Abstract Background Atrial fibrillation (AF) and heart failure (HF) frequently coexist, resulting in adverse outcomes. However, controversies remain regarding the efficacy of catheter ablation (CA) in AF patients with severe left ventricular dysfunction. Objectives The purpose of this study was to perform a meta-analysis of prospective randomized controlled trials to evaluate the efficacy of CA versus medical therapy (MT) in AF patients with left ventricular ejection fraction (LVEF) ≤45%. Methods We searched the literature for studies that compared CA to MT in AF patients with LVEF ≤45%. A meta-analysis of 7 clinical trials was performed, including 1163 patients with AF and HF. Subgroup analysis was performed based on baseline LVEF. All tests were 2-sided; only the p-value <0.05 was considered statistically significant. Results We found that CA was associated with lower all-cause mortality (risk ratio: 0.52, 95% CI: 0.37 to 0.72; p<0.01) and greater improvements in LVEF (mean difference: 4.80%, 95% CI: 2.29% to 7.31%; p<0.01) compared to MT. Patients in the CA group had a lower risk of HF hospitalization and AF recurrence and a significantly better quality of life than those in the MT group. The results of subgroup analysis indicated that patients with milder left ventricular dysfunction improved LVEF after AF ablation (mean difference: 6.53%, 95% CI: 6.18% to 6.88%; p<0.01) compared to patients with more severe disease (mean difference: 2.02%, 95% CI: 0.87% to 3.16%; p<0.01). Conclusions Our meta-analysis demonstrated that CA was associated with significant improvements in outcomes of AF patients with LVEF ≤45%. Additionally, AF patients with milder left ventricular dysfunction could benefit more from CA. (AF (HF coexist However (CA metaanalysis meta (MT (LVEF 45 ≤45% 116 2sided sided 2 2-sided pvalue p value 005 0 05 <0.0 allcause all cause ratio 052 52 0.52 95 CI 037 37 0.3 0.72 072 72 p<0.01 p001 01 mean difference 480 4 80 4.80% 229 29 2.29 7.31% 731 31 653 6 53 6.53% 618 18 6.18 6.88% 688 88 202 02 2.02% 087 87 0.87 3.16% 316 3 16 p<0.01. . Additionally ≤45 11 00 <0. 5 0.5 9 03 0. 0.7 07 p<0.0 p00 48 8 4.80 22 2.2 7.31 73 65 6.53 61 1 6.1 6.88 68 20 2.02 08 0.8 3.16 ≤4 <0 p<0. p0 4.8 2. 7.3 6.5 6. 6.8 2.0 3.1 ≤ < p<0 4. 7. 3. p<

Resumo Fundamento A fibrilação atrial (FA) e a insuficiência cardíaca (IC) coexistem frequentemente, resultando em desfechos adversos. No entanto, permanecem controvérsias quanto à eficácia da ablação por cateter (AC) em pacientes com FA com disfunção ventricular esquerda grave. Objetivos O objetivo deste estudo foi realizar uma metanálise de ensaios prospectivos randomizados e controlados para avaliar a eficácia da AC versus terapia médica (TM) em pacientes com FA com fração de ejeção do ventrículo esquerdo (FEVE) ≤45%. Métodos Procuramos na literatura estudos que comparassem AC com TM em pacientes com FA com FEVE ≤45%. Foi realizada uma metanálise de 7 ensaios clínicos, incluindo 1.163 pacientes com FA e IC. A análise de subgrupo foi realizada com base na FEVE basal. Todos os testes foram bilaterais; apenas o valor p <0,05 foi considerado estatisticamente significativo. Resultados Descobrimos que a AC estava associada a menor mortalidade por todas as causas (taxa de risco: 0,52, IC 95%: 0,37 a 0,72; p<0,01) e maiores melhorias na FEVE (diferença média: 4,80%, IC 95%: 2,29% a 7,31%; p<0,01) em comparação com TM. Os pacientes do grupo AC apresentaram menor risco de hospitalização