Abstract:Prevalence of heart failure (HF) is increasing as improved medical care has prolonged the lifespan of patients suffering heart disease. Patients with HF are often complicated by arrhythmias and at high risk of sudden cardiac death (SCD). How to prevent and treat arrhythmias and SCD in patients with HF (especially HF with reduced ejection fraction, HFrEF) is a difficult problem in clinical practice. The side effects of antiarrhythmic drugs (AAD)have greatly limited their clinical application in patients with HF and arrhythmias, and the role of drugs in preventing and treating SCD is extremely limited. In this paper, the latest views on the relationship between HF and arrhythmias in recent years and the clinical application of AAD in patients with HF will be briefly reviewed from the clinical perspective, so as to provide references for clinicians.

Abstract:Aim To observe the effects of different components of polyunsaturated fatty acids and their ratios on preventing atherosclerosis (As) in ApoE－/－ mice, and provide a scientific basis for rational consumption of fatty acids to prevent As. Methods The control group, the model group and three experimental oil groups were set up, and three kinds of experimental oil-made feeds were prepared according to the ratio of saturated fatty acid(SFA)∶monounsaturated fatty acid(MUFA)∶polyunsaturated fatty acid(PUFA)=0.25∶1∶1. The ratio of ω-6/ω-3PUFA in experimental oil group 1 and group 2 was designed to be 2.5∶1, and the ratio of ω-6/ω-3PUFA in experimental oil group 3 was designed to be 10∶1. The source of omega-3 PUFA in experimental oil group 1 is α-linolenic acid (ALA), and the source of omega-3 PUFA in experimental oil group 2 and experimental oil 3 is eicosapentaenoic acid (EPA) and docosahexaenoic acid. (DHA) and alpha-linolenic acid (ALA). The changes of body mass were recorded. The formation of atherosclerotic plaque was observed by oil red O staining of the entire aorta and aortic root HE staining. The hepaticmorphology and structure were observed by HE staining. The liver lipid accumulation was observed by oil red O staining. Serum levels of TG, TC, LDLC and HDLC and liver levels of TG and TC were detected by enzymatic methods. The effects of different ratio of ω-6/ω-3PUFA and different sources of ω-3 PUFA were compared. Results Compared with the model group, the three groups of experimental oil could reduce the formation of aortic As plaque (P<0.05), lower the level of TG, TC in liver (P<0.05), lower the lever of serum TG, TC, LDLC (P<0.05), and improve lipid accumulation in the liver ; Compared with the experimental oil group 1 and the experimental oil group 3, the experimental oil group 2 was more effective in inhibiting the formation of aortic As plaques (P<0.05) . The levels of TG, TC in liver were significantly decreased (P<0.05), the levels of serum TG, TC, LDLC were significantly decreased (P<0.05), the levels of serum HDLC were increased (P<0.05) in the experimental oil group 2, and thus improved liver lipid accumulation. Conclusions Reducing the intake of SFA and increasing the intake of MUFA and PUFA have anti-atherosclerosis effect. EPA, DHA, together with ALA as source of ω-3 PUFA have a stronger anti-atherosclerosis effect than ALA alone. The anti-atherosclerosis effect of low ω-6/ω-3 ratio is stronger than high ω-6/ω-3 ratio.

