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Electrophysiological actions of cyclosporin A and tacrolimus on rat hippocampal CA1 pyramidal neurons

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Acta Pharmacologica Sinica 2007年第12期28卷 1891-1897页

作者： Yong YU~2.Xue-qin CHEN~3,Yao-yuan CUI~(2.4.,Guo-yuan HU~(3,4.~2.Department of Neurosurgery,{2. hospital,Fudan University,shanghai 2.0032.China ~3 State Key Laboratory of Drug Research,shanghai institute of Materia Medica,Chinese Academy of Sciences,shanghai 2.12.3,China Department of Neurosurgery Zhongshan Hospital Fudan University Shanghai China State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China

Aim:The aim of the present study was to investigate the electrophysiologicalactions of cyclosporin A （CsA） and tacrolimus （FK506） on neurons in the brain,and to elucidate the relevant ***:Whole-cell current-clamprecording was made in CA1 pyramidal neurons in rat hippocampal slices;whole-cell voltage-clamp recording was made in dissociated hippocampal CA1 pyrami-dal neurons of ***:CsA （100 μmol/L） and FK506 （50 μmol/L） did notsignificantly alter the passive electrical properties of hippocampal CA 1 pyramidalneurons,but slowed down the repolarizing phase of the action ***（10-100 μmol/L） selectively inhibited the delayed rectifier K+current （IK） in aconcentration-dependent *** did not affect the kinetic properties of *** dialysis of CsA （100 μmol/L） had no effect on *** inhibition of IKby CsA （100 μmol/L） persisted under the low Ca2.conditions that blocked thebasal activity of ***:CsA exerted calcineurin-independentinhibition on the IKin rat hippocampal pyramidal *** together withour previous finding with FK506,it is conceivable that the spike broadening causedby the immunosuppressant drugs is due to direct inhibition on the IK.

关键词： action potential calcineurin cyclosporin A delayed rectifier K~+ channel hippocampus tacrolimus

Losartan inhibited expression of matrix metalloproteinases in rat atherosclerotic lesions and angiotensin Ⅱ-stimulated macrophages

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Acta Pharmacologica Sinica 2004年第11期 42-48页

作者： Chun LIANG, Zong-gui WU, Jian DING, Jian-fei JIANG, Gao-zhong HUANG, Rong-zeng DU, Jun-bo GEDepartment of Cardiology, Changzheng hospital, Second Military Medical University, shanghai 2.0003, China shanghai institute of Materia Medica, Chinese Academy of Sciences, shanghai 2.12.3, China shanghai institute of cardiovascular Diseases, zhongshan hospital, Fudan University, shanghai 2.0032. China

AIM: To explore whether the angiotensin Ⅱ (Ang Ⅱ) receptor 1 (AT1) antagonist, losartan could reduce activity and expression of matrix metalloproteinases (MMPs) in rat atherosclerotic plaques. METHODS: Male Wistar-Kyoto rats were ip injected a single dose of vitamin D3 600 kU·kg-1·month-1 and fed an atherogenic diet for 4.months to induce experimental atheroma. Then either placebo or losartan 50 mg·kg-1·d-1 was administered in rats for another 2.months. In vitro, the effect of losartan 0.1-10μmol/L on the expression of MMP-2.and MMP-9 was investigated in Ang II-stimulated rat peritoneal macrophages. The expression and activity of MMP-2.and MMP-9 were monitored by Western blot, RT-PCR, and SDS-PAGE zymography analysis. RESULTS: High levels of MMP-2.and MMP-9 were expressed in rat atherosclerotic lesions. Losartan significantly reduced the activity and expression of MMP-2.and MMP-9 compared with the placebo group (MMP-2. 5861±539 vs 8991±965, P2.±1002.vs 14.2.±2.0}2. P<0.01). In

关键词： losartan metalloproteinases angiotensin Ⅱ atherosclerosis peritoneal macrophages reverse tran-scriptase polymerase chain reaction Western blotting

Role of real-time three-dimensional transesophageal echocardiography in mitral valve repair

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Journal of Geriatric Cardiology 2008年第3期5卷 137-141页

