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BACKGROUND: This study aimed to investigate the associations between the triglyceride-glucose (TyG) index in young adulthood with incident cardiovascular disease (CVD) and mortality. METHODS: We included 4,754 participants from the Coronary Artery Risk Development in Young Adults study at baseline. The TyG index was calculated as ln (fasting TG [mg/dl] × fasting glucose [mg/dl]/2), and the TyG index trajectories were identified by using the latent class growth mixture model. We evaluated the association between the baseline and trajectories of the TyG index with incident CVD events and all-cause mortality using Cox proportional hazards regression analysis. The added value of the TyG index included in pooled cohort equations for CVD prediction was also analyzed. RESULTS: Among 4754 participants (mean age 24.72 years, 45.8% male, 51.2% black), there were 158 incident CVD events and 246 all-cause mortality during a median 25 years follow-up. After adjusting for multiple confounding variables, each one-unit increase in the TyG index was associated with a 96% higher CVD risk (hazard ratio [HR] 1.96, 95% confidence interval [CI] 1.44-2.66) and a 85% higher all-cause mortality risk (HR 1.85, 95% CI 1.45-2.36). Three distinct trajectories of the TyG index along the follow-up duration were identified: low (44.0%), moderate (45.5%), and high (10.5%). Compared with those participants in the low TyG index trajectory group, those in the high TyG index trajectory group had a greater risk of CVD events (HR 2.35, 95% CI 1.34-4.12) and all-cause mortality (HR 3.04, 95% CI 1.83-5.07). The addition of baseline TyG index to pooled cohort equations for CVD improved the C-statistics (P < 0.001), integrated discrimination improvement value (P < 0.001), and category-free net reclassification improvement value (P = 0.003). CONCLUSIONS: Higher baseline TyG index levels and higher long-term trajectory of TyG index during young adulthood were significantly associated with an increased risk of incident CVD events and all-cause mortality in later life.
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Doenças Cardiovasculares , Adulto , Biomarcadores , Glicemia/análise , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Triglicerídeos , Adulto JovemRESUMO
PURPOSE: We aimed to develop a simple risk score for patients with HFpEF and assessed the efficacy of spironolactone across baseline risk. METHODS: We developed risk stratification scheme for cardiovascular death in placebo arm of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial (TOPCAT). We screened candidate risk indicators and determined strong risk predictors using COX regression. The absolute risk reduction (ARR) in cardiovascular death with spironolactone was evaluated across baseline risk groups. COX regressions were performed to assess the hazard ratios (HRs) of spironolactone therapy for cardiovascular death and drug discontinuation in each risk category. RESULTS: A simple risk score scheme was constructed based on five risk indicators weighted by estimates from the model, including age, diastolic blood pressure, renal dysfunction, white blood cell, and left ventricular ejection fraction. The risk score scheme showed good discrimination in placebo cohort (C index=0.70). ARR with spironolactone therapy was observed only in patients at very high risk (7.9%). Spironolactone therapy significantly reduced the risk of cardiovascular death in the very high-risk group (HR: 0.57; 95%CI, 0.39-0.84; P =0.005 and P for interaction 0.03) but showed similar risk of drug discontinuation across risk categories (P for interaction=0.928). CONCLUSION: This simple risk score stratifies patients with HFpEF by their baseline risk of cardiovascular death. Patients at very high risk derive great benefits from spironolactone therapy. This easy-to-use risk score provides a practical tool that can facilitate risk stratification and tailoring therapy for those who benefit most from spironolactone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00094302.
