Background:The aim was to explore the effect of macrophage polarization and macrophage-to-myofibroblast transition(MMT)in silicosis.Methods:Male Wistar rats were divided into a control group and a silicosis group deve...Background:The aim was to explore the effect of macrophage polarization and macrophage-to-myofibroblast transition(MMT)in silicosis.Methods:Male Wistar rats were divided into a control group and a silicosis group developed using a HOPE MED 8050 dynamic automatic dusting system.Murine mac-rophage MH-S cells were randomly divided into a control group and an SiO_(2) group.The pathological changes in lung tissue were observed using hematoxylin and eosin(HE)and Van Gieson(VG)staining.The distribution and location of macrophage marker(F4/80),M1 macrophage marker(iNOS),M2 macrophage marker(CD206),and myofibroblast marker(α-smooth muscle actin[α-SMA])were detected using immu-nohistochemical and immunofluorescent staining.The expression changes in iNOS,Arg,α-SMA,vimentin,and type I collagen(Col I)were measured using Western blot.Results:The results of HE and VG staining showed obvious silicon nodule formation and the distribution of thick collagen fibers in the lung tissue of the silicosis group.Macrophage marker F4/80 increased gradually from 8 to 32 weeks after exposure to silica.Immunohistochemical and immunofluorescent staining results revealed that there were more iNOS-positive cells and some CD206-positive cells in the lung tissue of the silicosis group at 8 weeks.More CD206-positive cells were found in the silicon nodules of the lung tissues in the silicosis group at 32 weeks.Western blot analysis showed that the expressions of Inducible nitric oxide synthase and Arg protein in the lung tissues of the silicosis group were upregulated compared with those of the con-trol group.The results of immunofluorescence staining showed the co-expression of F4/80,α-SMA,and Col I,and CD206 andα-SMA were co-expressed in the lung tissue of the silicosis group.The extracted rat alveolar lavage fluid revealed F4/80+α-SMA+,CD206+α-SMA+,and F4/80+α-SMA+Col I+cells using immunofluorescence staining.Similar results were also found in MH-S cells induced by SiO_(2).Conclusions:The development of silicosis is accompanied by macrophage polarization and MMT.展开更多
Silicosis is an occupational lung disease caused by prolonged exposure to silica dust in the workplace.It has a complex pathogenesis and currently lacks effective treatments.Homoharringtonine(HHT)is a natural compound...Silicosis is an occupational lung disease caused by prolonged exposure to silica dust in the workplace.It has a complex pathogenesis and currently lacks effective treatments.Homoharringtonine(HHT)is a natural compound approved for the treatment of acute myeloid leukemia,but its effects on silicosis remain unclear.In the present study,we constructed a mouse model of silica(SiO_(2))-induced pulmonary fibrosis and evaluated the preventive and therapeutic effects of HHT.The results showed that HHT significantly attenuated the progression of SiO_(2)-induced pulmonary fibrosis in mice.We then used MRC-5,a human lung fibroblast cell line,to explore the mechanisms underlying HHT's inhibitory effects in vitro and found that HHT significantly inhibited the activation and migratory capacity of MRC-5 cells.Mechanistically,these effects were mediated by enhanced ubiquitination and degradation of the CCR1 protein.Furthermore,HHT exhibited favorable biocompatibility in vivo,and its preventive and therapeutic effects were validated in SiO_(2)-treated mice.Collectively,the current study demonstrates that HHT shows significant potential as a therapeutic agent for silicosis by targeting CCR1 and the PI3K/AKT/m TOR signaling pathway,highlighting it as a promising candidate for clinical translation for silicosis treatment.展开更多
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 s...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 silicosis was 47.83 years old. The risk of silicosis in workers with pulmonary tuberculosis was 2.57 folds as those without it （P〈0.01）. Ten deaths were recorded in those with silicosis, with a case-fatality rate of 20.83 percent three of them died of lung cancer, three of liver cancer, two of ischemic heart disease, and two of other diseases as their immediate causes of death. Incidence of silicosis in foundry workers positively correlated with their cumulative silica exposure （OR-3.00, 95% CI 2.34-3.83）. Risks of silicosis increased by 4.38 folds with an increase of 1 mg/m^3-year of cumulative silica exposure, and by 3.79 folds with smoking, respectively, adjusted for alcohol drinking and age. Based on a logistic regression model fitted, incidence of silicosis is expected to be 44.6 per thousand for those with daily exposure to silica of 4.18 mg/m^3 in average for 30 years, and if incidence of silicosis is expected to be less than 1 per thousand, daily exposure to silica should be controlled below 0.2 mg/m^3 for those with 20 years of employment, or below 0.1 mg/m^3 for those with 30 or 40 years of silica exposure. Conclusions At present, foundry workers in China still face high risk of developing silicosis. For lowering occurrence of silicosis in exposed workers, it seems necessary that current occupational exposure limits for silica at worksites in China should be reexamined and silica dust control measures be strengthend.展开更多
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 patie...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.展开更多
In the screening tests of drugs for silicosis in our laboratory, we found that TT, a type of alkaloid isolated from Stephania tetrandra, could inhibit the development of experimental silicosis of rats and the synthesi...In the screening tests of drugs for silicosis in our laboratory, we found that TT, a type of alkaloid isolated from Stephania tetrandra, could inhibit the development of experimental silicosis of rats and the synthesis of collagen in rat lung. Chest X-rays of silicotic patients treaied with TT for 1-3 years showed obvious changes. The silicotic nodules became smallel and shadows became clearer. PVNO was proved to have anti-silicotic effect on animal and clinically. This presentation reports the effect of them on collagen mRNA.Dot blot results showed that 1 (Ⅰ) and 1 (Ⅲ) mRNA levels increased significantly at 60 and 120 days after the rats were exposed to silica dust. The mRNA levels went down at 1 and 3 months after treated by TT and PVNO. In situ hybridization observation revealed that the silver grains of Type Ⅰand Type Ⅲ collagen were scattered within the fibroblasts in cellular nodules and in thickened interstitium of silicosis tissue. The amounts of mRNA silver grains decreased in the lung tissue treated by TT and PVNO. It was suggested that TT and PVNO may inhibil the gene expression of collagen during silicosis展开更多
