Circ_0004872 deficiency attenuates ox-LDL-induced vascular smooth muscle cell dysfunction by miR-424-5p-dependent regulation of FRS2.

Atherosclerosis (AS) is a pivotal pathological basis of cardiovascular and cerebrovascular diseases, and circular RNAs (circRNAs) has been disclosed to exert a vital part in the progression of AS. However, the functions of circ_0004872 in the progression of AS is indistinct. In this context, we aimed to elucidate the role of circ_0004872 and the potential mechanism in AS. The level of circ_0004872, miR-424-5p and fibroblast growth factor receptor substrate 2 (FRS2) was detected using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was monitored by Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine (EDU) assays. The invasion and migration capabilities of VSMCs were tested by transwell assays and wound-healing assay, respectively. Western blot was adopted to check the protein levels of CyclinD1, Vimentin and FRS2. Dual-luciferase reporter and RNA immunoprecipitation assay were executed to manifest the interaction between miR-424-5p and circ_0004872 or FRS2. The level of circ_0004872 was increased in the serum samples of AS patients and ox-LDL-exposed VSMCs. Ox-LDL exposure triggered cell proliferation, invasion and migration ability of VSMCs. depletion of circ_0004872 partly weakened ox-LDL-mediated effects in VSMCs. Mechanistically, circ_0004872 functioned as a sponge of miR-424-5p, and miR-424-5p inhibition partly alleviated circ_0004872 deficiency-mediated influences in VSMCs. Additionally, miR-424-5p interacted with FRS2, and miR-424-5p constrained dysfunction in ox-LDL-stimulated VSMCs via reducing FRS2 level. Notably, circ_0004872 functioned as a sponge of miR-424-5p to elevate FRS2 expression. Circ_0004872 accelerated ox-LDL-induced damage via mediating miR-424-5p/FRS2 axis.

Association between left bundle branch block and ventricular septal mid-wall fibrosis in patients with preserved left ventricular ejection fraction.

BACKGROUND: The left bundle branch block (LBBB) is associated with ventricular septal mid-wall fibrosis (SMF) in patients with dilated cardiomyopathy (DCM). However, whether LBBB is also associated with SMF in patients with preserved left ventricular ejection fraction (LVEF) remains unclear. METHODS: We performed a retrospective study of 210 patients with preserved LVEF (male, n = 116; female, n = 94; mean age, 44 ± 17 years). LBBB was defined as QRS duration ≥140 ms for men or ≥ 130 ms for women, QS or rS in V1-V2, mid-QRS notching or slurring in at least two leads (V1, V2, V5, V6, I, and aVL). SMF determined by late gadolinium-enhancement cardiovascular magnetic resonance was defined as stripe-like or patchy mid-myocardial hyper-enhancement in the interventricular septal segments. RESULTS: SMF was detected in 24.8% (52/210) of these patients. The proportion of patients with SMF with LBBB was higher than the proportion of patients with SMF without LBBB (58.3% vs. 20.4%; P < 0.001). In the forward multivariate logistic analysis, LBBB (OR, 4.399; 95% CI, 1.774-10.904; P = 0.001) and age (OR, 1.028; 95% CI, 1.006-1.051; P = 0.011) were independently associated with SMF. The presence of LBBB showed a sensitivity of 27%%, specificity of 94%, positive predictive value of 58%%, and negative predictive value of 80% for the detection of SMF. CONCLUSION: LBBB was significantly associated with SMF in hospitalized patients with preserved LVEF. Screening with a resting 12­lead ECG may help to identify patients who are at a high risk of the presence of SMF.

Loss-free pulverization by confining copper oxide inside hierarchical nitrogen-doped carbon nanocages toward superb potassium-ion batteries.

