Abstract:Atherosclerosis (As) poses a serious threat to human health, and modern medicine still faces many limitations in its treatment of this disease. However, components and compounds of traditional Chinese medicine (TCM) have unique advantages in anti-atherosclerosis by regulating macrophage autophagy, they exert anti-inflammatory, anti-oxidation, lipid metabolism-regulating and plaque-stabilizing effects. This paper reviews the application of TCM in regulating macrophage autophagy to prevent and treat atherosclerosis, and provides new insights into the application of TCM components and compounds in the treatment of As.

Abstract:Aim To evaluate the tyrosine nitration modification of specific proteins in vascular endothelial cells and its impact on mitochondria-mediated apoptosis. Methods Human umbilical vein endothelial cells were cultured in vitro and divided into three groups:control group (treatment with dimethyl sulfoxide), 3-morphansulam (SIN-1) group, and SIN-1＋Fe(III) 5,0,5,0-(tetraphenyl)porphyrin (FeTPP) group. After 24 h, the levels of hexokinase 1 (HK1) nitration modification, mitochondrial membrane potential, reactive oxygen species (ROS) production, and endothelial cell proliferation and apoptosis were assessed. A human umbilical vein endothelial cell line knockout of HK1 was constructed using gene editing technology, and its proliferation and apoptosis levels were detected. Results After treatment of human umbilical vein endothelial cells with peroxynitrite generator SIN-1, the level of HK1 protein nitration modification significantly increased (P＜0.01), reactive oxygen species production significantly increased, mitochondrial membrane potential significantly decreased, endothelial cell proliferation ability significantly decreased, and endothelial cell apoptosis level significantly increased (all P＜0.01). Peroxynitrite decomposition catalyst FeTPP could reverse the above effect (P＜0.01). In addition, HK1 gene knockout also exhibited similar antioxidant effects, with a significant decrease in endothelial cell proliferation ability and a significant increase in apoptosis levels (P＜0.01). Conclusion Peroxynitrite can induce an increase in the level of nitration modification of HK1 in vascular endothelial cells, which may be achieved by promoting the production of mitochondrial reactive oxygen species, thereby accelerating the process of endothelial cell apoptosis.

Abstract:Aim Systematic evolution of ligands by exponential enrichment (SELEX) techniquewas employed to screen and identify nucleic acid aptamers that specifically bind to mouse atherosclerotic pathological tissues, aiming to provide a research foundation for the development of molecular targets and diagnostic reagents for early atherosclerosis. Methods A single-stranded DNA (ssDNA) library with a capacity of 10¹⁵～10¹⁶ was constructed, which was then subjected to binding-elution (negative selection) with normal mouse vascular tissue slices. The eluted library was subsequently bound to atherosclerotic tissue slices for binding-elution (positive selection). PCR was used to amplify the positive and negative screening products, and agarose gel electrophoresis was used to verify the amplified products. The ssDNA library after multiple rounds of selection was sequenced using T-A cloning and sequencing to obtain the primary structure of the nucleic acid aptamers, and the secondary structure was predicted using the Mfold online software. The selected nucleic acid aptamers were labeled with a FAM fluorescent group at the 5′- end and were bound to both positive and negative selection tissue slices, with fluorescence intensity observed under a fluorescence microscope. Image Pro Plus 6.0 was used to calculate the relative average fluorescence intensity to evaluate the binding specificity of nucleic acid aptamers. Results After 8 rounds of selection, agarose gel electrophoresis imaging showed PCR amplification products in the positive selection lanes, while no PCR amplification products were observed in the negative selection lanes, indicating the successful acquisition of a nucleic acid aptamer library that specifically binds to atherosclerotic tissues. Five nucleic acid aptamers were identified by T-A cloning and sequencing, and their predicted secondary structures all had stem-loop structures. Immunofluorescence staining verified that five nucleic acid aptamers had different degrees of binding with As blood vessels, and the quantitative results of the relative average fluorescence intensity showed that nucleic acid aptamer No.11 had the highest relative average fluorescence intensity value, which can be used as a candidate nucleic acid aptamer for subsequent research. Conclusion Specific nucleic acid aptamers that bind to atherosclerotic vesselswere successfully obtained, providing a research foundation for further screening of early molecular targets of Asand developing in vivo early diagnostic reagents. [KEY WORDS]atherosclerosis; systematic evolution of ligands by exponential enrichment; nucleic acid aptamers

