1.Clinical observation of Zhengxintai granules in the treatment of microvascular angina for acute ST-segment elevation myocardial infarction patients with qi deficiency and blood stasis syndrome after PCI
Wenhui MA ; Ying ZHANG ; Lei LIU ; Xiuyan YU ; Yali CHEN ; Liming CHEN
China Pharmacy 2026;37(15):2023-2029
OBJECTIVE To investigate the clinical efficacy and safety of Zhengxintai granules as in the treatment of microvascular angina (MVA) following percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI) and qi deficiency and blood stasis syndrome. METHODS Patients with STEMI and qi deficiency and blood stasis syndrome who underwent PCI and developed MVA and were admitted to the Jinan Fourth People’s Hospital (Jinan Cardiovascular Hospital) from March 2022 to March 2025 were selected, they were randomly divided into the control group and the observation group according to a random number table, with 76 cases in each group. Patients in the control group received conventional Western medicine treatment combined with a placebo, while patients in the observation group received Zhengxintai granules (5 mg per dose, three times daily, for 8 weeks) in addition to conventional Western medicine treatment. The clinical efficacy [including the total effective rate of traditional Chinese medicine (TCM) syndrome improvement and the total effective rates of Western clinical efficacy] was compared between the two groups. The following indicators were detected before and after treatment: TCM syndrome scores, angina pectoris episodes [daily attack frequency, duration per attack, Visual Analogue Scale (VAS) score], cardiac function indicators [lactate dehydrogenase (LDH), N-terminal pro-B-type natriuretic peptide (NT-proBNP), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), left ventricular ejection fraction (LVEF), cardiac output (CO), fractional shortening (FS)], coagulation function indicators [thrombin time (TT), prothrombin time (PT), fibrinogen (FIB)], fibrinolytic marker (D-dimer), vascular endothelial function indicators [vascular endothelial growth factor (VEGF), nitric oxide (NO), endothelin-1 (ET-1)] and myocardial microcirculation hemodynamic indicators [end-diastolic velocity (EDV), peak systolic velocity (PSV), resistance index (RI), pulsatility index (PI)]. The quality of life [Seattle Angina Questionnaire (SAQ) score] and the incidence of adverse reactions were also compared between the two groups. RESULTS There was no patient dropout during the entire course of the study. The total effective rates of improvement in TCM syndromes and the total effective rates of Western clinical efficacy in the observation group were significantly higher than those in the control group (93.42% vs. 82.89%, 94.74% vs. 84.21%, P<0.05). Before the treatment, the comparison of each examination indicator between the two groups showed no statistically significant differences (P>0.05). Compared with before treatment, the TCM syndrome scores, the number of daily angina pectoris attacks and the duration of each attack, the VAS scores, LDH, NT-proBNP, FIB, D-dimer, ET-1 levels, LVEDD, LVESD, RI and PI after treatment in both groups were significantly reduced, shortened or decreased (P<0.05); VEGF and NO levels, LVEF, CO, FS, TT, PT, EDV, PSV, and the standard scores of five dimensions including angina pectoris stability, as well as the total scores of SAQ, all significantly increased or prolonged (P<0.05). Furthermore, the improvements in the aforementioned indicators (except for LVEF) in the observation group were significantly greater than those in the control group (P<0.05). There was no statistically significant difference in the total incidence of adverse reactions between the two groups (P>0.05). CONCLUSIONS Zhengxintai granules, when used as an adjunct to conventional Western medicine, can significantly alleviate the related symptoms of MVA in STEMI patients with qi deficiency and blood stasis syndrome after PCI, repair damaged cardiac function, restore the balance of the coagulation-fibrinolysis system, improve vascular endothelial function and myocardial microcirculation perfusion, and significantly enhance the quality of life of patients
2.Expression and clinical significance of RAB24 gene in hepatocellular carcinoma based on multi-source databases and clinical cohort validation
Yali GUO ; Yangchen WANG ; Jianhua YANG ; Xiang GAO ; Wenmei MA ; Nan DING ; Qiang HOU ; Wu DAI ; Limei WEN ; Junping HU
Acta Universitatis Medicinalis Anhui 2026;61(9):1647-1656