Taking the advantages of hierarchical nitrogen-doped carbon nanocages (hNCNCs) with nanocavities for encapsulation and multiscale micro-meso-macropores/high conductivity for mass/electron synergistic transportation, a conversion-type CuO anode material is confined inside hNCNCs for potassium storage. The so-obtained yolk-shelled CuO@hNCNC hybrids have tunable CuO contents in the range of 11.7-63.7 wt%. The unique architecture leads to the loss-free pulverization of the active components during charge/discharge, which increases the surface-controlled charge storage, shortens the K+ solid diffusion lengths with an enlarged K+ diffusion coefficient, and meanwhile enhances the rate capability and durability. Consequently, the optimized CuO@hNCNC delivers a high specific capacity of 498 mA h g-1 at 0.1 A g-1 and 194 mA h g-1 at 10.0 A g-1 based on the total mass of CuO@hNCNC, and a long-term stability. The capacity based on the CuO active component reaches a record-high 522 mA h g-1 at 1.0 A g-1 after 2000 cycles, which is ca. 2.5 times the state-of-the-art value in the literature. The evolution of the cycling performance with CuO loading is well understood based on the loss-free pulverization. This study demonstrates a new strategy to turn the generally harmful pulverization of active components into a beneficial factor for K+ storage, which paves the way for exploring high-performance anodes for rechargeable batteries.

Analysis of risk factors and short-term prognostic factors of arrhythmia in patients infected with mild/moderate SARS-CoV-2 Omicron variant.

Background: Complications, including arrhythmia, following severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection continue to be of concern. Omicron is the mainstream SARS-CoV-2 mutant circulating in mainland China. At present, there are few epidemiological studies concerning the relationship between arrhythmia and Omicron variant infection in mainland China. Objectives: To investigate the risk factors of arrhythmia in patients infected with the SARS-CoV-2 Omicron variant and the factors influencing prognosis. Methods: Data from 192 Omicron infected patients with symptoms of arrhythmia (AH group) and 100 Omicron infected patients without arrhythmia (Control group) were collected. Patients in the AH group were divided into the good and poor prognosis groups, according to the follow-up results 4-6 weeks after infection. The general and clinical data between the AH and Control groups, and between the good and poor prognosis groups were compared. The variables with differences between the groups were included in the multivariate logistic regression analysis, and the quantitative variables were analyzed by receiver operating characteristic curve to obtain their cut-off values. Results: Compared with the control group, the body mass index (BMI), proportion of patients with a history of arrhythmia, proportion of antibiotics taken, heart rate, moderate disease severity, white blood cell (WBC) count, and the aspartate aminotransferase, creatine kinase (CK), CK isoenzyme (CK-MB), myoglobin (Mb), high-sensitive troponin I (hs-cTnI), lymphocyte ratio and high sensitivity C-reactive protein (hs-CRP) levels in the AH group were significantly higher (p < 0.05). In addition, obesity (BMI ≥24 kg/m2), fast heart rate (≥100 times/min), moderate disease severity, and WBC, CK-MB and hs-cTnI levels were independent risk factors of arrhythmia for patients with Omicron infection (p < 0.05), and hs-CRP was a protective factor (p < 0.05). Compared with the good prognosis group, the age, proportion of patients with a history of arrhythmia, heart rate, proportion of moderate disease severity, and hs-CRP, CK, Mb and hs-cTnI levels were significantly higher in the poor prognosis group, while the proportion of vaccination was lower in the poor prognosis group (p < 0.05). Advanced age (≥65 years old), proportion of history of arrhythmia, moderate disease severity, vaccination, and hs-CRP, Mb and cTnI levels were independent factors for poor prognosis of patients with arrhythmia (p < 0.05). Conclusion: The factors that affect arrhythmia and the prognosis of patients infected with Omicron include obesity, high heart rate, severity of the disease, age. history of arrhythmia, WBC, hs-CRP, and myocardial injury indexes, which could be used to evaluate and prevent arrhythmia complications in patients in the future.

SGLT2 inhibitors alleviated podocyte damage in lupus nephritis by decreasing inflammation and enhancing autophagy.

