High hydrostatic pressure participates in atrial fibrosis through the p300/p53/Smad3 pathway.

As an independent risk factor of atrial fibrillation (AF), hypertension (HTN) can induce atrial fibrosis through cyclic stretch and hydrostatic pressure. The mechanism by which high hydrostatic pressure promotes atrial fibrosis is unclear yet. p300 and p53/Smad3 play important roles in the process of atrial fibrosis. This study investigated whether high hydrostatic pressure promotes atrial fibrosis by activating the p300/p53/Smad3 pathway. Biochemical experiments were used to study the expression of p300/p53/Smad3 pathway in left atrial appendage (LAA) tissues of patients with sinus rhythm (SR), AF, AF + HTN, and C57/BL6 mice, hypertensive C57/BL6 mice and atrial fibroblasts of mice. To investigate the roles of p300 and p53 in the process of atrial fibrosis, p300 and p53 in mice atrial fibroblasts were knocked in or knocked down, respectively. The expression of p300/p53/Smad3 and fibrotic factors was higher in patients with AF and AF + HTN than those with SR only. The expressions of p300/p53/Smad3 and fibrotic factors increased in hypertensive mice. Curcumin (Cur) and knocking down of p300 reversed the expressions of these factors. 40 mmHg hydrostatic pressure/overexpression of p300 upregulated the expressions of p300/p53/Smad3 and fibrotic factors in mice LAA fibroblasts. While Cur or knocking down p300 reversed these changes. Knocking down/overexpression of p53, the expressions of p53/Smad3 and fibrotic factors also decreased/increased, correspondingly. High hydrostatic pressure promotes atrial fibrosis by activating the p300/p53/Smad3 pathway, which further increases the susceptibility to AF.

High prevalence and distinctive clinical features of LMNA-associated atrioventricular block in young patients.

BACKGROUND AND AIMS: Atrioventricular block (AVB) is a degenerative disease and more commonly encountered in elderly patients, but unusual and often of unknown etiology in young patients. This study aimed to investigate the potential contributions of genetic variations to AVB of unknown reasons in young patients. METHODS: We enrolled 41 patients aged <55 years with high-degree AVB of unknown etiology whose clinical and genetic data were collected. RESULTS: Genetic variants were identified in 20 (20/41, 48.8%) patients, 11 (11/20, 55%) of whom had LMNA variants including 3 pathogenic (c.961C > T, c.936+1G > T and c.646C > T), 4 likely pathogenic (c.1489-1G > C, c.265C > A, c.1609-2A > G and c.1129C > T) and 3 of uncertain significance (c.1158-3C > G, c.776A > G and c.674G > T). Compared to those without LMNA variants, patients with LMNA variants demonstrated a later age at onset of AVB (41.45 ± 9.89 years vs 32.93 ± 12.07 years, P = .043), had more prevalent family history of cardiac events (81.8% vs 16.7%, P < .000), suffered more frequently atrial (81.8% vs 10.0%, P < .000) and ventricular (72.7% vs 10.0%, P < .000) arrhythmias, and were more significantly associated with enlargement of left atrium (39.91 ± 7.83 mm vs 34.30 ± 7.54 mm, P = .043) and left ventricle (53.27 ± 8.53 mm vs 47.77 ± 6.66 mm, P = .036). CONCLUSIONS: Our findings provide insights into the genetic etiology of AVB in young patients. LMNA variants are predominant in genotype positive patients and relevant to distinctive phenotypic properties.

Chinese guidelines for the diagnosis and management of atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, significantly impacting patients' quality of life and increasing the risk of death, stroke, heart failure, and dementia. Over the past two decades, there have been significant breakthroughs in AF risk prediction and screening, stroke prevention, rhythm control, catheter ablation, and integrated management. During this period, the scale, quality, and experience of AF management in China have greatly improved, providing a solid foundation for the development of the guidelines for the diagnosis and management of AF. To further promote standardized AF management, and apply new technologies and concepts to clinical practice timely and fully, the Chinese Society of Cardiology of Chinese Medical Association and the Heart Rhythm Committee of Chinese Society of Biomedical Engineering jointly developed the Chinese Guidelines for the Diagnosis and Management of Atrial Fibrillation. The guidelines comprehensively elaborated on various aspects of AF management and proposed the CHA2DS2­VASc­60 stroke risk score based on the characteristics of the Asian AF population. The guidelines also reevaluated the clinical application of AF screening, emphasized the significance of early rhythm control, and highlighted the central role of catheter ablation in rhythm control.

