Background Acute respiratory distress syndrome (ARDS) is characterized by impaired alveolar-capillary permeability and pulmonary edema. Alveolar fluid clearance (AFC) is strongly associated with patient prognosis. Objective This study aimed to investigate whether chronic alcohol consumption affects sodium channel regulation in ARDS via the Integrin αvβ6/TGF-β1/Smad4 signaling pathway. Methods We established chronic alcohol exposure models in mice and MLE-12 cells, followed by lipopolysaccharide (LPS)-induced ARDS in both systems. The Integrin αvβ6/TGF-β1/Smad4 pathway was inhibited to explore its regulatory effect on ENaC and Na⁺,K⁺-ATPase during alcohol-induced ARDS. Results We found that chronic alcohol consumption exacerbated lung injury by activating this signaling pathway, which suppressed ENaC and Na⁺,K⁺-ATPase protein expression. Inhibition of the pathway alleviated pulmonary edema and inflammation and improved survival rates. Both in vivo and in vitro results demonstrated that the Integrin αvβ6/TGF-β1/Smad4 pathway regulates ENaC and Na⁺,K⁺-ATPase in alcohol-induced ARDS. Conclusions These findings may clarify the regulatory mechanisms of sodium channels in ARDS associated with chronic alcohol consumption.

Acute respiratory distress syndrome (ARDS) is a critical condition characterized by diffuse alveolar injury, often precipitated by infections, trauma, and other etiological factors, and is associated with a high mortality rate. ARDS induced by serious infections is particularly challenging to manage, as the administration of antibiotics, while essential for infection control, is insufficient to mitigate the associated inflammation, thereby contributing to elevated mortality and intubation rates. Despite extensive research, the precise pathophysiological mechanisms underlying ARDS remain poorly understood. A key factor influencing the prognosis of ARDS is the polarization of alveolar macrophages. In this study, we demonstrated that high-concentration lipopolysaccharide (LPS) not only directly induces M1 macrophage polarization but also triggers macrophage apoptosis via Rab32 activation. Furthermore, the Apoptotic bodies (ABs) released by M1-macrophages exacerbated the inflammatory response by influencing neighboring macrophages through the Cxcl11/Ccl4/NF-κB signaling pathway, thereby aggravating the M1/M2 ratio imbalance. In conclusion, in addition to rigorous antibiotic therapy, targeting M1 macrophage apoptosis inhibition may represent a crucial therapeutic strategy for improving the clinical outcomes and survival rates of ARDS patients.

BACKGROUND:The underlying pathophysiology of acute respiratory distress syndrome (ARDS), a potentially fatal condition, remains poorly understood. In this work, we screened important genes associated with ARDS and M1 macrophage polarization using publicly available bioinformatics datasets and experimental validation in an attempt to identify potential candidate genes for further investigation in ARDS. METHODS:Bulk transcriptomic data from three independent murine ARDS models were analyzed to identify common differentially expressed genes. Single-cell RNA sequencing data from ARDS lungs were used to identify genes differentially expressed between M1 and M2 macrophages. Candidate genes were obtained by intersecting these two gene sets and were validated by qRT-PCR in the lungs of ARDS mice. The top candidate, TARM1, was further investigated in LPS-stimulated RAW264.7 macrophages and in vivo through macrophage-specific AAV6-mediated knockdown. RESULTS:One important potential gene, TARM1, was markedly elevated in ARDS lung tissue and colocalized with the macrophage marker CD68. TARM1 knockdown in vitro reduced pro-inflammatory cytokine expression and LPS-induced M1 macrophage polarization. In vivo, macrophage-specific TARM1 suppression reduced the lung wet-to-dry ratio, inflammatory cytokine levels, and lung damage. CONCLUSIONS:TARM1 may promote ARDS pathogenesis by regulating macrophage M1 polarization. Macrophage-specific TARM1 inhibition alleviates lung injury, suggesting that TARM1 may be a potential target for further research in ARDS. All transcriptomic and single-cell data analyzed in this study were obtained from public GEO repositories (GSE193958, GSE216943, GSE263867, and GSE217324).

