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Protective effect of clodronate-containing liposomes on intestinal mucosal injury in rats with severe acute pancreatitis

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Hepatobiliary & Pancreatic Diseases International 2011年第5期10卷 544-551页

作者： Jian-Xin Zhang, Sheng-Chun Dang, Kai Yin and De-Li Jiang department of General Surgery, affiliated hospital of Jiangsu university, Zhenjiang 212001, china school of Chemistry and Chemical Engineering of Jiangsu university, Zhenjiang 212013, china department of General Surgery Affiliated Hospital of Jiangsu University Zhenjiang 212001 China school of Chemistry and Chemical Engineering of Jiangsu university Zhenjiang212013 China

BACKGROUND: Severe acute pancreatitis (SAP) can result in intestinal mucosal injury. This study aimed to demonstrate the protective effect of clodronate-containing liposomes on intestinal mucosal injury in rats with SAP. METHODS: Liposomes containing clodronate or phosphate buffered saline (PBS) were prepared by the thin-film method SAP models were prepared by a uniform injection of sodium taurocholate (2 mL/kg body weight) into the subcapsular space of the pancreas. Sprague-Dawley rats were randomly divided into a control group (C group), a SAP plus PBS-containing liposomes group (P group) and a SAP plus clodronate-containing liposomes group (T group). At 2 and 6 hours after the establishment of SAP models, 2 mL blood samples were taken from the superior mesenteric vein to measure the contents of serum TNF-α and IL-12. Pathological changes in the intestine and pancreas were observed using hematoxylin and eosin staining, while apoptosis was detected using TUNEL staining. In addition, the macrophage markers cluster of differentiation 68 (CD68) in the intestinal tissue was assessed with immunohistochemistry. RESULTS: At the two time points, the levels of TNF-α and IL-12 in the P group were higher than those in the C group (P<0.05) Compared with the P group, the levels of TNF-α and IL-12 decreased in the T group (P<0.05). The pathological scores of the intestinal mucosa and pancreas in the T group were lower than those of the P group. In the T group, large numbers of TUNEL-positive cells were observed, but none or few in the C and P groups. The number of CD68-positive macrophages decreased in the T ***: Clodronate-containing liposomes have prote- ctive effects against intestinal mucosal injury in rats with SAP. The blockade of macrophages may provide a novel therapeutic strategy in SAP.

关键词： pancreatitis clodronate disodium macrophage intestinal mucosal injury

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No association between IRF3 polymorphism and susceptibility to hepatitis B virus infection in Chinese patients

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World Journal of Gastroenterology 2012年第4期18卷 388-392页

作者： Fang Yan,Feng Lv,Xu Li,Hua-Fa Yin,department of Infectious Diseases,The First affiliated hospital of Anhui Medical university,Hefei 230032,Anhui Province,china Yu-Feng Gao,department of Hepatopathy,The Second affiliated hospital of Anhui Medical university,Hefei 230601,Anhui Province,china Tian-Chen Zhang,department of Epidemiology and Biostatistics,school of Public Health,Anhui Medical university,Hefei 230032,Anhui Province,china department of Infectious Diseases The First Affiliated Hospital of Anhui Medical University Hefei 230032 Anhui Province China.

AIM:To investigate the association between three tag single nucleotide polymorphisms (tagSNPs) in inter-feron regulatory factors (IRF3) and the genetic suscep-tibility to chronic hepatitis B virus (HBV) ***:We performed a case-control study of 985 Chinese cases of chronic HBV infection and 294 self-limiting HBV-infected individuals as *** tagSNPs in IRF3 (rs10415576,rs2304204,rs2304206) were genotyped with the Multiplex SNaPshot *** genotype and allele frequencies were calculatedand ***:The three SNPs showed no significant geno-type/allele associations with chronic HBV *** allele P values were:rs10415576,P=0.0908,odds ratio (OR) [95% confidence interval (CI)]=1.1798 (0.9740-1.4291);rs2304204,P=0.5959,OR (95% CI)=1.0597 (0.8552-1.3133);rs2304206,P=0.8372,OR (95% CI)=1.0250 (0.8097-1.2976).Overall genotype P values were:rs10415576,P=0.2106;rs2304204,P=0.8458;rs2304206,P=*** were no statisti-cally significant differences between patients with chron-ic HBV infection and *** generated by these three SNPs were also not significantly different between the two ***:The three tagSNPs of IRF3 are not asso-ciated with HBV infection in the Han Chinese population.

