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Mesenchymal stem cells(MSCs) have functions such as immune regulation and tissue damage repair, but the specific mechanisms of their effects need to be further studied. Paracrine effect is an important mechanism for MSCs to achieve immune regulation, relieve inflammation and repair tissue damage. Tumor necrosis factor α(TNF-α) stimulated protein 6(TSG-6) is one of the paracrine factors of MSCs, which has significant inflammation inhibitory capability and tissue repair ability. It is an important cytokine of MSCs to exert their anti-inflammatory and anti-fibrotic effects. The MSCs can repair tissue damage in kidney, peritonea, skin, liver, lung, cornea, nervous system, and colon by secreting TSG-6. This powerful repair ability could be attributed to the ability of TSG-6 to inhibit the secretion of pro-inflammatory cytokines and pro-fibrogenic factors, such as TNF-α, interleukin(IL)-6, IL-1β and transforming growth factor-β1, thereby reducing the inflammatory response and fibrosis of the body.
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OBJECTIVE: To explore the association of serum Apelin level, silicosis stage and lung function in patients with occupational silicosis(hereinafter referred to as silicosis). METHODS: A case-control study was conducted. A total of 85 patients with silicosis were selected as the silicosis group(44, 28 and 13 patients with stage Ⅰ, Ⅱ and Ⅲ silicosis, respectively), and 120 healthy individuals without occupational hazard exposure were selected as the control group. Serum samples were collected from the cases of the two groups and the level of Apelin was determined by enzyme-linked immunosorbent assay. The pulmonary function of the silicosis group was examined. RESULTS: The median and the 25 th and 75 th percentiles \[M(P_(25),P_(75))\] of serum Apelin levels in the control group and silicosis group were 1.29(0.92, 1.77) and 0.80(0.62, 1.04) mg/L, respectively. The level of serum Apelin M(P_(25),P_(75)) in stage Ⅰ, Ⅱ and Ⅲ silicosis patients was 1.03(0.82, 1.31), 0.66(0.60, 0.80) and 0.50(0.30, 0.65) mg/L, respectively. The results of multiple linear regression analysis showed that the level of serum Apelin in the silicosis group was higher than that in the control group after excluding the influence of age and smoking(P<0.01). The level of serum Apelin decreased with the increase of silicosis stage in the silicosis group(P<0.001). Serum Apelin level in silicosis group was positively correlated with lung vital capacity, forced vital capacity, forced expiratory volume in the first second, and forced expiratory flow between 25% and 75%(all P<0.05). CONCLUSION: The lower level of serum Apein in silicosis patients, the more serious the disease and the more serious the damage to lung function. Apelin is of significance in the diagnosis, staging, treatment appraisal and prognostic evaluation of silicosis, and it can be use as a potential therapeutic target for silicosis.
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OBJECTIVE: To explore the mechanism of bone marrow mesenchymal stem cells(BMSCs) in alleviating silica-induced lung injury in mice. METHODS: Ten specific pathogen free healthy male C57 BL/6 mice were selected for isolating BMSCs and bone marrow macrophages(BMDMs). Transwell chamber was used, BMDMs were inoculated onto the upper chamber and BMSCs in the lower chamber. We divided them into sequencing control group and silica(SiO_2) exposure group. All cells were pre-stimulated with 50 μg/L mass concentration lipopolysaccharide for 4 hours. In the SiO_(2 ) group, 250 mg/L mass concentration SiO_2 was added to the upper chamber of transwell and cultured for 16 hours. Total RNA was extracted from the BMSCs collected from the lower chamber. HiSeq/MiSeq high-throughput sequencing technology was used to detect the BMSCs RNA paired-end sequencing. Transcriptome sequencing data was obtained and bioinformatics analysis was performed. Another 12 specific pathogen free healthy male C57 BL/6 mice were randomly divided into control group and experimental group. All mice received one intra-tracheal injection of 20.0 μL(250 g/L mass concentration) of silica dust suspension. After 6 hours, the mice in the control group was given 500.0 μL of 0.9% sodium chloride solution and mice in the experimental group was given 500.0 μL of BMSCs suspension(cell density 1×10~9/L) by tail vein infusion.Mice were sacrificed 12 hours later. The relative mRNA expression of interleukin(IL)-1 Ra, IL-10, tumor necrosis factor stimulating gene 6(TSG-6) and prostaglandin E2(PGE2) in lung tissues of mice were measured by quantitative real-time PCR(q-PCR). Meanwhile, BMDMs and BMSCs transwell co-culture models were established. The cells were divided into 5 groups: BMSCs group, BMSCs+BMDMs group, BMSCs+BMDMs+ lipopolysaccharide(LPS) group, 50 mg/L SiO_2 group, and 100 mg/L SiO_2 group. After 16 hours of corresponding SiO_2 stimulation, BMSCs of each group were collected and the relative mRNA expression levels of IL-1 Ra, IL-10, TSG-6, and PGE2 in the cells were detected by q-PCR. RESULTS: Compared with sequencing control group, BMSCs co-cultured with SiO_2 had 19 genes up-regulated and 21 genes down-regulated, including 10 genes up-regulated for more than 2.0-fold. The relative mRNA expression of IL-1 Ra, IL-10, PGE2 and TSG-6 in the lung tissue of mice increased in the experimental group than that of the control group(all P<0.05). The relative mRNA expression of TSG-6 increased by 37.5 times higher than that of the control group. Compared with the BMSCs+BMDM+LPS group, the level of TSG-6 mRNA relative expression increased in both the 50 mg/L SiO_2 group and the 100 mg/L SiO_2 group(all P<0.05). CONCLUSION: TSG-6 could be the key factor of BMSCs that can attenuate silica-induced lung injury.
