MAGI2-AS3 restrains proliferation, glycolysis, and triggers apoptosis in acute lymphoblastic leukemia via regulating miR-452-5p/FOXN3 pathway.

Objectives: MAGI2-AS3 is a cancer suppressor gene of multiple malignancies. Acute lymphoblastic leukemia (ALL) is an important type of leukemia that especially occurs in children. Our work evaluated the modulation of MAGI2-AS3 in ALL. Materials and Methods: qPCR and Western blotting were adopted for detection of target molecular expression. Growth and apoptosis were determined by CCK8 assay and Annexin V/PI staining. Glycolysis was detected by commercial kits. The direct binding between miR-452-5p and MAGI2-AS3 or FOXN3 was assessed by luciferase reporter assay. Tumor growth was measured in nude mice in vivo. Results: MAGI2-AS3 was down-regulated in ALL. Enforced expression of MAGI2-AS3 inhibited growth and glycolysis while promoting apoptosis of ALL cells. Moreover, MAGI2-AS3 up-regulated FOXN3 via sponging miR-452-5p. FOXN3 depletion abrogated MAGI2-AS3-mediated anti-cancer action. More importantly, MAGI2-AS3 repressed ALL cell growth in nude mice through regulation of miR-452-5p/FOXN3. Conclusion: MAGI2-AS3 inhibits ALL development via modulating miR-452-5p/FOXN3.

[Change of serum levels of pentraxin-3 and syndecan-4 in children with chronic heart failure].

OBJECTIVE: To study the change and significance of serum pentraxin-3 (PTX-3) and syndecan-4 in children with chronic heart failure (CHF). METHODS: A total of 40 children with CHF who were admitted to the Department of Pediatrics of the First Affiliated Hospital of Zhengzhou University were enrolled as the heart failure group, and 30 children who underwent physical examination in the outpatient service during the same period of time were enrolled as the control group. The serum levels of PTX-3, syndecan-4, and N-terminal pro-brain natriuretic peptide (NT-proBNP) were compared between the two groups. RESULTS: The children with CHF had significant reductions in the serum levels of PTX-3, syndecan-4, and NT-proBNP after treatment. The levels of these markers in children with CHF were significantly higher than the control group before and after treatment (P < 0.05). The CHF children with grade II/III/IV cardiac function had significantly higher serum levels of PTX-3 and syndecan-4 than the control group (P < 0.05). The levels of PTX-3 and syndecan-4 were related to the severity of cardiac function. Compared with the grade II cardiac function group, the grade IV cardiac function group had significant increases in the serum levels of PTX-3 and syndecan-4 (P < 0.05). The serum level of PTX-3 was positively correlated with that of syndecan-4 in children with CHF (rs=0.999, P < 0.05); the serum level of PTX-3 was positively correlated with NT-proBNP, left ventricular mass index (LVMI), and cardiac function grade (rs=0.726, 0.736, and 0.934 respectively, P < 0.05) and was negatively correlated with left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) (rs=-0.852 and -0.767 respectively, P < 0.05); the serum level of syndecan-4 was positively correlated with NT-proBNP, LVMI, and cardiac function grade (rs=0.733, 0.743, and 0.934 respectively, P < 0.05) and was negatively correlated with LVEF and LVFS (rs=-0.856 and -0.771 respectively, P < 0.05). CONCLUSIONS: Serum PTX-3 and syndecan-4 may be involved in the development and progression of ventricular remodeling in children with CHF and may be used as markers for the diagnosis, cardiac function grading, and treatment outcome evaluation of children with heart failure.

[Clinical manifestations and gene mutation analysis of children with noncompaction of the ventricular myocardium: an analysis of 6 cases].

This article summarizes and analyzes the clinical features and gene mutation characteristics of children with noncompaction of the ventricular myocardium (NVM). For the 6 children with NVM (4 boys and 2 girls), the age of onset ranged from 3 months to 12 years. Of the 6 children, 5 had arrhythmia, 3 had cardiac insufficiency, 1 had poor mental state, and 1 had chest distress and sighing. NVM-related gene mutations were detected in 4 children, among whom 2 had MYH7 gene mutation, 1 had PRDM16 gene mutation, and 1 had mutations in the ACTN2 and TNNT2 genes. Four children had improvement in cardiac function. The two children with no significant improvement in cardiac function had a younger age of onset, a greater reduction in systolic function on echocardiography, and greater increases in myocardial enzyme and N-terminal pro-brain natriuretic peptide. It is concluded that for children with the initial symptoms of chest distress, sighing, arrhythmia, enlarged heart shadow, and increased myocardial enzyme, echocardiography and cardiac magnetic resonance are recommended for the diagnosis of NVM. NVM can have various genetic mutations.

[Changes in serum chromogranin A and urotensin II levels in children with chronic heart failure].