por IC e recorrência de FA e qualidade de vida significativamente melhor do que aqueles do grupo TM. Os resultados da análise de subgrupo indicaram que pacientes com disfunção ventricular esquerda mais leve melhoraram a FEVE após a ablação de FA (diferença média: 6,53%, IC 95%: 6,18% a 6,88%; p<0,01) em comparação com pacientes com doença mais grave (diferença média : 2,02%, IC 95%: 0,87% a 3,16%; p<0,01). Conclusões Nossa metanálise demonstrou que a AC foi associada a melhorias significativas nos resultados de pacientes com FA com FEVE ≤45%. Além disso, pacientes com FA com disfunção ventricular esquerda mais leve poderiam se beneficiar mais com a AC. (FA (IC frequentemente adversos entanto (AC (TM (FEVE 45 ≤45% clínicos 1163 1 163 1.16 basal bilaterais 005 0 05 <0,0 significativo taxa 052 52 0,52 95% 95 037 37 0,3 0,72 072 72 p<0,01 p001 01 diferença 480 4 80 4,80% 229 2 29 2,29 7,31% 731 31 653 6 53 6,53% 618 18 6,18 6,88% 688 88 202 02 2,02% 087 87 0,87 3,16% 316 3 16 p<0,01. . disso ≤45 116 1.1 00 <0, 5 0,5 9 03 0, 0,7 07 p<0,0 p00 48 8 4,80 22 2,2 7,31 73 65 6,53 61 6,1 6,88 68 20 2,02 08 0,8 3,16 ≤4 11 1. <0 p<0, p0 4,8 2, 7,3 6,5 6, 6,8 2,0 3,1 ≤ < p<0 4, 7, 3, p<

Resumo Fundamento: O antibiótico quimioterápico antraciclina doxorrubicina (DOX) pode induzir cardiotoxicidade cumulativa e levar à disfunção cardíaca. RNAs não codificantes longos (lncRNAs) podem funcionar como importantes reguladores na lesão miocárdica induzida por DOX. Objetivo: Este estudo tem como objetivo investigar o papel funcional e o mecanismo molecular do RNA antisense lncRNA OXCT1 1 (OXCT1-AS1) na lesão celular miocárdica induzida por DOX in vitro. Métodos: Cardiomiócitos humanos (AC16) foram estimulados com DOX para induzir um modelo de lesão celular miocárdica. A expressão de OXCT1-AS1, miR-874-3p e BDH1 em células AC16 foi determinada por RT-qPCR. A viabilidade das células AC16 foi medida pelo ensaio XTT. A citometria de fluxo foi empregada para avaliar a apoptose de células AC16. Western blotting foi utilizado para avaliar os níveis proteicos de marcadores relacionados à apoptose. O ensaio repórter de luciferase dupla foi conduzido para verificar a capacidade de ligação entre miR-874-3p e OXCT1-AS1 e entre miR-874-3p e BDH1. O valor de p<0,05 indicou significância estatística. Resultados: A expressão de OXCT1-AS1 foi diminuída em células AC16 tratadas com DOX. A superexpressão de OXCT1-AS1 reverteu a redução da viabilidade celular e a promoção da apoptose celular causada pela DOX. OXCT1-AS1 está ligado competitivamente ao miR-874-3p para regular positivamente o BDH1. A superexpressão de BDH1 restaurou a viabilidade das células AC16 e suprimiu a apoptose celular sob estimulação com DOX. A derrubada do BDH1 reverteu a atenuação da apoptose de células AC16 mediada por OXCT1-AS1 sob tratamento com DOX. Conclusão: LncRNA OXCT1-AS1 protege células miocárdicas humanas AC16 da apoptose induzida por DOX através do eixo miR-874-3p/BDH1. Fundamento (DOX cardíaca lncRNAs (lncRNAs Objetivo OXCT OXCT1AS1 OXCTAS AS1 AS (OXCT1-AS1 vitro Métodos AC (AC16 OXCT1AS1, AS1, miR8743p miRp miR 874 3p p BDH AC1 RTqPCR. RTqPCR RT qPCR. qPCR RT-qPCR XTT OXCT1-AS p005 0 05 p<0,0 estatística Resultados Conclusão miR8743p/BDH1. miR8743pBDH1 miRpBDH 3p/BDH1. miR-874-3p/BDH1 OXCT1AS (OXCT1-AS (AC1 87 p00 p<0, miR8743p/BDH1 pBDH miR8743pBDH 3pBDH1 3p/BDH1 miR-874-3p/BDH (AC 8 p0 p<0 miR8743p/BDH 3pBDH 3p/BDH p<

