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Abstract Objectives This study aimed at exploring how using different kinds of sheaths will affect the very first ablation procedure of apprentices. Methods 15 patients with paroxysmal atrial fibrillation were randomized to used fixed-curve, conventional steerable or visualized steerable sheath, and received complete isolation of pulmonary veins. All ablations were the very first procedure performed by 15 ablation apprentices. The use of fluoroscopy and catheter stability during the PVI were analyzed. Results Procedure duration was much longer in the fixed-curve group (116.8 ± 27 vs. 62.2 ± 17 vs. 60.4 ± 17, p

Abstract Background Atrial fibrillation (AF) is associated with circulating inflammation. Short-chain fatty acids (SCFAs) derived from gut microbiota (GM) regulate leukocyte function and inhibit the release of inflammatory cytokines, which are partly mediated by the G-protein-coupled receptor 43 (GPR43) signaling. This study aimed to investigate the expression of GPR43/NOD-like receptors family pyrin domain containing 3 (NLRP3) in leukocytes and the interaction with intestinal SCFAs levels in AF patients. Methods Expressions of GPR43 and NLRP3 mRNA in peripheral blood leukocytes from 23 AF patients and 25 non-AF controls were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Expressions of leukocyte GPR43 and NLRP3 protein were evaluated by western blot analysis. The levels of plasma IL-1β were measured by enzyme-linked immunosorbent assay (ELISA). The fecal SCFAs levels based on GC/MS metabolome of corresponding 21 controls and 14 AF patients were acquired from our published dataset. To evaluate the expression of NLRP3 and GPR43 and the release of IL-1β, human THP-1 cells were stimulated with or without SCFAs (acetate, propionate, and butyrate), lipopolysaccharide (LPS), and nigericin in vitro, respectively. Results Compared to the controls, the mRNA expression in peripheral leukocytes was significantly reduced in AF patients (P = 0.011) coupled with the increase in downstream leukocyte NLRP3 mRNA expression (P = 0.007) and plasma IL-1β levels (P

Background: The diagnostic potential of circular RNAs (circRNAs) in circulating exosomes for acute myocardial infarction (AMI) is not well understood, despite existing research indicating their role in cardiovascular diseases. This study aimed to clarify the significance of exosomal circular RNAs as indicators for AMI. Methods: We examined 120 individuals diagnosed with AMI and 83 individuals with non-cardiogenic chest pain (NCCP), all previously enrolled in a conducted study. High-throughput sequencing to identify differentially expressed circRNAs in the circulating exosomes of AMI patients. To validate, we employed Real-Time polymerase chain reaction (RT-PCR) targeting five circRNAs that exhibited notable increase. Results: The sequencing identified 893 exosomal circRNAs with altered expression in AMI patients, including 118 up-regulated and 775 down-regulated circRNAs. Genes linked to these circRNAs were enriched in crucial Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, highlighting their direct relevance to AMI pathophysiology. Three exosomal circRNAs (hsa_circ_0001558, hsa_circ_0001535, and hsa_circ_0000972) showed significant up-regulation in AMI patients during the initial validation cohort. The corresponding area under the curve (AUC) values were 0.79, 0.685, and 0.683, respectively. Further validation of hsa_circ_0001558 in a second cohort showed a 4.45-fold increase in AMI patients, with AUC = 0.793. The rise was particularly noticeable in patients with non-ST-elevation myocardial infarction (NSTEMI) (2.80 times, AUC = 0.72) and patients with ST-elevation myocardial infarction (STEMI) (5.27 times, AUC = 0.831) compared to patients with NCCP. Conclusions: Our findings demonstrate significant differences in the expression patterns of circRNAs in plasma exosomes between AMI patients and NCCP patients. Specifically, hsa_circ_0001558 appears as a promising indicator for AMI diagnosis. Further research is necessary to fully evaluate the diagnostic potential of exosomal circRNAs in the context of AMI, emphasizing the importance of these findings.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reapproved for heart failure (HF) therapy in patients with and without diabetes. However, the initial glucose-lowering indication of SGLT2i has impeded their uses in cardiovascular clinical practice. A challenge of SGLT2i then becomes how to separate their anti-HF activity from glucose-lowering side-effect. To address this issue, we conducted structural repurposing of EMPA, a representative SGLT2 inhibitor, to strengthen anti-HF activity and reduce the SGLT2-inhibitory activity according to structural basis of inhibition of SGLT2. Compared to EMPA, the optimal derivative JX01, which was produced by methylation of C2–OH of the glucose ring, exhibited weaker SGLT2-inhibitory activity (IC50 > 100 nmol/L), and lower glycosuria and glucose-lowering side-effect, better NHE1-inhibitory activity and cardioprotective effect in HF mice. Furthermore, JX01 showed good safety profiles in respect of single-dose/repeat-dose toxicity and hERG activity, and good pharmacokinetic properties in both mouse and rat species. Collectively, the present study provided a paradigm of drug repurposing to discover novel anti-HF drugs, and indirectly demonstrated that SGLT2-independent molecular mechanisms play an important role in cardioprotective effects of SGLT2 inhibitors.

Summary: Background: Tafolecimab, a fully human proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody developed for the treatment of hypercholesterolemia, demonstrated robust lipid-lowering efficacy and favorable safety in previous short-term studies. We aimed to assess the long-term efficacy and safety of tafolecimab in Chinese non-familial hypercholesterolemia (non-FH) patients. Methods: Non-FH patients at high or very-high cardiovascular risk with screening low-density lipoprotein cholesterol (LDL-C) level ≥1.8 mmol/L or non-FH patients with screening LDL-C level ≥3.4 mmol/L and on stable lipid-lowering therapy for at least 4 weeks, were randomized in a 2:2:1:1 ratio to receive subcutaneous tafolecimab 450 mg Q4W, tafolecimab 600 mg Q6W, placebo 450 mg Q4W, or placebo 600 mg Q6W, respectively, in the 48-week double-blind treatment period. The primary endpoint was the percent change from baseline to week 48 in LDL-C levels. Findings: A total of 618 patients were randomized and 614 patients received at least one dose of tafolecimab (n = 411) or placebo (n = 203). At week 48, tafolecimab induced significant reductions in LDL-C levels (treatment differences versus placebo [on-treatment estimand]: −65.0% [97.5% CI: −70.2%, −59.9%] for 450 mg Q4W; −57.3% [97.5% CI: −64.0%, −50.7%] for 600 mg Q6W; both P

Abstract Background Microfibrillar-associated protein (MFAP4), initially identified as an extracellular matrix protein, has been demonstrated in multiple human disorders, but it is yet to be discovered following acute coronary syndrome (ACS) in clinical practice. Therefore, this study aimed to investigate the relationship between circulating MFAP4 levels and coronary stenosis in ACS. Methods We performed the study in 148 ACS subjects, including 75 ST-segment elevation myocardial infarction (STEMI), 27 non-ST-segment elevation myocardial infarction (non-STEMI) and 46 unstable angina (UA). Clinical variables were collected and Gensini and Syntax stenosis scoring systems were applied to assess the severity of coronary stenosis. Kaplan–Meier and logistic regression analysis were used to analyze the relationship between MFAP4 and the severity of coronary stenosis or ACS outcomes. Spearman analysis was used to describe the correlation between MFAP4 and clinical parameters. Results Circulating MFAP4 levels were significantly decreased in the STEMI group (0.008 ng/ml) compared with the non-STEMI group (0.014 ng/ml) and UA group (0.019 ng/ml) (p

