Objective This study aims to investigate the expression, phenotypic changes, and mechanisms of action of guanylate-binding protein 2 (GBP2) in the process of silica-induced pulmonary fibrosis. Methods The expression and localization of GBP2 in silicotic lung tissue were detected by immunohistochemical staining and immunofluorescence. An in vitro cell model was constructed, and methods such as Western blot and real-time quantitative reverse transcription polymerasechain reaction were utilized to investigate the function of GBP2 in different cell lines following silica stimulation. The mechanism of action of GBP2 in various cell lines was elucidated using Western blot analysis. Results GBP2 was highly expressed in the lung tissue of patients with silicosis. Immunohistochemical staining and immunofluorescence have revealed that GBP2 was localized in macrophages and epithelial cells. In vitro cell experiments demonstrated that silicon dioxide stimulated THP-1 cells to activate the c-Jun pathway through GBP2, promoting the secretion of inflammatory factors and facilitating the occurrence of M2 macrophage polarization. In epithelial cells, GBP2 promoted the occurrence of epithelial to mesenchymal transition (EMT) by upregulating Krueppel-like factor 8 (KLF8). Conclusion GBP2 not only activates c-Jun in macrophages to promote the production of inflammatory factors and the occurrence of M2 macrophage polarization, but also activates the transcription factor KLF8 in epithelial cells to induce EMT, collectively promoting the progression of silicosis.
Humans ; Silicosis/genetics* ; Macrophages/cytology* ; Epithelial Cells/pathology* ; GTP-Binding Proteins/physiology* ; Epithelial-Mesenchymal Transition ; Disease Progression ; Cell Line ; Male

BACKGROUND: Indonesia is among countries with a high incidence of multi drug-resistant tuberculosis (MDR-TB) globally. In this study, we aim to determine the prevalence of silico-tuberculosis among TB patients and to investigate the association of radiographic silicosis and the role of drug supervisor as well as other socio-clinical factors, in the development of MDR-TB in Indonesia. METHODS: A hospital-based study in West Java among 148 MDR-TB patients (case) and 164 drug-sensitive/DS-TB patients (control) was conducted. Chest x-rays were evaluated by two radiologists and one NIOSH B reader according to the ILO Classification. Face-to-face interviews were conducted using structured questionnaires to collect patients' information, including the task of drug supervisor. RESULTS: Findings indicate that supportive drug supervisor reduces the risk of developing MDR-TB, but silicosis showed no significant association. Nevertheless, in this study we found that 17 cases (5.4%) had silico-tuberculosis mostly exhibited as ILO profusion 3; predominated by q shape, 52.9% with large opacities and dominated by size A. Other factors significantly associated with the risk of developing MDR-TB were marital status, low income, longer traveling time to hospital, unsuccessful previous treatment and suffering drug side effects. CONCLUSION This study reveals that one of preventive healthcare strategy to protect TB patients from developing MDR-TB is supportive drug supervisor. While, the development of MDR-TB was not significantly influenced by silicosis; however, there is a notable prevalence of silicosis as determined by chest radiography, highlighting the critical need for dust control, occupational hygiene, and health screening for high-risk populations.
Indonesia/epidemiology* ; Humans ; Silicosis/diagnostic imaging* ; Male ; Tuberculosis, Multidrug-Resistant/etiology* ; Middle Aged ; Adult ; Female ; Prevalence ; Risk Factors ; Aged ; Antitubercular Agents/therapeutic use*

OBJECTIVE: Recent studies have overturned the traditional concept of the lung as a "sterile organ" revealing that pulmonary microbiota dysbiosis and abnormal surfactant proteins (SPs) expression are involved in the progression of silicosis. This study aimed to investigate the relationship between abnormal SPs expression and dysbiosis of lung microbiota in silica-induced lung fibrosis, providing insights into mechanisms of silicosis. METHODS: Lung pathology, SPs expression, and microbiota composition were evaluated in silica-exposed mice. A mouse model of antibiotic-induced microbiota depletion was established, and alveolar structure and SPs expression were assessed. The roles of the lung microbiota and SPs in silicosis progression were further evaluated in mice with antibiotic-induced microbiota depletion, both with and without silica exposure. RESULTS: Silica exposure induced lung inflammation and fibrosis, along with increased expression of SP-A expression. Antibiotics (Abx)-induced microbiota depletion elevated SP-A and SP-D expression. Furthermore, silica exposure altered lung microbiota composition, enriching potentially pathogenic taxa. However, antibiotic-induced microbiota depletion prior to silica exposure reduced silica-mediated lung fibrosis and inflammation. CONCLUSION Lung microbiota is associated with silica-induced lung injury. Overproduction of SP-A and SP-D, induced by Abx-induced microbiota depletion, may enhance the resistance of mouse lung tissue to silica-induced injury.
Animals ; Silicosis/prevention & control* ; Lung/metabolism* ; Mice ; Anti-Bacterial Agents/pharmacology* ; Microbiota/drug effects* ; Silicon Dioxide/toxicity* ; Mice, Inbred C57BL ; Male ; Pulmonary Surfactant-Associated Proteins/genetics*

