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Given the evidence that brachial artery flow-mediated dilation (FMD) is declined in children later after the onset of Kawasaki disease (KD), we hypothesized that indicators that detect the situation of the endothelium are useful parameters that can accurately reflect subclinical dysfunction in resistant patients and assist in differentiating patients with KD at a higher risk of IVIG resistance, which may be valuable in better understanding how to protect patients from endothelial and thrombotic complications.Fifty IVIG-resistant KD children, 120 IVIG-responsive KD children, 35 febrile children with acute upper respiratory infection, and 50 healthy controls were recruited, and indicators reflecting endothelial inflammation, including flow-mediated dilation (FMD), were measured. Receiver operating characteristic (ROC) curve analysis was utilized to determine the threshold values of these indicators of IVIG resistance. Multiple logistic regression analysis was performed to determine whether FMD was an independent predictor of IVIG-resistant patients.In comparison with the lab data, PCT, Na + , and FMD exhibited AUCs of 0.727, 0.653, and 0.698 (P 0.05), respectively, in predicting IVIG resistance in KD through ROC analysis. PCT 1.69 ng/ml, Na + 133.2 mmol/l, and FMD 5.79% were independent predictors of IVIG resistance in KD (OR 4.257, 3.516, 3.563, 95% CI 1.549 ~ 11.700, 1.277 ~ 9.680, 1.299 ~ 9.772, P 0.05).More severe endothelial dysfunction, especially lower FMD, was present in IVIG-resistant patients than in IVIG-responsive patients. It is a helpful diagnostic tool that provides supportive criteria to detect KD patients at a higher risk of IVIG resistance when FMD 5.79% in children. Key Points • IVIG-resistant KD patients have more severe endothelial dysfunction than IVIG-sensitive patients. • FMD 5.79% may indicate an increased risk of IVIG resistance in children with Kawasaki disease.

Background Repeated intravenous immunoglobulin (IVIG) resistance prediction is one of the pivotal topics in Kawasaki disease (KD). Those non-responders of repeated IVIG treatment might be improved by an early-intensified therapy to reduce coronary artery lesion and medical costs. This study investigated predictors of resistance to repeated IVIG treatment in KD. Methods A total of 94 children with IVIG-resistant KD treated at our hospital between January 2016 and August 2020 were retrospectively analyzed. According to the therapeutic effect of a second dose IVIG treatment, the children were divided into repeated IVIG-responsive group and repeated IVIG-resistant group, and the clinical and laboratory data were compared. Predictors of repeated IVIG resistance and the optimal cut-off value were determined by multiple logistic regression analysis and receiver operating characteristic (ROC) curve analysis. Results The Pre-IVIG laboratory data showed the percentage of neutrophils (N%) and levels of serum procalcitonin (PCT), N-terminal pro-brain natriuretic peptide (NT-proBNP) were significantly higher in repeated IVIG-resistant group compared with repeated IVIG-responsive group, while levels of serum sodium and albumin (ALB) were significantly lower (P P 1.81ng/ml (OR 4.1, 95 % CI 1.4 ~ 12.0, P 45 mg/L (OR 4.6, 95 % CI 1.3 ~ 16.2, P Conclusions Our study illustrates the serum PCT level before initial IVIG treatment and CRP after initial IVIG could be used to predict repeated IVIG resistance in KD.

Statistical values of group differences

Background: Infective endocarditis (IE) is an uncommon but a potentially life-threatening infectious disease in children. The epidemiology of IE has changed in the past three to four decades and its incidence has been increasing recently. This case with atypical present including culture-negative and no-cardiovascular diseases got cardiovascular structural damage that deteriorate in short time. Case presentation: This case was an infant less than one year old without basic cardiovascular disease,and this case was admitted with Kawasaki disease early. His diagnosis was infective endocarditic aortic valve abscess with perforation. The patient received intravenous injection of cefotaxime for two days and piperacillin sulbactam and cefazolin for six days. On 9 th day, piperacillin sulbactam combining with vancomycin were used. On 10 th day, the patient was sent to cardiac surgery department to receive aortic valve repair. The operation is successful.The abscess cavity of the inferior aortic valve and the vegetations on the aortic valve were completely removed, the left coronary valve was removed, and the left coronary valve was locally widened by autologous pericardial patch. Conclusions: Infective Endocarditis in children may be difficult to diagnosis and manage.and the treatment are becoming a new challenge for conventional antibiotic therapy. Some IE require serial follow-up to determine potential need for subsequent cardiovascular surgery (CVS) intervention despite microbiologic cure with antimicrobial therapy.

This study was to investigate the correlation of vagal activity with coronary artery lesion (CAL) in Kawasaki disease (KD) children, and assess the predictive value of heart rate deceleration capacity (DC) for CAL in acute phase of KD.50 KD children with CAL, 130 KD children without CAL, 30 children with acute upper respiratory infection and 100 healthy children were recruited and indicators reflecting vagal activity including DC were measstuogram. KD children with CAL showed decreased vagal activity with significantly lower values of DC. DC was negatively correlated with levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) in KD children. DC was a usable cardiac electrophysiological index to predict CAL in children with KD, with an area under the receiver operating characteristic curve (AUC) of 0.741. The cut-off value of DC for predicting CAL in KD children was 4.37 ms. DC was an independent predictor of CAL in children with KD, evaluated by multiple logistic regression analysis, KD children with DC ≤ 4.37 ms had an increased risk of CAL, with odds ratios (OR) of 5.94. Our study illustrates DC could be used to predict CAL in acute phase of KD.

