Clinical effect and safety of clopidogrel combined with aspirin in antithrombotic therapy for children with Kawasaki disease complicated by small/medium-sized coronary artery aneurysms / 中国当代儿科杂志

OBJECTIVE@#To study the clinical effect and safety of clopidogrel combined with aspirin in antithrombotic therapy for children with Kawasaki disease (KD) complicated by coronary artery aneurysm (CAA).@*METHODS@#A total of 77 KD children who were diagnosed with multiple small/medium-sized CAAs by echocardiography between January 2013 and June 2018 were enrolled. They were randomly divided into observation group with 38 children (treated with clopidogrel and aspirin) and control group with 39 children (treated with low-molecular-weight heparin and aspirin). All children were followed up regularly, and the first 3 months of the course of the disease was the observation period. The children were observed in terms of the change of the coronary artery and the incidence of complications.@*RESULTS@#At month 3 of follow-up, among the children in the observation group, 6 had normal coronary artery, 11 had coronary artery retraction, 19 had stable coronary artery, and 2 progressed to giant coronary aneurysm; among the children in the control group, 7 had normal coronary artery, 12 had coronary artery retraction, 19 had stable coronary artery, and 1 progressed to giant coronary aneurysm; there was no significant difference in the change of the coronary artery between the two groups (P>0.05). There were 2 cases of epistaxis and 6 cases of skin ecchymosis in the observation group, and 1 case of epistaxis and 7 cases of petechiae and ecchymosis at the injection site in the control group, and no other serious bleeding events were observed in either group.@*CONCLUSIONS@#Clopidogrel combined with low-dose aspirin is safe and effective in antithrombotic therapy for children with KD complicated by CAA.

Relationship between heart rate variability and coronary artery lesion in children with Kawasaki disease / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To explore the correlation of heart rate variability (HRV) indices with cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in children with Kawasaki disease (KD) and their prognostic value.</p><p><b>METHODS</b>A total of 130 children with KD were assigned into coronary artery lesion (CAL) group (n=47) and non-coronary artery lesion (NCAL) group (n=83). Meanwhile, 110 healthy children and 29 children in the recovery stage of non-cardiovascular diseases were selected as control and non-KD groups, respectively. Patients in the four groups received 24-hour HRV monitoring. Levels of serum cTnI and NT-proBNP were measured in the KD and the non-KD group.</p><p><b>RESULTS</b>Compared with the controls of the same sex and age, the KD patients had significantly reduced standard deviation of all normal sinus RR intervals (SDNN), mean of SDNN (SDNN index), percentage of successive normal sinus RR intervals>50 ms (pNN50), very low frequency (VLF), low frequency (LF), and high frequency (HF) but a significantly increased LF/HF ratio (P<0.05). The HRV indices including SDNN, standard deviation of all mean 5-minute RR intervals (SDANN), SDNN index, root mean squared successive difference, pNN50, VLF, LF, and HF in the CAL group all significantly decreased compared with those in the control and non-KD groups, while the LF/HF ratio was higher in the CAL group than in the control group (P<0.05). The serum levels of cTnI and NT-proBNP in the CAL and NCAL groups were significantly higher than those in the non-KD group (P<0.05). In children with KD, serum cTnI level was negatively correlated with SDNN and HF but positively correlated with the LF/HF ratio (P<0.05); serum NT-proBNP level was negatively correlated with SDNN, SDANN, and HF (P<0.05).</p><p><b>CONCLUSIONS</b>HRV indices have certain clinical significance in assessing CAL of children with KD.</p>

