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.

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.

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.

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.

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.

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.

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.

Oral static biofilm model is an important tool for in vitro simulation of oral microecological environment, which has become an important method for studying the pathogenesis of various oral diseases and testing the efficacy of various drugs, oral care products and foods due to its low cost, high throughput, good reliability and easy operation. The establishment of oral static biofilm models allows the selection of different devices, inoculum sources, media, substrates and culture conditions according to the purpose of the study, and the evaluation of biofilm growth by various methods such as measuring biomass, metabolic activity, community structure and performing visualization analysis. This paper summarizes the methodological elements reported in recent years for the establishment and evaluation of oral static biofilm models, and analyzes and discusses the applicability of various methods in the hope of contributing to the research and production practice in related fields.
Biofilms ; Reproducibility of Results