Activated Clec4nhi Neutrophils Aggravate Lung Injury in an Endothelial IGFBP7 Dependent Manner.

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 heterogeneity of lung immune cells. Specific antibodies were used to block IGFBP7 protein, and AAVshIGP7 was used to specifically knock down IGFBP7. Here, we found that Insulin-like growth factor binding protein 7 (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 (gCap) are the primary source of elevated serum IGFBP7 after ALI. Using single-cell RNA sequencing, we identified significantly increased Clec4nhi neutrophils in ALI mice, whereas IGFBP7 knockdown significantly reduced infiltration of Clec4nhi cells and mitigated barrier dysfunction in ALI. In addition, we found that IGFBP7 activated the NFκB 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 gCap reversed barrier damage in ALI. Therefore, targeting the IGFBP7 depletion could be a novel strategy for treating ALI.

Omentin-1 ameliorates pulmonary arterial hypertension by inhibiting endoplasmic reticulum stress through AMPKα signaling.

BACKGROUND: Endothelial dysfunction of the pulmonary artery contributes to hypoxia-induced pulmonary arterial hypertension (PAH). Omentin-1, as a novel adipocytokine, plays an important protective role against cardiovascular diseases. However, the effect and underlying mechanisms of omentin-1 against PAH remain unclear. METHODS: PAH was induced in SD (Sprague & Dawley) rats via a low-oxygen chamber for 4 weeks. Hemodynamic evaluation was undertaken using a PowerLab data acquisition system, and histopathological analysis was stained with hematoxylin and eosin (H&E). Endothelial function of pulmonary artery was assessed using wire myography. RESULTS: We found that omentin-1 significantly improved pulmonary endothelial function in rats exposed to hypoxia and attenuated PAH. Mechanistically, we found that omentin-1 increased phosphorylated 5'­adenosine monophosphate­activated protein kinase (p­AMPK) level and reduced endoplasmic reticulum (ER) stress and increased NO production in pulmonary artery from rats exposed to hypoxia. However, the effect of omentin-1 was abolished by treatment with AMPK inhibitor (Compound C). CONCLUSIONS: Our results reveal a protective effect of omentin-1 in PAH via inhibiting ER stress through AMPKα signaling and provide an agent with translational potential for the treatment of PAH.

Exploring the therapeutic role of early heparin administration in ARDS management: a MIMIC-IV database analysis.

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.

A phase 4 multicentre, 2×2 factorial randomised, double-blind, placebo-controlled trial to investigate the efficacy and safety of tobramycin inhalation solution for Pseudomonas aeruginosa eradication in bronchiectasis: ERASE.

Chronic Pseudomonas aeruginosa (PA) infection significantly contributes to morbidity and mortality in bronchiectasis patients. Initiating antibiotics early may lead to the eradication of PA. Here we outline the design of a trial (ERASE; NCT06093191) assessing the efficacy and safety of inhaled tobramycin, alone or with oral ciprofloxacin, in bronchiectasis patients with a new isolation of PA. This multicentre, 2×2 factorial randomised, double-blind, placebo-controlled, parallel-group trial includes a 2-week screening period, a 12-week treatment phase (with a combination of ciprofloxacin or a placebo at initial 2 weeks) and a 24-week follow-up. 364 adults with bronchiectasis and a new PA isolation will be randomly assigned to one of four groups: placebo (inhaled saline and ciprofloxacin placebo twice daily), ciprofloxacin alone (750 mg ciprofloxacin and inhaled saline twice daily), inhaled tobramycin alone (inhaled 300 mg tobramycin and ciprofloxacin placebo twice daily) or a combination of both drugs (inhaled 300 mg tobramycin and 750 mg ciprofloxacin twice daily). The primary objective of this study is to assess the proportion of patients successfully eradicating PA in each group by the end of the study. Efficacy will be evaluated based on the eradication rate of PA at other time points (12, 24 and 36 weeks), the occurrence of exacerbations and hospitalisations, time to first pulmonary exacerbations, patient-reported outcomes, symptom measures, pulmonary function tests and the cost of hospitalisations. To date no randomised trial has evaluated the benefit of different PA eradication strategies in bronchiectasis patients. The ERASE trial will therefore generate crucial data to inform future clinical guidelines.

Circulating microvesicles miR139-3p from bronchopulmonary dysplasia aggravates pulmonary vascular simplification by targeting 4E binding protein 1.

