Objective To study the action of death signal receptor pathway of apoptosis in the development of gallbladder carcinoma . Methods Streptavidin biotin peroxidase immunohistochemistry technique was used to study the expression of Fas L in gallbladder carcinoma tissues,and TUNEL method for in situ detection of the number of apoptotic infiltrating lymphocytes around the tumor. Results The positive rates of Fas L in gallbladder carcinoma , gallbladder adenoma, dysplasia of gallbladder epithelium and chronic cholecystis were 84.6%(22/26), 83.3%(15/18) ,100%(3/3) and 55%(11/20), respectively. The positive rate of Fas L in gallbladder carcinoma was significantly higher than in chronic cholecystis (P

The paper introduces American health informatization talents cultivation scheme, combining the current situation and ex-isting problems of medical information management talents cultivation in China, it proposes medical information management undergradu-ate talents cultivation strategies under the strategic background of population health informatization from three perspectives: curriculum system, teaching staff and teaching mode.

The mechanism and interaction among Rb/p16, Rb/E2F1 and HDAC1 proteins in gallbladder carcinoma were investigated. By using the immunoprecipitation method, the interactions among Rb, p16, E2F1, HDAC1 proteins in gallbladder carcinoma cell line (Mz-ChA-1) were studied. It was found that there were Rb and E2F1 proteins in the precipitates with anti-HDAC1, and there were HDAC1 and E2F1 proteins in the precipitate with anti-Rb. It was concluded that there are specific interactions among Rb, HDAC1 and E2F1 proteins in gallbladder carcinoma, indicating the existence of the direct Rb/E2F1/HDAC1 signal transduction pathway. There is no direct relationship between p16 proteins with Rb, HDAC1, and E2F1 proteins.

Objective To explore the regulating mechanism of inducible nitric oxide synthase(iNOS) in hepatic injury of obstructive jaundice (OJ) in vivo and in vitro experiments. Methods (1) Rat hepatocytes were isolated by in situ collagenase perfusion and primary culture. Hepatocytes were pretreated with various concentrations of iNOS inhibitor SMT for 20 min. After pretreatment, 50?M GCDC was added for an additional 24hr. Cells were next detected by FCM and TUNEL.(2) Experimental obstructive jaundice (BDL) was induced by double ligation of the bile duct in rats. After BDL for 3d、7d、14d、and 21d, the apoptotic status in liver of all rats were determined with TUNEL, and iNOS protein in liver of OJ was ditermined with immunohistochemistry method. Results (1) SMT decreased GCDC-induced apoptosis in a concentration-dependent manner. (2) The apoptotic rate of liver was related to length of time of OJ. Apoptosis index (AI) was highest from rats with 14d bile duct ligation. The stronger the iNOS expression, the higher was the number of apoptotic cells that was found in OJ. Conclusions iNOS is involved in the regulation and the occurrence and progression of hepatic injury of obstructive jaundice.

Objective To activate microglia N9 cell through the oxygen deficit, and to discuss the influence to the N9 cell by ginsenoside Rb1, laying the foundation for the basic study and the clinical medicine development. Methods Through ginsenoside Rb1 intervention, the cell morphology the proliferation ability were observed, ELISA, fluorescent probe DAF-FM DA, Griess the reagent examination, were used to measure TNF-α, the O-2 output, the NO content change, chemiluminescence, the immunofluorescence method, and plastochondria membrane potential, were carried out to detect the cytochrome C content. Results Regardless of being preventive or medical gives, ginsenoside Rb1 can decline the NO,O-2,TNF-α high expression; and reduce the plastochondria membrane potential changing, the cytochrome C redistribution. Conclusion Ginsenoside Rb1 can decline N9 cell activation to a certain extent, reduce expression of the nerve toxic factor, and to stabilize mitochondrial membrane potential and distribution of cytochrome C.

