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1.
Rev Cardiovasc Med ; 25(9): 322, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39355606

RESUMO

Rheumatic mitral valve disease often requires surgical interventions, such as percutaneous mitral commissurotomy, surgical mitral valve repair, or replacement, especially in severe cases. This necessitates a precise preoperative assessment of the extent of mitral valve disease. Currently, transthoracic echocardiography, the gold standard for preoperative assessment, has limitations, such as restricted acoustic windows and dependence on the operator, which can affect the evaluation of subvalvular structures and calcification of the mitral valve. Previous studies have shown that cardiac computed tomography (CT), with its high resolution, strong multiplanar reconstruction capabilities, and sensitivity to calcifications, can effectively overcome these limitations. Therefore, this study aims to summarize and evaluate the effectiveness of cardiac CT in examining mitral valve leaflets, annulus, and subvalvular structures. It also reviews the feasibility and guiding significance of using cardiac CT to assess characteristic rheumatic mitral valve lesions.

2.
J Thorac Dis ; 16(9): 5815-5825, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39444921

RESUMO

Background: Hypothermia and antegrade cerebral perfusion (ACP) strategies in open aortic arch surgery (AAS) have improved significantly. The significance of the gradual temperature rise to mild hypothermia is quite apparent, however, its safety remains a challenge. Therefore, our objective was to explore the safety and efficacy of mild hypothermic circulatory arrest (Mi-HCA, ≥30 ℃). Methods: This retrospective cohort study enrolled in a total of 372 patients, and was performed at the Beijing Anzhen Hospital between January 2017 and November 2022. Among the 372 patients, 81 received AAS at ≥30 ℃, and the remaining 291 received the same at 22-29.9 ℃. Most acute type A aortic dissection (ATAAD) patients received total arch replacement (TAR) and frozen elephant trunk (FET) operation. Results: Mi-HCA patients exhibited strongly augmented systemic temperature (26.19±1.63 vs. 31.40±0.79 ℃, P<0.01). The surgical, cardiopulmonary bypass (CPB), cross-clamp, circulatory arrest, and ACP durations were drastically diminished among Mi-HCA patients (all P<0.01). Moreover, the major adverse events (MAEs) incidence of Mi-HCA patients was significantly decreased (25.43% vs. 14.81%, P<0.05). Simultaneously, the Mi-HCA strategy also exhibited enhanced protection of blood cells, as well as myocardial and hepatic function. Nevertheless, multivariate logistic regression analysis revealed that Mi-HCA strategy (≥30 ℃) was not a stand-alone risk factor for MAEs following AAS. Conclusions: The short-term outcomes and safety of Mi-HCA, in combination with ACP, in AAS are satisfactory. Additionally, relative to the traditional moderate hypothermic circulatory arrest (MHCA) approach, it can substantially decrease operation duration while improving patient clinical outcomes.

3.
Int J Cardiol ; 416: 132480, 2024 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-39197727

RESUMO

AIMS: The aim of this study was to evaluate the relationship between preoperative left atrial function and recurrence of atrial fibrillation (AF) after mitral valve surgery and Cox Maze procedure in patients with moderate-to-severe rheumatic mitral stenosis (MS) combined with AF, in order to facilitate clinical risk stratification and to guide treatment strategies. METHODS AND RESULTS: Patients with moderate-to-severe rheumatic MS attending Beijing Anzhen Hospital of Capital Medical University from April 2022 to September 2023 were prospectively collected, and all of them underwent transthoracic two-dimensional speckle-tracking echocardiography to assess left atrial structure and function before undergoing mitral valve surgery and Cox Maze procedure and postoperative follow-up. 121 patients were enrolled, of whom 77.69 % (94/121) were female, with a median follow-up time of 9.56 ± 1.83 months, and 48 patients (39.7 %, 48/121) had postoperative recurrence of AF. Preoperative left atrial stiffness index (LASI) [3.76(3.10-5.44) vs. 2.41(1.75-3.33), P < 0.001] and left atrial mechanical dispersion (SD-TPS) (15.84 ± 5.92vs. 11.58 ± 5.96, P = 0.001) were significantly higher in the postoperative AF recurrence group than in the without recurrence group; Multivariable cox regression analysis showed that LASI>3.15 and SD -TPS > 13.2 were associated with independent risk factors for AF recurrence (hazard ratio = 2.957, 95 %CI,1.366-6.399, P = 0.006 and hazard ratio = 2.892, 95 %CI,1.381-6.057, P = 0.005). CONCLUSION: LASI and SD-TPS were effective predictors of postoperative recurrence of AF in patients with moderate-to-severe rheumatic MS, and LASI >3.15 and SD-TPS% >13.2 were independent influences on the recurrence of AF after Cox Maze in this group of patients.


