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1.
J Transl Med ; 18(1): 26, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31948436

RESUMO

Upon publication of the original article [1], it was noticed that Jun Tao's affiliation information is not complete. The full affiliation information for Jun Tao can be found below and in the complete affiliation list of this Correction article.

2.
J Neuroinflammation ; 17(1): 12, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31918729

RESUMO

BACKGROUND: Dickkopf-3 (Dkk-3) is implicated in the progression of atherosclerosis. This study aimed to investigate the association between serum Dkk-3 and the prognosis of ischemic stroke. METHODS: We measured serum Dkk-3 levels in 3344 ischemic stroke patients from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). The primary outcome was a combination of death and vascular events within 3 months after ischemic stroke. RESULTS: During 3 months of follow-up, the cumulative incidence rates of primary outcome among ischemic stroke patients in five quintiles of serum Dkk-3 (from low to high) were 4.49%, 3.74%, 2.54%, 5.23%, and 6.73%, respectively (log-rank p = 0.004). Multivariable Cox proportional hazards regression analyses showed that compared with the third quintile of serum Dkk-3, the adjusted hazard ratios (95% confidence intervals) associated with the first and fifth quintile were 3.49 (1.46-8.34) and 4.23 (1.86-9.64) for primary outcome, 3.47 (1.06-11.36) and 5.30 (1.81-15.51) for death, and 2.66 (1.01-7.01) and 3.35 (1.33-8.40) for vascular events, respectively. Multivariable-adjusted Cox proportional hazards regression model with restricted cubic splines showed a U-shaped association between serum Dkk-3 and the risk of primary outcome (p for nonlinearity = 0.030). Moreover, adding serum Dkk-3 to conventional risk factors could improve the predictive power for primary outcome (net reclassification improvement 28.44%, p < 0.001; integrated discrimination improvement 0.48%, p = 0.001). CONCLUSIONS: Both low and high serum Dkk-3 levels are associated with increased risks of death and vascular events within 3 months after ischemic stroke, indicating that serum Dkk-3 may have a special effect on the prognosis of ischemic stroke. We also found that serum Dkk-3 might be a prognostic biomarker for ischemic stroke. Further studies are needed to replicate our findings and to determine the optimal levels of serum Dkk-3.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31831364

RESUMO

BACKGROUND AND AIMS: High serum hepatocyte growth factor (HGF) levels increase the risk of ischemic stroke and are probably associated with outcomes after ischemic stroke. However, it remains unclear whether the association between HGF and ischemic stroke prognosis is modified by blood lipid status. METHODS AND RESULTS: Data were derived from the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke), and we measured baseline serum HGF levels in 3027 ischemic stroke patients. The primary outcome was a combination of death and major disability (modified Rankin Scale score≥3) at 2 years after ischemic stroke. Blood lipid status could modify association between HGF and ischemic stroke prognosis (Pinteraction = 0.002). After multivariate adjustment, the odds ratios of primary outcome associated with the highest tertile of HGF were 2.13 (95% CI, 1.45-3.14; Ptrend<0.001) for patients with dyslipidemia and 0.81 (95% CI, 0.54-1.22; Ptrend = 0.310) for those with normal lipids. Adding HGF to conventional risk factors improved risk prediction for primary outcome in patients with dyslipidemia (net reclassification improvement: 24.28%, P < 0.001; integrated discrimination index: 0.43%, P = 0.022) but not in those with normal lipids. Secondary analyses further revealed that HDL-C was the main lipid component to modify the prognostic significance of serum HGF among ischemic stroke patients. CONCLUSIONS: There was a modified effect of blood lipid status on the association between serum HGF and ischemic stroke prognosis. Elevated serum HGF was associated with outcomes in ischemic stroke patients with dyslipidemia, especially low HDL-C. Further studies are warranted to replicate our findings and clarify the potential biological mechanisms.

