Silicosis, caused by inhalation of crystalline silica (SiO2), remains a serious and persistent public health concern. Puerarin (Pue), a bioactive isoflavone derived from Pueraria lobata, is known for its anti-inflammatory and antioxidant properties; however, its protective effects and underlying mechanisms in silicosis have not been fully elucidated. In this study, alveolar type II (AT2) cells and male C57BL/6 J mice were used to investigate the anti-aging and anti-fibrotic effects of Pue and Pue-enriched Pueraria lobata tea (Plt) in experimental silicosis. Transcriptomic and molecular analyses revealed that SiO2 exposure induced epithelial-mesenchymal transition (EMT) and cellular senescence in AT2 cells, accompanied by mitochondrial DNA (mtDNA) leakage into the cytoplasm and activation of the cGAS-STING signaling pathway. Pharmacological inhibition of mtDNA transcription and replication attenuated mtDNA leakage, thereby alleviating AT2 cell senescence and EMT. Notably, Pue significantly reduced senescence and EMT by suppressing mtDNA leakage in SiO2-exposed AT2 cells. Consistently, both Pue and Pue-enriched Plt ameliorated pulmonary aging and fibrosis in SiO2-inhaled C57BL/6 J mice. Collectively, these findings suggest that Pue and Plt alleviate SiO2-induced pulmonary fibrosis by mitigating mtDNA leakage-induced senescence and EMT, highlighting a potential preventive and interventional strategy based on natural bioactive compounds for SiO2-induced pulmonary fibrosis.

Silicosis is a progressive occupational lung disease caused by the inhalation of crystalline silica (SiO₂), for which no effective therapy currently exists, making it a persistent global health burden. This study aimed to investigate the mechanisms through which inorganic arsenic (iAs) mitigates silica-induced pulmonary inflammation and fibrosis. Utilizing a combination of male C57BL/6J mice, NIH/3T3 mouse lung fibroblasts, and MH-S alveolar macrophages, we demonstrated that iAs administration markedly attenuated SiO₂-induced pulmonary fibrosis and inflammatory responses, as evidenced by microCT imaging, Masson’s trichrome and H E staining, and RT-qPCR analysis. In vitro, iAs suppressed the transforming growth factor-β (TGF-β)-induced myofibroblastic transition of NIH/3T3 cells. In MH-S macrophages, SiO₂ exposure promoted M1-type polarization, upregulating the expression of inducible nitric oxide synthase (iNos) and proinflammatory cytokines (Mcp-1, Mip-2, Tnf-α, Il-1β), alongside M2-associated cytokines (Il-10, Tgf-β); these effects were counteracted by iAs pretreatment. Further analysis revealed that iAs restored autophagolysosomal function by alleviating SiO₂-induced blockade of autophagic flux, impairment of autophagosome-lysosome fusion, and increased lysosomal membrane permeability (LMP). Our findings highlight the therapeutic potential of iAs in silicosis, likely mediated through the preservation of autophagolysosomal homeostasis, thereby providing new insights into the pathogenesis and treatment of this disease.

OBJECTIVE:This study aims to establish machine learning models using nonimaging data from health examinations of coal workers, which can screen the preclinical stage of coal workers' pneumoconiosis (CWP). METHODS:Nonimaging data from two centers, totaling 34,362 coal miners, were collected. From 84 initial variables, 19 were preliminarily screened, and LASSO selected eight key features. Six machine learning models were trained to predict the preclinical stage of CWP, evaluated using ROC curve. RESULTS:In the internal test set, GB achieved the best discrimination (AUC 88.19%), while DT yielded the highest accuracy (81.09%) and specificity (80.90%). In the external validation set, GB remained the top model by AUC (83.94%) and showed high sensitivity (87.67%). CONCLUSIONS:Age, FEV1, FEV1%, drinking status, smoking status, FVC, occupational category, and cumulative years of service are significant features for predicting the preclinical stage of CWP.

Bisphenol S (BPS) poses potential risks to the reproductive system, but its effects during pre-sexual maturity on follicle development and its underlying mechanisms remain unclear. This study aimed to investigate the association between pre-sexual BPS exposure and follicular dysplasia, as well as to decipher the molecular mechanisms involved. Urine samples from females aged 3-16 years were first analyzed, revealing a 95.7% detection rate of BPS, with a geometric mean concentration of 51.74 ng/L. Furthermore, the pre-sexual rat model revealed that BPS (0.05, 5, and 250 mg/kg body weight/day) revealed that BPS exposure impaired follicle development (reducing ovarian reserve and increasing abnormal follicles) through mediating granulosa cell death. In vitro experiments with granulosa cells showed that BPS exposure upregulated the expression of the cathepsin family (CTSL, CTSD, and CTSB), thereby activating the caspase 3 apoptotic pathway. CTSL knockdown further confirmed its critical role as a mediator of BPS induced granulosa cell death. These results demonstrate that BPS exposure impairs follicle development via CTSL mediated granulosa cell death, providing novel mechanistic insights into environmental pollutant induced female reproductive dysfunction.

