Ischemic stroke （IS） represents a major global health challenge with complex pathological mechanisms. Although modern therapies such as intravenous thrombolysis and endovascular thrombectomy have advanced， their application remains constrained by narrow therapeutic time windows， hemorrhagic risks， and uneven distribution of medical resources. Traditional Chinese medicine （TCM） demonstrates unique value in the prevention and treatment of IS， owing to its multi-component， multi-target， and holistic regulatory characteristics. This review summarized the molecular mechanisms by which active ingredients and compound formulations of TCM exert therapeutic effects against IS through the regulation of inflammatory responses， oxidative stress， excitatory toxicity， apoptosis， and autophagy. Studies have indicated that components such as curcumin， baicalin， and astragaloside Ⅳ inhibit microglial activation and the nucleotide-binding oligomerization domain （NOD）-like receptor protein 3 （NLRP3） inflammasome to attenuate neuroinflammation， activate the nuclear factor erythroid 2-related factor 2（Nrf2）/heme oxygenase-1 （HO-1） pathway to alleviate oxidative stress， modulate glutamate receptor function to counteract excitatory toxicity， and regulate the B-cell lymphoma 2（Bcl-2）/Bcl-2-associated X protein （Bax）， cysteine aspartate-specific protease （Caspase）， and phosphatidylinositol 3 kinases （PI3K）/protein kinase B （Akt） signaling pathways to suppress neuronal apoptosis. Recent research has further revealed that TCM can modulate ferroptosis by targeting key proteins glutathione peroxidase 4 （GPX4） and acyl-coenzyme A synthetase long-chain family member 4 （ACSL4） to maintain iron homeostasis， intervene in the "microbiota-gut-brain axis" to ameliorate dysbiosis and reduce neuroinflammation， utilize exosomes for brain-targeted drug delivery， and influence neural repair processes through epigenetic regulation. Furthermore， the review discussed the integrated mechanisms of compound formulations， such as Buyang Huanwu Decoction， in improving cerebral microcirculation and promoting neurovascular remodeling via multi-component synergy. It also analyzed the strategy and advantages of integrating TCM with Western medicine for IS treatment， providing a novel theoretical foundation and research directions for future investigations and clinical translation of TCM in IS management.

ObjectiveTo observe the clinical efficacy and safety of Zhuyuwan in the treatment of hyperlipidemia. MethodsIn this study， hyperlipidemia patients treated in the Hospital of Chengdu University of Traditional Chinese Medicine （TCM） from September 2022 to December 2023 were randomly assigned into a control group and an observation group. Finally， 162 valid cases were included， encompassing 74 cases in the control group and 88 cases in the observation group. The control group was treated with atorvastatin calcium tablets， and the observation group with atorvastatin calcium tablets + Zhuyuwan extract granules. Both groups were treated for 8 weeks. The efficacy in terms of blood lipid level recovery， blood lipid levels， TCM syndrome distribution， efficacy in terms of TCM syndrome， and TCM symptom scores were compared between the two groups as well as between before and after treatment. Liver and kidney functions were monitored for safety assessment. ResultsIn terms of blood lipid level recovery， the total response rate in the observation group was 86.36% （76/88） and that in the control group was 86.49% （64/74）， with no statistically significant difference between the two groups. After treatment， both groups showed declines in levels of triglyceride （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） （P<0.05） and elevations in the level of high-density lipoprotein cholesterol （HDL-C） （P<0.05）. Moreover， the observation group outperformed the control group in recovering the levels of TG， LDL-C， and HDL-C （P<0.05， P<0.01）. In terms of TCM syndrome， hyperlipidemia was mostly caused by phlegm turbidity and obstruction. The total response rate in terms of TCM syndrome in the observation group was 87.30% （55/63）， which was higher than that （63.46%， 33/52） in the control group （χ²=9.102， P<0.01）. After treatment， the scores of total TCM symptoms， primary symptoms， and secondary symptoms decreased in both groups （P<0.05）， and the observation group had lower scores than the control group （P<0.01）. The observation group was superior to the control group in alleviating obesity， chest tightness， and low food intake （P<0.05）. In terms of safety， the level of aminotransferase was slightly elevated in the control group， and no obvious adverse reaction was observed in the observation group， with no statistical significance in the incidence of adverse reactions. ConclusionZhuyuwan combined with atorvastatin can not only recover blood lipid levels and alleviate TCM symptoms but also reduce the occurrence of adverse reactions.