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 eviden...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].展开更多
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...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.展开更多
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 si...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.展开更多
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 no...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 a promising biomarker for the diagnosis and assessment of severity of silicosis.展开更多
OBJECTIVE:To explore the mechanisms of Yangqing Chenfei formula(养清尘肺方,YCF)in the treatment of silicosis through a comprehensive strategy consisting of serum pharmacochemistry,network pharmacology analysis,and in ...OBJECTIVE:To explore the mechanisms of Yangqing Chenfei formula(养清尘肺方,YCF)in the treatment of silicosis through a comprehensive strategy consisting of serum pharmacochemistry,network pharmacology analysis,and in vitro validation.METHODS:An ultrahigh-performance liquid chromatography-tandem mass spectrometry method was used to confirm the active components in YCF-medicated serum.Then,we obtained targets for active components and genes for silicosis from multiple databases.Furthermore,a protein-protein interaction network was constructed,and Kyoto Encyclopedia of Genes and Genomes pathway and biological process analyses were conducted to elucidate the mechanisms of YCF for the treatment of silicosis.Finally,we validated the important components and mechanisms in vitro.RESULTS:Altogether,19 active components were identified from rat serum after YCF administration.We identified 724 targets for 19 components,which were mainly related to inflammation[phosphatidy linositol 3 kinase/protein kinase B,forkhead box O,hypoxia inducible factor,and T-cell receptor signaling pathway,nitric oxide biosynthetic process],fibrotic processes[vascular endothelial growth factor signaling pathway,extracellular signal regulated kinase(ERK)1 and ERK2 cascade,smooth muscle cell proliferation],and apoptosis(negative regulation of apoptotic process).In addition,218 genes for silicosis were identified and were mainly associated with the inflammatory response and immune process[cytokine-cytokine receptor interaction,tumor necrosis factor alpha(TNF-α),toll-like receptor,and nucleotide binding oligomerization domain-like receptor signaling pathway].Taking an intersection of active component targets and silicosis genes,we obtained 61 common genes that were mainly related to the inflammatory response and apoptosis,such as the phosphatidylinositol-3-kinase/protein kinase B signaling pathway,mitogen activated protein kinases signaling pathway,TNF signaling pathway,toll-like receptor signaling pathway,biosynthesis of nitric oxide,and apoptotic process.In the herb-component-gene-pathway network,paeoniflorin,rutin and nobiletin targeted the most genes.In vitro,paeoniflorin,rutin and nobiletin decreased the mRNA levels of inflammatory factors[interleukin(IL)-6,TNF-α,and IL-1β],suppressed p-AKT and cleaved caspase-3,and increased B cell lymphoma(Bcl)-2 protein expression in silica-induced macrophages in a concentration-dependent manner.CONCLUSION:YCF could significantly relieve the inflammatory response of silicosis via suppression of the AKT/Bcl-2/Caspase-3 pathway.展开更多
AIM: To investigate the changes of oxidative stress indicators in the serum of silicosis patients and explore the mechanism of silicosis development.METHODS: Two hundred workers who were exposed to silica dust for mor...AIM: To investigate the changes of oxidative stress indicators in the serum of silicosis patients and explore the mechanism of silicosis development.METHODS: Two hundred workers who were exposed to silica dust for more than one year were recruited as dust-exposed group, 100 non-dust-exposed subjects served as control group, 32 patients with suspected 0+ silicosis as observation group, and 130 silicosis patients were taken as the silicosis group. Indicators of oxidative stress, including superoxide dismutase(SOD), nitric oxide(NO), serum glutathione peroxidase(GSHPx), total antioxidant capacity(T-AOC), nitric oxide synthase(NOS), and lipid malondialdehyde(MDA), were determined in all the groups. RESULTS: Compared with the control group, NO and GSH-Px in dust-exposed group and silicosis group increased, and SOD decreased significantly(81.162± 35.176, 270.469 ± 39.228 and 68.209 ± 21.528, respectively, P = 0.004, P = 0.002, P = 0.005). Compared with the control and dust-exposed group, T-AOC, NOS and MDA in silicosis group increased significantly(13.048 ± 4.153, 36.201 ± 7.782 and 5.054 ± 1.204, respectively, P = 0.018, P = 0.022, P = 0.011). Compared with dust-exposed group, GSH-Px in the silicosis group increased significantly(270.469 ± 39.228, P = 0.002). GSH-Px in phase Ⅲ silicosis was significantly higher than in phase Ⅰsilicosis(290.750 ± 39.129, P = 0.021). Pearson correlation analysis showed that serum GSH-Px was positively correlated with silicosis staging, length of dust exposure and type of occupation(47.109 ± 8.015, P = 0.001).CONCLUSION: The imbalance of oxidative and antioxidation system is associated with the development of silicosis. The surveillance of oxidative stress indicators will benefit the prognosis of silicosis patients.展开更多
