BACKGROUND AND AIMS:SARS-CoV-2 exposure has been linked to cardiovascular complications, including atrial fibrillation (AF), but the host pathways coupling viral factors to atrial remodeling and AF vulnerability remain incompletely understood. METHODS:We integrated multi-cohort human transcriptomes from SARS-CoV-2-infected cardiac models and AF tissues, applied WGCNA and machine-learning-based feature selection, and profiled immune infiltration. To approximate a sustained low-grade inflammatory milieu relevant to prolonged COVID-19-related cardiovascular sequelae, mice with cardiac SARS-CoV-2 N expression underwent repeated low-dose LPS administration. JUNB loss-of-function was evaluated by rAAV9-mediated cardiac knockdown, with echocardiographic, electrophysiological, histological, and molecular phenotyping. Mechanistic studies were performed in modified cardiomyocytes. RESULTS:Integrated transcriptomic analyses identified JUNB as a shared hub associated with SARS-CoV-2-related cardiac signaling and AF, with enrichment of inflammatory pathways relevant to atrial remodeling. In the chronic inflammatory model, cardiac N expression exacerbated atrial enlargement, inflammatory-fibrotic remodeling, AF inducibility and duration, and AERP shortening, whereas cardiac JUNB knockdown attenuated these changes. Mechanistically, co-immunoprecipitation and in-cell ubiquitination assays showed that SARS-CoV-2 N enhanced the JUNB-RCHY1 interaction, promoting K63-linked ubiquitination and stabilizing JUNB. Site-mapping and functional assays identified K36 as the dominant ubiquitination site required for N-driven JUNB stabilization, TNF-α/NF-κB activation, and downstream inflammatory and fibrotic gene programs. CONCLUSION:Cardiac SARS-CoV-2 N protein promotes atrial inflammatory-fibrotic remodeling and AF vulnerability under chronic inflammatory conditions relevant to post-acute or prolonged COVID-19-related cardiovascular sequelae through RCHY1-dependent ubiquitination and stabilization of JUNB, identifying the N-RCHY1-JUNB axis as a mechanistically defined pathway for future therapeutic investigation.

Background: Premature ventricular complex (PVC) induced cardiomyopathy (PVC-CMP) and exacerbated left ventricular systolic dysfunction (LVSD) are common in clinical scenarios. However, their precise risk factors are currently unclear. Methods: We performed a systematic review of PubMed, EMBASE, Web of Science, and Chinese-based literature database (CBM) to identify observational studies describing the factors associated with PVC-CMP and post-ablation LVSD reversibility. A total of 25 and 12 studies, involving 4863 and 884 subjects, respectively, were eligible. We calculated pooled multifactorial odds ratios (OR) and 95% confidence intervals (CI) for each parameter using random-effects and fixed-effects models. Results: The results showed that 3 independent risk factors were associated with PVC-CMP: being asymptomatic (OR and 95% CI: 3.04 [2.13, 4.34]), interpolation (OR and 95% CI: 2.47 [1.25, 4.92]), and epicardial origin (epi-origin) (OR and 95% CI: 3.04 [2.13, 4.34]). Additionally, 2 factors were significantly correlated with post-ablation LVSD reversibility: sinus QRS wave duration (QRSd) (OR and 95% CI: 0.95 [0.93, 0.97]) and PVC burden (OR and 95% CI: 1.09 [0.97, 1.23]). Conclusions: the relatively consistent independent risk factors for PVC-CMP and post-ablation LVSD reversibility are asymptomatic status, interpolation, epicardial origin, PVC burden, and sinus QRS duration, respectively.

目的 观察使用膀胱测温代替直肠测温控制医用降温毯启动和停止的效果.方法 在医用降温毯中加装适配测温尿管,将测温尿管监测的膀胱温信号传输至降温毯,替代直接测量的肛温探头控制启停.将改良后的降温毯与计量专用测温仪进行数据校准.选取高热重症患者32例为研究对象,应用改进后的降温毯行降温治疗;每4 h观察并记录膀胱温和直肠温,分析膀胱温和直肠温在重症患者降温监测中的一致性;进一步分析护士在使用改良降温毯前后执行安全降温的正确率.结果 改良后的降温毯与计量专用测温仪测得的温度差异无统计学意义(P＞0.05);改良降温毯测得的膀胱温与水银温度计直接测得的直肠温呈高度正相关(r=0.99,P＜0.05),在95％一致性界限范围内二者差值的绝对值最大为0.16℃,平均差值为0.01℃,具有高度一致性;护士因测量部位选择不正确造成降温毯温控启停信号错误的发生率为0.结论 改良降温毯能够通过膀胱测温替代直肠温,准确地为重症患者执行降温治疗,保证患者舒适度的同时,提升了护士执行降温毯操作的正确性和安全性.

