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Age-related cardiovascular diseases continue to be important issues that contribute to the societal burden. Unveiling the molecular mechanisms underlying age-related cardiovascular diseases provides novel opportunities to delay aging and facilitate early disease diagnosis and treatment. This study utilized knockout mice lacking melatonin receptors type 1A (MT1) and 1B (MT2). Ultrasonography, pathological staining, and transcriptomics were used to investigate the role of MT1/2 in the hearts of aging mice. Knockout of both receptors decreased ejection fraction and exacerbated fibrosis, inflammation, oxidative stress, and apoptosis levels in aging mice. Our findings indicated that the cardiac function of MT1 knockout mice was more severely affected than that of MT2 knockout mice. Additionally, we observed that intraperitoneal administration of melatonin (20 mg/kg/day for 90 days) ameliorated abnormal cardiac function in aging mice. However, the absence of MT1/2 resulted in the inability of melatonin to improve cardiac function. Our study, utilizing an aging polymerase chain reaction assay and cell experiments, revealed that melatonin receptors potentially influence cardiac function in aging mice through their effects on leukocyte differentiation antigen 14 (CD14) expression. Consequently, melatonin receptors, particularly MT1, are key contributors to cardiac aging, and therapeutic interventions targeting this receptor are promising for delaying the progression of cardiac aging., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Inflammatory indices derived from complete blood tests have been reported to be associated with poor outcomes in patients with atrial fibrillation (AF). The data about the relationship between inflammatory indices and left atrial appendage thrombus (LAAT) or dense spontaneous echo contrast (SEC) are limited., Aim: To explore the value of inflammatory indices for predicting the presence of LAAT or dense SEC in nonvalvular AF patients., Methods: A total of 406 patients with nonvalvular AF who underwent transesophageal echocardiography were included and divided into two groups based on the presence (study group) or absence (control group) of LAAT or dense SEC. Inflammatory indices, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), were calculated from complete blood analysis. The associations of inflammatory indices with LAAT/dense SEC were analyzed using logistic regression., Results: LAAT and dense SEC were detected in 11 (2.7%) and 42 (10.3%) patients, respectively. The PLR only showed an association with LAAT/dense SEC in the univariate model. Elevated NLR (odds ratio [OR] = 1.48, 95% confidence interval [CI]: 1.11-1.98, P = 0.007) and reduced LMR (OR = 0.59, 95%CI: 0.41-0.83, P = 0.003) were found to be independent risk factors for the presence of LAAT/dense SEC. The areas under the NLR and LMR curves for predicting LAAT/dense SEC were 0.73 (95%CI: 0.66-0.80, P < 0.001) and 0.73 (95%CI: 0.65-0.81, P < 0.001), respectively, while the cutoff values were 2.8 (sensitivity: 69.8%; specificity: 64.0%) and 2.4 (sensitivity: 71.7%; specificity: 60.6%), respectively., Conclusion: Increased NLR and decreased LMR may predict LAAT/dense SEC in patients with nonvalvular AF., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Nirmatrelvir, a pivotal component of the oral antiviral Paxlovid for COVID-19, targets the SARS-CoV-2 main protease (M pro ) as a covalent inhibitor. Here, we employed combined computational methods to explore how the prevalent Omicron variant mutation P132H, alone and in combination with A173V (P132H-A173V), affects nirmatrelvir's efficacy. Our findings suggest that P132H enhances the noncovalent binding affinity of M pro for nirmatrelvir, whereas P132H-A173V diminishes it. Although both mutants catalyze the rate-limiting step more efficiently than the wild-type (WT) M pro , P132H slows the overall rate of covalent bond formation, whereas P132H-A173V accelerates it. Comprehensive analysis of noncovalent and covalent contributions to the overall binding free energy of the covalent complex suggests that P132H likely enhances M pro sensitivity to nirmatrelvir, while P132H-A173V may confer resistance. Per-residue decompositions of the binding and activation free energies pinpoint key residues that significantly affect the binding affinity and reaction rates, revealing how the mutations modulate these effects. The mutation-induced conformational perturbations alter drug-protein local contact intensities and the electrostatic preorganization of the protein, affecting noncovalent binding affinity and the stability of key reaction states, respectively. Our findings inform the mechanisms of nirmatrelvir resistance and sensitivity, facilitating improved drug design and the detection of resistant strains.

With the improvement of oncology diagnosis and treatment, the survival time of cancer patients has been significantly prolonged, and the cancer therapy-related cardiovascular toxicity such as radiotherapy, chemotherapy, immunotherapy, and surgery are becoming more and more prominent, and it is in this context that the germ of Cardio-Oncology exploration has come into being. The multidisciplinary Cardio-Oncology team aims to establish a multidisciplinary prevention and control system to assess patients' baseline risk factors, individualized monitoring, and weighing the risk-benefit ratio of cancer therapy. At present, the connotation of the discipline of Cardio-Oncology has been expanded horizontally and deepened vertically in China, and Cardio-Oncology treatment centers have blossomed all over the country. Moreover, international and domestic scholars continue to improve Cardio-Oncology guidelines and consensus through their own practice, and develop artificial intelligence software to help the development of the discipline. It is believed that in the future, with the training of Cardio-Oncologists and the output of high-quality clinical research evidence, cardiovascular safety of cancer patients can be ensured more scientifically and effectively.

The heart undergoes pathological cardiac hypertrophy as an adaptive response to prolonged pathological stimulation, leading to cardiomyocyte hypertrophy, fibroblast proliferation, and an increase in extracellular matrix. Chinese medicine monomers are now receiving much attention for the treatment of cardiac hypertrophy and myocardial remodeling. Biochanin A (BCA) is a kind of flavonoid structural monomer, which has a certain therapeutic effect on bone thinning disease, aging syndrome, lung cancer, etc. Moreover, it exhibits hypoglycemic, anti-inflammatory, anti-oxidation, anti-bacteria and other pharmacological properties. It is still unknown whether BCA has an impact on the mechanism of TAC-induced cardiac hypertrophy. Here, cardiac remodeling was induced by TAC. BCA was injected intraperitoneally at 25 and 50 mg/kg/day one week in advance. Masson, WGA, DHE and other pathological staining and serum were used to detect the inhibitory effect of BCA on cardiac hypertrophy in mice. The anti-hypertrophic effect of BCA was demonstrated by studying the pathological manifestations of Neonatal rat cardiomyocytes (NRCMs) and cardiac fibroblasts (CFs) in vitro. The results showed that BCA significantly reduced TAC-induced fibrosis, inflammation, oxidative stress, and myocardial hypertrophy. BCA inhibited Ang II-induced cell hypertrophy and oxidative stress in NRCMs in vitro and Ang II-induced CF migration, proliferation, and collagen secretion. This suggests that BCA plays a key role in inhibiting the progression of myocardial remodeling, suggesting that BCA may be a promising agent for the treatment of myocardial hypertrophy and fibrosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: This study aimed to explore the roles of duration and burden of atrial high-rate episode (AHRE) on ischemic stroke in patients with pacemaker implantation., Methods: Patients with pacemaker implantation for bradycardia from 2013 to 2017 were consecutively enrolled. Data such as gender, age, combined diseases, type of AF, left atrial size, left ventricular size, left ventricular ejection fraction, CHA 2 DS 2 -VASc score, and anticoagulants were collected. The burden and duration of AHRE based on different interval partition were also recorded in detail to evaluate the impacts on ischemic stroke. Cox regression analysis with time-dependent covariates was conducted., Results: A total of 220 patients with AHRE were enrolled. The average follow-up time was 48.42 ± 17.20 months. Univariate regression analysis showed that diabetes (p = .024), high CHA 2 DS 2 -VASc score (≥ 2) (p = .021), long mean AHRE burden (p = .011), long maximal AHRE burden (p = .015), long AHRE duration lasting≥48 h (p = .001) or 24 h (p = .001) or 12 h (p = .005) were prone to ischemic stroke. Further multivariate regression analysis showed that long duration of AHRE (≥48 h) (HR 10.77; 95% CI 3.22-55.12; p = .030) were significantly correlated with stroke in patients with paroxysmal AF. There was no significant correlation between the type of AF and stroke (p = .927)., Conclusion: The longer duration of AHRE (≥48 h) was more favorable in predicting ischemic stroke than high CHA 2 DS 2 -VASc score (≥2)., (© 2023 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