OBJECTIVES: The protective role of sodium glucose cotransporter 2 (SGLT2) inhibitors in renal outcomes has been revealed by large cardiovascular outcome trials among patients with type 2 diabetes. However, the effect of SGLT2 inhibitors on lupus nephritis (LN) and its underlying mechanisms remain unknown. METHODS: We applied empagliflozin treatment to lupus-prone MRL/lpr mice to explore the renal protective potential of SGLT2 inhibitors. An SGLT2 knockout monoclonal podocyte cell line was generated using the CRISPR/Cas9 system to examine the cellular and molecular mechanisms. RESULTS: In MRL/lpr mice treated with empagliflozin, the levels of mouse anti-dsDNA IgG-specific antibodies, serum creatinine and proteinuria were markedly decreased. For renal pathology assessment, both the glomerular and tubulointerstitial damages were lessened by administration of empagliflozin. The levels of SGLT2 expression were increased and colocalised with decreased synaptopodin in the renal biopsy samples from patients with LN and MRL/lpr mice with nephritis. The SGLT2 inhibitor empagliflozin could alleviated podocyte injury by attenuating inflammation and enhanced autophagy by reducing mTORC1 activity. Nine patients with LN treated with SGLT2 inhibitors with more than 2 months of follow-up showed that the use of SGLT2 inhibitors was associated with a significant decrease in proteinuria from 29.6% to 96.3%. Moreover, the estimated glomerular filtration rate (eGFR) was relatively stable during the treatment with SGLT2 inhibitors. CONCLUSION: This study confirmed the renoprotective effect of SGLT2 inhibitors in lupus mice, providing more evidence for non-immunosuppressive therapies to improve renal function in classic autoimmune kidney diseases such as LN.

A novel risk model of three SUMOylation genes based on RNA expression for potential prognosis and treatment sensitivity prediction in kidney cancer.

Introduction: Kidney cancer is one of the most common and lethal urological malignancies. Discovering a biomarker that can predict prognosis and potential drug treatment sensitivity is necessary for managing patients with kidney cancer. SUMOylation is a type of posttranslational modification that could impact many tumor-related pathways through the mediation of SUMOylation substrates. In addition, enzymes that participate in the process of SUMOylation can also influence tumorigenesis and development. Methods: We analyzed the clinical and molecular data which were obtanied from three databases, The Cancer Genome Atlas (TCGA), the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC), and ArrayExpress. Results: Through analysis of differentially expressed RNA based on the total TCGA-KIRC cohort, it was found that 29 SUMOylation genes were abnormally expressed, of which 17 genes were upregulated and 12 genes were downregulated in kidney cancer tissues. A SUMOylation risk model was built based on the discovery TCGA cohort and then validated successfully in the validation TCGA cohort, total TCGA cohort, CPTAC cohort, and E-TMAB-1980 cohort. Furthermore, the SUMOylation risk score was analyzed as an independent risk factor in all five cohorts, and a nomogram was constructed. Tumor tissues in different SUMOylation risk groups showed different immune statuses and varying sensitivity to the targeted drug treatment. Discussion: In conclusion, we examined the RNA expression status of SUMOylation genes in kidney cancer tissues and developed and validated a prognostic model for predicting kidney cancer outcomes using three databases and five cohorts. Furthermore, the SUMOylation model can serve as a biomarker for selecting appropriate therapeutic drugs for kidney cancer patients based on their RNA expression.

Protocell Self-Assembly Driven by Sodium Trimetaphosphate.

