摘要：Arrhythmogenic right ventricular cardiomyopathy(ARVC)is a progressive disease characterized by adipose and fibrous replacement of the *** elevated testosterone levels have been implicated in the pathological process of ARVC,its exact contribution to cardiac fibrosis in ARVC remains *** this study,we analyzed the potential contribution of gender-based differences on the distribution of the low-voltage area in an ARVC cohort undergoing an electrophysiological study,which was indicated by feature ***,we established engineered cardiac spheroid models in vitro using patient-specific induced pluripotent stem cell(iPSC)-derived cardiomyocytes(iPSC-CMs)and iPSC-derived cardiac fibroblasts(icFBs).We elucidated the pathogenicity of abnormal splicing in the plakophilin-2(PKP2)gene caused by an intronic ***,pathogenic validation of the desmoglein-2(DSG2)point mutation further confirms the reliability of the ***,testosterone exacerbated the DNA damage in the mutated cardiomyocytes and further activated myofibroblasts in a chain *** conclusion,we designed and constructed an in vitro three-dimensionally-engineered cardiac spheroid model of ARVC based on clinical findings and provided direct evidence of the fibrotic role of testosterone in ARVC.

摘要：Biophysical restrictions regulate protein diffusion,nucleus deformation,and cell migration,which are all universal and important processes for cells to perform their biological ***,current technologies addressing these multiscale questions are extremely ***,through two-photon polymerization(TPP),we present the precise,low-cost,and multiscale microstructures(micro-fences)as a versatile investigating *** nanometer-scale printing resolution and multiscale scanning capacity,TPP is capable of generating micro-fences with sizes of 0.5-1000μ*** micro-fences are utilized as biophysical restrictions to determine the fluidity of supported lipid bilayers(SLB),to investigate the restricted diffusion of Src family kinase protein Lck on SLB,and also to reveal the mechanical bending of cell nucleus and T cell climbing *** together,the proposed versatile and low-cost micro-fences have great potential in probing the restricted dynamics of molecules,organelles,and cells to understand the basics of physical biology.

摘要：Dyspnea is a common and disabling symptom of respiratory and heart diseases, which is growing in incidence. During hospital admis- sion, breathlessness is under-diagnosed and under-treated, although there are treatments available for controlling the symptom. We have developed a tailored implementation strategy directed to medical staff to promote the application of these pharmacological and non-pharmacological tools in dealing with dyspnea. The primary aim is to decrease the rate of patients that do not receive an adequate relief of dyspnea. This is a four-stage quasi-experimental study. The intervention consists in two teaching talks that will be taught in cardiology and Respiratory Medicine Departments. The contents will be prepared by Palliative Care specialists, based on available tools for management of dyspnea and patients＇ needs. A cross-sectional study of dyspnea in hospitalized patients will be performed before and after the intervention to ascertain an improvement in dyspnea intensity due to changes in medical practices. The last phase consists in the creation of consensus protocols for dyspnea management based in our experience. The results of this study are expected to be of great value and may change clinical practice in the near future and promote a changing for the better of dyspnea care.

摘要：The pathogens of most infectious diseases invade the host through mucosal sites,and immunization with mucosal vaccines is the best means of combating these infectious *** delivery and nasal delivery are the most common methods of mucosal ***,the delivery process is inefficient,and mucosal vaccination is ineffective because the vaccine formulation is easily and rapidly removed and has difficulty in crossing the mucosal *** this paper,we investigated whether the mucosal immune response could be enhanced by ultrasound facilitation of nasal mucosal delivery of vaccine *** this purpose,we used manganese dioxide(MnO2)as the vaccine carrier/adjuvant,coated with chitosan oligosaccharide(COS)to enhance mucosal adsorption,and further physically adsorbed model antigen ovalbumin(OVA)to construct a nanoparticulate vaccine formulation MnO2@COS@*** treatment was found to promote antigen delivery and recruitment of dendritic cells(DCs)and macrophages as well as T-cell infiltration in nasal mucosal tissues through nasal mucosal immunization *** ultrasound assistance,MnO2@COS@OVA particles promoted the maturation of DCs in vitro and in vivo and promoted the production of effector memory T cells in vivo and cytokine secretion by splenocytes in *** particular,ultrasound treatment significantly increased the levels of secretory IgA antibodies in the nasal mucosa and genital tract mucosa of experimental *** addition,the experimental data showed that the MnO2@COS@OVA particles had good biocompatibility and caused no significant damage to the nasal mucosal and vital organ *** data suggest that ultrasound treatment can promote the induction of efficient immune responses to mucosal vaccines and provide new ideas for the opening and clinical translation of mucosal vaccines.

