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Biomedical and Environmental Sciences 2019年第5期32卷 376-379页

作者： HE La Gu WU Peng Fei PENG Yan Hua FENG Juan ZHONG Dai Ming ZHANG Gui Hua ZENG Lei ZHONG Yu Min WANG Xiao Ye YUAN Hua Min Department of Laboratory Medicine Hunan Prevention and Treatment Center for Occupational DiseasesChangsha 410000HunanChina School of Life Sciences Center for Medical GeneticsCentral South UniversityChangsha 410000HunanChina

Until now, although comprehensive management strategies have improved treatment, there are no treatments to alleviate symptoms and slow disease progression[1]. In the past few decades, there has been increasing evidence that inflammation plays a very important role in Silicosis. Injury-induced inflammation is an effective strategy to remove harmful stimuli and initiate a healing process. However, it might be harmful to the organism and result in a permanent disease state if the inflammation is prolonged[2].

关键词： Silicosis Prognostic Score

Combined Silicosis and mixed dust pneumoconiosis with rapid progression: A case report and literature review

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World Journal of Clinical Cases 2018年第16期6卷 1164-1168页

作者： Hee-Young Yoon Yookyung Kim Heae Surng Park Chung-Won Kang Yon Ju Ryu Division of Pulmonary and Critical Care Medicine Department of Internal Medicine College of Medicine Ewha Womans University Department of Radiology Ewha Womans University College of Medicine Department of Pathology Ewha Womans University College of Medicine Department of Occupational and Environmental Medicine Ewha Womans University College of Medicine

BACKGROUND Rapidly progressive pneumoconiosis(RPP) occasionally occurs in coal workers, particularly those with high exposure to silica. Here, we report the case of a 64-year-old male miller with RPP. CASE SUMMARY The patient had a persistent cough for one month and had been clinically diagnosed with pulmonary tuberculosis in 2011. He worked in a stone processing factory from the ages of 20 through 37 and has owned his own mill for the past 25 years. His chest radiograph showed significant increases in the size and number of lung nodules since his last follow-up in 2013. By percutaneous needle lung biopsy, the nodular lesions showed diffuse infiltration of phagocytic macrophages and birefringent crystals by polarizing microscopy. He was finally diagnosed with RPP of mixed dust pneumoconiosis combined with Silicosis. CONCLUSION In this case, mixed dust pneumoconiosis with Silicosis might be accelerated by persistent exposure to graindust from working in a mill environment.

关键词： Pathology Case report Pneumoconiosis Silicosis Dust Occupational diseases

Gefitinib and fostamatinib target EGFR and SYK to attenuate Silicosis:a multi-omics study with drug exploration

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Signal Transduction and Targeted Therapy 2022年第6期7卷 2066-2078页

作者： Mingyao Wang Zhe Zhang Jiangfeng Liu Meiyue Song Tiantian Zhang Yiling Chen Huiyuan Hu Peiran Yang Bolun Li Xiaomin Song Junling Pang Yanjiang Xing Zhujie Cao Wenjun Guo Hao Yang Jing Wang Juntao Yang Chen Wang State Key Laboratory of Medical Molecular Biology Institute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100005China Laboratory of Stem Cell and Tissue Engineering Orthopedic Research InstituteState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengdu 610041China Department of Pulmonary and Critical Care Medicine The First Hospital of Shanxi Medical UniversityTaiyuan 030001China NHC Key Laboratory of Pneumoconiosis Taiyuan 030001China Shanxi Province Key Laboratory of Respiratory Disease Taiyuan 030001China Department of Pulmonary and Critical Care Medicine Center of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Xi’an Jiao tong UniversityXi’an 710061China Key Lab of Transplant Engineering and Immunology MOHRegenerative Medical Research CenterWest China HospitalSichuan UniversityChengdu 610041China

Silicosis is the most prevalent and fatal occupational disease with no effective therapeutics,and currently used drugs cannot reverse the disease progress.Worse still,there are still challenges to be addressed to fully decipher the intricated pathogenesis.Thus,specifying the essential mechanisms and targets in Silicosis progression then exploring anti-Silicosis pharmacuticals are desperately needed.In this work,multi-omics atlas was constructed to depict the pivotal abnormalities of Silicosis and develop targeted agents.By utilizing an unbiased and time-resolved analysis of the transcriptome,proteome and phosphoproteome of a Silicosis mouse model,we have verified the significant differences in transcript,protein,kinase activity and signaling pathway level during Silicosis progression,in which the importance of essential biological processes such as macrophage activation,chemotaxis,immune cell recruitment and chronic inflammation were emphasized.Notably,the phosphorylation of EGFR(p-EGFR)and SYK(pSYK)were identified as potential therapeutic targets in the progression of Silicosis.To inhibit and validate these targets,we tested fostamatinib(targeting SYK)and Gefitinib(targeting EGFR),and both drugs effectively ameliorated pulmonary dysfunction and inhibited the progression of inflammation and fibrosis.Overall,our drug discovery with multi-omics approach provides novel and viable therapeutic strategies for the treatment of Silicosis.