4.
Atherosclerosis ; 293: 42-48, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31835040

RESUMO

BACKGROUND AND AIMS: Endostatin is implicated in the atherosclerosis process and serves as a promising cardiovascular biomarker, while its clinical significance in ischemic stroke patients remains unclear. We aimed to examine the association between endostatin and mortality and disability after ischemic stroke. METHODS: A total of 3463 acute ischemic stroke patients with measured plasma endostatin from the China Antihypertensive Trial in Acute Ischemic Stroke were included in this study. The primary outcome was death or severe disability (modified Rankin scale score of 4-6), and secondary outcomes included death and vascular events. RESULTS: After 3-month follow-up, 402 (11.61%) participants experienced severe disability or died. Compared with the lowest quartile of endostatin, odds ratios or hazard ratios (95% confidence intervals) for the highest quartile were 1.47 (1.04-2.09) for the primary outcome, and 2.36 (1.23-4.54) for death after adjustment for multiple covariates, including age, sex, admission NIH Stroke Scale score and systolic blood pressure. Each 1-SD higher log-transformed endostatin was associated with a 20% (6%-36%) increased risk for primary outcome. Adding plasma endostatin to the basic model constructed with conventional factors significantly improved risk stratification of primary outcome, as observed by the category-free net reclassification index of 20.5% (95% CI 10.1%-30.8%; p < 0.001) and integrated discrimination improvement of 0.3% (95% CI 0.01%-0.6%; p = 0.04). CONCLUSIONS: Increased baseline plasma endostatin levels in acute ischemic stroke were associated with increased risk of mortality and severe disability at 3 months. Plasma endostatin may serve as an important prognostic marker for risk stratification in patients with ischemic stroke.

5.
PLoS Genet ; 15(12): e1008500, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31869403

RESUMO

Most genome-wide association and fine-mapping studies to date have been conducted in individuals of European descent, and genetic studies of populations of Hispanic/Latino and African ancestry are limited. In addition, these populations have more complex linkage disequilibrium structure. In order to better define the genetic architecture of these understudied populations, we leveraged >100,000 phased sequences available from deep-coverage whole genome sequencing through the multi-ethnic NHLBI Trans-Omics for Precision Medicine (TOPMed) program to impute genotypes into admixed African and Hispanic/Latino samples with genome-wide genotyping array data. We demonstrated that using TOPMed sequencing data as the imputation reference panel improves genotype imputation quality in these populations, which subsequently enhanced gene-mapping power for complex traits. For rare variants with minor allele frequency (MAF) < 0.5%, we observed a 2.3- to 6.1-fold increase in the number of well-imputed variants, with 11-34% improvement in average imputation quality, compared to the state-of-the-art 1000 Genomes Project Phase 3 and Haplotype Reference Consortium reference panels. Impressively, even for extremely rare variants with minor allele count <10 (including singletons) in the imputation target samples, average information content rescued was >86%. Subsequent association analyses of TOPMed reference panel-imputed genotype data with hematological traits (hemoglobin (HGB), hematocrit (HCT), and white blood cell count (WBC)) in ~21,600 African-ancestry and ~21,700 Hispanic/Latino individuals identified associations with two rare variants in the HBB gene (rs33930165 with higher WBC [p = 8.8x10-15] in African populations, rs11549407 with lower HGB [p = 1.5x10-12] and HCT [p = 8.8x10-10] in Hispanics/Latinos). By comparison, neither variant would have been genome-wide significant if either 1000 Genomes Project Phase 3 or Haplotype Reference Consortium reference panels had been used for imputation. Our findings highlight the utility of the TOPMed imputation reference panel for identification of novel rare variant associations not previously detected in similarly sized genome-wide studies of under-represented African and Hispanic/Latino populations.