Background: Adult rodent studies showed that melatonin is very effective in treatment of ameliorating cardiovascular disease. Melatonin is also able to reduce cardiac hypertrophy and heart failure (HF) in juvenile rodents. Here, we study the effect of melatonin on the cardiac function of juvenile rats with HF. Methods: Juvenile rats with HF were induced by abdominal aortic constriction (AAC). Sham-operated rats were established in parallel. Five weeks after the surgery, rats with ventricular dysfunction were randomly divided into two groups: the treatment group was injected with melatonin (10 mg/kg/d, intraperitoneal injection), and the HF group was injected with placebo. Simultaneously, placebo was administered to the sham group. Results: After administration for 4 weeks, the treated rats did not exhibit a decline in cardiac function as assessed by echocardiography analysis. Moreover, the increase in expression of ANP, BNP, caspase-1, IL-1β, bax, CaMKII, PLN, and RyR2 was markedly blunted by melatonin, while the decrease in expression of bcl-2 was improved in the melatonin treated rats. Conclusions: Our findings support a protective role of melatonin in cardiomyocytes, at least in part via reducing cardiac pyroptosis, apoptosis and remaining calcium homeostasis.

BackgroundKawasaki disease is the leading cause of acquired heart disease in children from developed countries. The Interleukin-6/ Interleukin-12 cytokine family has many members, including the paradoxical anti- and pro-inflammatory Interleukin-27. Recent studies have demonstrated that Interleukin-27 plays a role in immune diseases. Given this, we sought to evaluate the association betweenInterleukin-27genetic polymorphisms and Kawasaki disease in Chinese children.Methods and resultsInterleukin-27 was genotyped in 100 Kawasaki disease children and 98 healthy children (controls), resulting in the direct sequencing of eight Single-nucleotide Polymorphisms: rs17855750, rs40837, rs26528, rs428253, rs4740, rs4905, rs153109, and rs181206). There were no significant differences in Interleukin-27 genotypes between Kawasaki disease and control groups. Of the eight Single-nucleotide Polymorphisms, there was a significant increase in the risk of Kawasaki disease with coronary arterial lesions in children with the rs17855750 (T>G), rs40837 (A>G), rs4740 (G>A), rs4905 (A>G), rs153109 (T>C), and rs26528 (A>G) Single-nucleotide Polymorphisms. This was particularly true for rs17855750 (T>G), which had a greater frequency in Kawasaki disease children with coronary arterial aneurysm.ConclusionThese findings may be used as risk factors when assessing a child’s likelihood of developing Kawasaki disease, as well as for the development of future therapeutic treatments for Kawasaki disease.

Purpose.Kawasaki disease (KD) is a systemic vasculitis and is a leading cause of coronary artery lesions (CALs) in childhood. Our previous study has shown higher levels of serum Resistin in KD patients with coronary aneurysm. This study aimed at examining the association of Resistin with inflammatory cytokine expression in mouse model of coronary arteritis and determining the potential mechanisms.Methods.C57BL/6 mice were injected withLactobacilluscell wall extract (LCWE) to induce coronary arteritis. The relative levels of Resistin, TNF-α, IL-1β, and MMP-9 expression and inflammatory infiltrates in the coronary arteries were determined longitudinally by quantitative RT-PCR, ELISA, and histology. The effect of TLR4 and NF-κB activation on Resistin-induced TNF-αand IL-1βexpression in human coronary artery endothelium cells (HCAECs) was examined by quantitative RT-PCR.Results.Higher levels of Resistin, TNF-α, IL-1β, and MMP-9 expression were associated with the degrees of inflammatory infiltrates in the coronary artery walls of the LCWE-injected mice. Resistin enhanced TNF-αand IL-1βexpression in HCAECs at 18 or 24 hours after stimulation. Pretreatment with anti-TLR4 attenuated Resistin-enhanced IL-1β, but not TNF-α, expression and pretreatment with parthenolide or QNZ demolished Resistin-enhanced TNF-αexpression in HACECs. Pretreatment with parthenolide, but not QNZ, blocked Resistin-enhanced IL-1βexpression in HCAECs.Conclusion.Resistin may enhance inflammation by cross-talking with TLR4/NF-κB signaling during the development of coronary arteritis in mice.

