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1.
Sci China Life Sci ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34668131

RESUMO

Diabetic cardiomyopathy (DCM) is a common complication in diabetic patients. The molecular mechanisms of DCM remain to be fully elucidated. The intronic long noncoding RNA of DACH1 (lncDACH1) has been demonstrated to be closely associated with heart failure and cardiac regeneration. In this study, we investigated the role of lncDACH1 in DCM and the underlying molecular mechanisms. The expression of lncDACH1 was increased in DCM hearts and in high glucose-treated cardiomyocytes. Knockout of lncDACH1 reduced mitochondrial oxidative stress, cell apoptosis, cardiac fibrosis and hypertrophy, and improved cardiac function in DCM mice. Overexpression of lncDACH1 exacerbated mitochondria-derived reactive oxygen species (ROS) level and apoptosis, decreased activity of manganese superoxide dismutase (Mn-SOD); while silencing of lncDACH1 attenuated ROS production, mitochondrial dysfunction, cell apoptosis, and increased the activity of Mn-SOD in cardiomyocytes treated with high glucose. LncDACH1 directly bound to sirtuin3 (SIRT3) and facilitated its degradation by ubiquitination, therefore promoting mitochondrial oxidative injury and cell apoptosis in mouse hearts. In addition, SIRT3 silencing abrogated the protective effects of lncDACH1 deficiency in cardiomyocytes. In summary, lncDACH1 aggravates DCM by promoting mitochondrial oxidative stress and cell apoptosis via increasing ubiquitination-mediated SIRT3 degradation in mouse hearts. Inhibition of lncDACH1 represents a novel therapeutic strategy for the intervention of diabetic cardiomyopathy.

2.
Signal Transduct Target Ther ; 6(1): 329, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471087

RESUMO

It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

3.
J Zhejiang Univ Sci B ; 22(8): 647-663, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34414700

RESUMO

Interstitial fluid (ISF) flow through vascular adventitia has been discovered recently. However, its kinetic pattern was unclear. We used histological and topographical identification to observe ISF flow along venous vessels in rabbits. By magnetic resonance imaging (MRI) in live subjects, the inherent pathways of ISF flow from the ankle dermis through the legs, abdomen, and thorax were enhanced by paramagnetic contrast. By fluorescence stereomicroscopy and layer-by-layer dissection after the rabbits were sacrificed, the perivascular and adventitial connective tissues (PACTs) along the saphenous veins and inferior vena cava were found to be stained by sodium fluorescein from the ankle dermis, which coincided with the findings by MRI. The direction of ISF transport in a venous PACT pathway was the same as that of venous blood flow. By confocal microscopy and histological analysis, the stained PACT pathways were verified to be the fibrous connective tissues, consisting of longitudinally assembled fibers. Real-time observations by fluorescence stereomicroscopy revealed at least two types of spaces for ISF flow: one along adventitial fibers and another one between the vascular adventitia and its covering fascia. Using nanoparticles and surfactants, a PACT pathway was found to be accessible by a nanoparticle of <100 nm and contained two parts: a transport channel and an absorptive part. The calculated velocity of continuous ISF flow along fibers of the PACT pathway was 3.6‒15.6 mm/s. These data revealed that a PACT pathway was a "slit-shaped" porous biomaterial, comprising a longitudinal transport channel and an absorptive part for imbibition. The use of surfactants suggested that interfacial tension might play an essential role in layers of continuous ISF flow along vascular vessels. A hypothetical "gel pump" is proposed based on interfacial tension and interactions to regulate ISF flow. These experimental findings may inspire future studies to explore the physiological and pathophysiological functions of vascular ISF or interfacial fluid flow among interstitial connective tissues throughout the body.