6.
J Transl Med ; 17(1): 368, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718666

RESUMO

BACKGROUND: Hypertension often presents with microvascular rarefaction (MVR), which is closely associated with impaired angiogenesis. Early detection of MVR is essential for systemic assessment in patient with hypertension. We aimed to determine the systemic MVR through both optical coherence tomography angiography (OCTA) and intravital capillaroscopy, and to investigate their respective efficacies and related mechanisms associated with late endothelial progenitor cells (LEPCs) dysfunction. METHODS: Seventy-one hypertensive and sixty-nine age-match normotensive subjects were included in this study. All subjects received intravital capillaroscopy for skin capillary density (SCD) and OCTA for retinal capillary density (RCD) and non-perfused areas (R-NPA). Subsequently, correlation of LEPCs activities and microvascular rarefaction were examined. RESULTS: Compared with normotensive subjects, hypertensive patients had significantly lower RCD [(52.9 ± 2.9)% vs. (57.8 ± 1.6)%, P < 0.01] and higher R-NPA [(0.12 ± 0.07) mm2 vs. (0.053 ± 0.020) mm2, P < 0.01]. SCD correlated positively with RCD but negatively with R-NPA [(RCD: OR = 0.40, 95% CI 0.25-0.67, P < 0.01); (R-NPA: OR = 0.39, 95% CI - 0.0029 to 0.0011, P < 0.01)]. The discriminative powers of RCD performed best (AUC 0.79 versus SCD AUC 0.59, P < 0.001) followed by R-NPA (AUC 0.73 versus SCD AUC 0.59, P < 0.001) for systolic blood pressure. Similar pattern is also found for diastolic blood pressure (RCD AUC 0.80 versus SCD AUC 0.54, P < 0.001; R-NPA AUC 0.77 versus SCD AUC 0.54, P < 0.001). Furthermore, LEPCs tube formation was impaired in hypertensive patients (36.8 ± 2.3 vs. 28 ± 3.7, P < 0.01). After multivariate adjustments, positive correlation existed between RCD or R-NPA with LEPCs tube formation (RCD: ß = 0.64, 95% CI 0.34-0.91, P < 0.01; R-NPA: ß = - 24.67, 95% CI - 43.14 to - 4.63, P < 0.05) but not with SCD (ß = 0.082, 95% CI 0.01-0.18, P = 0.085). CONCLUSION: Compared to intravital capillaroscopy, OCTA is a more precise technique for early detection of hypertensive microvascular rarefaction, which is associated with the fall in LEPC-mediated angiogenesis. Both of OCTA and LEPCs function can help identify hypertension-related capillary abnormality. Trail Registration The trial is a substudy of EXCAVATION-CHN1, registered at clinicaltrials.gov as NCT02817204 (June 26, 2016).

7.
Am J Kidney Dis ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31732235

RESUMO

RATIONALE & OBJECTIVES: Few studies have investigated racial disparities in survival among dialysis patients in a manner that considers risk factors and mortality during the phase of kidney disease before maintenance dialysis. Our objective was to explore racial variations in survival among dialysis patients and relate them to racial differences in comorbid conditions and rates of death in the setting of kidney disease not yet requiring dialysis therapy. STUDY DESIGN: Retrospective cohort study. SETTINGS & PARTICIPANTS: 3,288 black and white participants in the Chronic Renal Insufficiency Cohort (CRIC), none of whom were receiving dialysis at enrollment. EXPOSURE: Race. OUTCOME: Mortality. ANALYTIC APPROACH: Cox proportional hazards regression was used to examine the association between race and mortality starting at: (1) time of dialysis initiation and (2) entry into the CRIC. RESULTS: During 7.1 years of median follow-up, 678 CRIC participants started dialysis. Starting from the time of dialysis initiation, blacks had lower risk for death (unadjusted HR, 0.67; 95% CI, 0.51-0.87) compared with whites. Starting from baseline CRIC enrollment, the strength of the association between some risk factors and dialysis was notably stronger for whites than blacks. For example, the HR for dialysis onset in the presence (vs absence) of heart failure at CRIC enrollment was 1.30 (95% CI, 1.01-1.68) for blacks versus 2.78 (95% CI, 1.90-4.50) for whites, suggesting differential severity of these risk factors by race. When we included deaths occurring both before and after dialysis, risk for death was higher among blacks (vs whites) starting from CRIC enrollment (HR, 1.41; 95% CI, 1.22-1.64), but this finding was attenuated in adjusted models (HR, 1.08; 95% CI, 0.91-1.28). LIMITATIONS: Residual confounding. CONCLUSIONS: The apparent survival advantage among blacks over whites treated with dialysis may be attributed to selected transition of a subset of whites with more severe comorbid conditions onto dialysis.