关键词： Chronic hepatitis B virus infection Interferon regulatory factors tag single nucleotide polymorphisms Genetic susceptibility Haplotype

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Population pharmacokinetics of valproate in Chinese children with epilepsy

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Acta Pharmacologica Sinica 2007年第10期28卷 1677-1684页

作者： De-chun JIANG~(2,3),Li WANG~4,Yu-qin WANG~(2,6),Lin LI~3,Wei LU~5,Xiang-rong BAI~2~2 department of Pharmacy,Xuan-wu hospital of Capital Medical university,Beijing 100053,china ~4 department of Pediatrics,Peking universityFirst hospital,Beijing 100034,china ~3 department of Pharmacology,Xuan-wu hospital of Capital Medical university,Education Ministry KeyLaboratory for Neurodegenerative Diseases,Beijing 100053,china ~5 school of Pharmaceutical Science,Peking university,Beijing 100083,china department of Pharmacy Xuan-wu Hospital of Capital Medical University Beijing China department of Pharmacology Xuan-wu Hospital of Capital Medical University Education Ministry Key Laboratory for Neurodegenerative Diseases Beijing China department of Pediatrics Peking University First Hospital Beijing China school of Pharmaceutical Science Peking University Beijing China

Aim:The aim of the present study is to establish a population pharmacokinetic（PPK） model of valproate （VPA） in Chinese epileptic children to promote thereasonable use of anti-epileptic ***:Sparse data of VPA serumconcentrations from 417 epileptic children were *** patients weredivided into 2 groups:the PPK model group （n=317） and the PPK valid group（n=100）.The PPK parameter values of VPA were calculated by NONMEM soft-ware using the data of the PPK model group.A basic model and a final modelwere set *** validate the 2 models,the concentrations of PPK valid groupwere predicted by each model,*** mean prediction error （MPE）,mean squared prediction error （MSPE）,root mean squared prediction error（RMSPE）,weight residues （WRES）,and the 95% confidence intervals （95%CI） were also ***,the values between the 2 models were ***:The PPK of VPA was determined by a 1-compartment model with afirst-order absorption *** basic model was:Ka=3.09 (h-1),V/F=20.4（L）,CL/F=0.296 （L/h）.The final model was:Ka=0.251+2.24·（1-HS）(h-1),V/F=2.88+0.157·WT （L）,CL/F=0.1060.98·CO+0.0157·AGE （L/h）.For thebasic model,the MPE,MSPE,RMSPE,WRES,and the 95% CI were-23.53（-30.36,-16.70）,3728.96 （2872.72,4585.20）,39.62 （34.34,44.90）,and-0.06 （-0.14,0.02）,*** the final model,the MPE,MSPE,RMSPE,WRES,and the95% CI were-1.16 （-4.85,2.53）,1002.83 （1050.64,1143.61）,23.04 （21.12,24.96）,and0.08 （-0.04,0.20）,*** final model was more optimal than the ***:The PPK model of VPA in Chinese epileptic children wassuccessfully *** will be valuable to facilitate individualized dosageregimens.

关键词： population pharmacokinetics valproic acid epilepsy children Bayesian method NONMEM software individualized dosage regimens

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Clinicopathological features of gastric glomus tumor

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World Journal of Gastroenterology 2010年第36期16卷 4616-4620页

作者： Hui-Qiong Fang,Jing Yang,Fen-Fen Zhang,An-Jia Han,department of Pathology,First affiliated hospital of Sun Yat-Sen university,Guangzhou 510080,Guangdong Province,china Hui-Qiong Fang,department of Pathology,Foshan hospital of Traditional Chinese medicine,Foshan 528000,Guangdong Province,china Jing Yang,department of Pathology,People’s hospital of Zhu-hai City,Zhuhai 519000,Guangdong Province,china Yi Cui,department of Gastroenterology,First affiliated hospital of Sun Yat-Sen university,Guangzhou 510080,Guangdong Province,china department of Pathology First Affiliated Hospital of Sun Yat-Sen University Guangzhou 510080 Guangdong Province China.

