Identification and treatment of worsening heart failure in children with cardiomyopathy / 中国小儿急救医学

Cardiomyopathy is a group of highly heterogeneous myocardial diseases.Recurrent worsening heart failure(WHF) is the main reason for the high hospitalization rate and high mortality rate in children with cardiomyopathy, and makes children rapidly enter the end-stage of heart failure.The concept of WHF was first described in the literature on pediatric heart failure.Unfortunately, clinical studies of WHF in children during the past five decades are rare.Based on the current definition of adult WHF and the characteristics of pediatric heart failure, this review briefly introduced the concept, inducement and risk factors, identification and management of WHF in children with cardiomyopathy.

Predictive values of the Status Epilepticus in Pediatric Patients Severity Score and END-IT score for short-term prognosis of children with status epilepticus / 中华实用儿科临床杂志

Objective:To evaluate the predictive values of the Status Epilepticus in Pediatric Patients Severity Score (STEPSS) and END-IT score in the short-term prognosis of children with status epilepticus (SE).Methods:It was a retrospective study involving 103 children with SE who were admitted to the Qingdao Women and Children′s Hospital Affiliated to Qingdao University from January 1, 2012 to January 1, 2022.Glasgow Outcome Scale was used to evaluate the prognosis at discharge, and the children were divided into good prognosis group ( n=78) and poor prognosis group ( n=25). Risk factors for poor prognosis of SE in children were analyzed by Logistic regression.Receiver operating characteristic (ROC) curve was used to evaluate the prognostic values of STEPSS and END-IT score in children with SE. Results:Compared with those of the good prognosis group, significantly younger age [16 (9, 58) months vs.56 (21, 84) months, Z=-3.068, P=0.002], higher blood lactic acid levels [3.16 (2.43, 4.01) mmol/L vs.1.67 (1.32, 2.10) mmol/L, Z=-6.085, P<0.001], STEPSS scores [3.0(3.0, 4.0) points vs.1.0(1.0, 2.0) points, Z=-6.956, P<0.001], END-IT scores [3.0(1.5, 4.0) points vs.1.0(0, 1.0) points, Z=-5.502, P<0.001], proportion of developmental delay ( χ2=16.756, P<0.001), abnormal brain magnetic resonance imagine examination ( χ2=5.860, P=0.015), use of ventilator and multiple drugs (all P<0.001), and longer duration of anti-SE therapy time( Z=1.488, P=0.024) were detected in the poor prognosis group. Logistic regression analysis indicated that increased blood lactic acid ( OR=7.975, 95% CI: 2.705-23.518), increased drug types ( OR=14.562, 95% CI: 2.035-104.173), STEPSS scores( OR=8.914, 95% CI: 2.824-28.140) and END-IT scores ( OR=2.209, 95% CI: 1.046-4.667) were risk factors for the poor prognosis of SE in children.The area under the curve (AUC) of STEPSS in predicting the poor prognosis of SE in children was 0.939, with the cut-off value, sensitivity, specificity and Youden index of 2.5 points, 96.0%, 85.9% and 0.82, respectively.AUC of END-IT scores in predicting the poor prognosis of SE in children was 0.853, with the cut-off value, sensitivity, specificity and Youden index of 1.5 points, 76.0%, 75.6% and 0.52, respectively.AUC of STEPSS in predicting the poor prognosis of SE in children was significantly higher than that of END-IT scores ( U=36.91, P<0.05). The predictive value of STEPSS combined with END-IT was higher, and the sensitivity and negative predictive value of parallel test were 100.0%, while the specificity and positive predictive value of series test were 94.9% and 81.8%, respectively. Conclusions:STEPSS and END-IT scores may be used as predictors for the poor prognosis of SE in children.Their combination provides a better prediction.

Clinical characteristics, gene mutations and enzyme replacement therapy of 13 children with Pompe disease / 中华实用儿科临床杂志

Objective:To summarize the clinical features, gene mutations and experience of standardized enzyme replacement therapy (ERT) of Pompe disease (PD) in children.Methods:A retrospective analysis was performed on the clinical data of 13 children with PD, who were hospitalized in Qingdao Women and Children′s Hospital from December 2016 to August 2021.According to the age at onset, the children were divided into the infantile-onset Pompe disease (IOPD) group and late-onset Pompe disease (LOPD) group.At the same time, they were divided into the ERT group and non-ERT group according to whether recombinant human acid alpha-glucosidase (rhGAA) was infused.Furthermore, the ERT group was divided into the standard ERT group and non-standard ERT group.The standard ERT group received a dose of 20 mg/kg every 2 weeks for 52 weeks.The survival rate was compared between groups by using the Kaplan-Meier method.Results:Among the 13 children with PD, there were 7 males and 6 females.Ten cases belonged to the IOPD group and 3 cases belonged to the LOPD group.The most common cause of initial consultation in the IOPD group was cardiac involvement, which accounted for 60.0% (6/10 cases), while the LOPD group mainly presented with myasthenia, cardiac involvement and respiratory tract infection at the first diagnosis.The serum level of creatine kinase (CK) in all cases increased to varying degrees.Acid alpha-glucosidase (GAA) was completely deficient in 1 case and decreased in 12 cases.All the children in the IOPD group showed myocardial hypertrophy, electrocardiograph (ECG) suggested a short PR interval, increased QRS voltage and extensive T-wave inversion.Three new mutations were found by GAA gene analysis, and they were c. 1861T>G (p.Trp621Gly), c.2278A>T (p.K760X), and c. 949G>A (p.A317T). Five cases in the IOPD group were given ERT.Two of them were given standard ERT for 52 weeks, and the other 3 cases were treated with non-standard ERT.At the end of follow-up, 2 cases treated with standardized ERT survived and the remaining 8 cases died of heart failure or respiratory failure.In the LOPD group, only 1 case was given ERT one time.Finally, 2 cases survived and one died of respiratory failure.The total fatality rate was 69.2%(9/13 cases). The survival rate of the ERT group (50.0%) and standard ERT group (100.0%) was significantly higher than that of the non-ERT group (14.3%) ( Log Rank P=0.037, 0.044). Conclusions:The clinical manifestations of PD are diverse.GAA activity examination and GAA gene analysis are important for clinical diagnosis of PD.Standardized ERT can significantly delay the progression of PD and even reverse myocardial hypertrophy in children with IOPD.