4.
BMC Womens Health ; 21(1): 293, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34372846

RESUMO

BACKGROUND: To investigate the relationship between sweating from hot flashes, anxiety, depression, and sleep quality in peri- and postmenopausal women. And also the role of anxiety and depression in mediating sweating from hot flashes and sleep quality. METHODS: 467 women aged 40-60 years with menopausal problems were enrolled. The sleep quality; hot flashes; sweating; anxiety and depression symptoms were quantitatively evaluated by Pittsburgh Sleep Quality Scale (PSQI), Kupperman Menopause Index, Self-rating Anxiety Scale and Self-rating Depression Scale. Spearman correlation analysis and mediating effect model were used to analyze the relationship between the three. RESULTS: 262 patients' PSQI score were higher than 6 (58.2%). Total scores of sleep quality were positively correlated with hot flashes, sweating and anxiety and depression symptoms. Anxiety and depression played a mediating role between hot flashes, sweating and sleep quality where the mediating effect of anxiety symptoms accounted for 17.86% (P < 0.01) and depression symptoms accounted for 5.36% (P < 0.01). CONCLUSIONS: The hot flashes, sweating, anxiety and depression of peri/postmenopausal women are risk factors affecting sleep quality. By alleviating these risk factors, the sleep quality of peri- and postmenopausal women could be improved, which prevents the physical and mental diseases due to long-term severe insomnia.


Assuntos
Fogachos , Sudorese , Ansiedade , Feminino , Humanos , Menopausa , Perimenopausa , Pós-Menopausa , Sono
5.
Hypertens Res ; 44(9): 1158-1167, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34035483

RESUMO

Although emerging data suggest that circulating lipoprotein (a) [Lp (a)] could predict cardiovascular events (CVEs) in patients with cardiovascular disease, no study is currently available regarding the prognostic linkage of Lp (a) and hypertension in patients with coronary artery disease (CAD). This study sought to evaluate the association of Lp (a), hypertension and cardiovascular outcomes in patients with stable CAD. A total of 8668 patients with stable CAD were consecutively enrolled. Baseline Lp (a) concentrations were measured. All subjects were categorized according to Lp (a) levels of <10 (low), 10-30 (medium) and ≥30 mg/dL (high) and were further stratified by hypertension status. They were regularly followed-up for the occurrence of cardiovascular death, nonfatal myocardial infarction, and stroke. Over an average of 54.81 ± 18.60 months of follow-up, 584 (6.7%) CVEs occurred. Kaplan-Meier and multivariate Cox regression analyses showed that elevated Lp (a) levels had a significant association with CVEs in hypertensive patients, regardless of the control status of blood pressure, but not in normotensive subjects. Moreover, when analyzed by subgroups according to both Lp (a) category and hypertension status, the risk of CVEs was only significantly elevated in the high Lp (a) plus hypertension group compared with the reference group with low Lp (a) levels and normotension (hazard ratio: 1.80, 95% confidence interval: 1.11-2.91). Elevated Lp (a) was associated with an increased risk of CVEs in stable CAD patients with hypertension. Moreover, the coexistence of high Lp (a) concentrations and hypertension greatly worsened the clinical prognosis in patients with CAD, which may suggest a prognostic correlation between Lp (a) and hypertension.

6.
Aging (Albany NY) ; 13(6): 8055-8067, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33686961

RESUMO

The homeoprotein SIX1 is upregulated in non-small cell lung cancer (NSCLC) and associated with NSCLC tumorigenesis and progression. We identified microRNA-7160 (miR-7160) as a SIX1-targeting miRNA. RNA immunoprecipitation results confirmed a direct binding between miR-7160 and SIX1 mRNA in NSCLC cells. In the primary and established NSCLC cells, forced overexpression of miR-7160 downregulated SIX1 and inhibited cancer cell growth, proliferation, migration and invasion. Furthermore, miR-7160 overexpression induced apoptosis activation in NSCLC cells. Conversely, miR-7160 inhibition elevated SIX1 expression and enhanced NSCLC cell progression in vitro. Restoring SIX1 expression, by an untranslated region-depleted SIX1 expression construct, reversed miR-7160-induced anti-NSCLC cell activity. CRISPR/Cas9-inudced knockout of SIX1 mimicked miR-7160-induced actions and produced anti-NSCLC cell activity. In vivo, intratumoral injection of miR-7160-expressing lentivirus downregulated SIX1 mRNA and inhibited NSCLC xenograft growth in severe combined immunodeficient mice. Significantly, miR-7160 expression is downregulated in human NSCLC tissues and is correlated with SIX1 mRNA upregulation. Collectively, miR-7160 silenced SIX1 and inhibited NSCLC cell growth in vitro and in vivo.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Regulação Neoplásica da Expressão Gênica/fisiologia , Proteínas de Homeodomínio/metabolismo , Neoplasias Pulmonares/patologia , MicroRNAs/metabolismo , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Xenoenxertos , Proteínas de Homeodomínio/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , MicroRNAs/genética , Pessoa de Meia-Idade
7.
Hepatol Int ; 15(2): 413-423, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33740211