Assuntos
Fibrilação Atrial , Função do Átrio Esquerdo , Estenose da Valva Mitral , Recidiva , Cardiopatia Reumática , Índice de Gravidade de Doença , Humanos , Feminino , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/cirurgia , Fibrilação Atrial/diagnóstico por imagem , Estenose da Valva Mitral/cirurgia , Estenose da Valva Mitral/fisiopatologia , Estenose da Valva Mitral/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Cardiopatia Reumática/cirurgia , Cardiopatia Reumática/fisiopatologia , Cardiopatia Reumática/complicações , Cardiopatia Reumática/diagnóstico por imagem , Função do Átrio Esquerdo/fisiologia , Seguimentos , Estudos Prospectivos , Átrios do Coração/fisiopatologia , Átrios do Coração/diagnóstico por imagem , Adulto , Valor Preditivo dos Testes , Ecocardiografia/métodos
4.
Int J Biol Macromol ; 278(Pt 2): 134780, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39153683

RESUMO

Insulin resistance (IR) is one of the major complications of polycystic ovary syndrome (PCOS). This study aimed to investigate the effects and the molecular regulatory mechanism by which Dendrobium nobile-derived polysaccharides (DNP) improve IR in rats with letrozole and high-fat-diet induced PCOS. In vivo, DNP (200 mg/kg/d) administration not only reduced body weight, blood glucose, and insulin levels in PCOS rats, but also improve the disrupted estrous cycle. In addition, DNP treatment reduced atretic and cystic follicles and enhanced granulosa cell layer thickness, thereby restoring follicle development. In vitro, DNP treatment (100 µM) increased lactate levels and decreased pyruvate levels in insulin-treated (8 µg/mL) KGN cells. Additionally, DNP also decreased the expression of IGF1 and increased that of IGF1R, SIRT2, LDHA, PKM2 and HK2 both in vivo and in vitro. Also, SIRT2 expression was specifically inhibited by AGK2, while DNP significantly improved IR and glycolysis by reversing the effect of AGK2 treatment on lactate and pyruvate production, upregulating the expression levels of IGF1R, LDHA, HK2, and PKM2 and downregulating the expression level of IGF1. The results indicate that DNP can effectively improve IR and restore glycolytic pathway by activating SIRT2, which may provide a potential therapeutic approach for PCOS patients.


Assuntos
Dendrobium , Glicólise , Células da Granulosa , Resistência à Insulina , Síndrome do Ovário Policístico , Polissacarídeos , Sirtuína 2 , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/tratamento farmacológico , Feminino , Animais , Polissacarídeos/farmacologia , Glicólise/efeitos dos fármacos , Células da Granulosa/metabolismo , Células da Granulosa/efeitos dos fármacos , Ratos , Dendrobium/química , Sirtuína 2/metabolismo , Sirtuína 2/genética , Humanos , Insulina/metabolismo , Ratos Sprague-Dawley
5.
Nat Commun ; 15(1): 7249, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39179537

RESUMO

Imbalance of proinflammatory and anti-inflammatory responses plays a crucial role in the progression of abdominal aortic aneurysms. ILF3, a known modulator of the innate immune response, is involved in cardiovascular diseases. This study aims to investigate the role of ILF3 in abdominal aortic aneurysm formation. Here, we use multi-omics analyzes, transgenic male mice, and multiplex immunohistochemistry to unravel the underlying involvement of ILF3 in abdominal aortic aneurysms. The results show that macrophage ILF3 deficiency attenuates abdominal aortic aneurysm progression, while elevated macrophage ILF3 exacerbates abdominal aortic aneurysm lesions. Mechanistically, we reveal that macrophagic ILF3 increases NF-κB activity by hastening the decay of p105 mRNA, leading to amplified inflammation in macrophages. Meanwhile, ILF3 represses the anti-inflammatory action by inhibiting the Keap1-Nrf2 signaling pathway through facilitating the ILF3/eIF4A1 complex-mediated enhancement of Keap1 translational efficiency. Moreover, Bardoxolone Methyl treatment alleviates the severity of abdominal aortic aneurysm lesions in the context of elevated ILF3 expression. Together, our findings underscore the significance of macrophage ILF3 in abdominal aortic aneurysm development and suggest its potential as a promising therapeutic target for abdominal aortic aneurysms.


