Wei Shi

Bronchopulmonary dysplasia (BPD) is a major complication of prematurity, and endothelial dysfunction contributes to its pathogenesis. Although lactate metabolism is dysregulated in BPD, whether lactate-derived lysine lactylation contributes to endothelial dysfunction remains unknown. This study investigated the role of lactylation in endothelial injury and the involvement of SP1-Cdkn1a axis in BPD. We found that lactate levels and global lactylation levels were increased in both in vitro and in vivo models of BPD, accompanied by impaired endothelial proliferation, migration and angiogenic capacity. Integrated bioinformatic analysis identified Cdkn1a as a glycolysis-associated hub gene in BPD, and its upregulation in pulmonary vascular endothelial cells (PVECs) was confirmed experimentally. Subsequent Cdkn1a knockdown alleviated hyperoxia-induced endothelial dysfunction. In addition, inhibition of glycolysis reduced lactylation level in PVECs, suppressed Cdkn1a expression, and partially improved pulmonary microvascular injury. To explore the upstream mechanism, lactylome profiling identified SP1, a known transcription factor of Cdkn1a, as a lactylated candidate. Increased SP1 lactylation and enhanced binding at the Cdkn1a promoter were verified in PVECs from BPD mice. K640R mutation attenuated SP1-dependent Cdkn1a promoter activation. Overall, this study reveals the involvement of endothelial lactylation in pathogenesis of BPD and implicates the SP1-Cdkn1a axis as a potential therapeutic target.

Necrotizing enterocolitis (NEC) is an inflammatory intestinal disease that primarily affects premature infants and is a major cause of death in the neonatal period. Approximately half of the affected infants require surgical intervention, but there is no established consensus on the criteria or timing for surgery, making treatment decisions challenging. 291 patients between 2019 and 2023 were categorized into medical group, early surgery group, and late surgery group. The region of interest (ROI) on the abdominal stereotaxic film underwent color-channel transformation, and radiomics features were subsequently extracted. Statistical analysis was then performed using a two-sample independent t test and least absolute shrinkage and selection operator (Lasso) regression to assess the relevant features. By screening and analyzing abdominal X-ray features across different subgroups, three key features-Blue_variance, a_star_variance, and L_star_energy-were identified as common differential markers. These features may serve as imaging biomarkers for predicting the surgical necessity in NEC patients. We identified new parameters of abdominal X-rays in patients with NEC to assess the feasibility of surgical treatment and may provide supporting clinical guidance to clinicians.

Background: Feeding intolerance (FI) following surgery for neonatal necrotizing enterocolitis (NEC) can impact recovery and prognosis, making the early identification of FI risk essential for optimizing management and improving outcomes. Methods: We retrospectively collected data from patients who underwent surgery for NEC between January 2013 and December 2023. Multivariate binary logistic regression was performed to identify independent factors influencing postoperative feeding intolerance. Results: Of the 519 infants enrolled in this retrospective study, 155 (29.9%) were diagnosed with feeding intolerance, while 364 (70.1%) were identified as having feeding tolerance. Compared to infants with feeding tolerance, those with feeding intolerance had lower birth weight, smaller gestational age, and lower Apgar scores (all p < 0.01). A 5 min Apgar < 7 (OR 4.794; 95%CI 1.339–17.156), the interval between diagnosis and surgery (OR 0.973; 95%CI 0.947–1.000), and primary anastomosis resection (OR 0.278, 95%CI 0.139–0.555) were identified as significant factors influencing postoperative feeding intolerance. The results remained consistent after performing propensity score matching analysis. Feeding intolerance may result in prolonged hospital stays, and more complications such as retinopathy of prematurity, intestinal failure-associated liver disease, and intraventricular hemorrhage. Conclusions: A lower 5 min Apgar score, shorter interval from diagnosis to surgery and intestine resection with ostomy are associated with a higher incidence of FI after surgery. FI after NEC surgery can prolong recovery and increase family burden.

Objective: The objective of this study is to assess the relationship between non-invasive ventilation (NIV) and the colonisation of oral and nasal microbiota in preterm infants within the neonatal intensive care unit (NICU).Design: A prospective cohort study.Setting: The NICU of Zhejiang University Children’s Hospital.Patients: Patients include preterm infants with a gestational age of 28–35 weeks, enrolled within the first 24 hours of life.Interventions: Infants were categorised based on respiratory support: NIV, which included nasal continuous positive airway pressure, nasal intermittent positive pressure ventilation or high-flow nasal cannula; and no respiratory support, defined as room air or low-flow nasal cannula at ≤2 L/min.Main outcome measures: The primary outcome was the colonisation of oral and nasal microbiota at 5 days post birth, measured by colony-forming units per millilitre (CFU/mL), with colonisation defined as bacterial growth >10³ CFU/mL.Results: The study included 100 preterm infants, with 50 in each group. Nasal microbial colonisation was observed in 56% (28/50) of the NIV group, significantly higher than the 28% in the no respiratory support group. No significant differences were found in oral colonisation. Adjusted binary logistic regression showed an association between NIV and increased risk of nasal colonisation (adjusted OR=2.91, 95% CI 1.12 to 7.58, p=0.028).Conclusions: NIV in preterm infants was linked to a higher risk of nasal microbial colonisation. This finding suggests the need for further research and consideration of infection control strategies in the NICU.

Original Article Clinical and variant spectrum of patients harboring ATAD3A variants Hongfang Mei, Xinyin Zhang, Taixiang Liu, Mingyan Chen, Jiajing Ge, Dingwen Wu, Xiaolu Ma, Liping Shi, Wei Shi, Zheng Chen