Objective: We aimed to determine the epidemiological characteristics of asymptomatic AF in elder community population (≥65 years old) to analyze the detection rate of different screening methods. Methods: The study was a prospective cohort study. The elder (≥65 years old) residents who voluntarily participated in free physical examination in Dalian community were selected. The participants were randomly divided into screening group (including intensive screening group and single screening group) and control group. The control group received interrogation, medical history collection and routine 12-lead electrocardiogram (ECG) examination. Screening group received an additional single-lead ambulatory ECG equipment worn for 5-7 days. Intensive screening group received two equal-length wearings in 2020 and 2021 respectively, while one screening group only wore once in 2020. Results: Finally 3 340 residents ((70.7±5.0) years old) which consisted of 1 488 males (44.55%) were enrolled. There were 1 945 residents in screening group, including 859 in intensive screening group and 1 086 in one-time screening group. The control group included 1 395 people. Detection rate of asymptomatic AF was significantly higher in screening group than control group (79(4.06%) vs. 24(1.72%), P< 0.001). Higher detection rate was found in screening group than control group in AF risk factors (1 or 2-3) subgroups and CHA 2 DS 2 -VASc score (2-3 or≥4) subgroups ( P <0.05). Additionally, no difference was found between intensive screening group and single screening group (42(4.89%) vs. 37(3.41%), P =0.100). Intensive screening increased detection rate (7(6.93%) vs. 1(0.58%), P =0.009) only in residents those with low thrombosis risk (CHA 2 DS 2 -VaSc<2). Conclusions: Screening in elderly (≥65 years old) can significantly improve the detection rate of asymptomatic AF by wearing single lead dynamic ECG device. The rate increased significantly with the increase of risk factors associated with AF by single screening. In addition, repeat screening of the same method may only improve detection rates in the group with low risk thrombotic scores and non-combination of AF risk factors.Screening methods that are appropriate for different populations may require further exploration.

Objective: To identify the predictors of pacing-induced cardiomyopathy (PICM) and illustrate the safety and feasibility of conduction system pacing (CSP) upgrade on patients with long-term persistent atrial fibrillation (AF)., Methods: All patients with long-term persistent AF and normal left ventricular ejection fraction (LVEF) ≥50% were consecutively enrolled from January 2008 to December 2017, and all the patients with atrioventricular block (AVB) and high right ventricular pacing (RVP) percentage of at least 40%. The predictors of PICM were identified, and patients with PICM were followed up for at least 1 year regardless of CSP upgrade. Cardiac performances and lead outcomes were investigated in all patients before and after CSP upgrade., Results: The present study included 139 patients, out of which 37 (26.62%) developed PICM, resulting in a significant decrease in the left ventricular ejection fraction (LVEF) from 56.11 ± 2.56% to 38.10 ± 5.81% (p< .01). The median duration for the development of PICM was 5.43 years. Lower LVEF (≤52.50%), longer paced QRS duration (≥175 ms), and higher RVP percentage (≥96.80%) were identified as independent predictors of PICM. Furthermore, the morbidity of PICM progressively increased with an increased number of predictors. The paced QRS duration (183.90 ± 22.34 ms vs. 136.57 ± 20.71 ms, p < .01), LVEF (39.35 ± 2.71% vs. 47.50 ± 7.43%, p < .01), and left ventricular end-diastolic diameter (LVEDD) (55.53 ± 5.67 mm vs. 53.20 ± 5.78 mm, p = .03) improved significantly on patients accepting CSP upgrade. CSP responses and complete reverse remodeling (LVEF ≥50% and LVEDD < 50 mm) were detected in 80.95% (17/21) and 42.9% (9/21) of patients. The pacing threshold (1.52 ± 0.78 V/0.4 ms vs. 1.27 ± 0.59 V/0.4 ms, p = .16) was stable after follow-up., Conclusion: PICM is very common in patients with long-term persistent AF, and CSP upgrade was favorable for better cardiac performance in this patient population., (© 2023 Wiley Periodicals LLC.)

Elderly people without atrial fibrillation (AF) still have a high incidence of cardioembolic stroke, suggesting that thrombus formation within the left atrial appendage (LAA) may also occur in an AF-independent manner. In the present study, we explored the potential mechanisms for aging-induced LAA thrombus formation and stroke in mice. We monitored stroke events in 180 aging male mice (14-24 months) and assessed left atrium (LA) remodeling by echocardiography at different ages. Mice that had stroke were implanted with telemeters to confirm AF. Histological features of LA and LAA thrombi were examined, as well as collagen content, expression of matrix metalloproteinases (MMPs), and leukocyte density in the atria at different ages, in mice with or without stroke. Also, the effects of MMP inhibition on stroke incidence and atrial inflammation were tested. We detected 20 mice (11 %) with stroke, 60 % of which were within 18-19 months of age. Although we did not detect AF in mice with stroke, we detected the presence of LAA thrombi, suggesting that stroke originated from the hearts of these mice. Compared with 18-month-old mice without stroke, 18-month-old stroke mice had enlarged LA with a very thin endocardium, that was associated with less collagen and heightened MMP expression in the atria. During aging, we found that the expression of mRNAs for atrial MMP7, MMP8, and MMP9 peaked at 18 months, which closely correlated with reductions in collagen content and the time-window for cardioembolic stroke in these mice. Treatment of mice with an MMP inhibitor at 17-18 months of age reduced atrial inflammation and remodeling, and stroke incidence. Taken together, our study demonstrates that aging-induced LAA thrombus formation occurs through a mechanism involving upregulation of MMPs and breakdown of collagen, and that treatment with an MMP inhibitor may be effective as a treatment strategy for this heart condition., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2023. Published by Elsevier Ltd.)

