1.Proteome-wide Mendelian randomization analysis of plasma proteins identifies biomarkers for anxiety disorders
Xuelian LI ; Min DENG ; Rongting RAN ; Yuqian HE ; Geman WANG ; Yujie LI ; Zhili ZOU
Sichuan Mental Health 2026;39(1):63-69
BackgroundAnxiety disorder is a common mental disorder, with its prevalence showing a continuous upward trend, significantly affecting the quality of life and social function of patients. Due to the lack of objective and reliable biomarkers in clinical practice, the early identification and treatment of anxiety disorder have been somewhat limited. Plasma proteins have the potential to serve as biomarkers for mental diseases, however, the causal relationship between them and anxiety disorder remains unclear. ObjectiveTo identify the plasma proteins that have a causal relationship with anxiety disorders, and to elucidate the associated biological pathways, in order to provide references for the search for biomarkers of anxiety disorders and the exploration of potential therapeutic targets. MethodsBased on the protein quantitative trait locus (pQTL) data of 4 907 plasma proteins covering 35 559 Icelandic individuals from the deCODE database, and the genome-wide association studies (GWAS) data of 50 486 patients with anxiety disorders and 330 460 healthy controls, the inverse-variance weighted (IVW) method was used as the main analysis method, supplemented by MR-Egger method, weighted median method, simple model method, and weighted model method for bidirectional Mendelian randomization analysis. Enrichment analysis of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was conducted for the related proteins. Sensitivity analysis was performed using Cochran's Q test, MR-Egger intercept test, MR-PRESSO test, and leave-one-out analysis to evaluate the robustness of the results. ResultsA total of 10 plasma proteins were identified as significantly associated with anxiety disorders. Among these, SPATA9 (OR=0.856, 95% CI: 0.784–0.934, P<0.01) and PDE5A (OR=0.911, 95% CI: 0.864–0.961, P<0.01) were identified as protective factors, while CRYGD (OR=1.209, 95% CI: 1.095–1.334, P<0.01), BTN3A3 (OR=1.045, 95% CI: 1.018–1.073, P<0.01), SERPINB13 (OR=1.102, 95% CI: 1.040–1.168, P<0.01), ERBB4 (OR=1.283, 95% CI: 1.109–1.484, P<0.01), LSAMP (OR=1.096, 95% CI: 1.037–1.158, P<0.01), ICOSLG (OR=1.283, 95% CI: 1.104–1.490, P<0.01), DNAJB11 (OR=1.172, 95% CI: 1.076–1.277, P<0.01), and TREML1 (OR=1.115, 95% CI: 1.054–1.179, P<0.01) were identified as risk factors. The sensitivity analysis showed that the results were robust, with no heterogeneity (Cochran's Q test P>0.05) or pleiotropy (MR-Egger intercept test P>0.05). Enrichment analysis indicated that these plasma proteins were enriched in biological processes such as T-cell signal transduction, lymphocyte proliferation, cell membrane structure and synaptic function, as well as the intestinal immune network that produces IgA and the ErbB signaling pathway. ConclusionThis study identified 10 plasma proteins associated with anxiety disorders. The functions of these plasma proteins involve multiple biological processes such as neural development and immune regulation.
