Objective:To investigate the effect of lipopolysaccharide (LPS) on primary neonatal rat cardiomyocytes (CMs) and human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs).Methods:The hiPS-CMs and primary neonatal rat CMs were treated with different concentrations of LPS for 24 to 48 h. Then the cellular viability was analyzed by the xCELLigence RTCA Cardio system. The measurement of NPPB gene was studied by qRT-PCR and the gene expression analysis was performed by the qPCR array, in order to evaluate the cardiac inflammation effect induced by LPS.Results:The LPS exposure led to dysfunction in the primary neonatal rat CMs, which shown as an increase in beating rate and a decrease in contraction amplitude ( P<0.01), accompanied by an increased NPPB mRNA level ( P<0.01). There was no significant alteration in beating rate and the contraction amplitude in the corresponding concentration of the primary neonatal rat CMs ( P>0.05), as well as the NPPB mRNA level ( P>0.05). However, the expression of NPPB mRNA in hiPS-CMs was significantly different at a higher concentration of LPS (5 μg/mL~40 μg/mL) ( P<0.01), but the beating rate and the contraction amplitude showed no significant change, even the concentration of LPS up to 40 μg/mL ( P>0.05). Finally, the genes of C3, Gpnmb, Atf3, Il6r and Ly96 upregulated to 1.5 folds in the primary neonatal rat CMs. In comparison with primary neonatal rat CMs, the AK4, TOLLIP, SPP1, FABP1, IL6R, LY96 and C3 were over expression to 1.5 folds in the hiPS-CMs. Conclusions:In comparison with primary neonatal rat CMs, hiPS-CMs are markedly less injured by LPS and show a different pattern of inflammation gene expression.

Objective: To examine the mediating effect of frailty on social isolation and cognitive function among the elderly. Methods: Demographic information, smoking, alcohol consumption and cognitive function of the elderly at ages of 60 years and older were collected from the China Health and Retirement Longitudinal Study 2020. Social isolation and frailty were evaluated using social isolation index and frailty index, respectively. The mediating effect of frailty on social isolation and cognitive function was analyzed using the Process program, and the significance of the mediating role was tested using the Bootstrap test. Results: A total of 2 822 individuals were enrolled, including 1 483 males (52.55%) and 1 339 females (47.45%). There were 2 497 (88.48%) and 325 (11.52%) individuals at ages of 60-<75 years and ≥75 years, respectively. The median cognitive function score was 14 (interquartile range, 16) points. There were 432 cases with social isolation (15.31%), with a median social isolation index of 10 (interquartile range, 5) points. The median frailty index was 0.11 (interquartile range, 0.15). There were 1 111 individuals without frailty, accounting for 39.37%; 1 214 individuals with pre-frailty, accounting for 43.02%; and 497 individuals with frailty, accounting for 17.61%. Mediating effect analysis showed that social isolation affected cognitive function directly and negatively with the effect value of -0.773 (95%CI: -0.899 to -0.647), and also affected cognitive function by frailty indirectly and negatively with the effect value of -0.147 (95%CI: -0.188 to -0.110), with the mediating effect contributed 15.98% of the total effect. Conclusion Frailty can directly or indirectly affect cognitive function among elderly through social isolation.

Objective:To analyze the sepsis related long non-coding RNA (lncRNA) and mRNA expression profiles based on Gene Expression Omnibus (GEO) datasets and bioinformatic analysis, and to analyze the sepsis-associated competing endogenous RNA (ceRNA) network based on microRNA (miRNA) database.Methods:The sepsis-related lncRNA dataset was downloaded from the GEO database, and the differential expression analysis was conducted by Bioconductor on the sepsis dataset to obtain differentially expressed lncRNA (DElncRNA) and differentially expressed mRNA (DEmRNA), and cluster heat map was drawn. miRNA combined with DElncRNA were predicted by miRcode. mRNA targeted by miRNA was simultaneously met by three databases: TargetScan, miRDB, and mirTarBase. The interaction relationship of lncRNA-miRNA-mRNA was obtained. The regulatory network visualization software CytoScape was used to draw ceRNA networks. DEmRNA in the ceRNA networks were imported into the Search Tool for the Retrieval of Interacting Genes Database (STRING) online database to draw the protein-protein interaction (PPI) map. The gene ontology (GO) function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEmRNA were performed.Results:Dataset GSE89376 and GSE145227 were found from GEO database. Difference analysis showed there were 14 DElncRNA and 359 DEmRNA in the elderly group of GSE89376; 8 DElncRNA and 153 DEmRNA in the adult group of GSE89376; 1 232 DElncRNA and 1 224 DEmRNA in the children group of GSE145227. Clustering heatmap showed that there were significant differences in the expression of lncRNA and mRNA between the sepsis group and the control group. The ceRNA networks were constructed with miRNA. Several DElncRNA and multiple DEmRNA participated in the ceRNA network of sepsis. The PPI diagram demonstrated that several genes encoding proteins interacted with each other and form a multi-node interaction network with multiple genes encoding proteins. Functional annotation and enrichment analysis demonstrated that there might be a crosstalk mechanism on functionally related genes such as nuclear receptor activity, ligand-activated transcription factor activity, and steroid hormone receptor activity, and played a role in the occurrence and development of diseases through forkhead box transcription factor O (FoxO) signaling pathway, Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway, p53 signaling pathway, and phosphateidylinositol 3-kinase (PI3K)/Akt signaling pathway.Conclusion:Through sepsis-related lncRNA-miRNA-mRNA ceRNA network and combining with KEGG pathway analysis, there were several lncRNA and mRNA participating in the ceRNA network related sepsis, which played an important role in several signal pathways.