A better understanding is needed to explain the mechanism of therapeutic effect of combined use of tetradrine-PVNO and tetradrine-QOHP which play very important roles in treatment of silicosis. Blood prolidase (PLD), ...A better understanding is needed to explain the mechanism of therapeutic effect of combined use of tetradrine-PVNO and tetradrine-QOHP which play very important roles in treatment of silicosis. Blood prolidase (PLD), monoamine oxidase (MAO) and plasminogen (PLG) in silicotic rats after treatment with tetradrine-PVNO or tetradrine-QOHP were measured. The values obtained were compared with the untreated silicotic rats. It was found that the silicotic rats that received tetradrine-PVNO showed significant increase in PLD and decrease in PLG, but no significant change in MAO. The PLD in plasma of silicotic rats that received tetradrine-QOHP were elevated significantly, but PLG and MAO did not change appreciably. These findings suggest that the combined use of tetradrine-PVNO and tetradrine-QOHP can accelerate the degradation of collagen in silicotic rats展开更多
Objective: To explore the effects of respiratory rehabilitation training combined with Corbrin Capsule on the inflammatory response and pulmonary fibrosis in patients with silicosis complicated by COPD. Methods: A tot...Objective: To explore the effects of respiratory rehabilitation training combined with Corbrin Capsule on the inflammatory response and pulmonary fibrosis in patients with silicosis complicated by COPD. Methods: A total of 80 patients with silicosis complicated by COPD who were treated in our hospital between January 2013 and December 2016 were selected as the research subjects and randomly divided into control group (n=40) and observation group (n=40). Control group were treated with Corbrin Capsule on the basis of routine treatment, and observation group were treated with respiratory rehabilitation training combined with Corbrin Capsule on the basis of routine treatment. The differences in serum levels of inflammatory factors and pulmonary fibrosis indexes were compared between the two groups before intervention, after 6 months of intervention and after 1 year of intervention. Results: Before intervention, there was no statistically significant difference in serum levels of inflammatory factors and pulmonary fibrosis indexes between the two groups. After 6 months of intervention and after 1 year of intervention, serum inflammatory factors IL-6, IL-8, IL-12, IL-17, IL-18 and MCP-1 levels of observation group were lower than those of control group;serum pulmonary fibrosis indexes PCⅢ, LN, HA, ICAM-1 and HO-1 contents were lower than those of control group. Conclusion: Respiratory rehabilitation training combined with Corbrin Capsule therapy can effectively reduce the systemic inflammatory response and inhibit the pulmonary fibrosis process in patients with silicosis complicated by COPD.展开更多
OBJECTIVE: To predict the targets of Bufei Huoxue capsule( 补肺活血胶囊, BFHX) using network pharmacology analysis and to explore its effects and functional targets in a silicotic rat model. METHODS: The drug and dise...OBJECTIVE: To predict the targets of Bufei Huoxue capsule( 补肺活血胶囊, BFHX) using network pharmacology analysis and to explore its effects and functional targets in a silicotic rat model. METHODS: The drug and disease targets were correlated through network pharmacology analysis to explore the targets and signaling pathways of BFHX affecting silicosis. NR8383 cells were cultured to verify the core genes and pathways. A rat model of silicosis was established to verify whether the mechanism behind SiO2-caused pulmonary fibrosis was alleviated by BFHX(0.82 g/kg) and how it affected key targets and pathways. RESULTS: Overlapping BFHX and silicotic gene targets produced 159 interactive targets, and 55 were screened by network topology analysis. The results of gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses suggested that BFHX could affect silicosis through the nucleotide-like receptor containing pyrin domain 3(NLRP3) inflammasome. In NR8383 cells, the expression of core genes related to the NLRP3 inflammasome could be inhibited by BFHX treatment. BFHX reduced the degree of alveolitis and collagen deposition, attenuating pulmonary fibrosis in Si O2-induced rat model. Pulmonary macrophage pyroptosis after SiO2 exposure was observed under transmission electron microscopy. BFHX alleviated the morphological characteristics of pyroptosis. BFHX also reduced the expression of NLRP3, caspase-1, interleukin-1 beta(IL-1β), IL-18, IL-6, and tumor necrosis factor-alpha in lung tissues of silicotic rat model. BFHX affected the K ion content in bronchoalveolar lavage fluid when assessed by energy dispersive spectrometer testing. The expression of CD68+ and CD206+ were also reduced after BFHX intervention. CONCLUSION: NOD-like receptor signaling is vital for BFHX's effects on silicosis. It exerts anti-pulmonary fibrosis effects by inhibiting pulmonary macrophage pyroptosis and polarization through NLRP3 inflammasome activation.展开更多
To provide a scientific basis for determining the health surveillance period of dust-exposed workers, data of a retrospective cohort study was re-analyzed with emphasis on natural course of silicosis. 33640 workers ex...To provide a scientific basis for determining the health surveillance period of dust-exposed workers, data of a retrospective cohort study was re-analyzed with emphasis on natural course of silicosis. 33640 workers exposed to silica dust who were employed for at least 1 year from 1972 to 1974 in twenty Chinese mines or pottery factories were included as subjects, and were followed up till December 31, 1994. The cohort included subjects from 8 tungsten mines, 4 tin mines and 8 pottery factories. Our results showed that the mean latency of silicosis, for all the cases of the cohorts, was 22.9±9.8 y. 52.2 % of silicosis was diagnosed approximately 9.1±5.7 y after the dust exposure had ceased. The progression rates of silicosis from stage Ⅰ to Ⅱ and from stage Ⅱ to Ⅲ were 48.2 % and 18.5 %, and the duration was 4.1±0. 2 and 6.8±0.2 y, respectively. The survival times of silicosis stage Ⅰ , Ⅱ and Ⅲ, from the year of diagnosis to death, were 21.5, 15.8 and 6.8 years, respectively. There was 25 % of the silicosis patients whose survival time was beyond 33 y. The mean death age of all silicosis cases was 56.0 y. The death age inereased to 65.6 y in the middle of 1990s. Among dust-exposed workers, subjects who became suspected case （0^＋ ） accounted for 15.0 %. 48.7 % of the suspected silicosis cases developed to silicosis, and the average year from the time of being suspected of the disease to the first stage of silicosis was 5.1y. The natural characteristics, as mentioned above, varied with different mines and factories. We are led to conclude that silicosis is chronic in nature, but progress quickly. As a serious occupational disease it significantly reduces the life span of exposed workers. The study of its natural history is of importance for the development of health surveillance criteria for dust-exposed workers.展开更多
