Transcription factor Dmrt1 triggers the SPRY1-NF-κB pathway to maintain testicular immune homeostasis and male fertility

Bacterial or viral infections,such as Brucella,mumps virus,herpes simplex virus,and Zika virus,destroy immune homeostasis of the testes,leading to spermatogenesis disorder and infertility.Of note,recent research shows that SARS-CoV-2 can infect male gonads and destroy Sertoli and Leydig cells,leading to male reproductive dysfunction.Due to the many side effects associated with antibiotic therapy,finding alternative treatments for inflammatory injury remains critical.Here,we found that Dmrt1 plays an important role in regulating testicular immune homeostasis.Knockdown of Dmrt1 in male mice inhibited spermatogenesis with a broad inflammatory response in seminiferous tubules and led to the loss of spermatogenic epithelial cells.Chromatin immunoprecipitation sequencing(ChIP-seq)and RNA sequencing(RNA-seq)revealed that Dmrt1 positively regulated the expression of Spry1,an inhibitory protein of the receptor tyrosine kinase(RTK)signaling pathway.Furthermore,immunoprecipitation-mass spectrometry(IP-MS)and co-immunoprecipitation(Co-IP)analysis indicated that SPRY1 binds to nuclear factor kappa B1(NF-κB1)to prevent nuclear translocation of p65,inhibit activation of NF-κB signaling,prevent excessive inflammatory reaction in the testis,and protect the integrity of the blood-testis barrier.In view of this newly identified Dmrt1-Spry1-NF-κB axis mechanism in the regulation of testicular immune homeostasis,our study opens new avenues for the prevention and treatment of male reproductive diseases in humans and livestock.

Effects of nicorandil on myocardial infarct size in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention:study design and protocol for the randomized controlled trial

Previous studies have shown that nicorandil has a protective effect on cardiomyocytes.However,there is no study to investigate whether perioperative intravenous nicorandil can further reduce the myocardial infarct size in patients with ST-segment elevation myocardial infarction(STEMI)compared to the current standard of percutaneous coronary intervention(PCI)regimen.The CHANGE(China-Administration of Nicorandil Group)study is a multicenter,prospective,randomized,double-blind and parallel-controlled clinical study of STEMI patients undergoing primary PCI in China,aiming to evaluate the efficacy and safety of intravenous nicorandil in ameliorating the myocardial infarct size in STEMI patients undergoing primary PCI and provide evidence-based support for myocardial protection strategies of STEMI patients.

Should atrial fibrillation patients with hypertension as an additional risk factor of the CHA2DS2-VASc score receive oral anticoagulation？

高血压被发现了被增加在 atrial 纤维性颤动(AF ) 的击的风险。欧洲人和美国指南倡导 CHA 2 DS 2-VASc (充血的心失败，高血压，年龄 > 75 年，糖尿病 mellitus， stroke/transient ischemic 攻击，脉管的疾病，年龄 65-74 年，性别范畴) 为风险层化的计划。尽管维生素 K 对手是比在阻止 ischaemic 击的 acetylsalicylic 酸更有效的，它的利益是由增加的出血风险的 offs。在有 AF 和 CHA 2 1 的 DS 2-VASc 分数被认为是低风险并且不能被期望得益于 anticoagulation 治疗。然而，高血压带 ischemic 击的增加的风险它也是为在 AF 的出血的一个清楚的风险因素。因此，最佳的 antithrombotic 管理特别与一个仅仅风险因素与 AF 在病人被加亮高血压。

OCT6 inhibits differentiation of porcine-induced pluripotent stem cells through MAPK and PI3K signaling regulation

As a transcription factor of the Pit-Oct-Unc(POU)domain family,octamer-binding transcription factor 6(OCT6)participates in various aspects of stem cell development and differentiation.At present,however,its role in porcine-induced pluripotent stem cells(piPSCs)remains unclear.Here,we explored the function of OCT6 in piPSCs.We found that piPSCs overexpressing OCT6 maintained colony morphology and pluripotency under differentiation conditions,with a similar gene expression pattern to that of non-differentiated piPSCs.Functional analysis revealed that OCT6 attenuated the adverse effects of extracellular signal-regulated kinase(ERK)signaling pathway inhibition on piPSC pluripotency by activating phosphatidylinositol 3-kinase-protein kinase B(PI3K-AKT)signaling activity.Our research sheds new light on the mechanism by which OCT6 promotes PSC maintenance.

