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Impact of virus genotype on interferon treatment of patients with chronic hepatitis C: a multicenter controlled study

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Hepatobiliary & Pancreatic diseases International 2004年第3期3卷 369-374页

作者： Yao Xie, Dao-Zhen Xu, Zhi-Meng Lu, Kang-Xian Luo, Ji-Dong Jia, Yu-Ming Wang,Gui-Zhen Zhao, Shu-Lin Zhang and Da-Zhi Zhang department of Infeetious diseases , Beijing Ditan Hos-pital, Beijing 100011 , china department of Infec-tious diseases, Ruijin hospital, Shanghai 200025, china De-partment of infectious diseases, Naifang hospital, First Military medical U-niversity, Guangzhou 510515, china (Luo KX) Center of Liver disease,Beijing Friendship hospital, Beijing 100050, china (Jia J D ) Institute ofinfectious disease, Southwest hospital, Third Military medical university,Chongqing 410032, china department of infectious disea-ses, second hospital, china medical university, shenyang 110004, china department of infectious diseases, First hospital, Xi’ an Jiao-tong university, Xi’ an 710061 , china ) Liver disease Centerof Chongqing, second hospital, Chongqing medical university,Chongqing 410010, china department of infectious diseases Beijing Ditan Hospital Beijing 100011 China. xieyao@***

BACKGROUND: Some factors have been reported to besassociated with a greater likelihood of sustained viral re-sponse ( SVR) in the interferon (IFN) treatment of chronichepatitis C. The factors include HCV genotype, HCVRNA level in serum, state of liver disease, baseline bodyweight, age, sex, and race. The aim of this trial was to in-vestigate the influence of HCV genotype on the IFN treat-ment of patients with chronic hepatitis ***: The genotypes of HCV virus were determinedin the patients with chronic hepatitis C from several hospi-tals of china enrolled into the randomized, opened andcontrolled trial of Peg-IFN alpha-2a (pegasys) treatment,controlled with IFN-α-2a (roferon-A). The serum ALTlevels and HCV RNA concentrations of the patients weredetected before and at the end of treatment and during thefollow-up. The influence of HCV genotype on the IFNtreatment of patients with chronic hepatitis C was analyzedin intention-to-treat (ITT) ***: The HCV genotypes of 202 patients were deter-mined. Of these patients, 158(78.22%) were infected withgenotype 1 HCV and 44(21.78%) with genotype *** viral response at the end of treatment (ETVR) andsustained viral response (SVR) rates were 53.80% and25.32% respectively in patients with genotype 1 HCV, butthey were 61.36% and 43.18% in patients with genotypenon-1. The difference of SVR between patients with geno-type 1 HCV and those with genotype non-1 was significant(P =0.021). After being grouped by the used drugs, theETVR rates of patients infected with genotype 1 and non-1HCV were 76.83% and 80.95% in the patients treated withpegasys (P =0.686); but their SVR rates were 35.37% and66.67% (P =0. 01). The viral relapse rate of genotype 1HCV (55.56%) was significantly higher than that of geno-type non-1 HCV (23.53%) (P=0.02). In roferon-A group,the ETVR and SVR rates of patients with genotype 1 HCVwere 28.95% and 14.47% respectively, which were lowerbut not more significant than those of patients with ge

关键词： hepatitis C virus genotype chronic hepatitis C interferon PEG-IFN

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^(103)Pd-induced apoptosis of proliferative smooth muscle cells in bile ducts of dogs:significance and effects on related genes

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Hepatobiliary & Pancreatic diseases International 2007年第5期6卷 521-526页

作者： Gui-Jin He,Fa-Qiang Yu,Rong Wu,Qin-Yi Gao,Shu-He Xu,Hong Gao, Wei-Guo Jiang,Tao Jiang and Xian-Wei Dai department of General Surgery,second Affiliated hospital(Shengjing hospital),china medical university,shenyang 110004,china,Radiotherapy Center,second Affiliated hospital(Shengjing hospital),china medical university,shenyang 110004,china,Pediatrics Surgery Laboratory,second Affiliated hospital(Shengjing hospital),china medical university,shenyang 110004,china,department of Pathology,second Affiliated hospital(Shengjing hospital),china medical university,shenyang 110004,china Isotope Unit,First Affiliated hospital,china medical university,shenyang 110001,china and Isotope Research Institute,china Institute of Atomic Energy,Beijing 100050,china department of General Surgery Second Affiliated Hospital (Shengjing Hospital) China Medical University Shenyang 110004 China. 23318199@***

