Integrated causal inference modeling uncovers novel causal factors and potential therapeutic targets of Qingjin Yiqi granules for chronic fatigue syndrome

作     者：Junrong Li Xiaobing Zhai Jixing Liu Chi Kin Lam Weiyu Meng Yuefei Wang Shu Li Yapeng Wang Kefeng Li 

作者机构：Faculty of Applied SciencesMacao Polytechnic UniversityMacao SARChina Center for Artificial Intelligence Driven Drug DiscoveryFaculty of Applied SciencesMacao Polytechnic UniversityMacao SARChina National Key Laboratory of Chinese Medicine ModernizationTianjin Key Laboratory of TCM Chemistry and AnalysisTianjin University of Traditional Chinese MedicineTianjinChina Haihe Laboratory of Modern Chinese MedicineTianjinChina 

出 版 物：《Acupuncture and Herbal Medicine》 (针灸和草药（英文）)

年 卷 期：2024年第4卷第1期

页      面：122-133页

学科分类：1008[医学-中药学(可授医学、理学学位)] 1006[医学-中西医结合] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by an internal fund from Macao Polytechnic University(RP/FCSD-02/2022) 

主　　题：Causal factors Causal graph analysis Chronic fatigue syndrome Drug targets Mendelian randomization Qingjin Yiqi 

摘      要：Objective:Chronic fatigue syndrome(CFS)is a prevalent symptom of post-coronavirus disease 2019(COVID-19)and is associated with unclear disease *** herbal medicine Qingjin Yiqi granules(QJYQ)constitute a clinically approved formula for treating post-COVID-19;however,its potential as a drug target for treating CFS remains largely *** study aimed to identify novel causal factors for CFS and elucidate the potential targets and pharmacological mechanisms of action of QJYQ in treating ***:This prospective cohort analysis included 4,212 adults aged≥65 years who were followed up for 7 years with 435 incident CFS *** modeling and multivariate logistic regression analysis were performed to identify the potential causal determinants of CFS.A proteome-wide,two-sample Mendelian randomization(MR)analysis was employed to explore the proteins associated with the identified causal factors of CFS,which may serve as potential drug ***,we performed a virtual screening analysis to assess the binding affinity between the bioactive compounds in QJYQ and CFS-associated ***:Among 4,212 participants(47.5%men)with a median age of 69 years(interquartile range:69–70 years)enrolled in 2004,435 developed CFS by *** graph analysis with multivariate logistic regression identified frequent cough(odds ratio:1.74,95%confidence interval[CI]:1.15–2.63)and insomnia(odds ratio:2.59,95%CI:1.77–3.79)as novel causal factors of ***-wide MR analysis revealed that the upregulation of endothelial cell-selective adhesion molecule(ESAM)was causally linked to both chronic cough(odds ratio:1.019,95%CI:1.012–1.026,P=2.75 e^(−05))and insomnia(odds ratio:1.015,95%CI:1.008–1.022,P=4.40 e^(−08))in *** major bioactive compounds of QJYQ,ginsenoside Rb2(docking score:−6.03)and RG4(docking score:−6.15),bound to ESAM with high affinity based on virtual ***:Our integrated analytical framework combining epidemiological,genet