Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 176
Filtrar
1.
Br J Nutr ; : 1-26, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36348572

RESUMO

This study is design to explore the association between dietary betaine intake and risk of all-cause and cardiovascular death in patients with CAD. In this cohort study, 1292 patients with CAD were followed-up for a median of 9.2 years. Baseline dietary betaine intake was collected using a paper-based semi-quantitative food frequency questionnaire (FFQ) and assessed according to the US Department of Agriculture (USDA) Database and the data of betaine in common foods. Cox proportional hazards regression models were used to analyze the association between dietary betaine intake and risks of all-cause and cardiovascular mortality. During the follow-up periods, 259 deaths recorded in 1292 participants, of which 167 died of cardiovascular diseases. Patients in the highest tertile of dietary betaine intake had a lower risk of all-cause (P=0.007) and cardiovascular death (P<0.001) than those in the lowest tertile after adjusting for age and sex, traditional cardiovascular risk factors and other potential confounders. After further adjusting for plasma methionine metabolites and vitamins, HRs across tertiles of dietary betaine intake were 1.00, 0.84 and 0.72 for all-cause mortality (P for trend=0.124), and 1.00, 0.77 and 0.55 for cardiovascular mortality (P for trend=0.021). Higher dietary betaine intake was associated with a decreased risk of cardiovascular death after fully adjustment for cardiovascular risk factors, other potential confounders and plasma methionine metabolites and vitamins. However, the association between dietary betaine intake and risk of all-cause mortality was not statistically significant after further adjusting for plasma methionine metabolites and vitamins.

2.
Artigo em Inglês | MEDLINE | ID: mdl-36399394

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of performing cesarean section surgery before aortic repair after acute type A aortic dissection (ATAAD) during pregnancy. METHODS: A total of six patients who received ATAAD repair during their pregnancies were retrospectively identified in the hospital database from January 2002 to December 2021. RESULTS: The mean gestational period at the time of aortic repair was 35.3 ± 2.7 weeks, and the aortic root diameter ranged from 40 to 60 mm. The mean time from disease onset to arrival at the operation room was 20.3 ± 10.8 h (range 10-36 h). All patients successfully received aortic repair operations following cesarean section and survived the peri-surgery period without developing major complications. All fetuses were successfully delivered. After an average follow up of 25.8 months, all patients and their children had survived without developing major complications except for one mother who committed suicide 6 months after discharge as a result of postpartum depression. CONCLUSION: The present study suggested that ATAAD repair can be safely performed in the third-trimester.

3.
Front Endocrinol (Lausanne) ; 13: 1015747, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339437

RESUMO

Background: Insulin resistance (IR) is a significant risk factor for cardiometabolic diseases and a defining feature of type 2 diabetes mellitus (T2DM). This study aimed to examine the potential value of triglyceride-glucose (TyG) index as a predictor of prognosis in coronary heart disease (CHD) patients with T2DM after coronary artery bypass grafting (CABG) surgery and to facilitate the identification of those at high risk of major adverse cardiovascular events (MACEs) for closer monitoring or possible early intervention. Methods: This study enrolled 386 T2DM patients who underwent CABG surgery at Nanjing Drum Tower Hospital. Patients were separated into two groups according to the median preoperative TyG Index. The Kaplan-Meier plot was used to compare the rate of MACEs-free survival in T2DM patients after CABG. The independent risk factors for the occurrence of MACEs were investigated using multivariate analysis. Nomogram was used to depict the predictive model. Results: Significantly more MACEs occurred in individuals with higher medians of the TyG index (65 (33.7%) vs. 39 (20.2%), p=0.003). TyG index [hazard ratio (HR) 12.926], LVEF [hazard ratio (HR) 0.916], and NYHA functional class III/IV [hazard ratio (HR) 4.331] were identified as independent predictors of MACEs incidence in post-CABG T2DM patients by multivariate analysis. The area under the curve (AUC) for predicting MACEs using the TyG index was 0.89 at five years. Combining the TyG index, LVEF, and NYHA functional class III/IV to build a novel risk assessment model for postoperative MACEs, the AUC climbed to 0.93 at five years. With AUCs, the nomogram comprised of the TyG index, LVEF, and NYHA functional class III/IV demonstrated strong specificity in the training and test sets. Conclusions: The incidence of MACEs is high among post-CABG T2DM patients with a high TyG index. TyG index improves the diagnostic accuracy of MACEs, especially at long-term follow-up. A high TyG index may serve as an early warning signal for individuals to undertake lifestyle adjustments that can reduce the progression or incidence of MACEs.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Humanos , Triglicerídeos , Diabetes Mellitus Tipo 2/diagnóstico , Glucose , Glicemia , Estudos Retrospectivos , Biomarcadores , Ponte de Artéria Coronária/efeitos adversos
4.
Cell Discov ; 8(1): 106, 2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36220812

