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Objective The study objective was to determine whether mini-invasive transthoracoscopic atrial fibrillation ablation can delay the progression of atrial fibrillation from paroxysmal to persistent. Methods Patients aged 18 to 80 years with paroxysmal nonvalvular atrial fibrillation and a history of stroke or systemic thromboembolism were consecutively enrolled from September 2014 to June 2019. In the treatment group, patients underwent transthoracoscopic atrial fibrillation ablation plus left atrial appendage excision (atrial fibrillation ablation plus left atrial appendage excision group). Patients unwilling to receive surgical intervention were treated with antiarrhythmic drugs and oral anticoagulants and recruited as a control group (atrial fibrillation plus antiarrhythmic drugs group). The primary end point was the progression of atrial fibrillation from paroxysmal to persistent. Results This study included 49 patients in the atrial fibrillation plus antiarrhythmic drugs group (29 men) and 77 patients in the atrial fibrillation ablation plus left atrial appendage excision group (48 men). In the atrial fibrillation ablation plus left atrial appendage excision group, after a median follow-up of 951 days (interquartile range, 529-1366 days), 8 patients (10.4%) progressed to persistent atrial fibrillation. In the atrial fibrillation plus antiarrhythmic drugs group, after a median follow-up of 835 days (interquartile range, 548-1214 days), 14 patients (28.6%) progressed to persistent atrial fibrillation. The atrial fibrillation ablation plus left atrial appendage excision group had a significantly lower incidence of atrial fibrillation progression than the atrial fibrillation plus antiarrhythmic drugs group during follow-up (3.9 vs 12.3 per 100 person-years, log-rank 8.6, P = .003). Conclusions Patients with paroxysmal nonvalvular atrial fibrillation who chose to undergo transthoracoscopic atrial fibrillation ablation had a lower incidence of progression to persistent atrial fibrillation than patients who chose conservative therapy. This strategy might be especially suitable for patients with paroxysmal nonvalvular atrial fibrillation at high risk of stroke and high risk of bleeding.

Epicardial adipose tissue (EAT) accumulation is associated with the progression of atrial fibrillation. However, the histological features of EATs are poorly defined and their correlation with atrial fibrosis is unclear.The purpose of this study was to identify and characterize EAT subgroups in the persistent atrial fibrillation (PeAF) cohorts.EATs and the corresponding left atrial appendage samples were obtained from patients with PeAF via surgical intervention. Adipocyte markers, that is, Uncoupling Protein 1, Transcription Factor 21, and CD137, were examined. On the basis of expression of adipocyte markers, patients with PeAF were categorized into subgroups by using unsupervised clustering analysis. Clinical characteristics, histological analyses, and outcomes were subsequently compared across the clusters. External validation was performed in a validation cohort.The ranking of feature importance revealed that the 3 adipocyte markers were the most relevant factors for atrial fibrosis compared with other clinical indicators. On the k-medoids analysis, patients with PeAF could be categorized into 3 clusters in the discovery cohort. The histological studies revealed that patients in cluster 1 exhibited statistically larger size of adipocytes in EATs and severe atrial fibrosis in left atrial appendages. Findings were replicated in the validation cohort, where severe atrial fibrosis was noted in cluster 1. Moreover, in the validation cohort, there was a high degree of overlap between the supervised classification results and the unsupervised cluster results from the k-medoids method.Machine learning-based cluster analysis could identify subtypes of patients with PeAF having distinct atrial fibrosis profiles. Additionally, EAT whitening (increased proportion of white adipocytes) may be involved in the process of atrial fibrosis.

