Abstract:Objective:To observe the clinical efficacy of Tongbi Xinxue Granules in treating patients with coronary heart disease and diabetes mellitus.Methods:A total of 90 patients with coronary heart disease and diabetes,presenting with deficiency of both Qi and Yin and stasis blocking the heart meridian were randomly divided into the control group and the treatment group according to the random number table method,with 45 cases in each group.The control group received basic Western medicine treatment,while the treatment group was treated with Tongbi Xinxin Granules in addition to the Western medicine treatment.The observation period was 4 weeks.The changes in angina pectoris symptoms,traditional Chinese medicine symptom scores,clinical efficacy,electrocardiogram(ECG)changes,fasting blood glucose,glycosylated hemoglobin,blood lipids,left ventricular ejection fraction(LVEF),left ventricular end-systolic volume(LVESV),left ventricular end-diastolic volume(LVEDV),N-terminal pro-B-type natriuretic peptide(NT-proBNP),interleukin(IL)-6,blood and urine routine tests,liver and kidney functions were tested before and after treatment in both groups.Results:After the treatment,the improvement in angina pectoris symptoms,traditional Chinese medicine symptom scores,clinical efficacy,ECG changes,as well as blood glucose,glycosylated hemoglobin,blood lipids,LVEF,LVESV,LVEDV,NT-proBNP,and IL-6 levels in the treatment group were all better than those in the control group(P＜0.05).Conclusion:The efficacy of Tongbi Shuxin Granules in the treatment of coronary heart disease combined with diabetes is effective,which can significantly improve the clinical symptoms and cardiac function of the patients,reduce the levels of blood glucose and blood lipids,and reflect the multi-targeted therapeutic effect of traditional Chinese medicine.

Abstract:Objective:To explore the effect of running wheel training combined with electroacupuncture intervention on the improvement of behavioral ability of middle cerebral artery occlusion(MCAO)rats.Methods:A total of 40 male Wistar rats without specific pathogen(SPF)grade were selected and divided into normal group,model group,running wheel group,and combined group,10 in each group.MCAO model was established for all the rats except the normal group.After modeling,the normal group and the model group were not interfered,the running wheel group was treated with positioning wheel turbine,and the combined group was treated with electroacupuncture on the basis of running wheel.The intervention lasted for 4 weeks.The volume of cerebral infarction was evaluated by 2,3,5-triphenyl-tetrazolium chloride(TTC)method.The morphological characteristics of brain tissue were observed by hematoxylin-eosin(HE)staining,and the apoptosis of nerve cells was detected by terminal deoxyribonucleotidyl transferase(TdT)-mediated dUTP nick end labeling(TUNEL)staining.Western Blot assay was used to detect calmodulin(CaM),calmodulin dependent protein kinase Ⅱ(CaMKⅡ),cyclic adenosine phosphate response element binding protein(CREB),and PCR was used to detect brain-derived neurotrophic factor(BDNF)and basic fibroblast growth factor(bFGF).Results:Compared with model group,the cerebral infarction area of rats in running wheel group decreased(P＜0.05).Compared with the running wheel group,the cerebral infarction size of rats in the combined group decreased(P＜0.05).Compared with normal group,the apoptosis of neurons in model group increased,paw withdraw ther-mal latency(PWTL),paw withdrawal threshold(PWT),CaMKⅡ protein expression,CREB protein expression,BDNF mRNA expression,bFGF mRNA expression,and CaM protein expression decreased(P＜0.05).Compared with model group,apoptosis rate and CaM protein expression decreased,PWTL,PWT,CaMKⅡ protein expression,CREB protein expression,BDNF mRNA expression,and bFGF mRNA expression increased in running wheel group(P＜0.05).Compared with the running wheel group,the apoptosis rate and CaM protein expression of nerve cells in the combined group decreased,and PWTL,PWT,CaMKⅡ protein expression,CREB protein expression,BDNF mRNA expression,and bFGF mRNA expression increased(P＜0.05).HE staining showed that the cerebral cortex of the normal group was intact.In the model group,the cerebral cortex was seriously damaged,the cells showed swelling,vacuolar degeneration,and interstitial edema and obvious contraction.The adverse phenomena in both the running group and the combined group were improved,and the combined group showed the most significant change.Conclusion:Running wheel training combined with electroacupuncture can improve the behavioral ability of MCAO,and its mechanism may be related to inhibiting neuronal apoptosis,regulating neurotrophic factors and Ca2+/CaMKⅡ/CREB signaling pathway.