Background: The relationship between cumulative non-high-density lipoprotein cholesterol (non-HDL-C) burden and atherosclerotic cardiovascular disease (ASCVD) remains unclear., Objective: To prospectively examine the association between cumulative non-HDL-C burden and ASCVD risk in the Kailuan cohort of China., Methods: A total of 49,679 subjects who were free of ASCVD participated in three consecutive examinations in 2006, 2008 and 2010 were enrolled. Duration and concentration of cumulative exposure to non-HDL-C (cumNon-HDL-C) were respectively used to estimate the extent of cumulative non-HDL-C burden. The participants were divided into four groups according to durations of cumNon-HDL-C (0, 2, 4 and 6 years) and five groups according to the quintiles of cumNon-HDL-C concentration (<10.93, 10.93-12.68, 12.69-14.32, 14.33-16.72 and ≥16.73 mmol/L). Cox regression models were used to analyze the influence of cumulative non-HDL-C burden on ASCVD risk., Results: We identified 1,134 incident ASCVD cases during a mean of 4.89 years of follow-up. Multivariable adjusted analysis revealed that compared with no exposure, cumNon-HDL-C duration 2, 4 and 6 years increased ASCVD risk by 26% (HR: 1.26, 95% CI: 1.07-1.47), 56% (HR: 1.56, 95% CI: 1.31-1.86) and 91% (HR: 1.91, 95% CI: 1.59-2.31) respectively; The hazard ratios (HRs) for the fourth and fifth versus lowest quintile of cumNon-HDL-C concentration were 1.25 and 1.72 for ASCVD. Each standard deviation increment in cumNon-HDL-C concentration was associated with a 10% increased risk of ASCVD., Conclusion: Long-term and higher cumNon-HDL-C were all significantly associated with an increased risk of ASCVD independent of single non-HDL-C level., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Guan, Shi, Xu, Chen, Zhang, Dong, Gao, Wu and Xia.)

Aims: This study aimed to investigate the efficacy and safety of CSP in patients with a high percentage of ventricular pacing and heart failure with HFmrEF., Methods: Patients who underwent CSP for HFmrEF and ventricular pacing >40% were consecutively enrolled from January 2018 to May 2021. All participants were followed up at least 12 months. Clinical data including cardiac performance and lead outcomes were compared before and after the procedure. Left ventricular ejection fraction (LVEF) was measured using the biplane Simpson's method. HFmrEF was defined as heart failure with the LVEF ranging from 41%-49%., Results: CSP was successfully performed in 64 cases (96.97%), which included 16 cases of left bundle branch pacing (LBBP) and 48 cases of His bundle pacing (HBP). After a mean of 23.12 ± 8.17 months follow-up, NYHA classification ( P  < 0.001), LVEF (42.45 ± 1.84% vs. 49.97 ± 3.57%, P  < 0.001) and left ventricular end diastolic diameter (LVEDD) (55.59 ± 6.17 mm vs. 51.66 ± 3.48 mm, P  < 0.001) improved significantly. During follow-up, more than half (39/64,60.9%) of patients returned to normal LVEF and LVEDD with complete reverse remodeling. The pacing threshold in LBBP was lower (0.90 ± 0.27 V@0.4 ms vs. 1.61 ± 0.71 V@0.4 ms, P  < 0.001) than that in HBP. No perforation, electrode dislodging, thrombosis or infection was observed during follow-up., Conclusions: CSP could improve the clinical outcomes in patients with HFmrEF and a high percentage of ventricular pacing. LBBP might be a better choice because of its feasibility and safety, especially in patients with infranodal atrioventricular block., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Zhang, Zhao, Yang, Ma, Ma, Zhao, Xia, Gao, and Dong.)

Background: This study aimed to investigate whether increased arterial stiffness, measured by brachial-ankle pulse wave velocity (baPWV) is associated with cancer., Materials and Methods: A total of 45,627 Chinese adults underwent a baPWV examination. The participants were followed up from 1st January 2012 to 31st December 2018. Cox proportional hazards model was used to assess the association between the baPWV values and cancer., Results: During a total follow-up duration of 172,775.69 person-years, there were 553 new cases of cancer. The subjects in the highest baPWV group showed an increased risk of cancer when compared with the lowest baPWV group as confirmed by multivariate-adjusted hazard ratios (HR = 1.51, 95% CI = 1.14∼2.00) in the entire cohort. Compared with participants in the lowest baPWV group, the HRs (95% CI) for digestive cancer in the second and third groups were 1.55 (1.00∼2.40) and 1.99 (1.19∼3.33), respectively. The Kaplan-Meier analysis demonstrated a significant increase in cancer in participants with a baPWV ≥ 18 m/s ( P < 0.001). Compared with the lowest baPWV group, the highest baPWV group showed an increased risk of cancer in men (HR = 1.72, 95% CI = 1.22∼2.43) and those < 60 years (HR = 1.75, 95% CI = 1.20∼2.55), respectively., Conclusion: Increased arterial stiffness measured by baPWV is associated with cancer occurrence, especially digestive cancer occurrence., Clinical Trial Registration: ClinicalTrials.gov, identifier ChiCTR-TNRC-11001489., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jiang, Xing, Hidru, Li, Yang, Chen, Xia and Wu.)