Abstract:Aim To explore the risk factors for the progressive worsening of moderate coronary stenosis and construct a nomogram model for predicting the progression of moderate coronary stenosis based on coronary CT-fractional flow reserve (FFR). Methods 293 patients with moderate coronary stenosis admitted to the hospital from April 2020 to April 2023 were selected as the research subjects. Coronary CT angiography (CCTA) was performed on the selected patients, and CT-FFR software was used to analyze the CCTA images and obtain the FFR values. According to the progressive worsening of moderate coronary stenosis, the patients were divided into two groups:the progression group and the stable group, and the data of gender, age, hyperlipidemia, history of cerebral infarction, multivessel disease, obesity, diabetes, malnutrition, lack of physical activity, hypertension, drinking, smoking and place of residence of the patients in the two groups were collected. The ten-fold cross-validation in LASSO analysis was used to screen for predictive factors of progressive worsening of moderate coronary stenosis, Logistic regression was used to screen for risk factors of progressive worsening of moderate coronary stenosis,Rü (4.2.3) was used to establish a nomogram model of progressive worsening of moderate coronary stenosis, and this nomogram model was validated. Results Among 293 patients with moderate coronary stenosis, there were 61 cases of progressive worsening, and the incidence of progressive worsening of moderate coronary stenosis was 20.82% (61/293). The sex, age, hyperlipidemia, history of cerebral infarction, multivessel disease, malnutrition, hypertension, alcohol consumption and place of residence of the progression group and the stable group had no statistical significance (P＞0.05), while the proportion of obesity, diabetes, lack of physical activity and smoking in the progression group was significantly higher than those in the stable group, and the FFR was significantly lower than that in the stable group (P＜0.05). LASSO analysis showed that the history of cerebral infarction, obesity, diabetes, lack of physical activity, smoking and FFR were predictive factors with non-zero coefficients. After ten-fold cross-validation, six variables including the history of cerebral infarction, obesity, diabetes, lack of physical activity, smoking and FFR were retained into the model. Logistic regression analysis showed that obesity (OR＝2.1,5%CI:1.151～5.053), diabetes (OR＝3.1,5%CI:1.671～6.923), lack of physical activity (OR＝2.8,5%CI:1.427～5.564), smoking (OR＝3.7,5%CI:1.526～8.387) were all risk factors for progressive worsening of moderate coronary stenosis, and FFR (OR＝0.1,5%CI:0.000～0.036) was the antagonistic factor for progressive worsening of moderate coronary stenosis (P＜0.05). A dynamic nomogram model for the progressive worsening of moderate coronary stenosis was established based on risk factors, and the area under the ROC curve of the nomogram model was 0.777 (95%CI:0.711～0.842); The predicted values of the calibration curve are basically consistent with the actual values; When the decision curve showed a threshold probability of 2% to 64%, the nomogram model had a good benefit value for predicting the progressive worsening of moderate coronary stenosis. Conclusion The nomogram model constructed in this study has high accuracy in predicting the progression of moderate coronary stenosis and good clinical practicality.

Abstract:Aim To investigate the association of triglyceride-glucose (TyG) index with microvascular obstruction(MVO) after percutaneous coronary intervention(PCI) in patients with ST-segment elevated myocardial infarction(STEMI). Methods Individual patient-data were pooled from 310 patients with STEMI underwent emergency PCI in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from June 2018 to June 2021 for a prospective analysis. A week following the operation, cardiac magnetic resonance imaging was used to evaluate the MVO region and the patients were divided into two groups based on whether MVO occured after PCI:the MVO group (n＝183) and the non-MVO group (n＝127). The clinical data of the two groups were compared, and the linear relationship between TyG index and MVO was described using restricted cubic splines(RCS). Univariate and multivariate Logistic regression analysis were used to correct for confounding factors and identify independent risk factors for MVO occurrence. Results After adjustment for confounding factors, TyG index was an independent risk factor for MVO after emergency PCI in STEMI patients, and every 1-unit increased in TyG index, the risk of MVO increased by 1.24 times (OR＝2.4,5%CI:1.07～4.71, P＝0.033). The RCS curve analysis results showed that there was a linear relationship between the TyG index and the occurrence of MVO after emergency PCI (non-linear correlation test P＝0.47).When the TyG index was greater than 9.5, the risk of MVO after emergency PCI significantly increased. ConclusionAn increased TyG index is postively associated with the incidence of MVO in STEMI patients who have undergone PCI, and has clinical significantce for early prevention and risk stratification of MVO in STEMI patients.