Background Three-dimensional activation mapping during sinus rhythm can demonstrate the earliest atrial activation (EAA) site, which could be the sinoatrial node (SAN). We aimed to compare the electroanatomical characteristics of superior vena cava (SVC), myocardial sleeve, and SAN between patients with atrial fibrillation (AF) and non-AF. Materials and methods In this study, 136 patients with AF were assigned to the study group, and 20 patients with premature ventricular contractions (PVCs) who had no history of AF were assigned to the control group. The right atrium (RA) and SVC anatomical activation models were constructed, and the EAA of SAN was delineated using the CARTO3 mapping system. The length of the SVC myocardial sleeve (LSVC) was measured. Results Of the 136 patients, 93 patients had paroxysmal AF (PAF), and 43 patients had persistent AF (PsAF). The LSVC was not significantly different among AF and non-AF, PAF, and PsAF. The LSVC in men was longer than in women (42.1 ± 9.4 mm vs. 35.4 ± 8.1 mm, p < 0.001). The LSVC was longer in patients with EAA of SAN above the RA-SVC junction than in those with below the RA-SVC junction (p < 0.001). The EAA of SAN was below the RA-SVC junction in 64/136 (47.1%) and was above the junction in 72/136 (52.9%) patients with AF. The spatial distribution of the EAA of SAN between PAF and PsAF was not different. There was a trend of statistical difference in the distribution of the EAA of SAN between PsAF and non-AF. Conclusion The EAA of SAN was located in the SVC in most of the patients, especially in patients with PsAF.