The indispensable role of the SARS-CoV-2 main protease (Mpro) in the viral replication cycle and its dissimilarity to human proteases make Mpro a promising drug target. In order to identify the non-covalent Mpro inhibitors, we performed a comprehensive study using a combined computational strategy. We first screened the ZINC purchasable compound database using the pharmacophore model generated from the reference crystal structure of Mpro complexed with the inhibitor ML188. The hit compounds were then filtered by molecular docking and predicted parameters of drug-likeness and pharmacokinetics. The final molecular dynamics (MD) simulations identified three effective candidate inhibitors (ECIs) capable of maintaining binding within the substrate-binding cavity of Mpro. We further performed comparative analyses of the reference and effective complexes in terms of dynamics, thermodynamics, binding free energy (BFE), and interaction energies and modes. The results reveal that, when compared to the inter-molecular electrostatic forces/interactions, the inter-molecular van der Waals (vdW) forces/interactions are far more important in maintaining the association and determining the high affinity. Given the un-favorable effects of the inter-molecular electrostatic interactions-association destabilization by the competitive hydrogen bond (HB) interactions and the reduced binding affinity arising from the un-compensable increase in the electrostatic desolvation penalty-we suggest that enhancing the inter-molecular vdW interactions while avoiding introducing the deeply buried HBs may be a promising strategy in future inhibitor optimization., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Aims: Left atrial volume index (LAVI) is an adequate analysis to predicate the left ventricle (LV) filling pressures, providing a powerful predictive marker of LV diastolic dysfunction. LAVI is a dynamic morphophysiological marker, and whether LAVI changes can predicate clinical outcomes in HF with preserved ejection fraction (HFpEF) is unknown., Methods: HFpEF patients were retrospectively studied from the First Affiliated Hospital of Dalian Medical University. Patients were classified into deteriorated, stable and improved groups according to the change in LAVI. Rehospitalization was defined as the main endpoint, the composite outcome of rehospitalization or all-cause death was defined as the secondary endpoint., Results: A total of 409 patients were included. In this cohort, the percentage of deteriorated, stable, and improved LAVI were 99 (24.2%), 235 (57.4%), and 75 (18.4%), respectively. During the 22 months follow-up period, 168 patients (41.1%) were rehospitalized, 31 patients (7.5%) died and 182 patients (44.5%) experienced a composite outcome. Multivariate Cox regression showed that compared to improved LAVI, those with deteriorated and stable LAVI experienced higher risk of rehospitalization. Logistic regression showed atrial fibrillation (AF) and higher creatinine were independent predictors of deteriorated LAVI, whereas the use of loop diuretics, calcium channel blockers (CCB), and high level of high-density lipoprotein cholesterol (HDL-C) were significantly associated with improved LAVI., Conclusions: Change in LAVI provides a powerful and dynamic morphophysiological marker of LV filling status and can be used to evaluate the rehospitalization in HFpEF patients., (© 2022 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

The cardiovascular disease pathogenesis is extremely complex and seriously threatens human health. Cardiomyocyte death plays a significant role in cardiovascular disease occurrence and development. In addition to the previously revealed modes of cell death (apoptosis, autophagy, and pyroptosis), ferroptosis is highly related to the development of cardiovascular diseases, including arrhythmia, atherosclerosis, and myocardial ischemia/reperfusion. Ferroptosis is a novel cell death pathway driven by lipid peroxidation and iron overload. Lipid, amino acid, and iron metabolism regulate the ferroptosis pathway. Small molecule compounds (iron chelators, antioxidants, and ferroptosis inhibitors) and genetic programming can alleviate or prevent cardiovascular disease by inhibiting the ferroptosis pathway. Ferroptosis plays a key role in various cardiovascular disease occurrence and development, and inhibiting ferroptosis in cardiomyocytes is expected to become a feasible treatment method. In this mini-review, we systematically summarize the molecular mechanisms of ferroptosis in different cardiovascular diseases, delineate the regulatory network between ferroptosis and cardiovascular diseases, and highlight its potential therapeutic targets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Lin, Xia, Xie and Yang.)

Objective: To explore the incidence and risk factors of cardiovascular events in hematological neoplasms patients treated with anthracyclines in the real world. Methods: A total of 408 patients with lymphoma and leukemia, who were treated with anthracyclines during hospitalization in the First Affiliated Hospital of Dalian Medical University from January 1, 2018 to July 31, 2021, were included in this retrospective study. Patients were divided into cardiovascular event group ( n =74) and non-cardiovascular event group ( n =334). The primary endpoint was cardiovascular events (arrhythmia, heart failure, acute myocardial infarction etc.) after anthracyclines therapy. The secondary endpoint was all-cause mortality, cardiovascular-cause death, discontinued chemotherapy due to cardiovascular events. Multivariate regression analysis was used to investigate the risk factors of cardiovascular events. Kaplan-Meier was performed to calculate the incidence of all-cause mortality. Results: The mean age was (55.6±14.9) years, and there were 227 male patients (55.6%) in this cohort. The median follow-up time was 45 months. During follow-up, cardiovascular adverse events occurred in 74 patients (18.1%), including 45 heart failure (38 were heart failure with preserved ejection fraction), 30 arrhythmia, 4 acute myocardial infarction and 2 myocarditis/pericarditis. Multivariate regression analysis showed age ( OR =1.024, 95% CI 1.003-1.045, P =0.027) and history of hypertension over 10 years ( OR =2.328, 95% CI 1.055-5.134, P =0.036) were independent risk factors for the cardiovascular events. Kaplan-Meier survival curve showed mortality was significantly higher in cardiovascular event group than in non-cardiovascular event group (47.3% vs. 26.6%, P =0.001). In the cardiovascular event group, chemotherapy was discontinued in 9 cases (12.2%) due to cardiovascular events and cardiovascular death occurred in 7 cases (9.5%). Conclusions: Although heart failure is the main cardiovascular event in lymphoma and leukemia patients post anthracyclines therapy, other cardiovascular events especially arrhythmias are also common. The presence of cardiovascular events is associated with higher risk of all-cause mortality in these patients. Age and long-term hypertension are independent risk factors for cardiovascular events in lymphoma and leukemia patients after anthracyclines treatment.

Recent studies have demonstrated that hyperglycemia is a major risk factor for the development and exacerbation of cardiovascular disease (CVD). However, the molecular mechanisms involved in diabetic cardiomyopathy (DCM) have not been fully elucidated. In this study, we focused on the underlying mechanism of DCM. Leptin receptor-deficient db/db mice were used to model a type 2 diabetes mellitus (T2DM) model in our study. WT mice and db/db mice received 4-phenylbutyric acid (4-PBA) (25 mg/kg/day) and saline by intraperitoneal injection every other day for 4 weeks. WT and db/db mice were given tail vein injections of 100 μL of rAAV9-Sh-MAPK10 and rAAV9-Sh-GFP at the age of 6-8 weeks. Echocardiography was performed to measure cardiac function, histological examinations were used to evaluate ventricular hypertrophy and fibrosis. Quantitative RT-qPCR was used to assess the mRNA expression of Jun N-terminal kinase 3 (JNK3, MAPK10), atrial natriuretic factor (ANF), brain natriuretic peptide (BNP), and collagen I and III. Immunoblotting was performed to measure the levels of cardiac hypertrophy-related proteins, fibrosis-related proteins, endoplasmic reticulum stress (ERS)-related proteins and apoptosis-related proteins. TUNEL staining was performed to examine cardiomyocyte apoptosis. In contrast to 12-week-old db/db mice, 16-week-old db/db mice showed the most severe myocardial dysfunction. The DCM induced by hyperglycemia was largely alleviated by 4-PBA (25 mg/kg/day, intraperitoneal injection). Similarly, tail vein injection of rAAV9-Sh-MAPK10 reversed the phenotype of the heart in db/db mice including cardiac hypertrophy and apoptosis in db/db mice. The mechanistic findings suggested that hyperglycemia initiated the ERS response through the negative regulation of sirtuin 1 (SIRT1), leading to the occurrence of myocardial dysfunction, and specific knockdown of MAPK10 in the heart directly reversed myocardial dysfunction induced by hyperglycemia. We demonstrated that hyperglycemia promotes DCM in db/db mice through the ERS-MAPK10 signaling pathway in diabetic mice., (© 2022. The Author(s).)