Abstract:Aim To investigate the effect of interdialytic serum potassium levels on thrombosis of autologous arteriovenous fistula (AVF) in patients with chronic kidney disease (CKD) on maintenance haemodialysis (MHD). Methods 159 CKD patients who underwent MHD in our hospital from October 2021 to October 2022 were retrospectively analyzed. They were divided into hyperkalemia group (n＝53), normal serum potassium group (n＝61) and hypokalemia group (n＝45) according to the mean serum potassium level of patients with different dialysis intervals, and all patients were followed up for 1 year or followed up until AVF thrombosis. General datas were collected and the following indicators were detected at the time of patient enrolment, including biochemical indicators, inflammatory factors, ultrasound indicators of AVF and oxidative stress factors levels. Multifactorial Logistic regression equations were used to analyze the effects of clinical indicators on AVF thrombosis in MHD patients, receiver operating characteristic (ROC) curve was used to assess the predictive efficacy of clinical indicators on AVF thrombosis; And interval likelihood ratio was used to stratify interdialytic serum potassium levels, and further observe whether the relationship was stability between AVF thrombosis and interdialytic serum potassium levels in MHD patients. Results Compared with the normal serum potassium group, the levels of C-reactive protein (CRP), intact parathyroid hormone (iPTH), procalcitonin (PCT), triglyceride (TG), malondialdehyde (MDA), myeloperoxidase (MPO), brachial artery resistance index (RI), brachial artery pulsatility index (PI) and radial artery PI were significantly elevated in hyperkalemia group and hypokalemia group, while the levels of albumin (Alb), total cholesterol (TC), superoxide dismutase (SOD) and fistula blood flow were significantly reduced (P＜0.05).Systolic blood pressure, diastolic blood pressure, fistula blood flow, Alb and SOD levels were significantly lower in patients with AVF thrombosis than those in patients with AVF unthrombosis (P＜0.05); Interdialytic mean serum potassium level, CRP, iPTH, PCT, brachial artery RI, brachial artery PI, radial artery PI, radial artery RI, MDA and MPO levels were significantly higher in patients with AVF thrombosis (P＜0.05). The ROC curve was used to analyse the model established by the multifactorial Logistic regression equation, and it was found that model 1 and model 2 had good predictive efficacy, and model 2 had the best predictive efficacy. The results of the interval likelihood ratio showed that:when the patient's interdialytic serum potassium level was 3.5～4.5 mmol/L, the possibility of the patient's AVF thrombosis was the lowest, and when the patient's interdialytic serum potassium level was ＞5.5 mmol/L or ＜3.5 mmol/L, the possibility of the patient's AVF thrombosis was higher, and when the patient's serum potassium level was ＞5.5 mmol/L, the probability of AVF thrombosis was the highest in patients, which was 3.925 times higher than that of patients without AVF thrombosis. Conclusion Abnormal interdialytic serum potassium levels may induce AVF thrombosis in CKD patients. Serum potassium levels can be monitored during MHD treatment to enable timely intervention and improve clinical treatment outcomes for patients.

Abstract:Aim Based on coronary CT-fractional flow reserve (CT-FFR) combined with machine learning methods, a nomogram prediction model for coronary in-stent restenosis (ISR) was developed to assess the risk of ISR. Methods Retrospective analysis was performed on patients who underwent re-examination after PCI at our hospital from January 2022 to January 2025. According to the exclusion criteria, a total of 210 patients were enrolled, including 100 cases of ISR and 110 cases of non-ISR. The dataset was randomly divided into training and test sets at a 7∶3 ratio. After univariate analysis to screen potential predictors, LASSO regression was applied to identify feature variables with non-zero coefficients. Subsequently, three machine learning (ML) algorithms including random forest (RF), support vector machine (SVM), and extreme gradient boosting (XGB) were used to rank the importance of the significant factors. The intersection of the top 10 variables from each algorithm was used as input for bidirectional stepwise multivariate Logistic regression. An ISR risk score was then constructed and visualized using a nomogram. Results A total of 14 predictive factors were identified through LASSO regression, including diastolic blood pressure, C-reactive protein, triglycerides (TG), N-terminal pro-brain natriuretic peptide (NT-proBNP), low density lipoprotein cholesterol (LDLC), minimum stent diameter＜3 mm, systolic blood pressure, ΔCT-FFR, CT-FFR, interleukin-6 (IL-6), body mass index, glycosylated hemoglobin (HbA1c), history of hypertension, and high density lipoprotein cholesterol (HDLC). Following stepwise screening using three ML algorithms and Logistic regression, six independent risk factors for ISR were identified:elevated ΔCT-FFR, IL-6, NT-proBNP, TG and CT-FFR values, and minimum stent diameter＜3 mm. The area under the curve for the training set and test set were 0.995 (95%CI:0.989～1.000) and 0.965 (95%CI:0.927～1.000), respectively.Decision curve analysis demonstrated high net benefit across threshold probabilities of 0～1.00 in the training set and 0～0.92 in the test set. The nomogram integrating these six predictors exhibited high accuracy and clinical utility. Conclusion The ISR nomogram prediction model based on LASSO-ML combined with CT-FFR technology has high accuracy and clinical utility for ISR.