To the Editor: Dilated cardiomyopathy (DCM) is a type of primary myocardial disease with unknown etiology.[1] It is a disorder of the heart muscle mainly characterized by left ventricular dilation and systolic dysfunction, resulting from the response of the myocardium to genetic and environmental insults. The clinical manifestations are progressive heart failure, arrhythmia, thromboembolism, and even sudden death. The morbidity and mortality of DCM have been steadily increasing, which has become one of the main causes of death in cardiomyopathy. DCM may involve the conduction system and is often associated with various types of arrhythmias, such as atrial fibrillation (AF).[2] AF can increase the risk of vascular embolism. Studies have shown that patients with AF have a five-fold increased incidence of stroke and a two-fold increased mortality. About 15%-20% of ischemic strokes are caused by AF. The hemodynamic changes and increased risk of thromboembolic events caused by AF in patients with DCM increase their disability rate and mortality. Therefore, early prediction and intervention of AF in patients with DCM can effectively improve the prognosis and quality of life. An accurate risk classification of AF in patients with DCM is very important to guide intervention. The nomogram is based on the results of multivariate logistic regression analysis. It integrates multiple prediction indexes and visualizes the correlation among various variables for the outcome prediction in the form of a graph.[3] In this study, we aimed to identify patients with DCM who are likely to develop AF by developing a nomogram. Data of consecutive DCM patients were collected in this study at the First Affiliated Hospital of Nanjing Medical University from September 2009 to November 2015. Inclusion criteria were (1) left ventricular end-diastolic dimension (LVEDd) >5.5 cm in male and LVEDd >5.0 cm in female, or LVEDd >117% (>2 standard deviation [SD] of the predicted value of 112% corrected for age and body surface area); (2) left ventricular fractional shortening <25% (>2 SD) and/or left ventricular ejection fraction (LVEF) <45% (>2 SD); (3) no AF was found in the previous medical records and electrocardiogram (ECG) data. Exclusion criteria were (1) patients with hypertensive heart disease, valvular heart disease, congenital heart disease, or ischemic heart disease; (2) children <18 years of age and alcoholics; (3) severe hepatic and renal insufficiency. Basic clinical characteristics were collected by reviewing the electronic medical records of the enrolled patients. Patients were followed up at the clinical department or hospital every 3 months in this study. Follow-up information and death events were recorded. The primary endpoint was AF. AF is shown by ECG or a 24–hours dynamic ECG. Data were presented as mean ± SD or median (interquartile range). Categorical variables were presented as numbers with percentages. To generate the nomogram for the training set, multivariable logistic regression analysis was performed to predict the probability of AF using a forward stepwise method that included all variables with a probability (P) value <0.20 in the univariable analysis. Variables with P values that were <0.05 in the multivariable logistic regression were entered into the prediction model. The main outcome of this study was the risk of AF based on the baseline characteristics. The multivariate logistic regression model was used to estimate the odds ratio (OR) and 95% confidence intervals (CIs) of the risk of AF in the model. Theareaunder theROC curve (AUC) canbeconsidered as a generalization of the area under the receiver operating characteristic (ROC) curve and is calculated by analyzing all possible patients. The calibration of the model was validated by Hosmer-Lemeshow goodness-of-fittest (P> 0.05) and calibration plots. The clinical value of the predictive model was tested using a decision curve analysis (DCA). Nomogram was developed according to the logistic regression by the software R 3.6.3. (The R Foundation; http://www.r-project.org;version3.6.3). All P value < 0.05 (two tail) was considered statistically significant. Between September 2009 and December 2015, a total of 243 consecutive patients with DCM were admitted to the First Affiliated Hospital of Nanjing Medical University. Thirty patients with missing data and 16 patients lost to follow-up were excluded from this study. The remaining 197 patients were eligible for analysis. The demographics and clinical characteristics for the training set (n= 138, mean age = 56.4 ± 14.9 years, 80.4% male) and the test set (n = 59, mean age = 58.1 ± 14.7 years, 74.6% male) are listed in Supplementary Table 1, https://links.lww.com/CM9/A872. In the training set, 30 patients (21.7%) developed AF, whereas in the test set, 13 patients (22%) developed AF. The median follow-up was 92.9 (66.5–172.6) months. Multivariate analyses demonstrated that age (OR: 3.91, 95% CI: 1.71–8.93, P < 0.01), weight (OR: 5.11, 95% CI: 2.23–11.70, P < 0.01), thyroid stimulating hormone (TSH) (OR: 1.55, 95% CI: 1.11–2.16, P = 0.01), d-dimer (D-D) (OR: 1.47, 95% CI: 1.06–2.03, P = 0.02), left atrial diameter (LAD) (OR: 2.34, 95% CI: 1.04–5.25, P = 0.04), and LVEF (OR: 0.33, 95% CI: 0.15–0.75, P < 0.01) were independent risk factors for AF in patients with DCM [Supplementary Table 2, https://links.lww.com/CM9/A872]. The nomogram was developed by assigning a graphic initial score to each of the six independent prognostic factors (age, weight, TSH, D-D, LAD, and LVEF), with a point range from 0 to 100. The scores for all variables were then added to obtain the total score, and a vertical line was drawn from the total points row to indicate the estimated probability of AF being present [Figure 1]. It was predicted that a higher total score in the nomogram was associated with a higher likelihood of AF, whereas a lower total score was associated with a lower likelihood of AF.Figure 1: Nomogram used for predicting AF in patients with DCM. The final score (ie, total points) is calculated as the sum of the individual score of each of the six variables included in the nomogram. AF: Atrial fibrillation; DCM: Dilated cardiomyopathy; D-D: D-dimer; LAD: Left atrial diameter; LVEF: Left ventricular ejection fraction; TSH: Thyroid stimulating hormone.The AUC-ROC was 0.931 (95% CI: 0.86–0.99) in the training set and 0.90 (95% CI: 0.80–0.95) in the test set [Supplementary Figure 1, https://links.lww.com/CM9/A872]. The nomogram model was calibrated using the Hosmer-Lemeshow goodness-of-fit test and a calibration plot. The Hosmer-Lemeshow test revealed high concordance between the predicted and observed probabilities for both the training set (χ2 = 7.83, df = 8, P = 0.45) and the test set (χ2 = 8.51, df = 8, P = 0.49). The calibration plot also showed good agreement between the predicted and observed outcomes for the training and test sets [Supplementary Figure 2, https://links.lww.com/CM9/A872]. DCA was applied to assess the clinical validity of the nomogram [Supplementary Figure 3, https://links.lww.com/CM9/A872], which corroborated good clinical applicability of the nomogram in predicting AF because the ranges of threshold probabilities were wide and practical for the training and test sets. The main findings of this study were as follows: (1) DCM patients were susceptible to AF (21.8%). (2) Age, weight, TSH, D-D, LAD, and LVEF were independent predictors for AF occurrence in DCM patients. (3) The nomogram was feasible for predicting AF in DCM patients at our hospital and showed good predictive performance. Studies have shown that patients with DCM are susceptible to AF. This may be related to cardiac degenerative diseases, such as enlargement of cardiomyocytes, reduced atrioventricular compliance, and degeneration of fibrous tissue in patients with DCM.[4] Due to the non-regeneration of myocardial cells, atrial enlargement is often accompanied by the occurrence of cardiac chamber fibrosis, forming focal or patch-like scar, leading to slowing of local conduction speed, resulting in heterogeneity of electrical impulse conduction, and irregular impulse conduction of ectopic lesions with rapid discharge, which contributes to the occurrence of AF. AF leads to uncoordinated atrioventricular contraction. The atria cannot contract effectively and blood cannot be pumped out by the heart in a timely manner. Ventricular diastolic blood flow cannot be completely filled and ventricular filling volume decreases.[5] The above adverse effects on hemodynamics eventually lead to reduced perfusion of the heart, brain, kidney, and other important organs, which can progress to multi-organ damage and failure in the long-term. We developed and validated a new AF risk model primarily based on clinical baseline data and biomarkers and demonstrated that the model provides an acceptable level of performance for predicting AF in patients with DCM. The nomogram used these six independent variables to predict AF, which are easily and readily obtainable during the patients’ admission to the hospital. This nomogram for the individualized prediction of the probability of AF in patients with DCM. Nomogram has emerged as a simpler and more advanced tool for prediction. It is a pictorial representation of a statistical predictive model that generates a numerical probability of a clinical event, so it is more accurate.[6] The nomogram developed in this study assigns an accurate probability (from 0.1% to 90%) of AF outcome. The nomogram can provide individualized and highly estimated AF risk by combining six independent variables and assigning an appropriate weight to each variable based on its prognostic value, making it easy to use and facilitates management-related decision making for doctors. Our prediction model showed that older patients and those with severe or critical DCM had more frequent AF, which was associated with cardiac degenerative changes, such as cardiac enlargement, cardiomyocyte degeneration, and increased fibrous tissue resulting in electrical remodeling. Multivariate logistic regression analysis showed that LAD, left atrial enlargement, was one of the risk factors for DCM with AF, which was consistent with the previous reports. All the animal models with atrial fibrosis showed left atrium enlargement. Hence, we hypothesized that atrial enlargement and atrial fibrosis coexist and influence each other. Left atrial enlargement and fibrosis are concomitant in DCM patients, which can lead to atrial structural remodeling and AF.[7] Meanwhile, this prediction model also found that the lower the LVEF, the more frequent the AF. This may be associated with the occurrence of heart failure in patients with DCM, resulting in the reduced effective circulation of blood volume, reduced renal blood flow, and activation of the renin-angiotensin system. Elevated angiotensin II directly causes myocardial cell apoptosis and interstitial fibrosis, and further accelerates atrial structural remodeling. In patients with DCM, abnormal hemorheology is caused by the enlargement of the heart and weakened ventricular pulse, which makes the blood hypercoagulable and increases the D-2 polymer level.[8] This study found that elevated D-2 levels were associated with an increased risk of AF in patients with DCM. Previous studies showed that DCM patients typically have concomitant hyperthyroidism and heart disease; wherein TSH is decreased and thyroid hormone is increased, which can directly affect the cardiac muscle, decrease the sinoatrial node action potential time, increase atrial muscle excitability, and decrease refractory period. This is likely to lead to AF. In contrast, our study found that if TSH is higher in patients with DCM, they are more susceptible to AF, which may be due to the small sample size. Hence, we need to expand the sample size in future studies. This study had some limitations. First, this was a singlecenter retrospective study with a small sample size, which might have limited the statistical power of the results. Second, our model has not been validated in external cohorts. Third, our model cannot distinguish various subtypes of AF, such as persistent and paroxysmal AF. Further studies addressing these limitations are necessary so that this nomogram could be improved and has a better predictive performance. Conflict of Interest None. Funding This work was supported by the 333 project of Jiangsu Province (Grant/Award Number: BRA2017544); the Project of Qinghai science and Technology Department (Grant/Award Number: 2018-SF-114); Zhongnanshan Medical Foundation of Guangdong Province (No. ZNSA-2020017) and the Guiding project of Qinghai Health Commission (Grant/Award Number: 2019-wjzdx-35).