RESUMO

Neonatal heart undergoes metabolic conversion and cell cycle arrest preparing for the increased workload during adulthood. Herein, we report that neonatal ketone body elevation is a critical regulatory factor for postnatal heart development. Through multiomics screening, we found that the expression of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), the rate-limiting enzyme of ketogenesis, was transiently induced by colostrum in the neonatal heart. Hmgcs2 knockout caused mitochondrial maturation defects. Meanwhile, postnatal heart development was compromised and cardiomyocytes reacquired proliferation capacity in Hmgcs2 knockout mice. Consequently, over 40% of newborn Hmgcs2 knockout mice died before weaning. The heart function of surviving Hmgcs2 knockout mice was also impaired, which could be rescued by ketone body supplementation during the suckling stage. Mechanistically, ketone body deficiency inhibited ß-hydroxybutyrylation but enhanced acetylation of mitochondrial proteins, which might be responsible for the inhibition of the enzyme activity in mitochondria. These observations suggest that ketone body is critical for postnatal heart development through regulating mitochondrial maturation and metabolic reprogramming.

5.
J Inflamm Res ; 15: 5785-5799, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36238764

RESUMO

Purpose: The postoperative survival of patients with acute type A aortic dissection (aTAAD) remains unsatisfactory. The current study developed an easy-to-use survival prediction model and calculator. Methods: A total of 496 patients with aTAAD undergoing surgical repair were included in this study. The systemic immune-inflammation index (SII) and other clinical features were collected and subjected to logistic and Cox regression analyses. The survival prediction model was based on Cox regression analyses and exhibited as a nomogram. For convenience of use, the nomogram was further developed into calculator software. Results: We demonstrated that a higher preoperative SII was associated with in-hospital death (OR: 4.116, p < 0.001) and a higher postoperative overall survival rate (HR: 2.467, p < 0.001) in aTAAD patients undergoing surgical repair. A survival prediction model and calculator based on SII and four other clinical features were developed. The overall C-index of the model was 0.743. The areas under the curves (AUCs) of the 1- and 3-month and 1- and 3-year survival probabilities were 0.73, 0.71, 0.71 and 0.72, respectively. The model also showed good calibration and clinical utility. Conclusion: Preoperative SII is significantly associated with postoperative survival. Based on SII and other clinical features, we created the first easy-to-use prediction model and calculator for predicting the postoperative survival rate in aTAAD patients, which showed good prediction performance.

6.
Front Physiol ; 13: 1009007, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36299262

RESUMO

Background: Inflammation and oxidative stress are known to participate in the pathogenesis of hyperbilirubinemia. It has been known that acute type A aortic dissection (ATAAD) surgical repair often associates with complications which might affect the long-term prognosis. However, the clinical significance of postoperative hyperbilirubinemia (PH) has not been evaluated. Here in this study, we examined the incidence, risk factors, and prognosis of PH after ATAAD surgery. Methods: This retrospective study enrolled a total of 970 patients who received ATAAD surgical repair from January 2014 to December 2019. PH was defined as serum total bilirubin >3.0 mg/dl within the first week after the surgery. Propensity score matching was used to reduce selection bias and eliminate potential confounding factors. Kaplan-Meier survival and Cox proportional hazards regression analyses were conducted to explore the association between PH and postoperative long-term survival. Results: Development of PH (183 patients) was associated with a higher 30-Day mortality (20.8% vs. 9.0%, p < 0.001). Advanced age [odds ratio (OR) 1.538, p = 0.006], higher baseline total bilirubin level (OR 1.735, p = 0.026), preoperative pericardial tamponade (OR 3.192, p = 0.024), prolonged cardiopulmonary bypass (CPB) duration (OR 2.008, p = 0.005), and elevated postoperative central venous pressure (CVP) level (OR 2.183, p < 0.001) were associated with PH. The Kaplan-Meier analysis showed patients who developed PH were associated with poor long-term survival (p = 0.044). Cox analysis showed that the presence of PH (hazard ratio 2.006, p = 0.003) was an independent risk factor for increased mortality. Conclusion: PH is a common complication in patients undergoing ATAAD surgical repair that associates with worse short- and long-term prognosis. Our data indicated that age, preoperative total bilirubin level, pericardial tamponade, CPB duration, and postoperative CVP level were risk factors for the development of PH.