Abstract Background New-onset atrial fibrillation (NOAF) is a common complication in patients with acute myocardial infarction (AMI) during hospitalization. Galectin-3 (Gal-3) is a novel inflammation marker that is significantly associated with AF. The association between post-AMI NOAF and Gal-3 during hospitalization is yet unclear. Objective The present study aimed to investigate the predictive value of plasma Gal-3 for post-AMI NOAF. Methods A total of 217 consecutive patients admitted with AMI were included in this retrospective study. Peripheral venous blood samples were obtained within 24 h after admission and plasma Gal-3 concentrations were measured. Results Post-AMI NOAF occurred in 18 patients in this study. Patients with NOAF were older (p

BackgroundIt has been well acknowledged that disordered intestinal microflora and their fermented products play crucial role during the development of hypertension (HTN). Aberrant profiles of fecal bacteria have been documented in subjects with isolated systolic HTN (ISH) and isolated diastolic HTN (IDH) previously. Nevertheless, evidence regarding the association of metabolic products in the bloodstream with ISH, IDH and combined systolic and diastolic HTN (SDH) remains scarce.MethodsWe performed a cross-sectional study and conducted untargeted liquid chromatography-mass spectrometry (LC/MS) analysis on serum samples of 119 participants, including 13 subjects with normotension (SBP

Zn-BTC (H3BTC refers to 1, 3, 5-benzoic acid) MOF was used as a self-template and a zinc source to prepare ZnS/NiS2 with a layered heterogeneous structure as a promising electrode material using cation exchange and solid-phase vulcanization processes. The synergistic effect of the two metal sulfides enhances the application of ZnS/NiS2. And the high specific surface area and abundant active sites further promote the mass/charge transfer and redox reaction kinetics. In the three-electrode system, the specific capacitance was as high as 1547 F/g at a current density of 1 A/g, along with satisfactory rate capability (1214 F/g at 6 A/g) and cycling performance. Coupled with activated carbon (AC), the prepared hybrid device (ZnS/NiS2 as the positive electrode and AC as the negative electrode) (ZnS/NiS2/AC) can be operated under a potential window of 1.6 V and provides a high energy density of 26.3 Wh/kg at a power density of 794 W/kg. Notably, the assembled ZnS/NiS2//AC showed little capacity degradation after 5000 charge/discharge cycles.

Abstract Background Nerve injury-induced protein 1 (Ninj1) is elevated in various inflammatory diseases. The soluble form of Ninj1 yield by matrix metalloproteinase cleavage is a secreted protein and inhibits cell adhesion and inflammation. However, the role of plasma Ninj1 in atrial fibrillation (AF) has not been reported. The present study aimed to investigate the correlation between plasma Ninj1 levels and AF. Methods A total of 96 AF patients [age 66.00 (60.00, 72.00) years, male 56 (58.33%)] and 51 controls without AF [age 65.00 (55.00, 68.00) years, male 21 (41.18%)] were enrolled in this study. Plasma Ninj1 concentrations were detected using enzyme-linked immunosorbent assay. Also, the clinical characteristics, left atrial volume index (LAVI), CHA2DS2-VASc score, and HAS-BLED score were evaluated. Results Plasma Ninj1 levels were significantly higher in patients with AF than in controls (P

Background: Cigarette smoking is an important environmental risk factor for cardiovascular events of hypertension (HTN). Existing studies have provided evidence supporting altered gut microbiota by cigarette smoking, especially in hypertensive patients. Metabolic biomarkers play a central role in the functional potentials of the gut microbiome but are poorly characterized in hypertensive smokers. To explore whether serum metabolomics signatures and compositions of HTN patients were varied in smokers, and investigate their connecting relationship to gut microbiota, the serum metabolites were examined in untreated hypertensive patients using untargeted liquid chromatography-mass spectrometry (LC/MS) analysis.Results: A dramatic difference and clear separation in community features of circulating metabolomics members were seen in smoking HTN patients compared with the non-smoking controls, according to partial least squares discrimination analysis (PLS-DA) and orthogonal partial least squares discrimination analysis (OPLS-DA). Serum metabolic profiles and compositions of smoking patients with HTN were significantly distinct from the controls, and were characterized by enrichment of 12-HETE, 7-Ketodeoxycholic acid, Serotonin, N-Stearoyl tyrosine and Deoxycholic acid glycine conjugate, and the depletion of Tetradecanedioic acid, Hippuric acid, Glyceric acid, 20-Hydroxyeicosatetraenoic acid, Phenylpyruvic acid and Capric acid. Additionally, the metabolome displayed prominent functional signatures, with a majority proportion of the metabolites identified to be discriminating between groups distributed in Starch and sucrose metabolism, Caffeine metabolism, Pyruvate metabolism, Glycine, serine and threonine metabolism, and Phenylalanine metabolic pathways. Furthermore, the observation of alterations in metabolites associated with intestinal microbial taxonomy indicated that these metabolic members might mediate the effects of gut microbiome on the smoking host. Indeed, the metabolites specific to smoking HTNs were strongly organized into co-abundance networks, interacting with an array of clinical parameters, including uric acid (UA), low-denstiy lipoprotein cholesterol (LDLC) and smoking index.Conclusions: In conclusion, we demonstrated disparate circulating blood metabolome composition and functional potentials in hypertensive smokers, showing a linkage between specific metabolites in blood and the gut microbiome.

Abstract Background We aimed to investigate the predictive value of recently updated ACEF II score on major adverse cardiac and cerebrovascular events (MACCE) in patients with multi-vessel coronary artery disease (MVCAD) undergoing one-stop hybrid coronary revascularization (HCR). Methods Patients with MVCAD undergoing one-stop HCR were retrospectively recruited from March 2018 to September 2020. Several prediction risk models, including ACEF II score, were calculated for each patient. Kaplan-Meier curve was used to evaluate freedom from cardiac death and MACCE survival rates. Differences of prediction performance among risk scores for predicting MACCE were compared by receiver operating characteristic (ROC) curve. Results According to the ACEF II score, a total of 120 patients undergoing one-stop HCR were assigned to low-score group (80 cases) and high-score group (40 cases). During the median follow-up time of 18 months, the incidence of MACCE in the low-score group and high-score group were 8.8 % and 37.5 %, respectively (p

Abstract Objectives Atrial remodeling is the main developmental cause of atrial arrhythmias (AA), which may induce atrial fibrillation, atrial flutter, atrial tachycardia, and frequent premature atrial beats in acute myocardial infarction (AMI) patients. Thrombospondin-1 (TSP-1) has been shown to play an important role in inflammatory and fibrotic processes, but its role in atrial arrhythmias is not well described. The purpose of this study was to investigate the role of TSP-1 in AMI patients with atrial arrhythmias. Methods A total of 219 patients with AMI who underwent percutaneous coronary intervention and with no previous arrhythmias were included. TSP-1 were analyzed in plasma samples. Patients were classified into 2 groups, namely, with and without AA during the acute phase of MI. Continuous electrocardiographic monitoring was used for AA diagnosis in hospital. Results Twenty-four patients developed AA. Patients with AA had higher TSP-1 levels (29.01 ± 25.87 μg/mL vs 18.36 ± 10.89 μg/mL, p

Hydrogen (H2) has been considered an ideal alternative energy source for solving energy supply security and greenhouse gas reduction. Although platinum group metal (PGM) catalysts have excellent performance in hydrogen electrocatalysis, their scarcity and high cost limit their industrial application. Therefore, it is necessary to develop low-cost and efficient non-PGM catalysts. Transition metal nitrides (TMNs) have attracted much attention because of their excellent catalytic performance in hydrogen electrochemistry, including hydrogen evolution reaction (HER)/hydrogen oxidation reaction (HOR). In this paper, we review and discuss the mechanism of HER/HOR in alkaline media. We compare and evaluate electrocatalytic performance for the HER/HOR TMN catalysts recently reported. Finally, we propose the prospects and research trends in sustainable alkaline hydrogen electrocatalysis.