Precise localization of the site of origin of premature ventricular contractions (PVCs) before ablation can facilitate the planning and execution of the electrophysiological procedure.The purpose of this study was to develop a predictive model that can be used to differentiate PVCs between the left ventricular outflow tract and right ventricular outflow tract (RVOT) using surface electrocardiogram characteristics.A total of 851 patients undergoing radiofrequency ablation of premature ventricular beats from January 2015 to March 2022 were enrolled. Ninety-two patients were excluded. The other 759 patients were enrolled into the development (n = 605), external validation (n = 104), or prospective cohort (n = 50). The development cohort consisted of the training group (n = 423) and the internal validation group (n = 182). Machine learning algorithms were used to construct predictive models for the origin of PVCs using body surface electrocardiogram features.In the development cohort, the Random Forest model showed a maximum receiver operating characteristic curve area of 0.96. In the external validation cohort, the Random Forest model surpasses 4 reported algorithms in predicting performance (accuracy 94.23%; sensitivity 97.10%; specificity 88.57%). In the prospective cohort, the Random Forest model showed good performance (accuracy 94.00%; sensitivity 85.71%; specificity 97.22%).Random Forest algorithm has improved the accuracy of distinguishing the origin of PVCs, which surpasses 4 previous standards, and would be used to identify the origin of PVCs before the interventional procedure.

In this paper, we propose a novel multi-scale fusion framework for low-illumination image enhancement, which effectively enhances images taken under various low-light conditions. Based on the high dynamic range imaging technique, we first employ a novel remapping function to generate a sequence of artificial multi-exposure images. The generated sequence of images ensures that the contrast of each intensity interval of the input image is enhanced at least once. Then three fusion-relevant features, namely, exposure, global contrast and local contrast, are selected as the weight maps. Combined with the weight maps, a pyramid fusion scheme is introduced to do a layer-by-layer integration of the different frequency bands of the image layer by layer. In addition, a strategy for extracting details from the original image is designed, which effectively maintains the detail information without causing colour distortions. The framework is very efficient and suitable for mobile devices because most of the calculations are at the pixel-level. Extensive experiments have shown that the proposed approach yields comparable and better performances in comparisons with the state-of-the-art competing techniques in both qualitative and quantitative evaluations.

Transdermal drug delivery is an attractive route for dermatological disease therapy because it can directly target the lesion site on the skin, reduce adverse reactions associated with systemic administration, and improve patient compliance. However, the stratum corneum, as the main skin barrier, severely limits transdermal drug penetration, with compromised bioavailability. Microneedles (MNs), which are leveraged to markedly improve the penetration of therapeutic agents by piercing the stratum corneum and creating hundreds of reversible microchannels in a minimally invasive manner, have been envisioned as a milestone for effective transdermal drug delivery, especially for superficial disease therapy. Here, the emergence of versatile MNs for the transdermal delivery of various drugs is reviewed, particularly focusing on the application of MNs for the treatment of diverse skin diseases, including superficial tumors, scars, psoriasis, herpes, acne, and alopecia. Additionally, the promises and challenges of the widespread translation of MN-mediated transdermal drug delivery in the dermatology field are summarized.

Atrial fibrillation (AF) patients with a previous stroke are often at a high risk of recurrent stroke and bleeding. Anticoagulation therapy in such patients is a challenging dilemma. Thoracoscopic left atrial appendage excision (LAAE) plus AF ablation is an interventional approach offered to some AF patients. We hypothesized that this approach may be suitable as a secondary stroke prevention strategy for these high-risk patients. Between January 2013 and December 2016, a total of 44 patients (26 male; mean age 65.0 ± 9.1 years) with nonvalvular AF and a previous stroke or systemic thromboembolic event were enrolled. The patients underwent thoracoscopic LAAE plus AF ablation by experienced operators and were followed up for 2 years (at 1, 3, 6, 9, and 12 months postoperatively and every 6 months thereafter). Thromboembolic and major bleeding events were recorded. Cerebral computed tomography or magnetic resonance imaging and 7-day Holter monitoring were performed annually. Mean CHA2DS2-VASc and HAS-BLED scores were 4.2 ± 1.2 and 3.3 ± 0.7, respectively. All patients discontinued oral anticoagulation therapy after the surgical intervention. One patient suffered a periprocedural transient ischemic attack, and another was diagnosed with a new ischemic stroke at 491 days after surgery. The annual rate of total thromboembolism was 2.05%. No deaths or major bleeding events were observed postoperatively. The rate of successful AF ablation with no AF recurrence was 76.3%. Transthoracoscopic LAAE plus AF ablation may be a promising approach for this high-risk population. Thromboembolism event in this secondary prevention cohort was low, even without oral anticoagulation treatment.

