Abstract:Stress refers to the adaptive changes and reconstruction of the homeostasis of the body in order to meet the corresponding needs when the body feels the strong stimulation of various factors. Oxidative stress is a stress response involving reactive oxygen species (ROS) as the main effector. Through oxidation, it participates in the adaptation and repair response of tissues and cells. ROS can be used as the second messenger of cell signal transduction in this process. Free radicals involved in oxidative stress include ROS and reactive nitrogen species (RNS). The stress response involving RNS can also be called nitrative stress, which is specifically manifested as increased expression of nitric oxide synthase (NOS), and increased expression of nitric oxide (NO), which ultimately leads to activity nitrogen levels increase, and the increase in reactive nitrogen can nitrate proteins. Stress is manifested as the adaptive response of cells and the repair of tissues. Fibrotic repair is a kind of incomplete repair of tissues in the late stage of stress response. It is the main repair method of tissues containing permanent cells. It is also the adaptive response of tissues to external stimuli in the late stage of inflammatory response, which is manifested as fibrosis of tissues or organs. This review summarized the recent progress on the relationship between protein nitration and fibrosis.

Abstract:Pyroptosis is a novel lytic, pro-inflammatory form of death triggered by some inflammasomes, which induce the activation of Caspases, leading to the cleavage and polymerization of Gasdermin D (GSDMD), the release of certain pro-inflammatory cytokines like IL-1β and IL-18 and cell lysis. Pyroptosis has been reported to be closely associated to some diseases like viral disease, metabolic disease and neurogenic disease. Recent reports showed that pyroptosis participates in the occurrence and development of atherosclerotic plaque, regulated by some non-coding RNAs and other molecules. This paper provided an overview of morphological and molecular characteristics of pyroptosis. It also focused on roles of NOD-like receptor protein 3(NLRP3)-mediated pyroptosis in atherosclerosis as well as the underlying mechanism to explore potential diagnostic markers in atherosclerosis contributing to the prevention and treatment in atherosclerosis.

Abstract:Aim To explore the expression of proprotein convertase subtilisin kexin 9 (PCSK9) in polycystic ovary syndrome (PCOS) ovarian granulosa cells, and the relationship between PCSK9 expression and the lipid status of PCOS ovarian tissue and testosterone-treated KGN cells. Methods A rat model of PCOS was constructed by letrozole combined with high-fat diet. Oil red O staining was used to observe the lipid distribution in the ovarian tissue of PCOS rats. Transcriptome data from PCOS ovarian tissue and normal ovarian tissue was analyzed by bioinformatics, and the differentially expressed genes involved in lipid metabolism pathway were screened. Western blot and immunohistochemical techniques were used to detect the protein expression of PCSK9 in PCOS rat tissues. Immunofluorescence, qRT-PCR and Western blot techniques were used to detect the expression differences of PCSK9 and low density lipoprotein receptor (LDLR) in KGN cells treated with different concentrations of testosterone. Immunofluorescence microscope was used to observe the ability of KGN cells uptake Dil-LDL. Results The results of Oil Red O staining showed that the distribution of lipid droplets in granular cells of PCOS ovarian tissue was significantly less than that of normal ovarian tissue. The results of bioinformatics analysis showed that the up-regulated expression of PCSK9 in the ovarian tissue of PCOS rats was mainly involved in the cholesterol metabolism pathway. The results of immunohistochemistry and Western blot showed that the PCSK9 protein was mainly localized in granulosa cells and its expression increased in the granulosa cells of PCOS rats.The results of immunofluorescence, qRT-PCR and Western blot showed that PCSK9 expression was up-regulated with the increased concentration of testosterone, and LDLR expression was decreased with the increased concentration of testosterone in KGN cells. Testosterone (100 nmol/L) could reduce the uptake of Dil-LDL by KGN cells. Conclusion PCSK9 was highly expressed in PCOS ovarian granulosa cells, which could reduce the expression of LDLR protein and lead to insufficient lipid uptake of granulosa cells.

