1.Exploration in Mechanism of Sini San for Inhibiting Ferroptosis and Ameliorating Isoprenaline-induced Myocardial Infarction in Mice Based on Bioinformatics and Experimental Validation
Shupeng LIU ; Zhiguang HAN ; Jiaying LI ; Jiayao XU ; Weihao GAO ; Yanping WU ; Guangguo BAN ; Yongmin LI ; Hongxia YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):67-77
ObjectiveTo explore the mechanism by which Sini San (SNS) inhibits ferroptosis, alleviates inflammation and myocardial injury, and improves myocardial infarction (MI). MethodsThe active ingredients of SNS were obtained by searching the Traditional Chinese Medicine System Pharmacology Platform (TCMSP) database, its target sites were predicted using the SwissTargetPrediction Database, and the core components were screened out using the CytoNCA plug-in. The targets of MI and ferroptosis were obtained by using GeneCards, Online Mendelian Inheritance in Man (OMIM) database, DrugBank, Therapeutic Target Database (TTD), FerrDb database and literature review, respectively. The intersection of these targets of SNS-MI-ferroptosis was plotted as a Venn diagram. The protein-protein interaction (PPI) network was constructed using the STRING database, and the visualization graph was prepared using Cytoscape. The core targets were screened out using the CytoNCA plug-in, and the biological functions were clustered by the MCODE plug-in. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the David database. Molecular docking was performed using AutoDock and visualized with PyMOL2.5.2. The Kunming mice were randomly divided into the control group, the model group, the SNS group, and the trimetazidine (TMZ) group. The mice were subcutaneously injected with isoprenaline (ISO, 5 mg·kg-1·d-1) to establish an MI model. The drug was continuously intervened for 7 days. The ST-segment changes were recorded by electrocardiogram (ECG), and the tissue morphology changes were observed by hematoxylin-eosin (HE) staining. Cardiomyocyte ferroptosis was investigated by transmission electron microscopy. Serum creatine kinase (CK), creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), reduced glutathione (GSH), and malondialdehyde (MDA) levels were detected by biochemical assay. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of interleukin (IL)-6 and 4-hydroxynonenal (4-HNE). Immunohistochemical staining was employed to detect IL-6 and phosphorylated signal transducer and transcription activator 3 (p-STAT3) in cardiac tissues. Western blot was used to detect STAT3 and p-STAT3 in cardiac tissues. Real-time PCR was used to detect the levels of IL-6, IL-18, solute carrier family 7 member 11 (SLC7A11), arachidonic acid 15-lipoxygenase (ALOX15), and glutathione peroxidase 4 (GPx4) in cardiac tissues. ResultsA total of 121 active ingredients of SNS were obtained, and 58 potential targets of SNS in the treatment of MI by regulating ferroptosis were screened. The three protein modules with a score5 were mainly related to the inflammatory response. The GO function was mainly related to inflammation, and KEGG enrichment analysis showed that SNS mainly regulated ferroptosis- and inflammation- related signaling pathways. Molecular docking indicated that the core component had a higher binding force to the target site. Animal experiments confirmed that SNS reduced the level of p-STAT3 (P0.01), down-regulated the expression of ALOX15 mRNA (P0.01), up-regulated the level of serum GSH, and the expressions of SLC7A11 and GPx4 mRNA, reduced MDA and 4-HNE levels (P0.05, P0.01). Additionally, SNS improved the mitochondrial injury induced by cardiomyocyte ferroptosis, reduced the area of MI, alleviated inflammation and myocardial injury, lowered the levels of serum CK, CK-MB, LDH, IL-6, and the mRNA expression levels of IL-16 and IL-18 (P0.05), and improved ST segment elevation. ConclusionSNS can reduce ISO-induced STAT3 phosphorylation levels, inhibit ferroptosis in cardiomyocytes, alleviate inflammation and myocardial injury, thereby improving MI.
