Abstract:Severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) infects host cells through ACE2, CD147 and GRP78 receptors, causing 2019 coronavirus disease (COVID-19), and partially inducing acute myocardial injury and chronic damage to the cardiovascular system. Therefore, special attention should be paid to the protection of the heart during treatment for COVID-19. This issue continues with an expert presentation on SARS- CoV-2 infection and myocardial injury to deepen the understanding of COVID-19 and its cardiovascular injury and improve the prevention and treatment.

Abstract:Patients with coronavirus disease 2019 (COVID-19) are often associated with hypercoagulability as well as some cardiovascular disease requiring antithrombotic treatment including acute coronary syndrome, atrial fibrillation, veinous thrombosis and so on. During antithrombotic therapy for patients with COVID-19, the particularity of COVID-19, effectiveness of antithrombotic therapy and interaction of special drugs should be considered. This requires individualized treatment in combination with the characteristics of COVID-19 and cardiovascular disease, the risk assessment of thrombosis and hemorrhage and the patient's own situation. On this condition, antithrombotic treatment of cardiovascular diseases may need to be adjusted on the basis of conventional treatment norms to achieve higher treatment safety and effectiveness. A safe and effective antithrombotic strategy will be of great significance to the prognosis of patients with COVID-19.

Abstract:Patients with corona virus disease 2019 (COVID-19) presented typical respiratory symptoms, as well as a certain degree of cardiac injury. COVID-19 patients with cardiovascular diseases are prone to deterioration and high mortality. Coronary heart disease, as the most common cardiovascular disease in the middle-aged and the elderly, widely exists in severe COVID-19 patients, which has a serious impact on the course of disease. This article will discuss the influence of severe COVID-19 on the drug treatment of coronary heart disease, to optimize the treatment strategy and improve the prognosis of patients.

Abstract:Except for medical facilities, infected cases without symptom, with different severity of symptoms, and lethal cases are resulted from the interactions between the pathogen and the host. It is necessary to note that the relationship between epidemic untraceable and asymptomatic cases has some values in guiding the prevention and foreseeing the trends of a new outbreak of infectious disease.

Abstract:Since the discovery and spread of coronavirus disease 2019 (COVID-19), it has aroused widespread concern from all walks of life. There are different opinions on the relationship among angiotension converting enzyme (ACE)/ACE2, renin-angiotension system (RAS) inhibitors and COVID-19 in medical circles. ACE and ACE2 are similar in structure but have opposite effects. The positive ACE-AngⅡ-AT1R axis and the negative ACE2-Ang(1-7)-Mas axis in vivo check and balance each other to maintain the stability of blood pressure and internal environment. A number of basic studies have shown that different RAS inhibitors have inconsistent effects on ACE2. The causal relationship between ACE2 and COVID-19 has not been clarified, and no clinical evidence has been found that the use of RAS inhibitors aggravates COVID-19. The consideration of ACE2 influencing COVID-19 is basically derived from the theoretical derivation of RAS and the inference of the basic research results of SARS. Whether cardiovascular disease patients with COVID-19 use RAS inhibitors should be combined with clinical practice and weighing the pros and cons. Evidence-based RAS inhibitors cannot be arbitrarily discontinued in the current ambiguous situation.

Abstract:The 2019 novel coronavirus (2019-nCoV) was discovered in an unidentified viral pneumonia case in Wuhan, China in December 2019, and was named by the World Health Organization (WHO) on January 2,0. The disease caused by 2019-nCoV was named corona virus disease 2019 by WHO on February 2,0. Recent studies have shown that angiotensin converting enzyme 2 (ACE2) is likely to be a mediating receptor of 2019-nCoV-infected cells, and ACE2 is mostly expressed in type Ⅱ alveolar cells in the human lung cells. The high expression of ACE2 in type Ⅱ alveolar cells may explain acute respiratory distress syndrome (ARDS) after 2019-nCoV infection. The first completed pathologic dissection of a patient who died of 2019-nCoV-pneumonia revealed diffuse alveolar injury and lung transparent membrane formation, consistent with ARDS.

Abstract:Since December 2019, corona virus disease 2019 (COVID-19) infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) break out, and the outbreak has spread rapidly all over the world. In addition to respiratory symptoms, COVID-19 has damage to the cardiovascular system in some cases. And the patients with underlying cardiovascular diseases lead to increased mortality. SARS-CoV-2 belongs to the family of coronaviridae, subfamily coronovirinae, β-coronavirus. The sequence identity between SARS-CoV-2 and SARS coronavirus (SARS-CoV) has 79.5% homology, and SARS-CoV-2 uses the same cell entry receptor, receptor angiotensin-converting enzyme 2 (ACE2), as SARS-CoV. The type Ⅱ alveolar cells expressing ACE2 are the main target cells for SARS-CoV-2. Therefore, it is of great significance to understand the cardiovascular system damage caused by SARS-CoV-2 and its related mechanism for the development of SARS-CoV-2 vaccine and drug and the reduction of mortality.