9.
Aging (Albany NY) ; 11(21): 9893-9900, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31707361

RESUMO

This study aimed to dissect the direct effect of smoking and its indirect effect through body mass index (BMI) on leukocyte telomere length (LTL) and to distinguish the mediation and suppression effects of BMI. The study cohort included 1,037 adults (729 Whites and 308 African Americans; 42.1% males; mean age: 40.3 years) with LTL measurements by Southern blotting. General third variable models were used to distinguish the mediation and suppression effects of BMI on the smoking-LTL association. After adjusting for age, race, sex and alcohol drinking, the total effect of smoking on LTL was significant (standardized regression coefficient, ß= -0.061, p=0.034) without BMI included in the model. With additional adjustment for BMI, the indirect effect of smoking on LTL through BMI was estimated at ß= 0.011 (p=0.023), and the direct effect of smoking on LTL was strengthened to ß= -0.072 (p=0.012). The results were similar when pack-years of smoking was used. The effect parameters did not differ significantly between race and sex groups. These results suggest that BMI has a suppression effect, not a mediation effect, on the smoking-LTL association, which potentially contributes to previous inconsistencies in the effect of smoking on LTL.

10.
Metabolomics ; 15(12): 149, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31720858

RESUMO

INTRODUCTION: Chronic kidney disease (CKD) is a major public health challenge given its high global prevalence and associated risks of cardiovascular disease and progression to end stage renal disease. Although it is known that numerous metabolic changes occur in CKD patients, identifying novel metabolite associations with kidney function may enhance our understanding of the physiologic pathways relating to CKD. OBJECTIVES: The objective of this study was to elucidate novel metabolite associations with kidney function among participants of two community-based cohorts with carefully ascertained metabolomics, kidney function, and covariate data. METHODS: Untargeted ultrahigh-performance liquid chromatography-tandem mass spectrometry was used to detect and quantify blood metabolites. We used multivariate adjusted linear regression to examine associations between single metabolites and creatinine-based estimated glomerular filtration rate (eGFRcr) among 1243 Bogalusa Heart Study (BHS) participants (median eGFRcr: 94.4, 5th-95th percentile: 66.0-119.6 mL/min/1.73 m2). Replication, determined by statistical significance and consistent effect direction, was tested using gold standard measured glomerular filtration rate (mGFR) among 260 Multi-Ethnic Study of Atherosclerosis (MESA) participants (median mGFR: 72.0, 5th-95th percentile: 43.5-105.0 mL/min/1.73 m2). All analyses used Bonferroni-corrected alpha thresholds. RESULTS: Fifty-one novel metabolite associations with kidney function were identified, including 12 from previously unrelated sub-pathways: N6-carboxymethyllysine, gulonate, quinolinate, gamma-CEHC-glucuronide, retinol, methylmalonate, 3-hydroxy-3-methylglutarate, 3-aminoisobutyrate, N-methylpipecolate, hydroquinone sulfate, and glycine conjugates of C10H12O2 and C10H14O2(1). Significant metabolites were generally inversely associated with kidney function and smaller in mass-to-charge ratio than non-significant metabolites. CONCLUSION: The 51 novel metabolites identified may serve as early, clinically relevant, kidney function biomarkers.

11.
Zhongguo Zhong Yao Za Zhi ; 44(15): 3178-3186, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602870

RESUMO

Ziziphora bungeana is a kind of medicinal plants belongs to Labiatae,and it also a kind of geoherbs in Xinjiang. The main active ingredient linarin has a higher content in inflorescence than in other parts. In this study,high-throughput sequencing technology was used to reveal the transcriptome of the inflorescence of Z. bungeana,77 366 unigenes were acquired,of which 56 375 unigenes were annotated based on search of the database and classification. Through the analysis of metabolic pathways,sixty unigenes were probably encoding some enzymes involved in the flavonoid biosynthesis pathways. The contents of linarin in different parts were determined and the key genes were verified by qRT-PCR. The discovery provides the research basis for further analysis of the enzyme genes involved in the biosynthesis of the major flavonoid components in Z. bungeana.