The role of endogenous vascular elastase in coronary artery reconstruction in Kawasaki disease / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the role of endogenous vascular elastase (EVE) in coronary artery between reconstruction among pediatric patients with Kawasaki disease (KD).</p><p><b>METHODS</b>Sixty children who were diagnosed with KD between January 2012 and April 2013 were selected as the case group, and peripheral venous blood samples were collected on days 0-11 (pathological stage I) and days 12-25 (pathological stage II) after the onset of disease; another 60 children without KD who visited the hospital due to acute fever during the same period were selected as the control group, and fasting peripheral venous blood samples were collected in the acute stage of fever. For both groups, serum levels of EVE and interleukin-6 (IL-6) and plasma vascular endothelial growth factor (VEGF) level were measured by enzyme-linked immunosorbent assay. For the case group, ultrasonic cardiography was used to detect coronary artery lesions (CALs) at the first, second and fourth weekends. The correlations of EVE level with IL-6 and VEGF levels were evaluated by Pearson correlation analysis.</p><p><b>RESULTS</b>Serum levels of EVE and IL-6 in the case group in pathological stages I and II were significantly higher than in the control group (P<0.05), but plasma VEGF levels in stages I and II were significantly lower than in the control group (P<0.05); in the case group, EVE and IL-6 levels were significantly higher in stage II than in stage I (P<0.05). In pathological stage II, KD patients with CALs had significantly higher serum levels of EVE and IL-6 but significantly lower plasma VEGF levels compared with those without CALs (P<0.05); KD patients with coronary artery aneurysms (CAAs) had significantly higher serum levels of EVE and IL-6 but significantly lower plasma VEGF level compared with those without CAAs (P<0.05 for all). EVE level was positively correlated with IL-6 level (r=0.915, P<0.05), yet negatively correlated with VEGF level (r=-0.769, P<0.05).</p><p><b>CONCLUSIONS</b>EVE may participate in coronary artery reconstruction in children with KD. To interfere EVE activity may reduce and prevent CALs.</p>

Effect of glycemic control on progress of left ventricular structure and diastolic dysfunction in adolescent with type 1 diabetes mellitus / 中华实用儿科临床杂志

Objective To investigate the effect of glycemic control on progress of left ventricular structure and diastolic dysfunction in adolescents with type 1 diabetes mellitus (T1 DM).Methods A total of 36 T1DM adolescent patients(observation group) and 36 age-matched healthy controls (healthy control group),who consulted doctors in Chengdu Women and Children's Central Hospital between Dec.2009 and Dec.2010,were recruited into the study.Patients in the observation group were performed standard treatment for glycemic control.All patients were followed-up for 2 years.At the end of the study,the patients in observation group were divided into 3 subgroups according to the average HbA1 c level:excellent glycemic control group [glycosylated hemoglobin (HbA1 c) ＜ 7.6％],good glycemic control group(7.6％ ≤HbA1c≤9.0％) and bad glycemic control group(HbA1c ＞9.0％).All of the subjects were evaluated by means of echocardiography for assessment of left ventricular structural and functional parameters.Results Left ventricular posterior wall depth (LVPW),left ventricular mass index (LVMI) and isovolumic relaxation time (IVRT) were elevated,while E/A was decreased in the observation group compared with the healthy control group at baseline (all P ＜ 0.05).There was no significant difference between 2 groups in interventricular septum thickness (IVS),left ventricular end-diastolic dimension(LVEDd) and cardiac systolic function(all P ＞ 0.05).Echocardiographic parameters of left ventricular structure and function were unchanged in well-controlled patients.At the end of follow-up,mild-control group and non-control group demonstrated increased IVS,LVPW and LVMI,and exacerbated left ventricular diastolic function in the present of IVRT prolonging and E/A decreasing.Conclusions There is an inclination in T1 DM adolescent patients developing to left ventricular diastolic dysfunction,and improved glycemic control can delay the progress of left ventricnlar hypertrophy,but it can't ameliorate the decreased diastolic dysfunction.Whereas,non-improved glycemic control can accelerate left ventricular remodeling and exacerbate diastolic dysfunction in T1DM adolescent patients.

