Objective: To evaluate the relevance of diabetes mellitus and hepatitis B virus(HBV) infection in people by Meta-analysis. Methods: Databases we searched included CNKI, VIP China Science and Technology Journal Database, Wanfang Data Knowledge Service Platform, PubMed, Cochrane Library and Web of Science Core Collection database. Publication time was from January 1997 to May 2017. The Languages were limited to Chinese and English. English search terms include: diabetes, diabetes mellitus, hepatitis B and risk. Chinese search terms include: diabetes mellitus, hepatitis B and risk. We included all observational studies on diabetes and HBV infection. Firstly, the Newcastle-Ottawa Scale and the evaluation criteria of Cross-sectional study recommended by Agency for Healthcare Research and Quality were used to evaluate the quality of articles. Secondly, RevMan 5.3 software was used for heterogeneity testing. Subgroup analysis, random effects model and Mantel-Haenszel method were used to calculate the combined OR value. Finally, Stata 14.0 software was used to conduct the sensitivity analysis, and Begg rank correlation method was used to detect the publication bias. Results: A total of 12 studies were included, comprising 6 cross-sectional studies and 6 case-control studies. But the 12 articles were heterogeneous (χ²=42.10, P<0.001). After subgroup analysis, cross-sectional studies of diabetes and HBV infection were still heterogeneous (χ²=28.21, P<0.001), whose combined odds ratio (OR) was 1.36 (95%CI: 1.03-1.80). But the heterogeneity of case-control studies was not statistically significant (χ²=10.32, P=0.070), whose combined odds ratio (OR) was 1.55 (95%CI: 1.10-2.17). After the sensitivity analysis, the 95%CI of the combined OR of the 7 studies did not fluctuate, and the lower limit was above 1.07. No publication bias was detected in the cross-sectional study subgroup (Z=1.35, P=0.176) and the case-control study subgroup (Z=1.69, P=0.091). Conclusion Patients with diabetes are more likely to be infected with HBV than those without diabetes. Diabetes mellitus is likely to be a risk factor for HBV infection.

Objective To evaluate the effect of exosomes from different sources on the growth, metastasis and immune microenvironment of hepatocellular carcinoma ( HCC ) in a mouse model of orthotopic transplanted hepatoma so as to provide new insight into the clinical immunotherapy of hepatocellular carcinoma. Methods The serum-derived exosomes were obtained by ultracentrifugation from Hepa1-6 cells and 3-week orthotopically tumor-bearing HCC mice. The morphology and size of exosomes were identified by transmission electron microscopy. One-week tumor-bearing HCC C57BL/6 mice were randomly divided into 3 groups ( 3 mice for each group ) , and respectively treated with tail vein injection of 120 μl PBS(control group), 120 μl Hepa1-6 cell-derived exosomes (1μg/μl, TEXcel group), and serum-derived exosomes (1μg/μl) (TEXserum group). The treatments were conduced once a week for 3 consecutive weeks. The mice were sacrificed on the 4th day after the treatments, and the liver tissue and lung tissues were dissected. The volumes of the liver cancer tissues were measured. The expression of PD-L1 protein and CD3+and FoxP3+T lymphocytes infiltration in the liver cancer tissues were respectively detected by Western Blot and immunohistochemical staining. The lung metastasis of the liver cancer was detected by hematoxylin-eosin staining. Results The diameters of the Hepa1-6 cell- and serum-derived exosomes both were about 100 nm, and were uniform vesicles with complete membrane structure. Compared with the control group, Hepa1-6 cell-derived exosomes had a certain inhibitory effect on the growth and lung metastasis of HCC, while there was no significant difference for the TEXserum group. Western Blot results showed that compared with the control group, PD-L1 protein expression was significantly up-regulated in both TEXcel group and TEXserum group. Immunohistochemical staining showed that compared with the control group, the infiltration number of Foxp3+-labeled regulatory T cells (Treg) had no significant changes in TEXcel group and the TEXserum group, and the differences were no statistically significant (all P>0.05). However, the infiltration number of CD3+-labeled T lymphocytes was significantly reduced in the two groups, and the differences were statistically significant (all P<0.05). Conclusion The Hepa1-6 cell-derived exosomes have a certain inhibitory effect on the growth and lung metastasis of HCC, and have no obvious regulation effects on the immune microenvironment of HCC. The serum-derived exosomes from orthotopically tumor-bearing HCC mice can promote the growth and lung metastasis of HCC and immunosuppress the microenvironment. The Hepa1-6 cell-derived exosomes are expected to be used for immunotherapy studies of liver cancer.