2.Exploration in Mechanism of Sini San for Inhibiting Ferroptosis and Ameliorating Isoprenaline-induced Myocardial Infarction in Mice Based on Bioinformatics and Experimental Validation
Shupeng LIU ; Zhiguang HAN ; Jiaying LI ; Jiayao XU ; Weihao GAO ; Yanping WU ; Guangguo BAN ; Yongmin LI ; Hongxia YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):67-77
ObjectiveTo explore the mechanism by which Sini San (SNS) inhibits ferroptosis, alleviates inflammation and myocardial injury, and improves myocardial infarction (MI). MethodsThe active ingredients of SNS were obtained by searching the Traditional Chinese Medicine System Pharmacology Platform (TCMSP) database, its target sites were predicted using the SwissTargetPrediction Database, and the core components were screened out using the CytoNCA plug-in. The targets of MI and ferroptosis were obtained by using GeneCards, Online Mendelian Inheritance in Man (OMIM) database, DrugBank, Therapeutic Target Database (TTD), FerrDb database and literature review, respectively. The intersection of these targets of SNS-MI-ferroptosis was plotted as a Venn diagram. The protein-protein interaction (PPI) network was constructed using the STRING database, and the visualization graph was prepared using Cytoscape. The core targets were screened out using the CytoNCA plug-in, and the biological functions were clustered by the MCODE plug-in. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the David database. Molecular docking was performed using AutoDock and visualized with PyMOL2.5.2. The Kunming mice were randomly divided into the control group, the model group, the SNS group, and the trimetazidine (TMZ) group. The mice were subcutaneously injected with isoprenaline (ISO, 5 mg·kg-1·d-1) to establish an MI model. The drug was continuously intervened for 7 days. The ST-segment changes were recorded by electrocardiogram (ECG), and the tissue morphology changes were observed by hematoxylin-eosin (HE) staining. Cardiomyocyte ferroptosis was investigated by transmission electron microscopy. Serum creatine kinase (CK), creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), reduced glutathione (GSH), and malondialdehyde (MDA) levels were detected by biochemical assay. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of interleukin (IL)-6 and 4-hydroxynonenal (4-HNE). Immunohistochemical staining was employed to detect IL-6 and phosphorylated signal transducer and transcription activator 3 (p-STAT3) in cardiac tissues. Western blot was used to detect STAT3 and p-STAT3 in cardiac tissues. Real-time PCR was used to detect the levels of IL-6, IL-18, solute carrier family 7 member 11 (SLC7A11), arachidonic acid 15-lipoxygenase (ALOX15), and glutathione peroxidase 4 (GPx4) in cardiac tissues. ResultsA total of 121 active ingredients of SNS were obtained, and 58 potential targets of SNS in the treatment of MI by regulating ferroptosis were screened. The three protein modules with a score5 were mainly related to the inflammatory response. The GO function was mainly related to inflammation, and KEGG enrichment analysis showed that SNS mainly regulated ferroptosis- and inflammation- related signaling pathways. Molecular docking indicated that the core component had a higher binding force to the target site. Animal experiments confirmed that SNS reduced the level of p-STAT3 (P0.01), down-regulated the expression of ALOX15 mRNA (P0.01), up-regulated the level of serum GSH, and the expressions of SLC7A11 and GPx4 mRNA, reduced MDA and 4-HNE levels (P0.05, P0.01). Additionally, SNS improved the mitochondrial injury induced by cardiomyocyte ferroptosis, reduced the area of MI, alleviated inflammation and myocardial injury, lowered the levels of serum CK, CK-MB, LDH, IL-6, and the mRNA expression levels of IL-16 and IL-18 (P0.05), and improved ST segment elevation. ConclusionSNS can reduce ISO-induced STAT3 phosphorylation levels, inhibit ferroptosis in cardiomyocytes, alleviate inflammation and myocardial injury, thereby improving MI.