Should antiplatelet therapy be interrupted in drug eluting stent recipients throughout the periendoscopic period？ A very late stent thrombosis case re-port and review of the literature

在在有 drug-eluting stents (DES ) 的病人的 antiplatelet 药的停止以后的 In-stent 血栓是在诊所的一个重要问题，特别地在 perioperative 时期。我们与高血压，冠的动脉疾病和长期的衰退胃炎的病历报导一个 87 岁的人的一个案例。sirolimus-eluting stent 的很迟了的血栓发生了在培植，在 clopidogrel 的中止以后的七个月，和在一个选任的内视镜的胃肠的过程的准备的阿司匹林 13 天的打断以后的 1207 天与尖锐心肌的梗塞介绍了。病人与 thrombectomy 并且成功地被对待有二 sirolimus-eluting stents 的重迭的 revascularized。在 catheterization 实验室管理的药包括了低分子的重量肝磷脂和硝化甘油。流动在心肌的梗塞规模被定义为根据 thrombolysis 的等级 2。在揭示的过程以后的心电图坚持，但是减少，处于在前面偏一边的领先的圣片断举起。病人无止境地在阿司匹林和 clopidogrel 上恢复了并且被解除。在二个年后续时期期间没有心脏的事件。这个盒子加重维持血栓的平衡并且与低流血风险在病人之中在 periendoscopic 过程期间在为阿司匹林治疗的继续的非心脏的过程和可能的需要的 perioperation 期间流血的重要性收到了 DES。

Plasma levels of Elabela are associated with coronary angiographic severity in patients with acute coronary syndrome

Background Elabela(ELA) was newly discovered as a novel endogenous ligand of the apelin receptor(APJ) which has demonstrated to be crucial for cardiovascular disease such as myocardial infarction, hypertension and heart failure. Previous experiments have revealed that ELA reduced arterial pressure and exerted positive inotropic effects on the heart. However, the role of plasma ELA levels in patients with acute coronary syndrome(ACS) and its relationship with severity of coronary arteries have not been investigated. Methods Two hundred and one subjects who were hospitalized for chest pain and underwent coronary angiography were recruited in this study. One hundred and seventy five patients were diagnosed with ACS and twenty-six subjects with negative coronary angiography were included in the control group. Plasma ELA levels, routine blood test, blood lipid, liver and kidney functions were measured. The number of coronary arteries and SYNTAX(Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score of coronary lesions were used to evaluate the extent of coronary artery stenosis. Results ELA in patients with ACS was significantly higher than that in the control group(P < 0.01). There was no significant difference in plasma ELA levels among patients with single-, double-and triple-vessel diseases. However, in the generalized additive model(GAM), there was a threshold nonlinear correlation between the ELA levels and Syntax I score(P < 0.001). Plasma ELA levels were positively correlated with the Syntax I score when the ELA levels ranged from 63.47 to 85.49 ng/m L. There was no significant association between the plasma ELA levels and the extent of coronary artery stenosis when the ELA levels were less than 63.47 ng/m L or higher than 85.49 ng/m L. Conclusion The present study demonstrates for the first time that plasma ELA levels are increased in patients with ACS. The rise in endogenous ELA levels was associated with severity of coronary stenosis and may be involved in the pathogenesis of ACS.

A risk score model for predicting cardiac rupture after acute myocardial infarction