Objective To investigate the effect of 5-AZA-2'-dC on Angiotensin Ⅱ (Ang Ⅱ)-induced cardiomyocyte hypertrophy.Methods Cultured cells derived from neonatal heart of rat were divided into 5 groups:normal control,hypertrophic group,5-AZA-2'-dC treatment group,and 5-AZA-2'-dC pretreatment group.Neonatal rat cardiomyocyte hypertrophic response was assayed by the size of cardiomyocytes and atrial natriuretic polypeptide (ANP) expressive level.The level of sarcoplasmic reticulum Ca2+ ATPase (SERCA2a),total calmodulin kinase Ⅱ (CaMK Ⅱ) and phospho-CaMK Ⅱ (p-CaMK Ⅱ) detected by Western blot.The intracellular calcium changes of cardiomyocytes were imaged by confocal fluorescent microscopy.Results Cells treated with Ang Ⅱ at 10-6 mol/L for 48 h were chosen as hypertrophic cardiomyocyte model.The mRNA expression and protein level of ANP were significantly decreased in the treatment and pretreatment groups compared with hypertrophic group.The protein level of SERCA2a was significantly decreased in the hypertrophic group,and increased in the treatment and pretreatment group compared with hypertrophic group.The protein level of SERCA2a was significantly decreased in the hypertrophic group,and increased in the treatment and pretreatment group compared with hypertrophic group,whereas phospho-CaMK Ⅱ showed an opposite change tendency.The time required for increasing and declining to half of the intracellular calcium peak value were both delayed in hypertrophic group,as the treatment and pretreatment groups showed shorter time required compared with hypertrophic group.Conclusion 5-AZA-2'-dC could inhibit Ang Ⅱ-induced cardiomyocyte hypertrophy which might be related to regulate SERCA2a expression.Increased SERCA2a expression may maintain the calcium homeostasis through shortening the time of transfer Ca2+ from the cytosol of the cell to the lumen of the sarcoplasmic reticulum.

Objective: Catecholaminergic polymorphic ventricular tachycardia (CPVT) accounts for up to 10%-15% sudden cardiac death (SCD) in the children and young population. This study aimed to assess the current situation and challenges in CPVT clinical diagnosis. Method: A retrospective review included 11 children (7 male patients) at the First Hospital of Tsinghua University clinically diagnosed with CPVT from June 2014 to July 2017. Each patient was evaluated with detailed history, physical examination, resting 12-lead electrocardiogram(ECG), 24-h Holter, exercise stress test, Doppler echocardiography and genetic test. Result: During physical activity and/or emotional stress, ten children presented with recurrent syncope and one child presented with palpitation and chest distress. The mean age of symptom onset was 8.4 (4.0-13.7) years with a delayed diagnosis of 2.4 (0.04-5.00) years. Two children had a familial history of syncope or sudden death. Nine children were initially misdiagnosed as complex arrhythmic conditions (n=4), syncope of unknown origin (n=3), and drug-resistant epilepsy (n=2) treated with antiepileptic medication for several years. Bidirectional VT and (or) polymorphic VT were detected using Holter recording or exercise test ECG in all patients. Genetic test revealed CPVT-associated pathologic or possible pathologic mutations in nine patients. All patients were treated with beta-blockers. Six patients were asymptomatic, four patients reported infrequent syncope, and one sudden death occurred during a mean follow-up of 0.97 years. Conclusion CPVT mainly occurs in children and adolescents with recurrent syncope during physical activities and/or emotional stress. Early diagnosis of CPVT remains challenging due to delayed diagnosis or misdiagnosis. Detailed clinical history and exercise stress test improve the early diagnosis and intervention for CPVT patients.

