1.Integrated evidence chain (Eff-iEC) based effectiveness evaluation of a multifunctional traditional Chinese medicine formula: Taking Xiaoyao San as an example
Caiping HE ; Ye LUO ; Zhiqi LI ; Haocheng YANG ; Lu LIU ; Yingjie XU ; Xiaoyan CHEN ; Siqi HUANG ; Jincai WEN ; Xiaoyan ZHAN ; Zhaofang BAI ; Xu ZHAO ; Xiaohe XIAO
Science of Traditional Chinese Medicine 2026;4(1):96-103
The study focuses on the concept of multifunctional traditional Chinese medicine (TCM) formulas and aims to evaluate the efficacy of the classical formula Xiaoyao San (逍遥散). Study employs the integrated evidence chain (Eff-iEC) method to organize, integrate, and evaluate its therapeutic efficacy in treating different diseases with the same therapy, and to investigate the feasibility of using Eff-iEC to evaluate the multifunctionality of TCM formulas. The evaluation covered Xiaoyao San's therapeutic effects on depression, premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Concurrently, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system was used for evaluation, and authoritative medical documents were incorporated to corroborate the recognition of Xiaoyao San within the medical community. Depression and menopausal syndrome received higher ratings than other conditions in the Eff-iEC, GRADE, and Medical Community Recognition assessments. The Eff-iEC evidence grade for Xiaoyao San was rated as "High" or above for chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Premenstrual syndrome received a "Moderate +" rating. The GRADE evidence level was "Low-〇〇⨁⨁" for depression, premenstrual syndrome, and chronic hepatitis; "Moderate-〇⨁⨁⨁" for dyspepsia and menopausal syndrome; and "Very Low-〇〇〇⨁" for irritable bowel syndrome. Depression and menopausal syndrome had the highest inclusion frequency, appearing in all 4 categories. Premenstrual syndrome, chronic hepatitis, and dyspepsia are not recommended in Western medical guidelines, but they are included in TCM guidelines, the China National Basic Medical Insurance Drug List, and the China National Essential Drug List. Irritable bowel syndrome appears only in the China National Basic Medical Insurance Drug List and China National Essential Drug List. The evaluation results obtained using the Eff-iEC method align with Medical Community Recognition, providing an objective and comprehensive assessment of Xiaoyao San's efficacy. The findings suggest that Xiaoyao San has strong evidence for treating depression and menopausal syndrome. However, further experimental and clinical trials are needed to assess its efficacy in treating premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, and dyspepsia. These results support the clinical efficacy and rational use of Xiaoyao San, expand the application scope of the Eff-iEC method, and offer valuable insights and methodological references for the comparative evaluation of multifunctional TCM formulas.
2.A study on the correlation between regional hemodynamics and plaque morphology of middle cerebral artery in atherosclerotic stenosis using four-dimensional flow MRI
Yuanbin ZHAO ; Xiaoyan BAI ; Chao ZHANG ; Xue ZHANG ; Tong CHEN ; Xun PEI ; Yuehua PU ; Ligang SONG ; Binbin SUI
Chinese Journal of Radiology 2025;59(3):261-268
Objective:To explore the hemodynamic characteristics of the middle cerebral artery (MCA) in atherosclerotic stenosis using four-dimensional flow (4D Flow) MRI, and combining high-resolution magnetic resonance vessel wall imaging (HR VW-MRI) to analyze the relationship between hemodynamics and the degree of stenosis, as well as the morphological characteristics of plaques.Methods:The study was a cross-sectional study. A total of 24 patients with middle cerebral artery(MCA) M1 atherosclerotic stenosis and 10 age and sex matched healthy controls (HC group) were prospectively recruited from September 2018 to March 2021 at Beijing Tiantan Hospital, Capital Medical University. All subjects underwent MRI examination. The hemodynamic of MCA were collected by 4D Flow MRI, and the hemodynamic parameters of proximal and distal MCA stenosis were calculated by blood flow post-processing software, including average blood flow rate (FR avg), average blood flow velocity (V avg), peak blood flow velocity (V pk), time average wall shear stress (TAWSS), minimum wall shear stress (WSS min) and oscillatory shear index (OSI). The differences in hemodynamic parameters among the proximal and distal ends of MCA stenosis and the HC group were compared using one-way ANOVA or Kruskal-Wallis H test. The stenosis rate and characteristics of MCA plaque were analyzed by HR VW-MRI, including remodeling index (RI), normalized wall index (NWI) and plaque length. Pearson or Spearman correlation analysis was used to explore the correlation between stenosis rate and hemodynamic parameters. Taking the stenosis rate as the control variable, partial correlation analysis was used to explore the correlation between plaque morphological characteristics