Guangzhou, China
Guangzhou, China

Southern Medical University , formerly known as First Military Medical University, affiliated to the People's Liberation Army of China, is a Chinese institution of higher learning, located in Guangzhou, the capital city of Guangdong Province, China. It was founded in 1951 and became one of national key universities in 1979. Approved by the State Council and the Central Military Commission of the PLA, the university came under the jurisdiction of Guangdong Province in August 2004, whereupon it was renamed Southern Medical University.Southern Medical University is located at the foothills of the picturesque Baiyun Mountain in Guangzhou. The main campus, together with its south campus in the southern suburb of Guangzhou, covers an area of nearly one square kilometer. The university has been awarded the first-class garden-like university, for rows of green trees nourish and bouquets of flowers blossom on the campuses all throughout the year. Wikipedia.

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Chen D.-X.,Southern Medical University | Wu A.-G.,Southern Medical University
Chinese Journal of Cancer Prevention and Treatment | Year: 2016

OBJECTIVE: The insulin and insulin-like growth factor (IGF) signaling system is implicated in breast cancer biology including proliferation, differentiation, infiltration and metastasis, it provides new insights into the targeted therapy against breast cancer. This review focuses on the advances in breast cancer treatment targeting this system both in China and abroad. METHODS: All the references were searched in PubMed, ScienceDirect and Wanfang standards database through 1995. 10 to 2015. 10. The docuterm were “Insulin and insulin-like growth factor signaling system, breast cancer, targeted therapy”, and so on. There were 1431 English and 46 Chinese literatures. Inclusion criteria: (1) preclinical and clinical studies about IGF/insulin system and targeting therapy for breast cancer; (2) epidemiological surveys about IGF/insulin system and breast cancer risk; (3) researches about structure and signaling pathway of IGF/insulin system. Exclusion criteria: (1) Those exists problems in research designs or statistical methods; (2) Those has incomplete data or unclear results. Finally 67 papers were analyzed and reviewed. RESULTS: Circulating concentrations of IGF and its binding proteins (IGFBPs) are associated with an increased risk of breast cancer, and the expression of IGF-I receptors (IGF-1R) in breast cancer tissues are higher than those in normal healthy individuals. Lots of preclinical studies have demonstrated of the anti-tumor effect of the inhibitions which target the IGF, IGFBPs, IGF-1R, downstream signaling pathways of the IGF/insulin signaling system, or the combinations with related signaling systems. So far, several phase I~III trials that targeted the system showed evidences of response, while the others have not shown clear clinical benefit. These disappointing results may be due to the complication and variability of the IGF/insulin system. CONCLUSION: Targeting IGF/insulin system has become a new hot spot in breast cancer treatment, but more researches need to do about the mechanism of the system and better clinical application. © 2016, Editorial Board of Chinese Journal of Cancer Prevention and Treatment. All right reserved.

Li X.P.,Southern Medical University
Molecular cancer | Year: 2014

BACKGROUND: The molecular mechanisms underlying dysregulation of microRNAs have been documented in nasopharyngeal carcinoma (NPC). Our previous study demonstrated that plasma miR-124 was down-regulated in NPC using microarray analysis and quantitative PCR validation. Though growing studies showed that down-regulated miR-124 was closely related to tumourigenesis in various types of cancers, the role of miR-124 in NPC remains largely unknown.METHODS: The expression level of miR-124 was evaluated in NPC cell lines and patient specimens using quantitative reverse transcription-PCR (Real-time qPCR). The clinicopathological significance of the resultant data was later analyzed. Then, we explored the role of miR-124 in NPC tumorigenesis by in vitro and in vivo experiments. Homo sapiens forkhead box Q1 (Foxq1) was confirmed as a novel direct target gene of miR-124 by the dual-luciferase assay and western bolt.RESULTS: We found that miR-124 was commonly down-regulated in NPC specimens and NPC cell lines. The expression of miR-124 was inversely correlation with clinical stages and marked on T stages. Then, the ectopic expression of miR-124 dramatically inhibited cell proliferation, colony formation, migration and invasion in vitro, as well as tumor growth and metastasis in vivo. Furthermore, we identified Foxq1 as a novel direct target of miR-124. Functional studies showed that knockdown of Foxq1 inhibited cell growth, migration and invasion, whereas Foxq1 overexpression partially rescued the suppressive effect of miR-124 in NPC. In clinical specimens, Foxq1 was commonly up-regulated in NPC, and the level increased with clinical stages and T stages. Additionally, the level of Foxq1 was inversely correlated with miR-124.CONCLUSIONS: Our results demonstrate that miR-124 functions as a tumor-suppressive microRNA in NPC, and that its suppressive effects are mediated chiefly by repressing Foxq1 expression. MiR-124 could serve as an independent biomarker to identify patients with different clinical characteristics. Therefore, our findings provide valuable clues toward the understanding the of mechanisms of NPC pathogenesis and provide an opportunity to develop new effective clinical therapies in the future.

Han H.,Southern Medical University | Lopp L.,University of Illinois at Urbana - Champaign
Medical education online | Year: 2013

BACKGROUND: Electronic health records (EHRs) are structured, distributed documentation systems that differ from paper charts. These systems require skills not traditionally used to navigate a paper chart and to produce a written clinic note. Despite these differences, little attention has been given to physicians' electronic health record (EHR)-writing and -reading competence.PURPOSES: This study aims to investigate physicians' self-assessed competence to document and to read EHR notes; writing and reading preferences in an EHR; and demographic characteristics associated with their perceived EHR ability and preference.METHODS: Fourteen 5-point Likert scale items, based on EHR system characteristics and a literature review, were developed to measure EHR-writing and -reading competence and preference. Physicians in the midwest region of the United States were invited via e-mail to complete the survey online from February to April 2011. Factor analysis and reliability testing were conducted to provide validity and reliability of the instrument. Correlation and regression analysis were conducted to pursue answers to the research questions.RESULTS: Ninety-one physicians (12.5%), from general and specialty fields, working in inpatient and outpatient settings, participated in the survey. Despite over 3 years of EHR experience, respondents perceived themselves to be incompetent in EHR writing and reading (Mean = 2.74, SD = 0.76). They preferred to read succinct, narrative notes in EHR systems. However, physicians with higher perceived EHR-writing and -reading competence had less preference toward reading succinct (r= - 0.33, p<0.001) and narrative (r= - 0.36, p<0.001) EHR notes than physicians with lower perceived EHR competence. Physicians' perceived EHR-writing and -reading competence was strongly related to their EHR navigation skills (r=0.55, p<0.0001).CONCLUSIONS: Writing and reading EHR documentation is different for physicians. Maximizing navigation skills can optimize non-linear EHR writing and reading. Pedagogical questions remain related to how physicians and medical students are able to retrieve correct information effectively and to understand thought patterns in collectively lengthier and sometimes fragmented EHR chart notes.

Zhen W.,Southern Medical University | Lu C.,South China University of Technology | Ling Z.,Southern Medical University | Xuemin W.,Southern Medical University
Brain Research | Year: 2017

Paradoxical sleep is closely associated with depression, and brain monoamine oxidase A (MAOA) plays an important role in depression. However, the precise relationship between sleep and depression and the role of MAOA in this process remains unknown. Therefore, we established a paradoxical sleep deprivation model using the “multiple small platforms over water” protocol. Mice deprived of paradoxical sleep for 3 days showed no depressive-like behaviors; however, mice deprived of paradoxical sleep deprivation for 5 days (P5d) showed decreased locomotive activity in the first 3 days after P5d. Additionally, the P5d mice showed depressive-like behaviors one week after P5d, with a longer immobility time and a decreased sucrose preference rate. In addition, the levels of the MAOA protein and mRNA in the amygdala and hippocampus significantly increased. Furthermore, the immobility time and sucrose preference rate of P5d mice recovered when the mice were injected with phenelzine. The P5d mice displayed depressive-like behaviors, which were likely modulated by the MAOA levels in the amygdala and hippocampus. © 2017 Elsevier B.V.

Cai X.-J.,Southern Medical University | Li Z.,Southern Medical University | Chen W.-H.,Southern Medical University
Bioorganic and Medicinal Chemistry Letters | Year: 2017

Two tripodal squaramide conjugates having 4-(trifluoromethyl)phenyl and 3,5-bis(trifluoromethyl)phenyl substituents were synthesized and found to exhibit highly efficient transmembrane anion transport with the EC50 values being 0.14 and 0.75 mol%, respectively. Though one of them has been reported to act as a strong anion receptor, in particular for sulfate anions, these two compounds exhibit no significant selectivity with respect to the tested monovalent anions and a very low level of activity in the presence of sulfate anions. © 2017 Elsevier Ltd

Li Z.,Southern Medical University | Chen Y.,Southern Medical University | Yuan D.-Q.,Kobe Gakuin University | Chen W.-H.,Southern Medical University
Organic and Biomolecular Chemistry | Year: 2017

A dimeric 3α-hydroxy-7α,12α-diamino-5β-cholan-24-oate conjugate and its derivatives having alkyl chains of varying length from methyl to n-pentyl groups on the amido bonds were synthesized and fully characterized on the basis of NMR (1H and 13C) and ESI MS (LR and HR) data. Their transmembrane anion transport activities were investigated in detail by means of a chloride ion selective electrode technique and the pyranine assay. The data indicate that this set of compounds is capable of promoting the transmembrane transport of anions, presumably via an anion exchange process and a mobile carrier mechanism. Detailed kinetic analysis on the data obtained from both chloride efflux and pH discharge experiments reveals that an optimum log:P range may exist for the transport effectiveness in terms of both k2/Kdiss and EC50 values. The present finding highlights the importance of high anionophoric activity in clarifying the effect of lipophilicity on ion-transport effectiveness. © 2017 The Royal Society of Chemistry.

OBJECTIVE: To prepare a novel folate-targeted magnetic nanocomposites loaded with tissue facor pathway inhibitor 2 (TFPI-2) and cisplatin (CDDP) and to investigate its targeting ability and anti-tumor effect on nasopharyngeal carcinoma HNE-1 cells in vitro.METHODS: The copolymer folic acid-polyethylene glycol-polyethyleneimine (FA-PEG-PEI) was synthesized through amidation reaction, and then FA-PEG-PEI/ magnetic nanoparticles-CDDP/TFPI-2 (MNP-CDDP/TFPI-2) nanocomposites was obtained by electrostatic adsorption between TFPI-2 plasmid and magnetic nanoparticles loaded with CDDP (MNP-CDDP) with vortex FA-PEG-PEI. (1)H Nuclear Magnetic Resonance ((1)H NMR ) was used to determine if FA-PEG-PEI was synthesized. The particle size, zeta potential and morphology were detected by dynamic light scattering (DLS) and transmission electron microscope (TEM). The content of Fe and CDDP was measured by phenanthroline and o-phenylenediamine (OPDA) colourimetry. Agarose gel electrophoresis was used to analyze the binding ability of FA-PEG-PEI/MNP-CDDP to TFPI-2 plasmid. Molecular targeted uptake of FA-PEG-PEI/ MNP-CDDP/TFPI-2 coupling with green fluorescent protein (GFP) in NPC cells were observed by Prussian-blue iron staining and fluorescence microscope. The levels of TFPI-2 protein expression after transfection were evaluated by Western blot. The effects of nanocomposites on HNE-1 cells proliferation and apoptosis were measured with Cell Counting Kit-8(CCK-8) and flow cytometry.RESULTS: Special peak value of FA, PEG and PEI were showed on (1)H NMR spectrogram. The mean size and zeta potential of FA-PEG-PEI/MNP-CDDP/TFPI-2 were 141.1 nm and 21.5 mV. The nanocomposites showed a good monodispersity and an insufficient size uniformity under TEM. The content of Fe and CDDP were 116.2 μg/ml and 92.88 μg/ml, respectively. Agarose gel electrophoresis showed TFPI-2 could be encapsulated completely and protected from digestion of DNA enzyme as the mass ratio of FA-PEG-PEI/ MNP-CDDP and TFPI-2 plasmid was equal or higher than 1∶1. More blue-stained magnetic granulars and green fluorescence were seen in folate receptor (FR)-positive HNE-1 cells than in FR-negative CNE-2 (P<0.05) under microscope and fluorescence microscope. The level of TFPI-2 protein expression in HNE-1cells increased significantly after transfection by FA-PEG-PEI/ MNP-CDDP/TFPI-2, compared with other control groups (FA-PEG-PEI/MNP-CDDP group and TFPI-2 group), all P<0.05. The nanocomposites inhibitory effect on HNE-1 including cell growth inhibition rate (64.00%) and apoptosis rate (49.61%) were significantly higher than that in FA-PEG-PEI/MNP group (8.19%, 9.26%), FA-PEG-PEI/TFPI-2 group (40.35%, 19.85%) and FA-PEG-PEI/MNP-CDDP group(56.15%, 36.46%)(P<0.05).CONCLUSION: FA-PEG-PEI/MNP-CDDP/TFPI-2 nanocomposites was successfully synthesized using amidation and electrostatic adsorption technology and has a good molecular targeting and inhibitory effect on FR-positive HNE-1cells in vitro.

Huang Y.B.,Southern Medical University
Zhonghua yi xue za zhi | Year: 2016

OBJECTIVE: To investigate the characteristics of children male soccer players' ankle imaging features.METHODS: From October 2015 to February 2016, a total of 32 male children players of two soccer clubs in Guangzhou were enrolled in this study.The ages of all cases were from 10 to 14 years, average age was (11.3±0.9) years.A total of 15 male children in region ordinary primary and secondary school students were set as control group, ages were from 10 to 14 years, average age was (12.1±1.2) years. All objects' ankle were examined by X-ray for positive and lateral positions; routine CT scanning and then on the workstation restructuring for axial, coronal and sagittal slices; and examined by MR. MR scan was with special surface coil for ankle joint for horizontal axis T2WI; coronal T1WI; coronary proton density weighted imaging (PWI); sagittal T2WI with fat suppression; sagittal PWI with isotropic and fat suppression sequence of fast field echo. The ankle bone morphological structures were observed on X-ray; the ankle bone mineral density, cortical bone thickness and sesamoid bone quantity was being observed and measured on CT; and the tenosynovitis, Achilles tendinitis, synovitis, and cancellous bone edema signal were observed on MR.RESULTS: For study group, a total of 32 cases and 64 ankles joints were completed by X-ray, CT and MR examination.A total of 15 cases and 30 ankles joints were completed by X-ray in control group, 26 ankle joints were completed by CT scan and 22 ankle joints were completed by MR examination.X-ray examination showed there was no statistically significant difference between the two groups in ankle bone structure.CT showed that navicular bone CT value was (296±82) HU in research group and navicular bone CT value was (266±107) HU in control group, the difference was statistically significant (P=0.03). MR showed the incidence of diseases in research group that the tendon sheath peripheral inflammation was 92.2% (59/64), Achilles tendon lesions was 18.8%(12/64), edema of cancellous bone was 73.4% (47/64) , lateral malleous ligaments injuried was 43.8%(28/64), synovitis or effusion in posterior ankle was 87.5% (56/64). The incidence of diseases in control group was that tendon sheath peripheral inflammation was 31.8%(7/22), Achilles tendon lesions was 0/22, edema of cancellous bone was 0/22, lateral malleous ligaments injuried was 0/22, synovitis or effusion in posterior ankle was 54.5% (12/22). There was statistically significant difference between these two groups (all P<0.05).CONCLUSION: Compared with the control group, children's male soccer players ankle bone structure, bone cortex thickness and bone mineral density there were no obvious difference. In the tenosynovitis, Achilles tendinitis, synovitis, bone marrow edema, lateral malleous ligaments injuried were significantly higher than the control group.

Fang C.H.,Southern Medical University
Zhonghua wai ke za zhi [Chinese journal of surgery] | Year: 2016

Objective: To explore the value of near-infrared technology guided by indolecyanine green(ICG) in planning resection line and real-time surgical navigation in small liver cancer. Methods: From March to September 2015, 11 patients with hepatic tumors received hepatectomy were treated in First Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University.There were 5 male and 6 female patients with average age of (55±10)years (range 39-70 years). Among whom, there were 9 cases with hepatocellular carcinoma and 2 cases with colorectal cancer. A near-infrared light camera system was used to detect the liver surfaces before resection, and to plan resection line and surgical specimens. A student's t test was used to compare continuous parametric variables. Results: The ICG-fluorescent imaging and histological examination had been used in the 15 lesions of the 11 patients. Among the 15 lesions, 7 lesions were detected by visual inspections, palpation and ICG-fluorescent imaging, 6 lesions were identified only by ICG-fluorescent imaging, 2 lesions were detected only by ICG-fluorescent imaging after resection.Results of pathologic examination indicated that the total fluorescent type include 5 well differentiated hepatocellular carcinoma and 2 cirrhotic nodule; the partial fluorescent type include 3 moderately differentiated hepatocellular carcinomas and 1 well differentiated hepatocellular carcinomas; the rim fluorescent type included 2 liver metastatic carcinoma and 2 poorly differentiated hepatocellular carcinomas. The average diameter of the tumor size measured by CT was (1.7±0.2)cm, while the average diameter measured by ICG-fluorescent imaging was (1.7±0.3)cm(t=-0.188, P>0.05). Conclusion: Near-infrared technology guided by ICG has important value in planning resection line and real-time surgical navigation in small liver cancer.

Yu T.,Hong Kong University of Science and Technology | Guo W.,Hong Kong University of Science and Technology | Tian Y.,Hong Kong University of Science and Technology | Xu J.,Hong Kong University of Science and Technology | And 4 more authors.
Blood | Year: 2017

Macrophages are key components of the innate immune system and play pivotal roles in immune response, organ development, and tissue homeostasis. Studies in mice and zebrafish have shown that tissue-resident macrophages derived from different hematopoietic origins manifest distinct developmental kinetics and colonization potential, yet the genetic programs controlling the development of macrophages of different origins remain incompletely defined. In this study, we use zebrafish, where tissue-resident macrophages arise from the rostral blood island (RBI) and ventral wall of dorsal aorta (VDA), the zebrafish hematopoietic tissue equivalents to the mouse yolk sac and aorta-gonad-mesonephros for myelopoiesis, to address this issue. We show that RBI- and VDA-born macrophages are orchestrated by distinctive regulatory networks formed by the E-twenty-six (Ets) transcription factors Pu.1 and Spi-b, the zebrafish ortholog of mouse spleen focus forming virus proviral integration oncogene B (SPI-B), and the helix-turn-helix DNA-binding domain containing protein Irf8. Epistatic studies document that during RBI macrophage development, Pu.1 acts upstream of Spi-b, which, upon induction by Pu.1, partially compensates the function of Pu.1. In contrast, Pu.1 and Spi-b act in parallel and cooperatively to regulate the development of VDA-derived macrophages. Interestingly, these two distinct regulatory networks orchestrate the RBI- and VDA-born macrophage development largely by regulating a common downstream gene, Irf8. Our study indicates that macrophages derived from different origins are governed by distinct genetic networks formed by the same repertoire of myeloid-specific transcription factors. © 2017 by The American Society of Hematology.

Gao X.,Southern Medical University | Sun J.,Southern Medical University
Hormone and Metabolic Research | Year: 2017

Previous reports have shown that exercise improves serum leptin and adiponectin abnormalities in overweight and obese individuals; however, results to date are controversial. Here we performed a systematic review and meta-analysis of the available randomized controlled trials (RCTs) of the possible beneficial action of exercise on serum leptin and adiponectin levels in overweight and obese individuals. We searched PubMed, EMbase, The Cochrane Library, and the databases for relevant studies published between January 1980 and September 2015. Two independent reviewers extracted relevant data and assessed study quality and risk of bias. Data were pooled using a random-effects model for leptin and a fixed-effects model for adiponectin. Effect of size was expressed as mean difference (MD) with 95% confidence interval (CI). Heterogeneity was assessed (Cochran Q-statistic) and quantified (I 2). Twenty-eight RCTs (40 studies) were identified, of which 24 were on the effects of exercise on leptin (n=1 358) and 31 referred to changes in adiponectin (n=1 774). Our analysis revealed that exercise significantly reduced serum leptin (MD=−2.24 ng/ml; 95% CI, −3.26, −1.23; p<0.001) and increased adiponectin (MD=0.44 μg/ml; 95% CI, 0.13, 0.75; p=0.005) levels compared to no exercise as well as control (who were also overweight or obese). Exercise, particularly aerobic exercise, had a significant effect on serum leptin and a possible influence on adiponectin levels, suggesting its therapeutic implications. © Georg Thieme Verlag KGStuttgart · New York.

Liu Y.,Guangdong Medical University | Liang Y.,Guangdong Medical University | Zhang J.-F.,Chinese University of Hong Kong | Fu W.-M.,Southern Medical University
Experimental Cell Research | Year: 2017

MicroRNAs (miRNAs) belong to the family of small non-coding RNAs that mediate gene expression by post-transcriptional regulation. Increasing evidence have demonstrated that miR-133 is enriched in muscle tissues and myogenic cells, and its aberrant expression could induce the occurrence and development of cardiac disorders, such as cardiac hypertrophy, heart failure, etc. In this review, we summarized the regulatory roles of miR-133 in cardiac disorders and the underlying mechanisms, which suggest that miR-133 may be a potential diagnostic and therapeutic tool for cardiac disorders. © 2017.

Zhang X.,Peoples Hospital of Beijing University | Xu R.,Southern Medical University
Oncology Letters | Year: 2017

Glioma is the most common human brain cancer and has poor prognosis. Messenger RNA profiling identified that sineoculis homeobox homolog 1 (Six1) is dysregulated in glioma tumor progenitor cells from glial progenitor cells isolated from normal white matter. However, the expression and role of Six1 in glioma remains unclear. The purpose of the present study was to investigate the expression level of Six1 in glioma tissues and the association between Six1 expression and clinicopathological characteristics and prognosis of gliomas. The Six1 protein was detected by immunohistochemistry in 163 glioma tissues of distinct malignancy grades, and Kaplan-Meier survival analysis was performed to assess the prognosis of the patients. The Six1 protein was stained in 49.1% (80 out of 163) of the glioma tissues, including 34.2% of low-grade [World Health Organization (WHO) I/II] gliomas and 80.8% of high-grade (WHO III/IV) gliomas. Normal brain tissues rarely expressed the Six1 protein. In addition, Six1 expression was significantly associated with WHO grade (P<0.001). According to the log-rank test and Cox regression model, Six1 may be suggested as an independent prognostic factor, in addition to the WHO grade. Overall, Six1 protein expression varies between different grades of glioma and is associated with the WHO grade. Upregulation of Six1 is more frequent in high-grade glioma and is an independent prognostic factor of poor clinical outcome. © 2017, Spandidos Publications. All rights reserved.

Zhang L.,Guangzhou University | Yang M.,Southern Medical University | Lai W.,Southern Medical University
International Journal of Clinical and Experimental Pathology | Year: 2017

Rheumatoid arthritis is frequently complicated with respiratory failure, thus threatening patients' lives. Hypo-methylation of T cells plays a critical role in multiple diseases. DNMT1 is important for gene methylation and is the target gene of microRNA (miR)-126, which thus might regulate T cell gene methylation. This study, therefore, examined the expression of miR-126 during DNG hypo-methylation in T cells from rheumatoid arthritis patients, to illustrate the relationship between two factors. 33 rheumatoid arthritis patients complicated with respiratory failure were recruited based on ACR criteria, in parallel with 33 healthy individuals. 5 ml venous blood samples were collected to sort out T cells, whose RNA was extracted to quantify miR-126 and DNMT1 expression by qRT-PCR. Methylation test kit was used to reveal the change of methylation level of EGFL7 in T cells. T cell sorting had higher than 98% of purity in this study. Expression of miR-126 in study group was about 3.32 folds of control group, with significant difference (P < 0.05). DNMT1 expression was remarkably lower than control group (P < 0.05), and was negatively correlated with miR-126 expression (r=0.643, P=0.021). Methylation level of EGFL7 in disease group was significantly decreased compared to control group. Disease group showed lower DNA methylation level in T cells. In rheumatoid arthritis patients, miR-126 expression is negatively correlated with T cell methylation, probably via inhibition on DNMT1 expression after miR-126 up-regulation, causing hypo-methylation of T cell DNA. Elevated EGFL7 methylation further caused hypo-methylation of T cells via up-regulating miR-126.

Chakrabortti A.,Nanyang Technological University | Li J.,Southern Medical University | Liang Z.-X.,Nanyang Technological University
Genome Announcements | Year: 2016

Ochratoxin A (OTA) is a common mycotoxin that contaminates food and agricultural products. Sequencing of the complete genome of Aspergillus westerdijkiae, a major producer of OTA, reveals more than 50 biosynthetic gene clusters, including a putative OTA biosynthetic gene cluster that encodes a dozen of enzymes, transporters, and regulatory proteins. © 2016 Chakrabortti et al.

He Y.,Southern Medical University | Dong Z.,Southern Medical University | Xie G.,Southern Medical University | Zhou T.,Southern Medical University | Lu F.,Southern Medical University
Plastic and Reconstructive Surgery | Year: 2017

Background: Noninvasive external volume expansion device has been applied to stimulate nonsurgical breast enlargement in clinical settings. Although previous results demonstrate the capacity of external volume expansion to increase the number of adipocytes, this strategy alone is insufficient to reconstruct soft-tissue defects or increase breast mass. The authors combined a minimally invasive tissue dissection method with external volume expansion to generate large volumes of adipose tissue. Method: In vitro, various densities of adipose-derived stem cells were prepared to evaluate relations between cell contacts and cell proliferation. In vivo, dorsal adipose tissue of rabbits was thoroughly dissected and the external volume expansion device was applied to maintain the released state. External volume expansion without tissue dissection served as the control. Results: In the dissection group, the generated adipose tissue volume was much larger than that in the control group at all time points. A larger number of proliferating cells appeared in the dissection samples than in the control samples at the early stage after tissue dissection. At low cell density, adipose-derived stem cells displayed an increasing proliferation rate compared to high cell density. Protein expression analysis revealed that cell proliferation was mediated by a similar mechanism both in vivo and in vitro, involving the release of cell contact inhibition and Hippo/Yes-associated protein pathway activation. Conclusions: Adipose tissue dissection releases cell-to-cell contacts and induces adipose-derived stem cell proliferation. Preexpanded adipose-derived stem cells undergo adipogenesis under the adipogenic environment created by external volume expansion, leading to better adipose regeneration compared with the control. © 2017 by the American Society of Plastic Surgeons.

Yang C.,Southern Medical University | Lu W.,Southern Medical University
Chinese Journal of Interventional Imaging and Therapy | Year: 2016

Objective: To explore the changes of local biliary temperature and bile duct damage after catheter radiofrequency ablation (RFA) in ex-vivo porcine liver under different power parameters. Methods: Ten fresh ex-vivo porcine bile duct systmes (gallbladder and common bile duct preserved) filled with human bile were injected with contrast agent under DSA. Then, the RFA catheter (Habib™ EndoHPB) was inserted into the hilar biliary through the common bile duct. Ten groups of ablation parameters were conducted, i.e. 5 W (120 s), 6 W (120 s), 7 W (120 s), 8 W (120 s), 9 W (120 s), 10 W (120 s), 11 W (120 s), 12 W (120 s), 13 W (120 s), 14 W (120 s), the temperatures of distal radiofrequency pole and 1, 2 cm away from the pole were examined with temperature needles respectively under fluoroscopy. Pathology examinations were performed for evaluated damage of biliary and adjacent tissue. Results: After modeling on ex-vivo porcine liver filling with human bile, ten liver bile ducts were successfully ablated. The temperatures of ablation area were found to be gradually increasing with higher power (up to 90.3℃), while the temperatures of the other two sites were not rising obviously (28.4-40.2℃). Coagulation necrosis of the ablation bile duct area were observed, and no significant damage was detected in the bile duct and liver tissues which were 1, 2 cm away from the ablation area. Conclusion: The temperature of adjacent biliary slight rise without significant damage. Therefore, little effect of adjacent non-ablation biliary and liver tissue could be caused by bile heat conduction. Copyright © 2016 by the Press of Chinese Journal of Medical Imaging and Technology.

Huang W.,Southern Medical University | Zheng X.,U.S. Center for Disease Control and Prevention | Yang X.,Southern Medical University | Fan S.,Southern Medical University
Calcified Tissue International | Year: 2017

Saikosaponin-A (SA), a class of native compound with numerous biological activities, may exert protective effect against postmenopausal bone loss. However, it remains unknown whether SA regulates the osteogenic differentiation of bone marrow stromal cells (BMSCs) in the treatment and prevention of osteoporosis. In this study, BMSCs were treated with various concentrations of SA to stimulate osteogenic differentiation over a 14-day period. Additionally, a canonical ovariectomized (OVX) mouse model was used to evaluate the effect of 3-month SA treatment in preventing postmenopausal osteoporosis. In vitro, we found that SA promotes alkaline phosphatase activity/staining and Alizarin red assay, stimulated the expression of osteogenic markers, i.e., runt-related transcription factor 2 (Runx2), osterix, osteopontin, and osteocalcin (OCN) in BMSCs. In vivo, the trabecular number, trabecular thickness, and trabecular bone mineral density of the distal femoral metaphysis were significantly increased in OVX mice treated intraperitoneally with SA for 3 months compared with OVX mice that not treated with SA. Moreover, the expression of Runx2 and OCN in OVX + SA mice was significantly increased than that in OVX mice. Finally, we found that SA activated the WNT/β-catenin pathway and the expression of several downstream genes including T-cell factor-1 and lymphoid enhancer factor-1. Inhibition of WNT/β-catenin pathway by Dickkopf-related protein 1 blocked the positive role of SA on osteogenesis. Therefore, SA promoted the osteogenic differentiation of BMSCs through WNT/β-catenin signaling. © 2017 Springer Science+Business Media New York

Xiao N.,Southern Medical University | Li D.-R.,Southern Medical University | Wang Q.,Southern Medical University | Wang H.-J.,Southern Medical University
Journal of Forensic Sciences | Year: 2017

An elevated serum tryptase concentration is considered a specific marker for systemic mast cell activation, a central feature of anaphylaxis. However, in some cases of acute cardiovascular death, high concentrations of serum tryptase are also observed. We compared the postmortem serum tryptase concentrations in 74 cases assigned to the following four groups: anaphylactic deaths (Group A, n = 20), acute cardiac deaths (Group ACD, n = 30), acute dissecting aneurysm ruptures (Group ADA, n = 10), and controls (Group C, n = 14). Additionally, the cutoff between Group A and the other groups was calculated using receiver-operating characteristic (ROC) curve analysis. Tryptase concentrations were markedly elevated in Group A (p < 0.001), Group ACD (p = 0.015), and Group ADA (p = 0.005). The optimal cutoff was 43 ng/mL, the sensitivity was 90%, and the specificity was 98%. While elevated concentrations of tryptase were noted in practical autopsy cases, due attention should be paid to the differential diagnosis between anaphylactic and acute cardiovascular deaths. © 2017 American Academy of Forensic Sciences.

Zhang X.,Southern Medical University | Pan J.,Southern Medical University | Mo F.,Hezhou University
Journal of Electronic Materials | Year: 2017

A series of blue Na3Gd(BO3)2:Ce3+ and blue-to-green color-tunable Na3Gd(BO3)2:Ce3+,Tb3+ phosphors were synthesized by the solid-state method. The luminescence, concentration quenching and energy transfer (ET) process of Na3Gd(BO3)2:Ce3+,Tb3+ were investigated. Both Ce3+ and Tb3+ occupy the Gd3+ site in the Na3Gd(BO3)2 host. Na3Gd(BO3)2:Ce3+ exhibits strong ultraviolet absorption and broadband blue emission. The Ce3+ sensitization effect on Tb3+ has been verified by the variation of PL/PLE spectra, the Ce3+ decay lifetimes and the energy transfer efficiency of Na3Gd(BO3)2:Ce3+,Tb3+ phosphors. The maximum Ce3+–Tb3+ ET efficiency has been calculated to be 95%. The emitting color of the obtained phosphors can be modulated from blue (0.179, 0.204) through bluish-green (0.271, 0.391) to green (0.349, 0.551) by properly changing the ratio of Ce3+/Tb3+. © 2017 The Minerals, Metals & Materials Society

RATIONALE:: Childhood adiposity is associated with cardiac structure in later life, but little is known regarding to what extent childhood body weight affects adult left ventricular geometric patterns through adult body size and blood pressure (BP). OBJECTIVE:: Determine quantitatively the mediation effect of adult body weight and BP on the association of childhood BMI with adult left ventricular hypertrophy (LVH). METHODS AND RESULTS:: This longitudinal study consisted of 710 adults, age 26 to 48 years, who had been examined for BMI and BP measured 4 or more times during childhood and 2 or more times during adulthood, with a mean follow-up period of 28.0 years. After adjusting for age, race and sex, adult BMI had a significant mediation effect (76.4%, p<0.01) on the childhood BMI-adult LV mass index (LVMI) association. The mediation effects of adult systolic BP (SBP, 15.2%), long-term burden (12.1%) and increasing trends of SBP (7.9%) were all significant (p<0.01). Furthermore, these mediators also had significant mediation effects on the association of childhood BMI with adult LVH, eccentric and concentric hypertrophy. Importantly, the mediation effects of adult BMI were all significantly stronger than those of adult SBP on LVMI, LVH and LV remodeling patterns (p<0.01). Additionally, the mediation effect of SBP on concentric hypertrophy was significantly stronger than on eccentric hypertrophy (p<0.01). CONCLUSIONS:: These findings suggest that increased childhood BMI has long-term adverse impact on subclinical changes in adult cardiac structure, and early life excessive body weight and adult LVH are linked through later life excessive body weight and elevated BP. © 2017 American Heart Association, Inc.

BACKGROUND AND PURPOSE—: Elevated blood homocysteine concentration increases the risk of stroke, especially among hypertensive individuals. Homocysteine is largely affected by the methylenetetrahydrofolate reductase C677T polymorphism and folate status. Among hypertensive patients, we aimed to test the hypothesis that the association between homocysteine and stroke can be modified by the methylenetetrahydrofolate reductase C677T polymorphism and folic acid intervention. METHODS—: We analyzed the data of 20 424 hypertensive adults enrolled in the China Stroke Primary Prevention Trial. The participants, first stratified by methylenetetrahydrofolate reductase genotype, were randomly assigned to receive double-blind treatments of 10-mg enalapril and 0.8-mg folic acid or 10-mg enalapril only. The participants were followed up for a median of 4.5 years. RESULTS—: In the control group, baseline log-transformed homocysteine was associated with an increased risk of first stroke among participants with the CC/CT genotype (hazard ratio, 3.1; 1.1–9.2), but not among participants with the TT genotype (hazard ratio, 0.7; 0.2–2.1), indicating a significant gene–homocysteine interaction (P=0.008). In the folic acid intervention group, homocysteine showed no significant effect on stroke regardless of genotype. Consistently, folic acid intervention significantly reduced stroke risk in participants with CC/CT genotypes and high homocysteine levels (tertile 3; hazard ratio, 0.73; 0.55–0.97). CONCLUSIONS—: In Chinese hypertensive patients, the effect of homocysteine on the first stroke was significantly modified by the methylenetetrahydrofolate reductase C677T genotype and folic acid supplementation. Such information may help to more precisely predict stroke risk and develop folic acid interventions tailored to individual genetic background and nutritional status. CLINICAL TRIAL REGISTRATION—: URL: Unique identifier: NCT00794885. © 2017 American Heart Association, Inc.

Liao K.,Southern Medical University | Zeng Q.-L.,Southern Medical University
Chinese Journal of Interventional Imaging and Therapy | Year: 2015

Currently, foam sclerotherapy has been widely used in the treatment of varicose vein, it has the advantages of little trauma, rapid recovery, good efficacy and so on. In this article, the clinical application status of the foam sclerotherapy in the treatment of varicose vein of lower limbs and complication were reviewed. Copyright © 2015 by the Press of Chinese Journal of Medical Imaging and Technology.

This study aimed to assess distribution characteristics and digital typing of arteries supplying the extrahepatic bile duct for patients with biliary obstruction, and evaluate the three-dimensional (3D) model in surgical decision-making. Forty-one patients with biliary obstruction were retrospectively evaluated. Clinical data obtained by 64-slice multidetector CT angiography scanning were introduced into Medical Image Three-Dimensional Visualization System; then, 3D model of extrahepatic bile duct and its supplying arteries were reconstructed. Based on the 3D model, the origination and bifurcations of the bile duct artery were observed, and the digital types established. Afterwards, plans for preoperative procedures were formulated. Finally, postoperative observations were performed and the biliary complications recorded in detail. The 3D model clearly displayed the origin, course, and distribution of individualized arteries supplying the extrahepatic bile duct, as well as variations. According to 3D model characteristics, the digital types were established. Blood supply to the superior segment of the extrahepatic bile duct encompassed 6 (14.6%), 17 (41.5%), 12 (29.3%), and 6 (14.6%) cases of Types IA, IB, IC, and II, respectively; meanwhile, blood supply to the inferior segment comprised 13 (31.7%), 13 (31.7%), 4 (9.8%), 7 (17.0%), and 4 (9.8%) cases of Types IA, IB, IC, II, and III, respectively. This classification helped in preoperative surgical planning and corroborated intraoperative findings. No postoperative biliary complications were recorded. The 3D model reconstructed using Medical Image Three-Dimensional Visualization System displayed individualized anatomical structures of the extrahepatic bile duct and associated blood supplying arteries, and could contribute to preoperative surgical planning.

Yuan L.,Southern Medical University | Zhou C.,Guangdong Pharmaceutical University | Lu Y.,Southern Medical University | Hong M.,Southern Medical University | And 4 more authors.
Cancer Letters | Year: 2015

To investigate the clinicopathological significance and underlying mechanism of microRNA-29b (miR-29b) in colorectal cancer (CRC), the role of miR-29b was investigated using in vivo and in vitro assays. Luciferase reporter assays were conducted to determine the association between miR-29b and the insulin-like growth factor 1 (IGF1) 3' untranslated region (3'UTR). Chromatin immunoprecipitation (ChIP) assays were employed to assess the direct binding of interferon regulatory factor 1 (IRF1) to miR-29b. We found that interferon (IFN)-γ could induce miR-29b by recruiting IRF1 to binding sites in the miR-29b promoter. A low level of miR-29b was significantly associated with an aggressive phenotype. MiR-29b inhibited CRC cell growth and invasion. IGF1, an activator of PI3K/Akt signaling, was confirmed as a novel target of miR-29b. Moreover, miR-29b increased IRF1 expression, and the inhibition of miR-29b suppressed IFN-γ-induced apoptosis. We elucidated the potential signaling pathway, IFN-γ/IRF1/miR-29b/IGF1, and its implication for CRC tumorigenesis. A positive feedback loop between IRF1 and miR-29b may contribute to the sensitivity of CRC cells to IFN-γ. Targeting miR-29b may provide a strategy for blocking CRC growth and metastasis. © 2015 Elsevier Ireland Ltd.

Han H.,Southern Medical University
Medical Education Online | Year: 2013

Background: Electronic health records (EHRs) are structured, distributed documentation systems that differ from paper charts. These systems require skills not traditionally used to navigate a paper chart and to produce a written clinic note. Despite these differences, little attention has been given to physicians' electronic health record (EHR)-writing and -reading competence. Purposes: This study aims to investigate physicians' self-assessed competence to document and to read EHR notes; writing and reading preferences in an EHR; and demographic characteristics associated with their perceived EHR ability and preference. Methods: Fourteen 5-point Likert scale items, based on EHR system characteristics and a literature review, were developed to measure EHR-writing and -reading competence and preference. Physicians in the midwest region of the United States were invited via e-mail to complete the survey online from February to April 2011. Factor analysis and reliability testing were conducted to provide validity and reliability of the instrument. Correlation and regression analysis were conducted to pursue answers to the research questions. Results: Ninety-one physicians (12.5%), from general and specialty fields, working in inpatient and outpatient settings, participated in the survey. Despite over 3 years of EHR experience, respondents perceived themselves to be incompetent in EHR writing and reading (Mean =2.74, SD =0.76). They preferred to read succinct, narrative notes in EHR systems. However, physicians with higher perceived EHR-writing and -reading competence had less preference toward reading succinct (r= -0.33, p<0.001) and narrative (r= -0.36, p<0.001) EHR notes than physicians with lower perceived EHR competence. Physicians' perceived EHRwriting and - reading competence was strongly related to their EHR navigation skills (r =0.55, p<0.0001). Conclusions: Writing and reading EHR documentation is different for physicians. Maximizing navigation skills can optimize non-linear EHR writing and reading. Pedagogical questions remain related to how physicians and medical students are able to retrieve correct information effectively and to understand thought patterns in collectively lengthier and sometimes fragmented EHR chart notes. © 2013 Heeyoung Han and Lauri Lopp.

Zhou C.,Tongji University | Wu Y.-L.,Guangdong Academy of Medical science | Chen G.,Harbin Medical University | Feng J.,Jiangsu Province Cancer Hospital | And 19 more authors.
The Lancet Oncology | Year: 2011

Background: Activating mutations in EGFR are important markers of response to tyrosine kinase inhibitor (TKI) therapy in non-small-cell lung cancer (NSCLC). The OPTIMAL study compared efficacy and tolerability of the TKI erlotinib versus standard chemotherapy in the first-line treatment of patients with advanced EGFR mutation-positive NSCLC. Methods: We undertook an open-label, randomised, phase 3 trial at 22 centres in China. Patients older than 18 years with histologically confirmed stage IIIB or IV NSCLC and a confirmed activating mutation of EGFR (exon 19 deletion or exon 21 L858R point mutation) received either oral erlotinib (150 mg/day) until disease progression or unacceptable toxic effects, or up to four cycles of gemcitabine plus carboplatin. Patients were randomly assigned (1:1) with a minimisation procedure and were stratified according to EGFR mutation type, histological subtype (adenocarcinoma vs non-adenocarcinoma), and smoking status. The primary outcome was progression-free survival, analysed in patients with confirmed disease who received at least one dose of study treatment. The trial is registered at, number NCT00874419, and has completed enrolment; patients are still in follow-up. Findings: 83 patients were randomly assigned to receive erlotinib and 82 to receive gemcitabine plus carboplatin; 82 in the erlotinib group and 72 in the chemotherapy group were included in analysis of the primary endpoint. Median progression-free survival was significantly longer in erlotinib-treated patients than in those on chemotherapy (13.1 [95% CI 10.58-16.53] vs 4.6 [4.21-5.42] months; hazard ratio 0.16, 95% CI 0.10-0.26; p<0.0001). Chemotherapy was associated with more grade 3 or 4 toxic effects than was erlotinib (including neutropenia in 30 [42%] of 72 patients and thrombocytopenia in 29 [40%] patients on chemotherapy vs no patients with either event on erlotinib); the most common grade 3 or 4 toxic effects with erlotinib were increased alanine aminotransferase concentrations (three [4%] of 83 patients) and skin rash (two [2%] patients). Chemotherapy was also associated with increased treatment-related serious adverse events (ten [14%] of 72 patients [decreased platelet count, n=8; decreased neutrophil count, n=1; hepatic dysfunction, n=1] vs two [2%] of 83 patients [both hepatic dysfunction]). Interpretation: Compared with standard chemotherapy, erlotinib conferred a significant progression-free survival benefit in patients with advanced EGFR mutation-positive NSCLC and was associated with more favourable tolerability. These findings suggest that erlotinib is important for first-line treatment of patients with advanced EGFR mutation-positive NSCLC. Funding: F Hoffmann-La Roche Ltd (China); Science and Technology Commission of Shanghai Municipality. © 2011 Elsevier Ltd.

Li J.-W.,Southern Medical University | Li J.-W.,First Affiliated Hospital | Wu X.,Southern Medical University
European Review for Medical and Pharmacological Sciences | Year: 2015

OBJECTIVE: It has been shown that Mesenchymal stem cells (MSCs) could prevent or alleviate acute lung injury (ALI) when transplanted into lung; however, the mechanisms involved remains elusive.The study aimed to investigate the effect of MSCs in repairing alveolar fluid clearance (AFC) of alveolar type-II (AT-II) cells through paracrine factors. MATERIALS AND METHODS: Keratinocyte growth factor (KGF) concentration in the supernatant of MSC culture medium was measured, and MSCs in lung after intravenous administration was traced. Next, MSCs transfected with or without KGF SiRNA were injected intravenously into LPS-induced ALI rats. Histological change and wet/dry ratio were determined. AT-II cells were co-cultured with MSCs under different experimental situations to analyze the variation of α1 and β1 subunits of Na+-K+-ATPase in AT-II cells. RESULTS: LPS-induced ALI was characterized by the typical inflammatory infiltrates, interalveolar septal thickening and increased wet/dry ratio. MSC administration significantly reduced the injury, while MSCs with KGF knockdown did no show the same effect. In vitro study also confirmed that expressions of α1 and β1 subunit were up-regulated as impaired AT-II cells co-cultured with MSCs. Furthermore, expression of α1 subunit was down-regulated, while β1 subunit showed no apparent change as AT-II cells were co-cultured with MSCs that were transfected with KGF siRNA. CONCLUSIONS: AFC was impaired by inflammation insult. MSCs-derived KGF reduced the impaired AFC through up-regulated α1 subunit but not β1 subunit, which might provide a novel therapeutic strategy for ALI.

