In recent years, exercise testing has been increasingly used in pediatrics, especially in pediatric cardiovascular diseases.Its ability to monitor heart rate, blood pressure, electrocardiogram, oxygen saturation, and expiratory gas analysis is of great clinical value.In pediatric cardiovascular diseases, exercise testing can further evaluate arrhythmias, facilitate the differential diagnosis of syncope, and detect early myocardial perfusion defects in children with cardiomyopathy and Kawasaki disease; in addition, expiratory gas analysis of exercise testing can assess cardiorespiratory fitness in children and the operative results of congenital heart disease, etc.This article reviews the use of exercise testing in children with arrhythmias, cardiomyopathy, congenital heart disease, and Kawasaki disease.

Objective:To explore the expression patterns of inhibitor of differentiation(ID)family in patients with chronic myeloid leukemia(CML)and analyze their clinical implications.Methods:Quantitative PCR and quantitative methylation-specific PCR were conducted to de-tect the transcript levels of ID2/ID3/ID4 and the methylation levels of ID4 in the bone marrow mononuclear cells of non-hematological ma-lignancies(acting as controls)and patients with CML treated at The Affiliated People's Hospital of Jiangsu University from January 2010 to December 2017.The clinical implications of ID family alterations were further analyzed.Results:ID2 and ID3 expression was significantly up regulated(P<0.001 and P<0.05,respectively),whereas ID4 expression was markedly down regulated in patients with CML(P<0.01).The re-ceiver operating characteristic curve demonstrated that the ID2 transcript level is a potential biomarker for distinguishing CML from controls(AUC=0.895,P<0.001).The frequency of ID4 promoter methylation in patients with CML was drastically higher than that in the controls(P=0.001).Moreover,ID4 methylation was negatively correlated with ID4 expression in patients with CML(r=-0.424,P=0.002).Clinically,CML with high ID2 expression occurred more frequently in males(P=0.040).Patients with low ID4 expression or high ID4 methylation showed a markedly higher frequency of an accelerated phase/blast crisis(P=0.003 and P<0.001,respectively).In addition,patients with CML in an accelerated phase/blast crisis exhibited markedly lower ID4 expression and higher ID4 methylation levels than those in the chronic phase(both P<0.001).Furthermore,univariate and multiple Logistic regression analyses revealed that the ID4 methylation level was an inde-pendent risk factor for CML progression(P=0.007).Conclusions:The ID family was differentially expressed in patients with CML;specifically,ID2 and ID3 expression was significantly increased,whereas ID4 expression was markedly decreased and correlated with ID4 promoter hy-permethylation.Hence,ID4 expression and methylation are confirmed to be associated with CML progression,and ID4 methylation could be an independent risk factor for CML progression.

Objective: To investigate the impact of homocysteine inducible endoplasmic reticulum(ER) protein with ubiquitin like domain 1 protein (Herpud1) in the homocysteine (Hcy) -induced phenotypic switching of vascular smooth muscle cells (VSMCs). Methods: VSMCs were derived from thoracic aortic artery of male Sprague Dawley rats and cultured VSMCs (4-7 passage) were treated with various concentrations of Hcy (0, 100, 500 and 1 000 μmol/L) and applied to immunofluorescence to observe the morphological changes of VSMCs via SM-actin staining. Western blot was used to detect the expression of VSMCs phenotypic markers, including Osteopontin, Calponin and smooth muscle myosin heavy chain (SM-MHC) and the expression of endoplasmic reticulum stress (ERS) related proteins, including C/EBP-homologous protein (CHOP), inositol-requiring kinase 1 (IRE-1) and glucose regulating protein 78 (GRP78) in the absence and presence of non-selective inhibitor of ERS, 4-phenylbutyric acid (4-PBA, 2 mg/ml). The Herpud1 mRNA and protein levels were determined in Hcy-stimulated VSMCs treated with 4-PBA or transfected with specific siRNA targeting Herpud1. Results: Compared with the control group, SM-actin staining results showed that the shape of VSMCs treated with different concentrations of Hcy for 24 hours changed from long fusiform into round form, arrangement of myofilament became irregular and the most significant alteration was found in the 500 μmol/L Hcy group. After intervention of 24 hours, various concentration of Hcy increased protein expression of Osteopontin, and reduced Calponin and SM-MHC protein expressions in VSMCs (all P<0.05). In addition, the results showed that Hcy increased the expression of CHOP, IRE-1 and GRP78 in a dose-dependent manner, which could be reversed by 4-PBA treatment (all P<0.05). However, 4-PBA inhibited Hcy induced upregulation of Osteopontin and downregulation of Calponin and SM-MHC, suggesting that ERS was involved in Hcy-induced phenotypic switching of VSMCs. Herpud1 protein was mostly expressed in the cytoplasm and was also expressed in the nucli, both in the control, Hcy and Hcy+4-PBA groups. Moreover, Hcy increased mRNA and protein levels of Herpud1 (P<0.05), whereas treatment with 4-PBA could significantly reduce Hcy-induced upregulation of Herpud1 (P<0.05). Furthermore, knockdown of Herpud1 abrogated the effects of Hcy on VSMCs phenotype markers. Conclusion Herpud1 plays an important role in Hcy-induced phenotypic switching of VSMCs.