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Nanjing Medical University is a university in Nanjing, Jiangsu Province, China. It was established in 1934 in Zhenjiang, but subsequently relocated to Nanjing in 1957. The university has two main campuses: Wutai and Jiangning, both of which have international student apartments.In 2014, Academic Ranking of World Universities ranked it between 401-500 in the world and 26-32 in China. It was one of the first universities to offer an English taught Bachelor of Medicine, Bachelor of Surgery program, as approved by the Ministry of Education of the People's Republic of China . Wikipedia.

Zhu M.,Nanjing Medical University
Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] | Year: 2011

This research aimed to explore the application of ARIMA model of time series analysis in predicting influenza incidence and early warning in Jiangsu province and to provide scientific evidence for the prevention and control of influenza epidemic. The database was created based on the data collected from monitoring sites in Jiangsu province from October 2005 to February 2010. The ARIMA model was constructed based on the number of weekly influenza-like illness (ILI) cases. Then the achieved ARIMA model was used to predict the number of influenza-like illness cases of March and April in 2010. The ARIMA model of the influenza-like illness cases was (1 + 0.785B(2))(1-B) ln X(t) = (1 + 0.622B(2))ε(t). Here B stands for back shift operator, t stands for time, X(t) stands for the number of weekly ILI cases and ε(t) stands for random error. The residual error with 16 lags was white noise and the Ljung-Box test statistic for the model was 5.087, giving a P-value of 0.995. The model fitted the data well. True values of influenza-like illness cases from March 2010 to April 2010 were within 95%CI of predicted values obtained from present model. The ARIMA model fits the trend of influenza-like illness in Jiangsu province.

HIF-1α (hypoxia-inducible factor 1 alpha) is believed to promote oesophageal squamous tumour growth. Thus, an HIF-1α inhibitor is viewed as a therapeutic target in treating oesophageal cancer. Recently, YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole] has been widely used as a potential HIF-1α inhibitor and is being developed as a novel anticancer drug. However, little is known about the effects of YC-1 in human oesophageal cancer. In the present study, we aimed to investigate these effects in an esophageal squamous cancer cell line; i.e. Eca109 cells. We found that YC-1 abolished the hypoxia-induced up-regulation of HIF-1α. YC-1 arrested cell growth and inhibited cell migration activities in Eca109 cells. These results suggest that YC-1 may be a chemotherapy candidate against oesophageal squamous cancers.

Li Y.,Peking University | Tang H.-L.,Peking University | Hu Y.-F.,Peking University | Xie H.-G.,Nanjing Medical University
Journal of Thrombosis and Haemostasis | Year: 2012

Background:A large number of clinical studies have documented that a loss-of-function variant CYP2C19*2 affects clinical profiles of clopidogrel (efficacy and safety). However, data on the impact of a gain-of-function variant CYP2C19*17 on the response to that drug seem to be less consistent. Objectives:To systematically summarize all available clinical data assessing the role of the CYP2C19*17 variant in patients taking clopidogrel. Methods:A literature search was conducted and a meta-analysis was performed for 11 eligible studies. The endpoints included the major adverse cardiovascular events (MACE, representing non-fatal myocardial infarction, stroke, revascularization, or death), bleeding events, mortality, stent thrombosis and high platelet reactivity (HPR). Results:Data from six clinical studies demonstrated that carriers of the CYP2C19*17 variant had a marked protection against recurrent cardiovascular events in patients with coronary artery disease compared with non-carriers, as measured by a 16% decrease in the incidence of MACE (10.0% vs. 11.9%; OR, 0.82; 95% CI, 0.72-0.94; P=0.005). On the other hand, carriers had an increased risk of developing bleeding as expected (8.0% vs. 6.5%; OR, 1.25; 95% CI, 1.07-1.47; P=0.006; four studies). Moreover, the presence of the CYP2C19*17 variant might lead to increased response to clopidogrel, as shown by a marked lower prevalence of HPR in carriers than in non-carriers (37.9% vs. 50.8%; OR, 0.60; 95% CI, 0.45-0.79; P=0.0003; three studies). Conclusions:Carriers of the CYP2C19*17 variant have greater therapeutic responsiveness to clopidogrel than non-carriers, but they have an increased risk of developing bleeding as well. © 2011 International Society on Thrombosis and Haemostasis.

Bao N.R.,Nanjing Medical University
Zhongguo gu shang = China journal of orthopaedics and traumatology | Year: 2010

OBJECTIVE: To analyze the complications of bipolar hemiarthroplasty for the treatment of intertrochanteric fractures. METHODS: From Jan. 2004 to Dec. 2007, 62 patients over 80 years old with unstable interthochanteric fracture were treated with bipolar hemiarthroplasty, included 34 males and 28 females with an average age of 86.3 years ranging from 81 to 97 years. According to the Evans classification, there were 29 cases of Evans III, 26 of Evans IV and 7 of Evans V. The systemic and operation related complications were investigated. RESULTS: Among all the cases, 59 were followed up in outpatient department for 24 to 70 months (33 months on average). Systemic complications were found in 19 cases with no death during preoperative period and 5 deaths after leaving hospital. Operation related complications were found in 9 cases, included 3 cases of thigh pain, 1 iatrogenic fracture of proximal femur, 2 hip dislocations, 2 delayed union of fractures and 1 superficial infection. There were no aseptic loosening, peri-prosthetic infections,ectopic ossification or injuries of nerves and vessels. CONCLUSION: Bipolar hemiarthroplasty is indicated for patients over 80 years old with intertrochanteric fracture, thus the organic or systemic malfunctions should be corrected during perioperative period. Meanwhile, retaining of lesser trochanter and reconstruction of calcar femorale are important for improving periprosthetic biomechanics and reducing local complications.

Deng B.Y.,Nanjing Medical University
Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] | Year: 2010

To explore the prevalence and associated factors of anxiety and depression symptoms in hospitalized Chinese patients with coronary artery disease (CAD). From June 2007 to May 2009, 1083 hospitalized patients with confirmed coronary artery disease were recruited in this study. The ZUNG Self-rating Anxiety Scale (SAS) and the ZUNG Self-rating Depression Scale (SDS) were used for the psychological assessment. Economic status, living condition and the environment of both living and working places were evaluated by epidemiological questionnaires. The prevalence of pure anxiety, pure depression symptoms and the combination of anxiety and depression symptoms were 7.9%, 28.3% and 14.3% respectively. Incidence of anxiety and depression symptoms was significantly higher in female patients compared with in male patients (P = 0.003, 0.012 respectively) and in aged patients than in middle-aged patients (P = 0.001). The elderly, less than 9 years of education and poor sleep quality increased the risk of anxiety symptom with ORs of 1.63 (95%CI: 1.21 - 2.21), 1.54 (95%CI: 1.15 - 2.07) and 1.62 (95%CI: 1.34 - 1.96), respectively, while workplace noise, history of chronic disease and poor sleep quality increased the risk of depression symptom with ORs of 1.52 (95%CI: 1.18 - 1.98), 1.36 (95%CI: 1.06 - 1.75) and 1.27 (95%CI: 1.08 - 1.50), respectively. Female (OR = 1.91, 95%CI: 1.22-2.98), aged patient (OR = 1.84, 95%CI: 1.23 - 2.76), workplace noise (OR = 1.61, 95%CI: 1.07 - 2.42), history of chronic disease (OR = 1.84, 95%CI: 1.24 - 2.71) and poor sleep quality (OR = 1.73, 95%CI: 1.35 - 2.21) were significantly correlated with the combined incidence of anxiety and depression symptoms. Around half of the Chinese hospitalized CAD patients were complicated with various degrees of anxiety and/or depression symptoms. Female and aged patients were at higher risk for anxiety and depression symptoms. Sleep quality, workplace noise, years of education and history of chronic disease were independent risk factors for anxiety or depression symptoms.

Li C.,Nanjing Medical University | Hirsh J.,MacMaster University | Xie C.,MacMaster University | Johnston M.A.,Hemostasis Reference Laboratory | Eikelboom J.W.,Thrombosis service
Journal of Thrombosis and Haemostasis | Year: 2012

Background: Guidelines recommend stopping aspirin and clopidogrel 7 to 10days before surgery to allow time for replacement of permanently inhibited platelets by newly released uninhibited platelets.Objectives: The purpose of the present study was to determine the rate of offset of the anti-platelet effects of aspirin and clopidogrel after stopping treatment and the proportion of untreated donor platelets that are required to reverse their anti-platelet effects. Methods: Cohort 1 consisted of 15 healthy subjects who received aspirin 81mgday -1 or clopidogrel 75mgday -1 for 7days and underwent serial blood sampling until platelet function testing results normalized. Cohort 2 consisted of 36 healthy subjects who received aspirin 325mgday -1, clopidogrel 75mgday -1, aspirin 81mgday -1 plus clopidogrel 75mgday -1 or no treatment for 7days and underwent a single blood sampling. Results: In cohort 1, arachidonic acid (AA)-induced light transmission aggregation (LTA) returned to baseline levels in all subjects within 4days of stopping aspirin, coinciding with the partial recovery of plasma thromboxane B 2 concentrations. ADP-induced LTA did not return to baseline levels until 10days after stopping clopidogrel. In cohort 2, AA-induced LTA in patient treated with aspirin reached control levels after mixing with 30% untreated donor platelets whereas ADP-induced LTA in patients treated with clopidogrel reached control levels only after the addition of 90% or more donor platelets. Conclusions: Platelet aggregation recovers within 4days of stopping aspirin but clopidogrel must be stopped for 10days to achieve a normal aggregatory response. © 2012 International Society on Thrombosis and Haemostasis.

Objective: To investigate the influence of fluid balance and model of renal replacement therapy (RRT) on renal function and prognosis of patients suffering from septic acute kidney injury (AKI). Methods: A retrospective cohort analysis of 117 septic AKI patients who had undergone RRT between January 2009 and December 2014 was performed in the Second Affiliated Hospital of Nanjing Medical University. The patients were divided into positive fluid balance group (n = 52) and negative fluid balance group (n = 65) according to the total amount of fluid calculated from the difference between fluid administered and fluid lost during the first 1 week of RRT. The incidence of renal recovery and death of the patients by 60 days as the endpoint events were taken to judge the prognosis of two groups. RRT strategies included continuous renal replacement therapy (CRRT) and intermittent renal replacement therapy (IRRT). Multiple factors including estimated glomerular filtration rate (eGFR), sequential organ failure assessment (SOFA) score, RRT model, the accumulation of fluid before initiation of RRT, and negative fluid balance during RRT were analyzed for outcome predictors by Cox proportional hazards model. Results: There were no differences between two groups regarding clinical characteristics. The percentage of receiving CRRT in the negative fluid balance group was slightly higher than that of the positive fluid balance group (52.31% vs. 36.54%, χ2 = 2.899, P = 0.089). With Kaplan-Meier survival curves, it was shown that the patients of negative fluid balance group had a higher rate of recovery of renal function (χ2 = 4.803, P = 0.028) and significantly lower mortality rate (χ2 = 9.505, P = 0.002). The rate of recovery of renal function by 60 days was higher in the negative fluid balance group than that in the positive fluid balance group (47.69% vs. 28.85%, χ2 = 3.991, P = 0.046), while the mortality rate was significantly lowered in the negative fluid balance group compared with that of the positive fluid balance group (40.00% vs. 67.31%, χ2 = 4.378, P = 0.036). Cox multivariate regression was used for excluding confounding factors. After adjusting for the clinically relevant variables, RRT negative fluid balance was significantly associated with recovery of renal function [hazard ratios (HR) = 2.440, 95% confidence intervals (95%CI) = 1.089-5.464, P = 0.030] and mortality (HR = 0.443, 95%CI = 0.238-0.822, P = 0.010]. Higher eGFR before RRT and CRRT were independent favorable factors for recovery of renal function (HR = 1.014, 95%CI = 1.003-1.026, P = 0.012; HR = 3.138, 95%CI = 1.765-7.461, P = 0.002), and higher SOFA score was associated with a significantly higher risk of death (HR = 1.115, 95%CI = 1.057-1.177, P < 0.001). Conclusions: Once the patients with septic AKI showed the signs of fluid overload, timely RRT and effective removal of excessive liquid may reverse the adverse prognosis. RRT with negative fluid balance is beneficial for the recovery of renal function, and reduce the mortality in patients with septic AKI, and CRRT model is a good choice. © 2015, Heilongjiang Institute of Science and Technology Information. All rights reserved.

Zhang S.,Shandong University | Hou X.,Nanjing Medical University | Zi S.,Shandong University | Wang Y.,Shandong University | And 2 more authors.
Cellular Physiology and Biochemistry | Year: 2013

Background: Given the roles of receptor for advanced glycation end products (RAGE) in the pathogenesis of carcinogenesis, we propose that RAGE polymorphisms may be associated with risk of epithelial ovarian carcinoma (EOC). Method: This case-control study included 190 women over 40 years of age who were diagnosed with primary EOC and 210 healthy control subjects. RAGE gene polymorphisms, including 82G>S,-374T>A,-429C>T,and 1704G>T were determined. Results: We found that only the frequencies of the 82G>S polymorphisms were significantly different between the EOC cases and controls. The 82SS genotype was significantly higher in EOC patients than in controls (37.89% vs. 23.33%,P<0.001). With the 82 GG genotype as reference, the OR for 82SS homozygous carriers reached to 2.65 (95% CI: 1.54-4.58; P =0.0004) after adjustment for age, smoking status, body mass index, family history, usage of contraceptives, tubal ligation history, use of menopausal hormones and menopausal status. The 82S allele carriage presented a higher risk for EOC (OR=1.71; 95% CI, 1.29-2.26; P=0.0002). The polymorphisms of 1704G>T,-374T>A and-429C>T did not affect the EOC risk. Conclusion: This result suggests that the 82G>S polymorphism of RAGE gene may be associated with the susceptibility of EOC. © 2013 S. Karger AG, Basel.

Cai N.,Nanjing Medical University
World journal of gastroenterology : WJG | Year: 2012

To conduct a meta-analysis to estimate the determinants of the association between erosive esophagitis (EE) and body mass index (BMI). We identified the studies using PubMed. Studies were selected for analysis based on certain inclusion and exclusion criteria. Data were extracted from each study on the basis of predefined items. Meta-analyses were performed to verify the risk factors, such as obesity and gender. Twenty-one studies were included in this systematic review. These studies demonstrated an association between increasing BMI and the presence of EE [95% confidence interval (CI): 1.35-1.88, overweight, odds ratio (OR) = 1.60, P value homogeneity = 0.003, 95% CI: 1.65-2.55, obese, OR = 2.05, P < 0.01]. The heterogeneity disappeared by stratifying for gender. No publication bias was observed in this meta-analysis by the Egger method. This analysis demonstrates a positive association between BMI and the presence of EE, especially in males. The risk seems to progressively increase with increasing weight.

ABSTRACT: The costosternoclavicular region is not a common bone metastasis site, and symmetrical involvement is even rarer. Increased tracer uptake in the manubrium and sternoclavicular joints usually gives the typical “bull-horn” appearance seen in SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis). Herein, we report a case of a 47-year-old woman with a history of invasive ductal carcinoma who had undergone left radical mastectomy 3 years earlier and presented with typical increased tracer uptake in the bilateral sternocostoclavicular region resembling the so-called bull horn. The final diagnosis of metastasis from breast cancer was made histopathologically following biopsy. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Ren G.,Nanjing Medical University
Indian Journal of Surgery | Year: 2015

The present study was conducted to investigate the clinical efficacy of early parenteral and enteral nutrition (PN + EN) support in neurosurgical coma patients. Eighty cases of neurosurgical coma patients were randomly divided into intervention group and control group. The intervention group received early PN + EN support, and the control group received only total enteral nutritional (TEN) support. The levels of hemoglobin (HGB), serum albumin (ALB), prealbumin (PA), and retinol-binding protein (RBP) in two groups on days 1, 10, and 20 were observed. The incidences of pneumonia, stress ulcer, abnormal liver function, abdominal distension, and diarrhea between two groups were also compared. Results found that, on day 10, compared with the control group, the levels of HGB, PA, and RBP in the intervention group were significantly increased (P < 0.05). On day 20, ALB in the intervention group significantly increased (P < 0.05), and the incidences of pneumonia, abdominal distension, and diarrhea in the intervention group were significantly lower than those in the control group (P < 0.05). Compared with only TEN support, early PN + EN support can obviously improve the nutritional status of neurosurgical coma patients and reduce the occurrence of complications. © 2015, Association of Surgeons of India.

Study design:Randomized experimental study.Objectives:To investigate the molecular mechanisms of quercetin in spinal cord injury (SCI) rats.Setting:China.Methods:One hundred female Sprague-Dawley rats were randomly assigned into four groups: sham group, SCI group, SCI+Vehicle (Veh) group, and the SCI+Quercetin (Que) group. The influences of quercetin on proinflammatory cytokine levels, histological changes and locomotion scale were estimated.Results:SCI significantly promoted nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation and increased proinflammatory cytokine productions in the SCI group as compared with the sham group. Quercetin administration significantly decreased reactive oxygen species production, inhibited NLRP3 inflammasome activation and reduced inflammatory cytokine levels. Moreover, quercetin administration attenuated histopathology and promoted locomotion recovery.Conclusion:Quercetin can attenuate tissue damage and improve neurological function recovery, and the mechanism may be related to the inhibition of NLRP3 inflammasome activation.Spinal Cord advance online publication, 12 January 2016; doi:10.1038/sc.2015.227. © 2016 International Spinal Cord Society

He J.,Nanjing Medical University
Journal of thoracic imaging | Year: 2012

Azygos vein aneurysm is extremely rare. Herein we report a 41-year-old woman whose chest radiograph showed right paratracheal opacity. During 6-month follow-up, she underwent computed tomography scanning 3 times and magnetic resonance imaging. The mass enlarged gradually and changed its position from the posterior to the anterior upper right mediastinum. Venography and surgery were finally performed, which confirmed an aneurysm of the azygos vein. Pathologic findings indicated a congenital etiology. To the best of our knowledge, such an azygos vein aneurysm with changeable position during follow-up has not been reported previously.

Pan J.,Nanjing Medical University
Interactive cardiovascular and thoracic surgery | Year: 2013

We describe a case with left atrial volume reduction of a giant left atrium, treated successfully by partial cardiac autotransplantation, concomitant mitral and aortic valve replacement, and tricuspid valve plasty. We obtained good results at the 1-year follow-up.

Huang D.,Nanjing Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2013

Adrenal teratoma is a rare germline tumor with a malignant potential. We present a case of left adrenal teratoma complicated by diabetes. The 64-year-old female patient showed multiple cystic space-occupying masses in the left kidney in B-mode ultrasound examination, and plain and enhanced CT reported a 9.0 cm heterogeneous mass in the left adrenal gland. After effective control of blood glucose, the mass was surgically removed and sent for pathological examination. The mass consisted of multiple cysts containing lipid-like substance with a cyst wall thickness of 0.2-0.4 cm; bony structures were found on the sections of the mass with fat tissues on the mass surface. A final diagnosis of left cystic mature adrenal teratoma was made based on the clinical and pathological findings and literature review. The patient was followed up for 6 months and no local recurrence or metastasis was found. Mature adrenal teratoma can be easily diagnosed by ultrasound and CT examinations and should be distinguished from other tumors of an adrenal source. Early diagnosis and early surgical resection is key to the treatment, and a definite diagnosis can be made pathologically. Chemotherapy is necessary in inoperable cases or for such tumors with a malignant potential. The patients should be followed up for life time after the treatment.

Study design:Randomized experimental study.Objectives:The study aimed to investigate the therapeutic efficacy and molecular mechanisms of A-68930 in a rat model of spinal cord injury (SCI)–induced acute lung injury (ALI).Setting:China.Methods:The influences of A-68930 on the pulmonary edema, histological changes, proinflammatory cytokines levels, myeloperoxidase (MPO) activity and NLRP3 inflammasome protein expression were estimated.Results:SCI significantly promoted NLRP3 inflammasome activation, increased proinflammatory cytokine productions and MPO activity, and induced pulmonary edema and tissue damage in the SCI group as compared with the control group. A-68930 administration significantly inhibited NLRP3 inflammasome activation and reduced inflammatory cytokines levels and MPO activity. Moreover, A-68930 administration attenuated pulmonary edema and histopathology.Conclusion:Our experimental findings indicated that A-68930 exhibited a protective effect on SCI-induced ALI by the alleviations of inflammatory response with the inhibition NLRP3 inflammasome activation 72 h post injury. The present study indicated that A-68930 could be a potentially efficient therapeutic strategy for the treatment of SCI-induced ALI.Spinal Cord advance online publication, 12 April 2016; doi:10.1038/sc.2016.52. © 2016 International Spinal Cord Society

To determine the effects of diazoxide on oxygen free radicals and cell apoptosis in brain tissue after deep hypothermia cerebral ischemia reperfusion injury in young rats. Fifty-four 3-week-old Sprague-Dawley rats were randomly and equitably divided into sham-operated group, model group and diazoxide group respectively (n = 18). The model of hypothermia cerebral ischemia reperfusion injury was made. After 24 hours of operation, the brains of rats were removed and preserved. The content of superoxide dismutase (SOD) and malonaldehyde (MDA) in brain tissue were detected. Cytosolic C release of cytochrome was confirmed by Western Blot. The protein expression of Caspase-3 was determined by immunohistochemistry. In the model group, the content of SOD was (198 +/- 41) U/mg, lower than the sham-operated group's (321 +/- 36) U/mg (P < 0.01). The content of MDA was (212 +/- 21) nmol/mg, was higher than the sham-operated group's (100 +/- 23) nmol/mg (P < 0.01), and the expressions of cytochrome C (0.72 +/- 0.09) and Caspase-3 (83 +/- 10) were all significantly higher than those in the sham-operated group (0.17 +/- 0.02 and 115 +/- 9) (P < 0.01). Compared with the model group, the content of SOD in the diazoxide group [(264 +/- 34) U/mg] was markedly increased (P < 0.05). In addition, diazoxide provided significant reductions in the content of MDA [(174 +/- 19) nmol/mg] and the expressions of cytochrome C (0.41 +/- 0.05) and Caspase-3 (99 +/- 11) (P < 0.05). The neuroprotective effects of diazoxide against brain injury induced by deep hypothermia cerebral ischemia reperfusion through inhibiting oxygen free radicals and cell apoptosis. Diazoxide may become a new neuroprotective drug after infant complicated congenital cardiac operation.

Tan C.,Jiangsu Provincial Hospital of Traditional Chinese Medicine | Liu Y.,Jiangsu Provincial Hospital of Traditional Chinese Medicine | Min Z.-S.,Jiangsu Provincial Hospital of Traditional Chinese Medicine | Zhu W.-Y.,Nanjing Medical University
Journal of the European Academy of Dermatology and Venereology | Year: 2014

Background Pigmented fungiform papillae of the tongue (PFPT) is a disorder in which the fungiform papillae of the tongue have abnormal coloration. However, Chinese-specific clinical data for PFPT are lacking. Objective To determine the prevalence and characteristics of PFPT among the Chinese population. Methods A survey was carried out using a clinical examination and a questionnaire on 14,346 first-time outpatients in our dermatology department, and 58 cases of PFPT were subsequently diagnosed. Results The prevalence of PFPT was 0.4% among dermatological outpatients. All patients had pin-sized, brownish fungiform papillae on the tip, lateral or dorsal parts of the tongue. Of the three subtypes, type I was the most common (87.93%). PFPT generally coexisted with Hori's nevus (48.28%), melasma (20.69%), hysteromyoma (24.14%) and breast cystic hyperplasia (20.69%). Conclusion Our study confirms that PFPT is a relatively common disorder among Chinese outpatients, and it was presumed to be closely coupled with Hori's nevus, melasma and other disorders. © 2012 The Authors.

Gao J.,University of Nebraska - Lincoln | Qin R.,University of Nebraska - Lincoln | Qin R.,Nanjing Medical University | Li M.,University of Nebraska - Lincoln
Journal of Psychopharmacology | Year: 2015

The present study investigated how repeated administration of aripiprazole (a novel antipsychotic drug) alters its behavioral effects in two behavioral tests of antipsychotic activity and whether this alteration is correlated with an increase in dopamine D2 receptor function. Male adult Sprague-Dawley rats were first repeatedly tested with aripiprazole (3, 10 and 30 mg/kg, subcutaneously (sc)) or vehicle in a conditioned avoidance response (CAR) test or a phencyclidine (PCP) (3.20 mg/kg, sc)-induced hyperlocomotion test daily for five consecutive days. After 2-3 days of drug-free retraining or resting, all rats were then challenged with aripiprazole (1.5 or 3.0 mg/kg, sc). Repeated administration of aripiprazole progressively increased its inhibition of avoidance responding and PCP-induced hyperlocomotion. More importantly, rats previously treated with aripiprazole showed significantly lower avoidance response and lower PCP-induced hyperlocomotion than those previously treated with vehicle in the challenge tests. An increased sensitivity to quinpirole (a selective D2/3 agonist) in prior aripiprazole-treated rats was also found in the quinpirole-induced hyperlocomotion test, suggesting an enhanced D2/3-mediated function. These findings suggest that aripiprazole, despite its distinct receptor mechanisms of action, induces a sensitization effect similar to those induced by other antipsychotic drugs and this effect may be partially mediated by brain plasticity involving D2/3 receptor systems. © The Author(s) 2014.

We examined a possible relationship -420C>G SNP of the resistin gene with plasma resistin and C-reactive protein concentrations in intracerebral hemorrhage. Three hundred and forty-four Chinese Han patients with intracerebral hemorrhage and 344 age- and gender-matched healthy controls were included in our study. Plasma resistin and C-reactive concentrations were measured and SNP -420C>G was genotyped. The genotype frequencies in controls and patients were not significantly different (P = 0.672). Plasma resistin and C-reactive protein levels were significantly different between the SNP -420C>G genotypes, even after adjustment for age, gender and body mass index. The common homozygote (C-C) had the lowest resistin and C-reactive protein plasma concentrations; the plasma resistin and C-reactive protein concentrations in the heterozygote (C-G) and the rare allele homozygote (G-G) did not differ significantly. Plasma resistin levels were significantly associated with plasma C-reactive protein level. We conclude that SNP -420C>G of the resistin gene could be involved in the inflammatory component of intracerebral hemorrhage through enhanced production of resistin.

Zhang T.,Nanjing Medical University
Zhonghua yi xue za zhi | Year: 2011

To establish the cathepsin B over-expression group and cathepsin B gene-silencing group so as to investigate whether cathepsin B was capable of promoting the apoptosis of VSMC (vascular smooth muscle cell) induced by TNF-α/act D. Human aortic smooth muscle cell (HA-VSMC) was transfected with pcDNA3.1-cathepsin B and pSilencer2.1-cathepsin B plasmids by lipofection to establish the over-expression and gene-silencing groups. Through TNF-α induced apoptosis, the cell viability was observed by MTT assay, morphological observation and assays of apoptotic proteins as indicators of apoptosis. The cathepsin B over-expression and gene-silencing group were successfully established. MTT assay showed no significant difference between the transfected cell and blank control. After the intervention of TNF-α, the HA-VSMC viability decreased significantly. As compared with control group, the over-expression group significantly decreased (9.98% ± 1.04% vs 14.60% ± 1.34%). As compared with the over-expression group, the E64d and CA-074ME groups (18.23% ± 1.05%, 17.40% ± 1.03%) increased significantly while the silent group (21.30% ± 2.37%) significantly increased. The analysis of acridine orange/ethidium bromide staining showed similar results. Western blot showed the Bcl-2 protein were significantly higher in the silent group than that in the control group. And the over-expression group was significantly lower than the control group. The E64d and CA-074ME groups were significantly higher than that in the over-expression group. But the Bax protein level had no significant difference among all groups. The over-expression of cathepsin B promotes TNF-α-induced VSMC apoptosis while Cathepsin B gene silencing and the addition of cathepsin inhibitor in over-expression group inhibit the TNF-α induced VSMC apoptosis.

To investigate the effect of epidermal growth factor (EGF) on the expression of Matrix metalloproteinase-9 (MMP-9) and the signalling pathways involved in the trophoblast cell line JEG-3. The JEG-3 trophoblast cell line was used in this study. (1) JEG-3 cells were cultured with various concentrations of EGF (0, 1, 10, 20 ng/ml) for 24 hours and the expression of MMP-9 was tested by western blotting and reverse transcription PCR (RT-PCR). (2) Western blotting and RT-PCR were also used to investigate the expression of MMP-9 expression after incubation for 0, 4, 12 and 24 hours with EGF treatment (10 ng/ml) in JEG-3 cells. (3) According to the different added ingredients, JEG-3 cells were divided into some groups: control group (without EGF), EGF group (exposure to 10 ng/ml EGF), EGF+ inhibitors group (exposure to 10 ng/ml EGF+ 20 ng/ml SB203580 or exposure to 10 ng/ml EGF+ 10 ng/ml U0126), inhibitors group (exposure to 20 ng/ml SB203580 or exposure to 10 ng/ml U0126). Western blotting were used to investigate the expression levels of MMP-9, nuclear factor kappa B (NF-κB), p38MAPK, phospho-p38MAPK (p-p38MAPK), extracellular-signal regulated kinase (ERK) and phospho-ERK (p-ERK) protein in JEG-3 cells after incubation for 24 hours. (1) The profiles of MMP-9 mRNA were increased by various concentrations of EGF (0, 1, 10, 20 ng/ml) in JEG-3 cells after 24 h-culture. The expression of MMP-9 mRNA in JEG-3 cells exposure at 1 ng/ml of EGF (0.567±0.056), 10 ng/ml of EGF (1.392±0.133), 20 ng/ml of EGF (1.971±0.067) were significantly higher respectively (P<0.05), compared with 0 ng/ml of EGF treatment (0.166±0.015). Similarly, MMP-9 mRNAs were also increased with the increasing incubation time. Compared to EGF (10 ng/ml) stimulation for 0 h (0.253±0.044), the MMP-9 mRNA profiles were 0.470±0.026, 1.061±0.115, 1.453±0.180 for 4, 12 and 24 hours, respectively (P<0.05). (2) In accordance to the mRNA profiles, the expression of MMP-9 protein was also increased by different concentrations of EGF (0, 1, 10, 20 ng/ml) in JEG-3 cells after 24 h-culture. The abundance of MMP-9 protein in the three groups was 0.043±0.012, 0.085±0.008, 0.142±0.015, with a significantly higher expression, compared with 0 ng/ml of EGF treatment (0.004±0.001, P<0.05) respectively. Similarly, MMP-9 proteins were also increased with the increasing incubation time. Compared to EGF (10 ng/ml) stimulation for 0 h (0.030±0.009), the profiles of MMP-9 protein were 0.137±0.010, 0.240±0.010, 1.240±0.061 for 4, 12 and 24 hours, respectively (P<0.05). (3) Both p38MAPK and ERK signalling pathways were activated by EGF in JEG-3 cells. The expression of p-p38MAPK was significantly higher (without or with 10 ng/ml EGF, 234.1±4.1 vs. 260.9±2.5, P<0.05), however, the p38MAPK inhibitor SB203580 markedly suppressed the increase in p-p38MAPK content induced by EGF (227.9±2.4 vs. 260.9±2.5, P<0.05). Similarly, the expression of p-ERK was significantly higher with EGF treatment (812.2±3.5) vs. without EGF group (453.4±5.8) (P<0.05), while the ERK inhibitor U0126 significantly inhibited the increased p-ERK content in response to EGF treatment (71.0±1.2 vs. 812.2±3.5, P<0.05). (4) The p38MAPK inhibitor SB203580 significantly reduced the expression of EGF-induced MMP-9 (0.645±0.270 vs. 1.476±0.452, P<0.05) and NF-κB (0.530±0.026 vs. 0.959±0.017, P<0.05). (5) The ERK inhibitor U0126 also significantly reduced the expression of EGF-induced MMP-9 (0.623±0.030 vs. 2.112±0.056, P<0.05) and NF-κB (0.325±0.082 vs. 0.939±0.153, P<0.05). EGF induced the expression of MMP-9 in a time and dose-dependant manner in JEG-3 cells. EGF enhanced MMP-9 expression through the activation of p38MAPK and ERK signalling pathways in JEG-3 cells.

Jiang H.,Nanjing Southeast University | Tang R.-N.,Nanjing Southeast University | Wang J.,Nanjing Medical University
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2013

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of nosocomial pneumonia. Compared with glycopeptide antibiotics, linezolid achieves higher lung epithelial lining fluid concentrations, which may have an advantage in treating nosocomial pneumonia patients. The objective of this study was to evaluate the efficacy and safety of linezolid versus vancomycin or teicoplanin for the treatment of nosocomial pneumonia. Data were obtained from the Cochrane Central Register of Controlled Trials and the EMBASE and MEDLINE databases. Randomised controlled studies involving the use of linezolid versus vancomycin or teicoplanin in nosocomial pneumonia patients were included in the study. Twelve linezolid trials were included. There was no statistically significant difference between the two groups in the treatment of nosocomial pneumonia regarding the clinical cure rate [relative risk (RR) = 1.08, 95 % confidence interval (CI) = 1.00-1.17, p = 0.06]. Linezolid was associated with better microbiological eradication rate in nosocomial pneumonia patients compared with glycopeptide antibiotics (RR = 1.16, 95 % CI = 1.03-1.31, p = 0.01). There were no differences in the all-cause mortality (RR = 0.95, 95 % CI = 0.83-1.09, p = 0.46) between the two groups. However, the risks of rash (RR = 0.41, 95 % CI = 0.24-0.71, p = 0.001) and renal dysfunction (RR = 0.41, 95 % CI = 0.27-0.64, p < 0.0001) were higher with glycopeptide antibiotics. Although linezolid was more effective in eradicating microbiology than glycopeptide antibiotics for nosocomial pneumonia patients, it did not demonstrate superiority in clinical cure. The incidences of renal dysfunction and rash are higher in the glycopeptide antibiotics group. © 2013 Springer-Verlag Berlin Heidelberg.

Wei B.,Nanjing Medical University
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery | Year: 2013

To evaluate the feasibility and validity of chondrogenic differentiation of marrow clot after microfracture of bone marrow stimulation combined with bone marrow mesenchymal stem cells (BMSCs)-derived extracellular matrix (ECM) scaffold in vitro. BMSCs were obtained and isolated from 20 New Zealand white rabbits (5-6 months old). The 3rd passage cells were cultured and induced to osteoblasts, chondrocytes, and adipocytes in vitro, respectively. ECM scaffold was manufactured using the 3rd passage cells via a freeze-dying method. Microstructure was observed by scanning electron microscope (SEM). A full-thickness cartilage defect (6 mm in diameter) was established and 5 microholes (1 mm in diameter and 3 mm in depth) were created with a syringe needle in the trochlear groove of the femur of rabbits to get the marrow clots. Another 20 rabbits which were not punctured were randomly divided into groups A (n=10) and B (n=10): culture of the marrow clot alone (group A) and culture of the marrow clot with transforming growth factor beta3 (TGF-beta3) (group B). Twenty rabbits which were punctured were randomly divided into groups C (n=10) and D (n=10): culture of the ECM scaffold and marrow clot composite (group C) and culture of the ECM scaffold and marrow clot composite with TGF-beta3 (group D). The cultured tissues were observed and evaluated by gross morphology, histology, immunohistochemistry, and biochemical composition at 1, 2, 4, and 8 weeks after culture. Cells were successfully induced into osteoblasts, chondrocytes, and adipocytes in vitro. Highly porous microstructure of the ECM scaffold was observed by SEM. The cultured tissue gradually reduced in size with time and disappeared at 8 weeks in group A. Soft and loose structure developed in group C during culturing. Chondroid tissue with smooth surface developed in groups B and D with time. The cultured tissue size of groups C and D were significantly larger than that of group B at 4 and 8 weeks (P < 0.05); group D was significantly larger than group C in size (P < 0.05). Few cells were seen, and no glycosaminoglycan (GAG) and collagen type II accumulated in groups A and C; many cartilage lacunas containing cells were observed and more GAG and collagen type II were synthesized in groups B and D. The contents of GAG and collagen increased gradually with time in groups B and D, especially in group D, and significant difference was found between groups B and D at 4 and 8 weeks (P < 0.05). The BMSCs-derived ECM scaffold combined with the marrow clot after microfracture of bone marrow stimulation is effective in TGF-beta3-induced chondrogenic differentiation in vitro.

Zuo Y.-Z.,Shandong University | Zuo Y.-Z.,Nanjing Medical University | Liu C.,Shandong University | Liu S.-W.,Shandong University
Radiology | Year: 2013

Purpose: To describe the normal imaging appearance of pulmonary intersegmental planes on thoracic computed tomographic (CT) scans and determine the possible reasons related to their visualization in terms of aging and anatomy. Materials and Methods: The study was approved by the internal ethics review board. Informed consent was obtained. A retrospective review was undertaken of 104 thoracic multidetector CT scans of an older group (.65 years) and younger group (,55 years). The number, location, and appearance rate of intersegmental planes were assessed. Group comparisons were made, and linear regression analysis was used to assess relationships between age and visualization of intersegmental planes. Thirty lung samples (10 × 10 × 10 mm3) from autopsy were scanned by using micro-CT. Thicknesses of intersegmental planes were measured. Significant differences of the thickness between visible and invisible intersegmental planes were assessed with the independent t test. In five fetal specimens (17-21 weeks in gestational age), 7.0-T magnetic resonance (MR) imaging was performed to determine the congenital difference of thickness of intersegmental planes. Results: Within the right lung, appearance rates of visible intersegmental planes were 71.2% at S1-S3, 54.8% at S4-S5, and 70.2% at S7-S10. Within the left lung, appearance rates of visible intersegmental planes were 39.4% at S1+2 to S3, 64.4% at S4-S5, 18.3% at S7-S8, and 89.4% at S7-S10. Appearance rates of visible intersegmental planes on thoracic CT scans were not significantly different (P ≥ .38) between younger and older groups. Mean thicknesses of visible and invisible intersegmental planes were 681.3 μm ± 75.3 (standard deviation) and 221.7 μm ± 54.1, respectively. Visible intersegmental planes were significantly thicker than invisible intersegmental planes (P < .05). Visible intersegmental planes were also seen on fetal lung 7.0-T MR images. Conclusion: The thickness of pulmonary intersegmental planes and variation of intersegmental veins were closely related to visualization of intersegmental planes on thoracic CT scans. Aging was excluded as the possible reason. © 2013 RSNA.

