1.Prenatal ultrasonographic diagnosis of fetal central nervous system abnormalities during the first trimester
Fangming HUA ; Ling REN ; Qingxin ZENG ; Ling CHENG ; Mudan WU ; Jun YE
Chinese Journal of Ultrasonography 2017;26(5):410-413
Objective To investigate the display status of ultrasonography imaging check in central nervous system (CNS) in infants of early pregnancy and the diagnostic value of CNS malformation in infants of early pregnancy.Methods Gestational weeks of 2 751 enrolled subjects were divided according to the ultrasonic measurement of the crown rump length (CRL):11-11 +6 weeks group,12-12+6 weeks group,and 13-13 + 6 weeks group,prenatal ultrasound were performed to examine fetal CNS anatomy in infants of early pregnancy,record the display status in each groups of infants and analyze the relationship between the display situation and gestational age.Results Fourteen cases of fetal CNS malformation (20 malformations) in total were found by prenatal ultrasound,and the incidence of CNS malformation was about 5.09% (14/2 571).Wherein,12 cases of early pregnancy were diagnosed,and 2 cases of middle pregnancy were diagnosed.The sensitivity of ultrasound of early pregnancy in the diagnosis of fetal CNS malformation was 85.71%.In the group of research,the ultrasound display ratios of 11-11+6 weeks group,12-12+6 weeks group and 13-13+6 weeks group were 96.73%,97.94%,98.06%,respectively.There was no significant difference in early pregnancy fetal CNS display ratio among groups (x2 =1.56,v =2,x2< x0.05.2 =5.99,P > 0.05).Conclusions The display rate of CNS structure in infants of early pregnancy (11-13+6 weeks)is higher,and is not affected by gestational weeks.Prenatal ultrasound can effectively diagnose CNS severe malformation in infants of early pregnancy.
2.Study on Molecular Mechanism of Xiaochaihu Decoction for Sepsis Based on TCMIP Platform
Qingxin YANG ; Hongjun LYU ; Xiaobo WANG ; Jinsong REN ; Nan ZENG
China Pharmacy 2019;30(11):1506-1512
OBJECTIVE: To investigate the substance basis and mechanism of Xiaochaihu decoction in treatment of sepsis, and to provide reference for clinical application and R&D of the decoction. METHODS: Based on TCM integrative pharmacology platform (TCMIP), chemical component analysis of Xiaochaihu decoction, disease target prediction, gene function and pathway enrichment analysis were all performed. The multi-dimensional network relationship of “TCM-chemical components-core targets-key pathways” was established, and the mechanism of Xiaochaihu decoction in treatment of sepsis was investigated. RESULTS: A total of 224 predicted chemical ingredients of Xiaochaihu decoction (including saikoside, ginsenoside, glycyrrhizin, etc.) interacted with 118 key targets about sepsis, including PF4, MYD88, TLR4, CD14, NOS3, etc. Its anti-sepsis mechanism involved nervous system, endocrine system, immune response and energy metabolism, etc. CONCLUSIONS: Based on “neuronal- endocrine-immune-metabolism”, Xiaochaihu decoction achieved its role in regulating sepsis by multi-level, multi-channel and multi-channel. This research may reveal the potential mechanism of Xiaochaihu decoction for sepsis, and the prescription provide theoretical basis for further experimental research of pharmacodynamic substance basis and mechanism of action.
3.Targeting a novel inducible GPX4 alternative isoform to alleviate ferroptosis and treat metabolic-associated fatty liver disease.
Jie TONG ; Dongjie LI ; Hongbo MENG ; Diyang SUN ; Xiuting LAN ; Min NI ; Jiawei MA ; Feiyan ZENG ; Sijia SUN ; Jiangtao FU ; Guoqiang LI ; Qingxin JI ; Guoyan ZHANG ; Qirui SHEN ; Yuanyuan WANG ; Jiahui ZHU ; Yi ZHAO ; Xujie WANG ; Yi LIU ; Shenxi OUYANG ; Chunquan SHENG ; Fuming SHEN ; Pei WANG
Acta Pharmaceutica Sinica B 2022;12(9):3650-3666
Metabolic-associated fatty liver disease (MAFLD), which is previously known as non-alcoholic fatty liver disease (NAFLD), represents a major health concern worldwide with limited therapy. Here, we provide evidence that ferroptosis, a novel form of regulated cell death characterized by iron-driven lipid peroxidation, was comprehensively activated in liver tissues from MAFLD patients. The canonical-GPX4 (cGPX4), which is the most important negative controller of ferroptosis, is downregulated at protein but not mRNA level. Interestingly, a non-canonical GPX4 transcript-variant is induced (inducible-GPX4, iGPX4) in MAFLD condition. The high fat-fructose/sucrose diet (HFFD) and methionine/choline-deficient diet (MCD)-induced MAFLD pathologies, including hepatocellular ballooning, steatohepatitis and fibrosis, were attenuated and aggravated, respectively, in cGPX4-and iGPX4-knockin mice. cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes. Knockdown of iGPX4 by siRNA alleviated lipid stress, ferroptosis and cell injury. Mechanistically, the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress, and thus promotes ferroptosis. Co-immunoprecipitation and nano LC-MS/MS analyses confirmed the interaction between iGPX4 and cGPX4. Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis, and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.