作者： Cuizhen Pan~1 Xianhong Shu~1 Qiling Cao~2.Chunsheng Wang~1 Wenjun Ding~1 Haozhu Chen~1 1 Department of Echocardiography, zhongshan hospital, Fudan University, shanghai {2. of cardiovascular Diseases, shanghai 2.0032. China, 2.Rush University Medical Center, Chicago, USA Department of Echocardiography Fudan University Shanghai Institute of Cardiovascular Diseases Shanghai 200032 China Rush University Medical Center Chicago IL United States

Background and objective Pre-operative assessment of mitral valve (MV) anatomy is essential to surgical design in patients undergoing MV *** 2.dimensional (2.) echocardiography provides precise information regarding MV anatomy,RT-3D TEE could increase the understanding of MV apparatus and individual scallop *** aimed to investigate the value of RT- 3DTEE in MV *** RT-3DTEE was performed in six patients with mitral valve prolapse (MVP) by using Philips 1E33 with X7-2. *** RT-3DTEE studies were compared with surgical findings in patients undergoing surgical mitral valve repair,and quantitative evaluation was performed by QLab 6.0 software before and after surgical mitral valve *** RT- 3DTEE could display dynamic morphology of MV,the location of prolapse,and spatial relation to the surrounding *** could provide surgical views of the valves and the valvular *** results were consistent with surgical *** quantitative evaluation before and after surgical MV repair indicated that anterolateral to posteromedial diameter of annulus,anterior to posterior diameter of annulus,perimeter of annulus,and area of annulus in projection plane were significantly smaller after operation compared with those before operation (P<0.05).The length of posterior leaflet,the area of anterior and posterior leaflet,the maximal prolapse height,the volume of leaflet prolapse and the length of coaptation in projection plane were significantly reduced after operation (P<0. 05).Conclusion RT-3DTEE is a unique new modality for rapid and accurate evaluation ofmitral valve prolapse and mitral valve repair.

关键词： Echocardiography real-time transeophageal mitral valve repair

Cardiac stem cell therapy research in China

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Journal of Geriatric Cardiology 2006年第3期3卷 184-186页

作者： Junbo GE Center of Stem Cell and Tissue Engineering Shanghai Institute of Cardiovascular Disease Zhongshan HospitalFudan University Shanghai 200032 China

For more than two decades, the morbidity and mortality of coronary artery disease (CAD) has been increasing rapidly in China. Despite tremendous advances in treatment strategies of CAD, heart failure after acute myocardial infarction (AMI) continues to be one of the greatest medical challenges throughout the world. In 1994. Soonpaa and colleagues first reported the possibility of cardiomyocytes implantation and suggested that intracardiac cell grafting might provide a useful approach for myocardial repair.1 Cell implantation has become a novel therapeutic option for ischemic cardiac injury and heart failure.

关键词： stem cell Cardiac stem cell therapy research in China

Pravastatin activates platelet nitric oxide synthase (NOS) in patients with type 2.diabetes mellitus and NOS activation is accompanied by serine phosphorylation

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中华医学杂志(英文版) 2005年第19期000卷 72-75页

作者： YAO Kang, XU Biao, Gao Ling and GE Jun-bo shanghai institute of {2. Disease, zhongshan hospital, Fudan University, shanghai 2.0032. China Department of {2. Disease,Gulou hospital,Nanjing University,Nanjing2.0008,China shanghai institute of {2. Disease Zhongshan Hospital Fudan University Shanghai 200032 China Department of cardiovascular Disease Gulou Hospital Nanjing University Nanjing 210008 China

Statins cause reductions in myocardial infarction and also morbidity and mortality of type 2.diabetes related to atheromatous disease and its thrombotic complications beyond those predicted by reductions in low density lipoprotein cholesterol (LDL).~ 1,2.It has been suggested that the protective mechanism(s) may relate to improved endothelial function and/or antithrombotic effects, but the mechanism is not clear.

