Metallic atrial septal defect (ASD) occluders are associated with various mid- to long-term complications. To address this, our team developed a novel biodegradable Pansy ASD occluder, and this multicenter RCT aimed to evaluate its effectiveness and safety. A prospective, multicenter, randomized controlled trial was carried out on adult and pediatric patients using the Pansy occluder with a biodegradable polydioxanone (PDO) framework. The primary efficacy endpoint of this clinical trial is the closure success rate at six months post-operation. From May 2021 to March 2023, a total of 127 patients were screened across seven research centers, with 112 patients (including 71 pediatric patients; 57 to the experimental group, 55 to the metal occluder control group) ultimately underwent occluder implantation. In these patients, the average defect size was 8.48 ± 2.86 mm in the experimental group and 10.41 ± 5.21 mm in the control group. The closure success rate at six months post-operation was 100

Sleep staging is critical to assess sleep quality and diagnose sleep disorders. Traditional sleep staging methods usually ignore the interactions between different-scale features and lack concurrent attention to both long-term and short-term characteristics of EEG signals. Thus, distinctive features cannot be extracted and modeled exactly. To bridge these gaps, an automatic sleep staging model based on hierarchical feedback fusion aided full sequence encoder called HFSleepNet is proposed in this paper, using EEG sequence. The backbone module with multiple network layers is used to extract feature sequences at multiple time scales from single-channel EEG signals, capturing both long-term and short-term EEG characteristics. The hierarchical feedback fusion module reinforces and integrates EEG features through downward feedback fusion between convolutional layers and auxiliary feature fusion mechanism to extract multi-scale features and their interaction patterns. The full sequence encoder module outputs sleep staging results by capturing concurrent static and dynamic sequence dependencies in location coding. The model is tested on three public datasets, namely Sleep-EDF-2013, Sleep-EDF-2018, and SHHS. For the first two datasets, the classification accuracy of single-channel Fpz-Cz is 87.1% and 84.7%, respectively. For SHHS, the overall accuracy of single-channel C4-A1 is 85.3%. The experimental results show superiority of the proposed method over the state-of-the-art methods for automatic sleep staging.

Background:Pulmonary arteriovenous fistulas (PAVFs) are abnormal vascular malformations that connect pulmonary arteries and pulmonary veins, resulting in a right-to-left shunt. This anatomical shunt leads to a decrease in arterial oxygen saturation. Patients with PAVFs are usually treated with embolization or surgical procedures. Case summary:A 15-month-old child was diagnosed with PAVF in utero at 36 weeks' gestational age. The patient had no history of dyspnoea, repeated haemoptysis, or pneumonia, and there was no relevant family history. A chest computed tomography (CT) scan showed a bilobed opacity located in the inferior lobe of the right lung, and an echocardiogram detected a small atrial septal defect with positive contrast echocardiography. The patient underwent successful embolization using a detachable balloon catheter due to the relatively large diameter of the fistula. After the surgery, a significant decrease in flow was observed in the fistula, and the contrast is no longer visible. Discussion:Here, we report a case of a paediatric patient with congenital asymptomatic PAVF, diagnosed prenatally, and successfully treated with detachable balloon embolization. The case illustrates the detachable occlusion balloons appear to be an effective tool for embolization of PAVF in children, especially in cases involving large feeding vessels.

Abnormal valve development is the most common congenital heart malformation. The transcription factor Sox7 plays a critical role in the development of vascular and cardiac septation. However, it remains unclear whether Sox7 is required for heart valve development. In the present study, Sox7 was strongly expressed in the endocardial and mesenchymal cells of the developing aortic valve in mice and humans, and that endocardial cell specific deletion of Sox7 (Nfatc1 Cre;Sox7fl/fl) in mice leads to congenital aortic stenosis basing on our echocardiography data and multiple staining results. Mechanistically, Sox7 influences extracellular matrix (ECM) remodeling of the valve through regulating MMP9. Meanwhile, Sox7 also affects other valvular remodeling processes, including apoptosis and proliferation of valvular cells in Sox7 deficiency mice. Similarly, in valvular interstitial cells (VICs), Sox7 overexpression increased the protein levels of cleaved caspase3 and TUNEL-positive VICs, while Ki67-positive VICs decreased. The reverse trend was observed in VICs with Sox7 deficiency. Significant enhancement of Rbm25 transcriptional levels was observed in the Sox7 overexpression group, and the mRNA and protein levels of calcification markers such as Osterix, Osteopontin and Runx2 were reduced. The reverse trend was observed in VICs with Sox7 deficiency. Von Kossa staining and Alizarin Red staining also demonstrated that sever calcification in Nfatc1 Cre;Sox7fl/fl mice. Moreover, we detected the Sox7 protein expression in human fetal aortic valves in patients with aortic stenosis, in which Sox7 positive mesenchymal cells were decreased. Taken together, these findings identify Sox7 as a potential pathogenic gene responsible for congenital aortic stenosis in human. Our study provides novel strategies for the diagnosis and treatment of congenital valvular malformation.