Background:Cardiac rupture (CR) is a major lethal complication of acute myocardial infarction (AMI).However,no valid risk score model was found to predict CR after AMI in previous researches.This study aimed to establish a simple model to assess risk of CR after AMI,which could be easily used in a clinical environment.Methods:This was a retrospective case-control study that included 53 consecutive patients with CR after AMI during a period from January 1,2010 to December 31,2017.The controls included 524 patients who were selected randomly from 7932 AMI patients without CR at a 1:10 ratio.Risk factors for CR were identified using univariate analysis and multivariate logistic regression.Risk score model was developed based on multiple regression coefficients.Performance of risk model was evaluated using receiveroperating characteristic (ROC) curves and internal validity was explored using bootstrap analysis.Results:Among all 7985 AMI patients,53 (0.67%) had CR (free wall rupture,n=39;ventricular septal rupture,n=14).Hospital mortalities were 92.5% and 4.01% in patients with and without CR (P<0.001).Independent variables associated with CR included:older age,female gender,higher heart rate at admission,body mass index (BMI)<25 kg/m^2,lower left ventricular ejection fraction (LVEF) and no primary percutaneous coronary intervention (pPCI) treatment.In ROC analysis,our CR risk assess model demonstrated a very good discriminate power (area under the curve [AUC]= 0.895,95% confidence interval:0.845–0.944,optimism-corrected AUC= 0.821,P<0.001).Conclusion:This study developed a novel risk score model to help predict CR after AMI,which had high accuracy and was very simple to use.

Comparing the effects of depression,anxiety,and comorbidity on quality-of-life,adverse outcomes,and medical expenditure in Chinese patients with acute coronary syndrome

Background:Depression and anxiety have been correlated with elevated risks for quality-of-life (QOL),adverse outcomes,and medical expenditure in patients with acute coronary syndrome (ACS).However,the relevant data are lacking for Chinese ACS populations,especially regarding different effects of major depression,anxiety,and comorbidity.The objective of this study was to evaluate the dynamic changes of depression and/or anxiety over 12 months and examine the effects of depression,anxiety,and comorbidity on QOL,adverse outcomes,and medical expenditure in Chinese patients with ACS.Methods:For this prospective longitudinal study,a total of 647 patients with ACS were recruited from North China between January 2013 and June 2015.Among them,531 patients (82.1%) completed 12-month follow-ups.Logistic regression model was utilized for analyzing the association of baseline major depression,anxiety,and comorbidity with 12-month all-cause mortality,cardiovascular events,QOL,and health expenditure.Results:During a follow-up period of 12 months,7.3% experienced non-fatal myocardial infarction (MI) and 35.8% cardiac rehospitalization.Baseline comorbidity,rather than major depression/anxiety,strongly predicted poor 12-month QOL as measured by short-form health survey-12 (odds ratio [OR]:1.77,95% confidence interval [CI]:1.22–2.52,P = 0.003).Regarding 12-month non-fatal MI and cardiac re-hospitalization,baseline anxiety (OR:2.83,95% CI:1.33–5.89,P<0.01;OR:4.47,95% CI:1.50–13.00,P<0.01),major depression (OR:2.58,95% CI:1.02–6.15,P<0.05;OR:5.22,95% CI:1.42–17.57,P<0.03),and comorbidity (OR:6.33,95% CI:2.96–13.79,P<0.0001,OR:14.08,95% CI:4.99–41.66,P<0.0001) were all independent predictors,and comorbidity had the highest predictive value.Number of re-hospitalization stay,admission frequency within 12 months and medical expenditure within 2 months were the highest in patients with ACS with comorbidity.Conclusions:Major depression and anxiety may predict 12-month non-fatal MI and cardiac re-hospitalization.However,comorbidity has the highest predictive value with greater medical expenditure and worse QOL in Chinese patients with ACS.And depression with comorbid anxiety may be a new target of mood status in patients with ACS.

Resting heart rate control and prognosis in coronary artery disease patients with hypertension previously treated with bisoprolol:a subgroup analysis of the BISO-CAD study

