【Objective】 To observe the clinical effect of combination therapy of sacubitril valsartan and dapagliflozin in heart failure with reduced ejection fraction (HFrEF) and non-diabetes patients. 【Methods】 This study involved 96 patients with HFrEF and non-diabetes. The patients were randomly divided into control group (50 cases) and observation group (46 cases). On the basis of routine treatment, the control group was treated with sacubitril valsartan, while the observation group was treated with sacubitril valsartan and dapagliflozin. After 1-month and 6-month treatment, we monitored blood pressure, N-terminal pro brain natriuretic peptide (NT-proBNP), high sensitivity troponin T (cTnT), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDd), left atrial diameter (LAD), left ventricular posterior wall thickness (LVPW), Minnesota soda heart failure life quality score (MLHFQ), the incidence of rehospitalization and death, and major adverse cardiovascular events (MACE) in the two groups. 【Results】 After 6 months, systolic blood pressure, cTnT, NT-proBNP, LVEDd, LVPW, and LAD of the observation group were significantly decreased compared with the control group (P<0.05), the LVEF value was significantly increased (P<0.05), and the MLHFQ and MACE incidence were significantly decreased (P<0.05). However, the two groups did not significantly differ in FBG or HbA1c (P>0.05). 【Conclusion】 The combination treatment of sacubitril valsartan and dapagliflozin on HFrEF and non-diabetes patients can significantly improve cardiac function, inhibit myocardial remodeling, reduce the incidence of MACE, and improve the prognosis.

【Objective】 To explore the effects of insulin on the QT interval and induced arrhythmias of cardiomyocytes derived from human induced pluripotent stem cells （hiPSC-CMs）. 【Methods】 Immunofluorescence staining and flow cytometry were used to analyze the purity of hiPSC-CMs. Microelectrode array （MEA） was utilized to detect the electrophysiological changes including heart rate （HR）， field potential duration （FPD， which is similar to QT interval in ECG）， FPDc （FPD corrected by HR）， conduction velocity （CV）， and spike amplitude before and after insulin treatment. The effects of E4031 on QT interval prolongation and induced arrhythmias of hiPSC-CMs were evaluated before and after treatment with insulin. 【Results】 hiPSC-CMs highly expressed myocardial specific marker cTnT. The purity of hiPSC-CMs was 97.1%. After 5-day insulin treatment of hiPSC-CMs， HR increased by （11.9±3.3）%， FPD shortened by （22.7±2.8）%， FPDc shortened by （15.6±1.6）%， and spike amplitude increased by （39.1±7.9）% when compared with untreated group， but CV remained unchanged. 10 nmol/L of E4031 could prolong the FPDc of hiPSC-CMs by （37.8±9.0）%， and 30 nmol/L of E4031 could induce arrhythmias. After insulin treatment， 10 nmol/L of E4031 prolonged the FPDc of hiPSC-CMs by （21.8±3.1）% （compared with the untreated group， insulin decreased FPDc prolongation by E4031， 37.8%±9.0% vs. 21.8%±3.1%， P<0.05）， while 30 nmol/L of E4031 did not induce arrhythmias. 【Conclusion】 Insulin can shorten the QT interval of hiPSC-CMs and significantly reduce the QT interval prolongation and the risk of arrhythmias induced by drugs.

