BACKGROUND: Currently, a significant number of miners are involved in mining operations at the Gejiu tin mine in Yunnan. This occupational setting is associated with exposure to dust particles, heavy metals, polycyclic aromatic hydrocarbons, and radioactive radon, thereby significantly elevating the risk of lung cancer. This study aims to investigate the involvement of leptin-mediated extracellular regulated protein kinase (ERK) signaling pathway in the malignant transformation of rat alveolar type II epithelial cells induced by Yunnan tin mine dust. METHODS: Immortalized rat alveolar cells type II (RLE-6TN) cells were infected with Yunnan tin mine dust at a concentration of 200 μg/mL for nine consecutive generations to establish the infected cell model, which was named R₂₀₀ cells. The cells were cultured normally, named as R cells. The expression of leptin receptor in both cell groups was detected using the Western blot method. The optimal concentration of leptin and mitogen-activated protein kinase kinase (MEK) inhibitor (U0126) on R₂₀₀ cells was determined using the MTT method. Starting from the 20th generation, the cells in the R group were co-cultured with leptin, while the cells in the R₂₀₀ group were co-cultured with the MEK inhibitor U0126. The morphological alterations of the cells in each group were visualized utilizing hematoxylin-eosin staining. Additionally, concanavalin A (ConA) was utilized to detect any morphological differences, and an anchorage-independent growth assay was conducted to assess the malignant transformation of the cells. The changes in the ERK signaling pathway in epithelial cells after the action of leptin were detected using the Western blot method. RESULTS: Both the cells in the R group and R₂₀₀ group express leptin receptor OB-R. Compared to the R₂₀₀ group, the concentration of leptin at 100 ng/mL shows the most significant pro-proliferation effect. The proliferation of R₂₀₀ cells infected with the virus is inhibited by 30 μmol/L U0126, and a statistically significant divergence was seen when compared to the control group (P<0.05). Starting from the 25th generation, the cell morphology of the leptin-induced R₂₀₀ group (R₂₀₀L group) underwent changes, leading to malignant transformation observed at the 30th generation. The characteristics of malignant transformation became evident by the 40th generation in the R₂₀₀L group. In contrast, the other groups showed agglutination of P40 cells, and the speed of cell aggregation increased with an increase in ConA concentration. Notably, the R₂₀₀L group exhibited faster cell aggregation compared to the U0126-induced R₂₀₀ (R₂₀₀LU) group. Additionally, the cells in the R₂₀₀L group were capable of forming clones starting from P30, with a colony formation rate of 2.25‰±0.5‰. However, no clonal colonies were observed in the R₂₀₀LU group and R₂₀₀ group. The expression of phosphorylated extracellular signal-regulated kinase (pERK) was enhanced in cells of the R₂₀₀L group. However, when the cells in the R₂₀₀L group were treated with U0126, a blocking agent, the phosphorylation level of pERK decreased. CONCLUSIONS Leptin can promote the malignant transformation of lung epithelial cells infected by mine dust, and the ERK signaling pathway may be necessary for the transformation of alveolar type II epithelial cells induced by Yunnan tin mine dust.
Rats ; Animals ; Alveolar Epithelial Cells/pathology* ; Dust ; Tin/adverse effects* ; Lung Neoplasms/pathology* ; Leptin/adverse effects* ; Receptors, Leptin ; China ; Signal Transduction ; Epithelial Cells/pathology* ; Mitogen-Activated Protein Kinase Kinases/adverse effects*