Abstract:Aim To study the clinical characteristics and the time of nucleic acid conversion to negative in patients with Corona Virus Disease 2019 (COVID-19). Methods This study is a retrospective study. Patients with laboratory-confirmed COVID-19 from a hospital in Wuhan from February 2,0 to February 9,0 were divided into mild and common types, followed up to March 0,0, the clinical characteristics and nucleic acid test results of the patients were analyzed. Results A total of 75 patients were included in this study, with an average age of 41.2 ± 11.5 years, and 52.0% were male. Among the patients, 44.0% had fever and 54.7% had positive CT images. The positive rate of the first nucleic acid detection was 69.3%, and the median time of nucleic acid conversion to negative was 9.0 days (6.0~14.0 days). Follow-up to March 0,0, no patients became severe or died. There were no significant differences in age and white blood cell count between patients with mild type (34 cases) and patients with common type (41 cases). Compared with the common group, women in the wild group accounted for 61.8%, which was significantly higher than men (P＜0.05); there was no statistical difference in the time required for nucleic acid conversion to negative between the two groups (8.5 (7.0~13.8) vs 9.0 (5.0~14.0), P＝0.973). The subgroup analysis found that in mild patients, women had less nucleic acid conversion time than men (P＝0.020), and the Lianhuaqingwen capsule subgroup had less nucleic acid conversion time (P＝0.026). Conclusions There was no significant difference in the time of nucleic acid conversion to negative between mild and common patients under the same treatment, and the time of nucleic acid conversion for females and the patients taking Lianhuaqingwen was shortened in mild group. Many patients with moderate COVID-19 may be missed based on clinical manifestations and imaging findings, and accurate and prompt nucleic acid testing or other etiological determination methods are needed.

Abstract:Aim The aim of the present study is to determine the function of signal transducer and activator of transcription 4 (STAT4) signal in macrophage differentiationand foam cell formation during the development of atherosclerosis. Methods STAT4 knockout (STAT4－/－) mice were crossed with Apolipoprotein E knockout mice (ApoE－/－)to establish a novel atherosclerosis related mice model- APOE/STAT4 double knockout (DKO) mice. WT,STAT4－/－,ApoE－/－ and DKOmice (3-month-old adult mice) were challenged with high-fat diet for 12 weeks. The extent of atherosclerosis was determined by oil-red staining and HE staining. Changes in subsets of immune cells were evaluated by flow cytometry. Macrophage differentiation was induced from the CD11b⁺ myeloid cells directly isolated from the bone marrow of transgenic mice with macrophage colony stimulating factor (M-CSF) incubation. Realtime polymerase chain reaction (RT-PCR) and Westernblot were applied to detect the expression levels of related genes and protein. Results The expression of STAT4 was identified in CD11b⁺ myeloid cells in atherosclerotic plaque. Genetic deletion of STAT4 significantly exacerbated atherosclerosis in ApoE－/－ mice as evidenced by significant increases of oilred O-positive lipid-rich lesion, vascular inflammation, and necrotic core lesion in atherosclerotic plaques of DKO mice compared to ApoE－/－mice. The accelerated atherosclerotic process is associated with abnormal mobilization and differentiation of macrophages from CD11b⁺Gr-1⁺ immature myeloid cells and with the enhanced formation of macrophages-derived foam cells in DKO mice. Furthermore,the mechanism studies revealed that the disruption of STAT4 signal leads to the inhibition of phosphatidylinositol-3 kinase(PI3K)/serine-threonine kinases (Akt)/nuclear factor kappa B (NF-κB)/miR-9 signaling pathway and consequently up-regulates the expression of acyl coenzyme A:cholesterol acyltransferase-1 (ACAT-1), an enzyme that esterifies cholesterol and promotes its storage in macrophages and foam cells. Conclusion The results suggest that the STAT4 signal plays important roles in both immune responses and cholesterol metabolism during the differentiation of macrophages. Targeting STAT4 related signals may develop a novel pharmacotherapeutic target for the treatment of atherosclerotic diseases.

