The abnormalities of coagulation and fibrinolysis in acute lung injury caused by gas explosion.

Acute lung injury (ALI) caused by gas explosion is common, and warrants research on the underlying mechanisms. Specifically, the role of abnormalities of coagulation and fibrinolysis in this process has not been defined. It was hypothesized that the abnormal coagulation and fibrinolysis promoted ALI caused by gas explosion. Based on the presence of ALI, 74 cases of gas explosion injury were divided into the ALI and non-ALI groups. The results of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and platelet count (PLT) were collected within 24 hours and compared between the groups. ALI models caused by gas explosion were established in Sprague Dawley rats, and injuries were evaluated using hematoxylin and eosin (HE) staining and histopathological scoring. Moreover, the bronchoalveolar lavage fluid (BALF) was collected to examine thrombin-antithrombin complex (TAT), tissue factor (TF), tissue factor pathway inhibitor (TFPI), and plasminogen activator inhibitor-1 (PAI-1) levels by enzyme-linked immunosorbent assay (ELISA). The patients in ALI group had shorter PT and longer APTT, raised concentration of FIB and decreased number of PLT, as compared to the non-ALI group. In ALI rats, the HE staining revealed red blood cells in alveoli and interstitial thickening within 2 hours which peaked at 72 hours. The levels of TAT/TF in the BALF increased continually until the seventh day, while the PAI-1 was raised after 24 hours and 7 days. The TFPI was elevated after 2 hours and 24 hours, and then decreased after 72 hours. Abnormalities in coagulation and fibrinolysis in lung tissues play a role in ALI caused by gas explosion.

Urine Metabonomic Analysis of Interventions Effect of Soy Isoflavones on Rats Exposed to Di-(2-ethylhexyl) Phthalate.

OBJECTIVE: Di-(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental contaminant. As an endocrine disruptor, it seriously threatens human health and ecological environmental safety. This study examines the impact of intervention with soybean isoflavones (SIF) on DEHP-induced toxicity using a metabonomics approach. METHODS: Rats were randomly divided into control (H), SIF-treated (A, 86 mg/kg body weight), DEHP-treated (B, 68 mg/kg), and SIF plus DEHP-treated (D) groups. Rats were given SIF and DEHP daily through diet and gavage, respectively. After 30 d of treatment, rat urine was tested using UPLC/MS with multivariate analysis. Metabolic changes were also evaluated using biochemical assays. RESULTS: Metabolomics analyses revealed that p-cresol glucuronide, methyl hippuric acid, N1-methyl-2-pyridone-5-carboxamide, lysophosphatidycholine [18:2 (9Z, 12Z)] {lysoPC [18:2 (9Z, 12Z)]}, lysoPC (16:0), xanthosine, undecanedioic acid, and N6-acetyl-l-lysine were present at significantly different levels in control and treatment groups. CONCLUSION: SIF supplementation partially protects rats from DEHP-induced metabolic abnormalities by regulating fatty acid metabolism, antioxidant defense system, amino acid metabolism, and is also involved in the protection of mitochondria.

Sodium 4-phenylbutyrate Attenuates High-fat Diet-induced Impaired Spermatogenesis.

OBJECTIVE: To determine the mitigating effects of sodium 4-phenylbutyrate (4-PBA) on high-fat diet (HFD)-induced spermatogenesis dysfunction. METHODS: Male rats (n = 30) were randomly divided into three groups: control, HFD, and 4-PBA (HFD +4-PBA). After 13 weeks, rats were euthanized. Testes and epididymis were harvested for further analysis. Sex hormones were detected, and hematoxylin and eosin staining was performed to examine the histological changes in the testes. Semen samples were collected to evaluate sperm quality. Spermatogenic cell apoptosis was detected by TUNEL assay. RESULTS: Compared with the control group, the final body weight and body weight gain were significantly higher in HFD-fed rats, while the testicle/body weight ratios were lower (P < 0.05). In HFD-fed rats, obvious pathological changes in the testicular tissue were observed. Treatment with 4-PBA attenuated HFD-induced histological damage, ameliorated the HFD-induced decrease in serum testosterone (T), and reduced the rate of testicular cell apoptosis (P < 0.05) in obese male rats. Finally, 4-PBA significantly improved semen parameters in HFD rats (P < 0.05). CONCLUSION: HFD exposure induced detrimental effects on spermatogenesis, semen quality, serum T level, and testicular cell apoptosis in rats. Treatment with 4-PBA ameliorated HFD？induced impaired spermatogenesis via inhibition of apop-tosis in rats. 4-PBA may have therapeutic value in the treatment of obesity？related impairment of spermatogenesis.

