1.Multicenter machine learning-based construction of a model for predicting potential organ donors and validation with decision curve analysis
Xu WANG ; Wenxiu LI ; Fenghua WANG ; Shuli WU ; Dong JIA ; Xin GE ; Zhihua SHAN ; Tongzuo LI
Organ Transplantation 2026;17(1):106-115
Objective To evaluate the predictive value of different machine learning models constructed in a multicenter environment for potential organ donors and verify their clinical application feasibility. Methods The study included 2 000 inpatients admitted to five domestic tertiary hospitals from January 2020 to December 2023, who met the criteria for potential organ donation assessment. They were randomly divided into a training set and an internal validation set (7∶3). Another 300 similar patients admitted to the First Affiliated Hospital of Harbin Medical University from January 2024 to April 2025 were included as an external validation set. The area under the curve (AUC), sensitivity, specificity, accuracy and F1-score of three models were compared, and the consistency of the potential organ donor determination process was tested. Multivariate logistic regression analysis was used to identify predictive factors of potential organ donors. Decision curve analysis (DCA) was employed to verify the resource efficiency of each model, and the threshold interval and intervention balance point were assessed. Results Apart from age, there were no significant differences in other basic characteristics among the centers (all P>0.05). The consistency of the potential organ donor determination process among researchers in each center was good [all 95% confidence interval (CI) lower limits >0]. In the internal validation set, the XGBoost model had the best predictive performance (AUC=0.92, 95% CI 0.89-0.94) and the best calibration (P=0.441, Brier score 0.099). In the external validation set, the XGBoost model also had the best predictive performance (AUC=0.91, 95% CI 0.88-0.94), outperforming logistic regression and random forest models. Multivariate logistic regression showed that mechanical ventilation had the greatest impact (odds ratio=2.06, 95% CI 1.54-2.76, P<0.001). DCA indicated that the XGBoost model had the highest net benefit in the threshold interval of 0.2-0.6. The “treat all” strategy only had a slight advantage at extremely low thresholds. The recommended threshold interval, which balances intervention costs and clinical benefits, considers ≥50% positive predictive value (PPV) and ≤50 referrals per 100 high-risk patients. Conclusions The XGBoost model established in a multicenter environment is accurate and well-calibrated in predicting potential organ donors. Combined with DCA, it may effectively guide the timing of clinical interventions and resource allocation, providing new ideas for the assessment and management of organ donation after brain death.
2.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.
3.Epigenetic mechanism of Diwu Yanggan Capsule in improving liver regeneration microenvironment in a rat model of liver cancer
Minggang WANG ; Jiamei DONG ; Zhihua YE ; Xiang GAO ; Qi CHEN ; Xiaoqiao YU ; Hanmin LI
Journal of Clinical Hepatology 2026;42(2):362-371
ObjectiveTo investigate the epigenetic mechanism of Diwu Yanggan Capsule in improving liver regeneration microenvironment in a rat model of liver cancer by regulating DNA methylation, and to provide a basis for scientific clinical medication. MethodsA total of 48 specific pathogen-free Sprague-Dawley rats were divided into normal group, model group, and Diwu Yanggan Capsule group using a random number table, with 16 rats in each group. The Solt-Farber two-step method was used to establish a rat model of liver cancer. The rats in the Diwu Yanggan Capsule group were given Diwu Yanggan Capsule at a dose of 750 mg/kg/d by gavage, and those in the normal group and the model group were given an equal volume of normal saline by gavage. Liver tissue samples were collected from each group of rats after 16 weeks of continuous intervention; DNA methylation chips were used to analyze the change in DNA methylation in liver tissue, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used for data analysis. In addition, the MeDIP-PCR technique was used to detect the changes in candidate differentially methylated genes such as YWHAB, ADCK2, ERLIN2, SEMA3B, and TPH2 in the liver tissue of rats, and Western blot and RT-qPCR were used to verify the expression of key methylated genes. The independent-samples t test was used for comparison of continuous data between two groups, and a one-way analysis of variance was used for comparison between multiple groups, while the least significant difference t-test was used for further comparison between two groups. ResultsThe DNA methylation chip analysis showed that compared with the normal group, the model group had significant methylation changes in the promoter region of 2 422 genes in liver tissue of rats. The GO functional enrichment analysis and the KEGG pathway enrichment analysis showed that these differentially methylated genes were significantly enriched in metabolic pathways such as steroid hormone biosynthesis and drug metabolism-cytochrome P450. Compared with the model group, the Diwu Yanggan Capsule group had significant reversal of promoter methylation in 1 650 genes, and the KEGG enrichment analysis showed that these genes were mainly involved in the pathways closely associated with cell proliferation, apoptosis, and microenvironment regulation, such as the calcium ion signaling pathway, the cAMP signaling pathway, and the extracellular factor signaling pathway. Compared with the model group, the Diwu Yanggan Capsule group had a significant increase in the promoter methylation level of the ADCK2 gene (P<0.05) and significant reductions in the promoter methylation levels of the ERLIN2 and TPH2 genes (all P<0.05). Compared with the model group, the Diwu Yanggan Capsule group had significant reductions in the mRNA expression levels and the protein expression levels of the ADCK2 (all P<0.05). ConclusionAbnormal DNA methylation in liver tissue participates in the development and progression of liver cancer. The effect of Diwu Yanggan Capsule on DNA methylation level is an important epigenetic mechanism for its effect in the prevention and treatment of liver cancer.