Angiotensin II (Ang II) induced Atrial fibrillation (AF) often accompanied with reduced ATRAP which is a negative modulator of Ang II type 1 receptor (AT1R). Melatonin can protect against AF, but the underlying molecular mechanism remains poorly understood. In this study, Ang II was used to induce AF, and AF inducibility and duration were documented telemetrically. Ang II-infused mice had a higher AF incidence, which was associated with atrial fibrosis, inflammation, and oxidative stress. Melatonin partially inhibited these effects, and enforced expression of siRNA-ATRAP in atria counteracted the beneficial role of melatonin. Specifically, melatonin inhibited expression of Ang II-induced proteasome and immunoproteasome subunits β2, β2i, β5, and β5i as well as their corresponding trypsin-like and chymotrypsin-like activities and blocked ATRAP degradation. In turn, this inhibited AT1R-mediated NF-κB signaling, transforming growth factor (TGF)-β1/Smad signaling in the atria, and thereby affected atrial remodeling and AF. Melatonin receptor inhibition by the chemical inhibitor luzindole partially inhibited the inhibitory effects of melatonin on proteasome activity and also Ang II-induced pathological changes in the atria. Overall, our study demonstrates that melatonin protects against Ang II-induced AF by inhibiting proteasome activity and stabilizing ATRAP expression, and these effects are partially dependent on melatonin receptor activation., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Cancer patients treated with anthracyclines are susceptible to atrial fibrillation (AF), while the mechanisms remain unclear. Due to sudden and unpredictable features, prediction of anthracycline-induced AF at early phase is difficult. Clinically, we tested whether anthracycline-induced early atrial remodeling in patients could be detected by echocardiography. Experimentally, we investigated the mechanisms of doxorubicin-induced atrial remodeling and AF in mice, and the protective effects of dexrazoxane and antioxidants. Methods and Results: Postsurgery breast cancer patients with an anthracycline-containing or anthracycline exclusion regimen were recruited for echocardiography before chemotherapy, and 3 and 6 months after chemotherapy. Mice were injected with doxorubicin or vehicle (5 mg/kg/week, 4 weeks), and left atrial diameter, electrical transmission, and AF inducibility were measured. Meanwhile, the level of reactive oxygen species (ROS), activity of antioxidant enzymes, cardiomyocyte size, vacuolization, inflammation, and fibrosis were also measured in mouse atria. The therapeutic effects of dexrazoxane and antioxidants on doxorubicin-induced changes in the aforementioned parameters were also determined. While ventricular parameters and functions were unchanged in cancer patients receiving anthracyclines before and after chemotherapy, left atrial reservoir and conduit function were decreased at 3 months postchemotherapy versus prechemotherapy. Doxorubicin-induced susceptibility to AF occurred in mice before onset of ventricular dysfunction. Doxorubicin-induced AF was via inducing structural remodeling (cardiomyocyte death, hypotrophy, and vacuolization) and electrical remodeling (reduction and redistribution of connexin 43) in atria, which was effectively prevented by dexrazoxane or antioxidants through inhibiting ROS generation or enhancing ROS elimination. Innovation and Conclusion: AF inducibility was induced after doxorubicin injection, which can be inhibited by repressing the ROS level. Antioxid. Redox Signal . 37, 19-39. The Clinical Trial Registration number is PJ-KS-KY-2019-73.

The optimal catheter ablation (CA) strategy for patients with persistent atrial fibrillation (PeAF) and heart failure (HF) remains uncertain. Between 2016 and 2020, 118 consecutive patients with PeAF and HF who underwent the CA procedure in two centers were retrospectively evaluated and divided into the pulmonary vein isolation (PVI)-only and PVI + additional ablation groups. Transthoracic echocardiography (TTE) was performed at baseline, one month, and 12 months after the CA procedure. The HF symptoms and left ventricular ejection fraction (LVEF) improvements were analyzed. Fifty-six patients underwent PVI only, and 62 patients received PVI with additional ablation. Compared with the baseline, a significant improvement in the LVEF and left atrial diameter postablation was observed in all patients. No significant HF improvement was detected in the PVI + additional ablation group than in the PVI-only group (74.2% vs. 71.4%, P = 0.736), but the procedure and ablation time were significantly longer (137.4 ± 7.5 vs. 123.1 ± 11.5 min, P = 0.001). There was no significant difference in the change in TTE parameters and the number of rehospitalizations. For patients with PeAF and HF, CA appears to improve left ventricular function. Additional ablation does not improve outcomes and has a significantly longer procedure time. Trial registration number is as follows: ChiCTR2100053745 (Chinese Clinical Trial Registry; https://www.chictr.org.cn/index.aspx)., Competing Interests: The authors declare that they have no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Cheng-ming Ma et al.)

Objective: This study aimed to explore the outcomes of His-Purkinje conduction system pacing (HPCSP) and to screen the predictors of left ventricular (LV) complete reverse remodeling in patients with true left bundle branch block (LBBB) and heart failure with reduced ejection fraction (HFrEF)., Methods: Patients who underwent HPCSP for true LBBB and HFrEF from April 2018 to August 2020 were consecutively enrolled. All participants were followed up for at least 1 year. Thrombosis, infection, lead dislodgement, perforation, and other complications were observed after HPCSP. Clinical data, including echocardiographic parameters, electrocardiogram measurements, and cardiac function, were assessed before and after the procedure., Results: A total of 46 patients were enrolled. HPCSP was successfully deployed in 42 cases (91.30%), which included 37 cases with His bundle pacing (HBP) and 5 cases with left bundle branch pacing (LBBP). The QRS duration decreased significantly (169.88 ± 19.17 ms vs. 113.67 ± 20.68 ms, P < 0.001). Left ventricular end-systolic volume (LVESV) (167.67 ± 73.20 ml vs. 85.97 ± 62.24 ml, P < 0.001), left ventricular end-diastolic diameter (LVEDD) (63.57 ± 8.19 mm vs. 55.46 ± 9.63 mm, P = 0.003) and left ventricular ejection fraction (LVEF) (26.52 ± 5.60% vs. 41.86 ± 11.56%, P < 0.001) improved dramatically. Complete reverse remodeling of the LV with normalized LVEF and LVEDD was found in nearly half of the patients (45.24%). A short QRS duration after HPCSP was a strong predictor of normalized LVEF and LVEDD ( P < 0.001). The thresholds increased markedly in two patients approximately 6 months after HBP. No patients died during the total follow-up period of 20.07 ± 6.45 months., Conclusion: Complete reverse remodeling of the LV could be found in nearly half of the patients with HFrEF and true LBBB after HPCSP, and the short QRS duration after HPCSP was a strong predictor., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guan, Li, Zhao, Zhao, Yang, Dai, Dai, Gao, Xia and Dong.)

