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The Pathology Division at the National Institute for Occupational Health (NIOH) provides autopsy services for deceased workers who worked in controlled mines or works under the provisions of the South African Occupational Diseases in Mines and Works Act, 1973 (Act No. 78 of 1973). This report describes the ages, commodities, employment durations, and occupational cardio-respiratory diseases in miners whose organs were submitted for autopsies in 2019 and 2020. Data were exported from the PATHAUT database into STATA for analysis. Differences in the proportions of disease (expressed per 1 000) were calculated using the Pearson's chi-square test; significance was set at p ≤ 0.05. There were 759 and 557 records of deceased miners and ex-miners in 2019 and 2020, respectively. Pulmonary tuberculosis decreased from 192/1 000 in 2019 to 153/1 000 autopsies in 2020, and silicosis decreased from 246/1 000 to 223/1 000. However, neither decrease was significant. There was a significant increase in the rate of asbestosis from 50/1 000 in 2019 to 79/1 000 in 2020. Pulmonary tuberculosis (TB), emphysema, and silicosis were the most frequent diseases, with high rates. There was a non-significant decrease in occupational respiratory disease rates in 2020 from 2019, but these remain higher than the rates seen in the early 1990s. The NIOH continues to conduct autopsy surveillance on miners to support compensation for families, and the development of policy and intervention programmes in the mining industry
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Surveillance in Disasters , Compensation and RedressABSTRACT
By the end of 2021, a total of 915000 cases of occupational pneumoconiosis and 450000 existing cases have been reported nationwide. Silicosis is a common and serious pneumoconiosis disease caused by long-term inhalation of large amounts of free silica dust and extensive nodular fibrosis in the lungs. Because its specific pathogenic mechanism has not been elucidated and the relevant research progress is slow, there is still a lack of effective therapeutic and interventional drugs. With the increase of national attention and the unique advantages of Chinese materia medica in the treatment of silicosis, more and more studies have been conducted on the treatment of silicosis with active ingredients of Chinese materia medica in China, but most of them are still in preclinical research stage. This article mainly introduced the pharmacological action and mechanism of selected active components of Chinese materia medica in the intervention of silicosis from three aspects: anti-inflammation, anti-oxidation, and intervention of apoptosis, providing ideas for subsequent research and development of new drugs for silicosis. This article argues, it is considered that some traditional Chinese medicines must observe the pathological changes in the treatment of silicosis in the overall animal experiment, clarify their pharmacodynamic effects, and further study the multiple targets and pathways involved in them to elucidate their specific mechanisms of action. At the same time, it can strengthen the analysis of active ingredients of traditional Chinese medicine, or modify the structure of active ingredients, and then enhance its pharmacological activity in the treatment of silicosis, realizing the transformation of preclinical research stage to the results of clinical research.
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Silicosis is a diffuse pulmonary fibrosis disease caused by occupational exposure to silica, which is one of the occupational diseases with high incidence in developing countries. Up to now, there is no definite drug to relieve or reverse the lung injury caused by silicosis, so it is very important to prevent, diagnose and treat pulmonary fibrosis as soon as possible. Studies have shown that a chronic inflammatory environment contributes to pulmonary fibrosis to a certain extent. Interleukin-1β is a cytokine that increases the number of inflammatory factors in the microenvironment in the immune response and plays a key role in inflammatory reaction. Therefore, the release of interleukin-1β is of great significance in the pathogenesis of silicosis. This paper aims to systematically expound the development course of silicosis, the signal pathway of interleukin-1β production, and the relationship between them.
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Objective To analyze the epidemiological characteristics of newly diagnosed occupational pneumoconiosis (hereinafter referred to as "pneumoconiosis") in Guangdong Province from 2011 to 2020. Methods Clinical data of newly diagnosed pneumoconiosis in Guangdong Province from 2011 to 2020 was collected from the “Health Hazards Monitoring Information System” under “China Disease Prevention and Control Information System”. The distribution of the cases was analyzed retrospectively. Results A total of 2 731 cases of newly diagnosed pneumoconiosis were reported from 2011 to 2020 in Guangdong Province, with cases at stages Ⅰ,Ⅱ, and Ⅲ accounting for 61.6%, 23.8%, and 14.6%, respectively. Except for talc pneumoconiosis, 12 other types of pneumoconiosis were reported. The top three incidence of diseases were silicosis, other pneumoconiosis, and welder's pneumoconiosis, accounting for 58.8%, 22.0% and 11.0%, respectively. Males accounted for 97.5%, and females 2.5%. The median age of onset was 47 years old. The median dust exposure duration was 9.8 years, with 19.4% of cases having a dust exposure duration less than 5.0 years. And 80.7% of the cases were distributed in the Pearl River Delta region. The industries with the new cases were mainly the manufacturing (accounting for 69.4%), and 34.8% of cases were found in private limited liability companies. Cases in medium- and small-sized enterprises accounted for 35.7% and 34.3% respectively. Conclusion Silicosis, other pneumoconiosis, and welder's pneumoconiosis are predominant in Guangdong Province. The prevention and control of pneumoconiosis should focus on small- and medium-sized private enterprises in the concentrated manufacturing industry in the Pearl River Delta region.