3.Application of mild hypothermia arch-clamping technique for DeBakey Ⅰ aortic dissection
Chengnan LI ; Bo JIA ; Yipeng GE ; Yongliang ZHONG ; Hai YU ; Yi YANG ; Zhiyu QIAO ; Haiou HU ; Yongmin LIU ; Junming ZHU
Chinese Journal of Thoracic and Cardiovascular Surgery 2025;41(3):136-142
Objective:To evaluate the safety and efficacy of mild hypothermia arch-clamping technique in the surgical treatment of DeBakey Type Ⅰ aortic dissection.Methods:From December 2019 to November 2023, a total of 97 patients with DeBakey type Ⅰ aortic dissection who underwent arch-clamping technique in Beijing Anzhen Hospital were prospectively enrolled. The patients were divided into mild hypothermia group and moderate hypothermia group according to the lowest rectal temperature during the circulatory arrest period. The perioperative data of the two groups were compared, and complex adverse outcomes consisting of 30-day death, stroke, paraplegia and CRRT were used as the primary endpoint. Multivariate logistic regression was used to determine the predictors of clinical adverse outcomes. Survival analysis was evaluated by the Kaplan- Meier method. Results:The overall incidence of complex adverse outcomes was 20.6%, 13.6% in the mild hypothermia group and 22.7% in the moderate hypothermia group( P=0.535), and the incidence of stroke was 4.6% and 6.7%( P=1.000), respectively. The cardiopulmonary bypass time and aortic-clamping time in the mild hypothermia group were significantly shortened (147.5 min vs. 163.0 min, P=0.032; 89 min vs. 99 min, P=0.042). There was no significant difference in long-term survival and reintervention between the two groups(91.9% vs. 89.3%, P=0.87; 9.1% vs. 5.3%, P=0.13). Conclusion:Mild hypothermia arch-clamping technique is a safe and effective method for the treatment of DeBakey type Ⅰ aortic dissection, with satisfactory short-term and long-term efficacy.
4.Prediction of major adverse cardiovascular events after acute type A aortic dissection combined with coronary malperfusion by machine learning-based interpretable models
Hao ZHANG ; Bo JIA ; Zuo ZHANG ; Huanyu QIAO ; Bo YANG ; Jing YANG ; Feilong HEI ; Xiaotong HOU ; Junming ZHU ; Yongmin LIU
Chinese Journal of Thoracic and Cardiovascular Surgery 2025;41(3):129-135
Objective:To explore and model risk factors in patients with major adverse cardiovascular events (MACEs) after acute type A aortic dissection (ATAAD), and to develop and validate a personalized machine learning model to assess risk factors and predict MACEs in these patients.Methods:Clinical data of patients who attended Beijing Anzhen Hospital and underwent surgical treatment for ATAAD from January 2018 to October 2022 were retrospectively analyzed. Using MACEs as the endpoint, 70% of these patients were randomly divided into the training set and the remaining 30% into the validation set. LASSO regression was applied to explore key clinical variables in the training set. The optimal predictive model was selected from nine machine learning algorithms based on area under the curve. And Shapley Additive explanations was used to elucidate the predictive model. Results:Of the 481 patients included in this study, 135 (35.6%) patients experienced an endpoint event. By combining the results of the training and validation sets, when assessing the validity of the single model with the highest predictive accuracy for the outcome, it was shown that the logistic model (0.774, 95% CI: 0.717-0.830) was the most effective in the combined effect and had a high model accuracy (0.743, 95% CI: 0.720-0.766). According to the results of the LASSO, the factors most associated with postoperative MACEs were history of cerebrovascular disease, coronary artery involvement, shock status on admission to the operating room, FDP, PLT, CPB, ascending aortic clamping, and age. Conclusion:In this study, nine machine learning models were developed to predict the occurrence of postoperative MACEs in patients with acute type A aortic dissection. The logistic model performed significantly better compared to other algorithms. Our study successfully predicted postoperative MACES and identified the factors most associated with MACEs.