Abstract Background Mesenchymal stromal cells (MSCs) activated with IFN-γ elicit stronger physical effects. Exosomes (Exos) secreted from MSCs show protective effects against myocardial injury. This study aimed to determine whether Exos derived from IFN-γ-treated MSCs exhibit more potent cardioprotective function and the underlying mechanisms. Methods H9c2 cells or human umbilical vein endothelial cells (HUVECs) were treated with Exos isolated from MSCs (Ctrl-Exo) or IFN-γ-primed MSCs (IFN-γ-Exo) under oxygen and glucose deprivation (OGD) conditions in vitro and in vivo in an infarcted rat heart. RNA sequencing was used to identify differentially expressed functional transcription factors (TFs). Quantitative reverse transcription-PCR (qPCR) was used to confirm the upregulated TFs and miRNA in IFN-γ-primed MSCs. Dual-luciferase reporter gene assay was used to analyze the transcriptional regulation of miRNAs by STAT1. The target of miR-21-5p (miR-21) was determined by luciferase reporter assays and qPCR. The function of BTG2 was verified in vitro under OGD conditions. Result IFN-γ-Exo accelerated migration and tube-like structure formation and prevented OGD-induced apoptosis in H9c2. Similarly, IFN-γ-Exo treatment caused a decrease in fibrosis, reduced cardiomyocyte apoptosis, and improved cardiac function compared to Ctrl-Exo treatment. MiR-21 was significantly upregulated in IFN-γ-primed MSCs and IFN-γ-Exo. STAT1 transcriptionally induced miR-21 expression. Up-regulated miR-21 could inhibit BTG anti-proliferation factor 2 (BTG2) expressions. BTG2 promoted H9c2 cell apoptosis and reversed the protective effects of miR-21 under OGD conditions. Conclusion IFN-γ-Exo showed enhanced therapeutic efficacy against acute MI, possibly by promoting angiogenesis and reducing apoptosis by upregulating miR-21, which directly targeted BTG2.