2.Research progress of traditional Chinese medicine in the treatment of chronic eczema
Xia ZHANG ; Zhili RAO ; Xia LIU ; Ping SHEN ; Qin WANG
China Pharmacy 2026;37(6):817-822
Chronic eczema has a high prevalence in China, significantly impacting patients’ quality of life. Leveraging the unique advantages of pattern identification/syndrome differentiation and treatment, along with a holistic approach, traditional Chinese medicine (TCM), which integrates internal and external therapies, has been widely applied in the management of chronic eczema. It has demonstrated significant efficacy and distinctive strengths in alleviating symptoms, reducing recurrence rates, maintaining disease stability, and enhancing patients’ quality of life. Oral administration of TCM(e.g. modified Longdan xiegan decoction) can improve patients’ clinical symptoms through systemic regulation. External use of TCM can directly act on the skin lesion with the help of steaming and washing, hydropathic compress, ointment and other forms. At the same time, it can effectively relieve the clinical symptoms of chronic eczema by combining with non-drug therapies such as acupuncture, moxibustion, acupoint catgut embedding, blood-letting puncture and cupping. In addition, characteristic therapies such as oral administration of TCM combined with external treatment, a combination of various external treatments and a combination of Chinese and Western medicine have also demonstrated certain advantages in regulating immune function, alleviating skin lesions, and relieving itching symptoms. These therapies cooperate with each other, creating a synergistic effect that treats both the symptoms and the root cause simultaneously. It is suggested that more high-quality, large-scale clinical research should be conducted in the future to systematically confirm the therapeutic advantages of TCM and further explore the specific molecular mechanism of action.
3.Mechanisms of Dahuang Gancaotang in Improving Ferroptosis in Chronic Kidney Disease through SIRT3-mediated Deacetylation of p53
Mengdi CUI ; Yi AN ; Rui WANG ; Zhili XIONG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(17):59-69
ObjectiveTo investigate the mechanisms by which Dahuang Gancaotang (DHGC) alleviates ferroptosis in chronic kidney disease (CKD) via silent information regulator 3 (SIRT3)-mediated deacetylation of tumor protein p53 (p53). MethodsIn vivo, a CKD mouse model was established by feeding a 0.2% adenine-containing diet. Seventy-two C57BL/6 mice were randomly divided into six groups: blank group, model group, DHGC low-, medium-, and high-dose groups (0.975, 1.95, 3.90 g·kg-1), and valsartan group (0.025 g·kg-1), with 12 mice in each group. Renal function was evaluated by measuring serum blood urea nitrogen (BUN) and creatinine (SCr). Renal pathological changes were assessed using hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and Masson staining. Immunohistochemistry was used to detect the expression of collagen type (Col)Ⅰ, ColⅢ, and α-smooth muscle actin (α-SMA) in renal tissue to evaluate renal fibrosis. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) to assess inflammatory responses. Colorimetric assays were used to determine superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and renal total iron content to evaluate lipid peroxidation and iron metabolism. Western blot was used to detect the protein expression of the SIRT3/p53 signaling pathway, acetylated p53 (ac-p53), and glutathione peroxidase 4 (GPX4) in renal tissue. In vitro, a ferroptosis model of HK-2 cells was induced using erastin. Cells were divided into six groups: blank group, model group, DHGC-containing serum low-, medium-, and high-dose groups (15 rats were randomly divided into three groups, n = 5 per group, and gavaged with 0.675, 1.35, 2.70 g·kg-1 to prepare medicated serum), and ferrostatin-1 (Fer-1) group (5 μmol·L-1). The cell counting Kit-8 (CCK-8) assay was used to determine cell viability and to screen the optimal concentrations of erastin and DHGC-containing serum. Western blot was used to detect SIRT3/p53 pathway proteins, ac-p53, and GPX4 expression. Immunofluorescence confocal microscopy was used to observe p53 nuclear translocation. ResultsIn vivo, compared with the blank group, the model group showed significantly increased BUN and SCr levels (P<0.01). Severe renal pathological injury and aggravated renal fibrosis were observed. Lipid peroxidation and iron metabolism disorders were evident, as shown by significantly decreased SOD and GSH levels and significantly increased MDA and renal total iron levels (P<0.05, P<0.01). Compared with the model group, all the above indices were significantly improved after DHGC intervention in a dose-dependent manner (P<0.05, P<0.01). In vitro, compared with the blank group, HK-2 cell viability was significantly decreased in the model group. A concentration of 0.4 μmol·L-1 erastin was identified as the optimal induction dose, and high-dose DHGC-containing serum was identified as the optimal treatment condition. Compared with the model group, cell viability was significantly increased in all DHGC-containing serum groups (P<0.05, P<0.01). Mechanistically, compared with the blank group, protein expression of SIRT3 and GPX4 was significantly decreased in both in vivo and in vitro model groups, while p53 and ac-p53 expression and p53 nuclear translocation were significantly increased (P<0.01). Compared with the model group, these changes were significantly reversed after DHGC intervention (P<0.05, P<0.01). ConclusionDHGC exerts a protective effect against adenine-induced CKD in mice and erastin-induced ferroptosis in HK-2 cells. The mechanism is associated with its anti-ferroptosis effect mediated via the SIRT3/p53 signaling pathway.