Zhang J.Y.,Nanjing Medical University
Zhonghua nan ke xue = National journal of andrology | Year: 2013

MicroRNAs (miRNAs) are a kind of small non-coding single-stranded RNA molecules that negatively regulate gene expressions by binding to imperfect complementary sites in the 3 untranslated region of targeted mRNAs at the post-transcriptional level. The aberrant expression of some miRNAs has been discovered to be involved in the pathogenesis of various cancers, including prostate cancer. By analyzing miRNA expressions in prostate cancer tissues, serum and cell lines, and then investigating their mechanisms, we expect to provide some new theoretic bases for the clinical diagnosis and treatment of prostate cancer.

Zhang D.J.,Nanjing Medical University
Zhonghua er ke za zhi. Chinese journal of pediatrics | Year: 2010

To evaluate the value of flexible fiberoptic bronchoscopy in diagnosis and treatment of pulmonary atelectasis in children. Totally 104 patients with pulmonary atelectasis, who were admitted to this department, received flexible fiberoptic bronchoscopy from January 2006 to May 2010, were enrolled in a retrospective analysis. The analysis on causes of pulmonary atelectasis showed that 76 cases (73%) of the 104 patients had sputum obstructions, which was the main cause of atelectasis. Thirteen cases (13%) had bronchopulmonary dysplasia, 9 cases among these were infants. Twelve cases (12%) had foreign body aspiration, 8 cases among these were under the age of 3-year. After flexible fiberoptic bronchoscopy, 100 cases got expansion of pulmonary atelectasis. Sixty-five of the sputum obstruction cases got atelectasis reexpansion after one time of flexible fiberoptic bronchoscopy. Eight of the sputum obstruction cases got atelectasis reexpansion after two times of flexible fiberoptic bronchoscopy. Two of the sputum obstruction cases got atelectasis reexpansion after three times of flexible fiberoptic bronchoscopy. The rate of atelectasis reexpansion after one time of alveolus lavement was higher in the cases whose courses of disease were under 3 weeks, than in the cases whose courses of disease were beyond 3 weeks. Etiology of pulmonary atelectasis varied at different age. The morbidity of bronchopulmonary dysplasia was high in infants. Foreign body aspiration was the common cause of pulmonary atelectasis in children from 1 to 3-year of age. Sputum obstruction was the main cause of pulmonary atelectasis in over 3-year-old children. Most cases got atelectasis reexpansion after alveolar lavage. The patients who had shorter course of disease might have higher rate of atelectasis reexpansion after alveolar lavage once. Flexible fiberoptic bronchoscopy plays an important role in diagnosis and treatment of pulmonary atelectasis.

Xu L.,Nanjing Medical University
Journal of Spinal Disorders and Techniques | Year: 2015

STUDY DESIGN:: A retrospective study. OBJECTIVE:: To determine the definite cut-off value of initial correction rate (ICR) that could be predictive of bracing outcome in patients with adolescent idiopathic scoliosis. SUMMARY OF BACKGROUND DATA:: Earlier studies showed that braced patients with a better ICR could finally have a higher probability of successful outcome. However, it remains controversial what definitive cut-off value of ICR is required to accurately predict the outcome. MATERIALS AND METHODS:: A cohort of 488 adolescent idiopathic scoliosis patients who have completed the brace treatment with a minimum of 2-year follow-up were included in the current study. Curve progression of ≤5 degrees was used to define the success of brace treatment. The success group and the failure group were compared in terms of initial Risser sign, initial age, sex, curve pattern, initial curve magnitude, and ICR. The receiver operating characteristics curve was used to define the definite cut-off point of initial curve correction rate. A logistic regression model was created to determine the independent predictors of the bracing outcome. RESULTS:: At the beginning of brace treatment, the mean age of the cohort was 13.2±1.5 years, and the mean curve magnitude was 29.5 ± 6.6 degrees. At the final follow-up, 368 patients were successfully treated by bracing. Compared with the success group, the failure group was found to have significantly younger age, lower Risser sign, and lower ICR. According to the receiver operating characteristic curve, the best cut-off value of ICR was 10%. The logistic regression model showed that ICR was significantly associated with the outcome of brace treatment with an odds ratio of 9.61. CONCLUSIONS:: Patients with low ICR, low Risser sign, and young age could have a remarkably high risk of bracing failure. A rate of 10% was the optimal cut-off point for ICR, which can be used to effectively stratify braced patients. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Wei B.,Nanjing Medical University
PloS one | Year: 2013

Glutathione S-transferase P1 (GSTP1) is thought to be involved in the detoxification of reactive carcinogen metabolites. Numerous epidemiological studies have evaluated the association of GSTP1 Ile105Val polymorphism with the risk of prostate cancer. However, the results remain inconclusive. To derive a more precise estimation, a meta-analysis was performed. A comprehensive search was conducted to identify the eligible studies. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the relationship. The overall association was not significant (Val/Val vs. Ile/Ile OR = 1.06, 95% CI = 0.90-1.25, P = 0.50; Val/Val vs. Val/Ile+Ile/Ile: OR = 1.07, 95% CI = 0.91-1.25, P = 0.44). In subgroup analyses by ethnicity and prostate cancer grade, the similar results were observed. However, in stratified analysis by clinical stage, we found a significant association with low-stage prostate cancer (Val/Val vs. Ile/Ile: OR = 2.70, 95% CI = 1.73-4.22, P<0.001; Val/Val vs. Val/Ile+Ile/Ile: OR = 2.14, 95% CI = 1.38-3.33, P = 0.001). Moreover, there was no statistically significant evidence of multiplicative interactions neither between the GSTP1 Ile105Val polymorphism and GSTM1, nor between smoking status and GSTP1 on prostate cancer risk. This meta-analysis showed that GSTP1 Ile105Val polymorphism might not be significantly associated with overall prostate cancer risk. Further stratified analyses showed a significant association with low-stage prostate cancer.

Zhao H.,Shanghai JiaoTong University | Xu Z.,Shanghai JiaoTong University | Qin H.,Shanghai JiaoTong University | Gao Z.,Nanjing Medical University | And 3 more authors.
Biochemical Journal | Year: 2014

CRC (colorectal cancer) is one of the most malignant tumours in both developing and developed countries. It is estimated that 60% of CRC patients have liver metastasis. In the present study, we show that miR-30b is an important regulator in human CRC migration and invasion, which are vital steps in CRC liver metastasis. miR-30b was significantly down-regulated in primary CRC specimens compared with normal tissues. Furthermore, miR-30b was much lower in liver metastasis tissues than in CRCs. We validated SIX1 (SIX homeobox 1), a member of the SIX homeodomain family of transcription factors and an EMT (epithelial-mesenchymal transition)-promoting gene, as the directtarget of miR-30b. Forced expression of miR-30b inhibited CRCcell migration and invasion in vitro via its target gene SIX1. Furthermore, an inverse correlation between expression of SIX1 and miR-30b has been observed both in primary CRC specimens and liver metastasis. Taken together, miR-30b plays an important role in mediating metastatic related behaviour in CRC. miR-30b may serve as a potential diagnostic marker and therapeutic target for patients with CRC in the future. © 2014 Biochemical Society.

Zhang S.-J.,Sloan Kettering Cancer Center | Zhang S.-J.,Nanjing Medical University | Abdel-Wahab O.,Sloan Kettering Cancer Center
Current Hematologic Malignancy Reports | Year: 2012

The discovery of mutations activating JAK-STAT signaling in the majority of patients with myeloproliferativeneoplasms (MPNs) led to identification of tyrosine kinase activation as the common predominant mechanism driving MPN pathogenesis. Nevertheless, the existence of additional genetic events that modify the MPN phenotype, predate JAK2 mutations, or contribute to leukemic transformation of MPNs was suspected. Recent advances in genomic technologies have led to the discovery of mutations in a number of epigenetic modifiers in patients with MPNs, including mutations in TET2, ASXL1, IDH1, IDH2, and EZH2. In addition to mutation, alterations in the expression or activity of chromatin-modifying/reading proteins PRMT5 and L3MBTL1 have been found to be important in MPN development. Moreover, the JAK2 mutation itself recently has been shown to directly affect histone post-translational modifications. This article reviews the clinical and functional implications of epigenetic alterations in the pathogenesis of MPNs. © 2011 Springer Science+Business Media, LLC.

Xiao Y.,Nanjing Normal University | Wang Y.,Nanjing Normal University | Wu M.,Nanjing Normal University | Ma X.,Nanjing Medical University | Yang X.,Nanjing Normal University
Journal of Electroanalytical Chemistry | Year: 2013

This work presents a facile route to fabricate a highly sensitive platform for the recognition of lysozyme. Graphene oxide was coated on the surface of a glassy carbon electrode (GCE) followed by reduction with hydrazine to obtain a graphene (GR) coated GCE. After activation of GR-GCE with EDC and NHS, lysozyme binding aptamer (LBA) was molecularly tethered onto GR to obtain a highly sensitive platform named as LBA-GR-GCE. Results show that GR greatly promotes the electron transfer at electrode/electrolyte interface due to its excellent electrical conductivity. LBA-GR-GCE is able to quantitatively detect the analyte of lysozyme in real samples of human saliva and chicken egg white with high selectivity, with a linear range of 0.01-0.5 pmol L-1 and detection limit of 6 fmol L-1 (S/N = 3). Furthermore, the surface feature of the functionalized electrode was investigated to determine its effect on charge transfer resistance with two different electrochemical probes of [Fe(CN) 6]3-/4- and Ru(NH3)63+. © 2013 Elsevier B.V. All rights reserved.

Zhao X.-D.,Nanjing Medical University | Zhou Y.-T.,Wuxi Integrated Traditional Chinese and Western Medicine Hospital
Journal of Surgical Research | Year: 2011

Background: Subarachnoid hemorrhage (SAH) can induce a persistent inflammatory response, histopathologic changes in the gut. This study investigated whether progesterone administration modulates intestinal proinflammatory cytokine expression and structure alternations following SAH in male rats. Materials and Methods: A total of 48 male rats were randomly divided into four groups: control group (n = 12), SAH group (n = 12), SAH+vehicle group (n = 12) and SAH+progesterone group (n = 12). We measured intestinal wet/dry weight ratio; the concentrations of IL-1β, TNF-α, and IL-6 by enzyme-linked immunosorbent assay; intestinal mucosal morphologic changes by histopathologic study and electron microscopy. Results: Administration of progesterone following SAH could increase the appetite scores of SAH rats and decrease concentrations of proinflammatory cytokines and wet/dry weight ratio in the gut. SAH-induced damage of gut structure was ameliorated after progesterone supplementation. Conclusions: The results of the present study suggest that the therapeutic benefit of post-SAH progesterone supplementation might be due to its inhibitory effects on intestinal proinflammatory cytokine expression and gut structure amelioration. © 2011 Published by Elsevier Inc. All rights reserved.

Triggering receptor expressed on myeloid cells 2 (TREM2) gene is a recently identified susceptibility gene for Alzheimer's disease (AD), as its low-frequency variants increase the risk of this disease with an odds ratio similar to that of an APOE e{open}4 allele. To date, the expression and biologic functions of TREM2 under AD context remain largely unknown. Using APPswe/PS1dE9 mice, a transgenic model of AD, we showed that TREM2 was upregulated in microglia during disease progression. For the first time, we provided in vitro and in vivo evidence that this upregulation was attributed to the increased amyloid-β (Aβ)1-42 levels in the brain. By knockdown and overexpression of TREM2 in cultured primary microglia, we revealed that TREM2 modulated microglial functions under AD context, as it facilitated Aβ1-42 phagocytosis and inhibited Aβ1-42-triggered proinflammatory responses. Meanwhile, this modulation was dependent on DAP12, the adapter protein of TREM2. More importantly, overexpression of TREM2 in the brain of APPswe/PS1dE9 mice markedly ameliorated AD-related neuropathology including Aβ deposition, neuroinflammation, and neuronal and synaptic losses, which was accompanied by an improvement in spatial cognitive functions. Taken together, our data suggest that the upregulation of TREM2 serves as a compensatory response to Aβ1-42 and subsequently protects against AD progression by modulation of microglia functions. These findings provide insights into the role of TREM2 in AD pathogenesis, and highlight TREM2 as a potential therapeutic target for this disease.Neuropsychopharmacology advance online publication, 20 August 2014; doi:10.1038/npp.2014.164.

Background The endothelial nitric oxide synthase (eNOS) G894T gene polymorphism has been suggested to be linked to the risk of essential hypertension (EH), however the results are still debatable. Objective and Methods To assess the association between eNOS G894T gene polymorphism and EH, such electronic databases as Pubmed, Embase, Web of Science, China Biological Medicine Database (CBMD) and China National Knowledge Infrastructure (CNKI) were searched. The selection criteria were as follows: a) Evaluation of the association of eNOS G894T gene polymorphism and EH. b) EH diagnosis in compliance with EH diagnosis criteria of the World Health Organization (WHO) in 1999. c) The study results were in line with the Hardy-Weinberg equilibrium (HWE). In 23 separate studies with 11,248 subjects the relation between eNOS G894T gene polymorphism and EH was analyzed by current meta-analysis. Random effect model was used to calculate the pooled odds ratio (ORs) and its corresponding 95% confidence interval (95% CI). Results In this eNOS G894T gene polymorphism and EH meta-analysis in the Chinese population, the distribution of T allele frequency was 0.154 for EH group and 0.128 for the control group. A significant association was found between G894T gene polymorphism and EH (p=0.0007). The pooled OR for the distribution frequency of T allele was 1.33 (95% CI:1.13-1.56, P heterogeneity <0.00001). In the stratified analysis by ethnicity, there was a significant association in Han subgroup (p=0.005). The pooled OR for the distribution frequency of T allele was 1.31 (95% CI:1.09-1.59, P heterogeneity <0.00001). No significant increased risk for EH was found in the non-Han subgroup (p=0.08). Conclusion In the current meta-analysis, T allele of eNOS G894T gene was suggested to be related to the increased risk of EH in the Chinese population, particularly in those of Han ethnicity. © 2011 The Japanese Society of Internal Medicine.

Li W.,Nanjing Medical University
International journal of molecular sciences | Year: 2010

The report aims to investigate the relationship between the expression of cyclin D1 and Cyclooxgenase-2 (COX-2), thus to explore the molecular mechanisms of the antitumor efficacy of Celecoxib, a COX-2 inhibitor. Human ovarian SKOV-3 carcinoma cell xenograft-bearing mice were treated with Celecoxib by infusing gaster (i.g.) twice/day for 21 days. The mRNA levels of COX-2 and cyclin D1 were determined by RT-PCR. The expression of cyclin D1 at the protein level was detected by immunohistochemistry, while COX-2 protein expression was determined by Western blot. A high-dose of Celecoxib (100 mg/kg) significantly inhibited tumor growth (P < 0.05), and the expression of cyclin D1 was reduced by 61%. Celecoxib decreased the proliferation cell index by 40% (P < 0.001) and increased apoptotic index by 52% (P < 0.05) in high-dose Celecoxib treated group. Our results suggest that the antitumor efficacy of Celecoxib against ovarian cancer in mice may in part be mediated through suppression of cyclin D1, which may contribute to its ability to suppress proliferation.

Zhang L.-Y.,Ninth Peoples Hospital | Ren K.-W.,Nanjing Medical University
Archives of Medical Research | Year: 2011

Background and Aims: Matrix metalloproteinase-2 (MMP-2) is an enzyme with proteolytic activity on matrix proteins and abolishes a Sp-1 binding site and consequently decreases its activity. Many studies have been carried out on the association between MMP2 -1306C/T polymorphism and digestive cancer risk, but results were somewhat controversial and underpowered. Methods: To examine the risk of digestive cancer associated with -1306C/T polymorphism of MMP2, we performed a meta-analysis of ten case-control studies. Eligible studies were identified by searching the electronic literature using Pubmed and Embase. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Results: Overall, we found that -1306T allele can decrease digestive cancer risk in three different genotype models (T-allele vs. C-allele, OR = 0.73, 95% CI: 0.54-0.98, p = 0.034; TC vs. CC, OR = 0.64, 95% CI: 0.53-0.78, p <0.001; TT+TC vs. CC, OR = 0.68, 95% CI: 0.53-0.86, p = 0.002). Similarly, in the stratified analysis by cancer type, ethnicity and source of control, significantly decreased cancer risk was indicated. Moreover, in the subgroup of smokers, -1306T allele may protect people against digestive cancer risk (TT+TC vs. CC, OR = 0.71, 95% CI: 0.51-0.98, p = 0.037). Conclusions: Our meta-analysis showed evidence that MMP2 -1306T allele may be a protective factor for digestive cancer risk as well as a low-penetrance susceptibility digestive cancer biomarker. © 2011 IMSS.

Single-nucleotide polymorphisms in microRNAs (miRNAs) may alter miRNA expression levels or processing and, thus, may contribute to cancer development. We hypothesized that miRNA-196a2 polymorphism is associated with risk of colorectal cancer (CRC). In a case-control study of 573 patients with CRC and 588 cancer-free controls frequency matched by age and sex, we genotyped the functional polymorphism rs11614913 (T>C) and assessed its association with the risk of CRC in a Chinese population. We found that the CT/CC genotypes were associated with a significantly increased risk of CRC (odds ratio [OR]=1.44, 95% confidence interval [CI]=1.10-1.88), compared with the TT genotype. Further, the polymorphism was significantly associated with the risk of patients with advanced stage tumor (Dukes C and D) (OR=1.65, 95% CI=1.11-2.46). Our results suggest that the functional polymorphism rs11614913 in miRNA-196a2 is involved in the etiology of CRC and, thus, may be a marker for genetic susceptibility to CRC.

Tran C.M.,University of Pennsylvania | Mukherjee S.,University of Pennsylvania | Ye L.,Nanjing Medical University | Frederick D.W.,University of Pennsylvania | And 5 more authors.
Diabetes | Year: 2016

Rapamycin extends life span in mice, yet paradoxically causes lipid dysregulation and glucose intolerance through mechanisms that remain incompletely understood. Whole-body energy balance can be influenced by beige/brite adipocytes, which are inducible by cold and other stimuli via β-adrenergic signaling in white adipose depots. Induction of beige adipocytes is considered a promising strategy to combat obesity because of their ability to metabolize glucose and lipids, dissipating the resulting energy as heat through uncoupling protein 1. Here, we report that rapamycin blocks the ability of β-adrenergic signaling to induce beige adipocytes and expression of thermogenic genes in white adipose depots. Rapamycin enhanced transcriptional negative feedback on the β3-adrenergic receptor. However, ther-mogenic gene expression remained impaired even when the receptor was bypassed with a cell-permeable cAMP analog, revealing the existence of a second inhibitory mechanism. Accordingly, rapamycin-treated mice are cold intolerant, failing to maintain body temperature and weight when shifted to 4°C. Adipocyte-specific deletion of the mTORC1 subunit Raptor recapitulated the block in β-adrenergic signaling. Our findings demonstrate a positive role for mTORC1 in the recruitment of beige adipocytes and suggest that inhibition of β-adrenergic signaling by rapamycin may contribute to its physiological effects. © 2016 by the American Diabetes Association.

Lv Y.,Central South University | Lv Y.,Nanjing Medical University | Wolf A.,University of Oxford | Wang X.,Central South University
General Hospital Psychiatry | Year: 2013

Objective: To investigate experienced stigma and self-stigma in patients with schizophrenia in mainland China. Methods: Ninety-five patients with schizophrenia, enrolled between January 2011 and March 2011, completed Chinese versions of two self-report questionnaires: the Internalized Stigma of Mental Illness (ISMI) scale and the Modified Consumer Experiences of Stigma Questionnaire (MCESQ). They also completed two other self-report questionnaires: the Social Support Rating Scale (SSRS) and the World Health Organization Quality of Life (WHOQOL-BREF) questionnaire. Patients were also assessed by a senior psychiatrist using the Scale for Assessment of Positive Symptoms (SAPS) and the Scale for Assessment of Negative Symptoms (SANS).All analyses were performed using SPSS 17.0 and included descriptive statistics, correlation analysis and multiple linear regression. Results: On the ISMI, the percentage of participants who rated themselves above the mid-point of 2.5 (meaning high level of self-stigma) on subscales and overall score was 44.2% (n=42) for alienation, 14.7% (n=14) for stereotype endorsement, 25.3% (n=24) for perceived discrimination, 32.6% (n=31) for social withdrawal and 20.0% (n=19) on the overall score. On the MCESQ, the percentage of participants who rated themselves above the mid-point of 3.0 on subscales and overall score was 24.2% (n=23) for stigma, 1.1% (n=1) for discrimination and 1.1% (n=1) on the overall score. Some socioeconomic variables, but not positive or negative symptoms, were related to the severity of psychiatric stigma. Conclusions: Results document the seriousness of experienced stigma and self-stigma in persons with schizophrenia. Strategies are needed to improve how governments and persons with schizophrenia cope with stigma. © 2013 Elsevier Inc.

Shen G.,Nanjing Medical University
Zhonghua zheng xing wai ke za zhi = Zhonghua zhengxing waike zazhi = Chinese journal of plastic surgery | Year: 2012

To discuss the tumorigenicity of immortalized endothelial cells differentiated from embryonic stem cells. The embryoid bodies (EB) formed in vitro from embryonic stem cells, were induced to differentiate into many "round cells" (the precursor of endothelial cells). These "round cells" later formed the vascular tube-like structures. To immortalize these cells, human telomerase reverse transcriptase (hTERT) cDNA was transfected into "round cells" by lipofectin, RT-PCR and immunocytochemistry were used to evaluate the immortalized cells. And the tumorigenicity of these cells were evaluated by being injected into nude mice subcutaneously. 95% of these transfected cells expressed Flk-1, CD34 and vWF, and could proliferate in large quantity in vitro (cell number was doubled in 2 days, and increased 12 times in 3 days), and were able to form tubular structures. These results suggest that hTERT cDNA transfection can immortalize induced endothelial cells and tumorigenicity is found after immortalized cells are injected into nude mice subcutaneously.

Isom S.C.,University of Missouri | Li R.F.,University of Missouri | Li R.F.,Nanjing Medical University | Whitworth K.M.,University of Missouri | Prather R.S.,University of Missouri
Molecular Reproduction and Development | Year: 2012

Evidence in many species has suggested that those embryos that cleave earliest after fertilization are more developmentally competent than those that cleave relatively later after fertilization. Herein we document this phenomenon in porcine in vitro-fertilized (IVF), somatic cell nuclear transfer (SCNT), and parthenogenetic (PA) embryos. In vitro-matured pig oocytes were used to generate IVF, SCNT, and PA embryos. At 24hr post-activation (or insemination; hpa/hpi), embryos were visually assessed, and cleaved embryos were moved into a new culture well. This process was repeated at 30 and 48 hpa/hpi. All embryos were allowed to develop 7 days in culture. For IVF embryos, 39.9%, 24.6%, and 10.5% of fast-, intermediate-, or slow-cleaving embryos, respectively, developed into blastocysts by day 7. For SCNT embryos, 31.8% of fast-, 5.7% of intermediate-, and 2.9% of late-cleaving embryos achieved the blastocyst stage of development. For PA embryos, the percentages of those cleaved embryos that developed to blastocyst were 59.3%, 36.7%, and 7.5% for early-, intermediate-, and late-cleaving embryos, respectively. Using RNA collected from early-, intermediate-, and late-cleaving embryos, real-time PCR was performed to assess the transcript levels of 14 different genes of widely varied function. The qPCR results suggest that maternal mRNA degradation may not proceed in an appropriate pattern in slow-cleaving embryos. These findings (1) confirm that, as observed in other species, earlier-cleaving porcine embryos are more successful at developing in culture than are slower-cleaving embryos, and (2) implicate mechanisms of maternal transcript destruction as potential determinants of oocyte/embryo quality. © 2011 Wiley Periodicals, Inc.

Zheng Q.-Y.,The Military General Hospital of Beijing PLA | Jin F.-S.,Chongqing Medical University | Yao C.,Nanjing Medical University | Zhang T.,The Military General Hospital of Beijing PLA | And 2 more authors.
Biochemical and Biophysical Research Communications | Year: 2012

Ursolic acid (UA) has shown the anti-tumor properties against a number of human cancers both in vivo and in vitro, however, its effect in bladder cancer and the corresponding mechanisms of action remain largely unknown. Here we found that UA dose-dependently induced growth inhibition and apoptosis in human bladder cancer T24 cells, and activation of AMP-activated protein kinase (AMPK) may contribute to the process. Our Western-blot results demonstrated a significant AMPK activation after UA treatment in T24 cells. Notably, knockdown of AMPKα by the targeted shRNA largely inhibited UA-induced T24 cell growth inhibition and apoptosis, while an AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) or a constitutively active form of AMPK mimic UA's effect. We found the ceramide level was increased after UA treatment in T24 cells, and UA-induced AMPK activation and T24 cell apoptosis were inhibited by ceramide synthase inhibitor fumonisin B1, and was enhanced by exogenously adding cell permeable short-chain ceramide (C6), suggesting that ceramide might serve as an upstream signal for AMPK activation. Further, activation of AMPK by UA promoted c-Jun N-terminal kinase (JNK) activation, but inhibited mTOR complex 1 (mTORC1) signaling to cause survivin down-regulation. Our study suggests that activation of AMPK by UA contributes to growth inhibition and apoptosis in human bladder cancer cells. © 2012 Elsevier Inc.

ABCG2, CD133 and CD117 are pivotal markers of cancer stem cell, which are involved in carcinogenesis and cancer progression. The expression of these genes has been reported to be associated with the development and progression of many cancers, including non-small cell lung cancer (NSCLC). We selected and genotyped 9 potentially functional single-nucleotide polymorphisms in the 3 genes in a clinical cohort of 1001 NSCLC patients in a Chinese population. We found that variant genotypes of ABCG2 rs3114020 were associated with a significantly increased risk of death for NSCLC (additive model: adjusted hazard ratio=1.25, 95% confidence intervals=1.10–1.42, P<0.001). Further stepwise regression analysis suggested that rs3114020 was an independent risk factor for the prognosis of NSCLC. Besides, histology interacted with the genetic effect of rs3114020 in relation to NSCLC survival in the interaction analysis. Our findings show that ABCG2 rs3114020 might be one of the candidate biomarkers for NSCLC survival in this Chinese population, especially among patients with adenocarcinoma.The Pharmacogenomics Journal advance online publication, 8 March 2016; doi:10.1038/tpj.2016.2. © 2016 Macmillan Publishers Limited

Wang F.,Nanjing Medical University | Wang F.,Bonoi Academy of Science and Education | Stefano G.B.,New York University | Kream R.M.,New York University
Medical Science Monitor | Year: 2014

Cumulating evidence indicated that nerve injury-associated cellular and molecular changes play an essential role in contributing to the development of pathological pain, and more recent findings implicated the critical role of epigenetic mechanisms in pain-related sensitization in the DRG subsequent to nerve injury. In this part of the dyad review (Part II), we reviewed and paid special attention on the etiological contribution of DGR gene expression modulated by epigenetic mechanisms of CRPS. As essential effectors to different molecular activation, we first discussed the activation of various signaling pathways that subsequently from nerve injury, and in further illustrated the fundamental and functional underpinnings of nerve injury-induced pain, in which we argued for the potential epigenetic mechanisms in response to sensitizing stimuli or injury. Therefore, understanding the specific mediating factors that influence individual epigenetic differences contributing to pain sensitivity and responsiveness to analgesics possesses crucial clinical implications. © Med Sci Monit, 2014.

Che D.,Shanghai JiaoTong University | Zhou H.,Nanjing Medical University | He J.,Shanghai JiaoTong University | Wu B.,Shanghai JiaoTong University
BMC Health Services Research | Year: 2014

Background: The purpose of this study was to compare, from a Chinese societal perspective, the projected health benefits, costs, and cost-effectiveness of adding pneumococcal conjugate heptavalent vaccine (PCV-7) to the routine compulsory child immunization schedule. Methods. A decision-tree model, with data and assumptions adapted for relevance to China, was developed to project the health outcomes of PCV-7 vaccination (compared with no vaccination) over a 5-year period as well as a lifetime. The vaccinated birth cohort included 16,000,000 children in China. A 2 + 1 dose schedule at US$136.51 per vaccine dose was used in the base-case analysis. One-way sensitivity analysis was used to test the robustness of the model. The impact of a net indirect effect (herd immunity) was evaluated. Outcomes are presented in terms of the saved disease burden, costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio. Results: In a Chinese birth cohort, a PCV-7 vaccination program would reduce the number of pneumococcus-related infections by at least 32% and would prevent 2,682 deaths in the first 5 years of life, saving $1,190 million in total costs and gaining an additional 9,895 QALYs (discounted by 3%). The incremental cost per QALY was estimated to be $530,354. When herd immunity was taken into account, the cost per QALY was estimated to be $95,319. The robustness of the model was influenced mainly by the PCV-7 cost per dose, effectiveness herd immunity and incidence of pneumococcal diseases. With and without herd immunity, the break-even costs in China were $29.05 and $25.87, respectively. Conclusions: Compulsory routine infant vaccination with PCV-7 is projected to substantially reduce pneumococcal disease morbidity, mortality, and related costs in China. However, a universal vaccination program with PCV-7 is not cost-effective at the willingness-to-pay threshold that is currently recommended for China by the World Health Organization. © 2014 Che et al.; licensee BioMed Central Ltd.

Zhang Y.,Sun Yat Sen University | Jiang L.,Nanjing Medical University
Clinics and Research in Hepatology and Gastroenterology | Year: 2014

Background and objective: Previous studies have shown that C-reactive protein (CRP) 1059G/C and 1846G/A polymorphisms may play a role in cancer risk. However, the results from the published studies are conflicting. To derive a more precise estimation of the relationship between CRP 1059G/C and 1846G/A polymorphisms and cancer risk, we conducted a meta-analysis of 21 studies involving a total of 26,634 subjects. Methods: Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. Results: No significant association was found between CRP 1846G/A polymorphism and cancer risk. However, a significant association was found between CRP 1059G/C polymorphism and cancer risk (CC vs CG+GG: OR=3.60, 95% CI=1.63-7.92, PH=0.67; CC vs GG: OR=3.53, 95% CI=1.60-7.77, PH=0.69). In the subgroup analysis by ethnicity, a significant association was found for the CRP 1846G/A polymorphism among mixed population. Interestingly, when stratifying by cancer type, marginally increased risks were observed for CRP 1846G/A polymorphism in colorectal cancer (AA vs AG+GG: OR=1.17, 95% CI=1.00-1.36, PH=0.27) and significantly decreased risks were found for CRP 1846G/A polymorphism in breast cancer (AA vs GG: OR=0.73, 95% CI=0.56-0.95, PH=0.93; A vs G: OR=0.88, 95% CI=0.79-0.99, PH=0.54). For 1059G/C polymorphism, a significant association was found in colorectal cancer. Conclusion: This meta-analysis showed the evidence that CRP 1059G/C and 1846G/A polymorphisms were risk factors for the development of colorectal cancer, and CRP 1846G/A polymorphism is also a protective factor for decreasing breast cancer. © 2014 Elsevier Masson SAS.

Zheng X.,Nanjing Medical University
Journal of Spinal Disorders and Techniques | Year: 2014

RESULTS:: Of the 12 pigs enrolled in this study, 2 encountered substantial complications (one developed a postoperative infection, and the other experienced prolonged postoperative weakness). Of the 10 available for analysis, all pigs developed rapidly progressive, structurally three-dimenional, idiopathic-type curves with convex to the right in the lower thoracic spine. The mean coronal Cobb angle was 29° immediately postoperatively and progressed to 65° after the 8-week tethering period. Eight weeks after removal of the tether, the scoliosis continued to progress and averaged 68° (range, 58° to 78°). On the sagittal plane, a mean lordosis of 32° at the thoracic spine and a thoracolumbar kyphosis of 63° were observed at study completion.CONCLUSIONS:: A three-dimensional rapidly progressive scoliosis model, that is closely approximate to human EOS, can be successfully created in pigs by unilaterally tethering the thoracolumbar spine and the ribcage. This model provides an equivalent EOS-like deformity and leaves adequate skeletal growth potential for biomechanical research as well as validation of fusionless scoliosis correction systems.STUDY DESIGN:: An animal study.OBJECTIVE:: To create a reliable porcine scoliosis model representative of early onset scoliosis (EOS) without violation of the vertebral elements along the curve.SUMMARY OF THE BACKGROUND DATA:: To develop new nonfusion techniques for the treatment of early onset scoliosis, a reliable large animal model with remarkable growth potential is required. However, a long tethering period which consumed the majority of the rapid growth phase or violation of the vertebral elements was thought to be essential in most of the previous models. Therefore, these models may be suboptimal for mimics of human EOS which was usually idiopathic-type without vertebral anormalies.METHODS:: This study included twelve female Yorkshire pigs (age, 5–6 wk; weight, 5–7 kg) in which scoliosis was created by posterior asymmetric tethering from T5 to L3. At the index surgery, three separate incisions were preformed, and ipsilateral rib tethering from the 10th to the 13th rib was performed while maintaining the vertebral elements along the maximal curve in a pristine state. Progressive deformity was documented with monthly radiographs. Frontal and sagittal profiles were assessed using the Cobb method. After an 8-week tethering period, the whole instrumentations were removed, and the pigs were observed for an additional 8-week period with serial radiographs to document the progression of the deformity. © 2014 by Lippincott Williams & Wilkins, Inc.

Xie H.-G.,Nanjing Medical University | Zou J.-J.,Nanjing First Hospital Affiliated | Hu Z.-Y.,Nanjing First Hospital Affiliated | Zhang J.-J.,Nanjing First Hospital Affiliated | And 2 more authors.
Pharmacology and Therapeutics | Year: 2011

The widespread use of clopidogrel alone or in combination with aspirin has significantly benefited patients with acute coronary syndrome who are managed medically or by percutaneous coronary intervention and stent implantation, greatly improving their survival. Emerging data have documented that the clopidogrel response may vary from person to person and even from disease to disease, and that genetic and nongenetic factors contribute to that variability. Genetic polymorphisms affecting clopidogrel metabolic bioactivation and platelet function may be responsible, each exerting a small effect. CYP2C19*2,*3 and*17, CYP2C9*2 and*3, MDR1*2, and functional variants in the genes encoding platelet membrane receptors and intracellular signaling proteins are involved, and other genetic factors remain to be identified. In addition, nongenetic factors may be influential covariates, such as ethnicity, gender, age, body weight, co-existing diseases, drug-drug interactions, and other factors to be determined. Each piece of the puzzle would be useful to bridge and delineate identified knowledge gaps and to determine future research needs for the risk prediction of fatal complications associated with inadequate clopidogrel therapy in patient care. © 2010 Elsevier Inc. All rights reserved.

Feng W.-P.,Shangluo Vocational and Technical College | Zhang B.,Central Hospital of Shangluo | Li W.,Nanjing Medical University | Liu J.,Central Hospital of Shangluo
PLoS ONE | Year: 2014

Background: To assess the association of P2RX7 gene rs2230912 polymorphism with mood disorders using a meta-analysis. Methods: Data were collected from the following electronic databases: PubMed, Excerpta Medica Database, Elsevier Science Direct, Cochrane Library, and Chinese Biomedical Literature Database, with the last report up to April 1, 2013. Odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the association. Dependent on the results of heterogeneity test among individual studies, the fixed effect model (Mantel-Haenszel) or random effect model (DerSimonian-Laird) was selected to summarize the pooled OR. Results: We identified 13 separate studies using search (6,962 cases and 9,262 controls). We detected significant between-study heterogeneity. No significant association of this polymorphism with mood disorders was found (P>0.05). We also performed disease-specific meta-analysis in unipolar depression and bipolar disorder. No significant association of this polymorphism with unipolar depression or bipolar disorder was found (P>0.05). Additionally, we performed subgroup analysis by different types of cases. No significant association of this polymorphism with mood disorders in clinical cohorts or population-based cohorts (P>0.05). A significant association of this polymorphism with mood disorders was found for the allele contrast in family-based cohorts (OR = 1.26, 95%CI = 1.05-1.50, P = 0.01). Conclusions: Overall, our meta-analysis suggests that P2RX7 gene rs2230912 polymorphism may not contribute to the risk of developing mood disorders using a case-control design. Given the discordance in the subgroup analysis by different types of cases, further studies based on larger sample size are still needed. © 2014 Feng et al.

Zheng F.,St Jude Childrens Research Hospital | Zhou X.,Nanjing Medical University | Moon C.,Chonnam National University | Wang H.,Michigan State University
International Journal of Physiology, Pathophysiology and Pharmacology | Year: 2012

Brain-derived neurotrophic factor (BDNF) plays critical roles in many aspects of brain functions, including cell survival, differentiation, development, learning and memory. Aberrant BDNF expression has also been implicated in numerous neurological disorders. Thus, significant effort has been made to understand how BDNF transcription as well as translation is regulated. Interestingly, the BDNF gene structure suggests that multiple promoters control its transcription, leading to the existence of distinct mRNA species. Further, the long-and short-tail of the 3′ un-translated region may dictate different sub-cellular BDNF mRNA targeting and translational responses following neuronal stimulation. This review aims to summarize the main findings that demonstrate how neuronal activities specifically up-regulate the transcription and translation of unique BDNF transcripts. We also discuss some of the recent reports that emphasize the epigenetic regulation of BDNF transcription.