BACKGROUND:With the objective of developing a locally- produced radioactive stent,the present study used in vivo animal experiments to explore apoptosis of proliferative smooth muscle cells resulting from facilitation of the expression of genes caused byγ-radiation in order to prevent bile duct *** therefore explored the effects and significance ofγ-radiation on the activity of caspase-3,Fas and Bcl-2 genes in apoptosis of proliferative smooth muscle cells in the bile duct walls of dogs. METHODS:Twelve dogs were randomly divided into 2 groups(6 in each group).A postinjury bile duct stenosis model was established and radioactive 103 Pd( 103 palladium) or ordinary bile duct stents were implanted into the bile *** staining,RT-PCR and immunohistochemistry were used to detect the proliferation and apoptosis of bile duct smooth muscle cells in proliferative endomembrane and the expression of related caspase-3,Bcl-2 and Fas genes. RESULTS:The expression of caspase-3 and Fas genes in the bile duct tissues of dogs with radioactive stents was higher than that of dogs with ordinary *** was significant apoptosis of proliferative smooth muscle cells in the bile *** expression of the Bcl-2 gene in the bile duct tissues of dogs with radioactive stents was lower than that in those with ordinary *** was significant apoptosis of proliferative smooth muscle cells in the dogs with low Bcl-2 gene expression. CONCLUSIONS:Radiation increases the activity of caspase-3 and Fas genes and is associated with apoptosis. The radioactive 103 Pd stent may facilitate apoptosis of proliferative smooth muscle cells in the bile ducts of dogs by activating these *** Bcl-2 gene expression level is correlated with the occurrence of apoptosis and the radiosusceptibility of cells.

关键词： radioactive 103 Pd stent γ-radiation caspase-3 gene Fas gene Bcl-2 gene apoptosis

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Cyclooxygenase-2 polymorphisms and susceptibility to gastric carcinoma: A meta-analysis

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World Journal of Gastroenterology 2010年第43期16卷 5510-5517页

作者： Jia-Li Liu, Zhen-Ning Wang, department of Surgical Oncology and General Surgery, the First Affiliated hospital of china medical university, shenyang 110001, Liaoning Province, china Yuan Liang, department of Oncology, the Shengjing Affiliated hospital of china medical university, shenyang 110001, Liaoning Province, china Xin Zhou, department of Obstetrics and Gynecology, the Shengjing Affiliated hospital of china medical university, shenyang 110001, Liaoning Province, china Li-Li Xing, department of Oncology, the Fourth Affiliated hospital of china medical university, shenyang 110032, Liaoning Province, china department of Surgical Oncology and General Surgery the First Affiliated Hospital of China Medical University Shenyang 110001 Liaoning Province China. josieon826@***

AIM: To investigate the association of the cyclooxygenases-2 (COX-2) polymorphisms and susceptibility to gastric cancer (GC) by means of meta-analysis. METHODS: Publications addressing the association between polymorphisms of COX-2 and susceptibility to GC were selected from the MEDLINE, EMBASE and CBMdisc databases. Data was extracted from the studies by 2 independent reviewers. The meta-analyses were performed by RevMan 5.0.23. From these data, odds ratio (OR) with 95% confidence interval (CI) was ***: Ten studies were retrieved reporting a total of 11 COX-2 polymorphisms. Carriers of -765C, -1195A, -1290G, *2430T alleles and *429TT genotype revealed increased risk for GC (OR = 1.71, 95% CI: 1.01-2.90, P = 0.05; OR = 1.58, 95% CI: 1.05-2.38, P = 0.03; OR = 1.55, 95% CI: 1.01-2.39, P = 0.05; OR = 2.62, 95% CI: 1.20-5.73, P = 0.02 and OR = 0.74, 95% CI: 0.59-0.95, P = 0.02, respectively). CONCLUSION: The -765C, -1195A, -1290G, *2430T alleles and *429TT genotype of COX-2 polymorphisms were determined a significant association with susceptibility to GC.