7.
Front Oncol ; 12: 959322, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091173

RESUMO

Cancer is one of the most serious diseases threatening human health, so it is particularly important to develop effective tumor-targeting drugs. As the first CDK4/6 inhibitor, palbociclib effectively inhibits tumor proliferation by blocking the cell cycle to the G1 phase. 10-HCPT is a Topo I inhibitor; however, its clinical application has been greatly limited due to its high toxicity. Based on the successful development of double target inhibitors, three novel palbociclib derivatives (HP-1, HP-2, and HP-3) were designed and synthesized from Palbociclib and 10-HCPT, and their biological activities were investigated. At first, the possible binding sites of the three compounds to Topo I and CDK4/6 were predicted by molecular docking. Then, we evaluated the anti-proliferative effects of the three palbociclib derivatives. In general, human lung cancer cells were more sensitive to HP-1, HP-2, and HP-3, especially NCI-H460. In addition, cell cycle arrest and apoptosis induction were investigated by flow cytometry. The three palbociclib derivatives, especially HP-1, had obvious cell cycle arrest phenomenon on NCI-H460 cells and induced apoptosis of NCI-H460 cells significantly. In the end, it was proved that these three drugs had obvious cyclin-dependent kinase inhibitory activities. In short, all the data showed that HP-1, HP-2, and HP-3 could play anti-cancer roles by acting on dual targets and had the characteristics of high efficiencies and low toxicities, which opened up a new idea for the study of palbociclib derivatives.

8.
Front Surg ; 9: 969995, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36111225

RESUMO

Background: Acute Stanford-A aortic dissection (AAAD) is a devastating cardiovascular condition with high mortality, therefore identifying risk prognosis factors is vital for the risk stratification of patients with AAAD. Here, we investigated peripheral blood eosinophil (EOS) counts in patients with AAAD and their possible biological implications. Methods: We performed a single center retrospective cohort study. From 2011 to 2021, a total of 1,190 patients underwent AAAD surgery. Patients were categorized first by death and then admission EOS counts (0.00 × 109/L or >0.00 × 109/L). Demographics, laboratory data, and outcomes were analyzed using standard statistical analyses. Ascending aorta specimens were used for western blotting and histological assessments. Results: Death group patients had lower EOS counts than the non-death group (P = 0.008). When patients were stratified using mean blood EOS counts: 681 patients had low (0.00 × 109/L) and 499 had high (>0.00 × 109/L) counts. Patients with low EOS counts at admission were more likely to have a higher mortality risk (P = 0.017) and longer treatment in the intensive care unit (ICU) days (P = 0.033) than patients with normal EOS counts. Also, the five blood coagulation items between both groups showed significantly different (P < 0.001). Hematoxylin & eosin-stained cross-sections of the ascending aorta false lumen showed that EOSs were readily observed in thrombi in the false lumen of the aorta. Conclusions: Peripheral blood EOS counts may be involved in thrombosis and could be an effective and efficient indicator for the diagnosis, evaluation, and prognosis monitoring of patients with AAAD.