In order to provide scientific information on the prevention and treatment of silicosis,studies about changes of silicotic collagen in lungs were carried out. In this paper, we present experiments about the structural...In order to provide scientific information on the prevention and treatment of silicosis,studies about changes of silicotic collagen in lungs were carried out. In this paper, we present experiments about the structural changes of collagen in silicotic lungs of rats and patients. These included electron microscopy, circular dichroism and infrared spectroscopy studies of collagen fibers. The results indicated that fibers of silicotic collagen were shorter in length, smaller in diameter and decreased in α-helix content. The -Si-O-R- group and -OH group were found increased and -C-C- backbone shortened. The increase of -Si-O-R-group indicated that silica formed linking bridges between collagens which may be the cause of progressive enlargement of nodules展开更多
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 literat...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:Tetrandrine regulates the inflammatory response and epithelial-mesenchymal transition(EMT)through the RAF/MEK/ERK pathway and thus affects the early progression of silicosis.展开更多
[Objectives]This study was conducted to explore the combination of serum Apelin and MMP-9 in the assessment of silicosis and their correlation with lung function. [Methods] From January 2020 to January 2021, eight pat...[Objectives]This study was conducted to explore the combination of serum Apelin and MMP-9 in the assessment of silicosis and their correlation with lung function. [Methods] From January 2020 to January 2021, eight patients with silicosis(including 3, 2 and 3 patients with silicosis in stages I, II and III respectively) were selected as the observation group, and eight persons frees of silicosis were selected as the control group during the same period. All patients were detected for serum APJ endogenous ligand(Apelin) of G protein-coupled receptor, matrix metalloproteinase-9(MMP-9) and pulmonary function indexes. The levels of serum Apelin and MMP-9 and lung function in the two groups were compared, and the correlation between serum Apelin and MMP-9 indexes and lung function was analyzed. [Results] The serum Apelin and lung function in the observation group were lower than those in the control group, and the level of MMP-9 in the observation group was higher than that in the control group, and the differences were statistically significant(P<0.05). The MMP-9 index in patients with silicosis in stage III was higher than those in patients with silicosis in stage II and stage I, and the MMP-9 index in patients with silicosis in stage II was higher than that in patients with silicosis in stage I, and the differences were statistically significant(P<0.05). The serum Apelin and lung function indexes of patients with silicosis in stage III were lower than those of patients with silicosis in stage II and stage I, and the serum Apelin and lung function indexes of patients with silicosis in stage II were lower than those of patients with silicosis in stage I, and the differences were statistically significant(P<0.05). The correlation analysis showed a positive correlation between serum Apelin and lung function indexes, and a negative correlation between MMP-9 and lung function indexes. [Conclusions] A lower serum Apelin and a higher MMP-9 value in patients with silicosis indicate severer lung function impairment, and the combined detection of serum Apelin and MMP-9 is conducive to effective evaluation of the disease of silicosis. The serum Apelin index was negatively correlated with silicosis, and the level of MMP-9 was positively correlated with silicosis, which could provide a scientific basis for clinical diagnosis and treatment.展开更多
In the present study, we developed silicosis of rat model by bronchial perfusion SiO2 dust, and intervenes with AcSDKP, immunohisto chemistry was used to detect NF-κb and MCP-1 expression in lung tissue, and positive...In the present study, we developed silicosis of rat model by bronchial perfusion SiO2 dust, and intervenes with AcSDKP, immunohisto chemistry was used to detect NF-κb and MCP-1 expression in lung tissue, and positive cells were counted. We found that compared with silicotic model group, the positive cells of NF-κb and MCP-1 were decreased significantly in anti-fibrosis treatment of AcSDKP group. The findings suggest that AcSDKP could inhibit the expression of NF-κb and MCP-1 in lung tissue of silicosos, this may be related to AcSDKP inhibit of macrophage infiltration in lung tissue and reduced the degree of dust alveolitis.展开更多
The experimental time of this paper started in August 2020 and lasted until October of the following year. Mainly for the elderly patients with silicosis to carry out nursing, analyze the nursing effect. In this exper...The experimental time of this paper started in August 2020 and lasted until October of the following year. Mainly for the elderly patients with silicosis to carry out nursing, analyze the nursing effect. In this experiment, 70 patients with silicosis were selected as experimental subjects by data comparison method, and they were divided into control group and observation group according to before and after seeing a doctor. The former adopts general nursing, while the latter adopts comprehensive nursing. The psychological conditions, complications and so on of the two groups were compared. After nursing, it can be clearly seen that all indexes of the observation group are better than those of the control group, which shows that comprehensive nursing is more suitable for the nursing of elderly silicosis patients.展开更多
基金The National Natural Science Foundation of China(no.82204006)the Science and Technology of Project of Hebei Education Department(QN2022009)+1 种基金the Provincial Graduate Student Innovation Funding Project of Hebei Province(CXZZBS2022104)the National Natural Science Foundation of Hebei Province(H2020209292).