Abstract:Objective:To explore the protective effect of vericiguat on ox-LDL-induced endothelial dysfunction and its underlying mechanisms.Methods:Human umbilical vein endothelial cells(HUVECs)were divided into three groups:the control group received no intervention,the ox-LDL group was treated with ox-LDL for 24 hours,the vericiguat group was treated with ox-LDL for 24 hours and then intervened with vericiguat for another 24 hours.CCK-8 was used to detect cell viability.Transwell assays were used to assess cell migration.Lactate dehydrogenase release assays were used to evaluate cell damage.Nitrate reductase assays were used to measure nitric oxide levels.The DCFH-DA fluorescent probe was used to detect intracellular reactive oxygen species(ROS).The superoxide dismutase(SOD)levels in the cell culture supernatant were measured using a kit.Mitochondrial autophagy-related proteins tensin homolog induced putative kinase 1(PINK1),Parkin,microtubule-associated protein light chain 3 Ⅱ/Ⅰ(LC3Ⅱ/Ⅰ),and p62 were detected by Western Blot.The real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the mRNA expression of mitochondrial autophagy-related genes LC3 and p62.Results:ox-LDL significantly reduced the viability and mobility of HUVECs,increased LDH leakage,enhanced ROS production,and weakened intracellular SOD activity,whereas vericiguat could reverse these effects.ox-LDL could up-regulate the expression of mitochondrial autophagy molecules,including PINK1,Parkin,LC3Ⅱ/Ⅰ,and p62 protein,as well as LC3 and p62 mRNA.Vericiguat could further up-regulate the protein expression of mitochondrial autophagy molecules such as PINK1,Parkin,and LC3Ⅱ/Ⅰ,while down-regulate the expression of p62 protein and mRNA.Conclusion:Vericiguat can improve ox-LDL-induced endothelial cell dysfunction and reduce oxidative stress to some extent,and improvment of mitochondrial autophagic flux disorder is possible.

Abstract:Objective:To investigate the formulation patterns of traditional Chinese medicine for palpitations based on compound prescriptions from Chinese medicine patents in the patent database of the State Intellectual Property Office(SIPO).Methods:Patent data of Chinese medicine compound prescriptions for palpitations that met the inclusion criteria were collected from September 10,1985 to March 5,2024.The prescription data was processed,standardized,modeled,analyzed for drug frequency,association rules,clustering,co-occurrence frequency,and visualized by Excel 2022,R language(v4.2.0),and VOSviewer(1.6.20)to explore the formula composition rules of palpitations.Results:Finally,350 patent data with palpitations that met the criteria were included,involving 736 Chinese herbal medicines.The top 10 Chinese herbal medicines in terms of medication frequency were Salvia miltiorrhiza,Radix Ophiopogonis,Angelica sinensis,jujube seed,Schisandra chinensis,cassia twig,Astragali,baked licorice,Ginseng,and Radix Codonopsis.The analysis of association rules yielded 63 data points,and the combinations with higher associations were Salvia miltiorrhiza,safflower → peach kernel;oyster→dragon bone;dragon bone→oyster;Salvia miltiorrhiza,peach kernel→safflower;and peach kernel→safflower.Cluster analysis yielded six groups of drug combinations.The results of co-occurrence rules suggested that the drug pairs with the highest frequency of occurrence were Salvia miltiorrhiza-Angelica and Salvia miltiorrhiza-Radix Ophiopogonis.Conclusions:The results showed that the basic pathogenesis of palpitation was deficiency of Qi and Yin,accompanied by internal stagnation and heat.The treatment principle was to benefit Qi and nourish Yin,relieve stagnation,and clear heat.The core drugs used were Radix Ophiopogonis,Schisandra,Radix Rehmanniae,Cassia Twig,baked licorice,Radix Cynanchi,Coptidis Rhizoma,and Sophora flavescens.Deficiency of both