Abstract:Aim To investigate the role of GRP78 and Nur77 in myocardial ischemia-reperfusion injury in diabetic rats. Methods Healthy male SD rats were selected and some rats were ligated to the left anterior descending coronary artery to establish a model of cardiac ischemia-reperfusion. Rats were divided into I/R50 group (18 rats, reperfusion for 50 min), I/R120 group (19 rats, reperfusion for 120 min), diabetic group (13 rats), and normal group (14 rats). Echocardiography was performed 2 hours before and 2 days after surgery. The rats were sacrificed 5 h after operation, and the heart samples were collected. The subcellular organelles were separated by differential centrifugation. The expression of GRP-78 and Nur-77 protein in the nucleus and cytoplasm was detected by Western blot. Results The blood glucose of the diabetic group was significantly increased. Ultrasonic results showed that:The LVEF and LVFS were significantly decreased and the LVEDd was significantly increased in the I/R50 group and the I/R120 group (P<0.05);Compared with the I/R50 group, the LVEF and LVFS in the I/R120 group were slightly decreased, but the difference was not significant. Compared with the diabetic group, the levels of GRP78 and Nur77 in the I/R50 group and I/R120 group were significantly increased in the mitochondria (P<0.05). The Nur77 in the I/R50 group and the I/R120 group were lower in the nucleus (P<0.05). The endoplasmic reticulum I/R50 group and I/R120 group GRP78 were all low expression (P<0.05). Conclusion In ischemia-reperfusion of diabetic rats, GRP78 and Nur77 exhibit mitochondria-targeted translocation, which may be involved in cardiomyocyte apoptosis and lead to myocardial ischemia-reperfusion injury.

Abstract:Aim To study the role of endoplasmic reticulum stress (ERS) in the inhibition of vascular calcification by fibroblast growth factor 21 (FGF21) in rats. Methods Adult male SD rats were randomly divided into control group, model group, FGF21 group and FGF21＋tunicamycin (TM) group. Vitamin D3 combined with nicotine was used to establish vascular calcification model in the latter 3 groups. FGF21 group was intraperitoneally injected with 1 mg/(kg·d) of FGF21, and FGF21＋TM group was intraperitoneally injected with 1 mg/(kg·d) of FGF21 and 4.5 mg/(kg·w) of TM, for 28 consecutive days. Alizarin red staining, calcium content, alkaline phosphatase (ALP) activity, TUNEL staining, osteogenesis marker gene and ERS gene expression levels in thoracic aorta of rats were compared among groups. Results Alizarin red staining of thoracic aorta in FGF21 group was significantly weakened. Calcium content, ALP activity, positive rate of TUNEL staining and protein expression levels of Runt-related transcription factor 2 (RUNX2), bone morphogenetic protein 2 (BMP2), BMP4, osteoprotegerin (OPG), glucose-regulated protein 78 (GRP78), CCAAT/EBP homologous protein (CHOP) and cysteinyl aspartate specific proteinase-12 (Caspase-12) in the FGF21 group were significantly lower than those in the model group (P＜0.05). Positive rate of TUNEL staining and protein expression levels of RUNX2, BMP2, BMP4, OPG, GRP78, CHOP and Caspase-12 in the FGF21＋TM group were significantly higher than those in the FGF21 group (P＜0.05). Conclusion FGF21 can inhibit vascular calcification induced by vitamin D3 and nicotine, and blocking ERS-mediated cell apoptosis and osteogenic differentiation may be its molecular mechanism of inhibiting vascular calcification.

