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.Introduction of the main addition and revision of the Chinese Pharmacopoeia 2025 Edition(Volume Ⅱ)
ZHOU Yi ; WANG Zhijun ; YUE Zhihua ; CHENG Qilei ; YUE Ruiqi ; YANG Xi ; GUO Wei ; MA Shuangcheng
Drug Standards of China 2025;26(1):023-027
The Pharmacopeia of the People’s Republic of China 2025 Edition (referred to as the Chinese Pharmacopoeia 2025 Edition, ChP 2025) will be promulgated and implemented. This article introduces the process of development of ChP 2025 Edition (Volume Ⅱ), including the selection, the revision of general notices,the addition and revision of drug monographs, etc., and provides some analysis and examples to illustrate,which can facilitate the readers to understand and implement the ChP 2025 Edition (Volume Ⅱ).
6.Influencing factors of chronic dyslipidemia in T2DM patients with diabetes point system management in Qingpu District,Shanghai
Zhouli WU ; Sen WANG ; Jie CHEN ; Zhihua REN ; Kaiyou YE ; Yueqin JIANG ; Ya WU
Journal of Public Health and Preventive Medicine 2025;36(2):56-60
Objective To understand the influencing factors of chronic dyslipidemia in T2DM patients who signed a contract for diabetes point system management in Qingpu District, and to provide a basis for comprehensive intervention and prevention and control of dyslipidemia in T2DM patients and to optimize the management strategy of Qingpu District diabetes point system. Methods Among the T2DM patients who signed the diabetes point system from 2017 to 2023, patients with chronic dyslipidemia and normal blood lipids were selected and included in the case group and the control group, respectively. A case-control study was conducted with 1:1 matching by age and gender to analyze the factors influencing dyslipidemia. Results Multifactorial paired logistic regression analysis showed that overweight/obesity and central obesity and smoking in T2DM patients increased the risk of dyslipidemia by 1.93, 2.27, and 2.16 times, respectively. Long-term use of lipid-lowering drugs, duration of diabetes for 5 years or more, regular physical exercise, knowledge of blood lipid status, and married status could reduce the risk of dyslipidemia in T2DM patients (OR values were 0.547, 0.452, 0.685, 0.386 and 0.354, respectively). Current complications (history of stroke, coronary heart disease, and renal insufficiency) were also associated with dyslipidemia (OR=1.802, 95% CI:1.125-2.888). Conclusion The management of diabetes point system in Qingpu District should strengthen the feedback and interpretation of blood lipid monitoring results, improve patients’ health awareness of blood lipid management, and actively take comprehensive management of lifestyle intervention and drug treatment to effectively control blood lipid and reduce the occurrence of related complications.
7.Application of early screening scale and evaluation of behavioral intervention effect in children with autism spectrum disorder
Bin ZHANG ; Chunwei HU ; Zhihua LIU ; Huiting YANG ; Canjun WANG ; Xineng FENG
Journal of Public Health and Preventive Medicine 2025;36(4):77-80
Objective To understand the application effect of early screening scale and behavioral intervention effect in children with autism spectrum disorder (ASD). Methods A total of 348 children with suspected ASD were selected and evaluated using the Modified Checklist for Autism in Toddlers (M-CHAT) and Autism Behavior Checklist (ABC). The evaluation results were compared with those from the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). Children enrolled were given Early start Denver model (ESDM) intervention. The evaluation results of Gesell Developmental Scale and Autism Treatment Evaluation Checklist (ATEC) scores were compared before and after intervention. Results The sensitivity, specificity, accuracy and Kappa value of M-CHAT for evaluating ASD in children aged 1-3 years were 89.53%, 90.70%, 89.92% and 0.78. The corresponding values of ABC were 78.49%, 81.40%, 79.46% and 0.56. The sensitivity, specificity, accuracy and Kappa value of M-CHAT for evaluating children aged >3-6 years were 87.30%, 77.78%, 84.44% and 0.64. The corresponding values of ABC were 85.71%, 77.78%, 83.33% and 0.62. The sensitivity and accuracy of M-CHAT were higher than ABC for evaluating ASD in children aged 1-3 years (P<0.05). There were no significant differences in sensitivity, specificity and accuracy between M-CHAT and ABC for evaluating ASD in children aged 3-6 years (P>0.05). After intervention, development quotients (DQ) of personal-social aspects, adaptability, language, gross motor, and fine motor of children with ASD were higher than those before intervention (P<0.05). ATEC scores for language, behavior, sensation, and social contact of children with ASD were lower than those before intervention (P<0.05). Conclusion M-CHAT and ABC both can be used for early screening of ASD in children, especially M-CHAT. Early behavioral intervention can effectively improve the condition and developmental level of children with ASD.
8.Comparison of the effect of obesity indicators in predicting cardiovascular and cerebrovascular diseases among patients with type 2 diabetes mellitus
LU Jie ; ZHANG Ke ; WU Ya ; WANG Yue ; ZHANG Yue ; LU Ye ; WU Zhouli ; REN Zhihua ; HUANG Yiwen
Journal of Preventive Medicine 2025;37(9):886-891
Objective:
To explore the effect of different obesity indicators in predicting cardiovascular and cerebrovascular diseases (CVD) risk among patients with type 2 diabetes mellitus (T2DM), so as to provide the evidence for the early identification of CVD risk among T2DM patients.