Abstract:Aim To explore the effect and possible mechanism of tirofiban on oxidized low density lipoprotein (ox-LDL) -induced injury of umbilical vein endothelial cells (EA.hy926). Methods Low, medium and high doses of tirofiban were applied to ox-LDL-induced EA.hy926, and cell viability and apoptosis were detected by cell counting kit (CCK-8) and flow cytometry, respectively. The expression of miR-22 was detected by real-time fluorescent quantitative PCR (qRT-PCR). Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in cell culture supernatant. miR-22 mimics were transfected into EA.hy926 to up-regulate miR-22 expression, and the effect of up-regulating miR-22 on ox-LDL-induced EA.hy926 cell injury was detected by the above method. Results After tirofiban acted on ox-LDL-induced EA.hy926 cells, the cell survival rate was significantly increased, the apoptosis rate was significantly reduced, and the content of TNF-α and IL-6 in the cell culture supernatant was significantly reduced, the expression of miR-22 was significantly increased (P＜0.05). After up-regulating the expression of miR-22, the content of TNF-α and IL-6 in the culture supernatant of EA.hy926 cells induced by ox-LDL was significantly reduced, the cell survival rate was significantly increased, and the apoptosis rate was significantly reduced (P＜0.05). Conclusion Tirofiban could alleviate ox-LDL-induced apoptosis and inflammation of umbilical vein endothelial cells, and its mechanism may be related to the up-regulation of miR-22 expression.

Abstract:Aim Atherosclerosis is a chronic inflammatory disease, but the regression of plaques suggests the possibility of reversal of atherosclerotic disease. Thus, the establishment of a model of atherosclerosis regression in mice is of great significance for elucidating the mechanism of plaque regression. Methods In ApoE－/－ mice, three types of carotid ligation were performed to induce different types of blood flow. To establish the regression model, partial carotid ligation with a slipknot was firstly used to induce disturbed flow. After feeding on a high-fat diet for 2 weeks, the slipknot was removed, and followed by a chow diet for two weeks. The ultrasonic testing was performed to monitor the blood flow in real time caused afterligation or plaque formation; Sudan Ⅳ staining was used to assess atherosclerotic lesions; immunofluorescence staining with anti MOMA2 was applied to examine monocyte-macrophage infiltration. Results Three types of ligation induced different types of blood flow. The disturbed flow induced the largest atherosclerotic plaque area in ApoE－/－ mice. After restore of blood flow combined with chow diet, atherosclerotic plaques can be significantly reduced and reversed, and the macrophage infiltration also significantly decreased. Conclusion A novel atherosclerosis regression model in mice based on carotid ligation surgery was successfully constructed, which will help to understand the underlying mechanism of atherosclerosis regression.

Abstract:Aim To explore the regularity and difference of cardiovascular aging of Han nationality in Urumqi and Yili. Methods A total of 474 Han residents with self-rated health were selected from Urumqi and Yili, including 314 in Urumqi and 160 in Yili. The rules and differences of cardiovascular aging of Han nationality in Urumqi and Yili were compared by means of on-the-spot investigation, laboratory detection and cardiac color ultrasound examination. Results Among the cardiovascular aging related indexes of Han nationality in Urumqi and Yili, systolic blood pressure (SBP), pulse pressure (PP), pulse pressure index (PPI), blood urea nitrogen (BUN), serum creatinine (SCr), cystatin C (CysC), ascending aorta diameter (AAD), left atrial longitudinal diameter (LAD), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), right atrial diameter (RAD), right ventricular diameter (RVD) and pulmonary arterial diameter (PAD) increased with age. However, the indexes of plasma albumin (ALB) and left ventricular ejection fraction (LVEF) decreased with age, the indexes that can be used as markers of cardiovascular aging were SBP, PP, BUN, CysC, ALB, LAD, LVEDD, LVESD, RVD, LVEF. Comparison between different regions in the same age group:the progression of cardiovascular aging increased with age in the 30～44 years old group and the 45～59 years old group of the Han nationality in the two regions, and Urumqi progressed faster than Yili; The cardiovascular aging process of Han nationality was faster in 60～74 years old group than that of the former two age groups, and the progress in Yili was faster than that in Urumqi. In the group of ≥75 years old, the progression of cardiovascular aging in Han nationality was faster in Urumqi than in Yili. Conclusion With the increase of age, the cardiovascular aging process of healthy Han residents is not constant in Urumqi and Yili, among the four age groups, the cardiovascular aging process of Han nationality is the fastest in 60～74 years old group, and 60 years old may be the threshold inflection point of accelerated cardiovascular aging.