4.Mechanism of Zuogui Wan in Improving Nephrotic Syndrome in Rats Based on Regulating Gut Microbiota
Xinyu HU ; Tubei ZHANG ; Yixin HU ; Rui WANG ; Zhili XIONG ; Yan CAI ; Xuerong ZHANG ; Linqun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(19):32-41
ObjectiveTo investigate the protective effects of Zuogui Wan (ZGW) decoction on nephrotic syndrome (NS) through the regulation of gut microbiota. MethodsThirty male Sprague-Dawley (SD) rats were randomly divided into five groups, with 6 rats in each group: The control group, model group, low-dose group, medium-dose group, and high-dose group. The NS rat model was induced by tail vein injection of 6.5 mg·kg-1 doxorubicin. After successful modeling, the control and model groups were gavaged with normal saline (10 mL·kg-1) twice daily, while the low- (50 mg·kg-1), medium- (100 mg·kg-1), and high-dose (200 mg·kg-1) groups were gavaged with ZGW (10 mL·kg-1) twice daily. All rats were administered at fixed intervals daily for 8 consecutive weeks. The therapeutic effects of ZGW on NS in rats were observed, and the optimal dose was screened. Renal and intestinal pathological changes in rats were examined. Fecal samples were collected, and 16S rDNA sequencing technology was used to detect the diversity and abundance of gut microbiota in each group. ResultsCompared with the control group, 24-hour urinary protein, serum creatinine, urea nitrogen, and cholesterol levels significantly increased in the model group (P<0.01), while serum albumin levels decreased (P<0.01). These changes were ameliorated in the treatment groups (P<0.05, P<0.01). Renal pathology revealed intact and orderly arranged glomeruli and renal tubules in the control group. In the model group, glomerular atrophy, widened mesangial areas, podocyte swelling, disordered renal tubular arrangement, and numerous casts were observed. Varying degrees of glomerular atrophy and disordered renal tubular arrangement were seen in the treatment groups. Specific protein assays revealed increased serum levels of kidney injury molecule-1(KIM-1) and α1-microglobulin (P<0.01), and significantly decreased levels of E-cadherin, Podocin, and Nephrin in renal tissues (P<0.01), along with a significant increase in transforming growth factor-β(TGF-β) (P<0.01) in the model group. In the treatment groups, serum KIM-1 and α1-microglobulin levels decreased, E-cadherin levels significantly increased (P<0.01), and TGF-β levels significantly decreased (P<0.01). Podocin and Nephrin levels increased in the high-dose group (P<0.05). Additionally, intestinal mucosal atrophy, epithelial cell edema, decreased goblet cells, and multiple inflammatory infiltrations were observed in the model group. The sequencing results of gut microbiota demonstrate that ZGW can significantly ameliorate intestinal dysbiosis in rats, restore the abundance of beneficial bacteria, and exert a profound influence on the compositional profile of gut microbiota. ConclusionZGW can alleviate renal injury in rats with nephrotic syndrome by improving gut microbiota and protecting the intestinal barrier.
