Xiaoping Lei

Background: White matter repair requires coordinated myelin-debris clearance, inflammatory resolution, oligodendrocyte precursor cell (OPC) differentiation, remyelination and adaptive circuit reorganization. Murine paired immunoglobulin-like receptor B (PirB) and the functionally corresponding human leukocyte immunoglobulin-like receptor B2 (LILRB2) occupy potentially important but incompletely defined positions within this sequence. Main body: Direct evidence establishes neuronal PirB as a receptor for Nogo, myelin-associated glycoprotein and oligodendrocyte-myelin glycoprotein in mice, where it recruits SHP-1/2, suppresses Trk signalling and limits structural plasticity. Separately, human microglial systems show that LILRB2 can oppose TREM2–DAP12-dependent migration and phagocytosis. TREM2-dependent lipid adaptation is required for repair after demyelination, but no study has completed the causal chain from LILRB2 blockade to enhanced myelin-debris processing, OPC differentiation, ultrastructural remyelination and restored conduction. We therefore distinguish direct evidence, bridging evidence and testable predictions; prioritize multiple sclerosis as the most informative initial disease context; and define human-lesion, cell-specific, pharmacological and functional validation gates. Conclusion: PirB/LILRB2 is best considered a candidate, context-dependent neuroimmune checkpoint rather than an established remyelination target. Translation requires human lesion localization, demonstration of LILRB2–TREM2 engagement with myelin-relevant ligands, cell-selective target occupancy and repair defined by lineage, ultrastructural and electrophysiological endpoints.

Introduction: Janibacter melonis ( J. melonis ) is a rare environmental actinomycete with only three previously reported human infections, all presenting as bacteraemia — all in adults, two of whom were immunocompetent and one of whom had refractory diffuse large B-cell lymphoma. Bone marrow involvement in an immunocompetent paediatric host has not been described. Case presentation: A previously healthy 13-year-old girl presented with prolonged fever of unknown origin following an initial pneumonia-like illness. After extensive non-invasive investigations failed to identify an aetiological agent, bone marrow aspiration and culture identified J. melonis . She was successfully treated with a combination of intravenous linezolid and trimethoprim-sulfamethoxazole, achieving microbiological clearance by day 20 and sustained clinical remission at three-month follow-up. Conclusions: This case expands the known clinical spectrum of J. melonis to include deep-seated bone marrow infection in immunocompetent children, and suggests that combination therapy with linezolid and trimethoprim-sulfamethoxazole may be a reasonable treatment option, although further evidence is required to define the optimal regimen. In selected clinical scenarios — such as when initial blood cultures remain negative or when advanced molecular diagnostics (e.g., metagenomic next-generation sequencing) are declined by the patient’s family — bone marrow puncture with extended culture incubation may be considered, particularly when infection by slow-growing or fastidious organisms is suspected. Prolonging the incubation period beyond the standard timeframe may enhance the recovery of rare and fastidious pathogens.

Importance: The transition period from the delivery room to the neonatal intensive care unit (NICU) is critical for very preterm infants (VPIs) or very low birth weight (VLBW) infants, yet the association between physiological changes during transition period and early severe outcomes remains inadequately quantified. Objective: To investigate associations between physiological changes during transition period and early severe neonatal outcomes in VPIs or VLBW infants.Design: This cohort study utilized data from Chinese Neonatal Network (CHNN), prospectively collected from January 2019 to December 2023. Setting: National multicenter study.Participants: VPIs or VLBW infants with clear 5-minute APGAR score and the transport risk index of physiologic stability score (TRIPS) were included, and those admitted after the first day, discharged or transferred out within 7 days after birth, were excluded. Exposures: The exposure variable was a composite of the APGAR score and TRIPS. The APGAR score was analyzed as normal (7-10), low (0-6), and optimal (9-10). The TRIPS was grouped as low (0-10), intermediate (11-30), or high (>30). Main Outcome and Measures:The main outcome was a composite of early neonatal death and severe neurological injury (SNI). Adjusted odds ratios (aORs) and 95% confidence intervals (CI) were estimated using generalized estimating equation models. Results: Of the 40391 included VPIs or VLBW infants, the composite outcome occurred in 4753 (11·77%) infants, including 2326 (5·76%) early neonatal deaths and 2680 (6·64%) SNIs. Increased TRIPS was associated with elevated risks of early severe neonatal outcomes across all APGAR categories. In optimal APGAR subgroup, composite outcome incidence per 1000 infants was 52 in low-TRIPS reference group, 100 in intermediate-TRIPS group (aOR: 1·42, 95% CI: 1·12-1·80), and 211 in high-TRIPS group (aOR: 1·80, 95% CI: 1·16-2·80). The initial deterioration (intermediate-TRIPS group) was characterized by high rates of hypothermia (71·6%) and need for invasive respiratory support (37·1%), whereas hypotension was nearly absent in intermediate-TRIPS group and emerged predominantly in high-TRIPS group. Conclusions and Relevance: The quality of management during transition period was associated with early severe neonatal outcomes, thus maintenance of normothermia and effective respiratory support represent initial clinical priorities to mitigate physiological deterioration and improve clinical outcomes.