Automatic sleep staging is of great significance for the diagnosis and treatment of sleep disorders. However, the published works for sleep staging have not efficiently characterized temporal information from electroencephalogram (EEG), and thus face the problems of future information leakage and high time cost for model training. To address the above issues, this article proposes a novel network architecture named CausalAttenNet. It avoids future information leakage and extracts time-relevant sleeping features with a wide temporal receptive field through causal dilation convolution. The traditional recursive network is replaced by multihead attention (MHA) to largely reduce time cost and form a faster network for sleep staging. The accuracy rates of CausalAttenNet on the Sleep-EDF-20, Sleep-EDF-78, and Sleep Heart Health Study (SHHS) datasets are 84.7%, 81.6%, and 83.3%, respectively, which are better than those of the state-of-the-art methods. The performances of the proposed CausalAttenNet on different datasets demonstrate its effectiveness and superiority in the field on sleep staging. Individual difference is allowed and hand-crafted feature design is unnecessary for CausalAttenNet. The high accuracy and efficiency of the proposed method indicate its clinical potential for detecting sleep disorders.

心脏是高耗能器官,为了提供足够的三磷酸腺苷,心肌细胞中有大量线粒体.线粒体功能障碍会影响心肌的能量供给和多种细胞活动.该文介绍氧化应激、线粒体动力学失衡、线粒体自噬失调、线粒体膜通透性转换孔异常和线粒体金属离子通道异常对心肌细胞功能的影响.

肥厚型心肌病是儿童第二常见的心肌病,具有高度异质性,病因机制和临床表现各异,易发展为心源性猝死.目前临床诊断主要依赖超声心动图和磁共振成像,结合临床表现、胸片、心电图及其他特殊检查综合诊断,部分病因诊断可依赖于基因检测.同时,研究人员一直致力于早期评估心源性猝死风险并利用相关指标建立预测模型.现结合相关文献及最新的研究进展对以上方面展开论述.

Background: Patent ductus arteriosus (PDA) is one of the most common congenital heart defects causing pulmonary hypertension, infective endocarditis, and even death. The important role of genetics in determining spontaneous ductal closure has been well-established. However, as many of the identified variants are rare, thorough identification of the associated genetic factors is necessary to further explore the genetic etiology of PDA. Methods: We performed whole-exome sequencing (WES) on 39 isolated nonsyndromic PDA patients and 100 healthy controls. Rare variants and novel genes were identified through bioinformatic filtering strategies. The expression patterns of candidate genes were explored in human embryo heart samples. Results: Eighteen rare damaging variants of six novel PDA-associated genes (SOX8, NES, CDH2, ANK3, EIF4G1, and HIPK1) were newly identified, which were highly expressed in human embryo hearts. Conclusions: WES is an efficient diagnostic tool for exploring the genetic pathogenesis of PDA. These findings contribute new insights into the molecular basis of PDA and may inform further studies on genetic risk factors for congenital heart defects.

Background: The current coronavirus disease 2019 (COVID-19) pandemic, since first reported in Wuhan, has inspired worldwide efforts to develop effective COVID-19 vaccination strategies. mRNA vaccines encoding COVID-19 antigens have emerged prominantlyin this global race due to their high effectiveness and simple manufacturing process. Notably, two COVID-19 mRNA vaccines, mRNA-1273 and BNT162b2, have survived in clinical trials and been authorized for emergency use across variouscountries. Summary: Recent advances on mRNA vaccine development for COVID-19 are discussed in this perspective, including sequence design, chemical modification, manufacturing process, and in vivo delivery. Phase I to IV clinical trials of mRNA-1273 and BNT162b2 are then summarized, respectively. Conclusion: Using mRNA vaccines is a promising strategy to achieve mass vaccination in the COVID-19 pandemic. We hope that future studies of mRNA vaccine technology will overcome existing limitations and help people cope with COVID-19.