Objective:To evaluate the outcome of the patients receiving dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) delivered by first-responders who witnessed the out-of-hospital cardiac arrest (OHCA) before the Emergency Medical Service (EMS) arrived.Methods:We performed a search of the relevant literature exploring major scientific databases. We assessed the quality of the included cohort study according to the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. Meta-analysis was performed on three outcome indicators (recovery of spontaneous circulation survival to hospital discharge and survival with favourable neurologic outcome) using the Revman5.3 software.Results:A total of 21 studies with 349 822 patients were selected for the meta-analysis, including 182 125 patients in the DA-CPR group and 167 697 in the CPR-only group. The meta-analysis showed no significant difference between the DA-CPR and CPR-only groups in ROSC [ RR=1.10, 95% confidence interval ( CI): 0.94-1.29, P=0.24], survival to hospital discharge ( RR=1.10, 95% CI: 0.90-1.34, P=0.34) and survival with favourable neurologic outcome ( RR=1.01, 95% CI: 0.79-1.28, P=0.97) of the patients in America, Japan and Korea. However, there was a significant difference between the DA-CPR and the CPR-only groups in ROSC ( RR=2.61, 95% CI:1.53-4.46, P=0.0005), survival to hospital discharge( RR=6.08, 95% CI: 1.84-20.04, P=0.003), and survival with favourable neurologic outcome( RR=9.76, 95% CI: 1.87-51.02, P=0.007) of the patients in China. Conclusions:The overall effect of DA-CPR is significantly different for each country. In detail, DA-CPR offers a survival advantage (Return of spontaneous circulation, survival to hospital discharge and survival with favourable neurologic outcome) over CPR alone in China but no advantage in developed countries.

Objective:To evaluate the effect of mechanical chest compression device in patients with cardiac arrest.Methods:The relevant literatures about mechanical cardiopulmonary resuscitation and manual cardiopulmonary resuscitation were systematically searched from China Knowledge Network (CNKI), VIP, Wanfang, PubMed, Web of Science and other databases. The effective data were extracted and analyzed by RevMan5.3 software.Results:A total of 20 clinical studies involving 29 727 patients were included, of which 11 104 patients received mechanical cardiopulmonary resuscitation and 18 623 patients received traditional manual cardiopulmonary resuscitation. The results of meta-analysis showed that mechanical cardiopulmonary resuscitation could not effectively improve the restoration of spontaneous circulation (ROSC) rate, admission survival rate, discharge survival rate and neurological prognosis in patients with cardiac arrest compared with manual cardiopulmonary resuscitation. ROSC occurrence rate ( RR=1.10, 95% CI: 0.99-1.23, P<0.01), admission survival rate ( RR=1.01, 95% CI: 0.95-1.08, P=0.67), discharge survival rate ( RR=1.00, 95% CI: 0.86-1.15, P=0.14), and good neurological function rate ( RR=0.81, 95% CI: 0.61-1.06, P=0.69) showed no significant differences between the mechanical cardiopulmonary resuscitation and manual cardiopulmonary resuscitation. Conclusions:Mechanical chest compression device has no advantage compared with manual cardiopulmonary resuscitation. Mechanical cardiopulmonary resuscitation is not recommended to completely replace manual chest compression in cardiopulmonary resuscitation.

Rationale: With the widespread development of the interventional technique for cardiovascular diseases and the widespread use of contrast medium (CM), the incidence of contrast-induced nephropathy (CIN) has been increasing, which is associated with poor prognosis for cardiovascular diseases. This study aims to explore the effect of circulating exosomal microRNA from patients with myocardial infarction (MI) on CIN and related molecular mechanism. Methods: A rat MI model was established by ligating the left anterior descending coronary artery. Circulating exosomes were isolated from control (Exo-NC) and MI rats (Exo-MI) using a commercial kit. The in vivo and in vitro models of CIN were created using iodixanol. Reverse transcription quantitative PCR (RT-qPCR) was utilized to detect the expression of miR-1-3p. Western blot (WB) was used to detect the expression of exosomal surface markers, and apoptosis-related and autophagy-related proteins. The apoptosis rate was examined by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining and flow cytometry (FC). Transmission electron microscopy (TEM) was utilized to observe the exosomes and autophagosomes. Rat kidney injury was assessed by hematoxylin and eosin (H&E) staining and kidney injury molecule-1 (KIM-1) immunohistochemical staining. Renal function of rats was assessed by detecting the levels of blood urea nitrogen (BUN) and serum creatinine (Cr). The dual luciferase reporter assay was performed to identify the target gene of miR-1-3p. Results: The treatment of CM induced NRK-52E cell damage, which manifested as enhanced cell autophagy and enhanced apoptosis. The Exo-MI treatment significantly inhibited the CM-induced autophagy and apoptosis of NRK-52E cells. Furthermore, the Exo-MI treatment increased the Bcl-2 expression, but decreased the Bax expression and the ratio of LC3II/LC3I. Furthermore, the results of the TUNEL staining and FC showed that Exo-MI can reduce apoptotic rate. Through TEM, it was found that Exo-MI reduced the number of autophagosomes in NRK-52E cells. The rescue experiments revealed that the function of Exo-MI is to inhibit the CM-induced autophagy and apoptosis of NRK-52E cells, which can be inhibited by the miR-1-3p inhibitor. Furthermore, it was found that the overexpression of miR-1-3p can also inhibit the CM-induced autophagy and apoptosis of NRK-52E cells. Through dual luciferase reporter assay, ATG13 was found to be the target of miR-1-3p. In addition, the overexpression of miR-1-3p significantly reversed the CM-induced decrease in phosphorylation level of AKT. Furthermore, ATG13 silencing can also inhibit the CM-induced autophagy and apoptosis of NRK-52E cells. In vivo, Exo-MI significantly alleviated the renal injury, reduced the renal fibrosis, and improved the renal function of CIN rats. Conclusion: The circulating exosomal miR-1-3p after MI inhibited the CM-induced apoptosis and autophagy of renal tubular epithelial cells, and improved the renal function of rats by targeting ATG13 and activating the AKT signaling pathway.