Hashida N.,Osaka University | Ping X.,Nanjing Medical University | Nishida K.,Osaka University
BMC Ophthalmology | Year: 2013

Background: Noonan syndrome is an autosomal, dominantly inherited disease; it is physically characterized by short stature, short neck, webbed neck, abnormal auricles, high arched palate, and cardiovascular malformation. Its pathological condition is thought to be due to a gain-of-function mutation in the Ras-mitogen-activated protein kinase (MAPK) signal transduction pathway. Eyelid abnormalities such as ocular hypertelorism and blepharoptosis are the most commonly observed eye complications. Case presentation. We report a case of Noonan syndrome associated with mature cataract that required operation. A 42-year-old man was diagnosed with Noonan syndrome at the age of 1 year. He underwent an eye examination after complaining of decreased visual acuity in the right eye and was diagnosed with mature cataract, which was treated by cataract surgery. There were no intraoperative complications, and the postoperative course was uneventful. Protein analysis of lens capsule and epithelium at capsulorhexis showed MAPK cascade proteins such as ERK and p38MAPK were upregulated. An abnormality in the PTPN11 gene was also observed; a potential mechanism of cataract onset may be that opacity of the lens rapidly progressed due to abnormal activation of the Ras-MAPK signal transduction pathway. Conclusion: This case highlights the possible association of cataract formation with MAPK cascade protein upregulation in Noonan syndrome. © 2013 Hashida et al.; licensee BioMed Central Ltd.

Background: The restoration of damaged meniscus has always been a challenge due to its limited healing capacity. Recently, bone marrow-derived mesenchymal stem cells (BMSCs) provide a promising alternative to repair meniscal defects. However, BMSCs are not ideal chondroprogenitor cells for meniscus repair because they have a high propensity for cartilage hypertrophy and bone formation. Our hypothesis is that mesenchymal stem cells (MSCs) reside in meniscus maintain specific traits distinct from others which may be more conducive to meniscus regeneration. Methods: MSCs were isolated from bone marrow and menisci of the rabbits. The similarities and differences between BMSCs and MMSCs were investigated in vitro by a cell culture model, ex vivo by a rabbit meniscus defect model and in vivo by a nude rat implantation model using histochemistry, immunocytochemistry, qRT-PCR and western blotting. Results: Our data showed that two types of MSCs have universal stem cell characteristics including clonogenicity, multi-potency and self-renewal capacity. They both express stem cell markers including SSEA-4, Nanog, nucleostemin, strol-1, CD44 and CD90. However, MMSCs differed from BMSCs. MMSC colonies were much smaller and grew more slowly than BMSC colonies. Moreover, fewer MMSCs expressed CD34 than BMSCs. Finally, MMSCs always appeared a pronounced tendency to chondrogenic differentiation while BMSCs exhibited significantly greater osteogenic potential, whatever in vitro and in vivo. Conclusions: This study shows the similarities and differences between MMSCs and BMSCs for the first time. MMSCs are a promising source of mesenchymal stem cells in repairing meniscus defect. © 2015 Ding and Huang; licensee BioMed Central.

Zhu X.J.,Nanjing Medical University
Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery | Year: 2010

To investigate the association between the promoter polymorphism -509C/T of the transforming growth factor-β1 gene (TGFB1) and the disease severity of allergic rhinitis (AR) in childhood. A total of 96 Chinese patients with persistent AR aged 3 - 17 (9.4 ± 3.8) years old were enrolled in the study. Among these patients 53.1% were mild cases (n = 51) and 46.9% were moderate-to-severe cases (n = 45). Genotyping was performed on peripheral blood genomic DNA by using PCR-RFLP. Serum levels of TGF-β1 was measured by ELISA, and serum total IgE, specific IgE and eosinophil cationic protein (ECP) levels were determined using an ImmunoCAP100E system. Statistical analysis was conducted with SPSS11.0 software. Significant differences were found in genotype frequencies for the TGFB1-509C/T polymorphism between mild and moderate-to-severe AR patients (χ(2) = 8.361, P = 0.015). Children with persistent AR bearing the TT genotype of the -509C/T polymorphism had significantly increased risk for moderate-to-severe AR (Fisher's exact test, P = 0.007) compared to children with the CC/CT genotypes. There was no significant association between the -509C/T polymorphism and serum TGF-β1 levels (F = 0.389, P = 0.679); however, serum total IgE (F = 4.210, P = 0.018) and ECP (H = 6.297, P = 0.043) levels were found to be significantly associated with the polymorphism. The results suggest that the TGFB1 gene polymorphism -509C/T may play a potential role in the severity of persistent AR in childhood.

Han Y.P.,Nanjing Medical University
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology | Year: 2013

To study the immunoregulatory effect of hepatitis B virus (HBV) e antigen (HBeAg) on peripheral blood monocytes (PBMCs). PBMCs were isolated from patients with chronic hepatitis B (CHB; both HBeAg- and HBeAg+) and healthy controls, and cultured with recombinant HBeAg. The HBeAg-induced changes in expression of PD-1/PD-L1 were measured by flow cytometry of the cells and in secreted cytokines were measured by enzyme-linked immunosorbent assay of the supernatants. Comparisons between two groups were made by the independent-samples t-test; the relationship between PD-1/B7-H1 level and HBV DNA copy number was evaluated by Spearman's correlation analysis. Exposure to HBeAg led to a significant decrease in CD3+CD4+ T lymphocyte-specific expression of IFNa for both the CHB patients' and healthy controls' samples (t = 2.382 and -4.190 respectively, P less than 0.01). For the HBeAg- CHB patients' and healthy controls' samples, the HBeAg exposure led to increased levels of secreted cytokines IL-6, IL-10 and TNFa (t = 2.504, 3.583 and 4.324, P less than 0.01 and t = 3.542, 6.246 and 5.273, P less than 0.01 respectively) and of CD14+ PBMC-specific expression of PD-L1 (t = 4.815 and 3.454, P less than 0.05 respectively). Compared to the HBeAg-negative CHB patients' and healthy controls' samples, the HBeAg+ CHB patients' samples had significantly lower CD3+CD4+ T cell-specific expression of IFNa (t = -3.177 and -4.541, P less than 0.01 respectively), but significantly higher levels of secreted IL-4 (t = 3.382 and 4.393, P less than 0.01 respectively), of CD3+ T cells-specific expression of PD-1/PD-L1 (t = 4.755, 2.942 and 4.518, 4.595, P less than 0.01 respectively), and of CD14+ T cells-specific expression of PD-L1 (t = 5.092 and 5.473, P less than 0.01 respectively). The CD3+ T cells-specific expression of PD-L1 was significantly higher in the samples from HBeAg- CHB patients than from the healthy controls (t = 3.214, P less than 0.01). HBeAg was able to down-regulate the production of Th1-type cytokines (IFNgamma), and up-regulate the secretion of Th2-type cytokines (IL-6, IL-10) and the expression of PD-1/PD-L1on monocytes. These changes are conducive to the formation of immune tolerance to HBV. Therefore, HBeAg may play an important role in immune tolerance to chronic HBV infection.

Sun J.K.,Nanjing Medical University
Surgery today | Year: 2013

No consensus has been reached to define gastrointestinal failure (GIF) associated with severe acute pancreatitis (SAP). Reintam and colleagues proposed a scoring system of GIF for critically ill patients, but its suitability for patients with SAP is questionable. The present study evaluates a modified GIF score we developed to assess the GIF of patients with SAP. The subjects of this study were 52 patients with SAP treated between September 2010 and July 2011. We recorded the Reintam's GIF score, our modified GIF score, the acute physiology and chronic health evaluation (APACHE) II score, the sequential organ failure assessment (SOFA) score, and other clinical values during the first 3 days after admission. The prognostic value of the modified GIF score, for evaluating the severity and outcomes of SAP, was also assessed. Compared with the Reintam's GIF score, the modified GIF score seemed to be more valuable for predicting hospital mortality (the area under curve, AUC 0.915 vs. 0.850), multiple organ dysfunction syndrome (MODS) (AUC 0.829 vs. 0.766), and pancreatic infection (AUC 0.796 vs. 0.776). Moreover, combining the modified GIF score and the SOFA or APACHEII scores resulted in more accurate prediction of the prognosis of SAP than either score alone. The modified GIF score is useful for assessing gastrointestinal system function, which may serve as an early prognostic tool to evaluate the severity and predict the outcomes of SAP.

Coronary artery bypass grafting (CABG) is a mature procedure in treating patients with coronary artery diseases. We report a patient undergoing CABG had history of esophageal cancer and multiple underlying diseases: hypothyroidism, type 2 diabetes mellitus and hypertension. A CABG with midline sternotomy was safely performed in the presence of thyroid replacement therapy and intensive control of blood pressure and blood glucose. The patient recovered postoperatively with supportive care.

Tian T.,Nanjing Southeast University | Tian T.,Nanjing Medical University | Zhu Y.-L.,Nanjing Southeast University | Hu F.-H.,Nanjing Southeast University | And 3 more authors.
Journal of Cellular Physiology | Year: 2013

Cells release exosomes into extracellular medium. Although the important roles of exosomes in many physiological and pathological processes are being revealed, the mechanism of exosome-cell interaction remains unclear. In this article, employing real-time fluorescence microscopy, the motion of exosomes on the plasma membrane or in the cytoplasm of recipient PC12 cells was observed directly. In addition, several motion modes of exosomes were revealed by single particle tracking (SPT). The changes between motion modes were also detected, presenting the dynamic courses of exosome attachment onto plasma membrane and exosome uptake. Octadecyl rhodamine B chloride (R18) was found to be useful to distinguish endocytosis from fusion during exosome uptake. Colocalization with organelle markers showed exosomes were sorted to acidic vesicles after internalization. The results provide new sight into the exosome-cell interaction mode and the intercellular trafficking of exosomes. This study will help to understand the roles of exosomes at cell level. © 2012 Wiley Periodicals, Inc.

Zhu L.P.,Nanjing Medical University
Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery | Year: 2010

To investigate and describe the differences in age, sex, seasonality distribution, and related environmental factors between patients with non-allergic rhinitis (NAR) and allergic rhinitis (AR). One hundred and eleven patients with NAR and 112 patients with AR were enrolled in this study. All patients were first diagnosed in outpatient department between January and August 2010. Questionnaires were distributed to all participants to record the general information, medical history, and the factors relevant to symptom onset. Statistical analysis was performed using a SPSS13.0 software. The proportion of patients with NAR increased with age, compared to patients with AR. The peak age was 21 - 30 years old in patients with NAR, whereas 11 - 20 years old in patients with AR. In adults more than 18 years old, the average age (years, x(-) ± s) of patients with NAR (38.6 ± 14.5) was significantly higher than those with AR (32.8 ± 13.0; t = 2.58, P = 0.024). NAR was more likely to be males before 30 years old, while after 30 years old, it likely to be female predominance. The same case occurred in AR subjects but in their 20 years old. NAR was symptomatically worse in winter (χ(2) = 27.57, P = 0.000), whereas AR worse in spring (χ(2) = 13.75, P = 0.003). The cases of NAR were significantly more than those of AR during the winter season (χ(2) = 12.34, P = 0.000). Among the disease-related environmental factors, living or working place near the traffic artery had 1.94-fold increased risk for development of NAR compared with AR; however, living or working in ground floor or sunshine time less than 2 h per day had 1.77- or 1.91-fold increased risk for development of NAR compared with NAR. Subjects with personal or family history of allergic disease had 2.14 to 4.06-fold increased risk for development of AR compared with NAR. The self-reported predisposing factors in NAR patients were mainly including temperature shift (56.3%), common cold (52.8%), climate change (32.4%), and strong odors (31.1%). However, there were no significant differences in these nonspecific triggers between NAR and AR (all P > 0.05). There are significant differences in the distribution of age, sex and seasonality, personal and family history of allergic disease, and some environmental factors relevant to the onset of symptom between patients with NAR and AR.

Xiao M.,Southern Medical University | Xiao M.,Nanjing Medical University | Gao Y.,Southern Medical University | Wang Y.,Southern Medical University
International Journal of Clinical Practice | Year: 2014

Objective: Since the discovery of Helicobacter species in human biliary system, the association between Helicobacter species infection and cholangiocarcinoma is under debate. This meta-analysis aims to explore this issue. Methods: Literature search was carried out to identify all eligible articles. We performed overall meta-analysis of all included studies and subgroup analysis based on regional distribution. Subgroup analysis in the light of detection methods and specimens was also conducted. Results: Ten case-control studies were included. Overall meta-analysis favoured a significant association between Helicobacter species infection and cholangiocarcinoma (cumulative OR 8.88, 95% CI 3.67-21.49). Subgroup analysis based on geographic distribution indicated that Helicobacter species infection may serve as a risk factor not only in a region with high cholangiocarcinoma incidence (Asia, OR 6.68, 95% CI 2.29-19.49) but also in low incidence region (Europe, OR 14.90, 95% CI 4.79-46.35). The other subgroup analysis showed that PCR was the most effective and efficient method to detect Helicobacter species in surgically resected tissue and bile. There was significant heterogeneity among studies and obvious publication bias. Conclusion: Our meta-analysis supports the possible association between Helicobacter species infection and cholangiocarcinoma. Further investigations are required to clarify the role of Helicobacter species in this malignancy. © 2013 John Wiley & Sons Ltd.

Lu P.H.,Nanjing Medical University
Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] | Year: 2010

OBJECTIVE: To assess the association between tumor necrosis factor-alpha (TNF-alpha) gene promoter region -308 gene polymorphisms and gastric cancer (GC) susceptibility. METHODS: Published work about TNF-alpha-308 and GC from PubMed, EMBASE, Cochrane library in English and from Wanfang, CBM in Chinese were searched for relevant articles published by the end of July, 2009. Thirty-nine relevant articles were selected and 26 of them met the criteria. The correlated index was extracted for aggregate analysis in RevMan 4.2. RESULTS: There were 5225 GC patients and 8473 controls for TNF-alpha-308 in 26 papers. Overall, allele contrast (G:A and AA:GG) genotype of TNF-alpha-308 polymorphisms produced significant results in worldwide populations, the OR values were 0.85 (95%CI: 0.76 - 0.96, P = 0.01) and 1.19 (95%CI: 1.01 - 1.39, P = 0.03). Subgroup analysis showed that OR values of G:A and AA:GG in west population were 0.79 (95%CI: 0.70 - 0.89, P < 0.01) and 1.26 (95%CI: 1.04 - 1.52, P = 0.02), while in east populations subgroup analysis, the OR was 0.97 (95%CI: 0.75 - 1.26, P = 0.84). No significant association was observed in non-cardia GC and Helicobacter pylori positive GC, the OR values were 0.90 (95%CI: 0.79 - 1.02, P = 0.10) and 1.08 (95%CI: 0.62 - 1.88, P = 0.79). CONCLUSION: TNF-alpha-308 A allele and AA genotype were associated with a statistically significant increased risk of gastric cancer in western people.

Wani A.A.,University of British Columbia | Jafarnejad S.M.,University of British Columbia | Zhou J.,Nanjing Medical University | Li G.,University of British Columbia
Oncogene | Year: 2011

Integrin-linked kinase (ILK) is a highly conserved serine-threonine protein kinase involved in cell-extracellular matrix interactions, cytoskeletal organization and cell signaling. Overexpression of ILK in epithelial cells leads to anchorage-independent growth with increased cell cycle progression. Previously, we have shown that ILK upregulation strongly correlates with melanoma progression, invasion and inversely correlates with 5-year survival of melanoma patients. However, the molecular mechanism by which ILK enhances melanoma progression is currently unknown. In the present study, we found that proangiogenic molecule interleukin-6 (IL-6) is the downstream target of ILK in melanoma cells. ILK overexpression increased IL-6, whereas silencing of ILK suppressed IL-6 expression at both messenger RNA and protein levels. ILK also altered the activity and subcellular localization of nuclear factor-kappaB (NF-B) subunit p65. We further found that ILK enhanced the IL-6 gene transcription by promoting the binding of NF-B p65 to IL-6 promoter. Moreover, ILK overexpression in melanoma cells enhanced the tube-forming ability of endothelial cells in vitro and microvessel formation in vivo. ILK-induced tube and blood vessel formation of endothelial cells was significantly reduced upon IL-6 inhibition in ILK-overexpressing melanoma cells. To delineate the mechanism by which ILK-induced IL-6 production can enhance angiogenesis, further analysis of the downstream targets of IL-6 signaling showed an increased activity of the signal transducer and activator of transcription 3 (STAT3) in ILK-overexpressing cells. As STAT3 binds to vascular endothelial growth factor (VEGF) promoter, we found that VEGF levels were elevated in ILK-overexpressing cells and declined upon transfection of IL-6 small interfering RNA, suggesting that ILK may regulate VEGF expression through IL-6 pathway by activating STAT3. © 2011 Macmillan Publishers Limited All rights reserved.

Li Y.,Nanjing Medical University
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery | Year: 2013

To assess the efficacy and the transformation of IFN-gamma, IL-4, total IgE and specific IgE before and after specific immune therapy(SIT) in patients with allergic rhinitis. The subjective symptom and levels of IFN-gamma, IL-4, total IgE and specific IgE were observed in 40 patients with allergic rhinitis before and after SIT. Total effective rate in patients after SIT was 85%. There's no significant difference between the levels of specific IgE before and after SIT(P>0.05) ,while the levels of IL-4 and total IgE were significantly lower, the levels of IFN-gamma were significantly higher pre than that of post SIT. SIT is safe and effective,and can regulate the levels of IFN-gamma, IgE and IL-4. But the role of specific IgE in SIT is still unknown.

Xin-He Y.,Nanjing Medical University
The American journal of emergency medicine | Year: 2013

Spontaneous coronary artery dissection (SCAD) is a rare and lethal myocardial ischemic event, which usually causes acute coronary syndrome and sudden death. Emergency management of SCAD includes medical treatment, percutaneous coronary interventions, and coronary artery bypass grafting. Here, we report 1 case of 37-year-old young woman who was found to have a mid-distal SCAD of the left anterior descending artery, taking conservative management decision. In another case of a 50-year-old woman who was found to have a proximal-middle spiral SCAD of the right coronary artery, she underwent coronary angioplasty. After 6 months later at follow-up, 2 patients remained stable without symptom and in recovery of the left ventricular function; angiogram showed the SCAD healed.

Lv J.L.,Nanjing Medical University
Urolithiasis | Year: 2016

The objective of this study was to compare the results of shock wave lithotripsy (SWL) between patients treated with optical coupling control (OCC) and those treated with “blind” coupling during SWL to treat renal stones. Enrolled in the study were patients with urinary stones who underwent SWL between January 2014 and February 2015. The lithotripter used in the study was an electromagnetic Dornier Compact Delta II UIMS. The closed envelope method was used to randomize the enroled patients to OCC (Group A) or “Blind” coupling group (Group B). The stone-free rates (SFRs) were determined using KUB film with or without ultrasonography after 3 months. Treatment failure was defined as radiologically confirmed persistence of the stone with no fragmentation after second SWL sessions. Complications during the intraoperative or post-operative periods were recorded. A total of 336 patients satisfied the inclusion criteria for the study, of which 169 patients were treated in the Group A and 167 in the Group B. There was no significant difference in patient and stone characteristics between the two groups (Table 1). The locations of treated stones are shown in Table 2. The treatment results were stratified by stone location in Table 3, significant differences existed in all treatment results between the two groups (P < 0.05). The overall stone-free rates after 3 months were 78.2 % for kidney stones and 81.7 % for ureteral stones in patients from Group A. The corresponding SFRs for patients in Group B were 62.8 and 67.9 % for stones in the kidneys and ureters, respectively. There were statistical differences in these results between the two groups (P < 0.05). The lithotripter with OCC had excellent shock wave transmission properties with the least possible loss of energy; it can lead to the optimization of SWL treatment outcome and reduce the incidence of SW-induced adverse effects. We are confident that the OCC used in this study should be a standard feature in future lithotripters.(Table presented.)(Table presented.)(Table presented.) © 2016 Springer-Verlag Berlin Heidelberg

Sun B.,Nanjing Medical University | Karin M.,Cancer Center
Frontiers of Medicine | Year: 2013

Inflammation has been considered as one of the hallmarks of cancer, and chronic hepatitis is a major cause of liver cancer. This review will focus on the pathogenic role of inflammation in hepatocarcinogenesis and will discuss recent advances in understanding the chronic hepatitis-liver cancer link based on hot spots in liver cancer research, including cellular interaction, cytokines, microRNA and stem cells. All of these mechanisms should be taken into consideration because they are crucial for the development of more efficacious therapeutic strategies for preventing and treating human chronic hepatitis and hepatocellular carcinoma. © 2013, Higher Education Press and Springer-Verlag Berlin Heidelberg.

Zhang M.,Harvard University | Zhang M.,Nanjing Medical University | Qureshi A.A.,Harvard University | Guo Q.,Harvard University | Han J.,Harvard University
DNA Repair | Year: 2011

Reduced DNA repair capacity has been proposed as a predisposing factor for melanoma. We comprehensively evaluated 1463 genetic variants across 60 DNA repair-related pathway genes in relation to melanoma risk in a nested case-control study of 218 melanoma cases (20% on head and neck) and 218 matched controls within the Nurses' Health Study (NHS). We then genotyped the two variants with the smallest P value in two replication sets: 184 melanoma cases (28% on head and neck) and 184 matched controls in the Health Professionals Follow-Up Study (HPFS); and 183 melanoma cases (10% on head and neck) and 183 matched controls in the NHS. The SNP rs3219125 in the PARP1 gene was significantly associated with melanoma risk in the discovery set (odds ratio (OR) 3.14; 95% confidence interval (CI) 1.70-5.80) and in the HPFS replication set (OR, 1.92; 95% CI, 1.05-3.54) but not in the NHS replication set (OR, 1.07; 95% CI, 0.58-1.97). In the joint analysis, the OR was 1.89 (95% CI, 1.34-2.68) for this polymorphism, and this increased risk was more pronounced among patients with lesions in head/neck (OR, 3.19; 95% CI, 1.77-5.73 for head/neck, and OR, 1.54; 95% CI, 1.03-2.30 for other sites, P value for heterogeneity test. =0.036). Our findings suggest the possible involvement of the PARP1 variant in melanoma development, especially for sites with high sun exposure. Further work on fine-mapping and on the functional characterization of this and linked SNPs in this region is required. © 2010 Elsevier B.V.

Xu X.Y.,Nanjing Medical University
Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases | Year: 2010

To study the receptor for adhesion and endocytosis of Aspergillus fumigatus hyphae by human umbilical vein endothelial cells (HUVEC). Aspergillus fumigatus hyphae were incubated with the total protein of HUVEC for investigating the binding of N-cadherin and the fungus. After the model of adhesion and endocytosis of Aspergillus fumigatus by HUVEC was established, the capacity of adhesion and endocytosis was evaluated with the presence of the antibody to N-cadherin. N-cadherin sticked to the surface of Aspergillus fumigatus. Adhesion and endocytosis were inhibited with the presence of the antibody to N-cadherin. N-cadherin is a receptor for adhesion and endocytosis of Aspergillus fumigatus by HUVEC.

Tang N.-P.,Shanghai Institute of Pharmaceutical Industry | Wu Y.-M.,Peoples Hospital of Jiangsu Province | Wang B.,Nanjing Medical University | Ma J.,Shanghai Institute of Pharmaceutical Industry
European Journal of Surgical Oncology | Year: 2010

Background: A number of studies has evaluated the association between P53 codon 72 polymorphism and colorectal cancer. However, results were inconsistent. To clarify the role of this polymorphism in colorectal cancer, we conducted a meta-analysis on this topic. Methods: Two authors independently searched the PubMed and EMBASE database from 1966 to January 2010 for studies regarding the association of P53 codon 72 polymorphism with colorectal cancer. Summary odds ratios with their corresponding 95% confidence intervals were calculated by using random-effects model. Results: The combined results showed that P53 codon 72 variant genotypes were not associated with colorectal cancer risk when compared to Arg/Arg genotype (Pro/Pro: OR = 1.02, 95% CI = 0.80-1.29; Arg/Pro: OR = 1.00, 95% CI = 0.86-1.16; Pro allele: OR = 1.00, 95% CI = 0.86-1.17). When stratifying for study population, design and cancer location, no statistically significant results were observed either. Conclusion: Our data indicate that the P53 codon 72 polymorphism may be not associated with colorectal cancer risk. © 2010 Elsevier Ltd. All rights reserved.

Ding H.,Nanjing Medical University
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 expressions of caveolin-1, collagen-I and alpha-SMA in human fetal lung fibroblasts induced by transforming growth factor beta(1) (TGF-beta(1)). Human fetal lung fibroblasts (HFLF) were cultured in vitro, and exposed to TGF-beta(1) with different final concentrations (2, 5, 10 microg/L). Cells without TGF-beta(1) exposure served as the control. Caveolin-1 mRNA and protein, collagen-I and alpha-SMA proteins in cell (at least 5 x 10(8)) lysates, were detected at different points after the treatment of TGF-beta(1), by RT-PCR, Western blot and Immunohistochemistry. Each experiment was repeated 3 times. One-way analysis of variance (ANOVA) was used to compare data among groups, and linear regression was established for correlation analysis. TGF-beta(1) reduced caveolin-1 mRNA and protein expressions in a dose- and time-dependent manner, measured by integral optical density. Compared with the control group (1.22 +/- 0.12 and 1.45 +/- 0.06), caveolin-1 mRNA and protein expressions (0.59 +/- 0.06 and 0.53 +/- 0.04) were significantly reduced, with statistical significance (F = 29.279 and F = 95.786, P < 0.01), in cells exposed to TGF-beta(1) (5 microg/L) for 12 h. The collagen-I and alpha-SMA protein expressions (1.35 +/- 0.09 and 0.75 +/- 0.06) measured by integral optical density increased after stimulation, peaked at 24 h in 5 microg/L TGF-beta(1) group. At that time point, the collagen-I and alpha-SMA protein expressions were 4.2 and 4.8 times of the control group (0.28 +/- 0.04 and 0.18 +/- 0.04), F = 81.221 and F = 65.477, P < 0.01. Caveolin-1 expression had a negative correlation with collagen-I (r = -0.923, P < 0.05) and alpha-SMA protein expression (r = -0.793, P < 0.05). The reduced caveolin-1, which was negatively correlated with expressions of collagen-I and alpha-SMA proteins in HFLF cells exposed to TGF-beta(1), may be related to the development and progress of pulmonary fibrosis.

Gao W.T.,Nanjing Medical University
Zhonghua wai ke za zhi [Chinese journal of surgery] | Year: 2010

To identify HLA-restricted epitope of mucoprotein 4 (MUC4) antigen as a tumor associated antigen of pancreatic ductal adenocarcinoma (PDAC), and to validate its natural presentation in PDAC patient peripheral blood. Two epitope prediction databases (SYFPEITHI and ProPred-I) were used to predict HLA-A*0201 restricted MUC4 epitope, T2 cell assay was used to determine the peptide binding affinity with HLA-A*0201 molecule. Dendritic cells (DCs) were induced from the HLA-A* 0201-positive healthy individuals' peripheral blood mononuclear cells (PBMC). Mature DCs were pulsed with synthesized peptides. Autologous CD8(+) T cells from the HLA-A* 0201 healthy donor were stimulated with the peptide-pulsed DCs as CTL. CTL activity was assessed by lactate dehydrogenase release assay and IFN-γ released by enzyme-linked immunospot assay. Pentamer was synthesized for HLA-A* 0201 restricted epitope P1126, then was used to detect specific CTL in PBMC of PDAC patients. Five candidate HLA-A*0201 epitopes were predicted, LLLGVGTFV (P1125) and LLGVGTFVV (P1126) were determined as the two with more HLA-A*0201 affinity. Mature DCs could be induced from PBMCs. CTL induced by peptide P1126 could lyses T2 cells pulsed with peptide P1126 and HCT-116 cells [MUC4(+), HLA-A2(+)]. The number of CTL induced by peptide P1126 which could secret IFN-γ (130.3 ± 6.6) was obviously higher than that in the negative group. By Pentamer assay, P1126-pentamer and CD8 double positive CTL could be detected in PBMC of PDAC patients with MUC4(+) than patients with MUC4(-), but no significant difference of CTL frequency between patients with HLA-A2(+) and with HLA-A2(-) in MUC4(+) PDAC patients. Tumor associated antigen MUC4-derived HLA-A* 0201-restrictive cytotoxic T lymphocyte (CTL) epitope P1126 can induce CTL reaction. The CTL can secret immunologic active material to induce the specific target cells lysis. P1126 epitope can be naturally presented in PBMC of PDAC patients, but its HLA-restriction may not be perfect.

Ji F.Z.,Nanjing Medical University
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2013

To compare the efficacy and toxicity of intensity- modulated radiation therapy plus chemotherapy (IMRT-TP) with simple intensity-modulated radiation therapy (IMRT) in the treatment of locally advanced esophageal carcinoma. A total of 170 eligible patients with locally advanced esophageal carcinoma were recruited prospectively from September 2004 to April 2008 and randomly divided into IMRT-TP group and IMRT group. Two groups were treated with IMRT of 6MV-X. The radiation dose was 60 Gy in 30 fractions in IMRT-TP group and 66 Gy in 30 fractions in IMRT group. The regimen of chemotherapy consisted of docetaxel and cisplatin in IMRT-TP group for 2 cycles. Of 170 patients, 160 completed the trial, including 75 patients of IMRT-TP group and 85 of IMRT group. As compared to IMRT group, total recurrence rate [69.3% (52/75) vs. 84.7% (72/85), P=0.020] and local recurrence rate [50.7% (38/75) vs. 67.1% (57/85), P=0.035] decreased in IMRT-TP group, the 5-year overall survival (29.3% vs. 15.3%, P=0.031) and 5-year recurrence free survival (24.0% vs. 10.6%, P=0.015) increased in IMRT-TP group. While severe side effect ratio increased obviously in IMRT-TP group [54.7% (41/75) vs. 4.7% (4/85), P=0.000]. As compare to simple IMRT, IMRT plus docetaxel and cisplatin can decrease the local recurrence rate, prolong the overall survival and regression-free survival, but bring more side effects.

Luo W.Z.,Nanjing Medical University
Zhongguo zhen jiu = Chinese acupuncture & moxibustion | Year: 2010

To compare the therapeutic effects of insomnia accompanied with depressive disorders treated by acupuncture of relieving depression and regulating mind and oral administration of Trazodone. Sixty-five cases were randomly divided into a acupuncture group (33 cases) and western medication group (32 cases). In acupuncture group, Shenmen (HT 7), Baihui (CV 20), Hegu (LI 4) and Taichong (LR 3) were selected. In western medication group, Trazodone was applied with oral administration for 4 weeks. The curative effect comparison was carried on by Pittsburgh Sleep Quality Index (PSQI), Self-Rating Depression Scale (SDS), and Side Effect Rating Scale (SERS) of Asberg. The cured and markedly effective rate of 72.7% (24/33)in acupuncture group was superior to that of 46.8% (15/32) in western medication group; after treatment, the scores of all items and the total cumulative scores of PSQI and SDS of both groups were reduced (P < 0.01, P < 0.05), of which, the sleep quality and daytime function evaluation in acupuncture group reduced more obviously than those in western medication group (both P < 0.05); the SERS scores of Asberg in western medication group were higher than those in acupuncture group. Acupuncture treatment of relieving depression and regulating mind is superior to Trazodone with oral administration for sleep quality and daytime function, with milder adverse reactions.

Pan F.,Nanjing Medical University
Zhonghua nan ke xue = National journal of andrology | Year: 2010

Repeated spontaneous abortion (RSA), with very complicated pathogenesis, has an incidence of about 0.5% 2.0%. As for the paternal part which provides half of the genes for the embryo, current studies mainly focus on the genes of somatic cells or germ cells. Chromosome abnormality of somatic cells, chromosome disorder of sperm, defects in sperm quality, genetic mutation, senility, infection and any other paternal gene abnormalities that affect the embryo would induce RSA. This paper presents an update on the above mentioned paternal factors which might result in RSA.

Zhou B.,China Pharmaceutical University | Zhou B.,Nanjing University of Technology | Liu J.,Nanjing University of Technology | Wang Z.-M.,Nanjing Medical University | Xi T.,China Pharmaceutical University
PLoS ONE | Year: 2012

Purpose: Epidemiologic findings are inconsistent concerning the associations between C-reactive protein (CRP), interleukin 6 (IL-6) and lung cancer risk. We conducted a meta-analysis of epidemiologic studies to examine these associations. Methods: A systematic literature search up to October 2011 was performed in MEDLINE and EMBASE. Study-specific risk estimates were pooled using a random-effects model. Results: The 10 studies on CRP involved a total of 1918 lung cancer cases. The pooled RR of lung cancer for one unit change in natural logarithm (ln) CRP was 1.28 (95% CI 1.17-1.41). There was no statistically significant heterogeneity among studies (P = 0.116; I2 = 36.6%). We also found that CRP was significantly associated with increased risk of lung cancer among men (RR 1.18, 95% CI 1.09-1.28) but not among women. The 5 studies on IL-6 involved a total of 924 lung cancer cases. The pooled RR of lung cancer for one unit change in ln IL-6 was 1.28 (95% CI 0.92-1.79), however, statistically significant heterogeneity was found. After excluding the study contributing most to the heterogeneity, the summary estimate was essentially unchanged. Conclusion: CRP was associated with increased risk of lung cancer, especially among men. There was no significant association between IL-6 and lung cancer risk. © 2012 Zhou et al.

Chen D.,Nanjing Medical University
The West Indian medical journal | Year: 2010

To evaluate the feasibility of using magnetic nanoparticles (MNPs) as gene vector and the effect of magnetic field on efficiency of transfection. Magnetic nanoparticles were prepared by controlling some chemical reaction parameters through a partially reduction precipitation method with ferric chloride aqueous solution as precursor material. The surface of particles was modified by polyethyleneimine (PEI) agents. The appearance, the size distribution, structure and phase constitute of MNPs were characterized by Transmission electron microscope (TEM), X-ray diffraction (XRD); the potential of absorbing DNA of MNPs was analysed by electrophoresis. Transfection was determined by delivering reporter gene, PGL2-control encoding luciferase, to different cell lines using MNPs-PLL as vector. The effect of magnetic field on the efficiency of transfection was determined using Nd-Fe-B permanent magnet. Foreign gene could be delivered to various cell lines by MNPs-PLL and expressed with high efficiency but the transfection efficiency and time course varied in the different cell lines studied. Magnetic field could enhance the efficiency of transfection by 5-10 fold. MNPs- PLL can be used as a novel non-viral gene vector in vitro, which offers a basis for gene delivery in vivo.

Li Q.,Nanjing Medical University
Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery | Year: 2011

To analyze GJB2 235delC monoallelic mutation carrier individuals and test the possible presence and incidence of audiometric abnormalities among 30-60 years old carriers of the 235delC mutations. A total of 32 unrelated subjects with nonsyndromic hearing loss were screened for the 235delC mutation. Tonal audiometric analysis was performed on the 235delC mutation carrier group and on a non-carrier control group. Audiometric evaluations in the control group showed the presence of thresholds within normal limits at all frequencies, while carriers of the 235delC mutation presented with decreased hearing at 1000 Hz and 2000 Hz (age 40-49 years and 50-59 years), and 4000 and 8000 Hz (age 30-59 years), P < 0.05. The hearing loss of carriers gradually increased with age. GJB2 235delC heterozygous carriers may be a risk group for high-frequency hearing loss. Hearing thresholds may deteriorate in the intermediate frequencies over the age of 40.

Song L.,Nanjing Medical University
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2010

OBJECTIVE: To investigate the etiological role of hMLH1 gene A655 polymorphism in colorectal cancer. METHODS: A case-control study was carried out, including 115 colorectal cancer patients and 135 healthy people as control. Genomic DNA was extracted from peripheral white blood cell from all the subjects. Polymorphism was detected by PCR-based DHPLC analysis and verified by DNA sequencing. RESULTS: The hMLH1 gene A655G polymorphism was detected in 3.0% of healthy people and 11.3% of colorectal cancer patients (P<0.01), and the difference was significant (P<0.01). The hMLH1 gene A655G polymorphism was detected in 8.2% of tubular adenocarcinoma or tubular-papillary adenocarcinoma and 27.8% of mucinous adenocarcinoma, which was also significant (P<0.05).Meanwhile, hMLH1 gene A655G polymorphism was not associated with age, gender and lymphatic metastasis (all P>0.05). CONCLUSIONS: The hMLH1 gene A655G polymorphism may play a role in the pathogenesis of colorectal cancer. Determination of the polymorphism may be a potential marker to predict the prognosis of colorectal cancer patients.

Zhang H.Z.,Nanjing Medical University
Chinese journal of cancer | Year: 2012

Esophageal cancer is a common cancer worldwide and has a poor prognosis. The incidence of esophageal squamous cell cancer has been decreasing, whereas the incidence of esophageal adenocarcinoma has been increasing rapidly, particularly in Western men. Squamous cell cancer continues to be the major type of esophageal cancer in Asia, and the main risk factors include tobacco smoking, alcohol consumption, hot beverage drinking, and poor nutrition. In contrast, esophageal adenocarcinoma predominately affects the whites, and the risk factors include smoking, obesity, and gastroesophageal reflux disease. In addition, Asians and Caucasians may have different susceptibilities to esophageal cancer due to different heritage backgrounds. However, comparison studies between these two populations are limited and need to be addressed in the near future. Ethnic differences should be taken into account in preventive and clinical practices.

