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.

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.

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.

Rheumatoid arthritis(RA)is an autoimmune disease characterized by chronic,aggressive joint inflammation,which seriously harms mental and physical health of patients.Efficacy of clinical drugs for RA is limited,so it is a hot issue to seek new therapeutic targets and drugs.Zinc finger protein A20,a cytoplasmic ubiquitin modifier,is closely related to negative regulation of nuclear factor-kappaB(NF-κB),an inflammatory signaling pathway,and has anti-inflammatory and anti-apoptotic effects.A20 is involved in pathogenesis of RA and can improve inflammatory response and bone destruction of RA.Treatment of RA by traditional Chinese medicine has unique advantages of multi-target and multi-pathway,and studies have found that traditional Chinese medicine has a regulatory effect on A20.This paper expounds mechanism of A20 in RA and research progress of traditional Chinese medicine intervention in A20,in order to provide references for treatment and drug development of RA.

Objective To investigate the correlation between immune cells and the occurrence of cardiovascular disease(CVD)in patients with human immunodeficiency virus/acquired immunodeficiency syndrome(HIV/AIDS),and to construct a risk prediction model.Methods A total of 280 HIV/AIDS patients treated from June 2024 to August 2025 were selected as the research subjects and divided into a training set(n=200)and a test set(n=80)at a ratio of 5:2.The patients in the training set were subdivided into a CVD subgroup(n=60)and a non-CVD subgroup(n=140)according to whether they developed CVD.The baseline characteristics and immune cells of the two groups were compared,and the longitudinal trajectory changes of immune cells in the CVD subgroup and the non-CVD subgroup were analyzed.LASSO regression analysis was used to screen the independent influencing factors of CVD,multivariate Logistic regression analysis was used to screen the independent risk factors for the occurrence of CVD,and a risk prediction nomogram model was constructed.The area under the receiver operating characteristic(ROC)curve(AUC),Hosmer-Lem show test,calibration curve,and decision curve were used to compare the risk prediction nomogram model with the general cardiovascular risk assessment model,to evaluate its discrimination,goodness-of-fit,and clinical utility.Results There were significant differences in the baseline characteristics and immune cells between the two groups(P<0.05).The longitudinal trajectory plots revealed that the CD4+count,CD8+count,and CD4+/CD8+level in the CVD group exhibited substantial fluctuations,while the trajectories of these parameters in the non-CVD group remained relatively stable.After LASSO regression analysis screened out 11 non-zero coefficient variables,multivariate logistic regression analysis showed that age,hypertension,total cholesterol,smoking,high-sensitivity C-reactive protein,CD4+count at the time of HIV diagnosis,CD8+count at the time of HIV diagnosis,and globulin were all independent influencing factors for the occurrence of CVD in HIV/AIDS patients(P<0.05).The AUC of the risk prediction nomogram model was 0.960 in the training set and 0.914 in the test set,indicating good discrimination of the model.The Hosmer-Lem show test and calibration curve showed good accuracy and consistency of the model,and the decision curve showed a high net benefit value,indicating good clinical utility.Conclusion The CVD risk in HIV/AIDS patients is jointly affected by immune dysfunction and traditional metabolic factors.The risk prediction nomogram model constructed significantly improves the accuracy of risk prediction of CVD and can provide a basis for early identification of high-risk patients and the formulation of individualized intervention strategies.

Objective To explore the influencing factors of health-related quality of life in patients after ileal ureteral replacement,and to provide a reference for formulating effective management plans.Methods Based on the conceptual model of health-related quality of life,16 patients who underwent ileal ureteral replacement in the Department of Urology of a tertiary A hospital in Beijing were selected for semi-structured interviews using descriptive research methods and purposive sampling method.The data were analyzed using directed content analysis.Results There are 6 themes and 10 sub-themes:symptom factors(distress of tube-related symptoms,distress of gastrointestinal symptoms);individual characteristics factors(obvious negative emotions,health behavior development);environmental factors(support from relatives and colleagues,lack of primary medical services);functional status factors(physical function rehabilitation,social function recovery);physiological function factors(test abnormal test index,risk of primary disease recurrence);general health perception factors.Conclusion The health-related quality of life of patients undergoing ileal ureteral replacement surgery was affected by symptoms,negative emotions,health behaviors,social support,functional status et al.In view of the above factors,medical staff should carry out effective evaluation and intervention in time,so as to improve the quality of life of patients.

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.