Clinical characteristics, gene mutations and enzyme replacement therapy of 13 children with Pompe disease / 中华实用儿科临床杂志

Objective:To summarize the clinical features, gene mutations and experience of standardized enzyme replacement therapy (ERT) of Pompe disease (PD) in children.Methods:A retrospective analysis was performed on the clinical data of 13 children with PD, who were hospitalized in Qingdao Women and Children′s Hospital from December 2016 to August 2021.According to the age at onset, the children were divided into the infantile-onset Pompe disease (IOPD) group and late-onset Pompe disease (LOPD) group.At the same time, they were divided into the ERT group and non-ERT group according to whether recombinant human acid alpha-glucosidase (rhGAA) was infused.Furthermore, the ERT group was divided into the standard ERT group and non-standard ERT group.The standard ERT group received a dose of 20 mg/kg every 2 weeks for 52 weeks.The survival rate was compared between groups by using the Kaplan-Meier method.Results:Among the 13 children with PD, there were 7 males and 6 females.Ten cases belonged to the IOPD group and 3 cases belonged to the LOPD group.The most common cause of initial consultation in the IOPD group was cardiac involvement, which accounted for 60.0% (6/10 cases), while the LOPD group mainly presented with myasthenia, cardiac involvement and respiratory tract infection at the first diagnosis.The serum level of creatine kinase (CK) in all cases increased to varying degrees.Acid alpha-glucosidase (GAA) was completely deficient in 1 case and decreased in 12 cases.All the children in the IOPD group showed myocardial hypertrophy, electrocardiograph (ECG) suggested a short PR interval, increased QRS voltage and extensive T-wave inversion.Three new mutations were found by GAA gene analysis, and they were c. 1861T>G (p.Trp621Gly), c.2278A>T (p.K760X), and c. 949G>A (p.A317T). Five cases in the IOPD group were given ERT.Two of them were given standard ERT for 52 weeks, and the other 3 cases were treated with non-standard ERT.At the end of follow-up, 2 cases treated with standardized ERT survived and the remaining 8 cases died of heart failure or respiratory failure.In the LOPD group, only 1 case was given ERT one time.Finally, 2 cases survived and one died of respiratory failure.The total fatality rate was 69.2%(9/13 cases). The survival rate of the ERT group (50.0%) and standard ERT group (100.0%) was significantly higher than that of the non-ERT group (14.3%) ( Log Rank P=0.037, 0.044). Conclusions:The clinical manifestations of PD are diverse.GAA activity examination and GAA gene analysis are important for clinical diagnosis of PD.Standardized ERT can significantly delay the progression of PD and even reverse myocardial hypertrophy in children with IOPD.

Short-term and medium-term changes of the left ventricular ejection fraction in children with dilated cardiomyopathy complicated with complete left bundle branch block and the predictive value of relevant electrocardiogram indexes / 中华实用儿科临床杂志

Objective:To investigate the short-term and medium-term changes of the left ventricular ejection fraction (LVEF) and the predictive value of relevant electrocardiogram (ECG) indexes in children with dilated cardiomyopathy (DCM) complicated with complete left bundle branch block (CLBBB).Methods:Children clinically diagnosed with DCM in the Department of Heart Center, Women and Children′s Hospital, Qingdao University and Beijing Anzhen Hospital, Capital Medical University between November 2011 and August 2020 were retrospectively recruited.According to the combination of CLBBB, they were divided into CLBBB group and non-CLBBB group.Echocardiogram and ECG were regularly performed.Short-term and medium-term changes of LVEF based on the 1-5-year follow-up data were compared between groups.COX proportional hazards model and Kaplan-Meier multiplicative limit method were used to analyze the predictive value of ECG indexes of LVEF changes in children with DCM combined with CLBBB.Results:Ninety-four children with DCM were enrolled, including 35 cases in CLBBB group and 59 cases in non-CLBBB group.There was no difference in baseline LVEF between groups.However, significant differences were found in QRS duration, corre-cted QT interval(QTc), R peak time in lead V 5 (T V5R) and QRS notching or slurring between groups ( P<0.05). LVEF of all children showed an upward trend within one year after onset, while the Z value of eft ventricular end diastolic diameter(LVEDd) showed a downward trend, and the two indexes tended to be stable within 1 - 5 years.The Z value of LVEDd in CLBBB group was significantly higher than that of non-CLBBB group, while LVEF was significantly lower (all P<0.05). The mean LVEF of CLBBB group slightly fluctuated around 50%, that of LVEF in non-CLBBB group was 60%.The multivariate COX regression analysis showed that QRS duration ( HR=0.979; 95% CI: 0.960-0.999, P<0.05) and QTc ( HR=0.988; 95% CI: 0.979-0.998, P<0.05) were independent predictors of LVEF recovery in children with DCM.Kaplan-Meier method showed a significant difference of LVEF normalization between DCM children with different QRS durations ( P<0.05), which was also detected in those with QTc interval ( P<0.05). Conclusions:LVEF of children with DCM combined with CLBBB increases in the short term after standard treatment, and then being stable.CLBBB can affect the recovery of left ventricular systolic function in children with DCM.Moreover, QRS duration and QTc interval are independent predictors of LVEF recovery in DCM children.