Wang Y.,Peking University | Liu Q.-F.,Southern Medical University | Xu L.-P.,Peking University | Liu K.-Y.,Peking University | And 6 more authors.
Blood | Year: 2015

The effects of HLA-identical sibling donor (ISD) hematopoietic stem cell transplantation (HSCT) on adults with intermediate- or high-risk acute myeloid leukemia (AML) in the first complete remission (CR1) are well established. Previous single-center studies have demonstrated similar survival after unmanipulated haploidentical donor (HID) vs ISD HSCT for hematologic malignancies. To test the hypothesis that haploidentical HSCT would be a valid option as postremission therapy for AML patients in CR1 lacking a matched donor, we designed a disease-specific, prospective, multicenter study. Between July 2010 and November 2013, 450 patients were assigned to undergo HID (231 patients) or ISD HSCT (219 patients) according to donor availability. Among HID and ISD recipients, the 3-year disease-free survival rate was 74% and 78% (P = .34), respectively; the overall survival rate was 79% and 82% (P = .36), respectively; cumulative incidences of relapse were 15% and 15% (P = .98); and those of the nonrelapse-mortality were 13% and 8% (P = .13), respectively. In conclusion, unmanipulated haploidentical HSCT achieves outcomes similar to those of ISD HSCT for AML patients in CR1. Such transplantation was demonstrated to be a valid alternative as postremission treatment of intermediate- or high-risk AML patients in CR1 lacking an identical donor. This trial was registered at as #ChiCTR-OCH-10000940. © 2015 by The American Society of Hematology.

Wang W.-J.,Southern Medical University | Wu S.-P.,Southern Medical University | Shi Y.-S.,Southern Medical University | Huang X.,Southern Medical University | And 2 more authors.
Cancer Research | Year: 2013

Radiotherapy is the most successful nonsurgical treatment for nasopharyngeal carcinoma (NPC). Despite this, the prognosis remains poor. Although NPCs initially respond well to a full course of radiation, recurrence is frequent. The cancer stem cell (CSC) hypothesis provides a framework for explaining the discrepancy between the response of NPC to therapy and the poor survival rate. In this study, a stem cell-like subpopulation (PKH26+) was identified in NPC cell lines using a label-retention technique. PKH26 + cells were enriched for clonogenicity, sphere formation, side-population cells, and resistance to radiotherapy. Using genomic approaches, we show that the proto-oncogene c-MYC (MYC) regulates radiotolerance through transcriptional activation of CHK1 (CHEK1) and CHK2 (CHEK2) checkpoint kinases through direct binding to the CHK1 and CHK2 promoters. Overexpression of c-MYC in the PKH26+ subpopulation leads to increased expression of CHK1 and CHK2 and subsequent activation of the DNA-damage-checkpoint response, resulting in radioresistance. Furthermore, loss of CHK1 and CHK2 expression reverses radioresistance in PKH26+ (c-MYC high expression) cells in vitro and in vivo. This study elucidates the role of the c-MYC-CHK1/CHK2 axis in regulating DNA-damage-checkpoint responses and stem cell characteristics in the PKH26+ subpopulation. Furthermore, these data reveal a potential therapeutic application in reversal of radioresistance through inhibition of the c-MYC-CHK1/CHK2 pathway. Copyright © 2013 American Association for Cancer Research.

Ping Y.,National University of Singapore | Ping Y.,Institute of Materials Research and Engineering of Singapore | Liu C.,National University of Singapore | Zhang Z.,Institute of Materials Research and Engineering of Singapore | And 4 more authors.
Biomaterials | Year: 2011

Two water-soluble chitosan- graft-(polyethylenimine-β-cyclodextrin) (CPC) cationic copolymers were synthesized via reductive amination between oxidized chitosan (CTS) and low molecular weight polyethylenimine-modified β-cyclodextrin (β-CD-PEI). The two polycations, termed as CPC1 and CPC2, were characterized by proton nuclear magnetic resonance spectroscopy, gel permeation chromatography, and elemental analysis. These polycations exhibited good ability to condense both plasmid DNA (pDNA) and small interfering RNA (siRNA) into compact and spherical nanoparticles. Gene transfection activity of both polymers showed improved performance in comparison with native CTS in HEK293, L929, and COS7 cell lines. Further investigation of the gene transfection mediated by CPC2/DNA complexes showed both time-dependent and dose-dependent in the tested cell lines, where the polymer showed higher level luciferase expression than commercially available branched PEI (25 kDa) under the condition of high dose or extended time. Gene silencing activity mediated by CPC2/siRNA against luciferase expression showed superior knockdown effect in HEK293 and L929 cell lines. In addition, both polymers exhibited much lower cytotoxicity than PEI (25 kDa) in HEK293, L929, and COS7 cell lines. More interestingly, the pendent β-CD moieties of CPC copolymers allowed the supramolecular PEGylation though self-assembly of adamantyl-modified poly(ethylene glycol) with the β-CD moieties. The supramolecular PEGylation of the polyplexes significantly improved their stability under physiological conditions. The supramolecular PEGylated polyplexes of CPC with pDNA showed decreased transfection efficiency in all tested cell lines. However, remarkably, the supramolecular PEGylated polyplexes with siRNA exhibited even higher silencing efficiency in HEK293 and L929 cells (up to 84%), comparable to commercial DharmaFECT. The interesting mechanism for the enhanced silencing efficiency was discussed. With the pendent β-CD moieties on CTS chains, the system is expected to be further modified via inclusion complexation between β-CD unit and guest molecules to serve as a multifunctional delivery system. © 2011 Elsevier Ltd.

Hall A.B.,Virginia Polytechnic Institute and State University | Hall A.B.,Fralin Life Science Institute | Basu S.,Fralin Life Science Institute | Jiang X.,Virginia Polytechnic Institute and State University | And 16 more authors.
Science | Year: 2015

Sex determination in the mosquito Aedes aegypti is governed by a dominant male-determining factor (M factor) located within a Y chromosome-like region called the M locus. Here, we show that an M-locus gene, Nix, functions as an M factor in A. aegypti. Nix exhibits persistent M linkage and early embryonic expression, two characteristics required of an M factor. Nix knockout with clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 resulted in largely feminized genetic males and the production of female isoforms of two key regulators of sexual differentiation: doublesex and fruitless. Ectopic expression of Nix resulted in genetic females with nearly complete male genitalia. Thus, Nix is both required and sufficient to initiate male development. This study provides a foundation for mosquito control strategies that convert female mosquitoes into harmless males.

Chen H.,U.S. Food and Drug Administration | Chen X.,Southern Medical University | Hu Y.,U.S. Food and Drug Administration | Yan H.,Sun Yat Sen University
Applied Microbiology and Biotechnology | Year: 2013

Human enteric viruses are inherently a group of viruses that confer similar or overlapping clinical symptoms and pose a challenge for correct etiological diagnosis. DNA microarray technology has emerged to be of major interest to detect broad range of viral pathogens including enteric viruses. However, this approach requires a relative large amount of target nucleic acid for hybridization analysis. This feature limits its further applicability. To address this challenge, we evaluated a novel single primer linear isothermal amplification (Ribo-SPIA) procedure for preparation of single-stranded cDNA (sscDNA) from minute amount of starting RNA for microarray-based simultaneous detection and identification of three major human enteric viruses including hepatitis A virus, norovirus, and coxsachievirus B2. We performed a series of tests using different amounts of input RNA ranging from 30 ng to 55 pg to assess amplification yield, reproducibility, analytical sensitivity, and fidelity. We demonstrated that as little as 55 pg of viral RNA could produce adequate material by Ribo-SPIA to enable successful identification by microarray analysis without compromising detection specificity. Pairwise comparison of technical replicates hybridized to the microarrays by regression analysis showed excellent reproducibility in the appropriate sensitivity range.We also showed that the use of sscDNA as labeled targets offered increased microarray detection accuracy over complementary RNA generated by traditional T7 in vitro transcription amplification method. © Springer-Verlag 2013.

Qin X.,Anhui Medical University | Huo Y.,Peking University | Xie D.,Southern Medical University | Hou F.,Southern Medical University | And 2 more authors.
Clinical Nutrition | Year: 2013

Background & aims: The efficacy of homocysteine-lowering therapy with folic acid to lower homocysteine levels in an effort to reduce cardiovascular disease (CVD) risk in patients with kidney disease remains inconclusive. We conducted a meta-analysis of relevant randomized trials to further examine this issue. Methods: This meta-analysis included 8234 patients with kidney disease from nine qualified randomized trials using folic acid therapy, and with CVD reported as one of the endpoints. Relative risk (RR) was used to measure the effect of folic acid supplementation on risk of CVD using a random effects model. Results: When pooling the nine randomized trials, folic acid therapy reduced the risk of CVD by 10%[U+FF08]RR=0.90; 95% CI:0.81-1.00, P=0.046). A greater beneficial effect was observed among those trials without a history of grain fortification with folic acid (0.82; 0.70-0.96, P=0.01), with lower percent baseline diabetes (<30% (median), 0.80; 0.65-0.99, P=0.04), and in patients with end-stage renal disease (ESRD) or advanced chronic kidney disease (ACKD) (0.85; 0.77-0.94, P=0.002). Furthermore, a meta-regression analysis suggested a positive dose-response relationship between percent baseline diabetes and log-RR for CVD risk associated with folic acid supplementation (P=0.007). Most importantly, even the inclusion of three subgroup results did not substantially affect the results (n=11032, RR: 0.93; 95% CI:0.87-0.99, P=0.03). Conclusions: Our meta-analysis indicates that folic acid supplementation may be effective for CVD prevention in patients with kidney disease, particularly in trials among patients without a history of grain fortification with folic acid, with lower percent baseline diabetes, and in patients with ESRD or ACKD. © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.

Wan L.,Southern Medical University | Geng J.,Southern Medical University | Wu C.-L.,Harvard University | Bai X.,Southern Medical University
Journal of Thoracic Oncology | Year: 2012

INTRODUCTION:: Lung cancer contains a small population of cancer stem cells that contribute to its initiation and progression. We investigated the biological function and clinical significance of aldehyde dehydrogenase 1A1 (ALDH1A1) in non-small-cell lung carcinoma (NSCLC). METHODS:: ALDH1A1 assay or small interfering RNA transfection was employed to isolate ALDH1A1+ cells or knock down ALDH1A1 expression in H2087 cells, respectively. Biological functions of ALDH1A1+ and ALDH1A1 silenced cells were investigated using in vitro and in vivo methods. ALDH1A1 expression was analyzed using immunohistochemistry on tissue microarrays with 179 lung cancer tissues and 26 normal lung tissues. RESULTS:: The abilities of clone formation, proliferation, cell growth, and migration were increased in ALDH1A1+ and ALDH1A1 silenced cells. ALDH1A1+ lung cancer cells initiated tumors that resembled the histopathologic characteristics and heterogeneity of the parental lung cancer cells in mice. The silencing of ALDH1A1 expression in H2087 lung cancer cells inhibited cell proliferation and migration significantly. ALDH1A1 was expressed in 42% of normal lung tissues (11 of 26), with strong expression in the basal cells and globular cells of the normal bronchus and weak expression in the alveolar epithelial cells. Compared with normal lung tissues, 45% of NSCLC samples (81 of 179) were read as positive for ALDH1A1. Positive ALDH1A1 expression was correlated with patients' smoking status (p = 0.022), lymph-node metastasis (p = 0.006), clinical stage (p = 0.004), and a decreased overall survival time (p < 0.001). Positive ALDH1A1 expression in lung cancer tissues was an independent prognostic factor for NSCLC (odds ratio = 5.232, p < 0.001). CONCLUSION:: Elucidating the biological functions of ALDH1A1 could be helpful in studying lung tumorigenesis and for developing new therapeutic approaches. Copyright © 2012 by the International Association for the Study of Lung Cancer.

Zhang Z.-X.,Institute of Materials Research and Engineering of Singapore | Ding N.-N.,Institute of Materials Research and Engineering of Singapore | Zhang W.-H.,Institute of Materials Research and Engineering of Singapore | Zhang W.-H.,Soochow University of China | And 6 more authors.
Angewandte Chemie - International Edition | Year: 2014

A 2D coordination polymer prepared with bulky diethylformamide solvates exhibits channels which allow dipyridyl bridging ligands to diffuse into the crystal lattice. The absorbed dipyridyls thread through the pores of one layer and substitute the surface diethylformamide molecules on the neighboring layers to stitch alternate layers to form flexible interpenetrated metal-orgaic frameworks. The threading process also results in exchange of the bulky diethylformamide solvates for aqua to minimize congestion and, more strikingly, forces the slippage of two-dimensional layers, while still maintaining crystallinity. All stitched up: Dipyridyl ligands were found to diffuse into the channels in the crystal lattice of a two-dimensional polymeric complex. The absorbed dipyridyls thread through the pores of one layer and substitute the surface solvent molecules on the neighboring layers to stitch alternate layers to form flexible interpenetrated metal-organic frameworks (see picture). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Yang M.-H.,Southern Medical University | Yu J.,Southern Medical University | Chen N.,Southern Medical University | Wang X.-Y.,Southern Medical University | And 3 more authors.
PLoS ONE | Year: 2013

Several studies have brought about increasing evidence to support the hypothesis that miRNAs play a pivotal role in multiple processes of carcinogenesis, including cell growth, apoptosis, differentiation, and metastasis. In this study, we investigated the potential role of miR-31 in colorectal cancer (CRC) aggressiveness and its underlying mechanisms. We found that miR-31 increased in CRC cells originated from metastatic foci and human primary CRC tissues with lymph node metastases. Furthermore, the high-level expression of miR-31 was significantly associated with a more aggressive and poor prognostic phenotype of patients with CRC (p < 0.05). The stable over-expression of miR-31 in CRC cells was sufficient to promote cell proliferation, invasion, and migration in vitro. It facilitated tumor growth and metastasis in vivo too. Further studies showed that miR-31 can directly bind to the 3'untranslated region (3'UTR) of SATB2 mRNA and subsequently repress both the mRNA and protein expressions of SATB2. Ectopic expression of SATB2 by transiently transfected with pCAG-SATB2 vector encoding the entire SATB2 coding sequence could reverse the effects of miR-31 on CRC tumorigenesis and progression. In addition, ectopic over-expression of miR-31 in CRC cells induced epithelial-mesenchymal transition (EMT). Our results illustrated that the up-regulation of miR-31 played an important role in CRC cell proliferation, invasion, and metastasis in vitro and in vivo through direct repressing SATB2, suggesting a potential application of miR-31 in prognosis prediction and therapeutic application in CRC. © 2013 Yang et al.

Mai X.,Southern Medical University | Luo C.,Southern Medical University | Ai F.,Liuhuaqiao Hospital | Chen Q.,Southern Medical University
Spine | Year: 2011

Study Design. A cross-sectional survey of 2083 schoolchildren. Objective. To investigate the prevalence of nonspecific low back pain (LBP) among schoolchildren aged between 10 and 18 years in China. Summary of Background Data. LBP have been a serious health problem in schoolchildren. On the basis of literature, the lifetime occurrence of nonspecific LBP in children and adolescents varies between 7% and 72%, but little is known about LBP among this demographic group in China. Methods. Schoolchildren aged 10 to 18 years were sampled from two grades in an elementary school and four grades in a secondary school. Participants were asked to fill in a questionnaire on LBP. The questionnaire addressed demographic items, anthropometric factors and characteristics of nonspecific LBP, such as frequency, duration, nature, pain scale. Nonspecific LBP is defined as the pain in the back from the 12th ribs to the buttock area without organic factors. A total of 2235 questionnaires were distributed, of which 2100 were answered, a response rate of 93.7%. Among those answers, 2083 (977 from male students and 1106 from female students) provided measurable data. Results. The occurrence of nonspecific LBP was high, with 29.1% students suffering from this condition in the past 3 months (24.7% in boys, 33.1% in girls). In addition, an increased occurrence was observed with age. The occurrences of LBP in 10 to 14 years and 15 to 18 years were 21.5% and 38.2%, respectively. In several aspects of LBP, statistically significant differences were observed between boys and girls, including the frequency of the pain (P = 0.003), the nature of the pain (P = 0.000), the likelihood of seeking for medical assistance (P = 0.007), the impact on normal daily life (P = 0.016), and the occurrence of LBP after bending over the desk for a period of time (P = 0.024). Female students had more frequent LBP and were less willing to see a physician. In addition, more female students (45/366) had LBP accompanied with radiating pain than male students (20/241). Conclusion. There is a high prevalence of LBP in Chinese schoolchildren. The occurrence of LBP increases with age in both sexes. LBP is significantly more prevalent in girls. © 2011, Lippincott Williams & Wilkins.

Aims: To examine the correlation between hepatoma-derived growth factor (HDGF) expression and clinicopathological data in nasopharyngeal carcinoma (NPC), including patient survival. Methods and results: Using real-time polymerase chain reaction (PCR) and Western blot, mRNA and protein expression of HDGF was detected in normal nasopharyngeal tissues, NPC tissues and cell lines. HDGF levels were determined further by an immunohistochemical analysis in a retrospective series consisting of 160 primary NPC tissues and 71 non-cancerous nasopharynx tissues. Overexpressed mRNA and HDGF protein was present in NPC. By immunohistochemical analysis, we found that 53.8% (86 of 160) and 19.4% (32 of 160) of NPC biopsy specimens showed higher HDGF expression of the nucleus and cytoplasm, respectively. Statistical analysis showed that the higher expression of nuclear HDGF was associated significantly with T stage (P=0.005) and clinical stage (P=0.038), but there was no association with lymph node (P=0.059) or distant metastasis (P=0.563). Patients with increased HDGF expression levels had poorer overall survival rates than those with low expression of HDGF levels (P=0.006). Multivariate analysis revealed that high expression of nuclear HDGF was an independent prognostic indicator of patient survival. Conclusions: Increased nuclear expression of HDGF is a potential unfavourable prognostic factor for patients with NPC. © 2011 Blackwell Publishing Limited.

Xia Y.,Southern Medical University | Cai S.,Southern Medical University | Liedtke W.,Duke University
American Journal of Physiology - Cell Physiology | Year: 2013

Transient receptor potential vanilloid 4 (TRPV4) is a mechanosensitive channel in pulmonary arterial smooth muscle cells (PASMCs). Its upregulation by chronic hypoxia is associated with enhanced myogenic tone, and genetic deletion of trpv4 suppresses the development of chronic hypoxic pulmonary hypertension (CHPH). Here we further examine the roles of TRPV4 in agonist-induced pulmonary vasoconstriction and in the enhanced vasoreactivity in CHPH. Initial evaluation of TRPV4-selective antagonists HC-067047 and RN-1734 in KCl-contracted pulmonary arteries (PAs) of trpv4-/- mice found that submicromolar HC-067047 was devoid of off-target effect on pulmonary vasoconstriction. Inhibition of TRPV4 with 0.5 μM HC-067047 significantly reduced the sensitivity of serotonin (5-HT)-induced contraction in wild-type (WT) PAs but had no effect on endothelin-1 or phenylephrine-activated response. Similar shift in the concentrationresponse curve of 5-HT was observed in trpv4-/- PAs, confirming specific TRPV4 contribution to 5-HT-induced vasoconstriction. 5-HT-induced Ca2+ response was attenuated by HC-067047 in WT PASMCs but not in trpv4-/- PASMCs, suggesting TRPV4 is a major Ca2+ pathway for 5-HT-induced Ca2+ mobilization. Nifedipine also attenuated 5-HT-induced Ca2+ response in WT PASMCs but did not cause further reduction in the presence of HC-067047, suggesting interdependence of TRPV4 and voltage-gated Ca2+ channels in the 5-HT response. Chronic exposure (3-4 wk) of WT mice to 10% O2 caused significant increase in 5-HT-induced maximal contraction, which was partially reversed by HC-067047. In concordance, the enhancement of 5-HT-induced contraction was significantly reduced in PAs of CH trpv4-/- mice and HC-067047 had no further effect on the 5-HT induced response. These results suggest unequivocally that TRPV4 contributes to 5-HT-dependent pharmaco-mechanical coupling and plays a major role in the enhanced pulmonary vasoreactivity to 5-HT in CHPH. © 2013 by the American Physiological Society.

Huang H.,Sun Yat Sen University | Li X.,Sun Yat Sen University | Zhu J.,Beijing Cancer Hospital | Ye S.,Sun Yat Sen University | And 8 more authors.
JAMA - Journal of the American Medical Association | Year: 2014

Importance: Hepatitis B virus (HBV) reactivation is a serious complication for patients with lymphoma treated with rituximab-containing chemotherapies, despite lamivudine prophylaxis treatment. An optimal prophylactic antiviral protocol has not been determined.Objective: To compare the efficacy of entecavir and lamivudine in preventing HBV reactivation in patients seropositive for the hepatitis B surface antigen with untreated diffuse large B-cell lymphoma receiving chemotherapy treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).Design, Setting, and Patients: Randomized, open-label, phase 3 study conducted from February 2008 through December 2012 at 10 medical centers in China. This study was a substudy of a parent study designed to compare a 3-week with a 2-week R-CHOP chemotherapy regimen for untreated diffuse large B-cell lymphoma. Patients enrolled in the parent study who were seropositive for the hepatitis B surface antigen and had normal liver function, serum HBV DNA levels of less than 103 copies/mL, and no prior antiviral therapy were randomized to entecavir (n = 61) or lamivudine (n = 60).Interventions: Daily entecavir (0.5mg) or lamivudine (100mg) beginning 1 week before the initiation of R-CHOP treatment to 6 months after completion of chemotherapy.Main Outcomes and Measures: The primary efficacy end pointwas the incidence of HBV-related hepatitis. The secondary end points included rates of HBV reactivation, chemotherapy disruption due to hepatitis, and treatment-related adverse events.Results: The date of last patient follow-up wasMay 25, 2013. Incidence of HBV-related hepatitis was significantly lower for the entecavir group vs the lamivudine group.Conclusions and Relevance: Among patients seropositive for the hepatitis B surface antigen with diffuse large B-cell lymphoma undergoing R-CHOP chemotherapy, the addition of entecavir compared with lamivudine resulted in a lower incidence of HBV-related hepatitis and HBV reactivation. If replicated, these findings support the use of entecavir in these patients.

Deng J.,Southern Medical University | Liu W.,Shenzhen University | Wang Y.,Peking University | Dong M.,Shenzhen University | And 2 more authors.
Journal of Molecular and Cellular Cardiology | Year: 2012

Polydatin (PD), a resveratrol glucoside, has recently been suggested to have cardioprotective effects against heart diseases, including ischemia-reperfusion injury and pressure-overload induced ventricular remodeling. However, the mechanisms are poorly understood. This study aims to investigate the direct effects of PD on cardiac Ca2+ handling and excitation-contraction (EC) coupling to explore the potential role of which in PD-mediated cardioprotection. We found that micromolar PD decreased action potential-elicited Ca2+ transient, but slightly increased cell shortening. The contradictory response could be attributed to PD increasing myofilament Ca2+ sensitivity. Exploring the activities of the two types of Ca2+ channels, L-type Ca2+ channels (LCCs) and ryanodine receptors (RyRs), reveals that PD dose-dependently decreased LCC current (ICa), but increased frequency of spontaneous Ca2+ sparks, the elementary Ca2+ releasing events reflecting RyR activity in intact cells. PD dose-dependently increased the gain of EC coupling. In contrast, PD dose-dependently decreased SR Ca2+ content. Furthermore, PD remarkably negated β-adrenergic receptor (AR) stimulation-induced enhancement of ICa and Ca2+ transients, but did not inhibit β-AR-mediated inotropic effect. Inhibition of nitric oxide synthase (NOS) with L-NAME abolished PD regulation of ICa and Ca2+ spark rate, and significantly inhibited the alteration of Ca2+ transient and myocyte contractility stimulated by PD. These results collectively indicate that PD modulated cardiac EC coupling mainly by inversely regulating LCC and RyR activity and increasing myofilament Ca2+ sensitivity through increasing intracrine NO, resulting in suppression of Ca2+ transient without compromising cardiac contractility. The unique regulation of PD on cardiac EC coupling and responsiveness to β-AR signaling implicates that PD has potential cardioprotective effects against Ca2+ mishandling related heart diseases. © 2012 Elsevier Ltd.

Psaltis A.J.,University of Adelaide | Li G.,Southern Medical University | Vaezeafshar R.,Stanford University | Cho K.-S.,Pusan National University | Hwang P.H.,Stanford University
Laryngoscope | Year: 2014

Objectives/Hypothesis: To compare three existing endoscopic scoring systems and a newly proposed modified scoring system for the assessment of patients with chronic rhinosinusitis (CRS). Study Design: Blinded, prospective cohort study. Methods: CRS patients completed two patient-reported outcome measures (PROMs) - the visual analogue scale (VAS) symptom score and the Sino-Nasal Outcome Test-22 (SNOT-22) - and then underwent a standardized, recorded sinonasal endoscopy. Videos were scored by three blinded rhinologists using three scoring systems: the Lund-Kennedy (LK) endoscopic score; the Discharge, Inflammation, Polyp (DIP) score; and the Perioperative Sinonasal Endoscopic score. The videos were further scored using a modified Lund-Kennedy (MLK) endoscopic scoring system, which retains the LK subscores of polyps, edema, and discharge but eliminates the scoring of scarring and crusting. The systems were compared for test-retest and inter-rater reliability as well as for their correlation with PROMs. Results: One hundred two CRS patients were enrolled. The MLK system showed the highest inter-rater and test-retest reliability of all scoring systems. All systems except for the DIP correlated with total VAS scores. The MLK was the only system that correlated with the symptom subscore of the SNOT-22 in both unoperated and postoperative patients. Conclusions: Modification of the LK system by excluding the subscores of scarring and crusting improves its reliability and its correlation with PROMs. In addition, the MLK system retains the familiarity of the widely used LK system and is applicable to any patient irrespective of surgical status. The MLK system may be a more suitable and reliable endoscopic scoring system for clinical practice and outcomes research. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Qin X.,Anhui Medical University | Huo Y.,Peking University | Langman C.B.,Northwestern University | Hou F.,Southern Medical University | And 4 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2011

Background and objectives: The efficacy of folic acid therapy to lower homocysteine (Hcy) levels in an effort to reduce cardiovascular disease (CVD) risk in patients with ESRD or advanced chronic kidney disease (ACKD; creatinine clearance, <30 ml/min) remains inconclusive. We conducted a meta-analysis of relevant randomized trials to further examine this issue. Design, setting, participants, & measurements: This meta-analysis included 3886 patients with ESRD/ACKD from seven qualified randomized trials using folic acid therapy and with CVD reported as one of the end points. Results: When pooling the seven trials, folic acid therapy reduced the risk of CVD by 15% (RR, 0.85; 95% CI, 0.76 to 0.96; P = 0.009). A greater beneficial effect was observed among those trials with a treatment duration >24 months (RR, 0.84; 95% CI, 0.72 to 0.98; P = 0.02), a decrease in Hcy level >20% (RR, 0.83; 95% CI, 0.73 to 0.95; P = 0.007), and no or partial folic acid fortification (RR, 0.80; 95% CI, 0.65 to 0.99; P = 0.04). The beneficial effect also was seen when Hcy levels decreased >20%, even in the presence of folic acid fortification (RR, 0.85; 95% CI, 0.73 to 0.99; P = 0.04). In the corresponding comparison groups, the estimated RRs were attenuated and insignificant. Conclusions: Folic acid therapy can reduce CVD risk in patients with ESRD/ACKD by 15%. A greater beneficial effect was observed among those trials with no or partial folic acid fortification or a decrease in Hcy level >20% regardless of folic acid fortification. Copyright © 2011 by the American Society of Nephrology.

Ye X.,Southern Medical University | Ye X.,Guangdong Pharmaceutical University | Fu J.,Southern Medical University | Fu J.,Guangdong Pharmaceutical University | And 3 more authors.
PLoS ONE | Year: 2013

Background: In previous meta-analyses, aspirin use has been associated with reduced risk of colorectal cancer. However, uncertainty remains on the exact dose-risk and duration-risk relationships. Methods: We identified studies by searching several English and Chinese electronic databases and reviewing relevant articles. The dose-response meta-analysis was performed by linear trend regression and restricted cubic spline regression. Subgroup analyses were conducted to explore possible heterogeneity among studies. Potential heterogeneity was calculated as Q statistic and I2 value. Publication bias was evaluated using funnel plots and quantified by the Begg's and Egger's test. Results: Twelve studies were included in this meta-analysis. An inverse association between aspirin use and colorectal cancer was observed in both the overall group (RR = 0.74, 95% CI 0.64-0.83 for aspirin dose; RR = 0.80, 95% CI 0.75-0.85 for frequency of aspirin use; RR = 0.75, 95% CI 0.68-0.81 for years of aspirin use) and subgroups stratified by sex and cancer site. The dose-response meta-analysis showed that there was a 20% statistically significant decreased risk of colorectal cancer for 325 mg aspirin per day increment, 18% decreased risk for 7 times aspirin per week increment and 18% decreased risk for 10 years aspirin increment. Conclusion: Long-term (>5 years), low-dose (75-325 mg per day) and regular aspirin use (2-7 times per week) can effectively reduce the risk of colorectal cancer. © 2013 Ye et al.

Liu F.,Southern Medical University | Liu Y.,Anhui Medical University | Wang H.-W.,Anhui Medical University
Chest | Year: 2014

BACKGROUND: Lung ultrasonography is useful for the diagnosis of pneumonia in children and adults. This study investigated the lung ultrasound findings in severe neonatal pneumonia. METHODS: From September 2012 to October 2013, 80 neonates admitted to Bayi Children's Hospital, affiliated with the Beijing Military General Hospital, were divided into two groups: 40 neonates with severe pneumonia according to their medical history, clinical manifestations, and chest radiograph findings and 40 neonates with no lung disease (control group). All subjects underwent bedside lung ultrasound examination in a quiet state. A single expert physician performed all ultrasound examinations. Findings of pleural line abnormalities, B lines, lung consolidation, air bronchograms, bilateral white lung, interstitial syndrome, lung sliding, and lung pulse were compared between the groups. RESULTS: The lung ultrasound findings associated with infectious pneumonia included large areas of lung consolidation with irregular margins and air bronchograms, pleural line abnormalities, and interstitial syndrome. A large area of lung consolidation with irregular margins had 100% sensitivity and 100% specificity for the diagnosis of neonatal pneumonia. CONCLUSIONS: Lung ultrasonography is a reliable tool for diagnosing neonatal pneumonia. It is suitable for routine use in the neonatal ICU and may eventually replace chest radiography and CT scanning. © 2014 American College of Chest Physicians.

Li L.,Southern Medical University | Zeng X.-Q.,Guangdong Provincial Corps Hospital | Li Y.-H.,Southern Medical University
Journal of Vascular and Interventional Radiology | Year: 2010

Purpose: To evaluate the safety and effectiveness of percutaneous sodium morrhuate foam sclerotherapy of varicoceles with the use of fluoroscopic tracing technique. Materials and Methods: At baseline and at 6-month follow-up, 58 patients with grade II/III left varicocele (mean age, 21.1 years; range, 19-25 y) with abnormal semen parameters underwent clinical assessment, Doppler ultrasonography, and semen analysis between September 2002 and January 2007. In all 58 cases, selective catheterization of the spermatic vein was performed with a right transfemoral approach. The standardized sclerosing foam was prepared with the Tessari method. Foam sclerotherapy was performed by the "filling-defects technique" under fluoroscopic guidance, with the sclerosing foam visualized as translucent filling defects in the internal spermatic vein filled with contrast medium during injection of the foam. Results: Technical success was achieved in all patients. Sodium morrhuate foam dose ranged from 2 mL to 8 mL (0.4-1.6 mL of solution) per patient, with an average dose of 5.3 mL (approximately 1.1 mL of solution). There were no major side effects or complications of the procedure. At 6-month follow-up, 53 of 58 patients (91.4%) reported disappearance of previous varicoceles and five had slight, asymptomatic residual varicoceles. Seminal parameters showed significant increases after treatment. No major complications occurred, and no recurrent/persistent varicoceles were found. Conclusions: Fluoroscopy-guided transcatheter foam sclerotherapy is a safe and effective approach for varicoceles, and the filling-defects technique under fluoroscopy is a feasible method for tracing the sclerosing foam. © 2010 SIR.

Song D.,Foshan Hospital of Traditional Chinese Medicine | Chen Z.,Southern Medical University | Song D.,Mengyin County Hospital
Journal of Neurosurgery: Spine | Year: 2014

Isthmic spondylolisthesis, which is demonstrated in 4%-6% of the general population, is one of the most common types of spondylolisthesis. However, double-level isthmic spondylolisthesis is extremely rare. Only a few reports have examined the outcomes of surgical treatment of double-level spondylolisthesis. The authors present an unusual case of double-level isthmic spondylolisthesis of the lumbar spine. The patient had low-back pain for 20 years and did not respond to conservative treatment. Radiographs revealed bilateral pars defects at L-4 and L-5. Grade 2 isthmic spondylolisthesis was present, both at L4-5 and at L5-S1. The patient underwent decompression, reduction, and posterior lumbar interbody fusion with autogenous bone chips from posterior decompression. At follow-up after 12 months, the patient was free of pain, slippage was corrected, and fusion was achieved. Posterior lumbar interbody fusion with posterior instrumentation and reduction may yield good functional short-term results for double-level spondylolisthesis. ©AANS, 2014.

Wang Y.-X.,Southern Medical University | Hu D.,Centers for Disease Control and Prevention | Yan X.,Southern Medical University
European Review for Medical and Pharmacological Sciences | Year: 2013

BACKGROUND AND OBJECTIVES: The role of Cyfra 21-1 in diagnosing squamous cell carcinoma of head and neck is not yet clear. The present meta-analysis aimed to establish the overall diagnostic accuracy of Cyfra 21-1 for head and neck squamous cell carcinoma. METHODS: After a systematic literature review and selection of English language studies, sensitivity, specificity and other measures of accuracy of Cyfra 21-1 in the diagnosis of head and neck squamous cell carcinoma were pooled using random effects models. Summary receiver operating characteristic curve was used to summarize overall diagnostic performance. Publication bias was examined by Deeks' funnel plot. RESULTS: Thirteen studies with 2269 subjects met the inclusion criteria for the analysis. The pooled sensitivity and specificity of Cyfra 21-1 for diagnosing head and neck squamous cell carcinoma were 0.51 (95%CI: 0.48-0.54) and 0.97 (95%CI: 0.95-0.98), respectively. The positive likelihood ratio was 10.11 (95%CI: 6.50-15.71), negative likelihood ratio was 0.52 (95%CI: 0.41-0.66) and diagnostic odds ratio was 25.60 (95%CI: 13.39-48.96). The area under the summary receiver operating characteristic curve was 0.94. CONCLUSIONS: The evidence from current meta-analysis suggests Cyfra 21-1 plays a valuable role in the diagnosis of head and neck squamous cell carcinoma with high specificity. The results of tumor marker assays should be interpreted in parallel with clinical findings and the results of conventional tests.

Li L.,Southern Medical University | Li L.,Guangdong Provincial Corps Hospital | Zeng X.-Q.,Guangdong Provincial Corps Hospital | Li Y.-H.,Southern Medical University
American Journal of Roentgenology | Year: 2010

OBJECTIVE. The purpose of this article is to describe a modified technique of using digital subtraction angiography guidance combined with the double-needle technique and the filling-defects technique for foam sclerotherapy of peripheral venous malformations. The short-term efficacy and safety of the technique were evaluated. MATERIALS AND METHODS. Fourteen patients with peripheral venous malformations were treated with foam sclerotherapy. Sclerosing foam was prepared using the Tessari method to mix room air with 5% sodium morrhuate in a 4:1 ratio. Percutaneous foam sclerotherapy of venous malformations under digital subtraction angiography guidance was performed using a combined technique modified with the double-needle technique and the filling-defects technique. Follow-up clinical and radiologic assessment and evaluation of patient satisfaction were performed to evaluate the end result. RESULTS. At a mean of 9.3 months (range, 6-12 months) after the last session, the overall outcome was rated as excellent improvement (i.e., clinical obliteration and asymptomatic) in four (28.6%) of 14 patients, good improvement (i.e., substantial improvement in size and symptoms of > 50%) in nine patients (64.3%), or moderate improvement (i.e., significant decrease in size and symptoms of ≤ 50%) in one patient (7.1%). No major complications occurred. CONCLUSION. Digital subtraction angiography-guided percutaneous foam sclerotherapy modified with the double-needle technique and the filling-defects technique is an alternative method with favorable short-term results for treating peripheral venous malformations. © American Roentgen Ray Society.

Zhou D.,Linyi Peoples Hospital | Yu H.,Southern Medical University | Yu H.,Guangdong Medical College | He F.,Linyi Peoples Hospital | And 7 more authors.
American Journal of Clinical Nutrition | Year: 2014

Background: Many prospective cohort studies have investigated the association between nut consumption and risk of coronary artery disease (CAD), stroke, hypertension, and type 2 diabetes (T2D). However, results have been inconsistent. Objective: We aimed to investigate the association between nut consumption and risk of CAD, stroke, hypertension, and T2D. Design: PubMed and EMBASE databases were searched up to October 2013. All prospective cohort studies of nut consumption and risk of CAD, stroke, hypertension, and T2D were included. Summary RRs with 95% CIs were estimated by using a fixed- or random-effects model. Results: A total of 23 prospective studies (9 studies for CAD, 4 studies for stroke, 4 studies for hypertension, and 6 studies for T2D) from 19 publications were included in the meta-analysis. There were 179,885 participants and 7236 CAD cases, 182,730 participants and 5669 stroke cases, 40,102 participants and 12,814 hypertension cases, and 342,213 participants and 14,400 T2D cases. The consumption of each 1 serving of nuts/d was significantly associated with incident CAD (RR: 0.81; 95% CI: 0.72, 0.91; P < 0.001) and hypertension (RR: 0.66; 95% CI: 0.44, 1.00; P = 0.049). However, there was no association between the consumption of each 1 serving of nuts/d and risk of stroke (RR: 0.90; 95% CI: 0.71, 1.14) or T2D (RR: 0.80; 95% CI: 0.57, 1.14). Conclusions: A higher consumption of nuts was associated with reduced risk of CAD and hypertension but not stroke or T2D. Large randomized controlled trials are warranted to confirm the observed associations. © 2014 American Society for Nutrition.

Wang Z.,Shanghai JiaoTong University | Cai H.,Xuhui Central Hospital | Lin L.,Southern Medical University | Tang M.,Shanghai JiaoTong University | Cai H.,Shanghai JiaoTong University
Pediatric Blood and Cancer | Year: 2014

Background: MicroRNA-214 (miR-214) expression has been demonstrated to be dysregulated in human malignancies and to play various roles in tumor progression. While previous study of miRNA expression profiling found that it was one of the most upregulated miRNAs in osteosarcoma signature, the potential role of miR-214 in osteosarcomas has been unclear. Therefore, the aim of this study was to investigate association of miR-214 expression with clinicopathologic features and prognosis in pediatric patients with osteosarcoma. Procedure: Quantitative real-time reverse transcriptase-polymerase chain reaction analysis was performed to detect expression levels of miR-214 in cancerous and noncancerous bone tissues from 92 children treated for primary osteosarcomas. Then, the clinical significance of miR-214 dysregulation in pediatric osteosarcomas was also determined. Results: Compared with noncancerous bone tissues, the expression levels of miR-214 were significantly upregulated in osteosarcoma tissues (P<0.001). High miR-214 expression occurred more frequently in osteosarcoma tissues with large tumor size (P=0.01), positive metastasis (P=0.001) and poor response to pre-operative chemotherapy (P=0.006). Moreover, high miR-214 expression was significantly associated with both shorter overall (P<0.001) and progression-free survival (PFS; P=0.001). Multivariate analysis by the Cox proportional hazard model further confirmed that high miR-214 expression was an independent prognostic factor of unfavorable survival in pediatric osteosarcoma (for overall survival: P=0.008; for PFS: P=0.01). Conclusion: Our data offer evidence that upregulated expression of miR-214 may be linked to tumor progression and adverse prognosis in pediatric osteosarcoma. Further investigation in prospective studies would appear warranted. © 2013 Wiley Periodicals, Inc.

Dai X.,Southern Medical University | Zeng Z.,Southern Medical University | Fu C.,People's Care | Zhang S.,People's Care | And 2 more authors.
Critical Care | Year: 2015

Introduction: Neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (Cys-C), and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) are novel diagnostic biomarkers of acute kidney injury (AKI). We aimed to determine the diagnostic properties of these biomarkers for detecting AKI in critically ill patients with sepsis. Methods: We divided 112 patients with sepsis into non-AKI sepsis (n = 57) and AKI sepsis (n = 55) groups. Plasma and urine specimens were collected on admission and every 24 hours until 72 hours and tested for NGAL, Cys-C, and TREM-1 concentrations. Their levels were compared on admission, at diagnosis, and 24 hours before diagnosis. Results: Both plasma and urine NGAL, Cys-C, and sTREM-1 were significantly associated with AKI development in patients with sepsis, even after adjustment for confounders by using generalized estimating equations. Compared with the non-AKI sepsis group, the sepsis AKI group exhibited markedly higher levels of these biomarkers at diagnosis and 24 hours before AKI diagnosis (P <0.01). The diagnostic and predictive values of plasma and urine NGAL were good, and those of plasma and urine Cys-C and sTREM-1 were fair. Conclusion: Plasma and urine NGAL, Cys-C, and sTREM-1 can be used as diagnostic and predictive biomarkers for AKI in critically ill patients with sepsis. © 2015 Dai et al.; licensee BioMed Central.

Tang M.,Shanghai JiaoTong University | Lin L.,Southern Medical University | Cai H.,Xuhui Central Hospital | Tang J.,Xuhui Central Hospital | Zhou Z.,Shanghai JiaoTong University
OncoTargets and Therapy | Year: 2013

Purpose: Microribonucleic acid (miRNA)-145 (miR-145) has been identified as a tumor suppressor in several types of human cancers. Especially, miR-145 expression has been found to be significantly decreased in osteosarcoma tissues, and enforced expression of this miRNA could inhibit invasion and angiopoiesis of osteosarcoma cells. However, its clinical significance in osteosarcoma is still unclear. Therefore, the aim of this study was to analyze the association of miR-145 expression with clinicopathologic features and prognosis in patients suffering osteosarcoma. Methods: miR-145 expression was detected by quantitative real-time reverse transcriptase polymerase chain reaction analysis using 166 pairs of osteosarcoma and noncancerous bone tissues. Then, the associations of miR-145 expression with clinicopathological factors or survival of patients suffering osteosarcoma were determined. Results: The expression levels of miR-145 in osteosarcoma tissues were significantly lower than those in corresponding noncancerous bone tissues (P < 0.0001). In addition, miR-145 downregulation more frequently occurred in osteosarcoma specimens with advanced clinical stage (P = 0.003) and positive distant metastasis (P = 0.008). Moreover, the univariate analysis demonstrated that osteosarcoma patients with low miR-145 expression had poorer overall (P = 0.003) and disease-free survival (P < 0.001). Furthermore, the multivariate analysis identified low miR-145 expression as an independent prognostic factor for both overall (P = 0.01) and disease-free survival (P = 0.008). Conclusion: For the first time, the current data offer convincing evidence that the downregulation of miR-145 may be associated with tumor aggressiveness and tumor metastasis of osteosarcoma, and that this miRNA may be an independent prognostic marker for osteosarcoma patients. © 2013 Tang et al, publisher and licensee Dove Medical Press Ltd.

Zhang J.,Southern Medical University | Chen Z.,Southern Medical University | Zheng J.,Southern Medical University | Breusch S.J.,Royal Infirmary | Tian J.,Southern Medical University
Archives of Orthopaedic and Trauma Surgery | Year: 2015

Introduction: Venous thromboembolism (VTE) is a common complication after total hip arthroplasty (THA) or total knee arthroplasty (TKA) and may be the cause for a secondary PE and associated morbidity/mortality. We performed a systematic literature review of risk factors and risk reduction of VTE after THA or TKA. Materials and methods: A systematic search of PubMed database, the Cochrane Library, OVID MEDLINE and American Academy of Orthopaedic Surgeons (AAOS), without restriction of publication data and language, was conducted. We performed a meta-analysis of ten factors for VTE after THA or TKA. Four authors independently assessed data extraction and quality of the studies using the Newcastle-Ottawa Scale (NOS) as quality assessment tool. Assessment of heterogeneity and analysis of data were operated by Review Manager 5.2.9. Results: Fourteen retrospective case–control or prospective cohort studies, which included 18,075 patients who developed VTE after THA or TKA of a total of 1,723,350 cases, were selected. Our results demonstrated that, among all ten factors investigated, 3 main risk factors were significantly associated with VTE after THA or TKA: history of VTE (RR > 10.6), varicose vein (RR > 2.7) and congestive cardiac failure (RR 2). There was also an increase of VTE risk ranging from 8 to 30 % for female gender < age (≥80) < hypertension < (active) cancer < obesity (BMI ≥ 30) < (black) race. Data analysis revealed that diabetes mellitus had no significant relationship with VTE after THA or TKA. Conclusions: This study highlighted the role of nine significant risk factors in the development of VTE after THA or TKA. Among all risk factors, history of VTE seems the one main indication for more potent anticoagulation. All other risk factors need to be considered and discussed with patients individually and balanced against the risk of bleeding and infection. Individual patient risk assessment, rather than a “blanket policy”, is considered the best management strategy before deciding on the type of chemical prophylaxis. © 2015, Springer-Verlag Berlin Heidelberg.