文摘Background:The aim was to explore the effect of macrophage polarization and macrophage-to-myofibroblast transition(MMT)in silicosis.Methods:Male Wistar rats were divided into a control group and a silicosis group developed using a HOPE MED 8050 dynamic automatic dusting system.Murine mac-rophage MH-S cells were randomly divided into a control group and an SiO_(2) group.The pathological changes in lung tissue were observed using hematoxylin and eosin(HE)and Van Gieson(VG)staining.The distribution and location of macrophage marker(F4/80),M1 macrophage marker(iNOS),M2 macrophage marker(CD206),and myofibroblast marker(α-smooth muscle actin[α-SMA])were detected using immu-nohistochemical and immunofluorescent staining.The expression changes in iNOS,Arg,α-SMA,vimentin,and type I collagen(Col I)were measured using Western blot.Results:The results of HE and VG staining showed obvious silicon nodule formation and the distribution of thick collagen fibers in the lung tissue of the silicosis group.Macrophage marker F4/80 increased gradually from 8 to 32 weeks after exposure to silica.Immunohistochemical and immunofluorescent staining results revealed that there were more iNOS-positive cells and some CD206-positive cells in the lung tissue of the silicosis group at 8 weeks.More CD206-positive cells were found in the silicon nodules of the lung tissues in the silicosis group at 32 weeks.Western blot analysis showed that the expressions of Inducible nitric oxide synthase and Arg protein in the lung tissues of the silicosis group were upregulated compared with those of the con-trol group.The results of immunofluorescence staining showed the co-expression of F4/80,α-SMA,and Col I,and CD206 andα-SMA were co-expressed in the lung tissue of the silicosis group.The extracted rat alveolar lavage fluid revealed F4/80+α-SMA+,CD206+α-SMA+,and F4/80+α-SMA+Col I+cells using immunofluorescence staining.Similar results were also found in MH-S cells induced by SiO_(2).Conclusions:The development of silicosis is accompanied by macrophage polarization and MMT.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82473601 to Y.L.,82404234 to W.S.,and 82073518 to C.N.)the Foundation of Chongqing Key Laboratory of Prevention and Treatment for Occupational Diseases and Poisoning(Grant No.2022-2023ZYBKF04 to C.N.)。
文摘Silicosis is an occupational lung disease caused by prolonged exposure to silica dust in the workplace.It has a complex pathogenesis and currently lacks effective treatments.Homoharringtonine(HHT)is a natural compound approved for the treatment of acute myeloid leukemia,but its effects on silicosis remain unclear.In the present study,we constructed a mouse model of silica(SiO_(2))-induced pulmonary fibrosis and evaluated the preventive and therapeutic effects of HHT.The results showed that HHT significantly attenuated the progression of SiO_(2)-induced pulmonary fibrosis in mice.We then used MRC-5,a human lung fibroblast cell line,to explore the mechanisms underlying HHT's inhibitory effects in vitro and found that HHT significantly inhibited the activation and migratory capacity of MRC-5 cells.Mechanistically,these effects were mediated by enhanced ubiquitination and degradation of the CCR1 protein.Furthermore,HHT exhibited favorable biocompatibility in vivo,and its preventive and therapeutic effects were validated in SiO_(2)-treated mice.Collectively,the current study demonstrates that HHT shows significant potential as a therapeutic agent for silicosis by targeting CCR1 and the PI3K/AKT/m TOR signaling pathway,highlighting it as a promising candidate for clinical translation for silicosis treatment.
文摘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 silicosis was 47.83 years old. The risk of silicosis in workers with pulmonary tuberculosis was 2.57 folds as those without it （P〈0.01）. Ten deaths were recorded in those with silicosis, with a case-fatality rate of 20.83 percent three of them died of lung cancer, three of liver cancer, two of ischemic heart disease, and two of other diseases as their immediate causes of death. Incidence of silicosis in foundry workers positively correlated with their cumulative silica exposure （OR-3.00, 95% CI 2.34-3.83）. Risks of silicosis increased by 4.38 folds with an increase of 1 mg/m^3-year of cumulative silica exposure, and by 3.79 folds with smoking, respectively, adjusted for alcohol drinking and age. Based on a logistic regression model fitted, incidence of silicosis is expected to be 44.6 per thousand for those with daily exposure to silica of 4.18 mg/m^3 in average for 30 years, and if incidence of silicosis is expected to be less than 1 per thousand, daily exposure to silica should be controlled below 0.2 mg/m^3 for those with 20 years of employment, or below 0.1 mg/m^3 for those with 30 or 40 years of silica exposure. Conclusions At present, foundry workers in China still face high risk of developing silicosis. For lowering occurrence of silicosis in exposed workers, it seems necessary that current occupational exposure limits for silica at worksites in China should be reexamined and silica dust control measures be strengthend.
文摘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.