Abstract:Aim Rotational atherectomy (RA) is routinely used to treat calcified lesions during percutaneous coronary intervention (PCI), however, PCI related myocardial infarction (PMI) is found in some patients. This study aimed to explore the predictive factors for PMI in patients undergoing RA. Methods 198 patients enrolled in the present study were divided into two groups according to the occurrence of PMI after RA. All the patients received RA prior to drug-eluting stent implantation in severely calcified lesions. The differences of demographic characteristics, hematological profiles, echocardiography parameters and interventional characteristics were compared between the two groups. Predictors for PMI after RA were evaluated using univariable and multivariate Logistic regression analysis. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the independent factors. Results Syntax scores, diabetes, family history, low density lipoprotein cholesterol and slow flow were independently associated with PMI in patients undergoing RA. Combined use of these variables provided incremental predictive value for PMI after RA, and the area under the curve was 0.832 with 0.731 sensitivity and 0.823 specificity. Conclusion Syntax scores was an independent predictor for PMI after drug-eluting stent implantation following RA. In addition, combination of diabetes, family history, low density lipoprotein cholesterol and slow flow provided additional predictive value for PMI after RA than Syntax scores alone.

Abstract:Aim To evaluate left ventricular function in patients with non-ischemic cardiomyopathy (NICM) and ischemic cardiomyopathy (ICM) by two-dimensional speckle tracking echocardiography (2D-STE). Methods From September 2014 to February 7,4 patients with enlarged hearts and reduced left ventricular systolic function admitted to the Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were selected. According to the results of coronary angiography, the patients were divided into NICM group (n＝43) and ICM group (n＝41). Routine echocardiography and 2D-STE were performed to analyze left ventricular function in patients with NICM and ICM. Results The left ventricular ejection fraction (LVEF) in NICM group was significantly lower than that in ICM group (P＜0.05), but there was no significant difference in left ventricular end-diastolic diameter, interventricular septum thickness and left ventricular posterior wall thickness between the two groups. 2D-STE results showed that there was no significant difference in global longitudinal strain value between NICM group and ICM group. In NICM group, regional longitudinal strain value (RLS) in apical segment increased (P＜0.05), while RLS in basal segment decreased (P＜0.01). The results of receiver operating characteristic curve showed that the basal RLS/(middle RLS＋apical RLS) ratio had the highest value in distinguishing NICM from ICM, and the area under the curve was 0.792, the cut-off value was 0.47, the sensitivity was 63.4%, the specificity was 88.4%. Conclusions Patients with NICM and ICM have different characteristics of two-dimensional strain ultrasound. 2D-STE strain analysis is helpful in the differential diagnosis of NICM and ICM.

Abstract:Aim To investigate the value of serum CD147 level in evaluating the prognosis of non-infarction related artery (non-IRA) after percutaneous coronary intervention (PCI). Methods 103 patients with ST-segment elevation myocardial infarction (STEMI) complicated with multi-vessel disease admitted to our hospital from March 2017 to March 2019 were selected. All patients were treated with non-IRA PCI 3~7 days after PCI successfully opened IRA. According to whether major adverse cardiovascular event (MACE) occurred 6 months after operation, the patients were divided into two groups:non-MACE group (n＝75) and MACE group (n＝28). According to Killip cardiac function classification standard, the patients were graded. Echocardiography and left ventricular ejection fraction (LVEF) were recorded. Coronary angiography was performed by Judkins method and the stenosis was recorded. The differences of general information and serum biochemical indexes were compared between the two groups. ROC curve was drawn to evaluate the diagnostic value of serum CD147 level for MACE after multi-vessel PCI in STEMI patients. COX regression model was used to analyze the risk factors of MACE after multi-vessel PCI in STEMI patients. Results Compared with non-MACE group, the proportion of hyperlipidemia, Killip Ⅱ~Ⅲ ratio, low density lipoprotein cholesterol and CD147 levels were higher in MACE group (P＜0.05), and LVEF was lower (P＜0.05). ROC results showed that the area under curve of serum CD147 in diagnosing MACE after multi-vessel PCI in STEMI patients was 0.834, the cut-off value was 625.58 ng/L, the corresponding sensitivity and specificity were 78.60% and 81.30% respectively, and the Youden index was 0.599. COX regression model showed that Killip Ⅱ~Ⅲ, LVEF＜45% and high level CD147 were independent risk factors for MACE after multi-vessel PCI in STEMI patients (P＜0.05). Conclusions CD147 is closely related to the prognosis of STEMI patients undergoing multi-vessel PCI. It has a certain diagnostic value for MACE after PCI in STEMI patients, and can provide a reference for the prognosis evaluation of STEMI patients undergoing multi-vessel PCI.