Qian X.F.,Nanjing Medical University
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology | Year: 2012

Childhood acute lymphoblastic leukemia (C-ALL) is the most common pediatric cancer. Although its etiology remains poorly understood, the hypothesis of ALL correlated with a genetic basis was examined through association studies based on candidate genes. Recently, two independent large-scale genome-wide association studies reported that the five single nucleotide polymorphisms (rs7073837; rs10821936; rs10994982; rs7089424; rs10740055) in the gene AT rich interactive domain 5B (ARID5B) at 10q21.2, were associated with the high incidence risk of C-ALL, especially with hyperdiploid lymphoblastic leukemia. Variations in these single nucleotide polymorphisms influence the risk of specific disease subtypes, and also possess race- and sex-differences in leukemia incidence. Further elucidation of the mechanisms through which ARID5B variants are involved in C-ALL not only has a great diagnostic value, but also a guidance for the clinical therapy, ultimately improving the prognosis of disease. Therefore, the related studies of ARID5B with C-ALL were summarized briefly in this review.

Gasque G.,Rockefeller University | Conway S.,Rockefeller University | Huang J.,Nanjing Medical University | Rao Y.,Tsinghua University | And 2 more authors.
Scientific Reports | Year: 2013

Dysregulation of eating behavior can lead to obesity, which affects 10% of the adult population worldwide and accounts for nearly 3 million deaths every year. Despite this burden on society, we currently lack effective pharmacological treatment options to regulate appetite. We used Drosophila melanogaster larvae to develop a high-throughput whole organism screen for drugs that modulate food intake. In a screen of 3630 small molecules, we identified the serotonin (5-hydroxytryptamine or 5-HT) receptor antagonist metitepine as a potent anorectic drug. Using cell-based assays we show that metitepine is an antagonist of all five Drosophila 5-HT receptors. We screened fly mutants for each of these receptors and found that serotonin receptor 5-HT2A is the sole molecular target for feeding inhibition by metitepine. These results highlight the conservation of molecular mechanisms controlling appetite and provide a method for unbiased whole-organism drug screens to identify novel drugs and molecular pathways modulating food intake.

Background: The polymorphism of plasminogen activator inhibitor-1 (PAI-1) 4G/5G gene has been indicated to be correlated with coronary artery disease (CAD) susceptibility, but study results are still debatable. Objective and Methods: The present meta-analysis was performed to investigate the association between PAI-1 4G/5G gene polymorphism and CAD in the Chinese Han population. A total of 879 CAD patients and 628 controls from eight separate studies were involved. The pooled odds ratio (OR) for the distribution of the 4G allele frequency of PAI-1 4G/5G gene and its corresponding 95% confidence interval (CI) was assessed by the random effect model. Results: The distribution of the 4 G allele frequency was 0.61 for the CAD group and 0.51 for the control group. The association between PAI-1 4G/5G gene polymorphism and CAD in the Chinese Han population was significant under an allelic genetic model (OR = 1.70, 95% CI = 1.18 to 2.44, P = 0.004). The heterogeneity test was also significant (P<0.0001). Meta-regression was performed to explore the heterogeneity source. Among the confounding factors, the heterogeneity could be explained by the publication year (P = 0.017), study region (P = 0.014), control group sample size (P = 0.011), total sample size (P = 0.011), and ratio of the case to the control group sample size (RR) (P = 0.019). In a stratified analysis by the total sample size, significantly increased risk was only detected in subgroup 2 under an allelic genetic model (OR = 1.93, 95% CI = 1.09 to 3.35, P = 0.02). Conclusions: In the Chinese Han population, PAI-1 4G/5G gene polymorphism was implied to be associated with increased CAD risk. Carriers of the 4G allele of the PAI-1 4G/5G gene might predispose to CAD. © 2012 Yan-yan Li.

Zhang S.,Nanjing Medical University
Pancreas | Year: 2015

OBJECTIVES: To evaluate the regulation mechanism of heat shock protein 27 (HSP27) on gemcitabine (GEM) resistance of pancreatic cancer cell. METHODS: The expression vectors pEGFP-C1-HSP27 and the vectors of MicroRNA targeting Snail were introduced into GEM-sensitive pancreatic cancer SW1990 cells, and the vectors of small hairpin RNA targeting HSP27 were transfected into SW1990 and GEM-resistant SW1990/GEM cells. The expressions of HSP27, p-HSP27 (Ser82), Snail, ERCC1, and E-cadherin were evaluated by Western blotting. The sensitivity of transfected cells to GEM was detected by CCK-8 assay and Annexin V-FITC apoptosis assay. RESULTS: As compared to SW1990, SW1990/GEM showed significantly increased expressions of HSP27, p-HSP27, Snail and ERCC1 with decreased expression of E-cadherin. By increasing HSP27 expression, we found increase of Snail and ERCC1 with reduction of E-cadherin expressions, while reduction of HSP27 expression caused reduction of Snail and ERCC1 but increase of E-cadherin expressions. Downregulation of Snail resulted in the reduction of ERCC1 expression and increase of E-cadherin. Furthermore, downregulation of HSP27 or snail caused increased GEM sensitivity of pancreatic cancer cells, and upregulation of HSP27 showed the opposite results. CONCLUSIONS: There is an inverse correlation between HSP27 expression and GEM sensitivity of SW1990 cells, which might be realized by regulating E-cadherin and ERCC1 expressions through Snail. © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Cai Z.,Hubei University of Medicine | Chen G.,Hubei University of Medicine | He W.,Hubei University of Medicine | Xiao M.,Nanjing Medical University | Yan L.-J.,University of North Texas Health Science Center
Neuropsychiatric Disease and Treatment | Year: 2015

Alzheimer’s disease (AD) is characterized by cognitive impairment in clinical presentation, and by β-amyloid (Aβ) production and the hyper-phosphorylation of tau in basic research. More highlights demonstrate that the activation of the mammalian target of rapamycin (mTOR) enhances Aβ generation and deposition by modulating amyloid precursor protein (APP) metabolism and upregulating β- and γ-secretases. mTOR, an inhibitor of autophagy, decreases Aβ clearance by scissoring autophagy function. mTOR regulates Aβ generation or Aβ clearance by regulating several key signaling pathways, including phosphoinositide 3-kinase (PI3-K)/protein kinase B (Akt), glycogen synthase kinase 3 [GSK-3], AMP-activated protein kinase (AMPK), and insulin/insulin-like growth factor 1 (IGF-1). The activation of mTOR is also a contributor to aberrant hyperphosphorylated tau. Rapamycin, the inhibitor of mTOR, may mitigate cognitive impairment and inhibit the pathologies associated with amyloid plaques and neurofibrillary tangles by promoting autophagy. Furthermore, the upstream and downstream components of mTOR signaling are involved in the pathogenesis and progression of AD. Hence, inhibiting the activation of mTOR may be an important therapeutic target for AD. © 2015 Cai et al.

Wang W.J.,Nanjing Medical University
Orthopaedic surgery | Year: 2013

Treatment of distal femoral fracture in post-polio patients is difficult because the bone is usually osteopenic, small and deformed. This retrospective study aimed to investigate the outcomes of distal femoral fracture in post-polio patients treated by locking compression plates (LCP). The medical records of 19 post-polio patients (mean age 49 years at time of surgery) were reviewed and intraoperative data retrieved. Fracture union and callus formation were evaluated on radiographs taken at each postoperative visit. Functional outcome assessments included range of motion and Hospital for Special Surgery (HSS) score of the ipsilateral knee joint. Sixteen femoral fractures occurred in the poliomyelitis-affected limbs. The mean duration of operation was 86 min and mean blood loss 120 mL. All fractures healed (mean, four months) but union was delayed in one. At the final follow-up 2 yrs after surgery, the mean range of knee flexion was 105° (range, 90°-130°), and mean HSS score 76 points (range, 60-93). There were no cases of nonunion, implant cutout, or other complications. LCP provides stable fixation of distal femoral fractures in post-polio patients. Bony union and good functional outcomes are achieved, but delayed union and minimal callus may occur. © 2013 Chinese Orthopaedic Association and Wiley Publishing Asia Pty Ltd.

Chen G.,University of British Columbia | Wang Y.,University of British Columbia | Garate M.,University of British Columbia | Zhou J.,Nanjing Medical University | Li G.,University of British Columbia
Oncogene | Year: 2010

The inhibitor of growth family member 3 (ING3) has been shown to modulate transcription, cell cycle control and apoptosis. We previously reported that nuclear ING3 expression was remarkably reduced in melanomas, which correlated with a poorer patient survival, suggesting that decreased ING3 expression may be associated with melanoma progression. However, the mechanism of diminished ING3 expression in melanoma is not clear. Here we show that ING3 level was decreased in metastatic melanoma cells because of a rapid degradation. Furthermore, we showed that ING3 undergoes degradation through the ubiquitin-proteasome pathway. ING3 physically interacts with subunits of E3 ligase Skp1-Cullin-F-box protein complex (SCF complex). Knockdown of F-box protein S-phase kinase-associated protein 2 (Skp2) reduces the ubiquitination of ING3 and significantly stabilizes ING3 in melanoma cells. In addition, lysine 96 residue is essential for ING3 ubiquitination as its mutation to arginine dramatically abrogated ING3 degradation. Disruption of ING3 degradation stimulated ING3-induced G1 cell-cycle arrest and enhanced ultraviolet-induced apoptosis. Taken together, our data show that ING3 is degraded by the ubiquitin-proteasome pathway through the SCF Skp2 complex and interruption of ING3 degradation enhances the tumor-suppressive function of ING3, which provides a potential cancer therapeutic approach by interfering ING3 degradation. © 2010 Macmillan Publishers Limited All rights reserved.

Yao Z.,Tongji University | Shen C.,Nanjing Medical University | Zhong Y.,Fudan University
Clinical Therapeutics | Year: 2015

Background: Pregabalin has been used as an adjuvant in some trials to control postoperative pain after gynecologic surgery. However, the potential clinical advantage remains debatable. Objective: We performed a meta-analysis of clinical trials of pregabalin to evaluate its ability to control acute postoperative pain after gynecologic surgery. Methods: We searched PubMed, ScienceDiret, and the Cochrane Library of Randomized Controlled Trials up to January 2014. We performed a systematic review and meta-analysis of prospective controlled studies reporting pregabalin for gynecologic surgery. The primary outcome was pain outcomes and postoperative cumulative opioid consumption. Data were reported as weighted mean differences (WMDs) and 95% CIs. The secondary outcome was adverse effects after surgery. Results: Six valid randomized trials met the eligibility criteria and were included in the meta-analysis. Pooled data were collected from 452 patients between 2007 and 2012 (These trials were separately conducted in Greece 2012, India 2011-2012, Turkey 2011, Denmark 2009 and Australia 2007). The pregabalin-treated patients consumed fewer opioids during the first 24 hours postoperatively (WMD, -8.50 mg; 95% CI, -11.29 to -5.71 mg; P < 0.00001). Pain intensity at rest and on movement or coughing revealed a statistically significant pain relief effect of pregabalin during 24 hours postoperatively (at rest: WMD, -6.20 mm; 95% CI, -11.83 to -0.58 mm; P = 0.03; on movement or coughing: WMD, -5.32 mm; 95% CI, -9.73 to -0.91 mm; P = 0.02). No differences were found between the pregabalin and control groups for the adverse effects. Conclusions: Pregabalin has an analgesic and opioid-sparing effect and does not increase the frequency of adverse effects in acute postoperative pain management after gynecologic surgery. © 2015 Elsevier HS Journals, Inc. All rights reserved.

Chen H.,Nanjing Medical University
Circulation journal : official journal of the Japanese Circulation Society | Year: 2010

The incidence and clinical implication of dissociated pulmonary vein (PV) electrical activities after circumferential antrum PV ablation for paroxysmal atrial fibrillation (AF) remains unclear. A total of 196 patients with symptomatic paroxysmal AF who underwent circumferential antrum PV ablation were prospectively studied. Dissociated PV electrical activities were observed in 101 patients (Group 1), but absent in the remaining 95 patients (Group 2). There were no significant differences in the baseline clinical characteristics between them, except that Group 2 had a higher prevalence of hypertension (30 vs. 44%, P = 0.04). After 21.8 ± 7.9 months of follow-up, 148 had no recurrence of AF after the initial procedure. AF recurrence rate was significantly higher in Group 2 than in Group 1 (P = 0.023). Relapse of PV conduction was the major cause of AF recurrence in both groups (16/16 vs. 19/23, P = 0.08), and the overall procedural success rate after the redo ablation procedure was similar in the 2 groups (90 vs. 86%, P = 0.44). However, the total number of patients with non-PV foci was significantly higher in Group 2 than in Group 1 (12/95 vs. 2/101, P < 0.01). Dissociated PV electrical activities might identify a subgroup of patients with relatively higher initial procedural success with circumferential PV antrum ablation.

Feng K.,Nanjing Medical University
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine / Zhongguo Zhong xi yi jie he xue hui, Zhongguo Zhong yi yan jiu yuan zhu ban | Year: 2010

To investigate the inhibitory effect of cinobufotalin (CBT) on the growth of xenograft endometrial carcinoma cell line ishikawa in nude mice, and its impact on the expression of ribonucleotide reductase subunit M2 (RRM2). Eleven nude mice with xenograft were randomly divided into two groups, the CBT group and the control group, which received intra-tumor injection of CBT and saline respectively for one week. The sizes of xenografts were measured before and after the treatment to calculate the inhibition ratio of tumor proliferation; the RRM2-mRNA and protein expressions in tumor tissue were measured by RT-PCR and Western blot respectively. After treatment, the size of xenografts in the CBT group was (0.1314 +/- 0.0304) cm3, which was significantly lower than that in the control group (0.360 0 +/- 0.1145) cm3, (P < 0.05), the tumor proliferation inhibition ratio being 43.46%. The differences of RRM2 mRNA and protein expression levels between the two group were significant (P = 0.019 and P = 0.001). CBT significantly inhibits the growth of the xenografts of endometrial carcinoma Ishikawa in nude mice, and the action mechanism is possibly associated with the inhibition on RRM2 expression.

To establish a gemcitabine-resistant pancreatic cancer cell line SW1990/GZ, and to explore the relationship between drug-resistant cell line SW1990/GZ and pancreatic cancer stem cell. Gemcitabine-resistant pancreatic cancer cell line SW1990/GZ was obtained by treating parental cell line SW1990 in vitro with increasing dosage of gemcitabine in culture medium intermittently for 24 weeks. Stable cultures were obtained which were 77.2-fold increased in resistance relative to parental cells. Gene expressions of ABCB1/MDR1, ABCC1/MRP and ABCG2/BCRP were determined by real-time PCR. Tumorigenic potential was performed by nude mice xenograft transplant experiments. Side population analysis and CD24CD44 positive cells explore were determined by flow cytometry to examine cancer stem cell proportion. Gemcitabine-resistant cell line SW1990/GZ underwent obvious morphological and functional changes. Compared with the parental cell line, SW1990/GZ cell was small and turned into round shape. SW1990/GZ had a higher gene expression level of ABCB1/MDR1, ABCC1/MRP and ABCG2/BCRP than SW1990 (P < 0.01). Nude mice xenograft transplant experiments showed that only 1 × 10(5) SW1990/GZ cells were sufficient for tumor formation, whereas an injection of 1 × 10(5) SW1990 cells did not initiate tumors. Flow cytometry analysis showed that SP proportion in SW1990/GZ was (11.0 ± 1.0)%, whereas in parental SW1990 it was (4.6 ± 0.9)%, CD44CD24 positive cells was (8.73 ± 0.81)% in SW1990/GZ, whereas (1.1 ± 0.4)% in SW1990. Gemcitabine-resistant cell line SW1990/GZ has a higher proportion of pancreatic cancer stem cells compared to its parental cell line SW1990. CD44 is mainly responsible for acquired drug resistance, which can be a potential target to overcome acquired drug resistance in pancreatic cancer.

Yang Z.Y.,Nanjing Medical University
Zhonghua xin xue guan bing za zhi | Year: 2011

To evaluate the value of dual source computed tomography coronary angiography (DSCT-CA) on detecting in-stent restenosis (> 50% luminal narrowing) in symptomatic patients referred for quantitative coronary angiography (QAC). Fifty five patients (43 males) with chest pain after coronary stent implantation within 6 - 12 months were evaluated by DSCT-CA and QAC. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of DSCT-CA were calculated using coronary angiography as gold standard. Eighty nine stents were implanted. In-stent restenosis was evidenced in 28 stents (31.5%) by QAC. The sensitivity, specificity PPV and NPV of DSCT-CA for the diagnosis of in-stent restenosis was 89%, 87%, 76% and 95%, respectively. Diagnostic efficiency was not affected by heart rate and the sensitivity was 0.94 vs. 0.82, the specificity 0.88 vs. 0.90, the PPV 0.76 vs. 0.75 and the NPV 0.97 vs. 0.93 (all P > 0.05) between patients with heart rate < 70 beats/min and patients with heart rate ≥ 70 beats/min. The sensitivity (84% vs. 100%), specificity (81% vs. 96%), PPV (70% vs. 90%) and NPV (91% vs. 100%) were similar between overlapping or bifurcations stents and single stents. The specificity (100% vs. 80% vs. 66%) and PPV (100% vs. 95% vs. 53%) were significantly higher in the groups with stents ≥ 3.50 mm, stents 3.00 mm than in stents ≤ 2.75 mm (both P < 0.05). Diagnostic efficiency of in-stent restenosis with DSCT-CA in the large diameter stent is better than in the small diameter stent and the diagnosis efficacy is not affected by heart rate and stent distribution.

Li J.B.,Nanjing Medical University
Zhonghua nei ke za zhi [Chinese journal of internal medicine] | Year: 2011

To explore the relationship between plasma homocysteine levels and diabetic peripheral neuropathy (DPNP). A crossectional analysis was conducted on 227 patients with type 2 diabetes. Peripheral neuropathy was confirmed using electromyography (EMG). The risk factors possibly associated with diabetic neuropathy or plasma homocysteine levels were analyzed in relation to likelihood of occurrence of DPNP. Eighty patients with neuropathy and 147 patients without neuropathy were included. Plasma homocysteine levels were significantly higher in patients with diabetic neuropathy [(12.6 ± 3.6) μmol/L] than without diabetic neuropathy [(8.2 ± 0.9) μmol/L] (P < 0.001), and the relationship remained significant after adjusting for duration of diabetes, glycosylated hemoglobin A1c (HbA1c), age, renal status, serum folate acid and vitamin B(12), and metformin [OR 1.15 (1.02 - 1.28), P < 0.05]. In addition, per increase of 4.0 μmol/L plasma homocysteine was closely related to the occurrence of neuropathy after controlling for per unit increase of other confounding factors [OR 1.17 (0.94 - 1.33), P < 0.05]. Hyperhomocysteinemia was an independent risk factor for the occurrence of diabetic peripheral neuropathy.

Wang Y.L.,Nanjing Medical University
Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery | Year: 2012

To evaluate the correlation of exposure and sensitization to house dust mites among rhinitis patients, and the consistency of skin prick test (SPT) and serum specific IgE (sIgE) in the detection of sensitization in a steppe environment of inner Mongolia. Three hundreds and fourteen patients with rhinitis symptoms were recruited in this study in a hospital setting at Xilinhot City, inner Mongolia. All patients underwent medical history investigation, anterior rhinoscopy, and allergen tests in vivo (SPT) and in vitro (sIgE). Dust samples were collected from mattresses in patient's bedroom. The concentrations of group I major allergen of Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f) were measured by enzyme linked immunosorbent assay (ELISA). Statistical analysis was performed using a SPSS 17.0 software (t test, χ(2) test and so on). Among a total of 314 patients, the prevalence of positive SPT for Der p and Der f was 5.7% and 22.0%, respectively; and the prevalence of positive sIgE for Der p and Der f was 9.2% and 7.6%, respectively. Sensitization rates for house dust mites (Der p and/or Der f) were lower than those of pollens. The pollen allergen with the highest positive rate was mugwort (SPT, 51.9%; sIgE, 47.1%). Diagnostic tests using SPT as the gold standard for sensitization showed that the positive likelihood ratio of sIgE was 4.27 for Der p and 10.64 for Der f, and the Kappa value was 0.20 for Der p and 0.35 for Der f, respectively. A total of 276 dust samples collected from patient's mattresses were measured. The concentrations of Der p 1 and Der f1 were detectable in 2 (0.7%) and 4 (1.4%) mattress samples, respectively. There was positive correlation between the exposure levels of Derp 1 and the SPT positive reaction to Der p (r(s) = 0.156, P = 0.01), but no significant correlation was found between the exposure levels of Der p 1 and the sIgE positive reaction to Der p (r(s) = 0.116, P = 0.055). There was no significant correlation between the exposure levels of Der f 1 and the SPT as well as sIgE positive reaction to Der f 1(r(s) = 0.05, P = 0.931; r(s) = 0.07, P = 0.245). In the steppe environment of inner Mongolia, exposure to house dust mites are very low, and the Der p and Der f are not the major allergens in patients with allergic rhinitis. Also, it was not a simple dose-response relationship between exposure and sensitization to house dust mites. In such a specific environment, there is lower consistency between the results of SPT and sIgE in the detection of sensitization to house dust mites. Therefore, it is recommended that the allergen testing in vivo and in vitro should be combined for clinical diagnosis.

Zhang X.W.,Nanjing Medical University
Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] | Year: 2011

To investigate the relationship between genetic polymorphism in microRNAs (miRNAs) precursor and genetic predisposition of hepatocellular carcinoma (HCC) in Chinese population. A case-control study including 963 HCC cases and 829 HBsAg positive controls and 852 HBsAg negative controls was conducted. hsa-mir-146a rs2910164 C→G and hsa-mir-196-a2 rs11614913 T→C were selected, where the genotypes were determined by the primer introduced restriction analysis-PCR (PIRA-PCR) assay. Odd ratios (ORs) and 95% confidence intervals (CIs) were evaluated by logistic regression analysis to investigate the relationship between onset risk of HCC and different genotypes. The genotype frequencies of CC, CG and GG at rs2910164 gene locus were separately 34.5% (319/925), 48.6% (450/925) and 16.9% (156/925) in cases; 36.4% (274/753), 45.0% (339/753) and 18.6% (140/753) in HBsAg positive controls; and 36.1% (303/840), 46.0% (386/840) and 18.0% (151/840) in HBsAg negative controls. The genotype frequencies of TT, CT and CC at rs11614913 were respectively 29.7% (277/934), 48.1% (449/934) and 22.3% (208/934) in cases; 30.3% (238/785), 51.0% (400/785) and 18.7% (147/785) in HBsAg positive controls; and 28.6% (239/837), 49.8% (417/837) and 21.6% (181/837) in HBsAg negative controls. No significant relationships were observed between these two single nucleotide polymorphisms (SNPs) and onset risk of HCC after adjusting the factors as age, gender, smoking and drinking status in comparison with HBsAg positive controls: hsa-mir-146a rs2910164 (CG + GG vs CC): adjusting OR = 1.10, 95%CI: 0.90 - 1.36; hsa-mir-196-a2 rs11614913 (CC + CT vs TT): adjusting OR = 1.01, 95%CI: 0.81 - 1.25; as well as in comparison with HBsAg negative controls: hsa-mir-146a rs2910164 (CG + GG vs CC): adjusting OR = 1.06, 95%CI: 0.87 - 1.29; hsa-mir-196-a2 rs11614913 (CC + CT vs TT): adjusting OR = 0.94, 95%CI: 0.76 - 1.16. As well, no significant relationships were observed between these two SNPs and onset risk of HCC in the subgroups stratified by age, gender, smoking and drinking status. hsa-mir-146a rs2910164 C→G and hsa-mir-196-a2 rs11614913 T→C may not play an important role in the HCC predisposition among Chinese populations.

Smoking is a risk factor for idiopathic pulmonary fibrosis (IPF), but the mechanism of the association remains unknown. The aim of this study was to investigate the effects of cigarette smoke extract (CSE) on A549 cells and human lung fibroblasts treated with transforming growth factor-beta1. A transwell two-chamber coculture system was used to study the proliferation, differentiation, morphologic changes and soluble factors production of A549 cells and myofibroblasts. Low concentrations of CSE promoted myofibroblasts proliferation; however, high concentrations of CSE inhibited their proliferation. Low concentrations of CSE also markedly increased extracellular secretion of hydrogen peroxide, inhibited proliferation, induced apoptosis and produced epithelial-mesenchymal transition (EMT) in cocultured A549 cells. This cigarette smoke-induced A549 cells EMT may become a new pathophysiological concept in the development of IPF. CSE possibly takes part in the development and progress of IPF by increasing oxidative stress.

Wang Y.-N.-Z.,Nanjing Medical University
Hypertension | Year: 2016

Vascular remodeling is an important pathological feature of hypertension, leading to increased vascular resistance and reduced compliance. Endothelial cell (EC) and vascular smooth muscle cell (VSMC) dysfunction is involved in vascular remodeling. Long noncoding RNAs are potential regulators of EC and VSMC function. Herein, we determined whether long noncoding RNA–growth arrest–specific 5 (GAS5) is involved in hypertension-related vascular remodeling. We revealed that GAS5 knockdown aggravated hypertension-induced microvascular dysfunction as shown by increased retinal neovascularization and capillary leakage. GAS5 regulated the remodeling of arteries, including caudal arteries, carotid arteries, renal arteries, and thoracic arteries. GAS5 was mainly expressed in ECs and VSMCs, and its expression was significantly downregulated in hypertension. GAS5 knockdown affected endothelial activation, endothelial proliferation, VSMC phenotypic conversion, and EC-VSMC communication in vivo and in vitro. Mechanistically, GAS5 regulated EC and VSMC function through β-catenin signaling. This study identified GAS5 as a critical regulator in hypertension and demonstrated the potential of gene therapy and drug development for treating hypertension. © 2016 American Heart Association, Inc

This study aimed to evaluate the effectiveness of a rehabilitation intervention on physical dysfunction (PDF) and post-traumatic stress disorder (PTSD) in fracture victims 50 months after the Sichuan earthquake of 2008 and to identify risk factors for PTSD. This is a retrospective cohort study. Four hundred and fifty-nine earthquake-related fracture victims from Mianzhu city, Sichuan Province who did not qualify for disability pension participated. Two hundred and forty-five subjects received regular rehabilitation and 214 did not. Muscle strength, joint range of motion (ROM),sensory function, and sit-to-stand balance capacity were evaluated to assess PDF. The PTSD Checklist-Civilian Version (PCL-C) was administered to screen for PTSD. An ordinary least square regression was used to predict PTSD, and a logistic regression was used to predict PDF. In addition a Least Angle Regression (LARS) was carried out for PTSD to study the effects of rehabilitation and PDF at the same time. Unadjusted and adjusted group differences in physical dysfunction (p<0.01) and PTSD prevalence (p<0.05) were significant in favor of the rehabilitation group. In addition, being female, average or above family income, having witnessed death and fearfulness were found risk factors for PTSD symptoms 50 months after the earthquake. Both PDF and rehabilitation were selected predictors by LARS demonstrating opposite effects. PDF and PTSD were significantly reduced by the rehabilitation intervention. Future medical intervention strategies should consider rehabilitation in order to assist survivors in dealing with both physical and psychological effects of natural disaster.

Pan L.J.,Nanjing Medical University
Zhonghua nan ke xue = National journal of andrology | Year: 2012

To investigate the clinical effect of microsurgical varicocelectomy in the treatment of varicocele. We retrospectively analyzed the clinical data of 94 varicocele patients treated by microsurgical varicocelectomy, of whom 36 complained of testicular pain or dragging and distending discomfort, and 58 infertility or oligoasthenospermia. Microsurgical varicocelectomy was performed through inguinal or subinguinal approach. Complications were observed and semen parameters detected through follow-up visits at 1, 3 and 6 months after the operation. Testicular pain or discomfort disappeared in 21 (65.6%) of the 32 followed-up patients who had complained of such symptoms, was relieved in 6 (18.8%), and remained unimproved in the other 5 (15.6%). The 56 followed-up patients with infertility or oligoasthenospermia all showed significantly improved sperm concentration and motility (grade a + b sperm), (15.47 +/- 3.21) x 10(6)/ml and (13.34 +/- 5.16)% at 3 months, and (18.39 +/- 4.05) x 10(6)/ml and (17.23 +/- 4.69)% at 6 months after operation, as compared with (8.26 +/- 1.68) x 10(6)/ml and (5.25 +/- 1.09)% preoperatively (P < 0.01). Microsurgical varicocelectomy can effectively improve symptoms and semen parameters in varicocele patients.

Background: The α-adducin Gly460Trp (G460W) gene polymorphism may be associated with susceptibility to essential hypertension (EH), but this relationship remains controversial. In an attempt to resolve this issue, we conducted a meta-analysis. Methods: Twenty-three separated studies involving 5939 EH patients and 5021 controls were retrieved and analyzed. Four ethnicities were included: Han, Kazakh, Mongolian, and She. Eighteen studies with 5087 EH patients and 4183 controls were included in the Han subgroup. Three studies with 636 EH patients and 462 controls were included in the Kazakh subgroup. The Mongolian subgroup was represented by only one study with 100 EH patients and 50 controls; similarly, only one study with 116 EH patients and 326 controls was available for the She subgroup. The pooled and ethnic group odds ratios (ORs) along with the corresponding 95% confidence intervals (95% CI) were assessed using a random effects model. Results: There was a significant association between the α-adducin G460W gene polymorphism and EH in the pooled Chinese population under both an allelic genetic model (OR: 1.12, 95% CI: 1.04-1.20, P = 0.002) and a recessive genetic model (OR: 1.40, 95% CI: 1.16-1.70, P = 0.0005). In contrast, no significant association between the α-adducin G460W gene polymorphism and EH was observed in the dominant genetic model (OR: 0.88, 95% CI: 0.72-1.09, P = 0.24). In stratified analysis by ethnicity, significantly increased risk was detected in the Han subgroup under an allelic genetic model (OR: 1.13, 95% CI: 1.04-1.23, P = 0.003) and a recessive genetic model (OR: 1.43, 95% CI: 1.17-1.75, P = 0.0006). Conclusions: In a Chinese population of mixed ethnicity, the α-adducin G460W gene polymorphism was linked to EH susceptibility, most strongly in Han Chinese. © 2012 Yan-yan Li.

Jiang Y.,Nanjing Medical University
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology | Year: 2012

This study was aimed to quantify plasma circulating DNA level in patients with acute myeloid leukemia (AML) and to evaluate its clinical significance. 66 AML patients and 100 controls (60 healthy subjects for health examination, 20 cases of benign hematopathy, and 20 cases of solid tumors) were enrolled in this study. Blood samples were collected from AML patients at different status of disease and control groups. Circulating DNA were drew by using the BILATEST DNA Kit. The level of plasma DNA was determined by using duplex real-time quantitative PCR. The results showed that the median value of plasma DNA level in AML patients at diagnosis was 168.5 (73.4 - 245.1) ng/ml, significantly higher than those in three control groups, and the median level in male patients was significantly higher than that in female patients (P = 0.019). No significant difference was found in plasma DNA level of the patients at different ages and with different FAB subtypes. Compared with level before chemotherapy, the plasma DNA levels in complete remission patients and partial remission patients decreased significantly, and with no statistical difference from level of healthy controls, but was significantly different from level of non-remission patients (P < 0.05). Following up of 31 remission patients showed that the plasma DNA level increased in 5 out of 6 (83.3%) relapsed patients, but no increase was found in 22 out of 25 (88.0%) non-relapsed patients. It is concluded that the quantification of plasma DNA may be useful for evaluating therapeutic effects and monitoring relapse in AML patients.

Yang L.,Huaiyin Normal University | Lou Y.,Huaiyin Normal University | Wei J.,Nanjing Medical University
Oncology Reports | Year: 2010

Ikaros is a member of the Kruppel family of zinc finger DNA-binding proteins. The Ikaros protein contains two separate regions of zinc-finger domains: 4 DNA-binding zinc fingers near the N-terminus and 2 zinc fingers for proteinprotein interactions near the C-terminus. Here, we identified the Ikaros gene from 14 vertebrate genomes and found Ikaros existed in all kinds of vertebrate including fish, amphibians, birds and mammals. Moreover, except rat and Xenopus tropicalis Ikaros proteins, which lack the first C2H2-type 1 Zinc finger region, all identified Ikaros proteins contain six C2H2-type 1 Zinc finger regions. We found human Ikaros gene showed a predominant expression in the liver, lymph node, thymus, intestine, lung, mammary gland, bone marrow, brain, heart, placenta and prostate. Moreover, four available SNPs disrupted an existing exonic splicing enhancer were identified in Ikaros. Besides the reported acute lymphoblastic leukemia (ALL), the expression of Ikaros was related to the prognosis of 13 cases of cancers including blood cancers, breast, lung, ovarian and skin cancer. Moreover, the relationship between the expression of Ikaros and prognosis varied in different cancers, even in the same cancer from different database. Two tumor-related transcriptional factor (c-Fos and Elk-1) binding sites were identified within the 1.5-kb regions upstream of the transcriptional start site of human Ikaros, which may be involved in the effect of Ikaros in tumors.

Zeng K.,Nanjing Medical University
Journal of Human Hypertension | Year: 2016

Placental dysfunction and oxidative stress contribute to the pathogenesis of preeclampsia, which is a pregnancy-specific disorder. It has been suggested that the incidence of preeclampsia has a seasonal variation. Melatonin, as a seasonal factor, has been suggested to be involved in a successful pregnancy. In this study, we investigated the association of circulating levels of melatonin with preeclampsia. Serum was collected from women with preeclampsia (n=113) and gestation-matched healthy pregnant women, and the levels of melatonin were measured. In addition, the expression of melatonin receptors was examined in preeclamptic placentae (n=27). The association of the incidence of preeclampsia and seasonal variation was also analysed from 1491 women with preeclampsia within 77 745 healthy pregnancies. The serum levels of melatonin were significantly reduced in women with preeclampsia at presentation and these reduced serum levels of melatonin were not associated with the severity or time onset of preeclampsia nor with seasonal variation. The expression of melatonin receptor, MT1 was reduced in preeclamptic placentae. The incidence of preeclampsia was did exhibit seasonal variation, but this was largely due to the increase in the incidence of mild or late-onset preeclampsia. Our results demonstrate that reduced melatonin levels are associated with the development of preeclampsia but that the circulating levels of melatonin do not appear to be subject to seasonal variation during pregnancy.Journal of Human Hypertension advance online publication, 2 June 2016; doi:10.1038/jhh.2016.37. © 2016 Macmillan Publishers Limited

Zhang L.,Capital Medical University | Cheng L.,Nanjing Medical University | Hong J.,Shanghai JiaoTong University
Pharmacology | Year: 2013

Background: Cetirizine is among the first second-generation H1 antihistamines (SGAHs) developed to provide selective H1 receptor inhibition without central nervous system depression. Objective: The aim of this review is to summarize the amount of data collected over 25 years of clinical use of cetirizine and compare this with data available for other SGAHs in the management of patients with allergic rhinitis (AR). Methods: A comprehensive literature search for publications relating to cetirizine was performed using the Pubmed database, and relevant papers published in English were selected for detailed review. Results: Compared with the majority of other SGAHs, cetirizine was generally shown to have a more favourable pharmacological profile, to be well tolerated, be at least equally or more efficacious in attenuating/ inhibiting nasal and ocular symptoms and to improve the quality of life in AR patients. The majority of clinical trials investigating the effect of SGAHs in AR patients further indicated that cetirizine was often employed as the main comparator active drug. Conclusion: Based on the evidence that cetirizine is a commonly employed active comparator drug in AR, it is tempting to suggest that cetirizine may be a suitable benchmark in the development of novel pharmacotherapies for AR. Copyright © 2013 S. Karger AG, Basel.

Yang S.P.,Nanjing Medical University
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology | Year: 2011

To investigate the role of heme oxygenase(HO), a catalyzing enzyme of heme to produce CO, in modulation of systemic circulation in CCl4-induced cirrhotic rats. Saline(vehicle) and ZnPP were s.c. injected into the posterior necks of rats respectively and the rats were then anesthetized by pentobarbital sodium in four hours. Mean arterial pressure (MAP, kPa), heart rate (HR, b/min) and portal pressure (PP, cm/H2O) were measured by indwelling catheter. Plasma CO was determined by Chalmers method. Heme oxygenase acivity was determined by the rate of bilirubin formation. The cirrhotic rats showed significant hyperdynamic circulation indicated by decreased mean arterial pressure [MAP, (15.6+/-1.7) vs (18.9+/-0.9) kPa, t = 4.52, P less than 0.01] and increased portal pressure [PP, (16.7+/-0.8) vs (8.8+/-0.3) cm H2O, t = 23.10, P less than 0.01] as compared to normal control rats(NS). ZnPP could cause a significant increase in MAP [(17.3+/-1.5) vs (15.6+/-1.7) kPa, t = 2.18, P less than 0.05] and significant decrease in PP [(13.2+/-0.7) vs (16.7+/-0.8) cm H2O, t = 8.53, P less than 0.01] in cirrhotic rats. The cirrhotic group presented a significant increase in plasma CO [(18.0+/-1.9) vs (10.4+/-1.3)mumol/L, t = 8.42, P less than 0.01] and HO activity in the spleens [(11.1+/-0.9) vs (6.5+/-0.9) nmol bilirubin/mg protein/h, t = 9.28, P less than 0.01] and intestines [(2.5+/-0.1) vs. (1.3+/-0.2) nmol bilirubin/mg protein/h, t = 15.1, P less than 0.01]. ZnPP could cause significant decreases in plasma CO and HO activity in liver, spleen and intestine of both control and cirrhotic rats. HO-CO system activation may be an important reason for the hemodynamic disturbance of liver cirrhosis.

Objective: To provide appropriate evidence for treatment planning of patients with an impacted proximal ureteral stones ≥1.5 cm in size, by analyzing the therapeutic outcomes for those undergoing minimally invasive percutaneous antegrade ureterolithotripsy and retrograde ureterolithotripsy. Patients and methods: From September 2010 to November 2011, eligible patients with impacted proximal ureteral stones ≥1.5 cm in size referred to our institute were considered for this study. The closed envelope method was used to randomize the enrolled patients to mini-PCNL (30) or retrograde ureterolithotripsy (29). The efficiency quotient (EQ) was calculated to specifically address the efficiency for both the techniques. All preoperative and postoperative data for both groups were recorded. Results: The initial stone-free rate was 93.3 % in the mini-PCNL group and 41.4 % in the URSL group (p < 0.001). However, the overall stone-free rate at the 1-month follow-up visit after initial treatment was 100 % in the mini-PCNL group and 89.7 % in the URSL group (p = 0.07). The EQs for the mini-PCNL and URSL groups were 0.83 and 0.50, respectively. Conclusions: Our study shows that mini-PCNL removal of large impacted proximal ureteral calculi can achieve higher stone-free rates and safe. © 2013 Springer-Verlag Berlin Heidelberg.