Min D.,Shanghai JiaoTong University | Lv X.-B.,Sun Yat Sen University | Wang X.,Sun Yat Sen University | Zhang B.,Sun Yat Sen University | And 3 more authors.
British Journal of Cancer | Year: 2013

Background: NKG2D recognises several ligands, including polymorphic major histocompatibility complex class I chain-related chain-related proteins A and B (MICA/B) and unique long 16-binding proteins (ULBPs). These ligands are present on cancer cells and are recognised by NKG2D in a cell-structure-sensing manner, triggering natural killer (NK) cell cytotoxicity. However, the mechanisms that control the expression of NKG2D ligands in malignant cells are poorly understood. 1-α,25-Dihydroxyvitamin D3 (1,25(OH)2D3) was recently shown to enhance the susceptibility of melanoma cells to the cytotoxicity of NK cells. However, the function of 1,25(OH)2D3 in other cancers and its potential mechanisms of action remain unknown. Methods: The expression levels of miR-302c and miR-520c in Kasumi-1, K562, MCF7 and MDA-MB-231 cells were evaluated using quantitative real-time PCR. The targets of miR-302c and miR-520c were confirmed by luciferase reporter assay. The killing effects of NK92 cells against Kasumi-1, K562, MCF7 and MDA-MB-231 cells were examined using the CytoTox 96 Non-Radioactive Cytotoxicity Assay. The levels of cytokines IFN-γ and granzyme B, which indicate the activation of NK cells, were also measured by enzyme-linked immunosorbent assay.Results:Treatment with 1,25(OH)2D3 enhanced the susceptibility of both the haematological tumour cell line Kasumi-1 and solid tumour cell line MDA-MB-231 to NK92 cells. miR-302c and miR-520c expression was induced, and their levels inversely correlated with the levels of NKG2D ligands MICA/B and ULBP2 upon 1,25(OH)2D3 treatment. A luciferase reporter assay revealed that miR-302c and miR-520c directly targeted the 3′-UTRs of MICA/B and ULBP2 and negatively regulated the expression of MIA/B and ULBP2. Moreover, upregulation of miR-302c or miR-520c by transfection of their mimics remarkably reduced the viability of Kasumi-1 cells upon NK cell co-incubation. By contrast, the suppression of the activity of miR-302c or miR-520c by their respective antisense oligonucleotides improved the resistance of Kasumi-1 cells to NK cells. Conclusion: 1,25(OH)2D3 facilitates the immuno-attack of NK cells against malignant cells partly through downregulation of miR-302c and miR-520c and hence upregulation of the NKG2D ligands MICA/B and ULBP2. © 2013 Cancer Research UK. All rights reserved.

Yang R.,South China University of Technology | Yang W.,Southern Medical University | Chen Y.,Chinese Academy of Engineering | Chen Y.,Shanghai JiaoTong University | Wu X.,South China University of Technology
Journal of Lightwave Technology | Year: 2011

A three-dimensional (3-D) thermogram can provide spatial information; however, it is rarely applied because it lacks an accurate method in obtaining the intrinsic and extrinsic parameters of an infrared (IR) camera. Conventional methods cannot be used for such calibration because an IR camera cannot capture visible calibration patterns. Therefore, in the current study, a trinocular vision system composed of two visible cameras and an IR camera is constructed and a calibration board with miniature bulbs is designed. The two visible cameras compose a binocular vision system that obtains 3-D information from the miniature bulbs while the IR camera captures the calibration board to obtain the two dimensional subpixel coordinates of miniature bulbs. The corresponding algorithm is proposed to calibrate the IR camera based on the gathered information. Experimental results show that the proposed calibration can accurately obtain the intrinsic and extrinsic parameters of the IR camera, and meet the requirements of its application. © 2011 IEEE.

Cai H.,Shanghai JiaoTong University | Lin L.,Southern Medical University | Cai H.,Xuhui Central Hospital | Tang M.,Shanghai JiaoTong University | Wang Z.,Shanghai JiaoTong University
Medical Oncology | Year: 2013

MicroRNA-210 (miR-210) plays important roles in the regulation of cell growth, angiogenesis, and apoptosis in different cancer type. Previous study of miRNA expression profiling found that miR-210 was significantly elevated in osteosarcoma samples. However, its roles in this disease have not been fully elucidated. Thus, the aim of this study was to investigate the association of miR-210 expression with clinicopathologic features and prognosis in patients with osteosarcomas. Quantitative real-time reverse transcriptase-polymerase chain reaction analysis was performed to detect the expression level of miR-210 in cancerous and noncancerous bone tissues from 92 children treated for primary osteosarcomas. MiR-210 expression was significantly increased in osteosarcoma tissues compared with that in corresponding noncancerous bone tissues (P < 0.001). In addition, miR-210 upregulation more frequently occurred in osteosarcoma tissues with large tumor size (P = 0.02), poor response to preoperative chemotherapy (P = 0.008), and positive metastasis (P = 0.01). Moreover, miR-210 upregulation was associated with significantly decreased overall survival (P = 0.007) and progression-free survival (P = 0.01). In the Cox proportional hazard model, it was confirmed that its expression in the biopsy samples was an independent prognostic factor of unfavorable survival in osteosarcoma (for overall survival: P = 0.01; for progression-free survival: P = 0.02). These findings suggested that miR-210 upregulation showed a strong correlation with tumor aggressive progression of pediatric osteosarcoma and could help prognostic screening of patients with this malignancy. © 2013 Springer Science+Business Media New York.

Wang H.B.,Shanghai JiaoTong University | Jiang Z.B.,Southern Medical University | Li M.,Shanghai JiaoTong University
Pathology and Oncology Research | Year: 2014

To identify the typically expressed miRNAs in squamous cell carcinoma (SCC) and adenocarcinoma (ADC) of esophagus cancer and their target genes, and explore the related functions and pathways, providing potential biomarkers for esophageal carcinoma diagnosis and treatment. Gene expression profile GSE13937 was downloaded from Gene Expression Omnibus database which includes 152 samples, paired non-cancerous and cancerous, 44 SCC cases and 32 ADC cases; the differentially expressed miRNAs were identified with limma packages in R language after the data were normalized. Selected differentially expressed miRNAs were further analyzed using bioinformatics methods. Firstly, verified targets of miRNAs in two miRNA databases: miRecods and miRTarBase were integrated to select the targets genes of differentially expressed miRNAs. Next, String software was used to construct the target genes interaction network. Finally, function and pathway enrichment analysis of genes in the interaction network was carried out with Gestalt software. Up-regulated hsa-miR-21 and down-regulated hsa-miR-203 were identified by comparing normal and cancer tissue samples, and the targets genes regulated by these two miRNAs were most significantly related to cell cycle function and pathway, especially in the phase of G1/S. The two differentially expressed miRNA: hsa-miR-21 and hsa-miR-203 provide evidence for early diagnosis and treatment of esophageal carcinoma. The functions and pathways of target genes shows that deep understanding of cell cycle G1/S will help to illustrate the relationship between cell cycle regulation and pathogenesis of esophageal cancer. © 2014 Arányi Lajos Foundation.

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

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

Jin H.,Hong Kong University of Science and Technology | Li L.,Hong Kong University of Science and Technology | Xu J.,Hong Kong University of Science and Technology | Zhen F.,Hong Kong University of Science and Technology | And 5 more authors.
Blood | Year: 2012

Proper cell fate choice in myelopoiesis is essential for generating correct numbers of distinct myeloid subsets manifesting a wide spectrum of subset-specific activities during development and adulthood. Studies have suggested that myeloid fate choice is primarily regulated by transcription factors; however, new intrinsic regulators and their underlying mechanisms remain to be elucidated. Zebrafish embryonic myelopoiesis gives rise to neutrophils and macrophages and represents a promising system to derive new regulatory mechanisms for myeloid fate decision in vertebrates. Here we present an in vivo study of cell fate specification during zebrafish embryonic myelopoiesis through characterization of the embryos with altered Pu.1, Runx1 activity alone, or their combinations. Genetic analysis shows that low and high Pu.1 activities determine embryonic neutrophilic granulocyte and macrophage fate, respectively. Inactivation and overexpression of Runx1 in zebrafish uncover Runx1 as a key embryonic myeloid fate determinant that favors neutrophil over macrophage fate. Runx1 is induced by high Pu.1 level and in turn transrepresses pu.1 expression, thus constituting a negative feedback loop that fashions a favorable Pu.1 level required for balanced fate commitment to neutrophils versus macrophages. Our findings define a Pu.1-Runx1 regulatory loop that governs the equilibrium between distinct myeloid fates by assuring an appropriate Pu.1 dosage.

Li X.,Beihang University | Liu H.,Beihang University | Niu X.,Beihang University | Yu B.,Southern Medical University | And 4 more authors.
Biomaterials | Year: 2012

Carbon nanotubes (CNTs), one of the most concerned nanomaterials, with unique electrical, mechanical and surface properties, have been shown suitable for biomedical application. In this study, we evaluated attachment, proliferation, osteogenic gene expression, ALP/DNA, protein/DNA and mineralization of human adipose-derived stem cells cultured . in vitro on multi-walled carbon nanotubes (MWNTs) and graphite (GP) compacts with the same dimension. Moreover, we assessed the effect of these two kinds of compacts on ectopic bone formation . in vivo. First of all, higher ability of the MWNTs compacts to adsorb proteins, comparing with the GP compacts, was shown. During the conventional culture, it was shown that MWNTs could induce the expression of ALP, cbfa1 and COLIA1 genes while GP could not. Furthermore, alkaline phosphatase (ALP)/DNA and protein/DNA of the cell on the MWNTs compacts, was significantly higher than those of the cells on the GP compacts. With the adsorption of the proteins in culture medium with 50% fetal bovine serum (FBS) in advance, the increments of the ALP/DNA and protein/DNA for the MWNTs compacts were found respectively significantly more than the increments of those for the GP compacts, suggesting that the larger amount of protein adsorbed on the MWNTs was crucial. More results showed that ALP/DNA and protein/DNA of the cells on the two kinds of compacts pre-soaked in culture medium having additional rhBMP-2 were both higher than those of the cells on the samples re-soaked in culture medium with 50% FBS, and that those values for the MWNTs compacts increased much more. Larger mineral content was found on the MWNTs compacts than on the GP compacts at day 7. . In vivo experiment showed that the MWNTs could induce ectopic bone formation in the dorsal musculature of ddy mice while GP could not. The results indicated that MWNTs might stimulate inducible cells in soft tissues to form inductive bone by concentrating more proteins, including bone-inducing proteins. © 2012 Elsevier Ltd.

He S.-J.,Southern Medical University | Han J.-F.,Beijing Institute of Microbiology and Epidemiology | Ding X.-X.,Southern Medical University | Wang Y.-D.,Southern Medical University | Qin C.-F.,Beijing Institute of Microbiology and Epidemiology
International Journal of Infectious Diseases | Year: 2013

Background: Hand, foot, and mouth disease (HFMD) is an acute viral disease caused by human enteroviruses, especially human enterovirus 71 (HEV71) and coxsackievirus A16 (CVA16), and mainly affects infants and young children. After the outbreak in 2008 in Fuyang, China, HFMD was classified as a category C notifiable infectious disease by the Ministry of Health of China. Methods: In this study, we report the epidemiologic and clinical manifestations of HFMD in Guangdong Province, China in 2010, and characterize HEV71 and CVA16 isolated from clinical specimens. Results: Among the 542 HFMD patients, 495 (91.3%) were positive for enterovirus as detected by real-time reverse transcriptase PCR; 243 were positive for HEV71 (49.1%, 243/495) and 114 were positive for CVA16 (23.0%, 114/495). Most of the affected children were aged 5 years or under (93.7%, 508/542). Phylogenetic analyses of VP1 gene sequences showed that the HEV71 isolates belonged to C4a subgenotype, and CVA16 isolates belonged to B1 genotype. Conclusions: Our results demonstrate that HEV71 and CVA16 are the primary causative agents responsible for HFMD in Guangdong Province, and their co-circulation poses a potential risk to public health. © 2013 International Society for Infectious Diseases.

Tan G.,Southern Medical University | Zeng B.,University of South China | Zhi F.-C.,Southern Medical University
European journal of cell biology | Year: 2015

Human enteric α-defensins (HD5 and HD6), major antimicrobial peptides produced by Paneth cells in the intestine, play important roles in intestinal innate immunity. Since their expression is decreased in Crohn's disease (CD), with decreased expression being more pronounced in the presence of NOD2 mutations, it would be extremely interesting to investigate the mechanism by which NOD2 may regulate expression of human enteric α-defensins. Here we show that although NOD2 by itself can slightly up-regulate expression of enteric α-defensins mainly through activation of the NF-κB pathway, it can strongly down-regulates their expression during differentiation of the Paneth cell lineage mainly by inhibiting activation of the MAPK pathway. Since NOD2 is over-expressed in CD and mutant NOD2 cannot result in NF-κB activity, our finding can provide an explanation of the previous observation showing decreased expression of human enteric α-defensin in CD and even more so in the presence of NOD2 mutations. In addition, this finding provides a new view on the function of NOD2 in regulating intestinal innate immunity. Copyright © 2014 Elsevier GmbH. All rights reserved.

Naam N.H.,Southern Medical University | Nemani S.,Southern Illinois Hand Center
Orthopedic Clinics of North America | Year: 2012

Radial tunnel syndrome is a pain syndrome resulting from compression of the posterior interosseous nerve at the proximal forearm. It has no specific radiologic or electrodiagnostic findings. Treatment should be started conservatively; if not successful, surgical treatment is indicated. The posterior interosseous nerve may be explored through dorsal or anterior approaches. All the potential sites of entrapment should be released, including complete release of the superficial head of the supinator muscle. Surgical treatment is generally successful, but patients who have associated lateral epicondylitis or those who are involved in workers' compensation claims have less successful outcomes. © 2012 Elsevier Inc.

Li X.,New York Blood Center | Li X.,Southern Medical University | Zhong H.,New York Blood Center | Bao W.,New York Blood Center | And 5 more authors.
Blood | Year: 2012

B lymphocytes producing antiplatelet autoantibodies play a major role in autoimmune thrombocytopenia (ITP). However, certain B cells, including the human CD19+CD24hiCD38hi subpopulation, possess regulatory functions mediated partly by IL-10. In a cohort of chronic ITP patients with low platelet counts who consisted of patients off treatment, we found a lower frequency of CD19+CD24hiCD38hi in the peripheral compartment of nonsplenectomized patients (P =.03). IL-10 expression after activation was decreased in all ITP circulating CD19+ subpopulations (P <.03), and inhibition of monocyte TNF-α expression by activated B cells was reduced in patients with platelet numbers of < 50 × 109 cells/L (P =.001), indicating that regulatory B cells of patients with ITP are functionally impaired in their ability to dampen monocyte activation. Interestingly, in nonsplenectomized patients whose platelet counts were elevated after treatment with thrombopoietic agents, the frequency of CD19+CD24hiCD38hi B cells was increased compared with those before treatment (P =.02). Altogether, these data indicate a compromised regulatory B-cell compartment as an additional defect in immune regulation in patients with chronic ITP that may be restored in responders to thrombopoietic treatment. © 2012 by The American Society of Hematology.

Rahmim A.,Johns Hopkins University | Zhou Y.,Johns Hopkins University | Tang J.,Oakland University | Lu L.,Southern Medical University | And 2 more authors.
Physics in Medicine and Biology | Year: 2012

Due to high noise levels in the voxel kinetics, development of reliable parametric imaging algorithms remains one of most active areas in dynamic brain PET imaging, which in the vast majority of cases involves receptor/transporter studies with reversibly binding tracers. As such, the focus of this work has been to develop a novel direct 4D parametric image reconstruction scheme for such tracers. Based on a relative equilibrium (RE) graphical analysis formulation (Zhou et al 2009b Neuroimage 44 66170), we developed a closed-form 4D EM algorithm to directly reconstruct distribution volume (DV) parametric images within a plasma input model, as well as DV ratio (DVR) images within a reference tissue model scheme (wherein an initial reconstruction was used to estimate the reference tissue timeactivity curves). A particular challenge with the direct 4D EM formulation is that the intercept parameters in graphical (linearized) analysis of reversible tracers (e.g. Logan or RE analysis) are commonly negative (unlike for irreversible tracers, e.g. using Patlak analysis). Subsequently, we focused our attention on the AB-EM algorithm, derived by Byrne (1998, Inverse Problems 14 145567) to allow inclusion of prior information about the lower (A) and upper (B) bounds for image values. We then generalized this algorithm to the 4D EM framework, thus allowing negative intercept parameters. Furthermore, our 4D AB-EM algorithm incorporated and emphasized the use of spatially varying lower bounds to achieve enhanced performance. As validation, the means of parameters estimated from 55 human 11C- raclopride dynamic PET studies were used for extensive simulations using a mathematical brain phantom. Images were reconstructed using conventional indirect as well as proposed direct parametric imaging methods. Noise versus bias quantitative measurements were performed in various regions of the brain. Direct 4D EM reconstruction resulted in notable qualitative and quantitative accuracy improvements (over 35% noise reduction, with matched bias, in both plasma and reference-tissue input models). Similar improvements were also observed in the coefficient of variation of the estimated DV and DVR values even for relatively low uptake cortical regions, suggesting the enhanced ability for robust parameter estimation. The method was also tested on a 90 min 11C-raclopride patient study performed on the high-resolution research tomograph wherein the proposed method was shown across a variety of regions to outperform the conventional method in the sense that for a given DVR value, improved noise levels were observed. © 2012 Institute of Physics and Engineering in Medicine.

Wang Q.,Southern Medical University | Wang Q.,Subei Peoples Hospital | Cai J.,Subei Peoples Hospital | Wang J.,Subei Peoples Hospital | And 2 more authors.
Tumor Biology | Year: 2014

The molecular regulation of the invasion of osteosarcoma (OS) remains elusive. Here, we reported significant lower level of miR-143 and significant levels of phosphorylated EGFR and MMP9 in the resected OS from the patients, compared to the adjacent normal tissue. Moreover, strong correlation was detected among these three factors. We thus hypothesized existence of a causal link, which prompted us to use two human OS cell lines to study the interaction of miR-143, MMP9, and activation of EGFR signaling. We found that EGF-induced EGFR phosphorylation in both lines activated MMP9, and consequently cancer invasiveness. Both an inhibitor for EGFR phosphorylation and an inhibitor for ERK1/2 phosphorylation significantly inhibited the EGF-induced activation of MMP9. Moreover, miR-143 levels did not alter by EGF-induced EGFR phosphorylation, while overexpression of miR-143 antagonized EGF-induced MMP9 activation without affecting EGFR phosphorylation. Taken together, our data suggest that miR-143 inhibits EGFR signaling through its downstream ERK/MAPK signaling cascades to control MMP9 expression in OS. Thus, miR-143, EGFR, and MMP9 are therapeutic targets for inhibiting OS invasion. © 2014, International Society of Oncology and BioMarkers (ISOBM).

Huang Z.,Tsinghua University | Feng Q.,Tsinghua University | Yu B.,Southern Medical University | Li S.,Southern Medical University
Materials Science and Engineering C | Year: 2011

To meet the challenges of designing an injectable scaffold and regenerating bone with complex three-dimensional (3D) structures, a biomimetic and injectable hydrogel scaffold based on nano-hydroxyapatite (HA), collagen (Col) and chitosan (Chi) is synthesized. The chitosan/nano-hydroxyapatite/collagen (Chi/HA/Col) solution rapidly forms a stable gel at body temperature. It shows some features of natural bone both in main composition and microstructure. The Chi/HA/Col system can be expected as a candidate for workable systemic minimally invasive scaffolds with surface properties similar to physiological bone based on scanning electron microscopic (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR) results. © 2010 Elsevier B.V. All rights reserved.

Li B.,Southern Medical University | Li Z.,Shenzhen International Travel Healthcare Center | Situ B.,Southern Medical University | Dai Z.,Sun Yat Sen University | And 4 more authors.
Biosensors and Bioelectronics | Year: 2014

A novel electrochemical sensing assay for sensitive determination of HIV-1 in a homogeneous solution has been developed using an electrochemical molecular beacon combined with a nafion-graphene composite film modified screen-printed carbon electrode (nafion-graphene/SPCE). The electrochemical molecular beacon (CAs-MB), comprising a special recognition sequence for the conserved region of the HIV-1 gag gene and a pair of carminic acid molecules as a marker, can indicate the presence of the HIV-1 target by its on/off electrochemical signal behavior. It is suitable for direct, electrochemical determination of HIV-1, thereby simplifying the detection procedure and improving the signal-to-noise (S/. N) ratio. To further improve the sensitivity, the nafion-graphene/SPCE was used to monitor changes in the CAs-MB, which has notable advantages, such as being ultrasensitive, inexpensive, and disposable. Under optimized conditions, the peak currents showed a linear relationship with the logarithm of target oligonucleotide concentrations ranging from 40. nM to 2.56. μM, with a detection limit of 5. nM (S/. N=3). This sensing assay also displays a good stability, with a recovery of 88-106.8% and RSD<7% (n=5) in real serum samples. This work may lead to the development of an effective method for early point-of-care diagnosis of HIV-1 infection. © 2013 Elsevier B.V.

Fu L.,Sun Yat Sen University | Fu L.,U.S. Center for Disease Control and Prevention | Xu B.-T.,Southern Medical University | Xu X.-R.,CAS South China Sea Institute of Oceanology | And 4 more authors.
Food Chemistry | Year: 2011

In order to supply new information on the antioxidant function of selected fruits for nutritionists and the general public, antioxidant activities and total phenolic contents of 62 fruits were evaluated using ferric reducing antioxidant power (FRAP) and Trolox equivalent antioxidant capacity (TEAC) assays as well as the Folin-Ciocalteu method, respectively. The correlations between the FRAP value and the TEAC value as well as total phenolic content were also assessed. The results showed that different fruits had diverse antioxidant capacities and the variation was very large, and seven fruits, Chinese date, pomegranate, guava, sweetsop, persimmon, Chinese wampee and plum, possessed the highest antioxidant capacities and total phenolic contents among tested fruits, and could be important dietary sources of natural antioxidants for prevention of diseases caused by oxidative stress. © 2011 Elsevier Ltd. All rights reserved.

Wu Z.,Southern Medical University | Sun H.,Sun Yat Sen University | Zeng W.,Laura Biotech Co | He J.,Southern Medical University | Mao X.,Southern Medical University
PLoS ONE | Year: 2012

Forkhead box protein O1 (FOXO1), a key member of the FOXO family of transcription factors, acts as a tumor suppressor and has been associated with various key cellular functions, including cell growth, differentiation, apoptosis and angiogenesis. Therefore, it is puzzling why FOXO protein expression is downregulated in cancer cells. MicroRNAs, non-coding 20~22 nucleotide single-stranded RNAs, result in translational repression or degradation and gene silencing of their target genes, and significantly contribute to the regulation of gene expression. In the current study, we report that miR-370 expression was significantly upregulated in five prostate cancer cell lines, compared to normal prostatic epithelial (PrEC) cells. Ectopic expression of miR-370 induced proliferation and increased the anchorage-independent growth and colony formation ability of DU145 and LNCaP prostate cancer cells, while inhibition of miR-370 reduced proliferation, anchorage-independent growth and colony formation ability. Furthermore, upregulation of miR-370 promoted the entry of DU145 and LNCaP prostate cancer cells into the G1/S cell cycle transition, which was associated with downregulation of the cyclin-dependent kinase (CDK) inhibitors, p27Kip1 and p21Cip1, and upregulation of the cell-cycle regulator cyclin D1 mRNA. Additionally, we demonstrated that miR-370 can downregulate expression of FOXO1 by directly targeting the FOXO1 3′-untranslated region. Taken together, our results suggest that miR-370 plays an important role in the proliferation of human prostate cancer cells, by directly suppressing the tumor suppressor FOXO1. © 2012 Wu et al.

Wu Z.,Southern Medical University | Weng D.,Sun Yat Sen University | Li G.,Southern Medical University
Journal of Proteomics | Year: 2013

We previously found that Cripto-1 is involved in the tumorigenesis of nasopharyngeal carcinoma (NPC). Here, to identify new NPC related proteins and to investigate the clinicopathological correlations of it in NPC, Cripto-1 over-expressed cell (CNE1/CR1+) was established. Two-dimensional difference in gel electrophoresis (2D-DIGE) analysis and matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF MS) were used to identify 23 differential proteins in CNE1/CR1+ and parental cells. Among them, 14-3-3γ showed the potential to be a NPC related protein. 14-3-3γ expression was found in 58.3% (60/103) tumor tissues as detected by IHC, and 69.6% (16/23) NPC fresh tumors expressed higher 14-3-3γ than paired non-cancerous tissues as detected by Western blot. Moreover, 14-3-3γ expression was positively correlated with N classification (p=0.031), distant metastasis (M classification, p=0.018) and clinical stage (p=0.046) of NPC patients. As determined by the Kaplan-Meier method, 14-3-3γ expression in NPC was significantly associated with overall survival (p=0.015). Multivariate analysis also showed that the expression of 14-3-3γ protein was an independent prognostic factor for outcome of NPC. In this study, we identified upregulated 14-3-3γ by 2D-DIGE in CNE1/CR-1+. We also demonstrated that 14-3-3γ might be a potential biomarker for the prognosis of patients with NPC. Biological significance: We believe that three aspects of this manuscript will make it interesting to general readers of Journal of Proteomics. Firstly, based on our previous report, we further validated that Cripto-1 can promote the proliferation and invasion of nasopharyngeal carcinoma (NPC). In this context, we used 2D-DIGE to identify new NPC related proteins. As a result, 14-3-3γ showed the potential to be a candidate. Secondly, we reported for the first time that the expression level of 14-3-3γ was significantly increased in human NPC patient tissues, and 14-3-3γ overexpression correlated statistically with N classification, distant metastasis, and clinical stage. Our results highlight the clinical significance of 14-3-3γ in NPC. Finally, we found that high 14-3-3γ expression is associated with poor survival in NPC patients. Thus, this study has identified that the 14-3-3γ involves in the carcinogenesis of NPC. Our findings may also provide new insights into understanding the molecular mechanism involved in NPC carcinogenesis and progression, and may lead to the development of new approaches for effective diagnosis and therapy. © 2013 Elsevier B.V.

Wang J.,Southern Medical University | Wang J.,Jilin University | Bao W.,Jilin University | Zhang L.,Wenzhou University
Analytical Methods | Year: 2012

Glucose detection is very important for the diagnosis and management of diabetes, and nonenzymatic glucose sensors have attracted considerable attention due to their excellent stability, high sensitivity, and so on. Herein, a sensitive, cost-effective nonenzymatic glucose sensor using ultralong Ni nanowire (NW) modified glassy carbon electrode is presented. The current-time curve shows that the catalytic oxidation current is linearly dependent on glucose concentration in the range from 1 μM to 5 mM with a correlation coefficient 0.994, and a sensitivity of 367 μA mM-1 cm -2. The relative standard deviation is 3.7% for 8 successive measurements for 1 mM glucose. After 2-weeks storage in air at room temperature, the signal for 1 mM glucose maintains 97.2% of its initial value. What is more, the present Ni NW-based electrochemical sensing platform can successfully be used to detect glucose in human serum with satisfactory results. © 2012 The Royal Society of Chemistry.

Shao L.,Southern Medical University | Jiang D.,CAS Shanghai Institute of Ceramics | Gong J.,Tsinghua University
Advanced Engineering Materials | Year: 2013

Hardness characterization is a key issue for the evaluation of the resistance to contact damage of dental materials. In this study, nanoindentation tests were conducted on four commercial zirconia dental ceramics. For each material, the measured nanohardness exhibits significant indentation size effect, i.e., the measured hardness decreases with increasing peak load. The so-called load-independent nanohardness was determined based on a second-order polynomial analysis of the variation of the contact depth with the peak load. Finally, a brief discussion was conducted on the reliability and the applicability of the determined load-independent nanohardness. Nanoindentation tests were conducted on four commercial zirconia dental ceramics. For each material, the measured nanohardness exhibits significant indentation size effect. The so-called load-independent nanohardness was determined based on a second-order polynomial analysis of the variation of the contact depth with the peak load. Finally, a brief discussion was conducted on the reliability and the applicability of the determined load-independent nanohardness. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tian J.-W.,Sun Yat Sen University | Chen J.-W.,Sun Yat Sen University | Chen R.,Sun Yat Sen University | Chen X.,Southern Medical University
Respiratory Care | Year: 2014

OBJECTIVE: This meta-analysis was performed to evaluate the efficacy and safety of the addition of tiotropium to standard treatment regimens for inadequately controlled asthma. METHODS: A systematic search was made of PubMed, EMBASE, MEDLINE, and CENTRAL databases, and, and a hand search of leading respiratory journals. Randomized, double-blind clinical trials on the treatment of inadequately controlled asthma for > 4 weeks with the addition of tiotropium, compared with placebo, were reviewed. Studies were pooled to odds ratio (OR) and weighted mean differences (WMDs), with 95% CI. RESULTS: Six trials met the inclusion criteria. The addition of tiotropium, compared with placebo, significantly improved all spirometric indices, including morning and evening peak expiratory flow (WMD 20.59 L/min, 95% CI 15.36 -25.81 L/ min, P <.001; and WMD 24.95 L/min, 95% CI 19.22-30.69 L/min, P <.001, respectively), trough and peak FEV1 (WMD 0.13 L, 95% CI 0.09 - 0.18 L, P <.001; and WMD 0.10 L, 95% CI 0.06 - 0.14 L, P <.001, respectively), the area under the curve of the first 3 h of FEV1 (WMD 0.13 L, 95% CI 0.08 - 0.18 L, P <.001), trough and peak FVC (WMD 0.1 L, 95% CI 0.05-0.15 L, P <.001; and WMD 0.08 L, 95% CI 0.04 - 0.13 L, P <.001, respectively), the area under the curve of the first 3hofFVC(WMD0.11L,95%CI0.06-0.15L,P<.001).Themeanchangeinthe7-pointAsthma Control Questionnaire score (WMD 0.12, 95% CI 0.21 to 0.03, P.01) was markedly lower in tiotropium group, but not clinically important. There were no significant differences in Asthma Quality of Life Questionnaire score (WMD 0.09, 95% CI 0.01 to 0.20, P.09), night awakenings (WMD 0.00, 95% CI 0.05 to 0.05, P.99) or rescue medication use (WMD 0.18, 95% CI 0.36 to 0.00, P.06). No significant increase was noticed in adverse events in the tiotropium group (OR 0.80, 95% CI 0.62-1.03, P.08). CONCLUSIONS: The addition of tiotropium to standard treatment regimens has significantly improved lung function without increasing adverse events in patients with inadequately controlled asthma. Long-term trials are required to assess the effects of the addition of tiotropium on asthma exacerbations and mortality. © 2014 Daedalus Enterprises.

Wang B.,Southern Medical University | Zhang Q.,Sun Yat Sen University | Zhu B.,Southern Medical University | Cui Z.,Southern Medical University | Zhou J.,Southern Medical University
PLoS ONE | Year: 2013

Background: Activation of Kupffer cell (KC) is acknowledged as a key event in the initiation and perpetuation of bile duct warm ischemia/reperfusion injury. The inhibitory effect of gadolinium chloride (GdCl3) on KC activation shows potential as a protective intervention in liver injury, but there is less research with regard to bile duct injury. Methods: Sixty-five male Sprague-Dawley rats (200-250 g) were randomly divided into three experimental groups: a sham group (n = 15), a control group (n = 25), and a GdCl3 group (n = 25). Specimen was collected at 0.5, 2, 6, 12 and 24 h after operation. Alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin (TBIL) of serum were measured. Tumor necrosis factor-α (TNF-α), Capase-3 activity and soluble Fas (sFas) were detected. The pathologic changes of bile duct were observed. Immunochemistry for bile duct Fas was performed. Apoptosis of bile duct cells was evaluated by the terminal UDP nick end labeling assay. Results: GdCl3 significantly decreased the levels of ALT, ALP and TBIL at 2, 6, 12, and 24 h, and increased serum sFas at 2, 6 and 12 h (P<0.05). TNF-α was lower in the GdCl3 group than in the control group at 2, 6, 12 and 24 h (P<0.05). Preadministration of GdCl3 significantly reduced the Caspase-3 activity and bile duct cell apoptosis at 2, 6, 12 and 24 h. After operation for 2, 6 and 12 h, the expression of Fas protein was lower in the GdCl3 group than in the control group (P<0.05). Conclusions: GdCl3 plays an important role in suppressing bile duct cell apoptosis, including decreasing ALT, ALP, TBIL and TNF-α; suppressing Fas-FasL-Caspase signal transduction during transplantation. © 2013 Wang et al.

Huang L.,Sun Yat Sen University | Lin J.-X.,Sun Yat Sen University | Yu Y.-H.,Southern Medical University | Zhang M.-Y.,Sun Yat Sen University | And 2 more authors.
PLoS ONE | Year: 2012

Background: Small cell carcinoma of the cervix (SCCC) is very rare, and due to the long time period required to recruit sufficient numbers of patients, there is a paucity of information regarding the prognostic factors associated with survival. MicroRNAs (miRNAs) have been used as cancer-related biomarkers in a variety of tumor types, and the objective of this study was to determine whether microRNA expression profiles can predict clinical outcome in SCCC. Methodology/Principal Findings: Forty-four patients with SCCC who underwent radical hysterectomy between January 2000 and October 2009 were enrolled. Using the GeneCopoeia All-in-One™ Customized Human qPCR Primer Array, the expression profiles of 30 miRNAs associated with tumor metastasis was obtained from the formalin-fixed paraffin embedded samples of all 44 patients. Seven miRNAs, has-let-7c, has-miR-10b, has-miR-100, has-miR-125b, has-miR-143, has-miR-145 and has-miR-199a-5p were significantly down-regulated in advanced stage SCCCpatients (FIGO IB2-IV) compared to early stage SCCC patients (FIGOIB1). Among, downregulation of six miRNAs, has-let-7c, has-miR-100, has-miR-125b, has-miR-143, has-miR-145 and has-miR-199a-5p were significantly associated with lymph node metastasis and reduced survival in SCCC. Kaplan-Meier survival analyses revealed that SCCC patients with low expression of has-miR-100 (P = 0.019) and has-miR-125b (P = 0.020) projected a significant tendency towards poorer prognosis. Conclusions/Significance: This study demonstrates that downregulation of 7 miRNA associated with advanced stage, 6 miRNAs with metastasis and 2 with poor prognosis in SCCC. Functional analysis of these miRNAs may enhance our understanding of SCCC, as altered expression of specific miRNAs may regulate the metastatic pathway and provide novel targets for therapy. © 2012 Huang et al.

Chen B.,Sun Yat Sen University | Li Y.,GuangZhou Women and Childrens Medical Center | Yang X.,Sun Yat Sen University | Xu H.,GuangZhou Women and Childrens Medical Center | Xie D.,Southern Medical University
Osteoporosis International | Year: 2013

This study was designed to compare the effects of alendronate (ALN), strontium ranelate (SR), and zoledronic acid (ZOL) on bone-implant osseointegration in ovariectomized rats. Histological examination and biomechanical tests show that ZOL, ALN, and SR enhance bone-implant osseointegration; ALN and SR have similar effects, while ZOL enhances bone-implant osseointegration more than ALN and SR Introduction: This study aims to compare the effects of ALN, SR, and ZOL on bone-implant osseointegration in ovariectomized rats. Methods: Sixty female Sprague-Dawley rats were included in this study. Of them, 48 rats were ovariectomized (OVX) and assigned to four groups: OVX (OVX + Veh), ALN (OVX + ALN), SR (OVX + SR), and ZOL (OVX + ZOL). And another 12 rats were sham-operated as a control group (Sham). Four weeks after ovariectomy, HA-coated titanium implants were inserted into the tibias bilaterally in all rats. Then the rats in groups ALN, SR, and ZOL were systemically administrated with alendronate (7 mg/kg/week, orally), strontium ranelate (500 mg/kg/day, orally), or a single injection of zoledronic acid (0.1 mg/kg, iv), respectively. Twelve weeks after implantation, all rats were sacrificed to get the femurs and tibias. Histological examination and biomechanical tests were used to evaluate bone-implant osseointegration in all groups. Results: ALN, SR, and ZOL significantly increased distal femoral BMD when compared with group OVX; ZOL increased BMD significantly more than ALN and SR (P < 0.05). Significant increase of bone-to-implant contact and peri-implant bone fraction were observed in groups ALN, SR, and ZOL when compared with group OVX (P < 0.05). Groups ALN and SR were inferior to groups ZOL and Sham (P < 0.05) in bone-to-implant contact and peri-implant bone fraction. Similar results were found in biomechanical testing (max pushout force). Conclusions: In rats losing bone rapidly after ovariectomy, systemic administration of ZOL, ALN, and SR causes better bone-implant osseointegration when compared to OVX; ALN and SR have similar positive effects on osseointegration, while ZOL, that was given in a dose with more positive BMD effect than that of ALN or SR, causes better osseointegration than either ALN or SR. © 2013 International Osteoporosis Foundation and National Osteoporosis Foundation.

Hui W.,Sun Yat Sen University | Yuntao L.,Southern Medical University | Lun L.,Sun Yat Sen University | WenSheng L.,Sun Yat Sen University | And 3 more authors.
PLoS ONE | Year: 2013

Glioma proliferation is a multistep process during which a sequence of genetic and epigenetic alterations randomly occur to affect the genes controlling cell proliferation, cell death and genetic stability. microRNAs are emerging as important epigenetic modulators of multiple target genes, leading to abnormal cellular signaling involving cellular proliferation in cancers. In the present study, we found that expression of miR-195 was markedly downregulated in glioma cell lines and human primary glioma tissues, compared to normal human astrocytes and matched non-tumor associated tissues. Upregulation of miR-195 dramatically reduced the proliferation of glioma cells. Flow cytometry analysis showed that ectopic expression of miR-195 significantly decreased the percentage of S phase cells and increased the percentage of G1/G0 phase cells. Overexpression of miR-195 dramatically reduced the anchorage-independent growth ability of glioma cells. Furthermore, overexpression of miR-195 downregulated the levels of phosphorylated retinoblastoma (pRb) and proliferating cell nuclear antigen (PCNA) in glioma cells. Conversely, inhibition of miR-195 promoted cell proliferation, increased the percentage of S phase cells, reduced the percentage of G1/G0 phase cells, enhanced anchorage-independent growth ability, upregulated the phosphorylation of pRb and PCNA in glioma cells. Moreover, we show that miR-195 inhibited glioma cell proliferation by downregulating expression of cyclin D1 and cyclin E1, via directly targeting the 3′-untranslated regions (3′-UTR) of cyclin D1 and cyclin E1 mRNA. Taken together, our results suggest that miR-195 plays an important role to inhibit the proliferation of glioma cells, and present a novel mechanism for direct miRNA-mediated suppression of cyclin D1 and cyclin E1 in glioma. © 2013 Hui et al.

Liang L.,Southern Medical University | Li X.,Southern Medical University | Li X.,Guangdong Women and Children Hospital | Zhang X.,Southern Medical University | And 11 more authors.
Gastroenterology | Year: 2013

Background & Aims: Formin-like (FMNL)2 is up-regulated in colorectal tumors and has been associated with tumor progression, but little is known about regulatory mechanisms. We investigated whether microRNAs regulate levels of FMNL2 in colorectal cancer (CRC) cells. Methods: We used real-time polymerase chain reaction and immunoblot analyses to measure levels of miR-137, high-mobility group AT-hook (HMGA)1, and FMNL2 in CRC cells and tissue samples from patients (n = 50). We used luciferase reporter assays to determine the association between miR-137 and the FMNL2 3′ untranslated region, and HMGA1 and the miR-137 promoter. Chromatin immunoprecipitation assays were used to assess direct binding of HMGA1 to the miR-137 promoter. Results: miR-137 and miR-142-3p were predicted to bind FMNL2 based on bioinformatic data. Only the level of miR-137 had a significant inverse correlation with the level of FMNL2 protein in CRC cell lines and tissues. FMNL2 messenger RNA was targeted by miR-137; expression of miR-137 inhibited proliferation and invasion by CRC cells in vitro, and metastasis to liver and intestine by CRC xenografts in nude mice. HMGA1 bound to the promoter of miR-137 and activated its transcription, which reduced levels of FMNL2 in CRC cells. Ectopic expression of miR-137 in CRC cells inhibited phosphorylation of mitogen-activated protein kinase (MAPK) and Akt, which reduced levels of matrix metalloproteinase 2, matrix metalloproteinase 9, and vascular endothelial growth factor; it also reduced invasiveness of CRC cells, inhibiting signaling via phosphatidylinositol-4,5-bisphosphate 3-kinase, Akt, and MAPK. Conclusions: Levels of miR-137 and HMGA1 are reduced, and levels of FMNL2 are increased, in CRC samples compared with adjacent normal mucosa. In CRC cells, miR-137 targets FMNL2 messenger RNA and is regulated by the transcription factor HMGA1. Expression of miR-137 reduces CRC cell invasion in vitro and metastasis of tumor xenografts in mice. FMNL2 appears to activate phosphatidylinositol-4,5-bisphosphate 3-kinase, protein kinase B (Akt), and MAPK signaling pathways. © 2013 AGA Institute.

Liu X.,Tsinghua University | Chen Y.,Southern Medical University | Huang Q.,Tsinghua University | He W.,Tsinghua University | And 2 more authors.
Carbohydrate Polymers | Year: 2014

In order to get a water-soluble in situ gel-forming system, a thiolated chitosan, chitosan-4-thio-butylamidine (CS-TBA) conjugate was synthesized and used to replace the unmodified chitosan in the application of the in situ gel-forming system. A novel thermo-sensitive hydrogel was prepared based on CS-TBA/hydroxyapatite (HA)/beta-glycerophosphate disodium (β-GP). The gel formation, rheological properties, morphology, degradation, cytotoxicity, as well as protein release process of the novel gel system were investigated in this study. The CS-TBA/HA/β-GP gel showed a higher storage modulus (G′) and loss modulus (G″) and a decreased bovine serum albumin (BSA) release rate which was maintained the protein release for a longer time compared with the unmodified chitosan (CS)/HA/β-GP gel, due to the existence of thiol groups and/or disulfide bonds. The CS-TBA/HA/β-GP gel has a porous structure with a uniform distribution of nano-hydroxyapatite, an appropriate degradation rate and low cytotoxicity, showing potential applications in drug delivery and tissue engineering. © 2014 Elsevier Ltd.

Lu J.,Southern Medical University | Lu J.,Chinese University of Hong Kong | He M.-L.,Chinese University of Hong Kong | Wang L.,Southern Medical University | And 9 more authors.
Cancer Research | Year: 2011

Several microRNAs (miRNA) have been implicated in nasopharyngeal carcinoma (NPC), a highly invasive and metastatic cancer that is widely prevalent in southern China. In this study, we report that microRNA miR-26a is commonly downregulated in NPC specimens and NPC cell lines with important functional consequences. Ectopic expression of miR-26a dramatically suppressed cell proliferation and colony formation by inducing G1-phase cell-cycle arrest. We found that miR-26a strongly reduced the expression of EZH2 oncogene in NPC cells. Similar to the restoring miR-26 expression, EZH2 downregulation inhibited cell growth and cell-cycle progression, whereas EZH2 overexpression rescued the suppressive effect of miR-26a. Mechanistic investigations revealed that miR-26a suppressed the expression of c-myc, the cyclin D3 and E2, and the cyclin-dependent kinase CDK4 and CDK6 while enhancing the expression of CDK inhibitors p14ARF and p21CIP1 in an EZH2-dependent manner. Interestingly, cyclin D2 was regulated by miR-26a but not by EZH2, revealing cyclin D2 as another direct yet mechanistically distinct target of miR-26a. In clinical specimens, EZH2 was widely overexpressed and its mRNA levels were inversely correlated with miR-26a expression. Taken together, our results indicate that miR-26a functions as a growth-suppressive miRNA in NPC, and that its suppressive effects are mediated chiefly by repressing EZH2 expression. ©2011 AACR.

Yao W.,Southern Medical University | Luo C.,Southern Medical University | Ai F.,Liuhuaqiao Hospital | Chen Q.,Southern Medical University
Pain Medicine (United States) | Year: 2012

Objectives. The objective of this study was to gain a basic understanding of the influential factors for nonspecific low-back pain (LBP) among adolescents of southern China. Design. The study was designed as a school-based case control study. Setting. Nonspecific LBP is a common health problem in adolescence. Although some behaviors and socio-demographic factors are believed to contribute to the disorder, influential factors of LBP remain undefined. Moreover, until now there is no available information of influential factors for LBP in Chinese adolescents. Subjects. A total of 1,214 adolescents were involved in the study, including 607 cases with nonspecific LBP and 607 controls without history of nonspecific LBP. Outcome Measures. A self-administered questionnaire was designed for epidemiological survey to investigate the risk factors for nonspecific LBP. All cases and controls were investigated for their family histories of nonspecific LBP, physical activities, sedentary activities, schoolbag weights, school performances, living conditions, and etc. Method. A 1:1 matched case-control study was conducted on 1,214 adolescents from an elementary school and a secondary school in Guangzhou City, southern China. Results. Family history (odds ratio [OR] 2.57, 95% confidence interval [CI] 1.85-3.58), long duration of carrying schoolbag (OR 1.38, 95% CI 1.11-1.72) and rest position between classes (OR 1.18, 95% CI 1.01-1.39) were positively correlated with self-reported nonspecific LBP. Students regularly playing basketball (OR 1.58, 95% CI 1.09-2.30) was found to be significantly more likely to have LBP. Also, students who feel schoolbag uncomfortable (OR 1.38, 95% CI 1.11-1.72) was found to experience more LBP. Conclusions. Family history, feeling schoolbag uncomfortable, duration of schoolbag carrying, basketball playing and rest position between classes are the major risk factors for nonspecific LBP in adolescents. Wiley Periodicals, Inc.