Assuntos
Flavonoides/biossíntese , Lamiaceae/química , Transcriptoma , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala
12.
Medicine (Baltimore) ; 98(41): e17455, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593102

RESUMO

INTRODUCTION: Behçet disease (BD) is an autoimmune disorder characterized by oral aphthosis, genital aphthosis, ocular lesions, and arthritis. However, other fatal complications are often misdiagnosed, which implies that the early diagnosis of the disease is important for a good prognosis. PATIENT CONCERNS: A 51-year-old man complained of hematemesis for 5 hours and syncope once. DIAGNOSIS: BD as demonstrated by esophageal ulcer and aortic aneurysm rupture. INTERVENTIONS: Surgeries were conducted to repair the thoracic aortic aneurysm, proton-pump inhibitor was used to reduce acid secretion, antibiotics were applied for anti-infective therapy, and immunosuppressor was administered to control the injuries of BD. OUTCOMES: The patient was discharged and his medication dosage was reduced gradually until the minimum maintenance dose. In the follow-ups, the gastric ulcer and vascular aneurysm were not found. CONCLUSION: We presented a rare case of BD with the concurrence of huge esophageal ulcer and thoracic aortic aneurysms rupture, which helped us to diagnose BD at the early stage, while confronting atypical manifestations.


Assuntos
Aneurisma da Aorta Torácica/etiologia , Ruptura Aórtica/etiologia , Síndrome de Behçet/complicações , Doenças do Esôfago/etiologia , Hemorragia Gastrointestinal/etiologia , Humanos , Masculino , Pessoa de Meia-Idade
13.
Circ J ; 83(11): 2303-2311, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31564697

RESUMO

BACKGROUND: Matrix metalloproteinase-9 (MMP-9), a key determinant of extracellular matrix degradation, might cause cerebral damage after stroke and be involved in the development of depressive symptoms. This study aimed to evaluate the association of serum MMP-9 levels and post-stroke depression (PSD).Methods and Results:Serum MMP-9 levels were determined in 558 acute ischemic stroke patients from 7 hospitals comprising the China Antihypertensive Trial in Acute Ischemic Stroke. We assessed depression status using the 24-item Hamilton Depression Rating Scale and defined PSD as a cutoff score of 8. Logistic regression was performed to estimate the risk of PSD associated with serum MMP-9. Discrimination and reclassification for PSD by MMP-9 were analyzed. A total of 222 (39.8%) stroke patients were categorized as PSD within 3 months. Serum MMP-9 concentrations were higher among PSD patients than those without PSD (658.8 vs. 485.7 ng/mL; P<0.001). The multiple-adjusted odds ratio (95% confidence interval) for the highest MMP-9 quartile compared with the lowest quartile was 4.36 (2.49-7.65) for PSD, and 1 standard deviation higher log-MMP-9 was associated with 68% (37-106%) increased odds of PSD. Adding MMP-9 to the conventional risk factors model substantially improved discrimination and reclassification for PSD (all P<0.05). CONCLUSIONS: Elevated serum MMP-9 levels in the acute phase of ischemic stroke were associated with increased risk of PSD, suggesting an important prognostic role of MMP-9 for PSD.