9.
Heart Rhythm ; 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35934243

RESUMO

BACKGROUND: Epicardial adipose tissue (EAT) accumulation is associated with the progression of atrial fibrillation. However, the histological features of EATs are poorly defined and their correlation with atrial fibrosis is unclear. OBJECTIVE: The purpose of this study was to identify and characterize EAT subgroups in the persistent atrial fibrillation (PeAF) cohorts. METHODS: EATs and the corresponding left atrial appendage samples were obtained from patients with PeAF via surgical intervention. Adipocyte markers, that is, Uncoupling Protein 1, Transcription Factor 21, and CD137, were examined. On the basis of expression of adipocyte markers, patients with PeAF were categorized into subgroups by using unsupervised clustering analysis. Clinical characteristics, histological analyses, and outcomes were subsequently compared across the clusters. External validation was performed in a validation cohort. RESULTS: The ranking of feature importance revealed that the 3 adipocyte markers were the most relevant factors for atrial fibrosis compared with other clinical indicators. On the k-medoids analysis, patients with PeAF could be categorized into 3 clusters in the discovery cohort. The histological studies revealed that patients in cluster 1 exhibited statistically larger size of adipocytes in EATs and severe atrial fibrosis in left atrial appendages. Findings were replicated in the validation cohort, where severe atrial fibrosis was noted in cluster 1. Moreover, in the validation cohort, there was a high degree of overlap between the supervised classification results and the unsupervised cluster results from the k-medoids method. CONCLUSION: Machine learning-based cluster analysis could identify subtypes of patients with PeAF having distinct atrial fibrosis profiles. Additionally, EAT whitening (increased proportion of white adipocytes) may be involved in the process of atrial fibrosis.

10.
Front Cardiovasc Med ; 9: 948672, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35958404

RESUMO

Background: It has been well known that hyperlactatemia is an independent risk factor for postoperative mortality in patients who received acute type A aortic dissection (ATAAD) surgery. Some patients may require the assistance of continuous renal replacement therapy (CRRT) for acute postoperative renal deficiency and often associate with increased mortality rate. This study aimed to examine the association between the early dynamic change of lactate levels and postoperative CRRT in ATAAD patients who received surgical repairment. Methods: This retrospective study included 503 patients who received ATAAD surgeries. Serum lactate levels were measured before operation and at 0, 1, 3, 6, 12, 24 h post intensive care unit (ICU) admission. We examined the association between dynamic changes of lactate and CRRT. Results: Among all patients, 19.9% (100 patients) required CRRT. Our data showed that the lactate levels were higher in the CRRT group at all timepoints compared to the non-CRRT group. In a multivariate model, lactate levels at 12 h post ICU admission [odds ratio (OR), 1.362; p = 0.007] was identified as an independent predictor for requiring CRRT. Unsurprisingly, 30-day mortality in the CRRT group (41%) was 8.2 times higher than in the non-CRRT group (5%). To better understand the associations between CRRT and lactate levels, patients in the CRRT group were further stratified into the non-survivor group (n = 41) and survivor group (n = 59) based on the 30-day mortality. Elevated lactate levels measured upon ICU admission (OR, 1.284; p = 0.001) and decreased 24 h lactate clearance (OR, 0.237; p = 0.039) were independent risk factors for 30-day mortality in patients who received CRRT. The area under the curve to predict requirement for CRRT at 6 and 12 h post CICU admission were 0.714 and 0.722, respectively, corresponding to lactate cut-off levels of 4.15 and 2.45 mmol/L. Conclusion: The CRRT is commonly required in patients who received ATAAD surgery and often associated with worse mortality. Early dynamic changes of lactate levels can be used to predict the requirement of postoperative CRRT.