Abstract Objective To evaluate the predictive value of CHADS2 and CHA2DS2-VASc scores for coronary artery lesions and in-hospital prognosis of patients with acute ST-segment elevation myocardial infarction (STEMI). Methods A total of 524 patients who were diagnosed with STEMI from January 2016 to August 2017 were retrospectively reviewed. The correlation between CHADS2 and CHA2DS2-VASc scores with the patients’ clinical data, number of coronary lesions, Gensini scores, the target vessel and hospitalization time and in-hospital adverse events (AEs) was analyzed. Results The number of coronary lesions in STEMI patients was mainly single and double lesions. The CHADS2 and CHA2DS2-VASc scores were not meaningful for predicting the number of coronary lesions. However, for left main coronary artery lesion, CHADS2 score was significantly increased when the number increased (P 0.05). The incidence of target lesions in STMEI patients was mainly left anterior descending coronary artery (LAD) and right coronary artery (RCA). The two scores were not meaningful for predicting target lesions (P > 0.05). For the severity of coronary lesions, there was positive correlation between CHADS2 score with Gensini score (P 0.05). The stratifications of CHADS2 score and CHA2DS2-VASc score were significantly associated with hospitalization time and adverse events during hospitalization (P

Abstract Background The gut microbiota provides health benefits in humans by producing short-chain fatty acids (SCFAs), whose deficiency causes multiple disorders and inflammatory diseases. However, gut bacteria producing SCFAs in patients with atrial fibrillation (AF), an arrhythmia with increasing prevalence, have not been reported. To investigate major gut microbial organisms related to SCFA synthesis, SCFAs-associated KEGG orthologues (KOs), enzymatic genes, and potential producers were examined according to metagenomic data-mining in a northern Chinese cohort comprising 50 non-AF control and 50 AF patients. Results Compared with non-AF controls, individuals with AF had marked differences in microbial genes involved in SCFA-related synthesis, including 125 KOs and 5 SCFAs-related enzymatic genes. Furthermore, there were 10 species that harbored SCFA-synthesis related enzymatic genes, and were markedly decreased in the gut of AF patients. Notably, discriminative features about SCFA-synthesis related function, including 8 KOs (K01752, K01738, K00175, K03737, K01006, K01653, K01647 and K15023), 4 genes (menI, tesB, yciA and CO dehydrogenase acetyl-CoA synthase complex) and 2 species (Coprococcus catus and Firmicutes bacterium CAG:103), were selected as key factors based on LASSO analysis. Furthermore, PLS-SEM analysis showed that 72.8 and 91.14 % of the overall effects on gut microbiota diversity and key species on AF, respectively, were mediated by the key KOs. Meanwhile, 46.31 % of the total effects of SCFA-synthesis related function on left atrial enlargement was mediated by hsCRP. Upon incorporation of clinical properties in AF, the KO score was still significantly associated with AF incidence (OR = 0.004, P = 0.001). Conclusions The current study revealed that dysbiotic gut microbiota in AF is coupled with disrupted SCFA-synthesis related genes, characterized by decreased abundances of KEGG orthologues, synthesis enzymatic genes and harboring species.

Abstract Smoking not only is one of the most important risk factors of hypertension (HTN), but also alters the composition of gut microbiota (GM) in previous studies. Although dysbiosis of GM has been implicated in HTN, how GM alters in patients with HTN under smoking status is still not clear. This study aimed to explore the difference in intestinal microflora among smokers with HTN (S‐HTN), nonsmokers with HTN (NS‐HTN), and smokers without HTN (S‐CTR) and identify whether cigarette smoking led to disordered intestinal microbiota in patients with HTN. Metagenomic sequencing analysis of fecal specimens was conducted in nonsmokers without HTN (NS‐CTR, n = 9), S‐CTR (n = 9), NS‐HTN (n = 18), and S‐HTN (n = 23). Compared with S‐CTR or NS‐HTN, the GM in S‐HTN was disordered, with lower microbial α‐diversity and significant difference of β‐diversity on axes as compared to S‐CTR at genus and species level. The microbial enterotype in S‐HTN was inclined to Prevotella‐dominant type. Dramatic changes in the intestinal genera and species composition were observed in S‐HTN, including reduced enrichment of Phycisphaera and Clostridium asparagiforme. Moreover, the intestinal function altered in S‐HTN. Therefore, the findings of the present study revealed GM disorders in S‐HTN and clarified the role of smoking in impairing the intestinal microbiome in HTN. Tobacco control is particularly important for improving GM in patients with HTN, and might be beneficial in preventing future cardiovascular events.

Background: The purpose of this study was to explore whether consideration of FIB levels might improve the predictive value of the ACEF score in patients with ACS. Methods: A total of 290 patients with ACS were enrolled in this study. The clinical characteristics and MACE were recorded. Results: Multivariate logistic regression analysis revealed that the FIB level (odds ratio=7.798, 95%CI, 3.44–17.676, P

Abstract Background Galectin-3 (Gal-3) is currently recognized as a promising biomarker for myocardial fibrosis. This study aimed to explore the potential association between plasma Gal-3 concentrations and atrial fibrillation (AF) progression in paroxysmal AF (PAF) patients Methods A total of 213 PAF patients were included for analysis in this study. All peripheral blood samples were prospectively collected and stored at -80℃ for subsequent Gal-3 quantification. The AF progression was defined as transformation from PAF to persistent AF (PsAF). Results A total of 51 PAF patients progressed to PsAF during a mean follow-up period of 674.44 ± 19.48 days. Patients with AF progression had significantly higher baseline plasma Gal-3 concentrations than those stayed in PAF status (13.52 ± 0.94 vs. 7.93 ± 0.37, p

Abstract Background New-onset atrial fibrillation (NOAF) is common during acute myocardial infarction (AMI) and independently associated with worse prognosis. We aimed to validate the discrimination performance of CHA2DS2-VASc score combined with hs-CRP in the prediction of NOAF after AMI in elderly Chinese population. Methods 311 consecutive elderly patients (age ≥ 65 years old) with AMI from 1 January 2018 to 1 January 2019 without atrial fibrillation history were enrolled in our study. Univariable and multivariable logistic regression analyses were used to identify risk factors of NOAF. The discrimination performance of different score models were evaluated using ROC curve analysis and AUCs were compared using the Z test. Results 30 (9.65%) patients developed NOAF during hospitalization. The NOAF group were older and had higher hs-CRP, initial Killip class, BNP, LAD, CHADS2 score, CHA2DS2-VASc score, in-hospital mortality and lower LVEF and ACEI/ARB use (P

Abstract Background Hypertension (HTN) is one of the major cardiovascular risk factors, which contributes to increasing target organ damages and cardiovascular morbidity and mortality worldwide. Isolated systolic HTN (ISH) and isolated diastolic HTN (IDH) are two important subtypes of HTN. Previous researches have demonstrated the alteration of fecal bacteria in HTN, but not down to these two sub-types. In order to identify whether the composition of bacterial taxa and functional modules shift in ISH and IDH, we performed a metagenomic sequencing analysis of fecal samples from 15 controls, 14 ISH, and 11 IDH. Results Compared with control and ISH, IDH patients showed decreased gene number, bacterial richness, and evenness, although the bacterial alterations did not reach statistical significance in the Shannon index. Also, at the genus level, the β-diversity for intestinal flora in IDH was distinguishable from those with ISH. Furthermore, the taxonomic composition of ISH or IDH was different from that of healthy control at genus and species levels. Patients with IDH or ISH were confirmed to be enriched with Rothia mucilaginosa, along with reduced Clostridium sp. ASBs410. Lastly, the altered KEGG modules were significantly decreased in IDH compared with the control group, such as sodium transport system; while for ISH, functions relevant to biotin biosynthesis were decreased. Conclusions Overall, our results showed the disordered fecal bacteria profiles in subjects with ISH and especially IDH, emphasizing the significance of early intervention for IDH.

