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Objective@#To explore the mediation mechanism of coronary artery lesion among both male and female Kawasaki disease (KD) children.@*Methods@#Children with KD that hospitalized in the Wenzhou Medical University affiliated Yuying Children’s Hospital from January 2009 to December 2014, were included in this study. Differences on demographical characteristics, clinical manifestations, laboratory indicators, regimen and time of treatment, results from pre/post echocardiography and treatment between male and female patients, were compared. The independent effect of gender on the risk of coronary artery lesions (CAL) was evaluated, and the mediating effect of BMI, visiting time and KD type on the association between gender and CAL were also studied.@*Results@#The average BMI level of male patients was higher than that of female patients. The difference was statistically significant (P<0.001). The prevalence of overweight among male patients (20.9%) was higher than female (14.1%). The difference was statistically significant (P=0.011). Data from the multivariate logistic regression analysis confirmed that the incidence of CAL in male patients was higher than that in female patients (aOR=1.50, 95%CI: 1.06-2.12) but the CAL was mainly different before on the immunoglobulin therapy. Results from the mediation analysis showed that BMI was an important mediator in the association between gender and CAL, with the indirect effect as 1.05 (95%CI: 1.01- 1.10) and the proportion mediated as 13.0%.@*Conclusions@#Male patients presented higher incidence of CAL but was mainly reflected in the difference of CAL before the treatment. BMI was probably an important mediator related to the association between gender and CAL.
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Objective To study the expression of plasma oxidized low-density lipoprotein (oxLDL) in children with acute phase Kawasaki disease (KD), and investigate its value for early prediction of coronary artery lesions in KD. Methods Totally 80 children with KD were collected. Children were divided into four groups by the results of echocardiogram of coronary artery in different periods: CAL1 group (children with coronary artery lesions (CAL+) both in acute and sub-acute phase, 8 cases), CAL2 group (children with CAL+in acute phase but recovery normal (CAL-) in sub-acute phase, 10 cases), NCAL1 group (children with CAL-in acute phase but occur CAL+ in sub-acute phase, 10 cases) and NCAL2 group (children with CAL- both in acute and sub-acute phase, 52 cases). The serum samples (before the use of intravenous immunoglobulin) were collected in acute phase. Twenty healthy controls and twenty fever controls were enrolled into the study, and their serum samples were collected. OxLDL was measured by enzyme linked immunosorbent assay (ELISA). They were compared using ANOVA, pairwise comparison LSD-t test. And ROC curve analysis was used to determine the threshold. Results Compared with the control groups,plasma oxLDL levels were higher in children with KD, both CA+and CAL-[(15.0±3.3) mU/L, (12.3±3.5) mU/L vs (9.2±2.2) mU/L, (8.0±2.3) mU/L, F=20.435, P<0.05]. Plasma oxLDL levels were increased more significantly in children with CAL+ than children with CAL- in KD [(15.0 ±3.3) mU/L vs (12.3 ±3.5) mU/L, t=2.28, P=0.002]. There was significant difference in the concentration of oxLDL between the groups of Kawasaki disease (F=5.068, P=0.003). Plasma oxLDL levels were significantly higher in the NCAL1 group than those in the NCAL2 group [(14.5 ±3.8) mU/L vs (11.9±3.3) mU/L, t=2.29, P=0.02], but there were no statistically significant difference between the NCAL1 group and CAL1 or CAL2 group [(14.5±3.8) mU/L vs (15.9±3.9) mU/L, (14.5±3.8) mU/L vs (14.2±2.7) mU/L, t=0.73, 0.20;P=0.41, 0.84]. ROCs analysis indicated that oxLDL≥13.83 mU/L, could be the threshold for the prediction of coronary artery lesions with the sensitivity of 0.607 and a specificity of 0.75. Conclusion OxLDL plays an important role in coronary artery lesions in KD. The coronary endothelial dysfunction is earlier than coronary dilatation, and oxLDL is expected to become a reliable early predictor of coronary artery lesions in KD.
