1.Human umbilical cord mesenchymal stem cell-derived exosomes attenuate renal ischemia-reperfusion injury by up-regulating ATF3 to inhibit the TLR4/NF-κB pathway
Xingyu* WAN ; Yujia LIU ; Ruiyan WANG ; Hao WANG ; Yi ZHAO ; Lu GUO ; Zhihua YANG ; Xinghua LÜ
Organ Transplantation 2026;17(2):275-286
Objective To investigate the protective effect and underlying mechanism of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exo) on renal ischemia-reperfusion injury (IRI). Methods hucMSC-Exos were isolated and characterized. A mouse renal IRI model was established and the animals were divided into Sham, IRI, IRI+hucMSC-Exo, IRI+hucMSC-Exo+JY-2 and Sham+JY-2 groups. Serum creatinine (Scr) and blood urea nitrogen (BUN) were measured. Hematoxylin-eosin (HE) staining was used to evaluate renal histopathology. Enzyme-linked immune absorbent assay was performed to determine serum interleukin (IL)-1β and IL-18 levels. Western blotting was used to detect the expression of activating transcription factor 3 (ATF3), Toll-like receptor 4 (TLR4), nuclear factor (NF)-κB, NOD-like receptor protein 3 (NLRP3), cysteineyl aspartate specific proteinase (Caspase)-1 p20 and Gasdermin D(GSDMD). Real-time fluorescent quantitative polymerase chain reaction was employed to measure ATF3, TLR4 and NF-κB messenger RNA (mRNA). Immunohistochemistry was conducted to examine NLRP3, Caspase-1 p20 and GSDMD. An in vitro hypoxia/reoxygenation (H/R) model was established in HK-2 cells and divided into Control, H/R, H/R+hucMSC-Exo, H/R+hucMSC-Exo+JY-2 and Control+JY-2 groups. Western blotting was used to detect the expression of ATF3, TLR4 and NF-κB. Real-time fluorescent quantitative polymerase chain reaction was used to measure NLRP3, GSDMD and Caspase-1 mRNA. Results HucMSC-Exos were successfully isolated and identified. Compared with the Sham group, the IRI group exhibited elevated Scr and BUN, higher tubular injury scores, increased protein expression levels of ATF3, TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD, and raised mRNA expression levels of ATF3, TLR4, NF-κB. Compared with the IRI group, the IRI+hucMSC-Exo group showed decreased Scr and BUN, lower tubular injury scores, up-regulated ATF3 protein and mRNA, down-regulated TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD protein, and declined TLR4 and NF-κB mRNA. Compared with the IRI+hucMSC-Exo group, the IRI+hucMSC-Exo+JY-2 group exhibited increased Scr and BUN levels, elevated renal tubular injury scores, decreased ATF3 protein expression levels, elevated protein expression levels of TLR4, NF-κB p65, NLRP3, Caspase-1 p20, and GSDMD, decreased ATF3 mRNA expression levels, and elevated mRNA expression levels of TLR4 and NF-κB. (all P < 0.05). Compared with the Control group, the expression levels of ATF3, TLR4 and NF-κB p65 proteins were increased in the H/R group, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased. Compared with the H/R group, the expression level of ATF3 protein was increased, the expression levels of TLR4 and NF-κB p65 proteins were decreased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were decreased in the H/R+hucMSC-Exo group. Compared with the H/R+hucMSC-Exo group, the expression level of ATF3 protein was decreased, the expression levels of TLR4 and NF-κB p65 proteins were increased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased in the H/R+hucMSC-Exo+JY-2 group (all P < 0.05). Conclusions HucMSC-Exos alleviate renal IRI by up-regulating ATF3, thereby negatively regulating the TLR4/NF-κB signaling pathway and subsequently inhibiting pyroptosis.
2.The causal relationship between immune cells and heart failure risk and the mediating role of serum metabolites: A Mendelian randomization study
Yun ZHU ; Jiaming WEI ; Ruifang LIN ; Yongjun LIU ; Yue LIU ; Guohua ZHANG ; Zhihua GUO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(01):115-121
Objective To explore the causal relationship between immune cells and heart failure (HF), and the mediating role of serum metabolites, in order to identify potential biomarkers and therapeutic targets. Methods We employed a two-sample Mendelian randomization (MR) analysis method based on genome-wide association study (GWAS) data, analyzing the direct and indirect effects of 731 types of immune cells and 1 400 metabolites on HF. We selected valid instrumental variables and conducted statistical analyses using R software. The primary analysis was performed using the inverse variance weighted method, supplemented by MR-Egger analysis and weighted median method. The stability of the results was assessed through tests such as Cochran’s Q test. Results Our research found a negative causal relationship between PD-L1 on CD14−CD16+ and HF. Sensitivity analysis supported this result. The reverse MR analysis did not find an effect of HF on PD-L1 on CD14−CD16+, indicating that PD-L1 on CD14−CD16+ might play a unidirectional role in reducing the risk of HF. Further mediation MR analysis showed that PD-L1 on CD14−CD16+ might influence the risk of HF onset by regulating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), with a mediation effect ratio of 6.7%. Conclusion PD-L1 on CD14−CD16+ may reduce the risk of HF by elevating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), which provides a new perspective for understanding the pathogenesis of HF.