IntroductionThere is limited evidence regarding the effectiveness of drug-coated balloon (DCB) angioplasty in the percutaneous treatment of complex de novo ostial coronary lesions. This study primarily aimed to explore the feasibility and safety of this innovative approach for ostial lesions in the left anterior descending artery (LAD).MethodsPatients treated with paclitaxel DCB or second-generation drug-eluting stents (DES) were retrospectively enrolled from two large centers. The primary endpoints were major adverse cardiovascular events (MACE), including cardiovascular death, target lesion revascularization (TLR), target vessel revascularization, and recurrent myocardial infarction related to target artery occlusion. Cox regression analysis was used to identify risk factors for MACE, and propensity score matching was performed to minimize selection bias.ResultsA total of 388 patients were included; among them, 52 were treated with paclitaxel DCB, and 336 with DES for ostial LAD lesions. Using propensity score matching, 49 patients were treated with DCB-only and 49 with the DES strategy. The average follow-up time was 12 months; subsequently, a non-significant decrease in MACE rate was observed in the DCB-only angioplasty treatment group (MACE: 6 vs. 6%, p = 1.0; TLR: 2 vs. 4%, p = 0.56). Cox regression analysis indicated that DCB-only angioplasty was not an independent risk factor for adverse events after adjusting for confounding risk factors (hazard ratio: 1.713, p = 0.43).ConclusionThe use of the DCB-only approach is an innovative and optional strategy in the treatment of isolated ostial LAD disease. A further randomized trial is of necessity to confirm the feasibility and safety of drug-coated balloon-only angioplasty for LAD de novo ostial lesions.

Introduction The concept of chronic coronary syndrome (CCS) was first presented at the European Society of Cardiology Meeting in 2019. However, the roles of exosomal lncRNAs in CCS remain largely unclear. Material and methods A case-control study was performed with a total of 218 participants (137 males and 81 females), including 15 CCS patients and 15 controls for sequencing profiles, 20 CCS patients and 20 controls for the first validation, and 100 CCS patients and 48 controls for the second validation. Exosomes were isolated from the plasma of CCS patients and controls, and exosomal lncRNAs were identified by sequencing profiles and verified twice by qRT-PCR analysis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of exosomal lncRNAs for CCS patients. Results A total of 152 significantly differentially expressed lncRNAs with over two-fold changes were detected in plasma exosomes of CCS patients, including 90 upregulated and 62 downregulated lncRNAs. Importantly, 6 upregulated lncRNAs with the top fold changes were selected for validations. Exosomal lncRNAs ENST00000424615.2 and ENST00000560769.1 were significantly elevated in CCS patients in both validations compared with controls. The areas under the ROC of lncRNAs ENST00000424615.2 and ENST00000560769.1 were 0.654 and 0.722, respectively. Additionally, exosomal lncRNA ENST00000560769.1 was significantly higher in the CCS patients with more diseased vessels (p = 0.028). Conclusions Exosomal lncRNA ENST00000424615.2 and ENST00000560769.1 were identified as novel diagnosis biomarkers for patients with CCS. Moreover, exosomal lncRNA ENST00000560769.1 was significantly higher in the CCS patients with more diseased vessels, and might be associated with a poor prognosis.

Abstract Introduction The progression of paroxysmal AF (PAF) to persistent AF (PsAF) worsens the prognosis of AF, but its underlying mechanisms remain elusive. Recently, circular RNAs (circRNAs) were reported to be associated with cardiac fibrosis. In case of the vital role of cardiac fibrosis in AF persistency, we hypothesis that circRNAs may be potential regulators in the process of AF progression. Materials and methods 6 persistent and 6 paroxysmal AF patients were enrolled as derivation cohort. Plasma circRNAs expressions were determined by microarray and validated by RT-PCR. Fibrosis level, manifested by serum TGF-β, was determined by ELISA. Pathways and related non-coding RNAs involving in the progression of AF regulated were predicted by in silico analysis. Results PsAF patients showed a distinct circRNAs expression profile with 92 circRNAs significantly dysregulated (fold change ≥ 2, p

Accurate measurement of the surface three-dimensional deformation fields in a mined-out area is essential for understanding the law of mining subsidence and guiding the safe production and construction of mining areas. In this study, we proposed an improved fusion method to monitor this three-dimensional deformation. We used the Helmert variance component estimation (HVCE) method and the back-propagation neural network (BPNN) to fuse the global navigation satellite system (GNSS) and interferometric synthetic aperture radar (InSAR) measurements. Based on this improved fusion method, we measured the three-dimensional deformation in the West Second Mining Area of Jinchuan, Jinchang City, Gansu Province, China, from March 22, 2019, to June 8, 2020. The root mean square errors (RMSEs) based on our method for the three directions of east-west (E-W), north-south (N-S), and up-down (U-D) were 21.4 mm, 7.6 mm, and 34.2 mm, respectively. These RMSE values are lower than those obtained from previous methods. The results show that the spatial distribution of the three-dimensional deformation follows the law of mining subsidence.

Abstract Introduction Studies have been performed to identify the association between ABO blood groups and coronary artery disease. However, data is scarce about the impact of ABO blood groups on heart rupture (HR) after acute myocardial infarction (AMI). Methods We conducted a retrospective case–control study that included 61 consecutive patients with HR after AMI during a period from 1 January 2012 to 1 December 2019. The controls included 600 patients who were selected randomly from 8143 AMI patients without HR in a ratio of 1:10. Univariate and multivariate logistic regression analysis were used to identify the association between ABO blood groups and HR. Results Patients with blood group A had a greater risk of HR after AMI than those with non-A blood groups (12.35% vs 7.42%, P

BackgroundThymic stromal lymphopoietin (TSLP), a distant paralog of the cytokine IL-7, has been shown to be associated with atherosclerosis. However, the effect of plasma TSLP level after acute myocardial infarction (AMI) remains largely unclear. Thus, we aimed to assess the relationship between the concentration of TSLP at admission and the risk of major adverse cardiovascular events (MACE) in AMI patients.MethodsA total of 175 patients with AMI and 145 unstable angina (UA) controls were recruited in the present study. The clinical characteristics were collected, and MACE was recorded during hospitalization and the follow-up period after discharge.ResultsThe median value (25, 75 percentiles) of TSLP concentrations in the AMI group was higher than that in the UA group [11.18 (8.14–15.22) vs. 8.56 (5.26–11.94) pg/ml, p < 0.001, respectively]. Multivariate linear regression analysis revealed that Troponin-I (standardized β = 0.183, p = 0.004) was an independent factor for TSLP. According to the median of TSLP concentrations, all the AMI patients were divided into the high-level group (TSLP level ≥ 11.18 pg/ml, N = 91) and the low-level group (TSLP