Background:Resting heart rate(RHR)is considered as a strong predictor of total mortality and hospitalization due to heart failure in hypertension patients.Bisoprolol fumarate,a second-generation beta-adrenoreceptor blockers(β-blocker)is commonly prescribed drug to manage hypertension.The present study was to retrospectively evaluate changes in the average RHR and its association with cardiovascular outcomes in bisoprolol-treated coronary artery disease(CAD)patients from the CAD treated with bisoprolol(BISO-CAD)study who had comorbid hypertension.Methods::We performed ad-hoc analysis for hypertension sub-group of the BISO-CAD study(n=866),which was a phase IV,multination,multi-center,single-arm,observational study carried out from October 2011 to July 2015 across China,South Korea,and Vietnam.Multivariate regression analysis was used to identify factors associated with incidence of composite cardiac clinical outcome(CCCO),the results were presented as adjusted odds ratio(OR)along with 95%confidence interval(CI)and adjusted P value.Results::A total of 681 patients(mean age:64.77±10.33 years)with hypertension from BISO-CAD study were included in the analysis.Bisoprolol improved CCCOs in CAD patients with comorbid hypertension,with RHR<65 and<70 beats/min compared with RHR≥65 and≥75 beats/min,respectively,in the efficacy analysis(EA)set.In addition,it lowered RHR in both intent-to-treat(ITT)and EA groups after 6,12,and 18 months of treatment.Further,RHR 70 to 74 beats/min resulted in significantly higher risk of CCCOs EA set of patients(adjusted OR:4.34;95%CI:1.19-15.89;P=0.03).Also,events of hospitalization due to acute coronary syndrome were higher when RHR 69 to 74 beats/min compared to RHR<69 beats/min in ITT patients.Conclusion::Bisoprolol can effectively reduce RHR in Asian CAD patients with comorbid hypertension and hence,improve CCCO without affecting their blood pressure.

Assessing the association of appropriateness of coronary revascularization and 1-year clinical outcomes for patients with stable coronary artery disease in China

Background:The Chinese appropriate use criteria(AUC)for coronary revascularization was released in 2016 to improve the use of coronary revascularization.This study aimed to evaluate the association between the appropriateness of coronary revascularization based on the Chinese AUC and 1-year outcomes in stable coronary artery disease(CAD)patients.Methods:We conducted a prospective,multi-center cohort study of stable CAD patients with coronary lesion stenosis≥50%.After the classification of appropriateness based on Chinese AUC,patients were categorized into the coronary revascularization group or the medical therapy group based on treatment received.The primary outcome was a composite of death,myocardial infarction,stroke,repeated revascularization,and ischemic symptoms with hospital admission.Results:From August 2016 to August 2017,6085 patients were consecutively enrolled.Coronary revascularization was associated with a lower adjusted hazard of 1-year major adverse cardiovascular and cerebrovascular events(MACCEs;hazard ratio[HR]:0.62;95%confidence interval[CI]:0.45-0.86;P=0.004)than medical therapy in patients with appropriate indications(n=1617).No significant benefit in 1-year MACCEs was found after revascularization compared to after medical therapy in patients with uncertain indications(n=2658,HR:0.81;95%CI:0.52-1.25;P=0.338)and inappropriate indications(n=1810,HR:0.80;95%CI:0.51-1.23;P=0.308).Conclusions:In patients with appropriate indications according to Chinese AUC,coronary revascularization was associated with significantly lower risk of MACCEs at 1 year.No benefit was found in coronary revascularization in patients with inappropriate indications.Our findings provide evidence for using Chinese AUC to guide clinical decision-making.

Expression profile of circular RNAs in epicardial adipose tissue in heart failure

Background:Recent studies have reported circular RNA(circRNA)expression profiles in various tissue types;however,circRNA expression profile in human epicardial adipose tissue(EAT)remains undefined.This work aimed to compare circRNA expression patterns in EAT between the heart failure(HF)and non-HF groups.Methods:RNA-sequencing was carried out to compare circRNA expression patterns in EAT specimens from coronary artery disease cases between the HF and non-HF groups.Quantitative real-time polymerase chain reaction was performed for validation.Comparisons of patient characteristics between the two groups were using t test,Mann-Whitney U test,and Chi-squared test.Results:A total of 141 circRNAs substantially different between the HF and non-HF groups(P<0.05;fold change>2)were detected,including 56 up-regulated and 85 down-regulated.Among them,hsa_circ_0005565 stood out,for it had the highest fold change and was significantly increased in HF patients in quantitative real-time polymerase chain reaction validation.The top highly expressed EAT circRNAs corresponded to genes involved in cell proliferation and inflammatory response,including GSE1,RHOBTB3,HIPK3,UBXN7,PCMTD1,N4BP2L2,CFLAR,EPB41L2,FCHO2,FNDC3B,and SPECC1.The top enriched Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway were positive regulation of metabolic processes and insulin resistance,respectively.Conclusion:These data indicate EAT circRNAs may contribute to the pathogenesis of metabolic disorders causing HF.