Background Macroreentrant biatrial tachycardia (BiAT) associated with interatrial septal incisions after mitral valve (MV) surgery has been rarely reported. Objective The purpose of this study was to assess the mapping and ablation strategy of this special category of atrial tachycardia (AT). Methods We identified 10 BiATs from a total of 84 ATs after MV surgery performed at 3 institutions. Activation maps for both the right atrium (RA) and left atrium (LA) were obtained using an ultrahigh-density mapping system. We also performed entrainment pacing from multiple LA and RA site within the speculative circuit. Results By analyzing activation and propagation maps of both atria, we classified the circuit into 3 distinct types. In all types, posteroinferior interatrial connections act as a critical limb that, combined with other interatrial connections (Bachmann bundle, fossa ovalis, and coronary sinus ostium in 3 types, respectively), complete the circuit of BiATs. Most ATs (8/10) were terminated targeting the RA and LA end of posteroinferior interatrial connection sites. Conclusion Ultrahigh-density mapping provides a detailed description of the macroreentrant circuit of BiAT associated with interatrial septal incisions. Posteroinferior interatrial connections were essential for the circuit and should be the preferred target for ablation.

Polymeric microneedles (MNs) have been leveraged as a novel transdermal drug delivery platform for effective drug permeation, which were widely used in the treatment of various diseases. However, issues including limited loading capacity of hydrophobic drugs, uncontrollable drug release rates, and monotonic therapeutic strategy hamper the further application of polymeric MNs. As a recent emerging research topic, drawing inspiration from the ways that nanomedicine integrated with MNs have opened new avenues for disease therapy. In this review, we examined the recent studies employing nanoparticles (NPs)-encapsulated polymeric MNs (NPs@MNs) for transdermal delivery of various therapeutic cargos, particularly focused on the application of NPs@MNs for diabetes therapy, infectious disease therapy, cancer therapy, and other dermatological disease therapy. We also provided an overview of the clinical potential and future translation of NPs@MNs.

Synergistic anti-tumor effect of anti-PD-1/L1 antibody (aPD-1/aPD-L1) and 1-methyl-D,L-tryptophan (1-MT) in melanoma has been well demonstrated, while efficient topical delivery systems are still largely unexplored. Here, a highly drug-concentrated hybrid core-shell microneedle (CSMN) system for co-delivery of checkpoint inhibitors was developed. Based on the specific drug-matrix interaction, the system concentrated aPD-L1 in the tips of microneedles through electrostatic interactions, and increased the amount of 1-MT loaded in CSMN by preventing its premature crystallization using PVA, the material used to prepare CSMN core. The prepared CSMN exhibited high transdermal delivery efficiency and long topical retention time of aPD-L1 for 2 days. Drug-loaded CSMN achieved better anti-tumor efficacy than the intra-tumor injection group at the same dose, which was likely because the former recruited more T lymphocytes to the tumor site. These findings suggested that this CSMN system was a promising local delivery system of both aPD-L1 and 1-MT for melanoma immunotherapy, and its unique core-shell structure could be readily adapted as a modular platform for various diseases, where combination therapy of both biomacromolecular drugs and other small-molecular agents were required. STATEMENT OF SIGNIFICANCE: In the present study, a core-shell microneedle (CSMN) system was constructed to achieve targeted co-delivery of checkpoint inhibitors to melanoma, while preventing significant systemic exposure. To overcome the drawback of insufficient drug loading of microneedles and effectively encapsulate two drugs simultaneously, microneedles were divided into two independent functional areas, a charged shell and a hydrophilic core and encapsulated drugs based on respective drug-matrix interaction. The charged shell prepared by chitosan could concentrate aPD-L1 in the tips of microneedles through electrostatic interactions. The core prepared by PVA successfully increased the amount of 1-MT loaded in microneedles by preventing its premature crystallization. The prepared CSMN exhibited high transdermal delivery efficiency and better anti-tumor efficacy than intra-tumor injection at the same dose.