关键词： platelet · HMG-CoA reductase inhibitors · type 2.diabetes mellitus · nitric oxide synthase

DYNAMIC ANALYSIS OF FLUID-STRUCTURE INTERACTION OF ENDOLYMPH AND CUPULA IN THE LATERAL SEMICIRCULAR CANAL OF INNER EAR

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Journal of Hydrodynamics 2011年第6期23卷 777-783页

作者： WU Cai-qin HUA Cheng YANG Lin DAI Pei-dong ZHANG Tian-yu WANG Ke-qiang Department of Mechanics and Engineering Science Fudan University Shanghai 200433 China Eye and ENT hospital of Fudan University Shanghai 200031 China cardiovascular Disease institute Zhongshan Hospital of Fudan University Shanghai 200032 China

The semicircular canals, composed of lateral, anterior and posterior canals in the inner ear, are the sensors of equilibrium during head rotation movements in the three-dimensional space. Semicircular canals are filled with endolymph confined by the cupula. The study of the relationship between endolymph flow and cupular deformation is important in revealing the semicircular canals biomechanical behavior. To date, there are few studies focusing on the transient endolymph flow and cupular deformation in response to a head rotation motion. The lateral semicircular canal is mainly responsible for the sense of the horizontal rotation movement. In order to figure out the intricate dynamics in the lateral semicircular canal during the head rotation motion, the time evolutions of both endolymph flow and cupular deformation are analyzed in this article by using a fully coupled fluid-structure interaction model. It is shown that the cupular deformation provides cues for understanding the physiology of sensing the head rotation.

关键词： fluid-structure interaction endolymph cupula finite element method

Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97

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World Journal of Gastroenterology 2001年第5期7卷 630-636页

作者： Yan Li Zhao-You Tang Sheng-Long Ye Yin-Kun Liu Jie Chen Qiong Xue Jun Chen Dong-Mei Gao Wei-Hua Bao Liver Cancer institute and zhongshan hospital of Fudan University (Former Liver Cancer institute of shanghai Medical University),shanghai 2.0032.China Liver Cancer institute & zhongshan hospital of Fudan University 136 Yixueyuan Road Shanghai 200032China.

AIM: To establish clone cells with different metastatic potential for the study of metastasis-related mechanisms. METHODS: Cloning procedure was performed on parental hepatocellular carcinoma (HCC) cell line MHCC97, and biological characteristics of the target clones selected by in vivo screening were studied. RESULTS: Two clones with high (MHCC97-H) and low (MHCC97-L) metastatic potential were isolated from the parent cell line. Compared with MHCC97-L, MHCC97-H had smaller cell size (average cell diameter 4. microm vs 50 microm) and faster in vitro and in vivo growth rate (tumor cell doubling time was 34.2. vs 60.0h). The main ranges of chromosomes were 55-58 in MHCC97-H and 57-62.in MHCC97-L. Boyden chamber in vitro invasion assay demonstrated that the number of penetrating cells through the artificial basement membrane was (37.5 +/- 11.0) cells/field for MHCC97-H vs (17.7 +/- 6.3)/field for MHCC97-L. The proportions of cells in G0-G1 phase, S phase, and G2.M phase for MHCC97-H/MHCC97-L were 0.56/0.65, 0.2./0.2. and 0.16/0.10, respectively, as measured by flow cytometry. The serum AFP levels in nude mice 5wk after orthotopic implantation of tumor tissue were (2.0} +/- 66) microg.L(-1) for MHCC97-H and (91 +/- 66) microg.L(-1) for MHCC97-L. The pulmonary metastatic rate was 100% (10/10) vs 4.% (4.10). CONCLUSION: Two clones of the same genetic background but with different biological behaviors were established, which could be valuable models for investigation on HCC metastasis.

关键词： Albumins Animals Carcinoma, Hepatocellular Cell Division Chromosomes Clone Cells Flow Cytometry Hepatitis B Hepatitis B Surface Antigens Hepatitis B virus purification Humans Keratin Liver Liver Neoplasms, Experimental Male Mice Mice, Inbred BALB C Mice, Nude Neoplasm Invasiveness Research Support, Non-U.S. Gov't Tumor Cells, Cultured Virus Integration alpha-Fetoproteins

SF/HGF-c-Met autocrine and paracrine promote metastasis of hepatocellular carcinoma

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World Journal of Gastroenterology 2001年第6期7卷 816-820页

作者： Qian Xie Kang-Da Liu Mei-Yu Hu Kang Zhou Experimental Research Center of zhongshan hospital,Fudan University,shanghai,{2.China Experimental Research Center of zhongshan hospital Fudan University Shanghai 200032 China.

