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Mesenchymal stem cells (MSCs) have demonstrated significant therapeutic potential in heart failure (HF) treatment. However, their clinical application is impeded by low retention rate and low cellular activity of MSCs caused by high inflammatory and reactive oxygen species (ROS) microenvironment. In this study, monascus pigment (MP) nanoparticle (PPM) was proposed for improving adverse microenvironment and assisting in transplantation of bone marrow-derived MSCs (BMSCs). Meanwhile, in order to load PPM and reduce the mechanical damage of BMSCs, injectable hydrogels based on Schiff base cross-linking were prepared. The PPM displays ROS-scavenging and macrophage phenotype-regulating capabilities, significantly enhancing BMSCs survival and activity in HF microenvironment. This hydrogel demonstrates superior biocompatibility, injectability, and tissue adhesion. With the synergistic effects of injectable, adhesive hydrogel and the microenvironment-modulating properties of MP, cardiac function was effectively improved in the pericardial sac of rats. Our results offer insights into advancing BMSCs-based HF therapies and their clinical applications.

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OBJECTIVE: The benefits of rhythm control in early atrial fibrillation (AF) are increasingly recognized. This study aimed to investigate whether early AF ablation contributes to long-term sinus rhythm maintenance and to identify a suitable predictive score. METHODS: According to diagnosis-to-ablation time, this study prospectively enrolled 245 patients with very early AF, 262 with early AF, and 588 with late AF for radiofrequency ablation from June 2017 to December 2022. Clinical data, risk scores, and follow-up results were collected and analyzed. RESULTS: Baseline characteristics were similar among the three cohorts. During a median follow-up period of 26 months, AF recurrence was observed in 61 (24.9%), 66 (25.2%), and 216 (36.7%) patients in the very early, early, and late AF cohorts, respectively. In the multivariable-adjusted model, very early and early AF were associated with a reduced risk of AF recurrence, with hazard ratios of 0.72 (95% confidence interval [CI] 0.52-0.99) and 0.57 (95% CI 0.41-0.78), respectively. The APPLE score demonstrated the highest predictive power for very early AF, with an area under the curve (AUC) of 0.74. However, its predictive power decreased with time from diagnosis, showing low predictive power for late AF (AUC = 0.58). In addition, the time-dependent concordance index showed consistent results. For very early AF, the Akaike information criterion and decision curve analysis showed that APPLE had the highest predictive value. CONCLUSION: Very early AF ablation was associated with a lower recurrence rate, and the APPLE score provided a higher predictive value for these patients. (URL: https://www.chictr.org.cn/; Unique identifier: ChiCTR-OIN-17013021).

RESUMO

BACKGROUND: Atrial fibrillation (AF) is acknowledged as a disease continuum. Despite catheter ablation being recommended as a primary therapy for AF, the high recurrence rates have tempered the initial enthusiasm. Insulin resistance (IR) has been established as an independent predictor for the onset of AF. However, the correlation between non-insulin-based IR indices and late AF recurrence in patients undergoing radiofrequency catheter ablation remains unknown. METHODS: A retrospective cohort of 910 AF patients who underwent radiofrequency catheter ablation was included in the analysis. The primary endpoint was late AF recurrence during the follow-up period after a defined blank period. The relationship between non-insulin-based IR indices and the primary endpoint was assessed using multivariate Cox hazards regression models and restricted cubic splines (RCS). Additionally, the net reclassification improvement and integrated discrimination improvement index were calculated to further evaluate the additional predictive value of the four IR indices beyond established risk factors for the primary outcome. RESULTS: During a median follow-up period of 12.00 months, 189 patients (20.77%) experienced late AF recurrence, which was more prevalent among patients with higher levels of IR. The multivariate Cox hazards regression analysis revealed a significant association between these IR indices and late AF recurrence. Among the four indices, METS-IR provided the most significant incremental effect on the basic model for predicting late AF recurrence. Multivariable-adjusted RCS curves illustrated a nonlinear correlation between METS-IR and late AF recurrence. In subgroup analysis, METS-IR exhibited a significant correlation with late AF recurrence in patients with diabetes mellitus (HR: 1.697, 95% CI 1.397 - 2.063, P < 0.001). CONCLUSION: All the four non-insulin-based IR indices were significantly associated with late AF recurrence in patients undergoing radiofrequency catheter ablation. Addressing IR could potentially serve as a viable strategy for reducing the late AF recurrence rate.