The majority of cardioembolic strokes in patients with non-valvular atrial fibrillation (NVAF) are resulted from clot formation in the left atrial appendage (LAA). Current stroke risk stratification is based on the overall risks estimated from demographic and clinical profiles but not on individual anatomy or physiology. We aim to explore the differences in LAA morphological and hemodynamic parameters by comparing patients with and without a stroke history. Thirty-nine patients with persistent NVAF were included. Of these, 17 patients without a stroke history (non-stroke group) were compared with 22 patients with a history of stroke (stroke group). Their LAA geometric models were first reconstructed, and the morphological parameters were then measured. Furthermore, their LAA hemodynamic parameters were calculated by fluid-structure interaction analysis. Moreover, particle residual rates (PRR) and blood renewal rates (BRR) analyses were also employed to characterize the thrombogenesis dynamics. The results showed that compared to the non-stroke group, the stroke group had significant smaller LAA tortuosity and LAA orifice area, and significantly lower LAA orifice velocities (0.16 ± 0.10 vs 0.15 ± 0.06 cm/s; p = 0.044), but higher PRR (14.58 ± 9.43 vs 9.25 ± 4.67; p = 0.040) and BRR (52.41 ± 18.11 vs 38.36 ± 24.07; p = 0.044). These LAA morphological and hemodynamic parameters may be used to assess stroke risk in patients with NVAF.

Background Right-sided accessory pathway (RAP) ablation is sometimes challenging. Objective Our study aimed to demonstrate an alternative ablation approach to RAPs under the tricuspid valve, especially when the conventional ablation attempts at the atrial side failed. Methods Twelve patients with RAPs were enrolled, 8 of whom had previously failed ablation. With the help of a long sheath, the under-valve approach was attempted in 3 patients during tachycardia, in 2 patients during ventricular pacing, and in 7 patients during sinus rhythm. Three-dimensional electroanatomic mapping was performed in 3 patients during their repeat procedures. Results The acute outcomes of the procedures in all patients were successful. Patients were free of tachycardia or recurrence of accessory pathway conduction during a median follow-up of 12.5 months (range 7–45 months). No complications were found during the procedure or follow-up period. Conclusion Radiofrequency ablation under the tricuspid valve to eliminate RAPs is feasible because of its stable contact and the accurate ablation of the ventricular insertion site. It provides an alternative approach to tough RAP ablation.

Atrial fibrillation (AF) is the most common persistent cardiac arrhythmia. This study aimed to estimate its prevalence and explore associated factors in adults aged 18 years or older in China.Study data were derived from a national sample from July 2020 to September 2021. Participants were recruited using a multistage stratified sampling method from twenty-two provinces, autonomous regions, and municipalities in China. AF was determined based on a history of diagnosed AF or electrocardiogram results.A total of 114,039 respondents were included in the final analysis with a mean age of 55 years (standard deviation 17), 52·1% of whom were women. The crude prevalence of AF was 2·3% (95% confidence interval [CI] 1·7-2·8) and increased with age. The age-standardized AF prevalence was 1·6% (95% CI 1·6-1·7%) overall, and 1·7% (1·6-1·8%), 1·4% (1·3-1·5%), 1·6% (95% CI 1·5-1·7%), and 1·7% (1·6-1·9%) in men, women, urban areas, and rural areas, respectively. The prevalence was higher in the central regions (2·5%, 2·3-2·7%) than in the western regions (1·5%, 1·0-2·0%) and eastern regions (1·1%, 1·0-1·2%) in the overall population, either in the gender or residency subgroups. The associated factors for AF included age (per 10 years; odds ratio 1·41 [95% CI 1·38-1·46];The prevalence of AF was 1.6% in the Chinese adult population and increased with age, with significant geographic variation. Older age, male sex, and cardiovascular disease were potent factors associated with AF. It is crucial to increase the awareness of AF and disseminate standardized treatment in clinical settings to reduce the disease burden.This research was supported the Nature Science Foundation of Hubei province (No: 2017CFB204).