BACKGROUND:Silicosis is an occupational lung disease characterized by silicotic nodules and progressive pulmonary fibrosis, caused by long-term excessive inhalation of free silica. So far, no effective methods have been developed to delay or cure silicotic fibrosis. Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-Exos), which possess functions of intercellular communication, tissue repair and regeneration, offering a potential strategy for the treatment of silicosis. METHODS AND RESULTS:In this study, exosomes were extracted from human umbilical cord mesenchymal stem cells (huc-MSCs) using differential centrifugation and characterized for subsequent experiments. A silica-induced silicosis mouse model was established. Lung CT scans were performed to assess pulmonary lesions, while blood oxygenation status was monitored. Histopathological analysis of lung tissues was conducted, and Western blot was used to evaluate inflammatory and fibrotic markers, aiming to investigate the therapeutic effects of hucMSCs and their exosomes on silicotic mice. High-throughput transcriptome sequencing of lung tissues was employed to screen differentially expressed genes and signaling pathways in the two treatment groups, followed by in vitro validation of the proposed mechanisms. CONCLUSION:Our findings demonstrate that hucMSC-Exos alleviate pulmonary inflammation, slow lung fibrosis, inhibit macrophage pyroptosis, activate the actin cytoskeleton signaling pathway, and maintain plasma membrane integrity in silicotic mice. This study provides possible therapeutic targets and molecular mechanisms for silicosis, establishing a link among silicosis, cytoskeleton, and pyroptosis, while validating the protective effect of hucMSC-Exos on the lungs of silicotic mice.

Silicosis is a pulmonary disease characterized by inflammation and progressive fibrosis. Previous studies have shown that polydatin (PD) has potential biological activity in key signaling pathways regulating inflammation and apoptosis. To investigate the effect of PD on rats with silicosis, this study used network pharmacology and molecular docking methods to determine the target of PD treatment for silicosis. The therapeutic effect of PD on silicosis was confirmed by measuring the lung injury score, hydroxyproline content, and mRNA expression levels of key targets. In addition, metagenomic sequencing and gas chromatography-mass spectrometry were used to determine the gut microbiota composition and targeted metabolomics analysis, respectively. The results showed that PD could inhibit the expression of inflammation-related indexes and apoptosis-related indexes at protein and mRNA levels. PD also regulates the diversity of the intestinal flora and the content of short-chain fatty acids. In conclusion, the current data suggest that PD has a protective effect against silica-induced lung injury and plays a protective role in regulating intestinal flora diversity and short-chain fatty acid levels through the gut-lung axis.

This study detected and analyzed the changes in the metabolomics of respiratory flora and lung lavage fluid of rats in a pneumoconiosis model. Male SD rats were randomly divided into silicon dioxide group (using SiO2 dust, SiD), coal mine dust group (using coal mine dust, CMD) and control group (using sterile physiological saline). The changes of respiratory flora in rats were analyzed by 16S rDNA gene sequencing technology, the differential metabolites of lung lavage fluid were analyzed by non targeted metabolomics of UHPLC-Q-TOF-MS. The lung tissue structure of SiD rats was seriously damaged, and there were obvious silicon nodules. CMD rats showed a large number of cell nodules, while the alveolar structure of the control group was normal. In the upper respiratory tract, the abundance of muris and uncultured oligotrophomonas increased, while the abundance of Pasteurella, Bacteria, Rhodobacter and uncultured Rhodobacter decreased. In SiD group, the abundance of Pasteurella and Streptococcus without milk decreased. In the lower respiratory tract, the abundance of Bacteria in CMD group rats increased, and mycoplasma γ- Proteobacteria β- The abundance of proterozoic bacteria and berberidaceae decreased. In SiD group, the abundance of Bifidobacteria, Bifidobacteriaceae and Bacteria increased, β- The abundance of proterozoic bacteria and berberidaceae decreased. Among the metabolic pathways mainly involved, pyrimidine metabolism, D-glutamine and D-glutamate metabolism may be the key metabolic pathways in the development of pneumoconiosis. Dysregulation of Betaproteobacteriales, Burkholderiaceae, Bifidobacteriales, Bifidobacteriaceae, Streptococcus_agalactiae may lead to the occurrence of pyrimidine metabolism, D-glutamine and D-glutamate metabolism abnormalities in pneumoconiosis.