RESUMO

BACKGROUND: Although non-invasive liver fibrosis scores (LFSs) have already been considered as effective tools for estimating cardiovascular risk, their roles in predicting disease severity and cardiovascular event (CVEs) in patients with stable coronary artery disease (CAD) are not comprehensively evaluated. The aim of the present study was to investigate whether non-alcoholic fatty liver disease fibrosis score (NAFLD-FS) and fibrosis-4 (FIB-4) are associated with CVEs in a large cohort with long-term follow-up. METHODS: A cohort of 5143 patients with angiography-proven stable CAD were consecutively enrolled and followed up for CVEs. The degree of coronary severity was assessed using the number of diseased vessels, Gensini, Syntax, and Jeopardy scores. The predictive values of NAFLD-FS and FIB-4 scores to coronary severity, coronary calcification (CAC), and CVEs were assessed, respectively. RESULTS: During a median follow-up of 7 years, 435 CVEs were recorded. Both NAFLD-FS and FIB-4 were predictors for the presence of CAC. The degree of coronary stenosis was significantly higher in high NAFLD-FS categories while FIB-4 was only positively associated with the number of diseased vessels and Gensini score. In Kaplan-Meier analysis, the patients with intermediate and high NAFLD-FS and FIB-4 had higher risk of CVEs and cardiovascular mortality. In multivariate Cox regression analysis, NAFLD-FS and FIB-4 were independently associated with CVEs [hazard ratio (95% confidence interval): 1.150 (1.063-1.244), p < 0.001 and 1.128 (1.026-1.240), p = 0.012]. CONCLUSION: The current data first indicated that both NAFLD-FS and FIB-4 scores were not only significantly related to coronary severity but also associated with CAC and CVEs. CLINICAL TRIALS REGISTRATION: None.

8.
J Am Heart Assoc ; 10(3): e018869, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33506689

RESUMO

Background Previous studies have suggested a strong association of liver fibrosis scores (LFSs) with cardiovascular outcomes in patients with different cardiovascular diseases. Nonetheless, it is basically blank regarding the prognostic significance of LFSs in patients following percutaneous coronary intervention (PCI). This study sought to examine the potential role of LFSs in predicting long-term outcomes in a large cohort of patients with stable coronary artery disease after elective PCI. Methods and Results In this multicenter, prospective study, we consecutively enrolled 4003 patients with stable coronary artery disease undergoing PCI. Eight currently available noninvasive LFSs were assessed for each subject. All patients were followed up for the occurrence of cardiovascular events including cardiovascular death, nonfatal myocardial infarction, and stroke. During an average follow-up of 5.0±1.6 years, 315 (7.87%) major cardiovascular events were recorded. Subjects who developed cardiovascular events were more likely to have intermediate or high LFSs, including nonalcoholic fatty liver disease fibrosis score; fibrosis-4 score; body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes mellitus score (BARD); and aspartate aminotransferase/alanine aminotransferase ratio. Furthermore, compared with subjects with low scores, those with intermediate plus high score levels had significantly increased risk of cardiovascular events (adjusted hazard ratios ranging 1.57-1.92). Moreover, the addition of non-alcoholic fatty liver disease fibrosis score; fibrosis-4 score; or body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes mellitus score into a model with established cardiovascular risk factors significantly improved the prediction ability. Conclusions High LFSs levels might be useful for predicting adverse prognosis in patients with stable coronary artery disease following PCI, suggesting the possibility of the application of LFSs in the risk stratification before elective PCI.