The co-evolution of peptide formation and membrane self-assembly is considered an essential step in the origin of life. However, more research is required on both processes, particularly on the interaction between prebiotic simple fatty-acid membranes and peptide synthesis. In this study, the sodium trimetaphosphate (P3 m)-activated peptide formation reaction of phenylalanine (Phe) in an alkaline decanoic acid-decanol vesicle system was systematically investigated. The experimental results showed that peptide formation could competitively occur with N-acyl amino acid (NAA) formation. NAA formation did not follow the traditional P3 m-activated peptide formation reaction involving the intermediate cyclic acylphosphoramidate (CAPA). Decanoic acid was activated by P3 m to form a mixed anhydride, which then reacted with an amino acid to form the amide NAA. As a kind of membrane-forming amphiphile, NAA can form vesicles independently and reduce the critical vesicle concentration of the fatty-acid vesicles. Moreover, 11 other representative amino acids, namely alanine (Ala), aspartic acid (Asp), glutamic acid (Glu), glycine (Gly), isoleucine (Ile), leucine (Leu), proline (Pro), serine (Ser), threonine (Thr), valine (Val), and arginine (Arg), were selected for investigation. All of them reacted with decanoic acid to form NAA via the activation effect of P3 m. The abovementioned mechanism involving P3 m-activated carboxylic acid has not been reported in the literature. Our experimental results indicate that the participation of decanoic acid in the P3 m activation-based peptide formation reaction system plays a significant role in the emergence of functionalized protocells. The P3 m activation effect can provide diversified raw membrane materials to form and stabilize protocell membranes; moreover, the small peptides, such as Phe-Leu, formed in the same reaction system can induce the amplification of primitive cells. This implies that synergistic symbiosis between membrane and peptide can be realized via the P3 m activation effect.

Identification of a novel mutation in the factor XIII A subunit in a patient with inherited factor XIII deficiency.

Inherited factor XIII (FXIII) deficiency is an extremely rare and under-diagnosed autosomal recessive inherited coagulopathy, which is caused by genetic defects in the F13A1 or F13B gene. More than 200 genetic mutations have been identified since the first case of inherited FXIII deficiency was reported. This study aimed to identify underlying gene mutations in a patient with inherited FXIII deficiency who presented with recurrent intracerebral hemorrhage. Levels of plasma FXIII-A antigen were measured, F13A1 and F13B genes were sequenced, mutation information was analyzed, and the mutated protein structure was predicted using bioinformatics methods. Molecular genetic analysis identified four mutations of FXIII-related genes in the proband, including three previously reported mutations inherited from his parents (c.631G>A, p.Gly210Arg and c.1687G>A, p.Gly562Arg of F13A1 gene and c.344G>A, p.Arg115His of F13B gene) and a novel spontaneous mutation of F13A1 gene (c.2063C>G, p.Ser687Cys). Molecular structural modeling demonstrated that the novel Ser687Cys mutation may cause changes in the spatial structure of FXIII-A and increase its instability. In conclusion, we identified a novel and likely pathogenic mutation of the F13A1 gene, which enriched the gene mutation spectrum of inherited FXIII deficiency. The findings may provide promising targets for diagnosis and treatment of inherited FXIII deficiency.

Discovery of a novel 1H-pyrazole- [3,4-b] pyridine-based lysine demethylase 5B inhibitor with potential anti-prostate cancer activity that perturbs the phosphoinositide 3-kinase/AKT pathway.

Lysine demethylase 5B (KDM5B) is a member of the Jumonji AT-rich interactive domain 1 family. Its main function is to demethylate di/trimethyl histone H3 lysine 4 and it plays a crucial role in the occurrence and development of cancer. In this study, we performed structure-based optimization of KDM5B inhibitors based on our previous work and the most active compound we synthesized was 11ad. Molecular modeling studies and thermal shift assays revealed that 11ad specifically targets KDM5B at the molecular and cellular levels. Crucially, 11ad demonstrated good pharmacokinetic properties and anti-prostate cancer activity in a xenograft model. Furthermore, unexpectedly, the specificity of 11ad for prostate cancer was found to be related to its inhibition of the phosphoinositide 3-kinase/AKT pathway. This is the first report of a KDM5B inhibitor affecting this pathway. Taken together, our findings indicate that 11ad is a novel KDM5B inhibitor that may serve as a lead compound for the development of treatments for prostate cancer.

The CC-NB-LRR protein BSR1 from Brachypodium confers resistance to Barley stripe mosaic virus in gramineous plants by recognising TGB1 movement protein.