Association between polymorphisms of interleukin-17A and interleukin-17F genes and silicosis susceptibility in Chinese Han people.

BACKGROUND: To explore the relationship between polymorphisms of interleukin17 (IL-17) gene(A-832G 7488A/G) and the susceptibility to silicosis, a risk factor for lung cancer. MATERIALS AND METHODS: A total of 113 silicosis patients and 116 workers without silicosis were enrolled in the case-control study. IL-17A A-832G and IL-17F 7488A/G polymorphisms were evaluated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The frequencies of AA,GG and AG of IL-17A A-832G locus in the case and control groups were 46.9%, 8.0%, 45.1%, and 49.2%, 7.6%, 43.2%, respectively, with no significant differences (p>0.05).The GG genotype in the IL-17F (7488A/G) locus was not found. The frequencies of AA and GA of IL-17F 7488A/G locus in the case and control groups were 84.1%, 15.9% and 66.4%, 33.6%, respectively (p<0.05). Analysis of combined effects showed that the individuals with GG+AG genotype of IL-17A and GG+GA genotype of IL-17F are protected against silicosis (OR=0.469). CONCLUSIONS: IL-17F 7488A/G is associated with susceptibility to silicosis, and G allele may have a protective effect. No relationship was found between IL-17A gene polymorphisms at A-832G and silicosis.

N-acetylcysteine alleviated silica-induced lung fibrosis in rats by down-regulation of ROS and mitochondrial apoptosis signaling.

Reactive oxygen species (ROS) is a normal metabolic product of cellular respiration, but too much ROS can induce cell apoptosis. Here, we used N-acetylcysteine (NAC) to inhibit ROS activity to explore the effects of NAC on silica-induced pulmonary fibrosis in rats and provide evidence for study on the mechanism of silicosis. 24 adult male Sprague-Dawley rats weighing 180-220 g were randomly divided into three groups with eight rats in each group. Silicosis model group and NAC group were adopted non-tracheal exposure method of disposable intrapulmonary injection of 50 g/L, silica suspension 1 mL to establish animal silicosis model, NAC group treated with 600 mg/kg NAC by gavage from the right day of modeling, all animals were sacrificed after 28 days. The level of ROS contents and mitochondrial transmembrane potential changes of AM, the mRNA expression level of type I and type III procollagen, cytochrome C, cysteinyl aspartate specific protease-9 and caspase-3 were detected. The severity of pathological changes and pulmonary fibrosis were observed by pathologic specimens. It was showed that ROS contents and MTP changes were lower in the NAC group compared with the silicosis model group, other indexes were lower in the NAC group than the model group, but higher than those of the control group, the degree of lung fibrotic lesions observed from the pathological slices showed the same trend. These data indicated that NAC can reduce ROS content of AM in silica exposure rats, the mitochondrial apoptosis pathway can also be inhibited, the severity of pulmonary fibrosis alleviated as a result.

[Autophagy in lung tissue of rats exposed to silica dust].