11.
Metabolites ; 12(7)2022 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-35888709

RESUMO

Aortic dissection (AD) is a life-threatening cardiovascular disease with a dismal prognosis. Inflammation plays an important role in AD. Oxylipins are bioactive lipids involved in the modulation of inflammation and may be involved in the pathogenesis and progression of AD. This study aims to identify possible metabolites related to AD. A total of 10 type A Aortic dissection (TAAD) patients, 10 type B Aortic dissection (TBAD) patients and 10 healthy controls were included in this study. Over 100 oxylipin species were identified and quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis. Our investigation demonstrated substantial alterations in 91 oxylipins between AD and healthy individuals. Patients with TAAD had 89 entries accessible compared to healthy controls. According to orthogonal partial least squares discriminant analysis (OPLS-DA), fitness (R2X = 0.362 and R2Y = 0.807, p = 0.03) and predictability (Q2 = 0.517, p = 0.005) are the validation parameters between the two groups. Using multivariate logistic regression, 13-HOTrE and 16(17)-EpDPE were the risk factors in the aortic patients group compared to healthy people (OR = 2.467, 95%CI:1.256-7.245, p = 0.035; OR = 0.015, 95%CI:0.0002-0.3240, p = 0.016, respectively). In KEGG enrichment of differential metabolites, the arachidonic acid metabolism pathway has the most metabolites involved. We established a diagnostic model in distinguishing between AD and healthy people. The AUC was 0.905. Oxylipins were significantly altered in AD patients, suggesting oxylipin profile is expected to exploit a novel, non-invasive, objective diagnosis for AD.

12.
J Stroke Cerebrovasc Dis ; 31(8): 106622, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35802988

RESUMO

Backgroud The present study aimed to investigate the function and regulatory mechanisms of lncRNA KCNQ1OT1 in vascular smooth muscle cells under oxidation low lipoprotein stimulation. Methods RNA sequencing was used to detect transcriptome changes of vascular smooth muscle cells treated with oxidation low lipoprotein. KCNQ1OT1, miR-196a-5p, and FOXO1 expression levels in VSMCs after oxidation low lipoprotein treatment were assessed using qRT-PCR and western blotting. RNA immunoprecipitation, RNA pull-down, and dual-luciferase reporter assay were used to confirm the interaction among lncRNA KCNQ1OT1, miR-196a-5p, and FOXO1. The functions of KCNQ1OT1, miR-196a-5p, and FOXO1 were analyzed by CCK-8 and flow cytometry. The serum samples of high fat-feeding mice and atherosclerosis patients were collected, and the levels of KCNQ1OT1 and miR-196a-5p were analyzed. Results In vitro expression of KCNQ1OT1 and FOXO1 decreased in VSMCs treated with oxidation low lipoprotein, accompanied by overexpression of miR-196a-5p. As a ceRNA, KCNQ1OT1 positively regulated FOXO1 and imparted a negative regulatory effect on miR-196a-5p. Interference KCNQ1OT1/miR-196a-5p/FOXO1 could change roliferation/apoptosis imbalance in VSMCs under oxidation low lipoprotein stimulation. Higher levels of KCNQ1OT1 and lower levels of miR-196a-5p can be found in the thoracic aorta tissues of high fat-feeding mice and serum samples from individuals with carotid atherosclerosis. Conclusion Aberrant expression of KCNQ1OT1/miR-196a-5p/FOXO1 pathway mediated oxidation low lipoprotein-induced proliferation/apoptosis imbalance in VSMCs.


Assuntos
MicroRNAs , RNA Longo não Codificante , Animais , Apoptose , Proliferação de Células , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/farmacologia , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Músculo Liso Vascular/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
13.
BMC Anesthesiol ; 22(1): 135, 2022 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-35501683