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Insuficiência Cardíaca , Espironolactona , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Hospitalização , Humanos , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Medição de Risco , Espironolactona/efeitos adversos , Volume Sistólico/fisiologia , Resultado do Tratamento , Função Ventricular EsquerdaRESUMO
Objective: To explore the nutritional status of serum fat-soluble vitamins such as vitamin A, 25-hydroxyvitamin D, and vitamin E of minors in the Zhuzhou area to provide a scientific basis for clinical guidance to supplement fat-soluble vitamins reasonably. Method: A total of 6,082 minors who underwent physical examination from January 2017 to February 2019 in the Children's Health Department of Zhuzhou Hospital affiliated with XiangYa School of Medicine of Central South University were selected as the subjects to measure the levels of serum fat-soluble vitamins A, D, and E. Results: (1) Their average levels of serum vitamin A, 25-hydroxyvitamin D, and vitamin E were (0.34 ± 0.08) mg/mL, (34.65 ± 10.24) ng/mL, and (10.11 ± 2.65) mg/mL, respectively. (2) Serum vitamin E showed a gender difference (P < 0.001). (3) The average levels of serum 25-hydroxyvitamin D and vitamin E in infancy, early childhood, preschool age, school age, and adolescence decreased gradually (P < 0.05). In contrast, the average level of serum vitamin A ranged between 0.32 mg/mL and 0.37 mg/mL. (4) The age was negatively correlated with serum 25-hydroxyvitamin D (r = -0.517, P < 0.001) and weakly negatively correlated with vitamin E (r = -0.366, P < 0.001), but weakly positively correlated with vitamin A (r = 0.269, P < 0.001). Conclusion: Minors from infancy to adolescence in Zhuzhou should strengthen their supplementation of fat-soluble vitamins.
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Menores de Idade , Vitamina A , Criança , Adolescente , Pré-Escolar , Humanos , Vitaminas , Vitamina D , Vitamina E , Suplementos NutricionaisRESUMO
Wound exudate holds great clinical and research potential in wound repair via paracrine signaling. In essence, exudate is modified serum that contains a high concentration of exosomes. The aim of this study was to investigate the role of serum-derived exosomes in scald wound healing of NIH mice skin and to explore the underlying mechanisms. Hence, we constructed a deep second-degree scald model in NIH mice, testing the benefits of exosomes in the scald wound healing. The scratch wound assay, apoptosis assay and MTT assay were conducted to assess the effects of serum-derived exosomes on migration, apoptosis and proliferation of HaCaT cells and fibroblasts. Our results showed that serum-derived exosomes injected subcutaneously entered cells and effectively accelerated wound healing processes in mice. Additionally, serum-derived exosomes optimized functions of cells related to skin injury repair by stimulating fibroblast proliferation, promoting HaCaT cell migration, and suppressing apoptosis of HaCaT cells induced by heat stress. Further study revealed that serum-derived exosomes enhanced phosphorylation of the serine-threonine kinase Akt in scalded skin tissue. These results suggest a potential clinical use of serum-derived exosomes for treating skin scald.
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Exossomos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Cicatrização/efeitos dos fármacos , Animais , Produtos Biológicos/farmacologia , Linhagem Celular , Masculino , Camundongos , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/química , Ratos Sprague-Dawley , Soro/química , Pele/citologia , Pele/efeitos dos fármacos , Pele/lesõesRESUMO
Background: Previous studies have explored the associations between circulating inflammatory cytokines and blinding eye diseases, including glaucoma, cataract and macular degeneration. However, the causality of these associations remains controversial. This study employs a bidirectional Mendelian randomization (MR) study to investigate the causal relationships between 41 circulating inflammatory cytokines and these blinding eye diseases. Methods: Summary data for glaucoma, cataract, macular degeneration and 41 circulating inflammatory cytokines were publicly available. The inverse variance weighted (IVW) method was employed as the main analysis method. Additionally, various sensitivity tests, including MR-Egger regression, weighted median, weight mode, Cochran's Q test, MR pleiotropy Residual Sum and Outlier test, and leave-one-out test, were conducted to evaluate sensitivity and stability of results. Results: The IVW analysis identified six circulating inflammatory cytokines causally associated with the risk of blinding eye diseases: Monokine induced by interferon-gamma (MIG) for glaucoma, interleukin-1 receptor antagonist (IL-1ra), IL-6, IL-10, and platelet derived growth factor BB (PDGFbb) for cataract, and MIG and hepatocyte growth factor (HGF) for macular degeneration. However, it is noteworthy that none of these associations remained significant after Bonferroni correction (p < 0.0004). Reverse MR analyses indicated that cataract may lead to a decrease in vascular endothelial growth factor (VEGF) levels (OR: 3.326 × 10-04, 95% CI: 5.198 × 10-07 - 2.129 × 10-01, p = 0.0151). Conclusion: This study highlights the potential roles of specific inflammatory cytokines in the development of glaucoma, cataract and macular degeneration. Moreover, it suggests that VEGF is likely to be involved in cataract development downstream. These findings offer insights for early prevention and novel therapeutic strategies for these blinding eye diseases.
