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Fluvastatin inhibits activation of JAK and STAT proteins in diabetic rat glomeruli and mesangial cells under high glucose conditions

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Acta Pharmacologica Sinica 2007年第12期28卷 1938-1946页

作者： Yong-hong SHI~2.Song ZHAO~2.Chen WANG~2.Ying LI~3,Hui-jun DUAN~(2.4)~2.department of pathology,Hebei {2. University,Shijiazhuang 050017 ~3 Institute of Nephrology,Third Hospital,Hebei {2. University,Shijiazhuang 050051,china department of pathology Hebei Medical UniversityShijiazhuang 050017

Aim:The aim of the present study was to further elucidate the mechanism of theprotective role of fluvastatin on diabetic ***:Streptozotocin-induced diabetic rats were treated daily with fluvastatin (4 mg/kg body weight) *** animals were killed 4 weeks later and urine and blood samples *** kidney tissues were removed and subjected to the *** glomerular mesangial cells (GMC) were cultured under normalglucose (5.5 mmol/L),high glucose (HG,30 mmol/L),HG+AG490 (10 μmol/L),orHG with fluvastatin (1 μmol/L).Glomeruli or the GMC lysate was immunoprecipi-tared and/or immunoblotted with antibodies against Janus kinase 2.(JAK2.,SH2.domain containing tyrosine phosphatase-1 (SHP-1),phosphospecific SHP-2.andsignal transducer and activators of transcription (STAT),***-forming growth factor-β(TGF-β1) mRNA was measured by *** proteinsynthesis of TGF-β1 and fibronectin in the culture medium of GMC was detectedby ***:The phosphorylation levels of JAK2.STAT1,STAT3,andSHP-2.increased significantly,and SHP-1 phosphorylation was reduced in glom-eruli of diabetic *** with fluvastatin reduced phosphorylation levelsof JAK2.STAT1,STAT3,and SHP-2.in glomeruli of diabetic rats,but it had noeffect on the dephosphorylation of *** exposure of GMC to 30 mmol/Lglucose caused the activation of JAK2.STAT1,STAT3,and *** upregulatedTGF-β1 expression and increased protein synthesis of *** highglucose-induced changes were suppressed by fluvastatin,as well as AG490,aJAK2.***:The regulation of the phosphorylation of JAK/STATby fluvastatin may be responsible for its renal protective effects on diabeticnephropathy.

关键词： fluvastatin diabetic nephropathy Janus kinase signal transducer and activators of transcription

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Enteral nutrition and acute pancreatitis

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World Journal of Gastroenterology 2001年第2期7卷 185-192页

作者： Qiang Pu Chen department of Heptobiliary Surgery, The Affiliated Hospital of Binzhou medical College, Binzhou 2.6603,{2., china department of Hepatobiliary Surgery The Affiliated Hospital of Binzhou Medical College 661 2nd Huanghe Rd Binzhou 256603 Shandong Province China

INTRODUCTIONAcute pancreatitis (AP) is a common severe illness of the digestive tract with variable involvement of other regional tissues and / or remote organ sysems[1-3],Mild disease is associated with minimal organ dysfunction and rapid recovery ,while severe disease is associated with multiple organ system failure and local complications such as necrosis , abscess , fistulas and pseudocyst formation [4-6].

关键词： Enteral Nutrition Acute Disease Humans Pancreatitis Parenteral Nutrition

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Effect of a cancer vaccine prepared by fusions of hepatocarcinoma cells with dendritic cells

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World Journal of Gastroenterology 2001年第5期7卷 690-694页

作者： Juan Zhang~1 Jin-Kun Zhang~2.Shao-Hong Zhuo~3 Hai-Bin Chen~2.1 Clinical Laboratory,The First Affiliated Hospital of Shantou University medical College,Shantou 515041,Guangdong province,{2.2.Cancer pathology Laboratory,Shantou University medical College,Shantou 515031,Guangdong province,{2.3 department of Gastroenterology,Third Municipal Hospital of Shantou,Shantou 515073,Guangdong province,{2. Clinical Laboratory The First Affiliated Hospital of Shantou University Medical College Shantou 515041 Guangdong Province China. juanzh005@***