RESUMO

STUDY OBJECTIVE: The purpose of the present study was to evaluate the efficacy of levosimendan in patients with acute myocardial infarction related ventricular septal rupture (AMI-VSR) underwent cardiac surgery. DESIGN: Prospective observational cohort study with propensity score analysis. PATIENTS: There were 261 patients with AMI-VSR in our study. After 1:1 propensity matching, 106 patients (53 levosimendan and 53 control) were selected in the matched cohort. INTERVENTIONS: None. MEASUREMENTS: Patients who received levosimendan were assigned to the levosimendan group (n = 164). The patients who were not received were levosimendan assigned to the control group (n = 97). The levosimendan was initiated immediately after cardiopulmonary bypass. Then, it has been maintained during the postoperative 3 days. The poor outcomes were identified as follows: death and postoperative complications (postoperative stroke, low cardiac output syndromeneeded mechanical circulatory support after surgery, acute kidney injury (≥ stage III), postoperative infection or septic shock, new developed atrial fibrillation or ventricular arrhythmias). MAIN RESULTS: Before matching, the control group had more length of ICU stay (6.69 ± 3.90 d vs. 5.20 ± 2.24 d, p < 0.001) and longer mechanical ventilation time (23 h, IQR: 16-53 h vs. 16 h, IQR: 11-23 h, p < 0.001). Other postoperative outcomes have not shown significant differences between two groups. After matching, no significant difference was found between both groups for all postoperative outcomes. The Kaplan-Meier survivul estimate and log-rank test showed that the 90-day survival had no significant differences between two groups before and after matching. CONCLUSION: Our study found that a low-dose infusion of levosimendan in AMI-VSR patients underwent surgical repair did not associated with positively affect to postoperative outcomes.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Infarto do Miocárdio , Piridazinas , Ruptura do Septo Ventricular , Doença Aguda , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Cardiotônicos , Feminino , Humanos , Hidrazonas/uso terapêutico , Masculino , Infarto do Miocárdio/complicações , Infarto do Miocárdio/tratamento farmacológico , Complicações Pós-Operatórias , Pontuação de Propensão , Estudos Prospectivos , Piridazinas/uso terapêutico , Simendana , Ruptura do Septo Ventricular/tratamento farmacológico
14.
BMJ Open ; 12(5): e056264, 2022 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-35523485

RESUMO

INTRODUCTION: Heart failure (HF) is a growing global public health burden. However, due to the very limited regenerative capacity of mature cardiomyocytes in the adult mammalian heart, conventional treatments can only improve the symptoms of HF but fail to restore cardiac function. Heart transplantation is limited by a severe shortage of donors. Cell-based transplantation for the treatment of HF has become a promising strategy. Human-induced-pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been tested in animal models to assess safety and efficacy. This study aims at evaluating the safety and efficacy of epicardial injection of hiPSC-CMs in patients with advanced HF during coronary artery bypass grafting (CABG) surgery. METHODS: This study is a dose-escalation, placebo-controlled, single-centre phase I/IIa clinical trial. Dose escalation will be guided by a modified 3+3 design for three doses (1×108, 2×108 and 4×108 cells, sequentially). Patients with advanced heart failure will be enrolled and randomly allocated to receive epicardial injection of hiPSC-CMs during CABG surgery or CABG surgery alone, followed by a 12-month follow-up investigation. The primary endpoint is to assess the safety of hiPSC-CMs transplantation, including haemodynamic compromised sustained ventricular arrhythmias and newly formed tumours during 6 months postoperatively. The secondary endpoint is to evaluate the efficacy of epicardial injection of hiPSC-CMs and CABG surgery combination by comparison with CABG surgery alone. ETHICS AND DISSEMINATION: The study protocol has been approved by the Institutional Ethical Committee of Nanjing Drum Tower Hospital (No. SC202000102) and approved by National Health Commission of the PRC (MR-32-21-014649). Findings will be disseminated to the academic community through peer-reviewed publications and presentation at national and international meetings. TRIAL REGISTRATION NUMBER: NCT03763136.


Assuntos
Insuficiência Cardíaca , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Pluripotentes Induzidas , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Ponte de Artéria Coronária , Insuficiência Cardíaca/cirurgia , Humanos , Células-Tronco Pluripotentes Induzidas/patologia , Células-Tronco Pluripotentes Induzidas/transplante , Miócitos Cardíacos/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Cell Death Dis ; 13(5): 435, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508454