ObjectiveTo observe the clinical efficacy and safety of Zhuyuwan in the treatment of hyperlipidemia. MethodsIn this study， hyperlipidemia patients treated in the Hospital of Chengdu University of Traditional Chinese Medicine （TCM） from September 2022 to December 2023 were randomly assigned into a control group and an observation group. Finally， 162 valid cases were included， encompassing 74 cases in the control group and 88 cases in the observation group. The control group was treated with atorvastatin calcium tablets， and the observation group with atorvastatin calcium tablets + Zhuyuwan extract granules. Both groups were treated for 8 weeks. The efficacy in terms of blood lipid level recovery， blood lipid levels， TCM syndrome distribution， efficacy in terms of TCM syndrome， and TCM symptom scores were compared between the two groups as well as between before and after treatment. Liver and kidney functions were monitored for safety assessment. ResultsIn terms of blood lipid level recovery， the total response rate in the observation group was 86.36% （76/88） and that in the control group was 86.49% （64/74）， with no statistically significant difference between the two groups. After treatment， both groups showed declines in levels of triglyceride （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） （P<0.05） and elevations in the level of high-density lipoprotein cholesterol （HDL-C） （P<0.05）. Moreover， the observation group outperformed the control group in recovering the levels of TG， LDL-C， and HDL-C （P<0.05， P<0.01）. In terms of TCM syndrome， hyperlipidemia was mostly caused by phlegm turbidity and obstruction. The total response rate in terms of TCM syndrome in the observation group was 87.30% （55/63）， which was higher than that （63.46%， 33/52） in the control group （χ²=9.102， P<0.01）. After treatment， the scores of total TCM symptoms， primary symptoms， and secondary symptoms decreased in both groups （P<0.05）， and the observation group had lower scores than the control group （P<0.01）. The observation group was superior to the control group in alleviating obesity， chest tightness， and low food intake （P<0.05）. In terms of safety， the level of aminotransferase was slightly elevated in the control group， and no obvious adverse reaction was observed in the observation group， with no statistical significance in the incidence of adverse reactions. ConclusionZhuyuwan combined with atorvastatin can not only recover blood lipid levels and alleviate TCM symptoms but also reduce the occurrence of adverse reactions.

Artificial intelligence (AI) has emerged as a transformative technology in accelerating drug discovery and development within natural medicines research. Natural medicines, characterized by their complex chemical compositions and multifaceted pharmacological mechanisms, demonstrate widespread application in treating diverse diseases. However, research and development face significant challenges, including component complexity, extraction difficulties, and efficacy validation. AI technology, particularly through deep learning (DL) and machine learning (ML) approaches, enables efficient analysis of extensive datasets, facilitating drug screening, component analysis, and pharmacological mechanism elucidation. The implementation of AI technology demonstrates considerable potential in virtual screening, compound optimization, and synthetic pathway design, thereby enhancing natural medicines' bioavailability and safety profiles. Nevertheless, current applications encounter limitations regarding data quality, model interpretability, and ethical considerations. As AI technologies continue to evolve, natural medicines research and development will achieve greater efficiency and precision, advancing both personalized medicine and contemporary drug development approaches.
Biological Products/pharmacology* ; Artificial Intelligence ; Humans ; Drug Discovery/methods* ; Machine Learning ; Deep Learning

OBJECTIVE: Left ventricular remodeling induced by myocardial ischemia/reperfusion injury (MI/RI) is a common cardiac dysfunction. Accumulating evidence has demonstrated that autophagy plays a vital role in protecting against ventricular remodeling. This study aims to investigate the performance of Compound Danshen Tablets (CDT) in rescuing ventricular remodeling and whether autophagy as the potential mechanism. METHODS: The left anterior descending arteries of rats were temporarily ligated for 30 min to construct the MI/RI model. Ventricular remodeling was induced by reperfusion for 28 d, during which the MI/RI rats were administered CDT (300 mg/kg and 600 mg/kg), atorvastatin (2 mg/kg), and diltiazem (16 mg/kg). Cardiac function and structure were examined by echocardiography. Immunohistochemistry, Masson's trichrome staining, and hematoxylin-eosin (HE) staining were utilized to assess the fibrosis and histological alterations in the heart tissue. The expression of autophagy-related proteins was detected using Western blotting. RESULTS: CDT attenuated the cardiac dysfunction, structural changes, histopathological changes and fibrosis induced by MI/RI. CDT significantly enhanced the level of Beclin1 and microtubule-associated protein 1 light chain 3 beta (LC3β), and reduced p62 levels in MI/RI rats. Moreover, CDT significantly increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and inhibited mammalian target of rapamycin (mTOR) phosphorylation. CONCLUSION CDT ameliorated MI/RI-induced ventricular remodeling by activating autophagy and improving autophagic flux via the AMPK/mTOR signaling pathway.