Huang Y.,Southern Medical University | Cai X.,Southern Medical University | Zhang J.,Southern Medical University | Mai W.,Sun Yat Sen University | And 4 more authors.
American Journal of Kidney Diseases | Year: 2014

Background Studies of the association of prehypertension with the incidence of end-stage renal disease (ESRD) after adjusting for other cardiovascular risk factors have shown controversial results. Study Design Systematic review and meta-analysis of prospective cohort studies. Setting & Population Adults with prehypertension. Selection Criteria for Studies Studies evaluating the association of prehypertension with the incidence of ESRD identified by searches in PubMed, EMBASE, and Cochrane Library databases and conference proceedings, without language restriction. Predictor Prehypertension. Outcomes The relative risks (RRs) of ESRD were calculated and reported with 95% CIs. Subgroup analyses were conducted according to blood pressure (BP), age, sex, ethnicity, and study characteristics. Results Data from 1,003,793 participants were derived from 6 prospective cohort studies. Compared with optimal BP, prehypertension significantly increased the risk of ESRD (RR, 1.59; 95% CI, 1.39-1.91). In subgroup analyses, prehypertension significantly predicted higher ESRD risk across age, sex, ethnicity, and study characteristics. Even low-range (BP, 120-129/80-84 mm Hg) prehypertension increased the risk of ESRD compared with optimal BP (RR, 1.44; 95% CI, 1.19-1.74), and the risk increased further with high-range (BP, 130-139/85-89 mm Hg) prehypertension (RR, 2.02; 95% CI, 1.70-2.40). The RR was significantly higher in the high-range compared with the low-range prehypertensive population (P = 0.01). Limitations No access to individual patient-level data. Conclusions Prehypertension is associated with incident ESRD. The increased risk is driven largely by high-range prehypertension. © 2013 by the National Kidney Foundation, Inc.

Zhang Y.,Wuhan University of Technology | Zheng D.,Southern Medical University | Xiong Y.,Wuhan University of Technology | Xue C.,Wuhan University of Technology | And 4 more authors.
FEBS Letters | Year: 2014

MicroRNAs have emerged as important regulators of carcinogenesis. In the current study, we observed that microRNA-202 (miR-202) is downregulated in hepatocellular carcinoma (HCC) cells and tissues, indicating a significant correlation between miR-202 expression and HCC progression. Overexpression of miR-202 in HCC cells suppressed cell proliferation and tumorigenicity, while downregulation of miR-202 enhanced the cells' proliferative capacity. Furthermore, we identified low-density lipoprotein receptor-related protein 6 (LRP6) as a direct target of miR-202. miR-202 suppresses the expression of LRP6 by binding to the 3′-untranslated region (UTR) of its mRNA. Finally, we found that silencing the expression of LRP6 is the essential biological function of miR-202 during HCC cell proliferation. Collectively, our findings reveal that miR-202 is a potential tumor suppressive miRNA that participates in carcinogenesis of human HCC by suppressing LRP6 expression. © 2014 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.

To K.K.W.,Chinese University of Hong Kong | Yu L.,Southern Medical University | Liu S.,Southern Medical University | Fu J.,Sun Yat Sen University | Cho C.H.,Chinese University of Hong Kong
Molecular Carcinogenesis | Year: 2012

Esophageal squamous cell carcinoma (ESCC) is a highly malignant disease that is generally not responding to chemotherapy. It is particularly predominant in China. Although ESCC is significantly associated with cigarette smoking, the relationship between its molecular pathogenesis and responsiveness to chemotherapy and cigarette smoke remains elusive. This study reported the constitutive activation of aryl hydrocarbon receptor (AhR), leading to ABCG2 upregulation and the multidrug resistance (MDR) phenotype, in ESCC cell lines with acquired cisplatin resistance. Reporter gene assay, chromatin immunoprecipitation analysis and specific gene knockdown confirmed that the enhanced AhR binding to a xenobiotic response element (XRE) within the ABCG2 promoter is responsible for ABCG2 overexpression. A HSP90 inhibitor (17-AAG) and two AhR antagonists (kaempferol and salicylamide) were shown to inhibit ABCG2 upregulation, thereby reversing the ABCG2-mediated MDR. Our data therefore advocate the use of these inhibitors as novel chemosensitizers for the treatment of esophageal cancer. © 2011 Wiley Periodicals, Inc.

Wu J.-Y.,Southern Medical University | Lun Z.-R.,Sun Yat Sen University | James A.A.,University of California at Irvine | Chen X.-G.,Southern Medical University
American Journal of Tropical Medicine and Hygiene | Year: 2010

Dengue is an acute emerging infectious disease transmitted by Aedes mosquitoes and has become a serious global public health problem. In mainland China, a number of large dengue outbreaks with serious consequences have been reported as early as 1978. In the three decades from 1978 to 2008, a total of 655,324 cases were reported, resulting in 610 deaths. Since the 1990s, dengue epidemics have spread gradually from Guangdong, Hainan, and Guangxi provinces in the southern coastal regions to the relatively northern and western regions including Fujian, Zhejiang, and Yunnan provinces. As the major transmission vectors of dengue viruses, the biological behavior and vectorial capacity of Aedes mosquitoes have undergone significant changes in the last two decades in mainland China, most likely the result of urbanization and global climate changes. In this review, we summarize the geographic and temporal distributions, the serotype and genotype distributions of dengue viruses in mainland China, and analyze the current status of surveillance and control of vectors for dengue transmission. Copyright © 2010 by The American Society of Tropical Medicine and Hygiene.

Qiu S.,Sun Yat Sen University | Huang D.,Sun Yat Sen University | Yin D.,East Tennessee State University | Li F.,Sun Yat Sen University | And 3 more authors.
Biochimica et Biophysica Acta - Molecular Basis of Disease | Year: 2013

Deregulation of microRNAs (miRNAs) is implicated in tumor progression. We attempt to indentify the tumor suppressive miRNA not only down-regulated in glioblastoma multiforme (GBM) but also potent to inhibit the oncogene EZH2, and then investigate the biological function and pathophysiologic role of the candidate miRNA in GBM. In this study, we show that miRNA-138 is reduced in both GBM clinical specimens and cell lines, and is effective to inhibit EZH2 expression. Moreover, high levels of miR-138 are associated with long overall and progression-free survival of GBM patients from The Cancer Genome Atlas dataset (TCGA) data portal. Ectopic expression of miRNA-138 effectively inhibits GBM cell proliferation in vitro and tumorigenicity in vivo through inducing cell cycles G1/S arrest. Mechanism investigation reveals that miRNA-138 acquires tumor inhibition through directly targeting EZH2, CDK6, E2F2 and E2F3. Moreover, an EZH2-mediated signal loop, EZH2-CDK4/6-pRb-E2F1, is probably involved in GBM tumorigenicity, and this loop can be blocked by miRNA-138. Additionally, miRNA-138 negatively correlates to mRNA levels of EZH2 and CDK6 among GBM clinical samples from both TCGA and our small amount datasets. In conclusion, our data demonstrate a tumor suppressive role of miRNA-138 in GBM tumorigenicity, suggesting a potential application in GBM therapy. © 2013 The Authors.

He S.-M.,Southern Medical University | Li R.,Moffitt Cancer Center | Kanwar J.R.,Deakin University | Zhou S.-F.,University of South Florida
Current Medicinal Chemistry | Year: 2011

Multidrug ABC transporters such as P-glycoprotein (P-gp/MDR1/ABCB1) and multidrug resistance protein 1 (MRP1/ABCC1) play an important role in the extrusion of drugs from the cell and their overexpression can be a cause of failure of anticancer and antimicrobial chemotherapy. Recently, the mouse P-gp/Abcb1a structure has been determined and this has significantly enhanced our understanding of the structure-activity relationship (SAR) of mammalian ABC transporters. This paper highlights our current knowledge on the structural and functional properties and the SAR of human MRP1/ABCC1. Although the crystal structure of MRP1/ABCC1 has yet to be resolved, the current topological model of MRP1/ABCC1 contains two transmembrane domains (TMD1 and TMD2) each followed by a nucleotide binding domain (NBD) plus a third NH2-terminal TMD0. MRP1/ABCC1 is expressed in the liver, kidney, intestine, brain and other tissues. MRP1/ABCC1 transports a structurally diverse array of important endogenous substances (e.g. leukotrienes and estrogen conjugates) and xenobiotics and their metabolites, including various conjugates, anticancer drugs, heavy metals, organic anions and lipids. Cells that highly express MRP1/ABCC1 confer resistance to a variety of natural product anticancer drugs such as vinca alkaloids (e.g. vincristine), anthracyclines (e.g. etoposide) and epipodophyllotoxins (e.g. doxorubicin and mitoxantrone). MRP1/ABCC1 is associated with tumor resistance which is often caused by an increased efflux and decreased intracellular accumulation of natural product anticancer drugs and other anticancer agents. However, most compounds that efficiently reverse P-gp/ABCB1-mediated multidrug resistance have only low affinity for MRP1/ABCC1 and there are only a few effective and relatively specific MRP1/ABCC1 inhibitors available. A number of site-directed mutagenesis studies, biophysical and photolabeling studies, SAR and QSAR, molecular docking and homology modeling studies have documented the role of multiple residues in determining the substrate specificity and inhibitor selectivity of MRP1/ABCC1. Most of these residues are located in the TMs of TMD1 and TMD2, in particular TMs 4, 6, 7, 8, 10, 11, 14, 16, and 17, or in close proximity to the membrane/cytosol interface of MRP1/ABCC1. The exact transporting mechanism of MRP1/ABCC1 is unclear. MRP1/ABCC1 and other multidrug transporters are front-line mediators of drug resistance in cancers and represent important therapeutic targets in future chemotherapy. The crystal structure of human MRP1/ABCC1 is expected to be resolved in the near future and this will provide an insight into the SAR of MRP1/ABCC1 and allow for rational design of anticancer drugs and potent and selective MRP1/ABCC1 inhibitors. © 2011 Bentham Science Publishers Ltd.

Xiang Q.,Sun Yat Sen University | Chen W.,Southern Medical University | Ren M.,Sun Yat sen Memorial Hospital | Wang J.,Sun Yat Sen University | And 5 more authors.
Clinical Cancer Research | Year: 2014

Purpose: MET signaling has been suggested a potential role in hepatocellular carcinoma (HCC) and associated with prometastasis during antiangiogenesis therapy. We investigated the potential association between MET expression and therapeutic response to sorafenib in patients with HCC. Antitumor effects of cabozantinib, a dual inhibitor of MET and VEGFR2, were examined in cultured HCC cells as well as in vivo models. Experimental Design: Total MET and phosphorylated MET (p-MET) were measured in 29 resected HCC specimens, and correlated with response to sorafenib as postoperative adjuvant therapy. In the second set of experiments using cultured HCC cells, and mouse xenograft and metastatic models, effects of cabozantinib were examined. Results: High level of p-MET in resected HCC specimens was associated with resistance to adjuvant sorafenib therapy. In cultured HCC cells that expressed p-MET, cabozantinib inhibited the activity of MET and its downstream effectors, leading to G1-phase arrest. Cabozantinib inhibited tumor growth in p-MET-positive and p-MET-negative HCC by decreasing angiogenesis, inhibiting proliferation, and promoting apoptosis, but it exhibited more profound efficacy in p-MET-positive HCC xenografts. Cabozantinib blocked the hepatocyte growth factor (HGF)-stimulated MET pathway and inhibited the migration and invasion of the HCC cells. Notably, cabozantinib reduced the number of metastatic lesions in the lung and liver in the experimental metastatic mouse model. Conclusions: Patients with HCC with high level of p-MET are associated with resistance to adjuvant sorafenib treatment. The dual blockade of VEGFR2 and MET by cabozantinib has significant antitumor activities in HCC, and the activation of MET in HCC may be a promising efficacy-predicting biomarker. ©2014 AACR.

Lu Y.-X.,Southern Medical University | Yuan L.,Southern Medical University | Xue X.-L.,Southern Medical University | Zhou M.,Southern Medical University | And 7 more authors.
Clinical Cancer Research | Year: 2014

Purpose: To elucidate a novel mechanism of miR-200c in the regulation of stemness, growth, and metastasis in colorectal carcinoma (CRC). Experimental Design: Quantitative reverse transcription PCR was used to quantify miR-200c expression inCRCcell lines and tissues. Aluciferase assay was adopted for the target evaluation. The functional effects of miR-200c in CRC cells were assessed by its forced or inhibited expression using lentiviruses. Results: MiR-200c was statistically lower in CRC clinical specimens and highly metastatic CRC cell lines compared with their counterparts. Sox2 was validated as a target for miR-200c. The knockdown of miR-200c significantly enhanced proliferation, migration, and invasion in CRC cell lines, whereas the upregulation of miR-200c exhibited an inverse effect. Moreover, rescue of Sox2 expression could abolish the effect of the upregulation of miR-200c. In addition, the reduction of miR-200c increased the expression of CRC stem cell markers and the sphere-forming capacity of CRC cell lines. Further study has shown that miR-200c and Sox2 reciprocally control their expression through a feedback loop. MiR-200c suppresses the expression of Sox2 to block the activity of the phosphoinositide 3-kinase (PI3K)-AKT pathway. Conclusion: Our findings indicate that miR-200c regulates Sox2 expression through a feedback loop and is associated with CRC stemness, growth, and metastasis. © 2014 American Association for Cancer Research.

Xiong W.F.,Southern Medical University | Qiu S.J.,Southern Medical University | Wang H.Z.,Shantou University | Lv X.F.,Sun Yat Sen University
Journal of Magnetic Resonance Imaging | Year: 2013

Purpose: To detect radiation-induced changes of temporal lobe normal-appearing white mater (NAWM) following radiation therapy (RT) for nasopharyngeal carcinoma (NPC). Materials and Methods: Seventy-five H 1-MR spectroscopy and diffusion-tensor imaging (DTI) examinations were performed in 55 patients before and after receiving fractionated radiation therapy (total dose; 66-75GY). We divided the dataset into six groups, a pre-RT control group and five other groups based on time after completion of RT. N-acetylaspartic acid (NAA)/choline (Cho), NAA/creatine (Cr), Cho/Cr, mean diffusibility (MD), functional anisotropy (FA), radial diffusibility (λ⊥), and axial diffusibility (λ||) were calculated. Results: NAA/Cho and NAA/Cr decreased and λ ⊥ increased significantly within 1 year after RT compared with pre-RT. After 1 year, NAA/Cho, NAA/Cr, and λ⊥ were not significantly different from pre-RT. In all post-RT groups, FA decreased significantly. λ|| decreased within 9 months after RT compared with pre-RT, but was not significantly different from pre-RT more than 9 months after RT. Conclusion: DTI and H1-MR spectroscopy can be used to detect early radiation-induced changes of temporal lobe NAWM following radiation therapy for NPC. Metabolic alterations and water diffusion characteristics of temporal lobe NAWM in patients with NPC after RT were dynamic and transient. J. Magn. Reson. Imaging 2013;37:101-108. © 2012 Wiley Periodicals, Inc. Copyright © 2012 Wiley Periodicals, Inc.

Smith J.L.,Montana State University | Cech E.,Rice University | Metz A.,Southern Medical University | Huntoon M.,Montana State University | Moyer C.,Northern Arizona University
Cultural Diversity and Ethnic Minority Psychology | Year: 2014

Native Americans are underrepresented in science, technology, engineering, and math (STEM) careers. We examine communal goal incongruence-the mismatch between students' emphasis on communal work goals and the noncommunal culture of STEM-as a possible factor in this underrepresentation. First, we surveyed 80 Native American STEM freshmen and found they more highly endorsed communal goals than individualistic work goals. Next, we surveyed 96 Native American and White American students in STEM and non-STEM majors and confirmed that both Native American men and women in STEM highly endorsed communal goals. In a third study, we conducted a follow-up survey and in-depth interviews with a subset of Native American STEM students in their second semester to assess their experiences of belonging uncertainty, intrinsic motivation, persistence intentions, and perceived performance in STEM as a function of their initial communal work goals. Results demonstrate the prominence of communal goals among incoming Native American freshman (especially compared with White male STEM majors) and the connection between communal goals and feelings of belonging uncertainty, low motivation, and perceived poor performance 1 semester later. The interview data illustrate that these issues are particularly salient for students raised within tribal communities, and that a communal goal orientation is not just a vague desire to "help others," but a commitment to helping their tribal communities. The interviews also highlight the importance of student support programs for fostering feelings of belonging. We end by discussing implications for interventions and institutional changes that may promote Native American student retention in STEM. © 2014 American Psychological Association.

Fu C.,Southern Medical University | Dong W.-Q.,Southern Medical University | Wang A.,Sun Yat Sen University | Qiu G.,Guangzhou University
Tumor Biology | Year: 2014

Estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2) may play a role in the development of prostate cancer. Many studies focused on ESR1 rs9340799 and ESR2 rs1256049 polymorphisms to explore associations with prostate cancer risk. These studies showed inconsistent and conflicting results. The aim of this meta-analysis was to investigate the pooled association of ESR1 rs9340799 and ESR2 rs1256049 polymorphisms with prostate cancer risk. A systematic literature search was conducted to identify related studies (up to February 2014) in several online databases including PubMed, Google Scholar, CNKI and Wanfang online libraries. A total of 16 eligible articles were enrolled in this updated meta-analysis. The result suggested that ESR1 rs9340799 polymorphism was significantly associated with prostate cancer in overall populations (GG+GA vs. AA: P = 0.002; G vs. A: P = 0.004), Caucasians (GG+GA vs. AA: P = 0.008; G vs. A: P = 0.016) and Africans (GG+GA vs. AA: P = 0.005; G vs. A: P = 0.006), but not in Asians (GG+GA vs. AA: P = 0.462; G vs. A: P = 0.665). The result also showed that there was a significant association between ESR2 rs1256049 polymorphism and prostate cancer in Caucasians (AA+AG vs. GG: P = 0.016; A vs. G: P = 0.005), but no association in overall populations (AA+AG vs. GG: P = 0.826; A vs. G: P = 0.478), Asians (AA+AG vs. GG: P = 0.177; A vs. G: P = 0.703) and Africans (AA+AG vs. GG: P = 0.847; A vs. G: P = 0.707). The cumulative meta-analysis and sensitivity analysis showed the results were robust. In conclusion, this meta-analysis indicated that ESR1 rs9340799 polymorphism was associated with prostate cancer risk in overall populations, Caucasians and Africans, while ESR2 rs1256049 polymorphism was associated with prostate cancer risk in Caucasians. However, the biological mechanisms need to be further investigated. © 2014, International Society of Oncology and BioMarkers (ISOBM).

Shi B.,Southern Medical University | Li X.,Sun Yat Sen University | Li H.,Southern Medical University | Ding Z.,Southern Medical University
Spine | Year: 2012

STUDY DESIGN.: A dissection-based study of 30 embalmed cadavers. OBJECTIVE.: To determine the morphology and morphometry of the dorsal meningovertebral ligaments in the lumbosacral segments and to discuss their clinical significance. SUMMARY OF BACKGROUND DATA.: Postoperative cerebrospinal fluid leakage is associated with longer hospital stays and significant implications for the patient, the surgeons, and society as a whole. To protect the dural sac during lumbar surgery, knowledge of the surgical anatomy of the dorsal meningovertebral ligaments is crucial. METHODS.: A total of 30 adult embalmed cadavers (52-70 yr of age; mean age of 64 yr) were used. The vertebral canal was divided to expose the dural sac and the spinal nerve roots, and the spinal cord was removed. The morphology, quantity, and attachment of the dorsal meningovertebral ligaments in the lumbosacral region were observed, and the length, width, or diameter and thickness of the ligaments were measured with vernier calipers. RESULTS.: The dorsal meningovertebral ligaments in the lumbosacral region connect the dura to the ligamenta flava or the lamina. The number of the attachment points on the ligamenta flava was relatively larger than that on the lamina, and the occurrence rate of dorsal meningovertebral ligaments was 97% at L5-S1. The thickest ligaments were observed at the L5 and S1 vertebrae. The length of the ligaments varied from 5.16 to 40.24 mm, and the ligaments extended caudally from their origin on the dura to their attachment to the lamina or the ligamentum flavum. The morphology of the dorsal meningovertebral ligaments was divided into 5 types: strip type, cord type, "Y"-shaped type, grid type, and thin slice type. CONCLUSION.: The dorsal meningovertebral ligaments may contribute to dura laceration and epidural hemorrhage during flavectomy and laminectomy, and an appreciation of this relationship might help reduce the risk of such complications. Copyright © 2012 Lippincott Williams & Wilkins.

Gao K.,Southern Medical University | Huang Z.,Liuhuaqiao Hospital | Huang Z.,University of Colorado at Denver | Yuan K.-H.,Liuhuaqiao Hospital | And 2 more authors.
British Journal of Dermatology | Year: 2013

Background Pulsed-dye laser (PDL)-mediated photothermolysis is the current standard treatment for port-wine stain (PWS) birthmarks. Vascular-targeted photodynamic therapy (PDT) might be an alternative for the treatment of PWS. Objectives To compare clinical outcomes of PDT and PDL treatment of PWS. Methods Two adjacent flat areas of PWS lesions were selected from each of 15 patients (two male and 13 female; age 11-36 years) and randomly assigned to either single-session PDL or PDT. PDL was delivered using a 585-nm pulsed laser. PDT was carried out with a combination of haematoporphyrin monomethyl ether (HMME) and a low-power copper vapour laser (510·6 and 578·2 nm). Clinical outcomes were evaluated colorimetrically and visually during follow-up. Results A total of nine red PWS lesions and six purple PWS lesions were treated. For red PWS, colorimetric assessment showed that the blanching rates of PDL and PDT at 2 months ranged from -11% to 24% and 22% to 55%, respectively. For purple PWS, blanching rates of PDL and PDT ranged from 8% to 33% and 30% to 45%, respectively. Overall, there was a significant difference between the blanching effect of single-session PDL treatment and a single-session PDT treatment. Conclusions This side-by-side comparison demonstrates that PDT is at least as effective as PDL and, in some cases, superior. The true value of PDT for the treatment of PWS deserves further investigation. What's already known about this topic? To date, several Chinese studies of photodynamic therapy (PDT) for port-wine stains (PWS) indicate that this therapeutic modality is effective and safe for the treatment of PWS of all colour and in all ages. Our retrospective study suggested that PDT is as effective as pulsed-dye laser (PDL) treatment for pink PWS and more effective than PDL for purple PWS. What does this study add? This is the first side-by-side and quantitative comparison of PDL and PDT. The findings reported here confirm that PDT is at least as effective and safe as PDL, if not superior to, for the treatment of red and purple flat PWS. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

Huang Y.,Southern Medical University | Huang Y.,Chinese Institute of Clinical Medicine | Cai X.,Chinese Institute of Clinical Medicine | Li Y.,Southern Medical University | And 6 more authors.
Neurology | Year: 2014

Objective: In this meta-analysis, we sought to evaluate the association between prehypertension and the risk of stroke. Methods: We searched PubMed and EMBASE databases for studies with data on prehypertension and stroke. Two independent reviewers assessed the reports and extracted data. Prospective studies were included if they reported multivariate-adjusted relative risks (RRs) with 95% confidence intervals (CIs) for the associations between stroke and prehypertension or its 2 subranges (low-range prehypertension: 120-129/80-84 mm Hg; high-range prehypertension: 130-139/85-89 mm Hg). We conducted subgroup analyses according to blood pressure ranges, stroke type, endpoint, age, sex, ethnicity, and study characteristics. Results: Pooled data included the results of 762,393 participants from 19 prospective cohort studies. Prehypertension increased the risk of stroke (RR 1.66; 95% CI 1.51-1.81) compared with optimal blood pressure (,120/80 mm Hg). In the secondary outcome analyses, even lowrange prehypertension increased the risk of stroke (RR 1.44; 95% CI 1.27-1.63), and the risk was greater for high-range prehypertension (RR 1.95; 95% CI 1.73-2.21). The RR was higher with high-range than with low-range prehypertension (p , 0.001). There were no significant differences in any of the subgroup analyses (all p . 0.05). Conclusions: After adjusting for multiple cardiovascular risk factors, prehypertension is associated with stroke morbidity. Although the increased risk is largely driven by high-range prehypertension, the risk is also increased in people with low-range prehypertension.

Lin Z.-T.,South China Agricultural University | Song K.,Sun Yat Sen University | Bin J.-P.,Southern Medical University | Liao Y.-L.,Southern Medical University | Jiang G.-B.,South China Agricultural University
Journal of Materials Chemistry | Year: 2011

Blood compatibility exerts an essential role in designing medical materials. The negative surface charge possessed by N-succinyl-chitosan (SCCS) has the benefit of being nonthrombogenic. To enhance the self-aggregation of SCCS, 2-hydroxy-3-(octadecyloxy)propyl groups (HOP) were employed as hydrophobic groups on SCCS to synthesise amphiphilic chitosan derivatives (HOPSCCS). The degree of succinyl substitution (DS) significantly influenced the water solubility of SCCS. Due to the intermolecular electrostatic attraction, SCCS (H-DS39.1) was water-insoluble, while SCCS (H-DS67.51, 78.6) were water-soluble. The substitution degree of HOP was 0.99-4.05%. The size of HOPSCCS micelles mainly ranged from 117 nm to 194 nm, and their critical micelle concentrations (CMC) were in the range of 1.42-4.24 × 10 -3 mg mL -1, and their surface had a negative charge ranging from -27.0 mV to -35.6 mV, suggesting that they possessed excellent stability and dispersion stability which was beneficial to prolong their circulation half-life and reduce the frequency of drug use. Aspirin was encapsulated into HOPSCCS, and the value of maximum drug loading capacity (LC) reached 18.5%, indicating that it can be an effective vehicle for aspirin and a good strategy for the use of aspirin. 1H NMR confirmed the aggregation behaviour of the micelles. Aspirin-loaded HOPSCCS, HOPSCCS/aspirin mixture and the influence of DS of SCCS on order structure were measured by FTIR. Thermal behaviour was determined by DTA/TG. Anticoagulant assays indicated that HOPSCCS had a slight anticoagulant property. Cell toxicity assessment, anticoagulant assays and hemolysis test suggested that HOPSCCS possessed low cytotoxicity and excellent hemocompatibility as a potential drug carrier for systemic administration and therapy of some blood diseases. © 2011 The Royal Society of Chemistry.

Zou J.,Southern Medical University | Feng D.,Sun Yat Sen University
Molecular Nutrition and Food Research | Year: 2015

Scope: Elevated blood cholesterol is an important risk factor associated with atherosclerosis and coronary heart disease. Tomato lycopene has been found to have a hypocholesterolemic effect, and the effect was considered to be related to inhibition of cholesterol synthesis. However, since plasma cholesterol levels are also influenced by the absorption of cholesterol in the gut, the present study is to investigate whether lycopene affects cholesterol absorption in the intestinal Caco-2 cells. Methods and results: The Caco-2 cells were pretreated with lycopene at different concentrations for 24 h and then incubated with radioactive micellar cholesterol for 2 h. The absorption of radioactive cholesterol was quantified by liquid scintillation. The expression of Niemann-Pick C1-like 1 (NPC1L1) and liver X receptor α (LXRα) was analyzed by Western blot and qPCR. We found that lycopene dose dependently inhibited cholesterol absorption and the expression of NPC1L1 protein and NPC1L1 mRNA. The inhibitory effects of lycopene on cholesterol absorption and NPC1L1 expression could be prevented by blockade of the LXRα pathway. Conclusion: This study provides the first evidence that lycopene inhibits cholesterol absorption in the intestinal cells and this inhibitory effect of lycopene is mediated, at least in part, by LXRα-NPC1L1 signaling pathway. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Zhou C.,Southern Medical University | Shen W.D.,TEVA Pharmaceuticals
Methods in Molecular Biology | Year: 2012

Display technology has been developed and widely used in antibody screening and selecting. While phage can only display antibody fragments, mammalian cells can display not only fragments but full-length antibodies. Here we described the display of full length antibody on the surface of 293 cells. Both heavy chain and light chain genes were cloned in a single mammalian expression vector containing dual mammalian expression cassettes. While transfected into 293 cells of the vector, both heavy and light chains were expressed. With the help of transmembrane domain of platelet-derived growth factor receptor (PDGFR-TM) fused at the 3′-end of heavy chain in frame, expressed full-length antibodies were displayed on the cell surface and can be easily detected and analyzed by flow cytometry. © 2012 Springer Science+Business Media, LLC.

Wang Y.,Southern Medical University | Lin M.,Guangzhou Panyu Central Hospital | Weng H.,GuangDong Women and Children Hospital | Wang X.,Southern Medical University | And 2 more authors.
American Journal of Obstetrics and Gynecology | Year: 2014

Objective Protease-activated receptor 2 plays an important role in the pathogenesis of endometriosis. We studied the effect of ENMD-1068, a protease-activated receptor 2 antagonist, on the development of endometriosis in a noninvasive fluorescent mouse model. Study Design A red fluorescent protein-expressing xenograft model of human endometriosis was created in nude mice. After endometriosis induction, the mice were injected intraperitoneally with either 25 mg/kg or 50 mg/kg ENMD-1068 or with 200 μL of the vehicle control daily for 5 days. The endometriotic lesions that developed in the mice were then counted, measured, and collected. The lesions were assessed for the production of interleukin 6 and monocyte chemotactic protein-1 by enzyme-linked immunosorbent assays and evaluated for the activation of nuclear factor-κB and the expression of vascular endothelial growth factor by immunohistochemical analyses. Cell proliferation and apoptosis were assessed by immunohistochemistry for Ki-67 and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, respectively. Results ENMD-1068 dose-dependently inhibited the development of endometriotic lesions (P <.05) without apparent toxicity to various organs of the treated mice. Consistently, ENMD-1068 dose-dependently inhibited the expression of interleukin 6 and nuclear factor-κB (P <.05) and cell proliferation (P <.05) in the lesions, as well as increased the percentage of apoptotic cells (P <.05). ENMD-1068 reduced the levels of monocyte chemotactic protein-1 and vascular endothelial growth factor in the lesions (P <.05), but not in a dose-dependent manner. Conclusion Our study suggests that ENMD-1068 is effective in suppressing the growth of endometriosis, which might be attributed to the drug's antiangiogenic and antiinflammatory activities.

Feng Y.,Sun Yat Sen University | Feng Y.,Guangzhou University | Zhu J.,Sun Yat Sen University | Ou C.,Southern Medical University | And 5 more authors.
British Journal of Cancer | Year: 2014

Background: Recent studies have reported miR-145 dysregulated in colorectal cancer (CRC). In this study, miR-145 profiles were compared between CRC and corresponding non-tumour tissues. Methods: The expression levels of miR-145 were analysed in CRC cell lines and tumour tissues by real-time PCR. A luciferase reporter assay confirmed direct targets. The functional effects of miR-145 were examined in transfected CRC cells in vitro and in vivo using established assays. Results: Downregulation of miR-145 was detected in most primary CRC tumours, and was significantly correlated with a more aggressive phenotype of CRC in patients. In CRC cell lines, ectopic overexpression of miR-145 inhibited cell proliferation, motility and invasion in vitro. Stable overexpression of miR-145 suppressed tumour growth and pulmonary metastasis in vivo. Further studies indicated that miR-145 may directly interact with the 3′-untranslated region (3′-UTR) of Fascin-1 messenger RNA (mRNA), downregulating its mRNA and protein expression levels. In clinical specimens, Fascin-1 expression was negatively correlated with miR-145 expression. Conclusions: MiR-145 has a critical role in the inhibition of invasive and metastatic capacities of CRC, probably through directly targeting Fascin-1. This miRNA may be involved in the development and progression of CRC.© 2014 Cancer Research UK. All rights reserved.

Zheng Q.-Y.,The Military General Hospital of Beijing PLA | Li P.-P.,Southern Medical University | Jin F.-S.,Chongqing Medical University | Yao C.,Nanjing Medical University | And 3 more authors.
Cellular Signalling | Year: 2013

Here we studied the cellular mechanisms of ursolic acid's anti-bladder cancer ability by focusing on endoplasmic reticulum stress (ER stress) signaling. We show that ursolic acid induces a significant ER stress response in cultured human bladder cancer T24 cells. ER stress inhibitor salubrinal, or PERK silencing, diminishes ursolic acid-induced anti-T24 cell effects. Salubrinal inhibits ursolic acid-induced CHOP expression, Bim ER accumulation and caspase-3 activation in T24 cells. Ursolic acid induces IRE1-TRAF2-ASK1 signaling complex formation to activate pro-apoptotic ASK1-JNK signaling. We suggest that ER stress contributes to ursolic acid's effects against bladder cancer cells. © 2012 Elsevier Inc.

Shen G.,Guangzhou University | Jia H.,Guangzhou University | Tai Q.,Sun Yat Sen University | Li Y.,Southern Medical University | Chen D.,Guangzhou University
Carcinogenesis | Year: 2013

Aberrant activation of the Wnt/β-catenin signal pathway is frequently observed in hepatocellular carcinoma (HCC). β-Catenin is the major cellular effector of Wnt signaling and inactivation of adenomatous polyposis coli (APC) results in nuclear accumulation of β-catenin. Therefore, it was speculated that APC inhibition could play important roles in activating the Wnt/β-catenin pathway and in HCC progression. In this study, we report that miR-106b expression is markedly upregulated in hepatoma cells and hepatoma tissues compared with immortalized normal liver epithelial cells and normal hepatic tissues. Ectopic expression of miR-106b induces the proliferation and anchorage-independent growth of hepatoma cells, whereas inhibition of miR-106b reduced this effect. Furthermore, miR-106b upregulation in hepatoma cells modulated entry into the G. 1/S transitional phase by upregulating cyclin D1 and downregulating APC. Moreover, we demonstrated that miR-106b downregulates APC expression by directly targeting the 3'-untranslated region of APC messenger RNA. Taken together, our results suggest that miR-106b plays an important role in promoting the proliferation of human hepatoma cells and presents a novel mechanism of micro RNA-mediated direct suppression of APC expression in cancer cells. © The Author 2012. Published by Oxford University Press. All rights reserved.

Niu S.,Southern Medical University | Gao Y.,Southern Medical University | Bian Z.,Southern Medical University | Huang J.,Southern Medical University | And 4 more authors.
Physics in Medicine and Biology | Year: 2014

Sparse-view CT reconstruction algorithms via total variation (TV) optimize the data iteratively on the basis of a noise- and artifact-reducing model, resulting in significant radiation dose reduction while maintaining image quality. However, the piecewise constant assumption of TV minimization often leads to the appearance of noticeable patchy artifacts in reconstructed images. To obviate this drawback, we present a penalized weighted least-squares (PWLS) scheme to retain the image quality by incorporating the new concept of total generalized variation (TGV) regularization. We refer to the proposed scheme as 'PWLS-TGV' for simplicity. Specifically, TGV regularization utilizes higher order derivatives of the objective image, and the weighted least-squares term considers data-dependent variance estimation, which fully contribute to improving the image quality with sparse-view projection measurement. Subsequently, an alternating optimization algorithm was adopted to minimize the associative objective function. To evaluate the PWLS-TGV method, both qualitative and quantitative studies were conducted by using digital and physical phantoms. Experimental results show that the present PWLS-TGV method can achieve images with several noticeable gains over the original TV-based method in terms of accuracy and resolution properties. © 2014 Institute of Physics and Engineering in Medicine.

Zou J.,Southern Medical University | Feng D.,Sun Yat Sen University | Ling W.-H.,Sun Yat Sen University | Duan R.-D.,Lund University
Journal of Nutritional Biochemistry | Year: 2013

We recently showed that lycopene inhibited lipopolysaccharide (LPS)-induced productions of nitric oxide (NO) and interleukin-6 (IL-6) in murine RAW264.7 macrophages by mechanisms related to inhibition of ERK and nuclear factor-κB. Since the assembly of Toll-like receptor 4 (TLR4) in lipid rafts is a key element in LPS induced signaling, we investigated whether this process would be influenced by lycopene. We found that pretreatment of RAW264.7 cells with lycopene inhibited LPS-induced recruitment of TLR4 into fractions - enriched with lipid raft marker. By the methods of immunoprecipitation and immunoblotting, we also found that lycopene inhibited the subsequent formation of the complex of TLR4 with its adaptors including myeloid differentiation primary-response protein 88 and TIR domain-containing adaptor-inducing IFN-β. We also found that the lycopene induced inhibition was associated with reduced formation of reactive oxygen species (ROS), which was an upstream mechanism for the effects of lycopene, because treating the cells with the antioxidant N-acetyl-. l-cysteine and NADPH oxidase inhibitor diphenyleneiodonium chloride significantly inhibited LPS-induced recruitment of TLR4 into lipid raft-like domains as well as the production of proinflammatory molecule NO and IL-6. Thus, our findings suggest that lycopene may prevent LPS-induced TLR4 assembly into lipid rafts through reducing intracellular ROS level. © 2013 Elsevier Inc.

Tian Y.-M.,Sun Yat Sen University | Tian Y.-H.,Southern Medical University | Tian Y.-H.,Armed Police Hospital of Guangdong Province | Zeng L.,Sun Yat Sen University | And 4 more authors.
British Journal of Cancer | Year: 2014

Background:Intensity-modulated radiotherapy (IMRT) is the main salvage treatment for advanced locally recurrent nasopharyngeal carcinoma (NPC); however, survival outcomes vary. We aimed to construct a prognostic-score model to identify patients who could benefit from salvage IMRT.Methods:This retrospective study involved 251 patients with locally recurrent NPC. The following parameters were analysed following IMRT: patient performance status, age, gender, late complications, T-stage of recurrence, synchronous nodal recurrence, primary gross tumour volume (GTV-nx), disease-free interval, re-irradiation dose and chemotherapy. The model was based on the hazard ratio coefficients of six significantly negative prognostic factors for survival.Results:Significantly negative prognostic factors included Karnofsky Performance Status ≤70, age >50 years, late complications, recurrent T 3-4 stage, synchronous nodal recurrence and GTV-nx >30 cm 3. Three subgroups were defined according to model scores: low risk (0-4), intermediate risk (5-8) and high risk (9-15). The 5-year overall survival rates were 64.3%, 32.2% and 7.7%, respectively. The main cause of death was radiation-induced complications.Conclusion:The prognostic-score model demonstrated that re-irradiation with IMRT is suitable for low-risk and intermediate-risk patients but may be unsuitable for high-risk patients. Further research into the protection of critical adjacent organs to reduce late complications in these patients is warranted. © 2014 Cancer Research UK.

Chen B.,Sun Yat Sen University | Li Y.,GuangZhou Women and Childrens Medical Center | Yang X.,Sun Yat Sen University | Xie D.,Southern Medical University
Calcified Tissue International | Year: 2013

This study compared the effects of alendronate (ALN) and strontium ranelate (SR) on bone mineral density (BMD), bone histomorphometry, and biomechanics in ovariectomized (OVX) rats. We randomly assigned 48 3-month-old female Sprague-Dawley rats to four groups: sham, OVX, ALN, and SR. Rats in the OVX, ALN, and SR groups received bilateral OVX. Rats in the ALN and SR groups were orally administrated ALN (7 mg/kg/week) and SR (500 mg/kg/day). Rats in the sham and OVX groups were treated with saline. All treatments continued for 12 weeks. Femoral BMD examination, distal femoral bone histomorphometry analysis, and biomechanical tests at the femoral diaphysis and metaphysis were performed to evaluate the effects of treatments in OVX rats. Results showed that both ALN and SR significantly increased femoral BMD (total femur, diaphyseal BMD, and distal metaphyseal BMD), distal femoral bone histomorphometric parameters (BV/TV, Tb.N, and Tb.Th), and femoral biomechanical parameters (maximum load, failure load, stiffness) compared with the OVX group (P < 0.05). No differences were found between ALN and SR in increasing femoral BMD, distal femoral bone histomorphometric parameters (BV/TV, Tb.N, and Tb.Th), and femoral diaphysis biomechanical parameters (maximum load, failure load, stiffness) (P > 0.05). The SR group was inferior to the ALN group in femoral metaphysis biomechanical parameters (P < 0.05). In conclusion, ALN (7 mg/kg/week) and SR (500 mg/kg/day) have similar effects by increasing BMD, distal femoral bone histomorphometric parameters, and femoral metaphysis biomechanical properties. Although ALN has greater effects than SR on distal femoral metaphysis biomechanical properties, in general, ALN and SR have comparable effects on the femur in OVX rats. © 2013 Springer Science+Business Media New York.

Li B.,Sun Yat Sen University | Zeng M.,Sun Yat Sen University | He W.,Sun Yat Sen University | Huang X.,Sun Yat Sen University | And 3 more authors.
Endocrinology | Year: 2015

Alveolar macrophages (AMs) undergo increased apoptosis during sepsis-induced acute respiratory distress syndrome (ARDS). Ghrelin exhibits an antiapoptotic effect in several cell types and protects against sepsis-induced ARDS in rats; however, the molecular mechanisms underlying this antiapoptotic effect remain poorly understood. In this study, we first examined the antiapoptotic effect of ghrelin on lipopolysaccharide (LPS)-stimulated AMs in vitro. In AMs, GH secretagogue receptor-1a (GHSR-1a), the ghrelin receptor,wasexpressed,andtreatment ofAMswith ghrelin markedly reduced LPS-induced apoptosis, mitochondrial transmembrane potential decrease, and cytochrome c release. These effects of ghrelin were mediated by GHSR-1a because a GHSR-1a-targeting small interfering RNA abolished the antiapoptotic action of ghrelin. LPS treatment activated thec-Jun N-terminal kinase (JNK) signaling pathway but inhibited the Wnt/ß-catenin pathway. Interestingly, combined LPS-ghrelin treatment reduced JNK activation and increased Wnt/ß-catenin activation. Furthermore, like ghrelin treatment, the addition of the JNK inhibitor SP600125 or the glycogen synthase kinase-3ß inhibitor SB216763 rescued AMs from apoptosis. We also demonstrated that ghrelin altered the balance of Bcl-2-family proteins and inhibited caspase-3 activity. Next, we investigated whether ghrelin protected against septic ARDS in vivo. Sepsis was induced in male rats by performing cecal ligation and puncture; administration of ghrelin reduced sepsisinduced AMs apoptosis, pulmonary injury, protein concentrations in the bronchoalveolar lavage fluid, the lung neutrophil infiltration, and wet to dry weight ratio. However, administration of a specific ghrelin-receptor antagonist, [D-Lys-3]-GH-releasing peptide-6, abolished the beneficial effects of ghrelin. Collectively our results suggest that ghrelin exerts an antiapoptotic effect on AMs at least partly by inhibiting JNK and activating the Wnt/ß-catenin pathway and thereby helps alleviate septic ARDS in rats. © 2015 by the Endocrine Society Received April 18, 2014.

Luo S.,Sun Yat Sen University | Fang L.,Sun Yat Sen University | Wang X.,Sun Yat Sen University | Liu H.,Southern Medical University | And 3 more authors.
Journal of Chromatography A | Year: 2010

A simple and fast sample preparation method for the determination of nonylphenol (NP) and octylphenol (OP) in aqueous samples by simultaneous derivatization and dispersive liquid-liquid microextraction (DLLME) was investigated using gas chromatography-mass spectrometry (GC/MS). In this method, a combined dispersant/derivatization catalyst (methanol/pyridine mixture) was firstly added to an aqueous sample, following which a derivatization reagent/extraction solvent (methyl chloroformate/chloroform) was rapidly injected to combine in situ derivatization and extraction in a single step. After centrifuging, the sedimented phase containing the analytes was injected into the GC port by autosampler for analysis. Several parameters, such as extraction solvent, dispersant solvent, amount of derivatization reagent, derivatization and extraction time, pH, and ionic strength were optimized to obtain higher sensitivity for the detection of NP and OP. Under the optimized conditions, good linearity was observed in the range of 0.1-1000μgL-1 and 0.01-100μgL-1 with the limits of detection (LOD) of 0.03μgL-1 and 0.002μgL-1 for NP and OP, respectively. Water samples collected from the Pearl River were analyzed with the proposed method, the concentrations of NP and OP were found to be 2.40±0.16μgL-1 and 0.037±0.001μgL-1, respectively. The relative recoveries of the water samples spiked with different concentrations of NP and OP were in the range of 88.3-106.7%. Compared with SPME and SPE, the proposed method can be successfully applied to the rapid and convenient determination of NP and OP in aqueous samples. © 2010 Elsevier B.V.

