ObjectiveTo provide a reference for the rational clinical use of cold Chinese medicines by sorting and analyzing their properties， flavors， meridian tropism， primary therapeutic indications， methods of administration， dosages， and precautions as recorded in the 2020 edition of Pharmacopoeia of the People's Republic of China （Chinese Pharmacopoeia）. MethodsCold Chinese medicines for internal and external use included in the 2020 edition of Chinese Pharmacopoeia were entered one by one， and their efficacy， properties， flavors， meridian tropism， methods of administration， dosages， and usage precautions were statistically classified and summarized to guide clinical medication use. ResultsA total of 259 cold Chinese medicines for internal use were included and categorized into 18 efficacy groups， mainly comprising heat-clearing drugs， water-excreting and dampness-draining drugs， and phlegm-resolving， cough- and asthma-relieving drugs. Their predominant flavors were bitter， sweet， and pungent， and they primarily entered the liver， lung， and stomach meridians. The main methods of administration included decocting first， grinding into powder for oral use， or preparing into pills or powders， with most dosages ranging from 9 to 15 g. A total of 83 cold Chinese medicines for external use were included， involving 16 efficacy categories. Their main flavors were bitter， sweet， and pungent， primarily entering the liver， lung， and large intestine meridians. The main external application methods were grinding into powder for topical use or preparing decoctions for fumigation and washing， with most dosages ranging from 9 to 15 g. Whether for internal or external use， cold Chinese medicines should be used with caution or contraindicated in pregnant women. ConclusionThe cold Chinese medicines included in the 2020 edition of the Chinese Pharmacopoeia are mainly suitable for patients with carbuncles， swellings， and coughs. However， in clinical practice， it is necessary to strictly follow the principles of syndrome differentiation and treatment， pay attention to administration methods and dosages， and use cold medicines rationally and effectively to improve clinical efficacy.

Stroke is one of the leading causes of disability and mortality worldwide. Research into its mechanisms and the development of therapeutic strategies heavily rely on animal models that accurately replicate the pathological features of human disease. An ideal animal model for stroke should not only reproduce the neurological deficits and pathological changes observed in clinical patients but also demonstrate good reproducibility and translational value. This review focuses on the preparation and evaluation methods of ischemic stroke animal models. Firstly, it elaborates on the selection criteria, advantages, and disadvantages of experimental animals, including rodents (rats, mice) and non-rodents (non-human primates, miniature pigs, rabbits, zebrafish). Secondly, it provides a detailed overview of the modeling principles, key procedures, and application scopes for ischemic stroke models and hemorrhagic stroke models. Furthermore, the review summarizes advances in the applications of emerging technologies—including gene editing [e.g., clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing], multimodal imaging (e.g., two-photon microscopy, photoacoustic imaging), artificial intelligence, optogenetics, 3D bioprinting, organoid models, and multi-omics–in model optimization, precise assessment, and mechanistic investigation. Finally, based on a systematic analysis of relevant domestic and international literature from 2019 to 2024, this review discusses model selection strategies based on research objectives, a multidimensional evaluation system encompassing behavioral, imaging, and molecular pathological assessments, and envisions future directions involving technological integration to achieve model precision and individualization. This article aims to provide a comprehensive methodological reference to help researchers select appropriate animal models of stroke according to specific scientific questions.

