Aged ; Humans ; Lung ; pathology ; Male ; Middle Aged ; Pneumoconiosis ; complications ; diagnosis ; pathology ; Reference Standards

OBJECTIVETo investigate the differential gene expression profile of the lung tissues in experimental silicosis rats and to screen for and identify the key signal transduction pathways in pulmonary silicotic fibrosis.

METHODSA total of 80 rats were randomly divided into control group (n = 40) and silica-instilled group (n = 40). Each group was equally divided into five subgroups, and each subgroup was treated at 1, 7, 14, 21, or 28 d. Intratracheal instillation was used to give 1 ml of silica suspension (50 mg/ml) in the silica-instilled group and normal saline in the control group. Silicotic nodules and type I and III collagen were observed through hematoxylin and eosin staining and Sirius red staining, respectively. Differentially expressed genes in pulmonary silicotic fibrosis were selected by the rat whole-genome gene expression RatRef-12 BeadChip (Illumina, USA), and a fold change cutoff was applied. Quantitative real-time polymerase chain reaction (qRT-PCR) was also used to verify differentially expressed genes. Through bioinformatics databases such as Visualization and Integrated Discovery (DAVID) and Kyoto Encyclopedia of Genes and Genomes (KEGG), preliminary research was performed on the biological pathways of differential genes, key biological signal transduction pathways were identified, and key differentially expressed genes in each pathway at different time points were searched for.

RESULTSA total of 2694 genes were differentially expressed and changed dynamically. The KEGG pathway analysis showed that 141 signal transduction pathways were involved in the development and progression of pulmonary silicotic fibrosis, among which 48 pathways were more significant than others (P < 0.01), with the mitogen-activated protein kinase (MAPK) pathway exceptionally significant. The differentially expressed genes interleukin-1 receptor (IL-1R), tumor necrosis factor receptor (TNFR), and transforming growth factor beta (TGF-β) in the MAPK pathway were up-regulated at different time points after silica instillation. The results of real-time PCR showed that granulocyte-macrophage colony-stimulating factor (GM-CSF) was over-expressed at 4 time points and under-expressed at 1 time point compared with the control group.

CONCLUSIONThe MAPK signal transduction pathway plays a very important role in the development of pulmonary silicotic fibrosis. Both IL-1R and TNFR may play major roles during inflammation phase through the P38/Jun N-terminal kinase (JNK) pathway, and TGF-β may have important function through the extracellular-signal-regulated kinase (ERK) pathway in the formation of fibrosis.

Animals ; Gene Expression ; Lung ; metabolism ; pathology ; Male ; Pulmonary Fibrosis ; genetics ; metabolism ; pathology ; Rats ; Rats, Wistar ; Signal Transduction ; Silicosis ; genetics ; metabolism ; pathology

OBJECTIVETo analyze the relationship between occupational stress and diseases in secondary school teachers in a city of Sichuan Province, and to provide a basis for the evaluation of the long-term effects of occupational stress in teachers.

METHODSWith secondary school teachers as the target population, the stratified cluster sampling was adopted to conduct three studies among 780, 119, and 689 secondary school teachers in a city of Sichuan Province in 1999, 2005, and 2009, respectively. The Occupational Stress Inventory-Revised Edition (OSI-R) and working ability index (WAI) were used to investigate occupational stress and diseases in secondary school teachers. The variation of occupational stress in secondary school teachers was compared between different periods and the relationship between the intensity of stress and diseases was evaluated, on the basis of which the variation of the relationship over time was analyzed.

RESULTSThere were significant differences in occupational stress in secondary school teachers between different periods (P<0.05). The incidence rates of medium and high physiological stress and psychological stress were significantly higher in 2009 than in 1999 (P<0.05). Compared with the year of 1999, the intensity of occupational stress in 2009 changed with cardiovascular, respiratory, and mental diseases. The incidence of abnormal psychological stress was a risk factor for all chronic, respiratory, and mental diseases (OR: 1.88, 2.25, and 5.91). The time dependence of odds ratio was only found in the risk of respiratory diseases: occupational stress resulted in a significant increase in the risk of respiratory diseases over time (P<0.05). Physiological stress was a risk factor for mental diseases (OR=2.31).