14.
Clin Chem ; 65(11): 1448-1457, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31578216

RESUMO

BACKGROUND: Increases in cardiac and stress biomarkers may be associated with loss of kidney function through shared mechanisms involving cardiac and kidney injury. We evaluated the associations of cardiac and stress biomarkers [N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT), growth differentiation factor 15 (GDF-15), soluble ST-2 (sST-2)] with progression of chronic kidney disease (CKD). METHODS: We included 3664 participants with CKD from the Chronic Renal Insufficiency Cohort study. All biomarkers were measured at entry. The primary outcome was CKD progression, defined as progression to end-stage renal disease (ESRD) or 50% decline in estimated glomerular filtration rate (eGFR). Cox models tested the association of each biomarker with CKD progression, adjusting for demographics, site, diabetes, cardiovascular disease, eGFR, urine proteinuria, blood pressure, body mass index, cholesterol, medication use, and mineral metabolism. RESULTS: There were 1221 participants who had CKD progression over a median (interquartile range) follow-up of 5.8 (2.4-8.6) years. GDF-15, but not sST2, was significantly associated with an increased risk of CKD progression [hazard ratios (HRs) are per SD increase in log-transformed biomarker]: GDF-15 (HR, 1.50; 95% CI, 1.35-1.67) and sST2 (HR, 1.07; 95% CI, 0.99-1.14). NT-proBNP and hsTnT were also associated with increased risk of CKD progression, but weaker than GDF-15: NT-proBNP (HR, 1.24; 95% CI, 1.13-1.36) and hsTnT (HR, 1.11; 95% CI, 1.01-1.22). CONCLUSIONS: Increases in GDF-15, NT-proBNP, and hsTnT are associated with greater risk for CKD progression. These biomarkers may inform mechanisms underlying kidney injury.

15.
Medicine (Baltimore) ; 98(42): e17557, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626119

RESUMO

BACKGROUND: Mild cognitive impairment (MCI) and Alzheimer's disease (AD) are neurodegenerative diseases associated with aging. The major clinical features of both are progressive memory loss and progressive cognitive loss. The objective of this systematic review protocol is to provide the methods for evaluating the effectiveness of acupuncture in the treatment on cognitive deficits in transgenic mouse. METHODS AND ANALYSIS: We will search the electronic databases of PubMed, Web of Science, Embase, PsycINFO, as well as the Chinese databases such as Chinese Biomedicine Literature (CBM), Chinese Medical Current Content (CMCC), Chinese Scientific Journal Database (VIP), WanFang Database and China National Knowledge Infrastructure (CNKI) from their inceptions to July 2019. RevMan 5.3 software will be used for the data synthesis and the quality of each study was assessed independently by use of the CAMARADES checklist. RESULTS: This review will provide a high-quality synthesis based on present evidence of acupuncture treatment for AD and MCI in transgenic mouse models. CONCLUSIONS: This systematic review will provide evidence for weather acupuncture is an effective intervention for AD and MCI in transgenic mouse models. ETHICS AND DISSEMINATION: Ethical approval is not necessary since this protocol is only for systematic review and does not involve privacy data or conduct an animal experiment. This protocol will be disseminated by a peer-review journal or conference presentation. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019142985. STRENGTHS AND LIMITATIONS OF THIS STUDY: This systematic review will be the first to provide new knowledge underlying the effectiveness to improve cognitive function of acupuncture treatment for AD and MCI in transgenic mouse models. The result of this systematic review may provide experimental and theoretical basis for the future clinical application of acupuncture in the treatment of AD.The limitation of this systematic review may come from language barriers, because only English and Chinese can be included. Also, this study includes various kinds of acupuncture treatments which may result in essential heterogeneity.


Assuntos
Terapia por Acupuntura/métodos , Doença de Alzheimer/terapia , Cognição/fisiologia , Disfunção Cognitiva/terapia , Doença de Alzheimer/complicações , Doença de Alzheimer/fisiopatologia , Animais , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Modelos Animais de Doenças , Camundongos , Camundongos Transgênicos
16.
J Am Heart Assoc ; 8(21): e012336, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31645163

