Background: Neuroblastoma patients with MYCN amplification are associated with poor prognosis. However, the prognostic relevance of MYCN associated genes in neuroblastoma is unclear. Methods: The expression profiles of MYCN associated genes were identified from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) datasets. Enriched transcription factors and signaling pathways were determined using gene set enrichment analysis (GSEA). Kaplan-Meier plotter was used to identify the prognostic relevance of MYCN associated genes. Multivariate cox regression and Spearman’s correlation were used to determine the correlation coefficients of MYCN associated genes.Results: In TARGET and GSE85047 datasets, neuroblastoma patients with MYCN amplification were associated with worse prognosis. Transcription factor MYC was positively associated with MYCN amplification in GSEA assay. We identified 13 MYC target genes which were increased in neuroblastoma patients with MYCN amplification in TARGET, GSE19274 and GSE85047 datasets. Moreover, six out of the 13 MYC target genes ARMC6, DCTPP1, EIF4G1, ELOVL6, FBL and PRMT1 were associated with adverse prognosis in TARGET and GSE85047 datasets. Transcription factor E2F1 was up-regulated by MYCN amplification and associated with the poor prognosis of neuroblastoma. Furthermore, RPS19 in ribosome signaling pathway was also associated with MYCN amplification and correlated with the poor prognosis of neuroblastoma. At last, we showed that most of MYCN target genes were correlated with each other. However, EIF4G1 was an independent prognostic marker. And the prognostic effects of the combination of MYCN amplification and EIF4G1 expression were more significant than MYCN or EIF4G1 alone.Conclusions: MYCN target genes ARMC6, DCTPP1, EIF4G1, ELOVL6, FBL, PRMT1, E2F1 and RPS19 had significant prognostic effects in pediatric neuroblastoma. And neuroblastoma patients without MYCN amplification and low EIF4G1 expression had best prognosis.

ObjectivesFrom the first description by Leo Kanner [1], autism has been an enigmatic neurobehavioral phenomenon. The new genetic/genomic technologies of the past decade have not been as productive as originally anticipated in unveiling the mysteries of autism. The specific etiology of the majority of cases of autism spectrum disorder (ASD) is unknown, although numerous genetic/genomic variants and alterations of diverse cellular functions have been reported. Prompted by this failure, we have investigated whether the metabolomics approach might yield results which could simultaneously lead to a blood-based screening/diagnostic test and to treatment options. Methods Plasma samples from a clinically well-defined cohort of 100 male individuals, ages 2-16+ years, with ASD and 32 age-matched typically developing (TD) controls were subjected to global metabolomic analysis. ResultsWe have identified more than 25 plasma metabolites among the approximately 650 metabolites analyzed, representing over 70 biochemical pathways, that can discriminate children with ASD as young as 2 years from children that are developing typically. The discriminating power was greatest in the 2-10 year age group and weaker in older age groups. The initial findings were validated in a second cohort of 83 children, males and females, ages 2-10 years, with ASD and 76 age and gender-matched TD children. The discriminant metabolites were associated with several key biochemical pathways suggestive of potential contributions of increased oxidative stress, mitochondrial dysfunction, inflammation and immune dysregulation in ASD. Further, targeted quantitative analysis of a subset of discriminating metabolites using tandem mass spectrometry provided a reliable laboratory method to detect children with ASD. Conclusion Metabolic profiling appears to be a robust technique to identify children with ASD ages 2-10 years and provides insights into the altered metabolic pathways in ASD, which could lead to treatment strategies. ObjectivesTo uncover novel traits associated with nicotine and alcohol use genetics, we performed a phenome-wide association study in a large multi-ethnic cohort. Methods We investigated 7,688 African-Americans (AFR), 1,133 Asian-Americans (ASN), 14,081 European-Americans (EUR), and 3,492 Hispanic-Americans (HISP) from the Women's Health Initiative, analyzing risk alleles located in the CHRNA5-CHRNA3 locus (rs8034191, rs1051730, rs12914385, rs2036527, and rs16969968) for nicotine-related traits and ADH1B (rs1229984 and rs2066702) and ALDH2 (rs671) for alcohol-related traits with respect to anthropometric characteristics, dietary habits, social status, psychological circumstances, reproductive history, health conditions, and nicotine-and alcohol-related traits. ResultsThe investigated loci resulted associated with novel traits: rs1229984 were associated with family income (p=4.1*10 −12 ), having a pet (p=6.5*10 −11 ), partner education (p=1.8*10 −10 ), "usually expect the best" (p=2.4*10 −7), "felt calm and peaceful" (p=2.6*10 ), and num...