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This study analyzed 550 hemodialysis patients, 469 unvaccinated and 81 vaccinated against COVID-19, to assess the impact on infection rates, mortality, and clinical/laboratory parameters. Gender distribution was similar (p = 0.209), but the vaccinated group's median age was significantly lower (p = 0.005). Hospitalization rates showed no significant difference (p = 0.987), while mortality was lower in the vaccinated group (p = 0.041). Only uric acid levels were significantly higher in the vaccinated group (p = 0.009); other parameters, including creatinine and B-type natriuretic peptide, showed no significant differences. Age was an independent predictor of mortality (HR = 1.07, p < 0.001). Peak mortality occurred in December 2022 and January 2023, predominantly among unvaccinated patients. Although vaccination lowered mortality, it did not significantly affect long-term survival rates (p = 0.308). Logistic regression identified age and dialysis duration as significant mortality factors. Monthly death counts indicated higher mortality among unvaccinated patients during peak pandemic months, suggesting that vaccination provides some protection, though no significant long-term survival benefit was found.
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In this study, the height, sitting height, lower extremity length, growth status, and body proportions of elementary school students aged 6 to 12 years in Tianyuan District of Zhuzhou City, China, were analyzed. A total of 41,156 children from 38 elementary schools in the Tianyuan District of Zhuzhou City were selected for height measurement, employing the cluster sampling method. After the cluster data were obtained, the height and sitting height information were extracted, and calculations were performed for lower extremity length, sitting height-to-lower extremity length ratio, and sitting height-to-height ratio. Statistical analysis was conducted using SPSS 23.0 software. The height and sitting height measurements of boys and girls aged 6 to 12 years in Tianyuan District surpassed the 2005 national standard set for 9 cities, while the lower extremities of children within the 7 to 9 age range fell below the national standard. In alignment with the national average, the fitted curve representing height for both boys and girls aged 6 to 12 years in Tianyuan District exhibited an intersection point around 10 to 10.5 years. No discernible distinction was observed in the incidence of short stature, as analyzed through the P3 standard, between the fitted curve for Tianyuan District and the national standard. Moreover, tall children exhibited a significantly lower sitting height-to-height ratio compared to their shorter counterparts. The fitted height curve in Tianyuan District, Zhuzhou City, proves effective in discerning shorter-statured children within the region. Nevertheless, further research is warranted to elucidate the factors contributing to the comparatively shorter lower extremities observed in children from Tianyuan District, Zhuzhou City, in contrast to the national average.