Interpretation of the 2021 American Heart Association scientific statement: diagnosis and management of myocarditis in children / 中华实用儿科临床杂志

The diagnosis and management of myocarditis in children is a major challenge for pediatric cardiologists.In 2021, the American Heart Association redefined pediatric myocarditis after summarizing existing relevant information and treatment strategies for pediatric myocarditis, which emphasized the immunopathogenesis, new and conti-nuously changed main causes, modern laboratory testing methods and advances in the use of mechanical circulatory support.In particular, innovations of cardiac magnetic resonance in children myocarditis have been highlighted.The main contents of the statement to help pediatricians understand the diagnosis and management of myocarditis in children are interpreted.

The evaluation value of three scoring systems for the prognosis of pediatric acute liver failure / 中华实用儿科临床杂志

Objective:To investigate the prognosis value of the Child-Turcotte-Pugh (CTP), pediatrics end-stage liver disease/model for end-stage liver disease(PELD/MELD) and sequential organ failure assessment (SOFA) scores in pediatric acute liver failure (PALF) at 28 th day. Methods:Fifty-four PALF patients admitted in the Pediatric Intensive Care Unit (PICU) and Infection Department of Pediatrics, Qingdao Women′s and Children′s Hospital from June 1, 2012 to June 1, 2019 were included in the study.According to the survival of PALF patients on the 28 th day, they were divided into the survival group (28 cases) and the death group (26 cases). Baseline characte-ristics and laboratory examination data of PALF patients in both groups were collected and compared.Receiver operating characteristic (ROC) curve was used to evaluate the prognostic value of CTP, PELD/MELD and SOFA scores in PALF. Results:The mortality rate of 54 PALF patients was 48.1%.Compared with the survival group, PALF patients in the death group were significantly younger than those in survival group [11.0(3.8-39.0) months vs.14.5(7.3-84.0) months]( Z=-2.145, P=0.020). In addition, CTP, PELD/MELD and SOFA scores were significantly higher in the death group than those in survival group [14.0(11.7-15.0) vs.9.0(7.0-10.0), 32.0(29.0-36.0) vs.25.0(22.0-26.0), 13.0(11.0-16.0) vs.6.0(4.0-7.0)]( Z=-5.095, -4.894, -5.502, all P<0.05). Serum lactate level, blood ammonia level, total bilirubin, direct bilirubin and international normalized ratio were significantly higher in the death group than those in survival group [3.4(2.1-5.3) mmol/L vs.1.5(0.8-2.3) mmol/L, 69.5(46.9-102.9) μmol/L vs.41.7(27.3-50.3) μmol/L, 173.0(97.0-237.2) μmol/L vs.71.9(62.0-136.9) μmol/L, 132.3(53.6-206.2)μmol/L vs.59.3(62.0-99.7) μmol/L, 2.6(1.8-3.5) vs.1.7(1.5-1.9)]( Z=-4.027, -3.220, -2.649, -2.648, -3.807, all P<0.05). Prothrombin time (PT) was significantly prolonged in the death group than that of survival group [27.5(19.2-41.9)s vs.17.8(16.9-22.2)s]( Z=-3.489, P<0.05). Compared with those of survival group, serum albumin, alanine transaminase (ALT) and alpha fetoprotein (AFP) levels were significantly lower in the death group [(30.9±1.0) g/L vs.(33.6±0.9) g/L, 379.2(163.3-880.3) U/L vs.962.5(457.0-1 657.3) U/L, 7.5(0.7-115.8) μg/L vs.22.1(7.9-91.3) μg/L]( t=2.049, Z=-2.510, -2.342, respectively, all P<0.05). The incidence of alimentary tract hemorrhage was significantly higher in the death group than that of survival group (22/26 cases vs.11/28 cases)( χ2=13.340, P<0.05). The cut-off value of CTP, PELD/MELD and SOFA scores in predicting the prognosis of PALF were 11.5, 28.5 and 10.0, respectively.Among the three scoring systems, the specificity and positive predictive value of SOFA scores remained the highest.The sensitivity and specific of a combination of three scoring systems in predicting the prognosis of PALF were 92.3% and 89.3%, respectively, and its Youden index was the highest than that of a single scoring of either CTP, PELD/MELD or SOFA ( Z=2.19, P<0.05). Conclusions:CTP, PELD/MELD and SOFA scores have high predictive value for the short-term prognosis of PALF.The combined detection of the three scoring systems can improve the forecasting efficiency of PALD.