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Objectives To explore and compare the clinical characteristics and risk factors for mortality between patients with artificial quartz stone silicosis and those with classic silicosis. Methods A total of 48 patients with artificial quartz stone silicosis (experiment group) and 98 patients with classic silicosis (control group) were recruited as the research subjects using the convenience sampling method. Data of clinical symptoms, laboratory tests, high-resolution computed tomography (HRCT), and pulmonary pathology of the research subjects were retrospectively analyzed. The Cox proportional hazards regression model was used to analyze the influencing factors on the survival time of silicosis patients. Results Patients in the experiment group had shorter years of dust exposure, latency period and time since last exposure than those in the control group (all P<0.01). The positive rate of anti-nuclear antibodies and the expression of neuron-specific enolase in the experiment group were higher than those in the control group (39.6% vs 10.2%, median： 28.44 vs 16.25, both P<0.01). The PaO2 levels in the experiment group were lower than those in the control group (median： 66.0 vs 89.0, P<0.01). The patients in the experiment group had lower vital capacity, inspiratory reserve volume, forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and carbon monoxide diffusion capacity compared to the control group (all P<0.05), but the maximal expiratory flow in 75% vital capacity was higher than the control group (P<0.05). Compared with the control group, patients in the experiment group had the presence of ground-glass opacity (GGO) in both lungs, aggregation and fusion of subpleural nodules, and gradual formation of progressive massive fibrosis (PMF), with higher potential of pneumothorax. Within 5 years after diagnosis, the mortality of patients in the experiment group was higher than that in the control group (27.1% vs 4.1%, P<0.01). The Cox regression model analysis results showed that patients with nodule aggregation on lung HRCT images had a higher risk of mortality than those without nodule aggregation, and lower lung function including vital capacity, FVC, FEV1 and maximum expiratory flow in 25% vital capacity had higher risk of reduced survival time (all P<0.05). Conclusion Compared with patients with classic silicosis, patients with artificial quartz stone silicosis have higher level of serum neuron-specific enolase, increasing the risk of autoimmune diseases. Pulmonary imaging features in patients with artificial quartz stone silicosis include GGO, PMF and susceptibility to pneumothorax, and rare calcification of mediastinal lymph nodes, leading to a higher mortality rate within 5 years after diagnosis.
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Objective To explore the mechanism of action of curcumin in the treatment of silicosis by network pharmacology combined with molecular docking technology. Methods The targets prediction network of curcumin in treating silicosis was established based on the collection of targets of curcumin and silicosis in multiple databases, cross-targets were submitted to the STRING database, and their connectivity was analyzed by Cytoscape software. Gene ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the top 20 genes. The molecular docking was performed on the key targets to study the mechanism of action of curcumin in treating silicosis. Results A total of 311 targets related to curcumin, 270 targets related to silicosis, and 74 cross-targets were obtained from the databases. GO function analysis revealed 2 665 related pathways, and KEGG pathway enrichment analysis revealed 188 related pathways. Molecular docking results showed that curcumin had good binding ability with the targets of mitogen-activated protein kinase 3 (MAPK3), interleukin (IL) 6, serine/threonine kinase 1 (AKT1), vascular endothelial growth factor A (VEGFA), signal transducer and activator of transcription 3, albumin, Jun proto-oncogene, tumor necrosis factor (TNF), IL1B, tumor protein p53, C-C motif chemokine ligand 2 and fibronectin 1. Conclusion The therapeutical effects of curcumin on silicosis were implemented through multi-targets and multi-pathways. Curcumin may play a role in the treatment of silicosis by binding to the core targets MAPK3, IL6, AKT1, VEGFA and TNF and regulating the MAPK, IL6, TNF, phosphatidylinositol 3-kinase/protein kinase B and VEGF signaling pathways.
