Songling Fu

OBJECTIVE: To investigate the roles of serum Th1 and Th2 cytokines in Kawasaki disease (KD) and determine whether the Th1/Th2 cytokine profiles in children with KD may be involved in intravenous immunoglobulin (IVIG) resistance and development of coronary artery lesions (CALs). METHODS: Serum Th1 and Th2 cytokines, including interferon-γ (IFNγ), tumor necrosis factor α (TNFα), interleukin-10 (IL-10), IL-6, IL-4, and IL-2, were measured using a cytometric bead array in the serum of 143 patients with KD before and after treatment with IVIG (pre-IVIG, at 3 days after temperature normalization following IVIG treatment [post-IVIG], and 1 month posttreatment). RESULTS: Levels of IL-6, IL-10, TNFα, and IFNγ were significantly increased in KD patients pre-IVIG. Post-IVIG, the levels of IL-6, IL-10, and IFNγ quickly decreased. The levels of TNFα decreased significantly after IVIG treatment in KD patients without CALs post-IVIG and in KD patients who were IVIG responders, but increased slightly in KD patients with CALs post-IVIG and in KD patients who were IVIG nonresponders. Before IVIG treatment, the levels of IL-4, IL-6, IL-10, and IFNγ were significantly higher in KD patients with CALs than in those without CALs. The post-IVIG levels of IL-6 and IL-10 were significantly higher in IVIG nonresponders than in IVIG responders. Pre-IVIG, an IL-10 level >8 pg/ml had a sensitivity of 75.0% and a specificity of 64.4% for predicting CALs, while a TNFα level <2 pg/ml had a sensitivity of 66.7% and a specificity of 74.2% for predicting IVIG resistance. Post-IVIG, an IL-6 level >10 pg/ml had a sensitivity of 67.9% and a specificity of 81.7% for predicting CALs, while an IL-10 level >6 pg/ml had a sensitivity of 53.6% and a specificity of 86% for predicting CALs. CONCLUSION: Determination of the serum Th1/Th2 cytokine profile may be helpful for predicting the disease prognosis and targeting treatment strategies in patients with KD.

BACKGROUND: To assess the predictors for intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in Kawasaki disease (KD). METHODS: A total of 560 KD patients were reviewed retrospectively, including 410 complete KD (cKD) and 150 incomplete KD (iKD) patients. The laboratory data were compared between the IVIG-resistant and IVIG-responsive groups, as well as between the coronary artery lesions (CALs+) and without coronary artery lesions (CALs-) groups. RESULTS: In the cKD patients, C-reactive protein (CRP) levels had a sensitivity of 65.52% and a specificity of 62.7% for predicting IVIG-resistance at a cutoff point of >100 mg/L. When albumin <32 g/L, the sensitivity and specificity for predicting IVIG-resistance were 72 and 83.19%, respectively. N-terminal pro-brain natriuretic peptide (NT-proBNP) levels had a sensitivity of 73.91% and a specificity of 76.43% for predicting IVIG-resistance at a cutoff point of >1300 pg/ml. Interleukin-6 levels had a sensitivity of 76.19% and a specificity of 61.59% at a cutoff value of >45 pg/ml. Erythrocyte sedimentation rate (ESR) levels had a sensitivity of 53.26% and a specificity of 64.14% for predicting CALs at a cutoff point of >75 mm/h. In the iKD patients, the sensitivity and specificity for predicting IVIG-resistance were 80 and 54.1% when hemoglobin <110 g/L. When proportion of neutrophils >70%, the sensitivity and specificity for predicting IVIG-resistance were 68 and 66.94%, respectively. ESR levels had a sensitivity of 70.83% and a specificity of 65.81% for predicting IVIG-resistance at a cutoff point of >80 mm/h. NT-proBNP levels had a sensitivity of 78.57% and a specificity of 56.67% for predicting IVIG-resistance at a cutoff point of >360 pg/ml. Interleukin-6 levels had a sensitivity of 70.59% and a specificity of 66.28% at a cutoff value of >25 pg/ml. Interleukin-10 levels had a sensitivity of 64.71% and a specificity of 74.42% for predicting IVIG-resistance at a cutoff value of >8 pg/ml. ESR levels had a sensitivity of 61.82% and a specificity of 65.12% for predicting CALs at a cutoff point of >75 mm/h. CONCLUSIONS: The white blood cell count, proportion of neutrophils, hemoglobin, CRP, ESR, albumin, NT-proBNP, interleukin-6 and 10 may be effective predictors for IVIG resistance and CALs in KD patients.

To investigate the differential expression of microRNA-150-5p (miR-150-5p) and early growth response 1 (EGR1) in myocardial fibrosis (MF) cells, and determine the effect between miR-150-5p and EGR1 on MF. Human MF cells were generated via Trypanosoma cruzi (T. cruzi) infection, a mouse model of MF was generated via angiotensin II. The expression levels of miR-150-5p and EGR1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assay. The correlation between miR-150-5p and EGR1 was confirmed by a luciferase reporter assay. The viability, proliferation, and apoptotic rate were detected by cell counting kit-8 (CCK-8), colony-formation and flow cytometry assays. Hematoxylin-eosin (HE) staining and Masson staining visualized the degree of MF. Echocardiography was performed to obtain the levels of left ventricle fractional shortening (LVFS) and left ventricle ejection fraction (LVEF), computer algorithms and a videographics program were used to obtain the levels of left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP) and ±left ventricular dp/dt maximum (LV dp/dtmax). We found that the expression of miR-150-5p in MF cells was lower than normal cardiomyocytes, while the expression level of EGR1 in MF cells were higher than normal cardiomyocytes. Cell experiments demonstrated that EGR1 and miR-150-5p could influence the development of MF, and the expression of EGR1 in cardiomyocytes was regulated by miR-150-5p directly. Lastly, we confirmed that sh-Egr1 would decrease the severity of MF, while miR-150-5p antagomir could aggravate MF. Our results illustrate the mechanism of MF development, and provide a potential target for MF treatment.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme for folate metabolism in humans; it is encoded by the MTHFR gene. Several studies have assessed the association between MTHFR C677T polymorphism and the risk of congenital heart defects (CHDs), while the results were inconsistent. METHODS AND FINDINGS: Multiple electronic databases were searched to identify relevant studies published up to July 22, 2012. Data from case-control and TDT studies were integrated in an allelic model using the Catmap and Metafor software. Twenty-nine publications were included in this meta-analysis. The overall meta-analysis showed significant association between MTHFR C677T polymorphism and CHDs risk in children with heterogeneity (P heterogeneity = 0.000) and publication bias (P egger = 0.039), but it turned into null after the trim-and-fill method was implemented (OR = 1.12, 95% CI = 0.95-1.31). Nevertheless, positive results were obtained after stratified by ethnicity and sample size in all subgroups except the mixed population. For mothers, there was significant association between the variant and CHDs without heterogeneity (P heterogeneity = 0.150, OR = 1.16, 95% CI = 1.05-1.29) and publication bias (P egger = 0.981). However, the results varied across each subgroup in the stratified analysis of ethnicity and sample size. CONCLUSIONS: Both infant and maternal MTHFR C677T polymorphisms may contribute to the risk of CHDs.