摘要：Aims: The FREEZE-cohort study (NCT 01360008) is a prospective observational, multicenter and multinational study to evaluate safety and effectiveness of cryoballoon ablation for pulmonary vein isolation as compared to radiofrequency ablation in patients with paroxysmal or persistent atrial fibrillation (lasting < one year) under the conditions of clinical routine. Methods and Results: The study started in 2011 and anticipates inclusion up to 2000 patients in each of the two treatment groups. A total of 37 centers from 8 countries worldwide, all experienced in at least one of the two ablation techniques, participate in the study. The primary outcome parameter of the study is defined as atrial fibrillation recurrence rate during twelve months of follow-up. Secondary outcome parameters include primary success rates, complication rates in general, specific complications with respect to phrenic nerve palsy and pulmonary vein stenosis, radiation exposure, clinical course including death and repeat ablation. Finally specific procedural aspects will be evaluated in a descriptive manner. Preliminary data of the first 1882 patients show that in clinical practice cryoablation is preferentially performed in patients with paroxysmal atrial fibrillation, whereas application of radiofrequency ablation is equally distributed between patients with persistent and paroxysmal atrial fibrillation. Conclusion: Based on multi-center and multi-national data the FREEZE-cohort study will provide important information on long-term efficacy, clinical effectiveness, complication rates and procedural differences between atrial fibrillation patients treated with either cryoablation or radiofrequency ablation.

摘要：Background:When patients with cirrhosis develop ascites,it is associated with sharply increasedmortality and healthcare utilization with decreased quality of *** salt restriction is first-line therapy for ascites but it is limited by poor ***:We will recruit 40 patients with cirrhosis and ascites who have received a recent paracentesis or hospitalization for a 1:1 randomized trial of standard care(education on salt restriction)versus home-delivered *** primary outcome is the number of paracenteses needed over 12 *** outcomes include hospital-bed days,health-related quality of life(HRQOL,Ascites Symptom Inventory-7 and Visual Analogue Scale)and performance on batteries of physical function including hand grip(kg)and walk speed(m/s).All subjects follow up through a series of calls where any paracenteses,hospital readmissions,weight changes and diuretic dosage changes are *** a final Week 12 visit,knowledge of dietary sodium intake,quality of life and frailty are reassessed,and satisfaction with the meal-delivery program is *** comparison testing will be conducted between the two ***:A nutritionally standardized meal-delivery program for patients with cirrhosis and ascites post discharge has a variety of potential patient-based benefits,including the effective management of ascites,reduction of healthcare utilization and improvement of *** have three core ***,patients will report interest in and satisfaction with a home-delivered meals ***,subjects on a salt-restricted(2 g sodium)meal-delivery program will have fewer therapeutic paracenteses and all-cause readmissions than subjects receiving standard of ***,subjects on a saltrestricted(2 g sodium)meal-delivery program will report increased HRQOL compared to subjects receiving standard of care.

摘要：The coronary artery calcification score and pericardial fat volume have recently been reported to be strongly associated with the severity and presence of coronary atherosclerosis. However, no studies have explored the outcome of phased progression of atherosclerosis by non-contrast computed tomography in asymptomatic people in China. The population-based cohort study in outcome of phased progression of atherosclerosis in China （PERSUADE）, an observational, longitudinal and prospective cohort study in a target population of healthy sub- jects based in Jidong Oilfield （China）, prospectively analyzes the outcome of phased progression of atherosclerosis by non-contrast computed tomography in healthy population. The results of this study are expected to be of value for utilizing noninvasive imaging combine with tradi- tional cardiovascular risk factors to create a risk stratification and find pertinent biomarkers associated with the outcome of phased progres- sion of atherosclerosis in healthy people, thereby could help to establish a more personalized treatment of clinical practice.

