Citations

Abstract Metabolic reprogramming is a fundamental determinant of immune cell fate and effector function during inflammation, yet how distinct metabolic pathways regulate pathogenic lung macrophage activity and contribute to fibrotic remodeling remains incompletely understood. Here, we integrated single-cell RNA sequencing, lineage-specific genetic mouse models, and fate-mapping approaches to define the metabolic pathways that regulate the pro-fibrotic activity of lung macrophages. We found that such cells undergo pronounced aerobic glycolysis in the bleomycin-induced mouse model of pulmonary fibrosis. Myeloid cell-specific depletion of lactate dehydrogenase A (Ldha), but not of mitochondrial pyruvate carrier (Mpc), markedly attenuated lung fibrosis and improved survival. Mechanistically, enhanced glycolytic flux increased lactate production, which promoted histone lysine lactylation and facilitated Arginase 1 (Arg1) expression in lung macrophages, thereby driving fibrotic progression. Using monocyte fate-mapping, we further demonstrated that Arg1 expression is largely restricted to recruited monocyte-derived macrophages rather than lung-resident macrophages. Notably, selective deletion of Ldha in granulocyte-monocyte progenitors and their progeny was sufficient to suppress Arg1 expression and reduce fibrosis severity. In human lung samples, we observed significantly elevated expression of ARG1 and key glycolytic enzymes in patients with idiopathic pulmonary fibrosis, despite species-specific differences in the immune cell types expressing ARG1. Together, these findings identify an aerobic glycolysis–lactate–histone lactylation axis that regulates pro-fibrotic myeloid cell function and represents a potential therapeutic target in pulmonary fibrosis.

Abstract BackgroundMany studies have evaluated bundled interventions to improve hand hygiene compliance (HHC). However, the compliance rates remain low. We aimed to use Kotter's change model (KCM) to improve HHC and conduct a complete process evaluation for HHC among medical staff in the intensive care unit (ICU). MethodsKCM was administrated in the ICU of Zhongnan Hospital of Wuhan University from March 2018 to August 2021, and 41-month longitudinal monitoring of HHC was carried out. The primary outcome was the absolute change in monthly HHC. The secondary outcomes included the characteristics of HHC in different phases, the different change trends of HHC for different HH opportunities and occupations, the quarterly incidence of the central line-associated bloodstream infection (CLABSI), and the catheter-associated urinary tract infection (CAUTI).Results. 20,222 HH actions and 24,195 HH opportunities were included in this study. The overall HHC was 83.58% (95%CI, 83.11%-84.04%). After implementing the KCM project, the HHC increased from 35.71% (95%CI, 22.99%-50.83%) to 87.75% (95%CI, 85.53%-89.67%), with an increased rate of 145.73%. The fastest-growing rate of HHC was after contact patients, which increased from 35.29% to 89.8%. Quarterly trends of the CLABSI rate (0‰-3.53‰) and CAUTI rate (0.96‰-4.26‰) remained stable at a low level under the background of the number of cases and the treatment complexities of the patients increasing year by year.ConclusionsUsing KCM can systematically change the cognition of HH in healthcare providers and create an atmosphere to promote HH to improve and maintain the stability of the HHC of healthcare providers in ICU.