Estimated Prostate Volume by Semiautomatic Segmentation of MRI Is More Accurately Correlated with Radical Prostatectomy Specimen Weight than the Volume Calculated by Ellipsoid Formula.

INTRODUCTION: Accurate in vivo prostate volume (PV) estimation is important for obtaining prostate-specific antigen density (PSAD) and further predicting clinically significant prostate cancer (csPCa). We aimed to evaluate the accuracy of multiparametric magnetic resonance imaging (mpMRI)-estimated PV compared to both volume and weight of radical prostatectomy (RP). METHODS: We identified 310 PCa patients who underwent RP following combined targeted and systematic biopsy in our institution from September 2019 to February 2021. The MRI PV was determined using a semiautomated segmentation algorithm. RP PV was calculated using the prolate ellipsoid formula (length × width × height × π/6). Formula (prostate weight = [actual weight-3.8 g]/1.05 g/mL) was applied, and the resulting volume was used in further analysis. RESULTS: The median PV from MRI, RP, and RP weight were 39 mL, 38 mL, and 44 mL, respectively. Spearman's rank correlation coefficients (ρ) were 0.841 (MRI PV vs. RP weight), 0.758 (RP PV vs. RP weight), and 0.707 (MRI PV vs. RP PV) (all p < 0.001). Decreased correlation between the MRI PV and RP PV was observed in the larger (more than 55 mL) prostate. The PSAD derived from MRI PV showed most efficient to detect csPCa in RP specimen (57.9% vs. 57.6% vs. 45.4%). CONCLUSION: MRI PV is correlated better with RP weight than calculated RP PV, especially in larger prostate. The high csPCa detection rate in final pathology suggested that PSAD derived from MRI PV can be confidently used in clinical practice.

Enhanced biomethane production from waste activated sludge anaerobic digestion by ceramsite and amended Fe2O3 ceramsite.

Wastes recycling and reutilization technique could simultaneously fulfill waste control and energy recovery sustainably, which has attracted increasing attention. This work proposed a novel waste reuse technology utilizing ceramsite and amended Fe2O3-ceramsite made from waste activated sludge (WAS) as additives to promote the yield of methane from WAS anaerobic digestion (AD). Experimental results demonstrated that compared to the control (85.05 ± 0.2 mL CH4/g-VS), the cumulative methane yield was effectively enhanced by 14% and 40% when ceramsite and Fe2O3-ceramsite were added. Further investigation revealed that ceramsite, especially the Fe2O3-ceramsite, enriched the populations of key anaerobes involved in hydrolysis, acidification, and methanogenesis. Meanwhile, potential syntrophic metabolisms between syntrophic bacteria and methanogens were confirmed in the Fe2O3-ceramsite AD system. Mechanisms studies exhibited that ceramsite and Fe2O3-ceramsite reinforced intermediate processes for methane production. The favorable pore structure, enhanced Fe (III) reduction capacity and conductivity also contributed a lot to the AD process.

Green synthesis of Fe3O4@ceramsite from sludge improving anaerobic digestion performance of waste activated sludge.

Anaerobic digestion (AD) is a promising technique for waste management, which can achieve sludge stabilization and energy recovery. This study successfully prepared Fe3O4@ceramsite from WAS and applied it as an additive in sludge digestion, aiming to improve the conversion of organics to biomethane efficiency. Results showed that after adding the Fe3O4@ceramsite, the methane production was enhanced by 34.7% compared with the control group (88.0 ± 0.1 mL/g VS). Further mechanisms investigation revealed that Fe3O4@ceramsite enhanced digesta stability by strong buffering capacity, improved sludge conductivity, and promoted Fe (III) reduction. Moreover, Fe3O4@ceramsite has a larger surface area and better porous structure, which also facilitated AD performance. Microbial community analysis showed that some functional anaerobes related to AD such as Spirochaeta and Smithella were enriched with Fe3O4@ceramsite treatment. Potential syntrophic metabolisms between syntrophic bacteria (Syntrophomonas, associated with DIET) and methanogens were also detected in the Fe3O4@ceramsite treatment AD system.