Assuntos

Fibrilação Atrial , Ablação por Cateter , Resistência à Insulina , Recidiva , Humanos , Fibrilação Atrial/cirurgia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Masculino , Feminino , Ablação por Cateter/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Idoso , Fatores de Tempo , Medição de Risco , Resultado do Tratamento , Biomarcadores/sangue , Valor Preditivo dos Testes , Glicemia/metabolismo

RESUMO

OBJECTIVE: Sepsis can have severe implications on lung function, leading to acute lung injury (ALI), a major contributor to sepsis-related mortality. Anisodamine hydrobromide (Ani HBr), a bioactive constituent derived from the root of Scopolia tangutica Maxim, a plant endemic to China, has demonstrated efficacy in treating septic shock. We aim to explore whether Ani HBr can alleviate sepsis-triggered ALI and elucidate the fundamental mechanisms involved. MATERIALS AND METHOD: The protective effects of Ani HBr were assessed in two models: in vitro, lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and in vivo, cecal ligation puncture (CLP)-induced sepsis. To measure the cell viability of RAW264.7 cells after Ani HBr treatment, we used the CCK-8 assay. We quantified the levels of pro-inflammatory cytokines expression using ELISA. We also measured the expression of pyrotosis indicators by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence. RESULTS: Our study demonstrates that Ani HBr can alleviate pulmonary edema, bleeding, and excessive inflammation induced by CLP. Additionally, it exhibits protective effects against cytotoxicity induced by LPS in RAW264.7 macrophage cells. Furthermore, Ani HBr downregulates the mRNA and protein levels of NLRP3, Caspase-1, GSDMD, IL-18, and IL-1ß in both animal models and cell cultures, thereby inhibiting pyroptosis in a similar mechanism to AC-YVAD-CMK (AYC)'s blockade of Caspase-1. Moreover, Ani HBr suppresses the production and release of proinflammatory cytokines. CONCLUSION: These findings suggest that Ani HBr could serve as a protective agent against sepsis-induced ALI by suppressing pyroptosis.

Assuntos

Lesão Pulmonar Aguda , Modelos Animais de Doenças , Piroptose , Sepse , Alcaloides de Solanáceas , Animais , Camundongos , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/metabolismo , Piroptose/efeitos dos fármacos , Sepse/tratamento farmacológico , Sepse/complicações , Células RAW 264.7 , Alcaloides de Solanáceas/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Citocinas/metabolismo , Lipopolissacarídeos/toxicidade

RESUMO

BACKGROUND: There is sufficient evidence that women with atrial fibrillation (AF) have a greater symptom burden than men with AF and are more likely to experience recurrence after catheter ablation. However, the mechanisms underlying these sex differences are unclear. METHODS: We prospectively enrolled 125 consecutive patients, including 40 non-AF patients and 85 AF patients, who underwent high-density voltage mapping during sinus rhythm and AF patients who underwent first ablation. RESULTS: Overall, 37 (44%) female patients with AF and 24 (60%) female non-AF patients with a mean age of 61.7 ± 11.6 years and 53.6 ± 16.7 years, respectively, were enrolled in this study. The results showed that the atrial voltage of female AF patients was significantly lower than that of male AF patients (1.11 ± 0.58 mV vs. 1.53 ± 0.65 mV; P = 0.003), while there were no significant sex differences in non-AF patients (3.02 ± 0.86 mV vs. 3.21 ± 0.84 mV; P = 0.498). Multiple linear regression analysis revealed that female sex (- 0.29, 95% confidence interval [CI] - 0.64 to - 0.13, P = 0.004) and AF type (- 0.32, 95% CI - 0.69 to - 0.13, P = 0.004) were the only factors independently associated with voltage. Compared with men, women in the paroxysmal AF group had a 3.5-fold greater incidence of recurrence (adjusted hazard ratio 4.49; 95% CI 1.101-18.332, P = 0.036). Both globally and regionally, the results showed that sex-related differences in voltage values occurred prominently in paroxysmal AF patients but not in nonparoxysmal AF patients. CONCLUSION: Sex-related differences in atrial substrates and arrhythmia-free survival were found in paroxysmal AF patients, suggesting the existence of sex-related pathophysiological factors.

Assuntos

Fibrilação Atrial , Átrios do Coração , Humanos , Fibrilação Atrial/fisiopatologia , Feminino , Masculino , Pessoa de Meia-Idade , Átrios do Coração/fisiopatologia , Idoso , Estudos Prospectivos , Ablação por Cateter/métodos , Fatores Sexuais , Adulto , Caracteres Sexuais , Recidiva

