Islet dysfunction and destruction are the common cause for both type 1 and type 2 diabetes mellitus (T2DM). The islets of Langerhans are highly vascularized miniorgans, and preserving the structural integrity and full function of the microvascular endothelium is vital for protecting the islets from the infiltration of immune cells and secondary inflammatory attack. Mesenchymal stromal cell (MSC)-based therapies have been proven to promote angiogenesis of the islets; however, the underlying mechanism for the protective role of MSCs in the islet endothelium is still vague. In this study, we used MS-1, a murine islet microvascular endothelium cell line, and an MSC-MS1 transwell culturing system to investigate the protective mechanism of rat bone marrow-derived MSCs under oxidative stress in vitro. Cell apoptosis was detected by TUNEL staining, annexin V/PI flow cytometry analysis, and cleaved caspase 3 western blotting analysis. Endothelial cell activation was determined by expression of intercellular cell adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM), as well as eNOS phosphorylation/activation. The changes of VCAM-1, eNOS, and the β-catenin expression were also tested in the isolated islets of T2DM rats infused with MSCs. We observed that treating MS-1 cells with H2O2 triggered significant apoptosis, induction of VCAM expression, and reduction of eNOS phosphorylation. Importantly, coculturing MS-1 cells with MSCs prevented oxidative stress-induced apoptosis, eNOS inhibition, and VCAM elevation in MS-1 cells. Similar changes in VCAM-1 and eNOS phosphorylation could also be observed in the islets isolated from T2DM rats infused with MSCs. Moreover, MSCs cocultured with MS-1 in vitro or their administration in vivo could both result in an increase of β-catenin, which suggested activation of the β-catenin-dependent Wnt signaling pathway. In MS-1 cells, activation of the β-catenin-dependent Wnt signaling pathway partially mediated the protective effects of MSCs against H2O2-induced apoptosis and eNOS inhibition. Furthermore, MSCs produced a significant amount of Wnt4 and Wnt5a. Although both Wnt4 and Wnt5a participated in the interaction between MSCs and MS-1 cells, Wnt4 exhibited a protective role while Wnt5a seemed to show a destructive role in MS-1 cells. Our observations provide evidence that the orchestration of the MSC-secreted Wnts could promote the survival and improve the endothelial function of the injured islet endothelium via activating the β-catenin-dependent Wnt signaling in target endothelial cells. This finding might inspire further in-vivo studies.

Background: Kawasaki disease (KD) is an acute, self-limiting systemic vasculitis that predominately affects children. Neurological involvement is a known complication of KD, however, its association with KD severity remains elusive. We aimed to systematically describe the general manifestations of neurological involvement in KD, determine whether neurological involvement is a marker of disease severity in patients with KD, and assess the relationship of such involvement with intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs). Methods: We retrospectively reviewed data from 1582 patients with KD between January 2013 and December 2017. Profiles of patients with neurological symptoms (group A, n = 80) were compared to those of gender- and admission date-matched patients without neurological involvement (group B, n = 512). Multivariate logistic regression analyses were performed to determine whether neurological involvement was significantly associated with IVIG resistance. Results: Neurological involvement was observed in 5.1% (80/1582) of patients with KD. The neurological manifestations were diffuse, presenting as headache (13/80, 16.3%), convulsions (14/80, 17.5%), somnolence (40/80, 50.1%), extreme irritability (21/80, 26.3%), signs of meningeal irritation (15/80, 18.8%), bulging fontanelles (7/80, 8.8%), and facial palsy (1/80, 1.3%). Neurological symptoms represented the initial and/or predominant manifestation in 47.5% (38/80) of patients with KD. The incidence of IVIG resistance and levels of inflammatory markers were higher in group A than in group B. However, neurological involvement was not an independent risk factor for IVIG resistance or CALs. Conclusion: Rates of neurological involvement were relatively low in patients with KD. Neurological involvement was associated with an increased risk of IVIG resistance and severe inflammatory burden. Our results highlight the need for pediatricians to recognize KD with neurological involvement and the importance of standard IVIG therapy. Trial registration: Retrospectively registered.

