Identified OAS3 gene variants associated with coexistence of HBsAg and anti-HBs in chronic HBV infection.

The underlying mechanism of coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antigen antibody (anti-HBs) is still controversial. To identify the host genetic factors related to this unusual clinical phenomenon, a two-stage study was conducted in the Chinese Han population. In the first stage, we performed a case-control (1:1) age- and gender-matched study of 101 cases with concurrent HBsAg and anti-HBs and 102 controls with negative HBsAg and positive anti-HBs using whole exome sequencing. In the second validation stage, we directly sequence the 16 exons on the OAS3 gene in two dependent cohorts of 48 cases and 200 controls. Although, in the first stage, a genome-wide association study of 58,563 polymorphism variants in 101 cases and 102 controls found no significant loci (P-value ≤ .05/58563), and neither locus achieved a conservative genome-wide significance threshold (P-value ≤ 5e-08), gene-based burden analysis showed that OAS3 gene rare variants were associated with the coexistence of HBsAg and anti-HBs. (P-value = 4.127e-06 ≤ 0.05/6994). A total of 16 rare variants were screened out from 21 cases and 3 controls. In the second validation stage, one case with a stop-gained rare variant was identified. Fisher's exact test of all 149 cases and 302 controls showed that the rare coding sequence mutations were more frequent in cases vs controls (P-value = 7.299e-09, OR = 17.27, 95% CI [5.01-58.72]). Protein-coding rare variations on the OAS3 gene are associated with the coexistence of HBsAg and anti-HBs in patients with chronic HBV infection in Chinese Han population.

Rapamycin induces human acute promyelocytic leukemia cell HL-60 autophagic apoptosis.

OBJECTIVE: We aimed at investigating the effects of rapamycin on apoptosis and autophagy of human acute promyelocytic leukemia cell line HL-60, and to preliminarily explore the mechanism of extra medullary infiltration of leukemia cells with human acute promyelocytic leukemia cell line HL-60 as the object of study, providing a theoretical basis for the clinical treatment of leukemia. MATERIALS AND METHODS: After HL-60 cells were cultured in vitro, the effect of rapamycin on proliferation ability of HL-60 cells was determined by methyl thiazolyl tetrazolium (MTT) method, the cell apoptosis ratio was detected by flow cytometer, the change of autophagy after HL-60 cells acted by rapamycin was tested by monodansylcadaverine (MDC) fluorescence staining, the mRNA expression of autophagy-related molecule was detected by polymerase chain reaction (PCR), and the expressions of apoptosis-related protein and autophagy-related protein were determined by Western blotting (WB). RESULTS: HL-60 cell proliferation could be significantly inhibited by rapamycin (80 µg/mL-640 µg/mL), which was in a dose-dependent manner. HL-60 cell apoptosis ratio and apoptosis-related protein expression were distinctly improved by rapamycin. Cell autophagy level, mRNA expression of autophagy-related molecule and autophagy-related protein expression were remarkably induced by rapamycin. CONCLUSIONS: Rapamycin can induce HL-60 cell apoptosis, which is produced mainly by inducing cell autophagy.

MiR-16 regulates cell death in Alzheimer's disease by targeting amyloid precursor protein.

OBJECTIVE: The aim of this study was to investigate the role of miR-16 in Alzheimer's disease (AD) and to explore its mechanism of action. MATERIALS AND METHODS: A cellular AD model using PC12 cells and primary hippocampal neurons was established to evaluate the expression level of miR-16. Transfection of a miR-16 mimic and a miR-16 inhibitor were performed to explore its effect on cell apoptosis and cell viability. In addition, we carried out bioinformatics analysis, luciferase reporting gene assay, and gene expression analyses to identify the potential target of miR-16 and to verify the effect of the target gene on the cellular AD model. RESULTS: Downregulation of miR-16 was confirmed in the cellular AD model with both PC12 cells (p < 0.05) and primary hippocampal neurons (p < 0.05). Overexpression and inhibition of miR-16 in the cellular AD model with primary hippocampal neurons decreased and increased apoptosis, respectively. The gene encoding amyloid precursor protein (APP) was identified as the target gene of miR-16. Knockdown of APP in primary hippocampal neurons decreased cell apoptosis and increased cell viability in the cellular AD model. CONCLUSIONS: Our results demonstrate that downregulation of miR-16 in primary hippocampal neurons play an important role in the paracrine effect and might be involved in the development of AD.

Comparative study of clinical efficacy of laparoscopy-assisted radical gastrectomy versus open radical gastrectomy for advanced gastric cancer.

The purpose of this study is to compare the efficacy of laparoscopy-assisted radical gastrectomy (LARG) versus that of open radical gastrectomy (ORG). Clinical data of 355 patients who underwent radical gastrectomy (160 in the LARG group and 195 in the ORG group) were analyzed retrospectively. Efficacy indices were compared and analyzed between the two groups. The operating time of LARG was longer than that of ORG (228.43 ± 34.77 versus 207.59 ± 28.39 min). However, patients in the LARG group lost less blood than did those in the ORG group (169.46 ± 82.92 versus 193.86 ± 82.09 mL), and more lymph nodes were removed in the LARG group (19.84 ± 4.7 versus 18.04 ± 4.14 per case). The recovery of intestinal function was faster (3.72 ± 1.03 versus 4.41 ± 1.30 days) in the LARG group. Patients in the LARG group were administered a semi-fluid diet earlier (5.66 ± 2.27 versus 7.09 ± 2.33 days) and had a shorter hospital stay (9.44 ± 3.06 versus 11.07 ± 7.91 days) than did those in the ORG group, and these differences were statistically significant (P < 0.05). No significant differences were found in the length of proximal and distal resection margin and the incidence of complications (P > 0.05) between the two groups. Thus, LARG is safe, feasible, and effective for treating advanced gastric cancer.