Translational pediatrics最新文献

[This corrects the article DOI: 10.21037/tp-23-391.].

Background: Hirschsprung's disease (HSCR) is a complex congenital neurodevelopmental disorder affecting colons caused by both genetic and environmental factors. Although several genes have been identified as contributing factors in HSCR, the pathogenesis is still largely unclear, especially for the low prevalent long-segment HSCR (L-HSCR). Gap junction protein alpha 8 (GJA8) is involved in several physiological processes and has been implicated in several diseases. However, the relationship between GJA8 single nucleotide polymorphism (SNP) rs17160783 and HSCR in the southern Chinese population remains unknown. The study aimed to explore the association of genetic variants in GJA8 and HSCR susceptibility in southern Chinese.

Methods: SNP rs17160783 A>G in GJA8 was genotyped by TaqMan SNP Genotyping Assay in all samples, which included 1,329 HSCR children (cases) and 1,473 healthy children (controls). Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the association of GJA8 polymorphisms with HSCR susceptibility. The GTEx database and transcription factor binding site (TFBS) prediction were used to analyze the potential regulatory function of rs17160783.

Results: Genetic association analysis illustrated that rs17160783 could increase the risk of L-HSCR (P_adj=0.04, OR_adj =1.48, 95% CI: 1.02-2.14). We also found that GJA8 expression was increased in HSCR and neurodevelopmentally impaired animal models. External epigenetic data revealed that GJA8 rs17160783 may have the potential to regulate the expression of the GJA8, possibly by altering the binding of transcription factors for GJA8, and consequently impacting the PI3K-Akt signaling pathway during the enteric nervous system (ENS) development.

Conclusions: Our results suggested that rs17160783 might play a regulatory role in GJA8 expression and increase the susceptibility of L-HSCR in children from southern China.

Background: Astigmatism is closely associated with myopia progression, vision loss, eye fatigue and amblyopia, which seriously endangers children's eye health. This study aims to investigate the prevalence and characteristic distribution of astigmatism in children in Langzhong City, providing valuable insights for allocating resources and develop prevention and control strategies.

Methods: A cross-sectional study and random sampling survey were conducted. Between January and November 2021, 21,415 students aged 5 to 13 years from 14 primary schools in Langzhong City underwent non-cycloplegic refractive testing using autorefraction. The data on myopia were analyzed using SPSS (Statistical Package for the Social Sciences) version 23.0.

Results: The inclusion criterion was set at an absolute astigmatism value of ≥0.50D. Among the 21,415 children studied, 61.70% were found to have astigmatism. The prevalence of astigmatism varied significantly across different grades (χ²=501.414, P<0.001). The predominant types of astigmatism were mild astigmatism (0.50-1.00D) and with-the-rule astigmatism. Mixed astigmatism was primarily observed in children in grades 1 and 2, while compound myopic astigmatism was more common in children in grades 3 to 6. These differences were statistically significant. As the degree of astigmatism increased, the proportions of against-the-rule astigmatism, oblique astigmatism, compound myopic astigmatism, and simple hyperopic astigmatism decreased, whereas the proportions of with-the-rule astigmatism, mixed astigmatism, and compound hyperopic astigmatism increased.

Conclusions: The prevalence of astigmatism among school-age children aged 5 to 13 years in northeast Sichuan is notably high, with compound myopic astigmatism and with-the-rule astigmatism being the most common types. Regular refractive examinations are crucial for the early detection and management of astigmatism.

Background: Due to the incomplete standardization of the etiology and diagnostic criteria for fetal growth restriction (FGR), there has been uncertainty in the early prediction of FGR. The comprehensive estimation of FGR was mainly based on various factors, such as maternal characteristics and medical history, nuchal translucency (NT), and serum biochemical markers [pregnancy-associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (free β-hCG)]. Herein, we performed a retrospective cohort study to investigate the correlation and diagnostic value of maternal markers such as PAPP-A, free β-hCG, and NT in the first trimester with maternal characteristics, so as to provide theoretical basis for perinatal care and the application of low-dose aspirin.

Methods: A retrospective cohort study was conducted to analyze the data of an FGR group and a non-FGR group. Chi-square test and Mann-Whitney U test were used for univariate analysis of qualitative or quantitative data, respectively. Modified Poisson regression calculated the relative risk (RR) and 95% confidence interval (CI) of perinatal variables; P<0.05 was considered statistically significant.

Results: The multiple of median (MoM) of PAPP-A level and NT in the FGR group were lower than those of the non-FGR group [0.63 (0.12-2.08) vs. 1.01 (0.28-2.41) MoM, 1.30 (0.80-2.07) vs. 1.40 (0.80-2.20) cm, P<0.05]. The weight, score, and length of newborns in the FGR group were lower than those in the non-FGR group (all P<0.001). Modified Poisson regression analysis showed that gestational hypertension (GH) [RR =1.836 (95% CI: 1.188-2.836)], oligohydramnios [1.420 (95% CI: 1.022-1.973)], premature rupture of membranes (PROM) [0.641 (95% CI: 0.425-0.969)], female infant [1.539 (95% CI: 1.098-2.157)], low infant length [5.700 (95% CI: 3.416-9.509)], low birth weight [1.609 (95% CI: 1.012-2.559), and increased PAPP-A MoM [0.533 (95% CI: 0.369-0.769)] were associated with FGR. The cut-off value of PAPP-A + free β-hCG + NT for predicting FGR was 0.190, with a sensitivity of 0.547 and a specificity of 0.778.