BackgroundThis article aims to analyze the trends in global thyroid cancer mortality rate (ASMR) and disability adjusted life years (DALYs) from 1990 to 2021, and predict changes in disease burden by 2030. Through global data comparison and analysis, this study explores the impact of gender, age, and socioeconomic development level (SDI) on thyroid cancer mortality and disease burden.MethodThis study is based on data from the Global Health Data Exchange (GHDx) and analyzes the trends of thyroid cancer deaths, age-standardized mortality rate (ASMR), and DALYs over the period from 1990 to 2021. The annual average rate of change (EAPC) of the data was analyzed using a joinpoint regression model. Additionally, stratified analyses were conducted by gender, age group, and SDI, and the burden of thyroid cancer for the year 2030 was projected.ResultGlobal thyroid cancer deaths increased from 2,198 in 1990 to 5,255 in 2021. Despite the rise in total deaths, ASMR remained stable at 0.07/100,000 for females and 0.05/100,000 for males. DALYs increased from 61,815 to 144,955, with an average annual growth rate of 0.38%. The burden on men rose significantly, while the increase was slower for women. Regions with higher SDI showed a slight decrease in burden, whereas low-SDI regions saw an increase, with an annual growth rate of 0.76%. Fiji had the highest burden, with an ASMR of 0.25 and AS-DALYs of 6.07. Female mortality and disease burden were higher than in males, particularly among those aged 85 and above.ConclusionThe global disease burden of thyroid cancer has been increasing, particularly in the older adult. While high-SDI regions experienced a decrease in burden, low-SDI regions saw an increase. Predictions suggest that by 2030, the mortality rate and disease burden may remain stable with slow annual changes. However, attention should be given to the growing burden in low-income areas and the impact of socio-economic factors.

BACKGROUND:Silicosis is a systemic disease characterized by extensive fibrosis due to prolonged exposure to silica dust, with rising incidence rates significantly impacting global public health. ShengXian and JinShuiLiuJun Decoction (SXD) is a Chinese medicinal preparation containing a variety of medicinal plants. It has shown notable clinical efficacy in treating silicotic fibrosis in China. However, the precise mechanisms underlying its therapeutic effects remain unclear. This study integrates network pharmacology, multi-omics analysis, and experimental validation to investigate the potential mechanisms by which SXD treats silicotic fibrosis. OBJECTIVE:The study aims to investigate the therapeutic efficacy of SXD in treating silicotic fibrosis and to elucidate its underlying molecular mechanisms. METHODS:HPLC-Q-TOF-MS was used to identify the active components of SXD, and combined with network pharmacology, metabolomics, and transcriptomics, the mechanism of SXD in treating silicotic fibrosis was explored from multiple perspectives. The therapeutic effect of SXD was assessed through HE staining, Masson staining, Micro CT imaging, pulmonary function tests, and hydroxyproline content in lung tissue. Finally, network pharmacology and multi-omics findings were validated using molecular docking. CETSA, immunofluorescence, SPR, and Western blotting were used to analyze key factors in the NF-κB pathway at the animal, cellular, and molecular levels. RESULTS:SXD treatment improved lung function in silicosis rats, reduced inflammatory cell infiltration, collagen deposition, fibrosis and other pathological changes, and inhibited the protein expression of TNF-α, IL-17A, and IL-1β, and NF-κB in lung tissue. HPLC-Q-TOF-MS combined with network pharmacology identified key compounds such as Liquiritigenin, 3-Methoxynobiletin, Isomangiferin, Hesperidin, shogaol, and Ligustroflavone, which likely exert therapeutic effects through the TNF, IL-17, NF-κB, and TGF-β signaling pathways. Transcriptomics and metabolomics results revealed that SXD up-regulated the expression of NF-κB pathway-related genes (NFKBIA, NFKBIZ) and key regulators of the retinol metabolism pathway, while down-regulating pro-inflammatory genes (IL1B, IL17A, IL6). Experimental findings confirmed that SXD suppressed the expression of NF-κB pathway-related proteins and upstream activators TNF-α, IL-17A, and IL-1β, as well as their receptors, in both lung tissue and cellular models. Additionally, SXD-containing serum had a direct, non-toxic effect on MRC-5 cells, effectively inhibiting collagen expression and TGF-β secretion. SXD also had a positive effect on collagen production and extracellular matrix (ECM) aggregation in fibroblasts. Molecular dynamics studies showed that SXD directly binds to NF-κB and IκB. CONCLUSION:SXD exerts therapeutic effects on silicotic fibrosis by inhibiting NF-κB signaling transduction mediated by TNF-α, IL-17A, and IL-1β, and suppressing fibroblast activation.