5.From Spleen Deficiency with Dampness Excess to Stasis-toxin Damaging Collaterals: Dynamic Management Path in Whole-course Treatment Strategies for Ulcerative Colitis
Zhili ZHENG ; Hongzheng LI ; Shaoli WANG ; Tiantong JIANG ; Yuan DING ; Qiongqiong LU ; Zhen LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(19):147-153
Ulcerative colitis (UC), a chronic nonspecific inflammatory bowel disease characterized by unclear etiology, complex contributing factors, and a refractory course with malignant transformation potential, imposes a substantial burden on both individual patients and healthcare systems. There is an urgent need to explore effective therapeutic strategies and pharmacological interventions. Professor LIU Zhen, based on years of clinical practice, proposed a dynamic pathogenesis chain of UC: Spleen deficiency with dampness excess as the foundation, dampness obstruction as the nexus, stasis-toxin interaction as the key, and stasis-toxin damaging intestinal collaterals as the terminal outcome. The treatment, following the progression of deficiency (depression)-dampness-toxin-stasis (toxin), should focus on invigorating the spleen and resolving dampness. A stage-specific treatment approach is emphasized. During the susceptible stage, prevention is recommended, which relies on regulating the diet, maintaining a positive mental state, and adjusting daily routines to invigorate the spleen and replenish Qi. During the acute attack and remission stages, the treatment should be tailored according to clinical typing and disease severity, flexibly employing therapeutic strategies such as tonifying deficiency, resolving depression, eliminating dampness, clearing heat, detoxifying, arresting bleeding, and resolving stasis in order to interrupt disease progression. In the recovery stage, latent pathogenic factors should be addressed while the postnatal constitutional foundation be preserved to prevent recurrence. According to the TCM principle of treating disease before its onset, a whole-course management path of early protection-interception-stratified care-consolidation has been developed, covering all stages of UC, to inform its clinical prevention and treatment.
6.A prediction model for the death risk of aortic dissection based on machine learning and preoperative indicators
Jianke RONG ; Yeao WANG ; Zhili WEI ; Zunhui WAN ; Yundan DENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(10):1640-1649
Objective To construct a preoperative objective index-based model for predicting the mortality risk of aortic dissection, aiming to provide a quick risk assessment tool for primary healthcare. Methods The patients with aortic dissection from the Medical Information Mart for Intensive Care (MIMIC-Ⅳ) database between 2008 and 2019 were included. These patients were randomly divided into a training set, a validation set, and a test set at a ratio of 7:2:1. Based on the Akaike information criterion (AIC), forward regression was used to select the risk factors for patients with post-dissection mortality, and the XGBoost algorithm was employed to establish the prediction model. The SHAP (SHapley Additive exPlanations) theory was used for interpretive analysis. Results Out of the 271 patients of aortic dissection, 158 were males and 113 were females, with a median age of 70.3 (58.8, 79.5) years. The training set, validation set, and test set consisted of 189, 54, and 28 patients, respectively. During the follow-up period, 99 (36.5%) deaths occurred. Forward stepwise regression based on the AIC, clinical relevance assessment and literature review, was employed to identify 18 preoperative independent predictors. An XGBoost prediction model was constructed accordingly. After grid search optimization, the model demonstrated good discrimination in both the validation set [area under the curve (AUC)=0.681] and the test set (AUC=0.735). The SHAP analysis indicated that age (mean |SHAP|=0.081), activated partial thromboplastin time (mean |SHAP|=0.065), and red cell distribution width (mean |SHAP|=0.038) were the top three predictive contributors. Conclusion The aortic dissection mortality risk prediction model constructed based on the XGBoost algorithm can effectively predict the incidence of mortality outcomes. Characteristic indicators such as age, activated partial thromboplastin time, and red cell distribution width can assist clinicians in identifying high-risk patients, making triage referral decisions, and optimizing preoperative interventions within the golden time window, ultimately aiming to reduce the mortality rate of patients with aortic dissection.