Objective To investigate the correlation between single nucleotide polymorphisms(SNPs)of the EGF gene,including rs11569017(A>T),rs2237051(A>G),rs3733625(C>T),and rs4444903(A>G),and the risk of non-small cell lung cancer(NSCLC)in a Han population of Yunnan.Methods A total of 439 patients with NSCLC and 520 healthy controls were recruited in Yunnan Province between January 2022 and December 2023.Genotyping of four SNP loci in the EGF gene was performed using TaqMan probes,followed by analysis of allele,genotype,genetic model,and haplotype distribution frequencies between NSCLC and control groups.Stratified analyses were further conducted based on NSCLC pathological types and clinical stages.Results The rs2237051 locus showed significant differences in allele(P=0.011)and genotype(P=0.042)frequencies between the squamous cell carcinoma(SCC)group and the control group.The frequency of the A allele was lower in the SCC group than in the control group(OR=0.71,95%CI 0.54～1.85),but there was no difference after Bonferroni correction(P>0.0125).Under the log-additive model,the rs2237051-2G/G+A/G genotype was associated with an increased risk of SCC(P=0.01;OR=1.42,95%CI 1.08～1.86).However,the association lost statistical significance after Bonferroni correction(P>0.0125).The haplotype rs11569017-rs2237051-rs3733625-rs4444903 has no difference between the two groups(P>0.0125).The stratified analysis revealed no significant associations between the genetic loci and different disease stages(P>0.0125).Conclusion In the Yunnan Han population,the individuals carrying the rs2237051-A allele of the EGF gene have a significantly lower risk of squamous lung cancer,but further functional experiments are needed to verify the protective mechanism.

BACKGROUND:At present,the use of a locking bone plate combined with steel wire or steel cable for the treatment of periprosthetic femoral fracture often adopts monocortical fixation,which is not stable and the proximal end of the bone cannot be achieved anatomically fitted by plate.The customized anatomical plate system can effectively solve this problem. OBJECTIVE:To explore the biomechanical strength of a customized anatomical plate system in fixation of Vancouver BI periprosthetic femoral fracture. METHODS:CT thin layer scanning data of normal femurs of 1 006 cases were selected and input into the MIMICS 21.0 software to establish the three-dimensional reconstruction model of the femur,which was set as the three-dimensional reconstruction group.56 complete human femoral specimens were selected as the femoral specimen group.The measured results of the two groups for femoral anatomical appearance were compared.If there was no significant difference between the two groups,the approximate appearance of a customized anatomical plate system was designed based on the measurement results in MIMICS 21.0 software and NX11.0 software.The customized anatomical plate system was designed and prepared according to the above measurement results.Eight pairs of frozen human femurs were selected to make Vancouver BI periprosthetic femoral fracture,which of the left were thin layer scanned by dual-source CT to obtain data.The data were transferred to determine the customized anatomical plate system model by the above design software.Eight sets of customized anatomical plate systems were ultimately produced,relying on the instrument company.The eight pairs of models were numbered 1-8.The left side was fixed with the customized anatomical plate system(customized anatomical plate system group);the right side was fixed with a metal locking plate system-large locking plate(claw plate group).L1-L4 and R1-R4 were subjected to vertical short-cycle loading test and vertical loading test.L5-L8 and R5-R8 were subjected to horizontal short-cycle loading test and four-point bending test.The vertical loading test and four-point bending test were used to collect bending load,bending displacement,and bending strain.Two short cycle loading tests were used to collect strain displacement to compare the maximum load,maximum displacement,bending stiffness,and short-period displacement resistance of the two kinds of bone plates. RESULTS AND CONCLUSION:(1)There were no significant differences in all indexes between the three-dimensional reconstruction group and the femoral specimen group(P>0.05).Individual customized anatomical plate system was designed based on the measurement results combined with digital software.(2)In the vertical loading test,the maximum load was higher(P=0.015),the maximum bending displacement was smaller(P=0.014),and the bending stiffness was higher(P=0.005)in the customized anatomical plate system group compared with the claw plate group.(3)In the four-point bending test,the maximum load was higher(P=0.023),the bending stiffness was higher(P=0.005),and the maximum bending displacement was not significant(P=0.216>0.05)in the customized anatomical plate system group compared with the claw plate group.(4)In the vertical short-cycle loading test,the average level of bending displacement in the customized anatomical plate system group(0.23±0.10 mm)was significantly lower than that in the claw plate group(0.44±0.02 mm)(P<0.05).(5)There was no significant difference in the average level of bending displacement between the two groups in the horizontal short cycle loading test(P>0.05).(6)It is concluded that the customized anatomical plate system has personalized anatomical characteristics,and the fixation of Vancouver BI periprosthetic femoral fracture is more stable,which has certain significance for clinical treatment.