Objective: To explore the application effects of feedforward control theory in the rollover bed treatment of mass patients with burn-explosion combined injury. Methods: A retrospective observational research was conducted. From June 13 to 14, 2020, 15 patients with severe burn-explosion combined injury caused by liquefied natural gas tank car explosion and conforming to the inclusion criteria were admitted to the Second Affiliated Hospital of Zhejiang University School of Medicine. There were 13 males and 2 females, aged 33-92 (66±17) years. All the patients were treated with rollover bed from 48 h post admission, and the feedforward control theory was introduced, including establishing a special feedforward control management team for rollover bed, clarifying the duties of the medical staff in the rollover bed treatment of patients, implementing the cooperation strategy of multidisciplinary physician, training and examining for 80 nurses in the temporarily organized nurse team in the form of "rollover bed workshop", and formulating the checklist and valuation list of rollover bed treatment for continuous quality control. The frequency and the total number of turning over, and successful rate of one-time posture change with the rollover bed of patients within 30 days of admission were recorded, the occurrences of adverse events caused by improper operation for the rollover bed during the treatment were observed, including respiratory and cardiac arrests, treatment interruption, unplanned extubation, bed falling, and skin graft displacement. The lowest levels of arterial partial pressure of oxygen (PaO 2 ) and arterial partial pressure of carbon dioxide (PaCO 2 ), the number of patients with oxygenation index>300 mmHg (1 mmHg=0.133 kPa), and the occurrence of acute respiratory distress syndrome (ARDS) of patients within 2 days of admission and on the 30 th day of admission were recorded. Results: Within 30 days of admission, the patients were turned over with the rollover bed for 2 to 6 times each day, with a total of 1 320 turning over operations, the successful rate of one-time posture change reached 99.9% (1 319/1 320), and no adverse event occurred. Within 2 days of admission, the lowest levels of PaO 2 and PaCO 2 of the patients were (100±19) and (42±4) mmHg, respectively, and the number of patients with mild, moderate, and severe ARDS were 10, 2, and 3, respectively, and none of the patients had oxygenation index>300 mmHg. On the 30 th day of admission, the lowest levels of PaO 2 and PaCO 2 of the patients were (135±28) and (37±8) mmHg, respectively, 3 patients developed moderate ARDS, 1 patient developed severe ARDS, and 11 patients had oxygenation index>300 mmHg. Conclusions: The introduction of feedforward control theory in the treatment of rollover bed of mass patients with burn-explosion combined injury can ensure safe and successful completion of turning over with the rollover bed, promote the repair of burn wound, and improve respiratory function, and therefore improve the treatment quality of patients.

The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (RBD CoV2 ) has a higher binding affinity to the human receptor angiotensin-converting enzyme 2 (ACE2) than the SARS-CoV RBD (RBD CoV ). Here, we performed molecular dynamics (MD) simulations, binding free energy (BFE) calculations, and interface residue contact network (IRCN) analysis to explore the mechanistic origin of different ACE2-binding affinities of the two RBDs. The results demonstrate that, when compared to the RBD Co V2 -ACE2 complex, RBD Co V -ACE2 features enhanced dynamicsand inter-protein positional movements and increased conformational entropy and conformational diversity. Although the inter-protein electrostatic attractive interactions are the primary determinant for the high ACE2-binding affinities of both RBDs, the significantly enhanced electrostatic attractive interactions between ACE2 and RBD Co V2 determine the higher ACE2-binding affinity of RBD CoV2 than of RBD CoV . Comprehensive comparative analyses of the residue BFE components and IRCNs between the two complexes reveal that it is the residue changes at the RBD interface that lead to the overall stronger inter-protein electrostatic attractive force in RBD CoV2 -ACE2, which not only tightens the interface packing and suppresses the dynamics of RBD Co V2 -ACE2, but also enhances the ACE2-binding affinity of RBD Co V2 . Since the RBD residue changes involving gain/loss of the positively/negatively charged residues can greatly enhance the binding affinity, special attention should be paid to the SARS-CoV-2 variants carrying such mutations, particularly those near or at the binding interfaces with the potential to form hydrogen bonds and/or salt bridges with ACE2.

Background: This study explored the relationship between the TyG index/serum uric acid (SUA) panel and myocardial revascularization (MRT) for new-onset acute coronary syndromes (ACS)., Methods: Between January 2011 and July 2020, 13,271 new-onset ACS patients were enrolled. The logistic regression models and the odds ratios (ORs) were used to quantify the risk of TyG index/SUA and MRT. Then, interaction analyses of TyG index and SUA on MRT were applied., Results: Elevated TyG index was positively associated higher risks of MRT. However, SUA levels were negatively associated with MRT. Compared with those in the lowest quartile, the risk of MRT increased gradually among patients in Q1 of the SUA category (OR = 1.03, 1.11, and 1.28 for Q2, Q3, and Q4 of TyG index, respectively), Q2 of the SUA category (OR = 1.41, 1.68, and 2.18 for Q2, Q3, and Q4 of TyG index, respectively), Q3 of the SUA category (OR = 1.05, 1.45, and 1.45 for Q2, Q3, and Q4 of TyG index, respectively), and Q4 of the SUA category (OR = 1.20, 1.29, and 1.46 for Q2, Q3, and Q4 of TyG index, respectively). This pattern was observed in both male and female, as well as patients without type 2 diabetes mellitus., Conclusion: Patients with a higher TyG index have a higher proportion of MRT in new-onset ACS. This result also applies to patients with different levels of SUA during new-onset ACS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Lin, Li, Fan, Lin, Wang, Jiang, Xia, Zhang and Yang.)

Human UDP-glucuronosyltransferase 1A1 (hUGT1A1) is one of the most essential phase II enzymes in humans. Dysfunction or strong inhibition of hUGT1A1 may result in hyperbilirubinaemia and clinically relevant drug/herb-drug interactions (DDIs/HDIs). Recently, a high-throughput fluorescence-based assay was constructed by us to find the compounds/herbal extracts with strong inhibition against intracellular hUGT1A1. Following screening of over one hundred of herbal products, the extract of Ginkgo biloba leaves (GBL) displayed the most potent hUGT1A1 inhibition in HeLa-UGT1A1 cells (Hela cells overexpressed hUGT1A1). Further investigations demonstrated that four biflavones including bilobetin, isoginkgetin, sciadopitysin and ginkgetin, are key constituents responsible for hUGT1A1 inhibition in living cells. These biflavones potently inhibit hUGT1A1 in both human liver microsomes (HLM) and living cells, with the IC 50 values ranging from 0.075 to 0.41 μM in living cells. Inhibition kinetic analyses and docking simulations suggested that four tested biflavones potently inhibit hUGT1A1-catalyzed NHPN- O -glucuronidation in HLM via a mixed inhibition manner, showing the K i values ranging from 0.07 to 0.74 μM. Collectively, our findings uncover the key constituents in GBL responsible for hUGT1A1 inhibition and decipher their inhibitory mechanisms against hUGT1A1, which will be very helpful for guiding the rational use of GBL-related herbal products in clinical settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pang, Zhu, Zhou, Ai, Zhu, Wang, Dou, Xia, Ma and Ge.)