AIM: To prepare a cancer vaccine (H(2.)-DC) expressing high levels of costimulatory molecules based on fusions of hepatocarcinoma cells (H(2.)) with dendritic cells (DC) of mice and to analyze the biological characteristics and induction of specific CTL activity of H(2.)-DC. METHODS: DCs were isolated from murine spleen by metrizamide density gradient centrifugation, purified based on its characteristics of semi-adhesion to culture plates and FcR-,and were cultured in the medium containing GM-CSF and IL-4. A large number of DC were harvested. DCs were then fused with H(2.) cells by PEG and the fusion cells were marked with CD11c MicroBeads. The H(2.)-DC was sorted with Mimi MACS sorter. The techniques of cell culture, immunocytochemistry and light microscopy were also used to test the characteristics of growth and morphology of H(2.)-DC in vitro. As the immunogen, H(2.)-DC was inoculated subcutaneously into the right armpit of BALB/C mice, and their tumorigenicity in vivo was observed. MTT was used to test the CTL activity of murine spleen in vivo. RESULTS: DC cells isolated and generated were CD11c+ cells with irregular shape, and highly expressed CD80, CD86 and CD54 molecules. H2. cells were CD11c- cells with spherical shape and bigger volume, and did not express CD80, CD86 and CD54 molecules.H(2.)-DC was CD11c+ cells with bigger volume, being spherical, flat or irregular in shape, and highly expressed CD80, CD86 and CD54 molecules, too. H(2.)-DC was able to divide and proliferate in vitro, but its activity of proliferation was significantly decreased as compared with H(2.) cells and its growth curve was flatter than H(2.) cells. After subcutaneous inoculation over 60 days, H(2.)-DC showed no tumorigenecity in mice, which was significantly different from control groups (P2.) cells in mice implanted with fresh H(2.)-DC was significantly higher than control groups (P 2.)-DC could significantly st

关键词： Cancer Vaccines Animals Antigens, CD Antigens, CD80 Antigens, CD86 Cell Fusion Dendritic Cells Integrin alphaXbeta2 Intercellular Adhesion Molecule-1 Liver Neoplasms, Experimental control Male Membrane Glycoproteins Mice Mice, Inbred BALB C Research Support, Non-U.S. Gov't Spleen

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Effects of retinoic acid on proliferation,phenotype and expression of cyclin-dependent kinase inhibitors in TGF-β1-stimulated rat hepatic stellate cells

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World Journal of Gastroenterology 2000年第6期6卷 819-823页

作者： Guang Cun Huang Jin Sheng Zhang Yue E Zhang department of pathology School of Basic {2. Sciences,Fudan University.Shanghai 2.0032.china Guang Cun Huang Jin Sheng Zhang Yue E Zhang Department of Pathology School of Basic Medical Sciences Fudan University Shanghai 200032 China Guang Cun Huang graduated from Medical Center of Fudan University (former Shanghai Medical University) in 1996 majoring in forensic medicine now assistant and master at the Department of Pathology School of Basic Medical Sciences Fudan University specialized in the study of hepatic pathology having 3 papers published.

AIM To study the molecular mechanisms ofretinoic acid(RA)on proliferation andexpression of cyclin-dependent kinase inhibitors(CKI),i.e.p16,p2. and p2. in cultured rathepatic stellate cells(HSC)stimulated withtransforming growth factor beta 1(TGF-β1).METHODS HSC were isolated from healthy ratlivers and *** stimulated with1 mg/L TGF-β1,subcultured HSC were treatedwith or without 1 nmol/L *** assay,immunocytochemistry(ICC)for p16,p2.,p2.and α-smooth muscle actin(α-SMA)protein,insitu hybridization(ISH)for retinoic acidreceptor beta 2.RAR-β2.and p16,p2. and p2.mRNA and quantitative image analysis(partially)were *** RA inhibited HSC proliferation(41.50%,P2.*** addition,RAincreased the protein level of p16(2.8.75%,P2. protein expression;meanwhile,p2. was undetectable by ICC in bothcontrol and RA-treated ***,RA hadno influence on the mRNA levels of p16,p2. orp2. as determined by *** Up-regulation of p16 and p2. on post-transcriptional level may contribule, in part to RA inhibition of TGF-β1-initiated rat HSC activation in vitro.

关键词： retinoic acid cyclindependent kinase inhibitor hepatic stellate cell cell culture transforming growth factor beta 1 liver fibrosis

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Induced pluripotent stem cell-related genes influence biological behavior and 5-fluorouracil sensitivity of colorectal cancer cells

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2012年第1期13卷 11-19页

作者： Zhong SHI1,Rui BAI1,Zhi-xuan FU1,Yong-liang ZHU2.Rong-fu WANG3,Shu ZHENG1(1Cancer Institute(Key Laboratory of Cancer Prevention and Intervention,china National Ministry of Education,Key Laboratory of Molecular Biology in medical Sciences,Zhejiang {2.,china),the Second Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310009,china)(2.5} of Gastroenterology,the Second Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310009,china)(3Center for Cell and Gene Therapy,department of pathology and Immunology,Baylor College of Medicine,Houston,Texas 77030,USA) Cancer Institute Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education Zhejiang Province China.