Background: The prediction of intravenous immunoglobulin (IVIG) resistance and cardiovascular complications are critically clinical issues in Kawasaki disease (KD). This prospective study firstly aimed to determine the predictive ability of the systemic immune inflammation index (SII) for IVIG resistance and cardiovascular complications and compare the prognostic accuracy of SII with that of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR).Methods: Patients with KD were divided into different groups according to the presence of IVIG resistance or cardiovascular complications (coronary artery lesions, valve regurgitation, myocarditis, pericardial effusion, and Kawasaki disease shock syndrome [KDSS]). The clinical and laboratory parameters were compared. Further analysis stratified by platelet level was performed. Multivariate logistic regression analysis was used to identify predictors for IVIG resistance and cardiovascular complications. The receiver operating characteristic (ROC) curve was applied to assess and compare the ability of SII, NLR, and PLR for predicting IVIG resistance and cardiovascular complications.Results: SII was significantly higher in KD patients with IVIG-resistance, myocarditis, valve regurgitation, and KDSS. It was identified as an independent risk factor for IVIG resistance, myocarditis, and valve regurgitation. For KD patients with thrombocytopenia, there were no significant differences in SII between KD patients with IVIG resistance/cardiovascular complications and those without. The best cutoff values of SII for IVIG resistance, myocarditis, valve regurgitation, and KDSS prediction in the whole cohort were 1331.4 × 10⁹, 1368.6 × 10⁹, 1002.4 × 10⁹, and 1485.4 × 10⁹, with a corresponding sensitivity of 0.525, 0.614, 0.754, and 0.670, a specificity of 0.711, 0.723, 0.584, and 0.730, respectively. The predictive value of SII for both IVIG resistance and cardiovascular complications were not superior to that of NLR.Conclusion: Although the parameter of SII may predict IVIG resistance, myocarditis, valve regurgitation, and KDSS in KD as a single parameter, its predictive ability was not good enough and not superior to NLR. SII might not be applicable in patients with KD having thrombocytopenia.

Duchenne muscular dystrophy (DMD) is a clinically common X-linked recessive myopathy, which is caused by mutation of the gene encoding dystrophin on chromosome Xp21. The onset of heart injury in children with DMD is inconspicuous, and the prognosis is poor once it develops to the stage of heart failure. Cardiovascular complications remain an important cause of death in this patient population. At present, population and animal studies have suggested that Electrocardiogram (ECG) changes may be the initial manifestation of cardiac involvement in children with DMD. Relevant clinical studies have also confirmed that significant abnormal ECG changes already exist in DMD patients before cardiomegaly and/or LVEF decrease. With increases in age and decreases in cardiac function, the proportion of ECG abnormalities in DMD patients increase significantly. Some characteristic ECG changes, such as ST-segment changes, T wave inversion, Q wave at the inferolateral leads, LBBB and SDANN, have a certain correlation with the indexes of cardiac remodeling or impaired cardiac function in DMD patients, while VT and LBBB have demonstrated relatively good predictive value for the occurrence of long-term DCM and/or adverse cardiovascular events or even death in DMD patients. The present review discusses the electrocardiographic features in children with DMD.

Context: Intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) prediction are pivotal topic of interests in Kawasaki disease (KD). However, data on the predictive value of lipid profile for both IVIG resistance and CALs are limited. Purpose: To investigate the predictive validity of lipid profile for IVIG resistance and CALs in KD. Design: Prospective cohort study. Setting: West China Second University Hospital. Patients: 363 KD patients were divided into the initial IVIG-resistant group and initial IVIG-responsive group; repeated IVIG-resistant group and repeated IVIG-responsive group; CAL+ group and CAL− group. Main Outcome Measures: Validity of lipid profile in predicting IVIG resistance and CALs. Results: Triglycerides were significantly higher whereas total cholesterol (TC), high-densisty lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein A (Apo A) were significantly lower in initial IVIG-resistant subjects, with cut-off values of 1.625 mmol/L, 3.255 mmol/L, 0.475 mmol/L, 1.965 mmol/L, and 0.665 g/L, yielding sensitivities of 52%, 70%, 52%, 61%, and 50% and specificities of 68%, 53%, 78%, 71%, and 81%, respectively. TC, LDL-C, and Apo A levels were significantly lower in repeated IVIG-resistant subjects, with cut-off values of 3.20 mmol/L, 1.78 mmol/L, and 0.605 g/L, producing sensitivities of 91%, 70%, and 57% and specificities of 55%, 67%, and 70%, respectively. Apo A level was significantly lower in the CAL+ group, with cut-off value of 0.805 g/L, yielding sensitivity of 66% and specificity of 54%. Conclusions: Lipid profiles were significantly dysregulated in KD patients suffering IVIG resistance and CALs. Some of them, such as LDL-C and Apo A, could serve as complementary laboratory markers for predicting both IVIG resistance and CALs.

The evaluation of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for intravenous immunoglobulin resistance prediction was prospectively performed in a large cohort of Kawasaki disease patients. It was found that the predictive values of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio, alone or combined, were not good enough although they were identified as independent risk factors for intravenous immunoglobulin resistance.