Objective:To investigate the clinical effect of helium-oxygen mechanical ventilation on inflammation of the diseased lung segment and diaphragm function in patients with acute respiratory distress syndrome (ARDS) caused by pneumonia who suffered difficulty weaning from mechanical ventilation.Methods:A prospective controlled study was conducted. A total of 40 patients with ARDS caused by pneumonia and requiring tracheal intubation with difficulty weaning from mechanical ventilation, admitted to the department of critical care medicine in Pingtan Branch of Fujian Medical University Union Hospital from October 2020 to December 2021 were enrolled. Patients were divided into nitrogen oxygen ventilation group and helium-oxygen ventilation group according to random number table, with 20 cases in each group. The nitrogen oxygen ventilation group was given 60% nitrogen and 40% oxygen ventilation treatment, and the helium-oxygen ventilation group was given 60% helium and 40% oxygen ventilation treatment. Peak airway pressure (Ppeak), plateau airway pressure (Pplat), tidal volume (V T), minute ventilation volume (MV) and pulse oxygen saturation (SpO 2) were collected at 0, 1, 2, 3 hours after ventilation treatment. At the same time, the concentrations of inflammatory factors interleukin-6 (IL-6) and C-reactive protein (CRP) in epithelial lining fluid in patients with diseased lung segments were measured before and after ventilation treatment for 3 hours, and the diaphragmatic excursion and the diaphragmatic thickening fraction were measured before and after ventilation treatment for 3 hours. Results:There were no significant differences in gender, age, oxygenation index, serum CRP, serum procalcitonin (PCT), body temperature, serum creatinine (SCr), alanine aminotransferase (ALT), fasting blood glucose (FPG), hemoglobin (Hb), and basic heart and lung diseases between the two groups. Under the condition that V T and SpO 2 are relatively unchanged, the airway pressure in helium-oxygen ventilation group decreased significantly after 1 hour of ventilation [Ppeak (cmH 2O, 1 cmH 2O≈0.098 kPa): 22.80±4.47 vs. 28.00±5.07, Pplat (cmH 2O): 19.15±3.90 vs. 23.20±3.81, both P < 0.05], and the airway pressure in the nitrogen oxygen ventilation group increased significantly after 1 hour [Ppeak (cmH 2O): 22.35±2.13 vs. 19.75±1.94, Pplat (cmH 2O): 18.50±1.70 vs. 16.50±1.88, both P < 0.05]. There were no significant differences in CRP and IL-6 levels in epithelial lining fluid in the diseased lung segment before and after ventilation in the nitrogen oxygen ventilation group, while the levels of these indexes in the helium-oxygen ventilation group after ventilation were significantly lower than those before ventilation, and significantly lower than those in the nitrogen oxygen ventilation group [CRP (mg/L): 10.15 (6.39, 15.84) vs. 16.10 (11.63, 18.66), IL-6 (μg/L): 1.15 (0.78, 1.86) vs. 2.67 (1.67, 4.85), both P < 0.05]. There were no statistically significant differences in the diaphragmatic excursion and the diaphragmatic thickening fraction before and after ventilation in the nitrogen oxygen ventilation group, while the above indexes in the helium-oxygen ventilation group were significantly higher than those before ventilation, and were significantly higher than those in the nitrogen oxygen ventilation group [diaphragmatic excursion (cm): 1.93 (1.69, 2.20) vs. 1.34 (1.22, 1.83), diaphragmatic thickening fraction: (48.22±8.61)% vs. (33.29±11.04)%, both P < 0.05]. Conclusion:Helium-oxygen ventilation can reduce the airway pressure of patients with mechanical ventilation, alleviate the inflammatory response of lung segment, improve the function of respiratory muscle, and is expected to be an important treatment for severe lung rehabilitation.