关键词： Silicosis SYK drugs

TNF-α and IL-1RA Polymorphisms and Silicosis Susceptibility in Chinese Workers Exposed to Silica Particles:A Case-Control Study

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Biomedical and Environmental Sciences 2012年第5期25卷 517-525页

作者： WANG Yong Wei LAN Ya Jia YANG Yue Lin WANG De Jun KUANG Jie West China School of Public Health Sichuan University Chendu 610041 Sichuan China West China Fourth Hospital Sichuan University &Oceupational Diseases Hospital Chendu 610041 Sichuan China Shandong Provincial Center for Disease Control and Prevention Jinan 250014 Shandong China

Abstract Objective To assess the association of TNF-α and IL-1RA SNPs with the risk of Silicosis in Chinese workers exposed to silica particles. Methods Case-control study design was used to enroll 68 silicotic patients induced by silica particles and 68 healthy workers matched for length of silica particle exposure as controls. Both cases and controls were from the same company in southwest China, and each of them was requested to complete a questionnaire. Blood samples were drawn for genomic DNA extraction from each participant. The genotyping of TNF-α （-238 and -308） and IL-1RA （＋2018） was performed using polymerase chain reaction-based restriction fragment length polymorphism （PCR-RFLP） and SYBR green-based quantitative polymerase chain reaction {qPCR）, respectively. Unconditional logistic regression model was used to estimate odds ratios （ORs） and their 95% confidential intervals （Cl） for SNPs. Results No significant differences were found between cases and controls in particles exposure length, body mass index （BMI）, and status of smoking and alcohol consumption except for age （P=O.O01） and blood type （P=0.042）. The frequencies of TNF-c（（-238） and IL-1RA （＋2018） genotypes in cases were significantly different from those in controls, （P=O.O01 and P=0.O02, respectively）, while a borderline significant difference was found in the frequencies of TNF-α（-308） between cases and controls （P=0.063）. The variants of three SNPs increased the risk of Silicosis in the Chinese workers exposed to silica particles. The adjusted ORs of TNFα（-308）, TNF-α（-238） and IL-1RA （＋2018） were 2.8 （95% Ch 2.1-7.5）, 20.9 （95% Ch 2.8-236.4） and 4.0 （95% CI： 2.6-10.2）, respectively. Conclusion It is suggested that cytokine polymorphisms of TNF-ct （-238, -308） and IL-1RA （＋2018） are associated with the risk of Silicosis in the Chinese workers exposed to silica particles. Further independent studies on the interaction between SNPs and exposure to silica particles with a larger sample size are therefore warranted.

关键词： TNF-α, IL-1RA Polymorphism Silicosis Case-control study

The Relationship between Polymorphisms of Interleukin-4 Gene and Silicosis

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Biomedical and Environmental Sciences 2011年第6期24卷 678-682页

作者： FANG Guo Feng FAN Xue Yun SHEN Fu Hai Department of Occupational and Environmental Health School of Public Health Hebei United UniversityTangshan 063000 Hebei China

Objective To explore the relationship between polymorphisms of interleukin-4 （IL-4） gene （-33, ＋45, intron3, ＋429, ＋448） and the susceptibility of Silicosis. Methods A case-control study was carried out. 101 Silicosis patients were selected as cases. As strictly matching, 121 of non Silicosis workers were selected as the controls. The polymophisms of IL-4 （five locus） were detected by the method of polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） techniques. Results The GA genotype in the IL-4＋429 locus and the CC genotype in the IL-4＋448 locus were found. The frequencies ofAA, GG and AG of IL-4＋45 locus in the cases were 55.4%, 10.9%, and 33.7% and in the controls were 62.0%, 12.6%, and 26.4%. The differences between cases and controls were not significant. The frequencies of B1B1, B2B2, and B1B2 of intron3 VNTR locus in the cases were 73.3%, 1.0%, and 25.7% and in the controls were 68.6%, 1.7%, and 29.8%. The differences were not significant. The frequencies of TT, CC, and CT in -33 locus in the cases were 55.4%, 11.9%, and 32.7% and in the controls were 69.4%, 4.1%, and 26.4%. The differences were significant （P=0.034）. Conclusion The relationship between genetic polymorphism of IL-4-33 site and Silicosis has been found and -33TT is a protective genotype for Silicosis.

