Zhangxue Hu

Correction on: Tang B, Yu Q, Zhang J, Duan X, Meng T, Chen Z, Ran Q, Zhang Y, Tian S, Hu Z and Peng W (2026) Effect of fresh-frozen plasma transfusion on intraventricular hemorrhage risk in preterm infants with prolonged APTT: a target trial emulation with causal forest analysis. Front. Neurosci. 20:1950034. doi: 10.3389/fnins.2026.1950034 An incorrect number was provided for [8201908]. The correct number is [82201908]. The original version of this article has been updated.

Background: Coagulopathy is a common risk factor in the occurrence of intraventricular hemorrhage (IVH) and subsequent poor neurological outcomes in preterm infants. The causal effect of fresh-frozen plasma (FFP) transfusion and IVH needed to be identified urgently. Methods: Within the framework of target trial emulation (TTE), we mimic the process of a randomized controlled trial based on retrospective neonatal clinical data collected at Daping Hospital from 2015 to 2025, ultimately including 748 preterm infants with gestational age ≤34 weeks and prolonged activated partial thromboplastin time ≥70 s. Multiple causal inference models were conducted to minimize confounding and covariate imbalance, including inverse probability weighting with generalized boosted models (GBM-IPW) method, GBM-doubly robust (GBM-DR) estimation, covariate balancing propensity score (CBPS) model and other sensitivity analyses. Causal forests algorithm further triangulated the main results and explore individual-level heterogeneity and key determinants about FFP. Results: All causal models consistently demonstrated that FFP transfusion exerted no overall estimated protective effect against IVH (all odds ratio (OR) ≈ 1; p > 0.4). GA was found a protective factor of IVH and modified the effect of FFP transfusion ( p < 0.05). According the cutoff of 32.3-week cutoff, FFP transfusion significantly increased IVH risk in the more premature subgroup (OR = 2.16, p = 0.02). Causal forests also found individual heterogeneity exists between FFP and IVH, and relevant high-risk subgroups about FFP transfusion can be stratified by prematurity, Apgar scores, and coagulopathy. Conclusion: Routine FFP transfusion is not recommended for IVH prevention in preterm infants. FFP significantly increases IVH risk in more premature infants, while the adverse association of FFP attenuated with increasing GA.

ARDS is a life-threatening lung disease marked by severe AECS and ECs damage, causing rapid lung function loss and high mortality. MSCs are promising therapies due to their immunoregulatory and regenerative properties. While early studies highlighted MSCs’ anti-inflammatory effects in ARDS, recent findings emphasize their essential role in repairing the AECs and ECs. In this review, we detail the molecular mechanisms and synergistic effects of MSCs in epithelial and endothelial repair. We also examine how MSC-mediated immune regulation intersects with tissue repair, explore new combination approaches using drugs, gene editing, and bioengineering, and outline clinical limitations and ongoing challenges. Patient heterogeneity, disease stage, treatment timing, and safety issues limit the conduct of clinical trials and their translation. We summarize the roles, limitations, and challenges of MSCs in ARDS to guide future research and inform the development of new treatments.

Acute respiratory distress (ARDS) caused by sepsis is a critical inflammatory condition with high mortality rates in clinical settings. The gut-lung axis plays a crucial role in regulating the immune response in both the intestinal and pulmonary environments, significantly impacting the development of ARDS. Immunometabolic reprogramming, a fundamental regulator of immune cell function, has recently been shown to profoundly affect the activity of macrophages and endothelial cells (ECs), as well as their crosstalk, thereby shaping the pathogenesis of ARDS. While a great deal has been learned about the potential inflammatory pathways involved, few clinically actionable therapies are available in part due to an incomplete understanding of gut-lung crosstalk in their shared ecosystem of cells and molecules. The current review systematically advances novel insights into the immunometabolic reprogramming that influences macrophage-ECs interactions via sepsis-induced ARDS, with a specific regard to the gut-lung axis. Here, we summarize the key biochemical pathways that control immune cell phenotypes and endothelial function, review the latest experimental evidence for their intercellular crosstalk, and describe the molecular targets that might be targeted to inform therapeutic strategies. Integrating the current evidence, this review seeks to provide a comprehensive theoretical framework and novel methods for the precise treatment of sepsis-associated ARDS, which could be beneficial to clinical practices and patients’ prognoses.

Sepsis is characterized by high mortality and a complicated pathological mechanism. Macrophages play a crucial role in the initiation and progression of sepsis-associated acute respiratory distress syndrome (ARDS). Macrophage functional states and polarization phenotype have been significantly influenced by metabolic programming. This review delineates the metabolic reprogramming of macrophages from the initial ‘metabolic storm’ to subsequent ‘immune paralysis’ in sepsis-associated ARDS. It focuses on the interplay between macrophage polarization (classical activated macrophages (M1) and alternative activated macrophages (M2) phenotypes) and key metabolic pathways, including glycolysis and oxidative phosphorylation (OXPHOS). Furthermore, it explains the molecular mechanism underlying the metabolic pattern’s influence on macrophage and lung tissue damage. The final section of this review focuses on the therapeutic implications of bone marrow mesenchymal stem cells (BMMSCs) and myeloid-derived suppressor cells (MDSCs), which alter macrophage metabolic reprogramming. Based on the latest progress, this article aims to provide a comprehensive theoretical framework and cli Based on recent advances, nical guidance for immunometabolic therapy in sepsis-associated ARDS.

Alveolar macrophages (AMs), a type of immune cell, display remarkable plasticity and manifest diverse responses to stimuli by differentiating into distinct subgroups. These phenotypically distinct macrophage subtypes are primarily categorized as either classically activated or inflammatory (M1) macrophages, or alternatively activated or anti-inflammatory (M2) macrophages, the differentiation of which is underpinned by a complex regulatory network. Despite their crucial contribution to the pathobiology of acute lung injury/acute respiratory distress syndrome (ALI/ARDS), the research on AMs is currently limited. This study therefore aims to establish a comprehensive theoretical framework delineating the pathogenic role of AMs in ALI/ARDS, facilitating deeper mechanistic understanding of disease initiation and progression in ALI/ARDS and ultimately identifying novel therapeutic targets.

The Integrator complex plays essential roles in RNA polymerase II (RNAPII) transcription termination and RNA processing. Here, we identify INTS6, a subunit of the Integrator complex, as a novel gene associated with neurodevelopmental disorders (NDDs). Through analysis of large NDD cohorts and international collaborations, we identified 23 families harboring monoallelic likely gene-disruptive or de novo missense variants in INTS6. Phenotypic characterization revealed shared features, including language and motor delays, autism, intellectual disability, and sleep disturbances. Using a nervous-system conditional KO (cKO) mouse model, we show that Ints6 deficiency disrupts early neurogenesis, cortical lamination, and synaptic development. Ints6 cKO mice had a thickened ventricular zone/subventricular zone, thinning of the cortical plate, reduced neuronal differentiation, and increased apoptosis in cortical layer 6. Behavioral assessments of heterozygous mice revealed deficits in social novelty preference, spatial memory, and hyperactivity, mirroring phenotypes observed in individuals with INTS6 variants. Molecular analyses further revealed that INTS6 deficiency alters RNAPII dynamics, disrupts transcriptional regulation, and impairs synaptic gene expression. Treatment with a CDK9 inhibitor (CDK9i) reduced RNAPII phosphorylation, thereby limiting its binding to target genes. Notably, CDK9i reversed neurosphere overproliferation and rescued the abnormal dendritic spine phenotype caused by Ints6 deficiency. This work advances understanding of INTS-related NDD pathogenesis and highlights potential therapeutic targets for intervention.