (VAS: 0-4) were matched as group C. Specimens (including the sacro-ligaments of 20 women without endometriosis) were immunostained with specific antibodies of TRPV1. Western blot and real time PCR were performed to detect TRPV1 expression in endometriosis lesions and control group. (1) Immunohistochemnistry: the positive area of TRPV1 was found in endometriotic lesions in uterosacral ligament in group A, B and tissue of uterosacral ligament group C. The semi-qualitification of TRPV1 expression were 3 in group A, 1 in group B and 1 in group C by immunohistochemistry staining. There was significantly different expression between group B and group A (P = 0.005) or group C (P = 0.027). (2) mRNA expression:the expression of TRPV1 was 1.84 in group A, 0.80 in group B, 0.24 in group C, respectively. With higher VAS scores, the expression of TRPV1 exhibited increasing trends. The expression of TRPV1 mRNA was higher in group A than that in group B (P = 0.022). There was statistically different expression between group B and group C (P = 0.031). (3) Western blot: the expression of TRPV1 protein was 0.63 in group A, 0.19 in group B, 0.02 in group C. There was significant differences between group A and group B (P = 0.022), and between group B and group C (P < 0.01). The expression of TRPV1 was correlated with the degree of pain in patient with endometriosis.


CHEN B.,Peking Union Medical College
Zhonghua yi xue za zhi | Year: 2012

To investigate the clinical characteristics, diagnosis and treatment of Atypical Polypoid Adenomyoma of the uterus (APA). A retrospective study was made of 17 patients with APA, who were hospitalized at Peking Union Medical College Hospital from 2003 to 2010. Those patients' clinical characteristics, diagnosis, and treatments are analyzed respectively. The patients ranged from 19 to 53 (median 39) years old, Most of them (15/17) are during child-bearing period. There was one patient with infertility, two of the patients were postmenopausal. Fourteen cases had irregular vaginal bleeding clinically. Most of the pathology were polypous, which is more than 1 cm. Fifteen cases were characteristically polypoid, among which there were one case with multi polypoid and one case was extensive. Eight cases were located in the uterine cavity. Six cases were located in the lower uterine segment. Three cases were located in cervix. None of the cases were diagnosed, while all of them were diagnosed by pathology after primary surgical. Fifteen patients had polypectomy (among them, five patients took drug therapy after the surgical), while the remaining two patients had hysterectomy. Two of the five patients, who took drug therapy, were pregnant. One patient was deteriorated with carcinoma of endometrium. Although most cases of APA were benign, a few cases were associated with low malignant potential of recurrence. The treatment should depend on the age and reproductive desire of patient. And long-term follow-up is suggested.


Jinguang Z.,Peking Union Medical College
The Journal of craniofacial surgery | Year: 2010

To introduce our experience of correction of prominent ears by ear cartilage-folding method, which amalgamates some well-known techniques. Preoperative design was in a routine way. The anterior area of antihelix was dissected subcutaneously, and the surface of the cartilage was scored thoroughly. Satisfactory antihelix was established by folding with mattress suturing. One strip of skin was removed from the back of the concha with suture of the remaining cartilage to the mastoid periost to decrease the auricle-mastoid angle. Fifty-nine cases of prominent ears were followed up postoperatively from 1 to 24 months, and almost all of the ears achieved satisfactory effects. Both the antihelix and auricle-mastoid angle were improved markedly. Not only is this technique reliable, but it also has low recurrence.


Jin X.,Peking Union Medical College
Clinical nuclear medicine | Year: 2013

PET/CT scan was performed in a 43-year-old woman to evaluate pulmonary nodules/masses. The images showed that there was only minimal FDG activity in the masses. However, these soft tissue masses in the lungs had significantly elevated (99m)Tc 3PRGD(2) activity. Pathological examination demonstrated that this patient suffered benign metastasizing leiomyoma.