3.Epidemiological characteristics, outcome analysis, and management strategies for DAT-positive blood donors
Shiyu YIN ; Zhihua XU ; Xueqin GENG ; Zhuan LIU ; Hongliang HUANG
Chinese Journal of Blood Transfusion 2026;39(3):360-366
Objective: To investigate the epidemiological characteristics, outcome patterns, and management strategies for blood donors with a positive direct antiglobulin test (DAT). Methods: A retrospective analysis was conducted on donation data from 808 386 donors from 2013 to 2023, focusing on those whose blood was discarded due to DAT positivity. Follow-up was performed on 125 DAT-positive donors, and 98 blood samples were collected. The samples were re-tested for DAT, DAT typing (IgG/C3d), and unexpected antibody screening using both the tube method and the microcolumn gel method. Results: Epidemiological characteristics: Retrospective data revealed 147 DAT-positive blood donors, yielding a positivity rate of 1/5 500. The DAT positivity rate using the tube method was 0.118‰ (49/416 893), lower than that of the microcolumn gel method at 0.25‰ (98/391 493). Among DAT-positive individuals, 44.2% (65/147) exhibited agglutination intensity<2+. Outcome analysis: The proportion of donors with positive DAT test results that converted to negative was 54.1% (53/98), with a conversion interval ranging from 8 to 117 months (mean 49.9 months). All donors in the negative conversion group had a previous DAT intensity<2+, whereas 95.6% (43/45) of the non-negative conversion group had intensity ≥2+ (P<0.001). Unexpected antibodies (anti-E, anti-M, etc.) were detected in 18 cases. Methodological differences: Review of results revealed 35 cases positive by both the DAT tube assay and microcolumn gel method. An additional 10 cases were positive by only one method: 5 were positive only by the tube assay, and 5 were positive only by the microcolumn gel method. Clinical validation: Among 14 DAT-positive donors who became negative and donated blood again, the clinical infusion efficacy of red blood cell products could be assessed in 10 cases, with 9 cases demonstrating effective infusion. Conclusion: Some DAT-positive blood donors may naturally convert to negative status, with the intensity of previous test results potentially serving as a key predictive factor for conversion. It is recommended to employ a combined approach of tube-based and microcolumn gel-based methods for retesting, concurrently screening for irregular antibodies. A tentative tiered management strategy is proposed: individuals with DAT intensity <2+ should be deferred for 12 months before retesting, while those with ≥2+ intensity should be permanently deferred.
4.Construction of Syndrome Diagnosis Scale for Chronic Atrophic Gastritis with Turbid Toxin and Stomach Accumulation Based on Delphi Method and Analytic Hierarchy Process
Zhihua LIU ; Xiaoyu LIU ; Yuman WANG ; Runze LI ; Hua LI ; Runxue SUN ; Shaopo WANG ; Jianming JIANG ; Yanru DU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):235-243
ObjectiveTo construct a scale for the diagnosis of chronic atrophic gastritis (CAG) with turbid toxin accumulating in the stomach. MethodsFirst, a research group was established to construct the scale framework. Relevant literature of CAG with syndrome of turbid toxin accumulating in the stomach was searched in CNKI, Wanfang Database (WF), and VIP Database (CQVIP) from April 1, 2003 to April 1, 2023, and items were preliminarily selected after standardization of terms. Through clinical investigation, the discrete trend method, correlation coefficient method, Cronbach's coefficient method, and factor analysis method were used to screen symptom items, and the frequency method was used to screen signs, tongue coating, and pulse conditions. Three rounds of Delphi expert consultation were conducted to determine the items of the scale. The weight of each item was obtained by the analytic hierarchy process. ResultsA total of 49 articles were included, and 45 items were obtained after primary screening, including 28 symptoms, 2 signs, 10 tongue coatings, and 5 pulse conditions. After clinical investigation, 15 symptoms were retained, and 8 signs and pulse conditions of tongue coating were retained. The positive coefficients of experts in three rounds of Delphi expert consultation were 100%, 96.67%, and 100%, respectively. The expert authority coefficients were 0.86, 0.87, and 0.87, respectively, and the coordination coefficients were 0.18, 0.25, and 0.30. After core group discussion, Delphi method investigation, and AHP weight assignment, the diagnostic scale items of CAG with turbid toxin accumulating in stomach syndrome were finally established, namely, dark red or purplish tongue proper with yellow greasy (or dry) coating (30 points), epigastric stuffiness and fullness or pain (15 points), sticky and unsmooth defecation (10 points), taste disturbance (sticky mouth, fetid breath, bitter taste, 7 points), heartburn or acid regurgitation (6 points), dizziness and clouding (5 points), general heaviness and fatigue (5 points), slippery, string‑slippery, or slippery‑rapid pulse (5 points), dysuria (or yellow or deep yellow urine, 4 points), poor appetite (4 points), dull complexion (3 points), sticky, greasy, and fetid secretions (3 points), and poor sleep (3 points). ConclusionBased on the establishment, screening, confirmation, and weighting of an item pool, combined with subjective and objective approaches as well as qualitative and quantitative methods, a diagnostic scale for CAG with the syndrome of turbid toxin accumulating in the stomach was successfully constructed.
