1.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.
2.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.
3.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.
4.Application value of soluble C5b-9 in the diagnosis of delayed graft function after kidney transplantation
Lihong SHANG ; Zhihua WANG ; Wenyan ZHANG ; Jiaoxia LIANG ; Mingjun WANG ; Ning LI ; Shaohua SHI ; Linru ZHU
Organ Transplantation 2026;17(5):757-764
Objective To explore the diagnostic value of soluble C5b-9 (sC5b-9) for delayed graft function (DGF) following kidney transplantation. Methods Clinical data of 49 kidney transplant recipients who underwent sC5b-9 detection at the Second People’s Hospital of Shanxi Province between January 2024 and December 2025 were retrospectively analyzed. Recipients were divided into the DGF group (n=25) and the non-DGF group (n=24) according to the occurrence of DGF. Baseline characteristics and serum sC5b-9 levels were compared between the two groups. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic efficacy of sC5b-9 for DGF. A restricted cubic spline model was adopted to investigate the association between sC5b-9 and DGF. Results Among the 49 recipients, DGF occurred in 25 patients. Compared with the non-DGF group, the DGF group presented a higher proportion of male patients, a higher incidence of adverse transplant outcomes, and elevated final serum creatinine levels (all P<0.05). Within 30 days after transplantation, sC5b-9 concentrations were significantly higher in the DGF group than those in the non-DGF group (P<0.001). ROC analysis revealed that the area under the curve (AUC) of sC5b-9 for diagnosing DGF was 0.81, with a 95% confidence interval (CI) of 0.68-0.92, and the optimal cutoff value was 265.7 ng/mL. Recipients with elevated sC5b-9 (≥265.7 ng/mL) had a significantly higher incidence of DGF than those with low sC5b-9 levels (<265.7 ng/mL) (P<0.001). Recipients with adverse outcomes exhibited significantly higher sC5b-9 levels than those without adverse outcomes (P<0.001), and the AUC of sC5b-9 for identifying adverse outcomes was 0.82 (95%CI 0.63-0.95). A significant nonlinear correlation was observed between sC5b-9 and final serum creatinine (P<0.001). Conclusions Elevated sC5b-9 is correlated with the development of DGF after kidney transplantation and exhibits favorable diagnostic performance. It may serve as a potential biomarker for predicting early allograft dysfunction and adverse outcomes in kidney transplant recipients.
5.Distribution characteristics of smoking behavior among adult twins in China
Shunkai LIU ; Wenjing GAO ; Weihua CAO ; Jun LYU ; Canqing YU ; Shengfeng WANG ; Tao HUANG ; Dianjianyi SUN ; Chunxiao LIAO ; Yuanjie PANG ; Ruqin GAO ; Min YU ; Jinyi ZHOU ; Xianping WU ; Zhong DONG ; Fan WU ; Dezheng WANG ; Zhihua XU ; Yu LIU ; Jianrui WANG ; Jie YIN ; Shengli YIN ; Liming LI
Chinese Journal of Preventive Medicine 2025;59(7):1090-1096
This study aims to describe the population and regional distribution characteristics of smoking behavior among adult twins in the China Twin Registry (CNTR), as well as the concordance rates for smoking behavior in monozygotic and dizygotic twins, and estimate the heritability. The study population included adult twins in CNTR who had smoking questionnaire data. A random-effects regression model was used to describe the distribution of smoking behavior among different subgroups based on various characteristics. The concordance of smoking behavior between different zygosity groups was calculated, and heritability was estimated. A total of 28 444 twin pairs were included in this study, with an average age of (36.6±12.0) years. Among male twins, 41.2% were current smokers, while only 1.2% of females smoked. Higher smoking rates were observed among male smokers in the 50-59 age group ( z=23.0, P<0.001), northern regions ( z=2.9, P<0.01), rural areas ( z=-5.2, P<0.001), those who were divorced/widowed ( z=3.8, P<0.001), and first-born twins ( z=-4.3, P<0.001), while lower smoking rates were found in those with higher education ( z=-16.1, P<0.001) and unmarried individuals ( z=-16.0, P<0.001). The smoking concordance rate for male monozygotic twins was 69.6%, significantly higher than the 57.3% concordance rate for dizygotic twins ( χ 2=105.0, P<0.05). The heritability of smoking behavior in male twins was estimated at 28.9% (95% CI: 24.3%-33.4%). Stratified analyses showed differences in heritability across regions and age groups: the heritability in northern regions was 32.6% (95% CI: 27.3%-38.0%), higher than the 21.0% (95% CI: 12.4%-29.5%) observed in southern regions; the highest heritability of 35.1% (95% CI: 26.3%-43.9%) was found in the 18-29 age group, with heritability decreasing with age. In conclusion, the smoking rate and influencing factors in the twin population are similar to those in the general population, with unique characteristics, such as higher smoking rates in first-born twins. Genetic factors have a significant impact on smoking behavior.