AIM:To study the clinicopathological features of gastric glomus tumor and review the related Chinese literature published in ***:A case of gastric glomus tumor was *** findings in 56 cases of gastric glomus tumor were ***:Gastric glomus tumor was far more common in women than in men with a female to male ratio of 1.6:*** median age of the patients was 45 years(range 28-79 years).The patients often complained of epigastric pain and bloody *** tumor was located in antrum of the *** greatest diameter of the tumor was ***,the tumor was comprised of nests of glomus cells surrounding the *** cells were small,uniform and ***,smooth muscle actin and actin were expressed in the *** markers,including S-100 protein,CD34,CD117,desmin,CD56,synaptophysin,chromo-granin A,neuron specific enolase and cytokeratin were all ***:Gastric glomus tumor is a rare benign mesenchymal *** diagnosis depends on pathologic *** diagnosis includes gastrointestinal stromal tumor,paraganglioma and carcinoid tumor.

关键词： Stomach Glomus tumor Clinicopathology Immunohistochemistry

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A Novel Missense Mutation(L296Q)in Cholesteryl Ester Transfer Protein Gene Related to Coronary Heart Disease

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Acta Biochimica et Biophysica Sinica 2004年第1期36卷 33-36页

作者： Ke-Qin ZHENG, Si-Zhong ZHANG, Li ZHANG, De-Jia HUANG, Lin-Chuan LIAO, and Yi-Ping HOU ( department of Medical Genetics, West china hospital Division of Human Morbid Genomics, Key Laboratory ofBiotherapy of Human Diseases of Ministry of Education, Sichuan university, Chengdu 610041, china department of Cardiology, West china hospital, Sichuan university, Chengdu 610041, china school of Basic and Forensic medicine, Sichuan university, Chengdu 610041, china) department of Medical Genetics West China Hospital Division of Human Morbid Genomics Key Laboratory of Biotherapy of Human Diseases of Ministry of Education Sichuan University Chengdu 610041 China department of Cardiology West China Hospital Sichuan University Chengdu 610041 China school of Basic and Forensic medicine Sichuan University Chengdu 610041 China

Cholesteryl ester transfer protein (CETP) is a key participant in the reverse transport of cholesterol from the peripheral tissues to the liver. To understand the role that CETP gene plays in the pathogenesis of coronary heart disease (CHD) , the promoter region, all 16 exons and adjacent intronic regions of CETP gene were screened for single nucleotide polymorphisms (SNPs) in 203 CHD patients and 209 controls by a combination of PCR, denaturing high performance liquid chromatography (DHPLC), molecular cloning, and DNA sequencing. A novel missense mutation in the CETP gene was identified. This mutation (L296Q) was a T-to-A conversion at codon 296 of exon 10 which replaced the codon for leucine (CTG) with the codon for glutamine (CAG). Association study revealed that L296Q mutation was associated with CHD with a significantly higher mutant allele frequency in the CHD patients than that in the controls (0. 160 vs. 0.091,x2= 9.014, P = 0.003), and that the odds ratio for the development of CHD was 1.83 for

关键词： cholesteryl ester transfer protein gene (CETP gene) coronary heart disease (CHD) missense mutation plasma lipids single nucleoti.de polymorphism (SNP)

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Fine needle aspiration cytology in the diagnosis of liver lesions

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Hepatobiliary & Pancreatic Diseases International 2004年第1期3卷 90-92页

作者： Wei Ding and Xiao-Jun He Hangzhou, china departments of Pathology and Psychiatry , First affiliated hospital, Zhejiang university school of medicine, Hangzhou 310003 , china department of Pathology First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China. hzdw@***

BACKGROUND: Fine needle aspiration cytology (FNAC) is a less invasive, inexpensive and rapid method for patho- logic evaluation of hepatic masses. This study was to inves- tigate the role of fine needle aspiration cytology in the early diagnosis of liver disease. METHODS: Fourty-six patients received fine needle ( 1 mm diameter or 18G) aspiration for the diagnosis of liver disease under ultrasonography or computed tomography guidance. The diagnosis was verified by using hematoxylin and eosin (HE) staining and immunohistochemistry. RESULTS: Of the 46 patients, 19 had hepatocellular carci- noma (HCC), 2 cholangiocarcinoma, 1 lymphoma, 1 car- cinoid tumor, 1 squamous cell carcinoma, 1 tuberculosis, 14 no abnormality, and 6 red blood cells. Cytological diag- nosis of 3 patients was inconsistent with histological diagno- sis after surgery: incorrect diagnosis (2), and false-negative for failure of aspiration (1). CONCLUSIONS: Cytological diagnosis should mostly de- pend on cellular morphology. In addition, immunohisto- chemistry and special staining are helpful for diagnosis if cytologic preparation is available. Fine needle aspiration cy- tology of the liver is a diagnostic method that can be used to identify the vast majority of neoplasms of primary or metastatic nature.