关键词： Cyclooxygenases-2 Gastric cancer Polymorphisms Susceptibility Meta-analysis

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Effect of calcitonin gene-related peptide and nerve growth factor on spatial learning and memory abilities of rats following focal cerebral ischemia/reperfusion

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Neural Regeneration Research 2006年第8期1卷 673-676页

作者： Guangshun Zheng1, Yongjie Yang2, Xiubin Fang3 1department of Neurosurgery, second hospital of Xiamen, Xiamen 361021, Fujian Province, china 2department of Neurosurgery, second hospital Affiliated to china medical university, shenyang 110004, Liaoning Province, china 3department of Neurobiology, Basic medical College of china medical university, shenyang 110001, Liaoning Province, china department of Neurosurgery Second Hospital of Xiamen Xiamen 361021 Fujian Province China department of Neurosurgery China Medical University Shenyang 110004 Liaoning Province China department of Neurobiology Basic Medical College China Medical University Shenyang 110001 Liaoning Province China

BACKGROUND: Calcitonin gene-related peptide (CGRP) and nerve growth actor (NGF) cam improve spatial learning and memory abilities of rats with cerebral ischemia/reperfusion; however, the effect of combination of them on relieving learning and memory injury following cerebral ischemia/reperfusion should be further studied. OBJECTIVE: To study the effects of exogenous CGRP and NGF on learning and memory abilities of rats with focal cerebral ischemia/reperfusion. DESIGN: Randomized controlled animal study. SETTING: department of Neurosurgery, the second hospital of Xiamen; department of Neurosurgery, the second Affiliated hospital of china medical university; department of Neurobiology, Basic medical College of china medical university. MATERIALS: A total of 30 healthy male SD rats, aged 8 weeks, of clean grade, weighing 250-300 g, were provided by Experimental Animal department of china medical university. All rats were randomly divided into sham-operation group, ischemia/reperfusion group and treatment group with 10 in each group. The main reagents were detailed as the follows: 100 g/L chloral hydrate, 0.5 mL CGRP (2 mg/L, Sigma Company, USA), and NGF (1× 106 U/L, 0.5 mL, Siweite Company, Dalian). METHODS: The experiment was carried out in the department of Neurobiology, Basic medical College of china medical university from February to July 2005. Rat models of middle cerebral artery occlusion were established by method of occlusion, 2 hours after that rats were anesthetized and the thread was slightly drawn out for 10 mm under direct staring to perform reperfusion. Rats in the ischemia/reperfusion group received intraperitoneal injection of 1 mL saline via the abdomen at two hours later, while rats in the treatment group at 2 hours later received intraperitoneal injection of 2 mg/L CGRP (0.5 mL) and 1×106 U/L NGF (0.5 mL) once a day for 10 successive days. First administration was accomplished within 15 minutes after ischemia/reperfusion. Rats in the sham-operation

关键词： Effect of calcitonin gene-related peptide and nerve growth factor on spatial learning and memory abilities of rats following focal cerebral ischemia/reperfusion CGRP MCAO gene

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Corticosteroids or non-corticosteroids: a fresh perspective on alcoholic hepatitis treatment

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Hepatobiliary & Pancreatic diseases International 2011年第5期10卷 458-464页

作者： Fei Wang and Bing-Yuan Wang department of Gastroenterology, First Affiliated hospital, china medical university, shenyang 110001, china department of Gastroenterology First Affiliated Hospital China Medical University Shenyang 110001 China