and hemodynamic parameters. Results:There were statistically significant differences in FR avg, V avg, V pk, TAWSS, OSI, WSS min among the proximal and distal stenosis of MCA and HC groups ( P<0.05). The proximal end of the MCA stenosis had significantly higher FR avg, V avg, TAWSS and WSS min than those of the distal end of the stenosis ( P<0.01). The FR avg, V avg, V pk, TAWSS, and WSS min in the distal end of MCA stenosis were lower than those in the HC group, while the OSI was higher than that in the HC group ( P<0.01). The correlation analysis results showed that the MCA proximal V pk ( r=-0.425, P=0.027) and distal V pk ( r=-0.538, P=0.004) were negatively correlated with the diameter stenosis rate. When the stenosis rate was taken as the control factor, in the MCA proximal stenosis, V avg ( r=0.553, P=0.003), TAWSS ( r=0.543, P=0.004) and WSS min ( r=0.547, P=0.004) were positively correlated with RI, proximal OSI was negatively correlated with RI ( r=-0.492, P=0.011), and was positively correlated with the plaque length ( r=0.437, P=0.026). At the distal end of the stenosis, V pk was negatively correlated with NWI ( r=-0.556, P=0.003), OSI was negatively correlated with RI ( r=-0.511, P=0.008), NWI ( r=-0.390, P=0.049). TAWSS was positively correlated with RI ( r=0.393, P=0.047). Conclusions:The 4D Flow MRI demonstrates characteristic hemodynamic changes in the proximal and distal ends of the stenotic MCA. The local hemodynamic characteristics of the stenotic MCA are correlated with plaque morphological parameters, including lumen stenosis, plaque load, and RI. It suggests an interaction between the occurrence and development of MCA plaque and local hemodynamic changes.
3.Characteristics and advantages in finite element analysis techniques in knee biomechanics
Huanxuan GUO ; Zhijie KANG ; Xiaolong BAI ; Xiaoyan TIAN ; Feng JIN
Chinese Journal of Tissue Engineering Research 2025;29(15):3253-3261
BACKGROUND:Finite element analysis is an advanced computer-based engineering technique that uses mathematical approximations to simulate the human body.This method accurately reflects the biomechanical characteristics within the knee,providing a powerful tool for understanding knee disease pathogenesis,optimizing surgical protocols,and developing new implant materials.OBJECTIVE:To review the establishment of finite element modelling of the knee joint and its application in the study of knee joint diseases,and look forward to the future development trend.METHODS:The first author searched the PubMed and EI databases in April 2024 by applying a computer with English search terms"finite element analysis,FEA,knee joint,finite element model,knee biomechanics,knee osteoarthritis,knee prosthesis,knee ligaments,meniscus"and searched CNKI and WanFang databases with Chinese search terms"finite element analysis,finite element model,knee joint,biomechanics,osteoarthritis,computational model,knee prosthesis,knee ligament,meniscus."Finally,75 papers were included in the analysis.RESULTS AND CONCLUSION:(1)Finite element analysis method uses medical imaging data to obtain a three-dimensional human model,simplifies the complex human joint structure into finite and interconnected units,and visually displays the internal stress distribution of the knee joint by applying external loads to the model.(2)The researchers deeply study the internal stress and strain distribution of the knee joint under different working conditions by means of finite element analysis,revealing the overloading of the articular cartilage and the decrease of load in some areas when the balance of the internal load distribution of the knee joint is changed,and that such long-term abnormal stresses cause deformation,wear and tear,and eventual loss of cartilage,which is crucial for understanding how biomechanical factors cause degenerative changes of the knee joint.(3)The effect of physical therapy methods such as Tai Chi and gait adjustment in patients with osteoarthritis of the knee joint was evaluated by finite element analysis,and the results showed that these treatments reduced the overloading of the cartilage,which provided a scientific theoretical basis for clinical treatment.(4)Clinicians are able to optimize surgical treatment strategies by performing three-dimensional reconstruction,data measurement,and simulation of surgery before surgery through finite element analysis.Furthermore,the mechanical characteristics of different prostheses can be simulated to improve the shape,material,and fixation of the prostheses,reduce patient complications,and improve patient outcomes.(5)The combination of artificial intelligence and finite element analysis makes the construction of finite element models more accurate and easy to operate,greatly contributing to the efficiency of clinicians'medical practice and patient outcomes.(6)Finite element analysis is only a digital simulation,which is still somewhat different from the real physical state.
