Daily Respiratory Research Analysis

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterized by high mortality with no specific treatments. Fibroblast growth factor 10 (FGF10) is recognized for its tissue repair and anti-inflammatory roles in injured lungs; however, its clinical relevance and mechanistic role in ARDS remain unclear. METHODS: Serum FGF10 levels were measured in patients with ARDS and analyzed for associations with clinical outcomes. An LPS-induced mouse model of acute lung injury (ALI) was used to evaluate the effects of FGF10 treatment in vivo. Single-cell RNA sequencing of lineage-traced alveolar epithelial cells (AECs) was performed to identify transcriptional changes following FGF10 administration. In vitro co-culture systems involving macrophages or neutrophils with AECs were established to investigate immune cell-specific mechanisms. RESULTS: We found that serum FGF10 levels were significantly reduced in ARDS patients, and this reduction correlated with poor prognosis. Moreover, FGF10 treatment alleviated lung inflammation by decreasing inflammatory cell infiltration and pro-inflammatory cytokine release in mice. Leveraging single-cell RNA sequencing of lineage tracing alveolar epithelial cells (AECs), we identified that the mRNA expression of Ripk1, Casp8, and Casp3 were decreased after FGF10 treatment. In in vitro co-culture experiments, we noticed that FGF10 did not inhibit macrophage pyroptosis. Instead, FGF10 effectively blocked the downstream RIPK1/caspase-8/caspase-3/gasdermin E (GSDME) signaling pathway in AECs. Additionally, FGF10 suppressed AMP-activated protein kinase (AMPK) activation by modulating ATP production, thereby preventing RIPK1 cleavage. CONCLUSION: FGF10 alleviates acute lung injury by inhibiting AMPK-RIPK1/caspase-8/caspase-3/GSDME-mediated pyroptosis in AECs primed by distinct immune cell populations, supporting its potential as a therapeutic strategy for ARDS. KEY POINTS: Our study reveals a marked decrease of serum FGF10 levels in ARDS patients, correlating with P/F ratio, hospitalisation days and mortality rates. We clarify how FGF10 prevents AECs' pyroptosis triggered by different immune cell infiltrations in different ways. FGF10 restored ATP levels to attenuate RIPK1 phosphorylation via AMPK to disrupt pyroptosis in the AECs.

INTRODUCTION: Given the limitations of single-modality analgesia for rib fractures, this study aimed to determine whether combining systemic flurbiprofen axetil with a regional intercostal nerve block (ICNB) yields more effective and sustained preoperative pain relief than either technique used alone. METHODS: In this single-center, randomized, double-blind, controlled trial, 150 patients scheduled for surgery were allocated to one of three groups: Group F (flurbiprofen axetil + saline ICNB), Group FB (flurbiprofen axetil + ropivacaine ICNB), and Group B (saline + ropivacaine ICNB). The primary outcome was the Visual Analog Scale (VAS) score at quiet breathing 30 min post-intervention. Secondary outcomes included VAS scores at 6, 12, 18, and 24 h, rescue analgesia requirements, diaphragmatic excursion, arterial blood gas parameters, adverse events, and patient satisfaction. RESULTS: The FB group demonstrated significantly lower VAS scores at 30 min than the other groups (p < 0.001), along with significantly reduced rescue analgesia requirements across most time intervals (p < 0.05). No patients in the FB group required rescue thoracic paravertebral block versus eight in Group F (p < 0.001). The FB group also showed a significantly higher sum of pain intensity difference over 0-24 h (SPID CONCLUSION: The combination of flurbiprofen axetil and ultrasound-guided ICNB provided superior preoperative analgesia than either agent alone, reduced rescue medication needs, improved respiratory function, and enhanced patient satisfaction, with a favorable safety profile in patients with traumatic multiple rib fractures. TRIAL REGISTRATION: The study protocol was registered at the Chinese Clinical Trial Registry with registration no. ChiCTR2500105786 ( https://www.chictr.org.cn ).

Mycoplasma pneumoniae is a leading cause of bacterial community-acquired pneumonia, responsible for severe respiratory and extrapulmonary diseases in children and adults. The Community Acquired Respiratory Distress Syndrome (CARDS) toxin is a key virulence factor that exerts ADP-ribosylating and vacuolating activities on host cells, recapitulating the inflammatory and histopathological damage seen in infected airways. Although the host proteins annexin-A2 (AnxA2) and surfactant protein-A were previously identified as toxin receptors, their absence did not abrogate CARDS toxin activity. Intriguingly, our subsequent work identified an interaction between CARDS toxin and the ubiquitous membrane phospholipids sphingomyelin (SM) and phosphatidylcholine (PC). This study investigated whether CARDS toxin uses these lipids as functional cell surface receptors. Using enzyme-linked immunosorbent assays, we demonstrated that the carboxy region of CARDS toxin binds to SM and PC in a dose-dependent manner, exhibiting higher affinity for SM. Depletion of SM from airway epithelial cell surface significantly reduced CARDS toxin binding, internalization and retrograde transport, as shown by immunoblot, pull-down, immunofluorescence, and live-cell imaging. Furthermore, SM depletion markedly decreased toxin-induced vacuolation and its stability, a phenotype rescued by adding exogenous SM. Notably, combining SM depletion with AnxA2 suppression nearly abolished toxin binding, entry, and subsequent vacuolation. These findings establish that CARDS toxin utilizes SM as a functional receptor to mediate its activity, highlighting a critical lipid-dependent mechanism for host cell targeting.