Liu H.,Southern Medical University | Liu L.,Southern Medical University | Xiong Y.,Southern Medical University | Yang X.,Southern Medical University | Luan T.,Sun Yat Sen University
Journal of Chromatography A | Year: 2010

A simple, precise and accurate method for the simultaneous determination of four UV filters and five polycyclic musks (PCMs) in aqueous samples was developed by solid-phase microextraction coupled with gas chromatography-mass spectrometry (SPME-GC-MS). The operating conditions affecting the performance of SPME-GC-MS, including fiber thickness, desorption time, pH, salinity, extraction time and temperature have been carefully studied. Under optimum conditions (30μm PDMS fiber, 7min desorption time, pH 7, 10% NaCl, 90min extraction time at 24°C), the correlation coefficients (r2) of the calibration curves of target compounds ranged from 0.9993 to 0.9999. The limit of detection (LOD) and limit of quantification (LOQ) ranged from 0.2 to 9.6ngL-1 and 0.7 to 32.0ngL-1, respectively. The developed procedure was applied to the determinations of four UV filters and five PCMs in river water samples and internal standard was used for calibration to compensate the matrix effect. Good relative recoveries were obtained for spiked river water at low, medium and high levels. The proposed SPME method was compared with traditional SPE procedure and the results found in river water using both methods were in the same order of magnitude and both are quite agreeable. © 2010 Elsevier B.V.

Zhang Y.,Southern Medical University | Shui X.,Wenzhou University | Lian X.,Southern Medical University
Medical Science Monitor | Year: 2015

Background: Nesfatin-1, a member of the adipokine family, has been detected in synovial fluid (SF) from OA patients. This study aimed to determine whether there is a marked correlation of nesfatin-1 levels in serum and SF of knee OA patients with the disease severity of OA. Material/Methods: This cross-sectional research enrolled 202 knee OA subjects. The Kellgren-Lawrence grading system was utilized to evaluate the severity of knee OA. Results: Elevated nesfatin-1 concentrations in serum were found in knee OA patients compared with the controls. Nesfatin-1 concentrations were markedly elevated with increased KL grades. Serum and SF nesfatin-1 concentrations were both significantly associated with the disease severity evaluated by KL grading criteria. Conclusions: Our investigation indicates a marked association of serum and SF nesfatin-1 concentrations with OA disease severity. © Med Sci Monit.

Jiao Z.,Southern Medical University | Li D.,Hubei Provincial Corps Hospital
Tumor Biology | Year: 2013

The association between MHTFR Glu429Val polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 29 studies including 8,649 cases and 18,672 controls were involved in this meta-analysis. Overall, no significant associations were found between MTHFR Glu429Ala polymorphism and breast cancer risk when all studies were pooled into the meta-analysis (Glu/Glu vs Ala/Ala: OR = 0.891, 95 % CI = 0.782-1.015; Glu/Ala vs Ala/Ala: OR = 0.874, 95 % CI = 0.760-1.006; dominant model: OR = 0.885, 95 % CI = 0.775-1.012; and recessive model: OR = 0.989, 95 % CI = 0.931-1.051). In the subgroup analysis by ethnicity, significantly elevated breast cancer risk was associated with Glu/Glu variant genotype in homozygote comparison and recessive genetic model (Glu/Glu vs Ala/Ala: OR = 0.78, 95 % CI = 0.63-0.97; Glu/Glu vs Glu/Ala: OR = 0.92, 95 % CI = 0.85-0.99; recessive model: OR = 0.91, 95 % CI = 0.85-0.97), while no significant associations were found for all comparison models in other ethnicity populations. In conclusion, this meta-analysis suggests that the MTHFR Glu429Ala polymorphism may be not associated with breast cancer development. © 2013 International Society of Oncology and BioMarkers (ISOBM).

Liu G.-L.,Southern Medical University | Yang H.-J.,Nanchang University | Liu T.,Southern Medical University | Lin Y.-Z.,Wenzhou University
Asian Pacific Journal of Tropical Medicine | Year: 2014

Objective: To study the expression of E-cadherin, N-cadherin, TGF-β1 and Twist protein and investigate its significance in the occurrence and development of prostate cancer. Methods: The expression of E-cadherin, N-cadherin, TGF-β1 and Twist protein in 59 prostate cancer tissues and 21 adjacent tissues were detected by immunohistochemical SABC staining, and the correlation with clinicopathological features was analyzed. Results: Positive rates of E-cadherin, N-cadherin, TGF-β1 and Twist were 32.2%, 54.2%, 71.2% and 74.6%, respectively, in prostate cancer tissues and 85.7%, 9.52%, 19.0% and 9.52%, respectively, in cancer-adjacent tissues, with significant differences between the two groups (P<0.05). The reduced expression of E-cadherin was related to the differentiation of prostate cancer tissues and PSA level, but was not associated with clinical stage, lymph node metastasis, bony metastasis and age. The increased expression of N-cadherin, TGF-β1 and Twist was related to the differentiation of prostate cancer tissues, clinical stage, lymph node metastasis, bony metastasis, but not to age. The difference in positive expression of N-cadherin and TGF-β1 was significant between PSA≤20 μg/L group and PSA>20μg/L group, but the positive expression of Twist was not significant between groups. The expression of E-cadherin was highly negatively correlated with that of N-cadherin and also highly negatively correlated with that of Twist. The expression of TGF-β1 was correlated with those of E-cadherin, N-cadherin and Twist. Conclusions: The reduced expression of E-cadherin, abnormal expression of N-cadherin, transformation form E-cadherin to N-cadherin and the increased expression of TGF-β1 and Twist play an important role in the occurrence and development of prostate cancer. © 2014 Hainan Medical College.

Liu J.,University of Duisburg - Essen | Zhang E.,University of Duisburg - Essen | Ma Z.,University of Duisburg - Essen | Wu W.,University of Duisburg - Essen | And 10 more authors.
PLoS Pathogens | Year: 2014

Hepatitis B virus (HBV) persistence is facilitated by exhaustion of CD8 T cells that express the inhibitory receptor programmed cell death-1 (PD-1). Improvement of the HBV-specific T cell function has been obtained in vitro by inhibiting the PD-1/PD-ligand 1 (PD-L1) interaction. In this study, we examined whether in vivo blockade of the PD-1 pathway enhances virus-specific T cell immunity and leads to the resolution of chronic hepadnaviral infection in the woodchuck model. The woodchuck PD-1 was first cloned, characterized, and its expression patterns on T cells from woodchucks with acute or chronic woodchuck hepatitis virus (WHV) infection were investigated. Woodchucks chronically infected with WHV received a combination therapy with nucleoside analogue entecavir (ETV), therapeutic DNA vaccination and woodchuck PD-L1 antibody treatment. The gain of T cell function and the suppression of WHV replication by this therapy were evaluated. We could show that PD-1 expression on CD8 T cells was correlated with WHV viral loads during WHV infection. ETV treatment significantly decreased PD-1 expression on CD8 T cells in chronic carriers. In vivo blockade of PD-1/PD-L1 pathway on CD8 T cells, in combination with ETV treatment and DNA vaccination, potently enhanced the function of virus-specific T cells. Moreover, the combination therapy potently suppressed WHV replication, leading to sustained immunological control of viral infection, anti-WHs antibody development and complete viral clearance in some woodchucks. Our results provide a new approach to improve T cell function in chronic hepatitis B infection, which may be used to design new immunotherapeutic strategies in patients. © 2014 Liu et al.

Sun Z.,Southern Medical University | Fu Q.,Southern Medical University | Cao L.,Southern Medical University | Jin W.,Guangdong No2 Provincial Peoples Hospital | And 2 more authors.
PLoS ONE | Year: 2013

Background: Contrast-induced nephropathy (CIN) is one of the common causes of acute renal insufficiency after contrast procedures. Whether intravenous N-acetylcysteine (NAC) is beneficial for the prevention of contrast-induced nephropathy is uncertain. In this meta-analysis of randomized controlled trials, we aimed to assess the efficacy of intravenous NAC for preventing CIN after administration of intravenous contrast media. Study Design: Relevant studies published up to September 2012 that investigated the efficacy of intravenous N-acetylcysteine for preventing CIN were collected from MEDLINE, OVID, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and the conference proceedings from major cardiology and nephrology meetings. The primary outcome was CIN. Secondary outcomes included renal failure requiring dialysis, mortality, and length of hospitalization. Data were combined using random-effects models with the performance of standard tests to assess for heterogeneity and publication bias. Meta-regression analyses were also performed. Results: Ten trials involving 1916 patients met our inclusion criteria. Trials varied in patient demographic characteristics, inclusion criteria, dosing regimens, and trial quality. The summary risk ratio for contrast-induced nephropathy was 0.68 (95% CI, 0.46 to 1.02), a nonsignificant trend towards benefit in patients treated with intravenous NAC. There was evidence of significant heterogeneity in NAC effect across studies (Q = 17.42, P = 0.04; I2 = 48%). Meta-regression revealed no significant relation between the relative risk of CIN and identified differences in participant or study characteristics. Conclusion: This meta-analysis showed that research on intravenous N-acetylcysteine and the incidence of CIN is too inconsistent at present to warrant a conclusion on efficacy. A large, well designed trial that incorporates the evaluation of clinically relevant outcomes in participants with different underlying risks of CIN is required to more adequately assess the role for intravenous NAC in CIN prevention. © 2013 Sun et al.

Isaacs A.T.,University of California at Irvine | Li F.,University of California at San Diego | Jasinskiene N.,University of California at Irvine | Chen X.,Southern Medical University | And 5 more authors.
PLoS Pathogens | Year: 2011

Transposon-mediated transformation was used to produce Anopheles stephensi that express single-chain antibodies (scFvs) designed to target the human malaria parasite, Plasmodium falciparum. The scFvs, m1C3, m4B7, and m2A10, are derived from mouse monoclonal antibodies that inhibit either ookinete invasion of the midgut or sporozoite invasion of salivary glands. The scFvs that target the parasite surface, m4B7 and m2A10, were fused to an Anopheles gambiae antimicrobial peptide, Cecropin A. Previously-characterized Anopheles cis-acting DNA regulatory elements were included in the transgenes to coordinate scFv production with parasite development. Gene amplification and immunoblot analyses showed promoter-specific increases in transgene expression in blood-fed females. Transgenic mosquito lines expressing each of the scFv genes had significantly lower infection levels than controls when challenged with P. falciparum. © 2011 Isaacs et al.

Ren F.,University of Memphis | Ren F.,Southern Medical University | Bhana S.,University of Memphis | Norman D.D.,University of Memphis | And 5 more authors.
Bioconjugate Chemistry | Year: 2013

Nanotechnology-based photothermal therapy has emerged as a promising treatment for cancer during the past decade. However, heterogeneous laser heating and limited light penetration can lead to incomplete tumor cell eradication. Here, we developed a method to overcome these limitations by combining chemotherapy with photothermal therapy using paclitaxel-loaded gold nanorods. Paclitaxel was loaded to gold nanorods with high density (2.0 × 104 paclitaxel per gold nanorod) via nonspecific adsorption, followed by stabilization with poly(ethylene glycol) linked with 11-mercaptoundecanoic acid. Paclitaxel was entrapped in the hydrophobic pocket of the polymeric monolayer on the surface of gold nanorods, which allows direct cellular delivery of the hydrophobic drugs via the lipophilic plasma membrane. Highly efficient drug release was demonstrated in a cell membrane mimicking two-phase solution. Combined photothermal therapy and chemotherapy with the paclitaxel-loaded gold nanorods was shown to be highly effective in killing head and neck cancer cells and lung cancer cells, superior to photothermal therapy or chemotherapy alone due to a synergistic effect. The paclitaxel-gold nanorod enabled photothermal chemotherapy has the potential of preventing tumor reoccurrence and metastasis and may have an important impact on the treatment of head and neck cancer and other malignancies in the clinic. © 2013 American Chemical Society.

Xu J.,Southern Medical University | Li T.,Southern Medical University | Wu H.,Guangzhou Development District Hospital | Xu T.,Southern Medical University
Pulmonary Pharmacology and Therapeutics | Year: 2012

Thioredoxin system is a ubiquitous thiol oxidoreductase system that regulates cellular reduction/oxidation (redox) status. It includes thioredoxin (Trx), thioredoxin reductase (TrxR), and NADPH. Trx plays an essential role in cell function by limiting oxidative stress directly via antioxidant effects and indirectly by proteins interaction with key signal transduction molecules. A variety of signaling molecules have been implicated in the cytoprotection conferred by Trx, such as autophagic proteins, p38 mitogen-activated protein kinase, nuclear factor-κB, phosphatidylinositol 3-kinase. Recent studies indicated that Trx may contribute to the pathogenesis of COPD, asthma and lung injury. Enhanced Trx expression or application of recombinant Trx afforded protection in preclinical models of pulmonary tissue injury, which suggested Trx may be used in future therapeutic applications. The focus of this review is on the significance of Trx in various pulmonary diseases, which as a potential therapeutic strategy to protect against oxidative stress and inflammation. © 2012.

Liu Y.,State University of New York at Stony Brook | Liang Z.,State University of New York at Stony Brook | Ma J.,Southern Medical University | Lu H.,PLA Fourth Military Medical University | And 3 more authors.
IEEE Transactions on Medical Imaging | Year: 2014

Previous studies have shown that by minimizing the total variation (TV) of the to-be-estimated image with some data and/or other constraints, a piecewise-smooth X-ray computed tomography image can be reconstructed from sparse-view projection data. However, due to the piecewise constant assumption for the TV model, the reconstructed images are frequently reported to suffer from the blocky or patchy artifacts. To eliminate this drawback, we present a total variation-stokes-projection onto convex sets (TVS-POCS) reconstruction method in this paper. The TVS model is derived by introducing isophote directions for the purpose of recovering possible missing information in the sparse-view data situation. Thus the desired consistencies along both the normal and the tangent directions are preserved in the resulting images. Compared to the previous TV-based image reconstruction algorithms, the preserved consistencies by the TVS-POCS method are expected to generate noticeable gains in terms of eliminating the patchy artifacts and preserving subtle structures. To evaluate the presented TVS-POCS method, both qualitative and quantitative studies were performed using digital phantom, physical phantom and clinical data experiments. The results reveal that the presented method can yield images with several noticeable gains, measured by the universal quality index and the full-width-at-half-maximum merit, as compared to its corresponding TV-based algorithms. In addition, the results further indicate that the TVS-POCS method approaches to the gold standard result of the filtered back-projection reconstruction in the full-view data case as theoretically expected, while most previous iterative methods may fail in the full-view case because of their artificial textures in the results. © 1982-2012 IEEE.

Chen Y.,Southern Medical University | Yang X.,Southern Medical University | Wang L.,Dongsheng Hospital of Guangzhou | Zhang X.,Southern Medical University
Nurse Education Today | Year: 2013

Background: Previous studies suggested that mindfulness meditation effectively reduced stress-related anxiety and depression symptoms, but no research has evaluated the efficacy of mindfulness meditation in nurses and nursing students in China. Objectives: To evaluate the effects of brief mindfulness meditation on the anxiety and depression symptoms and autonomic nervous system activity in Chinese nursing students. Design: A randomized controlled trial. Setting: A medical university in Guangzhou, China. Participants: One hundred and five nursing students were randomly approached by email and seventy-two responded. Sixty recruited students were randomized into meditation and control group (n = 30 each) after screening and exclusion due to factors known to influence mood ratings and autonomic nervous system measures. Methods: The meditation group performed mindfulness meditation 30. min daily for 7 consecutive days. The control group received no intervention except pre-post treatment measurements. The Self-Rating Anxiety Scale and Self-Rating Depression Scale were administered to participants, and heart rate and blood pressure were measured. Pre- and post-treatment data were analyzed using repeated-measures analysis of variance. Results: Differences between pre- and post-treatment Self-Rating Anxiety Scale scores were significantly larger in the meditation group than in the control group, but no similar effect was observed for Self-Rating Depression Scale scores. Systolic blood pressure was reduced more after the intervention in the meditation group than in the control group, with an average reduction of 2.2 mm. Hg. A moderate level of anxiety was associated with the maximum meditation effect. Conclusions: Brief mindfulness meditation was beneficial for Chinese nursing students in reducing anxiety symptoms and lowering systolic blood pressure. Individuals with moderate anxiety are most likely to benefit from a short-term mindfulness meditation program. © 2012 Elsevier Ltd.

Ning Y.,Southern Medical University | Ning Y.,Inner Mongolia University | Li Z.,Southern Medical University | Qiu Z.,Hebei Medical University
Journal of Toxicological Sciences | Year: 2015

Mechanisms underlining oxidative stress-induced injury to cardiomyocytes during myocardial infarction (MI) or acute ischemia/reperfusion (I/R) are not well recognized. Forkhead box O (FOXO) transcription factors have been defined as critical mediators of oxidative stress resistance in multiple cell types, but their cardioprotective functions have not been reported previously. In the present study, we investigated the promotion to FOXO1 by the treatment with hydrogen peroxide (H2O2) during the H2O2-induced apoptosis in cardiomyocyte H9c2 cells. We then silenced FOXO1 with FOXO1-specific siRNA, and re-evaluated the H2O2-induced apoptosis. In addition, we also examined the H2O2-induced autophagy and the autophagy induction post FOXO1 silence. Results demonstrated that H2O2 induced a significantly high level of apoptosis in H9c2 cells. Interestingly, the FOXO1 in both mRNA and protein levels were not significantly regulated, however, the phosphorylated form of FOXO1 was significantly promoted in the H2O2-treated H9c2 cells. On the other hand, post the significant knockout of FOXO1 with the transfection with FOXO1-specific siRNA, the apoptosis induction was more significant in H9c2 cells subjected to H2O2. In addition, we found a significantly higher level of autophagy induction in the H2O2-treated H9c2 cells. However, the autophagy was markedly reduced by the knockout of FOXO1. In summary, these data support the critical role for FOXO1 in promoting cardiomyocytes against oxidative stress probably through inducing autophagy. © 2015, Japanese Society of Toxicology. All rights reserved.

Liu Y.,State University of New York at Stony Brook | Ma J.,State University of New York at Stony Brook | Ma J.,Southern Medical University | Fan Y.,State University of New York at Stony Brook | Liang Z.,State University of New York at Stony Brook
Physics in Medicine and Biology | Year: 2012

Previous studies have shown that by minimizing the total variation (TV) of the to-be-estimated image with some data and other constraints, piecewise-smooth x-ray computed tomography (CT) can be reconstructed from sparse-view projection data without introducing notable artifacts. However, due to the piecewise constant assumption for the image, a conventional TV minimization algorithm often suffers from over-smoothness on the edges of the resulting image. To mitigate this drawback, we present an adaptive-weighted TV (AwTV) minimization algorithm in this paper. The presented AwTV model is derived by considering the anisotropic edge property among neighboring image voxels, where the associated weights are expressed as an exponential function and can be adaptively adjusted by the local image-intensity gradient for the purpose of preserving the edge details. Inspired by the previously reported TV-POCS (projection onto convex sets) implementation, a similar AwTV-POCS implementation was developed to minimize the AwTV subject to data and other constraints for the purpose of sparse-view low-dose CT image reconstruction. To evaluate the presented AwTV-POCS algorithm, both qualitative and quantitative studies were performed by computer simulations and phantom experiments. The results show that the presented AwTV-POCS algorithm can yield images with several notable gains, in terms of noise-resolution tradeoff plots and full-width at half-maximum values, as compared to the corresponding conventional TV-POCS algorithm. © 2012 Institute of Physics and Engineering in Medicine.

Mao C.,Southern Medical University | Wang X.-W.,Southern Medical University | Qiu L.-X.,Fudan University | Liao R.-Y.,Southern Medical University | And 2 more authors.
Breast Cancer Research and Treatment | Year: 2010

Epidemiological studies have evaluated the association between catechol-O-methyltransferase (COMT) Val108/158Met polymorphism and breast cancer risk. However, the results remain conflicting rather than conclusive. In order to derive a more precise estimation of the relationship, we performed this meta-analysis. Systematic searches of the PubMed and Medline databases were performed. A total of 41 studies including 25,627 cases and 34,222 controls were identified. Genotype distributions of COMT in the controls of all studies were in agreement with the Hardy-Weinberg equilibrium (HWE) except for three studies. When all 41 studies were pooled into the meta-analysis, there was no evidence for significant association between COMT Val108/158Met polymorphism and breast cancer risk (for Val/Met vs. Val/Val: OR = 0.99, 95% CI = 0.93-1.04; for Met/Met vs. Val/Val: OR = 0.96, 95% CI = 0.88-1.04; for dominant model: OR = 0.97, 95% CI = 0.92-1.03; for recessive model: OR = 0.97, 95% CI = 0.90-1.04). In the subgroup analyses by ethnicity, menopausal status, no significant associations were found in all genetic models. When sensitivity analyses were performed by excluding HWEviolating studies, all the results were not materially altered. In summary, the meta-analysis strongly suggests that COMT Val108/158Met polymorphism is not associated with increased breast cancer risk. © Springer Science+Business Media, LLC. 2009.

Gong W.,Southern Medical University | Xiong Y.,252 Hospital | Zhi F.,Southern Medical University | Liu S.,Southern Medical University | And 2 more authors.
Endoscopy | Year: 2012

Background and study aim: Although the majority of submucosal tumors (SMTs) are benign, some do have a malignant potential. Resection of SMTs would aid in establishing the diagnosis and may be curative. Our aim was to examine the feasibility and safety of a novel method for endoscopic resection of upper gastrointestinal SMTs. Patients and methods: In 12 patients who presented with an upper gastrointestinal SMT of 40mm located in the esophagus or cardia, a submucosal tunnel was endoscopically created starting approximately 5cm proximal to the lesion. After careful submucosal dissection with carbon dioxide or air insufflation, the SMTs were completely removed, and the entrance of the tunnel closed using endoclips. Results: SMTs had a mean size of 19.5mm (range 10-40mm); eight were located in the esophagus and four in the cardia. SMT resection was successful in all patients with en bloc resection in 10 patients (83.3%) and resection in two pieces in the remaining two patients. The mean time required for the procedure was 48.3 minutes (range 30-60 minutes). Two patients had both pneumothorax and subcutaneous emphysema. All the complications resolved with conservative management. Conclusions: In this pilot study, endoscopic submucosal tunnel dissection (ESTD) of esophageal and cardia SMTs was effective and appeared to be safe. Larger studies that also examine its application for gastric SMTs are warranted. © Georg Thieme Verlag KG Stuttgart · New York.

Zeng Q.,University of Colorado at Denver | Zeng Q.,Southern Medical University | Jin C.,University of Colorado at Denver | Jin C.,Southern Medical University | And 7 more authors.
Circulation | Year: 2012

Background and Purpose-Calcific aortic stenosis is a chronic inflammatory disease, and aortic valve interstitial cells (AVIC) play an important role in valvular inflammation. Whereas AVIC from stenotic aortic valves exhibit an augmented response to Toll-like receptor 4 (TLR4) stimulation, the underlying mechanism is unclear. This study tested the hypothesis that an excessive cross-talk between the TLR4 and Notch1 pathways is responsible for augmentation of the inflammatory response to lipopolysaccharide (LPS) in AVIC of stenotic valves. Methods and Results-Human AVIC were isolated from normal and stenotic leaflets. Nuclear factor kappa-B (NF-κB) activation and production of interleukin-8, monocyte chemoattactrant protein-1, and intercellular adhesion molecule-1 were analyzed after treatment with LPS. The role of Notch1 in the inflammatory response was determined using inhibitor, siRNA, and specific ligand. Cells from diseased valves produced greater levels of chemokines and intercellular adhesion molecule-1 that are associated with enhanced NF-κB activation. Interestingly, diseased cells exhibited augmented Jagged1 release and Notch1 activation after TLR4 stimulation. Inhibition and silencing of Notch1 each resulted in greater suppression of the TLR4-induced inflammatory response in diseased cells. Conversely, activation of Notch1 with a specific ligand, Jagged1, enhanced the LPS-induced inflammatory response in normal AVIC. Further, Notch1 intracellular domain was coimmunoprecipited with the inhibitor of NF-κB kinase after LPS stimulation, and inhibition of Notch1 abrogated the difference in the level of NF-κB activation between diseased and normal cells. Conclusion-Notch1 enhances the inflammatory response to TLR4 stimulation in human AVIC through modulating NF-κB activation. Excessive cross-talk between the TLR4 and Notch1 pathways is responsible for augmentation of the TLR4 response in AVIC of stenotic valves. © 2012 American Heart Association, Inc.

Songtao Q.,Southern Medical University | Lei Y.,Southern Medical University | Si G.,Guangzhou Medical College | Yanqing D.,Southern Medical University | And 4 more authors.
Cancer Science | Year: 2012

Recent studies have shown that isocitrate dehydrogenase1/2 (IDH1/2) mutations occur frequently in secondary glioblastoma. This study aimed to investigate their impact on temozolomide chemosensitivity and relationship with O(6)-methylguanine DNA methyltransferase (MGMT) promoter methylation in secondary glioblastoma. Searches for IDH1 and IDH2 mutations, 1p19q codeletion, MGMT promoter methylation, and p53 expression were carried out in a series of 86 secondary glioblastomas and correlated with progression-free survival and overall survival. Response to temozolomide was evaluated by progression-free survival, as well as by tumor size on successive MRI scans, then correlated with molecular alterations. IDH (IDH1 or IDH2) mutations were found in 58/79 patients (73.4%). IDH mutation, MGMT promoter methylation, and 1p19q codeletion were associated with prolonged progression-free survival in univariate (P<0.001, P<0.001, P=0.003, respectively) and multivariate analysis (P<0.001, P<0.001, P=0.035, respectively). IDH mutation (P=0.001) and MGMT promoter methylation (P=0.011) were correlated with a higher rate of objective response to temozolomide. Further analysis of response to temozolomide showed that patients with both IDH mutation and MGMT promoter methylation had the best response rate to temozolomide. IDH mutation appears to be a significant marker of positive chemosensitivity in secondary glioblastoma. Use of IDH status combined with MGMT promoter status as a stratification factor seems appropriate in future clinical trials involving temozolomide for the treatment of patients with secondary glioblastoma. © 2011 Japanese Cancer Association.

Hung K.W.Y.,Hong Kong Baptist University | Suen M.F.K.,Hong Kong Baptist University | Chen Y.F.,Southern Medical University | Cai H.B.,Southern Medical University | And 2 more authors.
Biosensors and Bioelectronics | Year: 2012

Cytochrome P450 (CYPs) is significant in degradation of endogenous substrates and detoxification of carcinogens, therefore it is a biomarker for assessment of polycyclic aromatic hydrocarbons (PAHs) level in aquatic environment. In the present study, a transgenic line of zebrafish had been generated using a CYP-green fluorescence protein (CYP-GFP) construct, driven by CYP1A1 promoter. Polychlorinated biphenyls (PCBs) were used as toxicant, in concentrations of 0.02. μg/ml, 0.04. μg/ml, 0.08. μg/ml, 0.4. μg/ml, and 0.8. μg/ml. The transgenic control fish showed low intensity of fluorescence in the liver. After exposed to PCBs, zebrafish had morphological changes such as expansion of yolk, contortion of tails and inflation of pericardial area. Green fluorescence signals were found to express according to concentrations and time. The green fluorescence signal was most intense after treatment with 0.08. μg/ml PCBs. However, the maximum area of green fluorescent signal was found at 0.04. μg/ml PCBs. GFP started to express at 3. h exposure to PCBs, increasing its intensity until 6. h exposure, and then level off. Since the GFP expression is fast responding and is sensitive to low PAHs concentrations, transgenic fish is a good tool for live imaging and monitoring of aquatic contamination. © 2011 Elsevier B.V.

Wang P.,University of Maryland, Baltimore | Wang P.,University of Sichuan | Zhao L.,University of Maryland, Baltimore | Zhao L.,Southern Medical University | And 5 more authors.
Bone Research | Year: 2015

Tissue engineering is promising to meet the increasing need for bone regeneration. Nanostructured calcium phosphate (CaP) biomaterials/scaffolds are of special interest as they share chemical/crystallographic similarities to inorganic components of bone. Three applications of nano-CaP are discussed in this review: nanostructured calcium phosphate cement (CPC); nano-CaP composites; and nano-CaP coatings. The interactions between stem cells and nano-CaP are highlighted, including cell attachment, orientation/morphology, differentiation and in vivo bone regeneration. Several trends can be seen: (i) nano-CaP biomaterials support stem cell attachment/proliferation and induce osteogenic differentiation, in some cases even without osteogenic supplements; (ii) the influence of nano-CaP surface patterns on cell alignment is not prominent due to non-uniform distribution of nano-crystals; (iii) nano-CaP can achieve better bone regeneration than conventional CaP biomaterials; (iv) combining stem cells with nano-CaP accelerates bone regeneration, the effect of which can be further enhanced by growth factors; and (v) cell microencapsulation in nano-CaP scaffolds is promising for bone tissue engineering. These understandings would help researchers to further uncover the underlying mechanisms and interactions in nano-CaP stem cell constructs in vitro and in vivo, tailor nano-CaP composite construct design and stem cell type selection to enhance cell function and bone regeneration, and translate laboratory findings to clinical treatments. © 2014 Sichuan University All rights reserved.

Suen M.F.K.,Hong Kong Baptist University | Chan W.S.,Hong Kong Baptist University | Hung K.W.Y.,Hong Kong Baptist University | Chen Y.F.,Southern Medical University | And 2 more authors.
Biosensors and Bioelectronics | Year: 2013

Transgenic zebrafish are a common vertebrate model system for the study of addictive behavior. In the present study, plasmid constructs containing green fluorescent protein (GFP) and the promoter of tyrosine hydroxylase (TH), a key synthetic enzyme for catecholamines, were produced. The TH-GFP constructs were microinjected into zebrafish embryonic cells. Three days post-fertilization, GFP began expressing in distinct catecholaminergic areas. The TH-GFP transgenic zebrafish were employed as live biosensors to test the effects of the commonly abused drugs nicotine and ketamine. First, locomotion assays were used to study the general excitatory effects of the drugs. Maximal locomotor activity was obtained after treatment with a high concentration of nicotine (10. μM), but with a much lower concentration of ketamine (0.1. μM). Second, TH protein levels in zebrafish brains were assessed by Western blot. TH protein levels were significantly increased, with maximal protein levels found after treatment with the same drug concentrations that gave maximal locomotor activity. Importantly, analysis of GFP in the zebrafish catecholaminergic areas revealed the same expression patterns as was obtained by Western blot. The present results indicate that increased locomotor activity can be correlated to TH protein expression, as indicated by Western blot and expression of TH-GFP. We have shown that TH-GFP expression is a reliable method to show the effects of drugs on TH expression that may be employed as a novel high-throughput live biosensor for screening drugs of abuse. © 2012 Elsevier B.V.

Xu X.,CAS Kunming Institute of Zoology | Xu X.,Southern Medical University | Lai R.,CAS Kunming Institute of Zoology
Chemical Reviews | Year: 2015

Amphibians can live in a wide range of habitats and ecological conditions because of their morphologically, biochemically, and physiologically complex skins, which perform versatile functions and contain pharmacological compounds of interest because of their potential for drug development. Amphibian skin peptides are promising for treating cancer, HIV, and drug-resistant S. aureus, which are major problems facing the 21st-century medical community. More than 100 000 bioactive compounds are estimated to occur in amphibian skin secretions, but about one-third of 6300 amphibian species are endangered. Amphibians are a rich source of natural tachykinins (TK) and more than 28 TK-like peptides have been isolated from amphibian skin, gut, and brain. Most frog skin insulin-releasing peptides are cationic and possess considerable amphipathic character with an α-helix and amidated C-terminus.

Xie H.,Central South University | Xie H.,Southern Medical University | Xie H.,Johns Hopkins Hospital | Xie H.,Merck And Co. | Xie H.,Johns Hopkins University
Nature medicine | Year: 2014

Osteogenesis during bone modeling and remodeling is coupled with angiogenesis. A recent study showed that a specific vessel subtype, strongly positive for CD31 and endomucin (CD31(hi)Emcn(hi)), couples angiogenesis and osteogenesis. Here, we found that platelet-derived growth factor-BB (PDGF-BB) secreted by preosteoclasts induces CD31(hi)Emcn(hi) vessel formation during bone modeling and remodeling. Mice with depletion of PDGF-BB in the tartrate-resistant acid phosphatase-positive cell lineage show significantly lower trabecular and cortical bone mass, serum and bone marrow PDGF-BB concentrations, and fewer CD31(hi)Emcn(hi) vessels compared to wild-type mice. In the ovariectomy (OVX)-induced osteoporotic mouse model, serum and bone marrow levels of PDGF-BB and numbers of CD31(hi)Emcn(hi) vessels are significantly lower compared to sham-operated controls. Treatment with exogenous PDGF-BB or inhibition of cathepsin K to increase the number of preosteoclasts, and thus the endogenous levels of PDGF-BB, increases CD31(hi)Emcn(hi) vessel number and stimulates bone formation in OVX mice. Thus, pharmacotherapies that increase PDGF-BB secretion from preosteoclasts offer a new therapeutic target for treating osteoporosis by promoting angiogenesis and thus bone formation.

Xia Y.,Johns Hopkins University | Xia Y.,Southern Medical University | Wang K.-P.,Johns Hopkins University
Journal of Thoracic Disease | Year: 2013

Lung cancer, as the leading cause of cancer-related motility and mortality worldwide, usually ends up with poor prognosis, despite abundant progress of therapeutic approaches. Early diagnosis and staging is extremely critical and directly affects clinical managements and outcomes. Transbronchial needle aspiration (TBNA), serving as an effective tool, has been widely used for mediastinal and hilar lung cancer staging. Recent advance in bronchoscopy introduces ultrasound probe to regular bronchoscope, resulting in TBNA procedures real-time visualized. Here, we summarize the advantages and disadvantages of conventional TBNA (cTBNA) and ultrasound-guided TBNA by comparing the instruments, methodology as well as the anatomy. We believe these two techniques are not competitive but complementary, judging the indications of patients for different technique would be a raising issue applied for pulmonologists. © Pioneer Bioscience Publishing Company.

Tao R.,CAS Guangzhou Institute of Geochemistry | Ying G.-G.,CAS Guangzhou Institute of Geochemistry | Su H.-C.,CAS Guangzhou Institute of Geochemistry | Zhou H.-W.,Southern Medical University | Sidhu J.P.S.,CSIRO
Environmental Pollution | Year: 2010

This study investigated antibiotic resistance profiles and tetracycline resistance genes in Enterobacteriaceae family isolates from the Pearl rivers. The Enterobacteriaceae isolates were tested for susceptibility to seven antibiotics ampicillin, chloramphenicol, ciprofloxacin, levofloxacin, sulphamethoxazole/trimethoprim, tetracycline and trimethoprim. In Liuxi reservoir, with an exception to ampicillin resistant strains (11%) no other antibiotic resistance bacterial strains were detected. However, multiple drug resistance in bacterial isolates from the other sites of Pearl rivers was observed which is possibly due to sewage discharge and input from other anthropogenic sources along the rivers. Four tetracycline resistance genes tet A, tet B, tet C and tet D were detected in the isolates from the rivers. The genes tet A and tet B were widely detected with the detection frequencies of 43% and 40% respectively. Ciprofloxacin and levofloxacin resistant enteric bacteria were also isolated from the pig and duck manures which suggest a wider distribution of human specific drugs in the environment. This investigation provided a baseline data on antibiotic resistance profiles and tetracycline resistance genes in the Pearl rivers delta. © 2010 Elsevier Ltd. All rights reserved.

Chen L.,Southern Medical University | Chen H.,CAS Guangzhou Institute of Geochemistry | Shen M.,Southern Medical University
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2014

A fast, sensitive and specific hydrophilic interaction chromatography combined with tandem mass spectrometry (HILIC-MS/MS) method was developed for the determination of tobramycin in human plasma. With sisomycin as internal standard, the analysis was carried out on a hilic column (150. mm. ×. 2.1. mm, 3.5. μm) using a mobile phase consisting of acetonitrile: 5. mM ammonium acetate and 0.1% formic acid (60:40, v/v). The detection was performed by tandem spectrometry via electrospray ionization (ESI). Linear calibration curves were obtained in the concentration range of 10.51-1051. ng/mL for tobramycin, with a lower limit of quantification of 10.51. ng/mL. The intra- and inter-day precision (RSD) values were below 15% and accuracy (RE) was 1.3-5.7% at all QC levels. The method was applicable to the clinical study of the pharmacokinetics of tobramycin in healthy volunteers. © 2014 Elsevier B.V.

Gan Y.,Southern Medical University | Xu D.,Southern Medical University | Ding J.,The Affiliated Orthopedics Hospital of Kunming General Hospital of Chengdu Military Region | Xu Y.,The Affiliated Orthopedics Hospital of Kunming General Hospital of Chengdu Military Region
Knee Surgery, Sports Traumatology, Arthroscopy | Year: 2012

Purpose: The purpose of this study is to design a new fixation method to treat tibial eminence fractures and assess its stability compared with conventional fixation methods. Methods: Eighty fresh porcine knees were stripped of all soft tissue, leaving intact only the femur-anterior cruciate ligament (ACL)-tibia complex. A standardized type III fracture was simulated at the anterior cruciate ligament attachment region using an osteotome. Then, the 80 specimens were randomly divided into 4 groups consisting of 20 knees each. The bony fragments were, respectively, fixed with sutures, steel wire, screws, and the newly designed tension band wire. All specimens were subsequently tested on a Material Testing Machine at a load rate of 60 mm/min. The statistically significant difference between the methods in terms of ultimate failure load, yield load, and displacement of the fragment under single-cycle loading and cyclic loading were analysed. Results: Steel wire encircling K-wire fixation showed significantly higher maximum loads, yield loads, and less displacement than all the other fixation methods tested. Specimens fixed with steel wire had the second highest maximal load followed by fixation with the cannulated screw. The lowest maximal load was observed in the group using PDS II suture. Conclusions: The ultimate strength of tension band wire fixation of tibial eminence fractures in these specimens was significantly greater than those of the other three fixation methods. Tension band wire fixation of eminence fractures appears to provide biomechanical advantages over the other three fixation methods; hence, it is a practical alternative to conventional fixation techniques. © 2011 Springer-Verlag.

Froehler M.T.,University of Iowa | Fifi J.T.,St Lukes Roosevelt Hospital | Majid A.,Hyper Acute Stroke Research Center | Bhatt A.,Spectrum Health Medical Group | And 2 more authors.
Neurology | Year: 2012

The initial treatment of patients with acute ischemic stroke (AIS) focuses on rapid recanalization, which often includes the use of endovascular therapies. Endovascular treatment depends upon micronavigation of catheters and devices into the cerebral vasculature, which is easier and safer with a motionless patient. Unfortunately, many stroke patients are unable to communicate and sufficiently cooperate with the procedure. Thus, general anesthesia (GA) with endotracheal intubation provides an attractive means of keeping the patient comfortable and motionless during a procedure that could otherwise be lengthy and uncomfortable. However, several recent retrospective studies have shown an association between GA and poorer outcomes in comparison with conscious sedation for endovascular treatment of AIS, though prospective studies are lacking. The underlying reasons why GA might produce a worse outcome are unknown but may include hemodynamic instability and hypotension, delays in treatment, prolonged intubation with or without neuromuscular blockade, or even neurotoxicity of the anesthetic agent itself. Currently, the choice between GA and conscious sedation should be tailored to the individual patient, on the basis of neurologic deficits, airway and hemodynamic status, and treatment plan. The use of institutional treatment protocols may best support efficient and effective care for AIS patients undergoing endovascular therapy. Important components of such protocols would include parameters to choose anesthetic modality, timeliness of induction, blood pressure goals, minimization of neuromuscular blockade, and planned extubation at the end of the procedure © 2012 American Academy of Neurology.

Lin D.,Guangzhou Hexian Memorial Hospital | Li G.,Southern Medical University | Chen L.,Southern Medical University
Journal of Chromatographic Science | Year: 2013

A fast, sensitive, high-performance liquid chromatography-tandem mass spectrometry method was developed for the determination of voriconazole in human plasma. Carbamazepine was used as the internal standard and the sample pretreatment involved one-step protein precipitation. Chromatographic separation was conducted on an Ultimate C18 column with a mobile phase consisting of acetonitrile-water (containing 0.1% formic acid; 40:60, v/v) at a flow rate of 0.3 mL/min. The detection of voriconazole was performed on a triple-quadrupole tandem mass spectrometer by multiple reaction monitoring with an electrospray ionization source in the positive mode. The standard curve was linear (r 2 ≥ 0.99) within the concentration range of 2.49-293 ng/mL. The intra-day and inter-day precision values were below 5.3%, and the accuracy was within-4.3-5.7%. The method was applicable to the clinical study of the pharmacokinetics of voriconazole in healthy volunteers following oral administration. 2012 © The Author [2012].

Chen X.,Southern Medical University | Qin L.,Dana-Farber Cancer Institute | Pan D.,Guangdong Academy of Medical science | Pan D.,Southern Medical University | And 6 more authors.
Radiology | Year: 2014

Purpose: To prospectively compare the reproducibility of normal liver apparent diffusion coefficient (ADC) measurements by using different respiratory motion compensation techniques with multiple breath-hold (MBH), free-breathing (FB), respiratory-triggered (RT), and navigator-triggered (NT) diffusion-weighted (DW) imaging and to compare the ADCs at different liver anatomic locations. Materials and Methods: The study protocol was approved by the institutional review board, and written informed consent was obtained from each participant. Thirty-nine volunteers underwent liver DW imaging twice. Imaging was performed with a 1.5-T MR imager with MBH, FB, RT, and NT techniques (b = 0, 100, and 500 sec/mm2). Three representative sections-superior, central, and inferior-were selected on left and right liver lobes, respectively. On each selected section, three regions of interest were drawn, and ADCs were measured. Analysis of variance was used to assess ADCs among the four techniques and various anatomic locations. Reproducibility of ADCs was assessed with the Bland-Altman method. Results: ADCs obtained with MBH (range: right lobe, [1.641-1.662] x 10-3mm2/sec; left lobe, [2.034-2.054] x 10-3mm2/sec) were higher than those obtained with FB (right, [1.349-1.391] x 10-3mm2/ sec; left, [1.630-1.700] x 10-3mm2/sec), RT (right, [1.439-1.455] x 10-3mm2/sec; left, [1.720-1.755] x 10 -3mm2/sec), or NT (right, [1.387-1.400] x 10 -3mm2/sec; left, [1.661-1.736] x 10-3mm 2/ sec) techniques (P < .001); however, no significant difference was observed between ADCs obtained with FB, RT, and NT techniques (P = .130 to P >.99). ADCs showed a trend to decrease moving from left to right. Reproducibility in the left liver lobe was inferior to that in the right, and the central middle segment in the right lobe had the most reproducible ADC. Statistical differences in ADCs were observed in the left-right direction in the right lobe (P <.001), but they were not observed in the superior-inferior direction (P = .144-.450). However, in the left liver lobe, statistical differences existed in both directions (P = .001 to P = .016 in the left-right direction, P < .001 in the superior-inferior direction). Conclusion: Both anatomic location and DW imaging technique influence liver ADC measurements and their reproducibility. FB DW imaging is recommended for liver DW imaging because of its good reproducibility and shorter acquisition time compared with that of MBH, RT, and NT techniques. © RSNA, 2014.

Haijin C.,Southern Medical University | Xiaodong M.,101 Hospital | Jinlong Y.,Southern Medical University | Zonghai H.,Southern Medical University
International Immunopharmacology | Year: 2013

Alpinetin, a novel plant flavonoid derived from Alpinia katsumadai Hayata, has been reported to exhibit anti-inflammatory properties. However, the effect of alpinetin on mastitis has not been investigated. The aim of this study was to investigate the protective effect of alpinetin against lipopolysaccharide (LPS)-induced mastitis and to clarify the possible mechanism. In the present study, primary mouse mammary epithelial cells and an LPS-induced mousemastitis model were used to investigate the effect of alpinetin on mastitis and the possible mechanism. In vivo, we observed that alpinetin significantly attenuated the infiltration of neutrophilic granulocytes, and the activation of myeloperoxidase; down-regulated the level of pro-inflammatory cytokines, including TNF-α, IL-1β and IL-6; inhibited the phosphorylation of IκB-α, NF-κB p65 and the expression of TLR4, caused by LPS. In vitro, we also observed that alpinetin inhibited the expression of TLR4 and the production of TNF-α, IL-1β and IL-6 in LPS-stimulated primary mouse mammary epithelial cells. However, alpinetin could not inhibit the production of IL-1β and IL-6 in TNF-α-stimulated primary mouse mammary epithelial cells. In conclusion, our results suggest that the anti-inflammatory effects of alpinetin against LPS-induced mastitis may be due to its ability to inhibit TLR4-mediated NF-κB signaling pathways. Alpinetin may be a promising potential therapeutic reagent for mastitis treatment. © 2013 Elsevier B.V. All rights reserved.

