Aim To explore the characteristic of NO-cGMP signal pathway in the regulation of thoracic aortic relaxation in thyroxine-induced hypertensive rats.Methods Hyperthyroidism was induced by administering Lthyroxine(T4,0.5 mg?kg~-1,sc)daily for 16 days.Sham-treated euthyroid control rats received only vehicle saline for 16 days.SNAP,an NO donor,was used to define the differential relaxation in the thoracic aorta from euthyroid and hyperthyroid rats.To determine the mechanisms involved changes in NO-cGMP signal pathway in the regulation of aortic relaxation from hyperthyroid rats,BAY 41-2272(BAY)was used to activate soluble guanylate cyclase(sGC),ODQ was used to inhibit sGC,and 8-Br-cGMP was used to acti vate protein kinase G(PKG),respectively.Results Thyroid hormone excess for 16 days showed characteristic changes in body weight,heart rate and systolic blood pressure in rats.The body weight was significantly decreased,while heart rate,pulse pressure and systolic blood pressure were increased in T4-treated rats.SNAP caused relaxation in the aorta in both euthyroid and hyperthyroid rats.However,SNAP-induced aortic relaxation was significantly attennuated in hyperthyroid rats than in euthyroid rats.In the presence of ODQ,SNAP-induced aortic relaxation was blocked in both euthyroid and hyperthyroid rats.BAY and 8-BrcGMP-induced aortic relaxation was significantly attennuated in hyperthyroid rats than in euthyroid rats.Conclusion These data suggest that the attenuated effect of NO-cGMP signal pathway is involved in the regulation of aortic relaxation in the pathophysiology of hyperthyroidism,which may be related to the downregulation of sGC and PKG functions.

Aim To investigate the effects of T-and L-type calcium channel blockers on isolated thoracic aorta from thyroxine-induced hypertensive rats.Methods Hyperthyroidism was induced by administering L-thyroxine (T4,0.5 mg·kg~(-1),sc) daily for 16 days.Sham-treated euthyroid control rats were only received vehicle saline for 16 days. Experiments were performed in isolated thoracic aorta rings from euthyroid and hyperthyroid rats. Mibefradil and diltiazem were used to inhibit T-and L-type calcium channels,respectively.Results Thyroid hormone excess for 16 days induced characteristic changes in body weight,heart rate and systolic blood pressure in rats. The body weight was significantly decreased,heart rate and systolic blood pressure were increased in T4-treated rats. Thoracic aorta morphology was altered in T4-treated rats. The thickness of adventitia was increased with hypertrophy and hyperplasia of the smooth musle cells in T4-treated rats. Vasorelaxant effect of T-and L-type calcium channel blockers were accentuated in aortic rings from T4-treated rats.Conclusion These data suggest that T-and L-type calcium channels are functionally upregulated in isolated thoracic aorta from hyperthyroid rats and they,may be a therapeutic target in thyroxine-induced hypertension.

Objective Cryoballoon ablation of pulmonary vein (PV) ostia often induces a vagal response.This prospective study was designed to assess the effectiveness of prophylactic intravenous administration of atropine on hemodynamic impairment induced by cryoballoon ablation in patients with atrial fibrillation.Methods Twenty-five patients with paroxysmal atrial fibrillation undergoing cryoballoon ablation were prospectively enrolled and assigned to either the trial group on the control group.First twelve patients (the trial group) were administered 1 mg of atropine before deflation of the cryoballoon,while the following 13 patients (the control group) were given atropine only after the onset of the hemodynamic variation (decrease in heart rate and/or blood pressure).Treatment was considered effective when the hemodynamic variations were restored.Results In the trial group,three patients with transient hypotension did not require further supportive care throughout the procedures and one patient with hypotension required supportive management.In the control group,hypotension,bradycardia and mixed bradycardia with hypotension requiring supportive care occurred in six,three,and three patients,respectively.Overall,the rate of marked vagal responses was significantly lower when prophylactic atropine was administrated (4/12 vs.12/13 patients,P ＜ 0.01).Conclusions Atropine is effective in the prevention of all types of vasovagal responses induced by cryoballoon ablation in patients with atrial fibrillation.