BACKGROUND: Alcoholic hepatitis (AH) is a necrotizing inflammatory process caused by alcoholic liver injury. It carries a significant short-term mortality. The management of AH is challenging. Although corticosteroids have been demonstrated to exert anti-inflammatory and antifibrotic effects, their efficacy for the treatment of AH remains debatable. DATA SOURCES: A literature search was performed of MEDLINE, ScienceDirect, SpringerLink and Wiley InterScience using the key words 'alcoholic hepatitis', 'alcoholic liver disease', and 'corticosteroids'. The available data reported in the relevant literature were analyzed. RESULTS: More than 17 controlled trials and at least 13 meta-analyses have reported the efficacy of corticosteroids in the treatment of AH in the past 40 years. Many were poorly designed and used different inclusion/exclusion criteria, making it difficult to reach a consensus. In this review, we summarized all the controversial data in the past decade and analyzed the potential causes for the varying therapeutic effects of corticosteroids in AH. The focus of the controversy has changed from 'whether steroids are beneficial or harmful for AH patients' to 'how to accurately identify responders to steroids early and rationalize corticosteroid treatment'. An early response to glucocorticoids, as determined by calculating the Lille score after 7 days of treatment, has been shown to be a clinically useful indicator. Moreover, down-regulation of steroid sensitivity, risk of infection, and a rational therapeutic strategy of corticosteroids in AH patients are all crucial for therapeutic ***: An early and accurate determination of steroid sensitivity is important. Besides, we need to overcome the down-regulation of steroid sensitivity, reduce the infection risk and rationalize the therapeutic strategy of corticosteroids. A fresh perspective is needed on the use of corticosteroids in AH patients.

关键词： corticosteroids alcoholic liver disease alcoholic hepatitis steroid sensitivity scoring system

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Melatonin abates liver ischemia/reperfusion injury by improving the balance between nitric oxide and endothelin

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Hepatobiliary & Pancreatic diseases International 2006年第4期5卷 574-579页

作者： Wen-Hai Zhang, Jian-Yi Li and Yong Zhou department of 5th General Surgery, second Affiliated hospital , china medical university, shenyang 110004, china department of 5th General Surgery Second Affiliated Hospital (Shengjing Hospital) China Medical University Shenyang 110004 China. surgeonzwh@***

BACKGROUND: Melatonin exerts complex physiological and pharmacological effects on multiple systems and organs. We hypothesized that melatonin might abate ischemia/ reperfusion (I/R) injury in the liver by inhibiting excessive oxidative stress and keeping nitric oxide (NO) from being scavenged by free radicals. The aim of the present study was to investigate whether melatonin protects the liver from I/R injury and, if so, by what underlying mechanism. METHODS: Under anesthesia, Wistar rats were intraperi- toneally injected with 20 mg/kg melatonin (dissolved in physiological saline containing 4% ethanol, Mel group), 4% alcohol (Alc group), or physiological saline (NS group). The artery, portal vein and bile duct of the left lobe of the liver were clamped for 60 minutes and then released. At different time points after I/R, the rats were sacrificed and blood samples were collected to measure the levels of serum alanine aminotransferase (ALT), lactic dehydrogenase (LDH), and NO. Hepatic tissue samples were collected for measuring endothelin expression by immunohistochemical staining and for routine morphological and histological examination. RESULTS: The levels of both ALT and LDH in the Mel group were significantly reduced for up to 24 hours after I/R compared with the Alc and NS groups (P<0.05). The levels of NO in the Mel group were significantly elevated for up to 12 hours after I/R relative to the NS group (P<0.05). The NO levels were also elevated at 0.5 and 6 hours after I/R in the Alc group (P<0.05). The immunohistochemical staining of hepatic tissue showedthat endothelin-positive cells were significantly fewer in the Mel group than in the Alc and NS groups at 6 hours after I/R (P<0.01). The necrosis of hepatocytes and the destruction of hepatic cords in the Alc and NS groups were greatly improved in Mel-treated rats, which is in concert with our functional data. CONCLUSIONS: Pretreatment with melatonin increased NO bioavailability and decreased endothelin expre

关键词： melatonin liver ischemia/reperfusion nitric oxide endothelin

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Quantitative analysis of the ribbon synapse number of cochlear inner hair cells in C57BL/6J mice using the three-dimensional modeling method

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Science china(Life Sciences) 2009年第9期52卷 807-812页

作者： LIU Ke,LI ShuNa & JIANG XueJun department of Otolaryngology,the First Affiliated hospital,china medical university,shenyang 110001,china department of Otolaryngology the First Affiliated Hospital China Medical University Shenyang 110001 China