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Estatura , Nanismo , Criança , Masculino , Feminino , Humanos , Postura Sentada , Prevalência , Cidades , Extremidade Inferior , EstudantesRESUMO
NF-κB signaling has been discovered for nearly 40 years. Initially, NF-κB signaling was identified as a pivotal pathway in mediating inflammatory responses. However, with extensive and in-depth investigations, researchers have discovered that its role can be expanded to a variety of signaling mechanisms, biological processes, human diseases, and treatment options. In this review, we first scrutinize the research process of NF-κB signaling, and summarize the composition, activation, and regulatory mechanism of NF-κB signaling. We investigate the interaction of NF-κB signaling with other important pathways, including PI3K/AKT, MAPK, JAK-STAT, TGF-ß, Wnt, Notch, Hedgehog, and TLR signaling. The physiological and pathological states of NF-κB signaling, as well as its intricate involvement in inflammation, immune regulation, and tumor microenvironment, are also explicated. Additionally, we illustrate how NF-κB signaling is involved in a variety of human diseases, including cancers, inflammatory and autoimmune diseases, cardiovascular diseases, metabolic diseases, neurological diseases, and COVID-19. Further, we discuss the therapeutic approaches targeting NF-κB signaling, including IKK inhibitors, monoclonal antibodies, proteasome inhibitors, nuclear translocation inhibitors, DNA binding inhibitors, TKIs, non-coding RNAs, immunotherapy, and CAR-T. Finally, we provide an outlook for research in the field of NF-κB signaling. We hope to present a stereoscopic, comprehensive NF-κB signaling that will inform future research and clinical practice.
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NF-kappa B , Fosfatidilinositol 3-Quinases , Humanos , Imunoterapia , NF-kappa B/genética , Transdução de Sinais/genéticaRESUMO
Background and aims: The benefits of reaching ideal cardiovascular health (CVH) are well known, but it is unclear whether positive CVH changes from young adulthood to middle age reduce subclinical atherosclerosis risk. This study examined associations of changes in CVH from young adulthood to middle age and CVH in young adulthood with subclinical atherosclerosis. Methods: Data was analyzed from the Coronary Artery Risk Development in Young Adults (CARDIA) study. CVH was examined at years 0 and 20 using Life Simple 7 metrics from AHA guideline. Coronary artery calcium (CAC) was identified at years 20 and 25. Carotid intima-media thickness (IMT) was identified at year 20. Results: Among 2,935 participants (56.2% women, 46.7% black), the change of CVH score was -1.26 (2.13). For per 1-unit increase in CVH at baseline, the adjusted odds ratios (ORs) of presence of CAC and IMT were 0.81 (95% CI 0.78, 0.86) and 0.85 (95% CI 0.76, 0.94), respectively. For per 1-unit increase in CVH changes, the adjusted ORs of CAC and IMT were 0.86 (95% CI 0.82, 0.90) and 0.81 (95% CI 0.73, 0.90). Compared with stable moderate CVH, improvement from moderate to high was associated with a lower risk of CAC (0.64 [95% CI 0.43, 0.96]), while retrogression from moderate to low was associated with a higher risk of CAC (1.45 [95% CI 1.19, 1.76]). Conclusions: Positive changes of CVH during young adulthood are associated with negative subclinical atherosclerosis risk in middle age, indicating the importance of reaching an ideal cardiovascular health status through young adulthood.
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Aterosclerose , Doenças Cardiovasculares , Doença da Artéria Coronariana , Humanos , Feminino , Pessoa de Meia-Idade , Adulto Jovem , Adulto , Masculino , Vasos Coronários/diagnóstico por imagem , Espessura Intima-Media Carotídea , Aterosclerose/epidemiologia , Nível de Saúde , Fatores de Risco , Doenças Cardiovasculares/epidemiologiaRESUMO
Craniofacial dysmorphism, cardiac abnormalities, ectodermal abnormalities, psychomotor delay, intellectual disability, and short stature are all hallmarks of the extremely rare disorder known as cardiofaciocutaneous syndrome (CFCS). Although CFCS is considered rare, approximately 300 cases have been documented in the literature. In this report, we discuss a patient diagnosed with CFCS without the typical heart malformations but with craniofacial features, skin abnormalities, intellectual disability, and short stature. Genetic testing revealed the presence of three potentially harmful variants: one in the MAP2K1 gene and two in the ATP2B3 and CDC42BPB genes, the significance of which is currently not yet found. Our findings in this case report suggest that the clinical symptoms of CFCS may be atypical, thereby expanding our understanding of the symptom spectrum of the disease. Simultaneously, the link between the clinical symptoms of the patient and the two unknown pathogenic variants has not been established. This case report supplements existing clinical reference material by providing valuable insights into the specific scenario.
