Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is un-known.Here,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the acti-vation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signalling.Mechanistically,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphory-lation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK signalling.Knockdown of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by acti-vating TGR5.Consistently,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines.Overall,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.

OBJECTIVE: To explore the clinical and genetic characteristics of a patient with 17-hydroxylase/17,20-lyase deficiency. METHODS: The patient was infertile without contraception. Laboratory examination showed her chromosomal karyotype to be 46, XX. DNA sequencing was performed to detect variants of CYP17A1 gene in the patient and her family members. RESULTS: Sanger sequencing revealed that the patient has carried homozygous variant c.1486C>T in the exon 8 of the CYP17A1 gene, which resulted in substitution of arginine by cysteine (p.Arg496Cys). Her family members were all heterozygotes for the same variant. CONCLUSION Homozygous variant of the CYP17A1 gene c.1486C>T probably underlay the 17-hydroxylase deficiency in this patient. Above finding has enabled accurate genetic counseling and prenatal diagnosis for her family.

Objective To examine whether autophagy plays a role in the development of chronic intermittent hypoxia-induced cardiac hypertrophy,whether resveratrol can reverse the process by modulating autophagy and what molecular pathways are involved.Methods Rats were randomly divided into four groups.Eight rats were treated with normoxia (control group),eight were exposed to chronic intermittent hypoxia (CIH) (CIH group),eight were exposed to CIH plus resveratrol (RSV) (CIH+RSV group) and eight were exposed to CIH,RSV and chloroquine (Cq) (CIH + RSV+ Cq group).After treatment for seven weeks,the levels of LC3,Beclin,P62,ANP,β-MHC,AMPK,P-AMPK,mTOR,P-mTOR and cleaved-caspase 3 were detected by Western blot.The area of cardiomyocytes and the ratio of brotic area to the total area were obtained by HE and Sirius Red staining.Results Rats in the CIH+RSV group were associated with an increased ratio of LC3 Ⅱ /LC3 Ⅰ,increased Beclin levels and decreased P62 levels,compared with those in the control and CIH groups (all P＜0.05).After chloroquine injection,the ratio of LC3 Ⅱ/LC3 Ⅰ was markedly increased in the CIH+RSV+Cq group,compared with that in the CIH+RSV group (all P＜0.05).Moreover,the CIH group was associated with significantly increased area of cardiomyocytes,ratio of fibrotic area to the total area,and levels of ANP,β-MHC and cleaved-caspase 3,compared with the control group (all P＜0.05).However,their values markedly decreased in the CIH +RSV group and significantly increased in the CIH+RSV+Cq group,compared with the CIH group (all P＜0.05).Furthermore,there were tendencies of progressively increased levels of P-AMPK and decreased levels of P-mTOR among the control group,CIH group and CIH+RSV group (both P ＜ 0.05).However,levels of AMPK and mTOR were similar among the three groups (P ＞ 0.05).Conclusions Chronic intermittent hypoxia and resveratrol can affect the level of cardiac hypertrophy by autophagy through activating the AMPK/mTOR pathway.