POLG Mutations Are Probably Rare in the Han Chinese Population.

Objective Mutations in polymerase gamma gene (POLG) are believed to be an important cause of early and juvenile onset of non-syndromic intractable epilepsy. The aim of this study is to investigate the incidence/prevalence of POLG pathogenic variants in epilespy patients of Han population through sequencing it.Methods Han Chinese patients with seizures prior valproic acid (VPA) exposure at Shanghai Children's Hospital were collected from 2015 to 2019. The clinical diagnosis was based on the 2014 Consensus Statement of Epilepsy by the International League against Epilepsy (ILAE). Blood sampling were performed before VPA treatment. The POLG gene DNA was sequenced by either the first or the next generation sequencing (NGS). The POLG variant burden was illustrated. Liver functions were tested to describe whether they experienced VPA toxicity.Results Totally 216 Han Chinese patients were included, aged from 1 month to 15 years old, 102 were male and 114 were female. The onset age was 1 month old to 13 years old, and the epilepsy course ranged from 2 weeks to about 3 years. VPA treatment was delivered for the generalized or intractable partial seizures at standard dosage. No patient experienced hepatic toxicity following VPA exposure. DNA sequencing data showed no patient had either a homozygous mutation or compound heterozygous mutation of POLG. Single heterozygous mutations of c.1150G>T and p.D384Y were found in 2 patients, and single heterozygous mutation of c.156_158dupGCA was found in 1 patient. None of these variants showed clinical significance.Conclusions Functional modifying POLG homozygous mutations and compound heterozygous mutations were not detected and VPA toxicity was not seen in the current study. POLG mutation frequency might be rare in Han Chinese, and standard VPA therapeutic dosage might be safe for Han Chinese patients.

Monoterpenes from Paeonia albiflora and their inhibitory activity on nitric oxide production by lipopolysaccharide-activated microglia.

Eleven new monoterpenes, paeonidangenin (1), paeonidanin A (2), paeonidanin B (3), paeonidanin C (4), paeonidanin D (5), paeonidanin E (6), paeoniflorone (7), 4-O-methylbenzoylpaeoniflorin (8), 4-O-methylgalloylpaeoniflorin (9), 4-O-methyldebenzoylpaeoniflorin (10), and 4-O-methylalbiflorin (11), were isolated from the 60% ethanol extract of the roots of Paeonia albiflora. Their structures were determined primarily on the basis of 1D and 2D NMR techniques and MS studies. Paeonidanins D (5) and E (6) are unprecedented examples of "cage-like" monoterpene dimers. The inhibitory effects of the isolated compounds on nitric oxide production by lipopolysaccharide (LPS)-activated N9 microglia were evaluated.

A pair of 3-epimeric physalins from Physalis alkekengi L. var. franchetii.

A pair of new 3-epimeric steroids possessing a rare 13,14-seco-16,24-cycloergostane skeleton, 3alpha-methoxy-2,3-dihydro-4,7-didehydrophysalin B (1), and 3beta-methoxy-2,3-dihydro-4,7-didehydrophysalin B (2) were isolated from the 60% EtOH extract of the stems and leaves of Physalis alkekengi L. var. franchetii. Their structures were characterized on the basis of spectral evidence.

Steroids and flavonoids from Physalis alkekengi var. franchetii and their inhibitory effects on nitric oxide production.

Four new steroidal compounds possessing a rare 13,14-seco-16,24-cycloergostane skeleton, physalin Y ( 1), physalin Z ( 2), physalin I ( 6), and physalin II ( 7), were isolated from the 80% EtOH extract of calyces from Physalis alkekengi var. franchetii together with 11 known steroids ( 3- 5 and 8- 15) and eight flavonoids ( 16- 23). The structures of the new compounds were elucidated primarily on the basis of 1D and 2D NMR and mass spectroscopic studies. The relative configuration of the 3-OH group of 3, 4, and 5 was also established or re-established. The inhibitory effects of compounds 1- 23 on nitric oxide production in lipopolysaccaride-activated macrophages were evaluated.