BackgroundIdiopathic epicardial ventricular arrhythmias (VAs) are clustered in the areas of the summit and crux.ObjectiveTo report a group of idiopathic epicardial VAs remote from the summit and crux areas.MethodsIn total, 9 patients (6 males, mean age 32{plus minus}13 years) were enrolled. The locations were identified by epicardial mapping and ablation. The electrocardiographic and electrophysiological characteristics were compared to those of 9 patients who had VAs ablated at the opposite endocardial site.ResultsVAs were identified at the epicardium, with 4 patients had VAs located at the inferior wall, one at the anterior wall, one at the apex and 3 patients had VAs at the lateral wall. A "QS" type at the location-related leads was the only identified surface electrocardiogram indication suggesting epicardial origin (compared to that of the controls, 100% vs 0%, p

Primary fibrotic atrial cardiomyopathy (PF-ACM) is a novel type of cardiomyopathy characterized by primary atrial fibrosis with arrhythmogenicity and increased stroke risk without ventricular myocardium involvement. However, genetic analysis regarding PF-ACM and genotype-phenotype correlations is lacking. A cohort of PF-ACM patients was recruited and followed up. Whole-exome sequencing (WES) was applied, and genes were screened using a cardiovascular disease (CVD)-related gene panel. Echocardiography and cardiac magnetic resonance (CMR) were performed. The pathogenicity of the identified mutations was evaluated using in silico analysis. Thirty-three unrelated patients were referred for WES. Thirty-three rare variants of 19 CVD-related genes were identified in 21 patients, with 10 patients harboring more than one variation. TTN was the most frequent gene observed. Further analysis demonstrated that variations in sarcomeric (SV) or non-sarcomeric (NSV) genes were found in 16 and 10 patients, respectively. Patients carrying variants regardless of SV or NSV had larger left atrial dimensions determined by echo and larger left atrium areas determined by CMR. There was no discrepancy in disease severity between SV carriers and NSV carriers. Our genetic investigation into PF-ACM has identified several genetic culprits, providing further insight into its underlying pathophysiology and emphasizing a potential role for genetic testing for this condition.

Background: The COVID-19 mortality is very low in the regions with a low transmission rate and sufficient medical resources. However, strict prevention measures greatly altered people’s social activities, diet, and hygienic habits, which had potential impact on non-COVID-19 deaths. Therefore, this study is to evaluate the impact of short-term lifestyle change on non-COVID deaths in the region with a low COVID-19 transmission rate. Methods: We performed a retropective observational study with statiscal analysis via Student’s t-test (significance defined as P-value < 0.05). The number of registered deaths among 8.8 million permanent residents with specific causes from January 2018 to June 2020 were sourced from Xuzhou Center for Disease Control and Prevention. Death rates were calculated and compared by weeks, months, and years with a focus on the period of COVID-19 pandemic from Jan 24 to March 27, 2020 in Xuzhou, Jiangsu Province, China. Findings: Within the COVID-19 timeframe, all-cause mortality (138.03/105 vs. 158.28/105 vs. 152.57/105, P < 0.001), respiratory disorders (13.99/105 vs. 24.48/105 vs. 21.22/105, P < 0.001), cerebrovascular diseases (36.35/105 vs. 38.69/105 vs. 38.61/105, P < 0.05), and cardiovascular diseases (35.70/105 vs. 42.06/105 vs. 39.55/105, P < 0.001) are consistently lower than those in the same period in 2018 and 2019. The traffic death dropped significantly, while mortalities of mental health disorders and out-of-hospital sudden death significantly increased during the pandemic time. Interpretation: Our study suggests the short-term lifestyle alteration can have significant impact on all-cause mortality. This could provide evidences for adjusting future healthcare policies to reduce specific-cause mortalities such as respiratory, cardiovascular and cerebrovascular diseases. Trial Registration: This study was registered at the ClinicalTrials.gov (NCT 04550312). Funding: Xuzhou Talent Fellowship Program 2019. Conflict of Interest: We declare no competing interests. Ethical Approval: The medical research ethics committee of the affiliated hospital of Xuzhou Medical University, Xuzhou, approved the study (9th, September 2020, No. XYFY2020-KL142-01).