Summary: Surface immobilization of metal complexes or clusters with an exact metal number and coordination structure on solid supports is essential in many industrial applications. However, methods for physically isolating individual homogeneous catalyst molecules on a support surface are rare. By selectively depositing TiO2 sieving layers around supported Co(salen) single molecules or gold clusters with hydrophobic ligands, we realize molecular surface isolation via selective atomic layer deposition. The obtained catalysts are reusable in chiral hydrolytic kinetic resolution and styrene oxidation. Surface isolation also prevents the leaching and aggregation of gold clusters after removing the ligands at high temperature. The activity and selectivity for styrene oxidation to benzaldehyde over isolated single gold atoms are optimized with an enhanced Au-TiO2 interface. This method provides a simple way to immobilize homogeneous catalysts on inexpensive supports and shows excellent potential for industrialization.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACEI/ARB) are the first-line drugs for the treatment of essential hypertension (HTN), one of the most important risk factors for cardiovascular and cerebrovascular diseases. Intestinal flora and microbial metabolites have been demonstrated to play important roles in blood pressure (BP) regulation and HTN development. However, it remains elusive that intestinal bacteria and metabolites are associated with the protective effects of ACEI/ARB anti-hypertensive drugs against HTN. In this study, we evaluated the effect of ACEI/ARB on gut microbiome and metabolites in patients suffering from HTN. We performed 16S rRNA sequencing and fecal metabolomic analysis of 36 HTN patients placed on ACEI/ARB therapy and 19 newly diagnosed HTN patients with no history of anti-hypertensive treatment. Patients under medication treatment were further classified into well-controlled (n = 24) and poor-controlled (n = 12) groups according to their BP levels. The ACEI/ARB improved the intestinal microbiome of the HTN patients by reducing potentially pathogenic bacteria such as Enterobacter and Klebsiella and increasing beneficial bacteria such as Odoribacter. Moreover, ACEI/ARB therapy was correlated with significant metabolomic changes in the HTN patients, including progressively enhanced inositol from poor-controlled to well-controlled groups. The profiles of gut bacteria were linked to the production of metabolites, and inositol was negatively correlated with Klebsiella, Enterobacter, and Proteobacteria. Our study suggests that ACEI/ARB modulates gut microbial composition and functions and alters microbial metabolites in HTN patients.

IntroductionDysbiotic gut microbiota (GM) plays a regulatory role during the pathogenesis of several cardiovascular diseases, including atherosclerosis. GM-derived metabolite phenylacetylglutamine (PAGln) enhances platelet responsiveness and thrombosis potential, thereby inducing major adverse cardiovascular events. However, the role of GM and microbial metabolite PAGln in the pathogenesis of in-stent stenosis remains unknown.Methods16S rRNA sequencing was performed on fecal samples in 103 coronary artery disease (CAD) patients, including 35 individuals with in-stent patency (control), 32 individuals with in-stent hyperplasia (ISH), and 36 subjects with in-stent stenosis (ISS), and the levels of plasma PAGln were evaluated by enzyme-linked immunosorbent assay.ResultsThe results revealed significantly enhanced microbial diversity and disrupted composition, such as enrichment of Roseburia, Blautia, and Ruminococcus, were observed in CAD patients with in-stent stenosis. The imbalance of microbial function related to PAGln synthesis and elevated plasma GM-derived metabolite PAGln levels was detected in CAD patients with in-stent stenosis. The GM-dependent diagnostic model could identify CAD patients with in-stent stenosis.ConclusionThe current study revealed the disordered signature, altered functions, and potential diagnostic ability of GM in CAD patients with in-stent hyperplasia and stenosis. Enhanced microbiota-derived PAGln synthesis-related functions and elevated plasma PAGln levels were associated with in-stent stenosis and hyperplasia in CAD patients. Thus, an intervention targeting gut microbes may be a promising strategy to prevent stent stenosis in patients with CAD.

BackgroundAging is significantly associated with the incidence and progression of atrial fibrillation (AF) incidence. This study aimed to evaluate the potential predictive value of leukocyte telomere length (LTL) for progression from paroxysmal AF (PAF) to persistent AF (PsAF) after catheter ablation.Methods and ResultsA total of 269 patients with AF (154 patients with PAF and 115 patients with PsAF, respectively) were prospectively enrolled, and all patients with PAF at baseline were regularly followed up to determine whether and when they should progress to PsAF after catheter ablation therapy. Baseline relative LTL was measured by quantitative real-time PCR (rt-PCT). There was a significant negative association between LTL and age (r = −0.23, p < 0.001). Patients with PsAF had significantly shorter LTL than those with PAF. After a mean follow-up of 854.9 ± 18.7 d, progression events occurred in 35 out of the 154 patients with PAF. Those progressed patients with PAF were older (70.9 ± 8.0 vs. 62.3 ± 10.3, p < 0.001) and had shorter LTL (1.2 ± 0.3 vs. 1.5 ± 0.3, p < 0.001) than those who did not. The receiver operating characteristic (ROC) curve analysis showed a significant value of LTL in distinguishing patients with PAF from patients with PsAF, with an area under the ROC curve (AUC) of 0.63 (95% CI 0.56–0.70, p < 0.001), and the optimal cut-off value of LTL was 1.175, with a sensitivity and specificity of 56.03 and 82.04%, respectively. All patients with PAF were divided into two subgroups according to the optimal cut-off point of LTL calculated by the ROC curve analysis: high LTL group (≥1.175) and low LTL group (

Radiofrequency (RF) catheter ablation has emerged as an effective alternative for the treatment of atrial fibrillation (AF), but ablation lesions will result in swelling and hematoma of local surrounding tissue, triggering inflammatory cell infiltration and increased release of inflammatory cytokines. Some studies have shown that the inflammatory response may be related to the early occurrence of AF. The most direct way to inhibit perioperative inflammation is to use anti-inflammatory drugs such as glucocorticoids. Here, we prepared polylactic-co-glycolic acid (PLGA) nanoparticles loaded with budesonide (BUD) and delivered them through irrigation of saline during the onset of ablation. Local high temperature promoted local rupture of PLGA nanoparticles, releasing BUD, and produced a timely and effective local myocardial anti-inflammatory effect, resulting in the reduction of acute hematoma and inflammatory cell infiltration and the enhancement of ablation effect. Nanoparticles would also infiltrate into the local myocardium and gradually release BUD ingredients to produce a continuous anti-inflammatory effect in the next few days. This resulted in a decrease in the level of inflammatory cytokine IL-6 and an increase of anti-inflammatory cytokine IL-10. This study explored an extraordinary drug delivery strategy to reduce ablation-related inflammation, which may prevent early recurrence of AF.

Abstract Background This study focused on the roles of lncRNA THRIL in coronary atherosclerotic heart disease (CAD) through regulating AKT signaling pathway and directly interacting with FUS. Methods QRT-PCR was conducted to detect the expression of THRIL in CAD blood samples and endothelial progenitor cells (EPCs). Cell autophagy of EPCs was examined through Cyto-ID Autophagy Detection Kit. CCK-8 assay and flow cytometry were carried out to assess cell viability and apoptosis under various interference conditions. Western blotting was conducted to detect the expression of interest proteins. The expression levels of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were measured by qRT-PCR. The direct interactions between HCG18 and FUS was confirmed through RNA electrophoretic mobility shift assay (RNA EMSA) and RNA immunoprecipitation (RIP) assay. Results THRIL was upregulated in CAD blood samples and EPCs. Knockdown of THRIL in EPCs promoted cell viability, inhibited cell autophagy and further suppressed the development of CAD. Over-expression of THRIL induced inactivation of AKT pathway, while knockdown of THRIL played reversed effects. THRIL directly interacted with FUS protein and knockdown of FUS reversed the over-expressing effect of THRIL on cell proliferation, autophagy and the status of AKT pathway. Conclusion THRIL inhibits the proliferation and mediates autophagy of endothelial progenitor cells via AKT pathway and FUS.

