ABSTRACT
Objective:To explore the multi-component， multi-target and multi-pathway mechanism of Astragali Radix against immunoglobulin A nephropathy （IgAN） by network pharmacology， aiming to provide evidence for its basic research and clinical application. Method:The active chemical components and targets of Astragali Radix and targets associated with IgAN were obtained by literature mining and GeneCards， Traditinal Chinese Medicine Integrated Database （TCMID）， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） databases. Cytoscape 3.7.1 software was used to draw network interaction diagrams. The key targets of Astragali Radix against IgAN were searched by network topology. Gene ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis involved in the targets were analyzed by different packages in R programming language. On this basis， cell experiments <italic>in vitro</italic> were carried out to verify the activation effect of astragaloside Ⅳ on phosphatidylinositol 3-kinase/protein kinase B/tumor suppressor gene protein 53 （PI3K/Akt/p53） signaling pathway of human mesangial cells. Result:A total of 25 active components and 49 ingredient-disease targets of Astragali Radix were screened. The GO enrichment analysis included 84 items， which were related to nuclear hormone receptor binding， nuclear receptor activity， deoxyribonucleic acid binding transcriptional activation activity and other aspects. The KEGG pathway enrichment analysis included 88 KEGG pathways， which were closely related to PI3K/Akt signaling pathway， hypoxia inducible factor-1 （HIF-1） signaling pathway， advanced glycation end product/receptor of advanced glycation end product （AGE/RAGE） signaling pathway and others. Cell experiments <italic>in vitro </italic>confirmed that astragaloside Ⅳ could effectively inhibit the platelet derived growth factor-BB （PDGF-BB）-induced proliferation of human mesangial cells by regulating PI3K/Akt/p53 signaling pathway. Conclusion:The active ingredients of Astragali Radix may play a role in the treatment of IgAN by acting on targets and pathways related to apoptosis， oxidative stress， inflammation response and others， providing ideas and directions for the new drug development and mechanism study of IgAN.
ABSTRACT
Purpose@#The objective of the current study was to examine the potential effects of surgery start times (morning vs. afternoon) on the long-term prognosis of patients after hepatic resection (HR) for hepatocellular carcinoma (HCC). @*Methods@#All eligible patients were divided into 2 groups according to the start time of surgery: group M (morning surgery, 8 AM–1 PM) and group A (afternoon surgery, 1 PM–6 PM). Clinicopathologic and surgical parameters, as well as oncologic outcomes were compared between the 2 groups. @*Results@#In total, 231 patients were included in the study. There was no difference in age, body mass index, comorbidities, tumor size, tumor location, tumor stages, surgical procedures, or surgical margin between morning and afternoon surgery (all P > 0.05). In contrast, patients in group M experienced longer operation duration than those in group A (median, 240 minutes vs. 195 minutes, P = 0.004). However, no differences of overall survival were observed between morning and afternoon surgery groups in the whole cohort or stratified by surgical margin (all P > 0.05). @*Conclusion@#Surgery start times during the work day have no measurable influence on patient outcome following curative HR for HCC, indicating good self-regulation and professional judgment of surgeons for progressive fatigue during surgery.
ABSTRACT
Purpose@#The objective of the current study was to examine the potential effects of surgery start times (morning vs. afternoon) on the long-term prognosis of patients after hepatic resection (HR) for hepatocellular carcinoma (HCC). @*Methods@#All eligible patients were divided into 2 groups according to the start time of surgery: group M (morning surgery, 8 AM–1 PM) and group A (afternoon surgery, 1 PM–6 PM). Clinicopathologic and surgical parameters, as well as oncologic outcomes were compared between the 2 groups. @*Results@#In total, 231 patients were included in the study. There was no difference in age, body mass index, comorbidities, tumor size, tumor location, tumor stages, surgical procedures, or surgical margin between morning and afternoon surgery (all P > 0.05). In contrast, patients in group M experienced longer operation duration than those in group A (median, 240 minutes vs. 195 minutes, P = 0.004). However, no differences of overall survival were observed between morning and afternoon surgery groups in the whole cohort or stratified by surgical margin (all P > 0.05). @*Conclusion@#Surgery start times during the work day have no measurable influence on patient outcome following curative HR for HCC, indicating good self-regulation and professional judgment of surgeons for progressive fatigue during surgery.