BACKGROUND: Microvesicles (MVs) play a crucial role in bronchopulmonary dysplasia (BPD). There are many MVs in circulating plasma, and they are in direct contact with lung endothelial cells. However, the molecular mechanism and causative effect of circulating MVs on BPD remain unclear. METHODS: Clinical plasma samples were collected, circulating MVs were isolated, and microRNA (miRNA) sequencing was performed. The BPD model was established, and different MVs were administered. Alveoli and pulmonary vessels were examined by hematoxylin-eosin staining, and body weight and length were measured. In vitro, gene expression was disrupted by miRNA mimics, miRNA inhibitors or plasmid transfection. Cell proliferation and protein expression were detected by cell scratch assay, accurate 5-ethynyl-2-deoxyuridine test, western blotting, or immunofluorescence assay. RESULTS: BPD-derived MVs further aggravated pulmonary vascular simplification, while circulating MVs from control mice mitigated pulmonary vascular simplification. Micro-RNA sequencing and independent sample verification revealed that miR139-3p, but not miR6125 or miR193b-3p, was the most critical effector molecule in MVs. Mechanism studies showed that eukaryotic translation initiation factor 4E binding protein 1 was the target gene for miR139-3p. In addition, we found that supplementation of miR139-3p inhibitor partially alleviated pulmonary vascular simplification. CONCLUSIONS: These results indicate that circulating MVs are involved in forming BPD by carrying miR139-3p molecules and support miR139-3p inhibitors as a potential therapeutic strategy for alleviating pulmonary vascular simplification in BPD.

Identification of biomarkers associated with diagnosis of acute lung injury based on bioinformatics and machine learning.

BACKGROUND: Acute lung injury (ALI) is an acute inflammatory disease characterized by excess production of inflammatory factors in lung tissue and has a high mortality. This research was designed for the identification of novel diagnostic biomarkers for ALI and analyzing the possible association between critical genes and infiltrated immune cells. METHODS: The study used 2 datasets (GSE2411 and GSE18341) to identify differentially expressed genes (DEGs) between 2 groups. Then we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses to identify the functions of these DEGs. The study also used SVM-recursive feature elimination analysis and least absolute shrinkage and selection operator regression model to screen possible markers. The study further analyzed immune cell infiltration via CIBERSORT. Gene Set Enrichment Analysis was used to explore the molecular mechanism of the critical genes. RESULTS: DEGs were identified between 2 groups. In total, 690 DEGs were obtained: 527 genes were upregulated and 163 genes were downregulated. We identified PDZK1IP1, CCKAR, and CXCL2 as critical genes. And we then found that these critical genes correlated with Mast Cells, Neutrophil Cells, M1 Macrophage, dendritic cell Actived, Eosinophil Cells, B Cells Naive, Mast Cells, and dendritic cell Immature. Furthermore, we investigated the specific signaling pathways involved in key genes and derived some potential molecular mechanisms by which key genes affect disease progression by use of Gene Set Enrichment Analysis. Moreover, we predict transcription factors. Also, we obtained critical gene-related microRNAs through the targetscan database, and visualized the microRNA network of the genes. CONCLUSION: Our findings might provide some novel clue for the exploration of novel markers for ALI diagnosis. The critical genes and their associations with immune infiltration may offer new insight into understanding ALI developments.

Comprehensive Comparisons between Directing and Alternating Current Electrolysis in Organic Synthesis.

Organic electrosynthesis has consistently aroused significant interest within both academic and industrial spheres. Despite the considerable progress achieved in this field, the majority of electrochemical transformations have been conducted through the utilization of direct-current (DC) electricity. In contrast, the application of alternating current (AC), characterized by its polarity-alternating nature, remains in its infancy within the sphere of organic synthesis, primarily due to the absence of a comprehensive theoretical framework. This minireview offers an overview of recent advancements in AC-driven organic transformations and seeks to elucidate the differences between DC and AC electrolytic methodologies by probing into their underlying physical principles. These differences encompass the ability of AC to preclude the deposition of metal catalysts, the precision in modulating oxidation and reduction intensities, and the mitigation of mass transfer processes.

The association between early fluid strategy and prognosis of acute respiratory distress syndrome: A post hoc study of CHARDS.