Background: Mesenchymal stem cells (MSCs) activated with IFN-γ elicit more powerful physical effects. Exosomes (Exos) secreted from MSCs have protective against myocardial injury. The aim of this study was to investigate whether Exsos derived from IFN-γ-pretreated MSCs exhibit more potent cardioprotective function and the underlying mechanisms. Methods: Exos were isolated from MSCs (Ctrl-Exo) and IFN-γ-primed MSCs (IFN-γ-Exo) and were then delivered to H9c2 cells or human umbilical vein endothelial cells (HUVECs) in vitro under oxygen and glucose deprivation (OGD) condition or in vivo in an infarcted rat heart. RNA sequencing was to identify the different expressed functional transcription factor (TF). Quantitative reverse transcription-PCR (qPCR) was to confirm the upregulated TF and miRNA in IFN-γ-primed MSCs. Dual-luciferase reporter gene assay were to analyze the transcriptional regulation of miRNAs by STAT1. The target of miR-21-5p (miR-21) was disclosed by luciferase reporter assays and qPCR. The function of BTG2 was verified in vitro under OGD condition. Result: IFN-γ-Exo accelerated migration, tube-like structure formation, and prevented H9c2 from OGD-induced apoptosis. Similarly, IFN-γ-Exo leaded to further reduction in fibrosis size, reduced cardiomyocyte apoptosis and improved cardiac function compared to Ctrl-Exo. miR-21 was significantly upregulated in both IFN-γ-primed MSCs and IFN-γ-Exo. STAT1 transcriptionally induced miR-21 expression. Up-regulated miR-21 can inhibit the expression of BTG2. BTG2 promoted H9c2 cells apoptosis and reversed the protective effect of miR-21 under OGD environment. Conclusion: IFN-γ-Exo have enhanced therapeutic efficacy against acute MI possibly through promoting angiogenesis and anti-apoptotic effect through increasing the level of miR-21, which directly targeted on BTG2.

Background Exosome transplantation is a promising cell-free therapeutic approach for the treatment of ischemic heart disease. The purpose of this study was to explore whether exosomes derived from Macrophage migration inhibitory factor (MIF) engineered umbilical cord MSCs (ucMSCs) exhibit superior cardioprotective effects in a rat model of AMI and reveal the mechanisms underlying it. Results Exosomes isolated from ucMSCs (MSC-Exo), MIF engineered ucMSCs (MIF-Exo) and MIF downregulated ucMSCs (siMIF-Exo) were used to investigate cellular protective function in human umbilical vein endothelial cells (HUVECs) and H9C2 cardiomyocytes under hypoxia and serum deprivation (H/SD) and infarcted hearts in rats. Compared with MSC-Exo and siMIF-Exo, MIF-Exo significantly enhanced proliferation, migration, and angiogenesis of HUVECs and inhibited H9C2 cardiomyocyte apoptosis under H/SD in vitro . MIF-Exo also significantly inhibited cardiomyocyte apoptosis, reduced fibrotic area, and improved cardiac function as measured by echocardiography in infarcted rats in vivo . Exosomal miRNAs sequencing and qRT-PCR confirmed miRNA-133a-3p significantly increased in MIF-Exo. The biological effects of HUVECs and H9C2 cardiomyocytes were attenuated with incubation of MIF-Exo and miR-133a-3p inhibitors. These effects were accentuated with incubation of siMIF-Exo and miR-133a-3p mimics that increased the phosphorylation of AKT protein in these cells. Conclusion MIF-Exo can provide cardioprotective effects by promoting angiogenesis, inhibiting apoptosis, reducing fibrosis, and preserving heart function in vitro and in vivo . The mechanism in the biological activities of MIF-Exo involves miR-133a-3p and the downstream AKT signaling pathway.

目的 探讨左右心耳盐水灌注导管消融时,不同压力对组织消融损伤程度的影响.方法 将6头猪左右心耳组织,置于水浴37℃水浴槽中.根据导管压力分为A组(5 g)、B组(15 g)和C组(20 g).消融功率、灌注速度和温度分别设置为:30 W、17 m l/m in和43℃.每个心耳消融4次,共计消融48次,每组消融16次.实验中测量组织厚度;记录消融开始、结束阻抗;最大功率;最大温度;组织表面最大损伤宽度与长度;是否达到透壁损伤;是否发生pop等参数.结果 消融最大损伤宽度B组显著高于A组(P=0.05);C组与A组相比,差异更大(P=0.01),C组较B组有增加趋势,但无显著差异(P>0.05).消融最大损伤长度、最大损伤面积随着压力增加而增加,但在三组之间无显著差异(P均>0.05).透壁性损伤在A、B、C三组分别为75.0％,93.8％,100.0％(P=0.02).Po p发生率在A、B、C三组分别为25.0％,31.3％ 和43.8％(P=0.52).消融开始时阻抗、最大阻抗与最小阻抗随着消融导管与组织之间压力增加而增加.B组较A组相比,有显著差异(P=0.001),C组较A组相比,差异更大(P=0.000),但C组较B组相比,无显著差异(P>0.05).结论 心耳组织消融时,压力、功率、灌注速度分别设置为15 g、30 W和17 m l/m in可以获得较高的透壁性与较低po p发生率.