【Objective】 To explore B lymphocytes’ role and mechanisms in angiotensinⅡ/phenylephrine (AngⅡ/PE) induced cardiomyopathy so as to understand the role of inflammatory cells in myocardial injury. 【Methods】 AngⅡ/PE was administered to wild-type (WT) and B cells deficiency (μMT) mice for 14 days or 28 days. The mice were analyzed by blood pressure measurement, echocardiography imaging, flow cytometry, and histology. Cardiac fibrosis was evaluated by Masson staining. 【Results】 Compared with the control group, the left ventricular mass (P<0.01), heart mass/tibia length ratio (P<0.01) and cross-sectional area of cardiomyocytes in AngⅡ/PE group were significantly increased (P<0.01). After 2 weeks of AngⅡ/PE treatment, B lymphocytes (P<0.05), CD45⁺ leukocytes (P<0.05), CD64^-Ly6C⁺ monocytes (P<0.05), CD64⁺Ly6C^-macrophages (P<0.05) and Ly6g⁺ neutrophils (P<0.05) were recruited in myocardial tissue. Compared with WT_AngⅡ/PE group, the heart weight/tibia length ratio (P<0.05), left ventricular weight (P<0.05) and myocardial cell cross-sectional area (P<0.05) of μMT_AngⅡ/PE mice were significantly improved. CD45⁺Ly6C⁺CD64^- monocytes (P<0.05) and CD45⁺Ly6C^-CD64⁺ macrophages (P<0.05) were significantly decreased. 【Conclusion】 B lymphocytes deficiency improves AngⅡ/PE induced cardiac hypertrophy by reducing the infiltration of CD45⁺Ly6C⁺CD64^- monocytes and CD45⁺Ly6C^- CD64⁺ macrophages.

COVID-19 ; Cardiovascular Diseases ; Cardiovascular System ; Humans ; SARS-CoV-2

【Objective】 To explore the effect of bisoprolol on ICa，Lin volume overload combined with pressure overload heart failure in rabbits. 【Methods】 Totally 82 male New Zealand rabbits （2.5-3.0 kg） were randomly divided into three groups： SO （sham group）， HF （heart failure group）， and BF （heart failure with bisoprolol treatment group）. HF rabbits were duplicated by aortic valve insufficiency procedure combined with abdominal aorta constriction procedure. Real-time PCR and Western blot analysis were performed to detect the expression of ICa，L in left ventricular myocytes. Left ventricular myocytes were isolated； then the cell membrane capacitance， the current density， activation and inactivation of ICa，L were recorded by whole cell patch clamp. 【Results】 ① Bisoprolol could improve the heart function of heart failure rabbits according to the measurement of echocardiography and BNP. ② The expressions of ICa，L mRNA and protein decreased significantly in heart failing rabbits （P<0.01）， but remained unaltered after chronic bisoprolol treatment （P>0.05）. ③ Membrane capacitance was larger in heart failing groups than in sham group （P<0.01）. ICa，L current density decreased greatly in HF group （P<0.01）. Bisoprolol treatment could not change Cm or ICa，L density （P>0.05）. V1/2 of activation curve negative shift enlarged window currents in heart failure groups. Bisoprolol treatment caused window currents to decrease. 【Conclusion】 Bisoprolol could reverse the heart function of heart failure rabbits and also affect the function of ICa，L.

Objective: To explore the clinical and magnetic resonance imaging (MRI) features of papillary musclehypertrophic cardiomyopathy. Methods: Our research contained 2 groups: Papillary muscle hypertrophic cardiomyopathy group,n=21 patients treated in our hospital from 2013-01 to 2015-12 including 18 male and 3 female; Control group,n=50 subjects without cardiovascular disease those were conifrmed by our hospital at the same period of time. Clinical and MRI examinations were conducted in all patients, the ifndings were compared between 2 groups. Results: Compared with control subjects, papillary musclehypertrophic cardiomyopathy patients had the main symptoms of shortness of breath, chest tightness and pain; associated with systolic murmur; ECG could be normal or with T wave inversion; cardiac MRI showed that 1/2 papillary muscle diameter>1.1cm. Blood levels of triglyceride, left atrial diameter, inter-ventricular septum thickness, the values of E/A and EDT were statistically different between 2 groups, allP<0.05. Conclusion: Clinical features of papillary muscle hypertrophic cardiomyopathy were lack of speciifcity, the morbidity and clinical signiifcance should be further investigated.

