Background: Stimulation of epithelial sodium channel (ENaC) increases Na⁺ transport, a driving force of alveolar fluid clearance (AFC) to keep alveolar spaces free of edema fluid that is beneficial for acute lung injury (ALI). It is well recognized that regulation of ENaC by insulin via PI3K pathway, but the mechanism of this signaling pathway to regulate AFC and ENaC in ALI remains unclear. The aim of this study was to investigate the effect of insulin on AFC in ALI and clarify the pathway in which insulin regulates the expression of ENaC in vitro and in vivo. Methods: A model of ALI (LPS at a dose of 5.0 mg/kg) with non-hyperglycemia was established in Sprague-Dawley rats receiving continuous exogenous insulin by micro-osmotic pumps and wortmannin. The lungs were isolated for measurement of bronchoalveolar lavage fluid(BALF), total lung water content(TLW), and AFC after ALI for 8 hours. Alveolar epithelial type II cells were pre-incubated with LY294002, Akt inhibitor and SGK1 inhibitor 30 minutes before insulin treatment for 2 hours. The expressions of α-,β-, and γ-ENaC were detected by immunocytochemistry, reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting. Results: In vivo, insulin decreased TLW, enchanced AFC, increased the expressions of α-,β-, and γ-ENaC and the level of phosphorylated Akt, attenuated lung injury and improved the survival rate in LPS-induced ALI, the effects of which were blocked by wortmannin. Amiloride, a sodium channel inhibitor, significantly reduced insulin-induced increase in AFC. In vitro, insulin increased the expressions of α-,β-, and γ-ENaC as well as the level of phosphorylated Akt but LY294002 and Akt inhibitor significantly prevented insulin-induced increase in the expression of ENaC and the level of phosphorylated Akt respectively. Immunoprecipitation studies showed that levels of Nedd4-2 binding to ENaC were decreased by insulin via PI3K/Akt pathway. Conclusions: Our study demonstrated that insulin alleviated pulmonary edema and enhanced AFC by increasing the expression of ENaC that dependent upon PI3K/Akt pathway by inhibition of Nedd4-2.

Background: Miliary tuberculosis (TB) is an uncommon cause of acute respiratory distress syndrome (ARDS) with a high mortality. The aim of the present study was to evaluate the clinical characteristics, predictors and outcome of patients with ARDS caused by miliary TB. Methods: A retrospective study was conducted among patients with a diagnosis of ARDS with miliary TB in four hospitals from 2006 to 2010. Medical records and laboratory examinations of these patients were taken during the first 24 h of admission. Results: Eighty-five patients with miliary TB developed ARDS, 45 of whom survived (52.9%). The median age was 36.6 ± 12.5 years with 38 males (44.7%). Diabetes mellitus (DM) was the most common underlying disease (18.8%).ICU mortality was 47.1%. The time from admission to anti-tuberculosis therapy was 4.5 ± 2.0 days. Mean duration of mechanical ventilation was 8.5 ± 3.0 days in all patients. Duration of time to diagnosis, time from diagnosis to mechanical ventilation, and time to anti-tuberculosis therapy were significantly shorter in survivors than those in non-survivors. Diabetes mellitus (OR 5.431, 95%CI 1.471-20.049; P = 0.005), ALT (70-100U/L, OR 10.029, 95%CI 2.764-36.389; P = 0.001), AST (>94U/L,OR 8.034, 95%CI 2.200-29.341; P = 0.002), D-dimer (>1.6mg/L, OR 3.167, 95%CI 0.896-11.187; P = 0.042), hemoglobin (<90g/L, OR 14.824, 95%CI 3.713-59.179; P = 0.001), albumin (<25g/L, OR 15.896, 95%CI 3.975-63.566; P = 0.001) were independent predictors of ARDS development in the setting of miliary TB. Conclusions: Accurate diagnosis, early initiation of anti-tuberculosis therapy and mechanical ventilation are important for the outcome of patients with ARDS caused by miliary TB. DM, ALT, AST, D-dimer, hemoglobin, and albumin are independent predictors of ARDS development in patients with miliary TB.