文摘In the screening tests of drugs for silicosis in our laboratory, we found that TT, a type of alkaloid isolated from Stephania tetrandra, could inhibit the development of experimental silicosis of rats and the synthesis of collagen in rat lung. Chest X-rays of silicotic patients treaied with TT for 1-3 years showed obvious changes. The silicotic nodules became smallel and shadows became clearer. PVNO was proved to have anti-silicotic effect on animal and clinically. This presentation reports the effect of them on collagen mRNA.Dot blot results showed that 1 (Ⅰ) and 1 (Ⅲ) mRNA levels increased significantly at 60 and 120 days after the rats were exposed to silica dust. The mRNA levels went down at 1 and 3 months after treated by TT and PVNO. In situ hybridization observation revealed that the silver grains of Type Ⅰand Type Ⅲ collagen were scattered within the fibroblasts in cellular nodules and in thickened interstitium of silicosis tissue. The amounts of mRNA silver grains decreased in the lung tissue treated by TT and PVNO. It was suggested that TT and PVNO may inhibil the gene expression of collagen during silicosis
文摘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].
文摘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.
基金supported by the Science and Technology Department of Hebei Province,09276195D
文摘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.
基金Supported by Quanzhou Science and Technology Bureau,No.2018N053S.
文摘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 a promising biomarker for the diagnosis and assessment of severity of silicosis.
基金Special Project of Traditional Chinese Medicine Research in Henan Province:Evaluation and Characteristics of the Therapeutic Effect of Dialectical Treatment for Coal Worker Pneumoconiosis Based on Multicenter,Randomized,Double-Blind,and Parallel Controlled Trials(No.20-21ZYZD01)。
文摘OBJECTIVE:To explore the mechanisms of Yangqing Chenfei formula(养清尘肺方,YCF)in the treatment of silicosis through a comprehensive strategy consisting of serum pharmacochemistry,network pharmacology analysis,and in vitro validation.METHODS:An ultrahigh-performance liquid chromatography-tandem mass spectrometry method was used to confirm the active components in YCF-medicated serum.Then,we obtained targets for active components and genes for silicosis from multiple databases.Furthermore,a protein-protein interaction network was constructed,and Kyoto Encyclopedia of Genes and Genomes pathway and biological process analyses were conducted to elucidate the mechanisms of YCF for the treatment of silicosis.Finally,we validated the important components and mechanisms in vitro.RESULTS:Altogether,19 active components were identified from rat serum after YCF administration.We identified 724 targets for 19 components,which were mainly related to inflammation[phosphatidy linositol 3 kinase/protein kinase B,forkhead box O,hypoxia inducible factor,and T-cell receptor signaling pathway,nitric oxide biosynthetic process],fibrotic processes[vascular endothelial growth factor signaling pathway,extracellular signal regulated kinase(ERK)1 and ERK2 cascade,smooth muscle cell proliferation],and apoptosis(negative regulation of apoptotic process).In addition,218 genes for silicosis were identified and were mainly associated with the inflammatory response and immune process[cytokine-cytokine receptor interaction,tumor necrosis factor alpha(TNF-α),toll-like receptor,and nucleotide binding oligomerization domain-like receptor signaling pathway].Taking an intersection of active component targets and silicosis genes,we obtained 61 common genes that were mainly related to the inflammatory response and apoptosis,such as the phosphatidylinositol-3-kinase/protein kinase B signaling pathway,mitogen activated protein kinases signaling pathway,TNF signaling pathway,toll-like receptor signaling pathway,biosynthesis of nitric oxide,and apoptotic process.In the herb-component-gene-pathway network,paeoniflorin,rutin and nobiletin targeted the most genes.In vitro,paeoniflorin,rutin and nobiletin decreased the mRNA levels of inflammatory factors[interleukin(IL)-6,TNF-α,and IL-1β],suppressed p-AKT and cleaved caspase-3,and increased B cell lymphoma(Bcl)-2 protein expression in silica-induced macrophages in a concentration-dependent manner.CONCLUSION:YCF could significantly relieve the inflammatory response of silicosis via suppression of the AKT/Bcl-2/Caspase-3 pathway.
文摘AIM: To investigate the changes of oxidative stress indicators in the serum of silicosis patients and explore the mechanism of silicosis development.METHODS: Two hundred workers who were exposed to silica dust for more than one year were recruited as dust-exposed group, 100 non-dust-exposed subjects served as control group, 32 patients with suspected 0+ silicosis as observation group, and 130 silicosis patients were taken as the silicosis group. Indicators of oxidative stress, including superoxide dismutase(SOD), nitric oxide(NO), serum glutathione peroxidase(GSHPx), total antioxidant capacity(T-AOC), nitric oxide synthase(NOS), and lipid malondialdehyde(MDA), were determined in all the groups. RESULTS: Compared with the control group, NO and GSH-Px in dust-exposed group and silicosis group increased, and SOD decreased significantly(81.162± 35.176, 270.469 ± 39.228 and 68.209 ± 21.528, respectively, P = 0.004, P = 0.002, P = 0.005). Compared with the control and dust-exposed group, T-AOC, NOS and MDA in silicosis group increased significantly(13.048 ± 4.153, 36.201 ± 7.782 and 5.054 ± 1.204, respectively, P = 0.018, P = 0.022, P = 0.011). Compared with dust-exposed group, GSH-Px in the silicosis group increased significantly(270.469 ± 39.228, P = 0.002). GSH-Px in phase Ⅲ silicosis was significantly higher than in phase Ⅰsilicosis(290.750 ± 39.129, P = 0.021). Pearson correlation analysis showed that serum GSH-Px was positively correlated with silicosis staging, length of dust exposure and type of occupation(47.109 ± 8.015, P = 0.001).CONCLUSION: The imbalance of oxidative and antioxidation system is associated with the development of silicosis. The surveillance of oxidative stress indicators will benefit the prognosis of silicosis patients.