4.Effectiveness and text analysis of Chinese adolescents mental health promotion policy
FANG Yajuan, WU Xiaoyan, CHEN Xiaowan, CHEN Ren, BAI Zhongliang, YAN Jing
Chinese Journal of School Health 2025;46(2):234-238
Objective:
To analyze the issuance of Chinese adolescents mental health promotion policies and policy objects, and to explore the use of different object policy tools and the effectiveness of the policy, so as to provide reference for the improvement of the subsequent policy.
Methods:
Adolescents mental health promotion policies published and policy documents that included adolescents in mental health promotion policies and regulations in China from 2014 to the present were obtained, with the search period of July to August 2024. Policy content and effectiveness were analyzed by using content cross tabulation analysis and Policy Modeling Consistency Index Model (PMC index model). It coded with Nvivo 20 software to understand the types of tools that policy depends on.
Results:
A total of 41 documents were included. The number of adolescent mental health promotion policy texts rose by year, most of which were issued independently, accounting for 70% of the total number of texts issued; 30% were jointly issued, with the Ministry of Education and the National Health Commission as the core subjects. Supply type policy tools accounted for 47.45 % of the total, while environment type and demand type policy tools accounted for 29.68% and 22.87% respectively; the use of policy tools by different policy targets varies, with families and social organizations using more supply type and demand type policy tools, while the education system and healthcare institutions were more inclined to supply type policy tools, and the government departments were more inclined to supply type policy tools and environment type policy tools. In terms of policy effectiveness, there was a common problem of a lack of incentives and constraints, and the PMC values of two long term planning mental health policies were high (7.76, 7.56), and both reached the excellent level.
Conclusions
China has paid more attention to adolescents mental health, and the basic guarantees have been established and overall policy effectiveness is good, but the use of policy tools is uneven. There is a need to improve the operational content of medium and long term policies and to strengthen synergies between implementing departments.
5.Safety and effectiveness of lecanemab in Chinese patients with early Alzheimer's disease: Evidence from a multidimensional real-world study.
Wenyan KANG ; Chao GAO ; Xiaoyan LI ; Xiaoxue WANG ; Huizhu ZHONG ; Qiao WEI ; Yonghua TANG ; Peijian HUANG ; Ruinan SHEN ; Lingyun CHEN ; Jing ZHANG ; Rong FANG ; Wei WEI ; Fengjuan ZHANG ; Gaiyan ZHOU ; Weihong YUAN ; Xi CHEN ; Zhao YANG ; Ying WU ; Wenli XU ; Shuo ZHU ; Liwen ZHANG ; Naying HE ; Weihuan FANG ; Miao ZHANG ; Yu ZHANG ; Huijun JU ; Yaya BAI ; Jun LIU
Chinese Medical Journal 2025;138(22):2907-2916
INTRODUCTION:
Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD.
METHODS:
In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging.
RESULTS:
A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline.
CONCLUSIONS:
Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies.
REGISTRATION
ClinicalTrials.gov , NCT07034222.