Abstract Background: The anthracycline chemotherapeutic antibiotic doxorubicin (DOX) can induce cumulative cardiotoxicity and lead to cardiac dysfunction. Long non-coding RNAs (lncRNAs) can function as important regulators in DOX-induced myocardial injury. Objective: This study aims to investigate the functional role and molecular mechanism of lncRNA OXCT1 antisense RNA 1 (OXCT1-AS1) in DOX-induced myocardial cell injury in vitro. Methods: Human cardiomyocytes (AC16) were stimulated with DOX to induce a myocardial cell injury model. OXCT1-AS1, miR-874-3p, and BDH1 expression in AC16 cells were determined by RT-qPCR. AC16 cell viability was measured by XTT assay. Flow cytometry was employed to assess the apoptosis of AC16 cells. Western blotting was used to evaluate protein levels of apoptosis-related markers. Dual-luciferase reporter assay was conducted to verify the binding ability between miR-874-3p and OXCT1-AS1 and between miR-874-3p and BDH1. The value of p<0.05 indicated statistical significance. Results: OXCT1-AS1 expression was decreased in DOX-treated AC16 cells. Overexpression of OXCT1-AS1 reversed the reduction of cell viability and promotion of cell apoptosis caused by DOX. OXCT1-AS1 is competitively bound to miR-874-3p to upregulate BDH1. BDH1 overexpression restored AC16 cell viability and suppressed cell apoptosis under DOX stimulation. Knocking down BDH1 reversed OXCT1-AS1-mediated attenuation of AC16 cell apoptosis under DOX treatment. Conclusion: LncRNA OXCT1-AS1 protects human myocardial cells AC16 from DOX-induced apoptosis via the miR-874-3p/BDH1 axis. Background (DOX dysfunction noncoding non coding lncRNAs (lncRNAs DOXinduced induced Objective OXCT OXCT1AS1 OXCTAS AS1 AS (OXCT1-AS1 vitro Methods AC (AC16 model OXCT1AS1, AS1, miR8743p, miR8743p miRp miR 874 3p, 3p p BDH AC1 RTqPCR. RTqPCR RT qPCR. qPCR RT-qPCR apoptosisrelated related markers Dualluciferase Dual luciferase OXCT1-AS p005 0 05 p<0.0 significance Results DOXtreated treated stimulation OXCT1AS1mediated OXCTASmediated mediated treatment Conclusion miR8743p/BDH1 miR8743pBDH1 miRpBDH 3p/BDH1 miR-874-3p/BDH axis OXCT1AS (OXCT1-AS (AC1 87 p00 p<0. miR8743p/BDH pBDH miR8743pBDH 3pBDH1 3p/BDH (AC 8 p0 p<0 3pBDH p<

Abstract Background The influence of left atrial appendage volume (LAAV) on the recurrence of atrial fibrillation (AF) following radiofrequency catheter ablation remains unclear. Objectives We performed a meta-analysis to assess whether LAAV is an independent predictor of AF recurrence following radiofrequency catheter ablation. Methods The PubMed and the Cochrane Library databases were searched until March 2022 to identify publications evaluating LAAV in association with AF recurrence after radiofrequency catheter ablation. Seven studies that fulfilled the specified criteria of our analysis were found. We used the Newcastle-Ottawa Scale to evaluate the quality of the studies. The pooled effects were evaluated depending on standardized mean differences (SMDs) or hazard ratios (HRs) with 95% confidence intervals (CIs). P values < 0.05 were considered statistically significant. Results A total of 1017 patients from 7 cohort studies with a mean follow-up 16.3 months were included in the meta-analysis. Data from 6 studies (943 subjects) comparing LAAV showed that the baseline LAAV was significantly higher in patients with AF recurrence compared to those without AF (SMD: −0.63; 95% CI: −0.89 to −0,37; all p values < 0.05; I2= 62.6%). Moreover, higher LAAV was independently