Silica nanoparticles (SiNPs) exposure represents a significant environmental and occupational hazard leading to pulmonary fibrosis; however, the underlying molecular mechanisms remain incompletely understood. This study aimed to elucidate the role of JunB signaling in SiNPs-induced pulmonary fibrosis and evaluate its therapeutic potential. A comprehensive experimental approach combining in vitro macrophage-fibroblast co-culture systems and in vivo mouse models was employed, utilizing both pharmacological inhibition and genetic silencing strategies to investigate the function of JunB. RNA sequencing analysis was performed to identify differential gene expression patterns and potential regulatory pathways. SiNPs exposure induced macrophage pyroptosis, subsequently promoting fibroblast transdifferentiation through JunB/AP-1 pathway activation. Notably, genetic silencing of JunB significantly attenuated the expression of transdifferentiation markers in fibroblasts exposed to pyroptotic macrophage-conditioned medium. Furthermore, pharmacological inhibition of JunB using T-5224 effectively suppressed fibroblast transdifferentiation in vitro. Importantly, intraperitoneal administration of T-5224 substantially ameliorated pulmonary fibrosis in SiNPs-exposed mice, as evidenced by reduced collagen deposition and decreased expression of fibrotic markers. In conclusion, this study establishes JunB as a critical mediator of SiNPs-induced pulmonary fibrosis and demonstrates the therapeutic potential of JunB inhibition, which provides new insights for developing targeted treatments for lung fibrosis.

Objectives This study aims to integrate CT imaging with occupational health surveillance data to construct a multimodal model for preclinical CWP identification and individualized risk evaluation. Methods CT images and occupational health surveillance data were retrospectively collected from 874 coal workers, including 228 Stage I and 4 Stage II pneumoconiosis patients, along with 600 healthy and 42 subcategory 0/1 coal workers. First, the YOLOX was employed for automated 3D lung extraction to extract radiomics features. Second, two feature selection algorithms were applied to select critical features from both CT radiomics and occupational health data. Third, three distinct feature sets were constructed for model training: CT radiomics features, occupational health data, and their multimodal integration. Finally, five machine learning models were implemented to predict the preclinical stage of CWP. The model's performance was evaluated using the receiver operating characteristic curve (ROC), accuracy, sensitivity, and specificity. SHapley Additive exPlanation (SHAP) values were calculated to determine the prediction role of each feature in the model with the highest predictive performance. Results The YOLOX-based lung extraction demonstrated robust performance, achieving an Average Precision (AP) of 0.98. 8 CT radiomic features and 4 occupational health surveillance data were selected for the multimodal model. The optimal occupational health surveillance feature subset comprised the Length of service. Among 5 machine learning algorithms evaluated, the Decision Tree-based multimodal model showed superior predictive capacity on the test set of 142 samples, with an AUC of 0.94 (95% CI 0.88-0.99), accuracy 0.95, specificity 1.00, and Youden's index 0.83. SHAP analysis indicated that Total Protein Results, original shape Flatness, diagnostics Image original Mean were the most influential contributors. Conclusions Our study demonstrated that the multimodal model demonstrated strong predictive capability for the preclinical stage of CWP by integrating CT radiomic features with occupational health data.