Assuntos
Aneurisma da Aorta Abdominal , Inflamação , Macrófagos , Proteínas do Fator Nuclear 90 , Transdução de Sinais , Animais , Aneurisma da Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/genética , Masculino , Macrófagos/metabolismo , Macrófagos/imunologia , Camundongos , Proteínas do Fator Nuclear 90/metabolismo , Proteínas do Fator Nuclear 90/genética , Inflamação/metabolismo , Inflamação/patologia , NF-kappa B/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Humanos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Modelos Animais de Doenças , Camundongos Knockout
7.
Heart Lung Circ ; 33(10): 1450-1456, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38955596

RESUMO

BACKGROUND: Percutaneous mitral balloon commissurotomy (PMBC) is the standard treatment option for patients with rheumatic mitral stenosis (MS), according to current guidelines. This study aimed to compare the outcomes of rheumatic mitral valve repair (rMVR) and PMBC in this patient population. METHODS: Baseline, clinical, and follow-up data from 703 patients with rheumatic heart disease who underwent PMBC or rMVR at the current centre were collected and analysed. A 1:1 propensity score (PS) matching method was used to balance the differences in baseline characteristics between the two groups. The primary outcome was mitral valve reoperation, and the secondary outcome was all-cause mortality. RESULTS: Propensity score matching generated 101 patient pairs for comparison. In the matched population, there were no significant differences in the early clinical outcomes between the groups. The median follow-up time was 40.9 months. Overall, patients in the rMVR group had a statistically significantly lower risk of mitral valve reoperation than those in the PMBC group (HR 0.186; 95% CI 0.041-0.835; p=0.028). Regarding all-cause mortality, no statistically significant differences were observed between the rMVR and PMBC groups (HR 4.065; 95% CI 0.454-36.374; p=0.210). CONCLUSIONS: Compared with PMBC, rMVR has more advantages for the correction of valve lesions; therefore, it may offer a better prognosis than PMBC in select patients with rheumatic MS. However, this finding needs to be verified in future studies with larger sample sizes and longer follow-up periods.


Assuntos
Estenose da Valva Mitral , Valva Mitral , Cardiopatia Reumática , Humanos , Cardiopatia Reumática/cirurgia , Cardiopatia Reumática/complicações , Masculino , Feminino , Estenose da Valva Mitral/cirurgia , Estenose da Valva Mitral/diagnóstico , Estudos Retrospectivos , Valva Mitral/cirurgia , Pessoa de Meia-Idade , Seguimentos , Resultado do Tratamento , Valvuloplastia com Balão/métodos , Adulto , Taxa de Sobrevida/tendências , Pontuação de Propensão
8.
J Cardiothorac Surg ; 19(1): 392, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937772

RESUMO

BACKGROUND: Currently, the differentiation between benign and malignant cystic pulmonary nodules poses a significant challenge for clinicians. The objective of this retrospective study was to construct a predictive model for determining the likelihood of malignancy in patients with cystic pulmonary nodules. METHODS: The current study involved 129 patients diagnosed with cystic pulmonary nodules between January 2017 and June 2023 at the Neijiang First People's Hospital. The study gathered the clinical data, preoperative imaging features of chest CT, and postoperative histopathological results for both cohorts. Univariate and multivariate logistic regression analyses were employed to identify independent risk factors, from which a prediction model and nomogram were developed. In addition, The model's performance was assessed through receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis (DCA). RESULTS: A cohort of 129 patients presenting with cystic pulmonary nodules, consisting of 92 malignant and 37 benign lesions, was examined. Logistic data analysis identified a cystic airspace with a mural nodule, spiculation, mural morphology, and the number of cystic cavities as significant independent predictors for discriminating between benign and malignant cystic lung nodules. The nomogram prediction model demonstrated a high level of predictive accuracy, as evidenced by an area under the ROC curve (AUC) of 0.874 (95% CI: 0.804-0.944). Furthermore, the calibration curve of the model displayed satisfactory calibration. DCA proved that the prediction model was useful for clinical application. CONCLUSION: In summary, the risk prediction model for benign and malignant cystic pulmonary nodules has the potential to assist clinicians in the diagnosis of such nodules and enhance clinical decision-making processes.