5.Application of mild hypothermia arch-clamping technique for DeBakey Ⅰ aortic dissection
Chengnan LI ; Bo JIA ; Yipeng GE ; Yongliang ZHONG ; Hai YU ; Yi YANG ; Zhiyu QIAO ; Haiou HU ; Yongmin LIU ; Junming ZHU
Chinese Journal of Thoracic and Cardiovascular Surgery 2025;41(3):136-142
Objective:To evaluate the safety and efficacy of mild hypothermia arch-clamping technique in the surgical treatment of DeBakey Type Ⅰ aortic dissection.Methods:From December 2019 to November 2023, a total of 97 patients with DeBakey type Ⅰ aortic dissection who underwent arch-clamping technique in Beijing Anzhen Hospital were prospectively enrolled. The patients were divided into mild hypothermia group and moderate hypothermia group according to the lowest rectal temperature during the circulatory arrest period. The perioperative data of the two groups were compared, and complex adverse outcomes consisting of 30-day death, stroke, paraplegia and CRRT were used as the primary endpoint. Multivariate logistic regression was used to determine the predictors of clinical adverse outcomes. Survival analysis was evaluated by the Kaplan- Meier method. Results:The overall incidence of complex adverse outcomes was 20.6%, 13.6% in the mild hypothermia group and 22.7% in the moderate hypothermia group( P=0.535), and the incidence of stroke was 4.6% and 6.7%( P=1.000), respectively. The cardiopulmonary bypass time and aortic-clamping time in the mild hypothermia group were significantly shortened (147.5 min vs. 163.0 min, P=0.032; 89 min vs. 99 min, P=0.042). There was no significant difference in long-term survival and reintervention between the two groups(91.9% vs. 89.3%, P=0.87; 9.1% vs. 5.3%, P=0.13). Conclusion:Mild hypothermia arch-clamping technique is a safe and effective method for the treatment of DeBakey type Ⅰ aortic dissection, with satisfactory short-term and long-term efficacy.
6.Prediction of major adverse cardiovascular events after acute type A aortic dissection combined with coronary malperfusion by machine learning-based interpretable models
Hao ZHANG ; Bo JIA ; Zuo ZHANG ; Huanyu QIAO ; Bo YANG ; Jing YANG ; Feilong HEI ; Xiaotong HOU ; Junming ZHU ; Yongmin LIU
Chinese Journal of Thoracic and Cardiovascular Surgery 2025;41(3):129-135
Objective:To explore and model risk factors in patients with major adverse cardiovascular events (MACEs) after acute type A aortic dissection (ATAAD), and to develop and validate a personalized machine learning model to assess risk factors and predict MACEs in these patients.Methods:Clinical data of patients who attended Beijing Anzhen Hospital and underwent surgical treatment for ATAAD from January 2018 to October 2022 were retrospectively analyzed. Using MACEs as the endpoint, 70% of these patients were randomly divided into the training set and the remaining 30% into the validation set. LASSO regression was applied to explore key clinical variables in the training set. The optimal predictive model was selected from nine machine learning algorithms based on area under the curve. And Shapley Additive explanations was used to elucidate the predictive model. Results:Of the 481 patients included in this study, 135 (35.6%) patients experienced an endpoint event. By combining the results of the training and validation sets, when assessing the validity of the single model with the highest predictive accuracy for the outcome, it was shown that the logistic model (0.774, 95% CI: 0.717-0.830) was the most effective in the combined effect and had a high model accuracy (0.743, 95% CI: 0.720-0.766). According to the results of the LASSO, the factors most associated with postoperative MACEs were history of cerebrovascular disease, coronary artery involvement, shock status on admission to the operating room, FDP, PLT, CPB, ascending aortic clamping, and age. Conclusion:In this study, nine machine learning models were developed to predict the occurrence of postoperative MACEs in patients with acute type A aortic dissection. The logistic model performed significantly better compared to other algorithms. Our study successfully predicted postoperative MACES and identified the factors most associated with MACEs.
