Objective To investigate the therapeutic effect of fluvastatin in bleomycin-induced pulmonary fibrosis in rats. Methods Pulmonary fibrosis was induced in SD rats by intratracheal instillation of bleomycin A_ 5 . The rats were than divided randomly into three groups: the rats in the first group received daily fluvastatin 20mg/kg (group Flu),those of the second group received normal saline (group BLM) orally only,and those of controls (group N) received normal saline both intratracheally and orally. Five rats in each group were sacrificed 1,3,7,14 and 28 days after intratracheal instillation of bleomycin. Pathological changes in the lungs were evaluated by HE stain and Masson′s trichrome stain. Collagen content of the lung tissue was assessed by hydroxyproline concentration. Alveolar macrophages,polymorphonuclear leukocytes and lymphocytes in bronchoalveolar lavage fluid (BALF) were counted. Hyaluronic acid (HA) and laminin (LN) in BALF were determined by radioimmunoassay. Results The degree of alveolitis and pulmonary fibrosis in group Flu was improved as compared with that of group BLM. Hydroxyproline concentrations of group Flu were significantly lower than that of group BLM 7 days after bleomycin A_ 5 instillation. Total cell counts and percentage of polymorphonuclear leukocytes and lymphocytes in BALF were significantly reduced in group Flu. HA and LN levels in BALF were also lower in group Flu compared with group BLM. Conclusion Fluvastatin could alleviate bleomycin-induced pulmonary fibrosis in rats.

Objective:To observe the inhibitory effect of fluvastatin (Flu) on the proliferation of the rat lung fibroblasts cultured in vitro . Methods: Normal rat lung derived fibroblasts were cultured in media containing Flu. The influences of Flu on the growth curve of the fibroblasts were observed by cell count and MTT colorimetry. The inhibition effect of Flu serial dilutions on the fibroblasts proliferation was investigated. Influence of Flu on division index of the fibroblasts was analyzed by direct cell count. Chemical colorimetry was used to detect the hydroxyproline in the media. Results: Flu inhibited the proliferation of the normal rat lung fibroblasts in the manner of dose dependence( P

Objective To investigate the effect of radiation-induced heart injury on cardiac troponin I (cTnI)and endothelin-1(ET-1) and observe the preventive and therapeutic effect of fluvastatin. Methods Healthy female SD rats were randomly divided into three groups: control group(c), irradiation alone group(R) and fluvastatin therapeutic group (F). Rats of F group had been gastrogavaged with fluvastatin at dose of 20mg?kg -1?d -1 from 1week before irradiation to the end of the experiment. In C group and R group, rats were gastrogavaged with the same volume isotonic sodium chloride. The rats of R and F group were irradiated with accelerator linear at a dose of 20Gy thoracically. Rats were executed at 5,15,30d and 60d after irradiation, then cTnI in serum and ET-1 in blood plasma were detected. Results On 5d, the content of cTnI in R group increased significantly than that in C group(P

Objective To investigate autoantibody against endothelin receptor type A (ENRA-Ab) in patients with systemic lupus erythematosus associated pulmonary arterial hypertension (SLE-PAH).The possibility of autoantibody-mediated pathogenesis in the development of SLE-PAH has also been explored.Methods ENRA-Ab in the serum of SLE-PAH and controls were detected by using a human ETRA epitope peptide-based ELISA.The clinical relevance of ENRA-Ab in SLE-PAH was analyzed.Proliferation of vascular smooth muscle cells (SMCs) and permeability of endothelial cells in vitro under the stimulation of polyclonal ENRA-Ab IgG were assessed.The expressions of PAH-related markers, i.e., 5-HTT, PDGFR-b, VEGF-A and PDGF-B were measured by qPCR.The effect of ENRA-Ab in vivo was also determined in a suboptimaldose monocrotaline-induced model with the assessment of right ventricle hypertrophy index and pathology parameters.Independent t-test, Tukey-Kramer test of variance analysis and Pearson' s correlation analysis were used for statistical analysis.Results ENRA-Abs was presented in a higher occurrence in SLE-PAH (35/85,41％) compared with controls (0/60;0, 13/80, 16％).There was a significant correlation between ENRA-Ab and echocardiograph estimated pulmonary arterial systolic pressure (r=0.392, P=0.002) in SLE-PAH.ENRA-Ab could promote SMCs proliferation, disrupt endothelial barrier and up-regulate PAH-related markers expression,which could be blocked in the presence of ETR antagonist.ENRA-Ab aggravated right ventricle hypertrophy and vascular remodeling in vivo.Conclusion ENRA-Ab is a new biomarker, in SLE-PAH, which may mediate PAH development in SLE.