Objective To observe therapeutic effect and safety of tacrolimus on idiopathic membranous nephropathy(IMN)with nephrotic syndrome in different courses of treatment.Methods Twenty patients with nephritic syndrome caused by idiopathic membranous nephropathy were divided into short-term(10 cases)and long-term(10 cases)groups randomly.Short-term group and long-term group were treated with tacrolimus and prednisone for 6 months and 24 months repectively,then obersve treatment effect,concentration changes of tacrolimus,recurrence and side effects in 2 groups.Results Five patients obtained complete remission after 6 months of treatment in the short-term group;4 patients obtained partial remission;1 patient had no response.Average concentration of tacrolimus remained 5～7 ?g/L in the period of treatment,and 6 cases recurred.Six patients obtained complete remission and 3 patients obtained partial remission after 24 months of treatment in the long-term group;1 patient had no response.Concentration of tacrolimus in the long-term group remained same as the short-term group at 5～8 ?g/L at 6 months,3.38～4.36 ?g/L at 12 months;no case recurred after treatment,the rate of which was significantly lower than the short-term group.Conclusion Short-term and long-term treatment of tacrolimus can relieve IMN evidently;low concentration of tacrolimus in the long-term group can alleviate the state of illness persistently with low recurrence rate.

Hypermethylation of the promoter region is an important mean for the transcriptional repression of a number of cancer-associated genes, and over-expression and/or increased activity of DNA methyltransferase are considered to be the main cause of promoter hypermethylation. In order to further explore the epigenetic mechanism of tumor suppressor gene RASSF1A inactivation, 5-aza-2'-deoxycytidine (5-Aza-CdR), a DNA methyltransferase inhibitor, was used to treat the human biliary tract carcinoma cell line QBC-939 at the concentration of 5 micromol/L for 24 h in this study. After the chemical intervention with 5-Aza-CdR, the methylation status in the promoter region of RASSF1A gene was detected by methylation specific PCR (MS-PCR), and the expression alteration of RASSF1A mRNA and protein were observed by RT-PCR and Western Blot respectively. Following the treatment with 5-Aza-CdR, methylation status in the promoter region of RASSF1A gene was reversed from methylation to unmethylation. A 280 bp DNA band which represented RASS1FA expression at transcriptional level and a 40 kDa (1 kDa=0.9921 ku) protein band which represented RASSF1A expression at protein level were detected by RT-PCR and Western Blot respectively in the experimental group cells and there were no corresponding bands in the control group cells. The experimental results suggest that 5-Aza-CdR can induce demethylation in the promoter region of RASSF1A. It can also reverse epigenetic transcriptional silencing caused by DNA methylation and induce the re-expression of RASSF1A in QBC-939. This study also suggest that the mechanism of RASSF1A inactivation is very closely related to the methylation of the promoter region, which may provide a new epigenetic understanding for tumor related gene inactivation and the pathogenesis of biliary tract carcinoma.

Objective To investigate whether the effect of transient high glucose on inflammatory factors expression could be continuous in rat glomerular mesangial cell,and its relation with histone methylation modification.Methods Rat glomerular mesangial cells (HBZY-l) were divided into three groups:the high glucose group (25.0 mmol/L glucose),the hypertonic group (MA,5.5 mmol/L glucose+ 19.5 mmol/L mannitol) and the normal-glucose control group (5.5 mmol/L glucose),which were cultured for 24 h respectively.All 3 groups were then changed with normal-glucose medium to culture for 24 h,48 h and 72 h.Their protein,mRNA and supernatant were harvested.The protein expressions of mono-methylation of H3 lysine 4 (H3K4mel) was measured by Western blotting,and the mRNA expressions of NF-κB subunit p65 and set7/9 were determined by real timequantitative PCR.The expression of monocyte chemoattractant protein 1 (MCP-1) and vascular cell adhesion molecule 1 (VCAM-1) were detected by enzyme-linked immunosorbent assay.Results (1)Compared with those in normal control group,the expressions of H3K4mel protein and set7/9 mRNA were first up-regulated in high glucose group,then gradually down-regulated in the following 48 h normal-glucose medium (as compared with those at 0 h,all P ＜ 0.05).At 72 h there was no statistic difference between high glucose group and normal control group (all P ＞ 0.05).(2) Compared with those in normal control group,the up-regulated p65 mRNA,VCAM-1 and MCP-1 sustained at least for 72 h in high glucose group.Conclusions Transient high glucose can induce persistent inflammatory factors expression in rat glomerular mesangial cells,which may via histone modification.