Background: The increase of all-cause mortality in the areas with high COVID-19 transmission rate due to COVID-19 deaths and the collateral damage to other healthcare problems is well-known. However, the COVID-19 mortality is low in the regions with a low transmission rate and sufficient medical resources. In such regions, strict prevention measures altered people’s lifestyle and hygienic habits and had an impact on non-COVID-19 deaths. Yet, this aspect needs to be elucidated further. Methods: The number of registered deaths among 8.8 million permanent residents with specific causes from January 2018 to June 2020 were estimated. Death rates were calculated and compared by weeks, months, seasons and years with a focus on the period of the COVID-19 pandemic from January 24 to March 27, 2020. The numerical values of all-cause death and the death rates of non-COVID diseases were compared in various time points. Findings: During the pandemic in Xuzhou region, a total of 79 COVID-19 infected patients were diagnosed and treated. Meanwhile, stringent public health measures were taken to contain the virus transmission. Surprisingly, mortalities of all-cause casualty, respiratory disorders, cerebrovascular disease, and cardiovascular disease are consistently lower than those in the same periods in 2018 and 2019. Moreover, the first two weeks in the lunar new year presented the highest death rates from 2018–2020 and lowest in 2020 due to COVID-19 control. The traffic death dropped significantly, while mortality of mental health disorders and out-of-hospital sudden death significantly increased during the pandemic time. Interpretation: Control strategies in the region of low SARS-CoV-2 transmission rate during the COVID-19 outbreak alter the lifestyles of people and further exert an impact on non-COVID deaths, which could have a practical value in guiding clinical work and future management of chronic diseases. Funding Statement: Xuzhou Talent Fellowship Program 2019 Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was approved by the Institutional Review Board at the affiliated hospital of Xuzhou Medical University.

Background Idiopathic isolated fibrotic atrial cardiomyopathy (IIF-ACM) is a novel subtype of cardiomyopathy characterized by atrial fibrosis that does not involve the ventricular myocardium and is associated with significant atrial tachyarrhythmia. The mechanisms underlying its pathogenesis are unknown. Methods Atrium samples were obtained from 3 patients with IIF-ACM via surgical intervention. Control samples were consisted of 3 atrium biopsies from patients with congenital heart disease and normal sinus rhythm, matched for gender, age and basic clinical characteristics. Comparative histology, immunofluorescence staining, electron microscopy and proteomics analyses were carried out to explore the unique pathogenesis of IIF-ACM. Results IIF-ACM atria displayed disordered myofibrils, profound fibrosis and mitochondrial damages compared to the control atria. Proteomics profiling identified metabolic pathways as the most profound changes in IIF-ACM. Conclusions Our study suggested that metabolic changes in the atrial myocardium caused mitochondrial oxidative stress and potential cell damage, which further led to atrial fibrosis and myofibril disorganization, the characteristic phenotype of IIF-ACM.

Internet addiction among high school students is an emerging public health issue in China. The objective of this study was to investigate the association between internet addiction and quality of life, as well as the mediation effect of social support in such an association, among Chinese rural high school students. A total of 1277 high school students (mean age: 17.35 years; standard deviation: 1.39 years) from three rural high schools in the province of Henan in China were recruited. Internet addiction was measured by the Young’s Internet Addiction Scale, quality of life was assessed with a 16-item Quality of Life Questionnaire, and social support was evaluated by the Multidimensional Scale of Perceived Social Support. This study revealed that the prevalence rate of internet addiction was 11.51% among the participants. Internet addiction was negatively associated with overall quality of life (β = -0.06, p