We aimed to assess general fluid management in China and evaluate the association between fluid balance and survival outcomes in acute respiratory distress syndrome (ARDS) patients. A retrospective, multicenter study including ARDS patients was conducted. We described the fluid management of ARDS patients in China. Furthermore, clinical characteristics and outcomes of patients subdivided by cumulative fluid balance were also analyzed. Multivariable logistic regression analysis was performed with hospital mortality as the outcome. From June 2016 to February 2018, 527 ARDS patients were included in our study. The mean cumulative fluid balance was 1669 (-1101 to 4351) mL in the first 7 day after intensive care unit (ICU) admission. Patients were divided into four groups based on cumulative fluid balance of the first 7 day after ICU admission: Group I (≤0 L), Group II (>0 L, ≤3 L), Group III (>3 L, ≤5 L), and Group IV (>5 L). Significantly lower hospital mortality was observed in patients with a lower cumulative fluid balance on day 7 of ICU admission (20.5% in Group I vs. 32.8% in Group II, 38.5% in Group III, and 50% in Group IV, p < 0.001). A lower fluid balance is associated with lower hospital mortality in patients with ARDS. However, a large-scale and well-designed randomized controlled trial is needed in the future.

Interferon regulatory factor 1 (IRF1) inhibits lung endothelial regeneration following inflammation-induced acute lung injury.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a respiratory condition caused by severe endothelial barrier dysfunction within the lung. In ARDS, excessive inflammation, tissue edema, and immune cell influx prevents endothelial cell regeneration that is crucial in repairing the endothelial barrier. However, little is known about the molecular mechanism that underpin endothelial cell regeneration in ARDS. METHODS: R-based bioinformatics tools were used to analyze microarray-derived transcription profiles in human lung microvascular endothelial cells (HLMVECs) subjected to non-treatment or lipopolysaccharide (LPS) exposure. We generated endothelial cell-specific interferon regulatory factor 1 (Irf1) knockout (Irf1EC-/-) and Irf1fl/fl control mice for use in an endotoxemic murine model of acute lung injury (ALI). In vitro studies (qPCR, immunoblotting, and ChIP-qPCR) were conducted in mouse lung endothelial cells (MLECs) and HLMVECs. Dual-luciferase promoter reporter assays were performed in HLMVECs. RESULTS: Bioinformatics analyses identified IRF1 as a key up-regulated gene in HLMVECs post-LPS exposure. Endothelial-specific knockout of Irf1 in ALI mice resulted in enhanced regeneration of lung endothelium, while liposomal delivery of endothelial-specific Irf1 to wild-type ALI mice inhibited lung endothelial regeneration in a leukemia inhibitory factor (Lif)-dependent manner. Mechanistically, we demonstrated that LPS-induced Stat1Ser727 phosphorylation promotes Irf1 transactivation, resulting in downstream up-regulation of Lif that inhibits endothelial cell proliferation. CONCLUSIONS: These results demonstrate the existence of a p-Stat1Ser727-Irf1-Lif axis that inhibits lung endothelial cell regeneration post-LPS injury. Thus, direct inhibition of IRF1 or LIF may be a promising strategy for enhancing endothelial cell regeneration and improving clinical outcomes in ARDS patients.

Successful treatment with osimertinib for nonmucinous bronchioloalveolar carcinoma with massive bronchorrhea and respiratory failure: a case report and literature review.

Background: Correct diagnosis of bronchioloalveolar carcinoma (BAC) is often delayed due to the lack of familiarity with the condition among clinicians as its sporadic nature and its symptoms are similar to other respiratory issues. Among these, acute respiratory failure (ARF) caused by massive bronchorrhea is rarely associated with BAC. Here we first reported osimertinib in the treatment of BAC with bronchorrhea and ARF. Case Description: A 38-year-old woman presented with massive bronchorrhea and progressive dyspnea. A chest computed tomography (CT) scan showed consolidation with air bronchograms and multiple nodules in both lungs. The patient had no history of chronic pulmonary disease, diabetes mellitus, hypertension or smoke. The patient was initially diagnosed with pneumonia, but ARF developed despite the antibiotic therapy provided. Lung biopsy results revealed nonmucinous BAC. Osimertinib (80 mg daily) was prescribed and proved effective for the first time with an improved ARF and a decreased multiple nodules or consolidation in the lungs during the follow-up period. Conclusions: It is important for physicians to recognize the typical symptoms and radiological manifestations of BAC to avoid misdiagnosis or late diagnosis. This is especially important since early diagnosis allows for immediate epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy, which is a potentially beneficial treatment for patients with BAC.

Hepatic Nampt Deficiency Aggravates Dyslipidemia and Fatty Liver in High Fat Diet Fed Mice.

Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme in the salvage pathway of nicotinamide adenine dinucleotide (NAD) biosynthesis. Thus far, hepatic Nampt has not been extensively explored in terms of its effects on serum lipid stability and liver lipids metabolism. In this study, hepatocyte-specific Nampt knockout (HC-Nampt-/-) mice were generated by Cre/loxP system. Nampt mRNA expression was reduced in the liver, but not in other tissues, in HC-Nampt-/- mice compared with wild-type (WT) mice. Hepatic Nampt deficiency had no effect on body weight and fasting blood glucose, and it did not induce atherosclerosis in mice under both normal chow diet (NCD) and high fat diet (HFD). At baseline state under NCD, hepatic Nampt deficiency also did not affect liver weight, liver function index, including alanine aminotransferase, aspartate aminotransferase, albumin and alkaline phosphatase, and serum levels of lipids, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and non-esterified fatty acids (NEFA). However, under HFD, deficiency of hepatic Nampt resulted in increased liver weight, liver function index, and serum levels of TG, TC, HDL-C, and NEFA. Meanwhile, histopathological examination showed increased fat accumulation and fibrosis in the liver of HC-Nampt-/- mice compared with WT mice. Taken together, our results show that hepatic Nampt deficiency aggravates dyslipidemia and liver damage in HFD fed mice. Hepatocyte Nampt can be a protective target against dyslipidemia and fatty liver.

APELIN-13 AMELIORATES LPS-INDUCED ENDOTHELIAL-TO-MESENCHYMAL TRANSITION AND POST-ACUTE LUNG INJURY PULMONARY FIBROSIS BY SUPPRESSING TRANSFORMING GROWTH FACTOR-Β1 SIGNALING.

ABSTRACT: The pathophysiology of acute respiratory distress syndrome (ARDS) involves cytokine storms, alveolar-capillary barrier destruction, and fibrotic progression. Pulmonary interstitial fibrosis is an important factor affecting the prognosis of ARDS patients. Endothelial-to-mesenchymal transition (EndMT) plays an important role in the development of fibrotic diseases, and the occurrence of EndMT has been observed in experimental models of LPS-induced acute lung injury (ALI). Apelin is an endogenous active polypeptide that plays an important role in maintaining endothelial cell homeostasis and inhibiting fibrotic progression in various diseases. However, whether apelin attenuates EndMT in ALI and post-ALI pulmonary fibrosis remains unclear. We analyzed the serum levels of apelin-13 in patients with sepsis-associated ARDS to examine its possible clinical value. A murine model of LPS-induced pulmonary fibrosis and an LPS-challenged endothelial cell injury model were used to analyze the protective effect and underlying mechanism of apelin-13. Mice were treated with apelin-13 by i.p. injection, and human pulmonary microvascular endothelial cells were incubated with apelin-13 in vitro . We found that the circulating apelin-13 levels were significantly elevated in sepsis-associated ARDS patients compared with healthy controls. Our study also confirmed that LPS induced EndMT progression and pulmonary fibrosis, which were characterized by decreased CD31 expression and increased α-smooth muscle actin expression and collagen deposition. LPS also stimulated the production of transforming growth factor ß1 and activated the Smad signaling pathway. However, apelin-13 treatment significantly attenuated these changes. Our findings suggest that apelin-13 may be a novel biomarker in patients with sepsis-associated ARDS. These results demonstrate that apelin-13 ameliorates LPS-induced EndMT and post-ALI pulmonary fibrosis by suppressing transforming growth factor ß1 signaling.

Omadacycline for the treatment of severe pneumonia caused by Chlamydia psittaci complicated with acute respiratory distress syndrome during the COVID-19 pandemic.

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.

The Establishment of China Bronchiectasis Registry and Research Collaboration (BE-China): Protocol of a prospective multicenter observational study.