TSC2 inactivation, low mutation burden and high macrophage infiltration characterise hepatic angiomyolipomas.

AIMS: Although TSC1 or TSC2 inactivating mutations that lead to mTORC1 hyperactivation have been reported in hepatic angiomyolipomas (hAML), the role of other somatic genetic events that may contribute to hAML development is unknown. There are also limited data regarding the tumour microenvironment (TME) of hAML. The aim of the present study was to identify other somatic events in genomic level and changes in TME that contribute to tumorigenesis in hAML. METHODS AND RESULTS: In this study, we performed exome sequencing in nine sporadic hAML tumours and deep-coverage targeted sequencing for TSC2 in three additional hAML. Immunohistochemistry and multiplex immunofluorescence were carried out for 15 proteins to characterise the tumour microenvironment and assess immune cell infiltration. Inactivating somatic variants in TSC2 were identified in 10 of 12 (83%) cases, with a median allele frequency of 13.6%. Five to 18 somatic variants (median number: nine, median allele frequency 21%) not in TSC1 or TSC2 were also identified, mostly of uncertain clinical significance. Copy number changes were rare, but detection was impaired by low tumour purity. Immunohistochemistry demonstrated numerous CD68+ macrophages of distinct appearance from Küpffer cells. Multiplex immunofluorescence revealed low numbers of exhausted PD-1+/PD-L1+, FOXP3+ and CD8+ T cells. CONCLUSION: hAML tumours have consistent inactivating mutations in TSC2 and have a low somatic mutation rate, similar to other TSC-associated tumours. Careful histological review, standard IHC and multiplex immunofluorescence demonstrated marked infiltration by non-neoplastic inflammatory cells, mostly macrophages.

'Single-shot' pulmonary vein isolation using a novel lotos pulsed field ablation catheter: a pre-clinical evaluation of feasibility, safety, and 30-day efficacy.

AIMS: Pulsed field ablation (PFA) is emerging as a non-thermal, tissue-specific technique for pulmonary vein isolation (PVI) in atrial fibrillation therapy. This pre-clinical study aims to investigate the feasibility and safety of PVI using a novel PFA system including a nanosecond-scale PFA generator, a novel lotos PFA catheter, and a customized 12 Fr steerable sheath. METHODS AND RESULTS: A total of 11 Yorkshire swine were included in this study, with 4 in the acute cohort and 7 in the chronic cohort. Under general anaesthesia, transseptal puncture and pulmonary vein (PV) angiography was initially performed. The PFA catheter was navigated to position at the right and left PV antrum after the electroanatomic reconstruction of the left atrium. Biphasic PFA applications were performed on PVs in both the spindle-shaped and the lotos-shaped poses. Pulmonary vein isolation and PFA-associated safety were assessed 30 min after ablation in both cohorts and 30 days later in the chronic cohort. Detailed necropsy and histopathology were performed. Additional intracardiac echocardiography and coronary angiogram were evaluated for safety. All target PVs (n = 20) were successfully isolated on the first attempt. No spasm of coronary artery or microbubble was seen during the procedure. Eleven of 12 PVs (91.6%) remained in isolation at the 30-day invasive study. No evidence of PV stenosis was observed in any targets. However, transient diaphragm capture occurred in 17.6%. Histopathological examinations showed no evidence of collateral injury. CONCLUSION: This study provides scientific evidence demonstrating the safety and efficacy of the novel PFA catheter and system for single-shot PVI, which shows great potential.

Electrophysiological characteristics and long-term outcome of substrate-based catheter ablation for left posterior fascicular ventricular tachycardia targeting fragmented antegrade Purkinje potentials during sinus rhythm.