ObjectiveTo explore the mechanism of Shouhui Tongbian capsules in treating constipation based on the research foundation of its active components combined with network pharmacology and animal experiments. MethodsThe drug components were imported into SwissTargetPrediction to predict the targets of Shouhui Tongbian capsules， and constipation-related targets were collected from disease databases. A protein-protein interaction （PPI） network was constructed for the common targets shared by Shouhui Tongbian capsules and constipation to screen key targets， which was followed by gene ontology （GO） function and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment analyses. A "bioactive component-target-pathway" network was constructed， and the core components of Shouhui Tongbian capsules in treating constipation were screened based on the topological parameters of this network. Molecular docking was employed to predict the binding affinity of core components to key targets. A mouse model of constipation was constructed to screen the key pathways and targets of the drug intervention in constipation. ResultsThe PPI network revealed six key constipation-related targets： protein kinase B （Akt1）， B-cell lymphoma-2 （Bcl-2）， glycogen synthase kinase-3β （GSK-3β）， cyclooxygenase-2 （PTGS2）， estrogen receptor 1 （ESR1）， and epidermal growth factor receptor （EGFR）. The KEGG pathway analysis showed that the phosphatidylinositol 3-kinase （PI3K）/Akt signaling pathway was the most enriched. The topological parameter analysis of the "bioactive component-target-pathway" network screened out the top 10 core components： auranetin， isosinensetin， naringin， diosmetin， quercetin， apigenin， luteolin， hesperidin， isorhapontigenin， and chrysophanol. Molecular docking results showed that the 10 core components had strong binding affinity with the 6 key targets. Animal experiments showed that after intervention with different doses of Shouhui Tongbian capsules， the time to the first black stool excretion was reduced and the fecal water content and small intestine charcoal propulsion rate of mice were improved. After treatment with Shouhui Tongbian capsules， the colonic mucosal injury and glandular arrangement were alleviated， and the muscle layer thickness was increased. Western blot results showed that Shouhui Tongbian capsules recovered the expression of apoptosis-related molecules mediated by the PI3K/Akt pathway in the colonic tissue of constipated mice. Terminal-deoxynucleotidyl transferase-mediated nick end labeling （TUNEL） results showed that the cell apoptosis rate of the colon significantly reduced after intervention with Shouhui Tongbian capsules. ConclusionThe results of network pharmacology and animal experiments confirmed that Shouhui Tongbian capsules can treat constipation through multiple targets and pathways. The capsules can effectively intervene in loperamide-induced constipation in mice by regulating the constipation indicators and reducing cell apoptosis in the colon tissue via activating the PI3K/Akt signaling pathway.

Objective: To investigate the mechanism of action of Prim-O-glucosylcimifugin (POG) to improve cholesterol metabolism in osteoarthritic (OA) chondrocytes based on the long noncoding RNA nuclear-enriched transcript 1 (lncRNA NEAT1)/microRNA-128-3p (miR-128-3p) pathway. Methods: For in vivo experiments, 60 mice were divided into the normal, sham operation, model, and POG groups using the random number table method, with 15 mice per group. The osteoarthritis mouse model was constructed using the modified Hulth method in the model and POG groups. Mice in the POG group were administered 30 mg/(kg·d)POG by gavage. The other groups were administered an equal amount of normal saline for 8 weeks. The cartilage tissue structure of mice in each group was observed using hematoxylin and eosin staining. Real-time PCR was used to detect changes in the lncRNA NEAT1 and miR-128-3p mRNA expression levels in the cartilage tissues of mice. Western blotting was used to detect the protein expressions of ATP-binding cassette transporter A1 (ABCA1), liver X receptor β (LXRβ), matrix metalloprotein-3 (MMP-3), and B-lymphoblastoma-2-associated X protein (Bax) in articular cartilage of mice. An enzyme-linked immunosorbent assay was used to measure the tumor necrosis factor-α (TNF-α) content in the synovial fluid of mice. A biochemical microplate assay was used to measure the total cholesterol level in the synovial fluid of mice. The in vitro experiments were divided into the negative control, interleukin-1β(IL-1β), IL-1β+ POG, IL-1β+ oe-lncRNA NEAT1, IL-1β+ oe-lncRNA NEAT1 + POG, IL-1β + miR-128-3p inhibition, and IL-1β+ miR-128-3p inhibition+ POG groups. An OA model was established by inducing chondrocytes with IL-1β for 24 h, and 90 mg/L of POG and miR-128-3p inhibitor(50 nmol/L) were administered for 48 h as an intervention. lncRNA NEAT1 expression in chondrocytes was detected using fluorescence in situ hybridization. A dual luciferase assay was used to detect the targeting relationship between lncRNA NEAT1 and miR-128-3p. Lentiviral plasmids overexpressing lncRNA NEAT1 were used to transfect mouse chondrocytes. Real-time PCR was used to detect the effect of lncRNA NEAT1 overexpression on the mRNA level of miR-128-3p in chondrocytes. Western blotting was used to detect