Abstract:Aim To study effects of mangiferin on oxidative stress response and neuronal apoptosis in rats with hypoxic-ischemic brain injury by PI3K/Akt/mTOR pathway. Methods 144 neonatal SD rats were randomly divided into 6 groups:blank control group, model group, positive control group (Nimodipine), mangiferin low dose group (MAN-L), middle dose group (MAN-M) and high dose group (MAN-H). There were 24 rats in each group. The rat model of hypoxic-ischemic brain injury was made in all groups except the blank control group. After the model was made, the blank control group and the model group were given the same volume of normal saline, the positive control group was given nimodipine (0.4 mg/(kg·d)), and the mangiferin low, middle and high dose groups were given mangiferin 0,0, 200 mg/(kg·d) for 4 weeks. The neurological injury score of rats in each group was measured, the water content of brain tissue in each group was measured by dry and wet weight method, the pathomorphological changes of brain tissue were observed by hematoxylin-eosin (HE) staining, and the apoptosis of neurons in brain tissue of rats was detected by in situ apoptosis. The activities of superoxide dismutase (SOD), malondialdehyde (MDA), glutathion peroxidase (GSH-Px) and total antioxidant capacity (T-AOC) in brain tissue were measured by biochemical detection, and the expression of PI3K/Akt/mTOR mRNA in rat brain tissue was measured by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The contents of caspase-3, Bcl-2, Bcl-xL, Bad and Bax proteins in brain tissue were detected by Western blot. Results The nerve injury score, water content of brain tissue, apoptosis number of nerve cells, MDA content, PI3K expression and caspase-3 content in the model group were significantly higher than those in the blank control group. The number of intact neurons, the contents of SOD, GSH-Px, T-AOC, Akt, mTOR and the contents of Bcl-2, Bcl-xL and Bad in the brain tissue of the model group were significantly lower than those of the blank control group. The nerve injury score, water content of brain tissue, apoptosis number of nerve cells, MDA content, PI3K expression and caspase-3 content in each drug group were significantly lower than those in the model group. The number of intact neurons, the contents of SOD, GSH-Px, T-AOC, Akt, mTOR and the contents of Bcl-2, Bcl-xL and Bad in the brain tissue of the drug group were significantly higher than those of the model group. Conclusion Mangiferin can enhance the neuroprotective effect, inhibit neuronal apoptosis and improve the survival rate of nerve cells by down-regulating the expression of caspase-3, up-regulating the expression of Bcl-2 and Bcl-xL, and enhancing the expression of PI3K/Akt/mTOR pathway.

Abstract:Aim To examine the effect of probucol on major advanced cardiovascular events (MACE) in patients with coronary artery disease undergone PCI. Methods Electronic databases, including PubMed, EMBASE, ScienceDirect and the Cochrane Central Register of clinical trial, CNKI database and Wan-Fang Database were used. The search items of“antioxidant”or“probucol” or “vitamin C”or “vitamin E” or “N-acetylcysteine”and “angioplasty”or “stent” and “randomized” were selected. RevMan 5.3 provided by the Cochrane was used to perform this analysis. Results In the enrolled 349 articles, there were 7 articles reporting MACE events in patients with coronary heart disease undergone PCI. There were 72 events in antioxidant group (72/2,0.5%). 111 events occurred in control group (111/4,1.4%). Compared to control group, antioxidant (probucol) group significantly decreased the incidence of MACE (RR 0.5,5%CI 0.51~0.84, P=0.0008). Compared with control group (86/2,4.3%), there was a lower rate of repeat revascularization in antioxidant group (52/2,4.8; RR 0.1,5%CI 0.44~0.83, P=0.002). No difference was observed in myocardial infarction death between groups (P=0.34,P=0.49). In addition, total cholesterol (TC) and low density lipoprotein- cholesterol (LDLC) were significantly decreased in probucol group when compared with control group (standard mean reduction SMD －0.8,5%CI －0.87~－0.49, P<0.00001; SMD －0.8,5%CI －0.46~－0.11, P=0.001, respectively). Conclusions Antioxidant probucol combined with conventional treatment significantly decreased the rate of MACE in patients with coronary artery disease undergone PCI. This benefit may be related to the improvement of repeat revascularization and lipid profile.

Abstract:Aim To evaluate the correlation between the low-density lipoprotein subfractions detected by the Lipoprint method and the degree of coronary artery disease. Methods 139 patients with coronary heart disease were retrospectively analyzed, all patients undergo the quantitative analysis of low-density lipoprotein subfractions with Lipoprint systerm, coronary angiography, calculation of diseased vessel count and Gensini score, comparison of the clinical characteristics and lipoprotein subfractions of patients between three-vessel disease group and simple disease group as well as high scores in Gensini scores and low scores. Logistic regression was used to evaluate the correlation between low density lipoprotein subfractions and the severity of coronary lesions. Results Compared with the simple lesion group, the concentration oflowdensity lipoprotein(LDL3), small and dense low-density lipoprotein(sdLDL), and sdLDL percentage in the three-vessel disease group increased (P＜0.05), and the concentration percentage of LDL1~2 decreased (P＜0.05). The proportion of hypertension and diabetes in the three-vessel disease group was high (P＜0.05). Logistic regression analysis showed that hypertension, diabetes, hemoglobin A1c(HbA1c), LDL3, sdLDL and the concentration percentages of sdLDL were positively correlated with three-vessel disease, and the concentration percentage of LDL1~2 was negatively correlated with three-vessel disease. Compared with the Gensini Score(GS) low group, very low density lipoprotein (VLDL), total cholesteral(TC), non high denseity lipoprotein(nonHDL), triglyceride (TG), LDL3, LDL4, LDL6, sdLDL, and the concentration percentage of sdLDL increased in GS high group(P＜0.05), and the concentration percentage of LDL1~2 decreased (P＜0.05). Logistic regression analysis showed that hypertension, HbA1c, LDL6, LDL7, sdLDL and the concentration percentages of sdLDL were positively correlated with GS, and the concentration percentage of LDL1~2 was negatively correlated with Gensini score. Conclusion sdLDL and the concentration percentage of sdLDL was positively correlated with the degree of coronary artery disease. The concentration percentage of LDL1~2 was negatively correlated with the degree of coronary artery disease.

