Objective To identify the core genes in liver cirrhosis through bioinformatics screening,construct a network of their in-teractions,and explore the pathways and clinical significance of these genes.Methods Transcriptome datasets were obtained from the GEO database to screen for differential gene expression.GO analysis and KEGG pathway enrichment analysis were performed.A protein interaction network was constructed using the STRING database.The top 10 core genes were identified using the MCC algorithm,and the miRNA-mRNA regulatory relationships were established.The validation of the core gene expression was conducted with additional GEO datasets and clinical samples,and ROC analysis was used to evaluate the clinical significance.Results A total of 47 upregulated and 34downregulated genes were identified in this study.These differential genes were involved in biological processes such as extracellular matrix organization,urogenital system development,and cellular responses to copper,cadmium,and zinc ions.They performed the inter-action pathway function through the ECM receptor.The top 10 core genes were SPP1,SOX9,COL1A2,TAGLN,ACTA2,CCND1,CD24,VWF,JAG1 and MMP7.The expression of the core genes was increased in cirrhotic tissues,among which CCND1,CD24 and VWF showed high accuracy in distinguishing the cirrhotic tissues(AUC＞0.90).Conclusion The expression of the core genes in liver cirrhosis is increased and may lead to liver fibrosis through the ECM receptor interaction pathway,while the CCND1,CD24 and VWF could serve as effective targets for the diagnosis and treatment of liver cirrhosis.

Objective To identify the core genes in liver cirrhosis through bioinformatics screening,construct a network of their in-teractions,and explore the pathways and clinical significance of these genes.Methods Transcriptome datasets were obtained from the GEO database to screen for differential gene expression.GO analysis and KEGG pathway enrichment analysis were performed.A protein interaction network was constructed using the STRING database.The top 10 core genes were identified using the MCC algorithm,and the miRNA-mRNA regulatory relationships were established.The validation of the core gene expression was conducted with additional GEO datasets and clinical samples,and ROC analysis was used to evaluate the clinical significance.Results A total of 47 upregulated and 34downregulated genes were identified in this study.These differential genes were involved in biological processes such as extracellular matrix organization,urogenital system development,and cellular responses to copper,cadmium,and zinc ions.They performed the inter-action pathway function through the ECM receptor.The top 10 core genes were SPP1,SOX9,COL1A2,TAGLN,ACTA2,CCND1,CD24,VWF,JAG1 and MMP7.The expression of the core genes was increased in cirrhotic tissues,among which CCND1,CD24 and VWF showed high accuracy in distinguishing the cirrhotic tissues(AUC＞0.90).Conclusion The expression of the core genes in liver cirrhosis is increased and may lead to liver fibrosis through the ECM receptor interaction pathway,while the CCND1,CD24 and VWF could serve as effective targets for the diagnosis and treatment of liver cirrhosis.

Objective To assess the efficacy and safety of 100 mg or 200 mg yimitasvir phosphate combined with sofosbuvir in patients with non-cirrhotic chronic hepatitis C virus ( HCV) genotype 1 infection who were treatment-na?ve or had a virologic failure to prior interferon-based treatment.Methods A multicenter, randomized, open-label, phase 2 clinical trial was conducted.The patients were randomly assigned to yimitasvir phosphate 100 mg+sofosbuvir 400 mg group (Group 100 mg) and yimitasvir phosphate 200 mg+sofosbuvir 400 mg group ( Group 200 mg) in a 1∶1 ratio with the stratified factors of " treatment-naive" or"treatment-experienced" for 12 weeks and followed up for 24 weeks after the end of treatment.During the clinical trial, HCV RNA was tested in all patients.Resistance of virus in patients who didn′t achieved sustained virological response (SVR) was monitored.Safety and tolerability were assessed by monitoring adverse events , physical examination , laboratory examination, electrocardiogram, and vital signs during the study.The primary end point was SVR12 after the end of therapy.Descriptive statistics were used for categorical variables and eight descriptive statistics were used for continuous variables.Descriptive statistics were used and summarized according to HCV genotypes and treatment groups.Safety data were presented using descriptive statistics and summarized according to treatment groups.Results A total of 174 subjects were screened from July 31, 2017 to September 26, 2018.One hundred and twenty-nine patients were successfully enrolled and received treatment , and 127 completed the study.There were 64 patients and 65 patients assigned to Group 100 mg and Group 200 mg, respectively.Among the 129 patients who underwent randomization and were treated , 18.6% were treatment-experienced and: 100%were HCV genotype 1b infection.The total SVR rate was 98.4%(127／129), with 98.4%(63／64, 95%confidence interval [CI]: 91.60%-99.96%) in the Group 100 mg, and 98.50%(64／65, 95%CI: 91.72%-99.96%) in the Group 200 mg.There was no significant difference between the two groups (χ2 ＝0.000 2, P＝0.989 2).The SVR rates in treatment-naive group and treatment-experienced group were 98.10%(95%CI: 93.29%-99.77%) and 100.00%(24／24, 95%CI: 85.75%-100.00%), respectively.Virological failure during treatment ( including breakthrough , rebound and poor efficacy) and relapse after treatment did not occur during the trial.By Sanger sequencing , 11.6%(15／129) patients had baseline NS5A Y93H／Y or Y93H resistance-associated substitutions ( RAS), 1.6%( 2／129) patients had baseline NS5A L31M RAS.No mutation was observed in NS5B S282 at baseline.There was no S282 mutation in HCV NS5B.A total of 100 (77.5%) subjects had adverse events.No adverse events ≥Grade 3 or severe adverse events related to the study treatment.No patient prematurely discontinued study treatment owing to an adverse event.No life-threatening adverse event was reported.Conclusion Twelve weeks of yimitasvir phosphate 100 mg or 200 mg combined with sofosbuvir 400 mg daily is a highly effective and safe regimen for patients without cirrhosis with HCV genotype 1b infection who had not been treated previously or had a virologic failure to prior interferon-based treatment.

Objective To investigate microRNA(miRNA)expression profiles in peripheral blood and skin lesions of patients with psoriasis vulgaris(PV), and to seek miRNAs consistently expressed in peripheral blood and skin lesions. Methods A miRNA microarray was used to screen differentially expressed miRNAs in skin lesions and peripheral blood samples between 17 patients with PV and 4 healthy human controls, and real?time fluorescence?based quantitative PCR(RT?qPCR)to verify the differentially expressed miRNAs. The correlations of these differentially expressed miRNAs with psoriasis area and severity index(PASI)score were assessed by Pearson correlation analysis. Results The Agilent human miRNA microarray profiling revealed 15 miRNAs consistently expressed in skin lesions and peripheral blood of patients with PV. Of the 15 miRNAs, 7 were verified as consistently expressed miRNAs by RT?qPCR. Among the 7 miRNAs, the expression intensity of miR?30e?5p, miR?192?5p, miR?17?3p and miR?1227?5p was negatively correlated with PASI scores(all P<0.05), while that of miR?125b?5p, miR?642a?5p and miR?29a?5p was uncorrelated with PASI scores(all P>0.05). Conclusion Some miRNAs are consistently expressed in skin lesions and plasma of PV patients, which are expected to serve as biomarkers for evaluation of psoriasis severity.