BACKGROUND: Bronchiectasis is a highly heterogeneous chronic airway disease with marked geographic and ethnic variations. Most influential cohort studies to date have been performed in Europe and USA, which serve as the examples for developing a cohort study in China where there is a high burden of bronchiectasis. The Establishment of China Bronchiectasis Registry and Research Collaboration (BE-China) is designed to: (1) describe the clinical characteristics and natural history of bronchiectasis in China and identify the differences of bronchiectasis between the western countries and China; (2) identify the risk factors associated with disease progression in Chinese population; (3) elucidate the phenotype and endotype of bronchiectasis by integrating the genome, microbiome, proteome, and transcriptome with detailed clinical data; (4) facilitate large randomized controlled trials in China. METHODS: The BE-China is an ongoing prospective, longitudinal, multi-center, observational cohort study aiming to recruit a minimum of 10,000 patients, which was initiated in January 2020 in China. Comprehensive data, including medical history, aetiological testing, lung function, microbiological profiles, radiological scores, comorbidities, mental status, and quality of life (QoL), will be collected at baseline. Patients will be followed up annually for up to 10 years to record longitudinal data on outcomes, treatment patterns and QoL. Biospecimens, if possible, will be collected and stored at - 80 °C for further research. Up to October 2021, the BE-China has enrolled 3758 patients, and collected 666 blood samples and 196 sputum samples from 91 medical centers. The study protocol has been approved by the Shanghai Pulmonary Hospital ethics committee, and all collaborating centers have received approvals from their local ethics committee. All patients will be required to provide written informed consent to their participation. CONCLUSIONS: Findings of the BE-China will be crucial to reveal the clinical characteristics and natural history of bronchiectasis and facilitate evidence-based clinical practice in China. Trial registration Registration Number in ClinicalTrials.gov: NCT03643653.

Comparison of Clinical Characteristics and Predictors of Mortality between Direct and Indirect ARDS.

Background and Objectives: Acute Respiratory Distress Syndrome (ARDS) is a heterogeneous syndrome that encompasses lung injury from a direct pulmonary or indirect systemic insult. Studies have shown that direct and indirect ARDS differ in their pathophysiologic process. In this study, we aimed to compare the different clinical characteristics and predictors of 28-day mortality between direct and indirect ARDS. Materials and Methods: The data of 1291 ARDS patients from September 2012 to December 2021 at the Second Affiliated Hospital of Chongqing Medical University were reviewed. We enrolled 451 ARDS patients in our study through inclusion and exclusion criteria. According to the risk factors, each patient was divided into direct (n = 239) or indirect (n = 212) ARDS groups. The primary outcome was 28-day mortality. Results: The patients with direct ARDS were more likely to be older (p < 0.001) and male (p = 0.009) and have more comorbidity (p < 0.05) and higher 28-day mortality (p < 0.001) than those with indirect ARDS. Age and multiple organ dysfunction syndrome (MODS) were predictors of 28-day mortality in the direct ARDS group, while age, MODS, creatinine, prothrombin time (PT), and oxygenation index (OI) were independent predictors of 28-day mortality in the indirect ARDS group. Creatinine, PT, and OI have interactions with ARDS types (all p < 0.01). Conclusions: The patients with direct ARDS were more likely to be older and male and have worse conditions and prognoses than those with indirect ARDS. Creatinine, PT, and OI were predictors of 28-day mortality only in the indirect ARDS group. The differences between direct and indirect ARDS suggest the need for different management strategies of ARDS.

No sex differences in the incidence, risk factors and clinical impact of acute kidney injury in critically ill patients with sepsis.

Background: Sex-stratified medicine is an important aspect of precision medicine. We aimed to compare the incidence and risk factors of acute kidney injury (AKI) for critically ill men and women with sepsis. Furthermore, the short-term mortality was compared between men and women with sepsis associated acute kidney injury (SA-AKI). Method: This was a retrospective study based on the Medical Information Mart for Intensive Care IV database. We used the multivariable logistic regression analysis to evaluate the independent effect of sex on the incidence of SA-AKI. We further applied three machine learning methods (decision tree, random forest and extreme gradient boosting) to screen for the risk factors associated with SA-AKI in the total, men and women groups. We finally compared the intensive care unit (ICU) and hospital mortality between men and women with SA-AKI using propensity score matching. Results: A total of 6463 patients were included in our study, including 3673 men and 2790 women. The incidence of SA-AKI was 83.8% for men and 82.1% for women. After adjustment for confounders, no significant association was observed between sex and the incidence of SA-AKI (odds ratio (OR), 1.137; 95% confidence interval (CI), 0.949-1.361; p=0.163). The machine learning results revealed that body mass index, Oxford Acute Severity of Illness Score, diuretic, Acute Physiology Score III and age were the most important risk factors of SA-AKI, irrespective of sex. After propensity score matching, men had similar ICU and hospital mortality to women. Conclusions: The incidence and associated risk factors of SA-AKI are similar between men and women, and men and women with SA-AKI experience comparable rates of ICU and hospital mortality. Therefore, sex-related effects may play a minor role in developing SA-AKI. Our study helps to contribute to the knowledge gap between sex and SA-AKI.