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Background: Primary ciliary dyskinesia (PCD) is a group of autosomal recessive genetic diseases caused by abnormal ciliary ultrastructure and/or function, resulting in reduced ciliary clearance function or other dysfunctions. PCD is one of the causes of recurrent respiratory tract infections in children. At present, there is no gold standard for diagnosis. In patients clinically suspected with PCD, a variety of examination methods are available to assist in diagnosis, such as high-speed video microscopic imaging to analyze ciliary movement patterns, transmission electron microscopy to observe ciliary ultrastructure, genetic testing, and detection of nitric oxide content in nasal expiratory air. Case Description: We present a case summary of the clinical data and treatment process of a child with PCD and short stature induced by Novel exon 1 of CCNO mutation (NM-021147.5) at c.323del, and the proband father and mother were heterozygous mutators, who was diagnosed and treated in the Pediatric Healthcare Department of our hospital. We treated the child with recombinant human growth hormone to increase the height, and the patient was also advised to improve nutrition, prevent and control infections, and encouraged sputum expectoration. We also recommended regular follow-up visits to the outpatient department, and to seek other symptomatic and supportive treatments as necessary. Conclusion: The height and nutritional status of the child improved after treatment. We also reviewed relevant literature to help clinicians improve their understanding of this disease.
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Background: Floating-Harbor syndrome (FHS) is a rare autosomal dominant inherited disease characterized primarily by short stature, delayed language development, and typical facial features. There are currently few case reports, diagnoses and treatments for these syndromes at home and abroad. Case Description: This study reports a case of a boy with "growth and language development delay" as the predominant clinical manifestation. FHS was clinically diagnosed based on his growth hormone (GH) deficiency, significant bone age delay, left testicular hydrocele, and the whole exon gene in peripheral blood, which indicated heterozygous mutation of SRCAP gene. Following the treatment with recombinant human GH (rhGH), the child exhibited height increase benefits, and his articulation improved after language therapy. Conclusion: Genetic testing facilitates early detection, diagnosis, and treatment of the FHS. Additionally, treatment with rhGH effectively increases the height of these children, and language rehabilitation is especially important for their language development.
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AIMS: Prediabetes is a highly heterogenous metabolic state with increased risk of cardiovascular disease (CVD). Current guidelines raised the necessity of CVD risk scoring for prediabetes without clear recommendations. Thus, this study aimed to systematically assess the performance of 11 models, including five general population-based and six diabetes-specific CVD risk scores, in prediabetes. METHODS AND RESULTS: A cohort of individuals aged 40-69 years with prediabetes (HbA1c ≥ 5.7 and <6.5%) and without baseline CVD or known diabetes was identified from the UK Biobank, which was used to validate 11 prediction models for estimating 10- or 5-year risk of CVD. Model discrimination and calibration were evaluated by Harrell's C-statistic and calibration plots, respectively. We further performed decision curve analyses to assess the clinical usefulness.Overall, 56 831 prediabetic individuals were included, of which 4303 incident CVD events occurred within a median follow-up of 8.9 years. All the 11 risk scores assessed had modest C-statistics for discrimination ranging from 0.647 to 0.680 in prediabetes. Scores developed in the general population did not outperform those diabetes-specific models (C-statistics, 0.647-0.675 vs. 0.647-0.680), while the PREDICT-1° Diabetes equation developed for Type 2 diabetes performed best [0.680 (95% confidence interval, 0.672-0.689)]. The calibration plots suggested overall poor calibration except that the PREDICT-1° Diabetes equation calibrated well after recalibration. The decision curves generally indicated moderate clinical usefulness of each model, especially worse within high threshold probabilities. CONCLUSION: Neither risk stratification schemes for the general population nor those specific for Type 2 diabetes performed well in the prediabetic population. The PREDICT-1° Diabetes equation could be a substitute in the absence of better alternatives, rather than the general population-based scores. More precise and targeted risk assessment tools for this population remain to be established.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Humanos , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Fatores de Risco , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Bancos de Espécimes Biológicos , Medição de Risco/métodos , Fatores de Risco de Doenças Cardíacas , Reino Unido/epidemiologiaRESUMO