Assuntos
Neoplasias Pulmonares , Nomogramas , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Pessoa de Meia-Idade , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico , Diagnóstico Diferencial , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/patologia , Idoso , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/patologia , Curva ROC , Adulto , Radiômica
9.
Int J Surg ; 110(6): 3879-3887, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38502857

RESUMO

BACKGROUND: The efficacy of mitral valve repair (MVR) in combination with coronary artery bypass grafting (CABG) for moderate ischaemic mitral regurgitation (IMR) remains unclear. To evaluate whether MVR + CABG is superior to CABG alone, the authors conducted a systematic review and meta-analysis of existing randomized controlled trials (RCTs). METHODS: The authors searched PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials for eligible RCTs from the date of their inception to October 2023. The primary outcomes were operative (in-hospital or within 30 days) and long-term (≥ 1 year) mortality. The secondary outcomes were postoperative stroke, worsening renal function (WRF), and reoperation for bleeding or tamponade. The authors performed random-effects meta-analyses and reported the results as risk ratios (RRs) with 95% CIs. RESULTS: Six RCTs were eligible for inclusion. Compared with CABG alone, MVR + CABG did not increase the risk of operative mortality (RR, 1.244; 95% CI, 0.514-3.014); however, it was also not associated with a lower risk of long-term mortality (RR, 0.676; 95% CI, 0.417-1.097). Meanwhile, there was no difference between the two groups in terms of postoperative stroke (RR, 2.425; 95% CI, 0.743-7.915), WRF (RR, 1.257; 95% CI, 0.533-2.964), and reoperation for bleeding or tamponade (RR, 1.667; 95% CI, 0.527-5.270). CONCLUSIONS: The findings of this meta-analysis suggest that MVR + CABG fails to improve the clinical outcomes of patients with moderate IMR compared to CABG alone.


Assuntos
Ponte de Artéria Coronária , Insuficiência da Valva Mitral , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Insuficiência da Valva Mitral/cirurgia , Ponte de Artéria Coronária/efeitos adversos , Valva Mitral/cirurgia , Resultado do Tratamento , Implante de Prótese de Valva Cardíaca/efeitos adversos , Isquemia Miocárdica/cirurgia , Isquemia Miocárdica/complicações
10.
Gigascience ; 13(1)2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38373745

RESUMO

BACKGROUND: Cell clustering is a pivotal aspect of spatial transcriptomics (ST) data analysis as it forms the foundation for subsequent data mining. Recent advances in spatial domain identification have leveraged graph neural network (GNN) approaches in conjunction with spatial transcriptomics data. However, such GNN-based methods suffer from representation collapse, wherein all spatial spots are projected onto a singular representation. Consequently, the discriminative capability of individual representation feature is limited, leading to suboptimal clustering performance. RESULTS: To address this issue, we proposed SGAE, a novel framework for spatial domain identification, incorporating the power of the Siamese graph autoencoder. SGAE mitigates the information correlation at both sample and feature levels, thus improving the representation discrimination. We adapted this framework to ST analysis by constructing a graph based on both gene expression and spatial information. SGAE outperformed alternative methods by its effectiveness in capturing spatial patterns and generating high-quality clusters, as evaluated by the Adjusted Rand Index, Normalized Mutual Information, and Fowlkes-Mallows Index. Moreover, the clustering results derived from SGAE can be further utilized in the identification of 3-dimensional (3D) Drosophila embryonic structure with enhanced accuracy. CONCLUSIONS: Benchmarking results from various ST datasets generated by diverse platforms demonstrate compelling evidence for the effectiveness of SGAE against other ST clustering methods. Specifically, SGAE exhibits potential for extension and application on multislice 3D reconstruction and tissue structure investigation. The source code and a collection of spatial clustering results can be accessed at https://github.com/STOmics/SGAE/.


Assuntos
Benchmarking , Perfilação da Expressão Gênica , Animais , Análise por Conglomerados , Mineração de Dados , Drosophila/genética
11.
Eur Radiol ; 34(8): 4963-4976, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38252276

