Background Silica-induced pulmonary fibrosis (silicosis) is a diffuse interstitial fibrotic disease characterized by the massive deposition of extracellular matrix in lung tissue. Fibroblast to myofibroblast differentiation is crucial for the disease progression. Inhibiting myofibroblast differentiation may be an effective way for pulmonary fibrosis treatment. Methods The experiments were conducted in TGF-β treated human lung fibroblasts to induce myofibroblast differentiation in vitro and silica treated mice to induce pulmonary fibrosis in vivo. Results By quantitative mass spectrometry, we revealed that proteins involved in mitochondrial folate metabolism were specifically upregulated during myofibroblast differentiation following TGF-β stimulation. The expression level of proteins in mitochondrial folate pathway, MTHFD2 and SLC25A32, negatively regulated myofibroblast differentiation. Moreover, plasma folate concentration was significantly reduced in patients and mice with silicosis. Folate supplementation elevated the expression of MTHFD2 and SLC25A32, alleviated oxidative stress and effectively suppressed myofibroblast differentiation and silica-induced pulmonary fibrosis in mice. Conclusion Our study suggests that mitochondrial folate pathway regulates myofibroblast differentiation and could serve as a potential target for ameliorating silica-induced pulmonary fibrosis.

Objective This study aims to explore the clinical effect of Tetrandrine (Tet) on progressive massive fibrosis (PMF) of pneumoconiosis. Methods This retrospective study collected 344 pneumoconiosis patients with PMF, and 127 were eligible for the final analysis, including 57 patients in the Tet group and 70 patients in the control group. The progress of imaging and lung function were compared between the two groups. Results After 13 months (median) of treatment, the size of PMF was smaller in the Tet group than that in the control group (1526 vs. 2306, p=0.001), and the size was stable in the Tet group (1568 vs. 1526, p= 0.381), while progressed significantly in the control group (2055 vs. 2306, p=0.000). The small nodule profusion and emphysema were also milder than that in the control group (6.0 vs. 7.5, p=0.046 and 8.0 vs. 12, p=0.016 respectively). Pulmonary ventilation function parameters FVC and FEV1 improved in the Tet group (3222 vs. 3301, p=0.021; 2202 vs. 2259, p=0.025 respectively) and decreased in the control group (3272 vs. 3185, p= 0.00; 2094 vs. 1981, p=0.00 respectively). FEV1/FVC was also significantly higher in the Tet group than that in the control group (68.45vs. 60.74, p=0.001). However, similar result was failed to observed for DLco%, which showed a significant decrease in both groups. Conclusion Tet has shown great potential in the treatment of PMF by slowing the progression of pulmonary fibrosis and the decline of lung function.

Background: Although previous studies have shown that coal dust exposure can lead to decreased lung function, little is known regarding the prevalence of and risk factors for obstructive pulmonary dysfunction (OPD) in Chinese coal workers. The present study investigated the prevalence of and risk factors for OPD in Chinese coal workers. Methods: Health monitoring data were collected from 3534 workers in 8 different state-owned coal mines from January 1, 2021, to June 30, 2022. Ultimately, data from 3450 workers were eligible for analysis. OPD was defined as FEV1/FVC less than 70%. FVC dicline was defined as FVC/Pre less than 80%. High-intensity exposure refers to underground workers who basically work underground all day; correspondingly, low-intensity exposure refers to workers who only work underground for part of the day. Logistic regression analyses were used to analyze the relationships between clinical variables and OPD. The attributable risk percentage for each risk factor was calculated as follows: (（OR-1）/OR)x100%. Results: The overall prevalence of OPD was 2.6%, and the prevalence of FVC decline (FVC/Pre<80%) was 21.8%. The prevalence of OPD was higher in the high-intensity exposure group than in the low-intensity exposure group , higher in the smoking group than in the no smoking group, and higher among workers aged 50 years or older than among those under the age of 50. Risk factors for OPD included age greater than 50 years old, high-intensity exposure, duration of exposure more than 20 years, smoking, and dust concentration exceeding 2 mg/m3. High-intensity exposures were considered to contribute approximately equally to the prevalence of OPD as smoking. Conclusion: Coal dust exposure can lead to OPD. High-intensity exposure, a duration of exposure of more than 20 years, smoking, and dust concentrations exceeding 2 mg/m3 are major risk factors for OPD. Cigarette smoking and coal dust exposure are major preventable risk factors for the disease. Enhancing occupational protection, strengthening smoking control in underground workplaces and regular monitoring of lung function for early detection of abnormal lung function are important for protecting workers' health.