Abstract:Aim To investigate the predictive value of T wave changes in avL lead in patients with acute coronary syndrome. Methods Electrocardiogram and coronary angiography were performed in 142 patients with acute coronary syndrome, and imaging features were recorded. The prognosis of the patients were followed up. The prognosis group and the prognosis group were classified accorded to the prognosis, and the correlation analysis were performed on the observation items. Results There were 42 patients (poor prognosis group, 29.6%) were reached the end of the cardiovascular event, and 100 patients were good prognosis (good prognosis group, 70.4%). The the avL lead T wave change rates in the good prognosis group were 13.0%, which were significantly lower than 85.7% in the poor prognosis group (P<0.05). The ST segment elevation, ST segment depression, pathological Q wave, etc in the good prognosis group were significantly lower than the poor prognosis group (P<0.05). The rates of coronary artery stenosis in the good prognosis group were significantly higher in the poor prognosis group(P<0.05). COX model analysis showed that coronary stenosis rate, avL lead T wave change, ST segment elevation, and pathological Q wave had independent prognostic value (P<0.05). Conclusion T-wave changes in the avL lead in patients with acute coronary syndrome can predict their prognosis, and the T-wave change in the avL lead is an independent risk factor for the endpoint of cardiovascular events in patients.

Abstract:Aim To investigate the effect of non-infarct-related vessels chronic total occlusion (CTO) on the prognosis of elderly patients with acute ST-segment elevation myocardial infarction (STEMI) and related risk factors. Methods 210 elderly patients with STEMI who underwent percutaneous coronary intervention (PCI) in our hospital from March 2015 to June 2018 were included as the study subjects. Clinical data were compared between non-infarct-related vessels CTO patients (CTO group, n＝30) and non-infarct-related vessels non-CTO patients (non-CTO group, n＝180).The follow-up period was 12 months. Cox regression analysis was used to analyze the relevant risk factors affecting the clinical prognosis of patients. Results The in-hospital mortality and one-year mortality after operation in CTO group were significantly higher than those in non-CTO group (16.67% vs 6.11%, P＝0.03; 20.00% vs 8.39%, P＝0.03). Cox regression analysis showed that age, diabetes mellitus, lower left ventricular ejection fraction, cardiogenic shock and left anterior descending artery infarction were independent risk factors for in-hospital and one-year post-operative deaths in elderly STEMI patients. Complication of non-infarct-related vessels CTO was an independent risk factor for in-hospital mortality. Renal insufficiency and multi-vessel lesions were independent risk factors for 1-year mortality. ConclusionNon-infarct-related vessels CTO predicts poor short-term prognosis or increased risk of death in elderly STEMI patients after PCI.