Background. This study was undertaken to determine relative contributions of phosphorylation and oxidation to the increased activity of calcium/calmodulin-stimulated protein kinase II (CaMKII) in juveniles with cardiac myocyte dysfunction due to increased pressure overload.Methods. Juvenile rats underwent abdominal aortic constriction to induce heart failure. Four weeks after surgery, rats were then randomly divided into two groups: one group given valsartan (HF + Val) and the other group given placebo (HF + PBO). Simultaneously, the sham-operated rats were randomly given valsartan (Sham + Val) or placebo (Sham + PBO). After 4 weeks of treatment, Western blot analysis was employed to quantify CaMKII and relative calcium handling proteins (RyR2 and PLN) in all groups.Results. The deteriorated cardiac function was reversed by valsartan treatment. In ventricular muscle cells of group HF + PBO, Thr287 phosphorylation of CaMKII and S2808 phosphorylation of RyR2 and PLN were increased and S16 phosphorylation of PLN was decreased compared to the other groups, while Met281 oxidation was not significantly elevated. In addition, these changes in the expression of calcium handling proteins were ameliorated by valsartan administration.Conclusions. The phosphorylation of Thr286 is associated with the early activation of CaMKII rather than the oxidation of Met281.

Kawasaki disease (KD) arises due to the disorder of the inflammation response and faulty immune regulation. Interleukin-27 (IL-27) is a novel cytokine with both pro-inflammatory and anti-inflammatory effects. This study investigated the relationship between serum levels of IL-27, Interleukin-17A (IL-17A), Interleukin-10 (IL-10), Interleukin-6 (IL-6), Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and coronary artery lesions (CALs) in patients with KD. We obtained blood samples from 81 children with KD before intravenous immunoglobulin (IVIG) therapy. Levels of IL-27, IL-17A, IL-10, IL-6, IL-1β and TNF-α were measured in 251 cases, including 4 groups: the normal control group, NC (n = 90), febrile control, FC (n = 80), KD without coronary arteries (n = 41) and KD with coronary arterial lesions (n = 40). White blood cells counts (WBC), red blood cells counts (RBC), hemoglobin, C-reactive protein (CRP), erythrocyte sedimentation rate and procalcitonin (PCT) were tested in all subjects. Levels of IL-27, IL-10, IL-17A, IL-6, IL-1β and TNF-α were significantly elevated, and RBC and hemoglobin significantly decreased in the group of KD group compared with febrile and control groups. IL-27, IL-6, IL-1β and TNF-α serum levels are even higher in KD children with CALs. There was positive relationship between serum levels of IL-27 and WBC, CRP, PCT, IL-10, IL-17A, IL-6 and TNF-α in children with KD. The up-regulation of IL-27 may be closely linked to up-regulation of systemic pro-inflammatory markers in acute KD. Morover, IL-27 may be involved in the development of CALs in acute KD.

The effect of melatonin on juveniles with cardio fibrosis is poorly understood. We investigated whether HDACs participate in the anti-fibrotic processes regulated by melatonin during hypertrophic remodeling. Abdominal aortic constriction (AAC) was employed in juvenile rats resulting in pressure overload-induced ventricular hypertrophy and melatonin was subsequently decreased via continuous light exposure for 5 weeks after surgery. AAC rats displayed an increased cross-sectional area of myocardial fibers and significantly elevated collagen deposition compared to sham-operated rats, as measured by HE and Masson Trichrome staining. Continuous light exposure following surgery exacerbated the increase in the cross-sectional area of myocardial fibers. The expression of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 genes were all significantly enhanced in AAC rats with light exposure relative to the other rats. Moreover, the protein level of TNF-α was also upregulated in the AAC light exposure groups when compared with the sham. However, Smad4 protein expression was unchanged in the juveniles' hearts. In contrast, beginning 5 weeks after the operation, the AAC rats were treated with melatonin (10 mg/kg, intraperitoneal injection every evening) or vehicle 4 weeks, and sham rats were given vehicle. The changes in the histological measures of cardio fibrosis and the gene expressions of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 were attenuated by melatonin administration. The results reveal that melatonin plays a role in the development of cardio fibrosis and the expression of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 in cardiomyocytes.

BACKGROUND: Kernicterus still occurs around the world; however, the mechanism of bilirubin neurotoxicity remains unclear, and effective treatment strategies are lacking. To solve these problems, several kernicterus (or acute bilirubin encephalopathy) animal models have been established, but these models are difficult and expensive. Therefore, the present study was performed to establish a novel kernicterus model that is simple and affordable by injecting unconjugated bilirubin solution into the cisterna magna (CM) of ordinary newborn Sprague-Dawley (SD) rats. METHODS: On postnatal day 5, SD rat pups were randomly divided into bilirubin and control groups. Then, either bilirubin solution or ddH2O (pH = 8.5) was injected into the CM at 10 µg/g (bodyweight). For model characterization, neurobehavioral outcomes were observed, mortality was calculated, and bodyweight was recorded after bilirubin injection and weaning. Apoptosis in the hippocampus was detected by H&E staining, TUNEL, flow cytometry and Western blotting. When the rats were 28 days old, learning and memory ability were evaluated using the Morris water maze test. RESULTS: The bilirubin-treated rats showed apparently abnormal neurological manifestations, such as clenched fists, opisthotonos and torsion spasms. Bodyweight gain in the bilirubin-treated rats was significantly lower than that in the controls (P