RESUMO

Background Cardiac biomarkers may signal mechanistic pathways involved in heart failure (HF), a leading complication in chronic kidney disease. We tested the associations of NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity troponin T (hsTnT), galectin-3, growth differentiation factor-15 (GDF-15), and soluble ST2 (sST2) with incident HF in chronic kidney disease. Methods and Results We examined adults with chronic kidney disease enrolled in a prospective, multicenter study. All biomarkers were measured at baseline. The primary outcome was incident HF. Secondary outcomes included HF with preserved ejection fraction (EF≥50%) and reduced ejection fraction (EF<50%). Cox models were used to test the association of each cardiac biomarker with HF, adjusting for demographics, kidney function, cardiovascular risk factors, and medication use. Among 3314 participants, all biomarkers, with the exception of galectin-3, were significantly associated with increased risk of incident HF (hazard ratio per SD higher concentration of log-transformed biomarker): NT-proBNP (hazard ratio, 2.07; 95% CI, 1.79-2.39); hsTnT (hazard ratio, 1.38; 95% CI, 1.21-1.56); GDF-15 (hazard ratio, 1.44; 95% CI, 1.26-1.66) and sST2 (hazard ratio, 1.19; 95% CI, 1.05-1.35). Higher NT-proBNP, hsTnT, and GDF-15 were also associated with a greater risk of HF with reduced EF; while higher NT-proBNP GDF-15 and sST2 were associated with HF with preserved EF. Galectin-3 was not associated with either HF with reduced EF or HF with preserved EF. Conclusions In chronic kidney disease, elevations of NT-proBNP, hsTnT, GDF-15, sST2 were associated with incident HF. There was a borderline association of galectin-3 with incident HF. NT-proBNP and hsTnT were more strongly associated with HF with reduced EF, while the associations of the newer biomarkers GDF-15 and sST2 were stronger for HF with preserved EF.

17.
Mol Imaging Biol ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31650482

RESUMO

PURPOSE: Diabetic retinopathy (DR) is characterized by dopaminergic neuron loss in the retina of the eyes. [18F]fluoropropyl-(+)-dihydrotetrabenazine ([18F]FP-(+)-DTBZ) positron emission tomography (PET) has been shown to detect dopaminergic neuron loss. The study is to investigate the feasibility of PET imaging with [18F]FP-(+)-DTBZ for early diagnosis of diabetic retinopathy (DR) in diabetes mellitus (DM) rat models. METHODS: The DM rat model was established by a single intraperitoneal injection of streptozotocin (STZ) (65 mg/kg). After 4 weeks, 8 weeks, and 12 weeks of STZ injection, the retinas of the rats were evaluated by electroretinogram (ERG), color fundus photography (CFP), fundus fluorescein angiography (FFA), and small animal PET scan with [18F]FP-(+)-DTBZ by targeting vesicular monoamine transporter 2 (VMAT2). [18F]FP-(+)-DTBZ uptake in retina was quantified as standardized uptake value (SUV). Immunofluorescence staining and Western blot were also performed to confirm the expression level of VMAT2 in retina. RESULTS: ERG dysfunction was observed at 8 weeks in STZ-diabetic rats, evidenced by smaller amplitudes of oscillatory potentials (OPs) when compared with OPs in normal rats. CFP and FFA showed no significant difference in vascular leakage and neovascularization between STZ-diabetic retinas and normal ones until 8 weeks. PET imaging revealed that the SUV of [18F]FP-(+)-DTBZ was significantly lower in the STZ-diabetic retinas compared with the normal ones as early as of week 4. The results from immunofluorescence staining and Western blots confirmed the early findings in PET imaging studies. CONCLUSIONS: Early DR can be non-invasively detected with PET imaging using [18F]FP-(+)-DTBZ targeting VMAT2. The expression level of VMAT2 in retina may act as a new biomarker for early DR diagnosis.

18.
Neurology ; 93(18): e1675-e1685, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31551260

RESUMO

OBJECTIVE: To prospectively investigate the relationships between serum tissue inhibitor metalloproteinase-1 (TIMP-1) and clinical outcomes in patients with acute ischemic stroke. METHODS: We derived data from the China Antihypertensive Trial in Acute Ischemic Stroke. Baseline serum TIMP-1 concentrations were measured in 3,342 participants. The primary outcome was the combination of death and major disability (modified Rankin Scale score ≥3) at 3 months after ischemic stroke, and secondary outcomes included major disability, death, and vascular events. RESULTS: A total of 843 participants (25.2%) experienced major disability or died within 3 months. After adjustment for age, sex, admission NIH Stroke Scale score, and other important covariates, odds ratios or hazard ratios (95% confidence intervals) of 1-SD (0.17 ng/mL) higher log-TIMP-1 were 1.17 (1.06-1.29) for the primary outcome, 1.13 (1.02-1.25) for major disability, 1.49 (1.19-1.87) for death, and 1.34 (1.11-1.62) for the composite outcome of death and vascular events. The addition of serum TIMP-1 to conventional risk factors model significantly improved risk prediction of the primary outcome (net reclassification index 9.0%, p = 0.02; integrated discrimination improvement 0.2%, p = 0.03). Participants with both higher TIMP-1 and matrix metalloproteinase-9 levels simultaneously had the highest risk of all study outcomes. CONCLUSIONS: Higher TIMP-1 levels were associated with increased risk of mortality and major disability after acute ischemic stroke. Our findings provided evidence supporting the important prognostic role of extracellular matrix biomarkers after acute ischemic stroke.