RESUMO

BACKGROUND: The renal proximal tubule (RPT) plays a pivotal role in regulating sodium reabsorption and thus blood pressure (BP). Transient receptor potential ankyrin 1 (TRPA1) has been reported to protect against renal injury by modulating mitochondrial function. We hypothesize that the activation of TRPA1 by its agonist cinnamaldehyde may mitigate high-salt intake-induced hypertension by inhibiting urinary sodium reabsorption through restoration of renal tubular epithelial mitochondrial function. METHODS: Trpa1-deficient (Trpa1-/-) mice and wild-type (WT) mice were fed standard laboratory chow [normal diet (ND) group, 0.4% salt], standard laboratory chow with 8% salt [high-salt diet (HS) group], or standard laboratory chow with 8% salt plus 0.015% cinnamaldehyde [high-salt plus cinnamaldehyde diet (HSC) group] for 6 months. Urinary sodium excretion, reactive oxygen species (ROS) production, mitochondrial function, and the expression of sodium hydrogen exchanger isoform 3 (NHE3) and Na+/K+-ATPase of RPTs were determined. RESULTS: Chronic dietary cinnamaldehyde supplementation reduced tail systolic BP and 24-hour ambulatory arterial pressure in HS-fed WT mice. Compared with the mice fed HS, cinnamaldehyde supplementation significantly increased urinary sodium excretion, inhibited excess ROS production, and alleviated mitochondrial dysfunction of RPTs in WT mice. However, these effects of cinnamaldehyde were absent in Trpa1-/- mice. Furthermore, chronic dietary cinnamaldehyde supplementation blunted HS-induced upregulation of NHE3 and Na+/K+-ATPase in WT mice but not Trpa1-/- mice. CONCLUSIONS: The present study demonstrated that chronic activation of Trpa1 attenuates HS-induced hypertension by inhibiting urinary sodium reabsorption through restoring renal tubular epithelial mitochondrial function. Renal TRPA1 may be a potential target for the management of excessive dietary salt intake-associated hypertension.

Assuntos

Acroleína , Hipertensão , Camundongos Knockout , Mitocôndrias , Cloreto de Sódio na Dieta , Canal de Cátion TRPA1 , Animais , Canal de Cátion TRPA1/metabolismo , Canal de Cátion TRPA1/genética , Acroleína/análogos & derivados , Acroleína/farmacologia , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , ATPase Trocadora de Sódio-Potássio/metabolismo , Modelos Animais de Doenças , Espécies Reativas de Oxigênio/metabolismo , Trocador 3 de Sódio-Hidrogênio/metabolismo , Trocador 3 de Sódio-Hidrogênio/genética , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/efeitos dos fármacos , Camundongos , Pressão Sanguínea/efeitos dos fármacos

RESUMO

BACKGROUND: Insulin resistance (IR) is linked to both the complexity of coronary artery lesions and the prognosis of acute coronary syndrome (ACS). However, the precise extent of this correlation and its impact on adverse cardiovascular outcomes in ACS patients remain unclear. Therefore, this study aims to investigate the intricate relationship between IR, coronary artery lesion complexity, and the prognosis of ACS through a cohort design analysis. METHOD: A total of 986 patients with ACS who underwent percutaneous coronary intervention (PCI) were included in this analysis. IR was assessed using the triglyceride-glucose (TyG) index, while coronary artery lesion complexity was evaluated using the SYNTAX score. Pearson's correlation coefficients were utilized to analyze the correlations between variables. The association of the TyG index and SYNTAX score with major adverse cardiovascular events (MACEs) in ACS was investigated using the Kaplan-Meier method, restricted cubic splines (RCS), and adjusted Cox regression. Additionally, a novel 2-stage regression method for survival data was employed in mediation analysis to explore the mediating impact of the SYNTAX score on the association between the TyG index and adverse cardiovascular outcomes, including MACEs and unplanned revascularization. RESULTS: During a median follow-up of 30.72 months, 167 cases of MACEs were documented, including 66 all-cause deaths (6.69%), 26 nonfatal myocardial infarctions (MIs) (2.64%), and 99 unplanned revascularizations (10.04%). The incidence of MACEs, all-cause death, and unplanned revascularization increased with elevated TyG index and SYNTAX score. Both the TyG index (non-linear, P = 0.119) and SYNTAX score (non-linear, P = 0.004) displayed a positive dose-response relationship with MACEs, as illustrated by the RCS curve. Following adjustment for multiple factors, both the TyG index and SYNTAX score emerged as significant predictors of MACEs across the total population and various subgroups. Mediation analysis indicated that the SYNTAX score mediated 25.03%, 18.00%, 14.93%, and 11.53% of the correlation between the TyG index and MACEs in different adjusted models, respectively. Similar mediating effects were observed when endpoint was defined as unplanned revascularization. CONCLUSION: Elevated baseline TyG index and SYNTAX score were associated with a higher risk of MACEs in ACS. Furthermore, the SYNTAX score partially mediated the relationship between the TyG index and adverse cardiovascular outcomes.