Assuntos
Doença da Artéria Coronariana/cirurgia , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Cirrose Hepática/diagnóstico , Intervenção Coronária Percutânea/efeitos adversos , Medição de Risco/métodos , China/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Cirrose Hepática/epidemiologia , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco
9.
Cardiovasc Drugs Ther ; 35(1): 41-50, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32915349

RESUMO

PURPOSE: Antihypertensive treatment is the most important method to reduce the risk of cardiovascular events in hypertensive patients. However, there is scant evidence of the benefits of levoamlodipine maleate for antihypertensive treatment using a head-to-head comparison in the real-world. This study aims to examine the effectiveness of levoamlodipine maleate used to treat outpatients with primary hypertension compared with amlodipine besylate in a real-world setting. METHODS: This was a pragmatic comparative effectiveness study carried out at 110 centers across China in outpatients with primary hypertension treated with levoamlodipine maleate or amlodipine besylate, with 24 months of follow-up. The primary outcomes used for evaluating the effectiveness were composite major cardiovascular and cerebrovascular events (MACCE), adverse reactions, and cost-effectiveness. RESULTS: Among the included 10,031 patients, there were 482 MACCE, 223 (4.4%) in the levoamlodipine maleate group (n = 5018) and 259 (5.2%) in the amlodipine besylate group (n = 5013) (adjusted hazard ratio = 0.90, 95%CI: 0.75-1.08, P = 0.252). The levoamlodipine maleate group had lower overall incidences of any adverse reactions (6.0% vs. 8.4%, P < 0.001), lower extremity edema (1.1% vs. 3.0%, P < 0.001) and headache (0.7% vs. 1.1%, P = 0.045). There was a nearly 100% chance of the levoamlodipine maleate being cost-effective at a willingness to pay threshold of 150,000 Yuan per quality-adjusted life years (QALYs) gained, resulting in more QALYs (incremental QALYs: 0.00392) and cost savings (saving 2725 Yuan or 28.8% reduction in overall costs) per patient. CONCLUSION: In conclusion, levoamlodipine maleate could reduce cost by 29% with a similar MACCE incidence rate and lower occurrence of adverse reactions (especially edema and headache) compared with amlodipine besylate. TRIAL REGISTRATION: Clinicaltrials.gov NCT01844570 registered at May 1, 2013.

10.
J Hypertens ; 39(3): 511-518, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33186323

RESUMO

OBJECTIVE: Previous studies have demonstrated that small dense LDL-cholesterol (sdLDL-C) is related to the pathogenesis of coronary artery disease (CAD). However, its prognostic role in hypertensive patients with CAD has been undetermined. The aim of the study was to investigate the association between sdLDL-C with disease severity, hypertensive status and clinical outcome in patients with CAD. METHODS: A total of 4594 patients with angiography-proven CAD were consecutively enrolled and categorized into subgroups according to blood pressure status. Serum sdLDL-C levels were measured by direct quantitative measurement using automated chemistry analyzers. The severity of coronary artery lesions were determined by Gensini score, Syntax score and the number of lesion vessels. The associations of sdLDL-C with disease severity, hypertensive status and cardiovascular events (CVEs) were evaluated. RESULTS: Patients with hypertension had higher sdLDL-C levels than ones without (P = 0.010). In hypertensive patients, sdLDL-C was positively associated with the severity of CAD (P < 0.05). In addition, hypertensive patients with poorly controlled hypertension had higher sdLDL-C levels than those with well controlled (P < 0.05). Moreover, 149 CVEs occurred in patients with poorly controlled hypertension and Cox regression analysis indicated that elevated sdLDL-C levels were independently associated with CVEs in hypertensive patients with poorly controlled hypertension (adjusted hazard ratio: 1.673, 95% confidence interval: 1.105-2.535, P = 0.015). CONCLUSION: The current data, for the first time, showed that serum sdLDL-C levels were correlated with hypertension control, disease severity and worse outcomes in hypertensive patients with CAD, suggesting that paying more attention on sdLDL-C in these patients were warranted.

11.
Org Lett ; 23(2): 400-404, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33372804

RESUMO

Stereoselective syntheses of terpenoids in a more efficient manner have been a long-term pursuit for synthetic chemists. Herein we describe the two-step, enantiospecific and protecting-group-free synthesis of (+)-schisanwilsonene A from a carotane compound, which was produced in E. coli. We also completed the first enantiomeric synthesis of (+)-tormesol in five steps. The two-stage strategy offers a step- and redox-economical approach to prepare terpene natural products and their analogues.