AIMS: The aim of this study was to investigate the electrophysiological characteristics and long-term outcome of patients undergoing substrate-based ablation of left posterior fascicular ventricular tachycardia (LPF-VT) guided by targeting of fragmented antegrade Purkinje potentials (FAPs) during sinus rhythm. METHODS AND RESULTS: This study retrospectively analysed 50 consecutive patients referred for ablation. Substrate mapping during sinus rhythm was performed to identify the FAP that was targeted by ablation. FAPs were recorded in 48 of 50 (96%) patients during sinus rhythm. The distribution of FAPs was located at the proximal segment of posterior septal left ventricle (LV) in two (4.2%) patients, middle segment in 33 (68.8%) patients, and distal segment in 13 (27.1%) patients. In 32 of 48 (66.7%) patients, the FAP displayed a continuous multicomponent fragmented electrogram, while a fragmented, split, and uncoupled electrogram was recorded in 16 (33.3%) patients. Entrainment attempts at FAP region were performed successfully in seven patients, demonstrating concealed fusion and the critical isthmus of LPF-VT. Catheter ablation targeting at the FAPs successfully terminated the LPF-VT in all 48 patients in whom they were seen. Left posterior fascicular (LPF) block occurred in four (8%) patients after ablation. During a median follow-up period of 61.2 ± 16.8 months, 47 of 50 (94%) patients remained free from recurrent LPF-VT. CONCLUSION: Ablation of LPF-VT targeting FAP during sinus rhythm results in excellent long-term clinical outcome. FAPs were commonly located at the middle segment of posterior septal LV. Region with FAPs during sinus rhythm was predictive of critical site for re-entry.

Comparison of strategies for catheter ablation of left posterior fascicular ventricular tachycardia.

AIMS: Traditional ablation strategies including targeting the earliest Purkinje potential (PP) during left posterior fascicular (LPF) ventricular tachycardia (VT) or linear ablation at the middle segment of LPF during sinus rhythm are commonly used for the treatment of LPF-VT. Catheter ablation for LPF-VT targeting fragmented antegrade Purkinje (FAP) potential during sinus rhythm is a novel approach. We aimed to compare safety and efficacy of different ablation strategies (FAP ablation vs. traditional ablation) for the treatment of LPF-VT. METHODS AND RESULTS: Consecutive patients with electrocardiographically documented LPF-VT referred for catheter ablation received either FAP ablation approach or traditional ablation approach. Electrophysiological characteristics, procedural complications, and long-term clinical outcome were assessed. A total of 189 consecutive patients who underwent catheter ablation for LPF-VT were included. Fragmented antegrade Purkinje ablation was attempted in 95 patients, and traditional ablation was attempted in 94 patients. Acute ablation success with elimination of LPF-VT was achieved in all patients. Left posterior fascicular block occurred in 11 of 95 (11.6%) patients in the FAP group compared with 75 of 94 (79.8%) patients in the traditional group (P < 0.001). Fragmented antegrade Purkinje ablation was associated with significant shorter procedure time (94 ± 26 vs. 117 ± 23 min, P = 0.03) and fewer radiofrequency energy applications (4.1 ± 2.4 vs. 6.3 ± 3.5, P = 0.003) compared with the traditional group. One complete atrioventricular block and one left bundle branch block were seen in the traditional group. Over mean follow-up of 65 months, 89 (93.7%) patients in the FAP group and 81 (86.2%) patients in the traditional group remained free of recurrent VT off antiarrhythmic drugs (P = 0.157). CONCLUSION: Left posterior fascicular-ventricular tachycardia ablation utilizing FAP and traditional ablation approaches resulted in similar acute and long-term procedural outcomes. Serious His-Purkinje injury did occur infrequently during traditional ablation. The use of FAP ablation approach was associated with shorter procedure time and fewer radiofrequency energy applications, especially for non-inducible patients.

In-situ production of lactate driving the biotransformation of waste activated sludge to medium-chain fatty acid.