Assuntos

Síndrome Coronariana Aguda , Biomarcadores , Glicemia , Doença da Artéria Coronariana , Resistência à Insulina , Intervenção Coronária Percutânea , Humanos , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/terapia , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Glicemia/metabolismo , Fatores de Tempo , Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico , Triglicerídeos/sangue , Estudos Retrospectivos , Valor Preditivo dos Testes

RESUMO

Xiong, Shiqiang, Jun Hou, Haixia Yang, Meiting Gong, Xin Ma, Xuhu Yang, Hongyang Zhang, Yao Ma, Liang Gao, and Haifeng Pei. The profiles of venous thromboembolism at different high altitudes High Alt Med Biol. 25:223-225, 2024.-This study investigated the incidence of venous thromboembolism (VTE) in high altitude (HA) and very HA areas. Patients with deep vein thrombosis (DVT) or pulmonary embolism (PE) diagnosed between 2004 and 2022 in Yecheng, China, were retrospectively analyzed. The results showed that patients with PE at very HA had a higher risk of lower extremity DVT (OR 16.3 [95% CI 1.2-223.2], p = 0.036), than those at HA, especially in the early stages of very HA entry, and the harsh environment of very HA further exacerbated the risk of VTE. These findings emphasize the higher risk of PE development in very HA and the need for enhanced prevention and treatment in this area.

Assuntos

Altitude , Embolia Pulmonar , Tromboembolia Venosa , Trombose Venosa , Humanos , Estudos Retrospectivos , Pessoa de Meia-Idade , Feminino , Masculino , China/epidemiologia , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/etiologia , Adulto , Incidência , Fatores de Risco , Trombose Venosa/epidemiologia , Trombose Venosa/etiologia , Idoso , Extremidade Inferior/irrigação sanguínea

RESUMO

BACKGROUND: Diabetic cardiomyopathy (DCM) is a serious complication in patients with type 1 diabetes mellitus (T1DM), which still lacks adequate therapy. Irisin, a cleavage peptide off fibronectin type III domain-containing 5, has been shown to preserve cardiac function in cardiac ischemia-reperfusion injury. Whether or not irisin plays a cardioprotective role in DCM is not known. METHODS AND RESULTS: T1DM was induced by multiple low-dose intraperitoneal injections of streptozotocin (STZ). Our current study showed that irisin expression/level was lower in the heart and serum of mice with STZ-induced TIDM. Irisin supplementation by intraperitoneal injection improved the impaired cardiac function in mice with DCM, which was ascribed to the inhibition of ferroptosis, because the increased ferroptosis, associated with increased cardiac malondialdehyde (MDA), decreased reduced glutathione (GSH) and protein expressions of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), was ameliorated by irisin. In the presence of erastin, a ferroptosis inducer, the irisin-mediated protective effects were blocked. Mechanistically, irisin treatment increased Sirtuin 1 (SIRT1) and decreased p53 K382 acetylation, which decreased p53 protein expression by increasing its degradation, consequently upregulated SLC7A11 and GPX4 expressions. Thus, irisin-mediated reduction in p53 decreases ferroptosis and protects cardiomyocytes against injury due to high glucose. CONCLUSION: This study demonstrated that irisin could improve cardiac function by suppressing ferroptosis in T1DM via the SIRT1-p53-SLC7A11/GPX4 pathway. Irisin may be a therapeutic approach in the management of T1DM-induced cardiomyopathy.

Assuntos

Diabetes Mellitus Tipo 1 , Cardiomiopatias Diabéticas , Ferroptose , Humanos , Animais , Camundongos , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/prevenção & controle , Sirtuína 1 , Fibronectinas , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Proteína Supressora de Tumor p53 , Miócitos Cardíacos

RESUMO

Background: A novel non-contact system for remote parameter testing and reprogramming offers an alternative method for assessing device parameters during cardiac implantable electronic devices (CIEDs) implantation without the need for physical contact with the manufacturer's clinical service technician. The safety and feasibility of using this system in CIEDs implantation procedures remains to be determined. Objective: Evaluate the safety and feasibility of remote parameter testing in CIEDs implantation procedures. Methods: A single center, randomized, open-label, non-inferiority trial (ChiCTR2200057587) was conducted to compare the two approaches for interrogating CIEDs during implantation procedures: routine interrogation performed by on-site technicians or remote interrogation performed by technicians using the 5G-Cloud Technology Platform. Patients aged ≥18 years and elected to receive CIEDs were eligible for inclusion. The primary endpoint was the completion rate of the parameter test. Safety and efficiency were evaluated in all randomly assigned participants. Results: A total of 480 patients were finally enrolled and were randomly assigned to routine group (n = 240) or remote group (n = 240). The primary endpoint was achieved by 100% in both groups (P = 0.0060 for noninferiority). The parameters of sensing, threshold, and impedance regarding the right atrium, right ventricle, and left ventricle had no statistical significance between the two groups (P > 0.05). Procedure time, parameter testing time, and both duration and dose of x-ray irradiation were not significantly different between the two groups (P > 0.05). Shut-open door frequency was significantly higher in the routine group than the remote group [6.00 (4.00, 8.00) vs. 0, P < 0.0001]. Notably, no clinical or technical complications were observed in the remote group. Conclusions: Remote parameter testing is safe and feasible across various devices implantation procedures. The utilization of remote parameter testing and reprogramming could represent an innovative approach to improve healthcare accessibility and unlock the full potential of secondary centers in managing CIEDs. The Registration Identification: ChiCTR2200057587.