OBJECTIVE: To investigate the autophagy of effector cells in lung tissue at different time points when rats were exposed to free SiO2 dust. METHODS: Sixty Wistar rats (220∼230 g) were selected and allocated to experimental group (n = 30) and control group (n = 30). In the experimental group, a rat silicosis model was established by infusing SiO2 suspension into the trachea of rats. Six rats in each group were sacrificed on days 1, 7, 14, 21, or 28 of dust exposure. Lung tissue samples were collected to prepare lung tissue sections. The pulmonary inflammation and fibrosis were observed by HE staining. The proautophagosome, autophagosome, and autophagolysosome in lung tissue sections were observed under a transmission electron microscope. RESULTS: On day 1 of dust exposure, many proautophagosomes and autophagosomes were seen in both experimental group and control group. On day 7 of dust exposure, the experimental group had more autophagosomes in lung tissue than the control group. On day 14 of dust exposure, the experimental group had fewer autophagosomes than the control group. On days 21 and 28, autophagolysosomes were seen in macrophage plasma in both experimental group and control group; the autophagolysosomes in experimental group showed cloudy swelling and expansion, and some were vacuolated, and these changes were more significant on day 28. CONCLUSION: Free SiO2 dust can induce autophagy in the lung tissue of rats, with varying degrees at different time points of dust exposure.

Fas/FasL pathway-mediated alveolar macrophage apoptosis involved in human silicosis.

In vitro and in vivo studies have demonstrated that lung cell apoptosis is associated with lung fibrosis; however the relationship between apoptosis of alveolar macrophages (AMs) and human silicosis has not been addressed. In the present study, AM apoptosis was determined in whole-lung lavage fluid from 48 male silicosis patients, 13 male observers, and 13 male healthy volunteers. The relationships between apoptosis index (AI) and silica exposure history, soluble Fas (sFas)/membrane-bound Fas (mFas), and caspase-3/caspase-8 were analyzed. AI, mFas, and caspase-3 were significantly higher in lung lavage fluids from silicosis patients than those of observers or healthy volunteers, but the level of sFas demonstrated a decreasing trend. AI was related to silica exposure, upregulation of mFas, and activation of caspase-3 and -8, as well as influenced by smoking status after adjusting for confounding factors. These results indicate that AM apoptosis could be used as a potential biomarker for human silicosis, and the Fas/FasL pathway may regulate this process. The present data from human lung lavage samples may help to understand the mechanism of silicosis and in turn lead to strategies for preventing or treating this disease.

[Investigation about prevention behavior for dust workers in machinery, ceramic, and metallurgy industry].

OBJECTIVE: The purposes of this thesis were to study the behavior about workers exposed to dust and provide scientific basis for health promotion. METHODS: We designed a questionnaire and carry it on the 746 dust workers in the 3 representative corporations of Machinery, Ceramic, and Metallurgy Industry. All data were input into computer. And a database was established with Excel. SPSS11.5 statistical analysis software was used to analyze the influence on protecting behavioral between the application of qualifications, different jobs, training or protection, and other aspects etc. RESULTS: The rates were 94.4% and 75.3% about the regular physical examination and requirements for protective equipment. The rate of choosing an effective way of protection was generally low (15.4%). There was significant difference for among different educational background workers (P < 0.01). The rates of choosing an effective way of protection (20.3%), the regular physical examination (98.3%) and requirements for protective equipment (86.4%) in the dust workers who participated in the training of dust protection were superior than those who did not participated in the training. There was the significant difference (P < 0.05, P < 0.01). There was the significant difference for the rate of effective way of protection, regular physical examination, and requirements for protective equipment among the different corporations (P < 0.05). CONCLUSIONS: Dust workers' using rate about the choosing an effective way of protection was generally low in Machinery, Ceramic, and Metallurgy Industry. Those who were not educated had a lower using rate about the protection behavior, regular physical examination, and requirements for protective equipment than those educated.

[Macrophage apoptosis and the levels of interleukin-1 and interleukin-8 in the rats exposed to silica].