7.Current status and prospects of treatment for residual aortic dissection
Chinese Journal of Thoracic and Cardiovascular Surgery 2024;40(6):321-323
The initial repair of acute aortic dissection via open surgery and endovascular procedures is only a partial treatment. Persistent distal tears and residual dissections continue to affect the long-term prognosis of patients. An ideal treatment strategy should aim to repair the entire aortic pathology using minimally invasive, simple, safe, and effective methods. This review discusses the impact of residual dissection on patient prognosis, current therapeutic strategies, and future development trends, providing a reference for optimizing treatment strategies for residual aortic dissection.
8.Observation on early clinical results of one stage whole-course repair of acute aortic dissection
Huanyu QIAO ; Shouming LI ; Chen ZHANG ; Xiaohai MA ; Yongmin LIU
Chinese Journal of Thoracic and Cardiovascular Surgery 2024;40(6):335-338
Objective:To summarize and analyze the early clinical outcomes of aortic endovascular remodeling device (AERD) for single-stage complete repair of acute aortic dissection.Methods:A total of 19 patients with acute aortic dissection who underwent proximal aortic dissection repair combined with distal AERD implantation at the Center for Aortic Surgery of Beijing Anzhen Hospital, Capital Medical University between May 2023 and October 2023, of whom 6 had type A aortic dissection and 13 had type B aortic dissection, were retrospectively analyzed. One-month postoperative follow-up and aortic CTA were completed to compare pre- and postoperative abdominal branch outcomes and aortic wall remodeling.Results:The success rate of AERD implantation in this patient cohort was 100%, and no complications such as paraplegia or visceral ischemia were observed during the perioperative and postoperative follow-up periods. All abdominal branches were patent postoperatively, and 15 branches had preoperative " high-risk" subtype malperfusion, 14 of which improved postoperatively. All patients showed significant increase of the true lumen volume compared with the preoperative one, and 89.5% (17/19) had a postoperative true lumen/overall volume ratio of more than 70%.Conclusion:The single-stage complete repair of proximal aortic dissection repair combined with distal AERD implantation is simple, safe and effective, associated with satisfactory early outcomes.
9.Analysis of anatomical characteristics of residual aortic dissection based on CT imaging and its clinical guidance value
Shouming LI ; Huanyu QIAO ; Chen ZHANG ; Xiaohai MA ; Yongmin LIU
Chinese Journal of Thoracic and Cardiovascular Surgery 2024;40(6):345-350
Objective:This study aims to summarize the pathological anatomy characteristics of residual aortic dissection (RAD) in patients with acute aortic dissection (AAD) during the perioperative period by measuring and analyzing the preoperative and postoperative 60-day computed tomography angiography (CTA) images of the aorta, with the intention of guiding further clinical treatment.Methods:A retrospective cohort study design was adopted. A total of 224 patients hospitalized with acute aortic dissection from December 2021 to October 2022 at a single center were included according to inclusion and exclusion criteria and divided into two groups based on Stanford classification. Computed tomography angiography (CTA) images of the aorta during the perioperative period (preoperative or postoperative 60 days) were collected, and relevant indicators were measured to describe the pathological anatomy characteristics of residual aortic dissection.Results:Among the measured range, there were 4 patients (1.8%) without distal tears, with a total of 648 identified distal tears. The numbers of tears in the A, B, and C segments were 211 (32.6%), 203 (31.3%), and 234 (36.1%), respectively. The average numbers of tears in the A, B, and C segments were 0.9±1.1, 0.9±0.9, and 1.0±1.2 per person, respectively. The corresponding average tear areas were(34.9±46.7)mm 2, (29.0±30.5)mm 2, and(18.6±23.9)mm 2, respectively. The average distances from tears to the upper and lower edges of the celiac trunk were(36.8±33.2)mm and(2.3±3.8)mm, respectively; to