7.Clinical guideline for diagnosis and treatment of nonunion of osteoporotic vertebral fractures (version 2025)
Haipeng SI ; Le LI ; Junjie NIU ; Wencan ZHANG ; Fuxin WEI ; Jinqiu YUAN ; Qiang YANG ; Hongli WANG ; Guangchao WANG ; Shihong CHEN ; Yunzhen CHEN ; Xiaoguang CHENG ; Jianwen DONG ; Shiqing FENG ; Rui GU ; Yong HAI ; Tianyong HOU ; Bo HUANG ; Xiaobing JIANG ; Lei ZANG ; Chunhai LI ; Nianhu LI ; Hua LIN ; Hongjian LIU ; Peng LIU ; Xinyu LIU ; Sheng LU ; Shibao LU ; Chunshan LUO ; Lvy CHAOLIANG ; Lvy WEIJIA ; Xuexiao MA ; Wei MEI ; Chunyang MENG ; Cailiang SHEN ; Chunli SONG ; Ruoxian SONG ; Jiacan SU ; Honglin TENG ; Hui SHENG ; Beiyu WANG ; Bingwu WANG ; Liang WANG ; Xiangyang WANG ; Nan WU ; Guohua XU ; Yayi XIA ; Jin XU ; Youjia XU ; Jianzhong XU ; Cao YANG ; Maowei YANG ; Zibin YANG ; Xiaojian YE ; Hailong YU ; Xijie YU ; Hua YUE ; Zhili ZENG ; Xinli ZHAN ; Hui ZHANG ; Peixun ZHANG ; Wei ZHANG ; Zhenlin ZHANG ; Jianguo ZHANG ; Tengyue ZHU ; Qiang LIU ; Huilin YANG
Chinese Journal of Trauma 2025;41(10):932-945
Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.
8.Exploring Traditional Chinese Medicine Syndrome Characteristics Associated with Immunotherapy Efficacy in Cervical Cancer Using Propensity Score Matching
Zhili ZHUO ; Wenping LU ; Yongjia CUI ; Xiyue WANG ; Lei CHANG
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(8):1831-1838
Objective To investigate traditional Chinese medicine(TCM)syndrome characteristics associated with immunotherapy efficacy in cervical cancer using propensity score matching(PSM),aiming to identify the population benefiting from immunotherapy.Methods A retrospective analysis was conducted in 253 cervical cancer patients,who received the treatment with programmed death receptor 1(PD-1)inhibitors at Guang'anmen Hospital,China Academy of Chinese Medical Sciences from January 2020 to October 2024.Clinical data and TCM four-examination data were collected.After balancing the confounders via PSM(1∶1 matching)and with therapeutic efficacy as the dependent variable,multivariate logistic regression was performed to analyze the characteristics of TCM syndrome in the immunotherapy-response group and then a predictive model was constructed.Results(1)After matching with PSM,198 cases were included,99 cases in response group and 99 cases in non-response group.(2)Analysis of the distribution of TCM syndrome elements showed that the differences in the pathogenic syndrome elements of qi deficiency,qi stagnation,blood stasis,heat and phlegm between the two groups were statistically significant(P<0.05 or P<0.01),while there were no statistically significant differences in the disease-location syndrome elements of uterus,kidneys,lungs,spleen,liver,and heart,as well as in the pathogenic syndrome elements of blood deficiency,yin deficiency,yang deficiency,cold,and dampness(P>0.05).The main pathogenic syndrome elements in the response group were qi deficiency,blood deficiency and heat,while those in the non-response group were qi stagnation,heat and phlegm.(3)The results of univariate regression analysis showed that targeted therapy(P=0.040),programmed cell death-ligand 1(PD-L1)expression level(P<0.001),qi deficiency(P=0.009),blood deficiency(P<0.001),yang deficiency(P<0.001),yin deficiency(P<0.001),qi stagnation(P=0.003),blood stasis(P<0.001),cold(P<0.001),cold(P<0.001),heat(P<0.001),phlegm(P<0.001),and dampness(P<0.001)were the factors associated with the efficacy of PD-1 inhibitors.(4)The results of multivariate logistic regression analysis showed that previous targeted therapy(OR=0.36,95%CI:0.16-0.83)and pathogenic syndrome elements of qi stagnation(OR=0.23,95%CI:0.10-0.49),phlegm(OR=0.28,95%CI:0.13-0.61)were the risk factors of associated with the efficacy of PD-1 inhibitors,while PD-L1 expression level(OR=15.27,95%CI:2.60-89.63),and pathogenic syndrome element qi deficiency(OR=2.90,95%CI:1.42-5.89)were the protective factors associated with the efficacy of PD-1 inhibitors in cervical cancer.