associated with a significantly higher risk of AF recurrence after radiofrequency catheter ablation (HR: 1.10; 95% CI: 1.02 to 1.18). Conclusions The meta-analysis showed that there is a significant correlation between LAAV and AF recurrence after radiofrequency catheter ablation, and the role of LAAV in AF patients should not be ignored in clinical practice. (LAAV (AF unclear metaanalysis meta 202 found NewcastleOttawa Newcastle Ottawa SMDs (SMDs HRs (HRs 95 CIs. CIs . (CIs) 005 0 05 0.0 101 followup follow up 163 16 3 16. metaanalysis. analysis. 943 (94 subjects SMD (SMD −0.63 063 63 CI 089 89 −0.8 −0,37 037 37 I2 I 62.6%. 626 62.6% 62 62.6%) Moreover HR (HR 1.10 110 1 10 102 02 1.0 1.18. 118 1.18 18 1.18) practice 20 9 (CIs 00 0. 94 (9 −0.6 06 08 8 −0. −0,3 03 62.6 1.1 11 1. 2 ( −0 −0, 62. −

Resumo Fundamento A influência do volume do apêndice atrial esquerdo (VAAE) na recorrência de fibrilação atrial (FA) após ablação por cateter de radiofrequência permanece obscura. Objetivos Realizamos uma metanálise para avaliar se o VAAE é um preditor independente de recorrência de FA após ablação por cateter de radiofrequência. Métodos Os bancos de dados PubMed e Cochrane Library foram pesquisados até março de 2022 para identificar publicações avaliando o VAAE em associação com a recorrência de FA após ablação por cateter por radiofrequência. Foram encontrados 7 estudos que preencheram os critérios especificados de nossa análise. Usamos a Escala de Newcastle-Ottawa para avaliar a qualidade dos estudos. Os efeitos agrupados foram avaliados dependendo das diferenças médias padronizadas (DMPs) ou hazard ratios (HRs) com intervalos de confiança (ICs) de 95%. Valores de p < 0,05 foram considerados estatisticamente significativos. Resultados Um total de 1.017 pacientes de 7 estudos de coorte com um seguimento médio de 16,3 meses foram incluídos na metanálise. Dados de 6 estudos (943 indivíduos) comparando VAAE mostraram que o VAAE basal foi significativamente maior em pacientes com recorrência de FA em comparação com aqueles sem FA (DMP: −0,63; IC de 95%: −0,89 a −0,37; todos os valores de p < 0,05; I 2 = 62,6%). Além disso, maior VAAE foi independentemente associado a um risco significativamente maior de recorrência de FA após ablação por cateter de radiofrequência (HR: 1,10; IC de 95%: 1,02 a 1,18). Conclusões A metanálise mostrou que existe uma correlação significativa entre o VAAE e a recorrência de FA após ablação por cateter de radiofrequência, e o papel do VAAE em pacientes com FA não deve ser ignorado na prática clínica. (VAAE (FA obscura 202 análise NewcastleOttawa Newcastle Ottawa DMPs (DMPs HRs (HRs ICs (ICs 95 95% 005 0 05 0,0 significativos 1017 1 017 1.01 163 16 3 16, 943 (94 indivíduos DMP (DMP −0,63 063 63 089 89 −0,8 −0,37 037 37 62,6%. 626 62,6% . 62 62,6%) disso HR (HR 1,10 110 10 102 02 1,0 1,18. 118 1,18 18 1,18) clínica 20 9 00 0, 101 01 1.0 94 (9 −0,6 06 08 8 −0, −0,3 03 62,6 1,1 11 1, 1. ( −0 62, −