RESUMO

OBJECTIVE: We aimed to evaluate the mitral valve calcification and mitral structure detected by cardiac computed tomography (cardiac CT) and establish a scoring model based on cardiac CT and clinical factors to predict early good mitral valve repair (EGMR) and guide surgical strategy in rheumatic mitral disease (RMD). MATERIALS AND METHODS: This is a retrospective bi-center cohort study. Based on cardiac CT, mitral valve calcification and mitral structure in RMD were quantified and evaluated. The primary outcome was EGMR. A logical regression algorithm was applied to the scoring model. RESULTS: A total of 579 patients were enrolled in our study from January 1, 2019, to August 31, 2022. Of these, 443 had baseline cardiac CT scans of adequate quality. The calcification quality score, calcification and thinnest part of the anterior leaflet clean zone, and papillary muscle symmetry were the independent CT factors of EGMR. Coronary artery disease and pulmonary artery pressure were the independent clinical factors of EGMR. Based on the above six factors, a scoring model was established. Sensitivity = 95% and specificity = 95% were presented with a cutoff value of 0.85 and 0.30 respectively. The area under the receiver operating characteristic of external validation set was 0.84 (95% confidence interval [CI] 0.73-0.93). CONCLUSIONS: Mitral valve repair is recommended when the scoring model value > 0.85 and mitral valve replacement is prior when the scoring model value < 0.30. This model could assist in guiding surgical strategies for RMD. CLINICAL RELEVANCE STATEMENT: The model established in this study can serve as a reference indicator for surgical repair in rheumatic mitral valve disease. KEY POINTS: • Cardiac CT can reflect the mitral structure in detail, especially for valve calcification. • A model based on cardiac CT and clinical factors for predicting early good mitral valve repair was established. • The developed model can help cardiac surgeons formulate appropriate surgical strategies.


Assuntos
Valva Mitral , Cardiopatia Reumática , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Cardiopatia Reumática/diagnóstico por imagem , Cardiopatia Reumática/cirurgia , Estudos Retrospectivos , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Calcinose/diagnóstico por imagem , Calcinose/cirurgia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/cirurgia , Adulto , Valor Preditivo dos Testes , Estudos de Coortes
12.
Nat Commun ; 15(1): 227, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172093

RESUMO

Current treatment for functional dyspepsia (FD) has limited and unsustainable efficacy. Probiotics have the sustainable potential to alleviate FD. This randomized controlled clinical trial (Chinese Clinical Trial Registry, ChiCTR2000041430) assigned 200 FD patients to receive placebo, positive-drug (rabeprazole), or Bifidobacterium animalis subsp. lactis BL-99 (BL-99; low, high doses) for 8-week. The primary outcome was the clinical response rate (CRR) of FD score after 8-week treatment. The secondary outcomes were CRR of FD score at other periods, and PDS, EPS, serum indicators, fecal microbiota and metabolites. The CRR in FD score for the BL-99_high group [45 (90.0%)] was significantly higher than that for placebo [29 (58.0%), p = 0.001], BL-99_low [37 (74.0%), p = 0.044] and positive_control [35 (70.0%), p = 0.017] groups after 8-week treatment. This effect was sustained until 2-week after treatment but disappeared 8-week after treatment. Further metagenomic and metabolomics revealed that BL-99 promoted the accumulation of SCFA-producing microbiota and the increase of SCFA levels in stool and serum, which may account for the increase of serum gastrin level. This study supports the potential use of BL-99 for the treatment of FD.


Assuntos
Bifidobacterium animalis , Dispepsia , Probióticos , Humanos , Dispepsia/terapia , Probióticos/uso terapêutico , Fezes/microbiologia , Método Duplo-Cego
13.
Int J Surg ; 110(3): 1620-1626, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38052020

RESUMO

BACKGROUND: Data on new onset postoperative atrial fibrillation (POAF) after Stanford type A dissection (STAAD) surgery was limited. This study aimed to detect the risk factors for developing POAF after STAAD procedures and the association between POAF and in-hospital mortality. METHODS: A total of 1354 patients who underwent surgical treatment for STAAD in Beijing Anzhen hospital were enrolled in this single-center retrospective study from January 2015 to October 2020. POAF were defined as atrial fibrillation/flutter requiring treatment after surgery procedure. Logistic model was conducted to detect the predictors of POAF, and inverse probability of treatment weighting (IPTW) and subgroup analysis were used to compare the mortality of POAF and non-POAF groups. RESULTS: There were 176 patients (13.0%) diagnosed with POAF according to the definition. Multivariate logistics analyses revealed that advanced age [odds ratio (OR), 1.07; 95% CI: 1.05-1.08; P <0.001)], creatinine (OR, 1.00; 95% CI: 1.00-1.01; P =0.001) and cross-clamp time (OR, 1.00; 95% CI: 1.00-1.01; P =0.021) were independent risk factors of developing POAF in STAAD patients. POAF patients were associated with significantly higher in-hospital mortality compared with non-POAF patients (6.5 vs. 19.9%, OR, 3.60; 95% CI: 2.30-5.54; P <0.001), IPTW and subgroup analysis had reached consistent conclusions. CONCLUSIONS: The incidence of POAF was 13.0% after STAAD surgery, advanced age, creatinine, and cross-clamp time were independent risk factors of developing POAF in STAAD patients. POAF is associated with increased mortality after STAAD procedures.