PURPOSE: The aim of this study was to analyze the correlation between magnetic resonance imaging–based extramural vascular invasion (EMVI) and the prognostic clinical and histological parameters of stage T3 rectal cancers. METHODS: Eighty-six patients with T3 stage rectal cancer who received surgical resection without neoadjuvant therapy were included. Magnetic resonance imaging–based EMVI scores were determined. Correlations between the scores and pretreatment carcinoembryonic antigen levels, tumor differentiation grade, nodal stage, and vascular endothelial growth factor expression were analyzed using Spearman rank coefficient analysis. RESULTS: Magnetic resonance imaging–based EMVI scores were statistically different (P = 0.001) between histological nodal stages (N0 vs N1 vs N2). Correlations were found between magnetic resonance imaging–based EMVI scores and tumor histological grade (rs = 0.227, P = 0.035), histological nodal stage (rs = 0.524, P < 0.001), and vascular endothelial growth factor expression (rs = 0.422; P = 0.016). CONCLUSIONS: Magnetic resonance imaging–based EMVI score is correlated with prognostic parameters of T3 stage rectal cancers and has the potential to become an imaging biomarker of tumor aggressiveness. Magnetic resonance imaging–based EMVI may be useful in helping the multidisciplinary team to stratify T3 rectal cancer patients for neoadjuvant therapies. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

Zhang D.H.,Nanjing Medical University
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2011

To study the expression of HIF-1alpha in serum of primary hepatocellular carcinoma (PHC) and effects on tumor invasion and metastasis. The serum HIF-1alpha level from 60 cases of PHC patients and 60 cases of normal healthy individuals were detected by ELISA. The serum HIF-1alpha level of the PHC group was (161.14+/-80.79) pg/mL, the control group was (22.67+/-8.47) pg/mL, compared the different was significant (P<0.05). The serum HIF-1alpha level of distant metastasis of tumor group was (225.15+/-108.16) pg/mL, the no distant metastasis of tumor group was (101.26+/-55.18) pg/mL, compared the different was significant (P<0.05). The serum HIF-1alpha level of portal vein tumor thrombus group was (255.45+/-122.23) pg/mL. The no portal vein tumor thrombus group was (139.97+/-71.49) pg/mL, compared the different was significant (P<0.05). The serum HIF-1alpha level of tumor capsule group was (99.97+/-55.75) pg/mL. The no tumor capsule group was (187.36+/-91.52) pg/mL, compared the different was significant (P<0.05). The serum HIF-1alpha level was no significantly different among the different age, gender, TNM stage and tumor diameter. The serum HIF-1alpha has high expression in PHC. The serum HIF-1alpha expression has close relation with the whether distant metastasis of tumor, portal vein tumor thrombus and tumor capsule. The serum HIF-1alpha level can predict the invasion and metastasis of PHC.

Yu C.J.,Nanjing Medical University
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2011

To evaluate the prognostic value of metastatic lymph node ratio (MLR) for patients with gastric cancer. Data collected from 1247 patients with gastric cancer who underwent radical surgery (pT4 cases were excluded) at the First Affiliated Hospital of Nanjing Medical University between 2005 and 2009 were analyzed retrospectively. MLR was compared to pathological N staging (pN) in terms of prognostic accuracy, homogenicity, and applicability. MLR and pN were both positively correlated with the number of retrieved lymph nodes(both P<0.01). Significant differences were found in 5-year cumulative survival rate (5-YCSR) among different pN stages and MLR classification(all P<0.01). Multivariable analysis showed that both pN and MLR were independent prognostic factors(both P<0.01). The area under ROC curve(AUC) of MLR was larger than pN, however the difference was not statistically significant(P>0.05). There were significant differences in 5-YCSR among different MLR stages within the same pN stages(P<0.05), but not among different pN stages within the same MLR stage(P>0.05). Significant differences in 5-YCSR were also found among different retrieved-node groups within the same pN stage (P<0.05), but not within the same MLR stages (P>0.05). MLR is an independent prognostic factor for patients with gastric cancer. The prognostic homogenicity and applicability of MLR are better than those of pN, however the prediction accuracy is not favorable.

Deng G.-M.,Nanjing Medical University | Tsokos G.C.,Beth Israel Deaconess Medical Center
Nature Reviews Rheumatology | Year: 2015

Skin is the second most common organ (after the kidney) to be affected in patients with systemic lupus erythematosus (SLE), yet the aetiology of skin injury and the mechanisms involved in the development of dermal manifestations of SLE remain unclear. Ultraviolet light (UV), immune cells, cytokines and deposition of immunoglobulins all seem to have a role in the development of skin inflammation and damage in SLE. UV represents the most important environmental factor, and exposure to UV triggers the development of skin lesions in areas where immunoglobulin has been deposited and various other components of the immune system have accumulated. In addition, a number of intracellular kinases and transcription factors have also been demonstrated to be involved in the generation of skin lesions in lupus-prone mice. These molecules can be targeted by small-molecule inhibitors, leading to the prospect that treatments suitable for topical application, and with limited adverse effects, could be developed. Further studies to eliminate the burden of skin inflammation in patients with SLE are clearly required. © 2015 Macmillan Publishers Limited. All rights reserved.

Jia Z.,Nanjing Medical University | Wu A.,Interventional Imaging | Tam M.,University of Essex | Spain J.,Ohio State University | And 2 more authors.
Circulation | Year: 2015

Background-Limited penetration into the caval wall is an important securing mechanism for inferior vena cava (IVC) filters; however, caval penetration can also cause unintentional complications. The aim of this study was to assess the incidence, severity, clinical consequences, and management of filter penetration across a range of commercially available IVC filters. Methods and Results-The MEDLINE database was searched for all studies (1970-2014) related to IVC filters. A total of 88 clinical studies and 112 case reports qualified for analysis; these studies included 9002 patients and 15 types of IVC filters. Overall, penetration was reported in 19% of patients (1699 of 9002), and 19% of those penetrations (322 of 1699) showed evidence of organ/structure involvement. Among patients with penetration, 8% were symptomatic, 45% were asymptomatic, and 47% had unknown symptomatology. The most frequently reported symptom was pain (77%, 108 of 140). Major complications were reported in 83 patients (5%). These complications required interventions including surgical removal of the IVC filter (n=63), endovascular stent placement or embolization (n=11), endovascular retrieval of the permanent filter (n=4), and percutaneous nephrostomy or ureteral stent placement (n=3). Complications led to death in 2 patients. A total of 87% of patients (127 of 146) underwent premature filter retrieval or interventions for underlying symptoms or penetration-related complications. Conclusions-Caval penetration is a frequent but clinically underrecognized complication of IVC filter placement. Symptomatic patients accounted for nearly 1/10th of all penetrations; most of these cases had organ/structure involvement. Interventions with endovascular retrieval and surgery were required in most of these symptomatic patients. © 2015 American Heart Association, Inc.

Background: The intercellular adhesion molecule-1 (ICAM-1) E469K gene polymorphism has been implicated in increased coronary artery disease (CAD) susceptibility, but the individual study results are still controversial. Hypothesis: The ICAM-1 E469K gene polymorphism may be associated with CAD risk. Methods: The current meta-analysis involving 3065 subjects and 11 separate studies was conducted to explore the relationship between the ICAM-1 E469K gene polymorphism and CAD in the Chinese population. The pooled odds ratio (ORs) for the distribution of K allele frequency of ICAM-1 E469K gene and its corresponding 95% confidence interval (CI) was assessed by random effect model. Results: The distribution of the K allele frequency was 0.67 for the CAD group and 0.60 for the control group. The pooled OR for the distribution of the K allele frequency of the ICAM-1 E469K gene was 1.32 (95% CI, 1.02-1.72; P heterogeneity < 0.00001; inconsistency index I2 = 81.8%). The association between the ICAM-1 E469K gene polymorphism and CAD in the Chinese population was significant (P = 0.04). Conclusions: In the Chinese population, the distribution of the K allele frequency of the ICAM-1 E469K gene was indicated to be associated with CAD risk. The K allele of the ICAM-1 E469K gene might predispose to the CAD susceptibility. © 2011 Wiley Periodicals, Inc.

He F.,Nanjing Medical University
Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases | Year: 2012

To evaluate the therapeutic efficacy of hemoperfusion in the treatment of intermediate myasthenia syndrome (IMS) following acute organophosphate poisoning (AOPP). Eighty cases of IMS following AOPP, who were admitted to the Emergency Department of our hospital from 2006 to 2011 and had complete clinical records, were divided into HP treatment group (n = 36) and non-HP (NHP) treatment group (n = 44). The therapeutic efficacy of HP was evaluated by comparing the clinical data of the two groups. The HP treatment group showed significantly increased serum cholinesterase activity at 24h and 72 h after admission (P < 0.05), while the NHP treatment group showed significantly increased serum cholinesterase activity at 72 h after admission (P < 0.05). The serum cholinesterase activity in the HP treatment group was significantly higher than that in the NHP treatment group at 24 h after admission (P < 0.05). Compared with the NHP treatment group, the HP treatment group had significantly decreased total atropine dose, time of ventilatory assistance, length of ICU stay, recovery time from coma, incidence of pulmonary infection, and mortality due to respiratory failure (P < 0.05). There were no significant differences in the incidence of upper gastrointestinal hemorrhage and total mortality between the two groups (P > 0.05). Hemoperfusion is an effective therapy for improving clinical symptoms, shorten the course of disease, reducing complications, and decreasing the mortality due to respiratory failure in the patients with IMS following AOPP.

Qiu J.R.,Nanjing Medical University
Zhonghua yi xue za zhi | Year: 2011

To investigate the expression and its clinical significance of Trop-2 in human pancreatic cancer. Reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence assay were used to characterize the expression of Trop-2 in human pancreatic cancer. The expression of Trop-2 protein in 31 tumor tissue samples, including peritumoral tissue from patients with pancreatic cancer, was detected with immunohistochemistry by tissue microarray. The clinicopathological characteristics and the tissue expression of Trop-2 protein were analyzed statistically. RT-PCR, immunofluorescence assay and immunohistochemistry by tissue microarray showed a high expression of Trop-2 in pancreatic cancer. The expression rate of Trop-2 was much higher in pancreatic cancer than that in peritumoral tissues (87.1% vs 9.7%). And a high expression of Trop-2 in pancreatic cancer was correlated with the low-differentiated changes. It had statistical significance (P < 0.05). In contrast, no statistically significant correlation was found between the expression of Trop-2 and gender or age. The expression of Trop-2 is correlated with the development and malignancy of pancreatic cancer. As a clinical prognostic marker, Trop-2 may be a potential therapeutic target for pancreatic cancer.

Shen H.,Nanjing Medical University
Zhonghua nan ke xue = National journal of andrology | Year: 2011

To analyze the correlation between the size of prostatic middle lobe hyperplasia and the degree of bladder outlet obstruction (BOO) in patients with benign prostatic hyperplasia (BPH). This study included 131 BPH patients who presented with dysuria between May 2008 and June 2010. The prostate volume and intravesical prostatic protrusion (IPP) were measured by transabdominal ultrasound, Qmax and detrusor pressure at Qmax (P(det@ Qmax)) detected by urodynamic examination, the obstruction degree and detrusor contractility judged using the LinPURR Figure, and the AG value calculated (AG = P(det@ Qmax) -2Qmax). The degrees of BOO were compared between different groups of IPP by variance analysis, and the prostate volume, IPP and AG values underwent Bivariate correlation analysis. IPP was highly positively correlated with BOO when it was > 10 mm (r = 0.821, P < 0.01), while PV and BOO had a lower correlation (r = 0.475, P < 0.01). There was also a high positive correlation between IPP and P(det@ Qmax) (r = 0.865, P < 0.01). A close correlation exists between prostatic middle lobe hyperplasia and BOO, and evaluating IPP by ultrasound is a reliable method to determine the degree of BOO.

Differentiation of cardiac fibroblasts into myofibroblasts is a critical event in the progression of cardiac fibrosis that leads to pathological cardiac remodeling. Metformin, an antidiabetic agent, exhibits a number of cardioprotective properties. However, much less is known regarding the effect of metformin on cardiac fibroblast differentiation. Thus, in the present study, we examined the effect of metformin on angiotensin (Ang) II-induced differentiation of cardiac fibroblasts into myofibroblasts and its underlying mechanism. Adult rat cardiac fibroblasts were stimulated with Ang II (100 nM) in the presence or absence of metformin (10-200 μM). Ang II stimulation induced the differentiation of cardiac fibroblasts into myofibroblasts, as indicated by increased expression of α-smooth muscle actin (α-SMA) and collagen types I and III, and this effect of Ang II was inhibited by pretreatment of cardiac fibroblasts with metformin. Metformin also decreased Ang II-induced reactive oxygen species (ROS) generation in cardiac fibroblasts via inhibiting the activation of the PKC-NADPH oxidase pathway. Further experiments using PKC inhibitor calphostin C and NADPH oxidase inhibitor apocynin confirmed that inhibition of the PKC-NADPH oxidase pathway markedly attenuated Ang II-induced ROS generation and myofibroblast differentiation. These data indicate that metformin inhibits Ang II-induced myofibroblast differentiation by suppressing ROS generation via the inhibition of the PKC-NADPH oxidase pathway in adult rat cardiac fibroblasts. Our results provide new mechanistic insights regarding the cardioprotective effects of metformin and provide an efficient therapeutic strategy to attenuate cardiac fibrosis.

Fang C.,Nanjing Medical University
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi | Year: 2011

To evaluate the efficacy of combination chemoimmunotherapy of fludarabine, cyclophosphamide and rituximab (FCR) in chronic lymphocytic leukemia (CLL). Twenty-one patients with CLL were treated with FCR regimen which consisted of fludarabine (25 mg/m(2), days 2 to 4), cyclophosphamide (250 mg/m(2), days 2 to 4) and rituximab (375 mg/m(2), day 1) in a course of 28 days. The minimal residual disease (MRD) was determined by multiparameter flow cytometry. The correlation between the pretreatment characteristics and complete remission (CR) rate was analyzed. Eleven patients (52.4%) achieved CR, 7 (33.3%) achieved partial remission (PR) with a overall response (OR) rate of 85.7%. With a median follow-up time of 19 (7 - 73) months, the overall survival (OS) was 86.0%, and the progression-free survival (PFS) was 72.0%. Pretreatment parameters independently associated with higher CR rates were Binet stage A + B, IgVH mutated and ZAP-70 less than 20%. MRD was less than 1% in 6 patients. The most common toxicities were myelosuppression and gastrointestinal reaction. FCR is an effective regimen for CLL patients.

Zheng J.J.,Nanjing Medical University
Zhonghua nei ke za zhi [Chinese journal of internal medicine] | Year: 2011

To collect data and analyze the current status and prevalence changes of Crohn's disease (CD) in mainland China in recent decades. A computer-based literature search was previously performed by using 50-year (1950 to 2002) of records of CD from the Chinese Database of Biology and Medicine (CBM) (1979 to 2002) and a manual year-by-year search of the literature (1950 to 1978). Using similar method, descriptive epidemiological data from 2003 to 2007 were collected, analyzed and compared with previous research. Four hundred and seventeen relevant papers during 2003 and 2007 were collected and 62 papers were eligible for inclusion. Within 62 papers, a total of 2149 cases with CD from 2003 to 2007 have been reported nationwide, comprising 1288 male and 861 female patients, with a 1.50:1 male predominance, and indicating 1.41 time of increment as compared with our previous result (ie, 1526 cases from 1950 - 2002). There were no obvious changes in incidence age (younger and middle age were main components) and sex ratio (number of male was still larger than that of female). The extrapolated CD incidence and prevalence rates were 1.21/100 000 person·year and 2.29/100 000, respectively, which were higher than that of year 1950 - 2002, 0.28/100 000 person·year and 1.38/100 000, respectively. The incidence and prevalence rates of CD have been increasing rapidly, but these rates are still lower than those in Western world.

Zhong S.,Nanjing Medical University
European Journal of Cancer Prevention | Year: 2015

A number of epidemiologic studies have attempted to link the use of β blockers to mortality in cancer patients, but their findings have been inconclusive. A meta-analysis was carried out to derive a more precise estimation. Relevant studies were identified by searching PubMed and EMBASE to May 2015. We calculated the summary hazard ratios (HRs) and 95% confidence intervals (CIs) using random-effects models. Twenty cohort studies and four case–control studies involving 76 538 participants were included. The overall results showed that patients who used β blockers after diagnosis had an HR of 0.89 (95% CI 0.81–0.98) for all-cause mortality compared with nonusers. Those who used β blockers after diagnosis (vs. nonusers) had an HR of 0.89 (95% CI 0.79–0.99) for cancer-specific mortality. Prediagnostic use of β blockers showed no beneficial effect on all-cause mortality or cancer-specific mortality. Stratifying by cancer type, only breast cancer patients who used β blockers after diagnosis had a prolonged overall survival. A linear but nonsignificant trend was found between postdiagnostic β-blocker use and mortality of cancer patients. In conclusion, the average effect of β-blocker use after diagnosis but not before diagnosis is beneficial for the survival of cancer patients. © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Deng Y.,Nanjing Medical University
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery | Year: 2012

To observe the surgical results of atticotomy with canalopalsty and tympanoplasty for limited cholesteatoma. Thirty-one cases of limited epitympanic cholesteatoma and retraction pocket received atticotomy. The surgical procedure consisted of eliminating cholesteatoma and pocket, reconstructing lateral epitympanic wall and tympanoplasty with cartilage/perichondrium island flap. The anatomic pattern of external ear canal appeared near normal, and the hearing level improved or remained normal during 2-year follow up except for 2 cases with tympanosclerosis. No epitympanic retraction pocket or cholesteatoma relapsed. 1 case appeared tympanic perforation. Atticotomy, contemporaneous reconstruction of lateral epitympanic wall and tympanoplasty with cartilage/perichondrium, indicated to be a reliable treatment and prevention technique for epitympanic cholesteatoma. It can achieve good morphological and functional results.

To explore the effectivity and safety of single high-dose (HD) etoposide (Vp16) with granulocyte colony-stimulating factor (G-CSF) for mobilization of autologous peripheral blood stem cells (PBSC) in patients with hematologic malignancies. 80 patients of hematologic malignancies including 20 patients with acute leukemia (AL), 23 with multiple myeloma (MM), 35 with non-Hodgkin's lymphoma (NHL) and 2 with Hodgkin's lymphoma (HL) received Vp16 (1.6 g/m(2)) continuous intravenous infusion for 10 hrs on day 1. G-CSF at 10 μg/kg once daily subcutaneous injection began to use on day of ANC lower than 1×10(9)/L and continued until PBSC collection was completed. Autologous PBSC (APBSC) was collected on day of WBC greater than 5×10(9)/L and continuing until the collection goal was met (target value: MNC ≥ 6.0×10(8)/kg and CD34(+) ≥ 2.0×10(6)/kg). The patients received APBSC after conditioning regimen. The number of the cells collection, time of hematopoietic reconstruction, adverse effect and so on were observed during the course of stem cell mobilization and collection. PBSC was collected on day 11 (range: 7 - 25 days) of after Vp16 administration with a median collection time of 2 (range 1 - 5). 3/80 patients with AML got stem cell mobilization failure. 5 of 6 patients who failed to mobilize before got successful stem cell mobilization, 1/6 patient with AML-M(5) got a second failure after the mobilization of VP16 whose first time's mobilization using Ara-C did not succeed. The median number of CD34(+) cells collected in 77 patients who got successful mobilization was 4×10(6)/kg \[range (1.59 - 24.68)×10(6)/kg\]. The collection of 20 patients with AL and 23 with MM were got detection for minimal residual disease, no pollution of tumor cells were happened. All patients could tolerate the whole course of stem cell mobilization. 29/80 (36.25%) patients got a 4 grade leucopenia, 19/80 (23.75%) patients got infection. Single high-dose etoposide with G-CSF for mobilization of APBSC has a higher achievement ratio, a controllable adverse effect, a promising hematopoiesis recovery, which is an effective and safe mobilizing regimen for patients with hematologic malignancies.

Pang L.L.,Nanjing Medical University
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine / Zhongguo Zhong xi yi jie he xue hui, Zhongguo Zhong yi yan jiu yuan zhu ban | Year: 2010

To investigate the inhibitory effects and mechanism of apigenin (APG) on dominant response of Th2 cells in asthma model of mice. Thirty-two 6-week-old healthy BALB/c mice, SPF grade, were randomly divided into four groups equally, the normal control group (A), the asthma model group (B), and the two APG groups (C and D) consisted of asthma model mice treated respectively with high-dose (20 mg/kg per day) and low-dose (2 mg/kg per day) APG given by dissolving in 1% dimethyl sulphoxide via intraperitoneal injection. The murine asthma model was established by ovalbumin (OVA) sensitization and provocation. Twenty-four hours after the last airway provocation, acetylcholine (Ach) was administered via caudalis vein for measuring airway resistance by pulmonary function detector; levels of IL- 4 and IL-13 in bronchoalveolar lavage fluid (BALF) and total IgE in serum were determined by enzyme-linked immunosorbent assay (ELISA); total and differential cell counts in BALF were measured by light microscopy; the airway inflammatory infiltration was detected by haematoxylin and eosin (HE) staining; and the signal transducer and activator of transcription 3 (GATA-3) in the lung tissue was determined by Western blot analysis. As compared with Group A, the airway hyper-reactivity, airway inflammation, cell count and eosinophil percentage in BALF, levels of total serum IgE and BALF IL-4 and IL-13, and GATA-3 protein expression in the lung tissue were significantly increased in Group B (P < 0.05). As compared with Group B, all the above-mentioned indices in Group C and D were lower, showing respective significant difference (P < 0.05), and significant difference was also shown between the two APG treated groups (P < 0.05). APG could reduce the airway inflammation and hyper-reactivity by down-regulating the expressions of pulmonary GATA-3 and Th, cytokines, which is a potential drug for asthma therapy.

Deep vein thrombosis (DVT) after total hip or knee arthroplasty is relatively common and is associated with significant morbidity and mortality, presenting a large clinical burden. The objective of this study was to investigate the incidence and risk factors for DVT after total joint arthroplasty. This retrospective review was conducted in a single institution. The patients received postoperative DVT chemoprophylaxis (Fraxiparine or Rivaroxaban), followed by venography to check for DVT on the third to ninth postoperative day. The clinical characteristics were summarized and analyzed using SPSS version 17.0. From March 2010 to July 2013, 963 patients were enrolled in the study. DVT chemoprophylaxis was administered to all of the 963 patients. DVT occurred in 173 subjects (17.96%). Univariate analysis showed that age (P?

Wu H.F.,Nanjing Medical University
Zhonghua nan ke xue = National journal of andrology | Year: 2010

Ejaculatory duct obstruction (EDO) is an important cause of male infertility. Etiologically it can be either congenital or acquired. The diagnosis of EDO mainly depends on history, physical examination, semen analysis, and transrectal ultrasonography (TRUS). The semen of EDO patients is characterized by low ejaculate volume, oligospermia or azoospermia, low pH, and absence of fructose. Technetium (99Tc(m)) Sulphur Colloid Seminal Vesicle Scintigraphy is of great value in the differential diagnosis of functional, partial and complete obstruction. Definite diagnosis of EDO can be established by vasography, seminal vesicle aspiration and seminal vesiculography. Transurethral resection of the ejaculatory ducts (TURED), as the standard method of treatment for EDO, is effective for many of the patients. And the assistant reproductive technology (ART) is required if the procedure fails to restore the patient's fertility.

Lu T.,Mayo Medical School | Zhang D.-M.,Mayo Medical School | Wang X.-L.,Mayo Medical School | He T.,Mayo Medical School | And 4 more authors.
Circulation Research | Year: 2010

RATIONALE: The large conductance Ca2+-activated K+ (BK) channel, a key determinant of vascular tone, is regulated by angiotensin II (Ang II) type 1 receptor signaling. Upregulation of Ang II functions and downregulation of BK channel activities have been reported in diabetic vessels. However, the molecular mechanisms underlying Ang II-mediated BK channel modulation, especially in diabetes mellitus, have not been thoroughly examined. OBJECTIVES: The aim in this study was to determine whether caveolae-targeting facilitates BK channel dysfunction in diabetic vessels. METHODS AND RESULTS: Using patch clamp techniques and molecular biological approaches, we found that BK channels, Ang II type 1 receptor, Gαq/11 (G protein q/11 α subunit), nonphagocytic NAD(P)H oxidases (NOX-1), and c-Src kinases (c-Src) were colocalized in the caveolae of rat arterial smooth muscle cells and the integrity of caveolae in smooth muscle cells was critical for Ang II-mediated BK channel regulation. Most importantly, membrane microdomain targeting of these proteins was upregulated in the caveolae of streptozotocin-induced rat diabetic vessels, leading to enhanced Ang II-induced redox-mediated BK channel modification and causing BK channel and coronary dysfunction. The absence of caveolae abolished the effects of Ang II on vascular BK channel activity and preserved BK channel function in diabetes. CONCLUSIONS: These results identified a molecular scheme of receptor/enzyme/channel/caveolae microdomain complex that facilitates the development of vascular BK channel dysfunction in diabetes. Copyright © 2010 American Heart Association. All rights reserved.

Gao H.,Nanjing Medical University
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery | Year: 2011

The changes of the aquaporins 1 (AQP-1) expression may be related to the chondrocyte apoptosis. To explore the correlation between the expression of AQP-1 and chondrocyte apoptosis by observing the expression of the AQP-1 and the Caspase-3, so as to provide experimental evidence for the further study in the pathogenesis of osteoarthritis (OA). Seventy-two 8-week-old clean grade male Sprague Dawley rats, weighing 286-320 g (mean, 300 g), were randomly divided into the operated group (n = 24), the sham-operated group (n = 24), and the control group (n = 24). OA models were made by amputating the anterior cruciate ligament and medial collateral ligament, and partial excision of medial meniscus in operated group; the articular cavity was exposed only in sham-operated group; and no treatment was given in control group. The general condition of the rat was observed after model was established. At 1, 2, 4, and 8 weeks, the specimens of knee joints were harvested to perform the gross and histological observations; the mRNA expressions of AQP-1 and Caspase-3 were determined by real-time fluorescent quantitative PCR; and the activity of the Caspase-3 protease was detected. The correlations between the expression of AQP-1 mRNA and the expressions of Caspase-3 mRNA and protease were analyzed. Totally 6 rats died after operation, and the rats were supplied immediately; the other rats survived to the end of experiment. The appearance and structure of knee articular cartilage were normal in control group and sham-operated group. While in operated group, the cartilage had a rough surface with fissure and vegetation, and fibrosis and irregular cell arrangement were seen on the surface of cartilage. There were significant differences in the Mankin score between the operated group and sham-operated group, control group at 2, 4, and 8 weeks (P < 0.05). There was no significant difference in expressions of the AQP-1 mRNA and Caspase-3 mRNA, and the activity of the Caspase-3 protease among 3 groups at 1 week after operation (P > 0.05); while the expressions of the AQP-1 mRNA, Caspase-3 mRNA, and the activity of the Caspase-3 protease in operated group were significantly higher than those in sham-operated group and control group at 2, 4, and 8 weeks after operation (P < 0.05), and there was an increased trend over time. There was significantly positive correlation (r = 0.817, P = 0.000) between the expressions of AQP-1 mRNA and Caspase-3 mRNA, and the regression equation was y = 0.426 7x(2) + 0.051 5x; meanwhile, there was also significantly positive correlation (r = 0.945, P = 0.000) between the expression of AQP-1 mRNA and the activity of Caspase-3 protease, and the regression equation was y = 15.423 0x + 4.392 8. The up-regulation of AQP-1 expression in OA cartilage may be related to the chondrocyte apoptosis, and the changes of AQP-1 expression may involve in the pathogenesis of OA.

A method was developed to determine nine environmental phenols, including bisphenol A, 2,3,4-trichlorophenol, 2,4,5-trichlorophenol, pentachlorophenol, triclosan (2,4,4'-trichloro-2'-hydroxyphenylether), 4-tert-octylphenol, 4-n-octylphenol, 4-n-nolyphenol and benzophenone-3 (2-hydroxy-4-methoxybenzophenone) in human urine using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS). The analytes were extracted and preconcentrated with solid-phase extraction, and then quantified with UPLC-electrospray ionization (negative ion mode)-MS-MS using multiple reaction monitoring mode. Limits of detection of the nine phenols ranged from 0.02 to 0.90 ng/mL. This method was further validated by the determination of phenols in 325 human urine samples that generated data regarding the exposure of various phenols to Chinese adults without occupational exposure to phenols.

To evaluate the short-term and long-term efficacy of conservative laparoscopic surgery combine with goserelin in treatment of severe ovarian endometriosis. From January 2004 to December 2008, 206 patients with severe ovarian endometriosis underwent laparoscopy surgery in Nanjing Drum Tower Hospital, Affiliated Nanjing University Medical School were enrolled in this retrospective study. According to the revised classification American Fertility Society (r-AFS), 123 (123/206, 59.7%) cases were at stage III and 83 (83/206, 40.3%) patients were at stage IV. Among 138 cases presented pelvic pain. All the patients underwent laparoscopic cystectomy, of which 117 patients with childbearing preserving underwent hysteroscopy and hydrotubation examination, including 7 cases with bilateral salpingectomy, 2 cases with bilateral tubal obstruction and 108 cases with normal reproduction. After surgery, all cases were administered by goserelin treatment at dose of 3.6 mg per 28 days for 3 to 6 months. At 1 to 5 years following up, pelvic pain, pregnancy and recurrence were observed, those factors associated with pregnancy rate and endometriosis recurrence were analyzed. (1) Pelvic pain: complete remission rate of pelvic pain was 76.1% (105/138) at 1 to 5 years after surgery. (2) Pregnancy: total pregnancy rate was 70.4% (76/108), spontaneous pregnancy rate was 68.8% (66/96) and pregnant rate of in vitro fertilization and embryo transfer (IVF-ET) was 10/12. Pregnancy rate at 1 year was 57.3% (55/96) and accounting for 83.3% (55/66) in all pregnant women. Live birth rates of spontaneous pregnant and IVF-ET were 86.4% (57/66) and 9/10, respectively. (3) Recurrence: the total recurrence rate was 8.3% (17/206) at 1 to 5 years. The recurrence rates and the cumulative recurrence rates were 3.9% (8/206) and 3.9% (8/206) at the first year after operation, 2.0% (3/149) and 6.7% (10/149) at the second year, 1.0% (1/99) and 8.0% (8/99) at the third year, 10.9% (5/46) and 17.4% (8/46) at the fourth year, 0 and 2/18 at the fifth year, respectively. It was suggested that conservative laparoscopic surgery combined with goserelin in treatment of stage III or IV ovarian endometriosis could reduce the recurrence risk of severe ovarian endometriosis and improve the pregnant rate of endometriosis-associated infertility.

Xiao Z.,Harvard University | Xiao Z.,Massachusetts Institute of Technology | Ji C.,Harvard University | Ji C.,Nanjing Medical University | And 8 more authors.
Angewandte Chemie - International Edition | Year: 2012

Targeted cancer therapy: Inspired by the ability of DNA hybridization, a targeted near-infrared (NIR) light-responsive delivery system has been developed through simple DNA self-assembly (see picture; PEG=polyethylene glycol). This DNA-based platform shows the ability of releasing therapeutics upon near-infrared irradiation, and remarkable targeted thermo- and chemotherapeutic efficacy invitro and invivo. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

OBJECTIVE:: Pulmonary arterial hypertension (PAH) is characterized by increased vascular tone, altered vasoreactivity and vascular remodeling induced by smooth muscle cell proliferation. Similarities exist between cancer and PAH. Aberrant expression of the tumor suppressor protein is closely associated with PAH. Here, we tested the hypothesis that a tumor suppressor-axis inhibition protein 2 (Axin2) deficiency leads to PAH. METHODS AND RESULTS:: We measured right ventricular systolic pressure in Axin2 knockout mice and assessed the expression of Axin2 in patients. We found that Axin2 expression level was decreased in both mice exposed to chronic hypoxia and patients with PAH in remodeled pulmonary arterioles. Axin2 knockout mice showed elevated mean right ventricular systolic pressure and enhanced contraction in response to phenylephrine. An increase in the cross-sectional area of the vessels was occupied by the vessel wall, indicating pulmonary vascular remodeling. Furthermore, knocking down Axin2 with small interfering RNA inhibited apoptosis of pulmonary arterial smooth muscle cells (PASMCs). This inhibition was significantly abolished by β-catenin inhibitors, indicating that Axin2 through β-catenin increased vascular wall by inhibiting the apoptosis of PASMCs. Importantly, overexpression of Axin2 attenuates the development of hypoxia-induced PAH in mice. CONCLUSION:: Taken together, our study, for the first time, established that Axin2 plays a key role in the progression of PAH. We identified Axin2 as a novel mediator of pulmonary vasoconstriction and PASMC growth in hypoxia-mediated PAH. Our results suggest that downregulation of Axin2 in the pulmonary vasculature may be an underlying mechanism in the development of hypoxia-induced PAH. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

Wang L.L.,Nanjing Medical University
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology | Year: 2012

This study was aimed to detect the level of soluble interleukin-2 receptor (sCD25) and cytotoxic activity of NK lymphocytes in patients with hemophagocytic lymphohistiocytosis (HLH), and to explore their clinical significance in HLH. The enzyme-linked immunosorbent assay was used to detect the sCD25 level in serum of 20 patients with HLH, 15 healthy controls, 20 cases of acute myeloid leukemia and 20 cases of systemic lupus erythematosus. The NK cell cytotoxicity in peripheral blood of patients with HLH and controls were detected by flow cytometry with CD107a antibody labeling and LDH release assay. The results indicated that the level of sCD25 in HLH patients was significantly higher than that in healthy controls and disease groups (P < 0.001). The NK cell cytotoxicity in peripheral blood detected by both methods in patients with HLH were lower than that in healthy controls (P < 0.05), and the results detected by flow cytometry correlated significantly with those by LDH release assay (r = 0.73, P < 0.05). It is concluded that detection of sCD25 levels and NK cell activity in peripheral blood in HLH is of great value. Using flow cytometry following CD107a antibody labeling to measure NK activity is a simple, stability, reproducibility method and can be used for clinical diagnosis of HLH.

Zhong S.,Nanjing Medical University
Prostate Cancer and Prostatic Diseases | Year: 2016

Background:Previous studies concerning the association between body mass index (BMI) and mortality in prostate cancer yielded mixed results. We investigated the association by performing a meta-analysis of all available studies.Methods:Relevant studies were identified by searching PubMed and EMBASE to August 2015. We calculated the summary hazard ratio (HR) and 95% confidence interval (CI) using random-effects models. We estimated combined HRs associated with defined increments of BMI, using random-effects meta-analysis and dose–response meta-regression models.Results:Thirty-seven cohort studies and one case-control study involving 27 38 000 patients of prostate cancer were selected for meta-analysis. The summary results indicated higher prediagnosis BMI but not postdiagnosis BMI was associated with increased risk of death from prostate cancer. An increment of every 5 kg/m2 in prediagnosis BMI was associated with a 15% higher prostate cancer-specific mortality (HR=1.15, 95% CI: 1.07–1.23, P<0.01). Prediagnosis or postdiagnosis BMI showed no effect on all-cause mortality in prostate cancer patients.Conclusions:In conclusion, higher prediagnosis BMI is associated with a higher risk of death from prostate cancer. Considering the significant heterogeneity among included studies, these findings require confirmation in future studies.Prostate Cancer and Prostatic Diseases advance online publication, 12 January 2016; doi:10.1038/pcan.2015.64. © 2016 Macmillan Publishers Limited

Shao X.,Nanjing Medical University
Zhonghua wai ke za zhi [Chinese journal of surgery] | Year: 2010

To investigate the pulmonary dysfunction patterns in patients of scoliosis associated with neurofibromatosis type I (NF1) and to identify factors affecting the pulmonary function in patients with scoliosis associated with NF1. Preoperative pulmonary function tests (PFTs) were evaluated in 100 patients with scoliosis [NF1 group, 36 cases; idiopathic scoliosis (IS) group, 64 cases] from January 2003 to June 2009. According to location of apical vertebra and dystrophic change in patients with NF1, the parameters of pulmonary function [vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), maximal mid-expiratory flow (MMEF), maximal voluntary ventilation (MVV)] were compared between NF1 group and IS group, and between the subgroups of NF1. The correlation between pulmonary function parameters and radiographic parameters of scoliosis was analyzed. The VC, FVC, FEV1, MMEF, MVV in NF1 group and IS group were of no significant difference (P > 0.05). In NF1 patients, the pulmonary dysfunction was more severe in thoracic subgroup than non-thoracic subgroup (P < 0.05), while there was no difference between dystrophic scoliosis and non-dystrophic scoliosis (P > 0.05). The location of apical vertebra and the severity of scoliosis correlated significantly with the pulmonary dysfunction in NF1 group. The pattern of pulmonary dysfunction in scoliosis associated with NF1 is similar with IS. Pulmonary dysfunction is more severe in thoracic scoliosis. The location of apical vertebra and the severity of scoliosis are the risk factors influencing the pulmonary dysfunction.