ABCA1, LXRβ, MMP-3, and Bax protein expression in chondrocytes after lncRNA NEAT1 overexpression and miR-128-3p inhibition. Results: POG significantly reduced OA cartilage tissue damage. Compared with the model group, the lncRNA NEAT1 mRNA level decreased, whereas the miR-128-3p mRNA level increased in the cartilage tissue of the POG group (P<0.05). Compared with the model group, ABCA1 and LXRβ protein expression increased in the POG group, whereas MMP-3 and Bax protein expression decreased (P<0.05). The TNF-α levels decreased in the POG group compared to the model group (P<0.05). Compared with the model group, the total cholesterol level in the synovial fluid of the joint of mice in the POG group decreased (P<0.05). The mean fluorescence intensity of lncRNA NEAT1 in the IL-1β+ POG group decreased compared with the IL-1β group (P<0.05). The relative luciferase activity in the miR-128-3p mimics group bound to the lncRNA NEAT1-WT plasmid decreased compared with the miR-128-3p negative control group (P<0.05). The lncRNA NEAT1 mRNA levels decreased, whereas the miR-128-3p mRNA levels increased in the IL-1β+ oe-lncRNA NEAT1 + POG group compared with the IL-1β+ oe-lncRNA NEAT1 group (P<0.05). Compared with the IL-1β+ POG group, ABCA1 and LXRβ protein expression decreased, whereas MMP-3 and Bax protein expression increased (P<0.05). Conclusion POG mediates lncRNA NEAT1/miR-128-3p to improve cholesterol metabolism in OA chondrocytes.

ObjectiveThis paper aims to investigate the potential molecular biological mechanism of Buyang Huanwu Tongfeng decoction in treating hyperuricemia and gouty arthritis by network pharmacology and molecular docking technology and preliminarily verify the mechanism through animal experiments. MethodsThe active ingredients and targets in the Buyang Huanwu Tongfeng decoction were obtained by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and ETCM databases. The DisGeNET and GeneCards databases were utilized to acquire disease targets associated with hyperuricemia and gouty arthritis. These disease targets were then intersected with drug targets to identify key targets. The R language ClusterProfiler package and Python were employed for conducting gene ontology（GO） enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） enrichment analysis. The regulatory network diagram of the drug-key target-function-pathway was visualized using Cytoscape 3.9.1 software， and the protein-protein interaction （PPI） network for key targets was depicted. Finally， the hub gene was determined through topological analysis. Auto Dock， PyMOL， and other software were used for molecular docking to explore the possible therapeutic mechanism of Buyang Huanwu Tongfeng decoction for hyperuricemia and gouty arthritis. In animal experiments， a composite rat model of hyperuricemia induced by intraperitoneal injection of oteracil potassium combined with gouty arthritis induced by the modified Coderre method was established. Through hematoxylin-eosin（HE） staining， uric acid test， enzyme linked immunosorbent assay（ELISA）， Western blot， and real-time polymerase chain reaction（Real-time PCR）， the molecular mechanism and key targets of Buyang Huanwu Tongfeng decoction for treating hyperuricemia and gouty arthritis were observed. ResultsAfter screening and removing duplicate values， 76 active ingredients and 15 key targets were finally obtained. GO enrichment analysis yielded that the treatment of hyperuricemia and gouty arthritis with Buyang Huanwu Tongfeng decoction was significantly associated with acute inflammatory response， astrocyte activation， regulation of interleukin （IL）-8 production， nuclear receptor activity， and binding of growth factor receptor. KEGG pathway enrichment analysis obtained that the key target genes were significantly associated with the IL-17 signaling pathway， advanced glycosylation end/receptor of advanced glycation endproducts（AGE/RAGE） signaling pathway， anti-inflammatory， and other pathways. PPI network indicated that albumin（ALB）， peroxisome proliferator-activated receptor-γ （PPAR-γ）， IL-6， IL-1β， and C-reactive protein（CRP） were the key protein targets. The molecular docking results showed that ALB had the strongest binding force with beta-carotene （β-carotene）. Biochemical results showed that blood uric acid decreased in the Buyang Huanwu Tongfeng decoction groups. HE staining results showed that the low-dose （7.76 g·kg^-1·d^-1）， medium-dose （15.53 g·kg^-1·d^-1）， and high-dose （31.05 g·kg^-1·d^-1） groups of Buyang Huanwu Tongfeng decoction had different degrees of remission， and the remission of the high-dose group was the most obvious. Fibroblastic tissue hyperplasia in synovial joints accompanied with inflammatory cell infiltration， as well as inflammatory cell infiltration in renal tissue of the high-dose group was significantly reduced， followed by the medium-dose and low-dose groups， and the expression of ALB， PPAR-γ， IL-6， IL-1β， and CRP was down-regulated to different degrees. ConclusionBy regulating the targets such as ALB， PPAR-γ， IL-6， IL-1β， and CRP， inhibiting the PPAR-γ/nuclear transcription factor （NF）-κB pathway， and reducing AGEs/RAGE-mediated inflammation， Buyang Huanwu Tongfeng decoction exerts anti-inflammatory and analgesic effects and activates blood circulation and diuresis in the treatment of hyperuricemia and gouty arthritis.