5.Integrated traditional Chinese and Western medicine therapy for Wilson disease
Yumei GU ; Yeqing HUANG ; Bei ZHANG ; Aiqun LIU ; Zhongxing PENG ; Mingfan HONG ; Zhihua ZHOU
Journal of Clinical Hepatology 2026;42(3):529-534
Wilson disease (WD) is one of the few treatable neurogenetic disorders. Currently, Western medicine remains the main treatment method for WD, while since the 1990s, multiple studies conducted by Professor Yang Renmin and his team have shown that traditional Chinese medicine (TCM) also has a favorable therapeutic effect. Based on the principle of low-copper diet for WD, this article systematically elaborates on the advantages, limitations, and key considerations of current Western medicine therapies (pharmacotherapy, liver transplantation, and splenectomy) and reviews the research findings of TCM in China, especially the wide application of Gandou Decoction in clinical practice. Studies have shown that Gandou Decoction can effectively improve neurological symptoms, protect hepatic and renal function, and avoid the adverse drug reactions associated with metal chelating agents, and therefore, it can be used an effective long-term adjuvant therapy for WD. It should be noted that symptoms and signs should be considered in integrated traditional Chinese and Western medicine therapy for WD, and high-copper TCM drugs should be avoided to prevent deterioration.
6.Pathogenesis Evolution and Treatment Strategies of Inflammation-Cancer Transformation in Helicobacter Pylori-Associated Gastritis:Based on the Theory "Latent Wind in Stomach Collaterals"
Chuanyang LIU ; Lin CHENG ; Xinqiao CHU ; Shuxuan CHEN ; Zhihua TIAN ; Shaoli WANG ; Zhen LIU
Journal of Traditional Chinese Medicine 2026;67(13):1383-1389
It is considered that "latent wind in stomach collaterals" is the core pathogenesis underlying the inflammation-caner transformation of helicobacter pylori-associated gastritis (HpAG). The concept of "latent wind in stomach collaterals" integrates stomach wind theory, latent pathogen theory, and collateral disease theory, referring to wind pathogen deeply hidden in the stomach collaterals, characterized by both external and internal wind pathogen as well as latent pathogen that remain concealed and may be triggered under certain conditions. Accordingly, the Correa cascade is reclassified into four stages including the prodromal stage, progressive stage, transitional stage and carcinogenic stage. In the prodromal stage, the fundamental pathogenesis is described as "wind toxin invading externally with collateral deficiency and stirring of wind". In the progressive stage, wind is accompanied by qi constraint, fire pathogen, and dryness pathogen, manifesting as "wind pathogen complicated by constraint" "wind-fire agitation" and "wind-dryness interaction". In the transitional stage, "wind transforming into phlegm-drool and stomach collaterals being obstructed by stasis" is identified as a critical window for disease reversal. In the carcinogenesis stage, "wind-qi hyperactivity leading to pathological transformation, and collateral damage resulting in abdominal masses" drives tumor progression and metastasis. This paper proposes the treatment principle of "wind-dispelling throughout the entire process and stage-based treatment", according to the pathological evolution of "collateral deficiency-collateral stagnation-collateral accumulation". In the prodromal stage, it is suggested to dispel wind and resolve toxin, fortify spleen and tonify collaterals; in the progressive and transitional stage, the method of dispelling wind pathogen, clearing phlegm and eliminating stasis should be used; in the carcinogenesis stage, it is suggested to expel wind and remove pathogens from collaterals, disperse concretions and eliminate tumors.