Humans
;
Alzheimer Disease/drug therapy*
;
Male
;
Female
;
Aged
;
Middle Aged
;
Cognitive Dysfunction/drug therapy*
;
Aged, 80 and over
;
Amyloid beta-Peptides/metabolism*
;
Biomarkers
;
East Asian People
6.Investigation on the current status of residents′ cognition of doctor-patient relationship and its influencing factors in a certain area of Guangxi under the background of Healthy China
Wuzhao CHEN ; Ziwan NONG ; Xiaoyan PAN ; Li PAN ; Xinyu BAI ; Ziyi YANG
Chinese Journal of Hospital Administration 2025;41(4):294-301
Objective:To understand the current status of residents′ cognition of doctor-patient relationship and its influencing factors in a certain area of Guangxi under the background of Healthy China, so as to provide references for building the harmonious doctor-patient relationship.Methods:Convenience sampling was used to conduct an online questionnaire survey among permanent residents in a certain area of Guangxi from June 1 to July 31, 2023. The survey included residents′ sociodemographic characteristics and their perceptions of doctor-patient relationships. A logistic regression model was employed to analyze the influencing factors of residents′ perceptions of doctor-patient relationships.Results:A total of 114 796 residents participated in the survey. Among them, 44.1% (50 593) believed that the current doctor-patient relationship was harmonious, 47.8% (54 874) considered it neutral, and 8.1% (9 329) perceived it as discordant. The multinomial logistic regression model revealed that males, urban residents, older age groups, unmarried individuals, those with higher education levels, and those in poor health were more likely to perceive the doctor-patient relationship as discordant( P<0.05). Residents who valued health-related behaviors and knowledge, as well as those aware of health policies, were more likely to agree that the doctor-patient relationship was harmonious( P<0.05). Conclusions:Over 90% of residents in a certain area of Guangxi perceived the current doctor-patient relationship as either harmonious or neutral. Strengthening health education and enhancing the promotion of health policies can positively contribute to a harmonious doctor-patient relationship.
7.Integrated evidence chain-based effectiveness evaluation of traditional Chinese medicines (Eff-iEC): A demonstration study.
Ye LUO ; Xu ZHAO ; Ruilin WANG ; Xiaoyan ZHAN ; Tianyi ZHANG ; Tingting HE ; Jing JING ; Jianyu LI ; Fengyi LI ; Ping ZHANG ; Junling CAO ; Jinfa TANG ; Zhijie MA ; Tingming SHEN ; Shuanglin QIN ; Ming YANG ; Jun ZHAO ; Zhaofang BAI ; Jiabo WANG ; Aiguo DAI ; Xiangmei CHEN ; Xiaohe XIAO
Acta Pharmaceutica Sinica B 2025;15(2):909-918
Addressing the enduring challenge of evaluating traditional Chinese medicines (TCMs), the integrated evidence chain-based effectiveness evaluation of TCMs (Eff-iEC) has emerged. This paper explored its capacity through a demonstration study that evaluated the effectiveness evidence of six commonly used anti-hepatic fibrosis Chinese patent medicines (CPMs), including Biejiajian Pill (BP), Dahuang Zhechong Pill (DZP), Biejia Ruangan Compound (BRC), Fuzheng Huayu Capsule (FHC), Anluo Huaxian Pill (AHP), and Heluo Shugan Capsule (HSC), using both Eff-iEC and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The recognition of these CPMs within the TCM academic community was also assessed through their inclusion in relevant medical documents. Results showed that the evidence of BRC and FHC received higher assessments in both Eff-iEC and GRADE system, while the assessments for others varied. Analysis of community recognition revealed that Eff-iEC more accurately reflects the clinical value of these CPMs, exhibiting superior evaluative capabilities. By breaking through the conventional pattern of TCMs effectiveness evaluation, Eff-iEC offers a novel epistemology that better aligns with the clinical realities and reasoning of TCMs, providing a coherent methodology for clinical decision-making, new drug evaluations, and health policy formulation.
