To screen potential drugs for the treatment of acute Liver Injury(ALI)through network pharmacology and mitochondrial dynamics,and to investigate their actions and mechanisms.Based on the commonly utilized Liver Pure Tablets and Liver-Protecting Capsules in the market,a com-ponent library of liver disease drugs was screened and established.Pharmacological anchoring anal-ysis was carried out.Potential liver disease therapeutic drugs were screened out through molecular docking,and feedback verification was performed using animal experiments.Acute liver injury mouse models were established through excessive induction with acetaminophen(APAP),and the histopathological changes of liver tissues were examined.The protective effect of the drug on ALI was evaluated by detecting alanine aminotransferase(ALT),aspartate aminotransferase(AST),superoxide dismutase(SOD),catalase(CAT),glutathione(GSH),and malondialdehyde(MDA)using enzyme-linked immunosorbent assay(ELISA).qRT-PCR was employed to detect peroxi-some proliferator-activated receptor gamma coactivator 1-alpha(PPARG1A),mitofusin 1(MFN1),mitofusin 2(MFN2),dynamin-related protein 1(DRP1),optic atrophy 1 protein(OP A1),Steroid receptor coactivator(SRC),and advanced glycosylation end-product specific re-ceptor(AGER)to explore the protective mechanism of the drug on ALI.The result showed that Network pharmacology identified a total of 662 intersection targets of three types of prescription drugs and ALI.Eventually,72 core targets were screened out.Pathway enrichment analysis indi-cates that the potential mechanism might be associated with the lipid and atherosclerosis signaling pathways.The results of the relevant molecular docking indicate that the most likely optimal drug might be emodin(EMO).EMO ameliorated the pathological damage in mice with acute liver inju-ry,significantly decreased the contents of transferase factors ALT and AST,simultaneously in-creased the contents of antioxidant enzymes CAT,GSH and SOD,and reduced the content of oxi-dative metabolic end product MDA.It also upregulated the mRNA expression levels of MFN1、MFN2,OPA1,DRP1,SRC and PPARGC1A proteins in liver tissue,and inhibited the mRNA ex-pression level of AGER protein.The drug EMO,jointly screened out by network pharmacology through anchoring and molecular docking,might promote mitochondrial fusion metabolism,allevi-ate liver oxidative stress,and improve liver injury in ALI mice via the Lipid and atherosclerosis pathway.

To screen potential drugs for the treatment of acute Liver Injury(ALI)through network pharmacology and mitochondrial dynamics,and to investigate their actions and mechanisms.Based on the commonly utilized Liver Pure Tablets and Liver-Protecting Capsules in the market,a com-ponent library of liver disease drugs was screened and established.Pharmacological anchoring anal-ysis was carried out.Potential liver disease therapeutic drugs were screened out through molecular docking,and feedback verification was performed using animal experiments.Acute liver injury mouse models were established through excessive induction with acetaminophen(APAP),and the histopathological changes of liver tissues were examined.The protective effect of the drug on ALI was evaluated by detecting alanine aminotransferase(ALT),aspartate aminotransferase(AST),superoxide dismutase(SOD),catalase(CAT),glutathione(GSH),and malondialdehyde(MDA)using enzyme-linked immunosorbent assay(ELISA).qRT-PCR was employed to detect peroxi-some proliferator-activated receptor gamma coactivator 1-alpha(PPARG1A),mitofusin 1(MFN1),mitofusin 2(MFN2),dynamin-related protein 1(DRP1),optic atrophy 1 protein(OP A1),Steroid receptor coactivator(SRC),and advanced glycosylation end-product specific re-ceptor(AGER)to explore the protective mechanism of the drug on ALI.The result showed that Network pharmacology identified a total of 662 intersection targets of three types of prescription drugs and ALI.Eventually,72 core targets were screened out.Pathway enrichment analysis indi-cates that the potential mechanism might be associated with the lipid and atherosclerosis signaling pathways.The results of the relevant molecular docking indicate that the most likely optimal drug might be emodin(EMO).EMO ameliorated the pathological damage in mice with acute liver inju-ry,significantly decreased the contents of transferase factors ALT and AST,simultaneously in-creased the contents of antioxidant enzymes CAT,GSH and SOD,and reduced the content of oxi-dative metabolic end product MDA.It also upregulated the mRNA expression levels of MFN1、MFN2,OPA1,DRP1,SRC and PPARGC1A proteins in liver tissue,and inhibited the mRNA ex-pression level of AGER protein.The drug EMO,jointly screened out by network pharmacology through anchoring and molecular docking,might promote mitochondrial fusion metabolism,allevi-ate liver oxidative stress,and improve liver injury in ALI mice via the Lipid and atherosclerosis pathway.

