OBJECTIVE: To explore the correlation between mechanical power normalized to dynamic lung compliance (Cdyn-MP) and weaning outcomes and prognosis in mechanically ventilated patients. METHODS: A prospective, observational cohort study was conducted. Patients who underwent invasive mechanical ventilation (IMV) for more than 24 hours and used a T-tube ventilation strategy for extubation in the intensive care unit (ICU) of Lianyungang First People's Hospital and Lianyungang Second People's Hospital between January 2022 and December 2023 were enrolled. The collected data encompassed patients' baseline characteristics, primary causes of ICU admission, vital signs and laboratory indicators during the initial spontaneous breathing trial (SBT), respiratory mechanics parameters within the 4-hour period prior to the SBT, weaning outcomes and prognostic indicators. Mechanical power (MP) and Cdyn-MP were calculated using a simplified MP equation. Univariate and multivariate Logistic regression analyses were utilized to determine the independent risk factors associated with weaning failure in patients undergoing mechanical ventilation. Restricted cubic spline (RCS) analysis and Spearman rank-sum test were employed to investigate the correlation between Cdyn-MP and weaning outcomes as well as prognosis. Receiver operator characteristic curve (ROC curve) was constructed, and the area under the ROC curve (AUC) was computed to evaluate the predictive accuracy of Cdyn-MP for weaning outcomes in mechanically ventilated patients. RESULTS: A total of 366 patients undergoing IMV were enrolled in this study, with 243 cases classified as successful weaning and 123 cases classified as failed weaning. Among them, 23 patients underwent re-intubation within 48 hours after the successful withdrawal of the first SBT, non-invasive ventilation, or died. Compared with the successful weaning group, the patients in the failed weaning group had significantly increased levels of sequential organ failure assessment (SOFA) score, body temperature and respiratory rate (RR) during SBT, and respiratory mechanical parameters within the 4-hour period prior to the SBT [ventilation frequency, positive end-expiratory pressure (PEEP), platform pressure (Pplat), peak inspiratory pressure (Ppeak), dynamic driving pressure (ΔPaw), fraction of inspired oxygen (FiO₂), MP, and Cdyn-MP], dynamic lung compliance (Cdyn) was significantly reduced, and duration of IMV, ICU length of stay, and total length of hospital stay were significantly prolonged. However, there were no statistically significant differences in age, gender, body mass index (BMI), smoking history, main causes of ICU admission, other vital signs [heart rate (HR), mean arterial pressure (MAP), saturation of peripheral oxygen (SpO₂)] and laboratory indicators [white blood cell count (WBC), albumin (Alb), serum creatinine (SCr)] during SBT of patients between the two groups. Univariate Logistic regression analysis was conducted, and variables with P < 0.05 and no multicollinearity with Cdyn-MP were selected for inclusion in the multivariate Logistic regression model. The results demonstrated that SOFA score [odds ratio (OR) = 1.081, 95% confidence interval (95%CI) was 1.008-1.160, P = 0.030], and PEEP (OR = 1.191, 95%CI was 1.075-1.329, P = 0.001), FiO₂ (OR = 1.035, 95%CI was 1.006-1.068, P = 0.021) and Cdyn-MP (OR = 1.190, 95%CI was 1.086-1.309, P < 0.001) within the 4-hour period prior to the SBT were independent risk factors for weaning failure in patients undergoing IMV. The RCS analysis after adjusting for confounding factors showed that as Cdyn-MP within the 4-hour period prior to the SBT increased, the risk of weaning failure in patients undergoing IMV significantly increased (P < 0.001). The Spearman rank correlation test showed that Cdyn-MP within the 4-hour period prior to the SBT was positively correlated with respiratory mechanical parameters including ΔPaw and MP (r values were 0.773 and 0.865, both P < 0.01), and negatively correlated with Cdyn (r = -0.587, P < 0.01). Cdyn-MP within the 4-hour period prior to the SBT was positively correlated with prognostic indicators such as duration of IMV, length of ICU stay, and total length of hospital stay (r values were 0.295, 0.196, and 0.120, all P < 0.05). ROC curve analysis demonstrated that, within the 4-hour period preceding the SBT, Cdyn-MP, MP, Cdyn, and ΔPaw possessed predictive value for weaning failure in patients undergoing IMV. Notably, Cdyn-MP exhibited superior predictive capability, evidenced by an AUC of 0.761, with a 95%CI ranging from 0.712 to 0.810 (P < 0.001). At the optimal cut-off value of 408.5 J/min×cmH₂O/mL×10^-3, the sensitivity was 68.29%, and the specificity was 71.19%. CONCLUSION Cdyn-MP is related to weaning outcomes and prognosis in mechanically ventilated patients, and has good predictive ability in assessing the risk of weaning failure.