RESUMO

Idiopathic pulmonary fibrosis (IPF) was considered as a telomere-mediated disease. TERT and TERC correlated with telomere length. Although telomerase gene mutations were associated with IPF, majority patients did not carry mutations. The mechanism by which telomerase expression was regulated in IPF are still unclear. In this study, we aimed to delineate the mechanisms that how TERT protein expression were regulated in alveolar epithelial cells (AECs) in pulmonary fibrosis. Here, we found that P16, P21 and fibrosis markers (αSMA and Collagen-I) were prominently increased in lung tissues of IPF patients and bleomycin-induced mouse models, while the expression of KLF4 and TERT were decreased in AECs. In vivo experiments, AAV-6 vectors mediated KLF4 over-expression with specific SP-C promoter was constructed. Over-expression of KLF4 in AECs could protect TERT expression and suppress the development of pulmonary fibrosis in bleomycin-induced mouse models. In the mechanism exploration of TERT regulation, KLF4 and TERT were both down-regulated in bleomycin-induced senescent MLE-12 and BEAS-2B cells. Compared with control group, small-interfering RNA targeting KLF4 significantly reduced the TERT expression and telomerase activity, while overexpression of KLF4 can increased the expression of TERT and telomerase activity in senescent AECs. Furthermore, ChIP showed that KLF4 protein could bind to the TERT promoter region in MLE-12 cells, suggesting that KLF4 could implicate in pathogenesis of lung fibrosis through regulating TERT transcription in AECs. Taken together, this study identified that KLF4 might be a promising potential target for further understanding the mechanism and developing novel strategy for the treatment of lung fibrosis in IPF.


Assuntos
Fibrose Pulmonar Idiopática , Telomerase , Células Epiteliais Alveolares/metabolismo , Animais , Bleomicina/farmacologia , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Humanos , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/metabolismo , Pulmão/metabolismo , Camundongos , Telomerase/metabolismo
17.
Artigo em Inglês | MEDLINE | ID: mdl-35436075

RESUMO

INTRODUCTION: New-onset postoperative atrial fibrillation (POAF) is a common complication following coronary artery bypass grafting (CABG) surgery. OBJECTIVE: To explore predictive factors and potential mechanisms of new-onset POAF in isolated off-pump CABG patients. METHODS: Retrospective observational case-control study of 233 patients undergoing isolated off-pump CABG surgery between August 2018 and July 2020 at the Department of Thoracic and Cardiovascular Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School. Associations between predictor variables and new-onset POAF were identified. The main outcome was new-onset POAF after CABG surgery. RESULTS: A total of 75 (32.19%) patients developed new-onset POAF after CABG surgery. The new-onset POAF patients had advanced age, higher baseline systolic blood pressure, more preoperative use of diuretic drug, more transfusion of blood products, atrial dilation and postoperative positive inotropic drug treatment. Nineteen variates entered the multivariable logistic regression model with a Hosmer-Lemeshow test score of 7.565 (P=0.477). Postoperative left atrial enlargement, postoperative drainage in the first 24 hours and total length of hospital stay were statistically significant, while postoperative right atrial enlargement (OR and 95% CI, 7.797 [0.200, 304.294], P=0.272) and left atrial enlargement (3.524 [1.141, 10.886], P=0.029) assessed by echocardiography had the largest OR value. CONCLUSION: Atrial enlargement is strongly associated with new-onset POAF in patients with isolated off-pump CABG, thus it highlights the advantage of echocardiography as a useful tool for predicting new-onset POAF. Careful monitoring and timely intervention should be considered for these patients.

18.
BMC Surg ; 22(1): 75, 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35236329

RESUMO

BACKGROUND: Acute kidney injury (AKI) is a serious complication that often occurred after acute type A aortic dissection (ATAAD) surgery. Previous studies proved that the Kidney Disease Improving Global Outcomes (KDIGO) defined stage 3 AKI was associated with lower long-term survival rate. However, the risk factors for developing stage 3 AKI had not been identified. The aim of the study was to explore the risk factors for developing KDIGO stage 3 after ATAAD operation. METHODS: This study included 993 patients who received ATAAD operation from 2014 to 2019 at the Nanjing Drum Tower Hospital. Postoperative AKI was diagnosed according to the KDIGO criteria. Multivariate logistic regression analyses were applied to identify risk factors for stage 3 AKI. Kaplan-Meier survival analyses and Cox proportional hazards regression model were conducted to explore the association between different AKI stages and postoperative survival rate. RESULTS: The mean age of all enrolled patients was 53.0 ± 13.1 years. A total of 236 (23.8%) patients suffered postoperative stage 3 AKI including 165 patients who required renal replacement therapy. Advanced age (odds ratio [OR] 1.031; 95% confidence interval [CI] 1.005-1.057; P = 0.018), prolonged cardiopulmonary bypass (CPB) duration (OR 1.010; 95% CI 1.002-1.018; P = 0.013), and higher drainage volume 24 h after surgery (OR 1.000; 95% CI 1.000-1.001; P = 0.033) were identified as independent risk factors for developing stage 3 AKI. In addition, our result showed that the mortality rate was correlated significantly with the severity of AKI defined by KDIGO criteria and the Cox regression analysis showed that only stage 3 AKI, but not stage 1 and 2, was an independent risk factor for mortality (Hazard ratio 10.365, 95% CI 4.208 to 25.528; P < 0.001) after adjusting for important confounding factors. CONCLUSIONS: Our study suggested that stage 3 postoperative AKI was significantly associated with decreased postoperative survival rate after ATAAD surgery. Advanced age, increased CPB duration and drainage volume 24 h after surgery were identified as risk factors for developing stage 3 AKI.