OBJECTIVES: The phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is one of the main signaling pathways related to autophagy. Autophagy plays a key role in the formation of silicosis fibrosis. The phenotypic transformation of lung fibroblasts into myofibroblasts is a hallmark of the transition from the inflammatory phase to the fibrotic phase in silicosis. This study aims to investigate whether the PI3K/Akt/mTOR pathway affects the phenotypic transformation of silicosis-induced lung fibroblasts into myofibroblasts via mediating macrophage autophagy. METHODS: The human monocytic leukemia cell line THP-1 cells were differentiated into macrophages by treating with 100 ng/mL of phorbol ester for 24 h. Macrophages were exposed to different concentrations (0, 25, 50, 100, 200, 400 μg/mL) and different times (0, 6, 12, 24, 48 h) of SiO₂ dust suspension. The survival rate of macrophages was measured by cell counting kit-8 (CCK-8) method. Enzyme linked immunosorbent assay (ELISA) was used to measure the contents of transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) in the cell supernatant. The co-culture system of macrophages and HFL-1 cells was established by transwell. A blank control group, a SiO₂ group, a LY294002 group, a SC79 group, a LY294002+SiO₂ group, and a SC79+SiO₂ group were set up in this experiment. Macrophages in the LY294002+SiO₂ group were pretreated with LY294002 (PI3K inhibitor) for 18 hours, and macrophages in the SC79+SiO₂ group were pretreated with SC79 (Akt activator) for 24 hours, and then exposed to SiO₂ (100 μg/mL) dust suspension for 12 hours. The expression of microtubule-associated protein 1 light chain 3 (LC3) protein in macrophages was detected by the immunofluorescence method. The protein expressions of PI3K, Akt, mTOR, Beclin-1, LC3 in macrophages, and collagen III (Col III), α-smooth muscle actin (α-SMA), fibronectin (FN), matrix metalloproteinase-1 (MMP-1), tissue metalloproteinase inhibitor-1 (TIMP-1) in HFL-1 cells were measured by Western blotting. RESULTS: After the macrophages were exposed to SiO₂ dust suspension of different concentrations for 12 h, the survival rates of macrophages were gradually decreased with the increase of SiO₂ concentration. Compared with the 0 μg/mL group, the survival rates of macrophages in the 100, 200, and 400 μg/mL groups were significantly decreased, and the concentrations of TGF-β1 and TNF-α in the cell supernatant were obviously increased (all P<0.05). When 100 μg/mL SiO₂ dust suspension was applied to macrophages, the survival rates of macrophages were decreased with the prolonged exposure time. Compared with the 0 h group, the survival rates of macrophages were significantly decreased (all P<0.05), the concentrations of TGF-β1 and TNF-α in the cell supernatant were significantly increased, and the protein expression levels of Beclin-1 and LC3II were increased markedly in the 6, 12, 24, and 48 h groups (all P<0.05). Immunofluorescence results demonstrated that after exposure to SiO₂ (100 μg/mL) dust for 12 h, LC3 exhibited punctate aggregation and significantly higher fluorescence intensity compared to the blank control group (P<0.05). Compared with the blank control group, the protein expressions of Col III, FN, α-SMA, MMP-1, and TIMP-1 in HFL-1 cells were up-regulated in the SiO₂ group (all P<0.05). Compared with the SiO₂ group, the protein expressions of PI3K, Akt, and mTOR were down-regulated and the protein expressions of LC3II and Beclin-1 were up-regulated in macrophages (all P<0.05), the contents of TNF-α and TGF-β1 in the cell supernatant were decreased (both P<0.01), and the protein expressions of Col III, FN, α-SMA, MMP-1, and TIMP-1 in HFL-1 cells were down-regulated (all P<0.05) in the LY294002+SiO₂ group. Compared with the SiO₂ group, the protein expressions of PI3K, Akt, and mTOR were up-regulated and the protein expressions of LC3II and Beclin-1 were down-regulated in macrophages (all P<0.05), the contents of TNF-α and TGF-β1 in the cell supernatant were increased (both P<0.01), and the protein expressions of Col III, FN, α-SMA, MMP-1, and TIMP-1 in HFL-1 cells were up-regulated (all P<0.05) in the SC79+SiO₂ group. CONCLUSIONS Silica dust exposure inhibits the PI3K/Akt/mTOR pathway, increases autophagy and concentration of inflammatory factors in macrophages, and promotes the phenotype transformation of HFL-1 cells into myofibroblasts. The regulation of the PI3K/Akt/mTOR pathway can affect the autophagy induction and the concentration of inflammatory factors of macrophages by silica dust exposure, and then affect the phenotype transformation of HFL-1 cells into myofibroblasts induced by silica dust exposure.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Transforming Growth Factor beta1/metabolism* ; Silicon Dioxide/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Matrix Metalloproteinase 1/metabolism* ; Tissue Inhibitor of Metalloproteinase-1 ; Sirolimus ; Beclin-1/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Dust ; TOR Serine-Threonine Kinases/metabolism* ; Lung/metabolism* ; Fibroblasts/metabolism* ; Silicosis/metabolism* ; Macrophages/metabolism* ; Autophagy

