Background As the most frequent type of cyanotic congenital heart disease (CHD), tetralogy of Fallot (TOF) has a relatively poor prognosis without corrective surgery. Circular RNAs (circRNAs) represent a novel class of endogenous noncoding RNAs that regulate target gene expression posttranscriptionally in heart development. Here, we investigated the potential role of the ceRNA network in the pathogenesis of TOF. Methods To identify circRNA expression profiles in TOF, microarrays were used to screen the differentially expressed circRNAs between 3 TOF and 3 control human myocardial tissue samples. Then, a dysregulated circRNA-associated ceRNA network was constructed using the established multistep screening strategy. Results In summary, a total of 276 differentially expressed circRNAs were identified, including 214 upregulated and 62 downregulated circRNAs in TOF samples. By constructing the circRNA-associated ceRNA network based on bioinformatics data, a total of 19 circRNAs, 9 miRNAs, and 34 mRNAs were further screened. Moreover, by enlarging the sample size, the qPCR results validated the positive correlations between hsa_circ_0007798 and HIF1A. Conclusions The findings in this study provide a comprehensive understanding of the ceRNA network involved in TOF biology, such as the hsa_circ_0007798/miR-199b-5p/HIF1A signalling axis, and may offer candidate diagnostic biomarkers or potential therapeutic targets for TOF. In addition, we propose that the ceRNA network regulates TOF progression.

Congenital heart disease (CHD) is the most common congenital malformation in fetuses and neonates, which also represents a leading cause of mortality. Although significant progress has been made by emerging advanced technologies in genetic etiology diagnosis, the causative genetic mechanisms behind CHD remain poorly understood and more than half of CHD patients lack a genetic diagnosis. Unlike carefully designed large case-control cohorts by multicenter trials, we designed a reliable strategy to analyze case-only cohorts to utilize clinical samples sufficiently. Combined low-coverage whole-genome sequencing (WGS) and whole-exome sequencing (WES) were simultaneously conducted in a patient-only cohort for identifying genetic etiologies and exploring candidate, or potential causative CHD-related genes. A total of 121 sporadic CHD patients were recruited and 34.71% (95% CI, 26.80 to 43.56) was diagnosed with genetic etiologies by low-coverage WGS and WES. Chromosomal abnormalities and damaging variants of CHD-related genes could explain 24.79% (95% CI, 17.92 to 33.22) and 18.18% (95% CI, 12.26 to 26.06) of CHD patients, separately, and 8.26% (95% CI, 4.39 to 14.70) of them have simultaneously detected two types of variants. Deletion of chromosome 22q11.2 and pathogenic variants of the COL3A1 gene were the most common recurrent variants of chromosomal abnormalities and gene variants, respectively. By in-depth manual interpretation, we identified eight candidate CHD-causing genes. Based on rare disease-causing variants prediction and interaction analysis with definitive CHD association genes, we proposed 86 genes as potential CHD-related genes. Gene Ontology (GO) enrichment analysis of the 86 genes revealed regulation-related processes were significantly enriched and processes response to regulation of muscle adaptation might be one of the underlying molecular mechanisms of CHD. Our findings and results provide new insights into research strategies and underlying mechanisms of CHD.

Background: As the most frequent type of cyanotic congenital heart diseases (CHD), Tetralogy of Fallot (TOF) has a relatively poor prognosis without the corrective surgery. Circular RNA (circRNA) represents a novel class of endogenous noncoding RNAs that regulate target gene expression post-transcriptionally in heart development. Here, we investigate the potential role of ceRNA network in the pathogenesis of TOF. Methods: To identify circRNAs expression profiles in Tetralogy of Fallot, microarrays were used to screen the differentially expressed circRNA between 3 TOF and 3 control human myocardial tissue samples. Then, a dysregulated circRNA- associated ceRNA network was constructed via using the established multi-step screening strategy.Results: In summary, total 276 differentially expressed circRNAs were identified, including 214 up-regulated and 62 down-regulated ones in TOF samples. By constructing the circRNA-associated ceRNA network based on the bioinformatics data, a total of 19 key circRNAs, 9 key miRNAs and 34 key mRNAs were further screened. Moreover, by enlarging the samples size, the qPCR results validated that the positive correlations between hsa_circ_0007798 and HIF1A.Conclusions: The findings in this study provide a comprehensive understanding of the ceRNA network involved in TOF biology, such as hsa_circ_0007798/miR-199b-5p/HIF1A signal axis, and may offer candidate diagnostic biomarkers or potential therapeutic targets for TOF. In addtion, we propose that the ceRNA network regulates TOF progression.

Objective: To investigate the incidence and risk factors of acute renal injury (AKI) after cardiopulmonary bypass (CPB) cardiac surgery in infants with congenital heart disease(CHD). Methods: Single-center data from a total of 613 infants with congenital heart disease who underwent cardiothoracic surgery in Fujian Union Hospital.The included patients were divided into two groups according to the occurrence of AKI: AKI group (n = 68) and non-AKI group (n = 92). We obtained clinical data from the electronic hospitalization information system and the laboratory database. All infants were tested for serum creatinine at least twice within 12 hours of admission and after operation. We determined AKI events according to creatinine criteria for improving global prognosis of renal diseases.The general and clinical data of the infants were collected, and the related risk factors were explored by univariate analysis and Logistic regression analysis. Results: 160 patients had congruent lab and echocardiogram data foranalysis. Most of patients are male (56.26%). Original congenital cardiac malformation is similar with our study, the most common is left-to-right shunt CHD(58%), followed by right-to-left shunt CHD(18.75%). All patients showed differences in liver function, renal function, cardiac function and inflammatory indexes within 12 hours of admission and after operation(p<0.05). The AKI group and non-AKI group showed Significant statistical difference in arein age, serum myocardial enzyme , hepatic function, ejection fraction , hemoglobin , platelet count were significantly different meaning (p<0.05). Regression analyses showed that blood oxygen saturation (95%CI 1.003-2.999), CREA(95%CI 1.070-1.253), UREA(95%CI 1.180-3.325), CRP(95%CI 1.006-1.058), BNP(95%CI 0.999-1.000) at 12 hours postoperatively, and in admission to PCT (95%CI 0.461-0.936), Neu(95%CI 0.909-0.995), ALP(95%CI 1.070-1.253) , nadir intraoperative renal regional tissue oximetry to be independent predictors of postoperative kidney damage as measured by blood oxygen saturation, hepatic function, kidney function, cardiac function , Serum myocardial enzyme , inflammatory factor s and blood Routine . Conclusions: Choosing the best age for infants's cardiac surgery, actively preventing preoperative complica- tions, postoperative pneumonia, heart failure and hypoxia play an important role in preventing AKI.