AIM: To explore the role of SF/HGF-Met autocrine and paracrine in metastasis of hepatocellular carcinoma (HCC). METHODS: SF/HGF and c-met transcription and protein expression in HCC were examined by RT-PCR and Western Blot in 4.HCC cell lines, including HepG2. Hep3B, SMMC772. and MHCC-1, the last cell line had a higher potential of metastasis. sf/hgf cDNA was transfected by the method of Lipofectin into SMMC772.. SF/HGF and c-met antibody were used to stimulate and block SF/HGF-c-met signal transduction. Cell morphology, mobility, and proliferation were respectively compared by microscopic observation, wound healing assay and cell growth curve. RESULTS: HCC malignancy appeared to be relative to its met-SF/HGF expression. In MHCC-1, c-met expression was much stronger than that in other cell lines with lower potential of metastasis and only SF/HGF autocrine existed in MHCC-1. After sf/hgf cDNA transfection or conditioned medium of MHCC-1 stimulation, SMMC772. changed into elongated morphology, and the abilities of proliferation (P < 0.05) and mobility increased. Such bio-activity could be blocked by c-met antibody (P < 0.05). CONCLUSION: The system of SF/HGF-c-met autocrine and paracrine played an important role in development and metastasis potential of HCC. Inhibition of SF/HGF-c-met signal transduction system may reduce the growth and metastasis of HCC.

关键词： Autocrine Communication Carcinoma, Hepatocellular Hepatocyte Growth Factor Humans Liver Neoplasms Paracrine Communication Proto-Oncogene Proteins c-met Research Support, Non-U.S. Gov't Tumor Cells, Cultured

Sorafenib in treatment of patients with advanced hepatocellular carcinoma:a systematic review

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Hepatobiliary & Pancreatic Diseases International 2012年第5期11卷 458-466页

作者： Xin Zhang, Xin-Rong Yang, Xiao-Wu Huang, Wei-Min Wang, Ruo-Yu Shi, Yang Xu, Zheng Wang, Shuang-Jian Qiu, Jia Fan ,Jian Zhou Liver Cancer institute, zhongshan hospital, Fudan University, {2. Key Laboratory for Organ Transplantation, {2. {4. China,institute of Biomedical Sciences, Fudan University, {2. {4. China Liver Cancer institute Zhongshan Hospital Fudan University and Shanghai Key Laboratory for Organ Transplantation Shanghai 200032 Shanghai China institute of Biomedical Sciences Fudan University Shanghai 200032 Shanghai China

BACKGROUND: Sorafenib has become the standard first-line treatment for patients with advanced hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of sorafenib in advanced HCC patients and explore its true value for specific subgroups. DATA SOURCES: A computer-based systematic search from January 2.05 to June 2.11 with 'sorafenib' and 'advanced hepatocellular carcinoma' as search terms was performed for possible clinical trials. Hazard ratios (HR) and their 95% confidence intervals (CI) for overall survival (OS) and time to progression (TTP), rates of partial response (PR), rates of toxicity effects, and details of subgroup analysis were extracted. Meta-analyses were done using the software Review Manager (version 5.0). RESULTS: Six trials with 1164.patients were included. Based on three randomized controlled trials, the pooled HR (sorafenib/ placebo) was 0.66 for OS (95% CI: 0.56-0.78; P4.-0.68; P2.96 (95% CI: 0.96-9.15; P=0.06). For three single-arm trials, the pooled HR was 0.69 for OS (95% CI: 0.56-0.84. P=0.0002. and 0.64.for TTP (95% CI: 0.52.0.78; P2.-10.39; P=0.02.. Subgroup analysis indicated that sorafenib was less effective in patients with extrahepatic spread (with: P=0.13 vs without: P4.hand-foot skin reaction, diarrhea, fatigue, and rash/***: Sorafenib-based therapy benefits advanced HCC patients. Meanwhile, sorafenib is less effective for patients with extrahepatic spread, with normal AFP level and with elevated level of bilirubin.

关键词： advanced hepatocellular carcinoma sorafenib systematic review