BACKGROUND:Limited treatments for silicosis necessitate further study of pneumoconiosis characteristics and pathophysiology. This study employs metabolomics to investigate metabolite changes and identify biomarkers for understanding pneumoconiosis pathogenesis. METHODS:We explored pneumoconiosis pathogenesis through the lens of intestinal flora, using 18 healthy SPF male SD rats divided into three groups: control, coal dust, and silica. After dust exposure, metabolite changes were analyzed to identify metabolic markers and pathways. We assessed the relationship between intestinal flora and silicosis, aiming to provide early diagnostic evidence. Rats were exposed to coal dust, silica, or sterile saline for 8 weeks, after which blood, lung tissue, and feces were collected. Lung pathology was assessed, and inflammatory factors (IL-6, IL-11) were measured. 16S rDNA sequencing and UHPLC-QTOFMS metabolomics were used to analyze intestinal flora and fecal metabolites. RESULTS:After 8 weeks of dust exposure, silica-exposed rats showed significantly reduced weight and elevated serum IL-6 and IL-11 levels compared to controls (P < 0.05). Lung tissue pathology revealed normal alveolar structure in controls, whereas silica group rats exhibited lung damage, intensified inflammation, and silicon nodule formation. Coal dust group rats showed lung tissue changes with fibroblast aggregation. α diversity analysis showed a decreased Shannon index and increased Simpson index in the coal dust group, and a decreased Simpson index in the silica group, suggesting altered intestinal flora. β diversity analysis confirmed significant differences in gut microbiota between dust-exposed groups and controls. Metabolomics identified 11 differential metabolites in rat feces, meeting criteria of Fold change > 2, VIP > 1, and P < 0.05, indicating metabolic changes post-exposure. CONCLUSION:Dust exposure disrupts intestinal flora and metabolic state, with potential metabolic markers identified in both coal dust and silica groups, implicating fructose and mannose metabolism in coal dust exposure and sphingolipid metabolism in silica exposure. This study provides new insights into the pathogenesis of pneumoconiosis and potential biomarkers for early diagnosis.

Background:Acute lung injury (ALI) poses significant clinical challenges due to its irreversible alveolar damage and the limitation of available regenerative therapies. Emerging evidence suggests that macrophage-epithelial crosstalk plays a pivotal role in lung repair; however, the specific molecular mediators underlying this process remain largely undefined. Methods:To address this gap, we isolated and characterized macrophage-derived exosomes (MD-Exos) using dynamic light scattering, transmission electron microscopy (TEM), and immunoblotting. Proteomic analysis and molecular docking were employed to reveal interactions between BMPR2 on exosomes and BMPR1B on epithelial cells. Single-cell RNA sequencing (scRNA-seq) was utilized to map alveolar cell dynamics. Biochemical assays and confocal colocalization were performed to validate SMAD1 signaling activation. The biodistribution of exosomes was tracked via near-infrared imaging, and AT2-to-AT1 transdifferentiation was assessed through multiplex immunofluorescence and pseudotime trajectory analysis. Results:Proteomic profiling of MD-Exos identified BMPR2 as the predominant component. Molecular docking studies confirmed a strong binding affinity between exosomal BMPR2 and epithelial BMPR1B. Single-cell RNA sequencing and biochemical analyses revealed significant alterations in alveolar macrophage (34% vs 27%) and epithelial cell populations during injury, accompanied by enhanced cellular communication. The characterized macrophage-derived exosomes (163.6 ± 70.2 nm) demonstrated efficient pulmonary targeting, with peak accumulation occurring at 4 hours post-administration. Mechanistically, the formation of the BMPR2-BMPR1B complex activated SMAD1-dependent signaling pathways, as evidenced by strong BMPR1B-SMAD1 colocalization (correlation coefficient 0.94 ± 0.02) and enhanced ID1 expression. Conclusion:The BMPR2-BMPR1B interaction was demonstrated to accelerate type II to type I alveolar epithelial cell transdifferentiation, thereby facilitating tissue repair in ALI. Comprehensive toxicological assessment confirmed the safety profile of exosome administration across major organ systems. These findings establish exosomal BMPR2 as a crucial mediator of pulmonary repair through specific molecular recognition and signaling activation, providing new therapeutic strategies for treating acute lung injury.

Silicosis, caused by the inhalation of silicon dioxide (SiO2), is one of the most pressing public health problems. Nevertheless, there is currently no effective treatment. This study employed male C57BL/6 J mice and mouse alveolar macrophage cell line MH-S to investigate the biological mechanism in the development of silicosis, with a view to exploring the potential applications of puerarin (Pue) in the improvement of pulmonary inflammation and fibrosis in SiO2-exposed mice. This study elucidated that SiO2 could induce expression of inflammatory factors, accompanied by autophagy flux block, lysosome alkalization and membrane permeability in MH-S cells. Pue pretreatment could effectively inhibit expression of inflammatory factors in SiO2-exposed MH-S cells via alleviating autophagolysosomal dysfunction, and suppress TGF-β-induced myofibroblast differentiation. In addition, Pue was also been demonstrated to mitigate autophagolysosomal dysfunction, pulmonary inflammation and fibrosis in SiO2-exposed C57BL/6 J mice. Furthermore, the ingestion of Pue-enriched pueraria lobata tea (Plt), a traditional Chinese tea substitute that possesses anti-inflammatory, antioxidant, and cardiovascular benefits, was determined to improve imbalance of lysosome homeostasis, pulmonary inflammation and fibrosis in SiO2-exposed mice. This study illustrates the anti-inflammatory and antifibrotic properties of Pue and Plt by alleviating autophagolysosomal dysfunction and, consequently, reducing pulmonary inflammation and fibrosis. These findings provide insights into the pathogenesis mechanism of silicosis and indicate potential avenues for application of Pue and Plt in the mitigation of silicosis.