Objective: Differential flora and differential metabolites shared by the intestinal and respiratory tracts of rats were screened to analyze the possible role of changes in intestinal flora and metabolites in the progression of pneumoconiosis in rats. Methods: In April 2020, 18 SD rats were randomly divided into three groups (control group, coal mine dust group and silica group, 6 in each group) , rats in the coal mine dust group and silica group were perfused with 1 ml of 50 mg/ml coal mine well dust suspension and silica suspension by nontracheal exposure, respectively. While rats in the control group were perfused with an equal dose of sterilized normal saline. Twenty four weeks after dust staining, rat feces, throat swabs, and lung lavages were collected. 16SrDNA gene sequencing and UHPLC-QTOF-MS untargeted metabolomics were used to analyze the flora and metabolites in feces, throat swabs and lung lavage fluid of rats in each group, to screen for shared differential flora and shared differential metabolites in intestinal and respiratory tract, and the correlation analysis between the differential flora and metabolites was performed using Spearman's statistics. Results: Compared with the control group, a total of 9 species shared differential flora between intestinal and respiratory tract were screened at phylum level, and a total of 9 species shared differential genus between intestinal and respiratory tract were screened at genus level in the coal mine dust group, mainly Firmicutes, Actinobacteria, Streptococcus, Lactobacillus, etc. Compared with the control group, a total of 9 shared differential flora were screened at the phylum level, and a total of 5 shared differential genus were screened at the genus level in the silica group, mainly Proteobacteria, Actinobacteria, Allobactera, Mucilaginibacter, etc. Compared with the control group, a total of 7 shared differential metabolites were screened for up-regulation of Stigmatellin, Linalool oxide and Isoleucine-leucine in both intestinal and respiratory tract in the coal mine dust group. Compared with the control group , a total of 19 shared differential metabolites werescreened in the silica group, of which Diethanolamine, 1-Aminocyclopropanecarboxylic acid, Isoleucine-leucine, Sphingosine, Palmitic acid, D-sphinganine, 1, 2-dioleoyl-sn-glycero-3-phosphatidylcholine, and 1-Stearoyl-2-oleoyl-sn-glycerol 3-phosphocholine were up-regulated in both the intestinal and respiratory tract. Conclusion: There is a translocation of intestinal and respiratory flora in pneumoconiosis rats, and rats have an imbalance of lipid metabolism during the progression of pneumoconiosis.
Rats ; Animals ; Isoleucine ; Leucine ; Coal Mining ; Rats, Sprague-Dawley ; Pneumoconiosis ; Dust/analysis* ; Silicon Dioxide ; Coal

Objective: To explore the influencing factors of abnormal pulmonary function in dust-exposed workers and establish the risk prediction model of abnormal pulmonary function. Methods: In April 2021, a total of 4255 dust exposed workers from 47 enterprises in 2020 were included in the study. logistic regression was used to analyze the influencing factors of abnormal pulmonary function in dust-exposed workers, and the corresponding nomogram prediction model was established. The model was evaluated by ROC curve, Calibrationpolt and decision analysis curve. Results: logistic regression analysis showed that age (OR=1.03, 95%CI=1.02~1.05, P<0.001) , physical examination type (OR=4.52, 95%CI=1.69~12.10, P=0.003) , dust type (Comparison with coal dust, Cement dust, OR=3.45, 95%CI=1.45~8.18, P=0.005, Silica dust (OR=2.25, 95%CI=1.01~5.03, P=0.049) , blood pressure (OR=1.63, 95%CI=1.22~2.18, P=0.001) , creatinine (OR=0.08, 95%CI=0.05~0.12, P<0.001) , daily exposure time (OR=1.06, 95%CI=1.10~1.12, P=0.034) and total dust concentration (OR=1.29, 95%CI=1.08~1.54, P=0.005) were the influencing factors of abnormal pulmonary function. The area under the ROC curve of risk prediction nomogram model was 0.764. The results of decision analysis curve showed that the nomogram model had reference value in the prevention and intervention of abnormal pulmonary function when the threshold probability exceeded 0.05. Conclusion: The accuracy ofthe nomogram model constructed by logistic regression werewell in predicting the risk of abnormal lung function of dust-exposed workers.
Humans ; Dust/analysis* ; Lung ; Nomograms ; Risk Factors ; ROC Curve

