Abstract:Atherosclerosis (As) is the basis of many cardiovascular diseases (CVD). Macrophage, smooth muscle cell and endothelial cell are the main cell involved in As lesions, and many studies have confirmed that the programmed cell death (PCD) of these cells can affect the development of As, and the regulation of the PCD of these cells may become the key to prevent and control As. In recent years, many studies have found that non-coding RNA (ncRNA) is involved in PCD by regulating related factors, such as apoptosis, autophagy, pyroptosis, necroptosis,ferroptosis and cuproptosis. This article discusses the mechanisms by which ncRNA affect As by regulating PCD and provides new ideas for As treatment.

Abstract:Aim To explore the role of C-X-C motif chemokine receptor 4 (CXCR4) in the formation of atherosclerosis (As) induced by Chlamydia pneumoniae (C.pn) infection. Methods The As model in mice of ApoE－/－, ApoE－/－＋TLR2－/－ and ApoE－/－＋Toll-like receptor 2 (TLR2)－/－＋AMD3100 induced by C.pn infection was established on the basis of high fat diet. C.pn IgG and IgM antibody levels were detected by ELISA, and C.pn specific DNA was detected by PCR. Lipid deposition and As lesion area in aorta and aortic root were observed by oil red O and HE staining. Serum levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDLC) and high density lipoprotein cholesterol (HDLC) were analyzed by colorimetry, and ELISA was used to measure the contents of serum interleukin-1β (IL-1β) and interleukin-6 (IL-6). Results The ApoE－/－ mice model of C.pn infection was established successfully. Compared with the control group, lipid deposition in aorta and aortic root of ApoE－/－ mice increased by 89.08% and 71.83%, and As lesion area increased by 34.12% after C.pn infection (all P＜0.05). Compared with the C.pn infection group, lipid deposition in aorta and aortic root reduced by 46.16% and 75.73%, and the lesion area of As decreased by 63.37% in the TLR2－/－＋C.pn infection group (all P＜0.05). Compared with the TLR2－/－＋C.pn infection group, lipid deposition in aorta and aortic root decreased by 26.19% and 56.94%, and the lesion area of As decreased by 22.24 % in the TLR2－/－＋AMD3100＋C.pn infection group (all P＜0.05). Compared with the control group, serum levels of TC, TG and LDLC increased by 0.62 times, 1.43 times and 1.34 times after C.pn infection, respectively, while serum contents of IL-1β and IL-6 increased by 4.10 times and 6.00 times, respectively (all P＜0.05). Compared with the C.pn infection group, serum levels of TC, TG and LDLC in the TLR2－/－＋C.pn infection group decreased by 56.96%, 50.41% and 66.64%, and serum contents of IL-1β and IL-6 also decreased by 66.72% and 69.54% respectively (all P＜0.05). Compared with the TLR2－/－＋C.pn infection group, serum levels of TC, TG and LDLC in the TLR2－/－＋AMD3100＋C.pn infection group decreased by 52.18%, 58.56% and 60.61%, and serum contents of IL-1β and IL-6 and reduced by 28.84% and 43.18%, respectively (all P＜0.05). Conclusion CXCR4 enhances the roles of TLR2 in increasing the serum lipid levels and the contents of inflammatory factors, and then participates in the formation of As lesions induced by C.pn infection.

