The pathogenesis of pulmonary fibrosis (PF) is complex. It is characterized by myofibroblast hyperplasia and deposition of collagen protein. Indoleamine 2,3-dioxygenase 1 (IDO1) is expressed in lung fibroblasts and epithelial cells, but its functions in lung homeostasis and diseases remain elusive. Here, we characterize the critical role of IDO1 in PF patients and bleomycin (BLM)-induced PF mouse models. We find that IDO1 is significantly upregulated in the fibrotic lungs of patients and mice, showing a positive correlation with genes characteristic of fibrosis. Functionally, IDO1 knockout inhibits lung fibroblast proliferation, differentiation, mitochondrial biogenesis, and mitochondrial oxidative phosphorylation. Conversely, IDO1 overexpression and accumulation of kynurenine (Kyn) exacerbate progressive lung fibrosis. Mechanistically, IDO1-deletion activated profound mitochondrial fusion-enhanced potentially the capacity for fatty acid oxidation, along with activation of de novo glycolytic serine/glycine synthesis pathways and mitochondrial one-carbon metabolism. Wedelolactone (WEL), a small molecule IKK inhibitor, is found to strongly bind to IDO1 and effectively protect mice from PF in an IDO1-dependent manner. Collectively, this study characterizes a promotor role for IDO1 in PF and suggests a potential avenue of targeting IDO1 to treat lung diseases.

Objective To investigate the expression and clinical significance of serum homocysteine (Hcy),galectin-3 (GAL3) and monocyte chemotactic protein-1 (MCP-1) in patients with acute ischemic stroke (ACIS).Methods 100 patients with ACIS in our hospital from January 2016 to February 2018 were selected as the observation group,and 64 healthy persons in our hospital were selected as the control group during the same period.The levels of serum Hcy,GAL3 and MCP-1 were detected and compared between the two groups.The levels of serum Hcy,GAL3 and MCP-1 in patients with different pathological changes,different cerebral infarction areas and different prognosis in the observation group were compared.The correlation between serum Hcy,GAL3 and MCP-1 levels and ACIS cerebral infarction area and neurological deficit scale (NIHSS) was analyzed.The sensitivity,specificity and accuracy of MCP-1 in diagnosing ACIS alone and in combination.Results The levels of serum Hcy,GAL3 and MCP-1 in the observation group were higher than those in the control group (P ＜ 0.05).There were significant differences in serum Hcy,GAL3 and MCP-1 levels between the patients with different pathological degrees of disease (P ＜ 0.05).The level of the above-mentioned indicators in patients with severe injury was higher than that in patients with moderate injury.The patients with moderate injury were higher than those with mild injury (P ＜ 0.05).There were significant differences in serum Hcy,GAL3 and MCP-1 levels in patients with different cerebral infarction areas (P ＜ 0.05),and the above-mentioned index leve1 of patients with large-area infarction was higher than that of patients with moderate-area infarction.The patients with moderate-area infarction were higher than those with small-area infarction (P ＜ 0.05).The levels of serum Hcy,GAL3 and MCP-1 in the dead patients in the observation group were higher than those in the survivors (P ＜ 0.05);correlation analysis showed that serum Hcy,GAL3,MCP-1 levels were positively correlated with ACIS cerebral infract size and NIHSS score (P ＜0.05);the sensitivity (91.00％) and accuracy (83.54％) of combined diagnosis of ACIS were higher than the single-index diagnosis (P ＜ 0.05).Conclusions The levels of serum Hcy,GAL3 and MCP-1 in patients with acute ischemic stroke are highly expressed,and their levels are closely related to the degree of disease,cerebral infarction area and prognosis.The combined detection of Hcy,GAL3 and MCP-1 could improve the accuracy and sensitivity of diagnosis,and could be used as an effective index for clinical diagnosis,condition and prognosis evaluation of acute ischemic stroke.

Objective To understand the clinical distribution of Acinetobacter baumannii and its resistance to antibacterial drugs in order to provide reference for clinical rational drug use in the treatment of Acinetobacter baumannii infection.Methods 162 strains of Acinetobacter baumannii isolated from clinical specimens were collected and performed the statistical analysis on the dis-tribution and the sensitivity to 16 kinds of antibacterial drugs.Results The specimen distribution was dominated by sputum speci-mens(75.3%).The ICU ward had the highest detection rate(49.3%),in which,multidrug resistant strains accounted for 81.2%(65/80);the strains from ICU had the serious multidrug resistance,their resistance rates to 16 kinds of commonly used antibacterial drugs were significantly higher than those the strains isolated from other wards,the difference had statistical significance(P <0.01).The resistance rates of Acinetobacter baumannii to tobramycin,amikacin and cefperazone/sulbactam were relatively lower. Conclusion Strengthening the monitoring of multidrug resistant Acinetobacter baumannii strains and the sterilization and isolation of ICU ward has the important significance to prevent and control nosocomial infection.