Abstract:Aim To explore the characteristics of heart rate variability (HRV) and its short-term prognosis in patients with chronic heart failure complicated with type 2 diabetes mellitus (T2DM). Methods 105 patients with chronic heart failure were selected as heart failure group. Patients were divided into simple heart failure group and heart failure with T2DM group. 40 patients with organic heart disease without heart failure who were hospitalized at the same time were selected as control group. To collect the general data, the results of echocardiography and 24-hour ambulatory electrocardiogram of patients in each group, including the standard deviation of the mean of sinus rhythm normal-to-normal intervals (SDNN), ratio of the total number of sinus R-R intervals to the height of the histogram of sinus R-R intervals (TRI), the square root of the mean of the sum of the squares of differences between adjacent NN intervals (rMSSD) and the proportion of differences between successive R-R intervals that are greater than 50 ms (PNN50). The differences of clinical data between control group and heart failure group, heart failure subgroups were compared. The HRV indexes of different diabetic course in heart failure with T2DM group were analyzed. The patients in heart failure group were followed up for 3 months to compare the number of re-hospitalization due to heart failure. Results The course of disease, the total cost, B-type natriuretic peptide (BNP), left ventricular end diastolic diameter (LVEDd), the slowest heart rate and the average heart rate were higher in the heart failure group than those in the control group, and the hemoglobin (Hb), left ventricular ejection fraction (LVEF), cardiac output (CO), SDNN, TRI, rMSSD and PNN50 were lower than those in the control group. The multivariate logisitic regression analysis showed that the course of disease, BNP and the slowest heart rate were independent risk factors for heart failure in patients with organic heart disease. Total cost, the number of β-blocker used, course of disease, fasting blood glucose, BNP, NYHA class Ⅳ cases, the average heart rate and the fastest heart rate were higher in heart failure with T2DM group than those in simple heart failure group, and SDNN, TRI, rMSSD and PNN50 were lower than those of simple heart failure group (P<0.05). Fasting blood glucose was associated with T2DM in patients with heart failure. In patients with T2DM more than 10 years, the levels of rMSSD and PNN50 decreased significantly (P<0.05). The number of re-hospitalization in heart failure complicated with T2DM group was higher than that in simple heart failure group (P<0.05). Conclusions The heart autonomic nervous function in patients with chronic heart failure is lower than in patients with organic heart disease without heart failure. T2DM mellitus can further decrease the HRV of patients with chronic heart failure, damage the heart autonomic nervous function and affect the short term prognosis of patients with chronic heart failure.

Abstract:Aim To investigate the relationship between serum 25-hydroxyvitamin D (25-(OH)D) and parathyroid hormone (PTH) levels and hypertension in patients with type 2 diabetes. Methods A retrospective analysis of 128 patients with type 2 diabetes was divided into hypertension group (89 cases) and non-hypertension group (39 cases) according to whether they had priary hypertension. General information of the subjects and serum PTH, 25-(OH) VitD were collected. To analyze the relationship between 25-(OH)VitD, PTH and hypertension in diabetic patients. Results Serum 25-(OH)D levels were lower in the patients with hypertension than in the non-combined hypertension group (P<0.001). Difference in PTH of the two groups lacked statistical significance(P=0.132). Pearson correlation analysis showed that 25-(OH)D was negatively correlated with PTH (r=－0.182, P<0.05). Binary Logistic regression analysis showed that 25-(OH)D reduction was a risk factor for type 2 diabetes with hypertension (OR=0.5,5%CI 0.883-0.991, P=0.023), whereas elevated PTH is not a risk factor for hypertension in diabetic patients. Conclusion Diabetic patients are prone to decrease with 25-(OH)D, and 25-(OH)D reduction is a risk factor for hypertension in diabetic patients.