关键词： biopsy needle liver neoplasms

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Primary liver cancer in the elderly: report of 125 cases

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Hepatobiliary & Pancreatic Diseases International 2003年第1期2卷 59-61页

作者： Ying-Sheng Wu Ting-Bo Liang Shu-Sen Zheng the department of Hepatobiliary & Pancreas Surgery, First affiliated hospital, Zhejiang university school of medicine, Hangzhou 310003, china department of Hepatobiliary & Pancreas Surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China. walkaloner200@***

OBJECTIVES: To understand the characteristics of primary, liver camcer (PLC) in the elderly and summarize the experience in treatment of such patients. METHODS: The clinical data of PLC in the elderly group (≥60 years, 125 patients) and the young group (≤59 years, 295 patients) were analyzed retrospectively. RESULTS: In the elderly group, 64 patients were found HBsAg positive, 39 patients small PLC, 24 large PLC, 15 tumor emboli in the portal vein, 86 AFP positive, and 34 hepatectomy performed. In the young group, 205 patients were found HBsAg positive, 79 patients small PLC, 97 large PLC, 96 tumor emboli in the portal vein, 200 AFP positive, and 126 hepatectomy performed. The median survival was 44 and 25 months respectively, and no significant difference was observed in the mortality between the two groups (P>0.05). CONCLUSIONS: Hepatectomy is a choice of treatment for PLC in the elderly based on their liver function. AFP and B-ultrasonography are important methods for the diagnosis of PLC in the elderly.

关键词： primary liver cancer hepatectomy elderly

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Protective effect of probiotics on intestinal barrier function in malnourished rats after liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2011年第5期10卷 489-496页

作者： Zhi-Gang Ren, Hui Liu, Jian-Wen Jiang, Li Jiang, Hui Chen, Hai-Yang Xie, Lin Zhou and Shu-Sen Zheng Key Laboratory of Combined Multi-organ Transplan- tation, Ministry of Public Health, and department of Hepatobiliary and Pancreatic Surgery, First affiliated hospital, Zhejiang university school of medicine, Hangzhou 310003, china and Institute of Immunology, Zhejiang university school of medicine, Hangzhou 310058, china Key Laboratory of Combined Multi-organ Transplantation Ministry of Public Health and Department of Hepatobiliary and Pancreatic Surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China Institute of Immunology Zhejiang University School of Medicine Hangzhou 310058 China

BACKGROUND: Most patients waiting for liver transplantation have end-stage liver diseases with malnutrition, which is prone to induce intestinal barrier dysfunction after liver transplantation. We aimed to study the effect of probiotics on intestinal barrier function in malnourished rats following liver transplantation with long-term antibiotics. METHODS: Twelve Lewis rats were selected as donors. Twelve BN rats, which served as recipients, were subjected to malnutrition by semi-starvation for 4-5 weeks. They were randomly divided into two groups: a control group which received phosphate-buffered saline and a probiotics group which received Bifidobacterium and Lactobacillus. All recipients were injected with intramuscular imipenem and subcutaneous cyclosporine A. Furthermore, six normal BN rats without any drugs or operations served as a normal group. Eight days after operation, all rats were sacrificed for examination of the following parameters: serum levels of endotoxin and TNF-α, bacterial translocation, intestinal microflora, ileocecal sIgA, lymphocyte numbers, and phenotypes (CD4, CD8, αβTCR, γδTCR)ofPeyer’spatches. RESULTS: In recipients subjected to malnutrition, weight decreased by 20% and they survived until 8 days after operation. Compared with the normal group, all recipients on postoperative day 8 showed increased levels of serum endotoxin and TNF-α as well as increased counts oftranslocated bacteria. Meanwhile, there were decreases in counts of Bifidobacterium and Lactobacillus in the ileocecum, sIgA concentration, and lymphocytes of Peyer’s patches. Moreover, partial alteration in lymphocyte phenotypes was evidenced by elevated ratios of CD8 + and γδTCR + lymphocytes. In contrast, compared to the control group, supplementation with probiotics reduced the levels of serum endotoxin, TNF-α and bacterial translocation, increased the counts of Bifidobacterium and Lactobacillus, the concentration of sIgA and lymphocytes of Peyer’s patches, and also slightly

关键词： liver transplantation probiotics intestinal microflora intestinal barrier function

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Effects of navelbine and docetaxel on gene expression in lung cancer cell strains

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Acta Pharmacologica Sinica 2005年第8期26卷 1017-1024页