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Objective To analyze the distribution, survival conditions, and medical support of newly diagnosed occupational pneumoconiosis (hereinafter referred to as pneumoconiosis) patients in Zhangdian District, Zibo City. Methods A total of 1 189 newly diagnosed pneumoconiosis patients in Zhangdian District from 1956 to 2019 were selected as the study subjects using retrospective method. Data of their age of onset, years of occupational exposure, category of working industry, type of pneumoconiosis, and status of medical support was collected and analyzed. Results The median and the 25th-75th percentiles ［M (P25, P75)］ of the age of onset were 51.8 (45.5, 56.1) years, and the mortality was 37.0%. The majority of pneumoconiosis cases were silicosis (45.2%) and coal workers' pneumoconiosis (39.8%). The highest prevalence of pneumoconiosis was in the coal mining and washing industry (42.4%), followed by manufacturing (33.4%). Pneumoconiosis patients in stage Ⅰ,Ⅱ, and Ⅲ accounted for 89.1%, 8.7%, and 2.2%, respectively. The M (P25, P75) of the length of work exposed to dust were 24.1 (16.5, 29.9) years.The higher stage of pneumoconiosis the shorter of the length of work exposed to dust among these pneumoconiosis patients(all P<0.05). The overall survival rate, the 5-year survival rate and the 10-year survival rate of these pneumoconiosis patients were 63.0%, 92.3% and 85.9%, respectively. Among the 749 surviving cases, 60.8% were aged 60.0 to <80.0 years. In terms of social security, 100.0% surviving cases enjoyed basic medical insurance, meanwhile, 96.1% and 81.8% patients were covered by major medical insurances and occupational injury insurances, respectively. The M (P25, P75) of age at death were 73.1 (64.0, 77.1) years. The main causes of death were respiratory diseases (59.3%) and malignant tumors (20.4%). Conclusion The prevalent types of pneumoconiosis in Zhangdian District, Zibo City, are coal workers' pneumoconiosis and silicosis. Medical support and assistance are relatively limited. The pneumoconiosis prevention and control focus should be on silicosis and coal workers' pneumoconiosis, particularly in the manufacturing industry.
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Objective To analyze the feasibility of using minimally invasive thoracoscopic surgery to treat stage Ⅲ silicosis complicated by pulmonary tuberculosis and secondary pneumothorax. Methods This study retrospectively analyzed the clinical data of a patient with stage Ⅲ silicosis complicated by pulmonary tuberculosis and secondary pneumothorax. Results The patient had stage Ⅲ silicosis complicated with active pulmonary tuberculosis for 1.5 years. In March 2021, a left-sided pneumothorax occurred and was conservatively treated with closed chest drainage. In April 2022, the patient was admitted with sudden frequent coughing and left-sided chest discomfort. Based on occupational history, dust exposure history, high-kilovolt anterior-posterior chest radiography, chest computed tomography, and sputum smear results, the diagnosis was "stage Ⅲ silicosis; active tuberculosis (positive for acid-fast bacilli in sputum smear); left-sided pleural effusion, pulmonary bulla rupture; secondary pneumothorax (recurrent tension type in left, encapsulated in right); left pleural adhesion". On the second day of admission, left-sided closed chest drainage was performed with poor outcome. On the fifth day of admission, minimally invasive thoracoscopic treatment was performed, including left lung volume reduction, pleural adhesion cauterization, and pleural fixation. Postoperative anti-inflammation, anti-tuberculosis, and symptomatic supportive treatments were administered. Due to the patient's severe underlying disease, wound healing was slow postoperatively, but no serious complications occurred. The pneumothorax completely absorbed and recovered in 17.0 days. Conclusion Minimally invasive thoracoscopic surgery is an effective treatment for silicosis complicated with pulmonary tuberculosis and secondary pneumothorax, and it is worth promoting.