Evidence-based treatment of chronic heart failure in children / 中华实用儿科临床杂志

Heart failure (HF) is a common critical illness in pediatrics.At present, the evidence-based medicine for the treatment of chronic HF in children is significantly less than that in adults.There is a lack of relevant evidence on the effectiveness and safety of anti-HF drugs and technologies in children.Due to the fact that the treatment theory and experience are largely based on the research data about adults, and the domestic and foreign consensus or guidelines for the treatment of pediatric chronic HF are out of date, pediatric cardiologists are facing huge challenges.In recent years, the novel drugs and technologies in children have been adopted gradually, for instance, angiotensin receptor-neprilysin inhibitors and Ivabradine have attracted rising attention in the treatment of pediatric HF; Such technologies as cardiac resynchronization and radiofrequency ablation can significantly improve the prognosis of some kinds of chronic HF; the advancement of ventricular assist device provides the possibility for its wide application.Based on the current situation, the safety and efficacy of both traditional anti-HF drugs and new drugs and technologies shall be verified in future by multi-center, large-sample and high-quality clinical research, so as to provide a basis for the treatment strategy of chronic HF in children.

Effect of human umbilical cord mesenchymal stem cell exosomes on myocardial fibrosis in rats with Adriamycin-induced dilated cardiomyopathy / 中华实用儿科临床杂志

Objective:To evaluate the effects of human umbilical cord mesenchymal stem cells-derived exosomes (hUCMSCs-ex) injection on cardiac function and myocardial fibrosis in dilated cardiomyopathy (DCM) rats induced by Adriamycin(ADR).Methods:One hundred male SD rats were randomly divided into the normal group (20 rats) and the DCM group (80 rats). The rats in DCM group were treated with ADR by intravenous injection to induce DCM.DCM rats were randomly divided equally into DCM group, low-dose group, medium-dose group and high-dose group which were received intravenous injection 1 mL/kg Dulbecco′s modified eagle medium(DMEM), 20 μg/kg, 100 μg/kg and 250 μg/kg exosomes.After modeling, 10 rats in normal group and 30 rats in DCM group were randomly selected to receive echocardiography to evaluate the cardiac function.After exosomes treatment, 10 rats were randomly selected form each group for echocardiography to evaluate the cardiac function.The morphological changes in myocardial cells were observed by using Masson staining in each group; Western blot detection between groups of rats was used to analyze the expression of myocardial collagen Ⅰ type(COLⅠ), Smad2 and alpha smooth muscle actin (α-SMA).Results:Left ventricular ejection fraction(LVEF) and left ventricular fraction shortening (LVFS)in the DCM group [(64.30±3.51)% and (38.70±2.85)%] were significantly lower than those of the normal group [(78.80±1.52)% and (50.60±1.50)%], and the differences were statistically significant ( t=20.518, 22.311, all P<0.01). The left ventricular end-diastolic diameter(LVEDD) and left ventricular end-systolic diameter (LVESD) [(4.62±0.13) mm and (3.40±0.12) mm] of the DCM group were significantly higher than those of the normal group[(3.29±0.24) mm and (3.16±0.33) mm], and the differences were statistically significant( t=2.854, 3.800, all P<0.01). After exosomes treatment, LVEF[(84.3±2.6)% and (83.4±3.2)%] in the medium-dose and high-dose groups were significantly higher than that in the DCM group [(79.2±2.4)%], and the diffe-rences were statistically significant(all P<0.01). Masson staining found that collagen fibers were less in exosomes treating group than those in the DCM group; Western blot test showed that high-dose exosomes can reduce the expression of α-SMA and Smad2, high-dose and low-dose exosomes can both significantly reduce the expression of COLⅠ. Conclusions:It suggests that exosomes intravenous injection from hUCMSCs-ex can significantly improve myocardial fibrosis in DCM rats induced by ADR and cardiac function.

Multicenter investigation of extracorporeal membrane oxygenation application in pediatric intensive care unit in China / 中华儿科杂志

Objective@#To survey the conduction and evaluate the effectiveness of extracorporeal membrane oxygenation (ECMO) therapy in pediatric intensive care unit (PICU) in China mainland.@*Methods@#In a questionnaire-based survey, we retrospectively reviewed the application of ECMO in children's hospital and general hospital in China mainland to summarize and analyze the categories of diseases and prognosis of children treated with ECMO therapy.@*Results@#By December 31, 2017, a total of 23 hospitals using ECMO, including 22 tertiary referral hospitals and 1 secondary hospital, among which 16 were children′s hospitals and 7 were general hospitals. Thirty-seven ECMO equipment was available. A total of 518 patients treated with ECMO, within whom 323 (62.4%) successfully weaned from ECMO and 262 (50.6%) survived to discharge. Among 375 pediatric patients, 233 (62.1%) were successfully weaned from ECMO and 186 (49.6%) survived to discharge. Among 143 newborn patients, 90 (62.9%) successfully weaned from ECMO, 76 (53.1%) survived to discharge. ECMO was applied in veno-arterial (VA) mode to 501 (96.7%) patients, veno-venous (VV) mode to 14 (2.7%) patients, and VV-VA conversion mode to 3 (0.6%) patients. Sixty-nine patients required extracorporeal cardiopulmonary resuscitation (ECPR), including 20 newborn patients (29.0%) and 38 pediatric patients (71.0%), who were all with cardiovascular disease. Neonatal respiratory distress syndrome (26/61), persistent pulmonary hypertension of the newborn (PPHN) (12/61), and meconium aspiration syndrome (MAS) (11/61) are the most common pulmonary diseases in newborn patients; among whom, infants with PPHN had highest survival rate (10/12), followed by MAS (9/11). Among newborn patients with cardiovascular diseases, those who admitted were after surgery for congenital cardiac disease were the most common (54/82), while those with septic shock had the highest survival rate (2/3). In pediatric pulmonary diseases, acute respiratory distress syndrome was the most common (42/93), while plastic bronchitis was with the highest survival rate (4/4), followed by viral pneumonia (13/16). Among pediatric cardiovascular diseases, congenital cardiac defect was the most common (124/282), while fulminant myocarditis had the highest survival rate (54/77).@*Conclusion@#The application of ECMO as a rescue therapy for children with severe cardiopulmonary failure has dramatically developed in China mainland.