BACKGROUND: The pathological characteristics of pulmonary interstitial fibrosis are the proliferation of a large number of fibroblasts and the increasing deposition of matrix collagen that takes the place of normal lung structure. Fluvastatin can inhibit the proliferation of fibroblasts and many other cells.OBJECTIVE: To investigate the effects of fluvastatin in inhibiting the proliferation of rat lung fibroblasts cultured in vitro and its influence on bleomycin-induced pulmonary fibrosis and ventilation function.DESIGN: A randomized controlled trial.SETTING: Department of Respiratory Diseases, Xijing Hospital, Fourth Military Medical University of Chinese PLA; Teaching and Research Section of Pathology, Department of Basic Medicine, Fourth Military Medical University of Chinese PLA; Research Institute ofOrthopedics, Xijing Hospital,Fourth Military Medical University of Chinese PLA.PARTICIPANTS: The study was conducted in the laboratory of Department of Respiratory Diseases, Xijing Hospital of Fourth Military Medical University of Chinese PLA from January to December 2001. Thirty-one healthy adult male Sprague-Dawley(SD) rats of grade Ⅰ were selected in this study.INTERVENTIONS: The fibroblasts derived from the lung normal of one rat were cultured in vitro in media containing fluvastatin. The effect of fluvastatin on the growth curve and the effect of its different concentrations(0, 1 × 10-7,1 ×10-6, 1 ×10-5, 1 ×10-4, 1 ×10 3and 1 ×10-2 mol/L, fluvastatin of 0 mol/L was taken as the blank control group) in inhibiting the cultured cells were observed with MTT colorimetry. The effect of fluvastatin on the division index of the fibroblasts was analyzed by direct cell counting Hydroxyproline colorimetry was used to detect the influence of fluvastatin on the collagen secretion in the media. The other 30 SD rats were divided into six groups: normal control group, bleomycin-induced group and fluvastatin-treated groups(TH 1,TE1, TH15 and TL15 groups) named according to the date of giving fluvastatin,i. e. the 1st day and the 15th day, after the rats were given bleomycin A5. All the rats were killed 28 days later. The number of fibroblasts, the thickness of alveolar wall and the area of mesenchyma in lung tissue were measured by HE staining. The extracellular matrix and collagen in lung tissue were observed by Masson and sirius red staining, and hydroxyproline in lung tissue homogenates was measured.MAIN OUTCOME MEASURES: Fibroblast growth curve and division index of rat lung, hydroxyproline in the media and lung tissue homogenates,number of fibroblasts and the thickness of alveolar wall, the area of mesenchyma, extracellular matrix and collagen contents in lung tissue.RESULTS: Fluvastatin could inhibit the proliferation of the rat lung fibroblasts cultured in vitro(t=4.20 to 17.52, P < 0.01), and its inhibitory effect was increased with the increased dose of fluvastatin, which showed a dose-dependent effect. The 1 × 10-4 mol/L fluvastatin could completely inhibit the proliferation of the cultured cells, and the A490 value from the 2nd day on the fibroblasts by MTT colorimetry was not insignificantly different from those on the 1st day( P > 0.05) . The division index of the fibroblasts and secretion of collagen were obviously decreased by fluvastatin( t = 8. 037,P <0.01; t =3.99 to 10. 84, P <0.05 or P <0.01). In vivo, the number of fibroblasts, the thickness of lung alveolar wall, the area of mesenchyma and the content of hydroxyproline in lung tissue were significantly higher in bleomycin group than in control group( t =4. 62 to 11.93, P < 0. 01), while those in the fluvastatin-treated groups were lower than those in bleomycin group in different degrees( t = 2.69 to 7.65, P < 0.05 to 0.01 ) . The distribution of extracellular matrix and types Ⅰ and Ⅲ collagen in lung tissue were obviously increased in bleomycin group as compared with that in control group, but decreased in different degrees in fluvastatin-treated groups.CONCLUSION: Fluvastatin can significantly inhibit the proliferation of rat lung fibroblasts in vitro, suggesting that it may be an effective drug for pulmonary fibrosis. Treatment at earlier stage is more effective than at advanced stage.