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Background The pathogenesis of silicosis is complex and treatment methods are limited. SiO2-induced increase of transforming growth factor-β1 (TGF-β1) can activate fibroblasts to promote collagen deposition, ultimately leading to fibrosis. Previous studies have confirmed that lipid metabolism plays an important role in the progression of silicosis. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) mediates mitochondrial dysfunction and lipid metabolism pathways in diabetic models, but its role in silicosis has not been elucidated. Objective To investigate the effect of PGC1α on lipid metabolism disorder of macrophages induced by SiO2 and its effect on the progression of silicosis fibrosis. Methods (1) Macrophages were divided into four groups by transfecting and silencing PGC1α and its control sequence in macrophages and followed by SiO2 stimulation: negative control group (transfected with si-NC for 48 h), si-PGC1α group (transfected with si-PGC1α for 48 h), SiO2 stimulation group (stimulated with 50 μg·mL−1 SiO2 for 36 h after transfection with si-NC for 48 h), and si-PGC1α+SiO2 group (stimulated with 50 μg·mL−1 SiO2 for 36 h after transfection with si-PGC1α for 48 h). Western blot and cell immunofluorescence were used to test PGC1α expression, 4,4-difluoro-1,3,5,7,8-pentamethyl-4-bora-3a,4a-diaza-s-indacene (BODIPY 493/503) and total cholesterol (TC) and free cholesterol (FC) kits were used to test lipid accumulation, and the Oroboros2k-Oxygraph respiratory test system (O2K) was used to assess the effects of PGC1α on mitochondrial respiratory chain. ELISA kits were used to test TGF-β1 expressed in the macrophage supernatant. (2) Lung fibroblasts were divided into the same four groups as above, and stimulated with the supernatant of macrophages in the above groups. The expression of collagen Ι (COL Ι), E-cadherin (Eca), and fibronectin (FN) were detected by cell immunofluorescence and Western blot to further evaluate the effect of silencing PGC1α on fibrosis. Results The protein expression level of PGC1α stimulated by SiO2 was decreased, and the relative expression level of PGC1α was 0.78 times that of the control group (P<0.05). After transfection with si-PGC1α, the expression of PGC1α was decreased, and the relative protein expression level of the si-PGC1α group was 0.86 times that of the control group (P<0.05). Compared with the SiO2 stimulation group, the staining area of BODIPY 493/503 in the si-PGC1α+SiO2 group was enhanced, and the cholesterol-related indexes [TC, FC and cholesterol ester (CE)] were increased to 1.38, 1.10, and 2.26 times those in the SiO2 stimulation group (P<0.05). The activity of mitochondrial complex Ι was decreased, and the level of complex Ι in the si-PGC1α+SiO2 group was 0.63 times that in the SiO2 stimulation group (P<0.05). The secretion of TGF-β1 by macrophages increased, and the level of TGF-β1 in the si-PGC1α+SiO2 group was 1.15 times that of the SiO2 stimulation group (P<0.05). In addition, after stimulation of primary lung fibroblasts with macrophage supernatant, silencing PGC1α increased the expression levels of COL Ι and FN, while decreased the expression of Eca. The protein levels of COL Ι, FN, and Eca in the si-PGC1α+SiO2 group were 1.39, 1.18, and 0.82 times those in the SiO2 stimulation group, respectively (P<0.05). Conclusion Silencing PGC1α exacerbates SiO2-induced lipid metabolism disorder, inhibits mitochondrial respiratory chain, and aggravates the fibrosis induced by SiO2, suggesting that PGC1α may participate silicosis fibrosis by regulating mitochondrial respiratory chain and lipid metabolic disorder induced by SiO2.
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Background Osteoclast stimulatory transmembrane protein (OC-STAMP) is involved in silicosis fibrosis induced by silicon oxide (SiO2) exposure. Its role in silicosis fibrosis by inducing ferroptosis of alveolar type II epithelial cells and its related mechanism remain unclear. Objective To explore the effect and possible mechanism of OC-STAMP on ferroptosis of alveolar type II epithelial cells and silicosis fibrosis in rats under SiO2 exposure. Methods Twenty male Wistar rats of SPF grade were randomly divided into two groups: control (Sham) group and SiO2 group, 15 rats in each group. Rats in the SiO2 group were given 1 mL of 50 mg·L−1 SiO2 suspension at one time through the non-exposed intratracheal instillation method to establish an animal model of silicosis, and rats in the Sham group were give 1 mL of 0.9% sodium chloride solution in the same way. Rats were sacrificed after 8 weeks. Samples of lung tissue were fixed in glutaraldehyde or paraformaldehyde for observing ultrastructure of mitochondria by transmission electron microscopy; HE, Masson, VG, and Prussian blue were used to observe changes in lung tissue structure and iron deposition. The expression level of OC-STAMP and the degree of lung fibrosis were evaluated by immunohistochemistry and immunofluorescence. The expression level of OC-STAMP in rat lung tissue was detected and the transfection effect of OC-STAMP was verified by real-time fluorescence quantitative polymerase chain reaction (RT-PCR). Overexpression (OCS group) and inhibition expression (SI-OC group) models were constructed by OC-STAMP plasmid and OC-STAMP small interfering RNA (siRNA) transfection to cultured MLE-12 cells, respectively. The relative expression levels of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and other proteins in lung tissue and MLE-12 were detected by Western blotting. Results The results of HE, Masson, and VG staining showed that the silicosis modeling was successful after 8 weeks of SiO2 exposure. The immunofluorescence results showed that OC-STAMP and ATP binding cassette subfamily A member 3 (ABCA3) co-localized in alveolar type II epithelium. The immunohistochemical results showed that the levels of OC-STAMP and collagen I in the SiO2 group were significantly higher than those in the Sham group (P<0.01). The RT-PCR results showed that the OC-STAMP mRNA in the lung tissue of the SiO2 group was significantly higher than that of the Sham group (P<0.01). The Prussian blue staining in the lung tissue of the SiO2 group showed positive brownish-yellow particles. Compared with the Sham group which showed normal mitochondrial structure, the mitochondrial structure was generally swollen and the mitochondrial cristae dissolved and disappeared in the SiO2 group by transmission electron microscope observation. The Western blotting results showed that the expression levels of SLC7A11 and GPX4 both decreased in the lung tissue of the SiO2 group (P<0.05, P<0.01), and the expression level of Vimentin increased (P<0.01). In the transfected MLE-12 cells, compared with the Sham group, the expression levels of SLC7A11 and GPX4 in the OCS group were significantly reduced (P<0.05, P<0.01). Conclusion OC-STAMP may affect the expression of proteins related to ferroptosis, and promote lung fibrosis induced by SiO2 exposure.