Abstract:Angiogenesis is a critical process in the treatment of cardiac ischemic injury, and numerous research findings indicate that macrophages play a vital role in angiogenesis. This review summarizes how macrophages regulate angiogenesis through the secretion of key factors and the interactions with other cells. M1 macrophages promote new blood vessel formation in the early stages by secreting pro-angiogenic factors, while M2 macrophages are involved in vascular remodeling and maintaining vessel homeostasis. This review also discusses several new therapeutic strategies for promoting angiogenesis, including direct injection of macrophages, modulation of macrophage phenotype and function, and the use of macrophage-derived exosomes. Numerous studies have shown that macrophages have multiple functions in angiogenesis, and targeting macrophages provides new therapeutic targets and directions for promoting angiogenesis and treating ischemic diseases.

Abstract:Cardiac mechanical complications are important determinants of prognosis in patients with myocardial infarction. Early reperfusion therapy after myocardial infarction can significantly reduce the incidence of mechanical complications, however, the mortality rate from mechanical complications does not decrease at the same time. Early diagnosis and treatment are key to improving the prognosis of mechanical complications. Mechanical complications most commonly occur within one week of myocardial infarction, and echocardiography is usually preferred to determine the type, location, and hemodynamic status of mechanical complications. Surgery is the decisive treatment, but the optimal timing is difficult to determine. Percutaneous treatment is emerging as an alternative treatment option for patients with high surgical risk, but there are still shortcomings in clinical practice. There are still many unresolved issues regarding strategies for selecting surgical and percutaneous treatment options for mechanical complications. This article summarizes the key clinical evidence for early diagnosis of mechanical complications and new strategies for the management of mechanical complications, and presents relevant statistical data on mechanical complications in our center to provide insights for clinical diagnosis and treatment.

Abstract:Acute myocardial infarction is caused by continuous ischemia and hypoxia of myocardial cells, leading to myocardial cell necrosis. Reperfusion therapy is the standard strategy for reducing infarct size and improving the prognosis of myocardial infarction. However, myocardial injury caused by reperfusion therapy is accompanied by various pathophysiological processes, such as oxidative stress, inflammatory response, myocardial fibrosis, extracellular matrix remodeling, etc. Transcription factor EB (TFEB) is a central regulatory factor in the autophagy-lysosome signaling pathway, involved in signaling pathways such as stress response, myocardial energy metabolism, autophagy, and lysosomal biogenesis. It is closely related to the repair of myocardial injury after myocardial infarction. This review aims to elucidate the mechanism of TFEB in myocardial ischemic injury.

Abstract:Trimethylamine N-oxide (TMAO) is a small-molecule organic compound. Clinical studies over the past decade have shown that elevated blood levels of TMAO are positively correlated with an increased risk of cardiovascular diseases (CVD). Vascular remodeling (VR) is a critical pathophysiological process in the progression of CVD and is widely involved in the onset and development of conditions such as hypertension and atherosclerosis. Current research indicates that TMAO participates in regulating the process of VR through various mechanisms, including promoting inflammatory responses, enhancing oxidative stress, and inducing vascular endothelial dysfunction. Present interventional strategies targeting TMAO primarily focus on microbial modulation. This review summarizes the sources and metabolic pathways of TMAO, outlines its potential pathogenic mechanisms in VR, and explores the role of TMAO in VR as well as its potential value as a therapeutic target, aiming to provide a theoretical reference for related medical research.