Previous studies have investigated the lower embryo implantation rates in women with polycystic ovary syndrome, obesity and type 2 diabetes, and specifically the association between the abnormal oocyte and embryo and hyperinsulinemia. The importance of hyperinsulinemia on maternal endometrium receptivity remains to be elucidated. The present study used a hyperinsulinemic mouse model to determine whether hyperinsulinemia may affect endometrial receptivity. An insulin intervention mouse model was first established. The serum levels of insulin, progesterone and estradiol were subsequently detected by ELISA assay analysis. The number of implantation sites was recorded using Trypan blue dye and the morphology of mice uteri was investigated using hematoxylin and eosin staining. The expression levels of molecular markers associated with endometrial receptivity were detected by reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry analyses. Finally, the importance of mechanistic target of rapamycin (mTOR) expression following insulin treatment was determined. Mice treated with insulin developed insulin resistance and hyperinsulinemia. The number of implantation sites following insulin treatment did not differ between the control and insulin-treated groups. Additionally, no significant morphological alterations in mice uteri between control and insulin-treated groups were observed. However, the expression levels of estrogen receptor (Esr) 1, Esr2, progesterone receptor and homeobox A10 associated with endometrial receptivity, were imbalanced during endometrium receptivity when maternal hyperinsulinemia was induced. Western blot analysis revealed that expression levels of endometrial phosphorylated (p)-mTOR and p-ribosomal protein S6 kinase β-1 were significantly greater in the insulin-treated group. These results demonstrated that although an embryo may implant into endometrium, mice endometrium receptivity in early pregnancy may be impaired by maternal hyperinsulinemia. In addition, mTOR signaling may be involved in this process. The present study provides preliminary results demonstrating that female reproduction may be compromised during hyperinsulinemia, which requires further investigation in future studies.

Background and Objective: Amarogentin has been reported to have a preventive effect on liver cancer via inducing cancer cell apoptosis. We attempted to elucidate the roles of p53-associated apoptosis pathways in the chemopreventive mechanism of amarogentin. The findings of this study will facilitate the development of a novel supplementary strategy for the treatment of liver cancer. Materials and Methods: The purity of amarogentin was assessed by high-performance liquid chromatography. The inhibitory ratios of the liver cell lines were determined using a Cell Counting Kit-8 following treatment with a gradient concentration of amarogentin. Cell apoptosis was detected by flow cytometry using annexin V-fluorescein isothiocyanate/propidium iodide kits. The gene and protein expression of p53-associated molecules, such as Akt, human telomerase reverse transcriptase, RelA, and p38, was detected by real-time quantitative polymerase chain reaction, Western blotting, and immunohistochemical staining in liver cancer cells and mouse tumor tissues after treatment with amarogentin. Results: The inhibitory effect of amarogentin on cell proliferation was more obvious in liver cancer cells, and amarogentin was more likely to induce the apoptosis of liver cancer cells than that of normal liver cells. The gene and protein expression levels of Akt, RelA, and human telomerase reverse transcriptase were markedly higher in the control group than in the preventive group and treatment groups. Only the expression of human telomerase reverse transcriptase was downregulated, accompanied by the upregulation of p53. Conclusion: The results of our study suggest that amarogentin promotes apoptosis of liver cancer cells by the upregulation of p53 and downregulation of human telomerase reverse transcriptase and prevents the malignant transformation of these cells.

Background: This 5-year follow-up of the CCgenos cross-sectional study aimed to observe real-life outcomes in a cohort of 997 Han Chinese patients with chronic HCV infection and to explore the impacts of HCV genotype, patient characteristics and treatment status. Methods: Clinical information and centralized HCV RNA measures were collected every 6/3 months for untreated/ treated patients. Overall disease progression was defined as ≥1 of: de novo development of cirrhosis, Child-Turcotte-Pugh score increased by ≥2 points (if cirrhosis at baseline), progression to decompensated cirrhosis, hepatocellular carcinoma (HCC), liver transplant or death. Cox regression assessed risk factors for the time from estimated infection to cirrhosis or HCC. Logistic regression assessed risk factors for incidence rates of cirrhosis and overall disease progression. Results: 281 of 514 patients enrolled across China completed 5 years of follow-up. Overall disease progression occurred in 36/364 (9.9%) treated patients and 35/148 (23.6%) untreated patients (odds ratio = 0.35; 95% CI 0.21, 0.59; P<0.0001). Overall disease progression occurred in 6/231 (2.6%) patients achieving sustained virological response at 24 weeks (SVR24) versus 11/82 (13.4%) who did not (P=0.0002). Cirrhosis development was significantly associated with abnormal aspartate aminotransferase (AST), age ≥40 years, body mass index ≥28 kg/m 2 , HCV GT1, platelet count <100×10 9 /l, and AST to platelet ratio index (APRI) ≥2 (multivariate Cox regression, P<0.05). HCC was significantly associated with HCV GT1 and platelet count <100×10 9 /l (multivariate Cox regression, P<0.05). Conclusions: Achieving SVR24 significantly reduced the probability of overall disease progression but no significant difference was seen for both cirrhosis and HCC during 5 years of follow-up.Chronic HCV (cHCV) infection presents a major global public health burden [1,2]: the current estimate of global prevalence is 71 million [1,2]. The development of highly effective, well-tolerated, direct-acting antivirals (DAAs) has changed the treatment landscape for HCV, but global availability of these agents has been limited [1]. More than half of the world's HCV-infected population is in Asia [3]. In China, the

Background: Hepatitis B surface antigen clearance or seroconversion is rarely achieved for patients using nucleoside analogs or pegylated interferon alpha monotherapy approaches. Several recent studies have confirmed the benefit of a combination of these two approaches for selected chronic hepatitis B patients.However, few reports have investigated long-term outcomes or health economic evaluation for hepatitis B surface antigen clearance. The aim of this study was to perform a cost-effectiveness analysis of the long-term use of this combination strategy among selected hepatitis B e antigen-negative patients.Methods: Drawing on experience in China, we used a Markov model to simulate disease progression among a population of hepatitis B e antigen-negative chronic hepatitis B patients with surface antigen levels of ≤1,000 IU/mL through a discrete series of health states. We compared nucleoside analog monotherapy to the combination strategy over a prolonged period. We measured lifetime costs, quality-adjusted life-years and incremental cost-effectiveness ratios.Results: The combination therapy produced 15.8 quality-adjusted life-years, and cost US dollars (USD) 45,032 per patient. The monotherapy gave 13.9 quality-adjusted life-years, and had a cost of USD 52,064.The incremental cost-effectiveness ratio of the monotherapy (USD −3,755 per quality-adjusted life-year) did not obtain extended dominance over combination therapy. The most cost-effective option was combination therapy among patients with hepatitis B surface antigen levels of ≤10 IU/mL, which had the lowest calculated cost of USD 35,318 and most quality-adjusted life-years (16.7).Conclusions: A long-term combination treatment strategy for selected hepatitis B e antigen-negative chronic hepatitis B patients may prolong quality-adjusted life-years compared with nucleoside analog monotherapy. Chronic hepatitis B patients with a hepatitis B surface antigen level of ≤10 IU/mL were the most cost-effective population under this strategy.