OBJECTIVE: To determine whether time-averaged cumulative blood pressure (cumBP) is associated with the risk of cardiovascular outcomes among patients with heart failure with preserved ejection fraction. METHOD: Three thousand, three hundred and thirty participants from Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial were included in this analysis with a median follow-up of 3âyears. CumBP, expressed as mmHg-years, was the sum of mean BP for each pair of successive examinations multiplied by the time. Time-averaged cumBP was calculated by dividing cumBP by total exposure time, also expressed as mmHg. Clinical outcomes of our study including primary endpoint, all-cause death, cardiovascular death and heart failure hospitalization. Multivariable Cox hazard regression models and a restricted cubic spline model were used to assess the association and linearity between time-averaged cumBP and adverse outcomes. RESULTS: There is a U-shaped relationship between time-averaged cumBP and primary endpoint, all-cause death, cardiovascular death and heart failure hospitalization among participants with HFpEF, with the nadir risk around 120-129âmmHg of SBP and 70-79âmmHg of DBP after adjusting for confounding variables. Treatment with spironolactone did not affect the association significantly. The finding remained robust across sensitivity analyses. CONCLUSION: Higher or lower time-averaged cumBP was significantly associated with a higher risk of adverse events. Control of time-averaged cumulative BP within a reasonable range was an important component of hypertension management in HFpEF.
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Anti-Hipertensivos , Insuficiência Cardíaca , Antagonistas de Receptores de Mineralocorticoides , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea , Insuficiência Cardíaca/tratamento farmacológico , Hospitalização , Humanos , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Prognóstico , Espironolactona/efeitos adversos , Volume Sistólico/fisiologia , Resultado do TratamentoRESUMO
AIMS: We aimed to investigate whether the triglyceride-glucose (TyG) index, an easy-calculated and reliable surrogate of insulin resistance, was associated with the development of heart failure (HF) and left ventricular (LV) dysfunction. METHODS AND RESULTS: A total of 12 374 participants (mean age: 54.1 ± 5.7 years, male: 44.7%) free of history of HF and coronary heart disease at baseline from the Atherosclerosis Risk in Communities study were included. The TyG index was calculated as ln[fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. The long-term TyG index was calculated as the updated cumulative average TyG index using all available TyG index from baseline to the events of HF or the end of follow-up. We evaluated the associations of both the baseline and the long-term TyG index with incident HF using Cox regression analysis. We also analysed the effect of the TyG index on LV structure and function among 4889 participants with echocardiographic data using multivariable linear regression analysis. There were 1958 incident HF cases over a median follow-up of 22.5 years. After adjusting for potential confounders, 1-SD (0.60) increase in the baseline TyG index was associated with a 15% higher risk of HF development [hazard ratio (HR): 1.15, 95% confidence interval (CI): 1.10-1.21]. Compared with participants in the lowest quartile of the baseline TyG index, those in the highest quartile had a greater risk of incident HF [HR (95% CI): 1.25 (1.08-1.45)]. In terms of LV structure and function, a greater baseline TyG index was associated with adverse LV remodelling and LV dysfunction. Similar results were found for the long-term TyG index. CONCLUSION: In a community-based cohort, we found that a greater TyG index was significantly associated with a higher risk of incident HF and impaired LV structure and function.