CONCLUSIONThe intensity of occupational stress in secondary school teachers changes over time. Occupational stress elevates the risks of certain diseases and has a time-dependent effect on the risk of respiratory diseases. Occupational stress in secondary school teachers needs more attention and effective prevention.

Cardiovascular Diseases ; epidemiology ; Faculty ; Humans ; Mental Disorders ; epidemiology ; Respiratory Tract Diseases ; epidemiology ; Risk Factors ; Stress, Physiological ; Stress, Psychological ; Surveys and Questionnaires

OBJECTIVETo investigate the current status and characteristics of work-related fatigue among scientific and technical personnel and its associated factors, and to provide a scientific basis for further interventions.

METHODSA cross-sectional survey was conducted in the staff from a single scientific institution, using a self-administered questionnaire. Basic information of participants, Fatigue Scale-14, and Job Content Questionnaire were collected.

RESULTSThe prevalence of work-related fatigue among the scientific and technical personnel was 54.6%; work-related fatigue was positively correlated with occupational stress (rs = 0.384, P < 0.05). Significant differences in the scores, proportions, and types of fatigue were found between different types of occupational stress. The associated factors of work-related fatigue included occupational stress profiles, social support, and educational status. A higher risk of work-related fatigue was found in the staff under high stress, compared with those under low stress (OR = 8.5, 95%CI = 3.9∼18.7). Social support served as a protective factor for work-related fatigue, while a higher level of education was correlated with more severe work-related fatigue.

CONCLUSIONWork-related fatigue is common and serious among scientific and technical personnel, especially in those under high stress. Effective interventions according to occupational stress are of great importance to reduce work-related fatigue.

Cross-Sectional Studies ; Fatigue ; epidemiology ; Humans ; Occupational Diseases ; epidemiology ; Prevalence ; Research Personnel ; psychology ; Risk Factors ; Social Support ; Stress, Psychological ; epidemiology ; Surveys and Questionnaires

OBJECTIVETo explore the morphometric abnormalities of brain gray matter (GM) in patients with chronic low back pain (CLBP).

METHODSThirty patients with CLBP and 30 healthy individuals were enrolled and examined with a 3.0 T magnetic resonance (MR) scanner. High-resolution T1 structural MR data were acquired and data analysis was performed using voxel-based morphometry (VBM) in FMRIB Software Library. The morphological differences were compared between the two groups.

RESULTSs Compared with the healthy control subjects, patients with CLBP showed decreased GM volumes in several brain cortical areas including the bilateral superior frontal gyrus, right frontal pole, left insular cortex, left middle and left inferior temporal gyrus (P<0.05, after TFCE correction). Increased GM volumes were found in the patients in the subcortical structures including the left thalamus, bilateral putamen, bilateral nucleus accumben and right caudate nucleus (P<0.05, after TFCE correction).

CONCLUSIONPatients with CLBP have different patterns of GM abnormalities in different brain regions, characterized by reduced GM volume in cerebral cortical regions and increased GM volume in the subcortical nuclei. Such changes might be associated with the maladaptation of the brain in chronic pain state.

Cerebral Cortex ; Frontal Lobe ; Gray Matter ; diagnostic imaging ; pathology ; Humans ; Low Back Pain ; physiopathology ; Magnetic Resonance Imaging ; Temporal Lobe ; Thalamus

The aim of the present study was to investigate the effects of exercise on skeletal muscle autophagy. Trains of high-frequency electrical stimulation (pulses frequency: 100 Hz) were used to stimulate sciatic nerve and consequently induce muscle contraction of the left hindlimb. The unstimulated right hindlimb muscles were taken as control. The mice were sacrificed immediately (0), 30 or 60 min after the electrical stimulation by cervical dislocation, and gastrocnemius muscles were rapidly dissected and freeze-clamped in liquid nitrogen. AMP-activated protein kinase (AMPK) and the autophagy marker protein LC3 were detected by Western blotting, and muscle atrophy related genes including atrogin-1, MuRF-1, Bnip3, Bnip3l and CathepsinL were detected by using real-time qPCR. The results showed that, at 0 min after the electrical stimulation, the activity of AMPK and LC3-II/I ratio were significantly increased in left gastrocnemius muscles, compared with those of the muscles in the right hindlimb. The levels of atrogin-1, MuRF-1, Bnip3, Bnip3l and CathepsinL mRNA expressions were up-regulated by electrical stimulation. Meanwhile, the activity of autophagy related protein, ULK1 was significantly enhanced by electrical stimulation. These results suggest that electrical stimulation of sciatic nerve may induce the skeletal muscle autophagy, and this may be regulated through AMPK/ULK1-mediated signaling pathway.