the heart and spleen results in insufficiency of Qi and blood.The therapeutic approach were emphasized for reinforcing spleen function,nourishing blood,resolving phlegm,and promoting blood circulation.Key herbal components include Jujube,Longan Aril,White Peony Root,Prepared Rehmannia,Radix Codonopsis,Calamus,Polygala,Atractylodes,Tangerine Peel,Poria,and Licorice.Blood stasis is the core element.The treatment aims are invigorating blood circulation and eliminating blood stasis,and formulas are typically supplemented with Salvia miltiorrhiza.Palpitation refers to restlessness and an unsettled heart and mind,so sedatives such as Longmu or heart-nourishing agents like Zaobai may be used according to the pattern differentiation.The core formula consists of Salvia baked licorice,Schisandra chinensis,jujube seed,ginseng,Radix Ophiopogonis,Poria cocos,Radix codonopsis,Angelica sinensis,and Ligusticum wallichii.The new prescriptions and combinations obtained through data mining can serve as a reference for the clinical diagnosis and treatment of palpitations and for the development of new drugs.

Abstract:Objective:To investigate the epidemiological dynamics of ischemic stroke(IS)in Shanxi Province,quantify the effects of major risk factors,develop and validate a localized machine learning-based risk prediction model,and evaluate the preliminary effectiveness of an innovative regional comprehensive prevention and control network,thereby providing high-level evidence for targeted public health strategies.Methods:A population-based retrospective analysis of data from the Shanxi Health Information Platform(2015-2023)was conducted to describe the spatiotemporal distribution of standardized ischemic stroke incidence,prevalence,and mortality.A 1:1.2 frequency-matched case-control study(3 528 IS patients,4 150 controls)with multivariate Logistic regression to assess the impact of traditional and lifestyle-related risk factors on IS risk.Development of an IS risk prediction model with a Gradient Boosting Decision Tree(GBDT)algorithm based on case-control data,with its discrimination and calibration were assessed through 10-fold cross-validation and an independent test set.Finally,a quasi-experimental pre-post design was used to evaluate the one-year effectiveness of a"three-tier linkage,information synergy,and integrated prevention-treatment"network piloted in Taiyuan and Datong.Results:From 2015 to 2023,the standardized IS incidence in Shanxi increased from 185.6 to 240.2 per 100 000,and prevalence rose from 1 350.2 to 1 898.1 per 100 000,indicating a continuously growing disease burden.Multivariate analysis identified hypertension as the strongest independent risk factor(OR=3.52,95%CI 3.18-3.90),followed by atrial fibrillation or valvular heart disease(OR=3.15,95%CI 2.48-4.00)and family history of stroke(OR=2.45,95%CI 2.15-2.79).The GBDT risk prediction model showed excellent performance on the test set,with an area under the receiver operating characteristic(ROC)curve(AUC)of 0.923,it is superior to the traditional Logistic regression model.After the network pilot,the regional mean door-to-needle time(DNT)decreased significantly from 75 to 52 minutes,the intravenous thrombolysis rate within 4.5 hours increased from 12.5%to 18.9%,and the standardized management rate of high-risk populations improved from 35.6%to 62.3%(P＜0.01).Conclusion:The IS disease burden in Shanxi Province is rapidly increasing,with a risk profile characterized by distinct regional features.The localized machine learning-based prediction model can effectively improve early screening.The regional comprehensive control network constructed in this study has proven highly effective in optimizing treatment efficiency and strengthening primary prevention,offering a replicable,systematic solution of major chronic disease challenges.