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Objective To investigate the changes of serum 8-hydroxy-2'-deoxyguanosine(8-OHDG) in Kawasaki disease (KD) children and to explore the importance of 8-OHDG in predicting the severity of coronary artery lesions in Kawasaki Disease.Methods The serum 8-OHDG was measured in KD patients group (n =60),fever patients group (n =12) and health control group (n =12) by ELISA method.Among the KD patients,30 KD patients were in acute stage (10 cases had coronary artery lesions,20 coronary were normal) and 30 patients were in recovery stage.The serum 8-OHDG and brain natriuretic peptide (BNP) were also compared between patients with coronary artery lesions (CALs) and patients with no coronary artery lesions NCALs).ROC curve analysis was used to test the 8-OHDG and BNP predictive values in KD with coronary artery lesions.Results The serum level of 8-OHDG was higher in acute KD patients than recovery KD patients,fever patients and healthy children (P ＜ 0.05) The serum 8-OHDG was higer in CALs patients than the NCALs patients (P ＜ 0.05).The serum BNP was higer in CALs patients than the NCALs patients (P ＜ 0.01).Analysis of the ROC curve showed that serum 8-OHDG had a positive predictive value of 64.3％ and a negative predictive value of 93.8％for distinguishing KD with CALs from KD NCALs when cutoff value was 57.02pg/ml.The area under the curve was 0.820.The serum BNP had a a positive predictive value of 47.6％ and a negative predictive value of 100％ for distinguishing KD with CALs from KD NCALs when cutoff value was 815pg/ml.The area under the curve was 0.745.Conclusion The serum 8-OHDG may have better predictive value than BNP in diagnose KD children with coronary artery lesions.
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Objective To explore the effects of bone marrow mesenchymal stem cells (BMSCs) on viral myositis in mice. Methods Four-week-old BALB/C male mice were randomly divided into normal control group, myocarditis group, and BMSCs intervention group at different stages (3 days and 2 weeks). The mouse model of viral myocarditis was established by intraperitoneal injection of Coxsackie virus B3. The mice in the intervention group were injected with BMSCs in the tail vein at 3 days and 2nd week after the injection of the virus. Four weeks later, echocardiography was performed, and the pathological integral and collagen volume fraction (CVF) were observed and calculated by light microscopy. The qRT-PCR method was used to detect the mRNA expression of homogenates collagen I (col1α1) and collagen fiber III (col3α1) in myocardial tissue. Results Compared with the normal control group, the left anterior and posterior wall became thinner, the diameter and volume of the left ventricle at end systolic period was increased; left ventricular ejection fraction (LVEF) and short axis shortening rate (FS) decreased in the myocarditis group. The differences were statistically significant (P all<0.05). The LVEF and FS in each subgroup of the intervention group were better than those of the myocarditis group, and the improvement in the intervention group was more obvious at the 2nd week after the treatment of the myocarditis. The differences were significant (P all<0.05). Light microscope showed that myocardial CVF in myocarditis group was higher than in normal control group, and CVF in intervention group was reduced compared with myocarditis group and CVF in the 2nd week intervention group was lower than that in the 3 day intervention group. The differences were significant (P all<0.05). Compared with the control group, the mRNA expressions of col1α1 and col3α1 in the myocarditis group were increased, and they were lower in the intervention group than in the myocarditis group, and the differences were significant (P all<0.05). Conclusions BMSCs can reduce the degree of cardiac fibrosis and improve cardiac function in mice with viral myositis, and the intervention effect is better when the virus is infected in the 2nd week.
