RESUMO
BACKGROUND: The prenatal test of cell-free fetal DNA (cffDNA) is also known as noninvasive prenatal testing (NIPT) with high sensitivity and specificity. This study is to evaluate the performance of NIPT and its clinical relevance with various clinical indications. METHODS: A retrospective analysis was conducted on 14,316 pregnant women with prenatal indications, including advanced maternal age (≥35 years), maternal serum screening abnormalities, the thickened nuchal translucency (≥2.5 mm) and other ultrasound abnormalities, twin pregnancy/IVF-ET pregnancy, etc. The whole-genome sequencing (WGS) of maternal plasma cffDNA was employed in this study. RESULTS: A total of 189 (1.32%) positive NIPT cases were identified, and 113/189 (59.79%)cases were confirmed by invasive prenatal testing. Abnormal serological screening (53.14%) was the most common indication, followed by elderly pregnancy (23.02%). The positive prediction value for T21, T18, T13, sex chromosome abnormalities, other autosomal aneuploidy abnormalities, and CNV abnormalities were 91.84, 68.75,37.50, 66.67, 14.29, and 6.45%, respectively. The positive rate and the true positive rate of nuchal translucency (NT) thickening were the highest (4.17 and 3.33%), followed by the voluntary requirement group (3.49 and 1.90%) in the various prenatal screening indications. The cffDNA concentration was linearly correlated with gestational age (≥10 weeks) and the positive NIPT group's Z-score values. CONCLUSIONS: whole-genome sequencing of cffDNA has extremely high sensitivity and specificity for T21, high sensitivity for T18, sex chromosome abnormalities, and T13. It also provides evidence for other abnormal chromosomal karyotypes (CNV and non-21/18/13 autosomal aneuploidy abnormalities). The cffDNA concentration is closely related to the gestational age and determines the specificity of NIPT. Our results highlight NIPT's clinical significance, which is an effective prenatal screening tool for high-quality care of pregnancy.
Assuntos
Aberrações Cromossômicas/embriologia , Transtornos Cromossômicos/diagnóstico , Teste Pré-Natal não Invasivo , Gravidez de Alto Risco , Adolescente , Adulto , China/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Gravidez , Estudos Retrospectivos , Sensibilidade e Especificidade , Sequenciamento Completo do Genoma , Adulto JovemRESUMO
BACKGROUND: Current assessment tools for patients with acute chest pain are either traumatic (coronary angiography) or unreliable (measurement of cardiac troponin concentrations). We investigated whether the novel cardiovascular stress markers, serum growth differentiation factor-15 (GDF-15), Krüppel-like factor 4 (KLF4) and growth arrest-specific 6 (gas6) may be useful biomarkers of coronary artery disease (CAD). METHODS: A total of 350 male patients were enrolled, 198 with CAD and 152 controls, based on coronary angiography. GDF-15, KLF4 and gas6 concentrations were measured using commercial enzyme-linked immunosorbent assay kits. Multivariate logistic regression and multivariate linear regression were performed to evaluate potential associations of GDF-15, KLF4 and gas6 with risk of CAD or CAD severity. RESULTS: Serum GDF-15, KLF4 and gas6 concentrations were significantly higher in male patients with CAD than in control subjects (Pâ¯<â¯.05), and they correlated significantly with involvement of coronary vessels (Pâ¯<â¯.05). After adjusting for confounding factors, we found that circulating GDF-15 concentrations remained positively associated with the presence of CAD (odds ratio [OR] per 1-standard deviation [SD] increase, 3.182; 95% confidence interval [CI] 1.586 to 6.382; Pâ¯=â¯.001), as did KLF4 concentrations (OR per 1-SD increase, 13.05; 95% CI 2.940 to 57.921, Pâ¯=â¯.001). Moreover, circulating GDF-15 concentrations were positively associated with the Gensini score (estimated SD change per 1-SD increase, 22.091; 95% CI 9.147 to 35.035, Pâ¯=â¯.001), as were KLF4 concentrations (estimated SD change per 1-SD increase, 27.996; 95% CI 10.082 to 45.910, Pâ¯=â¯.002). Gas6, in contrast, showed no relationship to presence of CAD or Gensini score. , CONCLUSIONS: In this case-control study, increased concentrations of circulating GDF-15 and KLF4 were significantly associated with the presence and severity of CAD.
Assuntos
Doença da Artéria Coronariana/sangue , Fator 15 de Diferenciação de Crescimento/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Fatores de Transcrição Kruppel-Like/sangue , Idoso , Angiografia , Biomarcadores/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Diagnóstico Precoce , Humanos , Fator 4 Semelhante a Kruppel , Masculino , Pessoa de Meia-IdadeRESUMO
NEW FINDINGS: What is the central question of this study? The enzyme system that is responsible for extracellular matrix (ECM) turnover is the matrix metalloproteinases (MMPs), which can be blocked by the tissue inhibitors of MMPs (TIMPs). Whether renal sympathetic denervation (RSD) is able to ameliorate post-myocardial infarction left ventricular remodelling through attenuation of ECM via regulation of MMP activity and/or the MMP-TIMP complex remains unknown. What is the main finding and its importance? Renal sympathetic denervation has therapeutic effects on post-myocardial infarction left ventricular remodelling, probably by attenuating the ECM through regulation of the MMP9-TIMP1 complex in the transforming growth factor-ß1 (a profibrotic cytokine that accelerates ECM remodelling after ischaemia) signalling pathway. Whether renal sympathetic denervation (RSD) is able to ameliorate post-myocardial infarction (post-MI) left ventricular (LV) remodelling by attenuation of the extracellular matrix via regulation of matrix metalloproteinase (MMP) activity and/or the MMP-tissue inhibitor of matrix metalloproteinase (TIMP) complex remains unknown. Sixty-five Sprague-Dawley rats were randomly divided into the following four groups: normal (N, n = 15), RSD (RSD, n = 15), myocardial infarction (MI, n = 15) and RSD 3 days after MI (MI3d+RSD, n = 20). The bilateral renal nerves were surgically denervated 3 days after MI had been induced by coronary artery ligation. Left ventricular function was assessed using echocardiography and a Millar catheter at 6 weeks post-MI. Plasma noradrenaline, angiotensin II and aldosterone, collagen volume fraction, transforming growth factor-ß1 (TGF-ß1), MMP2, MMP9 and TIMP1 in heart tissue were measured 6 weeks after MI. In rats with MI3d+RSD compared with MI rats, RSD improved systolic and diastolic function, resulting in an improvement in ejection fraction (P < 0.05), fractional shortening (P < 0.05) and LV internal dimension in systole (P < 0.05) and diastole (P < 0.05). Additionally, RSD treatment decreased left ventricular end-diastolic pressure (P < 0.05) and increased LV systolic pressure (P < 0.05) and maximal and minimal rate of LV pressure (both P < 0.05). Meanwhile, RSD reduced collagen content (P < 0.01). TIMP1 was upregulated (P < 0.05), whereas MMP2, MMP9 and TGF-ß1 were downregulated in the LV of RSD-treated animals (P < 0.05). Renal sympathetic denervation has therapeutic effects on post-MI LV remodelling, probably owing to effects on the extracellular matrix by regulation of the MMP9-TIMP1 balance in the TGF-ß1 signalling pathway. Renal sympathetic denervation may be considered as a non-pharmacological approach for the improvement of post-MI cardiac dysfunction.