Although some nucleotide binding, leucine-rich repeat immune receptor (NLR) proteins conferring resistance to specific viruses have been identified in dicot plants, NLR proteins involved in viral resistance have not been described in monocots. We have used map-based cloning to isolate the CC-NB-LRR (CNL) Barley stripe mosaic virus (BSMV) resistance gene barley stripe resistance 1 (BSR1) from Brachypodium distachyon Bd3-1 inbred line. Stable BSR1 transgenic Brachypodium line Bd21-3, barley (Golden Promise) and wheat (Kenong 199) plants developed resistance against BSMV ND18 strain. Allelic variation analyses indicated that BSR1 is present in several Brachypodium accessions collected from countries in the Middle East. Protein domain swaps revealed that the intact LRR domain and the C-terminus of BSR1 are required for resistance. BSR1 interacts with the BSMV ND18 TGB1 protein in planta and shows temperature-sensitive antiviral resistance. The R390 and T392 residues of TGB1ND (ND18 strain) and the G196 and K197 residues within the BSR1 P-loop motif are key amino acids required for immune activation. BSR1 is the first cloned virus resistance gene encoding a typical CNL protein in monocots, highlighting the utility of the Brachypodium model for isolation and analysis of agronomically important genes for crop improvement.

CD36 aggravates podocyte injury by activating NLRP3 inflammasome and inhibiting autophagy in lupus nephritis.

A major cause of proteinuria in lupus nephritis (LN) is podocyte injury, and determining potential therapeutic targets to prevent podocyte injury is important from a clinical perspective in the treatment of LN. CD36 is involved in podocyte injury in several glomerulopathies and was reported to be a vital candidate gene in LN. Here, we determined the role of CD36 in the podocyte injury of LN and the underlying mechanisms. We observed that CD36 and NLRP3 (NLR family pyrin domain containing 3) were upregulated in the podocytes of lupus nephritis patients and MRL/lpr mice with renal impairment. In vitro, CD36, NLRP3 inflammasome, and autophagy were elevated accompanied with increased podocyte injury stimulated by IgG extracted from lupus nephritis patients compared that from healthy donors. Knocking out CD36 with the CRISPR/cas9 system decreased the NLRP3 inflammasome levels, increased the autophagy levels and alleviated podocyte injury. By enhancing autophagy, NLRP3 inflammasome was decreased and podocyte injury was alleviated. These results demonstrated that, in lupus nephritis, CD36 promoted podocyte injury by activating NLRP3 inflammasome and inhibiting autophagy by enhancing which could decrease NLRP3 inflammasome and alleviate podocyte injury.

Identification and picking point positioning of tender tea shoots based on MR3P-TS model.

Tea is one of the most common beverages in the world. In order to reduce the cost of artificial tea picking and improve the competitiveness of tea production, this paper proposes a new model, termed the Mask R-CNN Positioning of Picking Point for Tea Shoots (MR3P-TS) model, for the identification of the contour of each tea shoot and the location of picking points. In this study, a dataset of tender tea shoot images taken in a real, complex scene was constructed. Subsequently, an improved Mask R-CNN model (the MR3P-TS model) was built that extended the mask branch in the network design. By calculating the area of multiple connected domains of the mask, the main part of the shoot was identified. Then, the minimum circumscribed rectangle of the main part is calculated to determine the tea shoot axis, and to finally obtain the position coordinates of the picking point. The MR3P-TS model proposed in this paper achieved an mAP of 0.449 and an F2 value of 0.313 in shoot identification, and achieved a precision of 0.949 and a recall of 0.910 in the localization of the picking points. Compared with the mainstream object detection algorithms YOLOv3 and Faster R-CNN, the MR3P-TS algorithm had a good recognition effect on the overlapping shoots in an unstructured environment, which was stronger in both versatility and robustness. The proposed method can accurately detect and segment tea bud regions in real complex scenes at the pixel level, and provide precise location coordinates of suggested picking points, which should support the further development of automated tea picking machines.

The Stress Detection and Segmentation Strategy in Tea Plant at Canopy Level.