19.
Circ Res ; 125(9): 824-833, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31510868

RESUMO

RATIONALE: Previous EWASs (Epigenome-Wide Association Studies) suggest that obesity may be the cause, not a consequence, of changes in DNA methylation (DNAm). However, longitudinal observations are lacking. OBJECTIVE: To identify 5'-cytosine-phosphate-guanine-3' in DNA (CpG) sites associated with body mass index (BMI) and examine the temporal relationship between dynamic changes in DNAm and BMI in a longitudinal cohort. METHODS AND RESULTS: Race-specific EWASs were performed in 995 whites and 490 blacks from the Bogalusa Heart Study. Suggestive CpG sites were further replicated in 252 whites and 228 blacks from the Georgia Stress and Heart Study. Cross-lagged panel analysis was used to examine the temporal relationship between DNAm and BMI in 439 whites and 201 blacks who were examined twice 6.2 years apart. In discovery and replication samples, 349 CpG sites (266 novel) in whites and 36 (21 novel) in blacks were identified to be robustly associated with BMI, with 8 (1 novel) CpG sites overlapping between the 2 races. Cross-lagged panel analyses showed significant unidirectional paths (PFDR <0.05) from baseline BMI to follow-up DNAm at 18 CpG sites in whites and 7 in blacks; no CpG sites showed significant paths from DNAm at baseline to BMI at follow-up. Baseline BMI was associated with a DNAm score (calculated from DNAm levels at the associated CpG sites) at follow-up (P<0.001 both in blacks and in whites). CONCLUSIONS: The findings provide strong evidence that obesity is the cause, not a consequence, of changes in DNAm over time.

20.
Cerebrovasc Dis ; 48(1-2): 1-8, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31514186

RESUMO

BACKGROUND: Whether the renal function influences the association between antiphosphatidylserine antibodies (aPS) and prognosis of ischemic stroke remains unclear. We aimed to investigate the prognostic value of aPS after ischemic stroke stratified by renal function status. METHODS: This prospective study was based on China Antihypertensive Trial in Acute Ischemic Stroke, a randomized clinical trial in 26 hospitals across China from August 2009 to May 2013. A total of 2,874 ischemic stroke patients with blood samples or baseline records of estimated glomerular filtration rate (eGFR) were included in this study. Serum aPS levels were quantitatively measured at baseline, and abnormal renal function in this study was defined as eGFR <90 mL/min per 1.73 m2. The primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3) at 3 months after stroke. Secondary outcomes were death and major disability separately. RESULTS: The association between aPS and primary outcome was significantly modified by renal function status (p for interaction = 0.02). After adjustment for covariates, increased aPS were significantly associated with the primary outcome in the patients with abnormal renal function (OR 2.09; 95% CI 1.24-3.53; p for trend = 0.006), but not in those with normal renal function (OR 0.92; 95% CI 0.69-1.23; p for trend = 0.59), when 2 extreme tertiles were compared. Furthermore, multiple-adjusted spline regression model showed a linear association between aPS and risk of primary outcome in the patients with abnormal renal function (p for linearity = 0.02) but not in those with normal renal function (p for linearity = 0.71). CONCLUSIONS: Increased aPS were positively and independently associated with death or major disability after acute ischemic stroke in the patients with abnormal renal function.

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