RESUMO

Background: Fibrinogen is a potential risk factor for the prognosis of CAD and is associated with the complexity of CAD. There is limited research specifically investigating the predictive role of fibrinogen in determining the severity of CAD among patients with T2DM, as well as its impact on the prognosis following PCI. Methods: The study included 675 T2DM patients who underwent PCI at the Third People's Hospital of Chengdu between April 27, 2018, and February 5, 2021, with 540 of them remaining after exclusions. The complexity of CAD was assessed using the SYNTAX score. The primary endpoint of the study was the incidence of MACCEs. Results: After adjusting for multiple confounding factors, fibrinogen remained a significant independent risk factor for mid/high SYNTAX scores (SYNTAX score > 22, OR 1.184, 95% CI 1.022-1.373, P = 0.025). Additionally, a dose-response relationship between fibrinogen and the risk of complicated CAD was observed (SYNTAX score > 22; nonlinear P = 0.0043). The area under the receiver operating characteristic curve(AUROC) of fibrinogen for predicting mid/high SYNTAX score was 0.610 (95% CI 0.567-0.651, P = 0.0002). The high fibrinogen group (fibrinogen > 3.79 g/L) had a higher incidence of calcified lesions and an elevated trend of more multivessel disease and chronic total occlusion. A total of 116 patients (21.5%) experienced MACCEs during the median follow-up time of 18.5 months. After adjustment, multivariate Cox regression analysis confirmed that fibrinogen (HR, 1.138; 95% CI 1.010-1.284, P = 0.034) remained a significant independent risk factor for MACCEs. The AUROC of fibrinogen for predicting MACCEs was 0.609 (95% CI 0.566-0.650, P = 0.0002). Individuals with high fibrinogen levels (fibrinogen > 4.28 g/L) had a higher incidence of acute myocardial infarction (P < 0.001), MACCEs (P < 0.001), all-cause death (P < 0.001), stroke (P = 0.030), and cardiac death (P = 0.002). Kaplan-Meier analysis revealed a higher incidence of MACCEs in the high fibrinogen group (Log-Rank test: P < 0.001). Conclusions: Elevated fibrinogen levels were associated with increased coronary anatomical complexity (as quantified by the SYNTAX score) and a higher incidence of MACCEs after PCI in patients with T2DM.

Assuntos

Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Intervenção Coronária Percutânea , Humanos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/cirurgia , Diabetes Mellitus Tipo 2/complicações , Prognóstico , Fibrinogênio

RESUMO

OBJECTIVE: We probed whether the addition of hemoglobin (HGB) or the female sex (SEX) as variables would provide additional prognostic value to the APPLE score. METHODS: An optimized APPLE score was used to evaluate the AF recurrence risk in the consecutive populations with AF post-catheter ablation including the development (n = 562) and validation (n = 239) cohorts. RESULTS: In the populations of AF recurrence, most patients were female sex (103/164, 62.8%), and had the lower HGB levels. After adjusting for the APPLE score, HGB level (Odds Ratio [OR], 0.828; 95% Confidence Interval [CI], 0.749-0.915; P < 0.001) and female sex (OR, 1.596; 95% CI, 1.140-2.235; P = 0.006) independently predicted AF recurrence. Adjusting the APPLE score by HGB variable improved its predictive ability for AF recurrence (C-statistic value from 0.675 to 0.711, P = 0.010), which also increased the C-indexes in the external validation (from 0.653 to 0.725, p = 0.023). The female sex variable also enhanced the C-statistic value of the APPLE score for AF recurrence at both development and external validation (C-indices from 0.675 to 0.691, P = 0.004; C-indices from 0.653 to 0.704, p = 0.037, respectively). Decision curve analysis showed that the HGB plus APPLE score was better than the SEX plus APPLE score in predicting AF recurrence in two following AF populations. CONCLUSION: The inclusion of HGB level and female sex variables improved the predictability and clinical usefulness of adjusted APPLE score. Adjustment of the APPLE score by HGB levels may provide better predictive value than inclusion of the female sex variable.