Objective To observe the expression of microRNA-148b (miR-148b) induced by high glucose in rat mesangial cells,and to explore its effect on its target gene AMP-activated protein kinase α1 (AMPKα1) and extracellular matrix excretion.Methods Rat mesangial cells were divided ino 3 groups:normal glucose (NG,5.5 mmol/L glucose) group,hypertonic (MA,5.5 mmol/L glucose+19.5 mmol/L mannitol) group and high-glucose (HG,25.0 mmol/L glucose) group.MiR-148b expression was detected by real time PCR.Then miR-148b inhibitor was transfected to rat mesangial cells.Their protein expressions of AMPKα1,glucose regulated protein 78 (GRP78),C/EBP homologous protein (CHOP),fibronectin (FN) and collagen Ⅳ were detected by Western blotting.The expression of AMPKα1 mRNA was detected by real time PCR.The expression of collagen Ⅳ was also detected by immunofluorescence.Results Compared with NG group,HG group showed up-regulated miR-148bexpression,down-regulated AMPKαl mRNA and protein expressions,and up-regulated CHOP,GRP78,collagen Ⅳ and FN expressions (all P ＜ 0.05).HG-induced mesangial cells with miR-148binhibitor had up-regulated AMPKα1 mRNA and protein expressions,and down-regulated CHOP,GRP78,collagen Ⅳ,FN expressions as compared with HG-induced cells without miR-148b inhibitor (all P ＜ 0.05).Conclusions HG can up-regulate miR-148b expression and down-regulate AMPKα1 expression in rat mesangial cells,then activate endoplasmic reticulum stress to induce extracellular matrix excretion.MiR-148b inhibitor up-regulates AMPKα1 expression,inhibits endoplasmic reticulum stress and reduces extracellular matrix excretion.

Objective To investigate the expression vibration of microRNA-503(miR-503) and its effect on target gene Bcl-2,caspase enzyme activity and apoptosis of human renal tubular epithelial cells (HK-2) induced by high glucose,and to clarify the pathogenesis of renal tubular injury induced by high glucose.Methods HK-2 cells were cultured in normal glucose group (NG),mannitol hypertonic control group (MA),and high glucose group (HG).The morphology of apoptotic cells was observed using inverted microscope.The expression of miR-503 was determined using realtime quantitative PCR.The apoptosis rate of HK-2 cells was detected by Annexin V-FITC double dye using flow cytometry instrument.The expression of Bcl-2 and cleaved caspase-9 were detected by Western blotting.Results In the high glucose and mannitol groups HK-2 cell,an obviously increased apoptotic rate was observed under inverted microscope compared with normal glucose group (P ＜ 0.05).MA and HG up-regulated miR-503 expression (P ＜ 0.01),down-regulated anti-apoptotic protein Bcl-2 expression (P ＜ 0.05) and up-regulated cleaved caspase-9 (P ＜ 0.05).Conclusions The expression of miR-503 increases in HK-2 cells cultured by high glucose and mannitol.MiR-503 promotes apoptosis of HK-2 cells via activating mitochondrial apoptotic pathways and enhancing cleaved caspase-9 for Bcl-2 insufficiency.The tubular toxicity of high glucose is partly due to osmotic pressure.The miR-503 may be involved in diabetic tubular injury and may be a new therapeutic target of DN.