Abstract:Aim To investigate the relationship between plasma peroxiredoxin 5 (Prx5) level and prognosis in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods 148 ACS patients who received treatment from May 2016 to August 2017 were selected as the research objects, and the average follow-up time was 21.97 (8～24) months. Patients with ACS were divided into high Prx5 group (≥44.12 μg/L, n＝78) and low Prx5 group (＜44.12 μg/L, n＝70) according to the best cutoff point for evaluating the prognosis of ACS patients by Prx5. The plasma Prx5 level in ACS patients was detected by enzyme-linked immunosorbent assay, and its relationship with the prognosis of ACS patients after PCI was analyzed. Results Major adverse cardiovascular event (MACE) occurred in 32 (21.62%) patients with ACS. The area under the receiver operating characteristic curve, sensitivity, and specificity of Prx5 in evaluating the prognosis of patients with ACS were 0.3,3.75%, and 62.93%, respectively. The incidence of MACE in the high Prx5 group was lower than that in the low Prx5 group (P＜0.001). The average survival time of the high Prx5 group was 23.69 months (95%CI:23.34～24.04), which was higher than 20.06 months (95%CI:18.84～21.28) in the low Prx5 group (P＜0.001). COX univariate and multivariate analysis results showed age (HR＝1.1,5%CI:1.013～1.070, P＝0.005), family history of ACS (HR＝2.9,5%CI:1.022～5.677, P＝0.046) and history of chronic obstructive pulmonary disease (HR＝6.2,5%CI:1.953～19.700, P＝0.002) were independent risk factors for the prognosis of ACS patients, while Prx5 (HR＝0.1,5%CI:0.823～0.921, P＜0.001) was an independent protective factor for the prognosis of ACS patients. Conclusion Plasma Prx5 level is closely related to the prognosis of ACS patients after PCI, and the detection of Prx5 level is helpful to understand the prognosis.

Abstract:Aim To investigate the changes of lncRNA-ZFAS1/Caspase-3 axis in patients with ST-segment elevation myocardial infarction(STEMI) and its relationship with prognosis of emergency percutaneous coronary intervention(PCI). Methods STEMI patients who received emergency PCI were selected as STEMI group, and the healthy volunteers during the same period were selected as control group. The expression level of lncRNA-ZFAS1 in peripheral blood and the content of Caspase-3 in serum were detected. The occurrence of major adverse cardiovascular events(MACE) of STEMI patients within 6 months after PCI was followed up. Kaplan-Meier curve was used to analyze the difference of MACE in patients with different levels of lncRNA-ZFAS1 expression in STEMI group, ROC curve was used to analyze the predictive value of lncRNA-ZFAS1 for MACE in STEMI patients, Logistic regression model was used to analyze the influencing factors of MACE in STEMI patients. Results The expression level of lncRNA-ZFAS1 in peripheral blood and serum content of Caspase-3 in STEMI group were higher than those in the control group (P＜0.05), and lncRNA-ZFAS1 was positively correlated with Caspase-3. The cumulative incidence of MACE in patients with high lncRNA-ZFAS1 expression was higher than that in patients with low lncRNA-ZFAS1 expression in STEMI group, lncRNA-ZFAS1 expression had predictive value for MACE in STEMI group. cTnI peak value, multi vessel disease, and time from onset to PCI, Gensini score, lncRNA-ZFAS1 and Caspase-3 were the influencing factors of MACE in STEMI patients. Conclusion The lncRNA-ZFAS1/Caspase-3 axis was significantly changed in STEMI, and lncRNA-ZFAS1 expression level and Caspase-3 content were increased, which were related to MACE after PCI.