RESUMO

Statins are highly prevalent in patients with coronary artery disease. Statins exert their anti-inflammatory effects on the vascular wall and circulating levels of pro-inflammatory cytokines. However, increasing attention revealed the exacerbation of macrophage inflammation induced by statins, and a clear mechanistic explanation of whether the detrimental effects of statins on macrophage inflammatory phenotypes outweigh the beneficial effects is has not yet been established. Here, RNA-sequencing and RT-qPCR analyses demonstrated that statins significantly upregulated EphA2, Nlrp3, IL-1ß and TNF-α expression in macrophages. Mechanistically, we found that atorvastatin reduced KLF4 binding to the EphA2 promoter using KLF4-chromatin immunoprecipitation, suppressed HDAC11-mediated deacetylation and subsequently led to enhanced EphA2 transcription. The 4D-label-free proteomics analysis further confirmed the upregulated EphA2 and inflammatory signals. Furthermore, the proinflammatory effect of atorvastatin was neutralized by an addition of recombinant Fc-ephrinA1, a selective Eph receptor tyrosine kinase inhibitor (ALW-II-41-27) or EphA2-silencing adenovirus (siEphA2). In vivo, EphA2 was identified a proatherogenic factor and apoE-/- mice placed on a high-fat diet following gastric gavage with atorvastatin exhibited a consistent elevation in EphA2 expression. We further observed that the transfection with siEphA2 in atorvastatin-treated mice significantly attenuated atherosclerotic plaque formation and abrogated statin-orchestrated macrophages proinflammatory genes expression as compared to that in atorvastatin alone. Increased plaque stability index was also observed following the addition of siEphA2, as evidenced by increased collagen and smooth muscle content and diminished lipid accumulation and macrophage infiltration. The data suggest that blockage of EphA2 provides an additional therapeutic benefit for further improving the anti-atherogenic effects of statins.

Assuntos

Aterosclerose , Inibidores de Hidroximetilglutaril-CoA Redutases , Placa Aterosclerótica , Humanos , Camundongos , Animais , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Atorvastatina/farmacologia , Atorvastatina/uso terapêutico , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Aterosclerose/genética , Macrófagos/metabolismo , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/metabolismo , Inflamação/tratamento farmacológico

RESUMO

BACKGROUND: The Triglyceride-glucose (TyG) index, as a surrogate marker of insulin resistance, is independently associated with the severity of coronary artery lesions and the prognosis of coronary heart disease. The investigation aimed to explore the relationship between the TyG index and recurrent revascularization in individuals with type 2 diabetes mellitus (T2DM) resulting from the progression of lesions or in-stent restenosis (ISR) after percutaneous coronary intervention (PCI). METHOD: A total of 633 patients who met the inclusion and exclusion criteria were enrolled and divided into three groups based on the tertiles of the TyG index. The primary endpoint was recurrent revascularization resulting from the progression of lesions or ISR. All-cause death was considered as the competing risk event. Competing risk analysis and Cox regression analysis for predicting recurrent revascularization after PCI were conducted stepwise. Variables were standardized to make the hazard ratio (HR), subdistribution hazard ratio (SHR) and corresponding 95% CI more consistent prior to being used for fitting the multivariate risk model. The predictive ability of the TyG index was evaluated using several measures, including the ROC curve, likelihood ratio test, Akaike's information criteria, category-free continuous net reclassification improvement (cNRI > 0), and integrated discrimination improvement (IDI). Internal validation was conducted through bootstrapping with 1000 resamples. RESULTS: During a median follow-up period of 18.33 months, a total of 64 (10.11%) patients experienced recurrent revascularization, including 55 cases of lesion progression and 9 cases of in-stent restenosis. After controlling for competitive risk events, the TyG index was independently associated with a higher risk of recurrent revascularization [SHR:1.4345, (95% CI 1.1458-1.7959), P = 0.002]. The likelihood ratio test and Akaike's information criteria showed that the TyG index significantly improves the prognostic ability. Additionally, adding the TyG index improved the ability of the established risk model in predicting recurrent revascularization, indicated by a C-index of 0.759 (95% CI 0.724-0.792, P < 0.01), with a cNRI > 0 of 0.170 (95% CI 0.023-0.287, P < 0.05), and an IDI of 0.024 (95% CI 0.009-0.039, P = 0.002). These results remained consistent when the models containing TyG index were confirmed using an internal bootstrap validation method. CONCLUSION: The findings highlight the potential of the TyG index as a predictor of recurrent revascularization. Lesion progression emerged as the primary contributor to recurrent revascularization instead of in-stent restenosis. The incorporation of the TyG index into risk prediction models is likely to be beneficial for accurate risk stratification in order to improve prognosis.