As compared with the traditional visual discrimination methods, deep learning and image processing methods have the ability to detect plants efficiently and non-invasively. This is of great significance in the diagnosis and breeding of plant disease resistance phenotypes. Currently, the studies on plant diseases and pest stresses mainly focus on a leaf scale. There are only a few works regarding the stress detection at a complex canopy scale. In this work, three tea plant stresses with similar symptoms that cause a severe threat to the yield and quality of tea gardens, including the tea green leafhopper [Empoasca (Matsumurasca) onukii Matsuda], anthracnose (Gloeosporium theae-sinensis Miyake), and sunburn (disease-like stress), are evaluated. In this work, a stress detection and segmentation method by fusing deep learning and image processing techniques at a canopy scale is proposed. First, a specified Faster RCNN algorithm is proposed for stress detection of tea plants at a canopy scale. After obtaining the stress detection boxes, a new feature, i.e., RGReLU, is proposed for the segmentation of tea plant stress scabs. Finally, the detection model at the canopy scale is transferred to a field scale by using unmanned aerial vehicle (UAV) images. The results show that the proposed method effectively achieves canopy-scale stress adaptive segmentation and outputs the scab type and corresponding damage ratio. The mean average precision (mAP) of the object detection reaches 76.07%, and the overall accuracy of the scab segmentation reaches 88.85%. In addition, the results also show that the proposed method has a strong generalization ability, and the model can be migrated and deployed to UAV scenarios. By fusing deep learning and image processing technology, the fine and quantitative results of canopy-scale stress monitoring can provide support for a wide range of scouting of tea garden.

Association between complete right bundle branch block and atrial fibrillation development.

BACKGROUND: Complete right bundle branch block (CRBBB) is an important predictor of atrial fibrillation (AF) recurrence after pulmonary vein isolation. However, the association between CRBBB and AF development remains unclear. METHODS: We performed a retrospective study of 2639 patients (male, n = 1549; female, n = 1090; mean age, 58 ± 13 years). CRBBB was defined as a late R (R') wave in lead V1 or V2 with a slurred S wave in lead I and/or lead V6 with a prolonged QRS duration (≥120 ms). RESULTS: Among the 2639 patients, CRBBB was detected in 40 patients (1.5%), and the prevalence of AF was 7.4% (196/2639). The proportion of patients with AF and CRBBB was higher than the proportion of patients with AF without CRBBB (22.5% vs. 7.2%; p = 0.001). In the forward multivariate logistic analysis, CRBBB (odds ratio [OR], 3.329; 95% confidence interval [CI], 1.350-8.211; p = 0.009), complete left bundle branch block (OR, 2.209; 95% CI, 1.238-3.940; p = 0.007), age (OR, 1.020; 95% CI, 1.005-1.035; p = 0.009), valvular heart disease (OR, 2.332; 95% CI, 1.531-3.552; p < 0.001), left atrial diameter (OR, 1.133; 95% CI, 1.104-1.163; p < 0.001), left ventricular ejection fraction (OR, 1.023; 95% CI, 1.006-1.041; p = 0.007), and class I or III anti-arrhythmic drug use (OR, 10.534; 95% CI, 7.090-15.651; p < 0.001) were associated with AF. CONCLUSION: Complete right bundle branch block was significantly associated with AF development in hospitalized patients with cardiovascular diseases.

The Composite-Template Method to Construct Hierarchical Carbon Nanocages for Supercapacitors with Ultrahigh Energy and Power Densities.

3D hierarchical carbon nanocages (hCNC) are becoming new platforms for advanced energy storage and conversion due to their unique structural characteristics, especially the combination of multiscale pore structure with high conductivity of sp2 carbon frameworks, which can promote the mass/charge synergetic transfer in various electrochemical processes. Herein, the MgO@ZnO composite-template method is developed to construct hCNC and nitrogen-doped hCNC (hNCNC), which integrates the advantages of the in situ MgO template method and ZnO self-sacrificing template method. The hierarchical MgO template provides the scaffold for depositing carbon nanocages, while the self-sacrificing ZnO template helps create abundant micropores while promoting the graphitization degree, so that the microstructures of the products are effectively regulated. The optimized hCNC and hNCNC have an increased specific surface area and conductivity, which can further boost the mass/charge synergetic transfer. As the electrode materials of supercapacitors, the optimal hCNC(hNCNC) exhibits a high specific capacitance of 281(348) F g-1 in KOH and 276(297) F g-1 in EMIMBF4 electrolytes at 1 A g-1 . The ultrahigh energy and power densities are realized, accompanied by a high-rate capability and long cycling stability. The record-high energy densities of 141.8-71.4 Wh kg-1 are achieved in EMIMBF4 at power densities of 10.0-250.4 kW kg-1 .