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Objective@#To explore the impact of hydrogen sulfide (H2S) on the heme oxygenase-1/carbon monoxide pathway in Coxsackie virus B3 (CVB3)-induced murine myocarditis (VMC) model.@*Method@#A total of 70 inbred male Balb/c mouse (4-6 weeks old) were randomized into the following four groups: Normal, VMC, PAG and NaHS (n=10 for Normal, n=20 for VMC, PAG and NaHS groups). Mice in Normal group were non-infected mice treated with intraperitoneal injection of sterile phosphate-buffered saline daily for 10 days.Mice in VMC group received intraperitoneal CVB3 injection (0.1 ml 10-5.69TCID50m·ml-1·d-1 and PBS for 10 days), and mice in PAG group received additional intraperitoneal DL-proparglygylcine injection (40 mg·kg-1·d-1 for 10 days), mice in NaHS group received additional intraperitoneal NaHS injection (50 μmol·kg-1·d-1 for 10 days). All mice were sacrificed on day 10th, and body weight and heart weight, the ratio of heart weight to body weight were compared among groups.Pathological changes of heart tissues were observed microscopically by HE and the histopathologic scores were valued.The content of COHb was tested after the gathering of blood specimens while reverse transcription-polymerase chain reaction was used to detect myocardial HO-1 mRNA expression.@*Results@#(1) Pathological findings in myocardium: hearts sections in Normal group were normal and no inflammatory cells and necrosis were found.A notable cellular infiltration, interstitial edema, vascular hyperemia and necrosis were observed in heart section of VMC, PAG and NaHS group.Extensive inflammations and larger area of myocardial cells necrosis were evidenced in PAG group and above changes were significantly reduced in NaHS group.(2) Comparison of the ratio of heart weight to body weight and histological scores of myocardium: the ratio was significantly higher in the VMC, PAG, NaHS groups than in Normal group (P<0.05), which was higher in PAG group and lower in NaHS group as compared with VMC group (both P<0.05). The histopathologic scores of all CVB3 innoculation groups were higher than in the Normal group, which was higher in PAG group and lower in NaHS group as compared to VMC group (both P<0.05). (3) The content of blood COHb in VMC, PAG or NaHS group was significantly higher than that in Normal group (P<0.05), which was significantly lower in PAG group, and higher in NaHS group as compared to VMC group (both P<0.05). (4) The mRNA expression of myocardial HO-1 detected by RT-PCR: weak expression was observed in Normal group, which was significantly upregulated in VMC, PAG and NaHS groups (P<0.05), which was downregulated in PAG group and upregulated in NaHS group as compared to VMC group (both P<0.05). (5) Correlation analysis: blood COHb concentration was positively correlated with myocardial HO-1 mRNA expression(r=0.927, P=0.000), negatively correlated with histopathologic scores(r=-0.753, P=0.000)and the histopathologic scores were negatively correlated with the myocardial HO-1 mRNA expression (r=-0.754, P=0.000).@*Conclusions@#H2S could play a protective role in murine CVB3 myocarditis model through inducing HO-1 expression and upregulating HO-1/CO pathway.
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<p><b>OBJECTIVE</b>To explore the effects of tanshinone and JAK2/STAT1 signaling pathway related mechanism in CVB3-induced myocarditis in murine.</p><p><b>METHODS</b>A total of 110 inbred male Balb/c mice which were 4 to 6 weeks-old were randomly divided into five groups: normal control (N, n = 10), myocarditis control (C, n = 25), tanshinone group (T, 15 mg · kg⁻¹ · d⁻¹, i.p., n = 25), janus kinase 2 inhibitor AG490 group (A, 10 mg · kg⁻¹ · d⁻¹, i.p., n = 25), T+A group (H, n = 25). Myocarditis was induced by 0.5 ml 10(-9.51) TCID50/ml CVB3 i.p. injection for 10 days in group C, T and H. Myocardial histopathologic changes were observed and phospho-STAT1 expressions were detected by immunohistochemistry and Western blot analysis. The levels of serum cardiac troponin I were detected with chemiluminescence immunoassay.