ABSTRACT Antiviral drug resistance is the most important factor contributing to treatment failure using nucleos(t)ide analogs such as lamivudine for chronic infection with hepatitis B virus (HBV). Development of a system supporting efficient replication of clinically resistant HBV strains is imperative, and new antiviral drugs are needed urgently to prevent selection of drug-resistant HBV mutants. A novel fluorinated cytidine analog, NCC (N-cyclopropyl-4′-azido-2′-deoxy-2′-fluoro-β-d-cytidine), was recently shown to strongly inhibit human HBV in vitro and in vivo. This study was designed to evaluate the antiviral activity of NCC against lamivudine-resistant HBV. We generated a stable cell line encoding the major pattern of lamivudine-resistant mutations rtL180M/M204V and designated it "HepG2.RL1". Immuno-transmission electron microscopic examination and enzyme-linked immunosorbent assay were used to detect secretion of HBV-specific particles and antigens. Quantification of extracellular DNA and intracellular DNA of HepG2.RL1 cells by quantitative real-time polymerase chain reaction revealed >625-fold and >5556-fold increases in the 50% inhibitory concentration of lamivudine, respectively, compared with that for the wild-type virus. The results showed that NCC inhibited DNA replication and HBeAg production in wild-type or lamivudine-resistant HBV in a dose-dependent manner. In conclusion, screening for antiviral compounds active against lamivudine-resistant HBV can be carried out with relative ease using hepG2.RL1 cells. NCC is a potential antiviral agent against wild-type HBV and clinical lamivudine-resistant HBV and deserves evaluation for the treatment of HBV infection.

Spotted leaf mutant belongs to a class of mutants that can produce necrotic lesions spontaneously in plants without any attack by pathogens. These mutants have no beneficial effect on plant productivity but provide a unique opportunity to study programmed cell death in plant defense responses. A novel rice spotted leaf mutant (spl30) was isolated through low-energy heavy ion irradiation. Lesion expression was sensitive to light and humidity. The spl30 mutant caused a decrease in chlorophyll and soluble protein content, with marked accumulation of reactive oxygen species (ROS) around the lesions. In addition, the spl30 mutant significantly enhanced resistance to rice bacterial blight (X. oryzae pv. oryzae) from China (C1-C7). The use of SSR markers showed that the spl30 gene was located between markers XSN2 and XSN4. The genetic distance between the spl30 gene and XSN2 and between spl30 and XSN4 was 1.7 cM and 0.2 cM, respectively. The spl30 gene is a new gene involved in lesion production and may be related to programmed cell death in rice. The ability of this mutant to confer broad resistance to bacterial blight provides a model for studying the interaction between plants and pathogenic bacteria.

A simplified method based on ratio derivative ultraviolet spectrometry for simultaneous determination of bisphenol A (BPA) and bisphenol S (BPS) in environmental water is presented. The method provides a direct analysis of the samples without tedious sample preparation. In this method, the overlapping spectra of BPA and BPS were well resolved using the first derivative (Δλ = 1 nm) of the ratio of their absorption spectra. Measurements of absorbance were performed at wavelengths of 229.5 nm and 245.5 nm for BPA and BPS, respectively, using the ratio derivative spectrum method. Beer's law was followed in the concentration range of 8.8 X 10-7-2.2 X 10-4 mol dm-3 for BPA and 1.4 X 10-6-1.0 X 10-4 mol dm-3 for BPS. The limits of detection were 3.5 X -7 mol dm-3 for BPA and 4.4 X 10 7 mol dm ³ for BPS. Their 5:1 to 1:5 mixtures were resolved with recoveries between 90.5 % and 100.9 % for BPA and between 93.8 % and 101.1 % for BPS. The method was satisfactorily applied to the simultaneous determination of BPA and BPS in environmental water samples.