Objective To explore the feasibility using aluminum tripolyphosphate as the synthesis of aspirin model instead of sulfuric acid catalyst. Methods The thermodynamic functions of the reaction system of salicylic acid and acetic anhydride were calculated according to the Benson group contribution method and Joback group contribution method.The enthalpy change,entropy and Gibbs free energy along with the change of temperature as well as the influence of the molar rate of reactants on the equilibrium conversation rate were also studied.Results In the temperature range of 298.15 K to 358.15 K,the reaction enthalpy was less than zero,and was exothermic reaction,and increase of temperature was not conducive to the reaction.The improvement of mole ratio of salicylic acid and acetic anhydride was helpful to improve the equilibrium conversation rate.The theoretical conversion rate could reach 99.58% when the mole ratio of salicylic acid and acetic anhydride was 3.Conclusion From the viewpoint of thermodynamics, the reaction is practical and feasible.

BACKGROUND:Whether adipose-derived mesenchymal stem cells are able to exert immunomodulatory effects in the treatment of myocardial infarction, as wel as the best time, is less reported.
OBJECTIVE:To observe the effect of adipose-derived mesenchymal stem cells on inflammatory reaction and ventricular remodeling after myocardial infarction, and to explore the possible mechanisms of adipose-derived mesenchymal stem cells for the treatment of myocardial infarction.
METHODS:Enzyme digestion method was employed to isolate and culture rat adipose-derived mesenchymal stem cells. By ligation of the left anterior descending coronary artery, we established animal models of myocardial infarction in 40 rats. The rats were randomly divided into four groups:sham group, control group (injected high-glucose Dulbecco’s modified Eagle’s medium), 3-hour transplantation group (transplanted adipose-derived mesenchymal stem cells after 3 hours of myocardial infarction), 7-day transplantation group (transplanted adipose-derived mesenchymal stem cells after 7 days of myocardial infarction). After 14 days of operation, the levels of tumor necrosis factor-αand interleukin-10 in the plasma were detected by enzyme linked immunosorbent assay. After 28 days of operation, the left ventricular end diastolic diameter, left ventricular end systolic diameter, left ventricular ejection fraction and left ventricular fractional shortening were measured by echocardiography.
RESULTS AND CONCLUSION:Compared with the control group, in the 3-hour transplantation group and 7-day transplantation group, the levels of tumor necrosis factor-αwere significantly lower (P<0.01), and the levels of interleukin-10 were significantly higher (P<0.01) at postoperative 14 days;the left ventricular end diastolic diameter and left ventricular end systolic diameter in the two transplantation groups were also significantly smal er (P<0.05), but left ventricular ejection fraction and left ventricular fractional shortening were significantly elevated (P<0.05), which was more apparent in the 3-hour transplantation group than the 7-day transplantation group. Adipose-derived mesenchymal stem cells transplantation in acute phase of myocardial infarction can suppress the inflammatory response, regulate the cytokine network equilibrium, and thus delay ventricular remodeling and improve cardiac function.

10.3969/j.issn.2095-4344.2013.23.001

Objective We performed experiments using Neuregulin-1β (NRG-1β) treatment to determine a mechanism for the protective role derived from its beneficial effects by remodeling gap junctions (GJs) during heart failure (HF). Methods Rat models of HF were established by aortocaval fistula. Forty-eight rats were divided randomly into the HF (HF, n = 16), NRG-1β treatment (NRG, n = 16), and sham operation (S, n = 16) group. The rats in the NRG group were administered NRG-1β (10 μg/kg per day) for 7 days via the tail vein, whereas the other groups were injected with the same doses of saline. Twelve weeks after operation, Connexin 43 (Cx43) expression in single myocytes obtained from the left ventricle was determined by immunocytochemistry. Total protein was extracted from frozen left ventricular tissues for immunoblotting assay, and the ultrastructure of myocytes was observed by transmission electron microscopy. Results Compared with the HF group, the cardiac function of rats in the NRG group was markedly improved, irregular distribution and deceased Cx43 expression were relieved. The ultrastructure of myocytes was seriously damaged in HF rats, and NRG-1β reduced these pathological damages. Conclusions Short-term NRG-1β treatment can rescue pump failure in experimental models of volume overload-induced HF, which is related to the recovery of GJs structure and the improvement of Cx43 expression.