OBJECTIVE: To examine the changes in serum chromogranin A (CgA) and urotensin II (U II) levels in children with chronic heart failure (CHF) and their clinical significance. METHODS: A total of 58 children with CHF, among whom 17 had endocardial fibroelastosis (EFE) and 41 had dilated cardiomyopathy (DCM), were selected as CHF group, and 20 healthy children were selected as control group. Serum levels of CgA and U II were measured using enzyme-linked immunosorbent assay, and the level of N-terminal pro-brain natriuretic peptide (NT-proBNP) was determined by bi-directional lateral flow immunoassay. Ventricular remodeling indices were measured using echocardiography. The correlation between serum CgA and U II levels and ventricular remodeling was evaluated by Pearson correlation or Spearman's rank correlation analysis. RESULTS: There were no significant differences in serum CgA and NT-proBNP levels between children with grade II heart function and the control group (P>0.05). However, the serum CgA and NT-proBNP levels gradually increased as the heart function grade increased, and were significantly higher in grade III and IV children compared to those in the control group (P<0.05). U II levels were lower in children with grade II, III, or IV heart function than those in the control group (P<0.05), and significantly decreased with the aggravation of CHF (P<0.05). There were no significant differences in CgA and U II levels between patients with EFE and DCM (P>0.05). Serum CgA concentration was positively correlated with left ventricular mass index (LVMI), NT-proBNP, and cardiac function classification (r=0.279, 0.649, and 0.778 respectively; P<0.05), but was negatively correlated with left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and U II (r=-0.369, -0.322, and -0.718 respectively; P<0.05). Serum U II concentration was negatively correlated with NT-proBNP and cardiac function classification (r=-0.472 and -0.591 respectively; P<0.05), but was not correlated with LVMI, LVEF, and LVFS (P>0.05). CONCLUSIONS: CgA may play a role in ventricular remodeling in children with CHF. Serum CgA and U II may serve as a reference for the diagnosis and functional classification of heart failure.

[Change in serum follistatin-like protein 1 and its clinical significance in children with chronic heart failure].

OBJECTIVE: To investigate the change in the serum level of follistatin-like protein 1 (FSTL1) in children with chronic heart failure and its correlation with left ventricular remodeling. METHODS: A total of 45 children with chronic heart failure (CHF) between May 2014 and May 2015 were selected as the CHF group, among whom 21 had endocardial fibroelastosis (EFE) and 24 had dilated cardiomyopathy (DCM); another 30 healthy children were selected as the control group. Enzyme-linked immunosorbent assay was applied to measure the serum level of FSTL1. Radioimmunoassay was applied to measure N-terminal pro-brain natriuretic peptide, and echocardiography was applied to measure the indicators of left ventricular remodeling. The correlation between the serum level of FSTL1 and left ventricular remodeling was analyzed by Pearson correlation and Spearman′s rank correlation analysis. RESULTS: Before treatment, the CHF group had a significantly higher serum level of FSTL1 than the control group (P<0.05), which gradually increased with aggravation of CHF (P<0.05). The serum level of FSTL1 showed no significant difference between the EFE and DCM groups (P=0.176). Serum level of FSTL1 was positively correlated with left ventricular end-diastolic diameter (r=0.485, P=0.001), left ventricular mass (r=0.322, P=0.031), left ventricular mass index (r=0.353, P=0.017), and N-terminal pro-brain natriuretic peptide (r=0.562 P<0.001), and was negatively correlated with left ventricular ejection fraction (r=-0.436, P=0.003) and left ventricular minor axis decurtation rate (r=-0.436, P=0.003). CONCLUSIONS: FSTL1 might take part in the left ventricular remodeling in children with CHF, and the serum level of FSTL1 can be used as an objective index for clinical diagnosis and severity assessment of CHF in children.

[Comparison of prognosis in children with acute viral myocarditis induced ventricular premature beats originating from different positions and the clinical value of mgocardial perfusion ECT].

OBJECTIVE: To study the difference in prognosis for children with acute viral myocarditis induced ventricular premature beats (VPB) originating from different positions, and to study the role of 99Mtc-MIBI myocardial perfusion ECT in the prognostic evaluation of VPB. METHODS: The clinical data of 83 children with viral myocarditis induced VPB were retrospectively studied. They were divided into four groups according to the original site of VPB, as shown by the ECG: right ventricular (RV) outflow tract, RV anterior wall and apex, left ventricular (LV) outflow tract, LV anterior wall and apex. All patients were treated with anti-viral drugs and myocardial nutritional medicine. Short-term and long term outcomes in the four groups were compared. The relationship between the results of 99Mtc-MIBI myocardial perfusion ECT and prognosis in 40 patients was observed. RESULTS: There were no significant differences in short-term and long-term effective rates among the four groups (P>0.05). There were no differences in the ECT positive rates between the patients with VPB originating from RV and those with VPB originating from LV (P>0.05). The treatment effective rates of ECT-positive patients were higher than the treatment effective rates of ECT-negative ones (P<0.05). CONCLUSIONS: The short-term and long-term prognosis of children with VPB originating from different positions are not significantly different. In children with viral myocarditis induced VPB, positive ECT results suggest a better prognosis.