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Occupational silicosis features as irreversible pulmonary fibrosis, which is caused by long-term inhalation of free silica dust. The pathogenesis of silicosis is complex and there is no cure at present. Traditional Chinese medicine classifies silicosis fibrosis into the category of diseases as "pulmonary paralysis" and "pulmonary arthralgia", and its treatment is based on promoting blood circulation and activating qi. Traditional Chinese medicine for activating blood circulation is one of the commonly used medications, which has the effects of anti-oxidation, anti-inflammation, anti-fibrosis and immunomodulation, and has broad application prospect in the prevention and treatment of silicosis. At present, animal experiments and clinical studies have been carried out using the single Chinese herbs extracts that could activate blood circulation such as Salvia miltiorrhiza, Ligusticum chuanxiong Hort., Panax notoginseng, Curcuma longa L., peach kernel and Carthamus tinctorius L. as well as their compound herbs for the prevention and treatment of silicosis. The mechanisms of anti-pulmonary fibrosis and the efficacy and safety of treating silicosis and its complications were explored. There are also scholars studying Salvia miltiorrhiza, Curcuma longa L. and Danhong injection, Taohong Siwu Decoction and others for prevention and treatment of pulmonary fibrosis. Additionally, network pharmacological research, analyzing potential targets and pathways, were carried out to provide scientific rationale for prevention and treatment of silicosis. However, the effectiveness of research is still uncertain, and it cannot meet the clinical needs. In the future, it is necessary to explore the application of more high-quality active components of traditional Chinese medicine monomer or mixture of activating blood circulation in the prevention and treatment of silicosis, to provide new ideas and scientific basis for the prevention and treatment of silicosis using traditional Chinese medicine.
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Objective: To analyze the distribution feature of occupational pneumoconiosis in Sichuan Province. Methods: The cases of newly diagnosed occupational pneumoconiosis from 2012 to 2021 in Sichuan Province were collected from the Occupational Diseases and Hazards Monitoring Information System under China Disease Prevention and Control Information System, and were analyzed retrospectively. Results: From 2012 to 2021, there were 30 136 newly diagnosed occupational pneumoconiosis cases in Sichuan Province. The average age of patients was 55.2 years and the median work age was 12.1 years. There were 6 471 cases (accounting for 21.5%) exposed to dust for less than 5.0 years. The number of the cases declined in newly diagnosed occupational pneumoconiosis and occupational pneumoconiosis with less than 5.0 years of dust exposure. The numbers of coal workers' pneumoconiosis and silicosis were 16 210 and 13 577, respectively (accounting for 98.9% of the total cases). The majority of pneumoconiosis cases were classified as stage Ⅰ(accounting for 67.1%). The cases from Leshan City, Bazhong City, Dazhou City, Yibin City, Guangyuan City and Luzhou City accounted for 68.8% of the total cases. The main types of work were coal miner and excavation worker, which accounted for 31.7% and 18.8%, respectively. The scale of enterprises was mostly small and micro, accounting for 35.1% of the cases, and the industry distribution was mostly coal mining and washing, accounting for 53.4% of the cases. Conclusion: In Sichuan Province, the number of cases shows an overall decline in both newly diagnosed occupational pneumoconiosis and occupational pneumoconiosis with less than 5.0 years of dust exposure, with a relatively short duration of occupational exposure. The key cities for pneumoconiosis prevention and control are Leshan City, Bazhong City, and Dazhou City, while the key industry is coal mining and washing.