Acute respiratory distress syndrome (ARDS) is a critical illness characterized by endothelial barrier damage, and the present study investigates the specific role of clusterin (CLU). The study found that CLU concentrations were significantly lower in ARDS patients, particularly non-survivors, compared with non-ARDS patients and survivors; similarly, serum CLU levels were decreased in mice with lipopolysaccharide-induced ARDS. Both in vivo and in vitro experiments demonstrated that treatment with recombinant CLU protein significantly alleviated organ injury and suppressed the inflammatory response. Mechanistically, CLU improves mitochondrial oxidative phosphorylation by inhibiting the Wnt/β-catenin signaling pathway, thereby inhibiting the expression of inflammatory factors, repairing adherens junctions, and reducing vascular leakage, ultimately preserved intercellular junction protein expression. In summary, CLU ameliorates endothelial injury in ARDS models by inhibiting the Wnt/β-catenin pathway, playing a crucial protective role in host defense against ARDS.

Background:The association between the glucose-to-lymphocyte ratio (GLR) and adverse outcomes in intensive care unit patients receiving mechanical ventilation (MV) has not been clearly established. Aims:To examine the link between GLR and 28-day mortality in MV patients and to develop an interpretable machine learning model to predict mortality risk. Study Design:A retrospective study. Methods:Data were obtained from the Medical Information Mart for Intensive Care IV (MIMIC-IV, version 3.1) database. Receiver operating characteristic (ROC) and restricted cubic spline (RCS) curves were employed to assess the relationship between GLR and mortality. Patients were categorized into high and low GLR groups for Kaplan-Meier survival analysis. Subgroup analyses were performed to evaluate the association across different patient populations. Selected variables were used to construct eXtreme Gradient Boosting (XGBoost), support vector machine, Naive Bayes, and k-nearest neighbors models. Model interpretability was assessed using SHapley Additive exPlanations (SHAP) values. Results:A total of 5,738 patients met the inclusion criteria. RCS analysis indicated a nonlinear relationship between GLR and 28-day mortality. Patients with elevated GLR had significantly higher 28-day mortality rates (hazard ratio > 1, p < 0.05). Among the models, XGBoost demonstrated the best performance, achieving an area under the ROC curve of 0.969 and an F1-score of 0.963. SHAP analysis identified Acute Physiology Score III, GLR, and lactate as the three most important predictors. Conclusion:GLR is nonlinearly associated with 28-day mortality in patients undergoing MV and may serve as a valuable prognostic marker. The interpretable XGBoost model confirmed the significant association between GLR and short-term mortality.

Purpose:The non-high-density lipoprotein cholesterol-to-high-density lipoprotein cholesterol ratio (NHHR) is a new composite blood lipid index. We aimed to investigate the relationships of the NHHR with mortality from all-causes, cardiovascular disease (CVD), and chronic lower respiratory disease (CLRD) in US patients with COPD. Methods:We assessed the association between the NHHR and mortality via weighted multivariate Cox proportional hazards regression models with restricted cubic splines (RCSs). Between-group survival rates at specific time points were compared via Kaplan‒Meier (KM) curves and Log rank tests. Receiver operating characteristic (ROC) curves were constructed to evaluate the efficiency of the NHHR for predicting mortality risk in COPD patients. Results:After adjusting for confounding factors, weighted multivariate Cox proportional hazards regression model showed that higher NHHR was not significantly associated with all-cause mortality (HRs = 1.74), CVD mortality (HRs = 1.19), and CLRD-related mortality (HRs = 0.65), but HRs tended to increase as NHHR increased. RCS revealed U-shaped associations between the NHHR and all-cause mortality. KM survival analysis revealed a significantly lower survival rate for patients in the high-NHHR group (Log rank test P<0.001). In addition, the NHHR had superior performance in predicting mortality, with AUC values of 0.85 and 0.883 for all-cause mortality, 0.769 and 0.815 for CVD mortality, and 0.765 and 0.815 for CLRD-related mortality at 5 and 10 years, respectively. Conclusion:The higher the NHHR is, the greater the risk of all-cause mortality in COPD patients. The NHHR was significantly superior to other haematological biomarkers in predicting mortality.