Wang J.,Peking Union Medical College | Yu J.-C.,Peking Union Medical College | Kang W.-M.,Peking Union Medical College | Ma Z.-Q.,Peking Union Medical College
Nutrition | Year: 2012

Objective: Compared with soybean oil, a fish oil-enriched emulsion can improve the clinical outcomes of patients requiring parenteral nutrition. However, the superiority of fish oil emulsion to medium-chain triacylglycerols/long-chain triacylglycerols for short-term administration has seldom been discussed. Methods: Sixty-four adult patients with gastrointestinal diseases were randomly assigned to receive isocaloric and isonitrogenous total parenteral nutrition with an ω-3 fatty acid-enriched emulsion (Lipoplus; study group, n = 32) or medium-chain triacylglycerols/long-chain triacylglycerols (Lipofundin; control group, n = 32) for 5 d after surgery. Safety and efficacy parameters were assessed on postoperative days 1, 3, and 6. Results: Clinical outcomes including infectious complications and systemic inflammatory response syndrome were comparable between the two groups. Total bilirubin decreased over time in the study group versus an increase in the control group (P = 0.017). Activated partial thromboplastin time in the study group was prolonged significantly compared with the control group from days 1 to 3 (P = 0.002), although the prolongation stopped at the study termination. There were no differences in changes of C-reactive protein, interleukin (IL)-1, IL-8, IL-10, vascular endothelial growth factor (VEGF), and the distribution of the T-cell subpopulation between the two groups. However, fish oil consumption led to an increase in leukotriene B5/ leukotriene B4 and significant decreases in IL-6, tumor necrosis factor-α, and nuclear factor-κB. Furthermore, the overall changes in tumor necrosis factor-α and nuclear factor-κB were positively associated (R 2 = 0.295, P < 0.001). Conclusions: Gastrointestinal surgery patients benefited from a fish oil-enriched emulsion rather than medium-chain triacylglycerols/long-chain triacylglycerols in the amelioration of liver function and immune status. The positive association of tumor necrosis factor-α and nuclear factor-κB might be involved in the potential anti-inflammation mechanism of fish oil. © 2012 Elsevier Inc.


Shi Y.,Peking Union Medical College
Zhonghua nei ke za zhi [Chinese journal of internal medicine] | Year: 2012

To assess the value of procalcitonin (PCT) measurement to differentiate infection from non-infection in critically ill patients requiring long-term immunosuppressive therapy. A prospective study was conducted in patients with underlying diseases requiring corticosteroids or chemotherapy in ICU from January 2008 to December 2009. Patients were divided into the infection group and the non-infection group and their PCT levels were compared. A total of 103 patients (65 women) were enrolled in this prospective study [aged (47.9 ± 21.9) years old] with 84 in the infection group and 19 in the non-infection group. The baseline level of PCT was significantly higher in infection than in non-infection patients [2.58 (0.08 - 44.65) pg/L vs 0.62 (0.15 - 6.00) pg/L, P = 0.002]. Different levels of PCT were manifested in different pathogen groups with 3.41 (0.45 - 44.65) pg/L in bacteria infection, 0.99 (0.28 - 6.67) pg/L in fungus infection, 0.11 (0.08 - 0.20) pg/L in virus infection group (P = 0.018). The AUC(ROC) of PCT was 0.867 for diagnostic bacterial infection. By multivariate analysis, the factors associated with the level of PCT were bacteria infection (OR 5.1, P = 0.031) and septic shock (OR 7.5, P = 0.027), while the factors not associated with the level of PCT were age, renal function, infection site and prognosis (P > 0.05). The level of PCT is increased in the critically ill patients requiring immunosuppressive therapy with infection and it can be used for diagnosis for bacterial infection.


Zhou A.,Peking Union Medical College
Asia-Pacific Journal of Clinical Oncology | Year: 2012

Sunitinib is the gold standard of care for patients with metastatic renal cell carcinoma, demonstrating an overall survival benefit of over 2years in a pivotal phase 3 trial of 750 patients. While sunitinib is generally well tolerated with most adverse events, manifesting as mild to moderate in severity and manageability, it has a distinctive adverse event profile that benefits from careful monitoring during treatment. As sunitinib gains widespread use across the globe, best practices are being developed for specific patient groups. This review will focus on the current clinical trial data in Asian populations and on the mechanism, incidence and management of selected sunitinib-related adverse events, including hand-foot syndrome, hypertension, proteinuria, cardiac toxicities, myelosupression, fatigue/asthenia, hypothyroidism, diarrhea and hepatotoxicity. Taken together, the developing body of literature reviewed here demonstrates that sunitinib is well tolerated in Asian patients and provides efficacy that is similar, if not superior, to other patient groups. Asian patients, like all patients, should begin treatment of sunitinib at 50mg on Schedule 4/2 (4weeks on treatment/2weeks off). Prophylactic measures, good communication between patient and health-care providers, and early, aggressive intervention at the development of adverse events can limit the dose reductions required and maximize both patients' response to treatment and their quality of life. © 2012 Blackwell Publishing Asia Pty Ltd.