Background: Recent studies haveshown that ginsenoside Rg1, extracted from the dry roots of Panax notoginseng as a traditional Asian medicine, plays an anti-fibrosis role in myocardial remodeling. However, the mechanism still remains unclear. In the present study, we investigate the effect of ginsenoside Rg1on the collagenic remodeling of myocardium in chronic thromboembolic pulmonary hypertension (CTEPH), and its potential mechanism. Methods: A rat model of CTEPH was established by injecting thrombi through the jugular vein wice in2 weeks. Four weeks later, four groups (Group A: normal rats + normal saline; Group B: normal rats + Rg1; Group C: CTEPH model + normal saline; Group D: CTEPH model + Rg1) were established. Normal saline and Rg1 were administrated by intraperitoneal injection. Ineach group, we measured the hemodynamic parameters, as well as the right ventricle to left ventricle (RV/LV) thickness ratio. Myocardial tissue sections of the RV were stained by hematoxylin-eosin +gentian violet and the morphological characteristics were observed by light microscopy. The matrix metalloproteinases (MMP) -2 and −9 were detected by the western blot. Results: Compared with Group A and Group B, the right ventricular systolic pressure was significantly increased in Group C and significantly decreased in Group D. Compared with Group A and Group B, the RV/LV thickness ratio of the rats was significantly higher in Group C and Group D. There was significant fibrosis with collagen in Group C compared with Group A and Group B, and less significant changes in Group D were observed compared with those in Group C. The expression of MMP-2 and MMP-9 exhibited a significant decrease in Group C and was also significantly decreased in Group D compared withGroup A and Group B. Also, a negative linear relationship was shown between collagen-I and the expression of MMP-2 and MMP-9. Conclusions: Our animal study showed that ginsenoside Rg1 positively affects myocardial remodeling and pulmonary hemodynamics in CTEPH. Upregulation of the expression of MMP-2 and MMP-9 could explain the beneficial effects of ginsenoside Rg1 in CTEPH.

Introduction: Chlamydia 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.Methods: Sixteen 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.Results: Common 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.Conclusion: mNGS 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.

Background: The Endothelial Activation and Stress Index (EASIX), calculated as [lactate dehydrogenase (U/L) × creatinine (mg/dL)] ÷ platelet count (109/L), serves as a reliable biomarker for endothelial dysfunction. Endothelial damage significantly contributes to the pathophysiological mechanisms underlying acute respiratory distress syndrome (ARDS). However, the relationship between EASIX and ARDS patients remains to be fully elucidated.Methods: To evaluate the relationship between EASIX and outcomes in patients with acute respiratory distress syndrome (ARDS), in two cohorts we used Cox proportional hazards models and applied restricted cubic spline methods. Then we stratify EASIX into higher Log2_EASIX and lower Log2_EASIX groups, matched baseline data from the two stratified groups in both cohorts using propensity score matching to reduce confounding bias. Additionally, we further analyzed the differences in clinical outcomes between the higher Log2_EASIX and lower Log2_EASIX groups and performed Kaplan-Meier analysis on the matched data.Results: In the MIMIC-IV cohort, compared to the survival group, within the 28 days, the non-survival group had higher Log2_EASIX (Survival: Non-survival = 1.35 [0.16, 2.80]: 2.08 [0.79, 3.59], P = 0.002),and in the CQMU cohort, the non-survival group had higher Log2_EASIX (Survival: Non-survival = 1.91 [1.48, 2.43]: 2.34 [1.89, 3.01], P < 0.0001), Even after adjusting for potential confounders, individuals exhibiting elevated Log2_EASIX values still faced a greater risk of mortality during hospitalization and at 28-, 60-and 90-day post-admission.Conclusion: Elevated EASIX levels were found to be positively correlated with a higher risk of mortality in patients with ARDS. Assessing EASIX levels could be a promising biomarker for predicting overall survival in ARDS.