Shasha Han

Maternal hyperglycemia is associated with adverse neurodevelopmental outcomes in offspring, but the mechanisms by which it affects fetal brain development remain incompletely understood. Using a mouse model of pregestational diabetes mellitus (PGDM), we found that maternal hyperglycemia was associated with reduced cortical thickness and altered cortical lamination. These abnormalities were accompanied by changes in neural stem cell differentiation and asymmetric division, as well as impaired neuronal migration and dendritic development. Transcriptomic analysis identified the transcription factor Foxp1 as markedly downregulated in the PGDM embryonic cortex. Restoring Foxp1 expression in vivo substantially alleviated the observed cortical abnormalities. Mechanistic experiments showed that Foxp1 represses transcription of the Notch ligand Delta‐like 1 (Dll1) and attenuates Notch signaling. Together, these findings implicate the Foxp1–Dll1–Notch axis as one pathway contributing to disrupted corticogenesis in the PGDM model and provide insight into how an adverse intrauterine metabolic environment affects embryonic brain development.

Background In singleton pregnancies, gestational diabetes mellitus (GDM) causes maternal and neonatal complications. However, this association remains unclear in twin pregnancies. This study aimed to investigate the association between GDM and obstetric outcomes specifically in twin pregnancies. Methods A retrospective cohort study was conducted among women with twin pregnancies from January 2018 to July 2022. Maternal and neonatal outcomes were compared between women with and without GDM. Adjusted ORs, 95% CIs and SEs were estimated using logistic regression, adjusting for maternal age, prepregnancy body mass index and chorionicity. Results A total of 808 women (1616 neonates) were included in the study, of whom 178 had GDM, while 630 did not. GDM was found to be positively associated with (adjusted OR, (95% CI)) preterm birth (1.73 (1.17 to 2.54)), premature rupture of membranes (1.70 (1.03 to 2.79)) and hypothyroidism (2.58 (1.46 to 4.56)) in women with twin pregnancies. In regard to neonatal outcomes, GDM was positively associated with admission to neonatal ward (1.49 (1.13 to 1.96)), oxygen therapy (1.91 (1.45 to 2.52)), hyperbilirubinaemia (1.44 (1.08 to 1.90)), total use and prophylactic use of antibiotics (1.98 (1.17 to 3.33) and 1.88 (1.00 to 3.54), respectively). When stratified by gestational age, GDM remained positively associated with certain adverse outcomes exclusively in twin preterm infants. Conclusions Our study demonstrated that GDM is significantly associated with several adverse pregnancy outcomes in twin pregnancies, including hypothyroidism in pregnant women, preterm birth, admission to neonatal ward, oxygen therapy, hyperbilirubinaemia, the total and prophylactic use of antibiotics in twins. Specifically, in twin pregnancies, GDM may be more strongly associated with adverse outcomes in preterm infants than in term infants.

Background: Inhaled nitric oxide (iNO) has been shown to be effective in term and near-term infants with specific respiratory diseases. The effects and potential risks of iNO differ substantially in preterm infants with special pathophysiology. Specific study in this population is necessary. Purpose: To assess the short-term and long-term effects of iNO in preterm infants with respiratory diseases such as respiratory failure and respiratory distress syndrome. Methods: We conducted a meta-analysis of randomized controlled trials and cohort studies comparing iNO with placebo or blank control in preterm infants with respiratory diseases.Databases including PubMed, the Cochrane Library, Scopus, and Web of Science were searched from their inception until May 2025. The primary outcomes were death before discharge, death at 36 weeks’ postmenstrual age (PMA), bronchopulmonary dysplasia (BPD) and death or BPD. Results: Thirty-one trials met the inclusion criteria. iNO reduced the incidence of death or BPD (risk ratio [RR] 0.94, 95% confidence interval [CI] 0.88 to 0.99, 6 studies, 1954 infants) and BPD in the RCT subgroup (RR 0.91, 95% CI 0.84 to 0.99, 8 studies, 2196 infants).Increases of oxygenation index (Standardized mean difference (SMD) − 0.62, 95% CI − 0.81 to − 0.43, 2 studies, 441 infants) and Partial pressure of oxygen (PaO₂) (SMD 0.68, 95% CI 0.49 to 0.87, 2 studies, 441 infants) of preterm infants at 5 ppm initial concentration were observed in the iNO group. The iNO group demonstrated a higher risk of retinopathy of prematurity (RR 1.08, 95% CI 1.01 to 1.16, 17 studies, 7220 infants). No significant differences were observed in other neonatal morbidities or adverse events. Conclusions: iNO was associated with a reduced risk of death or BPD and a probably reduction of BPD. There was no effect on other morbidities or adverse events. Data on long-term respiratory and neurodevelopment outcomes are critically needed to further evaluate NO's efficacy in preterm infants, particularly Extremely low birth weight infants.