Li B.,Peking Union Medical College | Wang B.,Peking Union Medical College | Niu L.-J.,Peking Union Medical College | Jiang L.,Peking Union Medical College | Qiu C.-C.,Peking Union Medical College
Epigenetics | Year: 2011

This study was designed to determine the significance of DNA methyltransferases (DNMTs) in DNA hypermethylation in esophageal squamous cell carcinoma (ESCC) and to identify DNA methylation markers in serum for the early diagnosis of ESCC. A promoter methylation profile of 12 tumor-related genes was assessed using methylation-specific PCR in ESCC and paired non-tumor tissue samples from 47 patients. Expression levels of DNMTs were examined by real-time reverse transcription-PCR and immunohistochemistry. Using MethyLight, the methylation status of five genes was analyzed in serum samples from 45 patients and 15 healthy individuals. A total of 46 (97.9%) of 47 ESCC samples showed methylation in at least one of the examined genes, and methylation was most frequent for RAR-ß (46.8%), DAPK (46.8%), p16 (44.7%) and CDH1 (42.6%). Methylation of RASSF1A was significantly correlated with the poorly differentiated tumors and the early pathologic tumor classification (p = 0.035 and p = 0.046, respectively). Tumoral DNMT3b mRNA upregulation was significantly correlated with hypermethylation of multiple tumor-related genes (p = 0.021). In addition, hypermethylation of cell-free serum DNA was common in ESCC patients and diagnostic accuracy was increased when methylation of multiple genes (RAR-β, DAPK, CDH1, p16 and RASSF1A) were analyzed in combination (ROC AUC 0.911, 82.2% sensitivity and 100% specificity). The present study suggests that hypermethylation of multiple tumor-related genes may be involved in the pathogenesis of ESCC and mediated by the increase of DNMT3b expression. A cluster of multiple methylated genes in serum DNA has the potential as a novel biomarker for ESCC diagnosis. © 2011 Landes Bioscience.


Lu C.X.,Peking Union Medical College
Zhonghua yi xue za zhi | Year: 2011

To identify the pathogenic mutations of phenylalanine hydroxylase gene (PAH) in patients with phenylketonuria (PKU) from Hebei Province. Genomic DNA was extracted from 55 unrelated PKU patients from September 2007 to July 2009. All PAH exons and exon-intron junctions were amplified by polymerase chain reaction (PCR) and sequenced. Multiplex ligation-dependent probe amplifications (MLPA) was performed to detect the deletions or duplications of PAH. Gap-PCR was used to determine the breakpoints of large deletions. Among them, 108 mutant alleles (98.2%) were found. All PAH exons with the exceptions of exons 9 and 13 were affected. A total of 41 different mutations were detected, including missense (n = 24), nonsense (n = 7), splicing (n = 7), small deletion (n = 1) and large deletion (n = 2). Among them, 4 missense mutations (p.Pro147Leu, p.Gly289Arg, p.Phe392Ser, p.Ile421Thr) and 2 large deletions (-4163_-406del and -1932_+3402del) were novel. The most common mutations were p.Arg243Gln (12.7%), c.611A > G (11.8%) and c.1197A > T (9.1%). The mutations of PKU patients with from Hebei Province are scattered throughout the PAH gene. Most of them are of single nucleotide substitutions, but large deletions are not rare.


Guo F.P.,Peking Union Medical College
Zhonghua nei ke za zhi [Chinese journal of internal medicine] | Year: 2010

To evaluate the influence of highly active antiretroviral therapy (HAART)on bone mineral density(BMD) of human immunodeficiency virus (HIV) infected patients and correlating clinical factors. The clinical data from 2007 to 2008 were analyzed, including 50 patients treated with HAART (named treated group), 12 HIV-infected antiretroviral-naive patients (named untreated group) and 20 healthy people (named control group). Lumbar, femoral neck, femur, femoral greater trochanter and whole body BMD were measured by dual energy X-ray absorptiometry. The data were respectively analyzed. There were 19(38.0%) patients with osteopenia and 1 (2.0%) patient with osteoporosis in the treated group. There were 6 (50.0%) patients with osteopenia and 2 (16.7%) patient with osteoporosis in the untreated group. There were 5 (25.0%) patients with osteopenia, no one with osteoporosis in the control group. The prevalence of osteopenia/osteoporosis was statistically higher in the untreated group than that in the control group (P=0.02). The BMD of femur, femoral neck and greater trochanter [(0.97±0.14), (0.91±0.13), (0.76±0.12) g/cm2] in the HIV-infected group (including the treated and untreated group) were significantly lower than that in the control group [(1.04±0.12), (0.98±0.14), (0.84 ± 0.11) g/cm2, P<0.05]. There were no significantly differences in the BMD between the untreated group and the treated group. In the treated group, osteopenia/osteoporosis correlated with body weight less than 60 kg (r=0.074, P=0.004) and the viral load before HAART (r=5.103, P=0.021). The prevalence of osteopenia and osteoporosis in antiretroviral-naive HIV-infected patients is higher. The BMD of HIV-infected patients are reduced compared with the healthy people. The BMD is similar among HIV-infected patients irrespective of antiretroviral treatment. Body weight less than 60 kg and the viral load before HAART are the risk factors of osteopenia/osteoporosis for the HIV-infected antiretroviral patients.