the upper and lower edges of the superior mesenteric artery (SMA) were(2.3±4.1 )mm and(1.2±2.6) mm, respectively; to the upper and lower edges of the left renal artery were(0.1±0.6) mm and(38.5±24.4) mm, respectively; and to the upper and lower edges of the right renal artery were(0.7±2.6) mm and(8.1±17.3) mm, respectively. True lumen blood supply for the celiac trunk was observed in 151 cases (67.4%); dual luminal supply in 49 cases (21.9%); and false lumen supply in 24 cases (10.7%). True lumen blood supply for the SMA was observed in 187 cases (83.5%); dual luminal supply in 32 cases (14.3%); and false lumen supply in 5 cases (2.2%). True lumen blood supply for the left renal artery was observed in 150 cases (67.0%); dual luminal supply in 27 cases (12.1%); and false lumen supply in 47 cases (21.0%). True lumen blood supply for the right renal artery was observed in 148 cases (66.1%); dual luminal supply in 30 cases (13.4%); and false lumen supply in 46 cases (20.5%). True lumen blood supply for both renal arteries was observed in 83 cases (37.1%); dual luminal supply in 4 cases (1.8%); and false lumen supply in 1 case (0.5%). Conclusion:The results of this study suggest that the average number of distal tears per person in patients with AAD is 2.9±1.9, with only 1.8% of patients having no distal tears. The average tear areas in the A, B, and C segments are(34.9±46.7) mm 2, (29.0±30.5) mm 2, and (18.6±23.9) mm 2, respectively. 61.2% of patients have tears in the abdominal aortic branch segment, and the tears are located at the same level as the abdominal aortic branches. Among the branches of the abdominal aorta, the renal arteries are most commonly affected by dissection, while the SMA is least affected. This study elucidates the anatomical basis for the limitations of existing repair methods and provides a theoretical basis for the design of subsequent repair techniques.
10.Efficacy of stented elephant trunk procedure for right-sided aortic arch with Kommerell's diverticulum
Yongliang ZHONG ; Bing TANG ; Suwei CHEN ; Yipeng GE ; Hai' ; ou HU ; Zhiyu QIAO ; Chengnan LI ; Yongmin LIU ; Junming ZHU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(07):1020-1026
Objective To summarize our experience and the early and midterm outcomes of stented elephant trunk procedure for right-sided aortic arch (RAA) with Kommerell's diverticulum (KD). Methods From April 2013 to July 2020, patients with RAA and KD who underwent stented elephant trunk procedure at our center were collected. Surgery was performed under moderate hypothermic circulatory arrest combined with selective antegrade cerebral perfusion via median sternotomy. Results A total of 8 patients were included, including 7 males and 1 female with a mean age of 51.88±9.61 years. All patients had an aneurysmal KD and aberrant left subclavian artery. Preoperative comorbidities included acute Stanford type B aortic dissection in 1 patient, aortic arch pseudoaneurysm in 1 patient, acute type B intramural hematoma in 2 patients, and coronary artery disease in 1 patient. Concomitant procedures included reconstruction of the left subclavian artery in all patients and coronary artery bypass grafting in 1 patient. The mean time of operation, cardiopulmonary bypass, aortic cross-clamping, and selective cerebral perfusion was 6.25±1.16 h, 157.75±40.07 min, 77.75±33.10 min, and 28.50±5.55 min, respectively. No intraoperative death occurred. There was 1 in-hospital death. Follow-up was completed in all patients with a mean period of 3.58±2.08 years. No late death occurred. A persistent anastomotic leak of the proximal arch was detected in 1 patient, but reintervention was not performed because neither aortic dilatation nor symptoms of tracheal and esophageal compression were observed during the follow-up. The remaining 6 patients showed positive aortic remodeling with complete thrombosis of the aneurysmal KD, and neither aortic event nor tracheal and esophageal compression occurred. Conclusion Stented elephant trunk procedure is a safe and feasible technique for selected patients with RAA and KD, which can achieve favorable early and midterm outcomes.

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