Effect of human umbilical cord mesenchymal stem cells by intramuscular injection on cardiac function and mi-crovascular regeneration in rats with dilated cardiomyopathy / 中华实用儿科临床杂志

Objective To evaluate the effect of human umbilical cord mesenchymal stem cells (hUCMSCs) treatment through intramuscular administration on the heart function and angiogenesis of the myocardium in dilated car-diomyopathy (DCM)rats induced by Adriamycin(ADR). Methods One hundred male SD rats were randomly divided into the normal group and the DCM group. Rats in the DCM group were treated with ADR by intraperitoneal injection of 2. 0 mg/ kg dose per week for 8 weeks in order to induce DCM. Sixty modeled surviving rats with DCM were randomly divided equally into 3 groups,and they were treated with hUCMSCs or DMEM by intramuscular injection. Rats in the DMEM group (20 cases)received intramuscular infusion 2 mL DMEM alone;rats in the low - dose group (20 cases) underwent intramuscular infusion of 1 × 106 hUCMSCs/ 2 mL in DMEM;rats in the high dose group (20 cases)under-went intramuscular infusion of 10 × 106 hUCMSCs/ 2 mL in DMEM. Echocardiography and plasma brain natriuretic pep-tide(BNP)were used to assess cardiac function in modeled rats. The morphological changes in myocardial cells were observed by using HE and Masson staining after ADR injection stopped for one week. Four weeks after administration of hUCMSCs,echocardiography was performed to evaluate the cardiac function,and plasma BNP level was detected by en-zyme immunoassay kit. Western blot was used to analyze the expression of vascular endothelial growth factor(VEGF)in myocardium of rats in each group. Myocardial microvessel density was detected by using anti - CD34 monoclonal antibody and transmission electron microscopy (TEM)were performed to observe the ultrastructure of microvessel. Results Left ventricular ejection (LVEF)and left ventricular fractional shortening (LVFS)in the DCM groups [(66. 17 ± 3. 54)％,(31. 33 ± 3. 20)％]were significantly decreased compared to those in the normal group [(77. 25 ± 3. 40)％,(41. 00 ± 2. 94)％],and the differences were statistically significant(t = 10. 620,10. 328,all P < 0. 05);the morphological changes in myocardial cells was observed by using HE and Masson staining. Pit - induced typical his-tological lesion of myocardial tissue was observed in the DCM group,such as congestion,edema,a disorganization of myocytes and focal necrosis and myocardial tissue with wispy,broad collagen fibers predominating in the matrix. Four weeks after administration of hUCMSCs,LVEF in the low dose group or the high dose group were significantly higher compared with those in the DMEM group[(72. 27 ± 2. 44)％ or (70. 92 ± 2. 68)％ vs. (62. 89 ± 2. 54)％],and the differences were statistically significant(t = 2. 145,2. 131,all P < 0. 05);and LVFS were significantly higher compared with that in the DMEM group [(34. 96 ± 2. 08)％ or (33. 49 ± 2. 19)％ vs. (30. 98 ± 2. 22)％],and the differences were statistically significant (t = 2. 491,4. 086,all P < 0. 05). The plasma level of BNP was significantly declined in the hUCMSCs treated rats as compared to those before treatment [low dose group (352. 68 ± 41. 25)ng/ L vs. (202. 68 ± 20. 38)ng/ L,t = 2. 052,P < 0. 05;high dose group (355. 79 ± 48. 32)ng/ L vs. (193. 62 ± 15. 41)ng/ L,t = 2. 074,P < 0. 05]. Quantitative analysis demonstrated that microvessel density was significantly hi-gher in low - dose and high - dose hUCMSCs treated DCM rats than that in the DMEM treated DCM rats [(84. 00 ± 19. 18)/ mm2 or (86. 67 ± 20. 88)/ mm2 vs. (27. 14 ± 13. 97)/ mm2 ,t = 2. 109,2. 101,all P < 0. 05];Western blot test showed that there had high expression of VEGF in myocardium and TEM in the high dose group,and vessel injury in DMEM treated rats were more serious than that of hUCMSCs treated rats. Conclusion It suggests that hUCMSCs in-tramuscular injection may improve heart function and angiogenesis of myocardium in DCM rats induced by adriamycin.

Treatment of heart failure in children / 中国小儿急救医学

Research in the treatment field of heart failure in children is obviously lagging in that of adult,and its theory and experience are copied from adult results in a large extent. The domestic diagnosis and treatment guideline of heart failure in children is lack. At present,the treating status of digitalis in heart failure of children has declined, meanwhile the neuroendocrine modulation and body volume control draw more attentions. In addition,artificial assist device,continuous renal replacement therapy and stem cell therapy of heart failure in children is gradually paid more interests.