Guo L.L.,Peking Union Medical College
Zhonghua xin xue guan bing za zhi | Year: 2011

To investigate the cardiovascular risk profile in patients with glycogen storage disease (GSD) type I. The clinical information of 62 patients with GSD type I who admitted to Peking Union Medical Hospital were reviewed and the cardiovascular risk profile was analyzed. The age of the patient cohort was (8.4 ± 6.9) years and the ratio of male vs. female was 36:26. The median disease duration was (6.7 ± 6.2) years and treatment duration was (38.3 ± 35.2) months. The rate of abnormal change in electrocardiogram and echocardiography was 17.7% and 24.2%, respectively. The serum concentration of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and uric acid in patient before and after treatment were (6.18 ± 2.47) mmol/L vs. (5.61 ± 1.84) mmol/L (P = 0.020), (11.17 ± 9.85) mmol/L vs. (6.81 ± 5.97) mmol/L (P = 0.010), (2.55 ± 1.27) mmol/L vs. (2.78 ± 1.07) mmol/L (P = 0.617), (0.98 ± 0.37) mmol/L vs. (0.96 ± 0.23) mmol/L (P = 0.005), (526.53 ± 127.09) μmol/L vs. (490.78 ± 129.79) μmol/L (P = 0.977), respectively. The high-sensitivity C-reactive protein levels tended to be higher after therapy compared before treatment (2.33 ± 3.30) mg/L vs. (3.35 ± 3.39) mg/L, P = 0.431. Patients with GSD I are associated with an increased risk for cardiovascular disease.


Wang Q.,Peking Union Medical College | Wang J.,Peking Union Medical College
Journal of Craniofacial Surgery | Year: 2015

Various types of anterior chest flaps can be recruited in the reconstruction of faciocervical region. Most of them were created based on the internal mammary artery and the lateral thoracic artery, and the thoracoacromial artery (TAA) is usually used in pectoralis major musculocutaneous flap. An anterior chest flap with TAA perforator (TAAP) will have no sacrifice of the pectoralis major muscle, but less reports, especially expanded pedicled one, can be reviewed. Here, we reported a case using expanded pedicled TAAP flap to reconstruct the perioral scar contracture. In this technique, expanded TAAP flap could be easily harvested without the sophisticated microsurgical technology. Acceptable esthetic and functional results were achieved. © 2015 Mutaz B. Habal, MD.


Cheng Z.W.,Peking Union Medical College
Zhonghua xin xue guan bing za zhi | Year: 2010

To summarize the electrocardiography and echocardiography features of patients with cardiac amyloidosis (CA) diagnosed by endo-myocardial biopsy (EMB). A total of 20 consecutive patients [7 men, mean age (50 ± 12) years] referred for EMB because of clinical suspicion of CA from September 2006 to October 2009 were included in the study. Primary CA was diagnosed in 11 out of 20 patients (55%) by EMB and biomarkers examination. The electrocardiography and echocardiography features were analyzed. The voltage of all the limb leads were low in the 11 CA patients [mean values of (0.33 - 0.51) mV], the incidence of low voltage and pseudo-infarction patterns were 45% and 45%, respectively. Concentric hypertrophy and normal left ventricular diameters were evidenced in all CA patients on echocardiography, left atrial enlargement (n = 10, 91%), granular/sparking appearance of the myocardium (n = 9, 82%) and moderate to large pericardial effusion (n = 7, 64%) as well as left ventricular systolic dysfunction (n = 8, 73%) were often presented in CA patients. The diagnosis of primary CA should be considered in patients with unknown origin of heart failure, concentric hypertrophy and normal left ventricular diameters with granular/sparking appearance of the myocardium or pericardial effusion presented on echocardiography and low voltage of limb leads or pseudo-infarction pattern presented on electrocardiography. EMB and serum (urine) biomarkers examinations should be then performed to confirm or exclude the diagnosis of CA.