</p><p><b>RESULTS</b>(1) Compared with group C, the histopathologic scores were significantly higher in group A and H (3.35 ± 0.57 and 3.34 ± 0.54 vs. 2.12 ± 0.39, P < 0.01), but lower in group T (1.40 ± 0.34 vs.2.12 ± 0.39, P < 0.01). (2) The expression of p-STAT1 protein was similar in group A and H compared to group N (P > 0.05), but was significantly lower than that in group C (0.017 ± 0.010 and 0.020 ± 0.010 vs. 0.246 ± 0.010, P < 0.01). The expression of p-STAT1 protein was significantly higher in group T than in group C (P < 0.01). (3) The levels of serum cardiac troponin I in group C, A, T and H were significantly higher than in group N ((0.42 ± 0.06), (1.17 ± 0.25), (0.23 ± 0.05) and (1.04 ± 0.19) µg/L vs. (0.02 ± 0.01) µg/L, all P < 0.01). The levels of serum cardiac troponin I were significantly higher in group A and H compared with group C ((1.17 ± 0.25) and (1.04 ± 0.19) µg/L vs. (0.42 ± 0.06) µg/L, P < 0.01), but were significantly lower in group T than in group C ((0.23 ± 0.05) µg/L vs. (0.42 ± 0.06) µg/L, P < 0.01). (4) There was a negative correlation between the expression level of p-STAT1 and the histopathologic scores (y = -4.503 x + 3.371, R² = 0.738, P < 0.01), but a positive correlation between the levels of serum cardiac troponin I and the histopathologic scores (y = 1.935x + 1.165, R² = 0.766, P < 0.01).</p><p><b>CONCLUSION</b>Tanshinone could attenuate myocardial injury via upregulating the JAK2/STAT1 signaling pathway in this murine viral myocarditis model.</p>
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Animals , Male , Mice , Blotting, Western , Coxsackievirus Infections , Disease Models, Animal , Abietanes , Pharmacology , Heart Injuries , Janus Kinase 2 , Mice, Inbred BALB C , Myocarditis , Drug Therapy , Virology , Myocardium , STAT1 Transcription Factor , Signal Transduction , Troponin IABSTRACT
Objective To explore the clinical features and treatment of children with acute severe viral myocarditis.Methods The clinical data of presentation,diagnosis,therapy and prognosis of children who were admitted in our hospital from Jan 2005 to Jan 2012 with acute severe viral myocarditis(severe myocarditis group) were analyzed retrospectively.Twenty-three cases of normal healthy children in the same period were selected as control group.The levels of serum cardiac troponin(CTn)-Ⅰ and N-terminal pro-brain natriuretic peptide(NT-proBNP) were detected by ELISA method,the changes of left ventricular ejection fraction and left ventricular fraction shortening were understood by color doppler echocardiography.Results The level of CTn-Ⅰin severe myocarditis group was significantly higher than that of control group,the difference was statistically significant [(18.67 ± 12.31) ng/ml vs (0.02 ±0.01) ng/ml,P ＜0.05].Compared with the acute phase,the level of CTn-Ⅰshowed a trend of gradual decline in 7 d [(0.55 ±0.24) ng/ml],basic close to normal in 14 d [(0.06 ±0.03) ng/ml] (P ＜0.05).The level of NT-proBNP increased significantly in severe myocarditis group compared with control group [(3 067.26 ± 902.79) pg/ml vs (80.04 ± 17.79) pg/ml,P ＜0.05].Compared with acute phase,the levels of NT-proBNP were closed to normal in 7 d [(648.63 ±342.37) pg/ml] and 14 d [(213.58 ± 129.51) pg/ml] (P ＜ 0.05).The left ventricular ejection fraction [(52.63 ± 6.98) ％ vs (71.39 ± 2.41) ％] and left ventricular fraction shortening [(32.1 ± 2.97) ％ vs (40.04 ± 2.31) ％] in severe myocarditis group were significantly lower than those in control group (P ＜ 0.05).Conclusion Acute severe viral myocarditis of children was characterized by rapid onset,severe illness and high mortality.Early use of adrenal cortical hormone and gamma globulin under the comprehensive treatment and application temporary pacemaker can help patients to recover from the disease.
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Objective To evalute the incidence and epidemiologic characteristics of Kawasaki disease (KD) in Wenzhou,China.Methods We used a questionnaire survey and reviewed the medical records and reports of all patients with KD diagnosed during the 10 year periods from January,2001 to December,2010.Results We studied 827 inpatients diagnosed with KD during the 10-years period from 2001 to 2010.There were 613 cases (74.12％) with complete KD.The ratio of male to female ratio was 2.28∶1.Age at onset ranged from 37 days to 13 years old,and the peak age group was 1 year old.The disease occurred in all of the seasons,but the peak was from April to June.The incidence of cardiovascular damage in acute KD was 34.6％,and the most common sequela was coronary artery dilatation.There were16 patients with coronary aneurysm.Fifty-three patients did not respond to immunoglobulin (6.4％),and 12 patients (1.5％) developed recurrent KD.After treatment,114 cases (13.8％) developed neutropenia.There were no deaths during hospitalization.Conclusion Patients with KD has become more and more in Wenzhou.Cardiovascular damages were similar to those in Beijing and Guangzhou,but higher than that reported in Japan.