Objective:We aimed to perform a preliminary study of the association between induced pluripotent stem cell(iPS)-related genes and biological behavior of human colorectal cancer(CRC) cells,and the potential for developing anti-cancer drugs targeting these ***:We used real-time reverse transcriptase polymerase chain reaction(RT-PCR) to evaluate the transcript levels of iPS-related genes NANOG,OCT4,SOX2.C-MYC and KLF4 in CRC cell lines and cancer stem cells(CSCs)-enriched tumor *** was knockdowned in CRC cell line SW62. by lentiviral transduction.3-(4,5-Dimethylthiazol-2.yl)-2.5-diphenyltetrazolium bromide(MTT) assays,plate colony formation,and a mouse xenograft model were used to evaluate alterations in biological behavior in NANOG-knockdown SW62. ***,mock-knockdown and NANOG-knockdown cells were treated with 5-fluorouracil(5-FU) and survival rate was measured by MTT assay to evaluate drug ***:A significant difference in the transcript levels of iPS-related genes between tumor spheres and their parental bulky cells was *** knockdown suppressed proliferation,colony formation,and in vivo tumorigenicity but increased the sensitivity to 5-FU of SW62. cells.5-FU treatment greatly inhibited the expression of the major stemness-associated genes NANOG,OCT4,and ***:These results collectively suggest an overlap between iPS-related genes and CSCs in *** a certain gene NANOG may truncate the aggressiveness of CRC cells.

关键词： Induced pluripotent stem cell Cancer stem cell Colorectal cancer NANOG 5-Fluorouracil

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肝移植常见并发症病理诊断指南(2.2.版)

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中华消化外科杂志 2024年第8期23卷 1001-1021页

作者：中华医学会器官移植学分会中国医师协会器官移植医师分会中国医师协会器官移植医师分会移植病理学组中华医学会器官移植学分会移植病理学组中国抗癌协会肝癌专业委员会病理学组中华医学会病理学分会消化病理学组中华医学会病理学分会全国肝胆肿瘤及移植病理协作组王政禄郑树森薛武军不详天津市第一中心医院天津300192 浙江大学医学院附属第一医院/树兰(杭州)医院杭州311100 西安交通大学第一附属医院西安710000

移植病理学作为移植医学的重要分支学科,在疾病诊断、确认或否定临床诊断、缩小鉴别诊断范围等方面发挥重要作用.《肝移植常见并发症病理诊断指南(2.16版)》对推进我国肝移植病理的规范化发展起到重要作用.近年来,肝移植病理学研究不断... 详细信息

移植病理学作为移植医学的重要分支学科,在疾病诊断、确认或否定临床诊断、缩小鉴别诊断范围等方面发挥重要作用.《肝移植常见并发症病理诊断指南(2.16版)》对推进我国肝移植病理的规范化发展起到重要作用.近年来,肝移植病理学研究不断深入,知识体系迭代更新.为不断提高我国肝移植病理诊断水平,在中华医学会器官移植学分会等指导和组织下,我国肝移植病理和临床专家综合国内外研究成果和实践经验,制订《肝移植常见并发症病理诊断指南(2.2.版)》,为我国肝移植病理诊断提供科学指导和参考.

关键词：肝移植并发症病理诊断指南 2.2.版

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Overexpression of p2.^(KIP1)induced cell cycle arrest in G_1 phase and subsequent apoptosis in HCC-92.4 cell line

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World Journal of Gastroenterology 2000年第4期6卷 513-521页

作者： Jiang Li Xin Ke Yang Xin Xin Yu Meng Liang Ge Wen Liang Wang Jie Zhang Yun De Hou department of pathology,Fourth Military {2. University,Xi’an 710033,Shaanxi province,china State Key Laboratory for Molecular Virology and Genetic Engineering,Beijing 100052.china department of Dermatology,Beijing Hospital,Beijing 100016,china Institute of Radiation Medicine,Beijing 100085,china 第四军医大学陕西西安中国预防医学科学院病毒所北京中国预防医学科学院病毒所分子病毒基因工程国家重点实验室北京北京医院北京解放军军事医学科学院放射医学所北京