Assuntos
Fibrilação Atrial , Humanos , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Estudos Retrospectivos , Creatinina , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores de Risco
14.
Eur Heart J ; 45(4): 287-305, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-37992083

RESUMO

BACKGROUND AND AIMS: Stanford type A aortic dissection (AD) is a degenerative aortic remodelling disease marked by an exceedingly high mortality without effective pharmacologic therapies. Smooth muscle cells (SMCs) lining tunica media adopt a range of states, and their transformation from contractile to synthetic phenotypes fundamentally triggers AD. However, the underlying pathomechanisms governing this population shift and subsequent AD, particularly at distinct disease temporal stages, remain elusive. METHODS: Ascending aortas from nine patients undergoing ascending aorta replacement and five individuals undergoing heart transplantation were subjected to single-cell RNA sequencing. The pathogenic targets governing the phenotypic switch of SMCs were identified by trajectory inference, functional scoring, single-cell regulatory network inference and clustering, regulon, and interactome analyses and confirmed using human ascending aortas, primary SMCs, and a ß-aminopropionitrile monofumarate-induced AD model. RESULTS: The transcriptional profiles of 93 397 cells revealed a dynamic temporal-specific phenotypic transition and marked elevation of the activator protein-1 (AP-1) complex, actively enabling synthetic SMC expansion. Mechanistically, tumour necrosis factor signalling enhanced AP-1 transcriptional activity by dampening mitochondrial oxidative phosphorylation (OXPHOS). Targeting this axis with the OXPHOS enhancer coenzyme Q10 or AP-1-specific inhibitor T-5224 impedes phenotypic transition and aortic degeneration while improving survival by 42.88% (58.3%-83.3% for coenzyme Q10 treatment), 150.15% (33.3%-83.3% for 2-week T-5224), and 175.38% (33.3%-91.7% for 3-week T-5224) in the ß-aminopropionitrile monofumarate-induced AD model. CONCLUSIONS: This cross-sectional compendium of cellular atlas of human ascending aortas during AD progression provides previously unappreciated insights into a transcriptional programme permitting aortic degeneration, highlighting a translational proof of concept for an anti-remodelling intervention as an attractive strategy to manage temporal-specific AD by modulating the tumour necrosis factor-OXPHOS-AP-1 axis.


Assuntos
Doenças da Aorta , Dissecção Aórtica , Benzofenonas , Isoxazóis , Doenças Vasculares , Humanos , Fator de Transcrição AP-1 , Aminopropionitrilo , Estudos Transversais , Dissecção Aórtica/genética , Doenças da Aorta/patologia , Doenças Vasculares/patologia , Miócitos de Músculo Liso/patologia , Miócitos de Músculo Liso/fisiologia , Fatores de Necrose Tumoral
15.
J Am Heart Assoc ; 13(1): e031542, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38156459

RESUMO

BACKGROUND: Acute type A aortic dissection can extend upwards to involve the common carotid artery. However, whether asymptomatic common carotid artery dissection (CCAD) requires surgical repair remains controversial. This study aimed to explore the effect of asymptomatic CCAD without surgical intervention on the prognosis of patients who underwent surgery for acute type A aortic dissection. METHODS AND RESULTS: Between January 2015 and December 2017, 485 patients with no neurological symptoms who underwent surgery for acute type A aortic dissection were enrolled in this retrospective cohort study. The patients were divided into 2 groups based on the exposure factor of CCAD. CCAD was detected in 111 patients (22.9%), and after adjusting baseline data (standardized mean difference <0.1), the 30-day mortality (17.1% versus 6.0%, P<0.001) and incidence of fatal stroke (7.7% versus 1.6%, P=0.001) were significantly higher in the group with CCAD. Univariable and multivariable Cox regression analyses found CCAD as an independent risk factor for 30-day mortality (hazard ratio [HR], 2.8 [95% CI, 1.5-5.2]; P=0.001). At a median follow-up of 6.2 years (interquartile range, 5.6-6.9 years), landmark analysis with a cutoff value of 1 month postoperatively showed a significant increase in mortality in the group with CCAD, especially in the first month (log-rank P=0.002) and no significant difference in survival after the first month postoperatively between the 2 groups (log-rank P=0.955). CONCLUSIONS: Asymptomatic CCAD increased the risk of early fatal stroke and death in patients with acute type A aortic dissection after surgery but did not affect midterm survival in patients who survived the early postoperative period.