(5)Receiver operating characteristic(ROC)curve analysis demonstrated that the area under the ROC curve(AUC)of the predictive model for evaluating PD-1 inhibitor efficacy in cervical cancer was 0.78(95%CI:0.71-0.84),indicating certain predictive value.Conclusion PD-L1 expression level and TCM pathogenic syndrome elements such as qi deficiency,qi stagnation,and phlegm are the independent factors influencing PD-1 inhibitor efficacy in cervical cancer,providing insights for optimizing integrated TCM-western medicine treatment strategies.
9.Prospects for the development of space medicine experiments in China Space Station
Yinghui LI ; Zhaoxia LIU ; Lina QU ; Zhili LI ; GuangJun HE ; Chunyan WANG ; Zi XU
Space Medicine & Medical Engineering 2025;36(3):189-198
Space medicine,as a comprehensive discipline ensuring the safety,health,and efficient performance of astronauts during manned space missions,focuses on elucidating the underlying mechanisms of multi-system physiological effects induced by extreme space environments and developing corresponding protective strategies.With China's space program transitioning into an application and development phase,space medical experiments—a critical domain within space applications—face significant opportunities and challenges.This paper reviews the international development trend in the field of medical experiments and the progress in China from perspectives including platform system construction,utilization of novel technologies,and scientific discoveries.It further outlines the engineering framework,guiding ideology,and key research directions for space medical experiments under China's Space Station Application and Development Project.Deliberations and prospects center on the in-depth analysis of the adaptation law of life in space flight,the application of big data and artificial intelligence technology,the emerging challenges it faces,and the scientific research organization models.This work aims to provide a reference for the development of space medical experiment field in China.
10.Prediction model of knee osteoarthritis based on ultrasound score,MRI score,and serum TGF-β1 and Cat D levels
Zhili WANG ; Danfeng XU ; Nan LI ; Yan JIAO ; Ruisong SHANG
Journal of China Medical University 2025;54(9):802-807
Objective To construct a prediction model for the progression of knee osteoarthritis(KOA)based on ultrasound score,magnetic resonance imaging(MRI)score,and serum levels of transforming growth factor-β1(TGF-β1)and cathepsin D(Cat D).Methods Clinical data from 270 patients with KOA in Hengshui People's hospital from December 2022 to June 2024 were retrospec-tively analyzed.The patients were randomly divided into a modeling set(n=189)and validation set(n=81)at a ratio of 7∶3.The patients in the modeling set were categorized into mild-to-moderate and severe groups based on the degree of disease progression.Mul-tivariate logistic regression analysis was used to identify factors influencing KOA progression,and a prediction model was constructed using R software.Results Multivariate logistic regression analysis showed that body mass index,knee injury history,ultrasound score,WORMS score,TGF-β1,and Cat D were significant predictors of KOA progression(P<0.05).A nomogram-based prediction model was developed using these variables.The areas under the curve(AUC)of the nomograms for predicting disease progression in the modeling and validation sets were 0.889 and 0.860,respectively.The calibration curves showed that the predicted probability was in good agreement with the actual probability.Conclusion The prediction model developed in this study is effective in identifying patients at high-risk of KOA progression and may servce as a valuable tool for clinical assessment and decision making.

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