8.Rehabilitation effects of flash cupping method combined with respiratory training for occupational pneumoconiosis
Huijuan WANG ; Yuge NIU ; Gaoli ZHANG ; Yapeng SHE ; Xiaoyan ZHANG ; Jing BAI
China Occupational Medicine 2025;52(6):664-668
Objective To explore the rehabilitative effects of flash cupping combined with respiratory training in patients with occupational pneumoconiosis (hereinafter referred to as "pneumoconiosis"). Methods A total of 94 patients with pneumoconiosis were selected as the study subjects by the convenient sampling method. Participants were divided into treatment group and control group based on pneumoconiosis stage using the stratified block randomization method, with 47 cases in each group. The patients in the control group received routine symptomatic treatment, and the patients in the treatment group received flash cupping therapy combined with respiratory training in addition to the routine treatment for six weeks. Diaphragmatic displacement (DD), 6-minutes walking distance (6MWD), metabolic equivalents of task (MET), predicted percentage of forced vital capacity (FVC%), predicted percentage of forced expiratory volume in one second (FEV1%), Chronic Obstructive Pulmonary Disease Assessment Test (CAT) score, and the modified British Medical Research Council Respiratory Questionnaire (mMRC) were assessed before treatment, after six weeks of treatment, and three months after completion of treatment. Results Before treatment, no significant differences were observed in patients between the two groups in DD, 6MWD, MET, FVC%, FEV1%, CAT score, or mMRC grade (all P>0.05). DD, 6MWD, and MET of patients in the treatment group were higher than those before treatment in the same group and those of the control group at the corresponding time points after six weeks of treatment (all P<0.05). In addition, the CAT score of patients in the treatment group was lower than that before treatment (P<0.05). At three months after treatment, 6MWD and MET of patients in the treatment group were higher than those before treatment and those of the control group at the same time points (all P<0.05). There were no significant differences in FVC%, FEV1% and mMRC grade of patients between the two groups (all P>0.05). Conclusion Flash cupping combined with respiratory training can improve the diaphragmatic function, exercise endurance and quality of life of patients with pneumoconiosis, and has improved exercise endurance, which can be used as a useful supplementary treatment in the pulmonary rehabilitation of pneumoconiosis.
9.In-silico discovery of the hapten-based interaction between idiosyncratic hepatotoxic ingredients of Polygonum multiflorum and HLA-B*35:01
Dake XIAO ; Xu ZHAO ; Xiaoyan ZHAN ; Zhuo SHI ; Zhaofang BAI ; Jiang ZHENG ; Xiaohe XIAO ; Jiabo WANG
Science of Traditional Chinese Medicine 2025;3(1):15-27
Background: The previous research has confirmed the existence of idiosyncratic drug-induced liver injury (IDILI) caused by Polygonum multiflorum (PM-IDILI), and demonstrated that PM-IDILI is an immune-mediated injury, with HLA-B*35:01 identified as a genetic susceptibility marker. Additionally, emodin-8-O-β-D-glucoside (EG) and 2, 3, 5, 4′-tetrahyd roxystilbene-2-O-β-D-glucoside have been proposed as potential contributory ingredients in the pathogenesis of PM-IDILI. However, the precise mechanisms through which these susceptible factors contribute to the development of PM-IDILI remain unclear. Objectives: This study aims to explore the molecular characteristics of HLA-B*35:01 that contribute to PM-DILI and to propose a mechanistic hypothesis based on our previous research on PM-induced protein adducts. Methods: Key differences between HLA-B*35:01 and general Chinese HLA-B alleles were identified by comparing protein sequences, peptide binding motifs, and protein structures. Molecular docking was employed to assess whether PM-induced haptenated peptides can be presented by HLA-B*35:01 and other related alleles. Additionally, a simplified dipeptide model was used to evaluate the binding affinity of HLA-B*35:01 to EG-haptenated peptides. Results: Our findings revealed significant differences in the residues of the B and F peptide binding pockets of HLA-B*35:01 compared to general Chinese HLA-B alleles. Further analysis suggested that the F pocket of HLA-B*35:01 was capable of binding EG-cysteine adducts and might be a key feature in the PM-IDILI pathogenesis. Peptide docking using DINC and molecular dynamics simulations indicated that HLA-B*35:01 could form stable complexes with EG-haptenated peptides. Molecular dynamics simulations also highlighted the critical roles of both the B and F pockets in peptide binding. Specifically, the F pocket binds the EG-modified residue in haptenated peptides, while the B pocket, despite lacking shared features among PM-IDILI patients, may indirectly influence the incidence of PM-IDILI by filtering haptenated peptides. The binding affinity of HLA-B*35:01 to EG-modified cysteine residues was experimentally validated through a dipeptide-based assay, confirming that HLA-B*35:01 could bind EG-haptenated peptides. Conclusions: This study identified the unique B and F binding pockets of HLA-B*35:01 as key factors in PM-IDILI pathogenesis and demonstrated that HLA-B*35:01 could bind EG-haptenated peptides. These findings suggest that PM-IDILI may be a hapten-based drug hypersensitivity reaction driven by EG, providing a theoretical framework for further research aimed at elucidating the molecular mechanisms underlying PM-IDILI.