[B-type natriuretic peptide (BNP) levels and the effects of carvedilol on BNP levels in juvenile rats with right heart failure].

OBJECTIVE: To examine serum B-type natriuretic peptide (BNP) levels and BNP expression of protein and mRNA in the right ventricular myocardium in juvenile rats with right heart failure (RHF) and the effects of beta-adrenergic receptor blocker carvedilol on serum and myocardial BNP levels in order to investigate the role of BNP in the diagnosis and treatment of RHF. METHODS: Fifty-one four-week-old Sprague-Dawley rats were randomly assigned to 5 groups: RHF 1, RHF 2, carvedilol-treated RHF, control 1 and control 2. RHF was developed 4 weeks after an intraperitoneal injection of monocrotaline in the RHF 1, RHF 2 and carvedilol-treated RHF groups. The rats in the RHF 1 and the control 1 groups were sacrificed after the RHF event for observing pathological changes in the myocardium. After the RHF event, the carvedilol-treated group was given intragastric administration of carvedilol (3.5 mg/kg/d) for 2 weeks. The RHF 2 and the control 2 groups were given distilled water of equal dose instead. The rats were sacrificed 2 weeks after carvedilol or distilled water administration. Serum BNP levels were measured using ELISA. BNP protein and mRNA expression in the right ventricular myocardium were measured by immunohistochemistry and RT-PCR, respectively. Haemodynamics and some physiological indexes were measured. RESULTS: Serum BNP levels and BNP protein and mRNA expression in the right ventricular myocardium were significantly higher in the RHF 1 group than those in the control 1 group (p<0.01). Serum BNP levels and BNP protein and mRNA expression in the right ventricular myocardium increased more significantly in the RHF 2 group. There was a positive correlation between serum BNP levels and myocardial BNP protein expression in the RHF group (r=0.698, p<0.01). Serum BNP levels and BNP protein and mRNA expression in the carvedilol-treated RHF group were significantly reduced when compared with the RHF 2 group (p<0.05). Carvedilol treatment also resulted in improved hemodynamics and relieved right ventricular hypertrophy. CONCLUSIONS: BNP may serve an index for the diagnosis of RHF and the evaluation of severity in children with RHF. Carvedilol shows protections against RHF caused by pressure load.

[Levels of serum brain natriuretic peptide in children with congestive heart failure or with severe pneumonia].

OBJECTIVE: Some research has shown that B-type brain natriuretic peptide (BNF) is helpful in differentiating cardiac from pulmonary etiologies of dyspnea in adults. This study was designed to investigate whether BNP concentration could be similarly applied in children presenting with dyspnea. METHODS: Blood samples were collected from 65 children presenting with dyspnea, due to congestive heart failure (CHF, n=24), pneumonia (n=23) or pneumonia together with CHF (n=18). The samples from 15 healthy children were used as the controls. There were no significant differences in age among the four groups. Serum BNP levels were measured using ELISA. RESULTS: Serum BNP levels in the CHF group (141.55 +/- 75.99 pg/mL) were significantly higher than those in the Pneumonia group (26.00 +/- 14.57 pg/mL; P < 0.01), and the Pneumonia together with CHF group (113.73 +/- 87.05 pg/mL; P < 0.05), as well as the Control group (19.31 +/- 10.30 pg/mL; P < 0.01). The patients with pneumonia together with CHF had significantly higher serum BNP levels than those of the Pneumonia and the Control groups (P < 0.01). There were no significant differences in BNP levels between the Pneumonia and the Control groups. The area under the receive operator characteristic (ROC) curve, which demonstrated the diagnostic utility of BNP in differentiating CHF from pneumonia, was 0.978 (P < 0.01). At a cut-off of 49 pg/mL, BNP had a sensitivity of 87.5% and a specificity of 95.8% for differentiating CHF from pneumonia. In the 18 patients who were diagnosed with pneumonia together with CHF, 11 had BNP levels above 49 pg/mL. The mean levels of BNP of the 11 patients were significantly higher than those of the patients with pneumonia (172.08 +/- 56.47 pg/mL vs 25.00 +/- 14.57 pg/mL; P < 0.01) but were significantly decreased after treatment (26.12 +/- 15.71 pg/mL; P < 0.01). CONCLUSIONS: BNP level is of value in differentiating cardiac from pulmonary causes of dyspnea in children. BNP level is also helpful in assessing whether or not severe pneumonia couples with heart failure in children.