Twin pregnancies, accounting for a rising proportion of births globally, present significant public health challenges in China. Birthweight discordance (BWD), a critical complication, remains understudied in its epidemiological context, particularly regarding its population-level associations with adverse neonatal outcomes. This multi-center, retrospective cohort study leveraged data from 21 hospitals across 18 Chinese cities (2018–2020) to assess BWD and its epidemiological implications. Ordinal logistic regression with random effects was used to explore their association. BWD was defined as: [(larger birthweight − smaller birthweight) / larger birthweight] × 100% and categorized into four grades: I (≤15%), II (>15% to 20%), III (>20% to 25%), and IV (>25%). Among 6437 twin pairs, 73.6% were classified as Grade I (no BWD), while 10.7%, 7.1%, and 8.6% constituted Grades II, III, and IV discordance, respectively. Dose-response relationships emerged: each incremental BWD elevated risks of small vulnerable newborns (aOR = 1.83, 95% CI 1.76–1.90), small for gestational age (aOR = 1.23, 95% CI 1.18–1.29), low birthweight (LBW, aOR = 1.16, 95% CI 1.13–1.20), very LBW (aOR = 1.63, 95% CI 1.53–1.73) and extreme LBW (aOR = 1.82, 95% CI 1.61–2.05). Smaller twins exhibited disproportionately higher adverse outcome rates than larger twins. Sensitivity analyses confirmed robustness across specific subgroups. BWD exceeding 20% affects 15.7% of live-born twins in China, mirroring rates in high-income settings. BWD demonstrates strong dose-response relationships with adverse outcomes, validating its utility for twin health stratification. These findings call for integrating BWD assessment into prenatal surveillance and risk-adapted care to reduce neonatal morbidity/mortality, urging clinicians and policymakers to prioritize perinatal outcome equity.

Background: Numerous studies have explored interventions to reduce digital addiction outcomes, but inconclusive evidence makes it difficult for decision-makers, managers, and clinicians to become familiar with all available literature and find appropriate interventions. Objective: This study aims to summarize and assess the certainty of evidence of interventions proposed to decrease digital addiction from published meta-analyses. Methods: An umbrella review of published meta-analyses was performed. We searched PubMed, Cochrane Library, Web of Science, and Embase for meta-analyses published up to February 2024. Eligible studies evaluated interventions using randomized controlled trials, nonrandomized controlled trials, or quasi-experimental studies and were assessed for methodological quality using Assessment of Multiple Systematic Reviews version 2. A random effects model was used to analyze data, considering heterogeneity and publication bias. Grading of Recommendations, Assessment, Development, and Evaluations was applied to assess evidence with certainty. Results: A total of 5 studies assessing 21 associations were included in the umbrella review, of which 4 (80%) were high-quality meta-analyses. Weak evidence was observed in 19 associations, whereas null associations appeared in the remaining 2 associations. These associations pertained to 8 interventions (group counseling, integrated internet addiction [IA] prevention programs, psychosocial interventions, reality therapy, self-control training programs, cognitive behavioral therapy, interventions to reduce screen time in children, and exercise) and 9 outcomes (self-control, self-esteem, internet gaming disorder symptoms, time spent gaming, IA scores, screen use time, interpersonal sensitivity longlines, anxiety, and depression). Cognitive behavioral therapy reduces anxiety (standardized mean difference [SMD] 0.939, 95% CI 0.311 to 1.586), internet gaming disorder symptoms (SMD 1.394, 95% CI 0.664 to 2.214), time spent gaming (SMD 1.259, 95% CI, 0.311 to 2.206), and IA scores (SMD –2.097, 95% CI –2.814 to –1.381). Group counseling had a large effect on improving self-control (SMD 1.296, 95% CI 0.269 to 2.322) and reducing IA levels (SMD –1.417, 95% CI –1.836 to –0.997). Exercise intervention reduced IA scores (SMD –2.322, 95% CI –3.212 to –1.431), depression scores (SMD –1.421, 95% CI –2.046 to –797), and interpersonal sensitivity scores (SMD –1.433, 95% CI –2.239 to –0.627). Conclusions: The evidence indicates that current interventions to reduce digital addiction are weak. Data from more and better-designed studies with larger sample sizes are needed to establish robust evidence. Trial Registration: PROSPERO CRD42024528173; crd.york.ac.uk/PROSPERO/display_record.php?RecordID=528173