Background: Apoptosis, also called programmed cell death, is a genetically controlled process against hyperproliferation and malignancy. The Fas-Fas ligand (FasL) system is considered a major pathway for apoptosis in cells and tissues. Thus, this study aimed to investigate whether single nucleotide polymorphisms (SNPs) in Fas and FasL gene may have effects on the recurrence and survival of patients with hepatocellular carcinoma (HCC) after curative hepatectomy., Methods: We investigated the relationship between Fas rs1800682, rs2234767 and FasL rs763110 polymorphisms and recurrence-free survival (RFS) as well as overall survival (OS) in 117 Chinese Han patients with HCC who underwent hepatectomy., Results: In Kaplan-Meier survival analysis, only Fas rs1800682 (-670 A/G) was associated with RFS and OS. Compared with AA genotype, the AG/GG genotype was significantly associated with better RFS (P = 0.008) and OS (P = 0.020). Moreover, multivariate Cox regression analysis showed that Fas rs1800682 remained as a significant independent predictor of RFS for HCC patients with hepatectomy [AG/GG vs. AA: adjusted hazard ratio = 0.464, 95% confidence interval: 0.275-0.782, P = 0.004], but was not an independent predictor of OS (P = 0.395)., Conclusions: This study demonstrated that Fas -670 G allele may play a protective role in the recurrence and survival of HCC patients with hepatectomy. Furthermore, Fas rs1800682 polymorphism might be a promising biomarker for HCC patients after hepatectomy., (Copyright © 2021. Published by Elsevier B.V.)

Objective: To systematically evaluate and integrate the real experience of burn patients during rehabilitation, and to provide theoretical guidance for the continual nursing care for burn patients. Methods: The systematic evaluation method was adopted. Databases including the China National Knowledge Internet, Wanfang Database, China Biology Medicine disc were retrieved with the search terms in Chinese version of "/, //, ////", and PubMed, Embase , CINAHL , PsycINFO , Cochrane Library were retrieved with the search terms of "burn/burns, rehabilitation/recovery/survivor/survive, experience/views/perceptions/, qualitative/phenomenon/interview/grounded theory". The qualitative studies on the real experience of burn patients during rehabilitation published from the establishment of each database to June 2020 were searched. The quality of the included studies was evaluated according to the quality evaluation criteria for qualitative research of the Joanna Briggs Institute Evidence-Based Health Care Center. The research country, research method, research object, research content, and main research result were summarized, and meta-synthesis of the research results was conducted with the aggregative integration method. Results: A total of 12 studies were included, and the quality of all the studies was grade B. The studies were conducted in 8 countries including Australia, Canada, Norway, etc., the research method mainly was phenomenological research method, and all the studies were focused on adult burn patients. A total of 46 specific themes were extracted with totally 10 new categories formed after summarization, and 3 integrated results were obtained as follows: burn patients suffered from both physical and psychological burdens, and their normal life was broken; burn patients gained post-traumatic growth and could actively adjust to cope with life difficulties; burn patients had multiple needs. Conclusions: Burn patients experience both physical and psychological pains during rehabilitation, so they long for multiple support from family and society. Medical staff, social groups, and family members should pay attention to the psychological experience and needs of burn patients with different characteristics during rehabilitation, and build a multi-directional social support system to help patients return to the society and rebuild their lives.

Background: With the onset of the coronavirus disease 2019 (COVID-19) pandemic, many experts expected that asthma-associated morbidity because of severe acute respiratory syndrome coronavirus 2 infection would dramatically increase. However, some studies suggested that there was no apparent increasing in asthma-related morbidity in children with asthma, it is even possible children may have improved outcomes. To understand the relationship between the COVID-19 pandemic and asthma outcomes, we performed this article., Methods: We searched PubMed, Embase, and Cochrane Library to find literature from December 2019 to June 2021 related to COVID-19 and children's asthma control, among which results such as abstracts, comments, letters, reviews, and case reports were excluded. The level of asthma control during the COVID-19 pandemic was synthesized and discussed by outcomes of asthma exacerbation, emergency room visit, asthma admission, and childhood asthma control test (c-ACT)., Results: A total of 22,159 subjects were included in 10 studies. Random effect model was used to account for the data. Compared with the same period before the COVID-19 pandemic, asthma exacerbation reduced (odds ratio [OR] = 0.26, 95% confidence interval [CI] = [0.14-0.48], Z = 4.32, p < 0.0001), the odds of emergency room visit decreased as well (OR = 0.11, 95% CI = [0.04-0.26], Z = 4.98, p < 0.00001). The outcome of asthma admission showed no significant difference (OR = 0.84, 95% CI = [0.32-2.20], Z = 0.36, p = 0.72). The outcome of c-ACT scores were not analyzed because of the different manifestations used. Overall, c-ACT scores reduced during the pandemic., Conclusion: Compared to the same period before the COVID-19 pandemic, the level of asthma control has been significantly improved. We need to understand the exact factors leading to these improvements and find methods to sustain it., (© 2021 Wiley Periodicals LLC.)

Modeling antigenic variation in influenza (flu) virus A H3N2 using amino acid sequences is a promising approach for improving the prediction accuracy of immune efficacy of vaccines and increasing the efficiency of vaccine screening. Antigenic drift and antigenic jump/shift, which arise from the accumulation of mutations with small or moderate effects and from a major, abrupt change with large effects on the surface antigen hemagglutinin (HA), respectively, are two types of antigenic variation that facilitate immune evasion of flu virus A and make it challenging to predict the antigenic properties of new viral strains. Despite considerable progress in modeling antigenic variation based on the amino acid sequences, few studies focus on the deep learning framework which could be most suitable to be applied to this task. Here, we propose a novel deep learning approach that incorporates a convolutional neural network (CNN) and bidirectional long-short-term memory (BLSTM) neural network to predict antigenic variation. In this approach, CNN extracts the complex local contexts of amino acids while the BLSTM neural network captures the long-distance sequence information. When compared to the existing methods, our deep learning approach achieves the overall highest prediction performance on the validation dataset, and more encouragingly, it achieves prediction agreements of 99.20% and 96.46% for the strains in the forthcoming year and in the next two years included in an existing set of chronological amino acid sequences, respectively. These results indicate that our deep learning approach is promising to be applied to antigenic variation prediction of flu virus A H3N2., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Yuan-Ling Xia et al.)