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Objective To investigate the change of leptin,nitric oxide (NO) and interleukin-6 (IL- 6) levels in serum of children with Kawasaki disease (KD) and the possible relationship between leptin,NO and IL-6 levels,explore the role of leptin,NO and IL-6 in the pathogenesis of KD.Methods Fourty-five children with KD were studied.Twelve of them had coronary artery lesions and 33 had non-coronary artery lesions;thirty healthy children and 18 children with juvenile idiopathic arthritis or Henoch-Scholeion purpuru were enrolled as control subjects.Serum was collected from each patients during acute stage of KD and remission.Leptin,NO and IL-6 contents were detected by radioimmuno-assay and spectrophotometry and enzyme-linked immunoserbent assay.Meanwhile,C-reactive protein (CRP) were examined.Results ① The concentrations of serum leptin,NO,IL-6 and CRP in children with KD were significantly higher in the acute stage of KD than those at clinical remission and those of the normal control group (q=26.24,25.23; 21.38,31.30;35.37,33.68;16.32,15.66;P＜0.01,respectively).No significant differences in serum leptin, IL-6 and CRP were found between the clinical remission group and the normal control group (q=1.02,1.04, 0.61,P＞0.05,respectively);The concentrations of serum NO were significantly higher at clinical remission group than those of the normal control group (q=11.31,P＜0.01).② There was no significant difference in the concentrations of serum leptin,IL-6 and CRP at the acute stage of KD than those in patients with and without coronary artery lesions (q=1.17,1.92,1.60,P＞0.05).The concentrations of serum NO were significantly higher at the acute stage of KD with coronary artery lesions than those of KD without coronary artery lesions (q=6.91,P＜0.01).③ The concentrations of serum leptin in children with juvenile idiopathic arthritis or Henoch-Scholeion purpura were signifietantly higher than those of the normal control group (t=13.26,P＜ 0.01).No significant differences in serum leptin were found between children with juvenile idiopathic arthritis or Henoch-Seholeion purpura and children with KD (t=1.28,P＞0.05).④ Correlation was found between serum leptin values and levels of the following parameters (P＜0.01);NO (r=0.69),IL-6 (r=0.55),CRP (r=0.42).However,there were no associations between leptin and leukocytes (r=0.21,P＞0.05) or serum albumin level (r=-0.24,P＞0.05).Association was found between serum NO and IL-6 (r=0.45,P＜0.01)or CRP(r=0.49,P＜0.01).Conclusion These results suggest that leptin,NO and IL-6 may have a role in the immunoinflammatory process of KD,especially in the acute phase.Further in vivo and in vitro studies are needed to establish the roles of leptin,NO and IL-6 in the pathogenesis of KD.
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Objective To evaluate the efficiency and preliminary results of transcatheter closure of perimembrane ventricular septal defects (PMVSD) using Amplartzer occluder device in children.Methods There were 5 children using transthoracic echocardiography(TTE) to confirm the PMVSD before the intervention. The diameters of the PMVSD were measured by angiography; Each of the children were treated with Amplartzer occluder device for transcatheter closure of PMVSD under TTE and fluoroscopy. The TTE and elec-trocardiograph(ECG)、chest X-ray were performed 24 hours,1 and 3、6 months after the procedure to evaluate the therapeutic effect. Results The mean diameter of the PMVSDs measured by angiography was 5.0?2.4 mm(Ranging from 2.5 to 8.3 mm). The mean diameter of the occluder selected was 7.4?3.2 mm(Ranging from 4 to 10 mm). The success rate was 100%, and no complication occurred during the procedure. No residual shunts were found by angiography immediately after the procedure in all cases. There were no malpositions of occluder and no residual shunts in the 5 cases by TTE after the procedure 24 hours , 1 and 3、 6 months. There were no cardiac arrhythmia found by ECG. It showed that both pulmonary vascularity were improved.Conclusions Transcatheter closure of perimembrane ventricular septal defects using Amplartzer occluder device is an efficient therapy for children with PMVSD. The operation is simple with a high success rate of placement and a good occlusion effect. Further studies of long term results are required.
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To explore the clinical significance of serum cardiac troponin I (cTnI) for the detection of myocardial injury in children with Kawasaki disease (KD) in acute stage, the levels of serum cTn I, creatine kinase (CK), creatine kinase isoenzyme (CK-MB), lactic dehydrogenase (LDH) and glutamic oxalacetic transaminase (GOT) were determined in 40 children with KD and 23 controlled children without heart disease, respectively. The results showed that the levels of serum cTn I and CK-MB in the KD group were significantly higher than those in the controlled group (P＜0.001),while no obviously differences of CK, LDH and GOT were noticed between two groups (P＞0.05). cTn I was more sensitive comparing to CK-MB for the detection of myocardial injury (P＜0.05). It is concluded that the determination of cTn I and CK-MB will be available for the diagnosis of myocardial injury in children with KD in acute stage, and the determination of cTn I is more sensitivity and specificity comparing to CK-MB.