Objective: To explore the clinical features of atrial flutter (AFL) and evaluate the efficacy of radiofrequency catheter ablation (RFCA) for AFL in children. Method: Data were collected and analyzed on 50 consecutive pediatric AFL patients (male 37/female 13) who underwent electrophysiology study and RFCA from February 2009 to November 2016 in a case observational study. The average age was (6.2±3.5) years and body weight was (23.7±13.5) kg. Heart structure was normal in 26 patients. Twenty-four patients had congenital heart disease (CHD) and among them 22 patients underwent repaired surgery before. Patients were followed-up for 1 month to 7 years after RFCA. Clinical features and the outcomes of RFCA in AFL patients were analyzed. Result: The average onset age was (4.2±3.3) years. Of these patients, 84% had persistent AFL and 16% paroxysmal AFL. AFL with sick sinus syndrome (SSS) occurred in 36% patients without statistically significant difference between the groups with and without CHD (38.9%(7/18) vs. 61.1%(11/18), respectively, P=0.239 5); 49 patients underwent RFCA except one case with atrial standstill during the procedure. The total acute success rate was 96%. The follow-up recurrence rate was 8%.No complication of the procedures was observed. The cavotricuspid isthmus-dependent AFL occurred in all patients without CHD. However, in the children with CHD after the repair surgery 10 (45%) cases were with cavotricuspid isthmus-dependent AFL, 4 (8%) with atrial scars-dependent AFL, and 8(16%) with both cavotricuspid isthmus and atrial scars-dependent AFL. Conclusion RFCA was effective and safe for pediatric AFL. There is no difference on the acute success rate, the follow-up AFL recurrence rate, as well as occurrence of SSS between the groups with and without CHD. AFL patients with CHD included the cavotricuspid isthmus-dependent AFL, atrial scars-dependent AFL or both.

Objective: To investigate the clinical features and evaluate the efficacy of radiofrequency catheter ablation (RFCA) guided by 3D electronic-anatomy mapping system (CARTO3 System) in children with atrioventricular nodal reentrant tachycardia (AVNRT). Methods: This was a retrospective case-controlled study. Data were collected from 95 children with AVNRT who underwent RFCA using CARTO3 System in the first hospital of Tsinghua University from January 2014 to December 2017. The onset age, characteristic of electrophysiology and anatomy feature of Koch triangle were analyzed. The efficacy and safety of ablation and X-ray fluoroscopy were compared with control 135 children with AVNRT who underwent RFCA without using CARTO3 System. The t test or the chi-square test was used for group comparison. Linear regression equation was established for correlation analysis. Results: The onset age of the 95 children (male 55, female 40; the average age (8.0±3.6) years) with AVNRT was (0.2-17.0) years and 23(24.2%) children were less than 3 years old. Electrophysiologic study showed that 84.2% (80 cases) was AVNRT-slow fast (SF), 11.6% (11 cases) AVNRT-slowslow and 4.2%(4 cases) AVNRT-fast slow. The phenomena of atrio-Hisian(AH) jump occurred in 65.3% and the interval of AH jump was (73.0±10.6) ms. The height of Koch triangle (CSo-His) was (22.3±5.8) mm and related with the weight of children (Y=0.171X+ 16.660, r²=0.224, P<0.001).The distance between the successful ablation target and the lowest point of His zone (ABL-His) was (11.7±2.6) mm. And there was no relation with the body weight(Y=-0.005X + 11.650, r²=0.001, P=0.780) and CSo-His (Y=0.072X+9.914, r²=0.030, P=0.171). The acute success rate was 97.9% (93/95) and recurrent rate was 5.4% (5/93) during follow-up. No obvious complication was reported. Compared with control group, the fluoroscopy time ((3.3±2.5) vs. (10.7±5.8) min, t=13.190, P<0.05), radiation dose ((5.4±4.9) vs. (15.5±6.3) mGy, t=13.660, P<0.05), and dose area product (514±445) vs. (2 478±415) mGy·cm², t=33.850, P<0.05) were decreased significantly. Conclusions AVNRT-SF was the most common type of AVNRT. AVNRT incidence in infant and toddlers is lower than that in elder children. CSo-His is correlated with the body weight. ABL-His is relatively fixed. There is no correlation between ABL-His and the body weight and also no correlation between ABL-His and CSo-His. RFCA of AVNRT in children using the CARTO3 system is safe, effective and minimizes X-ray fluoroscopy.