Welding operations are widely present in the manufacturing production process, involving a large number of occupational groups, and are the key occupations where work injuries and occupational diseases occur in China. For different welding processes and welding materials, the content and focus of occupational health monitoring are different. At present, the item of occupational health examination in welding operation is in poor consistency with the on-site exposure of occupational hazard factors, and it is mainly concentrated in the stage of disease development, which can not reflect the early health damage caused by welding dust exposure in time. The emergence of biomarkers of welding dust can make up for this defect. Therefore, it is of great significance to describe the current situation of occupational health monitoring of welding dust and summarize the research progress of related biomarkers for the early prevention of diseases caused by welding dust and the practice of occupational health monitoring.
Occupational Health ; Welding ; Occupational Exposure/analysis* ; Dust/analysis* ; Biomarkers ; Air Pollutants, Occupational/analysis*

Objective: In order to understand the dust concentration in the workplace of dust exposure enterprises in Shenxian. To evaluate the degree of occupational hazard factors of dust exposure enterprises. And provide basis for the formulation of occupational protection standards and management system of dust exposure enterprises. Methods: In February 2022, the dust concentration monitoring data of 89 dust exposure enterprises from 2017 to 2020 by the Shenxian Center for Disease Control and Prevention were collected, and the qualified rates of dust concentration detection of dust exposure enterprises in different years, dust types and enterprise sizes were analyzed. Results: A total of 89 dust enterprises were monitored from 2017 to 2020, 2132 dust samples were collected, and 1818 qualified samples were taken, with a total qualified rate of 85.3%. From 2017 to 2020, the dust detection qualified rates showed a year-by-year increase trend, 78.7% (447/568), 84.1% (471/560), 88.6% (418/472) and 90.6% (482/532), respectively, with statistically significant differences (χ(2)=36.27, P=0.003). The differences in the qualified rates of dust detection samples of silicon dust (66.1%, 41/62), grain dust (86.7%, 1549/1786), cotton dust (84.1%, 106/126) and wood dust (77.2%, 122/158) were statistically significant (χ(2)=29.66, P=0.002). The qualified rate of dust samples in large and medium-sized enterprises (95.1%, 1194/1256) was higher than that of small-sized enterprises (71.2%, 624/876), and the difference was statistically significant (χ(2)=1584.40, P=0.001) . Conclusion: The qualified rate of dust concentration monitoring results of dust exposure enterprises in Shenxian showed an increase trend year by year, while the pualified rate of dust concentration monitoring in small-sized enterprises was low, and the occupational hazard of silica dust was still severe.
Dust ; Silicon ; Wood ; Workplace

Objective: To analyze the clinical and imaging characteristics of stage Ⅰ occupational cement pneumoconiosis patients. Methods: In October 2021, the data of patients with occupational cement pneumoconiosis diagnosed by the Third Hospital of Peking University from 2014 to 2020 were collected, and the data of the patients' initial exposure age, dust exposure duration, diagnosis age, incubation period, chest X-ray findings, lung function and other data were analyzed retrospectively. Spearman grade correlation was used for correlation analysis of grade count data. The influencing factors of lung function were analyzed by binary logistic regression. Results: A total of 107 patients were enrolled in the study. There were 80 male patients and 27 female patients. The inital exposure age was (26.2±7.7) years, the diagnosis age was (59.4±7.9) years, the dust exposure duration was (17.9±8.0) years, and the incubation period was (33.1±10.3) years. The initial dust exposure age and the dust exposure duration in female patients were less than those in men, and the incubation period was longer than that in men (P<0.05). The imaging analysis showed the small opacities as"pp"accounted for 54.2%. 82 patients (76.6%) had small opacities distributed in two lung areas. The lung areas distribution of small opacities in female patients was less than that in male patients (2.04±0.19 vs 2.41±0.69, P<0.001). There were 57 cases of normal pulmonary function, 41 cases of mild abnormality and 9 cases of moderate abnormality. The number of lung regions with small opacities on X-ray was the risk factor for abnormal lung function in cement pneumoconiosis patients (OR=2.491, 95%CI=1.197-5.183, P=0.015) . Conclusion: The patients with occupational cement pneumoconiosis had long dust exposure duration and incubation period, light imaging changes and pulmonary function damage. The abnormal lung function was related to the range of pulmonary involvement.
Humans ; Female ; Male ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Retrospective Studies ; Pneumoconiosis ; Dust ; Hospitals ; Image Processing, Computer-Assisted