Medium-chain fatty acids (MCFAs) have drawn great attention due to their high energy density and superior hydrophobicity. Waste activated sludge (WAS) has been documented as a renewable feedstock for MCFAs production via anaerobic fermentation. However, MCFAs production from WAS depends on exogenous addition of electron donor (ED, e.g., lactate) for chain elongation (CE) bioprocess, which results in increased economic cost and limited practical application. In this study, a novel biotechnology was proposed to produce MCFAs from WAS with in-situ self-formed lactate by inoculating Yoghurt starter powder containing with Lactobacillales cultures. The batch experimental results revealed that the lactate was in-situ generated from WAS and the maximum production of MCFAs increased from 1.17 to 3.99 g COD/L with the increased addition of Lactobacillales cultures from 6✕107 to 2.3✕108 CFU/mL WAS. In continuous long-term test over 97 days, average MCFA production reached up to 3.94 g COD/L with a caproate yield of 82.74% at sludge retention time (SRT) 12 days, and the average MCFA production increased to 5.87 g COD/L with 69.28% caproate and 25.18% caprylate at SRT 15 days. A comprehensive analysis of the metagenome and metatranscriptome demonstrated that the genus of Lactobacillus and Streptococcus were capable of producing lactate from WAS and upgrading to MCFAs. Moreover, another genus, i.e., Candidatus Promineofilum, was firstly revealed that it might be responsible for lactate and MCFAs production. Further investigation of related microbial pathways and enzyme expression suggested that D-lactate dehydrogenase and pyruvate ferredoxin oxidoreductase contributed to lactate and acetyl-CoA production, which were the crucial steps for MCFAs generation and were most actively expressed. This study provides a conceptual framework of MCFAs from WAS with endogenous ED, potentially enhancing the energy recovery from WAS treatment.

Transperineal Multiparametric Magnetic Resonance Imaging-Ultrasound Fusion Targeted Prostate Biopsy Combined with Standard Template Improves Prostate Cancer Detection.

PURPOSE: Transperineal (TP) prostate biopsy provides an effective approach to prostate cancer (PCa) detection. Although transrectal targeted biopsy has been well described, the specific advantage of the standard TP template or TP targeted biopsy using multiparametric (mp) magnetic resonance imaging (MRI)-ultrasound (US) fusion remains less understood and without consensus. MATERIALS AND METHODS: We identified all men who underwent a transperineal standard 20-core template in addition to a targeted biopsy with mpMRI-US fusion-guided software from September 2019 to February 2021. We assessed and compared clinical, MRI and biopsy characteristics between standard TP template and fusion targeted biopsies. RESULTS: A total of 301 men underwent TP fusion biopsy during the study period. Target lesions on MRI were sampled with 3 targeted cores per patient (IQR 3-4). The overall cancer detection rate was 74.1% and 63.5% by standard template and targeted biopsy, respectively, of which 52.5% and 59.7% were clinically significant (cs) PCa. Combined csPCa detection rate was 62.2%. Of 176 cases with a cancer diagnosis by both biopsy methods, 18.8% were upgraded with targeted biopsies while 18.2% were upgraded with template biopsies. CONCLUSIONS: In men with suspicious lesions on mpMRI, TP MRI fusion-guided biopsies combined with standard template provide a higher overall cancer detection rate and higher detection rate of csPCa than the standard template or targeted biopsy alone. In the setting of a suspicious mpMRI prostate lesion, targeted plus standard template should be included as part of the TP biopsy procedure.

Comparison of Effectiveness and Safety between High-Power Short-Duration Ablation and Conventional Ablation for Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Aim: We aimed to evaluate the effectiveness and safety between high-power short-duration (HPSD) radiofrequency ablation (RFA) and conventional RFA in patients with atrial fibrillation (AF). Methods: Studies comparing HPSD and traditional applications in patients undergoing initial catheter ablation for atrial fibrillation from inception through December 2021 were searched on Pubmed, Medline, Cochrane, and Clinicaltrials.gov. Results: The meta-analysis included seventeen studies with a total of 4934 patients. HPSD group decreased procedure duration (mean difference (MD) -38.28 min, P < 0.001), RF duration (MD -20.51 min, P < 0.001), fluoroscopy duration (MD -5.19 min, P < 0.001), and acute pulmonary vein reconnection (Odds ratio (OR) 0.40, P < 0.001), while improving the freedom from atrial arrhythmia at one year (OR 1.48, 95% confidence interval (CI) 1.12-1.94, P=0.005) and rates of first-pass isolation (OR 8.92, P=0.001). Compared with the conventional group, freedom from atrial arrhythmia at one-year follow-up was higher in the HPSD group without the guidance of AI/LSI (OR 1.66, P=0.01) and studies with a power setting of 40-50 W (OR 1.93, P=0.002). Nevertheless, the two groups had similar effectiveness with a power setting of 50 W in the HPSD RFA (OR 1.10, P=0.52). There was no difference in complications between the two groups (P=0.71). Conclusion: HPSD RFA was associated with shorter procedure duration, higher freedom from atrial arrhythmia, and comparable safety compared to conventional RFA.