Efficacy of low-dose corticosteroids in patients with acute respiratory distress syndrome: a prospective observational study.

Background: There is still no agreement on whether corticosteroids can reduce mortality in patients with acute respiratory distress syndrome (ARDS). The aim of this study was to investigate the efficacy of low-dose corticosteroid administration in patients with ARDS. Methods: A prospective observational study of patients with ARDS in 17 hospitals in China was performed between March 2016 and February 2018. Propensity score matching was performed to adjust for differences in baseline characteristics between different groups. The effects of corticosteroids were assessed by using the Kaplan-Meier method and a multivariate Cox regression. Results: A total of 527 ARDS patients were enrolled in the study. Sixty-five patients (12.3%) were administered low-dose (methylprednisolone ≤1 mg·kg-1·d-1) corticosteroids. The median dose was equivalent to 0.67 (0.57-0.81) mg/kg methylprednisolone for a median duration of 10 days. The control group included 224 patients (42.5%) who had never receive corticosteroids. In the matched sample, the hospital mortality rates in the low-dose (n=40) and control groups (n=80) were 27.5% and 42.5% (P=0.110), respectively. The length of hospital stay was significantly longer in the low-dose corticosteroid group than in the control group (24.0 vs. 17.0, P=0.002), and the multivariate Cox regression analysis suggested that the low-dose group had a significantly lower risk of death than the control group (HR: 0.48; 95% CI: 0.24-0.97; P=0.040). Conclusions: The administration of low-dose corticosteroids may reduce mortality in patients with ARDS.

Case Report: The Experience of Managing a Moderate ARDS Caused by SARS-CoV-2 Omicron BA.2 Variant in Chongqing, China: Can We Do Better?

Background: The severe coronavirus disease 2019 (COVID-19) pandemic is still raging worldwide, and the Omicron BA.2 variant has become the new circulating epidemic strain. However, our understanding of the Omicron BA.2 variant is still scarce. This report aims to present a case of a moderate acute respiratory distress syndrome (ARDS) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron BA.2 variant and to discuss some management strategies that may benefit this type of case. Case Presentation: A 78-year-old man, who had four negative nucleic acid tests and a fifth positive, was admitted to our hospital. This patient was generally good upon admission and tested negative for anti-SARS-CoV-2 antibodies even after receiving two doses of the COVID-19 vaccine. On the 7th day of hospitalization, he developed a moderate ARDS. Improved inflammatory index and decreased oxygen index were primarily found in this patient, and a series of treatments, including anti-inflammation and oxygen therapies, were used. Then this patient's condition improved soon and reached two negative results of nucleic acid tests on the 18th day of hospitalization. Conclusion: At-home COVID-19 rapid antigen test could be complementary to existing detection methods, and the third booster dose of COVID-19 vaccine may be advocated in the face of the omicron BA.2 variant. Anti-inflammatory and oxygen therapies are still essential treatments for ARDS patients infected with SARS-CoV-2 Omicron BA.2 variant.

CNTN-1 Upregulation Induced by Low-Dose Cisplatin Promotes Malignant Progression of Lung Adenocarcinoma Cells via Activation of Epithelial-Mesenchymal Transition.

Tumor metastasis and invasion are the main impediments to lung adenocarcinoma successful treatment. Previous studies demonstrate that chemotherapeutic agents can elevate the malignancy of cancer cells other than their therapeutic effects. In this study, the effects of transient low-dose cisplatin treatment on the malignant development of lung adenocarcinoma cells (A549) were detected, and the underlying epigenetic mechanisms were investigated. The findings showed that A549 cells exhibited epithelial-mesenchymal transition (EMT)-like phenotype along with malignant progression under the transient low-dose cisplatin treatment. Meanwhile, low-dose cisplatin was found to induce contactin-1 (CNTN-1) upregulation in A549 cells. Subsequently, we found that further overexpressing CNTN-1 in A549 cells obviously activated the EMT process in vitro and in vivo, and caused malignant development of A549 cells in vitro. Taken together, we conclude that low-dose cisplatin can activate the EMT process and resulting malignant progression through upregulating CNTN-1 in A549 cells. The findings provided new evidence that a low concentration of chemotherapeutic agents could facilitate the malignancy of carcinoma cells via activating the EMT process other than their therapeutic effects.