Background:The Prognostic Nutritional Index (PNI), an integrative measure of body's immune and nutritional status, has demonstrated its prognostic value across a range of diseases. However, its role in critically ill patients with Chronic Obstructive Pulmonary Disease (COPD) remains unclear. This study investigates the association between PNI levels and clinical outcomes in critically ill COPD patients, with a focus on identifying its role as a potential predictor of mortality. Methods:A retrospective analysis of 1,250 critically ill COPD patients from the MIMIC-IV (v2.2) database was conducted. Patients were grouped by PNI tertiles. Primary and secondary outcomes were 28-day and 90-day mortality, respectively. Associations were evaluated using restricted cubic splines, Cox proportional hazards regression analysis, and Kaplan‒Meier survival curves. The predictive performance of PNI was assessed via receiver operating characteristic (ROC) curves analysis, and a nomogram integrating Boruta-selected features was developed to enhance clinical utility. Results:The final cohort comprised 1,250 critically ill COPD patients, with observed mortality rates of 25.3% and 33.2% at 28 and 90 days, respectively. Higher PNI levels were associated with reduced risk of both 28-day and 90-day mortality [28-day HR: 0.95 (95% CI: 0.93-0.97), P < 0.001; 90-day HR: 0.94 (95% CI: 0.93-0.96), P < 0.001]. Restricted cubic spline analysis confirmed this trend. Furthermore, ROC analysis demonstrated the utility of PNI as a predictor for 28-day mortality (AUC: 0.61). Boruta-selected features reinforced the importance of PNI, and the constructed nomogram exhibited excellent predictive accuracy (AUC: 0.712). Conclusion:Higher PNI is linked to reduced mortality risk in critically ill COPD patients, indicating its potential as a prognostic marker.

Mechanical ventilation in critically ill patients can potentially result in ventilator-induced lung injury (VILI). Additionally, mechanical stretching might activate the pro-fibrotic signaling pathways, which could contribute to programmed cell death and the peripheral distribution of fibrosis observed in idiopathic pulmonary fibrosis (IPF). Based on our previous findings, we further explored whether lipoaspirate nanoparticles (Lipo-NPs) could offer protective effects against pulmonary fibrosis associated with VILI. The 8-week-old male SPF C57BL/6 mice were selected for endotracheal intubation after abdominal anesthesia, mechanical ventilation of the mice for 4 h, and tidal volume was set at 30 ml/kg. Lipo-NPs were extracted and identified using a tangential flow filtration (TFF) system. All the mice were divided into three groups: control, VILI, and VILI + Lipo-NPs. The Lipo-NPs were administered into the mice through the tail vein for 7 consecutive days, and an equivalent volume of PBS was administered into the VILI groups. Mice were sacrificed 7 days after mechanical ventilation. Our results suggested that Lipo-NPs could reduce lung tissue damage, pulmonary inflammation, and fibrosis of the VILI mice, accompanied by a reduction in the secretion of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), as well as a decrease in transforming growth factor-β (TGF-β) levels. RNA-sequencing followed by Ingenuity pathway analysis (IPA) was performed to explore downstream of Lipo-NPs and identified idiopathic pulmonary fibrosis (IPF) as the potential pathway. By the combined analysis of microRNAs (miRNAs) enriched by Lipo-NPs, we hypothesized that B cell lymphoma 2 (BCL-2) is a target that mediates the inhibitory effect of mmu-miR-143-3p on VILI-induced IPF. Analysis of lung tissue from mice experiencing VILI revealed elevated levels of antiapoptotic BCL-2 family proteins within α-smooth muscle actin-expressing (α-SMA+) fibroblasts. Treatment with Lipo-NPs induced fibroblast apoptosis, decreased fibroblast numbers, and reduced histologically evident fibrosis. Blocking Lipo-NPs mmu-miR-143-3p in vivo blunts the beneficial effects of Lipo-NPs. Lipo-NPs intervention can partially ameliorate pulmonary fibrosis induced by VILI. This effect is likely due to the enrichment of miR-143 in Lipo-NPs, which promotes fibroblast apoptosis by targeting the anti-apoptotic protein BCL-2. Adipose tissue from obese mice was extracted and subjected to TFF to obtain Lipo-NPs. VILI mice were then interfered with Lipo-NPs through tail vein injection. The study revealed that mmu-miR-143 enriched in Lipo-NPs promoted apoptosis of lung fibroblasts by targeting the anti-apoptotic protein BCL-2, ultimately alleviating IPF in VILI.