Treatment of heart failure in children / 中国小儿急救医学

Research in the treatment field of heart failure in children is obviously lagging in that of adult,and its theory and experience are copied from adult results in a large extent. The domestic diagnosis and treatment guideline of heart failure in children is lack. At present,the treating status of digitalis in heart failure of children has declined, meanwhile the neuroendocrine modulation and body volume control draw more attentions. In addition,artificial assist device,continuous renal replacement therapy and stem cell therapy of heart failure in children is gradually paid more interests.

Clinical analysis of purulent meningitis caused by Streptococcus agalactiae in young infants / 中华实用儿科临床杂志

Objective To investigate the clinical manifestations,treatment,prognosis of purulent meningitis caused by Streptococcus agalactiae in young infants.Methods The clinical data,treatment and prognosis of 15 young infants with purulent meningitis caused by Streptococcus agalactiae admitted to Qingdao Women and Children's Hospital from January 2013 to May 2016 were analyzed retrospectively.Results The cerebrospinal fluids of 15 cases aged 5 days to 3 months were all accorded with the diagnostic criteria of purulent meningitis and cultivated Streptococcus agalactiae.All of them had fever,10 cases with restlessness or irritability,7 cases with convulsions,5 cases with drowsiness,and 3 cases with sucking rejection or vomiting milk.Seven cases had subdural effusion,intracranial hemorrhage in 3 cases,hydrocephalus in 2 cases,and central respiratory failure in 1 case.All cases had complications,including pneumonia in 8 cases,sepsis in 6 cases,diarrhea in 1 case,and septic shock in 5 cases.The white blood cells were reduced in 13 cases.The serum of procalcitonin and C-reactive protein were elevated in 14 infants.The level of white blood cells in 4 cases' cerebrospinal fluid was ＞5 000 × 106/L,(1 000-5 000) × 106/L in 5 cases,＜ 1 000 × 106/L in 6 cases.The glucoses of cerebrospinal fluid were all ＜ 2.54 mmol/L,the protein of cerebrospinal fluid was all elevated (781-3 000 mg/L).In 14 cases,the head MRI and electroencephalogram(EEG) examination were completed within 1 week after admission.The head MRI showed normal in 2 cases,subdural effusion in 7 cases,intracranial hemorrhage in 3 cases,and hydrocephalus in 2 cases.EEG showed normal in 12 cases,and background activity slowed down in 2 cases.All cases had Streptococcus agalactiae growth in cerebrospinal fluid cultures.The sensitive rates to Linezolid,Vancomycin Ampicillin and Tigecycline were 100％.Ceftriaxone combined with Penicillin,Penicillin combined with Vancomycin or Vancomycin combined with Meropenem were the main combined therapy.Three out of 7 subdural effusion cases were treated with subdural drainage.Twelve cases were improved and discharged.Two cases lost to follow-ups after 2 weeks treatment.One case died after his giving up of treatment.Follow-up period was from 1 month to 3.5 years,6 cases had a normal development and 6 cases had motor retardation.Conclusions Purulent meningitis caused by Streptococcus agalactiae in the neonates and infants is more difficult in clinical treatment.High proportions of severe cases exist,some cases will have sequelae.It is imperative to apply sensitive antibiotics in time and timely prevention.

Intramuscular injection of human umbilical cord mesenchymal stem cells and its effect on the cardiac function and myocardial ultrastructure in rats with Adriamycin-induced dilated cardiomyopathy rats / 中华实用儿科临床杂志

Objective To explore the effects of intramuscular injection human umbilical cord mesenchymal stem cells(hUCMSC)intramuscular injection on the cardiac function and myocardial ultrastructure in rats with Adria-mycin -induced dilated cardiomyopathy (DCM)rats.Methods One hundred and sixty rats were randomly divided in-to a normal group (20 cases)and DCMgroups (1 40 cases),rats in DCMgroups receiving Adriamycin (2 mg/kg)in-traperitoneally once a week for 8 weeks to establish DCM models.The DCM rats were randomly divided into a model control group (served as model group),the supernatant of hUCMSC group (served as supernatant group),the low -dose hUCMSC group(served as low -dose group),the medial -dose hUCMSC group(served as medial -dose group), and the high -dose hUCMSC group(served as high -dose group).Echocardiography was performed to evaluate the car-diac function,plasma brain natriuretic peptide (BNP)level and serum cardiac troponin I (cTnI)level were detected by enzyme -linked immunosorbent assay kit;light microscope and transmission electron microscopy (TEM)were used to observe the ultrastructure of myocardium.Results Rats in the DCM group showed low spirit,declining food intake, progressive emaciation,slow growth,hair loss and ascites.After the intramuscular injection of hUCMSC,the above symp-toms of rats in the low -dose and the medial -dose hUCMSC groups were improved significantly.Before the administra-tion of hUCMSC,the left ventricular ejection fraction (LVEF)[(64.53 ±2.61 )%]and the left ventricular fractional shortening (LVFS)[(30.80 ±2.1 1 )%]were significantly decreased in the DCMgroup compared to those of the con-trol group[(79.67 ±3.02 )%,(43.08 ±3.1 5 )%,all P <0.01 ].After the administration of hUCMSC,LVEF [(75.5 ±7.4)%,(74.0 ±6.1 )%]and LVFS[(40.8 ±3.8)%,(40.2 ±5.0)%]were significantly increased in the low -dose and the medial -dose group compared with those of the model group [(65.8 ±4.5)%,(30.2 ± 2.9)%,all P <0.01 ].The concentration of plasma BNP level [(438.3 ±82.2)ng/L,(341 .7 ±68.9)ng/L]and serum cTnI level [(375.9 ±1 1 0.9)ng/L,(355.9 ±55.6)ng/L]were significantly decreased compared with those of the model group [(449.9 ±91 .8)ng/L,(425.9 ±42.6)ng/L,all P <0.05].The findings of HE staining showed that cardiomyocytes were orderly arranged,edema decreased and cell nucleus homogeneously stained in the low -dose and the medial -dose group.The outcomes of TEM revealed that the ultrastructure of cardiomyocytes was improved in the low -dose and the medial -dose group compared with that of model group,and the cardiomyocyte sarcolemma re-mained intact,and the swelling of mitochondria ameliorated and the cristae of mitochondria remained clear.Conclusions Intramuscular injection of hUCMSC could significantly increase LVEF and LVFS in the Adriamycin -induced DCM rats,and decrease the plasma BNP levels and the serum cTnI levels,attenuate the myocardial pathological damage and improve myocardial ultrastructure.