The association between hypertensive disorders of pregnancy (HDP) and bronchopulmonary dysplasia (BPD) in preterm infants remains controversial due to inconsistent findings in previous studies. However, systematic studies and meta-analyses evaluating the association remain limited. The study followed the Meta-analysis of Observational Studies in Epidemiology (PRISMA) reporting guideline. The PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and the Chinese Science and Technology Periodical Database (VPCS) databases were searched from January 1997 to October 2024. Search terms included gestational hypertension, preeclampsia, eclampsia, or superimposed preeclampsia on chronic hypertension; bronchopulmonary dysplasia; Premature Birth; and Stillbirth, Fetal Death or Perinatal Mortality. A random-effects meta-analysis model was used to clarify the relationships between HDP and 1) survival without BPD, 2) BPD, and 3) perinatal mortality. A total of 29538 publications were found, of which 21 were included in the meta-analysis. HDP was associated with reduced survival without BPD (RR 0.875, 95% CI 0.818, 0.935) and increased BPD risk (RR 1.211, 95% CI 1.101, 1.332), while no significant link with perinatal mortality (RR 1.005, 95% CI 0.781, 1.291). Stratified analyses suggested that gestational age, publication year, and geographic region may partly explain the heterogeneity among previous findings. HDP negatively correlates with survival without BPD and positively correlates with BPD in preterm infants, underscoring the need for targeted postnatal pulmonary monitoring.

Objectives: We aim to explore whether the long inter-pregnancy interval (IPI) modifies the association between previous cesarean section (CS) and adverse maternal and neonatal outcomes in a population with a high rate of CS and a long IPI. Methods: Adverse maternal and neonatal outcomes were compared between the previous CS and previous vaginal delivery groups. Logistic models were used to adjust for potential confounding factors and calculate the odds ratios (ORs) and 95 % confidence intervals (CIs). The interaction model and stratified analyses were used to evaluate the modifications of IPIs on the associations between previous CS and maternal and neonatal outcomes. Results: Compared with previous vaginal delivery, previous CS was associated with increased risks of uterine-related complications (aOR=1.57, 95 % CI 1.25–1.98), but with decreased risks of preterm birth (aOR=0.73, 95 % CI 0.63–0.85) and severe neonatal adverse outcomes (aOR=0.59, 95 % CI 0.46–0.78). There are synergistic biological interaction effects of previous CS and a long IPI (>60 months) on the risks of placental-related complications (RERI=0.32, 95 % CI 0.05–0.58; AP=0.39, 95 % CI 0.03–0.76) but an antagonistic biological interaction effect on the risk of preterm birth (RERI=−0.35, 95 % CI -0.68 to −0.01; AP=−0.09, 95 % CI -0.68 to −0.03). Conclusions: Previous CS was associated with increased risks of adverse maternal outcomes but decreased risks of certain adverse neonatal outcomes. Prolonged IPIs might not attenuate the adverse effects of previous CS on mothers, and might adversely exert harm on newborns.