Background Bronchiectasis is a disease with a global impact, but most published data come from high-income countries. We aimed to describe the clinical characteristics of patients with bronchiectasis in China. Methods The Chinese Bronchiectasis Registry (BE-China) is a prospective, observational cohort enrolling patients from 111 hospitals in China. Data on demographics, comorbidities, and aetiological testing results were collected from adult patients with bronchiectasis at baseline and annual follow-up. Patients who met the inclusion criteria (age >= 18 years; received chest high-resolution CT in the past year showing bronchiectasis affecting one or more lung lobes; and clinical history consistent with bronchiectasis, including chronic cough, daily sputum production, and history of exacerbations) were included. Patients with known cystic fibrosis were excluded. To investigate variations according to different economic regions, two groups were compared based on whether per capita disposable income of residents was greater than US$5553. Clinical characteristics were compared with the European (EMBARC) registry and other national registries. Findings Between Jan 10, 2020, and March 31, 2024, 10 324 patients from 97 centres were included in the study. Among 9501 participants with available data, the most common cause of bronchiectasis was post-infective disease (4101 [432%] patients), followed by idiopathic (2809 [296%] patients). 6676 (700%) of 9541 patients with available data had at least one exacerbation in the year before enrolment and 5427 (572%) of 9489 patients with available data were hospitalised at least once due to exacerbations. Treatments commonly used in high-income countries, such as inhaled antibiotics and macrolides, were infrequently used in China. Implementation of airway clearance in China was scarce, with only 1177 (122%) of 9647 patients having used at least one method of airway clearance. Compared with upper-middle-income regions, patients from lower-middle-income regions were younger (610 years [SD 140] vs 639 years [142]) with a higher proportion of pulmonary comorbidities (521 [178%] of 2922 patients vs 639 [86%] of 7402 with chronic obstructive pulmonary disease and 194 [66%] of 2922 patients vs 364 [49%] of 7402 patients with asthma), a higher tuberculosis burden (442 [160%] of 2768 patients vs 715 [106%] of 6733 patients), more severe radiological involvement (1160 [424%] of 2736 patients vs 2415 [354%] of 6816 patients with cystic bronchiectasis), more exacerbations (median 14 [IQR 0-2] in both groups; mean 14 [SD 16] vs 12 [14] in the previous year) and hospitalisations (1662 [606%] of 2743 patients vs 3765 [558%] of 6746 patients hospitalised at least once in the previous year), and poorer quality of life (median 574 [IQR 535-631] vs 587 [548-648] assessed by the Bronchiectasis Health Questionnaire). Interpretation The clinical characteristics of patients with bronchiectasis in China show differences compared with cohorts in Europe and India. Bronchiectasis is more severe with a higher burden of exacerbations in lower-income regions. The management of patients with bronchiectasis in China urgently needs standardisation and improvement. Copyright (c) 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

To investigate the effects and mechanisms of MFGE8 on LPS-induced endothelial-to-mesenchymal transition (EndoMT) and pulmonary fibrosis in human lung microvascular endothelial cells (HLMECs) and a mouse model of acute lung injury. Serum MFGE8 levels were compared between ARDS patients and controls. In vitro, HLMECs were treated with LPS, siRNA targeting MFGE8, and recombinant human MFGE8 (rhMFGE8).HLMEC morphology, invasion, migration, and EndoMT markers (CD31, ɑ-SMA) were evaluated. BMP/Smad1/5-Smad4 signaling and Snail expression were assessed via immunofluorescence, western blotting, and qRT-PCR. In vivo, rhMFGE8 effects on pulmonary fibrosis and EndoMT were analyzed in a mouse model of acute lung injury. MFGE8 levels were significantly reduced in ARDS patients, with higher levels correlating to better survival. In vitro, rhMFGE8 improved HLMEC morphology, reduced invasion and migration, and attenuated LPS-induced EndoMT by increasing CD31 and decreasing α-SMA. MFGE8 knockdown increased BMP/Smad1/5-Smad4 signaling and Snail expression, while rhMFGE8 inhibited these effects. In vivo, rhMFGE8 ameliorated pulmonary fibrosis and EndoMT in mice. MFGE8 regulates LPS-induced EndoMT in HLMECs via the BMP/Smad1/5-Smad4 pathway and protects against pulmonary fibrosis in acute lung injury, suggesting it as a therapeutic target for ALI and ARDS.