ObjectiveTo observe the effects of Coptidis Rhizoma-Fermentum Rubrum on non-alcoholic fatty liver disease （NAFLD） in mice and explore its possible mechanisms. MethodSixty male SPF C57BL/6J mice were randomly divided into six groups： control group， model group， low-， medium-， and high-dose Coptidis Rhizoma-Fermentum Rubrum group （0.75， 1.5， 3 g·kg^-1）， and metformin group （0.075 g·kg^-1）， with 10 mice in each group. NAFLD mouse models were induced by high-fat diet feeding for 24 weeks. The low， medium， and high-dose Coptidis Rhizoma-Fermentum Rubrum groups were administered corresponding doses of Coptidis Rhizoma-Fermentum Rubrum by gavage， while the control and model groups received an equivalent amount of saline for four weeks. Serum total cholesterol （TC）， triglycerides （TG）， free fatty acids （FFA）， and liver function markers including alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were measured using an automatic biochemical analyzer. Hematoxylin-eosin （HE） and oil red O staining were used to detect liver lipid deposition， and Prussian blue staining was used to measure liver ferrous ion levels. Western blot was performed to detect the expression of key proteins in the nuclear factor erythroid-2-related factor 2 （Nrf2）-glutathione peroxidase 4 （GPX4） axis. ResultAfter 24 weeks of high-fat feeding， compared with the control group， the model group showed significant increases in body weight， liver weight and liver index， and serum lipid levels （P<0.01）， as well as substantial hepatic lipid deposition with marked steatosis. Compared with the model group， Coptidis Rhizoma-Fermentum Rubrum intervention reduced body weight （P<0.01）， liver weight and liver index （P<0.01）， and serum lipid levels （P<0.05， P<0.01）， improved liver function （P<0.01）， and decreased hepatic lipid deposition， with the low-dose Coptidis Rhizoma-Fermentum Rubrum group showing the best effect. Western blot results showed that compared with those in the control group， the expression levels of Nrf2， heme oxygenase-1 （HO-1）， kelch-like ECH-associated protein 1（Keap1）， and GPX4 proteins in the model group were decreased （P<0.05， P<0.01）. Compared with the model group， Coptidis Rhizoma-Fermentum Rubrum increased the expression levels of these proteins （P<0.05， P<0.01）. ConclusionCoptidis Rhizoma-Fermentum Rubrum can alleviate fatty liver in mice， improve liver function， and reduce hepatic lipid deposition， possibly by regulating the Nrf2/GPX4 ferroptosis axis.