ObjectiveTo investigate the mRNA expression profile and clinical significance of the RAB24 gene in hepatocellular carcinoma (HCC) based on multi-source database including The Cancer Genome Atlas (TCGA) and clinical cohort validation. MethodsData from TCGA (n=424) were utilized to evaluate the prognostic value of RAB24 expression via Kaplan-Meier analysis and Cox regression models. An independent clinical cohort comprising 90 HCC and 30 paracancerous tissues was established to validate protein expression and histopathological features through immunohistochemistry (IHC) and routine histological staining. The TIMER database was employed to analyze the association between RAB24 and the tumor microenvironment (TME). Furthermore, integrated with LinkedOmics, GSEA and GSVA algorithms were used to quantitatively characterize the core molecular pathways regulated by RAB24. ResultsThe mRNA expression level of RAB24 in HCC was significantly higher than that in non-tumor liver tissues (P<0.05). Kaplan-Meier analysis revealed that the overall survival (OS) of patients in the RAB24 low-expression group was significantly longer compared to the high-expression group (HR=1.570, Log-rank P=0.01). Cox proportional hazards regression analysis demonstrated that RAB24 expression (HR=1.480, P=0.028), T stage (HR=2.949, P<0.001), M stage (HR=4.077, P=0.017), and tumor residual status (HR=2.317, P<0.001) were independent prognostic factors for HCC. RAB24 expression was highly correlated with alpha-fetoprotein (AFP) levels and immune infiltration levels (P<0.01), and showed a significant, low-level positive correlation with the TP53 gene (Rho=0.31, P<0.01). Quantitative analysis of the RAB24 protein in clinical samples validated that RAB24 expression in HCC tissues was significantly elevated compared to non-tumor liver tissues (P<0.05). TIMER analysis confirmed that RAB24 expression was highly associated with the infiltration of multiple immune cells (such as B cells and NK cells), as well as stromal and tumor purity scores in tumor tissues (P<0.01). GSEA/GSVA enrichment revealed that the P53, MYC, and mTORC1 signaling pathways were activated in the RAB24 high-expression group; correlation analysis confirmed that the RAB24 expression level exhibited a significant, low-level positive correlation with the ribosome pathway activity score (r=0.23, P<0.01). ConclusionsThe RAB24 gene, as a poor prognostic factor for HCC patients, is a potential biomarker for HCC diagnosis, treatment and prognosis. The study is expected to lay a theoretical foundation for the precise diagnosis and treatment of clinical HCC.
3.Development of the "Clinical Ethics" Course for the Eight-Year Clinical Medicine Program: Explorations and Practices by an Interdisciplinary Teaching Team
Jiangli HAN ; Yali CONG ; Qiong BAI ; Shu LI ; Guangkuan XIE ; Tongyan HAN ; Chuan MA ; Ying YAO ; Fei DONG ; Huilin LIU ; Rui WU ; Qinggang GE ; Liang WANG ; Yuxi XIA ; Shixian GU ; Xuan HE ; Ning SHEN
Medical Journal of Peking Union Medical College Hospital 2026;17(5):1223-1229
With the rapid advancement of medical technology and the increasing complexity of clinical environments, competence in clinical ethical decision-making has become an indispensable core competency for exemplary physicians. However, traditional medical ethics education has long been confronted with the persistent challenges of theory-practice dissociation and the disconnect between pedagogical settings and clinical realities. Thus, how to construct a "Clinical Ethics" curriculum that aligns with the objectives of training high-caliber medical professionals has emerged as a critical and challenging issue in current medical education reform. To effectively address this challenge, the Office of Education at Peking University Third Hospital, since 2021, has assembled a multidisciplinary "Clinical Ethics" teaching and management team comprising faculty from Peking University School of Humanities and key clinical specialists from the hospital. In 2022, the "Clinical Ethics" elective course was formally launched for fourth-year students in the eight-year MD program who had completed coursework in "Medical Ethics" and organ-system-based curricula, with the aim of exploring and operationalizing a pre-clinical ethics education model tailored for senior medical students. The course employs a modular instructional design encompassing "theoretical review-case-based deliberation-clinical workshop", which effectively facilitates the deep integration of medical humanities with clinical practice.Following four years of iterative refinement through the "plan-act-observe-reflect" cycle, the course has demonstrated positive outcomes in enhancing students' ethical awareness and decision-making capabilities, and has preliminarily established a sustainable collaborative mechanism among the multidisciplinary faculty team. This article systematically delineates the course development background, pedagogical model and methodological innovations, and the multidisciplinary collaborative framework, alongside reflections and summaries based on implementation outcomes, with the intent of providing references for the future development of "Clinical Ethics" curricula.