BackgroundAcute Respiratory Distress Syndrome (ARDS) remains a critical condition associated with high mortality rates, prolonged hospitalization, and reduced quality of life despite advances in critical care. The albumin-corrected anion gap (ACAG), an emerging biomarker reflecting acid-base disturbances, has been linked to poor outcomes in various critical illnesses. However, its prognostic value for mortality in ARDS patients remains unexplored.MethodsThis retrospective study analyzed data from ARDS patients admitted to intensive care units (ICUs) in the MIMIC-IV database. Patients were stratified into quartiles (Q1-Q4) based on ACAG levels. The association between ACAG and 28-day all-cause mortality was comprehensively evaluated using restricted cubic splines, Kaplan-Meier survival analysis, and Cox proportional hazards regression. We employed the Boruta algorithm and LASSO (Least Absolute Shrinkage and Selection Operator) regression to identify key predictive factors. Six machine learning algorithms were used to develop predictive models, with performance assessed by the area under the ROC curve (AUC).ResultsHigher ACAG levels were significantly associated with increased 28-day mortality risk in ARDS patients (P < 0.001). ACAG remained independently associated with 28-day all-cause mortality after comprehensive adjustment for confounders, with a hazard ratio (HR) of 1.04 (95% CI 1.01-1.07, P = 0.003) Subgroup analysis demonstrated that this association persisted across most demographic and clinical subgroups, with significant interactions observed only for myocardial infarction and malignancy (P for interaction < 0.05). Feature selection using Boruta and LASSO analyses consistently identified ACAG as a key predictor. Among the six machine learning models evaluated, the random forest (RF) algorithm demonstrated superior performance with an AUC of 0.73.ConclusionsHigher ACAG levels are independently associated with increased 28-day all-cause mortality in patients with ARDS. ACAG is a promising predictor of short-term mortality and may guide risk stratification in clinical practice.

Acute lung injury (ALI) represents a life-threatening condition with limited therapeutic options. Emerging evidence suggests that ferroptosis, an iron-dependent cell death pathway driven by lipid peroxidation, is a key pathological mechanism underlying ALI. Therefore, we systematically investigated the key role of ferroptosis in ALI pathogenesis using a lipopolysaccharide (LPS)-induced mouse model of sepsis-related ALI. Based on this finding, we engineered polyvinylpyrrolidone-assembled cobalt hexacyanoferrate nanocatalysts (CoHCF NCs) as a ferroptosis inhibitor. These nanocatalysts exhibited dual functions: efficient chelation of free iron ions and strong antioxidant activity. In vivo experiments showed the promising therapeutic efficacy of CoHCF NCs, while in vitro studies using erastin-induced ferroptosis in alveolar epithelial cells confirmed their strong ability to reverse ferroptotic processes. To explore the underlying mechanisms, we employed RNA sequencing, which revealed that CoHCF NCs exert their antiferroptotic effects through a transcriptional network involving antioxidant response enhancement, and iron ion homeostasis regulation. Due to their high ferroptosis-inhibitory capacity and biocompatibility, CoHCF NCs represent a promising therapeutic candidate for ALI.

Acute respiratory distress syndrome (ARDS) is an acute and severe disease with a high mortality rate. The outbreak of immune inflammation in the lung is an important pathogenic mechanism of ARDS. Notably, an imbalance in macrophage polarization is an important link in the occurrence and development of this inflammatory response. Recently, neuropeptides have been shown to regulate inflammation, but the role of neuropeptides in ARDS remains unclear. The aim of this study was to investigate the regulatory effect of calcitonin gene-related peptide (CGRP) on the inflammatory response in ARDS. We found that CGRP expression was increased in the serum of ARDS patients and in both in vitro and in vivo models of ARDS. CGRP can regulate the polarization of macrophages by targeting its receptor (receptor activity-modifying protein 1); reduce the proportion of M1 macrophages; increase the proportion of M2 macrophages; and reduce pathological injury, inflammation, oxidative stress, and apoptosis in lung tissue in LPS-induced ARDS both in vitro and in vivo. Additionally, we performed transcriptome sequencing and found that hypoxia-inducible factor-1α (HIF-1α) is involved in the above process and that CGRP can alleviate ARDS-related pathological damage, inflammation, and oxidative stress by inhibiting the HIF-1α pathway to regulate macrophage polarization balance. These results indicate that CGRP has good potential for clinical translation in the treatment of pulmonary infection in ARDS. Furthermore, this study provides new ideas for the treatment of inflammatory bursts in ARDS.