Disparities in Secondary Prevention between Stroke and Coronary Heart Disease in China: Cross-Sectional Community-Based Study, 2014-2016.

BACKGROUND: Health care quality and insurance coverage have improved with economic development in China, but the burden of cardiovascular diseases (CVDs) continues to increase with ongoing gaps in prevention. We aimed to compare the uptake of secondary CVD prevention between stroke and coronary heart disease (CHD) patients in China. METHODS: In a cross-sectional community-based survey of 47,841 adults (age ≥45 years) in 7 regions of China between 2014 and 2016, we identified those with a history of stroke or CHD to quantify disparities in conventional secondary CVD prevention strategies in multivariable logistic regression models. RESULTS: There were 4,105 and 1,022 participants with a history of stroke and CHD, respectively. Compared to participants with CHD, those with a history of stroke were significantly less likely to be taking blood-pressure-lowering (39.7% vs. 53%), lipid-lowering (13.7% vs. 36.8%), and antiplatelet (20.8% vs. 50.6%) agents, at least one (48.9% vs. 70.8%) or all 3 recommended medicines (6.1% vs. 24.0%), and were less likely to achieve a lipid-cholesterol target (30.3% vs. 44.0%). Participants with a history of stroke achieved less optimal secondary prevention goals for medication use, either from any (adjusted odds ratio [aOR] 0.54, 95% confidence interval [CI] 0.44-0.66) or all 3 medications (aOR 0.27, 95% CI 0.20-0.36), as well as better blood pressure (aOR 0.81, 95% CI 0.66-0.98) and low-density lipoprotein cholesterol (aOR 0.34, 95% CI 0.27-0.43) levels of control. There were no significant differences in weight, smoking, or physical activity between the groups. CONCLUSION: Stroke patients had lower use of secondary CVD-preventive medication and achieved lower levels of risk factor control than those of CHD patients in China. Nationwide disease-specific strategies, and better education of participants and health care providers, may narrow these gaps.

A Frequent Observation of Wolff-Parkinson-White Syndrome and Fasciculoventricular Pathways in Patients With Danon Disease.

BACKGROUND: Danon disease is typically associated with cardiomyopathy and ventricular pre-excitation. The study aimed to characterize the clinical profile of Danon disease, analyze electrocardiographic (ECG) and electrophysiologic features, and investigate their association with Wolff-Parkinson-White (WPW) syndrome and fasciculoventricular pathways (FVPs).Methods and Results:Clinical course, family history, ECG and electrophysiological data were collected from 16 patients with Danon disease. Over 0.4-8 years of follow up, 1 female patient died suddenly, and 5 male patients died of progressive heart failure by age 13-20 years. Family history analysis revealed that 3 mothers experienced hospitalization or death for heart failure at age 28-41 years. There was 100% penetrance for ECG abnormalities in 13 patients with original ECGs. Short PR intervals and delta waves were present in 9 and 8 patients, respectively. There were significant age-associated increases in the QRS complex width (r=0.556, P=0.048) and the number of leads with notched QRS (r=0.575, P=0.04). Four patients who underwent electrophysiological studies all had FVPs, and 2 of them still had left-side atrioventricular pathways. CONCLUSIONS: Danon disease causes a malignant clinical course characterized by early death caused by heart failure in both genders and progressive ECG changes as patients age. The pre-excited ECG pattern is related to FVPs and WPW, which is suggestive of extensive cardiac involvement.

Connexin 43 participates in atrial electrical remodelling through colocalization with calcium channels in atrial myocytes.