Yan B.,Nanjing Medical University
Circulation Research | Year: 2015

RATIONALE:: Pathological angiogenesis is a critical component of diseases such as ocular disorders, cancers, and atherosclerosis. It is usually caused by the abnormal activity of biological processes, such as cell proliferation, cell motility, immune, or inflammation response. LncRNAs have emerged as critical regulators of these biological processes. However, the role of lncRNA in diabetes-induced microvascular dysfunction is largely unknown.OBJECTIVE:: To elucidate whether lncRNA-MIAT is involved in diabetes-induced microvascular dysfunction.METHODS AND RESULTS:: Using quantitative PCR, we demonstrated increased expression of lncRNA-MIAT in diabetic retinas and endothelial cells cultured in high glucose medium. Visual electrophysiology examination, TUNEL staining, retinal trypsin digestion, vascular permeability assay, and in vitro studies revealed that MIAT knockdown obviously ameliorated diabetes-induced retinal microvascular dysfunction in vivo, and inhibited endothelial cell proliferation, migration, and tube formation in vitro. Bioinformatics analysis, luciferase assay, RNA immunoprecipitation, and in vitro studies revealed that MIAT functioned as a ceRNA, and formed a feedback loop with VEGF and miR-150-5p to regulate endothelial cell function.CONCLUSIONS:: This study highlights the involvement of lncRNA-MIAT in pathological angiogenesis and facilitates the development of lncRNA-directed diagnostics and therapeutics against neovascular diseases. © 2015 American Heart Association, Inc.

Wang D.L.,Nanjing Medical University
Zhonghua wai ke za zhi [Chinese journal of surgery] | Year: 2011

To investigate the clinical efficacy and safety of biopsy and Kyphoplasty in the diagnosis and treatment of osteoporotic thoracolumbar vertebral fracture nonunion, and to explore the clinical characteristics of the disease. From July 2005 to May 2010, the clinical data of 8 patients with nonunion of osteoporotic thoracolumbar vertebral fractures were studied. There were 3 males and 5 females, with the mean age of 73.5 years (range, 65 - 86 years). The fracture vertebrae were 3 cases in T(12), 4 in L(1), and 1 in L(2). All cases received radiography, CT and MRI examination. All patients were treated by using Kyphoplasty. Five patients were performed bone biopsy successfully, 3 patients were failed. The curative effect was evaluated by visual analogue scale (VAS), anterior vertebral height restoration at preoperative, postoperative and followed-up time. All patients tolerated the procedure well with immediate relief of back pain after Kyphoplasty. No severe complications were found in all patients. Three cases had the pathologic appearance of sequestrum, 2 cases were sparse cancellous bone, 3 cases were abortive to biopsy. All the patients were followed up of 22.6 months (range, 3 - 37 months), the VAS was 9.5 before operation, 2.1 at the third day postoperatively, there were significant difference between the two phase (P < 0.05), and 2.3 at last follow-up, there were no difference between postoperation and follow-up phase (P > 0.05). And the height of compressed body recovered markedly. The vertebral height had a recovery rate of 67.2% postoperatively, 64.1% and at last follow-up, there were no difference between the two phase (P > 0.05). Kyphoplasty is an effective and safe method in the treatment of osteoporotic throacolumbar vertebral fracture nonunion. Bone biopsy can play a further role of differential diagnosis.

Li Y.-Y.,Nanjing Medical University
Journal of Cardiovascular Medicine | Year: 2012

BACKGROUND: The angiotensinogen (AGT) A-6G gene polymorphism has been indicated to be related to the susceptibility of essential hypertension. However, the results are still unclear. OBJECTIVE AND METHODS: To survey the relationship between AGT A-6G gene polymorphism and essential hypertension, 18 separate studies with 9306 patients were analyzed through meta-analysis. The random-effect model was used to calculate the pooled odds ratio (OR) and its corresponding 95% confidence interval (CI). RESULTS: In this AGT A-6G gene polymorphism and essential hypertension meta-analysis of the Chinese population, the distribution of the G-allele frequency was 0.23 for the essential hypertension group and 0.21 for the control group. The association between the AGT A-6G gene polymorphism and essential hypertension in the entire sample population was not significant. The pooled OR for the frequency of the G allele was 1.10 (95% CI 0.96 to 1.27, Pheterogeneity < 0.00001, P=0.17). In the stratified analysis by ethnicity, a significant association in Li and Mongolian ethnicities (P≤0.05) was achieved. However, no significant association was found in other ethnicities such as Han, Tibetan, Kazakh, Bai and Yi (P>0.05). CONCLUSIONS: The current meta-analysis suggested that AGT A-6G gene polymorphism might not be related to the increased risk of essential hypertension in the entire Chinese population. However, the G-allele of AGT A-6G might predispose to essential hypertension in the Li and Mongolian ethnicities. © 2012 Italian Federation of Cardiology.

Chen H.W.,Nanjing Medical University
Zhonghua xin xue guan bing za zhi | Year: 2011

To summarize the clinical characteristics of congenital ventricular aneurysm and diverticula in inland China. To identify the literature of congenital aneurysm and diverticula from Wanfang, China National Knowledge Infrastructure (CNKI) and PubMed databases, and to analyze the clinical characteristics of congenital aneurysm and diverticula from January of 2001 to December of 2009. A total of 116 patients [78 men, 1 - 80 (33.5 ± 21.3) years old] with congenital aneurysm or diverticula were included in 109 articles. Twenty-five patients (13 men) were congenital ventricular aneurysm, including a family of 4 patients. Ninety-one patients (65 men) were congenital ventricular diverticula. One hundred patients were detected by echocardiography during medical examination, 34 patients combined with other cardiac anomalies, 4 of which with extracardiac structures. There were 8 patients with ventricular arrhythmia, 8 patients with thrombosis, 2 patients died of cardiac rupture, 4 patients died of sudden death, surgical operation was performed in 46 patients and 3 patients received ablation procedure. All patient did not receive implantable cardioverter defibrillator (ICD) implantation. Congenital ventricular aneurysm or diverticulum is a rare cardiac malformation. Most congenital left ventricular aneurysms and diverticula are asymptomatic and detected by echocardiography. Congenital ventricular aneurysm or diverticulum may cause ventricular tachycardia, ventricular wall rupture, systemic embolization or sudden death, which had to be treated individually.

Wu B.,Yeshiva University | Zhou B.,Yeshiva University | Zhou B.,Nanjing Medical University
Trends in Cardiovascular Medicine | Year: 2013

Heart valves arise from the cardiac endocardial cushions located at the atrioventricular canal (AVC) and cardiac outflow tract (OFT) during development. A subpopulation of cushion endocardial cells undergoes endocardial to mesenchymal transformation (EMT) and generates the cushion mesenchyme, which is then remodeled into the interstitial tissue of the mature valves. The cushion endocardial cells that do not undertake EMT proliferate to elongate valve leaflets. During EMT and the post-EMT valve remodeling, endocardial cells at the cushions highly express nuclear factor in activated T cell, cytoplasmic 1 (Nfatc1), a transcription factor required for valve formation in mice. In this review, we present the current knowledge of Nfatc1 roles in the ontogeny of heart valves with a focus on the fate decision of the endocardial cells in the processes of EMT and valve remodeling. © 2013 Elsevier Inc.

Wang B.,Nanjing Medical University
Zhonghua wai ke za zhi [Chinese journal of surgery] | Year: 2010

To investigate the impairment pattern and the influencing factors of pulmonary function in patients with Marfan and Marfanoid syndrome associated scoliosis (MS). In this retrospective study, totally 25 MS patients (aged 11 - 20 years, 11 boys and 14 girls) who received posterior instrumentation and fusion (Group A) and 38 adolescent idiopathic scoliosis (AIS) patients (Group B) (aged 10 - 19 years, 11 boys and 27 girls) were included from February 1998 to September 2007. The curve pattern was matched in both groups. The preoperative pulmonary function test (PFTs) were compared in two groups. And the parameters influencing the preoperative pulmonary function were analyzed in group A. In Group A, the Cobb angle of thoracic curve was negatively correlated with the percentage of predicted pulmonary volumes (VC%, FVC% and FEV1%) (r = -0.514, -0.503, -0.464, P < 0.05). And the reduction of lung function parameters (VC%, FVC%, FEV1% and MMEF%) was more severe in Group A than in Group B with compared magnitude of thoracic curve (P < 0.05). In Group A, the extent of impairment of pulmonary function in patients with the number of vertebrae involved ≥ 8 were more severe than those involved < 8 vertebrae (P < 0.05). However, there was no significant difference of deterioration of lung function between the higher apex (T) subgroup and lower apex (T) subgroup. And no correlation was found between thoracic kyphosis and the degrees of impairment of respiration function. Patients with MS have mixed ventilation dysfunction, which is more severe than AIS patients with matched age and Cobb angle. The pulmonary dysfunction in MS patients can be influenced by the severity of thoracic curve and the number of involved vertebrae.

Zhu D.X.,Nanjing Medical University
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

This study was purposed to establish a method for detecting miRNA expression by using fluorescent quantitative polymerase chain reaction (RQ-PCR), and to investigate the application value of this method in quantitative detection of miRNA. Total RNA was extracted from the peripheral blood or bone marrow of 82 patients with chronic lymphocytic leukemia (CLL) and 70 patients with acute leukemias (AL). Standard curves of U6 and miRNA were constructed from 10-fold serial dilutions of the cDNA, the quantitative detection was performed by using real-time quantitative PCR with SYBR Green by Roche Light Cycler. U6 RNA was used as the reference, the relative expression levels of miR-15a, miR-16-1, miR-29b, miR-181a and miR-181b in patients with CLL, while miR-128-1, miR-223, let-7b, miR-155 and miR-181a in patients with AL were analyzed by 2((-DeltaDeltaCT)) method. The relative parameters including specificity, linearity range, sensitivity and repeatability were evaluated. The results showed that the RQ-PCR assay could precisely detect the mature miRNA in as few as 10-50 ng of total RNA with the sensitivity of 0.05 ng RNA. Ct values of miRNA and U6 were all within 15 to 30. A good linear relationship (R(2) > 0.980) was obtained from the standard curves, also the efficiency of amplification was above 90%. Only a specific peak was shown on the melting curve diagram. The coefficients of variation (CV) of interrun and intrarun assay was < 4.8% and 6.3% respectively. It is concluded that the RQ-PCR is a sensitive and fast method for the detection of miRNA with its high-flux and low cost, this method will facilitate the research with detection of miRNA.

Xie H.H.,Nanjing Medical University
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2010

To investigate the association between perineural invasion(PNI) and clinicopathological factors and the effect of PNI on overall survival in patients with gastric carcinoma. A total of 178 patients with gastric carcinoma from January 2004 to May 2008 were analyzed retrospectively. Paraffin sections of surgical specimens from all the patients who underwent gastric resection were stained with laminin. PNI-positive was defined as infiltration of carcinoma cells into the perineurium or neural fascicles. The association of PNI with clinicopathologic features and prognosis of gastric carcinoma was studied. PNI was positive in 78 of 178 patients(43.8%). The proportions of T stage, lymph node metastasis and TNM stage were significantly higher in PNI-positive group than those in PNI-negative group(all P<0.01). The PNI positive rate was correlated with the depth of gastric mural invasion and clinical stage. The overall survival in PNI-positive group was significantly lower than that in PNI-negative group by univariate analysis(P<0.01). The mean survival of PNI-positive patients(28.6 months) was significantly shorter than that of PNI-negative patients (44.3 months, P<0.01), which was also influenced by pN stage, pT stage, and clinical stage(P<0.01). By multivariable Cox proportional hazards model of overall survival, the positivity of PNI appeared to be an independent prognostic factor (hazards ratio=2.257, 95% CI:1.268-4.019, P=0.006). PNI is associated with the degree of malignancy in gastric cancer. PNI can be a candidate of new prognostic factor.

Shen L.Z.,Nanjing Medical University
Zhonghua wai ke za zhi [Chinese journal of surgery] | Year: 2010

To compare the morphometry and endothelial nitric oxide synthase (eNOS) expression of radial artery (RA) between young and elderly patients with coronary atherosclerotic heart disease. From February 2008 to June 2009, 219 patients underwent coronary artery bypass grafting (CABG) with autologous RA, 57 patients aged beyond 70 years and 64 patients aged under 60 years. Before RA was harvested, a modified Allen test was routinely performed. If positive, RA would be further evaluated with Doppler ultrasound examination. In both groups RA was collected for HE staining to evaluate percentage of luminal narrowing (LN) and relationship between intima and media width at maximum intimal thickness (IMR). Immunofluorescence and Western blot were used to investigate the location and expression level of eNOS within the wall of RA. Morphometry of RA in both young and elderly patients represented mild or moderate intimal hyperplasia, and medial calcification was not found. LN in elderly patients was (22 ± 6)%, while in young patients, it was (23 ± 6)%. IMR in elderly patients was 0.36 ± 0.21, while in young patients, it was 0.42 ± 0.19. There was no significant difference in both LN and IMR between two groups (P > 0.05). Immunofluorescence indicated RA in both groups revealed a high expression of eNOS in intima and media, particularly in the smooth muscle of media. The values of relative integrated optical density in elderly patients was 1.21 ± 0.13, while in young patients, it was 1.25 ± 0.12. Also there was no significant difference in the expression level of eNOS within the wall of RA (P > 0.05). After preoperative assessment with modified Allen's test and Doppler analysis, RA used as graft in the elderly has similar quality and function with young patients, and it may lead to a high patency in long term.

Du R.-W.,Chaoyang Hospital | Du R.-H.,Nanjing Medical University | Bu W.-G.,Chaoyang Hospital
Journal of Neuroimmune Pharmacology | Year: 2014

Recent evidence has suggested that microglial activation plays an important role in the pathogenesis of depression. Activated microglia can secrete various pro-inflammatory cytokines, which may contribute to the development and maintenance of depression. Thus, inhibition of microglial activation may have a therapeutic benefit in the treatment of depression. In the present study, we found that fluoxetine significantly inhibited lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-α), interleukin- 6 (IL-6) and nitric oxide (NO) and reduced the phosphorylation of transforming growth factor-beta-activated kinase 1 (TAK1) and nuclear factor-kappa B (NF-κB) p65 nuclear translocation in microglia. We further found that fluoxetine increased the expression of β-arrestin 2 and enhanced the association of β-arrestin 2 with TAK1-binding protein 1 (TAB1) and disrupted TAK1-TAB1 interaction. Moreover, β-arrestin 2 knock-down abolished the anti-inflammatory effects of fluoxetine in lipopolysaccharide-stimulated microglial cells. Collectively, our findings suggest that β-arrestin 2 is necessary for the anti-inflammatory effects of fluoxetine and offers novel drug targets in the convergent fluoxetine/β-arrestin 2 and inflammatory pathways for treating microglial inflammatory neuropathologies like depression. © 2014 Springer Science+Business Media.

Ni R.,Nanjing Medical University
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery | Year: 2010

This study was to investigate the expression and significance of Integrins subunits in laryngeal squamous cell carcinoma (LSCC). The expression of Integrins subunits was detected by cDNA microarray in 4 cases of primary LSCC tissues and corresponding adjacent normal tissues. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) were used to identify the different expression of Integrins subunits in 24 cases of primary LSCC tissues and corresponding adjacent normal tissues. A cDNA microarray analysis revealed significant changes in the expression of Integrins subunits, with IntegrinalphaV, Integrinbeta8 being up-regulated and Integrinalpha8 being down-regulated. The result of RT-PCR was consistent with that of cDNA microarray. The mRNA levels of IntegrinalphaV and Integrinbeta8 were significantly higher in LSCC tissues than that in corresponding adjacent normal tissues (1.0131 +/- 0.4780 vs 0.7591 +/- 0.4678 for IntegrinalphaV, P<0.05, 1.7362 +/- 1.3849 vs 1.2267 +/- 0.9363 for Integrinbeta8, P<0.05). The mRNA levels of Integrinalpha8 were significantly lower in LSCC tissues than that in corresponding adjacent normal tissues (0.2646 +/- 0.2622 vs 0.5457 +/- 0.3827, P<0.05). The expression of IntegrinalphaV, Integrinbeta8, Integrinalpha8 were significantly up-regulated or down-regulated in laryngeal squamous cell carcinoma, which may relate to tumorigenesis and development of laryngeal squamous cell carcinoma.

Chen X.,Nanjing Medical University
Zhonghua yi xue za zhi | Year: 2010

To explore the clinical experiences, efficacies and postoperative left ventricular remodeling changes of surgical ventricular reconstruction in the treatment of post-infarction left ventricular aneurysm. The investigators reviewed retrospectively the clinical data, operative approaches and follow-up outcomes of consecutive 194 patients with post-infarction left ventricular aneurysm, who underwent surgical ventricular reconstruction between January 1997 and December 2009. There were 54 cases in the linear group and 137 cases in the endoventricular patch plasty group. The changes of ventricular remodeling were measured by peri-operative and follow-up echocardiography. All patients underwent surgery with a mean cardiopulmonary bypass duration of (103 ± 35) min and aortic cross clamp duration of (62 ± 26) min. There were 8 per-operative deaths with a mortality rate of 2.2%. Angina pectoris of other cases disappeared and heart function greatly improved. After operation, the ventricular remodeling results showed that in the linear group, there was not significant difference in the changes of ventricular remodeling of post-op 2 weeks, 6 months, 1 year and 5 years versus pre-operation. However, in the endoventricular patch group, the changes of ventricular remodeling of post-op 2 weeks and follow-up 6 months versus pre-operation were significantly reduced (P < 0.05). End-systolic volume (LVESV) reduced from (129 ± 27) ml to (65 ± 8) ml and end-systolic volume index (LVESVI) decreased from (104 ± 14) ml/m(2) to (44 ± 6) ml/m(2) and the subgroup of LVEF < 35% was the most significant in the changes of LVESV and LVESVI. But LVEF improved significantly at post-operation and follow-up (from preoperation 42% ± 11% to 52% ± 7% during follow-up). For patients with infarction left ventricular aneurysm, left ventricular reconstruction is quite effective. The choice of operative approaches is determined by the size and range of ventricular aneurysm. Both string suture and endoventricular patch plasty technique can yield similarly satisfactory surgical outcomes. After operation, ventricular volume significantly decreases and cardiac function greatly improves.

To investigate the effect of transforming growth factor β1 (TGF-β1) on the expression of matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), nuclear factor kappa B (NF-κB) and the possible signalling pathways in human amniotic cells WISH. The WISH cell line was cultured. WISH cells were added with TGF-β1 of different concentrations (0, 2, 10 and 20 ng/ml, respectively) for 24 hours. Then, reverse transcription (RT) PCR and western blotting were used to analyze the protein and mRNA expression of TIMP-1 and MMP-9; and the expression of NF-κB was analyzed by western blot. (1) The profile of TIMP-1 mRNA (0.413 ± 0.036, 0.623 ± 0.058, 1.392 ± 0.124, 1.387 ± 0.102) in WISH cells elevated when the concentration of TGF-β1 increased (0, 2, 10, 20 ng/ml). In accordance with TIMP-1 mRNA, the expression of TIMP-1 also elevated with the increase of TGF-β1 (0.357 ± 0.031, 0.596 ± 0.048, 1.243 ± 0.097 and 1.359 ± 0.121, respectively). And when 2, 10 or 20 ng/ml of TGF-β1 was added, the TIMP-1 mRNA and protein were significantly higher than the TIMP-1 mRNA and protein when no TGF-β1 was added (P < 0.05). (2) In contrast with TIMP-1, MMP-9 mRNA (1.325 ± 0.056, 0.987 ± 0.081, 0.610 ± 0.034, 0.347 ± 0.023) in WISH cells decreased when the concentration of TGF-β1 increased (0, 2, 10, 20 ng/ml). The MMP-9 protein (1.119 ± 0.064, 1.008 ± 0.052, 0.578 ± 0.041, 0.401 ± 0.015) also decreased with the increase of TGF-β1. And when 2, 10 or 20 ng/ml of TGF-β1 was added, the MMP-9 mRNA and protein were significantly lower than the MMP-9 mRNA and protein when no TGF-β1 was added (P < 0.05). (3) The NF-κB protein (1.423 ± 0.065, 1.116 ± 0.045, 0.796 ± 0.041, 0.359 ± 0.021) was significantly reduced with the increase of TGF-β1 (0, 2, 10, 20 ng/ml;P < 0.05). The mRNA and protein expression of TIMP-1 decreased when TGF-β1 was low in WISH cells, whereas those of MMP-9 elevated when TGF-β1 was low. The unbalance of TIMP-1 and MMP-9 was related to the pathology of the premature rupture of membrane. And the NF-κB singalling pathway might be an important mechanism in the regulation of TIMP-1 and MMP-9 system.

Zong F.,Nanjing Medical University
Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases | Year: 2010

To improve the understanding of the clinical manifestations of pulmonary coccidioidomycosis. A case of pulmonary coccidioidomycosis was reported, and the literature was reviewed. The epidemiologic, clinical and diagnostic aspects of coccidioidomycosis were discussed. A 74 year old male was admitted to the hospital because of physical examination revealing lung space occupying lesions for 9 months and cough for 2 weeks. Lung puncture biopsy was carried out and the diagnosis of cryptococcosis was established in another hospital. After 6 months' therapy with fluconazole, the chest CT showed no change. After being hospitalized, thoracoscopic wedge resection of lung was performed and the final diagnosis was pulmonary coccidioidomycosis. After the surgery, he was immediately started on voriconazole 200 mg daily for 1 month. Then oral fluconazole was prescribed for 5 months. A follow-up chest CT performed 6 months after surgery was normal. Coccidioidomycosis is uncommon. It's pathological appearance is similar to cryptococcus. With the extensive using of immune suppressive drugs, we should improve the recognition of coccidioidomycosis.

Shao P.F.,Nanjing Medical University
Zhonghua wai ke za zhi [Chinese journal of surgery] | Year: 2011

To evaluate the technique and clinical outcomes of modified transperitoneal laparoscopic radical prostatectomy. A total of 105 patients received the operation with age ranging from 51 to 73 years from January 2008 to June 2010. Mean level of serum prostate specific antigen was 13.6 μg/L and mean prostatic volume was 45 ml. Pathological studies of biopsy confirmed the prostate carcinoma with Gleason score 6-8. Radionuclide bone scan revealed no metastasis. Based on previously retroperitoneal radical prostatectomy, modified technique was applied involving surgical approach, bladder neck dissection and vesicourethral anastomosis. Mean operative time was 93 min (65 - 150 min). Intraoperative blood loss was 115 ml (50 - 400 ml). No complication of bowl injury occurred. Positive surgical margin was present in 24 patients. Normal continence were seen in 64 patients after catheter removed. Recovery of incontinence within 3 months was seen in 33 patients and 3 to 12 months in 5 patients respectively. Three patients with incontinence were still in the follow-up. Transperitoneal laparoscopic radical prostatectomy provides large working space and clear anatomic exposure. Higher efficiency and lower complication rate are obtained through modified laparoscopic technique involving seminal vesicle isolation, bladder neck dissection and vesicourethral anastomosis.

Gu L.,Nanjing Agricultural University | Liu H.,Nanjing Agricultural University | Gu X.,Rudong Third Hospital | Boots C.,University of Washington | And 2 more authors.
Cellular and Molecular Life Sciences | Year: 2015

Obesity, diabetes, and related metabolic disorders are major health issues worldwide. As the epidemic of metabolic disorders continues, the associated medical co-morbidities, including the detrimental impact on reproduction, increase as well. Emerging evidence suggests that the effects of maternal nutrition on reproductive outcomes are likely to be mediated, at least in part, by oocyte metabolism. Well-balanced and timed energy metabolism is critical for optimal development of oocytes. To date, much of our understanding of oocyte metabolism comes from the effects of extrinsic nutrients on oocyte maturation. In contrast, intrinsic regulation of oocyte development by metabolic enzymes, intracellular mediators, and transport systems is less characterized. Specifically, decreased acid transport proteins levels, increased glucose/lipid content and elevated reactive oxygen species in oocytes have been implicated in meiotic defects, organelle dysfunction and epigenetic alteration. Therefore, metabolic disturbances in oocytes may contribute to the diminished reproductive potential experienced by women with metabolic disorders. In-depth research is needed to further explore the underlying mechanisms. This review also discusses several approaches for metabolic analysis. Metabolomic profiling of oocytes, the surrounding granulosa cells, and follicular fluid will uncover the metabolic networks regulating oocyte development, potentially leading to the identification of oocyte quality markers and prevention of reproductive disease and poor outcomes in offspring. © 2014 Springer Basel.

PURPOSE: We evaluated percutaneous nephrostomy for adult kidneys with severe hydronephrosis due to ureteropelvic junction obstruction and less than 10% split renal function.MATERIALS AND METHODS: In this retrospective analysis we included patients who underwent percutaneous nephrostomy for unilateral ureteropelvic junction obstruction of the kidneys with hydronephrosis and less than 10% split renal function at our hospital between May 2009 and January 2012. Adults (age 18 years or greater) were divided into those 35 years or younger (young adults) and older than 35 years (older adults). The percutaneous nephrostomy remained in situ a mean ± SD of 6.62 ± 2.55 weeks and patients underwent repeat renography before pyeloplasty. When there was no significant improvement in split renal function (10% or greater) and drainage (greater than 400 ml per day), nephrectomy was performed. Otherwise pyeloplasty was performed. Patients were followed by renography, ultrasound and contrast computerized tomography at 3 and 6 months, at 1 year and annually thereafter.RESULTS: Of 53 patients 30 (56.6%) showed improvement after percutaneous nephrostomy drainage and urine output greater than 400 ml per day with percutaneous nephrostomy. Pyeloplasty was then performed. Of 29 young adults 24 (82.8%) showed improved split renal function vs 6 of 24 older adults (25%). Nephrectomy of the other 23 kidneys was performed. At a mean followup of 19.27 ± 7.82 months (range 12 to 36), no patient showed hypertension or urinary tract infection.CONCLUSIONS: Split renal function detected by renography may not accurately predict recovered, poorly functioning kidneys, especially in young adults. First observing the recoverability of hydronephrotic kidneys by percutaneous nephrostomy drainage and then preserving select kidneys may be an effective method to manage poorly functioning kidneys due to ureteropelvic junction obstruction. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Zhang R.-Z.,Bengbu Medical College | Zhu W.-Y.,Nanjing Medical University
Pediatric Dermatology | Year: 2012

Milia en plaque is a rare variant of miliathat occurs spontaneously on an erythematous base without identifiable causative factors. Approximately 40 cases have been recorded in the literature. Most occurred in the periauricular area, affected middle-aged patients, and showed a predilection for women. Here, we report a case of milia en plaque on the bilateral posterior helices in a 6-year-old Chinese boy. © 2011 Wiley Periodicals, Inc.

Wu D.,Nanjing Southeast University | Yuan Y.,Nanjing Southeast University | Bai F.,Nanjing Southeast University | You J.,Nanjing Medical University | And 2 more authors.
Journal of Affective Disorders | Year: 2013

Background: The functional neural network model has been a major method used to investigate mechanisms of neuropsychopathy. There is considerable evidence that late-onset depression (LOD) is the prodrome, or the early clinical manifestation, of Alzheimer's disease (AD). The default mode network (DMN) is one of the neural networks that can be used to explore the complex relationships between depressive symptoms, episodic memory deficits and other cognitive impairments. To date, no study has directly linked the DMN to LOD while focusing on episodic memory and the influence of apolipoprotein E4 (APOE4), a major genetic risk factor for AD in LOD patients. Methods: In total, 33 remitted LOD (rLOD) patients and 33 elderly controls underwent fMRI scanning using low-frequency BOLD signal imaging during the resting state and during an episodic memory task. Furthermore, function-based functional connectivities (FCs) in the region of interesting (ROI) (posterior cingulate cortex (PCC) of the DMN) were analysed to explore interactions between disease states, task states and genetic risk factors (APOE4). Results: Compared to healthy control subjects (HC), the FCs between the PCC and the right medial temporal lobe of the rLOD patients were significantly stronger during rest (p<0.005) and significantly weaker (p<0.05) during performance of the task. The mode of change from rest to task performance in the HC was in contrast to the mode of change in the rLOD patients. The FCs of the rLOD patients without APOE4 were significantly increased (p<0.05) in the resting state, but the rLOD patients who carried APOE4 showed a trend toward decreased FCs. Limitations: The sample size was small. While the study was cross-sectional, we did not differentiate between the various types of antidepressants the patients used, which may have had different effects on cognitive function, especially on episodic memory. Conclusion: Our results suggested that rLOD might be the prodrome, or the early clinical manifestation, of AD and that rLOD patients with APOE4 showed an increased risk for episodic memory decline and AD. © 2012 Elsevier B.V. All rights reserved.

Wang P.,Nanjing Medical University | Guo Z.S.,Pennsylvania State University | Guo Z.S.,Tongji University
International Journal of Clinical and Experimental Pathology | Year: 2013

The regulatory T (Treg) cells play an important role in the maintenance of homeostasis and the prevention of autoimmune diseases. Although most studies are focusing on the role of Treg cells in T cells and T cells-mediated diseases, these cells also directly affect B cells and other non-T cells. This manuscript updates the role of Treg cells on the B cells and B cell-mediated diseases. In addition, the mechanisms whereby Treg cells suppress B cell responses have been discussed.

To assess the correlation between metabolic syndrome and clinical progression in patients with benign prostatic hyperplasia (BPH). A total of 382 BPH patients with lower urinary tract symptoms were divided into two groups according to whether or not there was a diagnosis of metabolic syndrome (MS). MS was defined by the International Diabetes Federation (IDF) in 2005. Abdominal B-ultrasound was used to measure the total volume of prostate (TP) and its average annual growth rate was calculated. Body mass index, waist-hip ratio, blood biochemistry, blood pressure, blood glucose and other indicators were compared in these two groups of patients with regards to the clinical progression associated with BPH. A total of 187 MS cases were found in 382 (48.59%) BPH patients. It showed a higher body mass index, high glycemia, high triglycerides, high blood pressure and high IPSS, TP and PSA levels. Also it showed a higher occurrence of surgical rate (P < 0.05); its average annual growth rate of TP was significantly higher than those without MS (1.0 vs 0.64 ml/yr, P < 0.05). TP average annual growth rate and IPSS score are found significantly correlated with blood glucose and triglyceride levels (P < 0.01). Metabolic syndrome affects the clinical progression in patients with BPH. Clinical attention should be paid.

Jiang H.,Nanjing Southeast University | Wang J.,Nanjing Medical University | Zhao W.,Nanjing Southeast University
Clinica Chimica Acta | Year: 2013

Background: We investigated the prognostic value of cyclooxygenase-2 (COX-2) for survival of patients with non-small cell lung cancer (NSCLC). Methods: We performed a meta-analysis of literature to aggregate the available survival results, using studies published in English until June 2012. Eligible studies dealt with COX-2 protein assessment in NSCLC patients on primary lesions and reported survival data according to COX-2 expression. Results: Nineteen trials, comprising 2651 patients, provided sufficient information for the meta-analysis. Overall combined hazard ratio (HR) was 1.86 (95% CI: 1.58-2.20); it was calculated using a random-effects model, and associates high COX-2 expression with poor survival in all NSCLC patients. Aggregate survival data showed poor survival for patients with adenocarcinoma (ADC), squamous cell cancer (SCC) and Stage I NSCLC with high COX-2 expression, at 2.00 (95% CI: 1.38-2.88), 2.29 (95% CI: 1.58-3.33) and 1.95 (95% CI: 1.31-2.91) respectively. Conclusions: Our meta-analysis shows that the COX-2 expression status is an independent prognostic factor in NSCLC, and this tendency applies to SCC, ADC and stage I NSCLC. © 2013 Elsevier B.V.

Jiang Z.W.,Nanjing Medical University
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2012

To evaluate the safety, feasibility, and efficacy of robotic gastrectomy for gastric cancer using da Vinci surgical system. A total of 120 patients who underwent robotic gastrectomy using da Vinci surgical system for gastric cancer from May 2010 to April 2012. Data regarding surgical and early oncological outcomes were systematically collected in a specific database for statistical analysis. There were 74 males and 46 females, with a mean age of 58.5 (22-80) years old. The type of robotic operation included 62 distal subtotal gastrectomies, 35 total gastrectomies, and 23 proximal gastrectomies. Reconstruction of the alimentary tract was achieved using extracorporeal method through a minilaparotomy in 55 cases, and intracorporeal robot-sewn anastomosis in 65 cases. There was 1 conversion (0.9%). The operative time was (245±50) min and the docking time (17±5) min. The blood loss was (70±45) ml. The number of harvested lymph nodes was 22.5±10.7. The resection margins were negative in all surgical specimens. The postoperative pathological stage consisted of stage I B in 24 cases, stage II in 28, stage III A in 47, and stage III B in 21. Six patients (5%) developed postoperative complication including 1 case of duodenal stump leakage, 2 cases of esophagus-gastric leakage, 1 case of small bowel obstruction, 1 case of delayed gastric emptying, and 1 case of abdominal bleeding. All the complications were cured by reoperation or conservative therapy, and there were no postoperative 30-day deaths. The postoperative hospital stay was (6.3±2.6) days. Robotic gastrectomy for the treatment of gastric cancer is a feasible and safe procedure, and is advantageous in terms of lymphadenectomy and alimentary tract reconstruction.

Zhu G.,Nanjing Medical University | Lou W.,Zhengzhou University
Head and Neck | Year: 2014

Background Because of ease of harvest and low immunogenicity, xenogeneic acellular nerve graft (XANG) may be an alternative to autologous nerve to repair facial nerve defects. Methods Facial nerve defects of Wistar rats were repaired by XANG, and nerve gap regeneration was investigated by electrophysiological test, horseradish peroxidase (HRP) retrograde tracing and histomorphometric analysis, as compared to autograft. Results Twenty weeks after the grafting, electrophysiology showed that whisker pad muscles responded to the electrical stimuli given at the site proximal to the transplantation in 2 groups. Some HRP-labeled facial motorneurons were located on the facial nucleus of the operated side, and an abundance of myelinated axons were found at the middle of the grafts and obvious motor endplates in the target muscles in 2 groups, although they were inferior to the contralateral side in numbers. Conclusion XANG represents an alternative approach for the reconstruction of peripheral facial nerve defects. © 2013 Wiley Periodicals, Inc.

Zhu L.,Nanjing Medical University
Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery | Year: 2010

To investigate the safety profile of subcutaneous immunotherapy (SCIT) versus sublingual immunotherapy (SLIT) in patients with allergic rhinitis (AR) caused by house dust mites. The treatment compliance and related factors were also evaluated. A total of 160 patients with AR were enrolled in this study and received either SCIT (Alutard SQ, ALK-Abelló) or SLIT (Chanllergen-Df drops, Wolwo Pharma). All subjects were divided into two groups: SCIT group consisted of 81 patients aged 7 to 62 years [(21.5 ± 14.6) years, x ± s], and SLIT group consisted of 79 patients aged 6 to 53 years [(15.1 ± 10.3) years]. The selected patients were persistent and moderate to severe AR sensitized to Dermatophagoides pteronyssinus and Dermatophagoides farinae. Local and systemic reactions, as well as patient's adherence to the treatment, were carefully recorded and analyzed during the immunotherapy schedules (followed up for 6 months to 2 years). Statistical analysis was performed using a SPSS13.0 software. Local swelling commonly occurred following injections throughout the treatment duration (62.9% of overall injections) in the SCIT group. Oral itching associated with drop intakes was reported by 4 subjects (5.1%) in the SLIT group. All local reactions were mild, well tolerated and self-limiting in both groups. A total of 11 patients (13.6%) with 18 injections (0.9%) experienced systemic reactions in the SCIT group, involving respiratory distress, asthmatic attacks, and urticaria. These adverse effects were mostly immediate reactions, and occurred more frequently in patients during the maintenance phase of treatment. There were also 11 patients (13.9%) who experienced systemic reactions in the SLIT group, including gastrointestinal symptoms, urticaria, and rhinitis exacerbations. However, systemic reactions to SLIT were mainly observed in patients during the up-dosing phase of treatment. No significant difference in the overall incidence of systemic adverse effects was found between the SCIT and SLIT groups (13.6% and 13.9% respectively, χ(2) = 0.004, P > 0.05). There was only one case of non-life-threatening systemic reaction (severe asthma) in the SCIT group. Others were mild or moderate and no anaphylactic shock occurred in any group. No significant difference in treatment compliance was found between the SCIT and SLIT groups (86.4% and 79.7% respectively, χ(2) = 0.84, P > 0.05), with an overall rate of compliance (83.1%) among 160 patients. The most common cause for treatment withdrawal was insufficient ineffectiveness, in both groups of SCIT (6.2%) and SLIT (10.1%). The results suggest that the frequency of systemic adverse effects of SCIT is not significantly different from SLIT in mite-sensitized patients with AR, and both treatments are well tolerated and had favorable compliance during the study period.

Chen J.F.,Nanjing Medical University
Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] | Year: 2012

To evaluate the association between two single nucleotide polymorphisms located in the promoter of transforming growth factor-β1 receptor 2 (TGFBR2) gene and hypertension in Han Chinese population. The subjects were recruited from the population of cluster sampling survey for essential hypertension (EH) in two townships of Yixing city, Jiangsu province in 2009. Overall, 2012 patients with hypertension and 2116 age (± 2 years) and sex-matched unrelated controls were selected. Epidemiological data, physical measurements results and serum glucose and lipid biomarker were collected and detected. Linkage disequilibrium (LD) analysis were applied and two tagging single nucleotide polymorphisms (tagSNP) in 5' upstream of TGFBR2 gene (rs6785358, -3779A/G; rs764522, -1444C/G) were selected for genotyping and analyzing for the association with hypertension. The frequencies of AA, AG, GG in case and control of rs6785358 were 1455 (72.3%), 517 (25.7%), 40 (2.0%) and 1582 (74.8%), 490 (23.2%), 43 (2.0%) respectively, and CC, CG, GG of rs764522 were 1524 (75.7%), 464 (23.1%), 24 (1.2%) and 1654 (78.2%), 436 (20.6%), 26 (1.2%) respectively. SNP rs764522 was significantly associated with EH and OR (95%CI) were 1.17 (1.01 - 1.36) (P < 0.05) in dominant model after adjustment for confounding factors such as age, sex, glucose, lipids, smoking and alcohol drinking. Further stratification analysis by age, sex, smoking and alcohol drinking indicated that individuals carrying G allele (CG/GG genotype) of SNP rs764522 had higher susceptibility to EH than CC genotype (OR = 1.21, 95%CI: 1.01 - 1.45) (P < 0.05) in ≥ 55 years group. No statistical significance was detected in the distribution of genotypes and allele frequencies for SNP rs6785358 between cases and controls (P > 0.05). Haplotype analysis showed that no significant frequency difference of haplotype structured by rs6785358 and rs764522 was found between cases and controls (P > 0.05), and no significant blood pressure change was found between genotype variations of rs6785358 and rs764522 (P > 0.05). SNP rs764522 of TGFBR2 gene is associated with increased risk of EH in elderly Han Chinese population.