Humans ; Prospective Studies ; Ventilator Weaning ; Prognosis ; Respiration, Artificial ; Intensive Care Units ; Lung Compliance ; Female ; Male ; Middle Aged ; Aged

Mechanical ventilation (MV) is currently widely used in the treatment of respiratory failure and anesthesia surgery, and is a commonly used respiratory support method for critically ill patients; however, improper usage of MV can lead to ventilator-induced lung injury (VILI), which poses a significant threat to patient life. Alveolar epithelial cell (AEC) has the functions of mechanosensation and mechanotransduction. Physiological mechanical stretching is beneficial for maintaining the lineage homeostasis and normal physiological functions of AEC cells, while excessive mechanical stretching can cause damage to AEC cells. Damage to AEC cells is an important aspect in the occurrence and development of VILI. Understanding the effects of mechanical stretching on AEC cells is crucial for developing safe and effective MV strategies, preventing the occurrence of VILI, and improving the clinical prognosis of VILI patients. From the perspective of cell mechanics, this paper aims to briefly elucidate the mechanical properties of AEC cells, mechanosensation and mechanotransduction of mechanical stretching in AEC cells, and the injury and repair of AEC cells under mechanical stretch stimulation, and potential mechanisms with the goal of helping clinical doctors better understand the pathophysiological mechanism of VILI caused by MV, improve their understanding of VILI, provide safer and more effective strategies for the use of clinical MV, and provide theoretical basis for the prevention and treatment of VILI.
Humans ; Mechanotransduction, Cellular ; Ventilator-Induced Lung Injury ; Stress, Mechanical ; Alveolar Epithelial Cells ; Respiration, Artificial/adverse effects* ; Epithelial Cells ; Pulmonary Alveoli/cytology* ; Animals

Mechanical ventilation is commonly employed for respiratory support in patients with respiratory failure. Despite the optimization of ventilator parameters and treatment methods, mechanical ventilation can still lead to both acute and chronic lung injury in patients with acute respiratory distress syndrome (ARDS) as well as in those without ARDS, a phenomenon referred to as ventilator-induced lung injury (VILI). VILI can be categorized into four types: barotrauma, volumetric injury, atelectasis injury, and biotic injury. Among these, biotic injury, characterized by inflammation, plays a significant role in the pathogenesis of VILI. Numerous studies have investigated the inflammatory mechanisms underlying VILI; however, these mechanisms remain complex and not entirely understood. At present, clinical practice lacks specific prevention and treatment strategies for VILI, aside from the implementation of protective ventilation strategies. Long non-coding RNAs (lncRNA) are a category of non-coding RNA longer than 200 nucleotides. LncRNAs regulate physiological and pathological processes such as cell proliferation, apoptosis, inflammatory response, and immune regulation, this regulation occurs through mechanisms such as modulating gene activity, inhibiting specific states, assisting in transcription initiation, affecting pre-mRNA splicing modifications, influencing translation processes, and expressing biofunctional peptides. They play an important role in the course of multiple diseases. Studies have shown that compared with control animals and cell models, lncRNAs are differentially expressed in VILI animal models and cell stretch models. Experiments have verified that certain lncRNAs play a crucial role in the pathogenesis of VILI by regulating the expression of inflammatory factors, the transformation of macrophage types, neutrophil activation, and cell apoptosis. Given the adverse effects of VILI on mechanical ventilation in critically ill patients, the important role of lncRNAs in biological regulation, and the urgent need to explore more effective strategies for the prevention and treatment of VILI, this paper summarizes the mechanisms through which lncRNA contributes to the VILI process, and discusses its possibility as a diagnostic and therapeutic target of VILI, in order to provide a reference for the clinical treatment of VILI.