Assuntos
Injúria Renal Aguda , Aneurisma Dissecante , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Adulto , Idoso , Aneurisma Dissecante/complicações , Aneurisma Dissecante/cirurgia , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco
19.
J Cardiothorac Surg ; 17(1): 40, 2022 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-35305695

RESUMO

BACKGROUND: Acute type A aortic dissection (aTAAD) is a lethal disease and age is an important risk factor for outcomes. This retrospective study was to analyze the impact of age stratification in aTAAD, and to provide clues for surgeons when they make choices of therapy strategies. METHODS: From January 2011 to December 2019, 1092 aTAAD patients from Nanjing Drum Tower Hospital received surgical therapy. Patients were divided into 7 groups according to every ten-year interval (20-80 s). The differences between the groups were analyzed in terms of the baseline preoperative conditions, surgical methods and postoperative outcomes of patients of different age groups. During a median follow-up term of 17 months, the survival rates were compared among 7 groups through Kaplan-Meier analysis. RESULTS: The median age was 52.0 years old in whole cohort. The multiple comorbidities were more common in old age groups (60 s, 70 s, 80 s), while the 20 s group patients had the highest proportion of Marfan syndrome (28.1%). Preoperative hypotension was highest in 80 s (16.7%, P = 0.038). Young age groups (20-60 s) had a higher rate of root replacement and total arch replacement, which led to a longer duration of operation and hypothermic circulation arrest. The overall mortality was 14.1%, the tendency of mortality was increased with age except 20 s group (33.3% in 80 s, P = 0.016). The postoperative morbidity of gastrointestinal bleeding and bowel ischemia were 16.7% and 11.1% in 80 s group. CONCLUSIONS: Age is a major impact factor for aTAAD surgery. Old patients presented more comorbidities before surgery, the mortality and complications rate were significantly higher even with less invasive and conservative surgical therapy. But the favorable long-term survival indicated that the simple or less extensive arch repair is the preferred surgery for patients over 70 years old.


Assuntos
Aneurisma Dissecante , Síndrome de Marfan , Idoso , Aneurisma Dissecante/cirurgia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
20.
Ann Transl Med ; 10(2): 110, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35282122

RESUMO

Objective: To assess the role of indocyanine green in liver transplantation and to lay the foundation for its application in clinical practice. Background: Liver transplantation offers the best prognosis for patients with end-stage liver disease. However, this invasive procedure involves multiple well-known challenges, including complications due to graft rejection and dysfunction, surgical risks, and critical postoperative management. Intraoperative methods to assess graft function rely on conventional methods, such as blood chemistries and Doppler ultrasound. However, these methods are limited in their abilities to assess liver conditions, predict functional outcomes of the graft, and prevent surgical complications. Thus, identifying a more effective and comprehensive detection method is necessary. Methods: The information used to write this narrative review was collected from the references' opinions and conclusions. Conclusions: Indocyanine green can effectively monitor blood flow during surgery, evaluate donor graft function, and monitor the recipients functional status during and after surgery. It may also help surgeons to predict the prognosis of patients throughout the liver transplantation process, from assessing patients for liver transplantation status to postoperative management. Therefore indocyanine green should be routinely used in liver transplantation to help re-organize the transplant waiting list and improve the surgical outcomes of liver transplantation patients.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...