Li G.,Nanjing Medical University
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2013

To study the association of human epidermal growth factor receptor family molecules expression in gastric cancer tissues with the prognosis of patients with gastric cancer. Clinical data of 161 patients with gastric cancer undergoing gastrectomy in Jiangsu Cancer Hospital between January 2006 and January 2007 were analyzed retrospectively. The expression of HER1, HER2, HER3 and HER4 was detected by immunohistochemistry. Association of the expression of HER family with the prognosis of patients was examined. Kaplan-Meier method was used to analyze the survival. High expression rates of HER1, HER2, HER3 and HER4 were 46.0% (74/161), 10.6% (17/161),55.9% (90/161) and 68.3% (110/161) respectively. Univariate analysis revealed that high expression of HER3 was associated with tumor invasion depth, lymph node metastasis, stage, neurovascular invasion, and overall 4-year survival. High expression of HER4 was associated with tumor distant metastasis and stage. High co-expression of HER2 and HER3 was associated with overall 4-year survival (P=0.023). Multivariate analysis revealed that high expression of HER3 and stage were prognostic independent factors. Up-regulated expression of HER3 is associated with the poor prognosis in gastric cancer patients.

Although increasing evidence has documented that microRNA-145 (miR-145) acts as a tumor suppressor in breast cancer, its exact role in triple-negative breast cancer (TNBC) remains poorly defined. In this study, the expression of miR-145 in human TNBC cells and samples from 30 patients was analyzed by stem-loop real-time PCR. We found that miR-145 was significantly downregulated in TNBC tissues and cells. Upregulating miR-145 in HCC1937 cells dramatically suppressed cell proliferation and induced G1-phase arrest, whereas MDA-MB-231 cells did not show growth inhibition. MiR-145 exhibited an inhibitory role in cell invasion through the post-transcriptional regulation of the novel targets MMP11 and Rab27a in TNBC cells. Additionally, miR-145 silencing could be reversed by 5-aza-2′-deoxycytidine (DAC). These results demonstrated that miR-145 has an inhibitory role in TNBC malignancy by targeting MMP11 and Rab27a, which might be potential therapeutic and diagnostic targets for TNBC.Cancer Gene Therapy advance online publication, 01 July 2016; doi:10.1038/cgt.2016.27. © 2016 Nature America, Inc.

Chian R.-C.,McGill University | Chian R.-C.,Nanjing Medical University | Wang Y.,McGill University | Li Y.-R.,McGill University
Journal of Assisted Reproduction and Genetics | Year: 2014

Background: Recent advances in vitrification technology have markedly improved the efficacy of oocyte cryopreservation in terms of oocyte survival and pregnancy, as well as live birth rates. However, there still remains room for improvement in terms of vitrification techniques. Objective: The remaining challenges include the development of a less cytotoxic vitrification solution and of a safe vitrification device in order to have vitrification techniques considered as a standard clinical laboratory procedure. Methods: A systematic electronic literature search strategy has been conducted using PubMed (Medline) databases with the use of the following key words: oocyte, vitrification, cryoprotectant, preservation, pregnancy, and live birth. A list of published papers focused on the improvement of vitrification techniques to have the vitrification protocol standardized have been evaluated in full text for this review. Only key references were cited. Conclusions: Vitrification technology has made significant advancements and holds great promise, but many issues remains to be addressed before it becomes a standardized procedure in clinical laboratories such as the fact that oocyte vitrification may not require a high concentration of cryoprotectant in the vitrification solution when it has a suitable cooling and warming rate. There is also no consistent evidence that indicates the absence of risk to the vitrified oocytes when they are stored for a prolonged period of time in direct-contact with liquid nitrogen. The long-term development of infants born as a result of this technology equally remains to be evaluated. © 2014 Springer Science+Business Media New York.

Li T.-F.,Jiangsu University | Ren K.-W.,Nanjing Medical University | Liu P.-F.,Jiangsu University
DNA and Cell Biology | Year: 2012

The epidermal growth factor (EGF) pathway stimulates proliferation and differentiation of epidermal and epithelial tissues, and plays an important role in tumorigenesis. The association between EGF polymorphisms and cancer risk is controversial; thus, we performed this meta-analysis. Overall, 41 case-control studies with 9,779 cases and 15,932 controls were retrieved. We found that EGF +61A/G polymorphism increased overall cancer risk (G allele vs. A allele: OR=1.181, 95% CI=1.077-1.295, P heterogeneity < 0.001; GG vs. AA: OR=1.370, 95% CI=1.143-1.641, P heterogeneity < 0.001; GG+GA vs. AA: OR=1.175, 95% CI=1.047-1.318, P heterogeneity < 0.001). In the stratified analysis by cancer type, the +61G allele was a risk factor for colorectal cancer, esophageal carcinoma, gastric cancer, and hepatocellular carcinoma. Individuals who carried +61G allele had higher cancer susceptibility in mixed and European racial subgroups. An increased association was detected in the hospital-based subgroup. No significant association was found among EGF -1380A/G, -1744G/A, rs6983267T/G polymorphisms and cancer risk. © Mary Ann Liebert, Inc.

Chen H.Y.,Nanjing Medical University
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 aim of this study was to investigate bag3 gene expression in chronic lymphocytic leukemia (CLL)patients and its association with clinical prognosis. A total of 46 blood samples from untreated CLL patients were collected, SYBR Green-based real-time PCR was used to detect the bag3 mRNA expression, and its association with prognostic index was analyzed by statistical software. The results showed that the median values of bag3 level detected by real-time PCR in 46 CLL patients and normal controls were 0.021 (0.0007 - 1.124) and 0.0025 (0.0005 - 0.014) respectively, the former was significantly higher than the latter. The bag3 level in drug-resistant group was obviously higher as compared with the drug-responsive group. No association was found between bag3 expression and patient clinical baseline information (gender and age) as well as established prognostic factors (lymphocyte count, disease stage, IgVH mutation status, cytogenetics analysis and CD38, ZAP 70 expression). It is concluded that the bag3 expression in CLL patients is markedly higher than that in normal controls, while the high bag3 level in CML patients is probably related with drug resistance, but is not related with clinically established prognostic factors.

Huang Y.Y.,Tongji University | Gusdon A.M.,New York Medical College | Qu S.,Tongji University | Qu S.,Nanjing Medical University
Lipids in Health and Disease | Year: 2013

Along with rising numbers of patients with metabolic syndrome, the prevalence of nonalcoholic fatty liver disease (NAFLD) has increased in proportion with the obesity epidemic. While there are no established treatments for NAFLD, current research is targeting new molecular mechanisms that underlie NAFLD and associated metabolic disorders. This review discusses some of these emerging molecular mechanisms and their therapeutic implications for the treatment of NAFLD. The basic research that has identified potential molecular targets for pharmacotherapy will be outlined. © 2013Huang et al.; licensee BioMed Central Ltd.

Liu C.,Nanjing Medical University
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery | Year: 2010

To develop and evaluate the improved Chinese hearing questionnaire for school children (CHQS) for mass epidemiology study on hearing impairment in China. Using the probability proportion to size (PPS) method, 8412 residents were investigated in 40 clusters in Jiangsu province with the WHO ear diseases and hearing disorders survey protocol. 87.9% of the residents aged 7 years and over answered the questionnaire and accepted the pure tone audiometry. The prevalence of hearing impairment was 12.9% by the questionnaire. Compared with "golden standard" (pure tone audiometry), Sen = 58.5%, Spe = 96.7%, PV+ = 78.9%, PV- = 91.7%, overall accuracy = 90.0%. The sensitivity for women was higher than men. The questionnaire produced high efficiency and specificity values. It could be used in mass hearing screening, particularly in remote and rural area, although the sensitivity was as low as most questionnaires.

Zhang H.,Liaoning Medical University | Zeng X.,Nanjing Medical University | He S.,Liaoning Medical University
Mediators of Inflammation | Year: 2014

Protease activated receptors (PARs) have been recognized as a distinctive four-member family of seven transmembrane G protein-coupled receptors (GPCRs) that can be cleaved by certain serine proteases. In recent years, there has been considerable interest in the role of PARs in allergic inflammation, the fundamental pathologic changes of allergy, but the potential roles of PARs in allergy remain obscure. Since many of these proteases are produced and actively involved in the pathologic process of inflammation including exudation of plasma components, inflammatory cell infiltration, and tissue damage and repair, PARs appear to make important contribution to allergy. The aim of the present review is to summarize the expression of PARs in inflammatory and structural cells, the influence of agonists or antagonists of PARs on cell behavior, and the involvement of PARs in allergic disorders, which will help us to better understand the roles of serine proteases and PARs in allergy. © 2014 Huiyun Zhang et al.

Qin J.-J.,Texas Tech University Health Sciences Center | Nag S.,Texas Tech University Health Sciences Center | Wang W.,Texas Tech University Health Sciences Center | Zhou J.,Nanjing Medical University | And 4 more authors.
Biochimica et Biophysica Acta - Reviews on Cancer | Year: 2014

The NFAT signaling pathway regulates various aspects of cellular functions; NFAT acts as a calcium sensor, integrating calcium signaling with other pathways involved in development and growth, immune response, and inflammatory response. The NFAT family of transcription factors regulates diverse cellular functions such as cell survival, proliferation, migration, invasion, and angiogenesis. The NFAT isoforms are constitutively activated and overexpressed in several cancer types wherein they transactivate downstream targets that play important roles in cancer development and progression. Though the NFAT family has been conclusively proved to be pivotal in cancer progression, the different isoforms play distinct roles in different cellular contexts. In this review, our discussion is focused on the mechanisms that drive the activation of various NFAT isoforms in cancer. Additionally, we analyze the potential of NFAT as a valid target for cancer prevention and therapy. © 2014 Elsevier B.V.

Wang F.,Nanjing Medical University | Wang F.,Bonoi Academy of Science and Education | Stefano G.B.,New York University | Kream R.M.,New York University
Medical Science Monitor | Year: 2014

DRG is of importance in relaying painful stimulation to the higher pain centers and therefore could be a crucial target for early intervention aimed at suppressing primary afferent stimulation. Complex regional pain syndrome (CRPS) is a common pain condition with an unknown etiology. Recently added new information enriches our understanding of CRPS pathophysiology. Researches on genetics, biogenic amines, neurotransmitters, and mechanisms of pain modulation, central sensitization, and autonomic functions in CRPS revealed various abnormalities indicating that multiple factors and mechanisms are involved in the pathogenesis of CRPS. Epigenetics refers to mitotically and meiotically heritable changes in gene expression that do not affect the DNA sequence. As epigenetic modifications potentially play an important role in inflammatory cytokine metabolism, neurotransmitter responsiveness, and analgesic sensitivity, they are likely key factors in the development of chronic pain. In this dyad review series, we systematically examine the nerve injury-related changes in the neurological system and their contribution to CRPS. In this part, we first reviewed and summarized the role of neural sensitization in DRG neurons in performing function in the context of pain processing. Particular emphasis is placed on the cellular and molecular changes after nerve injury as well as different models of inflammatory and neuropathic pain. These were considered as the potential molecular bases that underlie nerve injury-associated pathogenesis of CRPS. © Med Sci Monit, 2014.

Luo X.,Nanjing Medical University
Psychiatric Genetics | Year: 2016

Our previous study confirmed that the ‘AA’ genotype carriers of DISC1 single nucleotide polymorphism (SNP) rs821616 had a significantly increased risk for schizophrenia (SCZ) in comparison with noncarriers. To further explore the relationship of DISC1 genetic variants with the risk of SCZ in Han Chinese, we designed the present two-step study. We sequenced the promoter and untranslated regions of the DISC1 gene using genomic DNA of 100 SCZ patients and identified 17 SNPs. All SNPs were then genotyped and analyzed through a case–control study with 1154 healthy controls and 1447 patients. In an association analysis, neither allelic nor genotypic modeling indicated a significant association between the risk of SCZ and all SNPs. In addition, we observed that a two-marker haplotype was nominally associated with protection for SCZ (P=0.0476). The present findings, at least in part, provide some clues for further investigating the association of DISC1 variants with SCZ susceptibility. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

Gusdon A.M.,Tongji University | Gusdon A.M.,New York Medical College | Song K.-X.,Tongji University | Qu S.,Tongji University | Qu S.,Nanjing Medical University
Oxidative Medicine and Cellular Longevity | Year: 2014

Nonalcoholic fatty liver disease (NAFLD) describes a spectrum of disorders characterized by the accumulation of triglycerides within the liver. The global prevalence of NAFLD has been increasing as the obesity epidemic shows no sign of relenting. Mitochondria play a central role in hepatic lipid metabolism and also are affected by upstream signaling pathways involved in hepatic metabolism. This review will focus on the role of mitochondria in the pathophysiology of NAFLD and touch on some of the therapeutic approaches targeting mitochondria as well as metabolically important signaling pathways. Mitochondria are able to adapt to lipid accumulation in hepatocytes by increasing rates of beta-oxidation; however increased substrate delivery to the mitochondrial electron transport chain (ETC) leads to increased reactive oxygen species (ROS) production and eventually ETC dysfunction. Decreased ETC function combined with increased rates of fatty acid beta-oxidation leads to the accumulation of incomplete products of beta-oxidation, which combined with increased levels of ROS contribute to insulin resistance. Several related signaling pathways, nuclear receptors, and transcription factors also regulate hepatic lipid metabolism, many of which are redox sensitive and regulated by ROS. © 2014 Aaron M. Gusdon et al.

Zhang Y.,Nanjing Medical University
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2013

To elucidate the application and the dosimetry characteristic of the simplified intensity modulated radiation therapy (sIMRT) for gastric cancer after operation, and to compare the dose distribution with intensity modulated radiation therapy (IMRT) and three-dimension conformal radiation therapy (3D-CRT). Twelve patients with gastric cancer after operation were enrolled in this study. 3D-CRT plan, 5-field IMRT plans (20 degree, 80 degree, 180 degree, 280 degree, 340 degree) and 5-field sIMRT plans (20 degree, 80 degree, 180 degree, 280 degree, 340 degree) were performed for each patient. The conformal index (CI), heterogeneity index (HI) of the planning target volume (PTV) and the dose of normal organs were analyzed with the dose volume histogram (DVH). The total MU and treatment time were also compared. The sIMRT and IMRT plans had comparable CI (sIMRT>IMRT>3D-CRT), and showed better dose conformity but worse homogeneity than 3D-CRT. The percentage of volume receiving 20 Gy, 25 Gy, 30 Gy and 40 Gy by liver were significantly lower in sIMRT than that in 3D-CRT, and comparable to IMRT. All the dose volumes to kidneys with sIMRT were still significantly lower as compared to 3D-CRT, and comparable to IMRT. The sIMRT plan was better than IMRT plan in total MU and treatment time. sIMRT has comparable dose distribution in patients with gastric cancer to IMRT, but is significantly better than 3D-CRT. Treatment time of sIMRT is the shortest. So sIMRT technique can be applied more simply.

Niu Y.-M.,Hubei University of Medicine | Yuan H.,Nanjing Medical University | Zhou Y.,Anhui Medical University
Mediators of Inflammation | Year: 2014

Epidemiological studies have suggested that interleukin-17 (IL-17) polymorphisms are associated with cancer risk. However, the results of these studies are inconsistent. Therefore, we performed a meta-analysis to obtain a precise conclusion. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association of the IL-17A rs2275913G > A and IL-17F rs763780T > C polymorphisms with cancer risk. Publication bias and sensitivity analyses were performed to ensure the statistical power. Overall, 10 relevant case-control studies involving 4,516 cases and 5,645 controls were included. The pooled ORs with 95% CIs indicated that the IL-17A rs2275913G > A polymorphism was significantly associated with increased cancer risk (for A versus G: OR = 1.28, 95% CI: 1.16-1.41, P < 0.001, I 2 = 61.1 %; for GA versus GG: OR = 1.12, 95% CI: 1.02-1.23, P = 0.015, I 2 = 27.8 %; for AA versus GG: OR = 1.71, 95% CI: 1.38-2.41, P < 0.001, I 2 = 69.6 %; for GA + AA versus GG: OR = 1.23, 95% CI: 1.13-1.34, P < 0.001, I 2 = 6.4 %; for AA versus GG + GA: OR = 1.62, 95% CI: 1.27-2.07, P < 0.001, I 2 = 81.4 %). Succeeding analysis of HWE and stratified analysis of gastric cancer and the Asian (and Chinese) population revealed similar results. The IL-17F rs763780T>C polymorphism was also significantly associated with gastric cancer development. Overall, the present meta-analysis suggests that IL-17 polymorphisms increase the risk of developing cancer, particularly gastric cancer, in the Asian (and Chinese) population. © 2014 Yu-Ming Niu et al.

Zhang B.,Nanjing Medical University
The West Indian medical journal | Year: 2013

We report a case of a 76-year old female presenting with symptomatic severe hypercalcaemia, and subsequently diagnosed with late onset SLE due to the presence of anaemia, leucopenia, antibodies of antinuclear (ANA), anti-dsDNA, and also kidney impairment. Serum levels of FGF23 and intact-parathyroid hormone (iPTH) were low in this patient. Serum calcium, FGF23 and iPTH levels responded to steroids, which occurred simultaneously with disease activity. On follow-up, the faster increase in FGF23 than in parathyroid hormone suggested that FGF23 might be involved in the pathogenesis of hypercalcaemia in SLE.

Wan Y.G.,Nanjing Medical University
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine / Zhongguo Zhong xi yi jie he xue hui, Zhongguo Zhong yi yan jiu yuan zhu ban | Year: 2011

To explore the potential molecular mechanisms of multi-glycoside of Tripterygium wilfordii Hook. f. (GTW) for ameliorating glomerulosclerosis (GS) by observing its intervention effect on transforming growth factor (TGF)-beta1/Smad signaling pathway in adriamycin-induced nephropathy (ADRN) model rat. Fifteen female Sprague-Dawley (SD) rats were randomly divided into three groups, the sham-operation group (A), the untreated model group (B), and the GTW treated model group (C). Rats in Group B and C were made into ADRN model by right nephrectomy and intravenous injection of adriamycin (ADR, 0. 4 mL and 0. 2 mL respectively in 4 weeks). After the model was successfully established, rats in Group C were orally given GTW (50 mg/kg per day), while rats in Group B were intervened with distilled water. The intervention for two groups was 6 weeks. Rats' body weight were weighed and 24 h urinary protein excretion (Upro) detected by the end of the 2nd, 4th, 8th and 10th week. All rats were sacrificed at the end of 10th week after operation to withdraw blood and kidney tissue to examine serum biochemical parameters, glomerular morphological changes, alpha-smooth muscle actin (alpha-SMA), and collagen type I expression. Besides, the mRNA expressions of TGF-beta1, Smad3 and Smad7, as well as protein expressions of TGF-beta1, and phosphorylated Smad2/3 (p-Smad2/3) in glomeruli were detected by RT-PCR or Western blotting. As compared with Group B, in Group C, Upro and serum albumin were improved significantly, but no difference between groups was found in levels of blood urea nitrogen(BUN), serum creatinine(SCr), or hepatic cell injury. Mesangial cell proliferation, extracellular matrix (ECM) and collagen deposition were suppressed by GTW. Expressions of alpha-SMA and collagen type I decreased, and the characteristic changes of GS were attenuated. The mRNA expressions of TGF-P,31, Smad3 and protein expression of TGF-beta1, p-Smad2/3 in renal tissues were down-regulated, while the protein expression of Smad7 mRNA was up-regulated. GTW showed effect in ameliorating GS in vivo. It could reduce the ECM deposition and improve GS by way of intervening TGF-beta1/Smad signaling pathway in the kidney through regulating the mRNA or protein expressions of key signal molecules, such as Smad3 and p-Smad2/3.

Tang X.,Nanjing Medical University
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery | Year: 2013

To investigate the expressions of high mobility group box B1 protein (HMGB1), matrix metalloproteinases-2(MMP-2) and matrix metalloproteinases-9 (MMP-9) in human laryngeal carcinoma and study their relationships with clinicopathological characteristics and prognosis. The expressions of HMGB1, MMP-2 and MMP-9 proteins were examined with the EnVision immunohistochemical method in 61 cases of laryngeal carcinoma. The expressions of HMGB1, MMP-2 and MMP-9 mRNA were detected by real-time quantitative RT-PCR method in 30 cases of laryngeal carcinoma. The positive expression rates of HMGB1, MMP-2 and MMP-9 proteins were significantly higher in laryngeal carcinoma than those in adjacent tissue (chi2=44.934, 49.923 and 36.054, P<0.01). The relative expression levels of HMGB1, MMP-2 and MMP-9 mRNA in laryngeal carcinoma were significantly higher than those in adjacent tissue (t=5.940, 7.005 and 7.664, P<0.01). The high level expression of HMGB1, MMP-2, MMP-9 proteins was closely associated with T stage, clinical stage and the status of lymph node metastasis (P<0.05 or P<0.01). There was a positive correlation between the expression of HMGB1 and MMP-9 protein (r=0.381, P<0.01). Univariate analysis indicated that the overall survival rate was lower in patients with a positive expression of HMGB1 and MMP-9 than those with negative expression (chi2= 4.974, 6.418, P<0.05). Multivariate analysis showed that HMGB1 was a risk predictor. A higher expression of HMGB1 was associated with a shorter survival time. HMGB1, MMP-2 and MMP-9 play a role in invasion and metastasis of laryngeal carcinoma; Also there is a synergistic effect between HMGB1 and MMP-9; Moreover HMGB1 may be a independent prognostic factor.

Song X.-F.,Nanjing University of Aeronautics and Astronautics | Han P.,Nanjing Medical University | Chen Y.-P.P.,La Trobe University
Journal of Medical Virology | Year: 2011

Avian influenza virus H9N2 has become the dominant subtype of influenza which is endemic in poultry. The hemagglutinin, one of eight protein-coding genes, plays an important role during the early stage of infection. The adaptive evolution and the positively selected sites of the HA (the glycoprotein molecule) of H9N2 subtype viruses were investigated. Investigating 68 hemagglutinin H9N2 avian influenza virus isolates in China and phylogenetic analysis, it was necessary that these isolates were distributed geographically from 1994, and were all derived from the Eurasian lineage. H9N2 avian influenza virus isolates from domestic poultry in China were distinct phylogenetically from those isolated in Hong Kong, including viruses which had infected humans. Seven amino acid substitutions (2T, 3T, 14T, 165D, 197A, 233Q, 380R) were identified in the HA possibly due to positive selection pressure. Apart from the 380R site, the other positively selected sites detected were all located near the receptor-binding site of the HA1 strain. Based on epidemiological and phylogenetics analysis, the H9N2 epidemic in China was divided into three groups: the 1994-1997 group, the 1998-1999 group, and the 2000-2007 group. By investigating these three groups using the maximum likelihood estimation method, there were more positive selective sites in the 1994-1997 and 1998-1999 epidemic group than the 2000-2007 groups. This indicates that those detected selected sites are changed during different epidemic periods and the evolution of H9N2 is currently slow. The antigenic determinant or other key functional amino acid sites should be of concern because their adjacent sites have been under positive selection pressure. The results provide further evidence that the pathogenic changes in the H9N2 subtype are due mainly to re-assortment with other highly pathogenic avian influenza viruses. © 2011 Wiley-Liss, Inc.

Chen S.L.,Nanjing Medical University
Chinese medical journal | Year: 2012

The predictive value of bifurcation angle (BA) for worse events after stenting bifurcation lesions remains to be unknown. The present study was to investigate the dynamic change of BA and clinical relevance for patients with coronary bifurcation lesions treated by drug-eluting stent (DES). BA was calculated by 3-D quantitative coronary analysis from 347 patients in DKCRUSH-II study. Primary endpoint was the occurrence of composite major adverse cardiac events (MACE) at 12-month, including cardiac death, myocardial infarction (MI) and target vessel revascularization (TVR). Secondary end points were the rate of binary restenosis and stent thrombosis at 12-month. Stenting was associated with the reduction of distal BA. The cut-off value of distal BA for predicting MACE was 60°. Distal BA in < 60° group had less reduction after stenting ((-1.96 ± 13.58)° vs. (-12.12 ± 23.58)°, P < 0.001); two-stent technique was associated with significant reduction of distal BA (Δ(-4.05 ± 14.20)°), compared to single stent group (Δ + 1.55 ± 11.73, P = 0.003); the target lesion revascularization (TLR), TVR and MACE rate was higher in one-stent group (16.5%, 19.0% and 21.5%), compared to two-stent group (3.8%, P = 0.002; 7.5%, P = 0.016; and 9.8%, P = 0.024), respectively. Among patients in ≥ 60° group, there were no significant differences in distal BA, stent thrombosis (ST), MI, MACE, death, TLR, TVR between one- and two-stent groups; after stenting procedure, there was only slight change of distal BA in left anterior descending (LAD)-left circumflex (LCX) subgroup (from (88.54 ± 21.33)° at baseline to (82.44 ± 31.72)° post-stenting), compared to either LAD-diagonal branch (Di), or LCX-obtuse marginal branch (OM), or RCA distal (RCAd) (all P < 0.001). Two-stent technique was associated with significant reduction of distal BA. DK crush stenting had reduced rate of MACE in patients in < 60° group, compared to one-stent technique.

Qiu Y.Y.,Nanjing Medical University
Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases | Year: 2013

To improve understanding of the clinical, radiological and pathological characteristics of acute fibrinous and organizing pneumonia (AFOP). The clinical data of 5 AFOP patients were retrospectively analyzed. AFOP was diagnosed via percutaneous lung biopsy guided by chest computerized tomography (CT) in the Affiliated Drum Tower Hospital of Nanjing University Medical School during March 2011 to June 2012. The clinical, radiological and pathological characteristics of those patients were summarized. Among the 5 patients, 2 were male and 3 were female, aging 43-61 years. They were all subacute onset. The main clinical manifestations were dyspnea, productive cough, fever and chest pain with hypoxemia via blood gas analysis. Bilateral infiltrates with diffuse and pathy distribution were the predominant features in chest HRCT. The pathological examination revealed slightly widened alveolar septa, 1ymphocyte and plasma cell infiltration and the presence of intra-alveolar fibrin in the form of fibrin "balls" (organization) within the alveolar spaces. No neutrophil, and eosinophil infiltration and hyaline membrane formation were detected, which was different from other well-recognized histologic patterns of acute lung injury, such as diffuse alveolar damage, cryptogenic organizing pneumonia and eosinophilic pneumonia. All patients were treated by corticosteroids and showed significant clinical and radiological improvement. AFOP has nospecific features, and its diagnosis depends on pathological examination. Treatment with corticosteroids is optimal. However, whether it is a unique interstitial disease needs to be further clinically investigated.

Liu X.,Nanjing Medical University
Chinese Journal of Oncology | Year: 2015

Objective: To explore the significance of multi-detector CT ( MDCT) in differential diagnosis of papillary renal cell carcinoma and chromophobe renal cell carcinoma. Methods Clinical data of forty-one cases of renal cancers confirmed pathologically were collected, including 21 cases of papillary renal cell carcinoma (PRCC) ( 14 type 1 , 7 type II ) and 20 cases of chromophobe renal cell carcinoma (ChRCC). Their morphological and MDCT characteristics were retrospectively analyzed. Receiver operator characteristic curve (ROC) was used to analyze the value of MDCT in differential diagnosis of PRCC and ChRCC. Two senior radiologists analyzed the morphological and the dynamic enhancement characteristics of the images. The attenuation of the lesions and the adjacent renal parenchyma were measured. The morphological indexes were compared with chi-square test and the quantitative indexes were compared with independent sample T-test. Receiver operator characteristic curve ( ROC ) was used to analyze the sensitivity, specificity and accuracy of diagnosis of PRCC and ChRCC. Results: Angioid enhancement and filled enhancement were more common in ChRCC than in PRCC, while delayed enhancement was more often seen in PRCC than in ChRCC. Calcification was more common in type I than type II PRCC. The enhancement value (ΔCT value) in corticomedullary phase was (29.08 ±20.12) Hu for PRCC, significantly lower than the (48.29 ± 26.70) Hu for ChRCC (t = -2.611, P=0.013). The ΔCT value of type I PRCC in corticomedullary phase was (26.36 ± 18.16) Hu, showing a significant difference from that of ChRCC (t = -2.666, P>=0.012). The lesion to kidney ratio (LKR) in corticomedullary phase was 0.44 ±0. 19 for PRCC and 0. 58 ± 0. 15 for ChRCC, with a significant difference between them (t = -2.587, P = 0.014). The LKR of type I PRCC in corticomedullary phase was 0. 39 ±0. 15, showing a significant difference from that of ChRCC (t = - 3. 628, P = 0. 001). The difference value ( D-value) of the attenuation of lesion between corticomedullary and nephrographic phases was ( -3.69 ±8.90) Hu for PRCC and (8.39 ±21.98) Hu for ChRCC, with a significant difference between them (t = -2.285, P = 0.031). The D-value of type I PRCC was ( - 4. 55 ± 9. 82 ) Hu, showing a significant difference from that of ChRCC (t = - 2. 323 , P = 0.028). There was no significant difference between the ΔCT, LKR and D-value of the type II PRCC and ChRCC (P>0.05 for all). The area under the curve ( AUC) for ΔCT value, LKR value in corticomedullary phase, and D-value were 0.718, 0.751 and 0.668, respectively, and there were no significant differences among them (z values were 0.896, 0.683 and 0.559, respectively, and P values were 0.370, 0. 495 and 0. 576, respectively). Using 49. 350 Hu as the cutoff value for ΔCT value in eorticomedullary phase, resulted in a sensitivity, specificity and accuracy of 50.0% , 90.5% and 70.7% , respectively. Corresponding values were 65. 0% , 81. 0% and 73. 2% , when using a cutoff value of 0. 532 for LKR in corticomedullary phase, and were 60.0% , 76. 2% and 68. 3% , when using a D-value of 0.400 Hu. Conclusions: The ΔCT value, LKR value in corticomedullary phase, and the D-value are all useful indexes for the differentiation of PRCC and ChRCC.

Zhang A.,Nanjing Medical University | Cao B.,Van Andel Research Institute
Journal of Biomedical Research | Year: 2012

Recently, serum Golgi protein 73 (GP73) levels have been found to be elevated in patients with hepatocellular carcinoma (HCC), and GP73 has been proposed as a novel marker for HCC. However, GP73 levels in patients remain controversial due to the specificity of the anti-GP73 antibody-based enzyme linked immunosorbent assay (ELISA). Therefore, an anti-GP73 antibody with high specificity was highly demanded. In the present study, by hybridoma screening, we generated an anti-GP73 monoclonal antibody (mAb) designated as 6A2 using recombinant GP73 protein produced by prokaryotic expression. The specificity of 6A2 was evaluated by Western blotting, immunohistochemistry and immunoprecipitation. The results showed that 6A2 recognized GP73 in both native and denatured forms. In addition, we have developed a sandwich ELISA using 6A2 and GP73 polyclonal antibody generated in New Zealand white rabbits according to standard procedures, and measured the serum GP73 level of patients using this assay. Our results showed that serum GP73 levels of HCC patients were significantly higher than those of healthy controls (P = 0.0036). Furthermore, for the first time, GP73 serum level was found to be elevated in patients with breast cancer compared with healthy controls (P = 0.0172). © 2012 The Editorial Board of Journal of Biomedical Research.

Liu H.,Nanjing Medical University
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery | Year: 2013

To evaluate the effectiveness of the submental island flap for repair of oral defects after radical resection of early-stage oral squamous cell carcinoma (OSCC). Between February 2010 and August 2011, 15 cases of early-stage OSCC were treated. Of 15 cases, 9 were male and 6 were female, aged from 48 to 71 years (mean, 63 years). The disease duration was 28-73 days (mean, 35 days). Primary lesions included tongue (3 cases), buccal mucosa (8 cases), retromolar area (2 cases), and floor of mouth mucosa (2 cases). According to TNM classification of International Union Against Cancer (UICC, 2002) of oral cancer and oropharyngeal cancer, 2 cases were classified as T1N0M0 and 13 cases as T2N0M0. The results of the pathologic type were high differentiated squamous cell carcinoma in 11 cases and moderately differentiated squamous cell carcinoma in 4 cases. The defect after resection of the lesion ranged from 5 cm x 3 cm to 8 cm x 6 cm. All the cases underwent radical resection of the primary lesion and immediate reconstruction with submental island flap except 1 case with radial forearm free flap because of no definite venous drainage. The sizes of the submental island flap varied from 6 cm x 4 cm to 9 cm x 6 cm. Operation time ranged from 4 hours and 30 minutes to 7 hours and 10 minutes (mean, 5 hours and 53 minutes) in 14 cases undergoing repair with submental island flap. All the flaps survived completely in 13 cases except 1 case having superficial necrosis of the flap, which was cured after conservative treatment. Temporary marginal mandibular nerve palsy occurred in 1 case, and was cured after 3 months; submandibular effusion was observed in 3 cases, and was cured after expectant treatment. The follow-up period ranged from 8 to 15 months (mean, 10.5 months) in 14 cases undergoing repair with submental island flap. Hair growth was seen on the flap and became sparse after 3 months in 2 male cases. The appearance of the face, opening mouth, swallowing, and speech were recovered well in 14 cases, and the donor site had no obvious scar. The follow-up period was 13 months in 1 case undergoing repair with radical free forearm flap, and the appearance and function were recovered well. No local recurrence was found during follow-up. The submental island flap has reliable blood supply, and could be harvested simply and rapidly. It can be used to repair oral defects in patients with early-stage OSCC after radical resection.

Wang Z.,Nanjing Medical University | Chen H.,Xuzhou Medical College | Wang F.-X.,Xuzhou Medical College
Cell Biochemistry and Biophysics | Year: 2011

Using vascular heat-exchange controller implemented mild hypothermia treatment, the authors established the cerebral vasospasm model in which blood was injected twice into dog's foramen magnum; and it was discussed the influence of the concentration of endothelin-1 and NO in blood plasma and cerebrospinal fluid through continuing treatment of mild hypothermia at different times in secondary brain vasospasm model after subarachnoid hemorrhage. Thirty healthy mongrel dogs were randomly divided into five groups; artificial cerebrospinal fluid group (group A), normal temperature control group (group C), mild hypothermia 8 h group (group H1), mild hypothermia 16 h group (group H2), and mild hypothermia 32 h group (group H3). The authors injected the artificial CSF into dog's foramen magnum in group A while the other four groups were injected with autologous arterial blood. The normal group's temperature maintained 38.5°C. The authors set the temperature at 33.5°C in mild hypothermia groups and this was maintained for 8, 16, and 32 h, respectively. ET-1 and NO levels in the cerebrospinal fluid and plasma were assayed in each group on days 0, 7, 14, and 21. Then the changes of the diameter of blood vessels of cerebral basilar artery and overall performance categories score in each group through application of CT angiography were recorded. In the cerebral vasospasm model which was constructed by injecting the blood to dog twice, mild hypothermia treatment, through the application of vascular heat-exchange controller, could reduce cerebral vasospasm. It was observed that the duration of the mild hypothermia is directly proportional to the longer duration of the relieving of cerebral vasospasm. The reciprocal changes observed in the levels of ET-1 and NO in cerebrospinal fluid and plasma revealed that it might be possible to reduce the cerebral vasospasm by regulating the rising amplitude of ET-1 and the decrease in NO in CSF and plasma. © 2011 Springer Science+Business Media, LLC.

Wang L.,Nantong University | Yao M.,Nantong University | Dong Z.,Nantong University | Zhang Y.,Nanjing Medical University | Yao D.,Nantong University
Tumor Biology | Year: 2014

Hepatocellular carcinoma (HCC) is one of the most common and rapidly fatal malignancies worldwide with a multi-factorial, multi-step, complex process and poor prognosis. Its early diagnosis and metastasis monitoring are of the utmost importance. Hepatoma tissues synthesize various tumor-related proteins, genes, enzymes, microRNA, etc. and then secrete into the blood. Detections of circulating biomarkers are useful to find tumor at an early stage or monitor metastasis after postoperative treatment. This paper summarizes recent studies of specific biomarkers at early diagnosis or in monitoring metastasis or postoperative recurrence of HCC.

Yang C.S.,Rutgers University | Fengb Q.,Nanjing Medical University
Journal of Biomedical Research | Year: 2014

Cancer is a major disease worldwide and different approaches are needed for its prevention. Previous laboratory and clinical studies suggest that cancer can be prevented by chemicals, including those from the diet. Furthermore, epidemiological studies have suggested that deficiencies in certain nutrients can increase the risk of some cancers. In this article on chemo/dietary prevention, examples will be given to illustrate the effectiveness of chemopreventive agents in the prevention of breast, colon and prostate cancers in high-risk populations and the possible side effects of these agents. The potential usefulness of dietary approaches in cancer prevention and the reasons for some of the failed trials will be discussed. Lessons learned from these studies can be used to design more relevant research projects and develop effective measures for cancer prevention in the future. The development of effective chemopreventive agents, the use of nutrient supplements in deficient or carcinogen-exposed populations, and the importance of cohort studies will be discussed in the context of the current socioeconomic situation in China. More discussions are needed on how we can influence society to pay more attention to cancer prevention research and measures. © 2014 by the Journal of Biomedical Research.