Abstract:Aim To investigate the effect of edaravone dexborneol (ED) on microglial polarization in rats with brain injury caused by hydraulic shock, and explore its mechanism based on Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway. Methods 32 rats of 205 healthy male SD rats were randomly selected as sham group, the remaining 173 rats were prepared with brain injury model by hydraulic shock method, and 160 model rats were randomly divided into model group, ED (7 mg/kg) group, TAK242 (ressatovir, TLR4 inhibitor, 2 mg/kg) group, ED (7 mg/kg)＋TAK242 (2 mg/kg) group and ED (7 mg/kg)＋lipolyaccharide (LPS, TLR4 agonist, 0.4 mg/kg) group, with 32 rats in each group. After 14 days of continuous intraperitoneal injection once a day, the nerve function, brain water content and blood-brain barrier (BBB) permeability were measured by modified neurological severity score (mNSS), weightlessness method or Evans blue (EB) penetration method, the brain histopathological changes was observed by HE and Nissl staining, the levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin (IL) 1β, IL-4 and IL-10 in brain tissue were detected by ELISA, the M1 polarization phenotype (CD86/Iba-1) and M2 polarization phenotype (CD206/Iba-1) of microglia cells were detected by immunofluorescence double staining, the mRNA and protein expressions of TLR4, NF-κB p65, NOD-like receptor protein 3 (NLRP3), aquaporin 4 (AQP4) were detected by RT-PCR or Western blot. Results Compared with the model group, the mNSS score, brain water content, BBB permeability of the rats in ED group, TAK242 group, ED＋TAK242 group were significantly were decreased (P＜0.05), the pathological changes such as brain structure disorder, sparse and disordered neuronal arrangement, vacuole-like transformation, inflammatory cell infiltration, decrease in the number of Nishi bodies were significantly improved, the levels of IFN-γ, TNF-α, IL-1β in brain tissue were significantly decreased, while the levels of IL-4, IL-10 were significantly increased (P＜0.05), the mRNA and protein expressions of TLR4, NF-κB p65, NLRP3, AQP4 were significantly decreased (P＜0.05). TAK242 could significantly enhance the regulatory effects of ED on nerve function, brain water content, BBB permeability, inflammatory response, microglia polarization, TLR4/NF-κB signaling pathway related mRNA and protein expression of the rats with hydraulic shock brain injury (P＜0.05), while LPS could significantly reverse the above regulatory effects of ED on the rats with hydraulic shock brain injury (P＜0.05). Conclusion ED may promote the polarization of microglia from M1 phenotype to M2 phenotype by inhibiting TLR4/NF-κB signaling pathway, inhibit inflammatory response and BBB permeability increasing, and thus play a protective role in brain injury caused by hydraulic shock in rats.

Abstract:Aim To investigate the risk factors of restenosis after stent implantation in patients with vertebral artery stenosis and construct the prediction model of nomogram. Methods The clinical data of 272 patients with digital subtraction angiography (DSA) confirmed vertebral artery stenosis and stent implantation admitted to the First Affiliated Hospital of Xinjiang Medical University from January 2016 to June 2023 were collected and retrospectively studied. According to the time of stent implantation, 272 patients were divided into modeling group (from January 2016 to December 1,0 cases) and verification group (from January 2022 to June 3,2 cases). In the modeling group, patients were divided into in-stent restenosis (ISR) group (50 cases) and non-ISR group (170 cases) according to CT angiography (CTA) or DSA results. Based on the independent risk factors of ISR analyzed by LASSO regression and multiple Logistic regression, a nomogram prediction model was constructed. The predictive ability of the prediction model was evaluated by the area under the receiver operating characteristic curve (AUC). The clinical application value of the prediction model was evaluated by clinical decision curve. Results In the modeling group, ISR occurred in 50 of 220 patients undergoing vertebral artery stenting, and the incidence of ISR was 22.72%. LASSO regression and multivariate Logistic regression analysis suggested that high ESSEN stroke risk score(ESRS), hyperhomocysteinemia (HHcy), moderate or higher stenosis of internal carotid artery and/or contralateral vertebral artery, low density lipoprotein cholesterol (LDLC) ≥1.8 mmol/L, low postoperative peak systolic velocity (PSV) of vertebral artery and small stent diameter were risk factors for ISR. A nomogram prediction model was built based on the above six variable factors. The nomogram predicted that the AUC of ISR after vertebral artery stenting was 0.857(95%CI:0.799～0.915) in the modeling group, and the AUC of the verification group was 0.847(95%CI:0.732～0.961), which suggested that the model had a good degree of differentiation. Conclusion The prediction model established in this study can better predict the risk degree of ISR in patients with metal stent implantation of vertebral artery, which is helpful for clinicians to find high-risk patients with ISR and make timely intervention, so that patients can get greater benefits.