Ischemic cardiomyopathy seriously endangers human health leading to a poor prognosis. Acute myocardial infarction (AMI) is the primary etiology, and the pathophysiological process concludes with the death of cardiomyocytes caused by acute and persistent ischemia and hypoxia in the coronary arteries. We identified a circRNA (circSNRK) which was downregulated in rats with myocardial infarction (MI), however, the role it plays in the MI environment is still unclear. This study contained experiments to investigate the role of circSNRK in the regulation of cardiac survival and explore the mechanisms underlying circSNRK functions. Quantitative real-time PCR (qRT-PCR) was performed to determine the circSNRK expression patterns in hearts. Gain-of-function assays were also conducted in vitro and in vivo to determine the role of circSNRK in cardiac repair. qRT-PCR, western blot, and luciferase reporter assays were used to study circRNA interactions with micro RNAs (miRNAs). Overexpression of circSNRK in cardiomyocytes reduced apoptosis and increased proliferation. Adeno associated virus 9 (AAV9) mediated myocardium overexpression of circSNRK in post MI hearts reduced cardiomyocyte apoptosis, promoted cardiomyocyte proliferation, enhanced angiogenesis, and improved cardiac functions. Overall, upregulation of circSNRK promotes cardiac survival and functional recovery after MI. Mechanistically, circSNRK regulates cardiomyocyte apoptosis and proliferation by acting as a miR-103-3p sponge and inducing increased expression of SNRK which can bind GSK3β to regulate its phosphorylated activity. And thus circSNRK may be a promising therapeutic target for improving clinical prognosis after MI.

Exosomes (Exo) secreted from mesenchymal stem cells (hMSCs) are protective against myocardial injury. The purpose of the study was to investigate the role and mechanisms by which exosomes promote cardiomyocyte survival and function following myocardial infarction (MI). hMSCs were cultured under hypoxic and normoxic conditions. Hypoxia-conditioned hMSC-derived exosomes (Hypo-Exo) and normoxic-conditioned hMSC-derived exosomes (Nor-Exo) were collected and intramyocardially injected into rats with MI. The therapeutic effects of Hypo-Exo and Nor-Exo were evaluated after 4 weeks. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of candidate long noncoding RNA urothelial carcinoma associated 1 (lncRNA-UCA1) in Nor-Exo and Hypo-Exo. Intramyocardial injection of lncRNA-UCA1-knockdown-Hypo-Exo in a rat model of MI was then performed and the cardiac function was characterized. The target and downstream of the molecular mechanism lncRNA-UCA1 was disclosed by luciferase reporter assays and western blot. Circulating exosomal lncRNA-UCA1 level in AMI patients and healthy volunteers was assessed. We found that (1) hMSC exosomal (from hypoxic and normoxic conditions) cardioprotection in vitro and in vivo correlated with the presence of encapsulated lncRNA-UCA1 in exosomes; (2) lncRNA-UCA1 targeted miR-873 via sponging, reducing the latter's suppressive effects on its target XIAP, and this translated into AMPK phosphorylation and increased level of the antiapoptotic protein BCL2; and (3) plasma derived from patients with AMI contained exosomes enriched with the lncRNA-UCA1, unlike that from normal subjects. This study demonstrates that Hypo-Exo lncRNA-UCA1 plays a cardioprotective role via the miR-873-5p/XIAP axis and circulating exosomal lncRNA-UCA1 may be a promising novel biomarker for the diagnosis of AMI.

目的 探讨新疆克州少数民族急性心肌梗死(AMI)病人的临床特点. 方法 收集南京医科大学附属克州人民医院2017年1月至2019年1月住院治疗的192例AMI病人,分为汉族组及少数民族组(维吾尔族及柯尔克孜族),少数民族非老年组及老年组,比较不同组别病人之间临床特征的差异. 结果 少数民族组病人的BMI、饮酒率、血压,WBC、RBC及PLT计数,心肌肌钙蛋白T(cTnT)、BNP水平均高于汉族组病人,既往“高血压”病史比例、 HDL-C水平及三支病变比例均低于汉族组病人(P＜0.05或P＜0.01).少数民族非老年组病人的男性比例、经皮冠状动脉介入术(PCI)史比例及TG水平均高于老年组病人,BNP水平低于老年组病人(P＜0.05或P＜0.01).结论 新疆克州少数民族AMI病人与汉族病人的临床特点存在差异,可能与生活方式、饮食习惯及遗传因素有关.