Assuntos

Reestenose Coronária , Diabetes Mellitus Tipo 2 , Intervenção Coronária Percutânea , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/complicações , Glucose , Triglicerídeos , Fatores de Risco , Intervenção Coronária Percutânea/efeitos adversos , Reestenose Coronária/etiologia , Reestenose Coronária/terapia , Glicemia/metabolismo , Medição de Risco , Biomarcadores

RESUMO

Diabetic cardiomyopathy (DCM), a common complication of diabetes, is defined as ventricular dysfunction in the absence of underlying heart disease. Noncoding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), play a crucial role in the development of DCM. Weighted Gene Co-Expression Network Analysis (WGCNA) was used to identify key modules in DCM-related pathways. DCM-related miRNA-mRNA network and DCM-related ceRNA network were constructed by miRNA-seq to identify hub genes in these modules. We identified five hub genes that are associated with the onset of DCM, including Troponin C1 (Tnnc1), Phospholamban (Pln), Fatty acid binding proteins 3 (Fabp3), Popeye domain containing 2 (Popdc2), and Tripartite Motif-containing Protein 63 (Trim63). miRNAs that target the hub genes were mainly involved in TGF-ß and Wnt signaling pathways. GO BP enrichment analysis found these miRNAs were involved in the signaling of TGF-ß and glucose homeostasis. Q-PCR results found the gene expressions of Pln, Fabp3, Trim63, Tnnc1, and Popdc2 were significantly increased in DCM. Our study identified five hub genes (Tnnc1, Pln, Fabp3, Popdc2, Trim63) whose associated ceRNA networks are responsible for the onset of DCM.

Assuntos

Diabetes Mellitus , Cardiomiopatias Diabéticas , MicroRNAs , RNA Longo não Codificante , Humanos , Cardiomiopatias Diabéticas/genética , Redes Reguladoras de Genes , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Via de Sinalização Wnt

RESUMO

The clinical risk factors associated with late recurrence in patients with non-valvular atrial fibrillation (AF) (NVAF) undergoing radiofrequency catheter ablation (RFCA) remain unknown. Furthermore, the current prognostic risk score system is commonly used in such patients as a noninvasive method to assess late AF recurrence. According to recent research, the Age, creatinine, and ejection fraction (ACEF) score is a useful risk score for cardiovascular morbidity and mortality. As a result, we hypothesized that pre-ablation ACEF score could be used to assess late recurrence in patients with NVAF. We included 325 NVAF patients undergoing RFCA. During a median follow-up period of 12 months, patients with late AF recurrence had higher ACEF scores (P < .001). The pre-ablation ACEF score was a risk factor for late AF recurrence after RFCA (P = .027). The ACEF score was a predictor of late AF recurrence after RFCA, with an AUC of 0.624 (P = .001). Moreover, the AUC of left atrial diameter (LAD) was 0.7 (P < .001), which was higher than the ACEF score, but no significant difference was found (P = .104). The ACEF score was positively correlated with LAD, advanced age, and B-type natriuretic peptide. In patients with NVAF, the pre-ablation ACEF score is a valuable risk score for assessing late AF recurrence after RFCA, as with LAD.

Assuntos

Fibrilação Atrial , Ablação por Radiofrequência , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Creatinina , Volume Sistólico , Átrios do Coração

RESUMO

The coronavirus disease 2019 (COVID-19) brought a healthy crisis all around the world. It's not only affected healthcare utilization, but also some disease's incidence. We collected pre-hospital emergency data in Chengdu from January 2016 to December 2021, and studied the demand for emergency medical services (EMSs), emergency response times (ERTs), and the disease spectrum in the city proper of Chengdu as a whole. A total of 1,122,294 prehospital emergency medical service (EMS) instances met the inclusion criteria. Under the influence of COVID-19, notably in 2020, the epidemiological characteristics of prehospital emergency services in Chengdu were considerably altered. However, as the pandemic was brought under control, they returned to normal or even earlier in 2021.The COVID-19 pandemic had an effect on people's medical care-seeking behavior and the performance of prehospital emergency services. Although the indicators associated with prehospital emergency services eventually recovered as the epidemic was brought under control, they remained marginally different from before the outbreak.