Objective To compare the performance of four commercial anti-dsDNA antibody assays,i.e,BioPlex 2200 (BioPlex),Farr radioimmunoassay (Farr),MESACUP DNA-Ⅱ TEST ds [MBL-enzyme linked immunosorbent assay (ELISA)] and Anti-dsDNA-NcX ELISA (IgG) (EURO-ELISA),Antoantibodies Profile Assay Kit (HOB-Chemiluminescent Immunoassay) in disease activity assessment of systemic lupus erythematosus (SLE).Methods SLE patients (n=119) as well as healthy controls (n=200) and disease controls (n=100) were recruited and their serum anti-dsDNA antibodies were detected by BioPlex,Farr,MBL-ELISA,EURO-ELISA,and a standard Crithidia luciliae indirect immunofluorescence test (CLIFT).The consistency between above four methods to CLIFT was analyzed.The correlation of anti-dsDNA antibody level of these four methods to SLE disease activity was assessed.All data analyses were performed with Statistical product and service solutions (SPSS) 16.0 (SPSS.Inc) and GraphPad Prism 4.0.3 (GraphPad).Unless otherwise specified,all data in this study were expressed as mean±standard deviation.Cut-off values of the anti-dsDNA quantification methods were set by the manufacturers.Chi square and kappa coefficients were adopted to assess the agreement determination and correlation analysis between anti-dsDNA level and SLE disease activity (SLEDAI).Receiver-operator characteristic (ROC) curve analysis was used to compare the specificity and sensitivity of the anti-dsDNA assays.Student's t test was adopted for the comparison of anti-dsDNA levels by different methods between SLE and SLE+LN groups.A p value small than 0.05 was considered statistically significant.Results Using cut-off values set by the manufacturers,BioPlex demonstrated the highest overall agreement with CLIFT,while MBL-ELISA and EURO-ELISA showed the highest positive agreement with CLIFT.Disease activity correlation analysis showed that SLEDAI score correlated poorly with anti-dsDNA level in Farr assay,but strongly with the other three assays.Bioplex had a better performance in terms of SLE activity index corelation (r=0.297 6,P=0.001 2).Moreover,anti-dsDNA level differed in SLE patients with renal lupus nephritis in BioPlex assay (P=0.026 8),but not in the other assays.In ROC curve analysis,BioPlex showed the largest area under the curve (AUC) over other assays.Conclusion Bio Plex assay has better sensitivity and specificity than Farr,MBL-ELISA and EURO-ELISA and correlates well with SLE disease activity.

Dermatomyositis (DM) with positive anti-melanoma differentiation-associated gene 5 (MDA5) antibodies (MDA5+DM) is a kind of occasional and rare autoimmune disease. Due to the fact that MDA5+DM patients are prone to suffer from the rapid progressive interstitial lung disease (RP-ILD), and the mortality rate is extremely high (all-cause mortality at 6 months is almost 50%). In addition to lung disease, patients with MDA5+DM also suffering from the skin and muscle symptoms. The biomarkers represented by the anti-MDA5 antibody titer, ferritin, KL-6 level and CD4 +/CXCR4 +T cell percentage are considered to relate with MDA5+DM-ILD′s severity, activity evaluation, therapeutic effect monitoring, and prognosis prediction. The current therapeutic strategies for the disease is mainly combined with immunosuppression. This work systemly summarizes the diagnosis and treatment progress of anti-mda5 antibody-related dermatomyositis, which not only contributes to the research work of related disciplines, but also provides reference for clinical diagnosis and treatment.

Background The hearing of Chinese young adults is far less sensitive than 0 dB defined by international standards, with the threshold values mostly being at double digits, which is worthy of investigation. Objective To study the influencing factors of hearing threshold measurement. Methods The hearing measurements were conducted in two different ways, one was a standard method performed in a specialized audiometry experiment room, and the other one was an on-site audiometry test which included a daily examination of hearing and an onsite hearing test. From the workers who participated in the occupational health examination, 300 people were randomly selected as experimental subjects, and their hearing was measured in the hearing examination room of the Occupational Disease Prevention and Treatment Institute according to standard methods. A total of 9 766 workers from the General Motors factory were included in the daily group, and their hearing thresholds were measured in the hearing examination room in the factory. There were 4 617 people in the onsite group, and their hearing was measured in the test chamber of our mobile medical vehicle in their factories. The hearing threshold data of the three groups, i.e. experiment, daily examination and on-site, was compared and analyzed. In addition, the environmental noise in the hearing examination room and the mobile test chamber was measured. Results The hearing threshold value of the experimental group was the lowest. Despite this, its dB value remained at double digits at any frequency band. The hearing value of the daily group was in the middle. The onsite group had the highest hearing threshold, which was 58.2% higher than that of the experimental group. As the hearing data was not normally distributed, Kruskal-Wallis non-parametric test was conducted for statistical analysis. It was found that the hearing threshold difference among the three groups was statistically significant at all the frequency band (P< 0.01). The ambient noise level was 23.9-28.3 dB(A) in the hearing examination room, and 32.5 - 67.9 dB (A) in the mobile test chamber. Age and gender were not confounding factors to the results. Conclusion The hearing test method and its environmental noise were able to make the threshold measurements shift up significantly. The environmental noise of the mobile test chamber in the examination vehicle has exceeded the standard and needs to be improved.