Mitochondrial diseases with the main manifestations of cardiomyopathy and respiratory muscle damage / 中华实用儿科临床杂志

Objective The 3243A ＞ G mutation in mitochondrial DNA is a common cause of the classical mitochondrial diseases characterized by neuro-muscular disorders.This study reports a rare case with the main manifestations of mitochondrial disease in children of mitochondrial cardiomyopathy and respiratory muscle damage.Methods The clinical characteristics,diagnosis and treatment,biochemical,pathological and genetic features of a 10-year-old girl were studied.Results The girl was admitted because of heart failure and respiratory failure at the age of 10.Ragged red fibers in skeletal muscles had been noticed.On her mitochondrial gene,3243A ＞ G mutation,Leu tRNA (UUR),was detected.The mutation rate in the peripheral blood cells was 94％.After the treatment with a high dose of creatine phosphate sodium,coenzyme Q10 and L-carnitine with assisted ventilation,the patient improved rapidly.The child was followed up for 2 years without recurrence.Meanwhile the growth,development and daily life were normal.Conclusions Cardiac and respiratory muscle impairments that appeared at the same time as the first manifestations of the children's mitochondrial disease is not common,and it is rare to have cardiomyopathy based mitochondrial gene 3243A ＞ G mutation is seldom seen clinically.Skeletal muscle biopsy and genetic test is the key for accurate diagnosis.Improving mitochondrial metabolism and assisted ventilation appear to be helpful treatments.

Effects of human umbilical cord mesenchymal stem cells via intramuscular injection on the myocardial micrangium and collagen expression in normal rats / 中国组织工程研究

BACKGROUND:To date, it is stil unclear whether the intramuscular injection of heterogeneous umbilical cord mesenchymal stem cel s (UC-MSC) can cause cardiac ectopic pathological angiogenesis as wel as increase col agen synthesis to promote myocardial fibrosis. OBJECTIVE:To explore the effects of intramuscular injection of human UC-MSCs on myocardial micrangium and col agen expression in normal Wistar rats. METHODS:After 2 weeks of feeding, 60 male SPF Wistar rats were randomly assigned to receive intramuscular injection of PBS (normal group), DMEM (culture medium group), human UC-MSCs supernatant (supernatant group), 0.25×105, 1.0×105, 4.0×105 human UC-MSCs (low-, moderate-and high-dose groups), respectively (n=10 per group). Al the rats were subjected to second injection (same dose) at 4 weeks after first intramuscular injection. Then, the rats were kil ed under anesthesia at 4 weeks after second injection, to take heart tissues from the left ventricle for pathological observation, immunohistochemical examination and Masson staining. RESULTS AND CONCLUSION:No alteration of the response, activity, victualage, faeces, weight growth, and fur was found, and there was no death in rats during the experiment. Al the rats had no symptoms of molt, inflammation, skin ulcer, scleroma. Strong positive expression of CD34 for the micrangium in the myocardial tissue was observed, and positive expression of the col agen in the myocardial tissue observed by Masson staining. There were no significant differences in the microvessel density and col agen expression in the myocardium among the groups (F=0.110 and 0.585, P>0.05). To conclude, hUC-MSCs or its supernatant via intramuscular injection has no effect on the micrangium and col agen expression in normal rats.