Abstract Background The purpose of this study was to explore whether exosomes derived from MIF engineered umbilical cord MSCs (ucMSCs) exhibit better cardioprotective effects in a rat model of AMI and the mechanisms underlying it. Results Exosomes isolated from ucMSCs (MSC-Exo), MIF engineered ucMSCs (MIF-Exo) and MIF down-regulated ucMSCs (siMIF-Exo) were used to investigate cellular protective function in human umbilical vein endothelial cells (HUVECs) and H9C2 cardiomyocytes under hypoxia and serum deprivation (H/SD) and infarcted hearts in rats. Compared with MSC-Exo and siMIF-Exo, MIF-Exo significantly enhanced proliferation, migration and angiogenesis of HUVECs and inhibited H9C2 cardiomyocytes apoptosis under H/SD in vitro; MIF-Exo also significantly inhibited cardiomyocytes apoptosis, reduced fibrosis area and improved cardiac function in infarcted rats in vivo. Exosomal miRNAs sequence and qRT-PCR confirmed miRNA-133a-3p remarkably increased in MIF-Exo. The biological effects of HUVECs and H9C2 cardiomyocytes were attenuated with incubation of MIF-Exo and miR-133a-3p inhibitors. And these effects were accentuated with incubation of siMIF-Exo and miR-133a-3p mimics, followed by p-AKT protein level up-regulated. Conclusion MIF-Exo enhance the effects on promoting angiogenesis, inhibiting apoptosis, reducing fibrosis and preserving heart function, in vitro and in vivo. The miR-133a-3p and its downstream AKT signal pathway were involved in these biological activities of MIF-Exo.

目的:对比导管介入封堵与胸部微创封堵治疗房间隔缺损在手术效果方面的差异.方法:通过计算机检索中国知网、万方、维普、PubMed、Embase和The Cochrane Library等数据库,搜索关于导管介入封堵与经胸小切口外科手术封堵和机器人技术经胸微创封堵治疗房间隔缺损的手术效果的研究文献,检索时限为2000年1月-2020年7月.应用RevMan 5.3软件进行Meta分析.结果:共纳入13个研究3603例患者,Meta分析结果显示,经导管介入封堵组治疗房间隔缺损对比胸部微创组手术封堵成功率(OR=0.30,95％CI:0.14～0.62,P＜0.05)、ICU停留时间(MD=-6.49,95％CI:-7.27～-5.72,P＜0.05)、术后心房颤动(房颤)发生率(OR=2.80,95％CI:1.26～6.18,P＜0.05)、围术期并发症发生率(OR =0.39,95％CI:0.21～0.74,P＜0.05)、手术时间(MD=-11.27,95％CI:-13.62～-8.92,P＜0.05)和住院时间(MD=-2.03,95％CI:-2.49～-1.56,P＜0.05)有明显差异.两组的残余分流发生率(OR=1.57,95％CI:0.95～2.61,P＞0.05)和术后心律失常发生率(OR=0.21,95％CI:0.02～1.76,P＞0.05)无明显差异.结论:经导管介入封堵手术切口小且美观,围术期并发症发生率小,手术时间、ICU停留时间及住院时间短,对患者创伤小,且术后恢复快.胸部微创手术封堵成功率稍大,适应证较广泛,术后房颤发生较少.经导管介入封堵和胸部微创手术在残余分流发生率、术后心律失常发生率上无统计学差异.

The composition and biological activity of donor cells is largely determined by the exosomes they secrete. In this study, we isolated exosomes from young (Young-Exo) and aged (Age-Exo) mesenchymal stem cells (MSCs) and compared their regeneration activity. Young Exo MSCs were more efficient than Aged-Exo at promoting the formation of endothelial tube, reducing fibrosis, and inhibiting apoptosis of cardiomyocytes in vitro; and improving cardiac structure and function in vivo in the hearts of rats following myocardial infarction (MI). MicroRNA sequencing and polymerase chain reaction (PCR) analysis revealed that miR-221-3p was significantly down-regulated in Aged-Exo. The aged MSCs were rejuvenated and their reparative cardiac ability restored when miR-221-3p was overexpressed in Aged-Exo. The protective effect was lost when miR-221-3p expression was knocked down in Young-Exo. These effects of miR-221-3p were achieved through enhancing Akt kinase activity by inhibiting phosphatase and tensin homolog (PTEN). In conclusion, exosomal miR-221-3p secreted from Aged MSCs attenuated the function of angiogenesis and promoted survival of cardiomyocytes. Up-regulation of miR-221-3p in aged MSCs improved their ability of angiogenesis, migration and proliferation, and suppressed apoptosis via the PTEN/Akt pathway.

There are unique advantages and disadvantages in the choice of contact mapping (CM) versus noncontact mapping (NCM) systems during ablation of right ventricular outflow tract (RVOT) arrhythmias. This study compared acute procedural success and clinical outcomes in matched patients undergoing CM‐ versus NCM‐guided RVOT ablation.