It is significant and challenging to develop a highly active, hyper stable and low-cost novel oxygen evolution reaction (OER) electrocatalyst to replace the noble metal-based electrocatalysts for large-scale electrocatalytic water splitting. To settle such issue, for the first time, FeNi alloy nanosphere homogenously embedded porous nitrogen-doped nanocarbon (FeNi@NC) hybrid has been synthesized by pyrolyzing a precursor composite composed of nickel hexacyanoferrate and nitrogen-doped nanocarbon under the inert atmospheres without any further post-treatments. The as-prepared uniform FeNi alloy nanosphere embedded porous nitrogen-doped nanocarbon (FeNi@NC) hybrid exhibits a very low overpotential of 298 mV (vs. RHE) at current density of 10 mA cm−2, a small Tafel slope of 48.4 mV dec−1 and excellent stability after 1.26 × 105 s (more than 35 h) at 10 mA cm−2 towards OER. In addition, the mass normalized activity of FeNi@NC hybrid measured at fixed potential of 1.7 V (vs. RHE) is 295.9 A g−1. The outstanding OER performance can be attributed to the porous nitrogen-doped nanocarbon structure, high specific surface area as well as good electrical conductivity. The results indicate that this work provides a new strategy to fabricate other transition bimetallic alloy embedded porous nitrogen-doped nanocarbon hybrid as OER electrocatalysts in the further.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a cardiomyopathy that primarily involves the right ventricle. Mutations in desmosomal genes have been associated with ARVC. But its prevalence and spectrum are much less defined in the Chinese population, especially Han Chinese, a majority ethnic group in China; also the genotype-phenotype correlation regarding left ventricular involvement is still poorly understood. The aim of this study was to elucidate the genotype in Han Chinese patients with ARVC and the phenotype regarding cardiac left ventricle involvement in mutation carriers of ARVC. 48 Han Chinese patients were recruited into the present study based on the Original International Task Force Criteria of ARVC. Clinical data were reassessed according to the modified criteria published in 2010. A total of 36 subjects were diagnosed with ARVC; 12 patients were diagnosed with suspected ARVC. Five desmosomal genes (PKP2, DSG2, DSP, DSC2 and JUP) were sequenced directly from genomic DNA. Among the 36 patients, 21 mutations, 12 of which novel, were discovered in 19 individuals (19 of 36, 53%). The distribution of the mutations was 25% in PKP2, 14% in DSP, 11% in DSG2, 6% in JUP, and 3% in DSC2. Multiple mutations were identified in 2 subjects (2 of 36, 6%); both had digenic heterozygosity. Eight mutations, of which six were novel, were located in highly conserved regions. Seven mutations introduced a stop codon prematurely, which would result in premature termination of the protein synthesis. Two-dimensional echocardiography showed that LDVd and LDVs parameters were significantly larger in nonsense mutation carriers than in carriers of other mutations. In this comprehensive desmosome genetic analysis, 21 mutations were identified in five desmosomal genes in a group of 48 local Han Chinese subjects with ARVC, 12 of which were novel. PKP2 mutations were the most common variants. Left ventricular involvement could be a sign that the patient is a carrier of a nonsense cardiac desmosomal gene mutation.

Background Catheter ablation of persistent atrial fibrillation (AF) has been performed with varying results using a combination of different techniques. We sought to evaluate the efficacy of additional linear lesion and defragmentation of left atrium (LA). Methods A cohort of 169 patients with persistent AF was studied. Ablation was performed following a sequential strategy consisted of circumferential pulmonary vein isolation (CPVI), LA roof linear ablation, posterior mitral area, coronary sinus and cavotricuspid isthmus, and complex fractionated electrograms ablation. Results During a mean follow-up of 15±8months after a single procedure, 84 (50%) patients were in sinus rhythm, 34 (20%) had an AF recurrence and 51(30%) developed atrial tachycardias (ATs). Repeat procedures were performed in 24 recurrent AF and 46 AT patients. A total of 81 different ATs were mapped and ablated in 46 AT patients, characterized as focal for 45 and macroreentry for 36 ATs. Most of the ATs were likely to be attributed to the previous lesions by an analysis of substrate and activation mapping in the redo procedure and a review of the lesions placed in the initial procedure. Overall, 75 (93%) ATs were ablated successfully. Procedural complications occurred in 11 of the 239 procedures. After a mean follow-up of 20±9months, 128 (76%) patients were free of arrhythmias after the final procedure. Conclusions CPVI supplemented by linear ablation and defragmentation does not seem to improve the overall success rate of persistent AF. The efficacy of linear ablation and defragmentation might be diluted by their proarrhythmic effects.