Expression of suppressors of cytokine signaling 1,suppressors of cytokine signaling 3 and changes in helper T cells,CD4 +CD25 +regulatory T cells in the peripheral blood of children with Kawasaki disease / 中华实用儿科临床杂志

Objective To investigate the immunological pathogenesis of Kawasaki disease( KD)through examination of changes in the expression of suppressors of cytokine signaling 1(SOCS1)and SOCS3,helper T cells and CD4 + CD25 + regulatory T cells(CD4 + CD25 + Treg)in peripheral blood from children with acute KD. Methods Six-teen children[10 boys,6 girls,aged 1 - 2 years old,averaged(1. 6 ± 0. 3)years old]in the acute phase of KD(KD group),16 children[9 boys,7 girls,aged 1 - 3 years old,averaged(1. 5 ± 1. 1)years old]with pneumonia(pneumo-nia group)and 8 normal children[5 boys,3 girls,aged 1 - 5 years old,averaged(2. 0 ± 1. 1)years old]of the same age(normal control group)from the Affiliated Hospital of Qingdao University who were admitted from October 2012 to March 2013 were recruited. The mRNA levels of SOCS1 and SOCS3 in the T cells from peripheral blood were examined by way of reverse transcription - polymerase chain reaction(RT - PCR). Interferon - γ( IFN - γ),interleukin - 4 (IL - 4)and CD4 + CD25 + Treg were quantified by means of fluorescence activated cell sorting(FACS). Results The expressions of SOCS1 and SOCS3,the percentage of IL - 4 T cells observed in the peripheral blood of the pneumonia group were similar to the normal control group(P ﹥ 0. 05),but significantly decreased in the percentage of INF - γ and the level of CD4 + CD25 + Treg(t = 3. 71,12. 81,all P ﹤ 0. 05). Compared to the normal control group and the pneumo-nia group,the expressions of SOCS1 and SOCS3,the percentage of INF - γ and IL - 4 T cells decreased significantly in the peripheral blood of the KD group(t = 2. 27,4. 48,17. 64,2. 73,2. 74,1. 25,2. 36,2. 59,all P ﹤0. 05 ). On the other hand,the level of CD4 + CD25 + Treg in the peripheral blood of the KD group was markedly lower than that in the normal control group(t =7. 70,P ﹤0. 05),but similar to the pneumonia group(P ﹥0. 05). Conclusions The function of helper T cells is inhibited in acute KD. The CD4 + CD25 + Treg may be involved in the immunological pathogenesis of KD.

Human umbilical cord mesenchymal stem cells via intramuscular injection influence the expression of cytokines related to dilated cardiomyopathy in rats / 中国组织工程研究

BACKGROUND:Studies have shown that intramuscular transplantation of xenogeneic umbilical cord mesenchymal stem cel s in a certain dose range is safe and reliable, and it also confirm that this approach is equal y safe and effective for heart failure in rats with dilated cardiomyopathy. OBJECTIVE:To explore the effect of human umbilical cord mesenchymal stem cel s through intramuscular injection on the cytokine expression in adriamycin-induced dilated cardiomyopathy (DCM) rats. METHODS:Total y 160 rats were randomly divided into control group (n=20) and DCM group (n=140). Rats in the DCM group were administered adriamycin intraperitoneal y to establish DCM model. The DCM rats were randomly subdivided into model control group (served as model group), cel supernatant group, the low-dose mesenchymal stem cel group (served as low-dose group), the middle-dose mesenchymal stem cel group (served as middle-dose group), and the high-dose mesenchymal stem cel s group (served as high-dose group). Secondary injection was performed at 4 weeks after first injection. RESULTS AND CONCLUSION:The ELISA test showed that the serum levels of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), leukemia inhibitor factor (LIF) and granulocyte macrophage colony stimulating factor (GM-CSF) were higher in the model group than the control group before and after intramuscular injection (P0.05). Both the immunohistochemical and RT-PCR results showed that the expressions of insulin-like growth factor-1, VEGF and HGF were increased in al the DCM rats as compared with the control group, which were increased most in the middle-dose group. These findings indicate that low-dose and middle-dose human umbilical cord mesenchymal stem cel s intramuscular injection can increase the serum levels of HGF, LIF, GM-CSF, VEGF and the expressions of IGF-1, HGF and VEGF in the myocardium of DCM rats.

Security of heterogeneous umbilical cord mesenchymal stem cells via intramuscular injection in Wistar rats / 中国组织工程研究

BACKGROUND:So far, the short-term changes of various organs after injection of umbilical cord mesenchymal stem cells have been reported, but there are few studies on the long-term changes of various organs in healthy rats after repeated intramuscular injection of umbilical cord mesenchymal stem cells. OBJECTIVE:To observe the security of intramuscular injection of heterogeneous umbilical cord mesenchymal stem cells. METHODS:Sixty male SPF Wistar rats were divided into six groups randomly:normal group (suspension liquid of umbilical cord mesenchymal stem cells);control group with culture solution;supernatant group (supernatant of human umbilical cord mesenchymal stem cells);low concentration group (0.25×105 human umbilical cord mesenchymal stem cells);moderate concentration group (1.0×105 human umbilical cord mesenchymal stem cells);high concentration group (4.0×105 human umbilical cord mesenchymal stem cells). Each rat was injected 0.8 mL liquid in muscle, 0.2 mL in each limb, twice at weeks 1 and 4. Biochemical tests were conducted before and after injection. At the end of 8 weeks, al the rats were kil ed and hematoxylin-eosin staining was done with the liver, spleen, lung, kidney, brain and muscle. RESULTS AND CONCLUSION:There was no abnormal change about biochemical tests and hematoxylin-eosin staining after the intramuscular injection of heterogeneous umbilical cord mesenchymal stem cells. No significant alteration was observed in the liver, spleen, lung, kidney, brain, and muscle of the limb after the injection of heterogeneous umbilical cord mesenchymal stem cells under suitable concentration. These findings indicate intramuscular injection of heterogeneous umbilical cord mesenchymal stem cells at certain concentrations is safe and reliable.