文摘A better understanding is needed to explain the mechanism of therapeutic effect of combined use of tetradrine-PVNO and tetradrine-QOHP which play very important roles in treatment of silicosis. Blood prolidase (PLD), monoamine oxidase (MAO) and plasminogen (PLG) in silicotic rats after treatment with tetradrine-PVNO or tetradrine-QOHP were measured. The values obtained were compared with the untreated silicotic rats. It was found that the silicotic rats that received tetradrine-PVNO showed significant increase in PLD and decrease in PLG, but no significant change in MAO. The PLD in plasma of silicotic rats that received tetradrine-QOHP were elevated significantly, but PLG and MAO did not change appreciably. These findings suggest that the combined use of tetradrine-PVNO and tetradrine-QOHP can accelerate the degradation of collagen in silicotic rats
基金Hubei Provincial Natural Science Foundation Project(Grant No.2014CFB478).
文摘Objective: To explore the effects of respiratory rehabilitation training combined with Corbrin Capsule on the inflammatory response and pulmonary fibrosis in patients with silicosis complicated by COPD. Methods: A total of 80 patients with silicosis complicated by COPD who were treated in our hospital between January 2013 and December 2016 were selected as the research subjects and randomly divided into control group (n=40) and observation group (n=40). Control group were treated with Corbrin Capsule on the basis of routine treatment, and observation group were treated with respiratory rehabilitation training combined with Corbrin Capsule on the basis of routine treatment. The differences in serum levels of inflammatory factors and pulmonary fibrosis indexes were compared between the two groups before intervention, after 6 months of intervention and after 1 year of intervention. Results: Before intervention, there was no statistically significant difference in serum levels of inflammatory factors and pulmonary fibrosis indexes between the two groups. After 6 months of intervention and after 1 year of intervention, serum inflammatory factors IL-6, IL-8, IL-12, IL-17, IL-18 and MCP-1 levels of observation group were lower than those of control group;serum pulmonary fibrosis indexes PCⅢ, LN, HA, ICAM-1 and HO-1 contents were lower than those of control group. Conclusion: Respiratory rehabilitation training combined with Corbrin Capsule therapy can effectively reduce the systemic inflammatory response and inhibit the pulmonary fibrosis process in patients with silicosis complicated by COPD.
基金Jiangsu Natural Science Foundation Youth Program:Regulation of Alveolar Macrophage Pyroptosis based on (Never in Mitosis Gene A)-Related Kinase 7/Nucleotide-like Receptor Containing Pyrin Domain 3 Inflammasome to Explore the Mechanism of Bufei Huoxue Capsule on Pulmonary Fibrosis in Silicosis (No. BK20220236)Key Research and Development Project of Xuzhou City:Evaluation of Pyroptosis Induced by Nucleotide-like Receptor Containing Pyrin Domain 3 Inflammasome Activation in Pneumoconiosis Patients by Bronchoalveolar Lavage Fluid Ion Assay Combined with High-Resolution Computed Tomography Quantitative Analysis (KC22212)Youth Medical Science and Technology Innovation Project of Xuzhou Municipal Health Commission and Development Fund of Affiliated Hospital of Xuzhou Medical University:Study on the Regulation of Various Cytokines and the Effect of c-Jun Activation Domain-Binding Protein 1 on Immune Response in Lung Cancer (XWKYHT20210565, XYFY2020051)。
文摘OBJECTIVE: To predict the targets of Bufei Huoxue capsule( 补肺活血胶囊, BFHX) using network pharmacology analysis and to explore its effects and functional targets in a silicotic rat model. METHODS: The drug and disease targets were correlated through network pharmacology analysis to explore the targets and signaling pathways of BFHX affecting silicosis. NR8383 cells were cultured to verify the core genes and pathways. A rat model of silicosis was established to verify whether the mechanism behind SiO2-caused pulmonary fibrosis was alleviated by BFHX(0.82 g/kg) and how it affected key targets and pathways. RESULTS: Overlapping BFHX and silicotic gene targets produced 159 interactive targets, and 55 were screened by network topology analysis. The results of gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses suggested that BFHX could affect silicosis through the nucleotide-like receptor containing pyrin domain 3(NLRP3) inflammasome. In NR8383 cells, the expression of core genes related to the NLRP3 inflammasome could be inhibited by BFHX treatment. BFHX reduced the degree of alveolitis and collagen deposition, attenuating pulmonary fibrosis in Si O2-induced rat model. Pulmonary macrophage pyroptosis after SiO2 exposure was observed under transmission electron microscopy. BFHX alleviated the morphological characteristics of pyroptosis. BFHX also reduced the expression of NLRP3, caspase-1, interleukin-1 beta(IL-1β), IL-18, IL-6, and tumor necrosis factor-alpha in lung tissues of silicotic rat model. BFHX affected the K ion content in bronchoalveolar lavage fluid when assessed by energy dispersive spectrometer testing. The expression of CD68+ and CD206+ were also reduced after BFHX intervention. CONCLUSION: NOD-like receptor signaling is vital for BFHX's effects on silicosis. It exerts anti-pulmonary fibrosis effects by inhibiting pulmonary macrophage pyroptosis and polarization through NLRP3 inflammasome activation.
