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Arsenic, an established human carcinogen, causes genetic toxicity. However, the molecular mechanisms involved remain unknown. MicroRNAs (miRNAs) are regulators that participate in fundamental cellular processes. In the present investigation, we selected, as research subjects, patients with arsenic poisoning caused by burning of coal in Guizhou Province, China. For these patients, the plasma levels of miR-145 were up-regulated. In L-02 cells, arsenite, an active form of arsenic, induced up-regulation of miR-145 and down-regulation of ERCC1 and ERCC2, and caused DNA damage. For L-02 cells, transfection with an miR-145 inhibitor prevented arsenite-induced DNA damage and decreased ERCC2 levels. Luciferase reporter assays showed that miR-145 regulated ERCC2 expression by targeting the 3'-UTR of ERCC2, but not that for ERCC1. The present results demonstrate that arsenite induces the over-expression of miR-145 and inhibits DNA repair via targeting ERCC2, thus promoting DNA damage. The information provides a new mechanism for arsenic-induced liver injury.

A recent study revealed that quantitative hepatitis B core antibody (qAnti-HBc) level could serve as a novel marker for predicting treatment response. In the present study, we further investigated the predictive value of qAnti-HBc level in HBeAg-positive patients undergoing PEG-IFN therapy. A total of 140 HBeAg-positive patients who underwent PEG-IFN therapy for 48 weeks and follow-up for 24 weeks were enrolled in this study. Serum samples were taken every 12 weeks post-treatment. The predictive value of the baseline qAnti-HBc level for treatment response was evaluated. Patients were further divided into 2 groups according to the baseline qAnti-HBc level, and the response rate was compared. Additionally, the kinetics of the virological and biochemical parameters were analyzed. Patients who achieved response had a significantly higher baseline qAnti-HBc level (serological response [SR], 4.52±0.36 vs. 4.19±0.58, p=0.001; virological response [VR], 4.53±0.35 vs. 4.22±0.57, p=0.005; combined response [CR], 4.50±0.36 vs. 4.22±0.58, p=0.009)). Baseline qAnti-HBc was the only parameter that was independently correlated with SR (p=0.008), VR (p=0.010) and CR(p=0.019). Patients with baseline qAnti-HBc levels ≥30,000 IU/mL had significantly higher response rates, more HBV DNA suppression, and better hepatitis control in PEG-IFN treatment. In conclusion, qAnti-HBc level may be a novel biomarker for predicting treatment response in HBeAg-positive patients receiving PEG-IFN therapy.

The objective of this study is to design novel dissolution-enhanced microparticles loaded poorly soluble drug nanocrystals used a low viscosity of hydroxypropylcellulose (HPC) as matrix carrier. An interesting approach combined homogenization and the spray-freeze-drying technique was developed. The results demonstrated that the ratio of HPC to drug played an important role in size-reduction efficiency of drug during homogenization. And the formation of cage-like structure of the composite particles depended on ratio of HPC to drug. The spray-freeze-dried composite particles with HPC ratio of 1:2, 1:1 and 2:1 possessed excellent redispersibility, which attributed to its porous matrix and large surface area (3000 m2/g). The dissolution of spray-freeze-dried composite particles with higher ratios of HPC (1:2 and 1:1) was significantly enhanced, which attributed to the particle size reduction of drug. The HPC could immobilize drug nanocrystals in its cage-like structure and prevent it from the subsequent agglomeration during storage. In conclusion, the prepared cage-like microparticles is a promising basis for further formulation development.

Clinically applicable models to predict hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) response to peginterferon (PEG-IFN) are scarce. This study aimed to develop simple scoring systems, based on multiple parameters, for predicting sustained HBeAg seroconversion to PEG-IFN.Eighty-five treatment-naïve patients with HBeAg-positive CHB underwent 52-week PEG-IFN treatment and 24-week follow-up. Logistic regression analysis assessed parameters at baseline and weeks 12, 24, and 52 to predict HBeAg seroconversion at week 24 off-treatment. The best three predictors at each time point were included in prediction models of PEG-IFN therapy efficacy.The three most meaningful predictors were alanine aminotransferase (ALT) 5 × ULN, HBeAg ≤ 500 S/CO, and antibody to hepatitis B core antigen (anti-HBc) 10.7 S/CO at baseline; HBeAg ≤ 20 S/CO, anti-HBc 11.7 S/CO, and HBeAg decline 1 logWe successfully established prediction models for PEG-IFN response in HBeAg-positive CHB.

Background and Aim Chronic hepatitis C virus (HCV) infection is relatively frequent in China. This study investigated the clinical, demographic, and viral and host genetic characteristics that may influence disease manifestations and clinical management. Methods In this cross-sectional observational study, treatment-naïve Han ethnic adults with recently confirmed chronic HCV infection were enrolled at 28 hospitals across China. HCV genotype and host interleukin 28B (IL28B) genotypes were determined and compared with patient demographic parameters and medical status. Results Among the 997 HCV-positive patients analyzed, 56.8% were infected with HCV genotype 1b, followed in prevalence by genotypes 2, 3, and 6, with substantial regional variation. Overall, 84.1% of patients were IL28B genotype CC (rs12979860), with little regional variation. Cirrhosis was reported in 10.1% of patients and was significantly associated with hepatitis B virus coinfection, low HCV viral load, low serum alanine aminotransferase, high serum aspartate aminotransferase, diabetes, and high pickled food consumption. Medical procedures were common transmission risk factors; however, lifestyle-associated risk factors, including intravenous drug abuse and tattoos or piercings, were more common in patients with HCV genotype 3 or 6. Conclusions Most HCV-infected Han Chinese patients were IL28B genotype CC (rs12979860). HCV genotypes varied by geographic region, and disease characteristics differed according to HCV genotype. Relatively frequent detection of advanced liver disease may reflect limitations on access to antiviral therapy, and suggests that greater awareness of factors that influence HCV-associated disease may help avoid clinical complications and improve patient outcomes.