Embryonic stem (ES) cells are pluripotent cells that differentiate into all cell types of the organism. In adult, multipotent tissue-specific stem cells undergo multi-lineage differentiation to preserve normal tissue homeostasis and repair potential injuries. The maintenance of stem cells and their differentiation follows defined epigenetic programs, including DNA methylation, histone modifications, and small non-coding RNAs that result in gene expression, morphologic, and functional changes. Recently, we reported for the first time the comprehensive characterization of the in vivo gene expression and DNA methylation profiles of four distinct populations of normal human mammary epithelial cells and the identification of cell type-specific DNA methylation patterns with clinical relevance. Our results together with other studies suggest an important role for epigenetic regulation in stem cell self-renewal, pluripotency, and differentiation, and imply that abnormalities in these processes may play a role in tumor initiation and progression.

γ-secretase inhibitors (GSIs), the indirect inhibitors of Notch, are emerging as a new class of anticancer agents for the treatment of solid and hematological malignancies, but little is known about their effects on gastric cancer. In this study, we demonstrate that DAPT, a potent GSI, was effective to inhibit γ-secretase activity in gastric cancer (GC) cell lines that contained a fragment with approximately the size of the Notch1 intracellular domain (NICD), but was limited in their ability to induce apoptosis. However, activation of extracellular signal-regulated kinase (ERK)1/2 upon DAPT treatment was detected. Selective inhibition of ERK1/2 activation dramatically sensitized GC cells to apoptosis via downregulating β-catenin signaling in these GC cells. Notably, in a xenograft mouse tumor model, combination therapy using ERK inhibitor PD98059 plus DAPT yielded additive antitumor effects as compared with either agent alone. Taken together, these data demonstrated that γ-secretase inhibition combined with ERK1/2 inhibitor enhances cell death in GC cells partly through downregulation of WNT/β-catenin pathways.

Hepatitis B virus (HBV) infection is a major risk factor for the development of hepatocellular carcinoma (HCC) in China. At present, there still are 9.3 million chronic HBV-infected Chinese. Numerous studies have explored the association between possible factors and hepatocellular carcinoma risk, however, the results remains inconsistent. Therefore, we did this pooled analysis so as to get a precise result. Here, we took the chronic HBV-infected Chinese as the object. We systematically searched for studies evaluating whether the proposed factors changed HCC risk in PubMed, Chinese National Knowledge Infrastructure, VIP database and Wanfang data. Odds ratios (OR) with 95% confidence intervals (CI) were calculated by Review Manager 5.0 and publication bias was determined by Begg’s test and Egger’s test. In total, 3165 cases and 10,896 controls from 27 studies were included in this meta-analysis. Our results showed that pooled OR with 95% CI for each of the factors investigated were: non-antiviral treatment 2.70 (2.01, 3.62), high HBV DNA levels 2.61 (1.73, 3.94), alcohol consumption 2.19 (1.53, 3.13), a family history of HCC 3.58 (2.53, 5.06) and male gender 2.14 (1.68, 2.73), respectively. Our meta-analysis supports that high HBV DNA levels, non-antiviral treatment, alcohol consumption, a family history of HCC and male gender contributed to the risk of hepatocellular carcinoma in chronic HBV-infected Chinese from currently available evidence. Given the high prevalence of the non-antiviral treatment and alcohol drinking, behavior interventions for the two factors should be tackled first.

The long-term persistence of hepatitis B surface antibody (anti-HBs) after hepatitis B vaccination among adults was not known clearly. This study aimed to assess the immunogenicity and persistence of antibodies 8 years after hepatitis B immunization with different vaccination schedules among adults who tested negative for hepatitis B surface antigen (HBsAg), anti-HBs, and hepatitis B core antibody (anti-HBc). A total of 771 participants who received the full vaccination course (three doses) and also had a blood sample taken 1 month after the first vaccination were recruited. Of these, 529 were excluded due to the missing data of anti-HBs 8 years after the first vaccination. Vaccinations were carried out at 0–1–3, 0–1–6 and 0–1–12 month vaccination schedules, and 104, 45, and 93 participants were included, respectively. The positive seroprotection rate was 85.9% 1 month after the third vaccination, and 58.3% 8 years later (χ² = 54.52, P < 0.001), while the geometric mean titer (GMT) of anti-HBs was 158.49 mIU/mL [95% confidence interval (CI): 131.83-190.55)] and 15.14 mIU/mL (95% CI: 10.96–20.42) after 1 month and 8 years, respectively. Compared with the standard 0–1–6 month vaccination schedule, the positive seroprotection rate and the GMT of the 0–1–3 month vaccination schedule had no difference. The long-term immune effect of the 0–1–3 month vaccination schedule was better than that of the 0–1–12 month vaccination schedule. No correlation was found between the GMT of anti-HBs 1 month and 8 years later.

Prevalence of hepatitis B is still high among adults in China, athough the prevalence in children has decreased dramatically. Immunization against hepatitis B among adults is urgently required. Through analyzing the immunogenicity of different doses, schedules and booster immunization among adults, we recommend 10 or 20 μg with a 0-1-6-month schedule or a 0-1-12-month schedule for migrant adults. For immunity failure, increasing the dose or covalent vaccine is suggested to provide protective antibodies. To enhance immunity among adults, hepatitis B vaccine should be included in health insurance.

The purpose of this study was to compare the response of hepatitis B vaccination with different vaccination schedules among seronegative adults, and to provide suitable vaccination schedules for floating and fixed population. The study included adults aged 20 to 39 y without prior history of vaccination with hepatitis B vaccine. The serum samples were collected and tested for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) levels. Out of all, 686 adults who were negative for anti-HBs, anti-HBc and HBsAg were vaccinated with 10 ug hepatitis B vaccine at 0, 1 and 3, 6 or 12 month schedules, and their antibody titers were monitored. The rates of completion of the vaccination in floating and fixed population were 90.4% and 94.1% respectively (p = 0.061). The anti-HBs positive rates in adults vaccinated at 0, 1 and 3 ,6 or12 month were 83.9%, 88.2% and 94.2% respectively (P = 0.0003). The corresponding geometric mean titers (GMTs) were 61.19 (95%CI:47.10-81.23) mIU/mL, 214.04(95%CI:157.14-291.61) mIU/mL and 345.78(95%CI:251.25-475.77) mIU/mL, respectively (P < 0.0001). Vaccination of hepatitis B with both 0-1-6 and 0-1-12 month schedules in adults result in better level of immune responses. Also, a longer vaccination schedule (0-1-12 month) may be more suitable for floating population and 0-1-6 month schedule is recommended for the fixed population.