Kawasaki disease (KD) is a febrile disease that affects children under 5 years of age and leads to serious cardiovascular complications such as coronary artery disease. The development of markers that can predict early is important to reduce the under- and misdiagnosis of KD. The aim of this research was to develop a diagnostic predictive model to differentiate Kawasaki disease (KD) from other febrile diseases using eosinophil-to-lymphocyte ratio (ELR) and other biomarkers. We recruited a total of 190 children with KD and 1604 children with other febrile diseases. We retrospectively collected clinical information from the children, which included laboratory data on the day of admission, such as white blood cells (WBC), hemoglobin (HGB), calcitoninogen (PCT), hypersensitive c-reactive protein (CRP), snake prognostic nutritional index (PNI), peripheral blood neutrophil–lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and ELR. We performed analyses using univariate analysis, multivariate logistic regression, and column line plots, and evaluated the diagnostic parameters of the predictive models. ELR was significantly increased in patients with KD. After multivariate logistic regression, WBC, HGB, CRP, NLR, ELR and PNI were finally included as indicators for constructing the prediction model. The ROC curve analysis suggested that the C-index of the diagnostic prediction model was 0.921. The calibration curve showed good diagnostic performance of the columnar graph model. The cut-off value of ELR alone for KD was 0.04, the area under the ROC curve was 0.809. Kids with KD show highly expressive level of ELR compared to children with febrile disease, which can be used to diagnose KD, and column line graphs constructed together with other indicators can help pediatricians to identify KD more effectively from febrile children.

Background Previous studies have suggested that lifestyle factors are associated with mortality in different population. However, little is known about the impact of lifestyle factors on all-cause mortality in non-communicable disease (NCD) population. Methods This study included 10,111 NCD patients from the National Health Interview Survey. The potential high-risk lifestyle factors were defined as smoking, excessive drinking, abnormal body mass index, abnormal sleep duration, insufficient physical activity (PA), overlong sedentary behavior (SB), high dietary inflammatory index (DII) and low diet quality. Cox proportional hazard model was used to evaluate the impact of the lifestyle factors and the combination on all-cause mortality. The interaction effects and all combinations of lifestyle factors were also analyzed. Results During 49,972 person-years of follow-up, 1040 deaths (10.3%) were identified. Among eight potential high-risk lifestyle factors, smoking (HR = 1.25, 95% CI 1.09–1.43), insufficient PA (HR = 1.86, 95% CI 1.61–2.14), overlong SB (HR = 1.33, 95% CI 1.17–1.51) and high DII (HR = 1.24, 95% CI 1.07–1.44) were risk factors for all-cause mortality in the multivariable Cox proportional regression. The risk of all-cause mortality was increased linearly as the high-risk lifestyle score increased (P for trend < 0.01). The interaction analysis showed that lifestyle had stronger impact on all-cause mortality among patients with higher education and income level. The combinations of lifestyle factors involving insufficient PA and overlong SB had stronger associations with all-cause mortality than those with same number of factors. Conclusion Smoking, PA, SB, DII and their combination had significant impact on all-cause mortality of NCD patients. The synergistic effects of these factors were observed, suggesting some combinations of high-risk lifestyle factor may be more harmful than others.

Kawasaki disease (KD) is a childhood vasculitis disease that is difficult to diagnose, and there is an urgent need for the identification of accurate and specific biomarkers. Here, we aimed to investigate metabolic alterations in patients with KD to determine novel diagnostic and prognostic biomarkers for KD. To this end, we performed untargeted metabolomics and found that several metabolic pathways were significantly enriched, including amino acid, lipid, and tryptophan metabolism, the latter of which we focused on particularly. Tryptophan-targeted metabolomics was conducted to explore the role of tryptophan metabolism in KD. The results showed that Trp and indole acetic acid (IAA) levels markedly decreased, and that l-kynurenine (Kyn) and kynurenic acid (Kyna) levels were considerably higher in patients with KD than in healthy controls. Changes in Trp, IAA, Kyn, and Kyna levels in a KD coronary arteritis mouse model were consistent with those in patients with KD. We further analyzed public single-cell RNA sequencing data of patients with KD and revealed that their peripheral blood mononuclear cells showed Aryl hydrocarbon receptor expression that was remarkably higher than that of healthy children. These results suggest that the Trp metabolic pathway is significantly altered in KD and that metabolic indicators may serve as novel diagnostic and therapeutic biomarkers for KD.

Background: Endothelial dysfunction is a marked feature of Kawasaki disease during convalescence, but its pathogenesis is currently unclear. Circulating microRNAs (miRNAs) are associated with the progression of Kawasaki disease. However, the role and mechanism of circulating miRNAs in endothelial dysfunction are largely unknown. Kawasaki disease patients were found to have a unique circulating miRNA profile, including upregulation of miRNA-210-3p, miR-184 and miR-19a-3p, compared to non-Kawasaki disease febrile controls. This study aimed to investigate the effects of these three miRNAs on endothelial function. Methods: Overexpression of miRNAs in human umbilical vein endothelial cells was done by transfection of miRNA mimics. The tube formation assay was used to evaluate the function of human umbilical vein endothelial cells. The potential binding sites of miRNAs on 3’untranslated regions were predicted by using TargetScan database and validated by dual luciferase reporter assay. The protein expression of AGO2, PTEN and VEGF in human umbilical vein endothelial cells was detected by Western blot. Overexpression of AGO2 in human umbilical vein endothelial cells was done by transfection of AGO2 expression plasmids. Results: Overexpression of miRNA-184 and miRNA-19a-3p, but not miR-210-3p, impaired the function of human umbilical vein endothelial cells. Mechanistically, miR-184 and miR-19a-3p could target the 3’untranslated regions of AGO2 mRNA to downregulate its expression and subsequently impede the AGO2/PTEN/VEGF axis. To be noted, the rescue of the expression of AGO2 remarkably recovered the function that was impaired by overexpression of miRNA-184 and miRNA-19a-3p. Conclusions: This study suggested that miR-184 and miR-19a-3p could target AGO2/PTEN/VEGF axis to induce endothelial dysfunction in Kawasaki disease.