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.Construction and application of clinical inapplicability evaluation system for instructions of oral Chinese patent medicines containing toxic decoction pieces
He TANG ; Longlong TANG ; Xiaoyu JU ; Youquan TANG ; Zhihua WANG ; Jie CHENG
China Pharmacy 2026;37(11):1398-1402
OBJECTIVE To construct a clinical inapplicability evaluation system for the instructions of oral Chinese patent medicines containing toxic decoction pieces, so as to provide references for the revision and improvement of such drug instructions and the formulation of instructions for new drugs. METHODS The initial indicator framework was determined based on policy documents and literature related to instruction registration and revision. Two rounds of Delphi consultation were conducted among 25 experts to refine and optimize the indicator system. The analytic hierarchy process was employed to construct judgment matrices and obtain indicator weights. The comprehensive weights were converted into a 100-point scale to evaluate 11 instructions of oral Chinese patent medicines containing toxic decoction pieces from the medical institution of the research team. RESULTS The average questionnaire recovery rate of the two rounds of consultation was 96%. The expert authority coefficients were 0.87 and 0.88, respectively, and the Kendall’s W was statistically significant ( P <0.001). The final evaluation system comprised 4 first-level indicators (defect of toxicity identification, defect of dosage information, defect of risk warning, and defect of information guidance) and 24 second-level indicators (e.g., failure to label toxic decoction pieces in 【warnings】, failure to indicate all decoction piece compositions, absence of medication course specifications, etc.). The total scores of the 11 oral Chinese patent medicine instructions ranged from 15.50 to 50.87 points. The main clinical inapplicability issues included the absence of medication course specifications and the failure to provide warnings in items such as 【precautions】 for decoction pieces involving the “eighteen incompatibilities and nineteen mutual antagonisms”. CONCLUSIONS The constructed indicator system can meet the requirements for evaluating the clinical inapplicability of instructions for oral Chinese patent medicines containing toxic decoction pieces. All evaluated instructions exhibited certain clinical applicability defects. Pharmaceutical manufacturers should revise the instructions in accordance with policy requirements and clinical needs.
6.Echocardiographic features of critically ill patients with concurrent infections and their predictive value for 28-day mortality and cardiac injury
Peng GUO ; Yushan ZHOU ; Yibing WANG ; Zhihua ZHANG ; Jie SHEN ; Weichun MO
Chinese Journal of Clinical Medicine 2026;33(3):414-423
Objective To explore the echocardiographic features of critically ill patients with infection, and to evaluate the predictive value of echocardiographic parameters for 28-day mortality and myocardial injury. Methods Using a single-center prospective cohort design, 120 critically ill patients with infection admitted to the Intensive Care Unit, Jinshan Hospital of Fudan University from January 2024 to January 2025 were enrolled consecutively. According to the severity of infection, patients were divided into the sepsis group (n=75) and the non-sepsis group (n=45). Cox proportional hazards models and modified Poisson regression were used to analyze risk factors of 28-day all-cause mortality and myocardial injury. Kaplan-Meier survival curve and log-rank test were used to assess prognosis differences among patients with different ultrasound parameters. ROC curve and area under the curve (AUC) were applied to evaluate the predictive performance of ultrasound parameters, and restricted cubic spline (RCS) model was used to explore nonlinear relationships. Results The E/e′ ratio was significantly higher in the sepsis group than in the non-sepsis group (P<0.001), while left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were lower in the sepsis group (P<0.05). The Cox proportional hazards model found no association between ultrasound parameters and 28-day all-cause mortality. Modified Poisson regression showed that, after adjusting for confounding factors, elevated E/e′ was an independent risk factor of myocardial injury (RR=1.12, 95% CI 1.07–1.17, P<0.001). Survival analysis demonstrated that patients with E/e′ >10.9 had lower 28-day survival rates (P=0.02), and the AUC for E/e′ predicting myocardial injury was 0.835. RCS analysis suggested a nonlinear relationship between E/e′ and myocardial injury risk (P<0.001). Conclusions E/e′, LVEF, and LVFS have no significant predictive value for 28-day mortality risk in critically ill patients with infections. Elevated E/e′ is an independent risk factor of myocardial injury in such patients, with a nonlinear relationship.