In mammals,the ribbon synapses of cochlear inner hair cells are a synaptic structure of the first sensory nerve in the pathway of acoustical signal transmission to the acoustic center,and it is directly involved in voice coding and neurotransmitter release. It is difficult to quantitatively analyze the ribbon synaptic number only using an electron microscope,because the ribbon synaptic number is relatively limited and their location is deep. In this study,the specific presynaptic structure-RIBEYE,and non-specific postsynaptic structure-GluR 2 & 3 in C57BL/6J mouse basilar membrane samples were treated by immunofluorescent labeling. Serial section was performed on the samples using a laser scanning confocal microscope,and then the serial sections were used to build three-dimensional models using 3DS MAX software. Each fluorescein color pair indicates one synapse,so the number of ribbon synapses of inner hair cells is obtained. The spatial distribution and the number of ribbon synapses of cochlear inner hair cells were clearly shown in this experiment,and the mean number of ribbon synapses per inner hair cell was 16.10±1.03. Our results have demonstrated the number of ribbon synapses is accurately calculated by double immunofluorescent labeling to presynaptic and postsynaptic structures,serial sections obtained using a laser scanning confocal microscope,and three-dimensional modeling obtained using 3DS MAX software. The method above is feasible and has important significance for further exploring the mechanism of sensorineural deafness.

关键词： inner hair cells Ribbon synapses laser scanning confocal microscope three-dimensional modeling

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Promoting hepatic growth factor in the treatment of heavy type hepatitis and severe chronic hepatitis: a multicenter clinical study

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Hepatobiliary & Pancreatic diseases International 2004年第3期3卷 381-385页

作者： Jing-Hang Xu, Yan-Yan Yu, Chong-Wen Si, Zheng Zeng, Qin-Huan Wang, Duan-De Luo,Yong-Xing Zhou, Min-De Zeng, Guang-Yan Qiao, Ji-Lu Yao and Wei-Lun Lu department of infectious diseases, First hospital ofBeijing university, Beijing 100034, china department of Gastroenterology, Wuhan Unionhospital, Wuhan 430022, china department of Gastroentero-logy , Affiliated Tangdu hospital, Fourth Military medical university, Xi’an 710038, china department of Gastroenterology, Renjihospital, Shanghai 200001 , china department of infectiousdiseases, second Affiliated hospital, china medical university, shenyang110004, china department of Gastroenterology, Third Affilia-ted hospital, china medical university, shenyang 110004 , china department of infectious diseases First Hospital of Beijing University Beijing 100034 China. ddcatjh@***

BACKGROUND: The mortality rate of heavy type hepatitisis high. No special treatment is available except generaltreatment. This multicenter clinical study was designed toobserve the safety and efficacy of promoting hepatic growthfactor (PHGF) in the treatment of heavy type hepatitis andsevere chronic ***: 347 patients with heavy type hepatitis and 324with severe chronic hepatitis were subjected to administra-tion of 120 μg of PHGF per day for 4 weeks on the basis ofgeneral treatment. Those who were being effectively treat-ed would last additional 2 to 4 weeks. Blood routine, urineroutine, blood urea nitrogen (BUN), blood creatinine(Cr), blood ammonia, alpha fetoprotein (AFP), electro-lyte, alanine transaminase (ALT), aspartate transaminase(AST), serum total bilirubin (TBIL), serum direct biliru-bin (DBIL), prothrombin time activity (PTA), total pro-tein (TP) and albumin (ALB) were detected in the pa-tients before treatment, 2 weeks after treatment, and at theend of the treatment. Any side-effect would be ***: In the patients with severe chronic hepatitis, thetotal effective rate of the treatment was 88. 9% The levelsof ALT, AST and TBIL decreased significantly (P<0.001),whereas those of PTA and ALB increased significantly (P <0.001), and the level of AFP increased slightly. In patientswith heavy type hepatitis, the total effective rate of thistreatment was 78.4%, and patients at different stage showeddifferent results. The total effective rates of patients withearly, medium and terminal stage heavy type hepatitis were89.9%, 84.8% and 27.5%, respectively. No severe side-effect was ***: PHGF is effective and safe in the treat-ment of patients with heavy type hepatitis and severe chro-nic hepatitis. But it should be administered early in patientswith heavy type hepatitis so as to get better curative effects.