AIM We have previously reported that inducible over-expresaion of Bak may prolong cell cycle in G1 phase and lead to apoptosis in HCC-92.4 cells. This study is to investigate whether p2.KIP1 plays an important role in this process. MEHODS In order to elucidate the exact function of p2.KIP1 in this process, a zinc inducible p2.KIP1 stable transfectant and transient p2.KIP1- GFP fusion transfectant were constructed. The effects of inducible p2.KIP1 on cell growth, cell cycle arrest and apoptosis were examined in the mock, control pMD vector, and pMD-KIP1 transfected HCC-92.4 cells. RESULTS This p2.KIP1-GFP transfectant may transiently express the fusion gene. The cell growth was reduced by 35% at 48 h of p2.KIP1 induction with zinc treatment as determined by trypan blue exclusion assay. These differences remained the same after 72.h of p2.KIP1 expression, p2.KIP1 caused cell cycle arrest after 2. h of induction, with 40% increase in G1 population. Prolonged p2.KIP1 expression in this cell line induced apoptotic cell death reflected by TUNEL assay. Fourty-eight h and 72.h of p2.KIP1 expression showed a characteristic DNA ladder on agarose gel electrophoresis.

关键词： p2.^(KIP1) apoptosis cell cycle inducible expression system carcinoma hepatocellular liver neoplasms

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抚触对早产儿胃肠运动的影响

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实用儿科临床杂志 2008年第14期23卷 1076-1077页

作者：牛峰海徐心坦济宁医学院附属医院儿科山东济宁272029

目的探讨抚触对早产儿胃肠运动的影响。方法早产儿58例,随机分为抚触组（2.例）及对照组（30例）。二组均行常规护理。抚触组从出生第2.开始进行抚触,2./d,5~2.min/次。于出生第7天口服少量活性炭作为标记物,记录二组活性炭排出所需... 详细信息

目的探讨抚触对早产儿胃肠运动的影响。方法早产儿58例,随机分为抚触组（2.例）及对照组（30例）。二组均行常规护理。抚触组从出生第2.开始进行抚触,2./d,5~2.min/次。于出生第7天口服少量活性炭作为标记物,记录二组活性炭排出所需时间。观察二组胎粪排尽时间及活性炭排出时间。应用放射免疫法测定二组出生第2.7天空腹血胃动素、促胃液素水平,并进行比较。采用SPSS11.0软件进行统计学分析。结果抚触组胎粪排尽和活性炭排出时间分别为（78.78±41.16）、（2..48±9.85）h,对照组分别为（101.84±32.84）、（34.66±13.2.）h,抚触组较对照组明显缩短（P〈0.05,0.01）;出生第2.抚触组血胃动素及促胃液素水平分别为（2.8.18±31.92.、（64.03±2..17）μg/L,对照组分别为（2.1.54±2..78）、（68.95±19.08）μg/L,二组比较均无明显差异（Pa〉0.05）。出生第7天抚触组血胃动素及促胃液素水平分别为（402.35±40.14）、（133.60±2..99）μg/L,对照组分别为（315.84±37.62.、（80.2.±33.50）μg/L,抚触组均较对照组明显升高（Pa〈0.05）。结论抚触可促进早产儿胃动素和促胃液素的分泌,从而促进早产儿胃肠运动。

关键词：婴儿,早产抚触胃动素促胃液素胃肠运动

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Population-based study of DNA image cytometry as screening method for esophageal cancer

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World Journal of Gastroenterology 2012年第4期18卷 375-382页

作者： Lin Zhao,Wen-Qiang Wei,Xin-Qing Li,Guo-Qing Wang,Qi Shang,You-Lin Qiao,department of Cancer Epidemiology,Cancer Institute/Hospital,Chinese Academy of medical Sciences and Peking Union medical College,Beijing 10002.,china De-Li Zhao,department of Epidemiology,Feicheng People’s Hospital,Feicheng 2.1600,shandong province,china Chang-Qing Hao,department of Endoscopy,Linzhou Cancer Hospital,Linzhou 456500,Henan province,china Dong-Mei Lin,Qin-Jing Pan,department of {12.,Cancer Institute/Hospital,Chinese Academy of medical Sciences and Peking Union medical College,Beijing 10002.,china Fu-Hua Lei,department of {12.,Feicheng People’s Hospi-tal,Feicheng 2.1600,shandong province,china Jin-Wu Wang,department of {12.,Linzhou Cancer Hospi-tal,Linzhou 456500,Henan province,china Lin Zhao Wen-Qiang Wei Xin-Qing Li Guo-Qing Wang Qi Shang You-Lin Qiao Department of Cancer Epidemiology Cancer Institute/Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021 China De-Li Zhao Department of Epidemiology Feicheng People’s Hospital Feicheng 271600 Shandong Province China Chang-Qing Hao Department of Endoscopy Linzhou Cancer Hospital Linzhou 456500 Henan Province China Dong-Mei Lin Qin-Jing Pan Department of Pathology Cancer Institute/Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021 China Fu-Hua Lei Department of Pathology Feicheng People’s Hospital Feicheng 271600 Shandong Province China Jin-Wu Wang Department of Pathology Linzhou Cancer Hospital Linzhou 456500 Henan Province China