BACKGROUND:Ferroptosis is a mode of programmed cell death distinct from apoptosis,necrosis,and other novel cellular deaths,which occurs mainly due to accumulated lipid peroxidation.Ferroptosis has been shown to be involved in the pathological process following subarachnoid hemorrhage.Baicalein,serving as an adept sequestered of iron,evinces its prowess by quelling lipid peroxidative cascades.Nonetheless,the enigma lingers as to whether baicalein possesses the capacity to ameliorate neuronal ferroptosis,elicited in the wake of early brain injury after subarachnoid hemorrhage. OBJECTIVE:To investigate the effect and mechanism of baicalein on neuronal ferroptosis after subarachnoid hemorrhage. METHODS:Primary neuronal cells were extracted from C57BL/6L fetal mice at 16-17 days of gestation.Hemoglobin was used to stimulate primary neuronal cells to simulate an in vitro subarachnoid hemorrhage model.The viability of primary neuronal cells treated with baicalein at concentrations of 5,15,25,50,and 100 μmol/L for 24 hours was detected by CCK-8 assay to determine the optimal concentration of baicalein.Primary neuronal cells were divided into control group,hemoglobin group,and hemoglobin+baicalein group.The levels of reactive oxygen species and malondialdehyde in cells were detected by kits.The mRNA expressions of ferroptosis-related markers PTGS2,SLC7A11,and glutathione peroxidase 4 were detected by RT-PCR.The primary neuronal cells were further divided into control group,SLC7A11 inhibitor Erastin group,hemoglobin group,hemoglobin+baicalein group,and hemoglobin+baicalein+Erastin group.The expression of the ferroptosis related markers SLC7A11 and glutathione peroxidase 4 was detected by western blot assay. RESULTS AND CONCLUSION:(1)Baicalein(25 μmol/L)was selected as the following experimental concentration.(2)Compared with the hemoglobin group,the level of malondialdehyde and the level of reactive oxygen species were significantly decreased(P<0.05)in the hemoglobin+baicalein group.(3)Compared with the hemoglobin group,the mRNA expression of PTGS2 significantly decreased,and the mRNA expression of SLC7A11 and glutathione peroxidase 4 significantly increased(P<0.000 1)in the hemoglobin+baicalein group.(4)SLC7A11 inhibitor Erastin could reverse the baicalin-improved ferroptosis effect to a certain extent(P<0.05).(5)The results showed that baicalein could alleviate the ferroptosis of neuronal cells after subarachnoid hemorrhage through the SLC7A11/GPX4 pathway.