Acute lung injury (ALI) is a devastating clinical syndrome without effective therapy. Celastrol, as a natural anti-inflammatory compound, has showed therapeutic potential against inflammatory diseases. In this study, we have investigated the potential effect of Celastrol on lipopolysaccharide (LPS)-induced ALI. C57BL/6J mice, Nrf1-knockout mice and A549 (human alveolar epithelial cell line) cells were used to investigate the protective role of Celastrol in LPS-induced ALI. Our data showed that administration of Celastrol significantly alleviated lung pathologic injury and increased the survival rate, which was associated with the improvement of mitochondrial function in the injured lung. Moreover, Celastrol enhanced phosphorylation of AMP-activated protein kinase (AMPK) and expression of peroxisome proliferator-activated receptor coactivator protein-1α (PGC-1α), thereby increasing the nuclear translocation of nuclear respiratory factor 1 (Nrf1) and subsequent up-regulation of its downstream mitochondria electron transport chain complex I (NDUF) gene expression, which induced an increase in mitochondrial complex Ⅰ activity. The beneficial effects of Celastrol on regulation of Nrf1 were abolished by inhibition of AMPK and PGC-1α. Finally, in Nrf1 deficient mice, the protective effects of Celastrol on LPS-induced ALI were largely vanished. Our data indicated that Celastrol can prevent LPS-induced ALI by improving mitochondrial function through AMPK/PGC-1α/Nrf1-dependent mechanism, suggesting that Celastrol may represent a novel therapeutic potential for LPS-induced ALI.

BACKGROUND:Inflammation and endothelial barrier dysfunction are the major pathophysiological changes in acute respiratory distress syndrome (ARDS). Sphingosine-1-phosphate receptor 3 (S1PR3), a G protein-coupled receptor, has been found to mediate inflammation and endothelial cell (EC) integrity. However, the function of S1PR3 in ARDS has not been fully elucidated. METHODS:We used a murine lipopolysaccharide (LPS)-induced ARDS model and an LPS- stimulated ECs model to investigate the role of S1PR3 in anti-inflammatory effects and endothelial barrier protection during ARDS. RESULTS:We found that S1PR3 expression was increased in the lung tissues of mice with LPS-induced ARDS. TY-52156, a selective S1PR3 inhibitor, effectively attenuated LPS-induced inflammation by suppressing the expression of proinflammatory cytokines and restored the endothelial barrier by repairing adherens junctions and reducing vascular leakage. S1PR3 inhibition was achieved by an adeno-associated virus in vivo and a small interfering RNA in vitro. Both the in vivo and in vitro studies demonstrated that pharmacological or genetic inhibition of S1PR3 protected against ARDS by inhibiting the NF-κB pathway and improving mitochondrial oxidative phosphorylation. CONCLUSIONS:S1PR3 inhibition protects against LPS-induced ARDS via suppression of pulmonary inflammation and promotion of the endothelial barrier by inhibiting NF-κB and improving mitochondrial oxidative phosphorylation, indicating that S1PR3 is a potential therapeutic target for ARDS.

IntroductionChlamydia psittaci infection in humans is a rare cause that mainly present as community-acquired pneumonia. Severe Chlamydia psittaci pneumonia can lead to acute respiratory distress syndrome (ARDS), septic shock, or multiple organ dysfunction with a mortality rate of 15%–20% before accurate diagnosis and targeted treatment. Metagenomic next-generation sequencing (mNGS) has an advantage in achieving early diagnosis. In the study, omadacycline implementation was described to provide a better understanding of effectiveness in severe psittacosis pneumonia with ARDS.MethodsSixteen patients with severe psittacosis pneumonia with ARDS were selected between September 2021 and October 2022. They were diagnosed using mNGS and treated with omadacycline. Retrospective analysis of clinical manifestations, laboratory data, disease progression, diagnostic tool, treatment, and prognosis was summarized.ResultsCommon symptoms included fever, dyspnea, and cough. All patients developed ARDS, accompanied by septic shock (43.7%) and pulmonary embolism (43.7%). Laboratory data showed normal leucocytes, increased creatine kinase isoenzyme, and decreased albumin with liver dysfunction in most patients. All patients had increased neutrophils, C-reactive protein, procalcitonin, and D-dimer with decreased lymphocytes. Airspace consolidation, ground glass opacity, and pleural effusion were found on chest CT. mNGS results were obtained in 24–48 h to identify the diagnosis of Chlamydia psittacosis. All patients received mechanical ventilation with omadacycline treatment. Fourteen patients experienced complete recovery, while the other two patients died from multidrug-resistant bacterial infection and renal failure.ConclusionmNGS has a significant value in the diagnosis of Chlamydia psittaci infection. Timely treatment of omadacycline can improve prognosis and provide a promising new option for the treatment of severe Chlamydia psittaci pneumonia with ARDS.

