Objective To investigate the anti-erythropoietin antibody level and its clinical significance in maintenance dialysis patients. Methods Eighty maintenance hemodialysis (HD) and 30 peritoneal dialysis (PD) patients were enrolled in the study. Serum anti-erythropoietin antibody levels of above 110 dialysis patients were measured by ELISA. Immunoreactive parathyroid hormone (iPTH), Scr, BUN, Hb, and CRP were determined by conventional methods at the same time. Correlations among these indexes were examined. Results The anti-erythropoietin antibody levels of the dialysis patients were significantly higher than those of healthy people (P＜0.05), but no significant difference was found between HD patients and PD patients. There were no significant differences of anti-erythropoietin antibody, Hb, BUN, Scr, iPTH and CRP among different primary diseases. Hb was negatively correlated with anti-erythropoietin antibody and CRP (r=-0.56, -0.20,P ＜0.05), but was not correlated with BUN, Scr, iPTH. There was no correlation of antierythropoietin antibody with BUN, Scr, CRP and iPTH. One patient receiving recombinant human erythropoietin (rHuEPO) treatment with anti-erythropoietin antibody 43.63 U/L developed pure red cell aplasia diagnosed by marrow biopsy. Conclusions The anti-erythropoietin antibody levels of the dialysis patients are significantly higher as compared to healthy people, but are not significantly different between HD and PD patients. Anti-erythropoietin antibody is not correlated with BUN, Scr,iPTH and CRP. Hb is negatively correlated with anti-erythropoietin antibody and CRP. The rHuEPO can induce the anti-erythropoietin antibody leading to pure red cell aplasia in dialysis patients.

Objective To investigate the effects of anti-sense hTERT on the expression of VEGF and the receptor in SGC7901 cells, and study the influence in angiogenesis and progression in gastric carcinoma. Methods SGC7901 cell line was transfected by the recombinant virus containing sense and anti-sense hTERT cDNA. Then the expression of VEGF-C and Flt-4 was observed with RT-PCR, distribution of cell cycles was determined with flow cytometry. The expression of VEGF-C and Flt-4 protein was assessed with immunohistochemistry. Result The distribution of cell cycle of antisense hTERT transfected SGC7901 cells was changed, and the mRNA and protein expression of VEGF-C and Flt-4 was significantly down-regulated. Conclusion Anti-sense hTERT can act as an agent for inhibiting VEGF-C and Flt-4 mRNA and protein level, and it blocks tumor angiogenesis and lymphogenous metastasis.

With the development of higher education reform, cultivating students' practice ability and innovation consciousness has become the key task of experimental teaching . Aimed at training innovative talent, human anatomy department of Mudanjiang Medical University took mea-sures to reform practical contents of human anatomy such as introduction of animal organs, development of scientific research, and by setting the abundant practical teaching content and appraisal method, constructed the anatomy practice teaching system based on cultivating the innovation ability of medical students, which stimulated the enthusiasm of students for anatomy and improved quality of human anatomy teaching.

AIM and METHODS: to elucidater the effect of poly(ADP-ribose) polymerase(PARP) on tracheal hyperreactivity of guinea - pig induced by peroxynitrite, the responses of guinea pig tracheas to histamine af- ter incubation with peroxynitrite in the absence and presence of 3 - aminobenzamide(3 - AB), a highly selective inhibitor for PARP, were observed in vitro. RESULTS: The exposure of tracheal strips to peroxynitrite led to epithelial damage and hyperreacitivity to histamine, both of which were reversed by 3 - AB(l mmol/L or 5mmol/L), whereas incubation of tracheal strips with 3 - AB(5 mmol/L) had no effect on the reponses. CONCLUSION:PARP is involved in the epithelial damage and hyperreactivity of guinea - pig tracheas induced by peroxynitrite. The results suggested that inhibition of excessive activation of PARP may represent a novel strategy for the prevention and therapy of airway hyperreactivity in asthma.