4.Research on the construction and application of a narrative nursing program based on Snyder’s hope theory for patients with advanced liver cancer
Sha NIE ; Yali SUN ; Yaxin ZHAO ; Xiaoling ZHU ; Yiyuan MA ; Jiaoqiong ZHANG
Chinese Medical Ethics 2026;39(9):1245-1253
ObjectiveTo establish a narrative nursing program for patients with advanced liver cancer based on the framework of Snyder’s hope theory, and verify its effectiveness. MethodsThe Johns Hopkins evidence-based nursing model and the Delphi method were employed to construct the narrative nursing program for patients with advanced liver cancer. Utilizing the convenience sampling method, 70 patients with advanced liver cancer hospitalized in the department of hepatobiliary surgery from May 2024 to May 2025 were selected and divided into the control group and the intervention group using the random number table method, with 35 patients in each group. The control group received routine nursing care, while the intervention group received the narrative nursing program based on Snyder’s hope theory for patients with advanced liver cancer. The Herth Hope Index, Connor-Davidson Resilience Scale (CD-RISC), Self-Rating Anxiety Scale (SAS), and Morisky Medication Adherence Scale-8 (MMAS-8) were used to compare the hope level, psychological resilience, anxiety, and medication adherence between the two groups before and after the intervention. Furthermore, nursing satisfaction was also compared. ResultsThe Delphi expert consultation results demonstrated high consistency among expert opinions, with an expert positive coefficient of 100%. Meanwhile, the authority coefficients (0.902, 0.912) and Kendall’s concordance coefficients (0.260, 0.283) were all satisfactory. Ultimately, a narrative nursing program was established, consisting of 3 primary indicators, 10 secondary indicators, and 19 tertiary indicators. Compared with the control group, the intervention group exhibited significant improvements in scores of the three dimensions regarding the hope level, the total score of psychological resilience, medication adherence, and nursing satisfaction after the intervention, and the anxiety score was markedly reduced. All differences were statistically significant (P<0.05). ConclusionThe narrative nursing program for patients with advanced liver cancer developed in this study is scientific and reliable. Its clinical application can effectively improve the psychological status and treatment behaviors of patients with advanced liver cancer, profoundly reflect the ethical care for the humanistic needs of patients, and provide an evidence-based basis for optimizing the psychological support for this population.
5.Mediating effects of psychological resilience on the relationship between perceived social support and health behavior capacity in patients with ischemic stroke
Yuqing GUO ; Yan XU ; Bei ZHAO ; Yali MA ; Shirong GE ; Shaomin WANG
Chinese Journal of Health Management 2025;19(2):140-146
Objective:To analyze the mediating effects of psychological resilience on the relationship between perceived social support and health behavior capacity in patients with ischemic stroke.Methods:In this cross-sectional study, 500 patients with ischemic stroke were consecutively recruited using purposive sampling in the First People′s Hospital of Lianyungang between July and September in 2023. The sociodemographic characteristics, perceived social support scale, psychological resilience questionnaire and self-rated abilities for health practices scale in the patients were collected. A total of 500 questionnaires were distributed and 493 questionnaires were collected, of which 473 (95.9%) were valid. The structural equation model was constructed to explore the mediating effects of psychological resilience on the relationship between perceived social support and health behavior capacity in patients with ischemic stroke.Results:Among the 473 patients included in the analysis, there were 254 males and 219 females, with an average age of (66.8±11.4) years. The duration of stroke was less than 3 months for 329 patients (69.6%); the scores for perceived social support, psychological resilience and health behavior capacity was (59.68±11.15), (23.68±6.52), and (60.54±23.52), respectively. Perceived social support exerted significant direct effect ( β=0.334, bias-corrected 95% CI: 0.232-0.438) on health behavior capacity in patients with ischemic stroke, accounting for 63.62% of the total effect. Psychological resilience played a mediating role in the relationship between perceived social support and health behavior capacity ( β=0.191, bias-corrected 95% CI: 0.142-0.248), accounting for 36.38% of the total effect (all P<0.05). Conclusion:The health behavior capacity of patients with ischemic stroke is at a moderately low level, perceived social support may positively affect health behavior capacity through the positive mediating effect of psychological resilience.