Abstract Background The gut bacteria-derived metabolite trimethylamine-N-oxide (TMAO) has been discussed in various cardiometabolic diseases. However, evidence characterizing the microbial population responsible for TMAO accumulation in patients with atrial fibrillation (AF), an increasingly prevalent arrhythmia, is yet lacking. In order to understand the key gut microorganisms that produce TMAO in AF, trimethylamine (TMA)-synthesis enzymes and metabolic pathways, as well as the potential TMA-producers in gut microbiome were assessed based on metagenomic data-mining in a northern Chinese cohort consisting of 50 non-AF controls and 50 patients with different types of AF. Results Compared to the control subjects, AF patients showed a marked increase in the microbial genes underlying TMA formation in the gut, which included 12 potential TMA-synthesis functional orthologs and 1 module. The specific bacterial genes, including choline-TMA lyase, carnitine monooxygenase, glycine betaine reductase, and TMAO reductase, were elevated in the gut of AF patients. Furthermore, 16 genera were assigned and significantly correlated with TMA-enzymatic genes, where 9 genera were remarkably enriched in the gut communities of AF patients. Neither of these TMA-synthesis pathways nor the microbial players showed a significant discrepancy between different types of AF in the current cohort. These gut microbes might participate in the formation of TMA by activating the key TMA-synthesis enzymes and contributing to the functional pathways in AF patients. Conclusions The present study provides an in-depth insight into the potential bacteria and metabolic pathways involved in TMA production in the gut of AF patients. These findings emphasize a key role of the gut bacteria in driving TMAO formation during AF pathogenesis, thereby indicating its therapeutic potential as an intervention strategy of AF by targeting TMA-synthesis pathways and dysbiotic gut microbiota.

Abstract Background There is a paucity of evidence on the combination of the SYNTAX score II (SSII) and erythrocyte sedimentation rate (ESR) in assessing the long-term prognosis of patients with ST-elevated myocardial infarction (STEMI) and multivessel disease. The objective of this study was to investigate whether the ESR could enhance the predictive value of SSII on the long-term prognosis of STEMI patients. Methods A retrospective cohort study involving 483 STEMI and multivessel disease subjects receiving primary percutaneous coronary intervention was conducted. Major adverse cardiovascular events (MACE) included cardiovascular death, acute heart failure, recurrent myocardial infarction, revascularization, and nonfatal stroke. The predicted values of different models were estimated by a likelihood ratio test, Akaike’s information criteria (AIC), receiver operating characteristic (ROC) curves, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results During the follow-up period of up to 52 months, both the SSII and ESR were independently associated with MACE (hazard ratio [HR] = 1.032, p

Abstract Aims The aim of this study was to investigate the impact of digoxin use on the outcomes of patients with heart failure with reduced ejection fraction (HFrEF) and its possible interaction with atrial fibrillation or use of currently guideline‐recommended treatments in the real world in China. Methods and results Patients hospitalized with HFrEF from 45 hospitals participating in the China National Heart Failure Registration Study (CN‐HF) were enrolled to assess the all‐cause mortality, HF mortality, all‐cause re‐hospitalization, and HF re‐hospitalization associated with digoxin use. Eight hundred eighty‐two eligible HFrEF patients in the CN‐HF registry were included: 372 patients with digoxin and 510 patients without digoxin. Among them, 794 (90.0%) patients were followed up for the endpoint events, with a median follow‐up of 28.6 months. Kaplan–Meier survival analysis showed that the all‐cause mortality (P < 0.001) and all‐cause re‐hospitalization (P = 0.020) were significantly higher in digoxin group than non‐digoxin group, while HF mortality (P = 0.232) and HF re‐hospitalization (P = 0.098) were similar between the two groups. The adjusted Cox proportional‐hazards regression analysis demonstrated that digoxin use remained as an independent risk factor for increased all‐cause mortality [hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.27–2.44; P = 0.001] and all‐cause re‐hospitalization (HR 1.27; 95% CI 1.03–1.57; P = 0.029) in HFrEF patients and the predictive value of digoxin for all‐cause mortality irrespective of rhythm or in combination with other guideline‐recommended therapies. Conclusions Digoxin use is independently associated with increased risk of all‐cause mortality and all‐cause re‐hospitalization in HFrEF patients.

Abstract Background ST resolution (STR) after AMI is a non-invasive indicator of IRA reperfusion. We investigated whether pre-angiography STR predicted spontaneous IRA reperfusion in STEMI patients. Method Patients with STEMI undergoing primary PCI were recruited. Standard 12-lead ECG tracings were recorded at first medical contact, immediately prior to arterial puncture and 60 min after PCI. STR was classified as total (≥70%; group I), partial (≥30 and 70% may predict a better clinical outcome. Conclusions Assessment of STR could potentially be used to stratify risk in patients with STEMI before PCI.

This study examined the effect of sleep disturbance on gut microbiota (GM), atrial substrate, and atrial fibrillation (AF) inducibility. C57BL/6 mice were subjected to six weeks of sleep deprivation (SD) using the method of modified multiple-platform. Transesophageal burst pacing was performed to evaluate AF inducibility. Feces, plasma, and an atrium were collected and analyzed by 16s rRNA sequencing, liquid chromatography–mass spectrometry (LC-MS)-based metabolome, histological studies, and transcriptome. Higher AF inducibility (2/30 of control vs. 15/30 of SD, p = 0.001) and longer AF duration (p < 0.001), concomitant with aggravated fibrosis, collagen, and lipid accumulation, were seen in the SD mice compared to control mice. Meanwhile, elevated alpha diversity, higher abundance of Flavonifractor, Ruminococcus, and Alloprevotella, as well as imbalanced functional pathways, were observed in the gut of SD mice. Moreover, the global patterns for the plasma metabolome were altered, e.g., the decreased butanoate metabolism intermediates in SD mice. In addition, disrupted metabolic homeostasis in the SD atrium, such as fatty acid metabolism, was analyzed by the transcriptome. These results demonstrated that the crosstalk between GM and atrial metabolism might be a promising target for SD-mediated AF susceptibility.

Background: In response to the outbreak of coronavirus disease 2019 (COVID-19) worldwide, inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are implemented. Dysbiosic gut microbiota is implicated in the COVID-19 patients. Whereas, how intestinal microbiota are affected by vaccination remains elusive, and it is important to investigate the microbial shifts during vaccines treatment. Methods: In the present study, we assessed the gut microbial composition in healthy adults, and performed comparison before and post an inactivated SARS-CoV-2 vaccine candidate, BBIBP-CorV vaccination. Results: Microbial diversity in shannon, pielou evenness, simpson and invsimpson index was remarkably suppressed by vaccination. Ruminococcus and Actinomyces were observed to be strikingly deficient, and Faecalibacterium was dramatically augmented after BBIBP-CorV treatment. Potential functional profiles of gut microbiome in amino acid metabolism, lipid biosynthesis proteins and steroid biosynthesis were remarkably increased, while the capacity in renin-angiotensin system was remarkably decreased following vaccines. Conclusions: Our study suggests that inactivated BBIBP-CorV against SARS-CoV-2 could elicit modulations on gut microbial composition and functions, which might favor host immune response and protect from COVID-19.

Disordered gut microbiota (GM) as the co-contributor of atrial fibrillation (AF) and hypertension (HTN) might be associated with AF risk in HTN. This study aimed to explore the altered GM community and metabolic patterns between 27 HTN patients with AF (HTN-AF) and 27 non-AF HTN patients through fecal metagenomic and serum metabolomic analysis. Compared to non-AF HTN patients, significant microbial alterations (p = 0.004), including increased microbial diversity (p < 0.05), shifted enterotype dominated by Prevotella to Bacteroides, and abundant disease-linked genera Ruminococcus, Streptococcus, Veillonella, Dorea, and Enterococcus, were observed in HTN-AF patients. A species-based random forest prediction model was associated with the risk of AF occurrence in HTN patients. Furthermore, GM metabolic profiles dramatically differed between HTN and HTN-AF patients, especially the imbalance of saturated and unsaturated fatty acids. In HTN-AF patients, circulating palmitic acid and arachidonic acid levels were significantly elevated, while the levels of tetracosahexaenoic acid, oleic acid, linoleic acid, and stearic acid were decreased (p < 0.001, VIP > 1), mediating 85.99% of gut microbial indirect effects on AF (p < 0.001). Thus, our findings preliminarily indicated that exacerbated dysbiosis of GM and relevant metabolites was associated with high AF susceptibility and might be a potential target for AF prediction and prevention in HTN.