Abstract:Aim To observe the effects of flavin adenine dinucleotide (FAD) on cardiac hypertrophy and cardiac fibrosis in spontaneously hypertensive rats (SHR), and to explore the mechanism of FAD on preventing and treating cardiac hypertrophy and cardiac fibrosis. Methods 12-week-old SHR and age-matched Wistar rats were selected and divided into Wistar control group, Wistar experimental group, SHR control group and SHR experimental group. After treated with FAD (1 μmol/(kg·d)) in the tail vein for 10 weeks, the sysbolic blood pressure and heart rate of the rats were detected by non-invasive blood pressure measuring instrument. Cardiac hypertrophy and cardiac fibrosis were observed by echocardiography and histology. The protein expression levels of SCAD (short-chain acyl-CoA dehydrogenase), Collagen Ⅰ, Collagen Ⅲ and α-SMA were detected by Western blot. Immunofluorescence single-label method was used to further verify the protein expression level of SCAD. The mRNA expression levels of SCAD, ANF, BNP, Collagen Ⅰ, Collagen Ⅲ and α-SMA were detected by quantitative PCR. SCAD enzyme activity, content of ATP, free fatty acids, brain natriuretic peptide (BNP) and reactive oxygen were detected. Results Systolic blood pressure and heart rate in SHR were significantly decreased after FAD treatment. Cardiac hypertrophy and cardiac fibrosis were significantly improved. SCAD mRNA, protein expression, enzyme activity and ATP content in the cardiac muscle of SHR were significantly increased. The levels of free fatty acids and reactive oxygen were significantly reduced(P＜0.05). ConclusionFAD may inhibit cardiac hypertrophy and cardiac fibrosis in SHR through activating SCAD, improving cardiac energy metabolism and reducing oxidative stress.

Abstract:Aim To investigate the effect and mechanism of metformin on lipid accumulation in Huh7 hepatocytes. Methods Huh7 cells were cultured in vitro and divided into:blank control group, 5 mmol/L, 10 mmol/L and 15 mmol/L metformin treatment group. After determing the optimal concentration, LDL was used to load fat, and then divided into:blank control group, LDL group, LDL+15 mmol/L metformin treatment group. Cell proliferation and toxicity test kits were used to detect cell survival rate, oil red O and BODIPY lipid probes were used to detect intracellular lipid content, Dil-LDL was used to detect cell lipid uptake capacity, and Western blot analysis was performed on sterol regulatory element binding protein-2 (SREBP-2), sterol regulatory element binding protein-1c (SREBP-1c), low density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin 9 (PCSK9) protein expression. Results Metformin can inhibit LDL-induced lipid accumulation in Huh7 hepatocytes and reduce protein expression of SREBP-2, SREBP-1c, LDLR, and PCSK9. Conclusion Metformin reduces intracellular lipid uptake by reducing LDLR expression and inhibiting the expression of the transcription factors SREBP-2 and SREBP-1c.

Abstract:Aim To investigate the long-term clinical efficacy of prophylactic intra-aortic balloon pump(pIABP) insertion before primary percutaneous coronary intervention in the patients with ST-segment elevation myocardial infarction.Methods 646 patients with ST-segment elevation myocardial infarction but without cardiogenic shock, who have received primary percutaneous coronary intervention were enrolled. pIABP group consists of the 25 patients who have received prophylactic intra-aortic balloon pump insertion before percutaneous coronary intervention, while the control group consists of 75 patients selected from the patients without prophylactic intra-aortic balloon pump insertion before percutaneous coronary intervention by propensity score matching method. The clinical features were analyzed and the clinical prognosis of the two groups was compared. Results After propensity score matching, there were no significant differences in the baseline data except the Killips classification and diabetes history(P=0.001 and P=0.018). The median follow-up time was 21 months (interquartile range 1～28 months). There were 7 cases (28%) of all-cause death in the pIABP group and 18 cases (24%) in the control group. There were 6 cases (24%) of cardiogenic death in the pIABP group and 9 cases (12%) in the control group. The incidence of major adverse cardiovascular and cerebrovascular events was 45.3% in the control group and 56% in the pIABP group. By Kaplan-Meier analysis, there were no significant differences in all-cause mortality and cardiogenic mortality between the two groups (P=0.519 and P=0.103 respectively). There was also no significant difference in the cumulative incidence of major adverse cardiovascular and cerebrovascular events between the two groups (P=0.275). The multivariate Cox regress analysis suggested that prophylactic intra-aortic balloon pump insertion did not influence the long-term prognosis after adjustment of Killips classification and diabetes history (P=0.917).Conclusion Prophylactic intra-aortic balloon pump insertion before primary percutaneous coronary intervention does not significantly improve long-term outcomes in hemodynamic stable patients with ST-segment elevation myocardial infarction.