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Pulmonary fibrosis is an interstitial lung disease caused by different pathogenic factors. It has the characteristics of high morbidity and poor prognosis, which seriously affects the quality of life of patients. However, its pathogenesis has not yet been fully elucidated. Surfactant protein(SP)-A and SP-D are lipoprotein complexes distributed at the air-liquid interface of alveoli, synthesized and secreted by alveolar type Ⅱ epithelial cells and bronchiolar cells. They are important parts of the innate immune system, which participate in the host defense process through a variety of regulatory methods, and play an important role in regulating cell apoptosis and lung inflammation, promoting the process of epithelial repair and maintaining the stability of alveolar structure. The disorder and mutation of SP-A and SP-D may be the influencing factors of the pathogenesis of pulmonary fibrosis. Serum SP-A and SP-D levels are differentially expressed in patients with pulmonary fibrosis and normal healthy individuals, and are related to the severity of pulmonary fibrosis. They are considered to be a class of biomarkers that sensitively reflect lung epithelial cell damage and can be used in the diagnosis, treatment and prognostic evaluation of pulmonary fibrosis.
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Acute 1,2-dichloroethane poisoning causes serious illness, deaths and is a social event of great influence. The compilation of Technical Plan for Emergency Treatment of Acute 1,2-Dichloroethane Poisoning provides scientific guidance for effective treatment of 1,2-dichloroethane poisoning events. The plan describes in detail the specific practice and technical requirements of six links in the process of handling emergency of acute 1,2-dichloroethane poisoning, including accident investigation and treatment, risk assessment, collection and testing of samples, medical treatment, health monitoring and emergency response, et al. The key contents of individual protection requirements, investigation content, etiology determination, medical assistance and health education in the disposal of poisoning incidents were clarified, and the procedures and requirements of health education were added. The technical scheme is scientific, objective and operable, which can provide scientific guidance for the effective treatment of 1,2-dichloroethane poisoning accidents.
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Objective To study the mechanism of bone marrow mesenchymal stem cell (BMSC)-mediated alleviation of pulmonary alveolitis in mice exposed to silica dust. Methods Thirty mice were randomly divided into 3 groups:control group, and two silica groups with or without BMSCs transplantation.Through the tracheal tube clearance, mice in control group received a single injection 20.0 μL of 0.90% sodium chloride solution by one time.Mice from in silica group and silica/BMSCs transplantation group first received a single injection of 20.0 μL silica dust suspension (mass concentration 250 g/L); followed by either 500.0 μL of 0.90% sodium chloride solution or by 500.0 μL of BMSCs suspension (cell density 1×109/L) through tail vein infusion 6 hours later.Mice were euthanized on the 3th day of the experiments.The levels of NALP3 inflammasome in lungs was determined by Western blot.Transwell system was used for co-culture of BMDM (in upper-chamber) and BMSC (in lower-chamber) co-culture.The level of cytokines IL-1β in BMDM cultural supernatant was detected by enzyme linked immunosorbent assay after stimulated by SiO2 stimulation.The levels of NALP3 inflammasome of in BMDM was determined by Western blot. Results The levels of pro-IL-1β, IL-1β, pro-caspase-1, caspase-1 in lungs of silica/BMSCs transplantation group were lower than that in silica group (P < 0.01).In the experiment in vitro, the concentrations of IL-1β in SiO2 exposed BMSC/BMDM co-culture group were lower than the SiO2 exposure only groups (P < 0.05).Meanwhile, the levels of pro-IL-1β, IL-1β, pro-caspase-1, caspase-1 in BMDM was lower than that in silica group (P < 0.01).The level of these proteins didn′t change while when the cell-free supernatant of BMSC culture was directly added. Conclusion The BMSC could inhibit NALP3 inflammasome of macrophages stimulated by SiO2.