BACKGROUND:The treatment of early knee osteoarthritis can be achieved through two knee preservation treatments:Unicondylar knee arthroplasty and high tibial osteotomy.However,further exploration is needed to determine whether there are differences in knee joint recovery between the two knee preservation surgeries at different stages after surgery. OBJECTIVE:To compare the efficacy and related complications of unicondylar knee arthroplasty and high tibial osteotomy in the treatment of varus osteoarthropathy of the knee,and to provide a reference for clinical decision. METHODS:A total of 103 patients with varus osteoarthritis of the knee underwent surgical treatment in the Affiliated Hospital of Nantong University from September 2018 to September 2022 were selected.Among them,86 patients were followed up for more than 1 year.According to different surgical methods,the patients were divided into unicondylar knee arthroplasty group(49 cases)and high tibial osteotomy group(37 cases).Knee function,pain,and line of force correction were evaluated before surgery,4 weeks,3 months,6 months,and 1 year after surgery in both groups.Hospital for special surgery knee score,functional score of Western Ontario and McMaster Universities Osteoarthritis Index,changes of lateral space of the knee joint,range of motion,proprioception(position sense),and postoperative activity recovery speed were evaluated comprehensively. RESULTS AND CONCLUSION:(1)There were no significant differences in preoperative hospital for special surgery knee score,Western Ontario and McMaster Universities Osteoarthritis Index score and lateral knee compartment size between the two groups.(2)The hospital for special surgery knee score of patients undergoing unicondylar knee arthroplasty was better than that of patients undergoing high tibial osteotomy within 4 weeks after surgery(P<0.05).At 3 and 6 months after surgery,compared with the improvement of the two groups,the hospital for special surgery knee score in the unicondylar knee arthroplasty group was lower than that in the high tibial osteotomy group,and the difference was significant(P<0.05).The range of motion flexion value and position perception of patients undergoing high tibial osteotomy were significantly better than those undergoing unicondylar knee arthroplasty 6 months after surgery(P<0.05).(3)The unicondylar knee arthroplasty group was better than the high tibial osteotomy group in terms of the speed of knee movement recovery(P<0.05).(4)However,there was no significant difference between the two groups in the change of hospital for special surgery knee score,range of motion,and the width of lateral knee space during 1-year follow-up.(5)All patients were followed up for more than 1 year,and no adverse complications were found during the follow-up.(6)It is indicated that the short-term effect of knee functional recovery in patients with high tibial osteotomy is better than that in patients with unicondylar knee arthroplasty,but there is no significant difference in medium-and long-term efficacy between the two kinds of surgery for medial knee arthritis.

ObjectiveTo explore the feasibility， evaluation methods and metabolic differences of high-fat diet（HFD） combined with myocardial ischemia-reperfusion injury（MIRI） to establish a rat model of myocardial ischemia-reperfusion with phlegm and blood stasis blocking collaterals syndrome（PBSBCS）. MethodsThirty-two SD rats were randomly divided into the sham operation， HFD， MIRI， and MIRI+HFD groups. Rats in the sham operation and MIRI groups were fed a standard diet（regular chow）， while the HFD and MIRI+HFD groups received a HFD for 10 weeks. Rats in the MIRI and MIRI+HFD groups underwent myocardial ischemia-reperfusion surgery， while the sham operation group underwent only thread placement without ligation. Cardiac function was assessed via small-animal echocardiography， including left ventricular ejection fraction（EF）， left ventricular fractional shortening（FS）， cardiac output（CO）， and stroke volume（SV）. Serum levels of creatine kinase（CK）， CK-MB， triglyceride（TG）， total cholesterol（TC）， high-density lipoprotein cholesterol（HDL-C）， low-density lipoprotein cholesterol（LDL-C）， lactate dehydrogenase（LDH）， endothelin-1（ET-1）， endothelial nitric oxide synthase（eNOS）， tumor necrosis factor-α（TNF-α）， interleukin-18（IL-18）， oxidized LDL（ox-LDL）， and cardiac troponin T（cTnT） were measured by biochemical assays and enzyme-linked immunosorbent