As one of the cornerstones of clinical cardiovascular disease treatment, statins have an extensive range of applications. However, statins commonly used have side reactions, especially muscle-related symptoms (SAMS), such as muscle weakness, pain, cramps, and severe condition of rhabdomyolysis. This undesirable muscular effect is one of the chief reasons for statin non-adherence and/or discontinuation, contributing to adverse cardiovascular outcomes. Moreover, the underlying mechanism of muscle cell damage is still unclear. Here, we discovered that ferroptosis, a programmed iron-dependent cell death, serves as a mechanism in statin-induced myopathy. Among four candidates including atorvastatin, lovastatin, rosuvastatin, and pravastatin, only atorvastatin could lead to ferroptosis in human cardiomyocytes (HCM) and murine skeletal muscle cells (C2C12), instead of human umbilical vein endothelial cell (HUVEC). Atorvastatin inhibits HCM and C2C12 cell viability in a dose-dependent manner, accompanying with significant augmentation in intracellular iron ions, reactive oxygen species (ROS), and lipid peroxidation. A noteworthy investigation found that those alterations particularly occurred in mitochondria and resulted in mitochondrial dysfunction. Biomarkers of myocardial injury increase significantly during atorvastatin intervention. However, all of the aforementioned enhancement could be restrained by ferroptosis inhibitors. Mechanistically, GSH depletion and the decrease in nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPx4), and xCT cystine-glutamate antiporter (the main component is SLC7A11) are involved in atorvastatin-induced muscular cell ferroptosis and damage. The downregulation of GPx4 in mitochondria-mediated ferroptosis signaling may be the core of it. In conclusion, our findings explore an innovative underlying pathophysiological mechanism of atorvastatin-induced myopathy and highlight that targeting ferroptosis serves as a protective strategy for clinical application.

VSD combined with other cardiac or extracardiac malformations (defined as “complex VSD” by us) is one of the major causes of perinatal morbidity and mortality. Functional non-coding SNPs (cis-regulatory SNPs) have not been systematically studied in CHDs, including complex VSD. Here we report an exome-wide association analysis using WES data of 60 PA/VSD cases, 20 TOF cases and 100 controls in Chinese children. We identify 93 low-frequency non-coding SNPs associated with complex VSD risk. A functional genomics pipeline integrating ATAC-seq, ChIP-seq and promoter CHi-C recognizes the rs2279658 variant as a candidate cis-regulatory SNP. Specifically, rs2279658 resides in a cardiac-specific enhancer bound by FOXH1 and PITX2, and would abrogate binding of these two transcription factors to the identified enhancer during cardiac morphogenesis. COQ2 and FAM175A are predicted to be target genes for “rs2279658-FOXH1 or PITX2” pairs in the heart. These findings highlight the importance of cis-regulatory SNPs in the pathogenesis of complex VSD and broaden our understanding of this disease.

目前,多巴胺及其受体在中枢神经系统中的作用被广泛报道,但其在外周尤其是在循环系统中的作用还有待研究.多巴胺受体分为D 1样受体和D2样受体,哺乳动物中D 1样受体包含D 1和D5受体,与腺苷酸环化酶刺激有关.D2样受体包含D2、D3和D4受体,与腺苷酸环化酶抑制有关.多巴胺通过这些不同亚型受体在心血管疾病的发生和发展中发挥重要作用.现主要对多巴胺受体在心肌肥厚、心肌缺血、高血压及心律失常等心血管疾病中的作用机制的最新进展进行综述,期望对多巴胺及其受体靶点药物研发及在慢性心血管疾病中的临床应用提供理论指导.

Congenital heart defect (CHD) is a rare and complicated disease with a high mortality rate. Its etiology remains unclear and includes many aspects. DNA methylation has been indicated to be involved in heart development in the early stage of life, and aberrant methylation level was related to CHDs. This study provides the first evidence of the cross talk of SNP variants and DNA methylation in clarifying CHD underlying genomic cause. We gathered whole exome sequencing (WES) data for Group 1 consisting of patients with PA (n = 78), TOF (n = 20), TAPVC (n = 78), and PDA (n = 40), and 100 healthy children as control group. Rare non-synonymous mutations and novel genes were found and highlighted. Meanwhile, we carried out the second analysis of DNA methylation data from patients with PA (n = 3), TAPVC (n = 3), TOF (n = 3), and PDA (n = 2), and five healthy controls using 850 K array in Group 2. DNA methylation was linked to WES data, and we explored an obvious overlap of hyper/hypomethylated genes. Next, we identified some candidate genes by Fisher's exact test and Burden analysis; then, those methylated genes were figured out by the criteria of the mutation located in the CpG islands of the genome, differential methylation sites (DMS), and DNA methylation quantitative trait loci (meQTLs) in the database, respectively. Also, the interaction of differentially methylated candidate genes with known CHD pathogenetic genes was depicted in a molecular network. Taken together, our findings show that nine novel genes (ANGPTL4, VEGFA, PAX3, MUC4, HLA-DRB1, TJP2, BCR, PKD1, and HK2) in methylation level are critical to CHD and reveal a new insight into the molecular pathogenesis of CHD.