Plasma concentration of growth-differentiation factor-15 in children with congenital heart disease: relation ship to heart function and diagnostic value in heart failure / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the correlation between growth differentiation factor-15(GDF-15) and cardiac function in pediatric patients with congenital heart disease, and the diagnostic value of GDF-15 in heart failure(HF).</p><p><b>METHODS</b>From March 2011 to May 2012, 97 pediatric patients with congenital heart disease(CHD) who consecutively attended Chengdu Women's & Children's Central Hospital were enrolled in the study and assigned to HF (patients with heart failure, n=71) and Non-HF(patients without heart failure, n=26) groups. HF was defined as patients presenting with modified Ross score≥3. Plasma concentrations of GDF-15 and NT-proBNP were determined using ELISA. Left ventricular ejection fraction(LVEF) was tested by echocardiography. The correlation between GDF-15 and modified Ross score, LVEF and NT-proBNP was evaluated with Spearman's analysis. The area under the receiver-operating characteristic(ROC) curve for GDF-15 was examined, and the cut-off concentration of GDF-15 for diagnosing HF was detected.</p><p><b>RESULTS</b>The HF group demonstrated higher levels of GDF-15 and NT-proBNP, and a lower LVEF level (P<0.01) than the Non-HF group. Plasma GDF-15 level was positively correlated with modified Ross score and plasma NT-proBNP concentration (r=0.705, r=0.810 respectively; P<0.01), and negatively correlated with LVEF(r=-0.391, P<0.01). According to ROC analysis, the AUC of GDF-15 for detection of HF was 0.757. Sensitivity and specificity was 68.8% and 71.2% respectively for the cut-off value of 1306 ng/mL.</p><p><b>CONCLUSIONS</b>Plasma GDF-15 levels are significantly elevated in children with HF induced by CHD. Plasma GDF-15 levels are related to cardiac function, LVEF and plasma concentration of NT-proBNP. GDF-15 may potentially indicate HF in pediatric patients with CHD.</p>

Risk factors for coronary artery lesions in children with Kawasaki disease / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study risk factors for the development of coronary artery lesions (CAL) in children with Kawasaki disease (KD).</p><p><b>METHODS</b>The clinical data of 527 children with KD between January 2006 and January 2009 were retrospectively reviewed. A total of 15 potential factors associated with occurrence of CAL were evaluated by univariate analysis and multivariate logistic regression analysis.</p><p><b>RESULTS</b>The univariate analysis showed that age, gender, KD type, starting time of intravenous immunoglobulin (IVIG) treatment, response to IVIG treatment, additional treatment with corticosteroids, duration of fever and serum C-reactive protein level were significantly different between patients with and without CAL (P<0.05). Multivariate logistic regression analysis showed that an age of less than 1 year (OR=2.076, P<0.05) or greater than 8 years (OR=1.890, P<0.05), male sex (OR=1.972, P<0.05), incomplete KD (OR=1.426, P<0.05), delayed starting time of IVIG treatment (10 days after onset) (OR=3.251, P<0.05), no response to IVIG (OR=2.301, P<0.05) and fever duration of more than 10 days (OR=1.694, P<0.05) were independent risk factors for the development of CAL, whereas early starting time of IVIG treatment (before 5 days after onset) was a protective factor (OR=0.248, P<0.05).</p><p><b>CONCLUSIONS</b>The occurrence of CAL is associated with many factors in children with KD. Age of less than 1 year or greater than 8 years, male sex, incomplete KD, delayed IVIG treatment after onset, no response to IVIG treatment and prolonged fever duration have been identified as risk factors for the development of CAL.</p>

Effect of doxycycline on the development of pulmonary hypertension induced by four methods in rats / 中华儿科杂志