assay（ELISA）. Myocardial histopathology was evaluated via hematoxylin-eosin（HE） staining， while myocardial infarction and no-reflow area were assessed using 2，3，5-triphenyltetrazolium chloride（TTC）， Evans blue， and thioflavin staining. Changes in syndrome characteristics［body weight， tongue surface red-green-blue ［RGB］ values， and pulse amplitude］ of PBSBCS were recorded. Serum differential metabolites were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）. ResultsCompared with the sham operation group， the HFD and MIRI+HFD groups showed significant increases in body weight（P<0.01）， RGB values and pulse amplitude decreased in the HFD， MIRI and MIRI+HFD groups， TC， TG， LDL-C and ox-LDL levels increased in the HFD and MIRI+HFD groups， while HDL-C decreased. Blood perfusion peak time and myocardial no-reflow area increased， serum eNOS level decreased， and CK-MB， LDH， and cTnT activities increased in the HFD， MIRI and MIRI+HFD groups（P<0.05， P<0.01）. Whole blood viscosity was increased in the HFD group at medium shear rate， and in the MIRI and MIRI+HFD groups at low， medium and high shear rates（P<0.05， P<0.01）. Platelet aggregation rate increased in the MIRI and MIRI+HFD groups， accompanied by elevated ET-1， TNF-α， and IL-18 levels， reduced cardiac function indices， expanded myocardial no-reflow and infarction areas， and increased serum CK， CK-MB， LDH， and cTnT activities（P<0.05， P<0.01）. Compared with the MIRI group， the HFD and MIRI+HFD groups showed significant increase in body weight， TC， TG， LDL-C and ox-LDL levels， and significant decrease in HDL-C content（P<0.01）. The MIRI+HFD group showed decrease in RGB values and pulse amplitude， and an increase in whole blood viscosity， platelet aggregation， blood perfusion peak time， myocardial no-reflow and infarction areas， elevated ET-1， TNF-α and IL-18 levels， decreased eNOS content， EF and SV， increased serum CK， CK-MB and cTnT activities， and worsened myocardial pathology（P<0.05）. Compared with the HFD group， the MIRI+HFD group showed similar aggravated trends（P<0.05， P<0.01）. Metabolomics results showed that 34 potential biomarkers involving 13 common metabolic pathways were identified in the MIRI+HFD group compared with the sham operation group. ConclusionThe MIRI group resembles blood stasis syndrome in hemodynamics and myocardial injury， and the HFD group mirrors phlegm-turbidity syndrome in lipid profiles and tongue characteristics. While the MIRI+HFD group aligns with PBSBCS in comprehensive indices， effectively simulating clinical features of coronary heart disease（CHD）， which can be used for the evaluation of the pathological mechanism and pharmacodynamics of CHD with PBSBCS.

ObjectiveTo explore the feasibility， evaluation methods and metabolic differences of high-fat diet（HFD） combined with myocardial ischemia-reperfusion injury（MIRI） to establish a rat model of myocardial ischemia-reperfusion with phlegm and blood stasis blocking collaterals syndrome（PBSBCS）. MethodsThirty-two SD rats were randomly divided into the sham operation， HFD， MIRI， and MIRI+HFD groups. Rats in the sham operation and MIRI groups were fed a standard diet（regular chow）， while the HFD and MIRI+HFD groups received a HFD for 10 weeks. Rats in the MIRI and MIRI+HFD groups underwent myocardial ischemia-reperfusion surgery， while the sham operation group underwent only thread placement without ligation. Cardiac function was assessed via small-animal echocardiography， including left ventricular ejection fraction（EF）， left ventricular fractional shortening（FS）， cardiac output（CO）， and stroke volume（SV）. Serum levels of creatine kinase（CK）， CK-MB， triglyceride（TG）， total cholesterol（TC）， high-density lipoprotein cholesterol（HDL-C）， low-density lipoprotein cholesterol（LDL-C）， lactate dehydrogenase（LDH）， endothelin-1（ET-1）， endothelial nitric oxide synthase（eNOS）， tumor necrosis factor-α（TNF-α）， interleukin-18（IL-18）， oxidized LDL（ox-LDL）， and cardiac troponin T（cTnT） were measured by biochemical assays and enzyme-linked immunosorbent assay（ELISA）. Myocardial histopathology was evaluated via hematoxylin-eosin（HE） staining， while myocardial infarction and no-reflow area were assessed using 2，3，5-triphenyltetrazolium chloride（TTC）， Evans blue， and thioflavin staining. Changes in syndrome characteristics［body weight， tongue surface red-green-blue ［RGB］ values， and pulse amplitude］ of PBSBCS were recorded. Serum differential metabolites were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）. ResultsCompared