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Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Humanos , Masculino , Pessoa de Meia-Idade , Glucose , Triglicerídeos , Glicemia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/epidemiologiaRESUMO
Endothelial cells play a critical role in supporting postnatal hematopoiesis in the bone marrow. Unique endothelial cells, together with various perivascular cells, form different types of vascular structures, constructing a vast microvascular delivery and trafficking network for blood cells, oxygen, and nutrition. These blood vessels build distinct hematopoietic stem and progenitor cell niches, which offer not only sites of residence for blood cells but also indispensable signals directing HSPC homing, self-renewal, and multilineage differentiation. Deep insight into the structure and function of the BM vasculature niche and its participation in hematopoiesis is necessary to develop advanced strategies for the reconstitution of hematopoiesis.
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Medula Óssea/irrigação sanguínea , Hematopoese , Microvasos , Animais , Células Endoteliais , Células-Tronco Hematopoéticas , HumanosRESUMO
HYPOTHESIS: Graphene-based microparticles materials are broadly utilized in all sorts of fields owing to their outstanding properties. Despite great progress, the present graphene microparticles still face challenges in the aspects of size uniformity, motion flexibility, and tailorable surface chemistry, which limit their application in some specific fields, such as versatile adsorption. Hence, the development of novel graphene microparticles with the aforementioned characteristics is urgently required. EXPERIMENTS: We presented a simple microfluidic electrospray strategy to generate magnetic Janus reduced graphene oxide/carbon (rGO/C) composite microspheres with a variety of unique features. Specifically, the microfluidic electrospray method endowed the obtaiend microspheres with sufficient size uniformity as well as magnetic responsive motion ability. Additionally, magnetic-mediated surface assembly of phase transition lysozyme (PTL) nanofilm on the microspheres rendered the deposited area hydrophilic while non-deposited area hydrophobic. FINDINGS: Such magnetic Janus rGO/C composite microspheres with regionalized wettability characteristics not only showed prominent performance in adsorbing organic liquids with high adsorption capacity and remarkable reusability but also displayed satisfying biocompatibility for the efficient uptake of bilirubin. More encouragingly, the microspheres could serve as adsorbents in a simulative hemoperfusion setup, which further demonstrated the clinical application potential of the magnetic Janus rGO/C microspheres. Thus, we anticipate that the obtained magnetic Janus rGO/C composite microspheres could show multifunctional properties toward water treatment and blood molecule cleaning.
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Grafite , Adsorção , Carbono , Grafite/química , Fenômenos Magnéticos , Microfluídica , Microesferas , PorosidadeRESUMO
Background The association between blood pressure control and clinical outcomes is unclear among patients with heart failure with preserved ejection fraction. Both too high and too low of systolic blood pressure (SBP) have been reported to be related to poor clinical prognosis. This study aimed to assess the association between time in SBP target range and adverse clinical events among patients with heart failure with preserved ejection fraction. Methods and Results This study was a secondary analysis of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, a randomized clinical trial that compared the efficacy and safety of spironolactone in patients with heart failure with preserved ejection fraction. Time in target range (TTR) was calculated using linear interpolation, with the target range of SBP defined as 110 to 130 mm Hg. The association between TTR with adverse outcomes was estimated using multivariable Cox regression to adjust for multiple confounders. Participants with greater TTR were younger, more likely to be White, had less comorbidities, and lower body mass index. After adjusting for multiple covariates including mean SBP, 1-SD increment (38.3%) of TTR was significantly associated with a decreased risk of primary composite end point (hazard ratio [HR], 0.81 [0.73-0.90]), as well as a lower risk of all-cause mortality (HR, 0.81 [0.73-0.90]), cardiovascular death (HR, 0.78 [0.68-0.90]), and heart failure hospitalization (HR, 0.85 [0.74-0.97]). Results were similar when participants were categorized by TTR groups. Subgroup analyses showed that the associations were more significant in young people than in the old (Pinteraction=0.028). Conclusions In patients with heart failure with preserved ejection fraction, greater time in SBP target range was statistically associated with a decreased risk of cardiovascular outcomes and mortality events beyond blood pressure level, especially among younger patients.