Objective: To explore the risk factors for prognosis in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF), and to establish a prognostic model. Methods: A total of 193 patients diagnosed with HBV-ACLF who were admitted to the Department of Infectious Diseases of the Third Hospital of Hebei Medical University were collected from 1st January 2013 to 1st November 2018 as a derivation cohort. Thirty-five patients diagnosed with HBV-ACLF who were admitted to the Fifth Hospital of Shijiazhuang during the period from 1st July 2017 to 1st November 2018 were collected as a validation cohort. The survival condition of all patients at week 12 of admission was observed. The risk factors associated with short-term prognosis were analyzed by using multivariate logistic regression analysis, and a logistic regression equation prediction model was established and verified. The diagnostic performance of the prognostic model was evaluated using the receiver operating characteristic (ROC) curve, and was compared with model for end-stage liver disease (MELD) scoring system, Child-Turcotte-Pugh (CTP) scoring system, sequential organ failure assessment (SOFA) scoring system and chronic liver failure (CLIF)-SOFA scoring system. Results: Multivariate logistic regression analysis showed that age (odds ratio(OR)=2.133, 95% confidence interval(CI)1.033-4.405), total bilirubin (OR=3.371, 95%CI 1.610-7.060), serum creatinine (OR=4.448, 95%CI 1.697-11.661), hepatic encephalopathy (OR=5.313, 95%CI 2.463-11.461), and ascites (OR=2.959, 95%CI 1.410-6.210) were independent risk factors for predicting the short-term prognosis of patients with HBV-ACLF. The newly established logistic regression model (LRM)=-1.726+ 0.757×age+ 1.215×total bilirubin+ 1.049 2×serum creatinine+ 1.670×hepatic encephalopathy (with=1, without=0) + 1.085×ascites (with=1, without=0). The area under the ROC curve of the LRM for predicting the short-term prognosis of patients with HBV-ACLF was 0.82 (95%CI 0.76-0.88). Furthermore, the areas under the ROC curve of the models of MELD, CTP, SOFA, CLIF-SOFA were 0.67 (95%CI 0.60-0.75), 0.73 (95%CI 0.66-0.80), 0.77 (95%CI 0.70-0.83) and 0.72 (95%CI 0.65-0.80), respectively. The ROC-area under curve of the validation cohort was 0.81 (95%CI 0.65-0.97). Conclusions Age, total bilirubin, serum creatinine, hepatic encephalopathy, and ascites are independent risk factors for the prognosis of HBV-ACLF. The prognostic model established based on these factors can accurately predict the patients′ short-term prognosis, which is superior to MELD, CTP, SOFA and CLIF-SOFA.

Objective To investigate SNP and distribution of haplotypes in differentially m ethylated region (DMR) upstream of H19 gene in Chinese Korean nationality in order to provide basic data for forensic application and population genetics research. Methods One hundred and one blood sam ples from unrelat-ed Chinese Korean individuals and 14 blood sam ples from 5 Chinese Korean intergenerational fam ilies which known genetic relationship were collected. The SNP in DMRupstream of H19 gene were investi-gated by PCR-cycle sequencing and McrB Cdigestion followed by PCR . The haplotypes detected by parentally im printed allele (PIA) m ethod and relevant genetic param eters were calculated. Results Thirteen SNPs (rs10840167, rs2525883, rs12417375, rs4930101, rs2525882, rs2735970, rs2735971, rs11042170, rs2735972, rs10732516, rs2071094, rs2107425, and rs4930098) and five haplotypes were detected in 1 174 bp target product in DMRupstream of H19 gene, with 9 SNPs having high discrim ination power as good genetic markers. The average gene diversity (GD) of haplotypes was 0.714. The maternal haplotype was confirm ed correctly by PIAm ethod from McrB C-digested products of genom ic DNA. Conclusion High polym orphism sexist in DMRupstream of H19 gene in Chinese Korean nationality. And determ ination of the maternal haplotype could furtherm ore enhance the forensic identification efficiency of im printed gene.