Chen M.-B.,Jiangsu University | Shen W.-X.,Jiangsu University | Yang Y.,Jiangsu University | Wu X.-Y.,Jiangsu University | And 2 more authors.
Journal of Cellular Physiology | Year: 2011

The molecular basis for induction of apoptosis in melanoma cells by vincristine remains unknown. Here we tested the potential involvement of AMP-activated protein kinase (AMPK) in this process. We found for the first time that vincristine induces AMPK activation (AMPKα, Thr 172) and Acetyl-CoA carboxylase (ACC, Ser 79) (a downstream molecular target of AMPK) phosphorylation in cultured melanoma cells in vitro. Reactive oxygen species (ROS) dependent LKB1 activation serves as the upstream signal for AMPK activation. AMPK inhibitor (compound C) or AMPKα siRNA knockdown inhibits vincristine induced B16 melanoma cell apoptosis, while AMPK activator 5-aminoimidazole-4-carboxamide-1-β-riboside (AICAR) enhances it. AMPK activation is involved in vincristine induced p53 phosphorylation and stabilization, the latter is known to mediate melanoma cell apoptosis. Further, activation of AMPK by vincristine inhibits mTOR Complex 1 (mTORC1) in B16 melanoma cells, which serves as another important mechanism to induce melanoma cell apoptosis. Our study provides new insights into understanding the cellular and molecular mechanisms of vincristine induced cancer cell death/apoptosis. We suggest that combining AMPK activator AICAR with vincristine may have potential to be used as a new therapeutic intervention against melanoma. © 2010 Wiley-Liss, Inc.

Li J.,Soochow University of China | Hu W.,Nanjing Medical University | Lan Q.,Soochow University of China
Journal of Neuro-Oncology | Year: 2012

We previously reported that sEH inhibitor t-AUCB suppresses the growth of human glioblastoma U251 and U87 cell lines and induces cell-cycle G0/G1 phase arrest. In present study, we found even 96 h-treatment of 200 μM t-AUCB can not induce apoptosis in U251 and U87 cells. We also revealed that 200 μM t-AUCB significantly elevates the activation of p38 MAPK, MAPKAPK2 and Hsp27. The p38 MAPK inhibitor SB203580 and the inhibitor of Hsp27 phosphorylation, KRIBB3, were used to investigate the mechanism of the apoptosis-resistance. The results showed that, after blocking the activation of Hsp27 by SB203580 or KRIBB3, 200 μM t-AUCB significantly induces apoptosis and increases caspase-3 activities in U251 and U87 cells. Our data demonstrated that t-AUCB induces cell apoptosis after blocking itself-induced activation of Hsp27, and that the activation of Hsp27 may confer chemoresistance in GBM cells. The combination of t-AUCB and the inhibitor of Hsp27 phosphorylation may be a potential strategy for treatment of glioblastoma. © 2012 Springer Science+Business Media, LLC.

Zhang X.-M.,Central South University | Li J.-X.,Nanjing Medical University | Zhang G.-Y.,Central South University | Li X.-H.,Central South University | Gu H.,Central South University
BMC Gastroenterology | Year: 2014

Background: Serum pepsinogen (PG) levels are valuable in the diagnosis of gastric diseases. However, PG levels are affected by many factors such as the area and race. This study aimed to investigate serum PG levels in patients with different gastric diseases who were Chinese Han people in Hunan Province, midsouth China. Methods: A total of 248 gastric disease patients and 34 healthy controls were enrolled. The patients included those with non-atrophic and chronic atrophic gastritis, gastric and duodenal ulcer, early and advanced gastric cancer. Serum PG I and II levels were detected by Biohit ELISA kit (Finland), and PG I/II ratio was calculated. Differences in patients with gastric disease and healthy controls were analyzed using paired t-test. Results: Compared with controls, patients with early and advanced gastric cancer had a significantly lower PG I level and PG I/II ratio (p <0.005). In contrast, patients with gastric and duodenal ulcer had a significantly higher PG I level (p <0.005). Compared with atrophic gastritis patients, patients with early and advanced carcinoma of the stomach had a significantly lower PG I/II ratio (p < 0.001). Combination of the cut-off levels of PG I (70 μg/L) and PG I/II ratio (6) provided 62.1% sensitivity of and 94.2% specificity for the diagnosis of gastric cancer. Conclusions: Decreased PG I level and PG I/II ratio are risk factors for gastric cancer. Combined use of serum PG I level and PG I/II ratio may help the early diagnosis of gastric cancer. © 2014 Zhang et al.; licensee BioMed Central Ltd.

Guo J.,Nanjing Medical University | Sachs F.,State University of New York at Buffalo | Meng F.,State University of New York at Buffalo
Antioxidants and Redox Signaling | Year: 2014

Significance: Three signaling systems, chemical, electrical, and mechanical, ubiquitously contribute to cellular activities. There is limited information on the mechanical signaling system because of a lack of tools to measure stress in specific proteins. Although significant advances in methodologies such as atomic force microscopy and laser tweezers have achieved great success in single molecules and measuring the mean properties of cells and tissues, they cannot deal with specific proteins in live cells. Recent Advances: To remedy the situation, we developed a family of genetically encoded optical force sensors to measure the stress in structural proteins in living cells. The sensors can be incorporated into specific proteins and are not harmful in transgenic animals. The chimeric proteins distribute and function as their wild-type counterparts, and local stress can be read out from changes in Förster resonance energy transfer (FRET). Critical Issues: Our original sensor used two mutant green fluorescence proteins linked by an alpha helix that served as a linking spring. Ever since, we have improved the probe design in a number of ways. For example, we replaced the helical linker with more common elastic protein domains to better match the compliance of the wild-type hosts. We greatly improved sensitivity by using the angular dependence of FRET rather than the distance dependence as the transduction mechanism, because that has nearly 100% efficiency at rest and nearly zero when stretched. Future Directions: These probes enable researchers to investigate the roles of mechanical force in cellular activities at the level of single molecules, cells, tissues, and whole animals. Antioxid. Redox Signal. 20, 986-999. © 2014 Mary Ann Liebert, Inc.

Pan F.,Johns Hopkins University | Fan H.,Tongji University | Lu L.,Nanjing Medical University | Liu Z.,Tongji University | Jiang S.,Tongji University
Science Signaling | Year: 2011

Substantial advances in our understanding of the developmental and functional relationship between regulatory T cells (Tregs) and T helper 17 (TH17) cells and their potential clinical applications have been made. In response to these break-throughs, the second international conference entitled "China Tregs/Th17 2010 Shanghai Conference," held in Shanghai, China, was dedicated to this topic. Various types of T regs and TH17 cells, as well as their relevant cytokines, were discussed. Here, we summarize some of the findings shared at the conference, specifically focusing on the biology of TH17 cells, including interleukin-17 (IL-17)-producing innate cells, Tregs, and the factors that control the critical balance between Tregs and cells of the TH17 lineage.

Luzzo K.M.,University of Washington | Wang Q.,Nanjing Medical University | Purcell S.H.,University of Washington | Chi M.,University of Washington | And 4 more authors.
PLoS ONE | Year: 2012

Background: Maternal obesity is associated with poor outcomes across the reproductive spectrum including infertility, increased time to pregnancy, early pregnancy loss, fetal loss, congenital abnormalities and neonatal conditions. Furthermore, the proportion of reproductive-aged woman that are obese in the population is increasing sharply. From current studies it is not clear if the origin of the reproductive complications is attributable to problems that arise in the oocyte or the uterine environment. Methodology/Principal Findings: We examined the developmental basis of the reproductive phenotypes in obese animals by employing a high fat diet mouse model of obesity. We analyzed very early embryonic and fetal phenotypes, which can be parsed into three abnormal developmental processes that occur in obese mothers. The first is oocyte meiotic aneuploidy that then leads to early embryonic loss. The second is an abnormal process distinct from meiotic aneuploidy that also leads to early embryonic loss. The third is fetal growth retardation and brain developmental abnormalities, which based on embryo transfer experiments are not due to the obese uterine environment but instead must be from a defect that arises prior to the blastocyst stage. Conclusions/Significance: Our results suggest that reproductive complications in obese females are, at least in part, from oocyte maternal effects. This conclusion is consistent with IVF studies where the increased pregnancy failure rate in obese women returns to the normal rate if donor oocytes are used instead of autologous oocytes. We postulate that preconceptional weight gain adversely affects pregnancy outcomes and fetal development. In light of our findings, preconceptional counseling may be indicated as the preferable, earlier target for intervention in obese women desiring pregnancy and healthy outcomes. © 2012 Luzzo et al.

To investigate the incidence of thoracic curve decompensation or proximal adding-on phenomenon after anterior selective fusion of thoracolumbar or lumbar curve in Lenke type 5 adolescent idiopathic scoliosis (AIS), and to identify its risk factors. From June 2001 to December 2008, 130 Lenke type 5 AIS patients with a Cobb angle of 40° - 73° treated with anterior selective thoracolumbar or lumbar fusion, and with a minimum 2-year postoperative regular follow-up were recruited in this study. The average age, Cobb angle and Risser sign of all patients was 14.8 ± 1.6 years, 46° ± 6° of major thoracolumbar or lumbar curve (TL or L), 25° ± 7° of proximal thoracic curve and 0-5, respectively. The patients were grouped according to the relationship between the upper instrumented vertebrae (UIV) and the upper end vertebrae (UEV), the patients' Risser sign and the relationship between UIV and C(7) plumb line (C(7)PL). The radiographic data of the patients were compared between patients with and without proximal adding-on by using t test, and the incidence of proximal adding-on was analyzed in terms of determination of UIV and Risser sign to identify the risk factors of this phenomenon by using Fisher's exact test. Eleven patients were identified with proximal adding-on, thus the incidence of it was 8.5%. At last follow-up postoperatively, the average Cobb angle of TL or L and proximal thoracic curve was 9° ± 4° and 11° ± 5°, respectively. Moreover, the incidence of adding-on in Rissex sign grade 0 to 1 (3/8) was higher than that of grade 2 to 3 (12.1%) and grade 4 to 5 (4.5%). In addition, the incidence of adding-on in UIV lower than UEV group (20.6%) was obviously higher than that of UIV higher than or equal to UEV group (4.2%). The incidence of adding-on for patients with C(7)PL falls away from UIV (19.5%) were obviously higher than that of patients with C(7)PL falls between the pedicle and lateral margin of UIV (3.6%) and between bilateral pedicles of UIV (3.0%). Each group showed significant difference for the incidence of adding-on by Fisher's exact test (P < 0.05). There exists the risk of proximal thoracic curve decompensation, with a not low rate, after anterior selective fusion for major TL or L curve AIS. The determination of UIV relative to UEV and the skeletal maturity of the patient are the two factors closely associated with the presence of such a phenomenon.

Sun B.,Nanjing Medical University | Karin M.,University of California at San Diego
Journal of Hepatology | Year: 2012

Obesity has become a universal and major public health problem with increasing prevalence in both adults and children in the 21st century, even in developing countries. Extensive epidemiological studies reveal a strong link between obesity and development and progression of various types of cancers. The connection between obesity and liver cancer is particularly strong and obesity often results in liver diseases such as non-alcoholic fatty liver disease (NAFLD) and the more severe non-alcoholic steatohepatitis (NASH). NASH is characterized by fatty liver inflammation and is believed to cause fibrosis and cirrhosis. The latter is a known liver cancer risk factor. In fact due to its much higher prevalence obesity may be a more substantial contributor to overall hepatocellular carcinoma burden than infection with hepatitis viruses. Here we review and discuss recent advances in elucidation of cellular and molecular alterations and signaling pathways associated with obesity and liver inflammation and their contribution to hepatocarcinogenesis. © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Dong C.G.,China Agricultural University | Wu W.K.K.,Chinese University of Hong Kong | Feng S.Y.,Soochow University of China | Wang X.J.,Chinese University of Hong Kong | And 2 more authors.
International Journal of Oncology | Year: 2012

MicroRNAs (miRNAs) are small non-coding RNAs that function as negative gene regulators. Alterations in the expression of miRNAs have been implicated in the pathogenesis and development of most human malignancies. Recent data indicate that microRNA-21 and microRNA-10b are significantly elevated in glioblastoma multiforme (GBM) suggesting their role in the regulation of multiple genes associated with cancer. In this study, U87MG human glioblastoma cells were treated with miRNA inhibitors targeting miR-10b and miR-21, alone or in combination. The results showed that the miR-21 inhibitor additively interacted with miR-10b inhibitor on U87MG cells. The 50% inhibitory concentration values were dramatically decreased in cells treated with the combination of miR-10b and miR-21 inhibitors. Furthermore, inhibitors synergistically combined, enhanced apoptosis significantly and reduced invasion ability assessed by flow cytometry and Transwell migration assay. Thus, the miR-21 inhibitor may interrupt the activity of EGFR pathways, increasing PDCD4 and TPM1 expression and reducing MMP activities, independently of PTEN status. Meanwhile, miR-10b inhibitor reduced by Twist proceeds to inhibit translation of the mRNA encoding HOXD10 leading to the increase of the expression of the well-characterized pro-metastatic gene RHOC. Taken together, these data strongly suggest that a combination of miR-21 inhibitor and miR-10b inhibitor could be an effective therapeutic strategy for controlling the growth of GBM by inhibiting oncogene expression and overexpressing tumor suppressor genes. Moreover, a regulatory strategy based on the combination of miRNA inhibitors may provide insights into the mechanisms of the modulation of signaling genes involved in tumor cell apoptosis and invasiveness.

Zhuang Y.,Nanjing Medical University
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology | Year: 2013

This study was purpose to investigate the clinical characteristics of B-cell chronic lymphoproliferative disorders (B-CLPD) complicated by autoimmune hemolytic anemia (AIHA) so as to improve the understanding of this disease. The clinical characteristics, laboratory data, therapy and outcome of 14 patients suffering from B-CLPD complicated by AIHA were retrospectively analyzed in Wuxi People Hospital and the First Affiliated Hospital of Nanjing Medical University from 2000 to 2012. The results showed that 9 cases of the 14 patients were patients with chronic lymphocytic leukemia (CLL), 5 cases were patients with lymphoma, at time of hemolysis the median level of hemoglobin was 61 (33 - 84)g/L, the median ratio of reticulocytes was 12.0 (3.1 - 35.0)%, the positive rate of Coombs test was 100%. 1 case received corticosteroid alone, 5 cases were treated with chemotherapy combined with corticosteroid, 8 cases were treated with immunochemotherapy rituximab combined with corticosteroid. Overall response rate was 100%, in which CR was 78.6% (11/14), PR was 21.4% (3/14). The follow-up for these patients were performed to now, 35.7% (5/14) patients relapsed with hemolysis again, but they showed therapeutic response to treatment with above-mentioned therapy. From patients treated with rituximab alone, only 1 patient relapsed. Among 14 patients, 6 cases died, 1 case was lost, the other cases are still alive. It is concluded that the AIHA is the commonest complication of B-CLPD, it can be observed at different stages of B-CLPD, the treatment with corticosteroids can give well therapeutic effect for these patients, but the long time CR is lower, the rituximab has been confirmed to be effective for B-CLPD complicated by AIHA.

Wu C.,Zhengde Polytechnic College | Huang H.,Nanjing Medical University
Advances in Information Sciences and Service Sciences | Year: 2012

BP neural network model shows strong superiority in dealing with fuzzy data computation. Based on large volumes of research achievements obtained by scholars domestic and overseas, the paper applies BP neural network model to quantitatively evaluate sports participants' sports psychology. On this basis, by integrating practically collected data, the evaluation results are compared with sports psychology evaluated by experience. According to the comparison result, we have found that it is feasible to conduct sports psychology evaluation with BP neural network model as the basic algorithm. Its computation result is quite consistent with the practical evaluation result. Accordingly, the feasibility and applicability of using BP neural network model for sports psychology evaluation is fully attested.

Qiao J.,Nanjing Medical University
Journal of spinal disorders & techniques | Year: 2012

A comparison between the smartphone-aided measurement method and the manual measurement method for the Cobb angle in adolescent idiopathic scoliosis. To evaluate the reliability and measurement error for the smartphone-aided Cobb angle measurement method and compare its reliability and measurement error with those of the manual method. The development of smartphones has provided new opportunities that integrate mobile technology into daily clinical practice. Smartphone applications can provide quick assistance in the diagnosis and treatment of disease. Cobbmeter is a smartphone application designed for the measurement of Cobb angle on Apple iPhone smartphones. There is no study on the reliability and measurement error of this smartphone-aided measurement method. : Fifty-three posteroanterior radiographs of adolescent idiopathic scoliosis patients with thoracic scoliosis were used for the standard Cobb method of measurement (manual set) and the smartphone-aided Cobb method of measurement (smartphone set). Five spinal surgeons measured the Cobb angle with the use of both the manual method and the smartphone-aided method. The measurement time was recorded for every measurement. The frequency and the cumulative percent distribution for intraobserver differences were tabulated, both for the individual examiners and for the overall results for the 5 examiners. The intraclass correlation coefficient (ICC) 2-way mixed model on absolute agreement was used to analyze measurement reliability. Summary statistics from analyses of variance calculations were used to provide 95% prediction limits for the error in measurements. A paired t test was used to compare the time consumed for the measurement between both sets. The intraobserver and interobserver ICCs were excellent in the smartphone set and in the manual set. Both the intraobserver ICC and the interobserver ICC were better in the smartphone set than in the manual set. The mean Cobb angle of all measured x-rays was 29.3 degrees (range, 17-58 degrees) in the manual set and 29.1 degrees (range, 18-56 degrees) in the smartphone set. The mean time consumed was 13.7 seconds (range, 8.6-18.5 s) for the smartphone set, whereas it was 37.9 seconds (range, 30.1-46.9 s) for the manual set, and the mean time consumed for the smartphone set was significantly shorter than that of the manual set (P<0.05). Smartphone-aided measurement for Cobb angle showed excellent reliability and efficiency. It is suggested to popularize the use of this method in clinical practice.

Cheng D.,Nanjing Medical University | Liang B.,Shenyang Medical College
BioMed Research International | Year: 2013

The Ginkgo biloba extract (GBE) has been reported to have a wide range of health benefits in traditional Chinese medicine. The aim of this study was to evaluate the antihyperglycemic effects of GBE on streptozotocin- (STZ-) induced diabetes in rats. Diabetes was induced in male Wistar rats by the administration of STZ (60 mg/kg b.w.) intraperitoneally. GBE (100, 200, and 300 mg/kg b.w.) was administered orally once a day for a period of 30 days. Body weight and blood glucose levels were determined in different experimental days. Serum lipid profile and antioxidant enzymes in hepatic and pancreatic tissue were measured at the end of the experimental period. Significant decreases in body weight and antioxidant ability and increases in blood glucose, lipid profile, and lipid peroxidation were observed in STZ-induced diabetic rats. The administration of GBE and glibenclamide daily for 30 days in STZ-induced diabetic rats reversed the above parameters significantly. GBE possesses antihyperglycemic, antioxidant, and antihyperlipidemia activities in STZ-induced chronic diabetic rats, which promisingly support the use of GBE as a food supplement or an adjunct treatment for diabetics. © 2013 Daye Cheng et al.

Chen X.,Soochow University of China | Hong Y.,Nanjing Medical University | Zheng P.,Ningbo No. 6 Hospital
Psychiatry Research | Year: 2015

Our study was to review and evaluate the efficacy and safety of extract of Gb (EGb) as an adjuvant therapy to antipsychotics in chronic schizophrenia treatment. We searched Pubmed/Medline, Embase, PsycINFO, the Cochrane library, and especially the Chinese periodical databases. Finally, eight randomized, double-blind, placebo-controlled trials (RCTs) of 1033 patients were enrolled, with 571 cases in EGb group and 462 in placebo. The result showed that EGb had a significant difference in ameliorating total and negative symptoms of chronic schizophrenia as an adjuvant therapy to antipsychotics. Thus, the EGb therapy plus antipsychotics might be more efficacious. Although the studies describing adverse reactions showed no distinguishable difference between EGb and placebo group in mean total scores of Treatment Emergent Symptom Scale (TESS) or a Rating Scale for Extrapyramidal Side Effects (RSESE), the results of subscores varied in different studies. In addition, the severity of side effects of EGb might be related to its daily dosage. Therefore, the safety of EGb therapy in chronic schizophrenia treatment might need more evidence. And all of these eight trials were carried out in China; thus, the results might be restricted to the race and we need more high-quality studies of multi-center and randomized double-blind clinical trials to compare, analyze, and confirm the findings further. © 2015 Elsevier Ireland Ltd.

Jin Z.Y.,Nanjing Medical University
Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi | Year: 2012

To examine the association between tea drinking and the risk of lung cancer in Chinese population. All relevant published articles in Chinese and English literature database were identified. Meta-analysis was conducted. Combined odds ratio (OR) and 95% confidence interval (CI) were calculated to estimate the associations and dose-response relationship between tea drinking and the risk of lung cancer. Twelve studies were included. An inverse association with lung cancer was observed on tea drinkers when compared to non-tea drinkers (OR = 0.66, 95%CI: 0.49 - 0.89). Tea drinking might serve as a protective factor on lung cancer in the Chinese population.

Huang W.S.,Nanjing Medical University
Zhonghua nan ke xue = National journal of andrology | Year: 2012

For lack of the biomarker, early diagnosis of prostate cancer is often difficult. Caveolin-1 (Cav-1) is an important oncogene and a major structural coat protein of caveolae, which is involved in multiple cellular functions including molecular transport, cell adhesion, and signal transduction, as well as in the development and progression of prostate cancer. Cav-1 is secreted as a biologically active molecule that promotes cell survival and angiogenesis within the tumor microenvironment, and is overexpressed in the metastatic and primary sites of human prostate cancer. Secreted Cav-1 can be detected in the peripheral blood, and its expression level has an indicative value in the diagnosis and prognosis of prostate cancer. This review focuses on the structure and biological characteristics of Cav-1 and its correlation with prostate cancer.

Wang W.J.,Nanjing Medical University
Orthopaedic surgery | Year: 2014

The molecular mechanism of low bone mass in girls with adolescent idiopathic scoliosis (AIS) has not been ascertained. Runx2 is a critical transcription factor regulating osteoblast differentiation and maturation. The present study aimed to explore the possible relationship between Runx2 expression in osteoblasts and bone mineral density (BMD) in subjects with AIS. Twenty-two girls with AIS scheduled to corrective surgery with iliac crest as donor site of autograft for spinal fusion were recruited. The BMD of lumbar spine and femoral neck were assessed by dual-energy X-ray absorptiometry, then patients were divided into two groups with either normal or reduced BMD. Cancellous bone was harvested from their iliac crests for primary culture of osteoblasts. mRNA and protein expression of Runx2 were assayed by reverse transcription-polymerase chain reaction and western blotting, respectively. Results were compared between the two groups and correlated with BMD. AIS patients with normal BMD showed comparable maturity and body mass index but significant lower Cobb angle of main curve than those of patients with reduced BMD. The mean BMD of lumbar spine and femoral neck were 0.993 g/m(2) and 0.911 g/m(2) in patients with normal BMD, and were 0.757 g/m(2) and 0.733 g/m(2) in those with reduced BMD, respectively. The differences were significant between two groups (P < 0.05). The relative mean mRNA and protein expression of Runx2 were 0.49 ± 0.12 and 0.062 ± 0.020 in AIS with normal BMD, 0.35 ± 0.12 and 0.042 ± 0.006 in AIS with reduced BMD, respectively. Significantly lower Runx2 mRNA and protein expression were found in patients with AIS patients with reduced BMD than in those with normal BMD (P < 0.05). After controlling for age, weight and body mass index, positive correlations were found between Runx2 expression of both mRNA and protein and BMD of lumbar spine and femoral neck. The abnormal expression of Runx2 in patients with AIS and reduced BMD indicates abnormal regulation of differentiation of their osteoblasts. Runx2 may play an important role in the pathogenesis of reduced BMD in patients with AIS. © 2014 Chinese Orthopaedic Association and Wiley Publishing Asia Pty Ltd.

Yu J.,Nanjing Medical University
Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] | Year: 2010

OBJECTIVE: To investigate whether Leptotrombidium scutellare could be naturally infected by both Hantaan virus (HV) and Orientia tsutsugamushi (OT) and transmission status by stinging. METHODS: 3459 Leptotrombidium scutellares from mice bodies and 3265 which were free were collected in the epidemic area of hemorrhagic fever with renal syndrome (HFRS) and tsutsugamushi disease.15 days later, the suspensions of lung and spleen of mice with 6 in a group stung by 1, 5 or 10 infected mites were injected intra-cerebrally into other mice for the detection of HV and OT in the next 6 generations of the mice, with immunofluorescent antibody technique (IFAT) and Giemsa staining technique. The passages of Vero-E6 cells inoculated on the aseptic filtrations from different number of infected mites were used to detect HV and OT pathogens. HV-RNA and OT-DNA were detected by PCR. RESULTS: After passage, HV positive mouse body mite group out of both 5 and 10 mites in the sixth generation, OT positive mouse body mite group out of the 10 mites in the sixth generation, both HV and OT positive mouse body mite group out of 1 mite in the fifth and sixth generation, both HV and OT positive mouse body mite group out of 5 and 10 mites in the sixth generation, and free mites group out of 1, 5 and 10 mites in the sixth generation, were found one mouse infected by both HV and OT, respectively. Out of the fourth generation of Vero-E6 cells, one sample was found both HV and OT positive out of 5 and 10 HV and OT mouse body mite group, respectively. In the sixth generation, both HV and OT positive cells were detected in one mouse mite group and the 1, 5, 10 free mite groups, respectively. HV-RNA and OT-DNA were all detected by PCR. CONCLUSION: Both HV and OT could be coexisted in wild Leptotrombidium scutellare and transmitted by stinging.

Jin L.,Nanjing Southeast University | Zeng X.,Nanjing Medical University | Liu M.,Nanjing Southeast University | Deng Y.,Nanjing Southeast University | And 3 more authors.
Theranostics | Year: 2014

Gene transfer methods are promising in the field of gene therapy. Current methods for gene transfer include three major groups: viral, physical and chemical methods. This review mainly summarizes development of several types of chemical methods for gene transfer in vitro and in vivo by means of nano-carriers like; calcium phosphates, lipids, and cationic polymers including chitosan, polyethylenimine, polyamidoamine dendrimers, and poly(lactide-co-glycolide). This review also briefly introduces applications of these chemical methods for gene delivery. © Ivyspring International Publisher.

To study the effect of pioglitazone, a synthetic peroxisome proliferator-activated receptor γ (PPARγ) agonist, on the RANKL-mediated osteoclastogenesis of osteoclast precursor cells, and to explore the function and mechanism of PPARγ in the osteoclast differentiation. Pioglitazone treatment of RAW264.7 murine macrophages were compared with those of simply cultured control and RANKL-mediated control. Accordingly, the RANKL-mediated cells were cultured with 30 ng/ml RANKL, then induced into significant multinuclear osteoclast formation. And pioglitazone treated cells were exposed to 10 μmol/L pioglitazone during the process of osteoclast differentiation under RANKL. The number of mature osteoclasts was calculated and the mRNA levels of RANK analyzed by real-time quantitative PCR. Pioglitazone significantly inhibited osteoclastogenesis of osteoclast precursor cells, the number of mature osteoclasts of pioglitazone treated group was (176 ± 58)/cm(2) and significantly less than the mature cells of RANKL induced group which number was (322 ± 74)/cm(2) (P < 0.01); and pioglitazone also significantly inhibited the mRNA expression of RANK, a typical differentiated factor of osteoclast, the number of the mRNA expression of RANK of pioglitazone treated group was 2.16 ± 0.74 and significantly less than the number of RANKL induced group (4.94 ± 0.39, P < 0.01). PPARγ agonist inhibited the differentiation of RAW264.7 towards osteoclast. It might be due to the suppression of RANK gene expression in the process of osteoclast differentiation.

To examine whether the anti-apoptotic effect of hepatocyte growth factor (HGF) in cardiomyocytes underwent ischemia/reperfusion (I/R) is associated with downregulation of calcium sensing receptor (CaSR) mRNA expression. Neonatal rat cardiomyocytes were isolated and randomly divided into 7 groups: control, I/R, GdCl(3), GdCl(3) + NiCl(2) + CdCl(2), GdCl(3) + LY294002, GdCl(3) + HGF, GdCl(3) + HGF + LY294002.I/R was established by incubating primary neonatal rat ventricular cardiomyocytes in ischemia-mimetic solution for 2 h, then reincubated in normal culture medium for 24 h. Cardiomyocyte apoptosis was detected by TUNEL. The expression of CaSR mRNA was detected by reverse transcriptase polymerase chain reaction (RT-PCR). The expression of Caspase-3, Bcl-2 and Phosphoinositide-3 Kinase (PI3K) was analyzed by Western blot. I/R enhanced the expression of CaSR mRNA (I/R: 2.62 ± 0.41, control: 1.00 ± 0.31, P < 0.01) and cardiomyocyte apoptosis [I/R: (15.32 ± 2.54)%, control: (2.90 ± 1.45)%, P < 0.01]. GdCl(3) further increased the expression of CaSR mRNA (GdCl(3): 4.46 ± 0.62, I/R: 2.62 ± 0.41, P < 0.01) and cardiomyocyte apoptosis [GdCl(3): (25.36 ± 2.60)%, I/R: (15.32 ± 2.54)%, P < 0.01], along with upregulation of Caspase-3 (GdCl(3): 1.93 ± 0.28, I/R: 1.50 ± 0.21, P < 0.01), downregulation of Bcl-2 (GdCl(3): 0.82 ± 0.18, I/R: 1.71 ± 0.30, P < 0.01) and PI3K phosphorylation inhibition (I/R: 0.87 ± 0.08, GdCl(3): 0.61 ± 0.07, P < 0.01). Combination of GdCl(3) with LY294002 further enhanced cardiomyocytes apoptosis [GdCl(3) + LY294002: (32.6 ± 3.42)%, GdCl(3): (25.36 ± 2.60)%, P < 0.01] but did not affect CaSR mRNA expression (GdCl(3) + LY294002: 4.27 ± 0.56, GdCl(3): 4.46 ± 0.62, P > 0.05). HGF decreased I/R- and GdCl(3)-induced apoptosis [GdCl(3) + HGF: (11.8 ± 1.89)%, GdCl(3): (25.36 ± 2.60)%, P < 0.05] by suppressing Caspase-3 (GdCl(3) + HGF: 1.12 ± 0.23, (GdCl(3): 1.93 ± 0.28, P < 0.05; GdCl(3) + HGF + LY294002: 1.87 ± 0.31, GdCl(3) + LY294002: 3.86 ± 0.47, P < 0.05) and promoting Bcl-2 (GdCl(3) + HGF: 2.56 ± 0.54, GdCl(3): 0.82 ± 0.18, P < 0.05; GdCl(3) + HGF + LY294002: 1.68 ± 0.28, GdCl(3) + LY294002: 0.68 ± 0.13, P < 0.05) and PI3K phosphorylation expression (GdCl(3) + HGF: 2.87 ± 0.21, GdCl(3): 0.61 ± 0.07, P < 0.05; GdCl(3) + HGF + LY294002: 2.01 ± 0.14, GdCl(3) + LY294002: 0.44 ± 0.10, P < 0.05) in accordance with downregulation of CaSR mRNA expression (GdCl(3) + HGF: 1.46 ± 0.37, GdCl(3): 4.46 ± 0.62, P < 0.01). HGF exerts protective role in I/R-induced apoptosis at least in part by inhibiting CaSR mRNA expression along with promoting Bcl-2, suppressing Caspase-3 expression and stimulating PI3K phosphorylation signaling pathway.

Background The transforming growth factor β1 (TGFB1) +869T/C gene polymorphism has been suggested to be linked to susceptibility to essential hypertension (EH). Objective and Methods To investigate the relationship between TGFB1 +869T/C gene polymorphism and EH, 5 separate studies with 2,708 subjects in the Chinese population on the relation between TGFB1 +869T/ C gene polymorphism and EH were analyzed by meta-analysis. The random effect model was selected to calculate the pooled odds ratio (ORs) and its corresponding 95% confidence interval (95%). Results There was a significant association between TGFB1 +869T/C gene polymorphism and EH. The pooled OR for CC/TC+TT genotype was 2.50 (95% CI: 1.46-4.28, P heterogeneity <0.0001, p=0.0008). The pooled OR for the frequency of C allele was 1.43 (95% CI:1.18-1.73, P heterogeneity =0.02, p=0.0002). Conclusion The current meta-analysis suggested that C allele and CC genotype of TGFB1 +869T/C gene polymorphism might be related to the increased risk of EH in the Chinese population.

Background: The angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been suggested to influence susceptibility to essential hypertension (EH), but the results of many individual studies are conflicting. Aim and methods: To explore the relationship between the ACE gene I/D polymorphism and EH in the Chinese population, 67 separated studies were analyzed in a meta-analysis including 21058 participants. The electronic databases PubMed, Embase, Web of Science, China Biological Medicine Database and China National Knowledge Infrastructure were searched. The pooled odds ratio (ORs) and its corresponding 95% confidence interval were calculated by the random effects model. Results: In this ACE I/D gene polymorphism meta-analysis, the distribution of the D allele frequency was 0.45 for the EH group and 0.40 for the control group. The summary OR for the distribution frequency of D allele was 1.27 (5% confidence interval 1.17-1.37). The heterogeneity among the 67 studies was also significant (P < 0.00001, I2= 71.4%). There was a significant association between distribution frequency of the D allele and EH risk in Han, Kazakh, Tibetan, Zhuang and unclassified nationalities (P < 0.05). In contrast, in the national minorities, such as Mongolian, Uigur, Yi, Dongxiang, Yugu, Korean and Gamel, the association between distribution frequency of the D allele and EH risk was not significant (P > 0.05). Conclusions: In the whole Chinese population, the D allele was significantly linked with EH susceptibility. However, the relation between the I/D polymorphism and EH is still inconclusive in some national minorities and must await larger scale studies. © 2011 The Author. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.

Yu H.,Yancheng First Peoples Hospital | Yang W.,Nanjing Medical University
Biochemical and Biophysical Research Communications | Year: 2016

MiR-211 has strong inhibitive effects on melanoma cell growth, invasion and metastasis. However, how it is downregulated and whether other genes are involved its downstream regulation in melanoma are not clear. In this study, we firstly verified the expression of miR-211 in melanoma cell lines and observed that its downregulation is associated with increased DNMT1 expression. By performing qRT-PCR and MSP analysis, we confirmed that DNMT1 is negatively correlated with miR-211 expression and can modulate DNA methylation in the promoter region of miR-211. By performing bioinformatics analysis, we found that RAB22A is a possible target of miR-211, which has two broadly conversed binding sites with miR-211 in the 3'UTR. Following dual luciferase assay, qRT-PCR and western blot analysis confirmed the direct binding between miR-211 and RAB22A and the suppressive effect of miR-211 on RAB22A expression. Knockdown of RAB22A increased epithelial properties and impaired mesenchymal properties of the melanoma cells, suggesting that miR-211 modulates epithelial mesenchymal transition (EMT) of melanoma cells via downregulating RAB22A. In summary, the present study firstly demonstrated that DNMT1 mediated promoter methylation is a mechanism of miRNA suppression in melanoma and revealed a new tumor suppressor role of the miR-211 by targeting RAB22A in melanoma. The DNMT1/miR-211/RAB22A axis provides a novel insight into the pathogenesis of melanoma, particularly in the EMT process. © 2016 Elsevier Inc.

Zhang R.S.,Nanjing Medical University
Zhonghua nan ke xue = National journal of andrology | Year: 2010

To explore the contents of trace elements in the blood and seminal plasma of men and their correlation with semen parameters. We detected and analyzed the contents of calcium, magnesium, copper, zinc, iron and lead in the blood and semen of 113 men with the BH-5100 5-channel atomic absorption spectrometer, YY-1001 blood lead instrument and Weili color sperm automatic analyzer to investigate the correlation of the contents of trace elements with quality. The contents of lead, copper, zinc and iron in the blood were significantly correlated with those in the seminal plasma, but not the contents of calcium and magnesium. The contents of lead, copper, zinc, calcium, magnesium and iron in the blood were significantly different from those in the semen. In the seminal plasma, the content of calcium showed a significant positive correlation with sperm motility, linear motile sperm motility (LMSM), straight line velocity (VSL), curvilinear velocity (VCL), mean angle of deviation (MAD), active sperm density (ASD), average path velocity (VAP) and lateral head amplitude (ALH), while that of lead was negatively correlated with sperm motility, LMSM, ASD, motile sperm density (MSD) and linear motile sperm density (LMSD), and so was that of magnesium with sperm motility, LMSM and LMSD, and those of calcium, magnesium and iron with seminal pH. In the blood, the content of zinc was negatively correlated with sperm motility and LMSM, and so was that of magnesium with sperm motility, LMSM and VAP, while that of lead was positively correlated with ALH. The contents of trace elements in different body fluids are differently correlated with sperm quality.

Mao W.,Nanjing Medical University
Surgery today | Year: 2013

Non-small-cell lung cancer (NSCLC) confined to the lung is generally treated by surgical resection. The extent of resection is determined by the location of the tumor and the patient's pulmonary function. This report presents a successful lung autotransplantation in a man with NSCLC that could not tolerate pneumonectomy or sleeve lobectomy. Right upper and middle bilobectomies were performed, the right lower lobe was resected and retrograde perfusion of Raffinose low-potassium dextran solution (4 °C) was administered. The isolated lower lobe was reimplanted by anastomosis of the bronchus, pulmonary artery, and vein. The patient was cancer-free 1 year after the surgery. Lung autotransplantation can therefore be successfully performed for selected patients with central NSCLC.