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Objective: To study the survival time and its risk factors of patients with occupational pneumoconiosis. Methods: A total of 11 011 newly diagnosed occupational pneumoconiosis patients in Guangdong Province from 1980 to 2019 were selected as study subjects. The life table method was used for survival analysis. The influencing factors of survival time of occupational pneumoconiosis patients were analyzed using the WilCoxon (Gehan) test and Cox proportional hazards regression model. Results: The median survival time of pneumoconiosis patients was 26.0 years. The median survival period of stage Ⅰpatients was 3.5 years longer than that of stage Ⅱ patients and 10.1 years longer than that of stage Ⅲ patients. The median survival time of patients with an initial diagnosis age under 40.0 years old was 34.8 years longer than that of patients with an initial diagnosis age over 60.0 years old. The median survival time of patients with dust exposure duration under 25.0 years old was 13.6 years longer than patients with dust exposure duration age over 45.0 years old. The results of the Cox proportional hazards regression model showed that the initial diagnosis stage, initial diagnosis age, dust exposure duration, and medical insurance were risk factors of the survival time of occupational pneumoconiosis patients (all P<0.01). The risk of reduced survival time for patients with stage Ⅱ and stage Ⅲ as the initial diagnosis stage was 1.15 and 2.04 times higher, respectively, compared with stage Ⅰ patients (both P<0.01). The risk of reduced survival time for patients without medical insurance was 60.22 times higher than those with medical insurance (P<0.01). Conclusion: The risk factors of the survival time of occupational pneumoconiosis patients in Guangdong Province are initial diagnosis stage, initial diagnosis age, the dust exposure age, and medical insurance. Earlier detection, earlier diagnosis, and improvement of medical insurance coverage for patients can effectively improve the survival time of occupational pneumoconiosis patients.
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Pneumoconiosis is the most common occupational disease in China, which severely endangers people's health. Depending on the inhaled air pollutants, pneumoconiosis is classified as anthracosis, silicosis, asbestosis, etc., among which silicosis is the most common and serious. Silicosis is a systemic, poor prognostic disease characterized by diffuse fibrosis of lung tissue, which is caused by long-term exposure to dust with high levels of free silicon dioxide (SiO2) in the occupational environment. Appropriate treatment in time is important for the disease. Unfortunately, no effective drugs have been approved to delay or even reverse pulmonary fibrosis caused by SiO2. This review briefly classifies potent therapeutic drugs and compounds in term of mechanisms, providing the probability for clinical treatment of silicosis.
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Silicosis is a common occupational disease caused by long-term inhalation of large amounts of free SiO2 dust and deposition in lung tissues, characterized by the formation of silicon nodules and diffuse fibrosis of lung tissues. Silicosis is one of the most common and serious occupational diseases in China, and its treatment imposes a huge economic burden on individuals and the country. The formation mechanism of silicosis is very complex, and no early screening indicators, effective drugs, and treatment methods are available yet. The current diagnosis of silicosis is based on occupational history and chest radiography findings, and it is irreversible once pulmonary fibrosis develops. Moreover, as silicosis is a continuously progressive disease, even if silicosis patients stop exposure to free SiO2 dust, their pulmonary fibrosis will continue to develop and deteriorate. Programmed cell death (autophagy, apoptosis, ferroptosis, etc.) is a key factor involved in the development of silicosis. This article summarized the important roles of programmed cell death, including autophagy, apoptosis, and ferroptosis, in silicotic fibrosis, and concluded that regulating different programmed cell death and related signaling pathways through effective means may delay the process of silicosis fibrosis, providing new ideas and clues for exploring potential mechanisms of silicosis formation and formulating prevention and treatment strategies.
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Objective: To analyze the epidemiological distribution of new occupational pneumoconiosis (hereinafter referred as pneumoconiosis) in Henan Province from 2006 to 2020. Methods: Clinical data of newly recruited pneumoconiosis cases from 2006 to 2020 in Henan Province were retrospectively analyzed. Results: A total of 9 624 cases of newly diagnosed pneumoconiosis were reported in Henan Province in the past 15 years, of which 98.6% were males. The number of cases had two peaks, one in 2009-2011 and the other in 2014-2017. There were 12 types of pneumoconiosis of all reported cases except for mica pneumoconiosis, in which coal workers' pneumoconiosis and silicosis accounted for 96.0%. The incidence of phase Ⅰ, Ⅱ and Ⅲ pneumoconiosis was 64.7%, 21.0% and 14.3%, respectively. The incidence of phase Ⅱ and Ⅲ silicosis was higher than that of coal miners' pneumoconiosis (56.3% vs 22.7%, P<0.01). Patients with pneumoconiosis were mainly distributed in Zhengzhou City, Sanmenxia City, Luoyang City, Pingdingshan City and Hebi City, accounting for 85.0%. The enterprises involved were mainly mining industry, large- and medium-sized enterprises, state-owned enterprises and collective enterprises. The top five position of patients were coal miners, rock drillers, excavators, coal mixed workers and pure coal miners, total accounting for 72.0%. There were 196 enterprises reported ≥10 cases, accounting for 17.2% of all enterprises and 80.3% of the total of newly diagnosed pneumoconiosis cases. The median (M) of onset age of new cases was 49 years old, and the M of onset of working age was 16 years. The onset age of silicosis was younger (M: 49 vs 48 years old, P<0.05), while the onset of working age was longer (M: 10 vs 20 years, P<0.05), compared with that of coal workers' pneumoconiosis. Conclusion: The incidence of pneumoconiosis in Henan Province were disease clustering distribution, regional distribution, industry of enterprise, enterprise scale, enterprise type, nature and working position distribution of enterprises. And it showed the characteristics of group incidence. The prevention and control treatment of pneumoconiosis should be strengthened in key areas, key enterprises and key diseases and jobs.