室性早搏诱发心肌病是一种潜在的可逆性疾病,频发室性早搏可引起左心室功能障碍及重构.既往对于成人及动物模型研究发现,心肌细胞本身以及细胞外机制可能参与了心肌病样改变发生.但该病的确切病理生理机制仍不清楚.并且,在儿童中如何进行该病的早期诊断和及时干预尚无明确指导.成人系列研究已经报道了多种导致室性早搏诱发心肌病的高危因素,包括室性早搏负荷量和室性早搏心率变异性等,但是针对儿童的相关研究仅限于病例报告和小型单中心回顾性系列研究.该文总结分析目前公认的可能导致儿童室性早搏诱发心肌病的高危因素以及该病现有的治疗策略.

Patent ductus arteriosus (PDA) is a common congenital cardiovascular malformation with both inherited and acquired causes. Several genes have been reported to be related to PDA, but the molecular pathogenesis is still unclear. Here, we screened a population matched cohort of 39 patients with PDA and 100 healthy children using whole exome sequencing (WES). And identified 10 copy number variants (CNVs) and 20 candidate genes using Gene ontology (GO) functional enrichment analysis. In gene network analysis, we screened 7 pathogenic CNVs of 10 candidate genes (MAP3K1, MYC, VAV2, WDR5, RXRA, APLNR, TJP1, ERCC2, FOSB, CHRNA4). Further analysis of transcriptome array showed that 7 candidate genes (MAP3K1, MYC, VAV2, APLNR, TJP1, FOSB, CHRNA4) were indeed significantly expressed in human embryonic heart. Moreover, CHRNA4 was observed the most important genes. Our data provided rare CNVs as potential genetic cause of PDA in humans and also advance understanding of the genetic components of PDA.

Objectives and Background. The conventional process of percutaneous balloon pulmonary valvuloplasty for critical pulmonary stenosis (CPS) and pulmonary atresia with intact ventricular septum (PA/IVS) is challenging because of the difficulty in positioning the catheter stably into the right ventricular outflow tract (RVOT), especially in young infants with a hypertrophic right ventricle. In this study, we introduced a novel transcatheter approach with the Simmons catheter to reach the RVOT and compared its efficacy and safety with those of the approaches using a floating catheter and the Judkins right coronary catheter. Methods and Results. We retrospectively reviewed 52 young infants, 41 of whom had CPS and 11 had PA/IVS, in a single center from June 2009 to October 2017. Patients were divided into three groups according to the type of catheter used to enter through the RVOT. The unique structure of the Simmons catheter allowed it to be maneuvered directly into the RVOT within a few minutes. Compared with the other two groups, the Simmons catheter group had a significantly shorter fluoroscopy time entering through the RVOT (P<0.001) and a shorter total X-ray exposure time (P<0.001). Furthermore, compared with the floating catheter group, the success rate of surgery was much higher in the Simmons catheter group (P<0.001). Conclusions. The Simmons catheter is a safe and effective method to enter through the RVOT in infants with CPS or PA/IVS. Therefore, the Simmons catheter could be an alternative catheter when entering through the RVOT in young infants, especially neonates with low birth weight.

We aimed to assess the risk factors for left ventricle (LV) enlargement in children with idiopathic frequent ventricular premature complexes (VPC) and discuss the clinical features and treatment strategies. Children diagnosed with idiopathic frequent VPC at Xinhua Hospital affiliated to the Shanghai Jiao Tong University during 2013 to 2019 were retrospectively evaluated. Gender, age, body mass index, weight, number and sources of frequent VPC, and changes in the LV structure were analyzed and compared. A total of 29 patient showed changes in LV enlargement at diagnosis [age 7.3 +/- 4.0 years, 8 (24.1%) had symptoms such as syncope, palpitations, fatigue, and dizziness], whereas 220 showed a normal LV structure [age 7.2 +/- 4.5 years, 77 (32.3%) with symptoms]. Patients with LV enlargement showed a higher percentage of VPC on Holter recordings (30.2 +/- 10.7 versus 9.4 +/- 6.9, p < 0.05), higher prevalence of ventricular tachycardia [22 (75.9%) vs 36 (16.4%), p < 0.0001], higher number of couplets [26 (96.7%) vs 132 (60.0%), p = 0.002], higher number of trigeminy [27 (97.8%) vs 133 (83.2%), p < 0.001], higher QRS wave width [80.0 +/- 5.9 vs 77.8 +/- 6.8, p = 0.021], and higher incidence of right bundle branch block [11 (37.9%) vs 2 (0.9%), p < 0.001]. Multivariate analysis suggested that right bundle branch block (Odds Ratio = 143.9 p < 0.001) and VPC burden (> 20%) (Odds Ratio = 132.6, p < 0.001) were the risk factors for LV enlargement in children with idiopathic frequent VPC. In conclusion, frequent VPC can induce prominent enlargement or LV dysfunction in children. LV enlargement are reversible after catheter ablation or medication. (C) 2020 Published by Elsevier Inc.