Background: Low-voltage zones (LVZs) were usually targeted for ablation in atrial fibrillation (AF). However, its relationship with AF initiation, perpetuation, and termination remains to be studied. This study aimed to explore such relationships.Methods: A total of 126 consecutive AF patients were enrolled, including 71 patients for AF induction protocol and 55 patients for AF termination protocol. Inducible and sustainable AF were defined as induced AF lasting over 30 and 300 s, respectively. Terminable AF was defined as those that could be terminated into sinus rhythm within 1 h after ibutilide administration. Voltage mapping was performed in sinus rhythm for all patients. LVZ was quantified as the percentage of the LVZ area (LVZ%) to the left atrium surface area.Results: The rates of inducible, sustainable, and terminable AF were 29.6, 18.3, and 38.2%, respectively. Inducible AF patients had no significant difference in overall LVZ% compared with uninducible AF patients (10.2 ± 11.8 vs. 8.5 ± 12.6, p = 0.606), while sustainable and interminable AF patients had larger overall LVZ% than unsustainable (16.2 ± 11.5 vs. 0.5 ± 0.7, p < 0.001) and terminable AF patients (44.6 ± 26.4 vs. 26.3 ± 22.3, p < 0.05), respectively. The segmental LVZ distribution pattern was diverse in the different stages of AF. Segmental LVZ% difference was initially observed in the anterior wall for patients with inducible AF, and the septum was further affected in those with sustainable AF, and the roof, posterior wall, and floor were finally affected in those with interminable AF.Conclusions: The associations between LVZ with AF initiation, perpetuation, and termination were different depending on its size and distribution.

Phenylacetylglutamine (PAGln), a gut microbiota (GM)-derived metabolite, is associated with cardiovascular disease. Studies have shown that disordered GM participated in the progression of atrial fibrillation (AF), but the relationship between PAGln and AF is unclear. This study investigated the characteristics of PAGln in AF patients and its impact on atrial myocytes. Based on our previous metagenomic data, the relative abundance of porA, a critical bacterial enzyme for PAGln synthesis, exhibited an increased tendency in AF. In an independent cohort consisting of 42 controls without AF and 92 AF patients, plasma PAGln levels were higher in AF patients than in controls (p < 0.001) by immunoassay. Notably, PAGln exerted a predictive potential of AF with an AUC of 0.774 (p < 0.001), and a predictive model constructed based on the PAGln and Taiwan AF score further improved the predictive potential. Furthermore, a positive correlation was determined between PAGln and LA diameter. Subsequently, the effect of PAGln intervention was examined on HL-1 cells in vitro, revealing that PAGln increased apoptosis, reactive oxygen species (ROS) production, CaMKII and RyR2 activation and decreased cell viability. In conclusion, increased PAGln was associated with AF, and PAGln might contribute to the AF pathogenesis by promoting oxidative stress and apoptosis in atrial myocytes.

The liquid chemical hydrogen storage technology has great potentials for high-density hydrogen storage and transportation at ambient temperature and pressure. However, its commercial applications highly rely on the high-performance heterogeneous dehydrogenation catalysts, owing to the dehydrogenation difficulty of chemical hydrogen storage materials. In recent years, the chemists and materials scientists found that the supported metal nanoparticles (MNPs) can exhibit high catalytic activity, selectivity, and stability for the dehydrogenation of chemical hydrogen storage materials, which will clear the way for the commercial application of liquid chemical hydrogen storage technology. This review has summarized the recent important research progress in the MNP-catalyzed liquid chemical hydrogen storage technology, including formic acid dehydrogenation, hydrazine hydrate dehydrogenation and ammonia borane dehydrogenation, discussed the urgent challenges in the key field, and pointed out the future research trends.

Purpose: Bartter syndrome (BS) and Gitelman syndrome (GS) are hereditary diseases characterized by hypokalemia with decreased or normal blood pressure (BP). However, BS or GS patients who present with elevated BP levels have been increasingly reported recently. Therefore, this study aimed to investigate the presence of BS and GS among individuals with unexplained hypokalemia with hypertension in a clinical setting. Methods: Patients presented with unexplained hypertension and hypokalemia admitted to Hypertension Center of Fuwai Hospital from November 2015 to February 2017 were enrolled. High-throughput sequencing for five BS and GS causative genes were performed. Variants were classified using American College of Medical Genetics (ACMG) consensus guidelines. Results: Thirty-four patients with unexplained hypertension and hypokalemia were included for genetic analysis. A total number of 10 rare variants were identified in six individuals (mutation detection rate, 17.65%). One homozygous variant carried by one of the 34 patients, KCNJ1 c.941A> G (p.Tyr314Cys), were categorized as likely pathogenic variant and resulted in a diagnostic yield of 2.94%. Eight of the remaining nine variants were predicted to be deleterious by ≥ three bioinformatics software and may give additional potential diagnostic yields. Conclusions: This is the first study performing combined genetic screening for BS and GS pathogenic genes among individuals with unexplained hypertension and hypokalemia. Our data suggested that BS or GS may contribute to the etiology of patients presented with hypertension and hypokalemia. Genetic testing for BS and GS pathogenic genes are recommended to facilitate precision diagnoses and targeted treatment.

Background: Elevated heart rate (HR) is associated with cardiovascular mortality and other events associated with acute myocardial infarction (AMI). The heart rate after discharge is likely superior to reflect the deteriorating heart function, which negatively responds to normal physical activity. This study aimed to explore the effect of HR at the first outpatient visit on clinical outcomes. Methods: We retrospectively identified 605 patients with AMI. HRs at admission, discharge, and first outpatient visits were measured. The primary endpoint was defined as major adverse cardiovascular events (MACEs), including cardiovascular (CV) death, readmission for worsening heart failure, recurrent nonfatal myocardial infarction (MI), repeated coronary revascularization, and ischemic stroke. Results: During the follow-up period, 145 cases of MACE occurred, including 34 CV deaths, 31 recurrent MI, 89 revascularizations, 41 heart failures, and 4 strokes. The event group displayed an elevated HR at the first outpatient visit compared to the event-free group (p < 0.001). After adjustment for confounding risk factors, Cox models showed that the outpatient HR had the best correlation with MACE [Hazard ratio (HR) = 1.33, 95% confidence interval (CI) = 10.8–59.3, p < 0.01 for increments of 1 standard deviation (SD) in the outpatient HR) and CV mortality (HR = 1.18, 95% CI = 1.052–1.325, p < 0.01) compared with the other two HRs. The restricted spline model indicated that HR at the first post-discharge above 71 bpm was associated with CV mortality. Conclusions: Elevated HR at the first outpatient visit over a period of 2–4 weeks is related to the adverse outcomes of AMI and may identify AMI patients at higher risk of CV mortality.