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OBJECTIVE: To explore the immune cytotoxic effect and the maximum non-effect dose of trichloroethylene( TCE) on Jurkat T cells in vitro. METHODS: i) Naive and activated Jurkat T cells were treated with different concentrations of TCE( 0. 10, 0. 50, 1. 00, 2. 00, 5. 00, 10. 00 mmol / L). Phorbol-12-myristate-13-acetate and ionomycin were used as agonist. No TCE was used in the control group and dimethyl sulfoxide( DMSO) was used as the solvent group. The morphology of Jurkat T cells was observed using a light microscope and the survival rate of Jurkat T cells was investigated using CCK-8 essay after cells were cultured for 24,48 and 72 hours. ii) Nave and activated Jurkat T cells were treated with different concentrations of TCE( 0. 00,0. 02,0. 20,2. 00 mmol / L). The apoptosis of cells was detected using flow cytometry and the level of interleukin-2( IL-2) in supernatant was detected using enzyme linked immunosorbent assay after cells were cultured for 24,48 and 72 hours. RESULTS: i) Cytotoxic effect was observed after cells were exposed to 10. 00 mmol / L TCE for 24 hours. Cells dispersed,cell volume diminished,cell membrane ruptured,cytoplasm condensed and increased outflow of intercellular organelles. The effect of interaction between exposure dose and exposure time was statistically significant on cell survival rate( P < 0. 01). Compared with the control and DMSO groups at the same time points,there were no significant differences in the 0. 10,0. 50,1. 00 and 2. 00 mmol / L TCE treatment groups in cell survival rates in three different time points( P > 0. 05),while the cell survival rates of 5. 00 and 10. 00 mmol / L TCE treatment groups were significantly decreased( P < 0. 01). ii) When TCE concentration was 0. 00-2. 00 mmol / L,there were no significant differences in the main effect of exposure dose and interactions of between exposure dose and cell type or exposure time on cell apoptosis rate( P > 0. 05). Compared with the same time points and groups of naive Jurkat T cells,the levels of IL-2 of activated Jurkat T cells were significantly increased( P < 0. 01). In the three different time points,the level of IL-2 of activated Jurkat T cells increased in accordance with the TCE exposure dose,showing a dose-effect relationship( P < 0. 01). The level of IL-2 of activated Jurkat T cells increased in accordance with TCE exposure time,showing a time-effect relationship( P < 0. 01). CONCLUSION:s TCE at the level of 2. 00 mmol / L had no observed effect in Jurkat T cells. High doses of TCE( ≥5. 00 mmol / L) showed cytotoxic damages to naive and activated Jurkat T cells and low doses of TCE( ≤2. 00 mmol / L) could stimulate activated Jurkat T cells secrete IL-2 in a dosedependent and time-dependent manner.