Wang J.,Peking Union Medical College
Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery | Year: 2012

To explore the assessment methods of dysphagia. The data of 37 patients with dysphagia were retrospectively analyzed. These patients took the Kubota drinking test, Tengdao's evaluation, videofluoroscopic swallowing study (VFSS) and fiberoptic endoscopic evaluation of swallowing (FEES). Fourteen out of thirty-seventh patients showed abnormal results during Kubota drinking test. Tengdao's evaluation results showed that 29/37 patients were abnormal. There 27/37 and 33/37 patients showed abnormalities in positive-aspiration score and swallow dysfunction score of VFSS. The number of abnormal patients in aspiration score of FEES was 19/21. The Kappa values were 0.137, 0.416 between Kubota drinking test. Tengdao's evaluation and VFSS. The FEES was measured against the VFSS for sensibility, specificity, positive predictive value, and negative predictive value, the values were 88.9%, 66.7%, 94.1% and 50.0%. Kubota drinking test and Tengdao's evaluation can be applied for screening purpose and evaluating result after treatment; VFSS and FEES can be used as more accurate assessments, they can study the dysphagia's character, position and severity. The combination of a variety of dysphagia evaluation methods is the most important basis for diagnosis and treatment of deglutition disorders.


Qiu Z.Q.,Peking Union Medical College
Zhonghua er ke za zhi. Chinese journal of pediatrics | Year: 2011

Glycogen storage disease type Ib (GSDIb, MIM: 232220) is an autosomal recessive inborn error of metabolism caused by deficiency of the glucose-6-phosphate translocase. The clinical manifestations include symptoms and signs of both the typical GSDIa, including hepatomegaly, fasting hypoglycemia, lactic acidemia and hyperlipidemia, and the dysfunction of neutrophils of recurrent infection and neutropenia. More than 84 mutations have been identified since the discovery of the SLC37A4 gene as the disease causing gene. Up to date, 5 mutations in 4 Chinese patients were reported from Hong Kang and Taiwan. In order to see the spectrum of the SLC37A4 gene mutations and the correlation between genotype and phenotype in patients with GSDIb of the mainland of China, the authors investigated 17 GSDIb patients from 15 families in this study. Data of 17 patients from 12 provinces, 11 male and 6 female, aged 6 months to 35 years, were collected from the genetic clinics of Peking Union Medical College Hospital from Oct. 2006 to Mar. 2009. All of them were Han Chinese in ethnicity. Consanguineous status was confirmed in 2 unrelated patients. All patients were presented with hepatomegaly, fasting hypoglycemia, lactic acidemia, hyperlipidemia and neutropenia with variable frequency of infections. The full coding exons, their relevant exon-intron boundaries, and the 5'- and 3'-flanking regions of the SLC37A4 gene were amplified and directly sequenced. RT-PCR was performed to verify the effect of the 2 novel splicing mutations. A total of 11 mutations were identified in 15 families. Four mutations, p.Gly149Glu, p.Pro191Leu, p.Arg415X and c.1042_1043 del CT, were previously reported, and seven mutations, p. Leu23Arg, p.Gly115Arg, p.Gly281Val, p.Arg415Gly, c.784 + 1G > A, c.870 + 5G > A and c.1014_1120del107, were novel. The frequent mutations are p.Pro191Leu, p.Gly149Glu and c.870 + 5G > A, accounting for 37%, 15% and 11% of mutant alleles respectively. RT-PCR analysis of novel mutation c.784 + 1G > A confirmed the splicing of exon 5 of 159 bp, causing inframe deletion. While mutation c.870 + 5G > A was proved to cause exon 6, 86 bp, deletion causing frame-shift. Among 15 families, 12 genotypes were identified, including 3 with homozygous mutation and 9 with compound heterozygous mutations. Homozygous p.Pro191Leu mutation was the only genotype detected in more than 1 family and was found in 4 unrelated families, including 1 patient from consanguineous marriage. A total of 11 SLC37A4 gene mutations were identified in 15 families of the mainland of China. The frequent mutations are p.Pro191Leu, p.Gly149Glu and c.870 + 5G > A. The number of Chinese SLC37A4 gene mutations was extended from 5 to 14.