Biological characteristics of molecular subtypes of ulcerative colitis characterized by ferroptosis and neutrophil infiltration.

Clinical ulcerative colitis (UC) is a heterogeneous condition. Moreover, medical interventions are nonspecific, and thus, treatment responses are inconsistent. The aim of this study was to explore the molecular subtypes and biological characteristics of UC based on ferroptosis and neutrophil gene sets. Multiple intestinal mucosa gene expression profiles of UC patients in the Gene Expression Omnibus (GEO) database were downloaded. Unsupervised clustering methods were used to identify potential molecular subtypes based on ferroptosis and neutrophil gene sets. Multiple immune infiltration algorithms were used to evaluate the biological characteristics of the molecular subtypes. Machine learning identifies hub genes for molecular subtypes and analyses their diagnostic efficacy for UC and predictive performance for drug therapy. The relevant conclusions were verified by clinical samples and animal experiments. Four molecular subtypes were identified according to the ferroptosis and neutrophil gene sets: neutrophil, ferroptosis, mixed and quiescent. The subtypes have different biological characteristics and immune infiltration levels. Multiple machine learning methods jointly identified four hub genes (FTH1, AQP9, STEAP3 and STEAP4). Receiver operating characteristic (ROC) curve analysis revealed that the four hub genes could be used as diagnostic markers for UC. The clinical response profile data of infliximab treatment patients showed that AQP9 and STEPA4 were reliable predictors of infliximab treatment response. In human samples the AQP9 and STEAP4 protein were shown to be increased in UC intestinal samples. In animal experiments, the ferroptosis and neutrophil phenotype were confirmed. Dual analysis of ferroptosis and neutrophil gene expression revealed four subgroups of UC patients. The molecular subtype-associated hub genes can be used as diagnostic markers for UC and predict infliximab treatment response.

Efficacy and safety of high-flow oxygen therapy application for chronic obstructive pulmonary disease with acute hypercapnic respiratory failure: A protocol for systematic review and meta-analysis.

BACKGROUND: Presently, there are no reviews or meta-analyses comparing the efficacy and safety of high-flow oxygen therapy (HFOT) and noninvasive ventilation (NIV) as first-line treatment in exacerbated chronic obstructive pulmonary disease (COPD) patients. The present protocol is conceived to evaluate whether HFOT is noninferior to NIV in treatment of patients with COPD and acute hypercapnic respiratory failure. METHODS: We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines and the recommendations of the Cochrane Collaboration to conduct this meta-analysis. Reviewers will search the PubMed, Cochrane Library, Web of Science, and EMBASE online databases using the key phrases "high-flow oxygen therapy," "chronic obstructive pulmonary disease," and "acute hypercapnic respiratory failure" for all English-language cohort studies published up to April, 2021. The cohort studies focusing on assess the efficacy and safety of HFOT and NIV in the treatment of patients with COPD and acute hypercapnic respiratory failure will be included in our meta-analysis. The primary outcome is treatment failure, whereas the secondary outcomes included arterial blood gas analysis, dyspnea score, comfort score, mortality, and total ICU and hospital lengths of stay. RESULTS: The trial is conducted to test the hypothesis that HFOT, administered immediately after extubation, is not inferior to the NIV in reducing the rate of treatment failure in patients with COPD who were previously intubated due to hypercapniac respiratory failure. REGISTRATION NUMBER: 10.17605/OSF.IO/Z2PEJ.