RNA, Long Noncoding ; Ventilator-Induced Lung Injury ; Humans ; Respiration, Artificial/adverse effects* ; Animals ; Respiratory Distress Syndrome ; Apoptosis

Since the beginning of the 21st century, the severe respiratory infectious diseases worldwide [such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), influenza A H1N1 and novel coronavirus infection have attracted wide attention from all walks of life due to their superior pathogenicity and transmissibility. Aerosols-carrying pathogens are the main transmission route of many severe respiratory infectious diseases, which can lead to severe respiratory failure and even acute respiratory distress syndrome (ARDS) in infected individuals. Mechanical ventilation is the primary treatment for ARDS, and the small tidal volume, appropriate level of positive end-expiratory pressure based lung protective ventilation strategy can effectively reduce the incidence of ventilator-induced lung injury (VILI). However, in the process of clinical treatment, it is sometimes necessary to briefly disconnect the connection between the artificial airway and the ventilator circuit, which will not only cause the residual aerosol in the respiratory system to spill out and pollute the surrounding environment, increase the risk of nosocomial infection including medical staff, but also interfere with the implementation of lung protective ventilation strategy and aggravate ventilator-induced lung injury. In addition, studies have shown that a lot of medical staff have nosocomial infections, especially staff involved in tracheal intubation, extubation and other airway related operations. In addition to enhancing personal protective measures, it is crucial to safeguard healthcare workers from aerosol contamination and minimize associated risks during airway management. At present, there are few researches on the temporary sealing of airway lines and ventilator system, and there is a lack of clear guidance. This review summarizes the research status in related fields to provide a reference for corresponding solutions and programs.
Humans ; Respiratory Distress Syndrome/etiology* ; Respiration, Artificial ; Ventilator-Induced Lung Injury/prevention & control* ; Severe Acute Respiratory Syndrome ; COVID-19 ; Clinical Relevance

OBJECTIVE: To investigate whether the G protein-coupled estrogen receptor (GPER) can attenuates acute lung injury in mice with exertional heat stroke (EHS) by inhibiting ferroptosis. METHODS: Sixty SPF-grade male C57BL/6 mice were randomly divided into four groups: normal control group (control group), EHS model group (EHS group), dimethyl sulfoxide (DMSO) solvent group (EHS+DMSO group), and GPER-specific agonist G1 group (EHS+G1 group), with 15 mice in each group. All mice underwent 14 days of adaptive training at 24-26 centigrade before modeling, and the EHS model was established using a high-temperature treadmill device. After successful modeling, the mice were allowed to cool naturally at room temperature. In the EHS+G1 group, 40 μg/kg of the GPER-specific agonist G1 was slowly injected intraperitoneally immediately after modeling. In the EHS+DMSO group, 40 μg/kg of DMSO was slowly injected intraperitoneally immediately after modeling. The control group received no treatment. Five hours after modeling, abdominal aortic blood was collected, and lung tissues were harvested after euthanasia. The lung coefficient was calculated to evaluate lung injury. Lung histopathological changes were observed under a light microscope after hematoxylin-eosin (HE) staining, and a lung histopathological score was assigned. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), malondialdehyde (MDA), and Fe²⁺ in lung tissue. Immunofluorescence was used to detect the expression of glutathione peroxidase 4 (GPX4). Real-time polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of GPX4, ferroportin 1 (FPN1), and ferritin heavy chain 1 (FTH1). Western blotting was performed to detect the protein expression of GPX4, FPN1, and FTH1. RESULTS: Compared with the control group, the lung coefficient and lung histopathological score were significantly increased in the EHS group. HE staining showed significant thickening and unevenness of the alveolar septa and alveolar walls, partial alveolar collapse, and extensive erythrocyte, inflammatory cell, and plasma-like material extravasation in the alveolar spaces. Serum levels of TNF-α, IL-1β, MDA, and Fe²⁺ were significantly elevated. Immunofluorescence staining showed a significant decrease in GPX4-positive expression in lung tissue. Western blotting and RT-PCR showed significantly reduced protein and mRNA expression of GPX4, FPN1, and FTH1 in lung tissue. Compared with the EHS group, the EHS+G1 group showed a significant reduction in lung coefficient and lung histopathological score [lung coefficient (mg/g): 3.9±0.1 vs. 4.6±0.3, lung histopathological score: 4.2±0.2 vs. 6.9±0.2, both P < 0.05]. HE staining revealed reduced severity of lung tissue fluid extravasation, inflammatory infiltration, decreased hemorrhage, and less severe alveolar structural damage. Serum levels of TNF-α, IL-1β, MDA, and Fe²⁺ were significantly reduced [TNF-α (ng/L): 44.3±0.2 vs. 64.6±0.3, IL-1β (ng/L): 69.3±0.4 vs. 97.8±0.2, MDA (nmol/L): 2.8±0.3 vs. 3.6±0.5, Fe²⁺ (nmol/L): 0.021±0.004 vs. 0.028±0.004, all P < 0.05]. Immunofluorescence staining showed a significant decrease in GPX4-positive expression in lung tissue (fluorescence intensity: 35.53±2.41 vs. 16.45±0.31, P < 0.05). RT-PCR and Western blotting showed significantly increased mRNA and protein expression of GPX4, FPN1, and FTH1 in lung tissue [mRNA expression: GPX4 mRNA (2^-ΔΔCt): 0.44±0.05 vs. 0.09±0.01, FPN1 mRNA (2^-ΔΔCt): 0.77±0.17 vs. 0.42±0.14, FTH1 mRNA (2^-ΔΔCt): 0.75±0.04 vs. 0.58±0.01; protein expression: GPX4/β-actin: 0.96±0.11 vs. 0.24±0.04, FPN1/β-actin: 1.26±0.21 vs. 0.44±0.14, FTH1/β-actin: 0.27±0.12 vs. 0.15±0.07; all P < 0.05]. However, there were no statistically significant differences in any of the above indicators between the EHS+DMSO group and the EHS group. CONCLUSION Activation of GPER can attenuate EHS-related lung injury in mice, and its mechanism may be related to the activation of the GPX4 signaling pathway and inhibition of ferroptosis.
Animals ; Mice, Inbred C57BL ; Male ; Mice ; Heat Stroke/metabolism* ; Receptors, G-Protein-Coupled ; Ferroptosis ; Receptors, Estrogen ; Acute Lung Injury/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-1beta/metabolism* ; Lung Injury ; Lung/metabolism*

OBJECTIVE: To investigate the distribution characteristics of polymorphonuclear neutrophil (PMN) in the lungs during the early stage of severe burns and the mechanism of neutrophil elastase (NE) promoting lung injury. METHODS: 6-8-week-old male C57BL/6J mice were selected for the experiments. A 30% total body surface area (TBSA) III degree burn mouse model was established (severe burn group); the Sham-injury group was treated with 37 centigrade water. In the sodium sivelestat intervention group (SV intervention group), NE competitive inhibitor, sivelestat, 100 mg/kg, was injected via tail vein immediately after injury, while other groups received an equal volume of saline. Ten mice were harvested from each group to observe survival for 72 hours. Respiratory function tests were tested at 0 (immediate), 3, 6, 12, and 24 hours after molding. hematoxylin-eosin (HE) and immunohistochemical staining were used to observe lung tissue structure, inflammatory changes and PMN infiltration. The PMN absolute count in mice lung tissue was detected buy flow cytometry. At 6, 12, and 24 hours after molding, PMN counts and the concentration of NE [enzyme linked immunosorbent assay (ELISA)] in peripheral blood plasma, lung tissue, and bronchoalveolar lavage fluid (BALF) were detected. RESULTS: (1) HE staining results showed that compared with the Sham-injury group, the lungs of mice in the severe burn group showed inflammatory changes and PMN infiltration, with more significant changes at 6 hours. Immunohistochemistry results also confirmed that the expression of NE protein released from PMN significantly increased after 6 hours of severe burn injury [(3.79±0.62)% vs. (0.18±0.05)%, t = 11.56, P < 0.01]. (2) Compared with the Sham-injury group, the number of PMN and the concentration of NE in the peripheral blood and lung tissues in the severe burn group were significantly increased (F values were 13.709, 55.350 and 29.890, 13.286, respectively, all P < 0.01), peaking at 6 hours [plasma PMN count (×10⁹/L): 2.92±1.01 vs. 0.92±0.29, lung tissue PMN absolute count (cells): 48 788.03±11 833.91 vs. 1 516.72±415.35, plasma NE (ng/L): 24 522.71±3 842.92 vs. 7 009.34±4 067.86, lung tissue NE (ng/L): 262 189.04±9 695.13 vs. 65 026.03± 16 016.31, all P < 0.01]. The number of PMN in the lung of severely burned mice was highly correlated with NE concentration (r = 0.892, P < 0.001). There was no significantly difference in the PMN absolute count in the BALF of mice between the Sham-injury group and severe burn group (F = 1.403, P > 0.05). The Sham-injury group and severe burn group contained a small amount of NE in the BALF, and the concentration of NE in the BALF of the severely burned 6 hours and 12 hours groups were significantly higher than those of the Sham-injury group (ng/L: 328.58±158.10, 415.30±240.89 vs. 61.95±15.80, both P < 0.05). (3) Kaplan-Meier survival curve showed that the 72-hour survival rate of mice in the SV intervention group was significantly higher than that in the severe burn group (100% vs. 10%, Log-Rank test: χ² = 19.12, P < 0.001). (4) Compared with the Sham-injury group, all lung function indices of the severe burn group decreased significantly. All lung function indices of SV intervention group improved gradually over time, which were significantly better than those of the severe burn group. (5) Compared with the Sham-injury group, the PMN absolute count in lung tissue and the concentration of NE in plasma and lung tissue were significantly higher in the SV intervention group (F values were 46.709, 3.535, 32.701, respectively, all P < 0.05), with a peak at 6 hours. Compared with the severe burn group, the SV intervention group had a higher PMN absolute count in lung tissue (cells: 8 870.80±7 013.89 vs. 25 974.92±22 240.8, P < 0.05), and higher plasma and lung tissue NE concentrations (ng/L: 14 955.94±3 944.41 vs. 21 972.75±4 573.05, 81 956.87±38 658.35 vs. 168 182.30±83 513.91, both P < 0.01) were significantly decreased. CONCLUSIONS In the early stage of severe burns, there is a significant infiltration of PMN into the lungs. The NE promotes lung injury in the early stage of severe burn, and improve lung injury by inhibiting the action of NE.
Animals ; Burns/metabolism* ; Leukocyte Elastase/metabolism* ; Male ; Mice, Inbred C57BL ; Mice ; Neutrophils/metabolism* ; Lung/metabolism* ; Disease Models, Animal ; Neutrophil Infiltration ; Lung Injury/metabolism* ; Glycine/analogs & derivatives* ; Sulfonamides

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a severe critical condition marked by rapid progression and high fatality. It results from direct/indirect lung-related or systemic triggers, leading to widespread injury of lung epithelial and endothelial cells. Its pathogenesis involves uncontrolled inflammation and breakdown of the lung's blood-air barrier due to leaky blood vessels and epithelial damage. Current management of ALI/ARDS remains primarily supportive, offering symptomatic relief but limited improvement in prognosis, necessitating deeper exploration of upstream pathogenic mechanisms to identify safer and more effective therapies. Exosomal microRNAs (miRNA), small extracellular vesicles (40-150 nm) containing non-coding single-stranded RNAs, regulate post-transcriptional cellular processes and participate in ALI/ARDS pathophysiology. Studies reveal that exosomes transport proteins, nucleic acids, and miRNAs to recipient cells, mediating intercellular communication. In ALI/ARDS models, exosomal miRNAs delivered to alveolar epithelial cells, endothelial cells, macrophages, and neutrophils critically modulate autophagy, pyroptosis, apoptosis, proliferation, inflammatory signaling, macrophage polarization, and neutrophil activation, either exacerbating or alleviating disease progression. Recent advances in engineering techniques have enhanced the therapeutic potential of exosomal miRNAs by overcoming limitations of natural exosomes. This review focuses on exosomal miRNA-mediated regulation of ALI/ARDS pathogenesis across key cell types, providing insights for novel therapeutic strategies.