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Objective: To investigate the role of surfactant associated protein-A (SP-A) in the development and progression of silicosis, and its mechanism. Methods: Homozygous and heterozygous mice of SP-A knockout of specific pathogen free (SPF) grade were selected for mating, and mice with SP-A-/- genotype were selected for subsequent experiments. SP-A wild-type (SP-A+/+) and SP-A-/- mice were divided into SP-A+/+ control group, SP-A-/- control group, SP-A+/+ silicosis group and SP-A-/- silicosis group with six mice in each group by random number table method. Mice in both silicosis groups were given 20.0 μL 250 g/L silica suspension by tracheal exposure, and mice in both control groups were injected with 0.9% sodium chloride solution at the same volume. On the 28th day after modeling, mice were sacrificed. Lung tissues were used for lung histopathology examination. The apoptosis of alveolar type Ⅱ epithelial cells of mice was detected by TUNEL method. The mRNA expression of B-lymphoblastoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), cysteinyl aspartate specific proteinase (Caspase)-3 and Caspase-9 in lung tissues of mice was detected by quantitative real-time polymerase chain reaction. Results: The histopathological result of mice showed that thickened alveolar septum, scattered silicon nodule and collagen fiber formation were observed in the mice lungs of SP-A+/+ silicosis group, and a large number of inflammatory cells were observed in silicosis nodule, after exposure to silica dust. SP-A-/- silicosis group resulted in a more severe pulmonary inflammation and interstitial fibrosis compared to SP-A+/+ silicosis group. The apoptosis of alveolar type Ⅱ epithelial cells and the mRNA relative expression levels of Bax, Caspase-3 and Caspase-9 in lung tissues of mice in each silicosis groups were increased compared with their control groups (all P<0.05). The above four indexes of mice in SP-A-/- silicosis group were higher than those in SP-A+/+ silicosis group (all P<0.05). There was no significant difference in the expression of Bcl-2 mRNA in lung tissues of these four groups (P>0.05). Conclusion: Knockout of SP-A can aggravate inflammation and pulmonary fibrosis in silicosis model mice, and promote apoptosis of alveolar type Ⅱ epithelial cells. The mechanism may be related to the Bcl-2/Bax/Caspase-3 signaling pathway which affects the apoptosis of mitochondrial pathway.
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Objective: To establish a convenient non-invasive tracheal perfusion method for constructing a mouse model of silicosis-induced pulmonary fibrosis. Methods: The specific pathogen-free C57BL/6 mice were randomly divided into control group and model group, with 15 mice in each group. After anesthesia, a 22G arteriovenous indwelling needle was used to inset into the trachea through the mice's mouth. The model group mice were perfused with 0.1 mL of silica suspension with a mass concentration of 25 g/L, and the mice in the control group were perfused with an equal volume of 0.9% sodium chloride solution. On the 7th, 14th, and 30th day after modeling, the body weight of the mice was measured, and the lung tissue morphology and pathological changes were observed. The expression of α-smooth muscle actin (α-SMA) and collagen type 1 alpha 1 (COL1A1) protein in lung tissue of mice was detected by immunofluorescence on the 30th day after modeling. Results: There was no death of mice in the two groups during the experiment. There was no significant difference in body weight between the two groups (P>0.05). The lung tissues of the mice in the model group were pinkish-gray and uneven in color on the 7th and 14th days after dust exposure. On the 30th day after dust exposure, the lung tissue of the mice in the model group was gray and hard, and unevenly distributed silicon nodules were visible by the naked eyes. The histopathology results of lung tissue showed that compared with the mice in control group, the model group mice exhibited persistent aggravation of pulmonary inflammation, thickening of alveolar septum, infiltration of inflammatory cells gradually clustering into clumps, and an increasing number of fibrous foci.On the 30th day after dust exposure, the relative expression of α-SMA and COL1A1 proteins in the lung of the model group was higher than those in the control group (median： 72.59 vs 5.91, 35.62 vs 10.07, both P<0.05). Conclusion: The method of tracheal perfusion silica suspension of mice using 22G arteriovenous indwelling needle can successfully construct an animal model of silicosis fibrosis. This method is convenient, safe and effective, and is worth promoting.