12.
Data Brief ; 33: 106512, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33304946

RESUMO

In this work, a lab-designed apparatus was developed to collect and record the CO2 amount during the hydroxyethyl modification of lignin. We presented the CO2 volume amount and the production rate under different reaction conditions (80 - 120 °C and 2 - 6 hrs). Nuclear magnetic resonance spectroscopy was performed to analyze the chemical structure of the hydroxyethyl lignin corresponding with different amounts of CO2 that evolved during the reaction. The aliphatic hydroxyl, aromatic hydroxyl, and carboxylic acid groups were analyzed and tabulated. The acetylated hydroxyethyl lignin samples were characterized by 13C NMR to obtain the aliphatic hydroxyl (primary and secondary), phenol (ortho substituted and ortho-free), hydroxyethyl, methoxy, and aromatic hydrogen groups semi-quantitatively. Fourier-transform infrared (FTIR) spectroscopy was adopted to analyze the surface functional groups including alkyl aryl ether bond, carboxylic acid groups, and aromatic hydroxyl groups. Gel permeation chromatography combined with a multi-angle light scattering detector and differential refractive index detector were used to obtain the molar mass of lignin before and after the modification.

13.
J Transl Med ; 18(1): 373, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004038

RESUMO

BACKGROUND: Elevated lipoprotein(a) [Lp(a)] and fibrinogen (Fib) are both associated with coronary artery disease (CAD). The atherogenicity of Lp(a) can be partly due to the potentially antifibrinolytic categories. We hypothesize that patients with higher Lp(a) and Fib may have worse outcomes. METHODS: In this prospective study, we consecutively enrolled 8,417 Chinese patients with stable CAD from March 2011 to March 2017. All subjects were divided into 9 groups according to Lp(a) (Lp(a)-Low, Lp(a)-Medium, Lp(a)-High) and Fib levels (Fib-Low, Fib-Medium, Fib-High) and followed up for CVEs, including nonfatal acute myocardial infarction, stroke, and cardiovascular mortality. Kaplan-Meier, Cox regression and C-statistic analyses were performed. RESULTS: During a median of 37.1 months' follow-up, 395 (4.7%) CVEs occurred. The occurrence of CVEs increased by Lp(a) (3.5 vs. 5.3 vs. 5.6%, p = 0.001) and Fib (4.0 vs. 4.4 vs. 6.1%, p < 0.001) categories. When further classified into 9 groups by Lp(a) and Fib levels, the CVEs were highest in the 9th (Lp(a)-High and Fib-High) compared with the 1st (Lp(a)-Low and Fib-Low) group (7.2 vs. 3.3%, p < 0.001). The highest risk of subsequent CVEs was found in the 9th group (HRadjusted 2.656, 95% CI 1.628-4.333, p < 0.001), which was more significant than Lp(a)-High (HRadjusted 1.786, 95% CI 1.315-2.426, p < 0.001) or Fib-High (HRadjusted 1.558, 95% CI 1.162-2.089, p = 0.003) group. Moreover, adding the combined Lp(a) and Fib increased the C-statistic by 0.013. CONCLUSION: Combining Fib and Lp(a) enhance the prognostic value for incident CVEs beyond Lp(a) or Fib alone.


Assuntos
Doença da Artéria Coronariana , Lipoproteína(a) , Biomarcadores , Estudos de Coortes , Fibrinogênio , Humanos , Prognóstico , Estudos Prospectivos , Fatores de Risco
14.
J Interv Cardiol ; 2020: 7905021, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33071677

RESUMO

Objectives: This study aimed to evaluate the antithrombotic efficacy between bivalirudin and unfractionated heparin (UFH) on radial artery thrombosis (RAT) during transradial coronary intervention (TRI) by optical coherence tomography (OCT). Methods and Results: We consecutively reviewed a total of 307 patients who underwent radial artery OCT inspection after TRI in our centre from October 2017 to January 2019; afterwards, 211 screened patients were divided into the UFH group (n = 144) and the bivalirudin group (n = 67) according to their anticoagulation strategy during TRI. The thrombosis in the radial artery was observed in 51 cases (24.17%) with a median thrombus volume of 0.054 mm3 (0.024, 0.334) and median thrombus score of 7 (4, 15). Thrombus occurred in 28 cases in the bivalirudin group with an incidence of 41.8%, which was significantly higher than that in the UFH group (n = 23, 16.0%, P < 0.001). This difference was even more remarkable after propensity score matching (bivalirudin group n = 22, 42.3% vs. UHF group n = 11, 13.9%, P < 0.001). Multivariate logistic analysis revealed that bivalirudin increased the RAT risk by 3.872 times (95% CI 2.006-8.354, P < 0.001) after adjustment for the other predictors. Conclusion: In this present study, the use of bivalirudin was associated with a higher risk of RAT than UFH. It highlighted UFH should be a more considerable choice to prevent radial artery access thrombosis in TRI.