Abstract:Aim To investigate the correlation between systemic immune-inflammation index (SII) and intracranial and extracranial atherosclerotic stenosis. Methods A retrospective analysis was conducted on 489 patients with cerebral infarction admitted to the Department of Neurology of the Affiliated Hospital of Xuzhou Medical University, and all of them were examined by head and neck computed tomography angiography (CTA). Based on the degree of stenosis in these patients, they were classified into three groups:no stenosis group, mild stenosis group (stenosis＜50%), moderate stenosis group (stenosis≥50% and ＜70%), severe stenosis group (stenosis≥70%), and the patient's baseline data, blood lipids, blood routine, etc., were recorded and statistically analyzed. Multivariate binary Logistic regression was used to explore the independent influences on whether stenosis occurred. Multivariate Logistic regression was used to explore the independent influences on the degree of stenosis. The ROC curve was used to explore the efficacy of SII in detecting intracranial and extracranial atherosclerotic stenosis. Results Multivariate binary Logistic regression analysis found that age (OR＝1.185, P＜0.05), SII (OR＝1.482, P＜0.05), gender (OR＝2.721, P＝0.003), hypertension (OR＝3.119, P＜0.001) were independent risk factors for intracranial and extracranial atherosclerotic stenosis. Multivariate Logistic regression analysis showed that hs-CRP (OR＝1.197, P＝0.011), SII (OR＝1.379, P＜0.001) and Hcy (OR＝1.517, P＝0.013) significantly affected the degree of vascular stenosis. ROC curve analysis showed that the area under the curve (AUC) of SII was 0.747, and the best cut-off value of SII was 447.89. Spearman correlation analysis showed that SII level was significantly positively correlated with the severity of intracranial and extracranial atherosclerotic stenosis (r＝0.4,0.482, P＜0.05). Conclusion SII level is positively correlated with the degree of intracranial and extracranial atherosclerotic stenosis in patients with cerebral infarction, and has a certain predictive value for intracranial and extracranial atherosclerotic stenosis.

Abstract:Aim To investigate the clinical value of real-time three-dimensional echocardiography (RT-3DE) combined with autostrain right ventricle (RV) technology in evaluating right ventricular function in patients with coronary heart disease (CHD)involving the right coronary artery stenosis. Methods A total of 132 patients with suspected CHD were enrolled. According to the results of coronary angiography, they were divided into control group without coronary artery stenosis of 50%, CHD without involving the right coronary artery stenosis group (simple CHD group), CHD involving the right coronary artery stenosis group. The three groups of subjects were analyzed by conventional echocardiography, autostrain RV technology and RT-3DE. Results Compared with control group, at the basal levels of the right ventricular free wall-longitudinal strain (Basal RVFWSL), at the middle levels of the right ventricular free wall-longitudinal strain (Medial RVFWSL), at the apical levels of the right ventricular free wall-longitudinal strain (Apical RVFWSL), right ventricular free wall-longitudinal strain (RVFWSL), right ventricular 4 chamber longitudinal strain (RV4CSL), right ventricular ejection fraction (RVEF), right ventricular stroke volume (RVSV) and right ventricular stroke volume index (RVSVI) were decreased, while right ventricular end-systolic volume (RVESV), right ventricular end-systolic volume index (RVESVI) were increased in simple CHD group and CHD involving the right coronary artery stenosis group. The differences were statistically significant (all P＜0.05). ROC curve analysis showed that RVFWSL of two-dimensional speckle tracking imaging (2D-STI) and RVEF of RT-3DE had higher diagnostic efficiency, with a sensitivity of 90.9% and a specificity of 95.3%. Conclusions RT-3DE combined with autostrain RV technology can improve the accuracy of evaluating right ventricular dysfunction in patients with CHD involving the right coronary artery stenosis, which provides a basis for early clinical treatment and has good application value.

Abstract:Aim To investigate the effect of Shunshi three decoction of Chinese herbal medicine in patients with carotid atherosclerotic (CAS) plaque. Methods 94 patients with CAS plaque were randomly divided into two groups with 47 cases in each group. The control group was treated with one party a day, and the observation group was treated with Shunshi three decoction of Chinese herbal medicine. The course of treatment was four months. The clinical efficacy was observed in two groups, as well as the traditional Chinese medicine (TCM) syndrome scores, blood lipids (total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC)), CD40/CD40L inflammatory signaling pathway, total plaque scores, carotid intima-media thickness (IMT), plaque area, liver and kidney function (alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine (Cr)) before and after treatment, and the adverse reactions were compared between the two groups. Results The total effective rate of the observation group after four months of treatment and six months after drug withdrawal (74.47% and 78.72%) was higher than that of the control group (46.81% and 44.68%, P＜0.05). After four months of treatment, there were no significant differences in the levels of ALT, AST, BUN, and Cr in the two groups compared with before treatment and between the two groups (P＞0.05); and there was no significant difference in the incidence of adverse reactions between the observation group (14.89%) and the control group (10.64%) (P＞0.05). After six months of drug withdrawal, the TCM symptom score of the observation group was lower than that of the control group (P＜0.05); the levels of interleukin-1 (IL-1), IL-6, soluble CD40 ligand (sCD40L) were lower in the observation group than those in the control group, while the level of IL-10 was higher than that in the control group (P＜0.05). The IMT, total plaque scores, and plaque area were lower in the observation group than those in the control group after six months of drug withdrawal (P＜0.05). Conclusion Compared with the conventional method of taking one dose a day, the use of the traditional Chinese medicine homeopathic three-dose method of taking Taohong Siwu decoction, Erchen decoction, and Simiao Yong'an decoction in the morning, afternoon, and evening, respectively, has shown more significant effects in terms of immediate efficacy, stable plaque area after drug withdrawal, and IMT, without significantly increasing adverse drug reactions and hepatotoxicity.