摘要：The subcutaneous implantable cardioverter-defibrillator(S-ICD)has recently been approved for commercial use in Europe,New Zealand and the United *** is comprised of a pulse generator,placed subcutaneously in a left lateral position,and a parasternal subcutaneous lead-electrode with two sensing electrodes separated by a shocking *** an entirely subcutaneous system it avoids important periprocedural and long-term complications associated with transvenous implantable cardioverter-defibrillator(TV-ICD)systems as well as the need for fluoroscopy during implant *** candidates include pediatric patients with congenital heart disease that limits intracavitary lead placements,those with obstructed venous access,chronic indwelling catheters or high infection risk,as well as young patients with electrical heart disease(e.g.,Brugada Syndrome,long QT syndrome,and hypertrophic cardiomyopathy).Nevertheless,given the absence of intracavitary leads,the S-ICD is unable to offer pacing(apart from shortterm post-shock pacing).It is therefore not suitable in patients with an indication for antibradycardia pacing or cardiac resynchronization therapy,or with a history of repetitive monomorphic ventricular tachycardia that would benefit from antitachycardia *** data from initial clinical studies and post-commercialization"real-life"case series,including over 700 patients,have so far been promising and shown that the S-ICD successfully converts induced and spontaneous ventricular tachycardia/ventricular fibrillation episodes with associated complication and inappropriate shock rates similar to that of ***,by using far-field electrograms better tachyarrhythmia discrimination when compared to TV-ICDs has been *** results from ongoing clinical studies will determine the S-ICD system’s long-term performance,and better define suitable patient profiles.

摘要：Every year there are more than 11000 hospitalizations related to heart failure in children resulting in significant morbidity and *** the last two decades,our understanding,diagnosis and management of pediatric heart failure is evolving but our ability to prognosticate outcomes in pediatric heart acute heart failure is extremely limited due to lack of *** adult heart failure patients,the role of cardiac biomarkers has exponentially increased over the last two *** guidelines for management of heart failure emphasize the role of cardiac biomarkers in diagnosis,management and prognostication of heart *** is also noteworthy that these biomarkers reflect important biological processes that also open up the possibility of therapeutic *** is however,a significant gap present in the pediatric population with regards to biomarkers in pediatric heart ***,we seek to review available data regarding cardiac biomarkers in the pediatric population and also explore some of the emerging biomarkers from adult literature that may be pertinent to pediatric heart failure.

摘要：Reproducibility of clinical output is important when investigating therapeutic efficacy in pre-clinical animal *** to its physiological relevance,a swine myocardial infarction(MI)model has been widely used to evaluate the effectiveness of stem cells or tissue-engineered constructs for ischemic heart *** methods are used to induce MI in the swine ***,it is difficult,using these approaches,to obtain a similar level of functional outcomes from a group of animals due to interpersonal variation,leading to increased experimental ***,in order to minimize human intervention,we developed an approach to use a customized occluder that has dimensional similarities with that of the coronary artery of animals in the case of the swine *** carried out angiography to measure the diameter of the middle left anterior descending artery of each individual animal to fabricate the customized occluder using a 3D-printing *** fabricated occluder contained a central hole smaller than that of the targeted middle left anterior descending artery to mimic an atherosclerotic coronary artery that has an approximately 20%blocked ***,the 3D-printed occluder can provide continuous blood flow through the central pore,indicating a high survival rate(88%)of up to 28 days *** method showed the possibility of creating consistent myocardial infarction induction as compared to the conventional representative closed-chest method(50%survival rate),thus highlighting how our method can have a profound effect on accelerating reliable experiments for developing new therapeutic approaches to ischemic heart diseases.