关键词： Silicosis Interleukin-4 Polymorphism Susceptibility

Exploring the key pathways of tetrandrine in the treatment of early Silicosis based on bioinformatics and in vitro experiments

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Journal of Hainan Medical University 2022年第23期28卷 32-42页

作者： LIANG Chao ZHOU Jia-wei LIU Ya-feng GUO Jian-qiang WANG Qing-sen SU Yixin XING Ying-ru HU Chun-xiao XIE Jun WU Jing HU Dong School of Medicine Anhui University of Science and TechnologyHuainan 232001China Anhui Occupational Health and Safety Engineering Laboratory Huainan 232001China Key Laboratory of Advanced Industrial Dust Purification and Occupational Health and Safety of Education Department Huainan 232001China Department of Clinical Laboratory Gengjiu Hospital of Anhui ZhongkeHefei 232001China Affiliated Cancer Hospital of Anhui University of Science and Technology/Huainan Oriental Hospital Group Cancer Hospital Huainan 232001China

Objective:Exploring the key pathways affecting the development of early Silicosis based on bioinformatics and in vitro experiments.Method:Collecting differentially expressed genes in Silicosis patients through literature mining;Collecting differentially expressed genes in silicon dioxide infusion mice by using a high-throughput gene expression database(GEO);Obtaining disease targets related to Silicosis by means of online human Mendelian genetic database(OMIM),GeneCards and comparative toxicgenomics database(CTD);differentially expressed genes and disease targets were subjected to gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genome(KEGG)enrichment analysis via R-package and Metascape platforms,respectively.The Schrödinger and Pymol software were used for molecular docking and modification.Silicon dioxide-stimulated macrophages and epithelial cells were modeled and analyzed by PCR and western blot(WB).Result:2065 differentially expressed genes in Silicosis patients,2291 differentially expressed genes in rat infused with silicon dioxide,and 803 targets for Silicosis-related diseases were screened out.GO enrichment analysis mainly involves G protein-coupled receptor binding,the regulation of inflammatory response,and participation in immune response.The enrichment analysis of KEGG pathway mainly included ECM-receptor interaction,TNF signaling pathway,and IL-17 signaling pathway.IL-17 signaling pathway was screened out from different genes and disease targets,indicating that IL-17 signaling pathway might be the key pathway for the development of Silicosis.Molecular docking results showed that the Silicosis drug tetrandrine had good binding effect with the RAF/MEK/ERK pathway in the IL-17 signaling pathway.Cellular experiments showed that tetrandrine reduced the expression of inflammatory factors such as IL-6 and TGF-βin macrophages by regulating the RAF/MEK/ERKpathway,and inhibited the epithelialmesenchymal transition and expression of inflammatory factors in epithelial cells.Conclusion:Te

关键词： Silicosis Tetrandrine Bioinformatics Molecular docking signal pathway

Silicosis in Automobile Foundry Workers: A 29-Year Cohort Study

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Biomedical and Environmental Sciences 2010年第2期23卷 121-129页

作者： MIN ZHANG YING-DONG ZHENG XIE-YI DU YANG LU WEN-JIE LI CHENG QI ZHENG-LAI WU Department of Epidemiology School of Basic Medicine Peking Union Medical College Institute of Basic Medical Sciences Chinese Academy of Medical Sciences Beijing 100005 China National Institute of Occupational Health and Poison Control Chinese Center for Disease Control and Prevention Beijing 100050 China Peking University Health Science Center Beijing 100191 China Dongfeng Institute of Occupational Health Shiyan 442001 Hubei China

Objectives The purposes were to determine the relationship between Silicosis among foundry workers and their cumulative exposure to silica dust, and to establish a regression model to predict the risk for developing Silicosis by a given length of employment and air concentrations of silica at worksites. Methods A 29-year cohort study was conducted, including all those employed for more than one year during January 1, 1980 to December 31, 1996 and all members of the cohort were followed-up to December 3 1, 2008. In total, 2 009 workers of an automobile foundry in Shiyan, Hubei province were recruited in the study, 1 300 at eight worksites including sand preparation, cast shakeout, and finishing, melting, moulding, core-making, overhead crane operation and pouring as exposed group, and the other 709 auxiliary workers at the same factory, such as electricians, inspectors, fitters, and so on, as control group. Person-years of observation were calculated by persons observed and years followed-up for each of them. Person-year incidence of Silicosis and its relative risk （RR） or odds ratio （OR） and 95% confidence intervals （CI） among the workers were estimated, adjusted for relevant factors with logistic regression model using SPSS version 15.0 software. Results Totally, 2 009 workers were followed-up for 37 151 person-years and 48 cases of Silicosis were found, with an overall incidence of 1.34 per thousand, 2.02 per thousand in exposed group, and 0.15 per thousand in control one. Risk of Silicosis was significantly higher in the exposed group than that in the control one （RR=13.13, 95% CI 3.18-54.13）, higher in men than that in women （RR=13.92, 95% CI 1.92-100.93）. Risks of Silicosis varied by job, highest in those exposed to cast shakeout and finishing （RR=28.14, 95% CI 6.43-123.11）, followed by those exposed to pouring （RR-22.23, 95% CI 5.01-98.55） in the foundry. Average length of employment at onset of Silicosis was 25.94 years, and Silicosis incidence increased with length of employment. Average age at onset of s