OBJECTIVE: To study the roles of macrophage apoptosis, IL-1, and IL-8 in the pathogenesis of rat pulmonary fibrosis induced by silica. METHODS: Forty eight male Wistar rats were divided into the 4 control groups (24 rats) and 4 experimental groups (24 rats). Rats in the control groups were treated with 1 ml normal saline by trachea instillation, whereas the rats in experimental groups were exposed 1 ml silica suspension (100 mg/ml) by trachea instillation for 1, 7, 14 and 28 days, respectively. Six rats of each group were sacrificed, then the bronchoalveolar lavage fluid and lung tissues were collected, respectively. Pulmonary inflammation, fibrosis and other pathological changes were detected with H.E. staining. Morphological changes of the early stage apoptosis in macrophages were detected with transmission electron microscope (TEM). The early apoptosis rates of macrophages in BALF were also assessed using Annexin V-FITC/PI kit. The IL-1 and IL-8 levels of serum were measured with the ELISA. RESULTS: The apoptotic rates (11.48% +/- 0.24%, 16.03% +/- 0.68%, 15.53% +/- 1.07%, 18.92% +/- 2.70%, respectively) of macrophage in the experimental groups increased obviously with time, as compared to the controls (5.47% +/- 2.06%, 6.39% +/- 0.215, 9.07% +/- 0.61% and 8.54% +/- 0.16%, Respectively) (P < 0.05). The IL-1 levels of serum in the experimental groups were 23.64 +/- 0.84, 23.38 +/- 1.10, 22.21 +/- 0.86 and 24.29 +/- 1.31 pg/ml, respectively, which were significantly higher than those (18.52 +/- 1.23, 18.40 +/- 1.6, 17.92 +/- 2.21 and 18.53 +/- 2.64 pg/ml, respectively) in the control groups (P < 0.05) without time-effect relationship. The serum IL-8 levels on the 1st, 7th and 14th days in the experimental groups were 21.32 +/- 1.44, 21.90 +/- 2.08 and 22.00 +/- 2.80 pg/ml, respectively, which were significantly higher than those (17.69 +/- 1.09, 16.98 +/- 2.09 and 17.54 +/- 1.62 pg/ml, respectively) in the control groups (P < 0.05). CONCLUSION: The early macrophage apoptosis and changes of IL-1 and IL-8 may in lungs may play an important role in the development of pulmonary fibrosis induced by silica.

[Relationship between gene polymorphism of fibronectin and pneumoconiosis].

OBJECTIVE: To explore the relationship between the genetic polymorphism of fibronectin (FN) (4 genetic locus) and pneumoconiosis. METHODS: 128 male I-period pneumoconiosis were selected as cases who were examined with radiography and diagnosed by the Pneumoconiosis Diagnosis Expert Panel, based on the Chinese National Diagnosis Criteria of Pneumoconiosis (GBZ 70 - 2002). According to 1:1 paired matching method, 128 dust exposure workers were selected as control who were exposed to same dust as cases. The difference of age and cumulative length of service between case and control was not over five years and two years, respectively. 5 ml peripheral venous blood was drawn and anticoagulated with 2% EDTA. The polymorphisms of FN (MspI, TaqIb, HindIII, HaeIIIb) were detected, using the method of polymerase chain restriction fragment length polymorphism (PCR-RFLP) techniques and PCR. RESULTS: The frequencies of FN Msp I (CC) in cases and control groups were 10.9% and 3.9%, respectively. The difference was significant (P < 0.05). The frequencies of FN (MspI) C allele were 41.8% and 31.2% in case and control, and the difference between cases and controls was significant (P < 0.05). The frequencies of FN HaeIIIb (AA) genotype in cases (24.2%) was higher than that in control groups (17.9%), OR = 5.0 (95% CI: 4.840 approximately 24.210). The frequencies of FN (HaeIIIb) A allele were 51.9% and 42.2% in case and control, and the difference was significant (P < 0.05). The difference of TaqIb and HindIII genotype between cases and controls were not significant (P > 0.05). CONCLUSION: The risk of suffering from pneumoconiosis increases in workers carrying FN (MspICC or HaeIIIb AA) genotype after exposure to dust. Workers both carrying FN (HaeIIIb AA) and (MspICC) genotypes are more susceptible to pneumoconiosis. The relationship between genetic polymorphism of FN (TaqIIb, HindIII) and pneumoconiosis has not been found.

[Effect of occupational stress on menses and sex hormones of female knitting workers].