<p><b>OBJECTIVE</b>Based on establishment of four rat models of experimental pulmonary hypertension (PH), the authors examined the inhibition of matrix metalloproteinases (MMPs) by doxycycline and its effect on the development of PH and associated pulmonary vascular remodeling.</p><p><b>METHOD</b>Healthy male Sprague-Dawley rats (weight 350 g to 400 g) were randomly divided into nine groups: Normal control group (N), four model groups (H, M, P, PM) and their corresponding drug intervention groups (HD, MD, PD, PMD) in which doxycycline was given by gavage at a 20 mg/kg daily dosage. On day 28 (day 35 for PM and PMD models), the animals were catheterized to record mean pulmonary arterial pressure (mPAP) and then sacrificed. Fulton Index [RV/(LV + S)] was measured immediately. Morphometric parameters, including percent vascular wall thickness and muscularization of non-muscularized peripheral pulmonary arterioles were determined microscopically. The activity of MMPs was measured by gelatin zymography in the lung tissue.</p><p><b>RESULTS</b>(1) Rats in all model groups (H, M, P, PM) developed significant pulmonary arterial hypertension and right ventricular hypertrophy in comparison with their corresponding drug intervention groups (HD, MD, PD, PMD) and normal control group (N) (P < 0.01). For example, mPAP (mm Hg)(1 mm Hg = 0.133 kPa):N: 18.10 +/- 1.45, H: 27.20 +/- 1.55, HD: 23.90 +/- 2.13; Fulton Inedx(%):N: 23.41 +/- 1.84, H: 34.44 +/- 2.70, HD: 27.55 +/- 2.45. (2) The percent vascular wall thickness (WT%) and percentage of muscularization of non-muscular pulmonary arterioles were significantly increased in all model groups compared with drug intervention groups and normal group (P < 0.01). For example, WT%:N: 10.90 +/- 3.11, H:41.41 +/- 5.21, HD: 17.73 +/- 3.12; Muscularization(%):N: 13.83 +/- 3.72, H: 44.93 +/- 2.43, HD: 29.89 +/- 4.45. (3) The activity of MMPs was inhibited by doxycycline effectively as assessed by gelatin zymography (P < 0.01). For example, the activity of MMP2 (A x 10(3)):N: 1.43 +/- 0.24, H: 3.58 +/- 0.28, HD: 2.29 +/- 0.31.</p><p><b>CONCLUSION</b>Doxycycline attenuated PH and associated pulmonary vascular remodeling in all rat PH models. The study suggests that high expression and enhanced activity of MMPs may play a brutial role in the development of PH. Such phenomenon seems to be common in a variety of PH models of different etiology.</p>

Expression of connective tissue growth factor and its down-regulation by simvastatin administration in pulmonary hypertensive rats / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore the role of expression of connective tissue growth factor (CTGF) in pulmonary vascular remodeling of pulmonary hypertensive rats, and investigate the regulation of CTGF expression by simvastatin in this animal model.</p><p><b>METHODS</b>Eighty male Sprague-Dawley rats (350 to 400 g) were randomized to 7 groups. The rats in group PM(1 - 21) (n = 10) and PM(1 - 35) (n = 12) were treated with pneumonectomy + monocrotaline (MCT), and sacrificed at the 21st or 35th experimental day;those in groups PMS(1 - 35) (n = 12), PMS(21 - 35) (n = 12), PMV(1 - 35) (n = 12) and PMV(21 - 35) (n = 12) were given daily lavage of simvastatin (or vehicle) as intervention measure which began from the 1st and 21st experimental days, respectively; additional 10 rats were used as control without any intervention. The animals were sacrificed at the end of experiment (35 th day) as hemodynamic measurements and study on the morphological parameters relevant to pulmonary vascular remodeling were performed on each group of rats. The expression of ET-1 mRNA, CTGF mRNA and protein, and synthesis of collagen in these pneumonectomized, MCT-treated rats were compared between control and rats treated with simvastatin.</p><p><b>RESULTS</b>Rats in PM(1 - 35) Group developed severe PAH (mPAP = 39.75 +/- 3.62 mm Hg) (1 mm Hg = 0.133 kPa), right ventricular hypertrophy [RV/(LV + S) ratio = 0.627 +/- 0.040], and arterial medial hypertrophy (WT% = 61.73 +/- 5.39), these parameters of the control animals were 17.10 +/- 1.20 mm Hg, 0.262 +/- 0.018 and 14.71 +/- 1.16, respectively. CTGF mRNA and protein were mainly located in pulmonary arterial smooth muscle cells and interstitial macrophage shown by in situ hybridization and immunohistochemistry, respectively. The expression of ET-1 mRNA and CTGF mRNA detected by fluorescent quantitative RT-PCR in Group PM(1 - 35) were significantly increased in comparison with controls, and so did the CTGF protein expression determined by Western blotting in these diseased rats. The content of hydroxyproline (1.30 +/- 0.19 microg/mg wet lung) was remarkably higher than that of control animals (0.56 +/- 0.10 microg/mg wet lung). The up-regulation of ET-1 and CTGF gene expression, and elevated synthesis of hydroxyproline were reversed in rats intervened with simvastatin. The pulmonary hypertension, right ventricular hypertrophy and medial hypertrophy were attenuated in all simvastatin-treated rats no matter the intervention was initiated from the beginning or midway of the study.</p><p><b>CONCLUSION</b>The up-regulation of CTGF gene expression may play an important role in the development of pulmonary vascular remodeling in PAH. Simvastatin can prevent and, to some extent, reverse the vascular remodeling via down-regulation of CTGF gene expression.</p>