Conclusions: Early screening markers combined with perinatal characteristics have better diagnostic value in predicting FGR and provide a scientific basis for the clinical use of low-dose aspirin to prevent FGR.

Background: Studies have revealed that inflammatory response is relevant to the tetralogy of Fallot (TOF). However, there are no studies to systematically explore the role of the inflammation-related genes (IRGs) in TOF. Therefore, based on bioinformatics, we explored the biomarkers related to inflammation in TOF, laying a theoretical foundation for its in-depth study.

Methods: TOF-related datasets (GSE36761 and GSE35776) were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between TOF and control groups were identified in GSE36761. And DEGs between TOF and control groups were intersected with IRGs to obtain differentially expressed IRGs (DE-IRGs). Afterwards, the least absolute shrinkage and selection operator (LASSO) and random forest (RF) were utilized to identify the biomarkers. Next, immune analysis was carried out. The transcription factor (TF)-mRNA, lncRNA-miRNA-mRNA, and miRNA-single nucleotide polymorphism (SNP)-mRNA networks were created. Finally, the potential drugs targeting the biomarkers were predicted.

Results: There were 971 DEGs between TOF and control groups, and 29 DE-IRGs were gained through the intersection between DEGs and IRGs. Next, a total of five biomarkers (MARCO, CXCL6, F3, SLC7A2, and SLC7A1) were acquired via two machine learning algorithms. Infiltrating abundance of 18 immune cells was significantly different between TOF and control groups, such as activated B cells, neutrophil, CD56dim natural killer cells, etc. The TF-mRNA network contained 4 mRNAs, 31 TFs, and 33 edges, for instance, ELF1-CXCL6, CBX8-SLC7A2, ZNF423-SLC7A1, ZNF71-F3. The lncRNA-miRNA-mRNA network was created, containing 4 mRNAs, 4 miRNAs, and 228 lncRNAs. Afterwards, nine SNPs locations were identified in the miRNA-SNP-mRNA network. A total of 21 drugs were predicted, such as ornithine, lysine, arginine, etc.

Conclusions: Our findings detected five inflammation-related biomarkers (MARCO, CXCL6, F3, SLC7A2, and SLC7A1) for TOF, providing a scientific reference for further studies of TOF.

Background: The Epstein-Barr virus-associated natural killer (NK) and T-cell lymphoma (EBV + NK/T cell lymphoma) is a severe illness mainly affecting children and young adults, often resulting in a poor prognosis. To date, there is no consensus on an established treatment strategy. This study aims to evaluate the efficacy and safety of the mSMILE (modified steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide) chemotherapy regimen in treating EBV+ NK/T-cell lymphoma and to provide insights into potential treatment outcomes.

Methods: In this study, we conducted a retrospective analysis of the clinical data and treatment outcomes for patients with EBV + NK/T cell lymphoma treated at Children's Hospital of Nanjing Medical University between July 2017 and January 2022. These patients received at least two cycles of the mSMILE chemotherapy, in which a single dose of pegaspargase was substituted for 7 doses of L-asparaginase per cycle.

Results: Eight patients were included in the study: one with extranodal NK/T-cell lymphoma, one with primary nodal NK/T-cell lymphoma, and six with Systemic EBV+ NK/T cell lymphoma of childhood. The results showed that five patients achieved complete remission, two achieved partial remission, and one showed progressive disease, resulting in a complete remission rate of 62.5% and an overall response rate of 87.5%. The 3-year overall survival (OS) and event-free survival (EFS) rates were 87.5% and 75%, respectively. The most common adverse reactions associated with chemotherapy were hematologic toxicities of stages III to IV. Nonhematologic adverse reactions mainly included impaired liver function, infections, and oral mucositis, which were resolved with aggressive anti-infective therapy.

Conclusions: Based on our clinical experience, the mSMILE appears to be a safe and effective treatment option for EBV + NK/T-cell lymphoma, meriting further investigation in late-phase clinical trials.

Background: In recent years, the incidence of asthma in children has been increasing. As a chronic disease, in addition to drug treatment, dietary management is also important. However, studies of carotenoids and asthma have shown mixed results. This study aimed to evaluate whether the relationship between carotenoid intake and current asthma holds significant importance.

Methods: We studied 9,118 children aged 6-16 years in the National Health and Nutrition Examination Survey (NHANES) of US from 2007 to 2016, and the relationship of dietary carotenoid and its subgroup with pediatric asthma. Current asthma was assessed by parent-reported, doctor-diagnosed, asthma using a standardized questionnaire. We used multivariate logistic regression to calculate the odds ratio (OR) for current asthma with a 95% confidence interval (CI).

Results: Total carotenoid intake was not associated with the risk of current asthma. Compared with the first quantile, the second quantile of β-cryptoxanthin intake was positively correlated with current asthma (Q2: 1.227; 95% CI: 1.025-1.470; P=0.03). The test of trend showed that, as the α-carotene intake increased, the risk of current asthma showed a decreasing trend, which was very close to the statistic confidence cutoff (Model I: P for trend =0.001; Model II: P for trend =0.003; Model III: P for trend =0.08). In subgroup analysis, family history of asthma interacted with carotenoid intake (P=0.005). The population without a family history of asthma, there were significant negative associations between carotenoid intakes and asthma (quartile 4: Model III: 0.720; 95% CI: 0.549-0.943; P=0.02).

Conclusions: In this study, pediatric current asthma was not related to total carotenoids in our total participants. Total dietary carotenoid intake has a protective effect on children without a family history of asthma. Meanwhile, β-cryptoxanthin intake is positively correlated with asthma.