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Insuficiência Cardíaca , Adolescente , Pressão Sanguínea/fisiologia , Humanos , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Prognóstico , Espironolactona/uso terapêutico , Volume Sistólico/fisiologiaRESUMO
Background: Chronically high blood pressure (HBP) is a known risk factor for cardiovascular diseases. We measured the intensity of hypertensive exposure in young adults and calculated its prognostic significance for subclinical atherosclerosis in middle age. Methods: The Coronary Artery Risk Development in Young Adults (CARDIA) study enrolled 5,115 healthy black and white Americans who were 18-30 years old at baseline (1985-1986). The intensity of hypertensive exposure was calculated as the area under the curve (mm Hg × years) from baseline to year 15. Coronary artery calcium (CAC) was identified at years 15, 20, and 25, and intima-media thickness (IMT) was identified at year 20. Results: At baseline, the mean age was 40.1 years; 55.1% of participants were women, and 46.5% were black. After adjustment, cumulative systolic BP (SBP) was positively associated with CAC [hazard ratio (HR) = 1.23 (1.14, 1.32)] and IMT [ß = 0.022 (0.017, 0.028)]. For CAC, the C-statistic for cumulative SBP was 0.643 (0.619, 0.667); compared to baseline SBP, the net reclassification index (NRI) of cumulative SBP was 0.180 (0.115, 0.256) and the integrated discrimination improvement (IDI) was 0.023 (0.012, 0.036). For IMT, the C-statistic for cumulative SBP was 0.674 (0.643, 0.705), the NRI was 0.220 (0.138, 0.305), and the IDI was 0.008 (0.004, 0.0012). Conclusion: Greater intensity of hypertensive exposure in early adulthood is associated with subclinical atherosclerosis in middle age and provides better prognostic value than baseline BP for early cardiovascular risk.
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BACKGROUND: Type 2 diabetes mellitus (T2DM) patients may have cardiac remodeling and dysfunction from the early stage of disease. This study aimed to determine the association between cystatin C (CysC) and early cardiac functional or structural impairment in T2DM patients without renal dysfunction. METHODS: A total of 1135 T2DM patients without renal dysfunction and known heart diseases were included in our study. Cardiac function and structure were evaluated by echocardiography. Patients were diagnosed as left ventricular hypertrophy (LVH), impaired left ventricular (LV) diastolic function, and categorized into four different LV geometry patterns including normal, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. RESULTS: In multivariate linear regression analyses, CysC was positively associated with interventricular septum, LV mass index, left atrial volume index, E/e' ratio, and negatively associated with Tissue Doppler e', E/A ratio (p < .05). As a continuous variable, increasing CysC levels were associated with prevalence of LVH (OR: 1.47, 95% confidence interval [CI]: 1.22-1.77), impaired LV diastolic function (OR: 1.58, 95% CI: 1.33-1.87), concentric hypertrophy (OR: 1.54, 95% CI: 1.23-1.93) and eccentric hypertrophy (OR: 1.34, 95% CI: 1.00-1.80) according to multivariate logistic regression analyses. While as a categorical variable, the highest CysC quartile (CysC > 1.04 mg/L) was associated with LVH (OR: 2.95, 95% CI: 1.74-5.00), impaired LV diastolic function (OR: 4.09, 95% CI: 2.54-6.60), and concentric hypertrophy (OR: 3.26, 95% CI: 2.05-5.18). CONCLUSIONS: CysC was significantly associated with early LV remodeling and cardiac functional impairment in T2DM patients with normal renal function. It could be a reliable and convenient biomarker detecting early impairment of cardiac function and structure in T2DM patients.