作者： Li CAI~2, Hai-ying DONG, Guang-jie SUI Internal medicine of Oncology, the Third affiliated hospital of Harbin Medical university, Harbin 150040, china Internal medicine of Oncology the Third Affiliated Hospital of Harbin Medical University Harbin China

Aim: To search genes sensitivity to the anti-cancer drugs navelbine (NVB) and docetaxel (DOC) in small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) cell strains. Methods: The sensitivity of 4 strains of SCLC and 6 strains of NSCLC to NVB and DOC was evaluated using the MTT assay. The expression of 1291 sensitive-related genes to the anti-cancer drugs in 10 lung cancer cell strains was measured using cDNA macroarrays and the relationship was analyzed. Results: In total, there were 56(r≥0.4) genes sensitive to NVB and DOC. For NVB: 36 genes were sensitive to NVB, 20 co-expressed genes between the SCLC+NSCLC set and the NSCLC set; 27 expressed genes and 7 specially expressed genes in the SCLC+NSCLC set; and 29 expressed genes and 9 specially expressed genes in the NSCLC set. For DOC, 50 genes were sensitive to DOC, 12 co-expressed genes between the SCLC+NSCLC set and the NSCLC set; 24 expressed genes and 12 specially expressed genes in the SCLC+NSCLC set; and 38 expressed genes and 26 specially xpressed genes in the NSCLC set. The genes sensitive to NVB and DOC in lung-cancer cell stains were mainly divided into the following 4 categories: signal transduction molecules, cell factors, transcription factors and metabolism-related enzymes and inhibitors. Conclusions: There were obvious differences in genes related to NVB and DOC between SCLC and NSCLC cell strains, but the same as categories of function.

关键词： cDNA macroarray lung neoplasms navelbine docetaxel

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Adenovirus-mediated expression of both antisense ODC and AdoMetDC inhibited colorectal cancer cell growth in vitro

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Acta Pharmacologica Sinica 2006年第3期27卷 353-359页

作者： Bing ZHANG~2 Xian-xi LIU~(2,5) Yan ZHANG~2 Chun-ying JIANG~3 Qing-shan TENG~4 Hai-yan HU~2 Wei WANG~2 Lei GONG~2 ~2Institute of Biochemistry and Molecular Biology,school of medicine.Shandong university,Jinan 250012,china ~3department of Coloproctology,affiliated hospital of Shandong university of Traditional Chinese medicine,Jinan 250014,china,~4department of Neurosurgery.Cleveland Clinic Foundation,Cleveland,OH 44195,USA Institute of Biochemistry and Molecular Biology School of Medicine Shandong University Jinan China department of Colo-proctology Affiliated Hospital of Shandong University of Traditional Chinese Medicine Jinan China department of Neurosurgery Cleveland Clinic Foundation Cleveland USA

Aim:To construct a recombinant adenovirus that can simultaneously expressboth antisense ornithine decarboxylase(ODC)and adenosylmethionine decar-boxylase(AdoMetDC)and detect its inhibitory effect on the intracellular polyaminepool and colorectal cancer cell ***:A 205-bp cDNA of AdoMetDCwas reverse-inserted into recombinant pAdTrack-ODCas vectors and recombinedwith pAdEasy-1 vectors in AdEasy-1 *** clones were selected andtransfected into the packaging cell HEK293 after they were linearized by *** fluorescent protein expression was used to monitor the process of adenovi-rus *** ODC and AdoMetDC protein levels were identified by west-ern blotting,and intracellular polyamine content was detected by reverse-phasehigh performance liquid chromatography.A viable cell count was used to deter-mine the growth of HT-29 cells with or without exogenous ***:Sequencing confirmed that AdoMetDC cDNA was successfully ligated into thepAdTrack-ODCas *** expression in 293 cells during virus packing andamplification was observed by fluorescence *** blotting dem-onstrated that both ODC and AdoMetDC were downregulated by Ad-ODC-AdoMetDCas,and consequently 3 kinds of polyamine(putrescine,spermidineand spermine)were reduced to very low ***-29 cell growth was signifi-cantly inhibited as compared with control conditions,and growth arrest was notreversed by exogenous ***:The successfully constructedrecombinant adenovirus,Ad-ODC-AdoMetDCas,blocked polyamine synthesisand has therapeutic potential for treating colorectal cancer in vitro.

关键词： polyamine ornithine decarboxylase adenosylmethionine decarboxylase adenovirus colorectal cancer

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