Assuntos
Dissecção Aórtica , Doenças das Artérias Carótidas , Acidente Vascular Cerebral , Humanos , Estudos Retrospectivos , Dissecção Aórtica/cirurgia , Prognóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Artéria Carótida Primitiva , Fatores de Risco , Resultado do Tratamento
16.
Int J Surg ; 109(12): 4263-4272, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37720926

RESUMO

IMPORTANCE: Coronary artery bypass grafting (CABG) remains the gold standard for the treatment of multivessel and left main coronary heart disease. However, the current evidence about the optimal surgical revascularization strategy is inconsistent and is not sufficient to allow for definite conclusions. Thus, this topic needs to be extensively discussed. OBJECTIVE: The aim of this present study was to compare the clinical outcomes of off-pump CABG (OPCAB), conventional on-pump CABG (C-CABG), and on-pump beating heart (ONBEAT) CABG via an updated systematic review and network meta-analysis of randomized controlled trials. DATA SOURCES: PubMed, Web of Science, and the Cochrane Central Registry were searched for relevant randomized controlled trials that were published in English before 1 December 2021. STUDY SELECTION: Published trials that included patients who received OPCAB, C-CABG, and ONBEAT CABG were selected. DATA EXTRACTION AND SYNTHESIS: Two authors independently screened the search results, assessed the full texts to identify eligible studies and the risk of bias of the included studies, and extracted data. All processes followed the Preferred Reporting Items for Systematic Review and Meta-analysis of Individual Participant Data. MAIN OUTCOMES AND MEASURES: The primary outcome was postoperative mortality in patients who underwent C-CABG, OPCAB, or ONBEAT CABG. The secondary outcomes were postoperative myocardial infarction, stroke, and renal impairment in the three groups. The time point for analysis of outcomes was all time periods during the postoperative follow-up. RESULTS: A total of 39 385 patients (83 496.2 person-years) in 65 studies who fulfilled the prespecified criteria were included. In the network meta-analysis, OPCAB was associated with an increase of 12% in the risk of all-cause mortality when compared with C-CABG [odds ratio (OR): 1.12; 95% CI: 1.04-1.21], a reduction of 49% in the risk of myocardial infarction when compared with ONBEAT (OR: 0.51; 95% CI: 0.26-0.99), a reduction of 16% in the risk of stroke when compared with C-CABG (OR: 0.84; 95% CI: 0.72-0.99) and a similar risk of renal impairment when compared with C-CABG and ONBEAT. CONCLUSIONS AND RELEVANCE: OPCAB was associated with higher all-cause mortality but lower postoperative stroke compared with C-CABG. OPCAB was associated with a lower postoperative myocardial infarction than that of ONBEAT. Early mortality was comparable among OPCAB, ONBEAT, and C-CABG.


Assuntos
Doença da Artéria Coronariana , Infarto do Miocárdio , Acidente Vascular Cerebral , Humanos , Metanálise em Rede , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/cirurgia , Infarto do Miocárdio/etiologia , Acidente Vascular Cerebral/etiologia
18.
Biomed Pharmacother ; 165: 115042, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37379639

RESUMO

Mesenchymal stem cells (MSCs) are pluripotent stem cells derived from a variety of tissues, such as umbilical cord, fat, and bone marrow. Today, MSCs are widely recognized for their prominent anti-inflammatory properties in a variety of acute and chronic inflammatory diseases. In inflammatory diseases, monocytes/macrophages are an important part of the innate immune response in the body, and the alteration of the inflammatory phenotype plays a crucial role in the secretion of pro-inflammatory/anti-inflammatory factors, the repair of injured sites, and the infiltration of inflammatory cells. In this review, starting from the effect of MSCs on the monocyte/macrophage phenotype, we have outlined in detail the process by which MSCs influence the transformation of the monocyte/macrophage inflammatory phenotype, emphasizing the central role of monocytes/macrophages in MSC-mediated anti-inflammatory and damage site repair. MSCs are phagocytosed by monocytes/macrophages in various physiological states, the paracrine effect of MSCs and mitochondrial transfer of MSCs to macrophages to promote the transformation of monocytes/macrophages into anti-inflammatory phenotypes. We also review the clinical applications of the MSCs-monocytes/macrophages system and describe novel pathways between MSCs and tissue repair, the effects of MSCs on the adaptive immune system, and the effects of energy metabolism levels on monocyte/macrophage phenotypic changes.