Objective:To explore the safety and efficacy of adenosine triphosphate (ATP) in terminating paro-xysmal supraventricular tachycardia (PSVT) in children and the correlation between its efficacy, age and dose.Methods:A retrospective analysis was performed on the clinical data, efficacy and adverse effects of intravenous ATP in 120 children who had received ATP emergency cardioversion among 1 488 children with PSVT hospitalized in the Department of Pediatric Cardiology, Heart Center, First Hospital of Tsinghua University from September 2014 to November 2019.There were 80 boys and 40 girls with the age of (3.50±3.66) years (25 d-15 years). As for the group comparison, the measurement data was subject to the independent samples t test and Mann- Whitney U test; the enumeration data was subject to χ2 test. Results:Among the 120 children with PSVT, there were 42 cases (35.0%) <1 year old, and 24 cases(20.0%) combined with congenital heart disease.There were 8.3% of them (10/120 cases) suffering from tachycardiomyopathy (TCM) secondary to PSVT, whose LVEF increased from (32.70±11.69)% to (40.50±11.63)% after successful control of PSVT ( t=-3.647, P=0.005). The complete termination of PSVT by intravenous ATP was achieved in 53 of 120 cases (44.2%). ATP was given at 0.3 mg/kg, 0.2 mg/kg and 0.1 mg/kg in dose, and the significant effective rate was 56.5%(13/23 cases), 36.4%(32/88 cases) and 0, respectively, which showed that there was a significant difference in the therapeutic effect between different dose groups ( χ2=10.058, P=0.007). There was a significant difference regarding the complete termination rate between children <1 year old and those ≥1 year old [31.0%(13/42 cases) vs.51.3%(40/78 cases), χ2=4.575, P=0.032]. For refractory PSVT, the intravenous ATP was performed based on the absence of cardioversion with continuous pumping of other antiarrhythmic drugs, which achieved a significantly complete termination rate of 55.6% (10/18 cases). The rate of ATP adverse reactions was 2.5%(3/120 cases), presented with sinus arrest in children >1 year old with the dose of 0.2-0.3 mg/kg. Conclusions:It was relatively safe and effective to terminate PSVT in children with ATP, which was related to dose and age.For refractory PSVT, ATP can be intravenously pushed on the basis of continuous pumping of other antiarrhythmic drugs, which can achieve a higher complete termination rate.

Objective:To identify the risk factors for cardiac events like recurrent syncope and fatal events in children with long QT syndrome (LQTS).Methods:A retrospective review involving 69 children with LQTS with the age of (7.6±4.2) years (43 male patients, 26 female patients) admitted in the Heart Center, Division of Pediatric Cardiology, First Hospital of Tsinghua University from August 2013 to March 2019 was conducted.Medical history, surface electrocardiogram, Doppler echocardiography and screening results of pathogenic genes of each patient were analyzed.Patients were divided into cardiac event group (32 cases) and non-cardiac event group (37 cases) according to the presence or absence of cardiac events like syncope or sudden death.Differences between 2 groups were compared using the independent sample Student′s t test and Chi- square test. Results:There were 32 cases among 69 children (46.4%) had recurrent syncope, involving 2 deaths, 14 cases among 69 children (20.3%) had a positive family history and 8 cases among 69 children (11.6%) had family history of sudden death.There were 52 cases among 69 children (75.4%) had arrhythmias.Among them, 32 patients (46.4%) with ventricular arrhythmia, including 11 cases (15.9%) with torsades de pointes (TdP). Ten LQTS-associated pathogenic or pathogenic pathologic mutations were found in 53 cases among 69 children (76.8%). Children with cardiac events had a younger mean age of onset [(4.7±4.1) years vs.(7.4±3.7) years, t=-2.856, P=0.006], a longer mean corrected QT (QTc) [(529±66) ms vs.(478±52) ms, t=3.537, P=0.001] and a higher incidence of TdP (34.4% vs.0%, P<0.001) compared with those who did not have cardiac events.Pathogenic mutations of KCNQ1 and KCNH2 were more frequent in children with cardiac events (62.5% vs.18.9%, χ2=14.178, P=0.001). Conclusions:Children with LQTS are prone to cardiac events.Children with a younger onset age, a longer QTc duration, malignant ventricular tachycardia and mutations of the KCNQ1 and KCNH2 genes are more frequently complicated by cardiac events.