Objectives: In this study, by comparing the difference in protein expression in bronchoalveolar lavage fluid between silicosis patients in different stages and healthy controls, the pathogenesis of pneumoconiosis was discussed, and a new idea for the prevention and treatment of pneumoconiosis was provided. Methods: The lung lavage fluid was pretreated by 10 K ultrafiltration tube, Agilent 1100 conventional liquid phase separation, strong cation exchange column (SCX) HPLC pre-separation, and C18 reverse phase chromatography desalting purification, and protein was labeled with isotope. GO, KEGG pathway, and PPI analysis of differential proteins were conducted by bioinformatics, and protein types and corresponding signal pathways were obtained. Results: Thermo Q-Exactive mass spectrometry identified 943 proteins. T-test analysis was used to evaluate the different significance of the results, and the different protein of each group was obtained by screening with the Ratio≥1.2 or Ratio≤0.83 and P<0.05. We found that there are 16 kinds of protein throughout the process of silicosis. There are different expressions of protein in stages Ⅲ/control, stages Ⅱ/control, stage Ⅰ/control, stages Ⅲ/ stages Ⅱ, stages Ⅲ/ stage Ⅰ and stages Ⅱ/ stage Ⅰ groups. The results of ontology enrichment analysis of total differential protein genes show that KEGG pathway enrichment analysis of differential protein suggested that there were nine pathways related to silicosis. Conclusion: The main biological changes in the early stage of silicosis are glycolysis or gluconeogenesis, autoimmunity, carbon metabolism, phagocytosis, etc., and microfibril-associated glycoprotein 4 may be involved in the early stage of silicosis. The main biological changes in the late stage of silicosis are autoimmunity, intercellular adhesion, etc. Calcium hippocampus binding protein may participate in the biological changes in the late stage of silicosis. It provides a new idea to understand the pathogenesis of silicosis and also raises new questions for follow-up research.

Background It is a research hotspot to study the changes of metabolites and metabolic pathways in the process of coal worker's pneumoconiosis (CWP) by metabonomics and to explore its pathogenesis. ObjectiveTo study the change of metabolites in bronchoalveolar lavage fluid (BALF) of patients with CWP and explore the metabolic regulation mechanism of the disease. MethodsPatients with CWP who met the national diagnostic criteria according to Diagnosis of occupational pneumoconiosis (GBZ 70-2015) and underwent massive whole lung lavage were selected as the case group, and patients with tracheostenosis who underwent bronchoscopy were selected as the control group. BALF samples were collected from the cases and the controls. After filtering out large particles and mucus, the supernatant was stored in a −80 ℃ refrigerator. The samples were detected and analyzed by liquid chromatography-mass spectrometry after adding extraction solution, cold bath ultrasonication, and high-speed centrifugation, and the metabolic profiles and related data of CWP patients were obtained. The differential metabolites related to the occurrence and development of CWP were screened by multiple statistical analysis; furthermore, we searched the Kyoto Encyclopedia of Genes and Genomes (KEGG) database for potential metabolic pathways involved in the progression. ResultsThere was no significant difference in the general conditions of the subjects, such as weight, height, age, and length of service among the stage I group, the stage II group, the stage III group, and the control group (P˃0.05). When comparing the CWP stage I group with the control group, 48 differential metabolites were screened out, among which 14 were up-regulated and 34 were down-regulated. A total of 66 differential metabolites were screened out between the patients with CWP stage II and the controls, 14 up-regulated and 52 down-regulated differential metabolites. Compared with the control group, 63 differential metabolites were screened out in the patients with CWP stage III, including 11 up-regulated and 52 down-regulated differential metabolites. There were 36 differential metabolites that may be related to the occurrence of CWP, among which 11 differential metabolites were up-regulated, and 25 were down-regulated. Four significant differential metabolic pathways were identified through KEGG database query: linoleic acid metabolic pathway, alanine metabolic pathway, sphingolipid metabolic pathway, and glycerophospholipid metabolic pathway. ConclusionThe metabolomic study of BALF show that there are 36 different metabolites in the occurrence and development of CWP, mainly associating with linoleic acid metabolism, alanine metabolism, sphingolipid metabolism, and glycerophospholipid metabolism pathways.