Nunes D.H.,Federal University of Santa Catarina | Esser L.M.H.,Southern Medical University
Anais Brasileiros de Dermatologia | Year: 2011

Background: Vitiligo is considered the most frequent acquired hypomelanosis. Although its pathogenesis is uncertain, it is believed that autoimmune etiology is the most plausible. This theory is based on the coexistence of vitiligo with autoimmune diseases. Objectives: To describe the epidemio-logical profile of vitiligo patients and to estimate the prevalence of the association of vitiligo with autoimmune thyroid diseases. Methods: A cross-sectional study was conducted through analysis of the medical records of patients diagnosed with vitiligo in the AME-UNISUL Outpatient Clinic of Dermatology and at HU-UFSC. The clinical and laboratorial characteristics of these patients were assessed. Results: 85 medical records were evaluated; 56 patients were female, with a mean age of 37.14 years and mean onset age of 25.25 years. Vitiligo vulgaris occurred in 70.6%. Autoimmune thyroid diseases were found in 22.4%. Other autoimmune diseases were identified in 5.9%. Patients with positive thyroid autoantibodies showed a probability of extension of vitiligo greater than 25%. There was no statistical difference with regard to the clinical characteristics of vitiligo in patients with or without autoimmune thyroiditis with hormonal change. Conclusion: The findings of this study are similar to those obtained by other authors, showing that autoimmune thyroid diseases are more common in patients with vitiligo. © 2011 by Anais Brasileiros de Dermatologia.

He X.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2013

Primary follicular immunoblastic lymphoma (FIBL) is an extremely rare lymphoma. The positive expression of CD10 suggests the lymphoma originating from germinal centers (GC) and CD138-positive expression generally indicates plasmablastic or plasmacytic differentiation. We report such a rare case in a Chinese female patient and analyze the clinicopathologic and immunohistochemical features of this disease. PET-CT examination was performed to detect signs of systemic lymph node metastasis. We also discussed the differential diagnosis of FIBL from follicular lymphoma (FL) and reactive follicular hyperplasia (RFH). As a rare variant of human follicular lymphoma, FIBL is featured by a neoplastic overgrowth of intrafollicular immunoblasts. Compared with FL, FIBL has a greater chance to evolve into diffuse large B-cell lymphoma with therefore a poorer prognosis.

Nie J.,Southern Medical University | Hou F.-F.,Southern Medical University
Chinese Medical Journal | Year: 2012

Renal fibrosis is a common pathway of progressive renal diseases leading to end-stage renal disease regardless of the etiology. Accumulating evidence indicates that oxidative stress, resulting in generation of reactive oxygen species (ROS), plays a critical role in the initiation and progression of fibrotic diseases. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is the predominant enzyme source for ROS generation and is now recognized as a key mediator of cell proliferation and matrix accumulation in renal disease. Multiple stimuli and agonists, such as transforming growth factor β1, tumor necrosis factor, platelet derived growth factor, angiotensin II, hyperglycemia, oxidized low-density lipoprotein and albumin have been shown to alter the activity or expression of the NADPH oxidase and ultimately increase ROS production. ROS directly incites damage to biologically important macromolecules and leads to generation of the so-called advanced oxidation protein products (AOPPs) and advanced glycation end products, which are not only markers of oxidative stress but also cause renal injury. Targeting NADPH oxidase and/or reducing AOPPs production might be a novel strategy for the therapeutic intervention of variety of fibrotic kidney disorders.

Chen Y.,Shantou University | Chen C.,Shantou University | Chen C.,Southern Medical University | Ke X.,University College London | And 6 more authors.
Circulation: Cardiovascular Genetics | Year: 2014

Background: Non-O type of ABO blood group has been associated with a predisposition to coronary heart disease. It is thought that this association is partly mediated by increased cholesterol levels in non-O-type individuals. In this study, we sought to estimate the mediation effect size. Methods and Results: In a group of individuals (n=6476) undergoing coronary angiography, we detected associations of non-O type with significant coronary artery disease with >50% stenosis in =1 coronary arteries (odds ratio, 1.24; 95% confidence interval, 1.10-1.39; P=2.6×10-4) and with prevalent or incident myocardial infarction (odds ratio, 1.22; 95% confidence interval, 1.09-1.37; P=1.2×10-3). Subjects of non-O type had higher levels of total cholesterol, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol (mean [SEM] in mmol/L: 4.931[0.021], 3.041 [0.018], and 3.805 [0.020] in non-O type compared with 4.778 [0.026], 2.906 [0.021], and 3.669 [0.024] in O type; P=3.8×10-7, P=1.5×10-7, and P=3.1×10-7, respectively). Mediation analyses indicated that 10% of the effect of non-O type on coronary artery disease susceptibility was mediated by increased low-density lipoprotein cholesterol level (P=7.8×10-4) and that 11% of the effect of non-O type on myocardial infarction risk was mediated by raised low-density lipoprotein cholesterol level (P=2.0×10-3). Conclusions: In a model in which it is presumed that cholesterol is a mediator of the associations of ABO group with coronary artery disease and myocardial infarction, around 10% of the effect of non-O type on coronary artery disease and myocardial infarction susceptibility was mediated by its influence on low-density lipoprotein cholesterol level. © 2014 American Heart Association, Inc.

Chen C.,Southern Medical University | Zhang Q.-S.,Southern Medical University
Chinese Journal of Contemporary Pediatrics | Year: 2013

Dramatic advances in neonatal medicine over recent decades have resulted in decreased mortality and morbidity rates for extremely low birth weight infants. However, the survival of these infants is associated with short- and long-term morbidity, including severe intraventricular hemorrhage, periventricular leukomalacia, nosocomial infection and necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity and adverse long-term neurodevelopmental sequelae. This article reviewed the latest advances in the medical care for extremely low birth weight infants including survival rate, ethical issues and short- and long-term morbidity, domestically and abroad.

Cheng Y.,Southern 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: 2013

To investigate effects of biejiajian pill (BP) on the proliferation, adhesion, and invasion of hepatoma carcinoma cells (HepG2), and to primarily explore the mechanisms for fighting against metastasis and invasion. Using sero-pharmacological methods, HepG2 cells were respectively cultured by high and middle dose BP containing serums and the vehicle serum. Using MTT colorimetry, cell adhesion test, and Transwell invasion test, effects of BP on the proliferation, adhesion, and invasion of HepG2 cells were detected, thus further exploring the mechanisms for fighting against the metastasis and invasion of HepG2 cells. High and middle dose BP containing serums could significantly prohibit the growth and proliferation, the adhesion and invasion of HepG2 cells on the basilar membrane. Besides, these effects were correlated with the concentrations of BP. BP could effectively inhibit the growth and proliferation, adhesion and invasion of HepG2 cells.

Li F.,Southern Medical University
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi | Year: 2011

To investigate the expression of miR-9 in B lymphocytes, B cell lymphoma and classical Hodgkin's lymphoma (cHL) cell lines and its significance. CD19(+) B lymphocytes were sorted from normal lymph node by magnetic beads. Total cellular micro-RNA was extracted from cHL cell line L428, B cell lymphoma cell lines Ly1 and Ly10 (diffuse large B cell lymphoma), Raji cells (Burkitt's lymphoma) and CD19(+) B lymphocytes, respectively. These micro-RNAs were separately transformed into cDNA by reverse transcription. The expression levels of miR-9 were measured by fluorescence quantitative PCR. In situ hybridization was used to detect the expression of miR-9 in cell lines. The expression of miR-9 was high in L428 cells (104.44 ± 1.61), and low in cell lines of B cell lymphoma (Ly1: 2.17 ± 0.38; Ly10: 1 ± 0.015; Raji: 2.65 ± 0.89), and extremely low in CD19(+) B lymphocytes (0.0026 ± 0.00040). Compared with that in the other cell lines, the expression of miR-9 in L428 cells was statistically significant (P < 0.05). miR-9 localized in the cytoplasm diffusely and strongly in L428, but scattered and slightly with some prominent distribution around the nuclear membranes in Ly1 and Ly10, and only weakly in Raji. miR-9 highly expressed in cHL cell line and might be a molecular marker for diagnosis and treatment of cHL.

Xian L.W.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2011

To investigate the association of advanced oxidation protein products (AOPP) with oxidative stress in colon cancer cells exposed to intermittent hypoxia (IH). Colon cancer SW480 cells were exposed to IH, continuous hypoxia, or normoxia. Enzyme-linked immunosorbent assay (ELISA) was employed to examine the levels of AOPP and vascular endothelial growth factor (VEGF), xanthine oxidase assay was used to determine malonaldehyde (MDA) and glutathione peroxidase (GSH-PX), and Western blotting and immunofluorescence assay were performed for detection of transforming growth factor-β(1) (TGF-β(1)) expression. Compared with the normoxia group, the two hypoxia groups showed significantly increased AOPP and MDA levels (P<0.05) and lowered SOD and GSH-PX levels (P<0.05). The concentration of AOPP was positively correlated to MDA, VEGF, and TGF-β(1) levels (P<0.05), but inversely to SOD. No significant correlation was found between AOPP and GSH-PX levels. Compared with continuous hypoxia, IH results in more obvious protein oxidation in relation to oxidative stress. The increased expression of VEGF and TGF-β(1) in the context of hypoxia is closely related to AOPP level.

Long X.,Southern 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 study the normal anatomy of aditus of antrum and antrum on the high-resolution CT (HRCT) and the three-dimensional reconstruction, testing the normal range. And comparison was carried out according to the age, sex and side. Ninety cases were randomly selected without ear lesions. Scanning were taken in sagittal, transverse and coronal planes on HRCT respectively. The structure of aditus and antrum was displayed by three-dimensional reconstruction. The left-right distances and up-down distances, antero-posterior distances were measured and analyzed. The image of antrum varied with age, while aditus remained constant on the HRCT and the three-dimensional reconstruction. The average of left-right distance of aditus was (5.19 +/- 1.39) mm, and the average of up-down distance of aditus was (5.74 +/- 1.16) mm. The average of left-right distance of antrum was (8.27 +/- 1.41) mm (<6 years old) and (5.41 +/- 1.32) mm (> or = 6 years old). The average of up-down distance of antrum was (11.78 +/- 1.65) mm (<6 years old) and (9.91 +/- 2.04) mm (> or = 6 years old). The average of antero-posterior distance of antrum was (12.25 +/- 1.23) mm (<6 years old) and (10.05 +/- 1.69) mm (> or = 6 years old). No statistically significant differences were seen in left-right distance of aditus by age, sex and side (P > 0.05). Significant differences in up-down distance of aditus was found between male and female, and the distance in male was greater than that in female (P < 0.05). Statistically significant differences were seen in left-right distance and up-down distance, antero-posterior distance of antrum by age (P < 0.05), but no statistically significant differences by sex or side (P > 0.05). Imaging of aditus ad antrum is relatively constant in the normal persons, while the aditus is more diverse. Significant gender differences were seen in up-down distance. There were significant differences in left-right distance, up-down distance, and antero-posterior distance of aditus among all age groups.

Li N.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2011

To investigate of the regulatory effect of Rho-kinase pathway activation on angiotensin II (Ang II)-induced contraction of human airway smooth muscle cells (HASMCs) in vitro. Cultured primary HASMCs were divided into control group, AngII group, AngII + irbesartan group and AngII + Y-27632 group with corresponding treatment. AngII-induced contraction of HASMCs was evaluated using collagen gel lattices and observed morphologically using immunofluorescence assay. Western Blotting was significantly performed to examine the protein expression of Rho-kinase signal pathway. AngII-induced HASMC contraction was inhibited by treatments with irbesartan and Y-27632 as shown by gel contraction assay (P<0.001). Y-27632 treatment produced a stronger inhibitory effect than irbesartan on the expression of phosphorylated moesin, a substrate of Rho kinase (P<0.05). AngII induces the contraction of HASMCs partially as a result of activation of Rho-kinase pathway.

Zhou Y.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2011

To construct a rheumatoid arthritis-specific full-length fully human mammalian display antibody libraries. Peripheral blood lymphocytes were isolated from patients with rheumatoid arthritis. The repertoires of kappa light chain (LCκ) and heavy chain variable region (VH) of the antibodies were amplified by RT-PCR. The amplified LCκ and VH genes were inserted into the vector pDGB-HC-TM separately, and the ligated libraries were transformed into competent E.coli TOPO-10 strain to construct the rheumatoid arthritis-specific antibody heavy and light chain libraries. 293T cells were co-transfected with the libraries and the full-length fully human antibody expressed on the surface of 293T cells were analyzed by flow cytometry. The libraries of rheumatoid arthritis-specific antibody LCκ and heavy chain (IgG1) were constructed. The expression of full-length fully human antibody on the surface of 293T cells was confirmed by flow cytometry. With the rates of correct LCκ and heavy chain sequence insertion reaching 80% and 60%, respectively, as shown by DNA sequence analysis of the randomly selected clones, the libraries showed an expressible combinatory diversity of 6.13×10(10). The constructed libraries provide a useful platform for screening rheumatoid arthritis-specific antibodies.

He B.F.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2011

To study the radiosensitizing effect of gefitinib on nasopharyngeal carcinoma cell line CNE2 in vitro. Nasopharyngeal carcinoma cell line CNE2 was cultured in RP2MI 1640. MTT assay was performed to evaluate the cell proliferation changes in response to gefitinib treatment and the radiosensitizing effect of gefitinib. The cell survival curves and sensitive enhancement ratio (SERs) were obtained with a clonogenic assay. Flow cytometry analysis was applied to detect the cell cycle changes and cell apoptosis. MTT assay showed that cells exposed to gefitinib and radiation had a significantly lower survival ratio compared to the cells with radiation exposure only (0.582∓0.012 vs 0.398∓0.016, P=0.002), with a SER of 1.535∓0.134. The S phase cell percentage was significantly decreased and G(2)-M phase cells increased in gefitinib plus radiation group (P=0.000), suggesting a synergistic effect of gefitinib and radiation. Gefitinib can enhance the radiosensitivity of nasopharyngeal carcinoma CNE2 cells in vitro possibly by inhibiting cell proliferation, inducing cell apoptosis, and causing changes in the cell cycle distribution.

Zhou X.T.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2011

To observe the effect of 25-hydroxyvitamin D3 on the permeability and ZO-1 expression in normal human airway epithelial cells. MTT assay was used to assess the viability of human airway epithelial cell line 16HBE following a 24-hour exposure to different concentrations of 25-hydroxy vitamin D3, and the transepithelial electrical resistance (TER) of the cell monolayer was measured using a Millicell-ERS voltohmmeter. Real-time quantitative RT-PCR was employed to determine the changes of ZO-1 mRNA expression in the cells following the exposures. Exposure to 25-hydroxyvitamin D3 resulted in significantly increased permeability of 16HBE cells, but the exspression of ZO-1 showed no obvious changes. 25-hydroxyvitamin D3 at 4×10(-9) mol/L showed the strongest effect in increasing the permeability of cell monolayer. 25-hydroxyvitamin D3 increases the permeability of normal bronchial airway epithelial cell monolayer in vitro, but this effect is not mediated by upregulation of ZO-1 expression.

Jiao H.L.,Southern Medical University
Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials | Year: 2011

To study the anti-tumor effect of total alkaloid of Sophora alopecuroides (TASA) on human colon adenocarcinoma SW480 cells and Balb/c nude mice tumor xenograft. The effect of TASA on cell proliferation was assessed using MTT assay and the cell apoptosis was detected using Annexin V-FITC apoptosis assay. The nude mouse model bearing transplanted solid tumor SW480 was established. The changes of the volume and weight of the tumor were determined after treatment the mice with TASA. Fluorescence quantitative PCR was used to detect Caspase-3, Caspase-9 and BCL-2 mRNA expressions in the tumor. TASA inhibited the proliferation of SW480 cells in a dose- and time-dependent manner. The apoptotic rate of cells was the best when the concentration of TASA was 0.92 mg/mL at 48 hours. The volume and weight of the tumor xenograft in TASA groups were decreased when compared with those of the control group. The results of RT-PCR showed that TASA activated the pro-apoptotic Caspase-3 and Caspase-9 and lowered expressions of BCL-2. TASA can inhibit the growth of SW480 cells and the growth of transplanted solid tumor of human SW480 cell line, the mechanism of which involves the effect of Caspase-3, Caspase-9 and BCL-2 expression.

LONG M.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2011

To study the effect of HIV-1 gp41 ectodomain (gp41-I90) on the cytoskeletal changes in human brain microvascular endothelial cells (HBMECs) induced by Cryptococcus neoformans. HBMECs were cultured on collagen-coated chamber slide or transwell to allow the formation of cell monolayers. After pre-treatment with gp41-I90 and infection with Cryptococcus neoformans, the HBMECs were examined for the expression of actin or filamin by immunofluorescence assay. HRP permeability of the HBMECs treated with gp41-I90 was detected by ELISA. Transcytosis of Cryptococcus neoformans through the gp41-I90-treated HBMECs was detected by direct counting from a hemocytometer. gp41-I90 obviously enhanced the cytoskeletal changes of the HBMECs infected by Cryptococcus neoformans, causing curved and sparse filamentous arrangement of actin and filamin. gp41-I90 treatment also resulted in obviously increased HRP permeability of the cells and transcytosis of Cryptococcus neoformans. gp41- I90 enhances Cryptococcus neoformans binding to HBMECs, which is related to its effect in enhancing Cryptococcus neoformans-induced cytoskeletal changes of the cells.

He X.F.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2011

To explore the association of CCR5δ32, CCR2-64I and SDFl-3 A gene polymorphisms with HIV-1-infection in Chinese population. A meta-analysis was performed to identify case-control studies of CCR5δ32, CCR2-64I and SDFl-3 A polymorphisms from the literatures. Fourteen studies of CCR5δ32 were found, involving a total of 1607 cases and 1632 controls. Compared with the wild-type homozygote wt/wt, the pooled odds ratios (95%CI) of wt/mt, mt/mt, and wt/mt+mt/mt genotypes of CCR5δ32 gene polymorphisms were 1.156 (0.808, 1.654), 0.997 (0.198, 5.022), and 1.149 (0.808, 1.634), respectively. Twelve studies of CCR2-64I were identified, including 1415 cases and 1239 controls. Compared with the wild-type homozygote wt/wt, the pooled odds ratios (95%CI) of wt/mt, mt/mt, and wt/mt+mt/mt genotypes of CCR2-64I gene polymorphisms were 1.005 (0.844, 1.197), 1.191 (0.808, 1.754), and 1.028 (0.870, 1.214), respectively. Ten studies of SDFl-3 A were found, involving 1179 cases and 1003 controls. Compared with the wild-type homozygote wt/wt, the pooled odds ratios (95%CI) of wt/mt, mt/mt, and wt/mt + mt/mt genotypes of SDF1-3 A gene polymorphisms were 1.010 (0.830, 1.228), 1.188 (0.860, 1.643), and 1.038 (0.861, 1.250). CCR5δ32, CCR2-64I and SDFl-3 A gene polymorphisms do not show strong correlations to HIV-1-infection in Chinese population. These 3 genes may not have protective effect against HIV-1 infection in Chinese population, suggesting the susceptibility of Chinese population to the infection.

Ai R.T.,Southern Medical University
Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials | Year: 2011

To study the effect of 1,2,6-Tri-O-galloyl-beta-D-glucopyranose (BJA32531) on the miRNA expression during BJA32531-induced cytotoxicity in human HepG2 hepatocarcinoma cells. Cell proliferation was assessed using a colorimetric assay (cell counting kit-8). Apoptosis was assessed by annexin V and propidium iodide staining. The miRNA expression profile of the cancer cells was analyzed by a miRNA array and quantitative real-time PCR. BJA32531 inhibited the cell proliferation and increased apoptosis in HepG2 cancer cells. Cellular exposure to BJA32531 influenced the miRNA expression pattern in the cells, including 19 upregulated and 85 down-regulated miRNAs in the cells. The up-regulations of let-7a and miR-10b as well as the down-regulations of miR-132 and miR-125b were verified to be consistent with the the results of the miRNA array. Our study suggests that the mechanisms by which BJA32531 exerted the antiproliferative effects on HepG2 cancer cells may be related to its regulation of miRNA.

Sun K.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2011

To investigate the regulatory effect of microRNA-221 (MIR221) on CDKN1C/p57 expression in colon carcinoma cells in vitro. Caco2 cells were treated with or without anti-p57-siRNA prior to the addition of pre-MIR221 or anti-MIR221. The MIR221 expression pattern was detected by real-time RT-PCR, and the mRNA and protein levels of CDKN1C/p57 expression were detected using semi-quantitative RT-PCR and Western blotting. Caco2 cell proliferation following the treatment was detected with MTT assay. CDKN1C/p57 3'-UTR fragment was amplified by PCR from the genome DNA of human colon and inserted into a luciferase reporter plasmid. The luciferase reporter plasmid construct was then transfected into Caco2 cells along with pre-MIR221 or anti-MIR221, and the luciferase activity in the transfected cells was detected. MIR221-specific inhibitor significantly up-regulated CDKN1C/p57 protein expression in Caco2 cells (P<0.01). Anti-MIR221 could markedly inhibit Caco2 cell proliferation, and the inhibitory effect was obviously abolished by pretreatment with anti-p57-siRNA, suggesting that the inhibition was mediated by CDKN1C/p57 (P<0.01). A significant increase of luciferase activity was detected in Caco2 cells co-transfected with the luciferase reporter plasmid construct and anti-MIR221 (P<0.01). MIR221 can interact with the target site on the 3'-UTR of CDKN1C/p57 mRNA to inhibit CDKN1C/p57 expression by post-transcriptional gene silencing to promote colon carcinoma cell proliferation, suggesting the value of MIR221 as a potential target for treatment of colon carcinoma.

Wan L.,Southern Medical University | Li X.,Southern Medical University | Shen H.,Southern Medical University | Bai X.,Southern Medical University
Clinical and Translational Oncology | Year: 2013

Introduction: Elevated Enhancer of Zeste Homologue 2 (EZH2) expression is involved in many human malignancies through epigenetically silencing related genes. However, the study of the EZH2 protein expression in lung cancer remains at the qualitative or semi-quantitative level. The present study is to elucidate the roles of EZH2 in the progression and metastasis of different subtypes of lung cancer at quantitative level. Materials and methods: Lung carcinoma tissue microarray was constructed containing 32 normal adult lung tissues, 113 lung carcinomas and 57 lymph-node metastases. EZH2 protein expression was detected by immunohistochemistry and assessed quantitatively with Leica Q500MC image analysis system. Positive unit (PU) value was used to evaluate the protein expression intensity of positive cells from systematically selected fields under the microscope. Results: Elevated Enhancer of Zeste Homologue 2 PU in lung carcinomas was significantly greater than that in normal lung tissues (p = 0.001). Increased EZH2 expression was correlated with histological subtypes, differentiation, TNM stage, and lymph-node metastases (p < 0.05). EZH2 PU of primary lung carcinomas was smaller than that of lymph-node metastasis (p = 0.002). EZH2 PU was not associated with patients' gender, age, smoking status, tumor location, and tumor size (p > 0.05). Conclusions: Elevated Enhancer of Zeste Homologue 2 PU is increased with the development of lung cancer. EZH2 may play an important role in the progression and metastasis of lung cancer. © 2012 Federación de Sociedades Españolas de Oncología (FESEO).

Guan J.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2011

To investigate the effects of lentivirus-mediated RNA interference (RNAi) targeting a proliferation-inducing ligand (APRIL) on the chemosensitivity to 5-FU of colorectal cancer cell line LoVo. The lentiviral vector siRNA-APRIL was constructed and verified by PCR and DNA sequencing. LoVo cells were transfected with siRNA-APRIL plasmid, non-targeting siRNA plasmid, or empty plasmid. Forty-eight hours after the transfection, the cells were examined for APRIL expression using Western blot. Seventy-two hours after treatment with 10 μg/ml 5-FU, flow cytometry was used to detect the cell apoptosis and cell cycle changes. The cell growth inhibition rate following 5-FU exposure was detected by MTT assay. PCR analysis and DNA sequencing demonstrated that the RNAi sequence targeting APRIL gene was successfully inserted into the lentiviral vector. siRNA-APRIL transfection resulted in obviously reduced expression of APRIL in LoVo cells. After 5-FU exposure, the apoptosis rate of siRNA-APRIL-transfected cells were increased to (21.12∓3.35)%, significantly higher than that in cells transfected with the non-targeting plasmid or the empty plasmid [(13.06∓1.92)% and (12.28∓1.79)%, respectively, P<0.01]; the cell number in G0/G1 phase increased while that in G2/M phase decreased in siRNA-APRIL-transfected cells. The growth inhibition rate in siRNA-APRIL group was (59.67∓5.03)%, significantly higher than that in the other two groups [(42.33∓4.16)% and (39.67∓4.73)%, respectively, P<0.01]. Lentivirus-mediated RNAi targeting APRIL can effectively suppress the expression of APRIL in LoVo cells and enhance the chemosensitivity of the cells to 5-FU.

Li M.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2011

To evaluate the effect of metformin on the apoptosis of renal cell carcinoma (RCC) cells in vitro and its mechanisms. Fluorescent microscopy and flow cytometry were used to examine the changes in the apoptosis of 786-O cells after metformin treatment. The possible signaling molecules involved in this process were analyzed by immunoblot analysis of AMP-activated protein kinase (AMPK) signaling and caspase 9. Metformin induced apoptosis and caspase 9 activation in 786-O cells in low-serum medium but not in normal-serum medium. Metformin also induced AMPK activation in 786-O cells, but this activation was not associated with the cell proliferation inhibition or apoptosis-inducing effect of metformin. Metformin can induce apoptosis of RCC cells in vitro, suggesting its potential as a therapeutic agent for RCC.

Li X.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2011

To investigate the variation of serum thyroid transcription factor-1 (TTF-1) in different patients and explore its significance in the diagnosis of lung carcinoma. Dot-enzyme linked immunosorbent assay (dot-ELISA) and Leica Q500 MC image analysis system were used to quantitatively detect TTF-1 protein in the serum samples from normal healthy adults and from patients with benign lung disease, lung cancer, thyroid carcinoma and non-thyroid carcinoma. The sensitivity, specificity, standardized positive predicative value, standardized negative predicative value, standardized accuracy and standardized wrong diagnostic rate of the method were 90.91%, 82.22%, 83.64%, 90.04%, 86.57% and 13.43%, respectively. The cutoff value of serum TTF-1 in healthy normal adults was 36.39, with a ROC value of 0.95. Serum TTF-1 PU was significantly higher in patients with lung adenocarcinoma, squamous cell lung carcinoma and thyroid carcinoma than in healthy adults and patients with benign lung diseases and non-thyroid carcinoma (P=0.000). Serum TTF-1 PU was similar in lung adenocarcinoma, squamous cell lung carcinoma, small cell lung carcinoma, large cell lung carcinoma and thyroid carcinoma (P=0.744, 0.677, and 0.333, respectively). Serum TTF-1 PU was greater than the PU in the corresponding homogenate of lung adenocarcinoma, squamous cell lung carcinoma, small cell lung carcinoma, large cell lung carcinoma and thyroid carcinoma (P=0.000). Serum and homogenate TTF-1 PU was correlated to TNM stage of lung cancer patients (P=0.000) but not to gender, tumor types, differentiation or lymph node metastasis. Lung adenocarcinoma, squamous cell lung carcinoma and thyroid carcinoma are suspected when serum TTF-1 PU is higher than 36.39. Serum TTF-1 is not helpful in differentiating the types of lung carcinomas and thyroid carcinoma. After exclusion of thyroid carcinoma, detection of serum TTF-1 can be helpful in the diagnosis of lung cancer. In different lung carcinomas and thyroid carcinomas, the serum TTF-1 is higher than the corresponding homogenate TTF-1 level. Serum TTF-1 increases with the progression of TNM stage of lung carcinoma.

Lu W.,Southern Medical University
Zhonghua nei ke za zhi [Chinese journal of internal medicine] | Year: 2011

To investigate the relationship between the oxidative injury induced by low glucose and mitochondrial membrane potential in HUVEC-12 cells. Human umbilical vein endothelial cells HUVEC-12 were cultured in low concentration glucose for 4 h. Cell viability of HUVEC-12 cell was assessed with MTT assay. Dihydroethidium (DHE) was used as a reactive oxygen species (ROS) capture, which was detected the mean fluorescence intensity of samples and Rhodamine 123 as a fluorescence detector was to measure the level of mitochondrial membrane potential (MMP) in cells. Comparing to HUVEC-12 cells viability in 5.5 mmol/L glucose group (96.80 ± 3.20)%, cells exposed to 2.8 mmol/L glucose group (66.40 ± 1.60)% and 0 mmol/L glucose group (58.93 ± 1.67)% were decreased by 32% and 40% respectively (P < 0.01). ROS level of 5.5 mmol/L glucose group, 2.8 mmol/L glucose group and 0 mmol/L glucose group were 0.59 ± 0.02, 0.74 ± 0.04 and 0.88 ± 0.05, respectively, increased by 25% in cells exposed to 2.8 mmol/L glucose and by 48% in cells without glucose exposure comparing to 5.5 mmol/L glucose group (P < 0.01); MMP levels of 5.5 mmol/L glucose group, 2.8 mmol/L glucose group and 0 mmol/L glucose group were 148.83 ± 3.51, 271.07 ± 19.54 and 357.74 ± 51.32 respectively, increased to 1.8 times in cells exposed to 2.8 mmol/L glucose and to 2.4 times in cells without glucose exposure comparing to 5.5 mmol/L glucose group (P < 0.01). Low glucose leads to injury in HUVEC-12 cells, which is probably induced by the oxidative stress via the increasing MMP.

Massoud A.H.A.,Al - Azhar University of Egypt | Massoud A.H.A.,Southern Medical University | Naam N.H.,Al - Azhar University of Egypt | Naam N.H.,Southern Medical University
Journal of Hand Surgery | Year: 2012

Perilunate injuries are complex and occasionally go unrecognized acutely. Open reduction and internal fixation is a valid treatment option for these injuries. The purpose of this study was to evaluate the functional outcome of treating chronic perilunate injuries with open reduction and internal fixation. Between 1998 and 2007, we treated 24 patients for chronic perilunate injuries. We excluded 5 patients from this study because they underwent proximal row carpectomy or limited wrist arthrodesis. We treated the remaining 19 patients with open reduction and internal fixation. Mean time from injury to surgery was 29 weeks. All patients were men, with a mean age of 27 years. A total of 13 patients had fracture dislocations (group 1); of these, 11 were transscaphoid and 2 were transscaphoid transcapitate fracture dislocations. Six patients had perilunate dislocations (group 2). Postoperative follow-up averaged 58 months. All carpal fractures healed at an average of 18 weeks. At final evaluation, the average pain scores during rest, daily activities, and manual work on a 20-point visual analog scale were 0, 2, and 3, respectively, with no significant difference between groups. The active extension and flexion of the wrist averaged 39% and 52% of the uninjured side, respectively. Grip strength averaged 87% of the uninvolved extremity. According to the Mayo wrist scoring system, 58% of all patients (69% of group 1 and 33% of group 2) achieved good to excellent results. A total of 18 patients returned to their original work activities; 14 patients (74%) were very satisfied. No patients required secondary procedures. Despite late presentation, patients with chronic perilunate injuries can be treated with open reduction internal fixation, with satisfactory results. Patients with lesser arc injuries have less successful outcome. Patients with irreducible dislocations or major articular damage may require wrist salvage procedures. Therapeutic IV. © 2012 American Society for Surgery of the Hand. All rights reserved.

Wen J.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2012

To explore the characteristics of the talonavicular joint movement in vivo and its effects on changes of the medial longitudinal arch. Foot CT images in the initial position (neutral position) and terminal position (maximum varus-adduction-dorsiflexion position) were acquired from 9 cases (5 healthy volunteers, including 4 males and 1 female) during foot varus-adduction-dorsiflexion motion. Based on the principle of rigid body kinematics, the CT data were reconstructed and analyzed with Mimics and Geomagic reverse engineering software. The changes of the talonavicular joint in three-dimensional in 6 degrees of freedom were calculated to determine its correlation to the medial longitudinal arch angle. During foot varus-adduction-dorsiflexion motion, the talonavicular joint underwent varus-adduction-plantarflexion motion, with the motion range of 38.82∓5.98° in varus, 19.71∓6.33° in adduction, and -5.09∓6.89° in plantarflexion. During talonavicular joint motion, the medial shift of the navicular was significantly correlated to the changes of foot medial longitudinal arch (P<0.05). Digital technology can solve the problem of measurement of talonavicular joint three-dimensional motion in vivo. Though as a ball-and-socket joint, the talonavicular joint mainly rotates around the sagittal axis, and its movement is a major factor to cause changes of foot medial longitudinal arch.

Peng Q.X.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2011

To investigate the effect of water extracts of Coptidis Rhizoma and Evodiae Fructus (CREF) on the proliferation and apoptosis of human gastric carcinoma cells (SGC-7901) and determine the optimal proportion of Coptidis rhizoma to Evodiae fructus. The growth inhibition of SGC-7901 cells treated with the water extracts of CREF of varying proportions was tested with MTT assay. The cell apoptotic rate and mitochondrial membrane potential were analyzed with flow cytometry. The water extract of CREF with Coptidis Rhizoma: Evodiae Fructus proportions at 1:6, 2:5, 3:4, 4:3, 5:2, and 6:1 all significantly inhibited the growth of SGC-7901 cells after a 24-h or 48-h treatment (P<0.05). The growth inhibition and cell death ratio both exhibited a dose-dependent pattern of Coptidis Rhizoma. Flow cytometry analysis showed that, after treatment of the cells with CREF at the proportions of 1:6, 2:5, 3:4, 4:3, 5:2, and 6:1, the apoptotic rate were (8.50 ∓ 1.59)%, (9.90 ∓ 1.01)%, (17.15∓1.68)%, (21.55 ∓ 1.97)%, (34.10 ∓ 1.06)% and (34.40 ∓ 1.02)%, respectively, all significantly higher than that in the control group [(1.69 ∓ 1.91)%, P<0.05]. JC-1 Kit staining showed that mitochondrial membrane potential of SGC-7901 cells was decreased and the ratio of green to red fluorescence increased significantly after incubation with CREF. CREF can inhibit the growth and induce apoptosis of SGC-7901 cells, and the strongest effect is achieved at the optimal proportion of Coptidis Rhizoma and Evodiae Fructus at 6:1.

Tian P.G.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2011

To select the peptides that specifically bind human cancer stem cell surface marker CD133 from the Ph.D.-7>(TM) phage peptide library. With a biotinylated extracellular fragment of human cancer stem cell surface marker CD133 as the target protein, the CD133 high-affinity peptides were screened from the phage peptide library by liquid phase panning. The clones with high-binding force with human CD133 were then identified by sandwich ELISA and their single-stranded DNA was extracted to test the specificity by competitive ELISA. The amino acid sequences of the selected peptides derived from the phage DNA sequences were synthesized after sequence alignment analysis, and their capacity of binding with colorectal carcinoma cells was assessed by immunofluorescence technique. After 4 rounds of liquid phase selection, the phages capable of specific binding with human CD133 were effectively enriched, with an enrichment ratio of 388 times compared to that at the fourth and first rounds. Thirteen out of the 20 clones from the fourth round of panning were identified as positive clones, among which 11 had identical amino acid sequence of TISWPPR, and 2 had the sequence of STTKLAL, and the former sequence showed a stronger binding specificity to CD133. We have successfully obtained a peptide that specifically binds human CD133 from the Ph.D.-7(TM) phage peptide library, demonstrating the feasibility of screening small molecule high-affinity polypeptides from phage peptide library by liquid-phase panning.

Ma Q.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2011

To develop an amplified luminescent proximity homogeneous immunoassay (AlphaLISA) kit for the detection of human hepatitis B virus e antibody (HBeAb). The neutralizing and competitive inhibition method was used to develop the AlphaLISA kit for detection of serum HBeAb. The working range of the kit was 0.003-16 NCU/ml with a sensitivity up to 0.003 NCU/ml. The intra- and inter-assay coefficient of variation was 5.3% and 6.8%, respectively. The kit showed no cross-reaction with HBcAb, and comparison of the detection results with those of a commercially available Elecsys HBeAb kit (Roche) for 136 samples showed a correlation coefficient of 0.961. The AlphaLISA kit for HBeAb detection meets the clinical requirements for detection HBeAb in human serum.

Lu Y.J.,Southern Medical University
Zhongguo zhen jiu = Chinese acupuncture & moxibustion | Year: 2011

After reviewing the literatures in recent years, it is of importance to investigate on the key brain region activated by needling with the baseline state fMRI in research of acupoint specificity and brain fMRI. It is valuable to define two ways to determine the key brain region: one is the so called Seek True, while the other one is the so called Prove Wrong, and some examples of applications of the two methods are given in order to prove that the methods are feasible on determining the key brain region.

Wang W.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2011

To investigate miRNA-221 expression in human colorectal carcinoma (CRC) cells and the effects of miR-221-specific inhibitor on the proliferation and apoptosis of CRC cells. Four human CRC cell lines (HT-29, Lovo, SW-480, and CaCO2) were examined for miRNA-221 expression using real-time Q-PCR. The specific 2,-methoxy-modified RNA oligonucleotides of miR-221 (anti-miR-221) were synthesized and transfected into Caco2 cells via liposome, and the changes in the expression of miR-221 in the cells were detected by real-time Q-PCR. The proliferation and apoptosis of the transfected CRC cells were detected using MTT assay and flow cytometry. The 4 human CRC cells showed significantly upregulated expression of miR-221 compare with HUVECs (P<0.01). The miR-221-specific inhibitor, anti-miR-221, significantly inhibited the expression of miR-221 in Caco2 cells and suppressed the cell proliferation, causing also obvious cell apoptosis (P<0.01). The miR-221-specific inhibitor shows potent inhibitory effect on the growth of CRC cells, suggesting its value as a potential anti-tumor candidate for treatment of CRC.

Li C.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2011

To establish a nasopharyngeal carcinoma (NPC) cell line with stable nestin gene silencing induced by short-hairpin RNA (shRNA) interference. The nestin mRNA levels in 8 NPC cell lines were detected by real-time PCR and immunofluorescence assay. The recombinant lentiviral shRNA expression plasmid targeting nestin was packaged into mature lentivirus by 293T cells, and the supernatant containing the virus was harvested, concentrated and titrated. The best target for RNA interference was selected by real-time PCR. 5-8F cells was then infected by the recombinant lentiviral vector, and the expression of nestin in the cells was detected by Western blotting and real-time PCR. The 8 NPC cell lines showed different nestin expression levels, among which 5-8F cells had the highest nestin expression. The recombinant lentiviral vector was successfully constructed and verified by PCR and sequencing. Nestin mRNA and protein levels was significantly reduced in 5-8F cells infected with shRNA-nestin lentivirus as compared with the negative control and the blank control cells. Using the recombinant lentiviral vector constructed, we have successfully established a 5-8F NPC cell line with stable nestin gene silencing.

Lu C.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2011

To investigate the biological effects of ultraviolet B (UVB) irradiation on human bronchial epithelial cells (16HBE cells) and explore the possible mechanism. The survival rates of 16HBE cells were detected by MTT assay at 12 h after UVB irradiation at different doses (0, 10, 30, 50, 70, and 100 J/m(2)) or at 50 J/m(2) for different durations (2, 4, 8, 12, and 24 h). The DNA ladder was detected by agarose gel electrophoresis, the cell cycle changes were analyzed by flow cytometry, and the expression of nuclear factor-κB (NF-κB)/p65 protein was assayed by Western blotting following the exposures. UVB irradiation of the cells resulted in lowered cell survival rates, DNA fragmentation, S phase arrest and up-regulation of NF-κB/p65 protein expression. UVB irradiation can induce growth inhibition and apoptosis of 16HBE cells, in which process NF-κB protein may play a key role.

Zhou Z.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2012

To investigate the surgical technique of skeletonization of the great saphenous vein (GSV) at the saphenofemoral junction (SFJ) in surgical intervention of primary varicosity and evaluate the outcomes one year after the operation. A total of 624 cases (774 limbs) of primary varicosity of the GSV were prospectively divided into skeletonization group (265 cases, 325 limbs) and control group (359 cases, 449 limbs). In the skeletonization group, skeletonization of the GSV at the SFJ, its branches and other aberrantly joined superficial veins was performed, and in the control group, routine high ligation of the GSV was performed, after which laser-ablation of the GSV, GSV stripping, Muller's operation, mutilation of the perforators and ulcer-related operations were performed in both groups. Twenty cases in the skeletonization group were found to have superficial veins directly joining into the femoral vein or into the GSV in different tissue layers. In 14 cases in the control group, the superficial veins of the internal femoris or lateral femoris were mistaken for the GSV. No difference was found in the operating time between the two groups (t=0.68, P>0.05), but the skeletonization group had a significantly less bleeding volume (t=1.75, P<0.05). Statistical differences were found between the two groups in intraoperative bleeding rate in the inguinal regions, venous clinical severity scores (2.1∓0.5 vs 4.6∓0.9, t=1.96, P<0.05), and residual varicosity and recurrences (3/325 vs 13/449, V=1.25, P<0.05) at the one year follow-up. Skeletonization of the GSV and its branches and other aberrantly joined superficial veins at the SFJ can decrease the postoperative residual varicosity and recurrence due to blood reflux.

Lin X.C.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2013

To evaluate the protective effect of licoflavone on gastric mucosa in rats with chronic superficial gastritis and explore the possible mechanism. SD rat models of chronic superficial gastritis was established by intragastric administration of 0.02% ammonia and long-term irregular diet. The rat models were then randomized into model group, vitacoenzyme group and 3 licoflavone groups of high, medium, and low doses. After 30 days of treatment, the gastric histopathology, mucosal lesions, scanning electron microscopy, mucin function production by the gastric mucosa epithelial cells, serum PGE(2) level and gastric microcirculation were assessed to evaluate the protective effect of licoflavone on gastric mucosa. Compared with normal control rats, the rat models of chronic superficial gastritis showed significantly higher gastric mucosal injury rate, histopathological scores and gastric mucin content. Licoflavone significantly ameliorated gastric pathology and increased serum PGE(2) level, enhanced acidic mucin secretion by the epithelial cells, and improved gastric microcirculation in the rat models. Licoflavone feeding suppresses gastric mucosa injury, protects and restores the injured mucosa in rats with chronic superficial gastritis, and these effects are related with the up-regulation of serum PGE(2) level.

Li R.,Southern Medical University
Medical science monitor : international medical journal of experimental and clinical research | Year: 2012

Osteochondral fracture (OCF) of the lateral femoral condyle has a low incidence and old OCF is even more rarely seen; it is difficult to differentiate from late osteochondritis dissecans (OCD). In this report, we present the case of a 20-year-old male patient with an old OCF of the lateral femoral condyle. The possible etiology of OCF is discussed, along with its clinical manifestation, diagnosis, and treatment. He underwent arthroscopically-assisted reduction and fixation with cannulated screws. Four months after the surgery, arthroscopy showed good osteochondral healing, and screws were removed. He had achieved good functional recovery by the follow-up visit. Old OCF should be distinguished from OCD in clinical practice, and osteochondral bodies should be preserved as much as possible. Osteochondral reduction and fixation under arthroscopy was minimal and the clinical effect was good.

Nan H.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2010

To assess the effect of local and intravenous transplantation of adipose tissue-derived stem cells (ADSCs) in promoting soft tissue wound healing in rats. ADSCs isolated from the adipose tissues of SD rats were cultured in vitro, and the third-passage cells were identified for their capacity of multipotent differentiation. Eighteen SD rats with 1.8 cm2 dorsal full-thickness soft tissue defects (0.5 cm deep) were randomized into 3 groups to receive injection of 3.0×106 DiI-labeled ADSCs via the tail vein, local injection of the cells at the wound site, or injection of saline (control). The wound healing was evaluated on days 3, 7, 11, and 14 postoperatively. On day 24 after the injury, tissue samples at the wound site were collected for fluorescent microscopy and HE staining. The ADSCs obtained were capable of adipogenic, osteogenic, and neurogenic differentiation in vitro. ADSCs transplantation significantly promoted wound healing as compared to the control group. Obvious wound contracture was observed in the local injection group on day 3 and in the intravenous injection group on day 7. Fluorescence microscopy revealed DiI-positive cells in the healing wound, and HE staining showed a greater tissue thickness at the wound in the two ADSCs transplantation groups. Compared to the control group, the two ADSCs transplantation groups showed more gland-like structures and better neovascularization at the wound. ADSCs can significantly promote wound healing in rats, and local injection of ADSCs allows more rapid and obvious wound healing than tail veil injection of the stem cells.

Li H.L.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2011

To discuss the optimal approach of percutaneous nephrolithotomy (PCNL) for treatment of complicated renal calculi. A total of 581 patients with complicated renal calculus were treated by PCNL through the upper pole calix access. Of the 581 patients, 55 had multiple upper pole calculi, 136 had staghorn stones, 145 had partial staghorn stones, and 245 had multiple renal calculi. PCNL through the upper pole calix access was completed successfully in all the cases. Of these patients, 90.3% (525/581) were stone-free after a single access, with a total stone-free rate of 94.6% (550/581). Thirty-five patients needed two accesses, 10 needed 3 accesses, 2 required 4 accesses, and 1 patients had 5 accesses. The operative time ranged from 30 to 150 min (mean 45 min). The successful rate of puncture was 100% without occurrence of severe injury of the pleura, intestine, peritoneum or other adjacent organs. Percutaneous nephrolithotomy through the upper pole calix access allows greater stone clearance rate due to its easy access into the intrarenal collecting system and can be an ideal approach for PCNL for complicated renal calculi.

Zhu Q.,Southern Medical University | Huang L.,Southern Medical University | Su J.,Southern Medical University | Liu S.,Southern Medical University
Chemical Communications | Year: 2014

A sensitive and visible fluorescence-turn-on probe for the critical micelle concentration (CMC) determination of ionic surfactants has been developed based on practically no emission in micelles but strong aggregation-induced emission in solution of racemate tetrahydropyrimide THP-1. CMC values were determined via the inflexion with the strongest fluorescence intensity. © 2014 The Royal Society of Chemistry.