7.Research progress on the impact of conversational artificial intelligence on proactive health behaviors in adolescents
LIU Yaowu,YIN Zhihua,ZHOU Qingyuan
Chinese Journal of School Health 2026;47(6):898-903
Abstract
Conversational artificial intelligence (CAI), as an emerging digital tool, holds distinct potential for enhancing adolescents health literacy and fostering proactive health behaviors. In light of the increasing need for upstream prevention and early intervention in adolescent physical and mental health, the review systematically synthesizes current evidence on the role of CAI in shaping proactive health behaviors. It dissects the underlying mechanisms of CAI through a triple logic framework: technological context driven, psychological motivation activation, and behavior generation and maintenance.It also maps the evolving applications of CAI in areas such as psychological support and lifestyle interventions. Finally, it outlines future prospects, emphasizing the strengthening of agency awareness cultivation and human-computer collaborative interventions, aiming to provide a theoretical foundation and practical guidance for leveraging CAI to power adolescents in developing proactive health behaviors.
8.The Effect of Active Muscle Action on Neck Injuries under High Gx Loading
Junyuan LIU ; Zhengyu MAO ; Shuai LIU ; Lijun CHANG ; Tao LI ; Tianhao WANG ; Zhihua CAI
Journal of Medical Biomechanics 2025;40(3):684-691
Objective To investigate the effect of active muscle response on mechanical responses and injuries of human neck under high Gx loading.Methods A refined finite element model of the head and neck with active muscle response was established and validated based on the existing post-crash volunteer experiments.The effects of active muscle action on the kinematic and biomechanical responses of the neck were investigated under different G-value loads and at each tilting angle using this model.Results The stress distribution of vertebrae under high Gx load was dispersed from C4-7 to the whole vertebrae,and the active muscle action reduced the stress change,and the effect was significant under 8 G acceleration,which reduced the peak vertebral bone stress by 23.6%and 11.6%,and the peak intervertebral disc stress by 42.3%and 63.4%under 8 G and 10 G conditions,respectively.The maximum stress difference of 34.3 MPa was achieved by the active muscle action at 15° backward tilting.Conclusions The neck showed better stability by the active muscle action under the impact of high Gx loading.At different tilting angles,the active muscle action was more obvious in the backward tilting posture compared with the forward tilting and upright seated postures,and the backward tilting posture was safer to meet the impact when the same active muscle action was applied.The results can provide a reference for the subsequent studies related to the neck injury.
9.Cervical Kyphosis Based on Cervical Rehabilitation Training System:A Biomechanical Model Study
Zhihua LIU ; Mingwen ZHANG ; Yang ZHOU ; Yankui SHEN ; Zhongzhong CHEN
Journal of Medical Biomechanics 2025;40(3):615-622
Objective A biomechanical model of cervical kyphosis under the effects of axial traction load and lateral push load was establised,so as to provide a theoretical basis for the treatment of cervical curvature abnormalities,and formulate the most appropriate treatment plan for patients.Methods Based on the CT scan data of patients,the axial data of the cervical spine was extracted to fit the cervical curvature curve.Using the Timoshenko beam theory and the cervical rehabilitation training system,a mathematical model of cervical kyphosis was established for analytical calculations to obtain the recovery curve of the cervical spine under load and the total load required to cure cervical kyphosis,and its rationality was also verified.Results The biomechanical model of cervical kyphosis was established.Under the effects of axial traction load and lateral push load,the cervical spine effectively developed in the direction of physiological bending.The total axial load and lateral load were 353 N and 5 649 N,respectively,and the total axial load increased with the increase in traction angle.The therapeutic moment of the total lateral load decreased as the Bordon value increased.The therapeutic moment of the axial load was smaller than that of the lateral load in the range of normal Bordon value,confirming the rationality of the loads.Conclusions The established biomechanical model of cervical kyphosis can accurately simulate the biomechanical characteristics of the cervical spine,and the analysis results were valid,providing a mechanical theoretical basis for the design of treatment plans for patients.
10.A medical theory teaching quality assessment model based on classroom behavior analysis
Yuchuan LIU ; Jun YI ; Zhihua QU ; Chengmin WANG ; Haibo YANG
Chinese Journal of Medical Education Research 2025;24(3):320-324
Objective:In response to the subjectivity and poor real-time performance in methods for evaluating the quality of medical theory teaching, this study aims to develop an objective and real-time evaluation method for medical theory teaching quality.Methods:Classroom behavior data from both teachers and students in the course "medical image processing" were collected. An approach combining chain-like agent genetic algorithm with support vector regression machines was employed to analyze the collected classroom behavior data, and a classroom behavior-based evaluation model for medical theory teaching quality was established.Results:The predicted value generated by the model showed minimal error compared to students' actual answer accuracy, with an average absolute error of 4.84%. Additionally, the model demonstrated low time computation, with an average modeling time of 8.63 seconds and an average prediction time of 21.00 milliseconds.Conclusions:The constructed teaching quality assessment model shows high fitting precision and low time consumption.


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