Objective The aim of this study was to compare the interventional effects of polydatin given by different administration modes on experimental silicosis rats.Methods Fifty SPF SD rats were randomly divided into five groups,namely the control group,silica model group,polydatin inhalation group,polydatin gavage group,and polydatin intraperitoneal injection group.There were 10 rats in each group.Among them,the control group did not have any treatment,the model group was only treated with silica molding,and the other 3 groups were treated with polydatin via different administration methods after silica molding.The general condition of rats in each group and the lung coefficient of each group were observed at 28 days and 56 days after dust treatment.Paraffin sections of rat lung tissue were stained with hematoxylin-eosin(HE)and Masson staining.The kit was used to detect the content of hydroxyproline(HYP)and malondialdehyde(MDA)in the lung tissue of rats in each group,and the degree of lung inflammation and pulmonary fibrosis in each group of rats was evaluated.Results At day 56 after dust exposure,the lung coefficient of rats in the model group was significantly increased(P＜0.001)compared with the control group;compared with the model group,the lung coefficient of rats in the intraperitoneal injection group was decreased(P＜0.05).The results of HE staining of lung tissue of rats in each group showed that the alveolar wall was thin and the alveolar structure was normal in the control group on the 28th and 56th days,and no collapse was seen;compared with the control group on the 28th day,the alveolar wall of the rats in the 28th day model group was significantly thickened,the alveolar septum was widened,and a large number of inflammatory cells infiltrated the alveolar cavity;compared with the 28th day model group,the alveolar structure of each intervention group of polydatin was relatively normal.At day 56,compared with the control group,the alveolar wall of fibroblasts and fibroblast hyperplasia were further thickened in the model group;compared with the model group,the alveolar spacing in the intraperitoneal injection group,gavage group,and nebulized inhalation group was reduced.The Masson staining examination of rat lung tissue showed that,compared with the control group,the lung tissue of the model groups on the 28th and 56th days had blue cord-like collagen fiber hyperplasia.The results of collagen volume analysis showed that on the 28th and 56th days,the collagen volume integration number of the model group increased significantly compared with the control group;compared with the model group,the collagen volume fraction of all three groups of polydatin-treated rats decreased(P＜0.01).Such effects were observed to be more pronounced in rats with the intraperitoneal injection compared to those of the other two groups.On the 56th day after treatment,the content of HYP in the lung tissues in all treated groups increased compared with the control group(P＜0.05);compared with the model group,the content of hydroxyproline decreased in the intraperitoneal injection group,gavage group,and nebulized inhalation group(P＜0.05).On the 28th day after treatment,there was no significant difference in the concentration of malondialdehyde in the serum of each group(P=0.140).On the 56th day after treatment,compared with the control group,the levels of MDA in the serum of the model group,the gavage group,and the aerosol inhalation group increased(P＜0.05);the content of MDA in the intraperitoneal injection group,gavage group,and nebulized inhalation group decreased(P＜0.05)compared with the model group,among which the MDA content in the intraperitoneal injection group had the best amelioration effect.Conclusions Polydatin,optimally administered by intraperitoneal injection,could effectively decelerate silicosis progression in SD rats,possibly via its anti-inflammatory and anti-fibrotic effects.

Objective To investigate pneumoconiosis patients'awareness of the disease and their acceptance of Traditional Chinese Medicine(TCM)treatment for pneumoconiosis,providing a basis for health education on pneumoconiosis and exploring the feasibility of TCM treatment for the disease.Methods A total of 40 patients with stage I,stage Ⅱ,and stage Ⅲ pneumoconiosis treated by Huaibei Occupational Disease Prevention and Control Hospital were selected as the investigation subjects by random sampling method.A self-designed questionnaire survey was done via telephone to collect general information about the subjects,their understanding of pneumoconiosis,and their acceptance of TCM treatment,followed by a multifactorial regression analysis of the influencing factors.Results All 120 pneumoconiosis patients were male,and all were involved in coal mining dust exposure.It showed that the older the patient,the lower the educational level,and the longer the exposure,the higher the stage of pneumoconiosis(P＜0.05).The awareness rate of the causes and influencing factors of pneumoconiosis was 100％,and the awareness of symptoms was 80.8％(97 patients).The implementation rate of protective measures in engineering operations was 81.7％(98 people),and the implementation rate of personal protective measures and knowledge improvement was 78.3％(94 people).The overall acceptance rate of pneumoconiosis patients for TCM treatment was 23.4％,while the overall approval rate of TCM treatment was 54.2％.Multivariate linear regression analysis showed that compared to patients with primary school education,those with high school education had an increased total score for awareness of pneumoconiosis of 0.224 points(P＜0.05);university education level increased the acceptance rate of TCM treatment by 9.171％(P＜0.05)and the approval rate of TCM treatment by 40.212％(P＜0.01).Conclusions There was a lack of awareness of pneumoconiosis symptoms among patients,and the rate of acceptance of TCM treatment was not high,but the degree of approval for TCM treatment was relatively high.Health education for the less educated patients and promotion of TCM treatment should be strengthened.

