Aim To investigate whether melatonin ( MT) can alleviate endoplasmic reticulum( ER) stress at an early stage of bleomycin( BLM)-induced lung fi-brosis in mice. Methods Adult healthy male ICR mice were divided randomly into control group, MT group, BLM group and MT + BLM group. In MT group, mice had saline treatment 30 minutes after hav-ing the intraperitoneal injection of MT (10 mg·kg-1 ) and had been intraperitoneally injected with MT once in the following every 24 hours. In BLM group, mice were intratracheally injected with a single dose of BLM (5 mg·kg-1). In MT+BLM group, mice had been intraperitoneally injected with BLM 30 minutes after having MT and had been injected with MT once in the following every 24 hours. In control group, mice re-ceived the same level of saline treatment in the same manner. All mice were dissected for collecting the tis-sue of lungs at different time points (24h, 72h) after BLM treatment. Inflammatory cell infiltration of lungs was determined by HE staining. The level of ER stress related proteins ( GRP78 , p-eIF2α, p-IRE1α) in lungs was determined using Western blot. The distribu-tion of ER stress related proteins ( GRP78 , p-IRE1α, ATF6α, p-PERK) in lungs was detected by immuno-histochemistry. Results The model of BLM-induced acute inflammation of lung fibrosis in mice had been successfully constructed. After BLM treatment, lung weight, lung weight ratio and inflammatory cell infiltra-tion were significantly increased with a significant cor-relation between time and effectiveness. After MT treatment, lung weight, lung weight ratio and inflam-matory cell infiltration were significantly reduced. The results of Western blot showed that MT pretreatment not only prevented the increase of BLM-induced GRP78 protein significantly, but also restrained the phosphorylation of eIF2α and IRE1α in mouse lungs. Immunohistochemistry also showed that MT pretreat-ment reduced the expression of GRP78 , p-IRE1α, ATF6α and p-PERK. Conclusion MT alleviates ER stress effectively at an early stage of BLM-induced lung fibrosis in mice.

Objective:To explore the clinical characteristics and prognostic risk factors of severe influenza.Methods:Clinical data of severe influenza patients admitted to the department of respiratory and critical care medicine of the Second Affiliated Hospital of Anhui Medical University from March 2014 to June 2019 were retrospectively analyzed. General information, laboratory test results, and etiological test results of the hospitalization outcomes for survival group and death group during the 28-day follow-up were analyzed using Logistic regression analysis.Results:Among the 37 patients, 29 were males and 8 were females. They aged 25-86 years old with an average of (59.59±15.16) years old. Twenty-one cases had chronic underlying diseases; 28 cases had co-infections, including 6 cases with bacterial infections, 7 cases with fungal infections, 3 case with other pathogens, and 12 cases with mixed infection. Among the 37 patients, 9 died during hospitalization and 5 died within 28-day of discharge. The overall mortality rate was 37.84%. Compared with the survival group, patients in the death group were older (years old: 66.57±3.94 vs. 55.35±14.53), British Thoracic Society's modified pneumonia score (CURB-65 score), acute physiology and chronic health evaluationⅡ(APACHEⅡ) score, neutrophil count, D-dimer, 48-hour C-reactive protein (CRP) and procalcitonin (PCT) were higher [CURB-65 score: 2 (2, 3) vs. 1 (0, 2), APACHEⅡ: 16.00±4.62 vs. 11.00±4.22, neutrophil count (×10 9/L): 8.87 (5.42, 11.33) vs. 3.58 (2.55, 7.13), D-dimer (mg/L): 7.97 (5.19, 12.68) vs. 2.91 (1.19, 5.02), 48-hour CRP (mg/L): 127.83±92.24 vs. 87.01±57.00, 48-hour PCT (μg/L): 1.79 (0.59, 4.44) vs. 0.37 (0.13, 0.99)], oxygenation index (PaO 2/FiO 2) and creatinine clearance rate were lower [PaO 2/FiO 2 (mmHg, 1 mmHg = 0.133 kPa): 109.52±49.30 vs. 204.82±67.61, creatinine clearance rate (mL·min -1·1.73 m -2): 55.49±21.23 vs. 77.59±29.73], and the differences were statistically significant (all P < 0.05). There was no significant difference in gender, combined chronic underlying diseases, lymphocyte count, albumin, lactate dehydrogenase (LDH), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), 24-hour CRP and PCT between the two groups. A total of 37 pathogens were cultured, including 17 Gram-negative bacteria (45.95%), 3 Gram-positive bacteria (8.10%), and 17 fungi (45.95%). The number of Acinetobacter baumannii infections in the death group was significantly higher than that in the survival group (cases: 7 vs. 2, P < 0.05). Logistic regression analysis showed that age, CURB-65 score, APACHEⅡ score, PaO 2/FiO 2, neutrophil count, creatinine clearance rate, combined Acinetobacter baumannii infection, deep vein catheterization, catheterization, and stomach preservation during hospitalization were risk factors for the prognosis of patients with severe influenza [hazard ratios ( HR) were 1.064, 4.920, 1.286, 0.975, 1.286, 0.965, 0.095, 0.083, 9.333, 0.089, respectively, all P < 0.05]. Multivariate analysis showed that low PaO 2/FiO 2 and Acinetobacter baumannii infection were risk factors for prognosis of severe influenza ( HR were 0.834 and 0.000, respectively, both P < 0.05). Conclusion:Old age, high CURB-65 score, high APACHEⅡ score, and co-infection are risk factors for the prognosis of patients with severe influenza.