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Background Pneumoconiosis is the most serious occupational disease in China, and silicosis accounts for about half of it. Any intervention effect of physical exercise as the key and core of lung rehabilitation training on silicosis is still unclear. Objective To explore potential intervention effect of physical exercise on silicotic mice. Methods Forty SPF C57BL/6 male mice were randomly divided into four groups, 10 in each group, including a control group, a physical exercise group, a silicosis model group, and a silicosis model + physical exercise intervention group. Silicotic mouse model was established by using 50 μL SiO2 suspension (200 mg·mL−1). A treadmill was used to prepare mice receiving physical exercise at 0° inclination, 12.3 m·min−1, 60 min·d−1, 5 d·week−1 for 4 weeks. Pathological morphology of lung tissues was evaluated after hematoxylin-eosin (HE) staining; deposition of collagen in lung tissues was evaluated after Van Gieson (VG) staining; expression of p-protein kinase R-like endoplasmic reticulum kinase (PERK) was detected by immunofluorescence staining; expressions of cyclin dependent kinase inhibitors (p21) and p-p38 mitogen activated protein kinase (p38) were detected by immunohistochemistry. The protein expressions of endoplasmic reticulum stress signal factors [p-inositol-requiring enzyme-1α (p-IRE-1α), p-PERK, and p-eukaryotic initiation factor-2α (p-eIF-2α)], senescence signal factors (p-p53, p21, and p16), mitogen-activated protein kinase (MAPK) signal factors [p-p38, p-extracellular regulated protein kinases (p-ERK), and p-stress-activated protein kinase (p-JNK)] were detected by Western blotting. Results After designed acute SiO2 exposure, the images of micro computed tomography (CT) showed high density shadows in lung tissues of the silicotic mice and less shadows in lung tissues of the physical exercise intervention mice. After HE staining, the proportions of silicotic nodule area in lung tissues was (18.67±3.89) % in the silicosis model group, and significantly decreased to (8.78±1.05) % in the silicosis model + physical exercise intervention group (P<0.05). After VG staining, the proportion of collagen fiber area of lung tissues was (10.37±2.18) % in the silicosis model group, and significantly decreased to (4.35±0.89) % in the silicosis model + physical exercise intervention group (P<0.05). The results of immunofluorescence staining showed that in the silicosis model group, the expression of p-PERK increased at the location of silicotic nodules, while in the silicotic model + physical exercise intervention group, the expression of p-PERK decreased. The immunohistochemical staining results showed that the expression of p21 and p-p38 increased in the lung tissues of the silicosis model group; the expression of p21 and p-p38 decreased in the lung tissues of the silicosis model + physical exercise intervention group. The results of Western blotting showed that compared with the control group, the expression levels of p-IRE-1α (0.11±0.03), p-PERK (0.95±0.40), p-eIF-2α (3.53±0.91), p-p53 (1.78±0.07), p21 (1.98±0.10), p16 (1.26±0.17), p-p38 (0.41±0.09), p-ERK (0.42±0.05), and p-JNK (3.20±1.23) of the silicosis model group were all upregulated (P<0.05). Compared with the silicosis model group, the expression levels of p-IRE-1α (0.03±0.01), p-PERK (0.31±0.12), p-eIF-2α (0.30±0.06), p-p53 (0.76±0.08), p21 (0.18±0.11), p16 (0.70±0.24), p-p38 (0.03±0.00), p-ERK (0.19±0.03), and p-JNK (0.46±0.21) of the silicosis model + physical exercise intervention group were downregulated (P<0.05). Conclusion Physical exercise may alleviate pulmonary fibrosis in silicotic mice, and inhibit abnormal expressions of endoplasmic reticulum stress signal, MAPK signal, and senescent signal.
ABSTRACT
In this paper, 177 cases of artificial stone-related silicosis in interior decoration workers from Israel, Spain, USA, Italy and Australia were analyzed. Interior decoration workers were from small businesses (or workshops), engaged in kitchen and/or bathroom artificial stone countertops cutting, grinding, polishing and other reprocessing. In the working environment, the content of crystalline silica in artificial stone was more than 70%, and the concentration of silica dust exceeded the relevant standards. Most workplaces used dry cutting without ventilation and dust removal and other dust-proof measures, and most workers did not wear qualified respiratory protective equipment. Taking comprehensive measures such as wet operation, ventilation and dust removal, and individual protection can effectively prevent the occurrence of artificial stone-related silicosis.