[Background]At present,the practice of pulmonary rehabilitation for pneumoconiosis in China is in a primary stage.The basis for formu-lating an individualized comprehensive pulmonary rehabilitation plan is still insufficient,which is one of the factors limiting the development of community-level rehabilitation work. [Objective]To formulate an exercise prescription based on maximum heart rate measured by cardiopulmonary exercise test(CPET),con-duct an individualized comprehensive pulmonary rehabilitation program with the exercise prescription for patients with stable pneumo-coniosis,and evaluate its role in improving exercise endurance and quality of life,thus provide a basis for the application and promotion of pulmonary rehabilitation. [Methods]A total of 68 patients were recruited from the Occupational Disease Prevention Hospital of Jinneng Holding Coal Industry Group Co.,Ltd.from April to August 2022,and were divided into an intervention group and a control group by random number table method,with 34 cases in each group.All the pneumoconiosis patients participated in a baseline test.The control group was given routine drug treatment,while the intervention group received multidisciplinary comprehensive pulmonary rehabilitation treatment on the basis of routine drug treatment,including health education,breathing training,exercise training,nutrition guidance,psychological interven-tion,and sleep management,whose exercise intensity was determined according to the maximum heart rate provided by CPET.The re-habilitation training lasted for 24 weeks.Patients were evaluated at registration and the end of study respectively.CPET was used to measure peak oxygen uptake per kilogram(pVO2/kg),anaerobic threshold(AT),carbon dioxide equivalent of ventilation(EqCO2),maximum metabolic equivalent(METs),and maximum work(Wmax).The modified British Medical Research Council Dyspnea Questionnaire(mMRC),Self-rating Anxiety Scale(SAS),Self-rating Depression Scale(SDS),Pittsburgh Sleep Quality Index(PSQI),Chronic Obstructive Pulmonary Disease Assessment Test(CAT),and Short Form of Health Survey(SF-36)were used to evaluate the potential effect of the comprehensive pulmonary rehabilitation program. [Results]Among the included 68 patients,63 patients were having complete data,then 31 cases were assigned in the control group and 32 cases in the interventional group.Before the intervention,there was no significant difference in pVO2/kg,AT,EqCO2,METs,or Wmax between the two groups(P>0.05).At the end of the trail,the indicators like pVO2/kg[(19.81±2.38)mL·(min·kg)-1],AT[(14.48±2.33)mL·(min·kg)-1],METs(5.64±0.69),and Wmax[(85.25±14)W]of patients in the intervention group were all higher than those[(13.90±2.37)mL·(min·kg)-1,(11.70±1.94)mL·(min kg)-1,(3.97±0.70),and(61.77±14.72)W,respectively]in the control group(P<0.001);there was no sig-nificant difference in EqCO2 between the two groups(P=0.083).Before the trial,there was no significant difference in mMRC,SAS,SDS,PSQI,or CAT scores between the two groups(P>0.05).At the end of the trail,the mMRC score(1.16±0.57),SAS score(27.93±2.12),SDS score(26.48±1.44),PSQI score(1.08±0.88),and CAT score(4.34±3.28)of patients in the intervention group were lower than those[(2.03±0.83),(35.87±6.91),(34.23±6.65),(5.37±3.03),and(13.87±7.53),respectively]in the control group(P<0.001).The SF-36 scores of bodily pain(94.13±10.72),general health(87.50±5.68),vitality(95.31±5.53),mental health(99.88±0.71),and health changes(74.22±4.42)in the intervention group were higher than those[(71.87±32.72),(65.81±15.55),(74.52±16.45),(86.97±16.56),and(29.84±13.50),respec-tively]in the control group(P<0.001),and no significant difference was found in social functioning and role emotional scores(P>0.05). [Conclusion]Comprehensive pulmonary rehabilitation can increase the oxygen intake and exercise endurance of pneumoconiosis patients,ameliorate dyspnea symptoms,elevate psychological state and sleep quality,and improve the quality of life.