Humans ; Coal ; Dust/analysis* ; Anthracosis ; China/epidemiology* ; Coal Mining ; Occupational Exposure

Objective:To investigate the value of nasal provocation test（NPT） in evaluating the efficacy of allergen immunotherapy（AIT） in patients with dust mite induced allergic rhinitis（AR）. Methods:A total of 83 patients with dust mite induced AR with/without asthma were included. Symptom score（SS）, daily medication score（DMS）, combined symptom and medication score（CSMS）, rhinoconjunctivitis quality of life questionnaire（RQLQ）, NPT and skin prick test（SPT） were assessed before and after 1 year AIT. Results:There were statistical differences in SS（P<0.000 1）, DMS（P<0.000 1）, CSMS（P<0.000 1）, and RQLQ（P<0.000 1） after 1 year of AIT compared with pre-treatment. The effective rate of CSMS was 73.49%, and the effective rate of NPT was 42.17%. CSMS was consistent with NPT in efficacy assessment（Kappa=0.437, P<0.001）; while in 54 patients with pre-treatment NPT concentrations other than the original concentration, CMSM and NPT showed better consistence（Kappa=0.895, P<0.001）. Among the 48 patients with ineffective NPT assessment in the first year, 25 patients completed the second-year follow-up, and 12 patients（48.00%） showed effective in NPT. However, 10 out of 12 patients（83.33%） with NPT concentration other than original solution pre-treatment showed effective NPT at the second year. Conclusion:NPT can be used as one of the indicators for efficacy evaluation for dust mite induced AR patients, especially for patients with positive NPT induced at lower concentrations before treatment.
Animals ; Humans ; Pyroglyphidae ; Allergens ; Nasal Provocation Tests ; Quality of Life ; Rhinitis, Allergic/therapy* ; Desensitization, Immunologic ; Skin Tests ; Dust

Objective: To understand the exposure level of dust and noise in the mining industry and provide data support for revising policy for the prevention and control of occupational diseases. Methods: In May 2022, Data was collected through the National Surveillance Program for Occupational Hazards in the Workplace. Descriptive analysis was conducted for dust and noise levels by industry type and enterprise size from 7, 679 enterprises in the mining industry among 29 provincial regions nationwide. Results: The enterprises in the mining industry included in the National Surveillance Program for Occupational Hazards in the Workplace are mainly small and micro, accounting for 47.97% (3684/7679) and 30.00% (230/7679) respectively. The industry is mainly compred of employers in the non-metallic ming and beneficiation industry, accounting for 50.25% (3859/7679). Among the enterprises with silica dust, coal dust, and noise hazards, the proportion of enterprises where total dust concentration and noise intensity exceed the standard is higher than 50%. 30% of the posts are with an exposure level of silica dust, coal dust, and noise that exceeds the standard. The exceedance rate and the median of the time-weighted average concentration of total coal dust among large and medium-sized enterprises are higher than those among small and micro-sized enterprises (P<0.05) . Conclusion: The dust and noise hazards in the mining industry are lower than in the past in China, but more than 25% of workers are still at a high risk of occupational pneumoconiosis and noise deafness. Therefore, intervention and surveillance strategies should be strengthened in the future.
Humans ; Dust/analysis* ; Occupational Exposure/analysis* ; Occupational Health ; Coal ; Silicon Dioxide/analysis* ; Coal Mining