Objective: Not all infants with persistent pulmonary hypertension of the newborn (PPHN) respond to inhaled nitric oxide (iNO) therapy, as it is known to improve oxygenation in only 50% to 60% of cases. In this study, we investigated whether ABO blood groups were a relevant factor affecting the improvement of oxygenation by nitric oxide (NO) therapy in infants with PPHN.Methods: This study was a retrospective, multicenter, and cohort-controlled trial that involved 37 medical units. Infants with PPHN who met the inclusion criteria and were treated with NO (a vasodilator) alone from July 1, 2015, to June 30, 2020, were selected and assigned into three groups: blood type A, blood type B, and blood type O (there were only 7 cases of blood type AB, with a small number of cases, and therefore, blood type AB was excluded for further analysis). The response to iNO therapy was defined as an increase in the ratio of the partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) > 20% from the basal value after treatment. Oxygenation was assessed mainly based on the two values, oxygenation index (OI) and PaO2/FiO2. The correlation of ABO blood groups with responses to iNO therapy and their influence on the efficacy of iNO therapy was analyzed based on the collected data.Results: The highest proportion of infants with PPHN who eventually responded to iNO therapy was infants with blood type O. Infants with blood type O more readily responded to iNO therapy than infants with blood type B. Oxygenation after iNO treatment group was optimal in the blood type O group and was the worst in the blood type A group among the three groups. Infants with blood type O showed better efficacy than those with blood types A and B.Conclusion: ABO blood groups are correlated with responses to iNO therapy in infants with PPHN, and different blood groups also affect the efficacy of NO therapy in infants with PPHN. Specifically, infants with blood type O have a better response and experience the best efficacy to iNO therapy.

Purpose: Sepsis is a significant threat in the intensive care unit (ICU) worldwide because it has high morbidity and mortality rates. Early recognition and diagnosis of sepsis are essential for the prevention of adverse outcomes. The present study aimed to quantitatively assess the association between serum anion gap (AG) levels and 30- and 90-day all-cause mortality among sepsis patients. Methods: Clinical data of patients diagnosed with sepsis were extracted from the Medical Information Mart for Intensive Care III (MIMIC III) database. Kaplan–Meier curves and Cox proportional hazards models were used to evaluate the association between serum AG levels and all-cause mortality. A receiver operating characteristic (ROC) curve was drawn to quantify the efficacy of using the serum AG level to predict all-cause mortality. Results: A total of 3811 patients were included in the study. The Kaplan–Meier curves showed that patients with higher serum AG levels had a shorter survival time than those with lower levels. Serum AG levels were found to be highly effective in predicting all-cause mortality secondary to sepsis (30-day: AUROC = 0.703; 90-day: AUROC = 0.696). The Cox regression model further indicated that the serum AG level was an independent risk factor for 30- and 90-day mortality in sepsis (HR 3.44, 95% CI 2.97-3.99 for 30-day; HR 3.17, 95% CI 2.76-3.65 for 90-day, P < 0.001 for both). Conclusions: High serum AG may be considered as an alternative parameter for predicting the death risk in sepsis when other variables are not immediately available. Prospective large-scale studies are needed to support its predictive value in the clinic.

Objectives: To provide an updated review and meta‐analysis on the efficacy and safety of sildenafil for treating persistent pulmonary hypertension in neonates (PPHN).Methods: PubMed/Medline, SCOPUS, Cochrane Central Register of Controlled Trials, and Web of Science were searched from the inception of publication to January 2021. The principal outcomes include oxygenation parameters, hemodynamic metrics and echocardiographic measurements, as well as adverse outcomes.Results: A total of eight studies were included with 216 term and premature neonates with PPHN. Compelling evidence showed the use of sildenafil could improve the prognosis of PPHN neonates, compared with baseline or placebo in neonates with PPHN, and a time‐dependent pattern of the improvements can be observed. After 24 h of treatment, the Oxygenation index suggested a steady decrease (SD: −1.80, 95% confidence interval [CI]: −2.92, −0.67) and sildenafil exerted peak effects after 72 h of treatment (SD: −4.02, 95% CI: −5.45, −2.59). No clinically significant side effects were identified. Egger's test and funnel plots of the major outcomes were performed, and the publication bias was not significant.Conclusion: Improvements were shown in oxygenation index, pulmonary arterial pressure, and adverse outcomes after using sildenafil for PPHN in neonates. However, future research with robust longitudinal or randomized controlled design is still needed.

Gestational diabetes mellitus (GDM) increases the risk of fetal heart malformations, though little is known about the mechanism of hyperglycemia-induced heart malformations. Thus, we aimed to reveal the global landscape of miRNAs and mRNAs in GDM-exposed fetoplacental arterial endothelial cells (dAECs) and establish regulatory networks for exploring the pathophysiological mechanism of fetal heart malformations in maternal hyperglycemia. Gene Expression Omnibus (GEO) datasets were used, and identification of differentially expressed miRNAs (DEMs) and genes (DEGs) in GDM was based on a previous sequencing analysis of dAECs. A miRNA-mRNA network containing 20 DEMs and 65 DEGs was established using DEMs altered in opposite directions to DEGs. In an in vivo study, we established a streptozotocin-induced pregestational diabetes mellitus (PGDM) mouse model and found the fetal cardiac wall thickness in different regions to be dramatically increased in the PGDM grouValidation of DEMs and DEGs in the fetal heart showed significantly upregulated expression of let-7e-5p, miR-139-5p and miR-195-5p and downregulated expression of SGOL1, RRM2, RGS5, CDK1 and CENPA. In summary, we reveal the miRNA-mRNA regulatory network related to fetal cardiac development disorders in offspring, which may shed light on the potential molecular mechanisms of fetal cardiac development disorders during maternal hyperglycemia. graphic abstract