[Predictive value of single nucleotide polymorphisms of HLA-C and UBE2L3 in evaluating the effect of telbivudine antiviral therapy during pregnancy].

Objective: To investigate the association between single nucleotide polymorphisms (SNPs) of rs3130542 and rs4821116 in the HLA-C and UBE2L3 genes and the effect of telbivudine antiviral therapy during pregnancy in HBeAg-positive mothers through a large-sample control study, and to provide a basis for the development of individualized blocking strategies for pregnant women with a high viral load. Methods: The genotypes of rs3130542 and rs4821116 were determined for 312 pregnant women with a high viral load who received telbivudine antiviral therapy during the second or third trimester of pregnancy, and the dominant model, recessive model, and additive model were used to analyze the association between the genotypes of these two loci and the reduction in HBV DNA load. The Shapiro-Wilk test and the Levene test were used to evaluate data normality and homogeneity of variances, and the t-test or the non-parametric Mann-Whitney U test was selected based on data type and was used for the comparison of means between groups. The Hardy-Weinberg equilibrium was used to determine the genotype of SNPs, and the dominant model, recessive model, and additive model were used for analysis. Results: Mothers with an AA/AG genotype of rs3130542 in the HLA-C gene had a significantly higher probability of HBV DNA load ≥10(3) IU/ml at the time of delivery (P < 0.05) and a significantly higher risk of failure in the prevention of mother-to-child transmission, no matter whether they started to take telbivudine at week 24 or 28 of pregnancy. The association between the genotype of rs4821116 in the UBE2L3 gene and the reduction in viral load in pregnant women needed to be confirmed by studies with a larger sample size. Conclusion: Pregnant women with a high viral load and an AA/AG genotype of rs3130542 in the HLA-C gene tend to have poor response to antiviral therapy during pregnancy, and early antiviral intervention is recommended for such patients.

Effects of renin-angiotensin system blockade on islet function in diabetic rats.

AIMS: To investigate the effects of renin-angiotensin system (RAS) blockade on islet structure and function in diabetic rats, and its mechanisms. METHODS: Diabetic rat models were created by high-fat high-caloric laboratory chow plus small dose (30 mg/kg) streptozotocin ip injection. After 8-week intervention with perindopril (AE, no.=10) or valsartan (AR, no.=10), all the animals' islet function was evaluated by iv glucose tolerance test. Pancreases were stained by immunohistochemistry technique to qualitative and/or quantitative analysis the content of insulin, inducible nitric oxide synthase (iNOS), transforming growth factors-beta1 (TGF-beta1) in islets. The apoptosis of islet cells was detected by transferase-mediated dUTP nick-end labeling dUTP nick end labeling (TUNEL). The expression level of angiotensinogen (AGT) and insulin mRNA in islets were detected by RT-PCR. RESULTS: Compared with normal control group (NC, no.=10), area under the curve of insulin from 0 to 10 min (AUCI0-10) of diabetes group (DM, no.=8) was decreased by 66.9%, the relative expression of local AGT was increased by 69.2%, the insulin relative concentration (IRC) of beta-cell and the expression of insulin mRNA were decreased significantly, the amount of apoptotic cells in unit islet area was increased by 2.1 times, the relative content of iNOS and TGF-beta1 positive cell relative volume (TRV) was increased by 23.0% and 2.52 times, respectively (all p<0.01). Compared with DM group, AUCI0-10 of AE and AR group was increased by 41.4% and 33.2%, respectively; the relative expression of local AGT was decreased by 21.4% and 23.4%, respectively; IRC and the expression of insulin mRNA were increased significantly; the amount of apoptotic islet cells was decreased by 79.0% and 36.2%, respectively; the relative content of iNOS was decreased by 16.5% and 18.9%, respectively; TRV was decreased by 43.8% and 35.6%, respectively (all p<0.01). There were no significant differences between group AE and AR. CONCLUSION: Blockade of RAS may improve diabetic rats islet function via the amelioration of intra-islets oxidative stress, fibrosis and apoptosis.