Effect of triptolide on the expression of matrix metalloproteinases 2 and 9 in lungs of experimental pulmonary hypertension / 中国当代儿科杂志

<p><b>OBJECTIVE</b>It has been shown that triptolide can attenuate pulmonary arterial hypertension in rats. This study was designed to investigate the therapeutic effect of triptolide on pulmonary hypertension in rats and possible mechanisms.</p><p><b>METHODS</b>Sixty Sprague-Dawley (SD) rats were randomly divided into 6 groups: normal control, model, continuous triptolide-treated, delayed triptolide-treated and two placebo groups for continuous and delayed fashions (n=10 each). The rats from the last 5 groups were injected with monocrotaline (MCT, 60 mg/kg) on day 7 after left pneumonectomy. The rats in the continuous triptolide-treated group received therapy from day 5 to 35 with triptolide (0.25 mg/kg intraperitoneally, every other day) and those in the delayed triptolide-treated received therapy with triptolide (0.20 mg/kg intraperitoneally, daily) from day 21 to 35 after operation. The hemodynamic parameters were detected by catheterization and the pathologic changes of small pulmonary arteries were evaluated by light microscopy 5 weeks post-operation. The expression of matrix metalloproteinases (MMPs) was assessed by immunohistochemistry and quantitative fluorescence PCR of relevant (MMP2 and MMP9) mRNAs.</p><p><b>RESULTS</b>By day 35 after operation, the mean pulmonary arterial pressure (mPAP, 38.10+/-1.20 vs 16.70+/-1.16 mmHg)the ratio of right ventricle/left ventricle plus septum [RV/(LV+S), 62.45+/-5.28% vs 22.76 +/-3.01%] and the vessel obstructive scores (VOS, 1.736 +/-0.080 vs 0.000 +/-0.000) increased significantly in the Model group compared with those of the normal control group (P < 0.01). The expression of MMP2 and MMP9 and their mRNA expression in lung tissues obviously also elevated in the Model group (P < 0.05). The continuous and the delayed triptolide-treated groups had significantly lower mPAP (20.80+/-1.03 and 26.20+/-1.03 mmHg, respectively) and less right ventricular hypertrophy and pulmonary arterial neointimal formation compared with the model and the placebo groups. The two treated groups also demonstrated decreased expression of MMP2 and MMP9 and their mRNA expression in lung tissues. There were significant differences in mPAP, RV/(LV+S) and VOS between the two triptolide-treated groups.</p><p><b>CONCLUSIONS</b>Triptolide attenuates the development of pulmonary hypertention and right ventricular hypertrophy and promotes regression of pulmonary arterial neointimal formation in pneumonectomized rats that received MCT, possibly through an inhibition of MMPs activity.</p>