Assuntos
Cateterismo Periférico/efeitos adversos , Heparina , Hirudinas , Fragmentos de Peptídeos , Intervenção Coronária Percutânea , Artéria Radial , Trombose , Cateterismo Periférico/métodos , Feminino , Fibrinolíticos/administração & dosagem , Fibrinolíticos/efeitos adversos , Heparina/administração & dosagem , Heparina/efeitos adversos , Hirudinas/administração & dosagem , Hirudinas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Artéria Radial/diagnóstico por imagem , Artéria Radial/patologia , Artéria Radial/cirurgia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Risco Ajustado/métodos , Trombose/etiologia , Trombose/prevenção & controle , Tomografia de Coerência Óptica/métodos , Resultado do Tratamento
15.
Cardiovasc Diabetol ; 19(1): 152, 2020 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-32981521

RESUMO

BACKGROUND: Recent guidelines highlighted the association between atherosclerosis and triglyceride-enriched lipoproteins in patients with impaired glucose metabolism. However, evidence from prospective studies for long-term prognostic utility of low-density lipoprotein triglyceride (LDL-TG) in real-world patients with prediabetes (Pre-DM) or diabetes mellitus (DM) and coronary artery disease (CAD) is currently not available. The aim of the present study was to evaluate the impact of LDL-TG on major adverse cardiovascular events (MACEs) in patients with stable CAD under different glucose metabolism status. METHODS: A total of 4381 patients with CAD were consecutively enrolled and plasma LDL-TG level was measured by an automated homogeneous assay. They were categorized according to both status of glucose metabolism [DM, Pre-DM, normal glycaemia regulation (NGR)] and tertiles of LDL-TG. All subjects were followed up for the occurrence of MACEs. RESULTS: During a median of 5.1 (interquartile range 3.9 to 5.9) years' follow-up, 507 (11.6%) MACEs occurred. Cubic spline models showed a significant association between LDL-TG and MACEs in DM and Pre-DM but not in NGR. When the combined effect of elevated LDL-TG and glucose disorders was considered for risk stratification, the medium tertile of LDL-TG plus DM, and the highest tertile of LDL-TG plus Pre-DM or plus DM subgroups were associated with significantly higher risk of MACEs after adjustment of confounders including triglyceride [hazard ratios (95% confidence intervals): 1.843 (1.149-2.955), 1.828 (1.165-2.867), 2.212 (1.396-3.507), all p < 0.05]. Moreover, adding LDL-TG into the original model increased the C-statistic from 0.687 to 0.704 (∆C-statistic = 0.016, p = 0.028) and from 0.734 to 0.749 (∆C-statistic = 0.014, p = 0.002) in Pre-DM and DM, respectively. CONCLUSIONS: In this longitudinal cohort study on real-world practice, higher LDL-TG was associated with worse outcomes among Pre-DM and DM patients with stable CAD.

16.
Front Pediatr ; 8: 391, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32850525

RESUMO

Background: Kawasaki diseases (KD) is a febrile systemic vasculitis in infants associated with coronary aneurysm. The etiology of KD remains unclear. Human neutrophils have great capacity to cause tissue damage in inflammatory diseases via their inappropriate activation to release reactive oxygen species (ROS). Brain natriuretic peptide (BNP) is a substantial modulator of neutrophil activation to regulate ROS production. It is increasingly released from the myocardium in heart failure and myocardial inflammatory states. Objective: The purpose of this study was to explore the potential role of neutrophil respiratory burst in the pathogenesis of coronary artery lesions (CAL) in KD. Materials and Methods: A total of 78 children were enrolled. Of all the cases, 20 cases are healthy control (HC), 20 are with coronary artery lesion (CAL), and 38 are with non-coronary artery lesion (NCAL). The activation ratio of neutrophils was evaluated by flow cytometry. In addition, plasma levels of BNP were detected. Results: Our results showed that the activation ratio of neutrophils in KD with CAL is significantly higher than the other two groups (HC and NCAL). Besides, the plasma levels of BNP in KD (with or without CAL) were higher than that in HC. Conclusions: These findings suggested that neutrophil respiratory burst may play a significant role in the pathogenesis of CAL, and predicts the risk of CAL in Kawasaki disease.