Effect of catheter ablation on clinical outcomes in patients with atrial fibrillation and significant functional mitral regurgitation.

BACKGROUND: In patients with atrial fibrillation (AF) and functional mitral regurgitation (MR), catheter ablation reduces the severity of MR and improves cardiac remodeling. However, its effects on prognosis are uncertain. METHODS: This retrospective study included 151 consecutive patients with AF and functional MR, 82 (54.3%) of whom were treated by catheter ablation (Ablation group) and 69 (45.7%) with drug therapy without ablation (Non-ablation group). Forty-three pairs of these patients were propensity matched on the basis of age, CHA2DS2-VASc scores, and left ventricular ejection fraction. The primary outcome evaluated was severity of MR, cardiac remodeling and the combined incidence of subsequent heart failure-related hospitalization and strokes/transient ischemic attacks. RESULTS: Patients in the Ablation group showed a significant decrease in the severity of MR (p < 0.001), a significant decrease in the left atrial diameter (p = 0.010), and significant improvement in the left ventricular ejection fraction (p = 0.015). However, patients in the Non-ablation group showed only a significant decrease in the severity of MR (p = 0.004). The annual incidence of the studied events was 4.9% in the Ablation group and 16.7% in the Non-ablation group, the incidence being significantly lower in the ablation than Non-ablation group (p = 0.026) according to Kaplan-Meier curve analyses. According to multivariate Cox regression analysis, catheter ablation therapy (hazard ratio [HR] 0.27, 95% confidence interval [CI] 0.09-0.84; p = 0.024) and heart failure at baseline (HR 3.84, 95% CI 1.07-13.74; p = 0.038) were independent predictors of the incidence of the studied events. CONCLUSIONS: Among patients with AF and functional MR, catheter ablation was associated with a significantly lower combined risk of heart failure-related hospitalization and stroke than in a matched cohort of patients receiving drug therapy alone.

PU.1 inhibition attenuates atrial fibrosis and atrial fibrillation vulnerability induced by angiotensin-II by reducing TGF-ß1/Smads pathway activation.

Fibrosis serves a critical role in driving atrial remodelling-mediated atrial fibrillation (AF). Abnormal levels of the transcription factor PU.1, a key regulator of fibrosis, are associated with cardiac injury and dysfunction following acute viral myocarditis. However, the role of PU.1 in atrial fibrosis and vulnerability to AF remain unclear. Here, an in vivo atrial fibrosis model was developed by the continuous infusion of C57 mice with subcutaneous Ang-II, while the in vitro model comprised atrial fibroblasts that were isolated and cultured. The expression of PU.1 was significantly up-regulated in the Ang-II-induced group compared with the sham/control group in vivo and in vitro. Moreover, protein expression along the TGF-ß1/Smads pathway and the proliferation and differentiation of atrial fibroblasts induced by Ang-II were significantly higher in the Ang-II-induced group than in the sham/control group. These effects were attenuated by exposure to DB1976, a PU.1 inhibitor, both in vivo and in vitro. Importantly, in vitro treatment with small interfering RNA against Smad3 (key protein of TGF-ß1/Smads signalling pathway) diminished these Ang-II-mediated effects, and the si-Smad3-mediated effects were, in turn, antagonized by the addition of a PU.1-overexpression adenoviral vector. Finally, PU.1 inhibition reduced the atrial fibrosis induced by Ang-II and attenuated vulnerability to AF, at least in part through the TGF-ß1/Smads pathway. Overall, the study implicates PU.1 as a potential therapeutic target to inhibit Ang-II-induced atrial fibrosis and vulnerability to AF.

Effect of pulmonary vein isolation on atrial fibrillation recurrence after accessory pathway ablation in patients with Wolff-Parkinson-White syndrome.