关键词： promoting hepatic growth factor hepatitis safety efficacy

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Decreased IgA+ plasma cells and IgA expression in acute liver necrosis mice

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World Journal of Gastroenterology 2010年第30期16卷 3827-3833页

作者： Jin-Long Fu, Zhao-Han Wang, Guo-Zhen Li, Yu-Rong Wang, Pei Liu, department of infectious diseases, The First Aff iliated hospital, china medical university, shenyang 110001, Liaoning Province, china department of infectious diseases The First Affiliated Hospital China Medical University No. 155 Nanjing Street Shenyang 110001 Liaoning Province China. syliupei2003@***

AIM: To investigate the number of intestinal immunoglobulin A (IgA+) plasma cells and expression of intestinal IgA in mice with acute liver necrosis. METHODS: A model of acute liver necrosis was established by intraperitoneal injection of galactosamine (GalN) and lipopolysaccharide (LPS). Sixty mice were randomly divided into one of 4 equal groups: normal control, acute liver necrosis, LPS, or GalN. Hematoxylin and eosin staining, immunohistochemistry, and an enzyme-linked immunosorbent assay were employed to assess liver and intestinal injury, count intestinal IgA+ plasma cells, and measure the expression level of IgA and interferon γ (IFN-γ) in the small intestinal mucosa of mice. RESULTS: Injured intestinal mucosa was observed in the acute liver necrosis group but not in the normal, LPS or GalN groups. Compared with the normal group,intestinal IgA+ plasma cells were slightly decreased in the LPS and GalN groups [429 ± 20 per high power f ield (HPF), 406 ± 18/HPF, respectively], whereas they were markedly decreased in the acute liver necrosis group (282 ± 17/HPF vs 495 ± 26/HPF in normal group, P 0.05). CONCLUSION: Intestinal IgA+ plasma cells and IgA expression levels indicating that mucosal immune barrier dysfunction, does exist in acute liver necrosis.

关键词： Acute liver necrosis Intestinal mucosa Immunity Immunoglobulin A

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TGF-β_1 in retinal ganglion cells in rats with chronic ocular hypertension: its expression and anti-apoptotic effect

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International Journal of Ophthalmology(English edition) 2011年第4期4卷 396-401页

作者： Yong-Jian Tao 1, Dian-Wen Gao 1, Miao Yu 2 1department of Ophthalmology, Shengjing hospital of china medical university, shenyang 110004, Liaoning Province, china 2 shenyang Pharmaceutical university, shenyang 110016, Liaoning Province, china department of Ophthalmology Shengjing Hospital of China Medical University Shenyang 110004 Liaoning Province China shenyang Pharmaceutical university Shenyang 110016 Liaoning Province China

AIM: To investigate the anti-apoptotic effect of transforming growth factor beta-1 (TGF-β1) on chronic ocular hypertension. METHODS: The expression of TGF-β1 in retinal ganglion cells (RCGs) was measured using the immunohistochemiscal S-P method and real-time PCR in the normally control group, the ocular hypertension group (experimental group A), the ocular hypertension plus antibody intervention group (experimental group B) and the ocular hypertension plus antigen intervention group (experimental group C) at 1, 2, 3 and 4 weeks postoperatively. The count of apoptotic RCGs was measured using the TUNEL method. RESULTS: The expression of TGF-β1 was significantly higher in experimental group C than that in other three groups (P<0.05). The expression was the lowest in experimental group B (4.17%). A statistically significant difference was noted between the four groups (P <0.01). The count of apoptotic RCGs was statistically significantly lower in experimental group C than that in the experimental groups A and B (P <0.01). A statistically significant difference was noted in the count of apoptotic RCGs between these three experimental groups (P <0.01). CONCLUSION: TGF-β1 can inhibit the apoptosis of RCGs in rats with chronic ocular hypertension.

关键词： glaucoma nerve protect TGF-β1 retinal ganglion cells chronic ocular hypertension

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