Background No randomized controlled study has prospectively compared the performance and clinical outcomes of remote magnetic control (RMC) vs manual catheter control (MCC) during ablation of right ventricular outflow tract (RVOT) ventricular premature complexes (VPC) or ventricular tachycardia (VT). Objective The purpose of this study was to prospectively evaluate the efficacy and safety of using either RMC vs MCC for mapping and ablation of RVOT VPC/VT. Methods Thirty consecutive patients with idiopathic RVOT VPC/VT were referred for catheter ablation and randomized into either the RMC or MCC group. A noncontact mapping system was deployed in the RVOT to identify origins of VPC/VT. Conventional activation and pace-mapping was performed to guide ablation. If ablation performed using 1 mode of catheter control was acutely unsuccessful, the patient crossed over to the other group. The primary endpoints were patients' and physicians' fluoroscopic exposure and times. Results Mean procedural times were similar between RMC and MCC groups. The fluoroscopic exposure and times for both patients and physicians were much lower in the RMC group than in the MCC group. Ablation was acutely successful in 14 of 15 patients in the MCC group and 10 of 15 in the RMC group. Following crossover, acute success was achieved in all patients. No major complications occurred in either group. During 22 months of follow-up, RVOT VPC recurred in 2 RMC patients. Conclusion RMC navigation significantly reduces patients' and physicians' fluoroscopic times by 50.5% and 68.6%, respectively, when used in conjunction with a noncontact mapping system to guide ablation of RVOT VPC/VT.

In the present study, we examined the mechanisms of ceramide-induced cell death in SH-SY5Y human neuroblastoma cells. Our results demonstrate a significant endoplasmic reticulum (ER) stress response in SH-SY5Y cells after short-chain ceramide (C6) treatment. Administration of ceramide (C6) to SH-SY5Y human neuroblastoma cells caused apoptotic cell death, which was inhibited by ER stress inhibitor salubrinal. Further, ceramide-induced cell death reduced significantly in stable SH-SY5Y cells expressing C/EBP homologous protein (CHOP) shRNA. Salubrinal inhibited ceramide-induced inositol-requiring enzyme 1α (IRE1α)/apoptosis signal regulating kinase 1 (ASK1)/c-Jun N-terminal kinase (JNK) phosphorylation. Taken together, these data suggest that ceramide-induced SH-SY5Y cell death may be linked to the ER stress-regulated intrinsic pathway, and proposed the potential protective effects of salubrinal.

Described by the drude model, the DNG metamaterials is essentially a dispersive media, the scattering analysis of it over broad band by asymptotic waveform evaluation (AWE) technique is difficult since the computation of high order differential coefficients for the impedance matrix elements, to reduce the differential order, the model-based parameter estimation (MBPE) technique based on two expanded points is applied to analysis the scattering characters of double-negative (DNG) metamaterials. A wavelet matrix transform (WMT) is used to get a sparse matrix equation in wavelet-domain, which is solved over a broad frequency band by the MBPE. As compared with AWE, the MBPE technique obtained more accurate results over a broader frequency band.

Objective To evaluate Tpeak-Tend(Tp-e) interval in surface standard ECG as a new risk factor for arrhythmic event in patient with Brugada syndrome. Methods 23 male patients with Brugada syndrome and 20 male patients with paroxysmal supraventricular tachycardia(PSVT) as the control group were investigated in this study. Tp-e interval in surface standard ECG was compared between BrS and PSVT patients. Results Tp-e interval in BrS patients was significantly longer than that in PSVT patients (109.57 ± 2.86 ms vs. 88.50 ± 3.08ms, P P P P > 0.05). Conclusion The prolongation of Tp-e interval could serve as a new noninvasive event predictor for arrhyth- mic events in patients with Brugada syndrome.

Objective: To investigate the incidence and relative risk factors of post coronary artery bypass grafting(post-CABG) atrial fibrillation (AF). Methods: 312 patients with CABG were reviewed and divided into an AF group and a non-AF group. Statistical analysis was used to compare the data between the two groups and screen for risk factors of post-CABG AF. Results: 103/312 (33.01%) patients developed post-CABG AF. Univariate analysis showed that patients in AF group compared with those in non-AF group were more likely to have advanced age (≥70 years), early postoperative withdrawal of β-blockers, hypertension, left atrial enlargement (≥40 mm), a history of AF, prolonged p-wave duration (≥120 ms) and increased number of grafts (≥3). Multivariate logistic regression analysis showed that advanced age (≥70 years), early postoperative withdrawal of β-blockers, hypertension, left atrial enlargement (≥40 mm) and a history of AF were highly related to post-CABG AF. Conclusion: The incidence of AF in patients following CABG was 33.01% in this study. Advanced age, early postoperative withdrawal of β-blockers, hypertension, left atrial enlargement and a history of AF were independent risk factors of post-CABG AF.