Exosomes ; Humans ; MicroRNAs ; Acute Lung Injury ; Respiratory Distress Syndrome ; Animals

OBJECTIVE: To investigate the role and mechanism of the cyclic guanosine monophosphate-adenosine monophosphate synthase/stimulator of interferon gene (cGAS/STING) pathway in oleic acid-induced acute lung injury (ALI) in mice. METHODS: Male wild-type C57BL/6J mice were randomly divided into five groups (each n = 10): normal control group, ALI model group, and 5, 50, 500 μg/kg inhibitor pretreatment groups. The ALI model was established by tail vein injection of oleic acid (7 mL/kg), while the normal control group received no intervention. The inhibitor pretreatment groups were intraperitoneally injected with the corresponding doses of cGAS inhibitor RU.521 respectively 1 hour before modeling. At 24 hours post-modeling, blood was collected, and mice were sacrificed. Lung tissue pathological changes were observed under light microscopy after hematoxylin-eosin (HE) staining, and pathological scores were assessed. Western blotting was used to detect the protein expressions of cGAS, STING, phosphorylated TANK-binding kinase 1 (p-TBK1), phosphorylated interferon regulatory factor 3 (p-IRF3), and phosphorylated nuclear factor-κB p65 (p-NF-κB p65) in lung tissue. Immunohistochemistry was performed to observe STING and p-NF-κB positive expressions in lung tissue. Serum interferon-β (IFN-β) levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the normal control group, the ALI model group exhibited significant focal alveolar thickening, intra-alveolar hemorrhage, pulmonary capillary congestion, and neutrophil infiltration in the pulmonary interstitium and alveoli, along with markedly increased pathological scores (10.33±0.58 vs. 1.33±0.58, P < 0.05). Protein expressions of cGAS, STING, p-TBK1, p-IRF3, and p-NF-κB p65 in lung tissue significantly increased [cGAS protein (cGAS/β-actin): 1.24±0.02 vs. 0.56±0.02, STING protein (STING/β-actin): 1.27±0.01 vs. 0.55±0.01, p-TBK1 protin (p-TBK1/β-actin): 1.34±0.03 vs. 0.22±0.01, p-IRF3 protein (p-IRF3/β-actin): 1.23±0.02 vs. 0.36±0.01, p-NF-κB p65 protein (p-NF-κB p65/β-actin): 1.30±0.02 vs. 0.53±0.02, all P < 0.05], positive expressions of STING and p-NF-κB in lung tissue were significantly elevated [STING (A value): 0.51±0.03 vs. 0.30±0.07, p-NF-κB (A value): 0.57±0.05 vs. 0.31±0.03, both P < 0.05], and serum IFN-β levels were also significantly higher (ng/L: 256.02±3.84 vs. 64.15±1.17, P < 0.05). The cGAS inhibitor pretreatment groups showed restored alveolar structural integrity, reduced inflammatory cell infiltration, and decreased hemorrhage area, along with dose-dependent lower pathological scores as well as the protein expressions of cGAS, STING, p-TBK1, p-IRF3 and p-NF-κB p65 in lung tissue, with significant differences between the 500 μg/kg inhibitor group and ALI model group [pathological score: 2.67±0.58 vs. 10.33±0.58, cGAS protein (cGAS/β-actin): 0.56±0.03 vs. 1.24±0.02, STING protein (STING/β-actin): 0.67±0.03 vs. 1.27±0.01, p-TBK1 protein (p-TBK1/β-actin): 0.28±0.01 vs. 1.34±0.03, p-IRF3 protein (p-IRF3/β-actin): 0.32±0.01 vs. 1.23±0.02, p-NF-κB p65 protein (p-NF-κB p65/β-actin): 0.63±0.01 vs. 1.30±0.02, all P < 0.05]. Compared with the ALI model group, positive expressions of STING and p-NF-κB in lung tissue were significantly reduced in the 500 μg/kg inhibitor group [STING (A value): 0.40±0.01 vs. 0.51±0.03, p-NF-κB (A value): 0.43±0.02 vs. 0.57±0.05, both P < 0.05], and serum IFN-β levels were also markedly reduced (ng/L: 150.03±6.19 vs. 256.02±3.84, P < 0.05). CONCLUSIONS The cGAS/STING pathway is activated in oleic acid-induced ALI, leading to exacerbated inflammatory responses and increased lung damage. RU.521 can inhibit cGAS, thereby down-regulating the expression of pathway proteins and cytokines, and providing protection to lung tissue.