Atrial fibrillation (AF) is associated with atrial conduction disturbances caused by electrical and/or structural remodelling. In the present study, we hypothesized that connexin might interact with the calcium channel through forming a protein complex and, then, participates in the pathogenesis of AF. Western blot and whole-cell patch clamp showed that protein levels of Cav1.2 and connexin 43 (Cx43) and basal ICa,L were decreased in AF subjects compared to sinus rhythm (SR) controls. In cultured atrium-derived myocytes (HL-1 cells), knocking-down of Cx43 or incubation with 30 mmol/L glycyrrhetinic acid significantly inhibited protein levels of Cav1.2 and Cav3.1 and the current density of ICa,L and ICa,T . Incubation with nifedipine or mibefradil decreased the protein level of Cx43 in HL-1 cells. Moreover, Cx43 was colocalized with Cav1.2 and Cav3.1 in atrial myocytes. Therefore, Cx43 might regulate the ICa,L and ICa,T through colocalization with calcium channel subunits in atrial myocytes, representing a potential pathogenic mechanism in AF.

Prevalence of congenital heart disease among school children in Qinghai Province.

OBJECTIVES: This study aimed to investigate the prevalence of congenital heart disease (CHD) among school children in Qinghai province, a high-altitude region in China. METHODS: A cross-sectional study was conducted among school-aged children in 2019. All subjects completed a survey with a structure questionnaire and underwent CHD screening. CHD was screened by standard physical examination and further confirmed by echocardiography. Multivariate logistic regression were used to estimate the association of CHD prevalence with gender, nationality, and altitude. RESULTS: A total of 43,562 children aged 3-19 years participated in the study. The mean (SD) age was 11.2 (3.3) years. 49.7% were boys, and 80.0% were of Tibetan. CHD was identified in 293 children, with an overall prevalence of 6.73 ‰. Among them, 239 were unrecognized CHD, yielding a prevalence of 5.49 ‰. Atrial septal defect accounted for 51.9% of the CHD, followed by patent ductus arteriosus (31.1%), ventricular septal defect (9.9%). The CHD prevalence was significantly higher in female (8 ‰), Han race (18 ‰), children lived in Qumalai county (13 ‰), and children lived in a higher altitude (13 ‰). Female had greater prevalence of total CHD, atrial septal defect, and patent ductus arteriosus, but insignificant difference was observed in ventricular septal defect prvalence than male. In multivariable logistic regression analyses, female (OR, 1.48; 95% CI, 1.17-1.87, P = 0.001), Han population (OR, 3.28; 95% CI, 1.67-6.42, P = 0.001), and higher altitudes (OR, 2.28; 95% CI, 1.74-3.00, P < 0.001) were shown to be independently association with CHD prevalence. CONCLUSIONS: The prevalence of CHD in Qinghai province was 6.73 ‰. Altitude elevation, female, and Han population were independently association with CHD prevalence.

Machine learning in a real-world PFO study: analysis of data from multi-centers in China.

PURPOSE: The association of patent foreman ovale (PFO) and cryptogenic stroke has been studied for years. Although device closure overall decreases the risk for recurrent stroke, treatment effects varied across different studies. In this study, we aimed to detect sub-clusters in post-closure PFO patients and identify potential predictors for adverse outcomes. METHODS: We analyzed patients with embolic stroke of undetermined sources and PFO from 7 centers in China. Machine learning and Cox regression analysis were used. RESULTS: Using unsupervised hierarchical clustering on principal components, two main clusters were identified and a total of 196 patients were included. The average age was 42.7 (12.37) years and 64.80% (127/196) were female. During a median follow-up of 739 days, 12 (6.9%) adverse events happened, including 6 (3.45%) recurrent stroke, 5 (2.87%) transient ischemic attack (TIA) and one death (0.6%). Compared to cluster 1 (n = 77, 39.20%), patients in cluster 2 (n = 119, 60.71%) were more likely to be male, had higher systolic and diastolic blood pressure, higher body mass index, lower high-density lipoprotein cholesterol and increased proportion of presence of atrial septal aneurysm. Using random forest survival (RFS) analysis, eight top ranking features were selected and used for prediction model construction. As a result, the RFS model outperformed the traditional Cox regression model (C-index: 0.87 vs. 0.54). CONCLUSIONS: There were 2 main clusters in post-closure PFO patients. Traditional cardiovascular profiles remain top ranking predictors for future recurrence of stroke or TIA. However, whether maximizing the management of these factors would provide extra benefits warrants further investigations.