Objective: To analyze the impact of cancer on the recurrence rate of atrial fibrillation (AF) after AF radiofrequency ablation and further evaluate the feasibility of radiofrequency ablation therapy in cancer patients with AF. Methods: This study was a single-center, retrospective study. Cancer patients with AF undergoing radiofrequency ablation for the first time in the First Affiliated Hospital of Dalian Medical University from May 30, 2008 to September 30, 2018 were included (cancer group). AF patients without cancer undergoing radiofrequency ablation for the first time during the same period served as non-cancer group. Clinical data including age, gender, past history, cancer and AF-related parameters, etc. were analyzed. Patients were followed up after radiofrequency ablation. The primary endpoints were AF recurrence or all-cause death. Kaplan-Meier survival analysis was used to analyze the effect of cancers on the recurrence after AF ablation. The multivariate cox regression analysis was further applied to correct for other confounding factors to analyze whether the impact of cancers on the recurrence of atrial fibrillation was statistically significant. Results: A total of 90 patients were enrolled, there were 30 patients in the cancer group (mean age (64.8±6.6) years, 16 (53.3%) males) and 60 patients in the non-cancer group (mean age (63.6±6.2) years, 32 (53.3%) males). Clinical data, such as age, gender, and cancer treatment, were similar between the two groups. During an average follow-up period of (328.7±110.2) days, there were 6 AF recurrences (recurrence rate 20.0%) in the cancer group, and 17 AF recurrences (recurrence rate 28.3%) in the control group. AF recurrence rate was similar between the two groups ( P >0.05). During the follow-up period, there was no all-cause death in the two groups. Kaplan-Meier survival analysis showed that cancer was not related to AF recurrence after radiofrequency ablation ( P = 0.383). After adjusting for other confounding factors, the multivariate Cox regression analysis showed that cancer was not an independent predictor of AF recurrence after radiofrequency ablation ( HR =0.508, 95% CI : 0.192-1.342, P = 0.172). Conclusions: The combination of cancer has no impact on the recurrence of AF after radiofrequency ablation. For cancer patients with AF, radiofrequency ablation therapy can be considered as a feasible heart rhythm control treatment strategy.

Introduction: The efficacy and safety of his-purkinje system pacing (HPSP) upgrades in patients with pacing-induced cardiomyopathy (PICM) and atrial fibrillation (AF) are still unknown., Methods and Results: Patients with PICM were continuously enrolled from January 2018 to March 2020. All patients were further divided into AF subgroup and sinus rhythm subgroup. Clinical data including echocardiographic examination parameters, electrocardiogram (ECG) measurements, and New York Heart Association (NYHA) classification, were assessed before and after the procedure. The HPSP upgrades, including his bundle pacing (HBP) and left bundle branch pacing (LBBP) were completed in 34 of 36 (94%) patients, Complications including electrode dislodged, perforation, infection or thrombosis were not observed in the perioperative period. During a mean of 11.52 ± 5.40 months of follow-up. The left ventricular ejection fraction (LVEF) increased significantly (33.76 ± 7.54 vs 40.41 ± 9.06, P < 0.001), and the QRS duration decreased (184.22 ± 23.76 ms vs 120.52 ± 16.67 ms, P < 0.001) after the upgrades. LVEDD reversed from 59.29 ± 7.74 mm to 53.91 ± 5.92 mm (P < 0.001), and the NYHA functional class also improved to 2.00 ± 0.76 from 2.55 ± 0.91 at the first follow-up (P < 0.001). The left atrium (LA) size also slightly decreased compared to the initial state (47.44 ± 7.14 mm VS 45.56 ± 7.78, P = 0.010). BNP significantly decreased from a median value of 458.06(256.35-755.10) to 172.31(92.69-552.14) (P = 0.004). The threshold did not increase significantly (1.18 ± 0.76 mv@0.4 ms vs 1.26 ± 0.91mv @ 0.4 ms, P = 0.581). These improvements in patients with AF were similar with those in patients without AF (P > 0.05)., Conclusions: HPSP upgrades improved the heart performance and reversed the left ventricular remodeling in patients suffering from PICM with or without AF, and it should be a promising choice in these patients., (Copyright © 2021. Published by Elsevier B.V.)

Objective: To investigate the efficacy and safety of His-bundle pacing (HBP) compared with the traditional biventricular pacing (BVP) on patients with brady-arrhythmias, who suffer from permanent atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF)., Methods: All patients with brady-arrhythmias, permanent AF and HFrEF were continuously enrolled from January 2017 to July 2019 and followed up for at least 12 months. The differences in QRS duration (QRSd), New York Heart Association (NYHA) classification, left ventricular ejection fraction (LVEF), tricuspid regurgitation grade, mitral regurgitation grade, left ventricular end-diastolic diameter (LVEDD), and left atrial size were compared., Results: A total of 52 patients were enrolled: 37 patients were with HBP and 15 patients with BVP. There was no electrode dislodged, perforation, infection or thrombosis during the follow-up of 18.12 ± 4.45 months. The success rate for HBP implantation was 88.10%. The capture threshold of his-bundle and the threshold of the left ventricular lead remained stable during follow-up. LVEF increased to higher than 50% in 11 patients with HBP (29.73%). The NYHA classification (both p < .001), LVEF (both p < .001) and LVEDD improved significantly during the follow-up in both groups. NYHA (p = .030), LVEF (p = .013), and LVEDD (p = .003) improved in patients with HBP compared with BVP., Conclusion: HBP was safe and more effective in improving the cardiac function and remodeling in patients with brady-arrhythmias, permanent AF and HFrEF compared with BVP., (© 2021 Wiley Periodicals LLC.)

Objective: A more extensively fibrotic left atrium contributes to atrial fibrillation (AF) occurrence, persistence, and recurrence. The soluble suppression of tumorigenicity 2 (sST2) has emerged as a ventricular fibrotic biomarker for patients with heart failure. The present study is to investigate associations between circulating sST2 and risk of recurrence after ablation in AF patients. Methods: We measured the baseline plasma level of sST2 from patients with persistent AF ( n = 117) and paroxysmal AF ( n = 93) patients. Patients were followed up for 15 months after ablation. The relationship between circulating sST2 and recurrence was assessed by multivariable Cox regression. The cutoff value of sST2 was determined by receiver operating characteristic curve. The relationship between baseline sST2 level and left atrial volume index (LAVI) was assessed by multivariate linear regression analysis. Serial sST2 measurements were also conducted after 24 h, 6 months, and 15 months of ablation. ST2 localization was examined in left atrial appendages of persistent AF patients by immunohistochemistry and Western blot. Results: Baseline sST2 positively associated with LAVI in the persistent AF group, and elevated sST2 (≥39.25 ng/ml) independently increased the risk of recurrence after ablation (area under the curve = 0.748), with hazard ratio of 1.038 (95% confidence interval 1.017-1.060, P < 0.001) when adjusted for co-variables. In contrast, elevated sST2 cannot predict recurrence in paroxysmal AF. Conclusions: In persistent AF patients, increased sST2 serves as a marker of recurrence after radiofrequency ablation. Patients with sST2 ≥ 39.25 ng/ml are more likely to develop recurrence within a year., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tan, Yu, Han, Liu, Yang, Xia and Yin.)