Hu S.,University of Electronic Science and Technology of China | Liao Z.,Sichuan Normal University | Chen W.,Southern Medical University
Mathematical Problems in Engineering | Year: 2012

Existing integer-order Nonlinear Anisotropic Diffusion (NAD) used in noise suppressing will produce undesirable staircase effect or speckle effect. In this paper, we propose a new scheme, named Fractal-order Perona-Malik Diffusion (FPMD), which replaces the integer-order derivative of the Perona-Malik (PM) Diffusion with the fractional-order derivative using G-L fractional derivative. FPMD, which is a interpolation between integer-order Nonlinear Anisotropic Diffusion (NAD) and fourth-order partial differential equations, provides a more flexible way to balance the noise reducing and anatomical details preserving. Smoothing results for phantoms and real sinograms show that FPMD with suitable parameters can suppress the staircase effects and speckle effects efficiently. In addition, FPMD also has a good performance in visual quality and root mean square errors (RMSE). © 2012 Shaoxiang Hu et al.

Zhao Y.,Southern Medical University | Gao J.,Southern Medical University | Lu F.,Southern Medical University
Experimental and Therapeutic Medicine | Year: 2013

The aim of this study was to determine the effects of paracrine regulation on the invasive ability of MCF-7 human breast cancer cells through human adipose-derived stem cell (hADSC) adipogenesis. hADSC differentiation of the third and fourth passages of cells was induced in different induction media: osteogenic, adipogenic and chondrogenic. Transwell migration assays in the differently conditioned media, flow cytometry, enzyme linked immunosorbent assay and western blot analysis for selected cytokines were performed. The flow cytometric analysis demonstrated positive expression of CD29, CD44 and CD105, while expression of CD34 and CD45 was not identified. The transwell migration assay showed that the invasive ability of MCF-7 cells was significantly enhanced during hADSC adipogenesis. hADSCs exerted a significantly positive effect on the invasive activity of MCF-7 cells during adipogenesis. The results indicate that the high expression levels of activating protein 2 (aP2) in MCF-7 and adipocytes induced for 12 days may be associated with cell growth, invasion and metastasis. Peroxisome proliferator-activated receptor γ may be involved in fatty syntheses during adipogenic initiation and following adipogenic differentiation, possibly acting as a protection factor resulting in cell maturation and differentiation. This study also demonstrated that the expression of vascular endothelial growth factor was repressed by hADSCs, while that of matrix metalloproteinase-2 and urokinase-type plasminogen activator was increased to a significant level.

Luo K.,Southern Medical University | Liu Z.,Southern Medical University | Karayiannis P.,Imperial College London
Journal of Viral Hepatitis | Year: 2010

Alpha-fetoprotein (AFP) is a marker of the presence of hepatocellular carcinoma (HCC), but is also elevated in advanced chronic hepatitis B. The detection and usage of AFP tests need to be improved. A cohort of 101 patients with advanced chronic hepatitis B and elevated AFP values was treated with entecavir (ETV) or peginterferon-α2a. ETV was more effective in reducing AFP levels; mean time to AFP normalization was 11.9 weeks after ETV treatment initiation vs 22.3 weeks in peginterferon treated patients (P = 0.000). An additional cohort of 93 hepatitis B virus (HBV) cirrhotic patients with elevated AFP were treated with ETV prospectively and maintained under intensive surveillance. HCC developed in 16 (17.2%) patients in whom the strongest independent predictor was a continued AFP rise in spite of ongoing treatment. In this context, nodules of sizes 10-14 mm and 15-20 mm were detected in 40% of patients each. In conclusion, HBV cirrhotic patients with rising AFP levels were at very high risk of HCC development. Early detection of minute lesions may be possible by monitoring AFP levels, whilst patients are on treatment in conjunction with enhanced computed tomography examination. © 2009 Blackwell Publishing Ltd.

Huang G.H.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2011

To investigate the diagnostic accuracy of flexirigid thoracoscopy for pleural diseases and the patients' compliance. Forty-seven patients with pleural effusion and thickening of unknown etiology underwent examinations with flexirigid thoracoscopy with subsequent pathological examination, and the diagnostic accuracy and the patients' compliance were observed. Thoracoscopy identified lesions in the pleural and/or diaphragm in 42 patients and no lesions in 5 patients. Malignancy was confirmed in 21 (44.7%), tuberculosis in 17 (36.2%), idiopathic hypereosinophilic syndrome in 1 (2.1%), nocardiasis in 1 (2.1%), constrictive pericarditis in 1 (2.1%), chronic empyema in 2 (4.3%), splenic artery embolization in 1 (2.1%), and negative result in 3 (6.4%) of the cases. The diagnostic accuracy rate of flexirigid thoracoscopy reached 93.6%, and no serious complications in relation to the examination was found. Flexirigid thoracoscopy is efficient and relatively safe for diagnosis of pleural diseases with or without hydrothorax.

Cai W.,Southern Medical University | Wang J.,Southern Medical University | Wang L.,Southern Medical University | Guo L.,Southern Medical University
Neurourology and Urodynamics | Year: 2015

Aims The prevalence and risk factors of urinary incontinence (UI) for post-stroke inpatients remain unclear. In this study, we aimed to investigate the risk factors associated with the development of UI for post-stroke inpatients in southern China. Design Cross-sectional survey. Subjects and Methods A total of 711 post-stroke patients from neurological units at 8 different hospitals in Guangzhou, a city in southern China, were interviewed face to face. Data were collected by a self-designed questionnaire which includes sociodemographic variables, characteristics of stroke, and medical history. Results The prevalence of UI among post-stroke inpatients was 44.3%. By multivariate logistic regression, we found that major risk factors for UI included health care assistant care (OR-=-3.935), hemorrhagic stroke (OR-=-1.755), mixed stroke (OR-=-2.802), parietal lobe lesion (OR-=-1.737), chronic cough (OR-=-2.099), aphasia (OR-=-3.541), and post-stroke depression (OR-=-3.398). Conclusions The prevalence of UI among post-stroke inpatients is high. Stroke inpatients looked after by health care assistant, hemorrhagic stroke, mixed stroke, parietal lobe lesion, chronic cough, aphasia, and post-stroke depression were high-risk groups for UI. These patients should be targeted when planning intervention programs. © 2013 Wiley Periodicals, Inc.

OBJECTIVE: To describe and compare video endoscopic inguinal lymphadenectomy via hypogastric and limb approach (VEIL-H vs VEIL-L) in patients with invasive vulvar cancer.METHODS: From March 2011 to August 2013, 7 women with early-stage vulvar cancer were selected for this integrated procedure with a combination of VEIL-H and VEIL-L in bilateral groins.VEIL-L was performed on limb with old surgical scar in ipsilateral hypogastric area of 3 patients and VEIL-H in contralateral limb. Both novel procedures were performed with triple trocars respectively. The boundaries of inguinal lymph node dissection were the same template of open inguinal lymphadenectomy. Preoperative data, surgical techniques and follow-up outcomes were compared.Standard statistical tests were used.RESULTS: The combination of VEIL-H and VEIL-L was successfully completed in 7 patients without conversion into open surgery. The great saphenous vein was spared in 13 limbs.No difference existed in mean operative duration, average blood loss volume and median total regional lymph nodes removed in two groups. All nodes were confirmed tumor-free. Mean drain duration was (4.7 ± 1.4) days in the VEIL-H group and (2.7 ± 0.9) days in VEIL-L group respectively (P < 0.01). Mean drain volume was (123 ± 55) ml in VEIL-H group and (62 ± 32) ml respectively (P < 0.05). Mean postoperative hospital stay was (8.6 ± 2.2) days.No major intraoperative complications occurred. However, hypercarbia in one patient 1 was completely reversible with hyperventilation.Unilateral great saphenous vein was injured in another one.Regarding postoperative complications, one patient suffered lymphocele in VEIL-H side and another had lymphorrhea through drain orifice in VEIL-L side. During a follow-up period of (19 ± 7) months, there was no disease recurrence so far.CONCLUSION: The combination of VEIL-H and VEIL-L has the reproducibility and therapeutic potentials in the treatment for patients with vulvar cancer. Both minimal invasive techniques are viable. Although short-term results are encouraging, larger series with a longer follow-up are required to fully evaluate the therapeutic efficacy of VEIL-H and VEIL-L.

Li W.,Guangzhou University | Jin X.,Guangzhou University | Zhang Q.,Southern Medical University | Zhang G.,Peoples Hospital of Gansu Province | And 2 more authors.
International Journal of Clinical and Experimental Pathology | Year: 2014

The identification of biomarkers in breast cancer diagnosis and therapy is important in achieving early cancer diagnosis and improving patient outcomes. The aim of this study was to examine clinical significance of miR-204 expression in tissues from breast cancer patients. The relationship between miR-204 expression and clinicopathological characteristics was investigated. MiR-204 expression was significantly associated with TNM stage and metastasis. Patients with low miR-204 expression had poorer overall survival time and disease free survival time than those with high miR-204 expression. Furthermore, miR-204 expression was correlated with chemotherapeutic resistance of breast cancer patients. In conclusion, the miR-204 may be a potential diagnostic and prognostic biomarker of breast cancer.

Peng S.L.,Southern 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 therapeutic mechanism of Weiweifang (WWF, a Chinese herbal preparation) on gastric ulcer in rats viewing from metabonomics. Wistar rats were made to gastric model by acetic acid cauterization and randomized into the model group, the spontaneously healing group and the three WWF treatment groups, and a group of normal rats was set for control. Metabolic spectra of gastric mucosa extraction of rats were acquired with gas chromatography-mass spectrometry (GC-MS) technique. After being pre-processing, data were subjected to partial least squares discriminant analysis (PLS-DA) to discover the biomarkers in rats of the normal group and the model group. The therapeutic effect of WWF on experimental gastric ulcer was assessed by principal component analyses (PCA), and its action of mechanism was explained viewing from the changes of biomarkers. Spectra of biomarkers, including organic acids, fatty acids, amino acids, etc. in model rats were statistically different to those in normal rats, which demonstrated that the energy and substance metabolisms were disordered in rats with gastric ulcer. WWF could cure gastric ulcer effectively by way of regulating the metabolism of gastric mucosa. The therapeutic mechanism of WWF on experimental gastric ulcer in rats is revealed integrally by metabonomics in this study, displaying prominently the characteristics of Chinese medicine multiple targets comprehensive therapy.

Li Z.W.,Southern Medical University
Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials | Year: 2010

To study the pharmacokinetics and bioavailability of sustained-release tablets of Matrine in dogs. 6 dogs were randomly assigned to receive sustained-release tablets or commercial capsules 300 mg, then a crossover trial was conducted 1 week later. Plasma samples were taken at different time points and the plasma concentration of Oxymatrine and Matrine in dogs was determined by HPLC. The pharmacokinetic parameters of self-made sustained-release tablets versus those of its control preparation were as follows: Tmax: (6.17 +/- 2.04) (M), (3.25 +/- 0.61) (OM), (4.75 +/- 1.17) (M), (2.42 +/- 0.38) (OM) h; Cmax: (3.79 +/- 1.11) (M), (4.76 +/- 0.60) (OM), (5.35 +/- 0.72) (M), (7.04 +/- 0.47) (OM) microg/mL; AUC(0-->infinity): (45.15 +/- 11.77) (M), (32.38 +/- 4.60) (OM) and (44.71 +/- 5.52) (M), (29.11 +/- 4.41) (OM) microg x h/mL. The self-made sustained-release tablets and commercial capsules bioequivalent.

Jiang X.,Southern Medical University
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery | Year: 2010

OBJECTIVE To explore the cytotoxicity, labeled time, marking rate, and effect on adhesion of quantum dot 655 (QD655) labeled rat bone marrow mesenchymal stem cells (BMSCs) in vitro, and to confirm its feasibility for stem cell labeling and tracer means for rat. BMSCs were collected from the femur and tibia bone marrow cavity of a 2-week-old SD rat, cultured and identified. The 3rd passage of BMSCs were incubated with QD655 as the experimental group according to the recommended concentration of the markers. The cells were not labeled by QD655 as control group. The cell survival rate after QD655 labeling was detected by trypan-blue exclusion. The effect of QD655 on cell proliferation was observed by MTT. The osteogenic differentiation potential was identified by Alizarin red staining, alkaline phosphatase (ALP) staining, and real-time fluorogenic quantitative PCR. At immediately, 1, 2, 4, and 6 weeks, fluorescent microscopy was used to observe the labeled rate and scanning electron microscope was used to observe the cell adhesion to scaffold (bioglass/collagen composite). The cell survival rates were more than 90% in both experimental group and control group, showing no significant difference (P > 0.05). There was no significant difference in the cell proliferation between 2 groups (P > 0.05). Alizarin red staining and ALP staining showed positive results. Real-time fluorogenic quantitative PCR result showed that the mRNA expression levels of osteopontin, osteocalcin, collagen type I, ALP, and BMP-2 in the experimental group was significantly higher than those in the control group. The labeled rates were 96.50% +/- 1.59%, 93.30% +/- 1.51%, 72.40% +/- 2.90%, 40.10% + 3.60%, and 10.00% +/- 1.70% immediately, 1, 2, 4, and 6 weeks after labeling, respectively. The labeled rate in the control group was 0. Scanning electron microscope showed a good distribution of fusiform or polygonal cells in the pores of scaffold. QD655 can be used as a labeling marker for BMSCs. Rat BMSCs labeled with QD655 is of high efficiency and safety.

Qian Y.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2010

To study the effects of Liuweidihuang pills in preventing diabetes in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Forty male OLETF rats were randomized equally into Liuweidihuang pill group and control group, with 10 male LETO rats as the normal control group. In Liuweidihuang pill group, the rats were given the pills intragastrically at the daily dose of 2.4 mg/kg since 8 weeks of age, and the rats in the other two groups received water instead. Blood glucose of the rats was determined by oral glucose tolerance test (OGTT), and the body weight and food intake were monitored on a weekly basis. At 8, 32 and 40 weeks, the rats were sacrificed and the expression level of adiponectin mRNA in the adipose tissue was detected using RT-PCR. Treatment with Liuweidihuang pills significantly lowered the increment of the blood glucose and postponed the onset of hyperglycemia in the rats. Compared with the control group, the rats in Liuweidihuang pill group showed significantly increased expression of adiponectin mRNA in the adipose tissue. The rats receiving Liuweidihuang pills developed diabetes at 30 weeks of age with an incidence of 28.6% at 40 weeks, significantly lower than that in the control group (P<0.01). Liuweidihuang pills can significantly increase the expression of adiponectin mRNA in the adipose tissue and decrease the incidence of type 2 diabetes in OLETF rats.

Xiong K.-Y.,Beijing Sport University | He H.,Beijing Sport University | Ni G.-X.,Southern Medical University
European Journal of Sport Science | Year: 2013

Nowadays, Tai chi chuan (TCC) is practiced by millions worldwide with a range of skill levels. However, the effect of skill level on physiological response to TCC performance has yet to be clarified. In this study, physiological parameters during practicing simplified 24-form TCC were investigated and compared in 10 young high-level (HL) male TCC athletes and 10 ordinary-level (OL) male TCC practitioners with similar age and body size. Significantly higher energy expenditure, heart rate, oxygen uptake and tidal volume were found in HL group than OL group during TCC performance. The respiratory frequency and exhalation time were similar between the two groups during practicing TC; however, significantly less inhalation time was found in HL group (1.02±0.2 s) than OL group (1.12±0.28 s). Our results suggested that skill level may have considerable impact on metabolic and cardiorespiratory responses to TCC performance. TCC practitioners with different skill levels may practice TCC in different ways, which was supposed to lead to distinguishable response between the two groups. © 2013 Copyright European College of Sport Science.

Zhu X.,Southern Medical University | Guo Y.,Southern Medical University | Li X.,Southern Medical University | Ding Y.,Southern Medical University | Chen L.,Southern Medical University
Journal of Thoracic Oncology | Year: 2010

Introdution: Little research has been done to test the usefulness of metastasis-associated protein 1 (MTA1) as a prognostic marker for non-small cell lung cancer (NSCLC). In this study, we investigated MTA1 expression and its prognostic value for NSCLC. Methods:NSCLC surgical tissue samples were taken from 100 patients with NSCLC who had been followed up for more than 2 years. The expression of MTA1 protein was evaluated by immunohistochemistry, and the correlations between the expression of MTA1 and clinical features and the prognosis were analyzed. The difference of MTA1 protein expression between NSCLCs and their adjacent nonneoplastic lung tissues was analyzed in a tissue microarray. The change of MTA1 mRNA expression and protein expression after RNA interference (RNAi) was detected by real-time polymerase chain reaction, Western blot, and immunocytochemistry in NSCLC cell line 95D. Results: Overexpression of MTA1 (immunoreactivity scoring >4) was shown in 61.0% of the NSCLC cases but only in 9.4% of their adjacent nonneoplastic lung tissues (p < 0.001). The MTA1 expression level was correlated with lymph node metastasis (p = 0.013) and clinical stage (p = 0.002). Survival analysis showed that the MTA1 overexpression group had a significantly shorter overall survival time than the MTA1 downexpression group (p = 0.003). However, multivariate analysis showed that MTA1 expression was not a significant and independent prognostic parameter for patients with NSCLC. After RNAi, the 95D cells exhibit consistent reduction in MTA1 mRNA expression and MTA1 protein expression. Conclusion: MTA1 protein expression is associated with tumor progression and clinical outcome in patients with NSCLC. Further molecular, cellular, and animal model studies on MTA1 gene will provide new clues for exploring the mechanism of carcinogenesis and tumor progression in patients with NSCLC. © 2010 by the International Association for the Study of Lung Cancer.

Yao H.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2010

OBJECTIV: To investigate the effect of Oviductus Ranae (OR) on the expressions of CyclinD1, CDK6 and P15 in the liver of aged male rats. Eighteen male SD rats were randomly divided into 3 equal groups, namely the OR group, VE group and ageing model group. The rats received subcutaneous injection of D-galactose for 6 weeks to establish the aging models, and another 6 rats were injected daily with normal saline (NS) to serve as the normal control group. From the third week of the experiment, the rats were given oral OR or Vitamin E (VE) accordingly till the sixth week. After completion of the drug administration, all the rats were sacrificed for detecting the expressions of CyclinD1, CDK6 and P15 in the liver tissue by Western blotting. The relative expression levels of CyclinD1, CDK6 and P15 in the liver of the rats in the OR group were 41.73-/+0.54, 23.29-/+0.30 and 1.49-/+0.30, respectively, significantly up-regulated as compared with those in the ageing model group (P<0.01). The expressions of the proteins were obviously down-regulated in the model group in comparison with those in the normal control group. OR treatment can lower the expressions of Cyclin D1 and CDK6 in the liver to enhance the liver cell proliferation in aged male rats. OR also promotes the expression of P15 through a feedback mechanism to prevent excessive proliferation of the cells. The effect of OR against ageing is mediated possibly by up-regulation of the proteins associated with the cell proliferation in the liver, a mechanism different from that of VE.

Hu Y.Y.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2010

To explore the effect of irbesartan on angiotensin-converting enzyme 2 (ACE2) mRNA expression in diabetic rat myocardium. Thirty 8-week-old male Wistar rats were randomly divided into control group (n=7), diabetic model group (n=14) and irbesartan group (n=9). Diabetes was induced by a single intraperitoneal injection of STZ (55 mg/kg), a blood glucose>16.7 mmol/L 72 h after the injection indicated successful establishment of diabetes. Four weeks after the modeling, the rats in irbesartan group were given 50 mg/kg irbesartan. ELISA was used to measure myocardial AngII content in the rats, and myocardial ACE2 mRNA expression was determined by real-time PCR. Myocardial AngII level in the diabetic model group was significantly higher than that in the control group (P<0.001). Irbesartan administration significantly lowered cardiac AngII levels in the diabetic rats (P<0.001). The rats in irbesartan group showed significantly increased myocardial ACE2 mRNA expression compared with those in the control and diabetic rat groups (P<0.05). Irbesartan can increase ACE2 mRNA expression in the myocardium, which might be one of the mechanisms underlying its effect in improving the cardiac function in diabetic rats.

Dai Z.X.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2010

To identify zebrafish mutants with myelopoiesis defects by ENU mutagenesis and large-scale forward genetic screening. Male zebrafish were mutagenized with N-ethyl N-nitrosourea to induce mutations in the spermatogonial cells to generate the founders, which were outcrossed with AB to raise F1 fish. The F1 fish from different founders were mated to generate the F2 families. The F3 embryos from F2 sibling crosses were screened by Sudan black B staining and neutral red staining. A total of 350 F2 families from F1 sibling crosses were screened, and 1424 F2 crosses were analyzed. Six mutations were identified resulting in abnormal Sudan black B staining and neutral red staining, indicating the involvement of neutrophil deficiency or macrophage abnormalities. It is simple and cheap to induce and screen myelopoiesis deficiency in zebrafish by ENU chemical mutagenesis and Sudan black B staining and neutral red staining. These mutants shed light on the identification of the genes important to myelopoiesis in zebrafish.

Huang J.J.,Southern Medical University
Zhonghua zheng xing wai ke za zhi = Zhonghua zhengxing waike zazhi = Chinese journal of plastic surgery | Year: 2010

To investigate the effect of Botulinum toxin type A (Botox) injection into the masseter muscle on mandibular development in rats. 12 28-day-old Wistar rats were divided into two groups as Botox group (n= 6) and control group (n = 6) which received anesthesia only. In Botox group, Botox was injected into the right masseter muscle, while only sterile saline into the left muscle. When the rats were 75-day-old, CT scan and 3D reconstruction were performed for cephalometry. The masseter muscles at both sides were weighed. Histologic study of masseter muscle and mandible was also performed. The weight of right masseter muscle was (0.4575 +/- 0.0940) g in Botox group, and (0.8899 +/- 0.1030) g in control group (< 0.05). The mandibular height II and III was (10.8 +/- 0.8) mm and (9.5 +/- 0.6) mm in Botox group and (12.5 +/- 0.6) mm and (10.7 +/- 0.4) mm in control group, respectively (P < 0.05). The intergonial distance was (11.6 +/- 0.6) mm and (12.4 +/- 0. 6) mm in Botox and control group, respectively (P > 0.05). When the rats receive Botox injection into the masseter muscle at young age, the grown-up rats have a decreased mandibular height, but the mandibular length and intergonial distance are not affected.

Chen X.W.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2010

To compare the effect of different approaches of bone marrow stromal stem cell (BMSCs) transplantation into the allogenic rat liver. Thirty male SD rats were randomized equally into local liver group, portal vein group, and femoral vein group, and received injection of 1×106/ml BMSCs directly into the rat liver, through the portal vein and through the femoral vein, respectively. The rat livers were scanned by magnetic resonance imaging (MRI) at 12 h and 1, 3, 5, 7, 14 days after the cell transplantation. Prussian blue staining of the rat liver sections was also performed 14 days after the transplantation. MRI showed decreased signal intensity in all the rat livers of the local liver group; the ovoid area of the signal intensity gradually shrunk and the signal intensity increased with the passage of time. Lowered signal intensity was also seen in the rat livers of the portal vein group, appearing constantly branch-shaped, indistinct and increased gradually. Decreased signal intensity did not occur in the livers of femoral vein group. Prussian blue staining of all the rat livers at day 14 showed the presence of cells containing blue particles in all the groups, most numerous in the local liver group followed by the portal vein group and then the femoral vein group. Direct intrahepatic injection of the BMSCs results in better effect than cell transplantation via the portal vein or the femoral vein.

Ma N.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2010

To perform the genetic identification of cloche(172) mutant zebrafish. The chemical mutagen N-ethyl-N-nitrosourea (ENU) was used to treat the AB stain male fish. Large-scale forward genetic screening was carried out to search for lyC-deficient zebrafish mutant by WISH. The morphology changes of the embryos at 3 days postfertilization (3dpf) stage were observed and the cloche(172) gene was identified by mapping and complementation test. We selected 4 lyC-deficient zebrafish by WISH. cloche(172) mutant showed morphological changes similar to cloche mutant in 3dpf stage. One fourth of the embryos showed cloche phenotype as found in complementation test, and the cloche(172) gene was mapped on the telomere of zebrafish 13 chromosome where cloche gene was located. Numerous red blood cells were observed in the cloche(172) mutant, while only a few cells were found in the cloche mutant in the tail region by o-dianisdine staining. cloche(172) gene which is responsible for the phenotype of cloche mutant may be a novel point mutation allele of the cloche mutant.

Zhu X.L.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2010

To prepare lidocaine nanoemulsion and investigate its transdermal delivery ability in vitro. The optimal Km (surfactant/cosurfactant) value and the component proportion were determined by pseudoternary phase diagrams combined with Origin software analysis. The diameter and distribution range were detected by Zeta particle size analysis instrument, and the morphology of the nanoemulsion was observed by electron microscope. The permeation flux of lidocaine was determined in vitro using the modified Franz diffusion cell combined with HPLC, and the cumulative transdermal absorption amount and the apparent skin transdermal velocity were compared among nanoemulsion, gel and tincture containing 5% lidocaine. The permeation mode of lidocaine nanoemulsion was analyzed. The average drop size of lidocaine nanoemulsion was 29.8-/+14.4 nm, and 98% of the drop sizes ranged from 15.1 to 45.5 nm and 2% from 77.9 to 261.3 nm. The nanoemulsion drop showed a spherical morphology in a polydisperse system. The Kp value of the nanoemulsion (3.07-/+0.74 cm/h) was significantly higher than that of gel (1.27-/+0.35 cm/h) and tincture (0.97-/+0.18 cm/h), and the permeation rate of the nanoemulsion was 69.82-/+7.48 microg x cm(-2) x h(-1), which fitted the the Zero-order release dynamic procedure. The component proportion of lidocaine nanoemulsion can be conveniently obtained through pseudoternary phase diagrams and Origin software analysis, and the drop size, distribution, morphology and system type can be determined by Malvern Zetasizer combined with electron microscopy. The results also indicate that the nanoemulsion system with high permeation rate may provide a new promising means for local anesthesia.

Xu J.G.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2010

To explore the effect of terbutaline on sodium transport in rat alveolar type I (ATI) and type II (ATII) cells of rats. The whole cell currents were recorded from ATII cells isolated from rat lungs perfused with or without amiloride (inhibitor of epithelial sodium channel) and ZnCl(2) (inhibitor of cyclic nucleotide-gated cation channel) in the whole cell recording mode using the patch-clamp technique. The effect of terbutaline on the currents was examined. The main currents recorded from ATII cells were amiloride-sensitive and Zn(2+)-sensitive. The amiloride-sensitive and Zn(2+)-sensitive current shared a similar proportion (P>0.05). Both currents could be significantly increased by terbutaline (P<0.05), and the proportion of amiloride-sensitive current was 1.7 times that of Zn(2+)-sensitive current (P<0.05). There are functional epithelial sodium channels (ENaC) and cyclic nucleotide-gated cation channels (CNG) on freshly isolated ATII cells, both serving as the main channels for sodium transport. Terbutaline increases the absorption of alveolar fluid primarily by increasing sodium transport of ENaC and CNG on ATI and AT II cells.

Luo Q.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2010

To compare the effects of amlodipine, benidipine and nifedipine on myocardial hypertrophy and evaluate the underlying mechanism. Myocardial hypertrophy model was created by transverse aortic constriction (TAC) in C57 BL/6 mice, and plasma catecholamine concentrations were measured 7 days after surgery to confirm the sympathetic activation. The 3 drugs were administered in TAC mice for 7 days and cardiac hypertrophy was evaluated according to the heart-to-body weight ratio (HW/BW). Effects of those drugs on the protein synthesis stimulated by phenylephrine in cultured neonatal cardiac myocytes were also examined. HW/BW and plasma concentrations of catecholamine were significantly increased in TAC mice one week after surgery in comparison with to sham-operated mice. One week after TAC, the HW/BW ratio was significantly lower in the amolodipine but not nifedipine-treated group than in the TAC group. Administration of nifedipine via minipump infusion for one week did not decrease HW/BW ratio. Treatment with amlodpine or benidipine, but not nifedipine, decreased the neonatal rat myocyte protein synthesis induced by phenylephrine stimulation. Antihypertrophic effect of DHEs on myocardium is dependent on their potential of blocking N-type calcium channel, and the underlying mechanism involves the sympathetic inhibition.

To study the effect of continuous passive motion (CPM) on basic fibroblast growth factor (b-FGF) expression during tendon-bone repair in rabbits and explore the role of stress in the postoperative repair after acute rotator cuff injury. Sixteen rabbits randomized into CPM group (n=8) and non-CPM group (n=8) were subjected to surgically induced acute rupture of the supraspinatus tendon and subsequent surgical repair, with another two rabbits serving as the control. Two weeks after the operation, the rabbits in CPM group underwent CPM training, and those in non-CPM group were normally fed only. At 2, 4, 6, and 8 weeks after the operation, 2 rabbits from each group were sacrificed and the tissue samples were obtained for detecting the changes in b-FGF expression. Two weeks after the operation, b-FGF expression was detected in both groups, and the CPM group showed slightly higher and more diffusive expression. At 4 weeks, b-FGF expression was significantly higher and distributed over a greater area in CPM group and in the non-CPM group. A large number of fibroblasts positive for b-FGF expression were identified in CPM group, aligning in parallel with the tendon membrane. At 6 weeks, b-FGF in the CPM group showed no obvious changes but that in the non-CPM group became lightened. At 8 weeks, b-FGF expression was reduced in both groups, which was more obvious in the non-CPM group. CPM can promote b-FGF expression to enhance type III collagen synthesis at the tendon-bone interface in early stage of tendon-bone repair following acute rupture of supraspinatus tendon in rabbits, thereby contributing to tendon-bone recovery after rotator cuff injury.

Long H.B.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2010

To investigate the effects of Shenkangwan on the expressions of angiotensin II (AngII) and its type I receptor (AT(1)R) and the renalprotection mechanism of Shenkangwan in rats with early diabetic nephropathy (DN). The rat models of DN established by a single injection of streptozotocin were randomly divided into 4 groups, namely the model group, Shenkangwan treatment group, irbesartan treatment group, and Shenkangwan and irbesartan treatment group, with normal rats as the control. All the rats received daily gavage for 8 weeks. The urinary protein quality in 24 h and plasma and renal contents of AngII were measured. The expressions of AT1R at the protein and mRNA levels in the kidney tissues were measured by immunohistochemistry and reverse transcription-polymerase chain reaction, respectively. The pathological changes of the kidney were observed microscopically. In DN rats, Shenkangwan reduced the urinary protein quantity in 24 h and the contents of AngII in the plasma and kidney tissues, decreased the renal expressions of AT(1)R protein and mRNA, and alleviated the morphological damage of the kidney. Shenkangwan offers renalprotection against DN probably by reducing the contents of AngII in the plasma and kidney tissues and inhibiting renal AT(1)R expressions.

Huang J.Y.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2010

To evaluate the analgesic effect of Corydalis yanhusuo on trigeminal neuropathic a rat model. Rat model of trigeminal neuralgia pain were established by inducing chronic constriction injury (CCI) of the infraorbital branch of the trigeminal nerve (ION). The effect of Corydalis yanhusuo, a traditional Chinese medicine, in ameliorating the pain was tested. Western blotting was performed to investigate the change of cannabinoid CB1 receptors in the Vc the injury of the infraorbital branch of the trigeminal nerve (ION-CCI). CB1 receptor antagonist AM 251 was applied to observe its effect on the analgesic effect of Yanhusuo. Administration of dl-THP (2 mg/kg) intraperitoneally increased the response threshold and the cut-off threshold to the mechanical stimulation in ION-CCI rat models. ION-CCI induced an upregulation of cannabinoid CB1 receptors within the ipsilateral of Vc. The effect of Yanhusuo was antagonized by the application of AM 251. The analgesic effect of Yanhusuo involves the participation of CB1 receptors, suggesting that Yanhusuo may offer a useful therapeutic approach for trigeminal neuropathic pain.

Deng C.,Southern 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 effect of Shenshuai Yangzhen Capsule (SYC) on hypothalamic leptin-neuropeptide Y (NPY) and proopiomelanocortin (POMC) axes in chronic renal failure (CRF) rats with malnutrition (MN). Forty-two male SD rats of SPF grade were established into CRF-MN model by 5/6 nephrectomy and 4% casein diet, the happening time of MN in them was recorded. Rats successfully modeled were randomized into three groups, 11 rats in Group A treated with SYC, 11 in group B treated with composite alpha-keto acid and 12 in Group C was untreated. Besides, a normal control group was set up with 8 healthy rats. After being treated for 4 weeks, the renal function related indices, including serum creatinine (Scr), blood urea nitrogen (BUN), 24 hour urine protein (24 h Upro), albumin (ALB), haemoglobin (Hb) insulin like growth factor-1 (IGF-1), total cholesterol (TC) and triglyeride (TG) were measured, and body weight, food intake in rats were observed dynamically, blood leptin and NPY level in rats were determined by radioimmunoassay; mRNA expressions of OB-Rb, NPY and POMC in hypothalamus were detected with RT-PCR. CRF rats revealed MN at the end of 10th week after modeling. Compared with Group C, the condition of MN in Group A was significantly improved, showing increase of food intake and body weight (P < 0.05), marked improvement of renal function (P < 0.05), decrease of LP and NPY levels in plasma (P < 0.05), as well as up-regulated NPY mRNA expression and down-regulated mRNA expressions of OB-Rb and POMC in hypothalamus (P < 0.01). SYC can improve the malnutrition condition in rats with CRF, which is possibly by way of depressing OB-Rb and POMC mRNA expression and upgrading NPY mRNA expression in hypothalamus.

Zhou B.J.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2010

To investigate the impact of high-dose microbubbles induced by high mechanical index myocardial contrast echocardiography (MCE) on vascular permeability and its recovery time in rats. Thirty male Wistar rats were randomized into 4 MCE groups (groups A-D) and a control group. In the MCE groups, Evans blue was injected at 10 s before MCE (A), immediately after the end of MCE (B), and at 5 min (C) and 20 min after the end of MCE (D). In the control group, the microbubbles and Evans blue were injected at the end of a 5-min ultrasound exposure. All the rats were sacrificed 5 min after Evans blue injection, and the content of Evans blue in the myocardium and the percentage of Evans blue leakage area were determined. The percentage of Evans blue leakage area in groups A, B and C were significantly higher than that in the control group (P<0.05), while the percentage was similar between group D and the control group (P>0.05). Evans blue contents in groups A and B were significantly higher than that in the control group (P<0.05), but groups C and D showed comparable contents with the control group E (P>0.05). No significant changes of the heart rates and premature beat number were observed during and after MCE in these groups (P>0.05). High mechanical index MCE and a high contrast dose may induce increased microvascular leakage in rats, and the vascular permeability can recover in 20 min after MCE.

Shi Y.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2010

To establish a microemulsion liquid chromatography system with direct sample loading for determining the serum level of emodin in rats. The separation was performed on C18 column (Hypersil BDS, 5 μm,150 mm×4.6 mm) with the microemulsion mobile phase consisting of 3.3% (w/V) SDS, 6.6% (V/V) n-butyl alcohol, and 1.0% (V/V) octane and water. The flow rate was 1.0 ml/min and the detection wavelength was 254 nm. The linear range of emodin detection was 0.333-5.32 μg/ml. The average recovery was 99.65% with a RSD of 3.60%. The limit of quantification was 0.1386 μg/mL. Microemulsion liquid chromatography system with direct sample loading allows simple, accurate and rapid determination of emodin in rat serum.

Qu H.,Southern Medical University | Qu H.,The First Affiliated Hospital | Li R.,Southern Medical University | Liu Z.,Inner Mongolia University | And 2 more authors.
International Journal of Clinical and Experimental Pathology | Year: 2013

Objective: To investigate the correlation between CD133-positive non-small cell lung cancer (NSCLC) and clinicopathological features and its impact on survival. Methods: A search in the Pubmed, Embase and Wanfang databases (up to July 15, 2013) was performed. Only articles in which CD133 antigen was detected in situ localization by immunohistochemical staining were included. This meta-analysis was done using RevMan 5.2 software. Outcomes included overall survival and various clinicopathological features. Results: A total of 1004 NSCLC patients from 11 studies were included. Meta-analysis showed that CD133 expression patients had a significant worse 5-year overall survival compared to the low expression ones (RR = 3.19, 95% CI: 2.05-4.98, P<0.0001 fixed random). With respect to clinicopathological features, CD133 expression by IHC method was closely correlated with tumor T stage (OR = 0.91, 95% CI: 0.59-1.39, P = 0.67 fixed-effect) and tumor grade (OR = 1.20, 95% CI: 0.80-1.79, P = 0.37 fixed-effect). Conclusion: CD133-positive NSCLC patients had worse prognosis, and was associated with common clinicopathological poor prognostic factors.

Xu A.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2012

To summarize our initial experience with laparoendoscopic single-site (LESS) retroperitoneal lymph node dissection (RPLND) for treatment of nonseminomatous testicular cancer. From September 2010 to June 2011, 3 patients (aged 19-27 years) with right testicle enlargement and elevated alpha-fetoprotein level underwent right radical orchidectomy. Histopathological analysis revealed nonseminomatous germ cell tumor. LESS-RPLND was performed 3 weeks after orchiectomy. The homemade port was inserted through a 3-cm right pararectal incision in the right lower quadrant for unilateral RPLND using nerve-sparing technique and modified right-sided template removal similar to those in open RPLND. The operation was successfully performed with a mean operative time of 240 min and a mean estimated blood loss of 50 ml. No conversion to open or conventional laparoscopic surgery was required. No major perioperative complications were observed. For the first case, the number of lymph nodes obtained for final histopathological examination was 11, and two positive nodes were detected. For the other 2 cases, no positive nodes were detected. Chemotherapy was administered in the first case. Alpha-fetoprotein level decreased close to the baseline one week postoperatively and no relapse occurred in these cases 3 month after RPLND. Follow-up at 1 year after the surgery showed good tumor control and preservation of the sexual function. LESS-RPLND is safe and feasible for treatment of nonseminomatous testicular cancer, and the pararectal incision provides an ideal surgical approach with good cosmetic result, but the long-term effect needs to be tested by further large population-based study.

Cheong K.B.,Southern Medical University | Zhang J.-P.,Southern Medical University | Huang Y.,Southern Medical University
Complementary Therapies in Medicine | Year: 2014

Background: Postoperative gastroparesis syndrome (PGS) which is mainly manifested as delayed gastric emptying is often caused by upper abdominal and sometimes lower abdominal surgery. In view of the side effects of drugs therapy, the search of supplementary and alternative has been of increasing interest. Objective: This paper included a systematic review and meta-analysis on the use of acupuncture and acupoints selection in PGS. Quality for meta-analysis was evaluated using GRADE while each trial was assessed with CONSORT and STRICTA for TCM. Methods: Randomized controlled trials (RCTs) comparing acupuncture with non-acupuncture treatment were identified from databases PubMed, EBSCO, Ovid, Cochrane, CNKI and Wanfangdata. Meta-analysis on eligible studies was performed using fixed-effects model with RevMan 5.2. Results were expressed as relative risk (RR) for dichotomous data, and 95% confidence interval (CI) were calculated. Results: Of the 348 studies reviewed, 16 RCTs met the inclusion criteria for review while 7 RCTs, 188 patients (intervention) and 182 patients (control) met the criteria for meta-analysis. Both acupuncture and acupuncture combined with medication showed significant higher total effective rate than control (usual care/medication); with (RR 1.27, 95% CI 1.13, 1.44; P<. 0.0001) and (RR 1.37, 95% CI 1.18, 1.58; P<. 0.0001) respectively. All included RCTs reported positive effect of acupuncture in PGS treatment. ST36, CV12 and PC6 seemed to be the common acupoints selected. Conclusions: The results suggested acupuncture might be effective to improve PGS, however, a definite conclusion could not be drawn due to low quality of trials. Further large-scale, high-quality randomized clinical trials are needed to validate this. Study registration: PROSPERO CRD42013005485. © 2014 Elsevier Ltd.

Xu D.,Southern 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

To provide a comprehensive review for development and existing problems of the perforator flaps. The related home and abroad literature concerning perforator flaps was extensively reviewed. The perforator flaps are defined as the axial flaps nourished solely by small cutaneous perforating vessels (perforating arteries and veins), which are exclusively composed of skin and subcutaneous fat. The perforator flaps have the advantages as follows: less injury at donor site, less damage to the contour of the donor site, good reconstruction and appearance of the recipient site flexible design, and short time of postoperative recovery, which have been widely used in reconstructive surgery. The perforator flaps are the new development of the microsurgery, which usher an era of small axial flaps; However, the controversies of the definition, vascular classification, the nomenclature, and the clinical application of the perforator flaps still exist, which are therefore the hot spot for future study.

Wang C.,Southern Medical University | Wang C.,West Virginia University | Yang X.-M.,Southern Medical University | Zhuo Y.-Y.,Southern Medical University | And 5 more authors.
International Journal of Neuropsychopharmacology | Year: 2012

β-amyloid (Aβ) peptides play an important role in cognition deficits, neuroinflammation, and apoptosis observed in Alzheimer's disease (AD). Activation of cyclic AMP (cAMP) signalling enhances memory and inhibits inflammatory and apoptotic responses. However, it is not known whether inhibition of phosphodiesterase-4 (PDE4), a critical controller of intracellular cAMP concentrations, affects AD-associated neuroinflammatory and apoptotic responses and whether these responses contribute to deficits of memory mediated by cAMP signalling. We addressed these issues using memory tests and neurochemical measures. Specifically, rats microinfused with aggregated Aβ25-35 (10 Îg/side) into bilateral CA1 subregions displayed deficits in learning ability and memory, as evidenced by decreases in escape latency during acquisition trials and exploratory activities in the probe trial in the water-maze task and 24-h retention in the passive avoidance test. These effects were reversed by rolipram (0.1, 0.25 and 0.5 mg/kg.d i.p.), a prototypic PDE4 inhibitor, in a dose-dependent manner. Interestingly, Aβ25-35-treated rats also displayed decreases in expression of phosphorylated cAMP response-element binding protein (pCREB) and Bcl-2, but increases in expression of NF-ΰB p65 and Bax in the hippocampus; these effects were also reversed by rolipram in a dose-dependent manner. Similar neurochemical results were observed by replacing Aβ25-35 with Aβ1-42, a full-length amyloid peptide that quickly forms toxic oligomers. These results suggest that PDE4 inhibitors such as rolipram may reverse Aβ-induced memory deficits at least in part via the attenuation of neuronal inflammation and apoptosis mediated by cAMP/CREB signalling. PDE4 could be a target for treatment of memory loss associated with AD. © 2011 CINP.

Chen J.,University of Manitoba | Qiu X.,Southern Medical University | Ouyang J.,Southern Medical University | Kong J.,University of Manitoba | And 3 more authors.
Biomacromolecules | Year: 2011

This study develops novel pH and reduction dual-sensitive micelles for the anticancer drug doxorubicin (DOX) delivery owing to the fact that the tumor tissues show low pH and high reduction environment. These sub-100 nm micelles present a core-shell structure under physiological conditions, but quickly release the loaded drugs responding to acidic and reductive stimuli. With disulfide bonds in each repeat unit of poly(β-amino ester)s, the novel copolymer was synthesized via Michael addition polymerization from 2,2′-dithiodiethanol diacrylate, 4,4′-trimethylene dipiperidine, and methoxy-PEG-NH 2. DOX released faster from micelles in a weakly acidic environment (pH 6.5) than at pH 7.4 or in the presence of a higher concentration (5 mM) of reducing agent (DTT). The release is even more effective in a scenario of both stimuli (pH 6.5 and 5 mM DTT). MTT assay showed that the DOX-loaded micelles had a higher cytotoxicity for HepG2 tumor cells than DOX at higher concentrations, and that blank micelles had a very low cytotoxicity to the tumor cells. Confocal microscopy observation showed that the micelles can be quickly internalized, effectively deliver the drugs into nuclei, and inhibit cell growth. These results present the copolymer as a novel and effective pH and reduction dual-responsive nanocarrier to enhance drug efficacy for cancer cells. © 2011 American Chemical Society.

Sheng H.-F.,Southern Medical University | Zhou H.-W.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2015

Microbiome is a novel research field related with a variety of chronic inflamatory diseases. Technically, there are two major approaches to analysis of microbiome: metataxonome by sequencing the 16S rRNA variable tags, and metagenome by shot-gun sequencing of the total microbial (mainly bacterial) genome mixture. The 16S rRNA sequencing analyses pipeline includes sequence quality control, diversity analyses, taxonomy and statistics; metagenome analyses further includes gene annotation and functional analyses. With the development of the sequencing techniques, the cost of sequencing will decrease, and big data analyses will become the central task. Data standardization, accumulation, modeling and disease prediction are crucial for future exploit of these data. Meanwhile, the information property in these data, and the functional verification with culture-dependent and culture-independent experiments remain the focus in future research. Studies of human microbiome will bring a better understanding of the relations between the human body and the microbiome, especially in the context of disease diagnosis and therapy, which promise rich research opportunities.