Sex Differences in Primary and Secondary Prevention of Cardiovascular Disease in China.

BACKGROUND: Despite improvements in diagnostic and therapeutic interventions to combat cardiovascular disease (CVD) in recent decades, there are significant ongoing access gaps and sex disparities in prevention that have not been adequately quantified in China. METHODS: A representative, cross-sectional, community-based survey of adults (aged ≥45 years) was conducted in 7 geographic regions of China between 2014 and 2016. Logistic regression models were used to determine sex differences in primary and secondary CVD prevention, and any interaction by age, education level, and area of residence. Data are presented as adjusted odds ratios (ORs) and 95% CIs. RESULTS: Of 47 841 participants (61.3% women), 5454 (57.2% women) had established CVD and 9532 (70.5% women) had a high estimated 10-year CVD risk (≥10%). Only 48.5% and 48.6% of women and 39.3% and 59.8% of men were on any kind of blood pressure (BP)-lowering medication, lipid-lowering medication, or antiplatelet therapy for primary and secondary prevention, respectively. Women with established CVD were significantly less likely than men to receive BP-lowering medications (OR, 0.79 [95% CI, 0.65-0.95]), lipid-lowering medications (OR, 0.69 [95% CI, 0.56-0.84]), antiplatelets (OR, 0.53 [95% CI, 0.45-0.62]), or any CVD prevention medication (OR, 0.62 [95% CI, 0.52-0.73]). Women with established CVD, however, had better BP control (OR, 1.31 [95% CI, 1.14-1.50]) but less well-controlled low-density lipoprotein cholesterol (OR, 0.66 [95% CI, 0.57-0.76]), and were less likely to smoke (OR, 13.89 [95% CI, 11.24-17.15]) and achieve physical activity targets (OR, 1.92 [95% CI, 1.61-2.29]). Conversely, women with high CVD risk were less likely than men to have their BP, low-density lipoprotein cholesterol, and bodyweight controlled (OR, 0.46 [95% CI, 0.38-0.55]; OR, 0.60 [95% CI, 0.52-0.69]; OR, 0.55 [95% CI, 0.48-0.63], respectively), despite a higher use of BP-lowering medications (OR, 1.21 [95% CI, 1.01-1.45]). Younger patients (<65 years) with established CVD were less likely to be taking CVD preventive medications, but there were no sex differences by area of residence or education level. CONCLUSIONS: Large and variable gaps in primary and secondary CVD prevention exist in China, particularly for women. Effective CVD prevention requires an improved overall nationwide strategy and a special emphasis on women with established CVD, who have the greatest disparity and the most to benefit.

Novel immune-related signature for risk stratification and prognosis in prostatic adenocarcinoma.

A substantial proportion of prostatic adenocarcinoma (PRAD) patients experience biochemical failure (BCF) after radical prostatectomy (RP). The immune microenvironment plays a vital role in carcinogenesis and the development of PRAD. This study aimed to identify a novel immune-related gene (IRG)-based signature for risk stratification and prognosis of BCF in PRAD. Weighted gene coexpression network analysis was carried out to identify a BCF-related module in a discovery cohort of patients who underwent RP at the Massachusetts General Hospital. The median follow-up time was 70.32 months. Random forest and multivariate stepwise Cox regression analyses were used to identify an IRG-based signature from the specific module. Risk plot analyses, Kaplan-Meier curves, receiver operating characteristic curves, univariate and multivariate Cox regression analyses, stratified analysis, and Harrell's concordance index were used to assess the prognostic value and predictive accuracy of the IRG-based signature in the internal discovery cohort; The Cancer Genome Atlas database was used as a validation cohort. Tumor immune estimation resource database analysis and CIBERSORT algorithm were used to assess the immunophenotype of PRAD. A novel IRG-based signature was identified from the specific module. Five IRGs (BUB1B, NDN, NID1, COL4A6, and FLRT2) were verified as components of the risk signature. The IRG-based signature showed good prognostic value and predictive accuracy in both the discovery and validation cohorts. Infiltrations of various immune cells were significantly different between low-risk and high-risk groups in PRAD. We identified a novel IRG-based signature that could function as an index for assessing tumor immune status and risk stratification in PRAD.