6.Real world clinical data analysis of fuzuloparib for the treatment of ovarian epithelial cancer patients
Danhui WENG ; Jie JIANG ; Yingjie YANG ; Mingqian LU ; Jiaying BAI ; Ming LIU ; Xiaoling LI ; Jun TIAN ; Yutao GUAN ; Quan LI ; Liang CHEN ; Qiubo LYU ; Lixia MA ; Yali WANG ; Huicheng XU ; Hailong GUO ; Li SUN ; Ding MA ; Qinglei GAO
Chinese Journal of Obstetrics and Gynecology 2025;60(8):590-599
Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.
7.The expression of LAMB3 and ITGB4 in esophageal squamous cell carcinoma and their relationship with clinicopathological features
Yali ZHAO ; Sheng WU ; Wei PENG ; Wanxiang WANG ; Haoran ZHANG ; Zhenzhong FENG ; Li MA ; Xian WANG
Chinese Journal of Clinical and Experimental Pathology 2025;41(10):1301-1307,1313
Purpose To investigate the expression of LAMB3 and ITGB4 in esophageal squamous cell carcinoma(ESCC)and analyze their associations with clinicopathological features.Methods Bioinformatics was used to assess the expression of LAMB3 and ITGB4 in pan-cancer and ESCC.Immunohistochemistry was performed to evaluate their expression and distribution in ESCC tissues,and correlations clinicopathological features were analyzed.Follow-up data were collected to construct Kaplan-Meier survival curves,and Cox regression analysis was proformed to determine their prognostic significance.Results Bioinformatics analysis showed that LAMB3 and ITGB4 were highly expressed in ES-CC tissues(P<0.001).Immunohistochemistry confirmed that both proteins were localized in the cytoplasm and membrane of tumor cells.High LAMB3 expression was significantly associated with poor differentiation(P<0.001),lymph node metastasis(P=0.015),and T staging(P<0.001).High ITGB4 expression was significantly correlated with poor differentiation(P=0.004)and advanced T staging(P=0.004).Cox regression analysis identified high ex-pression of LAMB3 and ITGB4 as independent prognostic factors for overall survival[HR=4.97(95%CI:2.73-9.02);HR=2.33(95%CI:1.36-3.99)].Conclusion LAMB3 and ITGB4 are highly expressed in ESCC.High LAMB3 expression is associated with tumor differentiation,lymph node metastasis,and T staging,while high ITGB4 expression is correlated with tumor differentiation and T staging.Patients with high expression of LAMB3 or ITGB4 have poorer overall survival,suggesting that these proteins may serve as prognostic biomarkers for unfavorable outcome in ESCC.