Abstract:Aim To investigate the serum microRNA-129-5p (miR-129-5p) level and its significance in patients with acute coronary syndrome (ACS). Methods 245 patients with ACS after percutaneous coronary intervention (PCI) admitted to our hospital from November 2016 to October 2017 were selected as subjects of study. According to the optimal cut-off point (0.92) of serum miR-129-5p in predicting the prognosis of ACS patients, the patients were divided into high miR-129-5p group (n＝109) and low miR-129-5p group (n＝136). The relative expression of miR-129-5p in serum was detected by real-time fluorescence quantitative PCR, and its relationship with the prognosis of ACS patients was analyzed. Results Major adverse cardiovascular events (MACE) occurred in 88 cases (35.92%) of 245 ACS patients after PCI. Area under curve of ROC, sensitivity, specificity and optimal cut-off point of serum miR-129-5p in predicting the prognosis of ACS patients were 0.3,9.55%, 77.71% and 0.92, respectively. The incidence of MACE in the high miR-129-5p group was higher than that in the low miR-129-5p group, the difference was statistically significant (P＜0.05). The median survival time of high miR-129-5p group was lower than that of low miR-129-5p group, the difference was statistically significant (P＜0.05). Cox regression analysis showed that chronic obstructive pulmonary disease, left ventricular ejection fraction, and miR-129-5p were closely associated with the prognosis of patients with ACS. Conclusion MiR-129-5p is closely related to the prognosis of ACS patients after PCI, and the detection of serum miR-129-5p level is helpful to understand the prognosis of patients.

Abstract:Aim To research the connection between the changes of plasma platelet-derived growth factor C (PDGF-C) concentration and coronary heart disease and the degree of coronary artery disease. Methods The research includes 52 patients with acute coronary syndrome (ACS), 52 patients with stable angina pectoris (SAP), and 50 patients with normal angiography as the control group. Among patients with coronary heart disease (ACS and SAP), there were 60 cases of coronary artery multivessel disease, 25 cases of double vessel disease, and 19 cases of single vessel disease. The enzyme-linked immunosorbent assay (ELISA) method was used to determine the plasma PDGF-C concentration in each group of patients. The plasma PDGF-C concentration levels were compared between groups, and Spearman correlation analysis, Logistic regression analysis, and ROC curve were drawn. Results The concentration of PDGF-C in the ACS group and the SAP group was higher than that in the control group(P<0.05). The plasma PDGF-C concentration in the multivessel and double disease groups was higher than that in the single disease group(P<0.05). The results of Spearman correlation analysis indicated that there was a correlation between plasma PDGF-C concentration and Gensini score(r=0.163, P<0.05). Logistic regression analysis found that patients with high concentration of PDGF-C had a higher risk of coronary heart disease than patients with low concentration of PDGF-C (OR=1.6,5%CI 1.002~1.011). The area under the ROC curve of plasma PDGF-C concentration was 0.645, and the sensitivity was 77.88%.Conclusion High-concentration plasma PDGF-C may be a risk factor for coronary heart disease and may be related to the severity of coronary artery disease.

Abstract:Many human and animal model studies have shown a link between infection and atherosclerosis. Infectious factors provide major stimuli for the development and progression of inflammation by causing changes in cells and molecules. Inflammation is an important mechanism of atherosclerosis. Infection can be divided into direct and indirect effects on atherosclerosis. From the current part of the experiment,the anti-infective treatment may have a positive effect on the formation of atherosclerosis. It can reduce the formation of atherosclerosis by reducing inflammatory stimuli and regulating cytokines. It introduces two hypotheses of infection burden and molecular mimicry. The possible mechanism of negative antibiotic test has guiding significance for further clinical and experimental research in the future.

Abstract:With the progress of genome-wide analysis and RNA sequencing technology, a variety of non-coding RNA has gradually become a research hotspot. Circular RNA (circRNA) has many cellular functions, and its expression changes are related to many pathophysiological processes and the occurrence and development of diseases. The circRNA has been proved to be an important regulator of cardiovascular diseases, such as hypertension, atherosclerosis, acute myocardial infarction, heart failure, cardiac fibrosis, etc. Therefore, circRNA is expected to be a potential therapeutic target and biomarker for cardiovascular diseases. In this review, based on the biological mechanism of circRNA, we reviewed the current research progress on circRNA as a regulatory factor and biomarker of cardiovascular diseases.