AIM:To explore the DNA image cytometry (DNA-ICM) technique as a primary screening method for esopha-geal squamous precancerous ***:This study was designed as a population-based screening study.A total of 582.local residents aged 40 years-69 years were recruited from Linzhou in Henan and Feicheng in ***,only 452.subjects had results of liquid-based cytology,DNA-ICM and *** sensitivity and specificity of DNA-ICM were calculated and compared with liquid-based cytology in moderate dysplasia or ***:Sensitivities of DNA-ICM ranging from at least 1 to 4 aneuploid cells were 90.91%,86.36%,79.55% and 77.2.%,respectively,which were better than that of liquid-based cytology (75%).Specifici-ties of DNA-ICM were 70.83%,84.07%,92.65% and 96.81%,but the specificity of liquid-based cytology was 91.91%.The sensitivity and specificity of a combination of liquid-based cytology and DNA-ICM were 84.09% and 85.78%,***:It is possible to use DNA-ICM tech-nique as a primary screening method for esophageal squamous precancerous lesions.

关键词： DNA image cytometry Aneuploidy Screen-ing Esophageal cancer Precancerous lesions

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Glutamine synthetase as an early marker for hepatocellular carcinoma based on proteomic analysis of resected smal hepatocel ular carcinomas

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Hepatobiliary & Pancreatic Diseases International 2010年第3期9卷 296-305页

作者： Jiang Long,Zhen-Wei Lang,Hua-Guang Wang,Tai-Ling Wang,Bao-En Wang and Si-Qi Liu Liver Research Center,Beijing Friendship Hospital, Capital medical University,Beijing 100050,china {2. of Hepatology,{2. of pathology, Beijing Youan Hospital,Capital medical University,Beijing 100069,china {2. of Pharmaceutical Affairs,Beijing Chaoyang Hospital,Capital medical University,Beijing 10002.,china {2. of pathology,china-Japan Friendship Hospital,Beijing 10002.,china Beijing Genomics Institute,Chinese Academy of Science,Beijing Airport Industrial Zone B-6,Shunyi,Beijing 101300,china Liver Research Center Beijing Friendship Hospital Capital Medical University Beijing China.

BACKGROUND:Hepatocellular carcinoma(HCC)is a highly malignant tumor with a poor *** small HCCs possess most of the characteristics of early HCC,we investigated small HCCs to screen potential biomarkers for early ***:Proteins were extracted from 10 sets of paired tissue samples from HBV-infected small-HCC *** extracted proteins were well resolved by two-dimensional *** HCC-associated proteins were then identified by MALDI-TOF/TOF MS following image *** blotting and immunohistochemistry were used to assess glutamine synthetase(GS)and phenazine biosynthesislike domain-containing protein(PBLD)expression in liver ***-linked immunosorbent assays in 152.serum samples(from 49 healthy donors,2. patients with liver cirrhosis,and 79 with HCC)were used to further assess the significance of GS ***:Fifteen up-regulated and three down-regulated proteins were *** blotting confirmed GS overexpression and decreased PBLD expression in liver *** showed that GS was expressed in 70.0%(84/12.)of HCCs and 35.8%(43/12.)of nontumor tissues;PBLD was expressed in 74.2.(89/12.) of nontumor tissues and 40.8%(49/12.)of *** Chi-square test showed significant expression differences between HCCs and adjacent *** with this,serum GS levels in HCC patients were significantly higher than those in liver cirrhosis patients and healthy donors,while the latter two groups were also significantly *** addition, a diagnostic cutoff value of 2.6 mg/ml was used for GS;it was elevated in 19(76.0%)of 2. HCC patients with AFP≤2. ng/ml and 47(88.7%)of 53 HCC patients with AFP≤2.0 ng/***:GS and PBLD are abnormally expressed in most *** may be a novel serum marker for early HCC, especially for those patients with low AFP levels(≤2.0 ng/ml).

关键词： glutamine synthetase phenazine biosynthesis-like domain-containing protein proteomics

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