Influence of UGT2B7 and UGT1A6 polymorphisms on plasma concentration to dose ratio of valproic acid in Chinese epileptic children.

We explored the potential effects of genetic variations on the concentration to dose ratio (CDR) of valproic acid (VPA) in paediatric epilepsy patients.Two hundred and twenty-nine epileptic children on VPA monotherapy were included, and the VPA trough concentrations at steady-state of all subjects were determined.Nineteen single nucleotide polymorphisms (SNPs) of seven selected genes related to the metabolising enzymes and transporters of VPA were identified, and their influences on CDRVPA (a logarithmic transformation was performed if abnormally distributed) were evaluated.UGT2B7 rs7668258 (C>T) TT genotype was associated with a decrease in lnCDRVPA among epileptic children receiving VPA monotherapy (ß=-0.191, p = 0.036). Significantly lower lnCDRVPA was also observed in paediatric patients with UGT1A6 rs2070959 (A>G) GG genotype compared to those AA genotype (ß=-0.270, p = 0.021).This research indicated that UGT2B7 rs7668258 (C>T) and UGT1A6 rs2070959 (A>G) polymorphisms may be correlated to the normalised plasma concentrations of VPA in Chinese epileptic children. The associations could be abolished after Bonferroni's correction and our findings need to be validated in further and larger investigations.

[A retrospective analysis of medication in children with SARS-CoV-2 infection in Wuhan, China].

OBJECTIVE: To study the medication in children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Wuhan, China, and to provide a reference for rational drug use in clinical practice. METHODS: A retrospective analysis was performed on the medical data of the children who were diagnosed with SARS-CoV-2 infection from January 26 to March 5, 2020. The children were divided into an asymptomatic group with 41 children and a symptomatic group with 73 children. A subgroup analysis was performed to investigate the effect of different antiviral regimens (monotherapy, double therapy, or triple therapy) and whether interferon α-1b was used in combination with azithromycin on the length of hospital stay and the clearance time of SARS-CoV-2 nucleic acid. RESULTS: A total of 114 children with SARS-CoV-2 infection (72 boys and 42 girls) were enrolled. The median age of the children was 7.1 years. The median length of hospital stay was 10 days and the clearance time of SARS-CoV-2 nucleic acid was 6 days. In either group, the subgroup analysis showed no significance differences in the length of hospital stay and the clearance time of SARS-CoV-2 nucleic acid between the subgroups treated with different combinations of antiviral drugs and the subgroups treated with interferon α-1b alone or in combination with azithromycin (P > 0.05). CONCLUSIONS: It is not recommended to use the routine combinations of antiviral drugs for children with SARS-COV-2 infection or combine with azithromycin for the purpose of antiviral therapy.

Apoptosis induction activity of polysaccharide from Lentinus edodes in H22-bearing mice through ROS-mediated mitochondrial pathway and inhibition of tubulin polymerization.

BACKGROUND: Lentinus edodes is a medicinal mushroom widely used in Asian countries for protecting people against some types of cancer and other diseases. OBJECTIVE: The objective of the present study was to investigate the direct antiproliferation activity and the antitumor mechanisms of water-extracted polysaccharide (WEP1) purified from L. edodes in H22 cells and H22-bearing mice. DESIGN: The extraction, isolation, purification, and structure determination of the water-soluted L. edodes polysaccharide WEP1 were performed. The growth inhibitory effects of WEP1 on H22 cells and H22-bearing mice were determined by 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) method and animal studies. Flow cytometry, scanning electron microscopy, and laser scanning confocal microscopy were used to observe the morphological characteristics of apoptotic cells. The levels of intracellular reactive oxygen species (ROS) were detected by flow cytometry using 2',7'-dichlorofluorescein-3',6'-diacetate (DCFH-DA). Western blot was used to determine the expressions of cell cycle proteins and apoptosis-related proteins. RESULTS: Results showed that WEP1 with a molecular weight of 662.1 kDa exhibited direct antiproliferation activity on H22 cells in a dose-dependent manner. In vivo, WEP1 significantly inhibited the growth of tumor at different doses (50, 100, and 200 mg/kg) and the inhibition rates were 28.27, 35.17, and 51.72%, respectively. Furthermore, morphological changes of apoptosis and ROS overproduction were observed in H22 cells by WEP1 treatment. Cell cycle assay and western blot analyses indicated that the apoptosis induction activity of WEP1 was associated with arresting cell cycle at G2/M phase and activating mitochondrial-apoptotic pathway. Besides, WEP1 disrupted the microtubule network accompanied by alteration of cellular morphology. CONCLUSION: Results suggested that the antitumor mechanisms of WEP1 might be related to arresting cell cycle at G2/M phase, inhibiting tubulin polymerization and inducing mitochondrial apoptosis. Therefore, WEP1 possibly could be used as a promising functional food for preventing or treating liver cancer.

Effects of SCN1A and SCN2A polymorphisms on responsiveness to valproic acid monotherapy in epileptic children.

PURPOSE: This study was conducted to explore the influence of genetic variations on responsiveness to valproic acid (VPA) monotherapy among Chinese children with epilepsy. METHODS: One hundred and forty epileptic children taking VPA as monotherapy were enrolled, and at least one-year follow-up was obtained to assess the therapeutic outcome. Twenty-seven single nucleotide polymorphisms (SNPs) within twelve candidate genes correlated with the metabolic enzymes, transporters and targets of VPA were genotyped. The effects of selected polymorphisms on VPA efficacy were identified by binary logistic regression analysis adjusting for potential confounders. RESULTS: SCN2A rs2304016 (A > G) AG genotype was more common among the VPA-resistant patients in comparison with the VPA-responsive patients (OR = 3.18, 95 % CI = 1.10-9.14, P = 0.032), and in subgroup of focal seizure, lower frequency of VPA resistance was found in epileptic children with SCN1A rs2298771 AG genotype than those with AA genotype (OR = 0.11, 95 % CI = 0.01-0.91, P = 0.040). CONCLUSIONS: Our study indicated that SCN2A rs2304016 and SCN1A rs2298771 polymorphisms might be associated with the response to VPA monotherapy in Chinese epileptic children. Further and larger researches are required to validate these results.