基金This project was supported by a grant from the ChineseCenter for Disease Control and Prevention ( CDC) ( No .2001BA704B04)
文摘To provide a scientific basis for determining the health surveillance period of dust-exposed workers, data of a retrospective cohort study was re-analyzed with emphasis on natural course of silicosis. 33640 workers exposed to silica dust who were employed for at least 1 year from 1972 to 1974 in twenty Chinese mines or pottery factories were included as subjects, and were followed up till December 31, 1994. The cohort included subjects from 8 tungsten mines, 4 tin mines and 8 pottery factories. Our results showed that the mean latency of silicosis, for all the cases of the cohorts, was 22.9±9.8 y. 52.2 % of silicosis was diagnosed approximately 9.1±5.7 y after the dust exposure had ceased. The progression rates of silicosis from stage Ⅰ to Ⅱ and from stage Ⅱ to Ⅲ were 48.2 % and 18.5 %, and the duration was 4.1±0. 2 and 6.8±0.2 y, respectively. The survival times of silicosis stage Ⅰ , Ⅱ and Ⅲ, from the year of diagnosis to death, were 21.5, 15.8 and 6.8 years, respectively. There was 25 % of the silicosis patients whose survival time was beyond 33 y. The mean death age of all silicosis cases was 56.0 y. The death age inereased to 65.6 y in the middle of 1990s. Among dust-exposed workers, subjects who became suspected case （0^＋ ） accounted for 15.0 %. 48.7 % of the suspected silicosis cases developed to silicosis, and the average year from the time of being suspected of the disease to the first stage of silicosis was 5.1y. The natural characteristics, as mentioned above, varied with different mines and factories. We are led to conclude that silicosis is chronic in nature, but progress quickly. As a serious occupational disease it significantly reduces the life span of exposed workers. The study of its natural history is of importance for the development of health surveillance criteria for dust-exposed workers.
文摘In order to provide scientific information on the prevention and treatment of silicosis,studies about changes of silicotic collagen in lungs were carried out. In this paper, we present experiments about the structural changes of collagen in silicotic lungs of rats and patients. These included electron microscopy, circular dichroism and infrared spectroscopy studies of collagen fibers. The results indicated that fibers of silicotic collagen were shorter in length, smaller in diameter and decreased in α-helix content. The -Si-O-R- group and -OH group were found increased and -C-C- backbone shortened. The increase of -Si-O-R-group indicated that silica formed linking bridges between collagens which may be the cause of progressive enlargement of nodules
基金National Natural Science Foundation of China(No.81971483)Anhui University Collaborative Innovation Project(No.GXXT‑2020‑058)Anhui University of Science and Technology Innovation and Entrepreneurship Project(No.2021CX2125,2021CX2126,2021CX2124)。
文摘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:Tetrandrine regulates the inflammatory response and epithelial-mesenchymal transition(EMT)through the RAF/MEK/ERK pathway and thus affects the early progression of silicosis.
基金Supported by Science and Technology Fund Project of Guizhou Provincial Health Commission (gzwjkj2020-1-184)。
文摘[Objectives]This study was conducted to explore the combination of serum Apelin and MMP-9 in the assessment of silicosis and their correlation with lung function. [Methods] From January 2020 to January 2021, eight patients with silicosis(including 3, 2 and 3 patients with silicosis in stages I, II and III respectively) were selected as the observation group, and eight persons frees of silicosis were selected as the control group during the same period. All patients were detected for serum APJ endogenous ligand(Apelin) of G protein-coupled receptor, matrix metalloproteinase-9(MMP-9) and pulmonary function indexes. The levels of serum Apelin and MMP-9 and lung function in the two groups were compared, and the correlation between serum Apelin and MMP-9 indexes and lung function was analyzed. [Results] The serum Apelin and lung function in the observation group were lower than those in the control group, and the level of MMP-9 in the observation group was higher than that in the control group, and the differences were statistically significant(P<0.05). The MMP-9 index in patients with silicosis in stage III was higher than those in patients with silicosis in stage II and stage I, and the MMP-9 index in patients with silicosis in stage II was higher than that in patients with silicosis in stage I, and the differences were statistically significant(P<0.05). The serum Apelin and lung function indexes of patients with silicosis in stage III were lower than those of patients with silicosis in stage II and stage I, and the serum Apelin and lung function indexes of patients with silicosis in stage II were lower than those of patients with silicosis in stage I, and the differences were statistically significant(P<0.05). The correlation analysis showed a positive correlation between serum Apelin and lung function indexes, and a negative correlation between MMP-9 and lung function indexes. [Conclusions] A lower serum Apelin and a higher MMP-9 value in patients with silicosis indicate severer lung function impairment, and the combined detection of serum Apelin and MMP-9 is conducive to effective evaluation of the disease of silicosis. The serum Apelin index was negatively correlated with silicosis, and the level of MMP-9 was positively correlated with silicosis, which could provide a scientific basis for clinical diagnosis and treatment.
文摘In the present study, we developed silicosis of rat model by bronchial perfusion SiO2 dust, and intervenes with AcSDKP, immunohisto chemistry was used to detect NF-κb and MCP-1 expression in lung tissue, and positive cells were counted. We found that compared with silicotic model group, the positive cells of NF-κb and MCP-1 were decreased significantly in anti-fibrosis treatment of AcSDKP group. The findings suggest that AcSDKP could inhibit the expression of NF-κb and MCP-1 in lung tissue of silicosos, this may be related to AcSDKP inhibit of macrophage infiltration in lung tissue and reduced the degree of dust alveolitis.
文摘The experimental time of this paper started in August 2020 and lasted until October of the following year. Mainly for the elderly patients with silicosis to carry out nursing, analyze the nursing effect. In this experiment, 70 patients with silicosis were selected as experimental subjects by data comparison method, and they were divided into control group and observation group according to before and after seeing a doctor. The former adopts general nursing, while the latter adopts comprehensive nursing. The psychological conditions, complications and so on of the two groups were compared. After nursing, it can be clearly seen that all indexes of the observation group are better than those of the control group, which shows that comprehensive nursing is more suitable for the nursing of elderly silicosis patients.
