Objective To investigate the modulation of electrophysiological properties of hyperpolarization-activated cyclic nucleotide-gated channels(HCN) HCN1 and HCN2 by transfecting MinK-related peptide 1(MiRP1) in Chinese hamster ovarian(CHO) cells.Methods CHO cells were co-transfected with plasmid DNA encoding either of the cardiac HCN isoforms(HCN1,HCN2) with MiRP1 to observe the effect of MiRP1 on HCN whole-cell currents.Whole-cell patch clamp technique was used to record the 2 channel currents of the transfected cells.Results MiRP1 significantly increased whole-cell current density of HCN2 [(37.8?4.8) pA/pF(n=11) vs control(25.9?1.7) pA/pF(n=10);at-140 mV,P0.05].Moreover,MiRP1 accelerated the activation kinetic of HCN1 [tau(180.9?8.6) ms vs control(306.1?45.6) ms;at-80 mV,P

Background Coronary slow flow(CSF)phenomenon is characterized by delayed opacification of coronary vessels in normal coronary angiogram.Although clinical and pathological features have been previously described,its pathogenesis remains unclear.Objective To explore the risk factors related to coronary slow flow.Methods Thirty three patients with documented coronary slow flow which were defined according to TIMI frame count method(TFC)and 33 patients with normal coronary flow were enrolled.Clinical data and biochemical parameters were determined.Results Baseline data analysis showed that CSF group had higher baseline level of platelets count [(149.2?41.5)?109 vs(128.1?38.7)?109,P=0.037] and serum uric acid [(328.1?85.2)vs(282.8?82.4)?mol/L,P=0.032],while other variables were similar between the two groups.After adjustment for BMI,total cholesterol,urea,logistic regression showed that blood platelets count(?2=8.350,?=0.026,P=0.004),2-hour postprandial blood glucose(?2=4.920,?=0.289,P=0.026)and serum uric acid level(?2=5.305,?=0.009,P=0.021)were independent predictors for CSF.Conclusion These data suggest that elevated blood platelets count,2-hour postprandial blood glucose and serum uric acid level may predisposed to coronary slow flow.

Objective To observe the incidence of fragmented QRS complex (fQRS)and ST Segment depression fQRS (STD fQRS)during the first 48 hours after non-ST elevation myocardial infarction(NSTE MI)and discuss the value of predicting mortality in patients with NSTE MI .Methods Based on the ECGs ,the patients with NSTE MI were divided into two groups :fQRS and non fQRS group .And then fQRS group was divided into two sub-groups :STD fQRS and non-STD fQRS group .Their mortality was studied during long-term follow-up .Results (1)731 patients with NSTE ACS [the NSTE MI group(n=609) and the UA group(n=122)] were studied .The incidence of fQRS in the NSTE MI group was higher than that of the UA group .(2)All cause mortality in the fQRS group were higher than that in the non-fQRS group ,and all-cause mortality in the STD fQRS group were higher than that in the non-STD fQRS group ,all the above results were not only in the early stages of NSTE MI ,but also in the long term fol-low-up .(3) Multivariate Cox regression analysis revealed that STD fQRS was an independent significant predictor for all cause mortality ,but not of the fQRS .Conclusion The STD fQRS may be an independent predictor of mortality in patients with NSTE MI .

Objective:To investigate the relationship between double mutations of myosin heavy chain gene (MYH6) p.Gly743Arg and p.Glu1389Lys and the cardiac phenotype.Methods:Patients carrying double mutations in the MYH6 gene p.Gly743Arg and p.Glu1389Lys were screened from 52 unrelated left ventricular hypertrophy (LVH) who were admitted to the Second Hospital of Chongqing Medical University from 2015 to 2020, and the genetic testing of peripheral blood of patients by second-generation whole-exome sequencing assay technology and genomic DNA of their family members Sanger sequencing was performed to validate the genomic DNA of the family members. The cardiac phenotype was evaluated by electrocardiogram, coronary computed tomography angiography (CTA), echocardiography, and cardiac magnetic resonance imaging (MRI) as adjuncts.Results:All whole-exome gene were detected in 52 unrelated patients with LVH, of which 1 patient (1.9%) had double mutations in MYH6 gene p.Gly743Arg and p.Glu1389Lys (proband). Two members of the maternal line of this patient carried p.Glu1389Lys mutation, but there was no obvious clinical phenotype. Two members of the paternal line carried p.Gly743Arg mutation and had obvious clinical phenotype of bradycardia, but there was no LVH. The male proband, aged 21 years old, presented with LVH and sinus bradycardia but no coronary artery stenosis on CTA before treatment, MRI showed that the left ventricular end diastolic diameter was 58 mm. After treatment with angiotensin receptor-enkephalinase inhibitor (ARNI), electrocardiogram showed that the heart rate increased significantly (from 43 bpm to 72 bpm). Echocardiography showed that the left ventricular end diastolic diameter decreased significantly (from 60 mm to 49 mm).Conclusions:The p.Glu1389Lys mutation of the MYH6 gene may not manifest the phenotype of heart disease. MYH6 gene p.Gly743Arg mutation may be manifested asymptomatic sinus bradycardia, but there is no LVH phenotype. The cardiac disease phenotype caused by the double mutations of p.Gly743Arg and p.Glu1389Lys in the MYH6 gene is more obvious. Asymptomatic LVH and sinus bradycardia can appear in adolescence, but the LVH phenotype can be reversed in a short period of time after ARNI treatment.

Objective:To investigate the lowering effect on lipid and safety of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor in patients with extremely high risk atherosclerotic cardiovascular disease (ASCVD).Methods:The outpatients and in-patients with extremely high risk ASCVD admitted to the Second Affiliated Hospital of Chongqing Medical University from April to October in 2019 were enrolled. The enrolled patients were divided into two groups by random number table method. The patients in the atorvastatin group were given only 20 mg atorvastatin orally every night for 4 weeks. In the combined group, oral atorvastatin was administered with subcutaneous injection of 140 mg evolocumab, a PCSK9 inhibitor, once every 2 weeks, and the course of treatment was 4 weeks. Serum lipid profile was measured before and 4 weeks after treatment, including triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and lipoprotein-a (Lp-a). Adverse events were recorded.Results:During the study period, a total of 40 patients were enrolled, with 20 patients in the atorvastatin group and 20 in the combined group. There was no significant difference in blood lipid profile before treatment between the two groups. After 4 weeks of treatment, the levels of TC and LDL-C in the two groups and Lp-a level in the combined group were significantly lower than those before treatment, while the levels of TG and HDL-C in the two groups were not statistically significant. Further analysis showed that the differences in TC, LDL-C and Lp-a between before and after treatment in the combined group were significantly higher than those in the atorvastatin group [TC difference (mmol/L): 2.78±1.98 vs. 0.54±0.83, LDL-C difference (mmol/L): 1.91±1.38 vs. 0.39±0.72, Lp-a difference (mg/L): 115.87±138.93 vs. -84.19±251.85, all P < 0.05]. Only 1 patient in the combined group developed allergic reaction, mainly manifested as skin rash, who alleviated after anti-allergic treatment. No other adverse reactions such as abnormal liver function and increased myozyme occurred in the two groups. Conclusion:PCSK9 inhibitor could rapidly and effectively reduced the levels of TC, LDL-C and Lp-a in extremely high risk ASCVD patients, while had little effect on the levels of TG and HDL-C. It is safe to some extent.