17.
J Lipid Res ; 61(9): 1254-1262, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32641433

RESUMO

TG-rich lipoprotein (TRL)-related biomarkers, including TRL-cholesterol (TRL-C), remnant-like lipoprotein particle-cholesterol (RLP-C), and apoC-III have been associated with atherosclerosis. However, their prognostic values have not been fully determined, especially in patients with previous CAD. This study aimed to examine the associations of TRL-C, RLP-C, and apoC-III with incident cardiovascular events (CVEs) in the setting of secondary prevention of CAD. Plasma TRL-C, RLP-C, and total apoC-III were directly measured. A total of 4,355 participants with angiographically confirmed CAD were followed up for the occurrence of CVEs. During a median follow-up period of 5.1 years (interquartile range: 3.9-6.4 years), 543 (12.5%) events occurred. Patients with incident CVEs had significantly higher levels of TRL-C, RLP-C, and apoC-III than those without events. Multivariable Cox analysis indicated that a log unit increase in TRL-C, RLP-C, and apoC-III increased the risk of CVEs by 49% (95% CI: 1.16-1.93), 21% (95% CI: 1.09-1.35), and 40% (95% CI: 1.11-1.77), respectively. High TRL-C, RLP-C, and apoC-III were also independent predictors of CVEs in individuals with LDL-C levels ≤1.8 mmol/l (n = 1,068). The addition of RLP-C level to a prediction model resulted in a significant increase in discrimination, and all three TRL biomarkers improved risk reclassification. Thus, TRL-C, RLP-C, and apoC-III levels were independently associated with incident CVEs in Chinese CAD patients undergoing statin therapy.

18.
Cardiovasc Diabetol ; 19(1): 111, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32646432

RESUMO

BACKGROUND: Merging studies have reported the association of lipoprotein(a) [Lp(a)] with poor outcomes of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). However, the prognostic importance of Lp(a) for recurrent cardiovascular events (CVEs) is currently undetermined in patients with T2DM and prior CVEs. METHODS: From April 2011 to March 2017, we consecutively recruited 2284 T2DM patients with prior CVEs. Patients were categorized into low, medium, and high groups by Lp(a) levels and followed up for recurrent CVEs, including nonfatal acute myocardial infarction, stroke, and cardiovascular mortality. Kaplan-Meier, Cox regression and C-statistic analyses were performed. RESULTS: During 7613 patient-years' follow-up, 153 recurrent CVEs occurred. Lp(a) levels were significantly higher in patients with recurrent CVEs than counterparts (20.44 vs. 14.71 mg/dL, p = 0.002). Kaplan-Meier analysis revealed that the event-free survival rate was dramatically lower in high and medium Lp(a) groups than that in low group irrespective of HBA1c status (< 7.0%; ≥ 7.0%, both p < 0.05). Furthermore, multivariate Cox regression models indicated that Lp(a) was independently associated with high risk of recurrent CVEs [HR(95% CI): 2.049 (1.308-3.212)], such data remains in different HBA1c status (HR(95% CI): < 7.0%, 2.009 (1.051-3.840); ≥ 7.0%, 2.162 (1.148-4.073)). Moreover, the results of C-statistic were significantly improved by 0.029 when added Lp(a) to the Cox model. CONCLUSIONS: Our data, for the first time, confirmed that Lp(a) was an independent predictor for recurrent CVEs in T2DM patients with prior CVEs, suggesting that Lp(a) measurement may help to further risk stratification for T2DM patients after they suffered a first CVE.


