Objectives To explore if the rat bone marrow mesenchymal stem cells (BMSCs) modified by human heme oxygenase 1 (hHO-1) gene combined with GATA-4 gene may promote the ability of anti-apoptosis and myocardial transdifferentiation in vitro in hypoxia ischemic environment.Methods The rat BMSCs were isolated and cultured by whole bone marrow adherence and identified in vitro,and then were transfected with recombinant adenovirus;Western blotting was used to determinate the optimal time of gene expression;the genetically modified BMSCs were taken to hypoxia serum-free conditions simulating ischemia hypoxia microenvironment in vivo;CCK-8 kit and trypan blue staining were performed to detect the 12,24,48 and 72h survival rates in hypoxia ischemia respectively;flow cytometry was used to detect the apoptosis of BMSCs in hypoxia ischemia for 24h.The cardiomyocyte-specific cardiac troponin Ⅰ (cTnI) was detected by Western blotting and cellular immunofluorescence.Results The 12,24,48 and 72h survival rates were higher in hHO-1+GATA-4 group cultured in ischemia and hypoxia condition than in hHO-1 group (P＜0.05) and GATA-4 group (P＜0.05).After 24h cultivation in ischemia hypoxia condition,the apoptotic rates were lower in hHO-1+GATA-4 group than in hHO-1 group (P＜0.05) and GATA-4 group (P＜0.05).No significant difference existed in cTnI expressions between GATA-4 group and hHO-1+GATA-4 group.Conclusion Compared with transfection of hHO-1 or GATA-4 single gene,hHO-1 combined with GATA-4 transduction can significantly increase the survival rate of BMSCs in hypoxia ischemic condition,but myocardial transdifferentiation does not increase significantly.

OBJECTIVETo identify risk factors of hepatocellular carcinoma (HCC) in cirrhotic patients with chronic hepatitis B (CHB).

METHODSA total of 715 cirrhotic patients with CHB were recruited from the Zhongshan Hospital Affiliated to Fudan University and enrolled in this case-control study between January 2009 and September 2014. All participants were Chinese Han residing in Shanghai and the surrounding areas. The patients were divided into a cirrhosis group (n =281) and a HCC group (n=434). History of hepatitis B infection and HCC, as well as clinical data from serological, imaging and pathological examinations were collected for analysis.SPSS software, version 19.0, was used for all statistical comparisons.

RESULTSSingle factor analysis indicated that development of HCC in cirrhotic patients with CHB was significantly associated with male sex, age of 50 years or more, family history of HCC, alcohol consumption,fatty liver, detectable levels of hepatitis B virus (HBV) DNA, and history of HBV infection without effective antiviral treatment. Multivariate logistic regression analysis indicated that age of 50 years or more (P =0.005, odds ratio [OR] =1.766), history of alcohol consumption (P =0.002, Or = 2.570), family history of HCC (P =0.014, Or = 2.268), fatty liver (P =0.023, Or = 3.390), and history of HBV infection without effective antiviral treatment (P < 0.001,Or = 5.389) were risk factors of HCC.The risk factors for development of HCC in cirrhotic patients with hepatitis B after achieving sustained virologic suppression (SVS) were family history of HBV infection (P =0.014, Or = 2.537), family history of HCC (P =0.037,Or = 3.339) and fatty liver (P =0.018, Or = 11.646).

CONCLUSIONRisk factors of HCC in cirrhotic patients with CHB include age,drinking history,family history of HCC, fatty liver, and ineffective antiviral treatment of CHB.Family history of HBV infection or HCC, and fatty liver disease, were significantly associated with HCC development after SVS in patients with hepatitis B-related cirrhosis.

Alcohol Drinking ; Antiviral Agents ; Carcinoma, Hepatocellular ; Case-Control Studies ; China ; Fatty Liver ; Hepatitis B virus ; Hepatitis B, Chronic ; Humans ; Liver Cirrhosis ; Liver Neoplasms ; Male ; Odds Ratio ; Risk Factors