OBJECTIVE: Pneumoconiosis, a lung disease caused by irreversible fibrosis, represents a significant public health burden. This study investigates the causal relationships between gut microbiota, gene methylation, gene expression, protein levels, and pneumoconiosis using a multi-omics approach and Mendelian randomization (MR). METHODS: We analyzed gut microbiota data from MiBioGen and Esteban et al. to assess their potential causal effects on pneumoconiosis subtypes (asbestosis, silicosis, and inorganic pneumoconiosis) using conventional and summary-data-based MR (SMR). Gene methylation and expression data from Genotype-Tissue Expression and eQTLGen, along with protein level data from deCODE and UK Biobank Pharma Proteomics Project, were examined in relation to pneumoconiosis data from FinnGen. To validate our findings, we assessed self-measured gut flora from a pneumoconiosis cohort and performed fine mapping, drug prediction, molecular docking, and Phenome-Wide Association Studies to explore relevant phenotypes of key genes. RESULTS: Three core gut microorganisms were identified: Romboutsia ( OR = 0.249) as a protective factor against silicosis, Pasteurellaceae ( OR = 3.207) and Haemophilus parainfluenzae ( OR = 2.343) as risk factors for inorganic pneumoconiosis. Additionally, mapping and quantitative trait loci analyses revealed that the genes VIM, STX8, and MIF were significantly associated with pneumoconiosis risk. CONCLUSIONS This multi-omics study highlights the associations between gut microbiota and key genes ( VIM, STX8, MIF) with pneumoconiosis, offering insights into potential therapeutic targets and personalized treatment strategies.
Humans ; Male ; East Asian People/genetics* ; Europe ; Gastrointestinal Microbiome ; Lung ; Macrophage Migration-Inhibitory Factors/metabolism* ; Mendelian Randomization Analysis ; Multiomics ; Pneumoconiosis/microbiology* ; Intramolecular Oxidoreductases

Humans ; Nutrition Assessment ; Prognosis ; Silicosis/prevention & control* ; Occupational Diseases ; China/epidemiology* ; Occupational Exposure ; Silicon Dioxide

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

Pulmonary fibrosis is end-stage of variety of heterogeneous interstitial lung disease, characterizedby excessive proliferation of fibroblasts and extracellular matrix deposition and destruction of lung parenchyma. Thyroid and lung are derived from the same endodermal cells, thyroid hormone affect the occurrence、development and prognosis of the chronic obstructive pulmonary disease, lung cancer and other lung diseases, This article reviews the role and mechanism of thyroid hormone in pulmonary fibrosis in order to provide new idea for the study of the role and mechanism of thyroid hormone in silicosis.
Humans ; Pulmonary Fibrosis/pathology* ; Lung/pathology* ; Silicosis ; Lung Diseases, Interstitial ; Fibroblasts ; Thyroid Hormones ; Fibrosis

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

Pneumoconiosis is the largest and most serious disease among the legal occupational diseases in China, which causes long-term heavy disease burden to individuals, enterprises and society. How to scientifically and reasonably measure and reduce the health impact and economic loss caused by pneumoconiosis has become a key and difficult research topic. In recent years, with the development of global burden of disease (GBD) research, some scholars have adopted disease burden index to evaluate the disease burden of pneumoconiosis, but the research results and data are relatively independent, and there is a lack of systematic evaluation system and framework. This paper summarized the application of disease burden assessment index for pneumoconiosis, epidemiological and economic burden of pneumoconiosis, and the cost-effectiveness of reducing the burden. This paper aims to understand the present situation of pneumoconiosis disease burden in our country, discover the problems and challenges of pneumoconiosis disease burden research in our country now. It provides scientific basis for the research and application of pneumoconiosis and other occupational disease burden in China, as well as the formulation of comprehensive intervention measures, optimization of health resources allocation and reduction of disease burden.
Humans ; Pneumoconiosis/epidemiology* ; Occupational Diseases ; China/epidemiology* ; Cost of Illness

Objective: To construct and verify a light-weighted convolutional neural network (CNN), and explore its application value for screening the early stage (subcategory 0/1 and stage Ⅰ of pneumoconiosis) of coal workers' pneumoconiosis (CWP) from digital chest radiography (DR) . Methods: A total of 1225 DR images of coal workers who were examined at an Occupational Disease Prevention and Control Institute in Anhui Province from October 2018 to March 2021 were retrospectively collected. All DR images were collectively diagnosed by 3 radiologists with diagnostic qualifications and gave diagnostic results. There were 692 DR images with small opacity profusion 0/- or 0/0 and 533 DR images with small opacity profusion 0/1 to stage Ⅲ of pneumoconiosis. The original chest radiographs were preprocessed differently to generate four datasets, namely 16-bit grayscale original image set (Origin16), 8-bit grayscale original image set (Origin 8), 16-bit grayscale histogram equalized image set (HE16) and 8-bit grayscale histogram equalized image set (HE8). The light-weighted CNN, ShuffleNet, was applied to train the generated prediction model on the four datasets separately. The performance of the four models for pneumoconiosis prediction was evaluated on a test set containing 130 DR images using measures such as the receiver operating characteristic (ROC) curve, accuracy, sensitivity, specificity, and Youden index. The Kappa consistency test was used to compare the agreement between the model predictions and the physician diagnosed pneumoconiosis results. Results: Origin16 model achieved the highest ROC area under the curve (AUC=0.958), accuracy (92.3%), specificity (92.9%), and Youden index (0.8452) for predicting pneumoconiosis, with a sensitivity of 91.7%. And the highest consistency between identification and physician diagnosis was observed for Origin16 model (Kappa value was 0.845, 95%CI: 0.753-0.937, P<0.001). HE16 model had the highest sensitivity (98.3%) . Conclusion: The light-weighted CNN ShuffleNet model can efficiently identify the early stages of CWP, and its application in the early screening of CWP can effectively improve physicians' work efficiency.
Humans ; Retrospective Studies ; Anthracosis/diagnostic imaging* ; Pneumoconiosis/diagnostic imaging* ; Coal Mining ; Neural Networks, Computer ; Coal