Abstract:Aim To explore the effect of levosimendan on survival and prognosis of elderly patients undergoing coronary artery bypass grafting (CABG). Methods 84 elderly patients with coronary heart disease undergoing selective CABG were randomly divided into treatment group (44 cases) and control group (40 cases). 10 minutes before cardiopulmonary bypass, levosimendan was administered in treatment group for 24 hours, and equal amount of normal saline was administered instead of levosimendan in control group. Mean arterial pressure (MAP), pulmonary capillary wedge pressure (PCWP), mixed venous oxygen saturation (SvO2), systemic vascular resistance index (SVRI) and cardiac index (CI) were monitored. The postoperative incidence of low cardiac output syndrome (LCOS), intensive care unit (ICU) stay time, ventilator assist time, intra-aortic balloon pump usage and norepinephrine usage were compared between the two groups. Postoperative follow-up of 180 days, the event-free survival rate was compared between the two groups. Results The levels of CI and MAP in the treatment group at 2 and 24 hours after operation were significantly higher than those in the control group (P＜0.05), while the levels of SVRI and PCWP in the treatment group were significantly lower than those in the control group (P＜0.05). The postoperative incidence of LCOS, ICU stay time, ventilator assist time and norepinephrine use rate in the treatment group were significantly lower than those in the control group (P＜0.05). The 180-days event-free survival rate was 88.5% in the treatment group and 67.1% in the control group, and Log-rank test showed that there was a significant difference in the event-free survival rate between the two groups (P＜0.05). Conclusion Levosimendan can improve the postoperative hemodynamic indexes of elderly CABG patients, prevent and treat LCOS, increase the event-free survival rate after operation, and improve the clinical prognosis of patients.

Abstract:High density lipoproteins (HDL) are heterogeneous lipoproteins, the HDL subclass exhibits different atherosclerotic protective effects and cardiovascular protection. The distribution of HDL subclasses also changes dynamically with age, gender, etc. Drugs that affect HDL function and subclass distribution may be more effective ways to protect from cardiovascular risk. This article reviews the detection of HDL subclasses, anti-atherosclerotic function and its association with cardiovascular disease, and provides a new perspective for the prevention and treatment of cardiovascular diseases in humans.

Abstract:Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) belongs to the lncRNA family, which is approximately 8 778 bp in length. With the rapid development of high-throughput sequencing, microarray chips and other scientific technologies, MALAT1 is increasingly researched in the cardiovascular field. At present, MALAT1 has been involved in research and development of congenital heart disease, coronary heart disease, myocardial ischemia/reperfusion injury, and diabetic cardiomyopathy. As a biomarker, MALAT1 may play an important role in the early diagnosis, timely treatment and long-term prognosis of cardiovascular diseases. However, the mechanism of cardiovascular diseases remains to be further studied.

Abstract:Adaptive change in vascular wall structure is known as vascular remodeling, which can occur in arterial hypertension, aneurysms, restenosis after vascular intervention and atherosclerosis. MicroRNAs (miRs) play an important role in regulating the major cytokines involved in arterial remodeling, which may promote or inhibit the changes of vascular wall structure, regulate the phenotype of smooth muscle cells (SMC), and control the inflammatory response of endothelial cells and macrophages. Different types of miRs induce SMC to be contractile or synthetic, respectively; SMC is mainly induced to be synthetic during arterial remodeling. Thus, remodeling process can be regulated by reprogramming SMC phenotypes via targeted miRs. In addition, the stimulations of inducing endothelial cell remodeling, such as shear stress, angiotensin Ⅱ, oxidized low density lipoprotein and cell apoptosis, are mediated by miRs. For example, endothelial cell-specific miR-126 is transferred in microvesicles of apoptotic endothelial cells and plays a protective role in the formation of atherosclerosis; it promotes arterial remodeling, especially through the inflammatory response of the innate immune system of macrophages. MiR-155 induces the expression of inflammatory cytokines, while miR-146a and miR-147 participate in the elimination of inflammation. However, data on the role of miRs in vascular remodeling are still lacking, because it is necessary to test the therapeutic potential of currently available and highly effective miR inhibitors for cardiovascular diseases.

Abstract:In lupus nephritis, laboratory indicators such as serum creatinine and urinary protein are often used to evaluate disease activity and curative effect, but these indicators are not necessarily positively correlated with renal activity and renal pathological types. Although renal biopsy is a golden index for evaluating pathological changes, it is invasive It seems that the microRNA(miRNA) in human body fluid are correlated with the diagnosis of lupus nephritis, the assessment of disease activity and the pathological type of kidney.