In the earliest existing pharmacological monograph in China,Shennong Bencao Jing,there is a record of a parasitic plant known as"desert ginseng"——Cistanche deserticola.It exerts beneficial effects on the function of the heart,kidney,spleen,and lung.As research into its pharmacological properties has progressed,the active components of Cistanche deserticola also have shown promise for treating intestinal disorders.Due to the complex pathological mechanisms of sepsis,which often accompany multiple organ dysfunction,aligns closely with the multi-target pharmacological characteristics of Cistanche deserticola's.Furthermore,because Cistanche deserticola is both edible and medicinal,and exhibits a wide therapeutic window,it has a natural advantage in the clinical transformation and application after drug development.Currently,to expand its medicinal range,a review of the main active components of Cistanche deserticola and their related pharmacological effects is conducted,and combined with the specific characteristics of intestinal injury in sepsis,the potential value of Cistanche deserticola in intestinal barrier protection,microbial coordination,and intestinal motility regulation is further elaborated,providing new ideas and a theoretical basis for the application of Cistanche deserticola in sepsis-induced intestinal injury.

Objective To observe the effects of Yixintai on lipid metabolism and the protein expressions of CPT-1 and CD36 in rats with heart failure;To explore the mechanism of its treatment of heart failure.Methods 106 out of 120 SD rats were selected to establish the heart failure model induced by myocardial infarction by ligating the left anterior descending coronary artery,and 14 rats were selected as the sham-operation group.The successful model rats were randomly divided into model group,trimetazidine group and Yixintai low-,medium-and high-dosage groups,with 14 rats in each group.The administration group was given corresponding drugs by gavage once a day for 4 weeks.LVEF,LVFS,LVIDd and LVIDs were measured by color doppler ultrasonography,the contents of ANP,BNP,LA and FFA in serum were detected by ELISA,the contents of TG,TC,LDL and HDL were detected by automatic biochemical analyzer,HE and Masson staining were used to observe the morphology of myocardial tissue,the expressions of CPT-1 and CD36 protein in myocardial tissue were detected by Western blot.Results Compared with the sham-operation group,LVEF and LVFS in the model group decreased(P<0.05),the LVIDs and LVIDd increased(P<0.05);the contents of serum ANP,BNP,LA,FFA,TG,TC and LDL increased(P<0.05),while the content of HDL decreased(P<0.05),with myocardial edema,irregular arrangement of myocardial fibers,increased inflammatory cell infiltration and collagen fiber deposition;the protein expressions of CPT-1 and CD36 in myocardial tissue decreased(P<0.05).Compared with the model group,the LVEF and LVFS in Yixintai each dosage groups and trimetazidine group increased(P<0.05),LVIDs and LVIDd decreased(P<0.05);the contents of ANP,BNP,LA,FFA,TG,TC and LDL in serum of Yixintai medium-and high-dosage groups and trimetazidine group decreased(P<0.05),the content of HDL increased(P<0.05);myocardial edema was improved,inflammatory cell infiltration was reduced,collagen fiber deposition was reduced,and the protein expressions of CPT-1 and CD36 in myocardial tissue increased(P<0.05).Conclusion Yixintai may improve myocardial energy metabolism and treat heart failure by increasing the expression of CPT-1 and CD36 protein in myocardial tissue and promoting fatty acid β oxidation.

Objective:To investigate the role and molecular mechanisms of transcription factor EB (TFEB) and its target genes in the treatment of multiple myeloma (MM) with bortezomib.Methods:TFEB target genes were predicted using the GTRD database (http://gtrd.biouml.org/), identifying Ptch1 gene for further study. Expression changes of Ptch1 in RPMI8226 and U266 MM cell lines after bortezomib treatment were assessed by real time fluorogenic quantitative PCR (RT-qPCR) and Western blot. RPMI8226 and U266 cell lines were transfected with siRNA-TFEB, and mRNA and protein levels of key factors (Ptch1, Gli1) in the Ptch1/Hedgehog signaling pathway were measured by RT-qPCR and Western blot. Furthermore, Ptch1 was overexpressed in MM cell lines via lentiviral transduction. Autophagy was evaluated by acridine orange staining, and protein levels of LC3B, Beclin-1, and Lamp-1 were measured by Western blot. Lysosomal quantity changes were assessed by lysosomal fluorescent probes.Results:Bortezomib (6.0×10 -6 mmol/L, 24 h) significantly reduced Ptch1 mRNA and protein levels in both cell lines compared with blank control group (all P<0.05). siRNA-TFEB transfection reversed bortezomib’s inhibition of Hedgehog pathway key factors Ptch1 and Gli. Ptch1 overexpression in bortezomib-treated RPMI8226 and U266 cells significantly reduced the relative expression of autophagy-related proteins LC3B, Beclin-1, and Lamp-1 (all P=0.001). Acridine orange staining showed fewer acidic vesicular organelles within two cell lines (all P=0.001). The relative fluorescence expressions of lysosomal probes reflecting the number of lysosomes were also decreased ( P values of RPMI8226 and U266 cell lines were 0.001 and 0.007, respectively) . Conclusion:The knockdown of TFEB can specifically promote the expression of the Ptch1/Hedgehog signaling pathway, thereby reducing bortezomib-induced autophagy in MM cells and reversing the inhibitory effect of bortezomib on the proliferation of MM cell lines.