Abstract:Aim To evaluate the therapeutic effect of Dushen decoction on patients with acute myocardial infarction (AMI) and its influence on cardiac function and myocardial reperfusion. Methods 74 AMI patients in convalescent stage after myocardial infarction were randomly divided into two groups. The control group (37 cases) was treated with aspirin enteric coated tablets, atorvastatin and low molecular weight heparin calcium, while the observation group (37 cases) was treated with Dushen decoction on the basis of conventional therapy. The changes of serum biochemical indexes of AMI, cardiac function, hemodynamic indexes and quality of life were observed. Results After treatment, the levels of cardiac troponin I (cTnI), creatine kinase isoenzyme (CK-MB) and myoglobin in the observation group were lower than those in the control group (P＜0.05). Compared with the control group, left ventricular end diastolic volume(LVEDV) and left ventricular end systolic volume(LVESV) were significantly lower in the observation group after treatment (P＜0.05), left ventricular ejection fraction(LVEF), systolic blood pressure(SBP), diastolic blood pressure(DBP) and cardiac output, physical function, emotional cognition, health status, social function and total score of QLQC30 were significantly higher in the observation group after treatment (P＜0.05). Logistic regression analysis showed that serum biochemical indexes of AMI, heart function, blood pressure and hemodynamic indexes were independent risk factors for myocardial injury in patients with myocardial infarction. Conclusion The patients with AMI in convalescent stage after myocardial infarction were treated with traditional Chinese medicine Dushen decoction, which can improve myocardial reperfusion, cardiac function and hemodynamic indexes, and create better conditions for patients' quality of life after treatment.

Abstract:Sonic hedgehog (Shh) signaling pathway not only plays an important role in embryo development, but also participates in many physiological and pathophysiological processes. The pathological mechanism of the occurrence and development of ischemic stroke is complex, which has not been fully understood, and the current treatment is limited to an acute time window. As the role of Shh signaling pathway in ischemic stroke being increasingly reported, it was found that genes and proteins related to the pathway may participate in various stages of ischemic stroke and play different roles.This review summarizes main findings of the role played by Shh signaling pathway in the early stage, acute stage and recovery stage of ischemic stroke. It is expected that further study of Shh signaling pathway will help to provide valuable reference to new mechanisms and drug new target for the ischemic stroke.

Abstract:Atherosclerotic vascular disease is one of the leading cause of mortality and disability of humans, thrombosis caused by atherosclerotic vulnerable plaque rupture is a common pathological basis for the occurrence of multiple acute cardiovascular and cerebrovascular diseases. There are divergent opinions on the exact mechanism of its pathogenesis. This article focuses on the current literature on immunology, and explores the role of immune abnormalities in the development of atherosclerosis.

Abstract:Acute coronary syndrome (ACS) is a serious type of coronary heart disease, which has high morbidity rate and mortality rate. Inflammation plays an important role in the initiation and development of ACS. In clinical practice, monitoring inflammation related factors is conducive to risk stratification and prognosis evaluation of ACS patients. Some studies have shown that leukocyte differential count may be one of the reliable inflammatory markers for clinical evaluation of prognosis in patients with ACS. This article reviews the research progress of leukocyte differential count in predicting the prognosis of ACS.

Abstract:S100A8 and S100A9, as endogenous risk-associated molecular patterns, recognize Toll-like receptor 4 and advanced glycation end product receptors, participate in immune response, change endothelial permeability and promote inflammation within the plaque, which affects the development of atherosclerosis. In addition, the elevated plasma levels of S100A8 and S100A9 are associated with an increased risk of future cardiovascular events. This article reviews the research status of S100A8 and S100A9 and their application prospects in the prevention, treatment and prognosis evaluation with coronary heart disease.