OBJECTIVE: To investigate the effect of occupational stress on menses and sex hormones. METHODS: 415 female knitting workers were investigated using the generic job stress questionnaire. Their venous blood were collected and the six sex hormones were detected by using radio-immune method. The different rate of abnormal menses and sex hormones level between different stress degree groups were analyzed. RESULTS: The abnormal rate of menses, menstrual blood volume, menstrual cycle, menstrual period was 36.24%, 19.80%, 14.43%, 11.41% respectively. The prevalence rate of dysmenorrheal and premenstrual syndrome was 1.01% and 29.19% respectively. The more depression, the higher menses disorders in non-intrauterine device (IUD) group. The more job demands, the higher daily stress in IUD group while the longer work time, the more abnormal menstrual period in two groups. More physical symptoms and deeper depression in non-IUD group were related to higher abnormal rate of menstrual blood volume. The level of blood E2 was lower in the group of prolonged work-time than that of in normal work-time group. The increasing FSH level and decreasing T level was associated with higher job demands. Multiple factor analysis showed that physical symptom, control of resource and negative life affairs were the risk factors of menses disorder; The physical symptom was the risk factor of menstrual blood volume; More physical symptoms, less positive feeling and shift were the risk factors of premenstrual syndrome; Less positive feeling was the risk factor of menstrual cycle; Prolonged daily work-time was the risk factor of menstrual period. CONCLUSION: Higher stress degree can lead to higher FSH and E2 and lower T level,and induce menses disorder.

[A case-control study on serum organochlorines residues, genetic polymorphisms of glutathione S-transferase T1 and the risks of breast cancer].

OBJECTIVE: To study the potential effect of gene-environment interaction between glutathione S-transferase T1 (GSTT1) and serum organochlorines residues on the risk of breast cancer in women, in China. METHODS: 70 newly diagnosed female breast cancer patients and 30 controls from September 2006 to October 2007 were interviewed using the same questionnaire to obtain information regarding exposure to those risks. Organochlorine residues level in serum was measured by gas chromatography (GC). Genotypes of GSTT1 polymorphisms were analyzed by multiplex allele-specific polymerase chain reaction (PCR). Interaction indexes (gamma) were calculated to determine the type of gene-environment interaction. RESULTS: After adjusting the confounding factors, results showed that interaction existed in genetic polymorphisms of GSTT1 and dichlorodiphenyltrichloroethane (DDT)/hexachlorocyclohexane (HCH) residues, with interaction indexes (gamma) value as 1.352 and 1.528. CONCLUSION: Genetic and environmental hazard factors had a co-effect on the development of breast cancer while genetic polymorphisms of GSTT1 and DDT/HCH expressed an interaction to breast cancer.

[Regulation role of superoxide dismutase coenzyme on Fas/FasL signal transduction and apoptosis in alveolar macrophages of pneumoconiosis patients].

OBJECTIVE: To explore the role of superoxide dismutase (SOD) coenzyme in regulation of Fas/FasL signal transduction and apoptosis of alveolar macrophages in pneumoconiosis patients. METHODS: 50 male and Han nationality cases, including the dust exposed workers, Phase I, II pneumoconiosis patients confirmed by local pneumoconiosis diagnosis group according to GBZ 70 - 2002 diagnosis standard, who underwent whole lung lavage treatment were chosen as subjects. Their alveolar macrophages (AMs) were collected and purified. The cells were divided into three groups: the untreated group, the Fas/FasL group and the SOD group. 5 x 10(6) purified AMs were added into incubating bottles containing DMEM for 2 hours for purifying, added with SOD coenzyme and other block reagents separately, and then incubated for 24 hours in CO(2) incubation. The cells were harvested and lysed. Western-blot were used to analyze the expressions of Fas, FasL, Caspases-8 and Caspases-3. Software of Quantity One 7.0 was used to analyze the relative quantity of Fas, FasL, Caspase-8 and Caspase-3. TUNEL and DNA fragment analysis were used to analyze AMs apoptosis. RESULTS: The apoptosis index in SOD coenzyme group (9.50 +/- 2.76)% and Fas/FasL group (14.01 +/- 2.56)% was significantly lower than that of in untreated group (19.18 +/- 2.83)% (P < 0.05). The catachrestic DNA ladder appeared in untreated group, was looming in Fas/FasL group, and was not found in the SOD group. The expressions of Fas, FasL, Caspase-8 and Caspase-3 of phase I and II in SOD group were higher than in the other two groups (P < 0.05). There was no significant difference in the expression of Fas, FasL, Caspase-8 and Caspase-3 among different phases of pneumoconiosis (P > 0.05). CONCLUSION: SOD coenzyme can effectively regulate Fas/FasL signal transduction and block AMs apoptosis.