Abstract:Aim To investigate the predictive value of right ventricular features on three-dimensional echocardiography for heart failure (HF) after percutaneous coronary intervention (PCI) in patients with inferior wall myocardial infarction (INFMI). Methods 261 patients with INFMI from October 2018 to October 2021 were included. Patients were divided into heart failure group (n＝42) and no heart failure group (n＝219) based on one-year follow-up records after PCI. Clinical data and echocardiographic characteristics of the two groups were compared. LASSO-Logistic regression was used to screen the independent influencing factors for the occurrence of postoperative HF. A column-line diagram model was constructed and validated. Results After screening, the LASSO model at the optimal λ value incorporated free wall mid-segment and global longitudinal strain, inflow tract end-diastolic volume and ejection fraction, and body end-diastolic volume and ejection fraction in INFMI patients. Higher predictive value for HF was found in lower postoperative body ejection fraction (cutoff value 43.27%), lower inflow tract ejection fraction (cutoff value 51.49%), and higher global longitudinal strain (cutoff value －13.52%). Ultrasound indices combined with age, Killip classification, and N-terminal pro-brain natriuretic peptide (NT-proBNP) were used to construct a columnar graphical model. The model was highly discriminative, with a consistency index of 0.981 (95%CI:0.872~0.997). The model predicted values fitted well with the actual values. Conclusion Right ventricular global longitudinal strain, inflow tract ejection fraction, body ejection fraction, age, Killip classification, and NT-proBNP in patients with INFMI have a high predictive value for the risk of HF one year after PCI. The jointly constructed prediction model can be used as a clinical decision-making tool.

Abstract:Ferroptosis is defined as an iron-dependent regulated form of cell death driven by lipid peroxidation, which is not only regulated by a variety of cellular metabolic pathways, but it is also related to neurodegenerative diseases, tumors, cardiovascular diseases and so on. Recent studies have found that ferroptosis plays a crucial part in the process of atherosclerosis. This article reviews the role and molecular mechanism of ferroptosis in the pathological processes of atherosclerosis, such as vascular endothelial cell dysfunction, macrophage polarization, foam cell formation, vascular smooth muscle cell proliferation and migration, and summarizes the ferroptosis inhibitors and related targets that may have therapeutic effects on atherosclerosis. The aim is to provide a new therapeutic direction for atherosclerosis from the perspective of ferroptosis.

Abstract:Circular RNA (circRNA), an emerging non-coding RNA, is closely related to the processes of lipid deposition, inflammatory response, apoptosis, proliferation and repair in atherosclerosis (As), and affects the development of As. Traditional Chinese medicine (TCM) has an important academic value in the prevention and treatment of As, and its regulatory mechanism has not been comprehensively summarized. This paper reviewed the association of circRNA with lipid deposition, inflammatory response and macrophage in As, and summarized the research progress of the correlation between circRNA and atherosclerosis and the regulation of traditional Chinese medicine.

Abstract:Macrophages play multiple roles in atherosclerosis. The progression of atherosclerosis is associated with morphological and functional changes in the lymphatic vessels of the diseased arteries, but the mechanism is not fully understood. This paper mainly reviews the origin and classification, the markers and the function of macrophage in atherosclerosis, the origin, the structure function and the markers of lymphatic vessels in atherosclerosis, the changes of arterial wall lymphangiogenesis in different stages of atherosclerotic lesions, the functional role of lymphangiogenesis in atherosclerosis, the lymphatic migration of macrophages and its mechanism involved in lymphangiogenesis, in order to provide a basis for the mechanism research and clinical treatment of atherosclerosis.

Abstract:Periodontitis, a common disease, is considered to be closely associated with many systemic diseases, especially cardiovascular disease. Atherosclerosis is the basic pathological change of cardiovascular disease, and recent evidence has indicated that periodontitis promotes the onset and progression of atherosclerosis. This article reviews the roles of periodontitis in accelerating atherosclerosis and highlights the involved mechanisms to provide new strategies for diagnosis and treatment of atherosclerosis.