Assuntos
Doenças Cardiovasculares/sangue , Diabetes Mellitus Tipo 2/sangue , Lipoproteína(a)/sangue , Idoso , Pequim/epidemiologia , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Causas de Morte , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Prospectivos , Recidiva , Medição de Risco , Fatores de Risco , Fatores de Tempo
19.
Cardiovasc Diabetol ; 19(1): 104, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631321

RESUMO

BACKGROUND: The atherogenicity of remnant cholesterol (RC) has been underlined by recent guidelines, which was linked to coronary artery disease (CAD), especially for patients with diabetes mellitus (DM). This study aimed to examine the prognostic value of plasma RC in the patients with CAD under different glucose metabolism status. METHODS: Fasting plasma RC were directly calculated or measured in 4331 patients with CAD. Patients were followed for the occurrence of major adverse cardiovascular events (MACEs) and categorized according to both glucose metabolism status [DM, pre-DM, normoglycemia (NG)] and RC levels. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals. RESULTS: During a mean follow-up of 5.1 years, 541 (12.5%) MACEs occurred. The risk for MACEs was significantly higher in patients with elevated RC levels after adjustment for potential confounders. No significant difference in MACEs was observed between pre-DM and NG groups (p > 0.05). When stratified by combined status of glucose metabolism and RC, highest levels of calculated and measured RC were significant and independent predictors of developing MACEs in pre-DM (HR: 1.64 and 1.98; both p < 0.05) and DM (HR: 1.62 and 2.05; both p < 0.05). High RC levels were also positively associated with MACEs in patients with uncontrolled DM. . CONCLUSIONS: In this large-scale and long-term follow-up cohort study, data firstly demonstrated that higher RC levels were significantly associated with the worse prognosis in DM and pre-DM patients with CAD, suggesting that RC may be a target for patients with impaired glucose metabolism.


Assuntos
Glicemia/metabolismo , Colesterol/sangue , Remanescentes de Quilomícrons/sangue , Doença da Artéria Coronariana/sangue , Diabetes Mellitus/sangue , Estado Pré-Diabético/sangue , Idoso , Biomarcadores/sangue , China/epidemiologia , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
20.
Nutrients ; 12(6)2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32521609

RESUMO

AIMS: The effect of algae and its extract supplementation on glycolipid metabolism has not been finalized. Therefore, the purpose of the meta-analyses was to assess the effects of its supplementation on glycolipid metabolism concentration. METHODS: We have systematically searched PubMed, Web of Science, the Cochrane Library and Embase to identify randomized controlled trials (RCTs) that investigated the impact of algae and its extracts supplementation on glycolipid metabolism. Effect size analysis was performed using weighted mean difference (WMD) and 95% CI between the methods of the experiment group and the control group. Subgroup analyses were performed to explore the possible influences of study characteristics. Publication bias and sensitivity analysis were also performed. RESULTS: A total of 27 RCTs (31 trials) with 1221 participants were finally selected for the meta-analysis. The algae and its extract intervention significantly decreased glycosylated hemoglobin (HbA1c, WMD = -0.18%; 95% CI: -0.27 to -0.10; p < 0.001), high-density lipoprotein cholesterol (HDL-C, WMD = -0.22 mmol/L; 95% CI: -0.38 to -0.06; p = 0.008), and triglycerides (TC, WMD = -0.31 mmol/L; 95% CI: -0.37 to -0.25; p < 0.001) levels and increased insulin (WMD = 6.05 pmol/mL; 95% CI: 4.01 to 8.09; p < 0.001) levels. It did not significantly change the blood glucose, homeostasis model assessment-insulin resistance index (HOMA-IR), 2-h post-meal blood glucose (2hPBG) and other lipid profiles. Subgroup analyses based on the duration of intervention and subjects demonstrated that the intervention of algae and its extracts for 10 weeks or fewer and more than 40 subjects decreased TC levels (p < 0.05). Moreover, the intervention reduced TC and 2hPBG concentrations for East Asians (p < 0.05). CONCLUSIONS: Our findings provided evidence that algae and its extract interventions were beneficial for the regulation of human glycolipid metabolism. More precise RCTs on subjects are recommended to further clarify the effect of algae, seaweed polysaccharide, seaweed polypeptide, algae polyphenol and its products intervention on glycolipid metabolism.


Assuntos
Suplementos Nutricionais , Glicolipídeos/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Alga Marinha/química , Estramenópilas/química , Grupo com Ancestrais do Continente Asiático , Glicemia/metabolismo , Feminino , Humanos , Masculino , Extratos Vegetais/isolamento & purificação , Período Pós-Prandial , Triglicerídeos/metabolismo
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