Antenatal corticosteroids (ACS) can improve the outcomes of preterm infants and have been widely adopted as the standard practice in managing pregnancies at high risk of preterm delivery between 22⁺⁰ and 33⁺⁶ weeks. Due to their significant benefit for the majority of pregnant women, several guidelines also state that maternal diabetes is not a contraindication for the use of ACS. However, no such evidence has been obtained from diabetic pregnancies. The Chinese Neonatal Network (CHNN), a national multicenter cohort study, recruited 31,915 very preterm infants (VPIs) from 79 NICUs. The outcomes were mortality and morbidity in hospital. Logistic regression models were employed to calculate the odds ratios (ORs) and its 95% confidence intervals (CIs) to estimate the associations between ACS and these outcomes. Stratification and sensitivity analyses were conducted to test the robustness of the results in different population. A total of 4337 VPIs born to diabetic mothers enrolled in the present study: 3605 VPIs were exposed to ACS and 732 were not. ACS was associated with a lower risk in the combined outcome (death or any severe morbidity) (adjusted OR [aOR] 0.66, 95% CI 0.54–0.79), in-hospital death (aOR 0.55, 95% CI 0.41–0.73), severe bronchopulmonary dysplasia (BPD, aOR 0.69, 95% CI 0.55–0.85), low Apgar score (aOR 0.76, 95% CI 0.61–0.96), respiratory distress syndrome (RDS, aOR 0.79, 95% CI 0.66–0.94), or the need for invasive ventilation (aOR 0.62, 95% CI 0.52–0.73). However, a significantly higher risk of maternal chorioamnionitis (aOR 2.09, 95% CI 1.61–2.72) was observed in the ACS group. Similar results were observed in stratification and sensitivity analyses. Conclusions: In VPIs of diabetic mothers, ACS exposure was associated with lower mortality and reduced risks of BPD, low Apgar score, RDS, and invasive ventilation, but with higher odds of maternal chorioamnionitis. What is Known: • Antenatal corticosteroids (ACS) are standard care for reducing neonatal morbidity and mortality in pregnancies at high risk of preterm birth between 22⁺⁰ and 33⁺⁶ weeks. • However, recommendations for ACS use in pregnant women with diabetes at risk of preterm delivery remain inconsistent due to limited evidence.  What is New: • This large, national multicenter cohort study provides the first specific evidence that ACS administration in diabetic pregnancies is associated with significantly lower risks of neonatal mortality, bronchopulmonary dysplasia, respiratory distress syndrome, and the need for invasive ventilation. • Our findings support the benefit of ACS in this understudied population, demonstrating a favorable risk-benefit profile.

Objective To investigate whether gestational diabetes mellitus (GDM) was associated with survival without bronchopulmonary dysplasia (BPD) in very preterm infants (VPIs). Design Retrospective multicentre cohort study. Setting A total of 79 neonatal intensive care units across China, January 2019 to December 2021. Participants A total of 23 752 VPIs (Main outcome measures The primary outcomes are survival without BPD at 36 weeks’ postmenstrual age (PMA) and its components. Results Infants exposed to GDM were associated with a higher rate of survival without BPD (aOR 1.12, 95% CI 1.04 to 1.21) at 36 weeks PMA and lower mortality (aOR 0.75, 95% CI 0.64 to 0.84) before 36 weeks PMA than unexposed infants. However, no significant association was observed between GDM and BPD at 36 weeks PMA (aOR 0.94, 95% CI 0.87 to 1.02), respiratory distress syndrome, need for advanced resuscitation or mechanical ventilation. After propensity score matching, GDM-exposed VPIs maintained higher survival without BPD (aOR 1.13, 95% CI 1.02 to 1.26) and lower mortality (aOR 0.81, 95% CI 0.68 to 0.97). These associations were strongest in infants born before 28 weeks (aOR 1.32, 95% CI 1.11 to 1.57) and those small for gestational age (aOR 1.41, 95% CI 1.11 to 1.80). Conclusions GDM was not associated with worsened BPD in VPIs. The positive association with survival and survival without BPD warrants could reflect a selection bias.