Animals ; Acute Lung Injury/chemically induced* ; Male ; Nucleotidyltransferases/metabolism* ; Mice ; Signal Transduction ; Mice, Inbred C57BL ; Membrane Proteins/metabolism* ; Oleic Acid/adverse effects* ; Transcription Factor RelA/metabolism* ; Lung/pathology* ; Interferon Regulatory Factor-3/metabolism* ; Disease Models, Animal

OBJECTIVE: To analyze the clinical effectiveness of veno-venous extracorporeal membrane oxygenation (VV-ECMO) in rescuing children with severe pulmonary contusion. METHODS: A retrospective analysis was conducted on the clinical data of four children with severe pulmonary contusion who were treated with VV-ECMO in the pediatric intensive care unit of Xi'an Children's Hospital from April 2021 to December 2024. The general data, laboratory indicators within 24 hours after admission, imaging features, bronchoscopic findings, diagnostic and treatment processes, as well as therapeutic outcomes of the children were analyzed. RESULTS: All four pediatric cases were male, aged 4 years and 9 months, 6 years and 5 months, 8 years and 10 months, and 9 years and 7 months, respectively. One case resulted from a high-altitude fall and three from traffic accidents, all presenting with multiple fractures. All four cases progressed to dyspnea within 1-4 hours post-injury and received endotracheal intubation with invasive ventilator support within 2-5 hours. Three cases exhibited tachycardia upon admission and were treated with norepinephrine, all four cases presented with fine moist rales in the lungs. Imaging studies revealed diffuse exudative changes in all four cases. Bronchoscopy identified diffuse pulmonary hemorrhage, with one case additionally showing rupture of the right intermediate bronchus. Conventional mechanical ventilation failed to correct oxygenation in all cases, prompting initiation of VV-ECMO therapy within 8-22 hours post-injury. One case underwent right thoracic exploration under ECMO support. Following treatment, all four cases demonstrated gradual reduction in bloody airway secretions, resolution of pulmonary exudative changes on imaging, and absence of hemorrhage on bronchoscopy. They were successfully weaned off ECMO and ultimately discharged as cured. CONCLUSIONS Severe pulmonary contusion rapidly leads to respiratory distress, requiring ventilator-assisted ventilation within hours of injury. When conventional ventilator support is ineffective, ECMO can be life-saving, with timely intervention yielding favorable prognosis.
Humans ; Extracorporeal Membrane Oxygenation/methods* ; Male ; Retrospective Studies ; Child, Preschool ; Child ; Contusions/therapy* ; Lung Injury/therapy* ; Treatment Outcome

PANoptosis is a newly defined type of programmed cell death (PCD), which is triggered by a variety of stimuli and covers three known forms of PCD: apoptosis, pyroptosis and necroptosis. In physiological state, cell death plays an important protective role against pathogen invasion, but its over-activation may aggravate inflammatory response and cause tissue damage. Studies have shown that the occurrence and progression of acute lung injury/acute respiratory distress syndrome (ALI/ARDS), asthma, chronic obstructive pulmonary disease (COPD) and other lung diseases are closely related to PANoptosis. The purpose of this review is to deeply explore the molecular mechanism of PANoptosis and its regulatory factors in lung diseases, in order to discover potential therapeutic targets and provide new targets and innovative ideas for clinical treatment for lung diseases.
Humans ; Lung Diseases ; Apoptosis ; Pyroptosis ; Pulmonary Disease, Chronic Obstructive ; Necroptosis ; Acute Lung Injury