10.In-silico discovery of the hapten-based interaction between idiosyncratic hepatotoxic ingredients of Polygonum multiflorum and HLA-B*35:01
Dake XIAO ; Xu ZHAO ; Xiaoyan ZHAN ; Zhuo SHI ; Zhaofang BAI ; Jiang ZHENG ; Xiaohe XIAO ; Jiabo WANG
Science of Traditional Chinese Medicine 2025;3(1):15-27
Background: The previous research has confirmed the existence of idiosyncratic drug-induced liver injury (IDILI) caused by Polygonum multiflorum (PM-IDILI), and demonstrated that PM-IDILI is an immune-mediated injury, with HLA-B*35:01 identified as a genetic susceptibility marker. Additionally, emodin-8-O-β-D-glucoside (EG) and 2, 3, 5, 4′-tetrahyd roxystilbene-2-O-β-D-glucoside have been proposed as potential contributory ingredients in the pathogenesis of PM-IDILI. However, the precise mechanisms through which these susceptible factors contribute to the development of PM-IDILI remain unclear. Objectives: This study aims to explore the molecular characteristics of HLA-B*35:01 that contribute to PM-DILI and to propose a mechanistic hypothesis based on our previous research on PM-induced protein adducts. Methods: Key differences between HLA-B*35:01 and general Chinese HLA-B alleles were identified by comparing protein sequences, peptide binding motifs, and protein structures. Molecular docking was employed to assess whether PM-induced haptenated peptides can be presented by HLA-B*35:01 and other related alleles. Additionally, a simplified dipeptide model was used to evaluate the binding affinity of HLA-B*35:01 to EG-haptenated peptides. Results: Our findings revealed significant differences in the residues of the B and F peptide binding pockets of HLA-B*35:01 compared to general Chinese HLA-B alleles. Further analysis suggested that the F pocket of HLA-B*35:01 was capable of binding EG-cysteine adducts and might be a key feature in the PM-IDILI pathogenesis. Peptide docking using DINC and molecular dynamics simulations indicated that HLA-B*35:01 could form stable complexes with EG-haptenated peptides. Molecular dynamics simulations also highlighted the critical roles of both the B and F pockets in peptide binding. Specifically, the F pocket binds the EG-modified residue in haptenated peptides, while the B pocket, despite lacking shared features among PM-IDILI patients, may indirectly influence the incidence of PM-IDILI by filtering haptenated peptides. The binding affinity of HLA-B*35:01 to EG-modified cysteine residues was experimentally validated through a dipeptide-based assay, confirming that HLA-B*35:01 could bind EG-haptenated peptides. Conclusions: This study identified the unique B and F binding pockets of HLA-B*35:01 as key factors in PM-IDILI pathogenesis and demonstrated that HLA-B*35:01 could bind EG-haptenated peptides. These findings suggest that PM-IDILI may be a hapten-based drug hypersensitivity reaction driven by EG, providing a theoretical framework for further research aimed at elucidating the molecular mechanisms underlying PM-IDILI.


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