Background Acute respiratory distress syndrome (ARDS) is a severe respiratory condition characterized by a high mortality rate, the management of which relies on supportive care and a profound understanding of its pathophysiology. Heparin, with its anticoagulant and potential anti-inflammatory properties, offers a new therapeutic opportunity for the treatment of ARDS. Methods In this retrospective cohort study, we examined the MIMIC-IV database for ARDS patients who received prophylactic heparin within the first 72 h of ICU admission. Employing propensity score matching and inverse probability weighting (IPW) analysis, we evaluated the impact of early heparin use on patient outcomes, focusing on mortality rates. Results Patients who received prophylactic heparin had a significantly lower in-hospital mortality rate compared to those who did not (13.55% vs 17.93%, HR = 0.71, 95% CI: 0.54–0.93, P = 0.012). This result remained significant after propensity score matching (12.75% vs 17.93%, HR = 0.65, 95% CI 0.47–0.90, P = 0.010). Analysis using five different statistical models indicated that early use of heparin significantly reduced the in-hospital mortality rate, with HR = 0.669 (95% CI 0.487–0.919, P = 0.013) in the doubly robust model without balanced covariates; HR = 0.705 (95% CI 0.515–0.965, P = 0.029) with all covariates considered; HR = 0.660 (95% CI 0.491–0.888, P = 0.006) in the propensity score (IPW) model; HR = 0.650 (95% CI 0.470–0.900, P = 0.010) in the propensity score matching model; and HR = 0.706 (95% CI 0.536–0.930, P = 0.013) in the multivariate Cox regression model. Secondary outcomes indicated that heparin use was also associated with reduced mortality rates at 60 days, and 90 days. Conclusion This research highlights that early prophylactic administration of heparin may substantially lower mortality in ARDS patients. These findings underscore the potential of heparin as a key component in the management of ARDS, offering a new perspective and novel strategies for clinical treatment.

The role of endothelial cells in acute lung injury (ALI) has been widely elaborated, but little is known about the role of different subtypes of endothelial cells in ALI. ALI models were established by lipopolysaccharide. Single-cell RNA sequencing was used to identify differential molecules in endothelial subtypes and the heterogeneity of lung immune cells. Specific antibodies were used to block insulin-like growth factor binding protein 7 (IGFBP7), and AAVshIGP7 was used to specifically knock down IGFBP7. Here, we found that IGFBP7 was the most differentially expressed molecule in diverse subsets of endothelial cells and that IGFBP7 was strongly associated with inflammatory responses. Elevated IGFBP7 significantly exacerbated barrier dysfunction in ALI, whereas blockade of IGFBP7 partially reversed barrier damage. General capillary cells are the primary source of elevated serum IGFBP7 after ALI. Using single-cell RNA sequencing, we identified significantly increased Clec4nhi neutrophils in mice with ALI, whereas IGFBP7 knockdown significantly reduced infiltration of Clec4nhi cells and mitigated barrier dysfunction in ALI. In addition, we found that IGFBP7 activated the NF-κB signaling axis by promoting phosphorylation and ubiquitination degradation of F-box/WD repeat-containing protein 2 (FBXW2), thereby exacerbating barrier dysfunction in ALI. Taken together, our data indicate that blockade of serum IGFBP7 or IGFBP7 depletion in general capillary cells reversed barrier damage in ALI. Therefore, targeting IGFBP7 depletion could be a novel strategy for treating ALI.