6.Study on the medication rules of traditional Chinese medicine in treating breast cancer based on data mining
Yuan LI ; Lin QIAN ; Chao TIAN ; Tao WU ; Lyuhui HU ; Bingmei ZHU ; Zhihua YE ; Zhizhen TAO ; Min YANG ; Qinxi LIU ; Bihui YANG ; Hang LUO ; Fan QU ; Yi YANG
China Modern Doctor 2025;63(24):68-72,129
Objective To analyze the medication rules of traditional Chinese medicine in treating breast cancer based on real-world data mining.Methods Inpatients with breast cancer who received traditional Chinese medicine treatment at the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from January 2017 to December 2021 were selected.Python 3.10 software was used to mine traditional Chinese medicine prescription data;SPSS 23.0 software was applied for descriptive analysis,and systematic cluster analysis was performed on high-frequency drugs.Results A total of 3026 consultation records of inpatients with breast cancer were collected.The main traditional Chinese medicine syndrome diagnosis of"predominantly liver depression and Qi stagnation"accounted for 60.94%of the total consultations.A total of 240 kinds of traditional Chinese medicine were used,with a cumulative frequency of 35 462 times.Among them,29 kinds of traditional Chinese medicine such as Danggui,Fuling,Baizhu,Chaihu had a cumulative usage frequency exceeding 300 times.Regarding the four natures of drugs,cold-natured(43.55%),warm-natured(30.05%),and neutral-natured(23.34%)drugs were predominant;In terms of five flavors,sweet(46.12%),bitter(30.91%),and pungent(20.02%)were the main ones.The most frequently used drugs were tonifying herbs(32.77%),followed by heat-clearing herbs(15.96%)and phlegm-resolving herbs(14.71%).Systematic cluster analysis yielded 7 groups of drug combinations.Conclusion In real-world clinical practice,traditional Chinese medicine for breast cancer mainly uses tonifying herbs,reflecting the traditional Chinese medicine principle of"strengthening healthy Qi and cultivating the root"in treating tumors.The four natures and five flavors of drugs follow syndrome differentiation and the combination of cold and heat.The clustered drug combinations have extensive therapeutic effects,covering various syndromes of breast cancer at different stages,which can provide a reference for clinical medication.