关键词： Foundry Silica Silicosis Occupational exposure limit Cohort study Incidence Person-year Relative risk （RR） Odds ratio （OR）

Serum neuron-specific enolase:A promising biomarker of Silicosis

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World Journal of Clinical Cases 2021年第5期9卷 1016-1025页

作者： Hong-Bo Huang Jun-Ling Huang Xiao-Ting Xu Kun-Bo Huang Yi-Jian Lin Jie-Bin Lin Xi-Bin Zhuang Department of Pulmonary and Critical Care Medicine Quanzhou First Hospital Affiliated to Fujian Medical UniversityQuanzhou 362000Fujian ProvinceChina Department of Clinical Laboratory Quanzhou First Hospital Affiliated to Fujian Medical UniversityQuanzhou 362000Fujian ProvinceChina Department of Internal Medicine Infectious Disease Hospital of QuanzhouQuanzhou 362000Fujian ProvinceChina

BACKGROUND Silicosis is a type of chronic pulmonary fibrosis caused by long-term inhalation of silica dust particles.There has been no ideal biomarker for the diagnosis and differential diagnosis of Silicosis until now.Studies have found that elevated neuron-specific enolase(NSE)concentration in the serum of Silicosis patients is helpful for diagnosis and severity assessment of the disease.However,the number of cases in these studies was not enough to arouse attention.AIM To investigate the clinical significance of serum NSE in the diagnosis and staging of Silicosis.METHODS From January 2017 to June 2019,326 cases of Silicosis confirmed in Quanzhou First Hospital Affiliated to Fujian Medical University were included in the Silicosis group.A total of 328 healthy individuals or medical patients without Silicosis were included in the control group.Serum NSE concentrations of all subjects were determined by electrochemical luminescence.RESULTS There were no significant differences in sex,age,smoking index and complications between the Silicosis and control groups.The mean serum NSE concentration was 26.57±20.95 ng/mL in the Silicosis group and 12.42±2.68 ng/mL in the control group.The difference between the two groups was significant(U=15187,P=0.000).Among the 326 patients with Silicosis,103 had stage I Silicosis,and the mean serum NSE concentration was 15.55±6.23 ng/mL.The mean serum NSE concentration was 21.85±12.05 ng/mL in 70 patients with stage II Silicosis.The mean serum NSE concentration was 36.14±25.72 ng/mL in 153 patients with stage III Silicosis.Kruskal-Wallis H test suggested that the difference in serum NSE concentration in Silicosis patients in the three groups was significant(H=130.196,P=0.000).Receiver operating characteristic curve analysis indicated that the area under the curve was 0.858(95%confidence interval:0.828-0.888;P=0.000).When the NSE concentration was 15.82 ng/mL,the Jorden index was the largest,the sensitivity was 72%,and the specificity was 90%.CONCLUSION Serum NSE concentration may be

关键词： Silicosis Neuron-specific enolase Receiver operating characteristic curve Disease stage Biomarker Diagnosis

The study of the impact by atractylenolide-1 on inflammatory cytokine,autophagy and apoptosis in alveolar macrophages of Silicosis patients

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China Medical Abstracts(Internal Medicine) 2022年第1期39卷 17-18页

作者：谭诗旖 Med Sch Hunan Normal UnivChangsha 410000

Objective To explore the effect of atractylenolide-1( ATL-Ⅰ) on alveolar macrophages in Silicosis patients.Methods In December 2019,12 male Silicosis patients treated in Beidaihe Sanatorium for Chinese Coal Miners from July to September 2019 were selected by random sampling.Their alveolar macrophages were collected and divided into control group,ATL-Ⅰ group( 100 μmol/L) and dimethyl sulfoxide( DMSO) group( 100 μmol/L).

关键词： patients alveolar Silicosis

Progress in The Treatment of Silicosis（Review）

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Progress in The Treatment of Silicosis（Review）