Zhao R.,Southern Medical University | Wang N.,Southern Medical University | Huang H.,Guangdong Medical College | Ma W.,Southern Medical University | Yan Q.,Southern Medical University
Liver International | Year: 2014

Background: Chromodomain helicase DNA binding protein 5 (CHD5) has recently been identified as a potent tumour suppressor by acting as a master regulator of a tumour-suppressive network. Its inactivation resulted from aberrant methylation in the promoter occurs in several types of human malignancy and is associated with malignant tumour behaviour. In human hepatocellular carcinoma (HCC), CHD5 gene expression, methylation status and tumour-suppressive function have not been elucidated. Aims: In this study, we focused on the epigenetic modification and tumour-suppressive mechanism of CHD5 gene in HCC. Methods: CHD5 expression in nine HCC cell lines and 30 pairs of HCC specimens and adjacent non-cancerous tissues were analysed by quantitative reverse transcription PCR and Western blotting. Methylation-specific sequencing and methylation-specific PCR were performed to examine DNA methylation status of the CHD5 promoter in HCC cell lines and samples. The effect of CHD5 restoration on proliferation, colony formation, senescence, apoptosis and tumourigenicity were examined. Results: CHD5 expression was sinificantly down-regulated in HCC cell lines and tissues examined, and the -841 to -470 region of CHD5 promoter was hypermethylated in these samples. Treatment with DNA methyltransferase inhibitor 5-aza-2-deoxycytidine resulted in a striking regional demethylation of the -841 to -470 region of CHD5 promoter and an increase in CHD5 expression. The restoration of CHD5 expression inhibited tumour cell proliferation, colony formation and tumourigenicity and caused cellular senescence. Conclusions: Our findings demonstrate that CHD5 is a potential tumour suppressor gene epigenetically silenced in HCC. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Shi M.,Southern Medical University | Zheng H.,Southern Medical University | Nie B.,Southern Medical University | Gong W.,Southern Medical University | Cui X.,Southern Medical University
BMJ Open | Year: 2014

Objective: Statins are commonly prescribed cholesterol-lowering drugs. Preclinical studies suggest that statins may possess cancer preventive properties. The primary objective of this meta-analysis was to determine the association between statin use and risk of liver cancer. Design: Meta-analysis. Setting: International. Participants: A comprehensive literature search of PubMed, BIOSIS Previews, Web of Science, EMBASE, EBSCO and Cochrane Library was conducted through March 2014. The effect estimate was reported as pooled relative risk (RR) with 95% CIs, using the random-effects model. Results: A total of 12 studies (1 individual patient data analysis of 22 randomised controlled trials, 5 cohorts and 6 case-controls) were qualified for this meta-analysis, involving 5 640 313 participants including 35 756 liver cancer cases. Our results indicated a significant risk reduction of liver cancer among all statin users (RR=0.58, 95% CIs 0.51 to 0.67). The difference of the study designs can partly explain the significant heterogeneity found in the overall analysis (I2=65%, p=0.0006). No evidence of publication bias was observed in this meta-analysis. Similar risk reductions were found in the subgroups analysis of Western and Asian countries, lipophilic and hydrophilia statins. There was a trend towards more risk reductions in subgroups with higher baseline risk, inadequate adjustment and higher cumulative dosage of statin use. Conclusions: This meta-analysis suggests that statin is associated with a significant risk reduction of liver cancer when taken daily for cardiovascular event prevention. However, this preventive effect might be overestimated due to the exposure period, the indication and contraindication of statins and other confounders. Statins might be considered as an adjuvant in the treatment of liver cancer.

Li L.-F.,Southern Medical University | Wei Z.-J.,Southern Medical University | Sun H.,Southern Medical University | Jiang B.,Southern Medical University
World Journal of Gastroenterology | Year: 2014

AIM: To evaluate the effect of β-catenin immunohistochemical expression on the prognosis of gastric cancer (GC). METHODS: We searched Pubmed and Embase to identify eligible studies. The search ended on November 10, 2013, with no lower date limit. The citation lists associated with the studies were used to identify additional eligible studies. We included studies reporting sufficient information to estimate the HR and 95%CI, and information to estimate the OR in the analysis of clinicopathological features. The qualities of these studies were assessed using the Newcastle-Ottawa Quality Assessment Scale. HRs and ORs and their variance were calculated and pooled using Review Manager Version 5.2. RESULTS: A total of 24 studies were identified and comprised 3404 cases. β-catenin expression was significantly correlated with poor overall survival (OS) in GC patients (HR = 1.85, 95%CI: 1.39-2.46), but showed a significant degree of heterogeneity (I2 = 71%, P < 0.0001). Subgroup analysis indicated that an abnormal pattern of β-catenin expression had an unfavorable effect on OS (HR = 1.79, 95%CI: 1.39-2.32). However, accumulation in the nucleus or loss of membrane did not influence the survival of GC patients independently. Moreover, the combined OR of β-catenin indicated that β-catenin expression was associated with Lauren classification (OR = 1.98, 95%CI: 1.19-3.29), lymph node metastasis (OR = 2.00, 95%CI: 1.44-2.77), distant metastasis (OR = 2.69, 95%CI: 1.35-5.38) and grade of differentiation (OR = 2.68, 95%CI: 1.66-4.34). β-catenin expression did not correlate with TNM stage (OR = 1.34 95%CI: 0.96-1.86), the depth of invasion (OR = 1.48, 95%CI: 0.94-2.33) or vascular invasion (OR = 1.11, 95%CI: 0.70-1.76). CONCLUSION: Abnormal β-catenin immunohistochemical expression may be associated with tumor progression and could be a predictive factor of poor prognosis in patients with GC. © 2014 Baishideng Publishing Group Inc. All rights reserved.

Sun Y.,Southern Medical University | Bai Y.,Southern Medical University | Zhang F.,Southern Medical University | Wang Y.,Southern Medical University | And 2 more authors.
Biochemical and Biophysical Research Communications | Year: 2010

MicroRNAs (miRNAs) represent an abundant group of small non-coding RNAs that regulate gene expression, and have been demonstrated to play roles as tumor suppressor genes (oncogenes), and affect homeostatic processes such as development, cell proliferation, and cell death. Subsequently, epidermal growth factor-like domain 7 (EGFL7), which is confirmed to be involved in cellular responses such as cell migration and blood vessel formation, is identified as a potential miR-126 target by bioinformatics. However, there is still no evidence showing EGFL7's relationship with miR-126 and the proliferation of lung cancer cells. The aim of this work is to investigate whether miR-126, together with EGFL7, have an effect on non-small cell lung cancer (NSCLC) cells' proliferation. Therefore, we constructed overexpressed miR-126 plasmid to target EGFL7 and transfected them into NSCLC cell line A549 cells. Then, we used methods like quantitative RT-PCR, Western blot, flow cytometry assay, and immunohistochemistry staining to confirm our findings. The result was that overexpression of miR-126 in A549 cells could increase EGFL7 expression. Furthermore, the most notable finding by cell proliferation related assays is that miR-126 can inhibit A549 cells proliferation in vitro and inhibit tumor growth in vivo by targeting EGFL7. As a result, our study demonstrates that miR-126 can inhibit proliferation of non-small cell lung cancer cells through one of its targets, EGFL7. © 2009 Elsevier Inc. All rights reserved.

Zeng J.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2011

To investigate the distribution of pathogenic C.albican genotype and Candida species in association with the severity of vulvovaginal candidiasis (VVC). Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) of the internal transcribed spacer analysis was employed to identify the Candida species isolated from the vaginal secretions of 198 patients with acute VVC. SSCP and GeneScan analyses of microsatellite locus I polymorphism were used to determine the genotypes of the clinical isolates of C. albican associated with VVC. All the patients were scored for clinical signs and symptoms to evaluate the severity of VVC. A total of 198 Candida strains were isolated from VVC patients, including 140 (70.7%) C. albicans strains and 58 (29.3%) non-albicans strains. In the 95 patients with severe VVC and 103 with mild-moderate VVC, C.albican was detected in 62.1% and 76.6% of the patients, respectively (P=0.011). Thirty-eight microsatellite locus I genotypes were detected in 140 unrelated C. albican strains, among which the dominant genotypes 30-45 (44 strians, 31.43%) and 32-46 (23 strains, 16.43%) were the most common, followed by genotypes 30-46 (4 strains, 2.86%) and 32-47 (9 strains, 6.42%). The overall frequencies of the 4 genotypes were significantly higher in severe VVC than in mild-moderate VVC cases (77.9% vs 42.0%, P<0.001). C. albicans remains the most common pathogenic Candia species in patients with VVC, but the non-alibcans species seem more likely to cause severe VVC. The dominant genotypes of C. albicans with a tropism for the vagina are correlated to the severity of VVC.

Sun J.,General Hospital of Guangzhou Military Command | Zheng G.,General Hospital of Guangzhou Military Command | Gu Z.,Southern Medical University | Guo Z.,General Hospital of Guangzhou Military Command
Journal of Neuro-Oncology | Year: 2015

It is suggested that microRNAs play important roles in the development of various cancers. Here, we showed that miR-137 is downregulated in glioblastoma (GBM) cell lines and that low levels of miR-137 are associated with a poor prognostic phenotype of GBM patients. Ectopic expression of miR-137 significantly inhibited GBM cell proliferation and angiogenesis. In addition, ectopic expression of miR-137 inhibited tumor growth and angiogenesis in a SCID mouse xenograft model. EZH2 was identified as a direct target of miR-137 by using luciferase reporter and Western blot assays, and EZH2 overexpression can rescue the inhibitory effect of miR-137 on cell proliferation and angiogenesis. Furthermore, tumor samples from GBM patients showed an inverse relationship between miR-137 and EZH2 levels. Our results suggest that miR-137 may serve as a biomarker in GBM, and the modulation of its activity may represent a novel therapeutic strategy for the treatment of GBM patients. © 2015, Springer Science+Business Media New York.

Mei S.,Southern Medical University | Mei S.,Shenyang Normal University | Zhu H.,Southern Medical University
BMC Bioinformatics | Year: 2014

Background: Human T-cell leukemia viruses (HTLV) tend to induce some fatal human diseases like Adult T-cell Leukemia (ATL) by targeting human T lymphocytes. To indentify the protein-protein interactions (PPI) between HTLV viruses and Homo sapiens is one of the significant approaches to reveal the underlying mechanism of HTLV infection and host defence. At present, as biological experiments are labor-intensive and expensive, the identified part of the HTLV-human PPI networks is rather small. Although recent years have witnessed much progress in computational modeling for reconstructing pathogen-host PPI networks, data scarcity and data unavailability are two major challenges to be effectively addressed. To our knowledge, no computational method for proteome-wide HTLV-human PPI networks reconstruction has been reported. Results: In this work we develop Multi-instance Adaboost method to conduct homolog knowledge transfer for computationally reconstructing proteome-wide HTLV-human PPI networks. In this method, the homolog knowledge in the form of gene ontology (GO) is treated as auxiliary homolog instance to address the problems of data scarcity and data unavailability, while the potential negative knowledge transfer is automatically attenuated by AdaBoost instance reweighting. The cross validation experiments show that the homolog knowledge transfer in the form of independent homolog instances can effectively enrich the feature information and substitute for the missing GO information. Moreover, the independent tests show that the method can validate 70.3% of the recently curated interactions, significantly exceeding the 2.1% recognition rate by the HT-Y2H experiment. We have used the method to reconstruct the proteome-wide HTLV-human PPI networks and further conducted gene ontology based clustering of the predicted networks for further biomedical research. The gene ontology based clustering analysis of the predictions provides much biological insight into the pathogenesis of HTLV retroviruses. Conclusions: The Multi-instance AdaBoost method can effectively address the problems of data scarcity and data unavailability for the proteome-wide HTLV-human PPI interaction networks reconstruction. The gene ontology based clustering analysis of the predictions reveals some important signaling pathways and biological modules that HTLV retroviruses are likely to target. © 2014 Mei and Zhu; licensee BioMed Central Ltd.

Zhou X.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2010

To study the incidence and characteristics of coagulation factor VIII (FVIII) inhibitor development in Chinese patients with hemophilia A. A 24-month continuous follow-up was conducted among 215 Chinese patients with hemophilia A to observe the characteristics of FVIII inhibitor development and the clinical characteristics of the patients. The cumulative incidence of FVIII inhibitor development in 24 months was 11.6% (25/215) in these patients. Of the 25 patients with FVIII inhibitor development, 18 (72%) had low-titer inhibitors and 7 (28%) had high-titer inhibitors. The patients developed the inhibitors after a median of 150 exposure days at a median age of 25 years (6-59 years). Fifteen patients with low-titer inhibitors (median 1.25 BU/ml) showed gradual disappearance of the inhibitors in a median of 10 months (6-15 months) without any treatment, and 5 patients with high-titer inhibitors (median 100 BU/ml) remained positive in 24 months; the other 5 FVIII inhibitor-positive cases showed no significant changes. In the 25 patients developing FVIII inhibitors, the bleeding frequency increased significantly (P=0.025), and in 18 of the patients who continued to use FVIII products, a significant increase in the dose of medication was noted (P=0.015), but the number of target joints did not increase in 24 months (P=0.329). The incidence and characteristics of factor VIII inhibitor development differ between Chinese patients with hemophilia A and those in developed countries.

Zhou H.,Southern Medical University | Chen L.,Indiana University | Gao X.,Indiana University | Luo B.,Southern Medical University | Chen J.,Indiana University
Journal of Neuropathology and Experimental Neurology | Year: 2012

Traumatic brain injury (TBI) causes cell death predominantly in the cerebral cortex, but there is additional secondary cell death in the hippocampus. We previously found that most of the dying cells in the mouse hippocampus are newborn immature granular neurons in amouse model of lateral controlled cortical impact (CCI) injury with amoderate level of impact. It is not known how long this selective cell death in the hippocampal dentate gyrus lasts, and how it is induced. Using Fluoro-Jade B and immunohistochemistry, we show that most of the neuron death in the hippocampus occurs within 24hours after TBI and that cell death continues at low level for at least another 2 weeks in this lateral CCI model. Most of the dying immature granular neurons did not exhibit morphologic characteristics of apoptosis, and only a small subpopulation of the dying cells was positive for apoptotic markers. In contrast, most of the dying cells coexpressed the receptor-interacting protein 1, a marker of necrosis, suggesting that immature neurons mainly died of necrosis. These results indicate that moderate TBI mainly triggers rapid necroticdeath of immature neurons in the hippocampus in a mouse CCI model. © 2012 American Association of Neuropathologists, Inc.

Zhou H.-W.,Southern Medical University | Li D.-F.,CAS Beijing Institute of Genomics | Tam N.F.-Y.,City University of Hong Kong | Jiang X.-T.,CAS Beijing Institute of Genomics | And 5 more authors.
ISME Journal | Year: 2011

Pyrosequencing of 16S rRNA (16S) variable tags has become the most popular method for assessing microbial diversity, but the method remains costly for the evaluation of large numbers of environmental samples with high sequencing depths. We developed a barcoded Illumina paired-end (PE) sequencing (BIPES) method that sequences each 16S V6 tag from both ends on the Illumina HiSeq 2000, and the PE reads are then overlapped to obtain the V6 tag. The average accuracy of Illumina single-end (SE) reads was only 97.9%, which decreased from 99.9% at the start of the read to less than 85% at the end of the read; nevertheless, overlapping of the PE reads significantly increased the sequencing accuracy to 99.65% by verifying the 3′ end of each SE in which the sequencing quality was degraded. After the removal of tags with two or more mismatches within the medial 40-70 bases of the reads and of tags with any primer errors, the overall base sequencing accuracy of the BIPES reads was further increased to 99.93%. The BIPES reads reflected the amounts of the various tags in the initial template, but long tags and high GC tags were underestimated. The BIPES method yields 20-50 times more 16S V6 tags than does pyrosequencing in a single-flow cell run, and each of the BIPES reads costs less than 1/40 of a pyrosequencing read. As a laborsaving and cost-effective method, BIPES can be routinely used to analyze the microbial ecology of both environmental and human microbiomes. © 2011 International Society for Microbial Ecology All rights reserved.

Wang Q.-S.,Southern Medical University
Southern Medical Journal | Year: 2010

Objective: Lymphoma can arise at any anatomic site, but it is rare to find kidney involvement. The aim of this study was to assess the role of F-flourodeoxyglucose (F-FDG) positron emission tomography (PET)/computed tomography (CT) in detecting lymphoma with renal involvement. Reports of such use of F-FDG PET/CT are limited. MethodS: Twelve lymphoma patients with renal involvement and 12 renal carcinoma patients were studied with F-FDG PET/CT. Intense F-FDG uptake, suggestive of positivity, was measured in mean standardized uptake values (standardized uptake values [SUV] mean). Results: The results of PET/CT were validated by bone marrow, biopsy tissue and/or surgery. F-FDG PET/CT detected lymphoma with renal involvement lesions or renal carcinoma lesions in at least one site in the 24 patients. F-FDG uptake by the lymphoma lesions was much higher than the F-FDG uptake by the renal clear cell carcinomas (SUV mean 6.37 ± 2.28 vs 2.58 ± 0.62), and similar to that of renal cell carcinoma and renal collecting duct carcinoma (SUV mean 6.37 ± 2.28 vs 6.27 ± 1.15). There were dissimilar morphological changes in the homologous CT. Differing from renal cancer, lymphoma in the spleen, uterus, and bone marrow can easily be diagnosed by F-FDG PET/CT. Conclusion: The lesions of lymphoma with renal involvement, and especially those of primary renal lymphoma, are F-FDG avid. PET/CT appears to be useful in comparing these lesions with those of renal carcinoma, especially for primary renal lymphoma. Copyright © 2010 by The Southern Medical Association.

Qiu B.H.,Southern Medical University
Zhonghua zhong liu za zhi [Chinese journal of oncology] | Year: 2010

To review the clinical manifestations, imaging, tumor markers, treatment methods, pathology results and clinical curative effects of pineal region tumors and to evaluate the characteristics and intervention strategies for those tumors. The clinicopathological data of 132 patients with pineal region tumor treated in our department between January 2000 and May 2008 were retrospectively studied. A moderate predominance in males was presented. The clinical manifestations of the disease included increased intracranial pressure and ocular movement impairment. There were some features but no regularity and specific appearance on imaging including CT and MRI. 88.6% of patients associated with hydrocephalus. A high serum level of alpha-fetoprotein (AFP) was presented in 14 cases and high HCG in 9 cases. Eighteen cases received direct radiation therapy and 7 had radiotherapy post biopsy. 107 cases were treated surgically and 63 cases received postoperative adjuvant treatment. 114 cases had pathology results including 56 germ cell tumors. The patients were followed up for 12 approximately 132 months. Recurrence developed in 23 cases and 12 cases died. The 5-year survival rate was 89.3%. Pineal region tumors are often associated with hydrocephalus and this makes preoperative diagnosis difficult. Imaging examination may help diagnosis but less specific. Germ cell tumors may diagnosed by some tumor markers. Radiation therapy is the choice of treatment for pure germinomas. Other types of pineal region tumors should receive surgical treatment. Postoperative adjuvant treatment based on pathology can provide a good prognosis in pineal region tumor.

Xu J.,Southern Medical University | Wu S.,Southern Medical University | Shi X.,Southern Medical University
Journal of Orthopaedic Research | Year: 2010

Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a novel membrane-anchored matrix metalloproteinase inhibitor, have been shown to be associated with prognosis and suppress tumor progression through angiogenesis inhibition in many cancers. In this study, the expression of RECK in osteosarcoma was examined, and its clinical significance was firstly evaluated. RECK expression was immunohistochemically examined in osteosarcoma from 49 patients. By summing intensity and proportion scores, these patients were categorized as weak and strong. RECK expression in the primary tumor was strong in 27 patients (55.1%) and was weak in the rest of the patients. The 5-year survival rate of patients with RECK-strong tumor (81.5%) was significantly higher than that of patients with RECK-weak tumor (36.4%; p = 0.003). Reduced RECK expression significantly correlated with metastasis (p = 0.010) and recurrence (p = 0.004). A multivariate analysis confirmed that reduced RECK expression was an independent and significant factor to predict a poor prognosis (p = 0.017). RECK status is a useful prognostic factor in osteosarcoma, and an independent prognostic factor contributing to the determination of more adequate therapy strategies for each patient. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Zhou D.,University of Pittsburgh | Liu Y.,University of Pittsburgh | Liu Y.,Southern Medical University
Kidney International | Year: 2016

Chronic kidney disease (CKD) is a public health challenge worldwide. As CKD is associated with high rates of morbidity and mortality, identification of novel targets for effective therapy is urgently needed. Yan et al. provide evidence that the Src kinase plays a critical role in the pathogenesis of CKD by integrating multiple fibrogenic signal inputs. Therefore, targeted inhibition of Src kinase may hold promise as a new strategy in the fight against CKD. © 2016 International Society of Nephrology.

Guo J.,Pennsylvania State University | Xie Z.,Pennsylvania State University | Tran R.T.,Pennsylvania State University | Xie D.,Academy of Orthopedics of Guangdong Province | And 6 more authors.
Advanced Materials | Year: 2014

Click chemistry plays a dual role in the design of new citrate-based biodegradable elastomers (CABEs) with greatly improved mechanical strength and easily clickable surfaces for biofunctionalization. This novel chemistry modification strategy is applicable to a number of different types of polymers for improved mechanical properties and biofunctionality. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Wei Q.,U.S. National Institute of Diabetes and Digestive and Kidney Diseases | Wei Q.,Southern Medical University | Costanzi S.,U.S. National Institute of Diabetes and Digestive and Kidney Diseases | Costanzi S.,American University of Washington | And 3 more authors.
Purinergic Signalling | Year: 2013

The role of the A2B adenosine receptor (AR) in prostate cell death and growth was studied. The A2B AR gene expression quantified by real-time quantitative RT-PCR and Western blot analysis was the highest among four AR subtypes (A1, A2A, A2B, and A3) in all three commonly used prostate cancer cell lines, PC-3, DU145, and LNCaP. We explored the function of the A2B AR using PC-3 cells as a model. The A2B AR was visualized in PC-3 cells by laser confocal microscopy. The nonselective A2B AR agonist NECA and the selective A2B AR agonist BAY60-6583, but not the A2A AR agonist CGS21680, concentration-dependently induced adenosine 3′,5′-cyclic monophosphate (cyclic AMP) accumulation. NECA diminished lactate dehydrogenase (LDH) release, TNF-α-induced increase of caspase-3 activity, and cycloheximide (CHX)-induced morphological changes typical of apoptosis in PC-3 cells, which were blocked by a selective A2B AR antagonist PSB603. NECA-induced proliferation of PC-3 cells was diminished by siRNA specific for the A2B AR. The selective A2B AR antagonist PSB603 was shown to inhibit cell growth in all three cell lines. Thus, A2B AR blockade inhibits growth of prostate cancer cells, suggesting selective A2B AR antagonists as potential novel therapeutics. © 2013 Springer Science+Business Media Dordrecht (outside the USA).

Bai L.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2012

To obtain streptavidin-tagged human granulocyte-macrophage colony-stimulating factor (SA/hGM-CSF) fusion protein and evaluate its bioactivity . PET24a-6His-SA-L-hGM-CSF and PET24a-hGM-CSF-L-SA-6His plasmids were constructed and expressed in Rosetta (DE3) host bacteria to generate the fusion proteins. The two fusion proteins were refolded by gradient dialysis after Ni-NTA affinity chromatography and finally purified using DEAE-sepharose FF anion exchange chromatography. MTT method was used to evaluate the effect of SA/hGM-CSF fusion proteins in inducing the proliferation of human erythroleukemia cells (TF-1). The efficiency of the fusion proteins for surface modification of biotinylated MB49 tumor cells was evaluated by flow cytometry. The recombinant fusion proteins SA-hGM-CSF and hGM-CSF-SA were highly expressed in Rosetta (DE3) at about 20% of the total bacterial proteins, with a purity of about 96% after purification. The two fusion proteins exhibited bifunctional activities, namely the pro-proliferation effect on human erythroleukemia cells (TF-1) and SA-mediated high-affinity binding to biotinylated cell surfaces (with an anchoring modified rate of about 99%). SA/hGM-CSF bi-fusion proteins obtained in this study lays the groundwork for the development of cancer cell vaccines with surface modification by hGM-CSF.

Tang J.,Washington University in St. Louis | Tang J.,Southern Medical University | Yang W.,Washington University in St. Louis | Suga N.,Washington University in St. Louis
Journal of Neurophysiology | Year: 2012

The central auditory system consists of the lemniscal and nonlemniscal pathways or systems, which are anatomically and physiologically different from each other. In the thalamus, the ventral division of the medial geniculate body (MGBv) belongs to the lemniscal system, whereas its medial (MGBm) and dorsal (MGBd) divisions belong to the nonlemniscal system. Lemniscal neurons are sharply frequency-tuned and provide highly frequency-specific information to the primary auditory cortex (AI), whereas nonlemniscal neurons are generally broadly frequency-tuned and project widely to cortical auditory areas including AI. These two systems are presumably different not only in auditory signal processing, but also in eliciting cortical plastic changes. Electric stimulation of narrowly frequency-tuned MGBv neurons evokes the shift of the frequency-tuning curves of AI neurons toward the tuning curves of the stimulated MGBv neurons (tone-specific plasticity). In contrast, electric stimulation of broadly frequency-tuned MGBm neurons augments the auditory responses of AI neurons and broadens their frequency-tuning curves (nonspecific plasticity). In our current studies, we found that electric stimulation of AI evoked tone-specific plastic changes of the MGBv neurons, whereas it degraded the frequency tuning of MGBm neurons by inhibiting their auditory responses. AI apparently modulates the lemniscal and nonlemniscal thalamic neurons in quite different ways. High MGBm activity presumably makes AI neurons less favorable for fine auditory signal processing, whereas high MGBv activity makes AI neurons more suitable for fine processing of specific auditory signals and reduces MGBm activity. © 2012 the American Physiological Society.

Jing X.W.,Southern Medical University
Zhonghua nan ke xue = National journal of andrology | Year: 2011

To investigate the mRNA and protein expression levels of cysteine-rich secretory protein 2 (CRISP2) in the sperm of asthenospermia patients, and explore their relationship with sperm motility and related molecular mechanism. We collected 78 semen samples from adult male patients with asthenospermia and another 70 from healthy volunteers as controls. We extracted total RNA and total protein from the sperm following purification of the sperm by Percoll gradient centrifugation, and detected the relative expressions of CRISP2 mRNA and protein in the two groups by RT-PCR, SYBR Green real-time PCR and Western blot. The expression of CRISP2 mRNA was down-regulated by 4.3 times and that of the CRISP2 protein by 1.71 times in the asthenospermia patients, significantly lower than in the normal control group (P < 0.05). The down-regulation of CRISP2 mRNA and protein expressions in the sperm of asthenospermia patients may be closely related with decreased sperm motility, which suggests that CRISP2 may serve as a potential molecular target for the research of asthenospermia.

Guo Z.H.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2011

OBJECTIVE: Tumors originating from the muscularis propria layer of esophagus are usually removed by thoracoscopic resection. With the introduction of new endoscopic therapeutic techniques, some of these tumors could be treated by endoscopic submucosal dissection (ESD). However, the above endoscopic methods are associated with a high risk of perforation and it is hard to close the perforation through the endoscopy. Recently we successfully resected a tumor originating from the muscularis propria layer of the esophagus by submucosal tunneling endoscopic resection (STER), which was based on peroral endoscopic myotomy (POEM) and ESD. Compared with ESD, STER is a safe, economic and less invasive treatment. Even when perforation happens, it is easier to close the tunnel with the endoscopic clips which can help stopping the leak of air and digestive fluids. In this case, we found STER wss an effective and safe endoscopic procedure to remove tumors originating from the muscularis propria layer in the esophagus.

Zhang S.,Southern Medical University | Zhang K.,Southern Medical University | Jia Y.,Inner Mongolia University | Yu B.,Southern Medical University | Feng W.,Inner Mongolia University
Orthopedics | Year: 2013

The goal of this study was to compare the outcomes of unstable trochanteric fractures treated with the InterTan nail (Smith & Nephew, Memphis, Tennessee) and the Proximal Femoral Nail Antirotation (PFNA-II) (Synthes, Solothurn, Switzerland). A total of 132 consecutive patients with unstable trochanteric fractures of the femur were enrolled in the study. The only intervention was InterTan nail or PFNA-II fixation of the unstable trochanteric fractures. Follow-up occurred at 1, 3, 6, and 12 months postoperatively and yearly thereafter. Radiographs were obtained at each follow-up, and all implant position changes, complications, and fixation failures were recorded. A total of 113 patients meeting the criteria were evaluated at a mean last follow-up of 18.36 months (range, 12-30 months). Intraoperative complications and length of hospital stay were comparable between the groups. Patients treated with the PFNA-II experienced shorter fluoroscopy and operative times, less intraoperative blood loss, and less femoral neck shortening. The incidence of thigh pain was significantly higher in the PFNA-II group (30.4%) than in the InterTan group (10.3%) (P=.001). No statistically significant differences existed in general complications, local complications, walking ability, Harris Hip Scores, or hip range of motion at final follow-up.

Zhou Z.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2012

To characterize a new alternative splicing isoform of human vascular endothelial growth factor (VEGF) gene. The total RNA was extracted from the lung tissue of a legally aborted 4-month-old fetus and amplified by RT-PCR. The amplified product was cloned into the plasmid pMD18-T and plasmid pcDNA3.1- for sequence analysis. Electrophoresis of the RT-PCR products displayed one short band for VEGF(121) (487 bp) and a long band. The latter was characterized to contain two fragments: one was normal VEGF(165) (619 bp), and the other (639 bp) had an identical nucleotide sequence to VEGF(165) with a 20 bp fragment inserted between exons 3 and 4. Sequence analysis showed that this 20-bp nucleotide was inserted from the 3' end of the third intron containing a splicing signal, thus causing shift mutation in the reading frame of VEGF gene and early appearance of the stop codon UAG in the middle of exon 4. A new alternative splicing isoform of VEGF probably exists in the lung tissue of a legally aborted human fetus, and its biological significance remains to be further investigated.

Liu C.X.,Southern Medical University
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2010

To report the first case and detailed techniques of laparoendoscopic single-site surgery (LESS) radical cystectomy with orthotopic taenia myectomy sigmoid neobladder for organ-confined bladder cancer. A 74-year-old man presented with gross hematuria for 2 months and biopsy revealed bladder cancer. LESS radical cystectomy and bilateral pelvic lymphadenectomies were performed using a single multilumen port inserted through a solitary 3.5 cm lower abdominal incision with conventional laparoscopic instruments. The taenia myectomy sigmoid pouch was then constructed by open procedure. The total operative time was 9.5 h, and the LESS procedure lasted for about 5.5 h. No other port incision was added. The final pathology revealed urothelial carcinoma. The estimated intraoperative blood loss was 600 ml with blood transfusion of 400 ml. The pelvic lymph nodes and the surgical margins of the ureters and urethra were all free of tumor invasion. No water electrolyte and metabolic acid-base balance disorders were observed perioperatively. The neobladder capacity was about 280 ml, with a residual urine volume of 10 ml and peak flow rate of 11.1 ml/s 3 months postoperatively. Although with a steep learning curve, LESS surgery can be a less invasive and promising alternative to muscle-invasive bladder carcinoma.

Chen X.,Southern Medical University | Chen S.-L.,Southern Medical University
Fertility and Sterility | Year: 2011

Objective: To inform clinicians about the reproductive damage of Tripterygium wilfordii Hook.f. (TW) associated with subsequent premature ovarian failure. Design: Case report. Setting: Reproductive medicine center in a university-affiliated hospital. Patient(s): A 36-year-old infertile woman presenting amenorrhea and elevated FSH levels (65.56 mIU/mL) after using TW. Intervention(s): Estradiol valerate, two month course of oral contraceptives, GnRH agonist, stimulation cycle with urine FSH, triggered ovulation using 5000 IU of hCG and IVF-ET. Main Outcome Measure(s): Serum hormone levels, antral follicle count (AFC), oocyte retrieval number, embryo quality and birth. Result(s): Serum hormone levels and AFC of the POF woman were restored, and she gave birth to a healthy child after IVF-ET. Through IVF-ET she was found to have had oocyte and granulosa cell damage because of TW. Conclusion(s): This is a real-life manifestation of reproductive damage of TW. The medicamentous amenorrhea, hormone levels and AFC decline induced by TW are reversible, but oocyte and granulosa cell damage may be irreversible. This will help clinicians to avoid using TW for nulligravida. © 2011 by American Society for Reproductive Medicine.

Mao C.,Chinese University of Hong Kong | Yang Z.Y.,Chinese University of Hong Kong | Hu X.F.,Chinese University of Hong Kong | Chen Q.,Southern Medical University | Tang J.L.,Chinese University of Hong Kong
Annals of Oncology | Year: 2012

Background: We conducted a systematic review and meta-analysis to dissect the association between PIK3CA mutations and resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs) according to PIK3CA exon of mutations in metastatic colorectal cancer (mCRC). Methods: We systematically identified studies exploring the association between PIK3CA mutations and clinical outcomes of mCRC patients treated with anti-EGFR MoAbs. The primary clinical outcomes included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The pooled relative risk (RR) or hazard ratio (HR) was estimated by using fixed effect model or random effect model according to heterogeneity between studies. Results: Thirteen studies were considered eligible, with 576 mCRC patients included. In KRAS wild-type mCRC patients, we observed a lower ORR in patients with PIK3CA exon 20 mutations [3 studies, 377 patients; ORR = 0% versus 37%; RR = 0.25; 95% confidence interval (CI) 0.05-1.19; P = 0.082], although the result was not statistically significant because of the small sample size. Only one study provided survival data according to the PIK3CA exon of the mutations, in which PIK3CA exon 20 mutations were statistically significantly associated with shorter PFS (HR = 2.52; 95% CI 1.33-4.78; P = 0.013) and OS (HR = 3.29; 95% CI 1.60-6.74; P = 0.006) in KRAS wild-type mCRC patients treated with anti-EGFR MoAbs. The predictive power of exon 20 mutation is greater than exon 9 mutations and all exons mutations in terms of ORR, PFS, and OS. Conclusion: These analyses suggest that PIK3CA exon 20 mutations may be a potential biomarker for resistance to anti-EGFR MoAbs in KRAS wild-type mCRC. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Up to now, the precise molecular and morphological changes underlying the invasive and metastatic properties of nasopharyngeal carcinoma (NPC) remain largely unresolved. We speculate that neoplastic spindle cells, which are prominently found in the invasive tumor front and the surrounding stroma, might be responsible for the aggressive patterns. Expression profiling of various biomarkers relevant to cancer stem cells (CSCs) and epithelialmesenchymal transition (EMT) was performed by tissue microarray-based immunohistochemistry in NPC samples. The expression of EBER and LMP1 was detected by in situ hybridization and immunohistochemistry, respectively. We found that overexpression of CSCs-related markers (ALDH1, Nanog and ABCG2) and up-regulation of EMT markers (Fibronectin, MMP-2, Periostin, SPARC, Snail and Slug), together with E- to N-cadherin switching, occurred preferentially in tumors containing a large proportion of spindle-shaped malignant cells. Furthermore, CSCs-like properties were highly present in spindle cells compared with non-spindle cells of tumors, and correlated strongly with EMT features. In addition, EBV-related factors EBER and LMP1 were highly expressed and correlated strongly with CSCs and EMT characteristics in neoplastic spindle cells. Importantly, high proportion of spindle cells (?20%) correlated significantly with various aggressive aspects including lymph node metastasis (P = 0.031) and local recurrence ( P = 0.014). Patients with high proportion of spindle cells had poor survival (P = 0.004), though it was not an independent value. In conclusion, we demonstrate that spindle cells could be valuable morphological indicators of tumor progression and unfavorable prognosis of NPC. An integrated molecule-morphology model of NPC firstly constructed may shed significant light on the metastatic cascade and clinical relevance of patients. © 2013 Luo, Yao.

Liu Y.,Southern Medical University | Zheng W.,Southern Medical University | Song Y.,Southern Medical University | Ma W.,Southern Medical University | Yin H.,Southern Medical University
PLoS ONE | Year: 2013

MicroRNAs (miRNAs) can function as tumor suppressors or oncogene promoters during tumor development. In this study, low levels of expression of miR-196b were detected in patients with chronic myeloid leukemia. Bisulfite genomic sequencing PCR and methylation-specific PCR were used to examine the methylation status of the CpG islands in the miR-196b promoter in K562 cells, patients with leukemia and healthy individuals. The CpG islands showed more methylation in patients with chronic myeloid leukemia compared with healthy individuals (P<0.05), which indicated that low expression of miR-196b may be associated with an increase in the methylation of CpG islands. The dual-luciferase reporter assay system demonstrated that BCR-ABL1 and HOXA9 are the target genes of miR-196b, which was consistent with predictions from bioinformatics software analyses. Further examination of cell function indicated that miR-196b acts to reduce BCR-ABL1 and HOXA9 protein levels, decrease cell proliferation rate and retard the cell cycle. A low level of expression of miR-196b can cause up-regulation of BCR-ABL1 and HOXA9 expression, which leads to the development of chronic myeloid leukemia. MiR-196b may represent an effective target for chronic myeloid leukemia therapy. © 2013 Liu et al.

Gao S.,Michigan State University | Li A.,Michigan State University | Li A.,Southern Medical University | Liu F.,Southern Medical University | And 8 more authors.
Cancer Cell | Year: 2013

Type 2 diabetes (T2D) and male gender are associated with hepatocellular carcinoma (HCC) development. We demonstrate that heterozygous deletion of the Ncoa5 gene causes spontaneous development of HCC exclusively in male mice. Tumor development is preceded by increased interleukin-6 (IL-6) expression, early-onset glucose intolerance, and progressive steatosis and dysplasia in livers. Blockading IL-6 overexpression averts glucose intolerance and partially deters HCC development. Moreover, reduced NCOA5 expression is associated with a fraction of human HCCs and HCCs with comorbid T2D. These findings suggest that NCOA5 is a haploinsufficient tumor suppressor and that NCOA5 deficiency increases susceptibility to both glucose intolerance and HCC, partially by increasing IL-6 expression. Thus, our findings open additional avenues for developing therapeutic approaches to combat these diseases. © 2013 Elsevier Inc.

Wu X.-B.,Southern Medical University | Na R.-H.,Southern Medical University | Wei S.-S.,Southern Medical University | Zhu J.-S.,Virginia Polytechnic Institute and State University | Peng H.-J.,Southern Medical University
Parasites and Vectors | Year: 2013

As an important contributor to vector-borne diseases in China, in recent years, tick-borne diseases have attracted much attention because of their increasing incidence and consequent significant harm to livestock and human health. The most commonly observed human tick-borne diseases in China include Lyme borreliosis (known as Lyme disease in China), tick-borne encephalitis (known as Forest encephalitis in China), Crimean-Congo hemorrhagic fever (known as Xinjiang hemorrhagic fever in China), Q-fever, tularemia and North-Asia tick-borne spotted fever. In recent years, some emerging tick-borne diseases, such as human monocytic ehrlichiosis, human granulocytic anaplasmosis, and a novel bunyavirus infection, have been reported frequently in China. Other tick-borne diseases that are not as frequently reported in China include Colorado fever, oriental spotted fever and piroplasmosis. Detailed information regarding the history, characteristics, and current epidemic status of these human tick-borne diseases in China will be reviewed in this paper. It is clear that greater efforts in government management and research are required for the prevention, control, diagnosis, and treatment of tick-borne diseases, as well as for the control of ticks, in order to decrease the tick-borne disease burden in China. © 2013 Wu et al.; licensee BioMed Central Ltd.

Objective: To explore the therapeutic effects of sequential intensified conditioning regimen followed by graft-versus-leukemia (GVL) induction in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for refractory advanced acute myeloid leukemia (AML). Methods: A total of 72 patients with refractory AML undergoing allo-HSCT from May 2001 to June 2013 were enrolled in this prospective study. Intensified conditioning included fludarabine + cytarabine plus total body irradiation + cyclophosphamide + etoposide. Cyclosporine A was withdrawn rapidly in a stepwise fashion if patients who did not experience acute graft-versus-host disease (aGVHD) at Day + 30 post-transplantation. Donor lymphocytes were infused in patients without grade II or more than grade II aGVHD at Day + 60 post-transplantation. Results: The median follow-up time was 655 (1-4 200) d post-transplantation. Except for one died of infection and one died of regimen-related toxicity (RRT), the other 70 patients achieved complete remission at the time of neutrophil reconstitution. The mortality of RRT was 1.4% (1/72). The 1-year cumulative incidence of aGVHD and 2-year incidence of chronic GVHD (cGVHD) post-transplantation were 60.7% ± 5.0% and 58.5% ± 4.7%. The 5-year cumulative incidence of relapse post-transplantation was 29.6% ± 6.6%. The 5-year non-relapse mortality was 28.8% ± 6.0%. The 5-year overall and disease-free survival were 51.0% ± 6.5% and 49.9% ± 6.4%. Multivariate analysis revealed that donor lymphocyte infusion, cGVHD and bone marrow blasts at Day 0 were independent prognostic factors for relapse (HR( 95% CI):0.042 (0.007-0.688), 0.009 (0.003-0.345), 3.385 (1.451-7.899)) and survival (HR(95% CI):0.315 (0.146-0.621), 0.416 (0.200-0.866), 1.332 (1.158-1.533)). Conclusion: The strategy of sequential intensified conditioning followed by GVL induction has an acceptable toxicity profile, and could decrease the relapse rate and improve the survival for refractory AML. © 2015, Chinese Medical Association. All rights reserved.

Wang X.-J.,Southern Medical University | Deng H.-Z.,Southern Medical University | Jiang B.,Southern Medical University | Yao H.,Southern Medical University
International Journal of Colorectal Disease | Year: 2012

Introduction Sophora alopecuroides L., a traditional Chinese herbal remedy, has been widely used for treating enteritis and bacillary dysentery for many years. Sophocarpine is a major ingredient of S. alopecuroides L. and has a wide range of pharmacological effects. Materials and methods In this study, we investigated the therapeutic potential of sophocarpine for treating dextran sulfate sodium (DSS)-induced experimental ulcerative colitis in C57BL/6 mice, a well-characterized murine model of ulcerative colitis. Experimental colitis was induced in these mice by dissolving 5% DSS in their drinking water for 7 days and sophocarpine (60, 30, and 15 mg/kg of body weight) and sulfasalazine (520 mg/kg) were administered orally once a day for 7 days. Results Sophocarpine significantly ameliorated DSS-induced colitis as identified by a reduced disease activity index and wet weight of colons as well as recovery of body weight. Furthermore, the oral administration of sophocarpine significantly decreased myeloperoxidase activity and the level of interleukin (IL)-1 and IL-6 in serum (P<0.01), while there was no significant effect on the level of IL-4. Conclusions In conclusion, sophocarpine significantly ameliorated DSS-induced colitis in mice by regulating the pro- and anti-inflammatory cytokine production. Based upon our results, we suggest that sophocarpine is an effective agent for treating colonic inflammation. © 2011 CARS.

Zhou D.,University of Pittsburgh | Zhou D.,Nanjing University | Li Y.,University of Pittsburgh | Lin L.,University of Pittsburgh | And 4 more authors.
Kidney International | Year: 2012

Β-Catenin is a unique intracellular protein functioning as an integral component of the cell-cell adherens complex and a principal signaling protein mediating canonical Wnt signaling. Little is known about its function in adult kidneys in the normal physiologic state or after acute kidney injury (AKI). To study this, we generated conditional knockout mice in which the Β-catenin gene was specifically disrupted in renal tubules (Ksp-Β-cat-/-). These mice were phenotypically normal with no appreciable defects in kidney morphology and function. In the absence of Β-catenin, γ-catenin functionally substituted for it in E-cadherin binding, thereby sustaining the integrity of epithelial adherens junctions in the kidneys. In AKI induced by ischemia reperfusion or folic acid, the loss of tubular Β-catenin substantially aggravated renal lesions. Compared with controls, Ksp-Β-cat-/- mice displayed higher mortality, elevated serum creatinine, and more severe morphologic injury. Consistently, apoptosis was more prevalent in kidneys of the knockout mice, which was accompanied by increased expression of p53 and Bax, and decreased phosphorylated Akt and survivin. In vitro activation of Β-catenin by Wnt1 or stabilization of Β-catenin protected tubular epithelial cells from apoptosis, activated Akt, induced survivin, and repressed p53 and Bax expression. Hence, endogenous Β-catenin is pivotal for renal tubular protection after AKI by promoting cell survival through multiple mechanisms. © 2012 International Society of Nephrology.

Xu S.Y.,Southern Medical University
Medical science monitor basic research | Year: 2013

The discrepancy in results regarding neuroprotective agents in animal experiments compared to clinical trials is a major problem. While many neuroprotective agents have been proven effective in a variety of animal ischemic stroke models, none have been shown to work in phase III clinical trials. This review retrospectively summarizes the neuroprotectants selected for human randomized controlled trials (RCT) and explores the reasons behind the clinical translational failure of these agents. Here, we suggest that there are many factors (model selection, anesthetic choice, physiological monitoring, model success criteria, embolus property, reperfusion damage, infarction area, therapeutic time window, drug penetration, blood concentration, gender difference, and outcome evaluation) responsible for this phenomenon. Ultra-early treatment using a "home run" drug and multi-target therapy may be the most promising for future consideration.

Li X.,Southern Medical University | Zhang Y.,Southern Medical University |