目的 探讨新生儿心律失常合并先天性心脏病患儿的临床特点及治疗转归.方法 选取2000年1月至2018年2月上海交通大学医学院附属新华医院新生儿科收治诊断的新生儿心律失常合并先天性心脏病患儿临床资料,对其临床特点、治疗及转归情况进行回顾性分析.结果 共纳入患儿95例,其中男54例,女41例,胎龄(38.4±1.8)周,出生体重(3283±497)g.95例患儿心律失常类型为窦性心动过速14例(14.7％),房性期前收缩、房性心动过速49例(51.6％),室性期前收缩11例(11.6％),阵发性室上性心动过速8例(8.4％),心房扑动6例(6.3％),心房颤动1例(1.0％),窦性心动过缓4例(4.2％),Ⅱ度房室传导阻滞1例(1.0％),Ⅲ度房室传导阻滞1例(1.0％).主要合并先天性心脏病类型为房间隔缺损、动脉导管未闭、室间隔缺损.95例患儿中60例(63.2％)给予改善血流动力学药物治疗后临床症状好转,心律失常消失;35例(36.8％)给予抗心律失常药物治疗.出院后随访62例,复发4例(房性期前收缩1例、阵发性室上性心动过速2例、心房扑动1例).结论 新生儿心律失常合并先天性心脏病的病理分型和心律失常类型无相关性,多数经对症处理后缓解.

目的 探讨微小核糖核酸(miRNA)对Fontan术后血小板活化程度及血栓形成影响的精确预测价值.方法 选取单心室行Fontan术后病儿6例作为实验组(TG组),体检正常儿童6例作为对照组(CG组),分别提取两组血清、血小板和白细胞内miRNA;选取和心血管病相关的miRNA(miR-126、miR-150、miR-197、miR-223及miR-21),通过qRT-PCR检测其表达情况;通过流式细胞仪检测血小板活化程度;通过Western Blot方法检测经慢病毒转染抑制miR-223表达后对细胞核因子κB(NF-κB)信号通路蛋白表达的影响.结果 CG组和TG组血清中miR-126、miR-223表达水平比较,差异有显著性(t=3.22、3.45,P＜0.05).两组外周血血小板和白细胞中miR-223表达水平比较,差异有显著性(t=5.62、4.32,P＜0.05).流式细胞仪检测结果显示,TG组血小板中CD62 p、CD41a的表达率较CG组显著升高(t=17.57、87.78,P＜0.01);Western Blot检测结果显示,TG+病毒无转录抑制因子组(TC组)白细胞I小蛋白表达下调,p-p65蛋白表达上调;CG+病毒含转录抑制因子组(CI组)白细胞中Iκb蛋白表达上调,p-p65蛋白表达下调;与CI组组比较,TG+病毒含转录抑制因子组(TI组)白细胞中kb蛋白表达下调,p-p65蛋白表达上调;Ikkb和NF-κB蛋白表达在不同处理组间无明显变化.结论 Fontan术后病儿血清中miR-223表达水平升高,血小板活化率增加;miR-223表达升高后可能通过NF-κB信号路径来促进血小板活化和血管内皮损伤,从而影响血栓形成.

The occurrence rate of long QT syndrome is 1/2 000,which accounts for approximately 10％ of cases of the sudden infant death syndrome.The morbidity is decreased after receiving appropriate therapy in early stage.Electrocardiogram (ECG) screening,with reliable results,is simple and feasible in infancy and can be used to conduct appropriate genetic testing.Neonatal screening is controversial because of individual differences in ECG results.Even there are some defects,it is still necessary to perform neonatal ECG screening which can improve prognosis in children with long QT syndrome.