BACKGROUND: Although successful ablation of the accessory pathway (AP) eliminates atrial fibrillation (AF) in some of patients with Wolff-Parkinson-White (WPW) syndrome and paroxysmal AF, in other patients it can recur. HYPOTHESIS: Whether adding pulmonary vein isolation (PVI) after successful AP ablation effectively prevents AF recurrence in patients with WPW syndrome is unknown. METHODS: We retrospectively studied 160 patients (102 men, 58 women; mean age, 46 ± 14 years) with WPW syndrome and paroxysmal AF who underwent AP ablation, namely 103 (64.4%) undergoing only AP ablation (AP group) and 57 (35.6%) undergoing AP ablation plus PVI (AP + PVI group). Advanced interatrial block (IAB) was defined as a P-wave duration of >120 ms and biphasic (±) morphology in the inferior leads, using 12-lead electrocardiography (ECG). RESULTS: During the mean follow-up period of 30.9 ± 9.2 months (range, 3-36 months), 22 patients (13.8%) developed AF recurrence. The recurrence rate did not differ in patients in the AP + PVI group and AP group (15.5% vs 10.5%, respectively; P = .373). Univariable and multivariable Cox regression analyses showed that PVI was not associated with the risk of AF recurrence (hazard ratio, 0.66; 95% confidence interval, 0.26-1.68; P = .380). In WPW patients with advanced IAB, the recurrence rate was lower in patients in the AP + PVI group vs the AP group (90% vs 33.3%, respectively; P = .032). CONCLUSIONS: PVI after successful AP ablation significantly reduced the AF recurrence rate in WPW patients with advanced IAB. Screening of a resting 12-lead ECG immediately after AP ablation helps identify patients in whom PVI is beneficial.

[Protective effect and mechanism of curcumin on aorta in rats with metabolic syndrome].

To investigate the protective effect and mechanism of curcumin on aorta in rats with metabolic syndrome,72 SD rats were randomly divided into blank control group,model control group,positive control group,curcumin low,middle and high dose groups.The rat model of metabolic syndrome was established in all groups except the blank control group. After the intervention by curcumin,the blood pressure,blood lipid,blood glucose,serum insulin and insulin sensitivity index were measured. The contents of serum leptin(LP),adiponectin(ADP) and tumor necrosis factor-α(TNF-α) in rat aorta were detected by enzyme-linked immunosorbent assay(ELISA),and the pathological changes of rat thoracic aorta were observed by HE staining and electron microscope scanning. Western blot assay was used to detect the expression of inducible nitric oxide synthase(i NOS) and endothelial nitric oxide synthase(e NOS) in rats. The results showed that the blood lipid level,fasting blood glucose,fasting insulin,insulin sensitivity index,systolic blood pressure,LP,TNF-α and intima/media thickness ratio in the model control group were significantly higher than those in the blank control group. As compared with the model control group,the levels of blood lipids,fasting blood glucose,fasting insulin,insulin sensitivity index,systolic blood pressure,LP,TNF-α and intima/media thickness ratio were significantly decreased in positive control group,low,middle and high dose curcumin groups. The difference was statistically significant. The results of HE staining showed that the intima of the thoracic aorta in the model group was significantly thickened; the endothelial cell membrane was wrinkled and the organelle was ruptured. The intima of the thoracic aorta in the positive control group was slightly thickened and the structure of endothelial cells was intact,with no foam cells and no abnormality in the adventitia. There was no significant thickening of the thoracic aorta in the low,middle and high dose curcumin groups,and the endothelial cells were still intact. The results of Western blot assay showed that the expression levels of i NOS and e NOS were decreased significantly in the model group,while the expression levels of i NOS and e NOS were increased significantly in the positive control group and curcumin groups. The results indicated that curcumin had a certain protective effect on the aorta of rats with metabolic syndrome and improves the aortic endothelial dysfunction,and its mechanism may be related to the fact that curcumin could reduce the production of oxygen free radicals and up-regulate the expression of i NOS and e NOS in aorta.