OBJECTIVETo explore factor IX gene mutations and molecular mechanism of haemophilia B in 3 unrelated families.

METHODSThe activated partial thromboplastin time (APTT) and FIX activity (FIX: C) assay were used for phenotypic diagnosis. The STR loci gene polymorphisms for genetic linkage analysis in the patients and their family members were assayed. All of the 8 exons and the exon-intron boundaries of FIX gene were amplified by polymerase chain reaction (PCR) and direct sequencing.

RESULTS AND CONCLUSIONMutations were found in the FIX gene of the propositi. Proband 1 had a G22119A mutation in exon 6, proband 2 a G7392C mutation in exon 2 and proband 3 a T32685C mutation in exon 8.

DNA Mutational Analysis ; Factor IX ; genetics ; Genetic Linkage ; Hemophilia B ; genetics ; Humans ; Mutation ; Pedigree ; Polymorphism, Genetic

OBJECTIVETo investigate the mechanism by which heat shock protein 90 (HSP90) regulates 26S proteasome in hyperthermia.

METHODSHyperthermic HepG2 cell models established by exposure of the cells to 42 degrees celsius; for 3, 6, 12, and 24 h were examined for production of reactive oxygen species (ROS) and cell proliferation, and the changes in Hsp90α and 26S proteasome were analyzed.

RESULTSROS production in the cells increased significantly after hyperthermia (F=28.958, P<0.001), and the cell proliferation was suppressed progressively as the heat exposure time extended (F=621.704, P<0.001). Hyperthermia up-regulated Hsp90α but decreased the expression level (F=164.174, P<0.001) and activity (F=133.043, P<0.001) of 26S proteasome. The cells transfected with a small interfering RNA targeting Hsp90α also showed significantly decreased expression of 26S proteasome (F=180.231, P<0.001).

CONCLUSIONThe intracellular ROS production increases as the hyperthermia time extends. Heat stress and ROS together cause protein denature, leading to increased HSP90 consumption and further to HSP90 deficiency for maintaining 26S proteasome assembly and stability. The accumulation of denatured protein causes unfolded protein reaction in the cells to eventually result in cell death.

HSP90 Heat-Shock Proteins ; metabolism ; Hep G2 Cells ; Hot Temperature ; Humans ; Proteasome Endopeptidase Complex ; metabolism ; RNA, Small Interfering ; genetics ; Reactive Oxygen Species ; metabolism ; Up-Regulation

OBJECTIVETo investigate the mechanism by which propofol exposure causes PC12 cell apoptosis under hypoxic conditions.

METHODSPC12 cells were exposed to room air, 35% oxygen, or 5% oxygen (hypoxia) for 24 h in the presence of either 10 µmol/L lipid emulsion or 10 µmol/L propofol. After the treatments, the cell apoptosis was measured by flow ceytometry, and the level of reactive oxygen species (ROS) and the activity of superoxide dismutase (SOD) were evaluated.

RESULTSIn room air, PC12 cells treated with propofol showed increased apoptosis rate and ROS production as compared with the cells treated with the lipid emulsion; propofol treatment of the cells exposed to 35% oxygen showed obvious enhancement of the apoptosis rate, ROS production and SOD activity. Under the hypoxic condition, propofol treatment even further increased the apoptosis rate, ROS production and SOD activity. Lipid emulsion caused no such changes in cells exposed to room air, 35% oxygen or 5% oxygen.

CONCLUSIONUnder hypoxic conditions, propofol can cause apoptosis in PC12 cells by inducing oxidative stress injury.

Animals ; Apoptosis ; drug effects ; Cell Hypoxia ; Oxidative Stress ; PC12 Cells ; Propofol ; pharmacology ; Rats ; Reactive Oxygen Species ; metabolism ; Superoxide Dismutase ; metabolism