Objective To investigate associations of herpes simplex virus(HSV)infection with elevated high-sensitivity C-reactive protein(hsCRP)level and the development of atrial fibrillation(AF) in elderly individuals.Methods Through screening a total of 2,603 individuals,49 patients aged 60 years or over with AF and without structural heart diseases and known risk factors for AF were selected for data collection.Fifty-five elderly healthy control subjects were selected from a population based Chinese Arrhythmia Registry.Baseline characteristics,plasma antibody levels against HSV-1 and-2,and level of hsCRP were analyzed.Results Level of antibodies against HSV-1 was significantly higher in AF patients[(314.5±63.6)mg/L than in control subjects(216.0±50.7) mg/L,P＜0.01].Level of antibodies against HSV-2 was significantly higher in AF patients[(400.1±50.7) mg/L than in control subjects (306.3 ± 64.5) mg/L,P ＜ 0.01].Linear regression analysis demonstrated a positive correlation of plasma levels of hsCRP with both anti-HSV-1 and anti-HSV-2 IgG antibodies (r =0.291,0.188,all P ＜ 0.01).In multiple logistic regression analysis,HSV-1 and HSV-2 antibody levels were significantly associated with AF occurrence(OR =1.035 and 1.034,all P ＜0.01).The optimal cut-off point for predicting AF occurrence was 284.96 mg/L for anti-HSV-1 with sensitivity of 67.3％ and a specificity of 92.7％,and was 366.26 mg/L for anti-HSV-2 with a sensitivity of 67.3％ and a specificity of 85.5％,respectively.Conclusions The increased plasma levels of anti-HSV-1 and anti-HSV-2 antibodies are significantly associated with AF occurrence in elderly adults.

Objective: To analyze the interpretation results on the pathogenic classification of KCNH2 variants and SCN5A variants of long QT syndrome (LQTS) based on American College of Medical Genetics and Genomics (ACMG) guidelines by 4 clinical gene screening agencies from Beijing. Methods: Pathogenic classification of 16 variants in KCNH2 and SCN5A was made by 4 clinical gene screening agencies from Beijing based on ACMG guideline. Krippendorff's alpha was used to assess the inter-agency variation consistency. Results: All 4 agencies made pathogenic assessment on all the variants and provided the interpretation results for the classification. For the eight variants from the patients with LQTS, the consistency of classification was only 1/8 and the alpha test value was - 0.01. For the eight variables from incidental findings, the consistency of classification was 4/8 and the alpha test value was 0.407. Evidence analysis of the 4 variants with large differences in classification among agencies showed that the main reasons for the discrepancies originated from the comprehensiveness of the literature search and the inconsistency of the subjective determination of the evidence grade. Conclusion The consistency of the pathogenic classification of LQTS gene variants based on ACMG guidelines among clinical gene screening agencies from Beijing is poor, which will result in great impact on the clinical treatment strategies of the patients with LQTS. The standardization of pathogenic evaluation of variants in clinical gene screening agencies needs to be improved urgently.

Objective:To determine the blood level of homocysteine （Hcy） and its influencing factors among Shanghai rural residents with high risk of stroke and to verify if hyperhomocysteinemia （HHcy） is a main biomarker of stroke. Methods:With a clustered random sampling method， questionnaire survey and physical examination were conducted among 4 073 rural residents， aged 55 years and above， in Luojing community， Shanghai， in 2018. A total of 470 residents were at high-risk for stroke based on screening of plasma Hcy and other blood indicators. Multivariate logistic regression method was performed for data analysis. Results:The overall level of Hcy was （18.92±6.37）μmol/L， with （20.40±5.89）μmol/L for men and （17.87±2.12）μmol/L for women （t=5.431，P<0.001）. HHcy was detected in 78.94%（371/470） of the participants， in which 85.77%（235/274） were men and 69.39%（136/196） were women （χ²=12.400，P=0.001）. In the high-risk male group， subjects with smoking history， overweight or obesity， exercise frequency <1 h/d， and hypertension has a higher detection rate of HHcy than those without smoking history， normal body mass index， exercise frequency ≥1 h/d and without hypertension （χ²=11.340，8.170，8.200， and 12.400， respectively， all P<0.01）. However， there was no significant difference in HHcy detection rate in different age groups and between the patients with or without diabetes， and dyslipidemia（χ²=3.120，2.311， and 0.984， respectively， all P>0.05）. In the high-risk women group， HHcy detection rate increased with age （χ²=13.874，P<0.01）， and it was higher in participants with overweight or obesity， exercise frequency < 1 h/d， hypertension， and dyslipidemia（χ²=10.278， 13.840， 14.100， and 12.330， respectively， all P<0.01）. Unconditional logistic regression analysis showed that the factors affecting HHcy in the high-risk population of stroke include being male， smoking， hypertension， overweight and obesity. Conclusion:Screening of high-risk populations for stroke should include blood level of Hcy.