with the sham operation group， the HFD and MIRI+HFD groups showed significant increases in body weight（P<0.01）， RGB values and pulse amplitude decreased in the HFD， MIRI and MIRI+HFD groups， TC， TG， LDL-C and ox-LDL levels increased in the HFD and MIRI+HFD groups， while HDL-C decreased. Blood perfusion peak time and myocardial no-reflow area increased， serum eNOS level decreased， and CK-MB， LDH， and cTnT activities increased in the HFD， MIRI and MIRI+HFD groups（P<0.05， P<0.01）. Whole blood viscosity was increased in the HFD group at medium shear rate， and in the MIRI and MIRI+HFD groups at low， medium and high shear rates（P<0.05， P<0.01）. Platelet aggregation rate increased in the MIRI and MIRI+HFD groups， accompanied by elevated ET-1， TNF-α， and IL-18 levels， reduced cardiac function indices， expanded myocardial no-reflow and infarction areas， and increased serum CK， CK-MB， LDH， and cTnT activities（P<0.05， P<0.01）. Compared with the MIRI group， the HFD and MIRI+HFD groups showed significant increase in body weight， TC， TG， LDL-C and ox-LDL levels， and significant decrease in HDL-C content（P<0.01）. The MIRI+HFD group showed decrease in RGB values and pulse amplitude， and an increase in whole blood viscosity， platelet aggregation， blood perfusion peak time， myocardial no-reflow and infarction areas， elevated ET-1， TNF-α and IL-18 levels， decreased eNOS content， EF and SV， increased serum CK， CK-MB and cTnT activities， and worsened myocardial pathology（P<0.05）. Compared with the HFD group， the MIRI+HFD group showed similar aggravated trends（P<0.05， P<0.01）. Metabolomics results showed that 34 potential biomarkers involving 13 common metabolic pathways were identified in the MIRI+HFD group compared with the sham operation group. ConclusionThe MIRI group resembles blood stasis syndrome in hemodynamics and myocardial injury， and the HFD group mirrors phlegm-turbidity syndrome in lipid profiles and tongue characteristics. While the MIRI+HFD group aligns with PBSBCS in comprehensive indices， effectively simulating clinical features of coronary heart disease（CHD）， which can be used for the evaluation of the pathological mechanism and pharmacodynamics of CHD with PBSBCS.

The analysis presented here is based on the blood components of Guanxin Qiwei tablets, the key anti-atherosclerosis pathway of Guanxin Qiwei tablets was screened by network pharmacology, and the anti-atherosclerosis mechanism of Guanxin Qiwei tablets was clarified and verified by cell experiments. HPLC-Q-Exactive-MS/MS technique was used to analyze the components of Guanxin Qiwei tablets into blood, to determine the precise mass charge ratio of the compounds, and to conduct a comprehensive analysis of the components by using secondary mass spectrometry fragments and literature comparison. Finally, a total of 42 components of Guanxin Qiwei tablets into blood were identified. To better understand the interactions, we employed the Swiss Target Prediction database to predict the associated targets. Atherosclerosis (AS) disease targets were searched in disease databases Genecard, OMIM and Disgent, and 181 intersection targets of disease targets and component targets were obtained by Venny 2.1.0 software. Protein interactions were analyzed by String database. The 32 core targets were selected by Cytscape software. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed in DAVID database. It was found that the anti-atherosclerosis pathways of Guanxin Qiwei tablets mainly include lipid metabolism and atherosclerosis and AGE-RAGE signaling pathway in diabetic complications and other signal pathways. The core targets and the core compounds were interlinked, and it was found that cryptotanshinone and tanshinone ⅡA in Guanxin Qiwei tablets were well bound to TNF, PPARγ, AKT1, PTG2 and other targets. The lipid metabolism and atherosclerotic pathway was verified using human hl-7702 hepatocytes. This study preliminarily identified the potential pharmacodynamic components of Guanxin Qiwei tablets in the treatment of AS diseases and predicted their pathways of action, and verified the relationship between regulating lipid metabolism and atherosclerosis of Guanxin Qiwei tablets in vitro, providing a reference for the further study of the pharmacodynamic material basis and mechanism of action of this prescription. This experiment was approved by the Medical Ethics Committee of Inner Mongolia Medical University (No. YKD202401262).