Xin Su Ning (XSN), a China patented and certified multi-herbal medicine, has been available in China since 2005 for treating cardiac ventricular arrhythmia including arrhythmia induced by ischemic heart diseases and viral myocarditis, without adverse reactions being reported. It is vitally important to discover pharmacologically how XSN as a multicomponent medicine exerts its clinical efficacy, and whether the therapeutic effect of XSN can be verified by standard clinical trial studies. In this paper we report our discoveries in a cellular electrophysiological study and in a three-armed, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. Conventional electrophysiological techniques were used to study the cellular antiarrhythmic mechanism of XSN. Data was then modeled with computational simulation of human action potential (AP) of the cardiac ventricular myocytes. The clinical trial was conducted with a total of 861 eligible participants randomly assigned in a ratio of 2:2:1 to receive XSN, mexiletine, or the placebo for 4 weeks. The primary and secondary endpoint was the change of premature ventricular contraction (PVC) counts and PVC-related symptoms, respectively. This trial was registered in the Chinese Clinical Trial Register Center (ChiCTR-TRC-14004180). We found that XSN prolonged AP duration of the ventricular myocytes in a dose-dependent, reversible manner and blocked potassium channels. Patients in XSN group exhibited significant total effective responses in the reduction of PVCs compared to those in the placebo group (65.85% vs. 27.27%, P < 0.0001). No severe adverse effects attributable to XSN were observed. In conclusion, XSN is an effective multicomponent antiarrhythmic medicine to treat PVC without adverse effect in patients, which is convincingly supported by its class I & III pharmacological antiarrhythmic mechanism of blocking hERG potassium channels and hNaV1.5 sodium channel reported in our earlier publication and prolongs AP duration both in ventricular myocytes and with computational simulation of human AP presented in this report.

ABSTRACT Dysbiotic gut microbiota (GM) and disordered metabolic patterns are known to be involved in the clinical expression of atrial fibrillation (AF). However, little evidence has been reported in characterizing the specific changes in fecal microbiota in paroxysmal AF (PAF) and persistent AF (psAF). To provide a comprehensive understanding of GM dysbiosis in AF types, we assessed the GM signatures of 30 PAF patients, 20 psAF patients, and 50 non-AF controls based on metagenomic and metabolomic analyses. Compared with control subjects, similar changes of GM were identified in PAF and psAF patients, with elevated microbial diversity and similar alteration in the microbiota composition. PAF and psAF patients shared the majority of differential taxa compared with non-AF controls. Moreover, the similarity was also illuminated in microbial function and associated metabolic alterations. Additionally, minor disparity was observed in PAF compared with psAF. Several distinctive taxa between PAF and psAF were correlated with certain metabolites and atrial diameter, which might play a role in the pathogenesis of atrial remodeling. Our findings characterized the presence of many common features in GM shared by PAF and psAF, which occurred at the self-terminating PAF. Preventative and therapeutic measures targeting GM for early intervention to postpone the progression of AF are highly warranted. IMPORTANCE Atrial fibrillation has been identified to be associated with disordered gut microbiota. Notably, atrial fibrillation is a progressive disease and could be categorized as paroxysmal and persistent based on the duration of the episodes. The persistent atrial fibrillation patients are accompanied by higher risk of stroke and lower success rate of rhythm control. However, the microbial signatures of different categories of atrial fibrillation patients remain unknown. We sought to determine whether disordered gut microbiota occurs in the self-terminating PAF or intestinal flora develops dynamically during atrial fibrillation progression. We found that different types of atrial fibrillation show a limited degree of gut microbiota shift. Gut microbiota dysbiosis has already occurred in mild stages of atrial fibrillation, which might act as an early modulator of disease, and therefore may be regarded as a potential target to postpone atrial fibrillation progression.

Accumulating studies have suggested that epicardial adipose tissue (EAT) play an important role in the pathogenesis of atrial fibrillation (AF), but few have characterized the underlying mechanism between their interactions. Recent evidence suggested that bioactive molecules secreted from EAT, including exosomes carrying long non-coding RNAs (lncRNAs), may modulate atrial remodeling. LncRNAs are associated with cardiovascular disorders, including AF, but their roles in EAT remain elusive. The aim of the present study was to investigate the expression profile of lncRNAs in EAT with AF. Differentially expressed lncRNAs and nearby mRNAs interaction networks were constructed.Epicardial adipose samples were collected from patients with persistent non-valvular AF (n = 6) and sinus rhythm (SR) (n = 6), and the expression of lncRNAs and mRNAs were profiled using RNA-sequencing method.A total of 46,577 transcripts, including 35,552 protein-coding pattern, corresponding to 15,404 genes in EAT, among which, 655 mRNAs (265 upregulated and 390 downregulated) and 57 lncRNAs (17 upregulated and 40 downregulated) were differentially expressed between AF and SR (P 1.5). GO enrichment, KEGG pathway analysis and interaction network construction showed that these differentially expressed lncRNAs were enriched in functional categories, including metabolism and stress response, which might contribute to the pathogenesis of AF.Our study demonstrated a differentially expressed lncRNA profile in EAT with AF, and provide a novel insight into the interactions between EAT and AF.

Aim. Hypertension is a complicated disorder with multifactorial etiology and high heritability. Our previous work has identified L3MBTL4 as a novel susceptibility gene for the development of essential hypertension, accompanied with activation of p38/JNK. Yet, little evidence has been reported whether p38/JNK contributed directly to L3MBTL4-induced vascular remodeling and exploring the potential mechanism of L3MBTL4 in vascular smooth muscle cells (VSMCs). Methods. We evaluated the contribution of L3MBTL4 on proliferation, migration, and phenotype changes of VSMCs and further explored the critical role of p38 and JNK signaling pathway underlying. Results. In L3MBTL4 transgenic rats, we found that the elevated blood pressure, increased left ventricular hypertrophy, and thickened vascular media layer were significantly relieved by both p38 and JNK inhibitors. Meanwhile, increased cell proliferation, advanced cell cycle progression, greater migratory capability, and synthetic phenotype were observed in L3MBTL4 overexpressed VSMCs, which could be blocked by either p38 or JNK inhibitor. Conclusions. Our findings pinpointed that p38 and JNK were required for the proliferation and phenotype changes of VSMCs induced by L3MBTL4 in hypertension. These novel findings yield new insights into the genetic and biological basis of hypertension and are fundamental for further studies to explore the intervention strategies targeting L3MBTL4 and p38/JNK to counteract the progression of hypertension.

ABSTRACT Atrial fibrillation (AF) has been shown to be associated with disordered gut microbiota (GM). The underlying factors governing persistent AF (psAF) are not well understood, and the association between AF duration and GM profiles remains to be characterized. Thus, the present study aimed at investigating the dysbiosis of GM in patients with short and long psAF duration and illuminating the relationship between the GM and psAF maintenance. Based on metagenomic sequencing and metabolomic analyses, we assessed the metabolic and GM signature in 12 patients with psAF of 12 months (Pers>12m), and 20 controls. We found that the GM in patients with both Pers12m was significantly perturbed, with an elevated microbial diversity, distinct structure, and discrepant composition. Although Pers12m patients shared a large number of common bacteria with controls, including 84 genera and 404 species, certain bacteria were differently enriched at different AF durations. Furthermore, disturbance in gut microbial function and GM-linked metabolic alterations were detected in both the Pers12m groups. The connection of GM and metabolites with psAF is consistent with interaction and potential modulation of host metabolic pathways due to GM dysbiosis with AF persistence. Our results showed that patients of the Pers12m groups shared many common disordered GM and metabolic features, which might occur in early disease, while prolonged psAF duration was related to certain unique alterations. Preventative strategies targeting GM and microbial metabolites for early intervention to treat AF patients are highly warranted. IMPORTANCE Atrial fibrillation was associated with a disordered gut microbiota in previous research. However, the gut microbiota signature of patients at different stages of atrial fibrillation remains largely unknown. We sought to determine whether the shift in the gut microbiota and metabolic profiles occurs early and remains stable or develops gradually during atrial fibrillation. We found that patients with persistent atrial fibrillation of 12 months shared most of the common features of gut microbiota dysbiosis. However, some distinctive and progressive alterations in the gut microbiota and metabolic structure, which may contribute to the progression of atrial fibrillation, were identified. The present study provides a comprehensive description of the dysbiotic gut microbiota and metabolic profiles in patients of short and long persistent atrial fibrillation, and our findings may help identify therapeutic strategies targeting the gut microbiota to treat atrial fibrillation at an early stage.