Assuntos
Células-Tronco Mesenquimais , Monócitos , Monócitos/metabolismo , Macrófagos/metabolismo , Fenótipo , Anti-Inflamatórios/metabolismo , Células-Tronco Mesenquimais/metabolismo
19.
Exp Physiol ; 108(5): 683-691, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36934370

RESUMO

NEW FINDINGS: What is the central question of this study? Hypoxaemia can lead to increased postoperative mortality in patients: what are the independent risk factors for severe hypoxaemia after acute Stanford type A aortic dissection? What is the main finding and its importance? Severe postoperative hypoxaemia was found in 36.4% of patients, and it was determined that high preoperative bradykinin levels and increased BMI were independent predictors of severe postoperative hypoxaemia in patients with acute Stanford type A aortic dissection. For obese patients with high preoperative bradykinin levels, more attention should be paid to preventing severe postoperative hypoxaemia. ABSTRACT: Severe hypoxaemia after cardiac surgery is associated with serious complications and a high risk of mortality. The purpose of this study is to investigate the independent risk factors of severe postoperative hypoxaemia in patients with acute Stanford type A aortic dissection. We collected 77 patients with acute Stanford type A aortic dissection who underwent surgical treatment. The primary outcome was severe postoperative hypoxaemia (PaO2 /FiO2  ≤ 100 mmHg), and a multivariate logistic regression analysis was performed to assess the independent predictors of risk for this. A mixed-effects analysis of variance model and a receiver operating characteristic (ROC) curve were generated to evaluate the predictive probabilities of risk factors for severe postoperative hypoxaemia. A total of 36.4% of patients developed severe postoperative hypoxaemia. The multivariate logistic regression analysis identified high preoperative bradykinin level (odds ratio (OR) = 55.918, P < 0.001) and increased body mass index (BMI; OR = 1.292, P = 0.032) as independent predictors of severe postoperative hypoxaemia in patients with acute Stanford type A aortic dissection. The mixed-effect analysis of variance model and ROC curve indicated that high preoperative bradykinin level and BMI were significant predictors of severe postoperative hypoxaemia (area under the ROC curve = 0.834 and 0.764, respectively). High preoperative bradykinin levels and obesity were independent risk factors for severe postoperative hypoxaemia in patients with acute Stanford type A aortic dissection. For obese patients with high levels of bradykinin before surgery, clinicians should actively take measures to block bradykinin-mediated inflammatory reactions.


Assuntos
Dissecção Aórtica , Bradicinina , Humanos , Dissecção Aórtica/cirurgia , Hipóxia , Fatores de Risco , Obesidade , Estudos Retrospectivos
20.
J Cardiothorac Surg ; 18(1): 6, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36609343

RESUMO

OBJECTIVE: Acute kidney injury (AKI) after cardiac surgery is associated with serious complication and high risk of mortality. The relationship between hemostatic system and the prognosis of patients with acute type A aortic dissection (ATAAD) has not been evaluated. The purpose of this study was to investigate the association between preoperative serum fibrinogen level and risk of postoperative AKI in patients with ATAAD. METHODS: A total of 172 consecutive patients undergoing urgent aortic arch surgery for ATAAD between April 2020 and December 2021 were identified from Beijing Anzhen Hospital aortic surgery database. The primary outcome was postoperative AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The univariate and multivariate logistic regression analysis were done to assess the independent predictors of risk for postoperative AKI. Receiver operating characteristic (ROC) curve was generated to evaluate the predictive probabilities of risk factors for AKI. RESULTS: In our study, 51.2% (88/172) patients developed postoperative AKI. Multivariate logistic regression analysis identified low preoperative serum fibrinogen level (OR, 1.492; 95% CI, 1.023 to 2.476; p = 0.021) and increased body mass index (BMI) (OR, 1.153; 95% CI, 1.003 to 1.327; p = 0.046) as independent predictors of postoperative AKI in patients with ATAAD. A mixed effect analysis of variance modeling revealed that obese patients with low preoperative serum fibrinogen level had higher incidence of postoperative AKI (p = 0.04). The ROC curve indicated that low preoperative serum fibrinogen level was a significant predictor of AKI [area under the curve (AUC), 0.771; p < 0.001]. CONCLUSIONS: Low preoperative serum fibrinogen level and obesity were associated with the risk of postoperative AKI in patients with ATAAD. These data suggested that low preoperative serum fibrinogen level was preferred marker for predicting the postoperative AKI, especially in obese patients with ATAAD.


Assuntos
Injúria Renal Aguda , Dissecção Aórtica , Humanos , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Obesidade/complicações , Dissecção Aórtica/complicações , Dissecção Aórtica/cirurgia , Fibrinogênio
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