7.Correlation between serum MIF,25(OH)D and cognitive function in patients with vestibular migraine
Xiao JIN ; Yanhong WANG ; Lianqi YANG ; Dong ZHANG ; Yong LI ; Zhihua REN ; Caihong WANG
Tianjin Medical Journal 2025;53(11):1175-1179
Objective To explore the correlation between serum macrophage migration inhibitory factor(MIF),25-hydroxyvitamin D[25(OH)D]and cognitive function in patients with vestibular migraine(VM).Methods A total of 200 patients with VM were selected and used as the VM group.Based on the Montreal Cognitive Assessment(MoCA)criteria,patients were divided into the cognitively normal group(128 cases)and the cognitively impaired group(72 cases).Additionally,200 healthy individuals undergoing routine health examination were selected as the control group.Serum MIF and 25(OH)D levels were measured using enzyme-linked immunosorbent assay.Multivariate Logistic regression was used to analyze influencing factors of cognitive impairment in VM patients.The value of serum MIF and 25(OH)D levels in diagnosing cognitive impairment in patients with VM was analyzed by using the receiver operating characteristic(ROC)curve.Results The serum MIF was higher in the VM group than that of the control group,and serum 25(OH)D was lower in the VM group(P<0.05).The serum MIF was higher in the cognitive impairment group than that of the cognitive normal group,while the serum 25(OH)D was lower in the cognitive impairment group than that of the cognitive normal group(P<0.05).Multivariate Logistic regression found that increased serum MIF level and decreased 25(OH)D level were independent risk factors for cognitive impairment in VM patients(P<0.05).ROC curve analysis showed that the AUC(95%CI)of the combined diagnosis of cognitive impairment in VM patients using serum MIF and 25(OH)D levels was 0.900(0.850-0.938),which was higher than that of MIF diagnosed alone[0.797(0.735-0.851)]and 25(OH)D alone[0.817(0.756-0.868),P<0.05].Conclusion VM patients with cognitive impairment have elevated serum MIF levels and decreased 25(OH)D levels.The combined diagnostic value of the two markers has a relatively high value for VM patients with cognitive impairment.
8.Multivariate analysis of factors influencing prognosis in IDH wild-type glioblastoma
Yan YANG ; Wanfu YANG ; Hailiang LI ; Zhihua YANG
Tianjin Medical Journal 2025;53(12):1290-1294
Objective To investige clinicopathological features and prognostic factors in patients with isocitrate dehydrogenase(IDH)wild-type glioblastoma(GBM).Methods A total of 137 patients with GBM diagnosed by surgical pathology at the General Hospital of Ningxia Medical University from January 2014 to July 2024 were retrospectively enrolled in this study.Clinical data,including age,gender,ethnicity,presence of epilepsy,neurological function status and Karnofsky Performance Status(KPS)score prior to radiotherapy,were collected.Tumor-related parameters,such as extent of resection,histological classification,tumor location,maximum tumor diameter,IDH mutation status,Ki-67 proliferation index,methylation status of the O6-methylguanine-DNA methyltransferase(MGMT)promoter and postoperative treatment regimens—including concurrent chemoradiotherapy and the number of adjuvant chemotherapy cycles were also recorded.Multivariate Cox proportional hazards regression analysis was conducted to identify independent prognostic factors.Kaplan-Meier survival curves were used to evaluate overall survival according to clinical characteristics.Results The median overall survival(OS)of the 137 GBM patients was 20.9 months,and their 1-year,2-year and 3-year survival rates were 79.7%,36.9%and 16.4%,respectively.Pre-radiotherapy KPS score,MGMT promoter methylation status,receipt of postoperative concurrent chemoradiotherapy and the number of adjuvant chemotherapy cycles were significantly associated with median survival of GBM patients(P<0.05).Multivariate Cox analysis revealed that absence of MGMT promoter methylation,lack of postoperative concurrent chemoradiotherapy after surgery and the number of adjuvant chemotherapy cycles<6 were independent risk factors for reduced survival in patients with GBM(P<0.05).Patients with a pre-radiotherapy KPS score<80,MGMT promoter unmethylation,lack of postoperative concurrent chemoradiotherapy and the number of adjuvant chemotherapy cycles<6 demonstrated significantly lower cumulative overall survival rates compared to those with these characteristics(P<0.05).Conclusion MGMT promoter unmethylation,lack of postoperative concurrent chemoradiotherapy and adjuvant chemotherapy cycles<6 are independent risk factors affecting overall survival in patients with IDH wild-type GBM.