Methods:
The patients with T2DM under community management in Qingpu District, Shanghai Municipality were selected as the study subjects in January 2025. Basic information such as gender, age, and blood glucose control status were collected through the Shanghai Chronic Disease Information Management System, while history of CVD were obtained from residents' electronic health records and the Shanghai Disease Control Information Platform. Obesity was assessed using body mass index (BMI), waist circumference (WC), BMI combined with WC, waist-to-height ratio (WHtR), and triglyceride (TG) combined with WC indicators. The association between obesity and CVD was analyzed using multivariable logistic regression models. The predictive effect of each obesity indicators for CVD was evaluated using the area under the receiver operating characteristic curve (AUC).
Results:
A total of 4 367 patients with T2DM were included, including 2 121 males (48.57%) and 2 246 females (51.43%). The average age was (68.71±8.05) years. The prevalence of CVD was 44.49%. Multivariable logistic regression analysis showed that after adjusting for age, education level, history of hypertension, duration of T2DM, use of glucose-lowering medications, renal function, and blood glucose control status, obese T2DM patients had a 389.4% increased risk of CVD compared to those with normal BMI; centrally obese T2DM patients had a 100.4% increased risk compared to those with normal WC; T2DM patients with isolated general obesity and compound obesity had 161.0% and 241.1% increased risks of CVD, respectively, compared to those with normal BMI and WC; centrally obese T2DM patients had a 100.4% increased risk compared to those with normal WHtR; T2DM patients with normal TG-high WC and high TG-high WC phenotypes had 83.1% and 68.8% increased risks of CVD, respectively, compared to those with normal TG and normal WC (all P<0.05). BMI had the highest AUC, at 0.714, with sensitivity and specificity of 0.675 and 0.642, respectively. This was followed by BMI combined with WC, which had an AUC of 0.707, with sensitivity and specificity of 0.635 and 0.679, respectively.
Conclusions
Obesity defined by BMI, WC, BMI combined with WC, WHtR, and TG combined with WC increases the risk of CVD among patients with T2DM. BMI and BMI combined with WC have better predictive effect in predicting CVD risk among patients with T2DM, and can be used as the primary obesity indicators for CVD risk screening.
9.Experience and insights from sexuality education curriculum in Ireland
WANG Yanfang, JIANG Jiajun, LI Mengwei, YIN Zhihua
Chinese Journal of School Health 2025;46(11):1526-1529
Abstract
To promote the development of sexuality education for Chinese adolescents, the study analyses Ireland s relationships and sexuality education (RSE) curriculum and concludes that it centers on student development in terms of curriculum philosophy and objectives, emphasizing its educational value. At the content level, it employs a staged teaching approach to achieve comprehensive coverage based on students physical and mental development characteristics. In terms of implementation, it adopts a spiral organization to ensure the scientific integrity of the curriculum. In addition, it utilizes diverse evaluation methods to strengthen the systematic nature of the curriculum. Based on these insights, China could collaborate with multiple stakeholders to advance the development of RSE, establish a scientific and systematic framework for RSE, and constructing a comprehensive implementation and teacher support system, thereby promoting the refinement and innovation of RSE programs.
10.Dihydromyricetin mitigates abdominal aortic aneurysm via transcriptional and post-transcriptional regulation of heme oxygenase-1 in vascular smooth muscle cells.
Weile YE ; Pinglian YANG ; Mei JIN ; Jiami ZOU ; Zhihua ZHENG ; Yuanyuan LI ; Dongmei ZHANG ; Wencai YE ; Zunnan HUANG ; Jiaojiao WANG ; Zhiping LIU
Acta Pharmaceutica Sinica B 2025;15(3):1514-1534
Abdominal aortic aneurysm (AAA) is a deadly condition of the aorta, carrying a significant risk of death upon rupture. Currently, there is a dearth of efficacious pharmaceutical interventions to impede the advancement of AAA and avert it from rupturing. Here, we investigated dihydromyricetin (DHM), one of the predominant bioactive flavonoids in Ampelopsis grossedentata (A. grossedentata), as a potential agent for inhibiting AAA. DHM effectively blocked the formation of AAA in angiotensin II-infused apolipoprotein E-deficient (ApoE-/-) mice. A combination of network pharmacology and whole transcriptome sequencing analysis revealed that DHM's anti-AAA action is linked to heme oxygenase (HO)-1 (Hmox-1 for the rodent gene) and hypoxia-inducible factor (HIF)-1α in vascular smooth muscle cells (VSMCs). Remarkably, DHM caused a robust rise (∼10-fold) of HO-1 protein expression in VSMCs, thereby suppressing VSMC inflammation and oxidative stress and preserving the VSMC contractile phenotype. Intriguingly, the therapeutic effect of DHM on AAA was largely abrogated by VSMC-specific Hmox1 knockdown in mice. Mechanistically, on one hand, DHM increased the transcription of Hmox-1 by triggering the nuclear translocation and activation of HIF-1α, but not nuclear factor erythroid 2-related factor 2 (NRF2). On the other hand, molecular docking, combined with cellular thermal shift assay (CETSA), isothermal titration calorimetry (ITC), drug affinity responsive target stability (DARTS), co-immunoprecipitation (Co-IP), and site mutant experiments revealed that DHM bonded to HO-1 at Lys243 and prevented its degradation, thereby resulting in considerable HO-1 buildup. In summary, our findings suggest that naturally derived DHM has the capacity to markedly enhance HO-1 expression in VSMCs, which may hold promise as a therapeutic strategy for AAA.


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