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OBJECTIVE: To analyze the usage of glucocorticoid in patients who were treated with occupational medicamentose-like dermatitis due to trichloroethylene( OMDT),in order to provide a reference for regulating the glucocorticoid treatment of the disease. METHODS: Using a retrospective survey method,144 OMDT cases of patients who were diagnosed and cured by Guangdong Province Hospital for Occupational Disease Prevention and Treatment from 2001 to2013 were selected. The general information,clinical data and the use of glucocorticoid were collected and analyzed.RESULTS: i) The usage of glucocorticoid. The median and the 0th to 100 th percentile [M( P_0-P_(100)) ] of first dose of methylprednisolone was 100. 00( 40. 00-1 000. 00) mg / d; 58 patients( 40. 3%) using the first dose of treatment were ineffective. The dosage of glucocorticoid was increased one week after admission,the M( P_0-P_(100)) to an initial dose of120. 00( 40. 00-1 000. 00) mg / d; The M( P_0-P_(100)) of maintenance time of initial dose was 5. 5( 1. 0-14. 0) days. After treating effectively,should the decrement to stop using gradually the first glucocorticoid. The dose was gradually cut down to 20-50 mg every 1 to 3 days if the glucocorticoid dose was more than 100 mg / d; it was cut down to 10 mg every 2 to 3days if the glucocorticoid dose was less than 100 mg / d. The M( P_0-P_(100)) of glucocorticoid using time was 66. 0( 22. 0-229. 0) days. The M( P_0-P_(100)) of total amount of glucocorticoid was 3 510. 0( 420. 0 ~ 27 336. 3) mg. ii) The first dose of glucocorticoid in patients of erythema multiforme group were less than those of exfoliative dermatitis group and bullous epidermal necrolysis group( P < 0. 05),the initial dose and total amount of glucocorticoid were less than the other 3 types of rash( P < 0. 05). iii) Compared with the patients with severe impaired liver function,the first dose,the initial dose and the total amount of glucocorticoid were significantly higher than those in mild impaired liver function( P < 0. 05),and the time of using glucocorticoid was longer than that in mild impaired liver function( P < 0. 05). iv) The first dose and the initial dose of glucocorticoid in patients were positively correlated with the total amount of glucocorticoid [Spearmen correlation coefficient( r_S) were 0. 73 and 0. 78 respectively,P < 0. 01). The maintenance time of the initial dose of glucocorticoid was not correlation with the time of patients who were out of contact with trichloroethylene or the urinary level of trichloroacetic acid at admission( r_Swere- 0. 14 and 0. 10 respectively,P > 0. 05). v) Binary Logistic regression analysis showed that,if the patients who had no erythema multiforme,the more severe the degree of liver dysfunction or the white blood cell count higher than 9. 5 × 10~9/ L,the first dose of glucocorticoid used should be more than 120 mg / d( P <0. 05). CONCLUSION: Liver function and type of rash are important factors that affect the usage of glucocorticoid in patients with OMDT. Glucocorticoid therapy should be prescribed in reference to the liver function and skin lesion of patients with OMDT.
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OBJECTIVE: To establish the clinical pathway of chronic mild occupational cadmium poisoning,and to promote the application of clinical pathway in the treatment of occupational diseases. METHODS: Chronic mild occupational cadmium poisoning was selected as a disease for a pilot study based on GBZ 17-2015 Diagnosis of Occupational Cadmium Poisoning. The diagnosis and treatment scheme and the clinical pathway were developed based on the theory of evidencebased medicine and expert consultation. It was then used and evaluated in clinical practice in several hospitals. RESULTS: The content of clinical pathway of chronic mild occupational cadmium poisoning included the standard in-hospital treatment process protocol,the clinical pathway forms and the consent document for patients. The clinical application of the pathway significantly improved the outcome of treatment,shortened hospital stays and effectively control hospitalization expenses.CONCLUSION: The clinical pathway for chronic mild occupational cadmium poisoning is rational and feasible. The result confirms that the clinical pathway may have good application prospect for the treatment of occupational diseases.
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OBJECTIVE: To analyze the clinical features of occupational chronic toxic peripheral neuropathy caused by1-bromopropan( 1-BP). METHODS: Clinical data of 4 patients who suffered from occupational chronic toxic peripheral neuropathy caused by 1-BP were collected for retrospective analysis. RESULTS: The 4 male patients were ultrasonic cleaning operation workers in a hardware vacuum coating enterprise. They were exposed to high levels of 1-BP for 9-11 months. The main clinical manifestations were varying degrees of sensory disorder and dyskinesia. The main symptoms were progressive increase of numbness and fatigue in the lower extremities. These symptoms might be accompanied by unsteady gait.Physical examination showed muscle strength weakness in the double lower limbs. The hypalgesia,pselaphesia,topesthesia and pallesthesia decreased in the double lower limbs or 4 limbs. The bilateral achilles tendon reflex mainly showed reduced or disappeared. One case had sensory ataxia. Electroneuromyography examination showed different levels of peripheral nerve damage among the cases. The motor nerve conduction velocity and sensory nerve conduction velocity reduced commonly. The axon and myelin sheath damage were visible. On the basis of GBZ / T 247-2013 Diagnosis of Occupational Chronic Toxic Peripheral Neuropathy Caused by Chemicals,these cases were diagnosed as occupational chronic toxic peripheral neuropathy caused by 1-BP. CONCLUSION: Long-term exposure to high level 1-BP can lead to chronic poisoning with peripheral nervous system damage. The diagnosis can be made based on the 1-BP exposure history,clinical features and the neurogenic damage found in electroneuromyography examination.