9.Correlation between serum MIF,25(OH)D and cognitive function in patients with vestibular migraine
Xiao JIN ; Yanhong WANG ; Lianqi YANG ; Dong ZHANG ; Yong LI ; Zhihua REN ; Caihong WANG
Tianjin Medical Journal 2025;53(11):1175-1179
Objective To explore the correlation between serum macrophage migration inhibitory factor(MIF),25-hydroxyvitamin D[25(OH)D]and cognitive function in patients with vestibular migraine(VM).Methods A total of 200 patients with VM were selected and used as the VM group.Based on the Montreal Cognitive Assessment(MoCA)criteria,patients were divided into the cognitively normal group(128 cases)and the cognitively impaired group(72 cases).Additionally,200 healthy individuals undergoing routine health examination were selected as the control group.Serum MIF and 25(OH)D levels were measured using enzyme-linked immunosorbent assay.Multivariate Logistic regression was used to analyze influencing factors of cognitive impairment in VM patients.The value of serum MIF and 25(OH)D levels in diagnosing cognitive impairment in patients with VM was analyzed by using the receiver operating characteristic(ROC)curve.Results The serum MIF was higher in the VM group than that of the control group,and serum 25(OH)D was lower in the VM group(P<0.05).The serum MIF was higher in the cognitive impairment group than that of the cognitive normal group,while the serum 25(OH)D was lower in the cognitive impairment group than that of the cognitive normal group(P<0.05).Multivariate Logistic regression found that increased serum MIF level and decreased 25(OH)D level were independent risk factors for cognitive impairment in VM patients(P<0.05).ROC curve analysis showed that the AUC(95%CI)of the combined diagnosis of cognitive impairment in VM patients using serum MIF and 25(OH)D levels was 0.900(0.850-0.938),which was higher than that of MIF diagnosed alone[0.797(0.735-0.851)]and 25(OH)D alone[0.817(0.756-0.868),P<0.05].Conclusion VM patients with cognitive impairment have elevated serum MIF levels and decreased 25(OH)D levels.The combined diagnostic value of the two markers has a relatively high value for VM patients with cognitive impairment.
10.Distribution characteristics of smoking behavior among adult twins in China
Shunkai LIU ; Wenjing GAO ; Weihua CAO ; Jun LYU ; Canqing YU ; Shengfeng WANG ; Tao HUANG ; Dianjianyi SUN ; Chunxiao LIAO ; Yuanjie PANG ; Ruqin GAO ; Min YU ; Jinyi ZHOU ; Xianping WU ; Zhong DONG ; Fan WU ; Dezheng WANG ; Zhihua XU ; Yu LIU ; Jianrui WANG ; Jie YIN ; Shengli YIN ; Liming LI
Chinese Journal of Preventive Medicine 2025;59(7):1090-1096
This study aims to describe the population and regional distribution characteristics of smoking behavior among adult twins in the China Twin Registry (CNTR), as well as the concordance rates for smoking behavior in monozygotic and dizygotic twins, and estimate the heritability. The study population included adult twins in CNTR who had smoking questionnaire data. A random-effects regression model was used to describe the distribution of smoking behavior among different subgroups based on various characteristics. The concordance of smoking behavior between different zygosity groups was calculated, and heritability was estimated. A total of 28 444 twin pairs were included in this study, with an average age of (36.6±12.0) years. Among male twins, 41.2% were current smokers, while only 1.2% of females smoked. Higher smoking rates were observed among male smokers in the 50-59 age group ( z=23.0, P<0.001), northern regions ( z=2.9, P<0.01), rural areas ( z=-5.2, P<0.001), those who were divorced/widowed ( z=3.8, P<0.001), and first-born twins ( z=-4.3, P<0.001), while lower smoking rates were found in those with higher education ( z=-16.1, P<0.001) and unmarried individuals ( z=-16.0, P<0.001). The smoking concordance rate for male monozygotic twins was 69.6%, significantly higher than the 57.3% concordance rate for dizygotic twins ( χ 2=105.0, P<0.05). The heritability of smoking behavior in male twins was estimated at 28.9% (95% CI: 24.3%-33.4%). Stratified analyses showed differences in heritability across regions and age groups: the heritability in northern regions was 32.6% (95% CI: 27.3%-38.0%), higher than the 21.0% (95% CI: 12.4%-29.5%) observed in southern regions; the highest heritability of 35.1% (95% CI: 26.3%-43.9%) was found in the 18-29 age group, with heritability decreasing with age. In conclusion, the smoking rate and influencing factors in the twin population are similar to those in the general population, with unique characteristics, such as higher smoking rates in first-born twins. Genetic factors have a significant impact on smoking behavior.

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