8.Bioinformatic analysis of TCGA database based on INPP4B gene expression in hepatocellular carcinoma and its experimental validation
Limei WEN ; Yali GUO ; Wenmei MA ; Taotao XUE ; Ruoyu GENG ; Chong MA ; Xinhong ZHANG ; Jianhua YANG
Journal of Jilin University(Medicine Edition) 2025;51(6):1618-1629
Objective:To discuss the expression and clinical significance of inositol polyphosphate-4-phosphatase type Ⅱ(INPP4B)gene in hepatocellular carcinoma(HCC)based on The Cancer Genome Atlas(TCGA)database and experimental verification with clinical samples.Methods:Based on data from 424 clinical samples in the TCGA database(including 374 HCC tissues and 50 paracarcinoma tissues),Kaplan-Meier method and Cox regression analysis were used to evaluate the relationship between INPP4B gene and the clinical characteristics and survival prognosis of the HCC patients.The correlations between INPP4B gene and the number of 24 types of immune cells,matrix,immune cell infiltration and tumor purity in tumor tissue,and the expression level of the high-frequency mutant gene tumor protein 53(TP53)in HCC were analyzed.The clinicopathological data and paraffin-embedded tissue sections of 60 HCC patients treated with surgical resection from December 2022 to December 2023 were collected.According to clinical diagnosis,they were divided into poorly differentiated group(HCC-L group),moderately differentiated group(HCC-M group)and well-differentiated group(HCC-H group),with 20 cases in each group;20 patients during the same period who underwent biopsy and were pathologically diagnosed as non-tumor were selected as normal group,and their clinicopathologic data and liver tissue paraffin sections were collected.HE staining was used to observe the pathomorphology of HCC tissue and normal liver tissue of the subjects in various groups;immunohistochemistry method was used to detect the expressions of Ki-67 and INPP4B proteins in the HCC tissue and normal liver tissue of the subjects in various groups.Results:The TCGA database analysis results showed that compared with normal tissue,the expression level of INPP4B mRNA in HCC tissue was significantly increased(P<0.01).Compared with INPP4B low expression group,the overall survival(OS)of the patients in INPP4B high expression group was significantly prolonged(P<0.05).The univariate Cox regression analysis results showed that tumor stage,pathological stage,tumor status and residual tumor had impacts on OS of the HCC patients(P<0.05).The univariate regression analysis results showed that the INPP4B prognostic risk model score ratio was HR=0.781,95%confidence interval(CI):0.552-1.105,P=0.168.The AUC value for the impact of INPP4B on OS of the HCC patients was 0.558,indicating that the INPP4B gene prognostic risk model had certain predictive value in survival prognosis.The INPP4B mRNA expression level was not correlated with TNM stage,stage,patient gender,age,race or body mass index(BMI)(P>0.05).In tumor tissue with high and low INPP4B expression,22 types of immune cells showed statistically significant differences(P<0.05);the INPP4B mRNA expression level was positively correlated with the number of 23 types of immune cells except T helper(Th)17 cells(r>0),among which all Th cells except natural killer(NK)CD56+cells were statistically significant(P<0.01);INPP4B was significantly correlated with matrix(r=0.475),immune cell infiltration(r=0.641)and tumor purity(r=0.599)in tumor tissue(P<0.01).INPP4B was correlated with TP53(r=0.287,P<0.01).The HE staining results showed that clear and complete lobular structure,neatly arranged cells and slight inflammatory cell infiltration were observed in liver tissue of the subjects in normal group;completely destroyed lobular structure,significant hepatocellular steatosis,massive inflammatory cell infiltration,and lesions such as ballooning degeneration and small cell hyperplasia in some cells were observed in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups,and the lower the HCC differentiation degree,the more severe the tissue destruction;The immunohistochemistry results showed that compared with normal group,the expression levels of Ki-67 protein in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups were significantly increased(P<0.01),and the lower the differentiation degree of the HCC patients,the higher the Ki-67 positive rate.Brownish-yellow granules evenly distributed in the cells and INPP4B protein was highly expressed in liver tissue of the subjects in normal group;compared with normal group,the expression levels of INPP4B protein in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups were significantly decreased(P<0.01),and the lower the differentiation degree of the HCC tissue,the lower the INPP4B positive rate.Conclusion:INPP4B is a protective factor for the prognosis of HCC patients;as a new tumor suppressor gene,INPP4B may become a potential target for new drug screening in HCC treatment.
9.Establishment and Evaluation of Rat Model of Myocardial Ischemia-reperfusion Injury with Phlegm and Blood Stasis Blocking Collaterals Syndrome Based on Metabolomics
Longxiao HU ; Jiabei GAO ; Weihao MA ; Jieming LU ; Yunxiao GAO ; Yue YUAN ; Qiuyan ZHANG ; Xiaoxiao CHEN ; Yali SHI ; Jianxun LIU ; Junguo REN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):41-51
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.
10.Establishment and Evaluation of Rat Model of Myocardial Ischemia-reperfusion Injury with Phlegm and Blood Stasis Blocking Collaterals Syndrome Based on Metabolomics
Longxiao HU ; Jiabei GAO ; Weihao MA ; Jieming LU ; Yunxiao GAO ; Yue YUAN ; Qiuyan ZHANG ; Xiaoxiao CHEN ; Yali SHI ; Jianxun LIU ; Junguo REN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):41-51
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.

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