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OBJECTIVE: To observe whether bone marrow mesenchymal stem cell( BMMSC) could be induced by alveolar epithelial cell( AEC) of rats exposed to silica dust or not. METHODS: BMMSCs were isolated and cultivated from 6specific pathogen free healthy male SD rats through bone marrow adherent method. The AECs from other 6 rats randomly selected from the same batch were cultivated by immune adherent purification method. Three rats were treated with 1. 0 m L( 40 g/L mass concentration) of silicosis dust suspension by one time intratracheal injection as silicosis dust exposure model,and the other 3 rats were given 0. 9% sodium chloride solution as normal. Experimental group was the co-culture of BMMSCs and AECs from silicosis dust exposure rats. Control group A was the co-culture of BMMSCs and AECs from normal rats. Control group B was the culture of BMMSCs alone. The morphology changes were observed by the inverted phase contrast microscope at the time points of the 4th and the 8th day. Double immunofluorescence staining using aquaporin 5( AQP5) and surfactant protein C( SP-C) was performed on the treated BMMSCs. The fluorescence staining was observed using the inverted fluorescence microscope( IFM) and laser scanning confocal microscope( LSCM). Integral optical density( IOD) analysis was conducted on fluorescence of 2 kinds of proteins by Image-pro plus 6. 0 graphic analysis software. RESULTS: After the co-culture,the BMMSCs in experimental group and control group A changed from long spindle shape to cubic and polygonal shape,the variation of morphology on day 8 was more obvious than that on day 4,and the change in control group A was less obvious than that of experimental group. There was no obvious morphology change in BMMSCs of control group B. By IFM and LSCM,on day 4 and day 8,the expression of green fluorescence AQP5 and red fluorescence SP-C were all observed in BMMSCs of experimental group and control group A. The BMMSCs of control group B only showed a little green fluorescence expression of AQP5,no expression of red SP-C fluorescence was seen. Both by IFM and LSCM,on day 4 and day 8,the 2 kinds of IOD of BMMSCs in experiment group were higher than those of control group A and B at the same time points( P < 0. 01); the IOD of control group A was higher than that of control group B at the same time point( P < 0. 01). The IOD of experiment group and control group A on day 8 were higher than those on day4 in the same group( P < 0. 01). CONCLUSION: AEC of rats exposed to silica dust can effectively induce BMMSC to be differentiated into AEC.
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<p><b>OBJECTIVE</b>To explore the mechanism of occupational medicamentosa-like dermatitis (OMDT) induced by trichloroethylene (TCE) and some immunity indexes in workers occupationally exposed to TCE.</p><p><b>METHODS</b>The blood samples from 8 cases with medicamentosa-like dermatitis in 1st, 2nd, 3rd, 4th and 5th weeks after admitting to hospital were examined for liver function, immunoglobulin and some complement indexes. Thirty nine workers occupationally exposed to TCE were investigated for urinary TCE and some immuno-complement indexes. The TCE concentrations of air in workplaces were monitored.</p><p><b>RESULTS</b>C3d-CIC and C3 of patients before admission were (92.86 ± 44.80) mg/L and 0.91 ± 0.19 mg/L, respectively. C3d-CIC and C3 of patients before discharge were (52.41 ± 17.75) mg/L and (1.14 ± 0.22) mg/L, respectively. There were significant differences between admission and discharge (P < 0.05). The average TCE concentration in 4 workplaces was (351.96 ± 36.72) mg/m(3), which was higher than the occupational exposure limits (OELs). The number of workers exposed to the TCE concentration-time weighted and TCA in urine over OELs were 28.21% and 56.41% of total subjects, respectively. The serum IgG and CIC levels of patients before discharge were (10.03 ± 1.21) mg/L and 103.50 ± 29.17 mU/L, which were significantly lower than those (17.21 ± 1.85) mg/L and (227.46 ± 111.67) mU/L of patients before admission (P < 0.01).</p><p><b>CONCLUSION</b>The type II and III hypersensitivity may be associated with OMDT and the organ injure induced by TCE.</p>