7.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.
8.Common pathogens isolated from eczematous dermatitis patients and their associations with clinical stages
Yuan JIANG ; Wenming ZENG ; Zhihua SONG ; Chen WANG ; Meiyan WANG
Chinese Journal of Nosocomiology 2025;35(14):2100-2104
OBJECTIVE To detect the common pathogens for the patients with eczematous dermatitis and analyze associations between the pathogens and the clinical stages.METHODS A total of 206 patients with eczematous der-matitis who were treated in Jinhua Central Hospital from Jan.2014 to Jan.2024 were enrolled in the study and were divided into the secondary skin lesion group with 92 cases and the non-secondary skin lesion group with 114 cases according to the characteristics of the lesions.Meanwhile,the people who received physical examination and had no history of eczematous dermatitis were chosen as the control group with 91 cases.The distribution and den-sity of the common pathogens were compared among the three groups and among the patients with different clini-cal stages(the acute stage,the subacute stage and the chronic stage)of eczematous dermatitis.The scores of skin lesion were compared among the patients.RESULTS Staphylococcus aureus,Staphylococcus epidermidis and Malassezia were dominant among the isolated pathogens;both the positive rates of pathogens and the densities of pathogens,from the high to the low,were as follows:the secondary skin lesion group>the non-secondary skin lesion group>the control group(P<0.05).The isolation rate of S.aureus of the secondary skin lesion group and the non-secondary skin lesion group were higher than that of the control group(P<0.05);the isolation rate of Malassezia of the secondary skin lesion group was higher than that of the non-secondary skin lesion group(P<0.05).The score of skin lesion of the patients detected positive for pathogens was higher than that of the patients detected negative(P<0.05).Among the patients detected positive for pathogens,the score of skin lesion of the a-cute stage patients was higher than that of the subacute stage patients and the chronic stage patients(P<0.05);the isolation rates of S.aureus and Malassezia and the density of pathogens of the acute stage patients were higher than those of the chronic stage patients(P<0.05),and the density of pathogens of the subacute stage patients was higher than that of the chronic stage patients(P<0.05).CONCLUSIONS S.aureus,S.epidermidis and Malassezia are the common pathogens isolated from the patients with eczematous dermatitis.The positive rates and densities of pathogens are higher among the patients with secondary skin lesions,and the infections with the pathogens are associated with the severity of skin lesion and the clinical stage.
9.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.
10.Current situation and prevention and control of coal-burning-borne endemic fluorosis in key areas of the disease in Zhenxiong County, Yunnan Province
Kailian HUANG ; Anwei WANG ; Zhihua ZHAO ; Yujie LI ; Jiaguo LI ; Changyan PENG ; Tingting QIAN
Chinese Journal of Endemiology 2025;44(8):647-651
Objective:To investigate the current prevalence and control status of coal-burning-borne endemic fluorosis in key areas of the disease in Zhenxiong County of Yunnan Province, thereby providing scientific basis for formulating subsequent prevention strategies and measures.Methods:From October to November 2023, a simple random sampling method was used to conduct a survey in three key townships (towns) in Zhenxiong County, Chishuiyuan Town, Yanyuan Town, and Linkou Yi and Miao Ethnic Township. Three administrative villages were selected from each township (town) as survey sites, and dental fluorosis examination on children aged 8 - 12 years who were born and lived in the local area was conducted. Thirty households were selected from each survey site, the use of household stoves and the formation of related healthy living behaviors were investigated. At the same time, a survey was conducted among primary school students and housewives to investigate their knowledge of coal-burning-borne endemic fluorosis prevention and control. The control and elimination of endemic areas were evaluated according to the "Assessment Protocol for Control and Elimination of Key Endemic Diseases (2019 Edition)".Results:A total of 1 172 children were examined, and the detection rate of dental fluorosis was 7.76% (91/1 172), with a dental fluorosis index of 0.11. A total of 295 households were investigated, and the qualified improved stoves rate and the correct use rate of qualified improved stoves were 95.59% (282/295) and 100% (282/282), respectively. The correct drying rate of edible corn and chili peppers was 79.66% (235/295). The awareness rates of coal-burning-borne endemic fluorosis prevention and control knowledge among housewives and primary school students were 46.69% (409/876) and 82.49% (440.5/534), respectively. Among the 9 villages investigated, two villages had met the criteria for eliminating endemic disease areas, two villages had met the criteria for controlling endemic disease areas, and the remaining 5 villages were uncontrolled.Conclusions:After implementing the comprehensive prevention and control measures mainly based on changing stoves, coal-burning-borne endemic fluorosis condition in Zhenxiong County has been effectively controlled, but there is still a significant gap between the elimination goals of some endemic fluorosis areas. Therefore, it is necessary to continue to strengthen prevention and control measures and promote health education.

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