Abstract 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 explore the changes in the absolute value and decline rate of early serum cTnT and NT-proBNP in neonates who underwent V-A ECMO support therapy within one week of birth. Methods: Clinical data and laboratory test results of 17 neonates who underwent V-A ECMO support therapy within one week of birth from January 2020 to January 2023 were retrospectively collected from the electronic medical record system. The patients were divided into the survival group and the death group. The absolute values and decline rate of cTnT and NT-proBNP were compared between the two groups on the day, 24, 48, and 72 hours after ECMO treatment. Result: Of the 17 neonates, 10 survived, and 7 died, with a survival rate of 58.8%. The absolute values of cTnT and NT-proBNP in the survival group were significantly lower than those in the death group, and the decline rate was significantly higher than in the death group. In this study, neonates with no early decline in cTnT and NT-proBNP were all in the death group. Conclusion: The changes in the absolute value and decline rate of early serum cTnT and NT-proBNP in neonates who underwent V-A ECMO may predict their prognosis.

Objective Extracorporeal membrane oxygenation (ECMO) has been increasingly used for severe neonatal respiratory failure refractory to conventional treatments. This paper summarized our operation experience of neonatal ECMO via cannulation of the internal jugular vein and carotid artery. Methods The clinical data of 12 neonates with severe respiratory failure who underwent ECMO via internal jugular vein and carotid artery in our hospital from January 2021 to October 2022 were collected. Results All the neonates were successfully operation. The size of arterial intubation was 8 F, the size of venous intubation was 10 F. The operation time was 29 (22–40) minutes. ECMO was successfully removed in 8 neonates. They were successfully reconstructed the internal jugular vein and carotid artery. Arterial blood flow was unobstructed in 5 patients, mild stenosis in 2 patient, moderate stenosis in 1 patient. Venous blood flow was unobstructed in 6 patients, mild stenosis in 1 patient, and moderate stenosis in 1 patient. The complications were as follows: 1 case had poor neck incision healing after ECMO removing. No complications such as incisional bleeding, incisional infection, catheter-related blood infection, cannulation accidentally pulling away, vascular laceration, thrombosis, cerebral hemorrhage, cerebral infarction, and hemolysis occurred in all the patients. Conclusion Cannulation of the internal jugular vein and carotid artery can quickly establish an effective ECMO access for neonates with severe respiratory failure. Careful, skilled and delicate operation was essential. In addition, during the cannulation process, we should pay special attention to the position of cannulation, firm fixation and strict aseptic operation.

Background The aim of this study was to determine a predictive index for the risk of anastomotic leak following esophageal atresia anastomosis, Methods This article reviewed the clinical data of 74 children with esophageal atresia in Fujian Children's hospital. The risk factors for anastomotic leak were analysed, and a new predictive index was proposed. Results The incidence of anastomotic leak was 29.7% after anastomosis in 74 children with esophageal atresia. Birth weight and gap length were risk factors for anastomotic leak. Logistic regression analysis showed that birth weight (Wald 2 = 4.528, P = 0.033, OR = 0.273) was a protective factor for anastomotic leak, whereas gap length (Wald 2 = 7.057, P = 0.008, OR = 2.388) was a risk factor for anastomotic leak. The ratio of gap length to birth weight had a positive predictive effect on the occurrence of anastomotic leak (AUC = 0.732, P = 0.002). Conclusion Birth weight and gap length are important predictors of anastomotic leak in esophageal atresia. Measurement of the ratio of gap length to birth weight is a helpful predictive index for anastomotic leak following the anastomosis of esophageal atresia.

No abstract

Background: 22q11.2 deletion syndrome (22q11.2DS) is a disorder caused when a small part of chromosome 22 is missing. Diagnosis is currently established by the identification of a heterozygous deletion at chromosome 22q11.2 through chromosomal microarray analysis or other genomic analyses. However, more accurate identification of the breakpoint contributes to a clearer understanding of the 22q11.2 deletion syndrome.Methods: In this study, we present a feasible nanopore sequencing method of 22q11.2 deletion. This DNA enrichment method—region-specific amplification (RSA)—is able to analyze the 22q11.2 deletion by specific amplification of an approximately 1-Mb region where the breakpoint might exist. RSA introduces universal primers into the target region DNA by a Y-shaped adaptor ligation and a single primer extension. The enriched products, completed by amplification with universal primers, are then processed by standard ONT ligation sequencing protocols.Results: RSA is able to deliver adequate coverage (>98%) and comparable long reads (average length >1 Kb) throughout the 22q11.2 region. The long nanopore sequencing reads, derived from three umbilical cord blood samples, have facilitated the identification of the breakpoint of the 22q11.2 deletion, as well as by Sanger sequencing.Conclusion: The Oxford Nanopore MinION sequencer can use RSA to sequence the target region 22q11.2; this method could also be used for other hard-to-sequence parts of the genome.