An understanding of the molecular basis of liver regeneration will open new horizons for the development of novel therapies for chronic liver failure. Such therapies would solve the drawbacks associated with liver transplant, including the shortage of donor organs, long waitlist time, high medical costs, and lifelong use of immunosuppressive agents. Regeneration after partial hepatectomy has been studied in animal models, particularly fumarylacetoacetate hydrolase-deficient (FAH^-/-) mice and pigs. The process of regeneration is distinctive, complex, and well coordinated, and it depends on the interplay among several signaling pathways (eg, nuclear factor κβ, Notch, Hippo), cytokines (eg, tumor necrosis factor α, interleukin 6), and growth factors (eg, hepatocyte growth factor, epidermal growth factor, vascular endothelial growth factor), and other components. Furthermore, endocrinal hormones (eg, norepinephrine, growth hormone, insulin, thyroid hormones) also can influence the aforementioned pathways and factors. We believe that these endocrinal hormones are important hepatic mitogens that strongly induce and accelerate hepatocyte proliferation (regeneration) by directly and indirectly triggering the activity of the involved signaling pathways, cytokines, growth factors, and transcription factors. The subsequent induction of cyclins and associated cyclin-dependent kinase complexes allow hepatocytes to enter the cell cycle. In this review article, we comprehensively summarize the current knowledge regarding the roles and mechanisms of these hormones in liver regeneration. Articles used for this review were identified by searching MEDLINE and EMBASE databases from inception through June 1, 2019.

Preclinical studies have suggested the antitumorigenic properties of metformin on prostate cancer; results from epidemiological studies remain contradictory. We aim to investigate the evidence of metformin and the risk of prostate cancer. PubMed, Embase, Cochrane Library, and Web of Science databases were searched for eligible studies. Meta-analyses were carried out using the most fully adjusted hazard ratios and the corresponding 95% confidence intervals. Eighteen cohort studies and six case–control studies representing 2 009 504 male patients with type 2 diabetes mellitus were identified. The pooled HR of prostate cancer for metformin therapy was 0.97 (0.84–1.12) in case–control studies and 0.94 (0.79–1.12) in cohort studies, respectively. In cohort studies, we found that there was a modest association in studies with samples from Europe, but not in studies with samples from North America, Asia, and Oceania. In addition, metformin showed a slightly protective effect compared with sulfonylurea, but not insulin and other comparators. Meta-regression analyses found that obesity and prostate-specific antigen adjustment in statistical models may be the sources of heterogeneity. However, there were no significant differences in subgroups stratified by time-related biases, analytical approaches, types of risk estimates, study quality, publication year, and whether adjusted for smoking, alcohol abuse, hemoglobin A1c, diabetes duration, and other confounding factors. Our study showed that metformin therapy was not associated with the risk of prostate cancer in patients with type 2 diabetes mellitus. However, exploratory analyses suggest that metformin use may be protective in a certain subgroup of patients.

Environmental related data are increasing rapidly in China andhave been used in many fields based on data processing and miningmethods or technology.