Objective By comparing the changes in cerebral blood flow,neuronal morphology in brain tissue,and the levels of serum oxidation and inflammatory factors in models of cerebral hypoperfusion,three experimental rat models were assessed for their suitability as subjects of studies on the mechanisms and therapeutic drugs of cerebrovascular diseases and neurodegenerative diseases.Methods A total of 88 male SD rats were randomly divided into a sham operation group(n=16),classic bilateral common carotid artery occlusion group(classic 2-VO group,n=24),modified 2-VO group(n=24),and intraluminal thread technique group(n=24).Bilateral common carotid artery ligation was performed on the classic 2-VO group,while blood was drawn from the common carotid artery before ligation in the modified 2-VO group(1 mL/100 g).Middle cerebral artery occlusion was performed on the intraluminal thread technique group.In the sham operation groups of the first two models,the common carotid artery was separated but not ligated,while the proximal end of the common carotid artery and the external carotid artery were ligated;in addition,the bolt thread was not inserted in the sham group of the intraluminal thread technique group.Cerebral blood flow,infarct volume,serum inflammatory factor levels,hematoxylin and eosin-stained morphology,and ultrastructure of the hippocampal tissue were assessed at 1,3,and 7 days after the operations.Results Laser speckle interferometry showed a decrease in cerebral blood flow of the modified 2-VO group that was more obvious than that of the other two groups.On day 7,only the modified 2-VO group still had significant differences in cerebral blood flow compared with the sham group,and it remained in a state of hypoperfusion(cerebral blood flow decreased by 30％compared with that before the operation).TTC staining showed that infarcts in the striata of the three groups gradually increased with time after the operation;4 rats(about 26.7％)in the modified 2-VO group and 10 rats(about 66.7％)in the intraluminal thread technique group had infarcts in both the cortex and striatum.ELISA showed that the levels of inflammatory factors,such as TNF-α,IL-1 β,and hs-CRP,in the three groups were increased after the operations,and levels of the pro-oxidation factor ROS were also increased.In contrast,levels of the antioxidant factor SOD decreased.On postoperative day 7,there was no significant difference in the hs-CRP of the classic 2-VO and intraluminal thread technique groups compared with that of the sham group.However,the modified 2-VO group still exhibited significant differences in all the above indicators compared with the sham group.Hematoxylin and eosin staining showed that the modified 2-VO group had more severe damage to the hippocampal CA1 and CA3 regions compared with the other groups.Transmission electron microscopy demonstrated that the modified 2-VO group showed more severe damage to the mitochondrial and endoplasmic reticulum in the hippocampal region compared with the other groups.Conclusions A cerebral hypoperfusion model was successfully established.Compared with the classic 2-VO and intraluminal thread techniques,the modified 2-VO method can induce more complete cerebral hypoperfusion and more severe neural damage within the same time frame,resembling the pathological state of human cerebral hypoperfusion more closely.

Objective The aim of this study was to analyze the predictive value of an immune scoring model based on im-mune cell infiltration for the efficacy and prognosis of immunotherapy in early gastric cancer.Methods The gene expression data and related clinical parameters of 167 early gastric cancer patients were downloaded from the Cancer Genome Atlas(TCGA)as the training set.The clinical information of 92 early gastric cancer patients who first visited our hospital from January 2017 to January 2020 was collected as a validation set.The infiltration of 22 immune cells in tumor tissues was calculated by the Cibersort software.The key pre-dictive factors for early gastric cancer patients were further screened and determined by lasso analysis and multivariate Cox regression analysis.The eligible immune cells were used to construct the prognostic risk scoring model and verify it.Based on the risk model,a nomograph model was established to predict the probability of death and treatment failure in early gastric cancer patients,and evaluate the differentiation,accuracy,and reliability of the model.Results There was no statistically significant difference in the general infor-mation of patients between the training set and the validation set(P＞0.05).Compared with normal tissues,the content of CD8+T cells,activated memory CD4+T cells,M0 macrophages,M1 macrophages,resting dendritic cells,and activated dendritic cells in early gastric cancer tumor tissues decreased.The contents of regulatory T cells(Treg cells)and eosinophils increased,and the difference was statistically significant(P＜0.05).The LASSO analysis further screened five types of infiltrating immune cells,including activated memory CD4+T cells,M1 macrophages,Treg cells,activated dendritic cells and eosinophils.The survival curve results showed that the immune scoring model could effectively distinguish the survival time of patients.The total score of the prognostic nomogram model was 274,corresponding to risk of death of 72%.The total score of the treatment effect nomograph model was 307,corresponding to a 75%risk of ineffective treatment.The model validation results showed that the nomograph model has high discrimination,accuracy and reli-ability.Conclusion The immune scoring model based on immune cell infiltration has a certain predictive value for the efficacy and prognosis of immunotherapy in patients with early gastric cancer.