Assuntos

COVID-19 , Serviços Médicos de Emergência , Humanos , COVID-19/epidemiologia , Pandemias , Hospitais , Estudos Retrospectivos

RESUMO

AIMS: The predictive value of the stress hyperglycemia ratio (SHR) for long-term prognosis in acute coronary syndrome (ACS) is inconsistent. Whether the SHR provides additional prognostic value in addition to the GRACE score in ACS patients undergoing percutaneous coronary intervention (PCI) remains unknown. METHODS: A development-validation method was adopted to develop an algorithm to adjust the GRACE score using the SHR in ACS patients undergoing PCI from 11 hospitals. RESULTS: During a median follow-up of 31.33 months, the occurrence of major adverse cardiac events (MACEs), defined as a composite of all-cause mortality and nonfatal myocardial infarction, was more frequent in the patients with a higher level of SHR. The SHR independently predicted long-term MACEs (hazard ratio 3.3479; 95% CI 1.4103-7.9475; P = 0.0062). Adjustment of the GRACE risk by addition of the SHR increased the C-statistic from 0.706 (95% CI: 0.599-0.813) to 0.727 (95% CI: 0.616-0.837) (P < 0.01), with a continuous net reclassification improvement of 30.5% and an integrated discrimination improvement of 0.042 (P < 0.01) in the derivation cohort; and addition of the SHR showed superior discrimination and good calibration in the validation cohort. CONCLUSIONS: The SHR is an independent predictor of long-term MACEs in ACS patients undergoing PCI and markedly improves the performance of the GRACE score.

Assuntos

Síndrome Coronariana Aguda , Hiperglicemia , Intervenção Coronária Percutânea , Humanos , Síndrome Coronariana Aguda/cirurgia , Estudos Retrospectivos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Medição de Risco , Prognóstico , Hiperglicemia/diagnóstico , Hiperglicemia/etiologia , Fatores de Risco

RESUMO

AIM: The triglyceride-glucose (TyG) index has been shown to be an independent predictor for the progression and prognosis of coronary artery disease (CAD). Whether the TyG index predicts the severity of CAD in patients presenting with acute coronary syndrome (ACS) remains unknown. METHODS: A total of 1,007 individuals presenting with ACS undergoing coronary angiography were stratified according to the tertiles of the TyG index and The Synergy Between Percutaneous Coronary Intervention (SYNTAX) score (SYNTAX score ≤ 22 versus SYNTAX score > 22). CAD complexity was determined by the SYNTAX score. RESULTS: After adjusting for multiple confounding factors, the TyG index was still an independent risk factor for mid/high SYNTAX scores (SYNTAX score > 22, OR 2.6452, 95% CI 1.9020-3.6786, P < 0.0001). Compared with the lowest tertile of the TyG (T1) group, the risk for a mid/high SYNTAX score in the T2 and T3 groups was 2.574-fold higher (OR, 2.574; 95% CI 1.610-4.112; P < 0.001) and 3.732-fold higher (OR, 3.732; 95% CI 2.330-5.975; P < 0.001), respectively. Furthermore, there was a dose‒response relationship between the TyG index and the risk of complicated CAD (SYNTAX score > 22; nonlinear P = 0.200). The risk for a mid/high SYNTAX score in the T2 and T3 groups was significantly higher in normoglycemia, prediabetes mellitus, and diabetes mellitus subgroups. CONCLUSIONS: A higher TyG index was associated with the presence of a higher coronary anatomical complexity (SYNTAX score > 22) in ACS patients, irrespective of diabetes mellitus status. The TyG index might serve as a noninvasive predictor of CAD complexity in ACS patients and could potentially influence the management and therapeutic approach.

Assuntos

Síndrome Coronariana Aguda , Doença da Artéria Coronariana , Diabetes Mellitus , Humanos , Glucose , Síndrome Coronariana Aguda/terapia , Triglicerídeos , Fatores de Risco , Glicemia , Medição de Risco , Biomarcadores

RESUMO

Cardiac microvascular injury can be a fundamental pathological process that causes high incidence cardiovascular diseases such heart failure, diabetic cardiomyopathy, and hypertension. It is also an independent risk factor for cardiovascular disease. Oxidative stress is a significant pathological process in which the body interferes with the balance of the endogenous antioxidant defense system by producing reactive oxygen species, leading to property changes and dysfunction. It has been demonstrated that oxidative stress is one of the major causes of cardiac microvascular disease. Therefore, additional investigation into the relationship between oxidative stress and cardiac microvascular injury will direct clinical management in the future. In order to give suggestions and support for future in-depth studies, we give a basic overview of the cardiac microvasculature in relation to physiopathology in this review. We also summarize the role of oxidative stress of mitochondrial and non-mitochondrial origin in cardiac microvascular injury and related drug studies.

Assuntos

Cardiomiopatias Diabéticas , Estresse Oxidativo , Humanos , Espécies Reativas de Oxigênio