[Investigation on job stress of pediatricians and nurses working in pediatric department].

OBJECTIVE: To investigate the occupational stressors and modifiers of pediatricians and nurses in order to find the measurements for control of the job stress. METHODS: 427 pediatricians and nurses working in five hospitals of a city served as subjects. Of them, the staff in section of pharmacy and toll offices in each hospital mentioned above served as control group. The General Job Stress Questionnaire was used to investigate the job stress by self-assessment. RESULTS: The scores of job demand, job risk, drug using, daily job stress, positive feelings, patient A behavior, physical environment and feeling balance in pediatricians and nurses were higher than those of control group, but the scores of job-person conflict, environmental control, technology utility, mental health, responsibility on things were lower than those of control group (P<0.05). The points of job future, job locus of control, self-esteem, job satisfaction, job load variance, depression in nurses were higher than those of pediatricians, and non-work activities, job risk and daily life stress were lower than those of doctors (P<0.05). The main affecting factors on job strain of pediatric staff included job monotony, higher job demand, more non-work job, lower job control, more job risk, job future ambiguous, poorer social support, lower job locus control and lower self-esteem. CONCLUSION: The stress degree of pediatric staff is higher than that of controls. The pediatricians have more job stress than that of nurses. The main stressors of pediatric staff are job monotony, higher job demand, more non-worker activity, lower job control, higher job risk and ambiguous job future. The main modifiers are good social support, external job locus of control and higher self-esteem.

[Relationship between gene polymorphism of transforming growth factor-beta and pneumoconiosis].

OBJECTIVE: To explore the association between genetic polymorphisms of TGF-beta (TGF-beta) and susceptibility to pneumoconiosis. METHODS: One hundred and seventeen patients with pneumoconiosis were selected as case. The control group was workers exposed to dust but without pneumoconiosis who had the same sex, nationality, and workshop or work site as case. The differences in the age and cumulative exposure time between the case and control group were not move than five years and two years, respectively. The case matched with the control according to 1:1. Polymerase chains reaction-restriction fragment length polymorphism was used to determine the frequencies of TGF-beta genes in the two groups. RESULTS: The frequencies of this TGF-beta (-509) genotypes were CC (22.2%), CT (43.6%) and TT (34.2%) in cases, which was significantly different from the control group, respectively (OR = 1.390, P < 0.05). There was no significant difference for frequency of TGF-beta+869 genotypes and allelic between case and control (P > 0.05). The frequencies of the TGF-beta (+915) genotypes in case [GG (70.9%), GC (29.1%)] were significantly different from the control group (OR = 1.455, P < 0.05). The frequency of TGF-beta (+915) * C allele in the case and control was 14.5% and 8.5%, respectively (P < 0.05). The frequencies of carrying TGF-beta (-509) CC and (+915) GG genotypes were 12.8% and 29.9% in case and control. The frequencies of carrying TGF-beta (-509) * T and (+915) * C alleles were 9.8% and 5.1% in pneumoconiosis and control (P < 0.05). CONCLUSIONS: TGF-beta (-509)CC genotype may be the protective factor for the pneumoconiosis. TGF-beta (+915)GC genotype may be a susceptible factor for the pneumoconiosis. The workers of carrying TGF-beta (-509) * T and (+915) * C alleles are more susceptible to pneumoconiosis.