AIM: To explore the effects of cellular signal transduction pathways of heme oxygenase-1(HO-1)-carbon monoxide (CO)-cyclic GMP (cGMP) and nitric oxide synthase (NOS)-nitric oxide (NO)-cGMP on cholecystokinin octapeptide (CCK-8) reversed vascular hyporeactivity in endotoxemic rats. METHODS: According to the treatments given in vivo , rats were devided into four groups: control; lipopolysaccharide (LPS); CCK and CCK+LPS. Using isolated vascular ring tension detecting technique, thoracic aortic rings (TARs) were prepared and accumulation of contractive responses to phenylephrine (PE) were measured under which the TARs were incubated with Hemin (He, donor of CO), Zinc-protoporphyrin-IX (ZnPP-IX, selective inhibitor of HO-1), L-arginine (L-Arg, substrate of NOS), aminoguanidine (AG, selective inhibitor of iNOS), N ?-nitro-L-arginine (L-NNA, inhibitor of NOS) or methylene blue (MB, inhibitor of guanylyl cyclase), respectively. RESULTS: CCK-8 alone did not affect vascular tension. Injection of LPS induced the hyporeactivity of the TARs and was reversed by pretreatment of CCK-8. In LPS and CCK+LPS groups, the hyporeactivity was partly reversed by incubation of TARs with ZnPP-IX or AG, and restored to normal by incubation of TARs with L-NNA or MB. Incubation of TARs with He or L-Arg showed to make the vascular hyporeactivity worse in different degree. CONCLUSIONS: CCK-8 alone did not affect the activity of HO-1 and iNOS but influenced the activity of these enzymes induced by LPS, which lead to reduced CO/NO production, decreased the content of cGMP and plays its important role in reversing vascular hyporeactivity in endotoxemic rats.

AIM: To verify the effect of cholecystokinin octapeptide(CCK-8) on cardiac function in endotoxin shock (ES) rats.METHODS: The rats were divided into four groups:control,lipopolysaccharide(LPS),CCK-8 and CCK-8+LPS.The left ventricle pressure(LVP),the maximal/minimum rate of LVP(?LVd p /d t max ),heart rate (HR) and mean arterial pressure (MAP) were measured.The activity of superoxide dismutase (SOD),the contents of malondialdehyde (MDA) and nitric oxide (NO) in both serum and myocardium were also measured,respectively.RESULTS: CCK-8 (40 ?g?kg -1 , iv) elicited bradycardia in short time and gently increase MAP,LVP and ?LV d p /d t max . Lipopolysaccharide(LPS, 8 mg?kg -1 , iv) caused a variation in heart rate (HR)(a bradycardia following a tachycardia) and rapid decreases in MAP,LVP and ?LVd p /d t max . The rapid variation of HR and the decline of MAP,LVP and ?LVd p /d t max were reversed by pretreatment with CCK-8 in ES rats, but didn't restore to normal.The activity of SOD was increased and the contents of MDA and NO were decreased by pretreatment with CCK-8 in ES rats.CONCLUSION: The decline of cardiac function in ES rats could be reversed by pre-administration of CCK-8 and the decrease in NO production may be one of the mechanisms.

AIM: To study the mechanism responsible for ONOO --induced the airway epithelial injury. METHODS: Effects of 3-aminobenzamide(3-AB), a poly-(ADP-ribose) polymerase(PARP) inhibitor, and Ac-DEVD-CHO, a caspase-3 inhibitor, on LDH release and apoptosis of cultured rat tracheal epithelial (RTE) cells induced by ONOO - were examined. The cleavage of PARP was analysed by Western blot. RESULTS: 3-AB inhibited the release of LDH induced by ONOO - partially, and had no effect on the apoptosis of RTE cells. Caspase-3 inhibitor Ac-DEVD-CHO obviously prevented the apoptosis of RTE cells induced by ONOO - in a dose-dependent manner. The cleavage of PARP was observed in the process of apoptosis of RTE cells induced by ONOO -. CONCLUSIONS: PARP activation represents one of the pathways of ONOO --mediated epithelial injury, and the excessive activation of PARP contributes to the necrosis in RTE cells induced by ONOO -. Cleavage of PARP by activated caspase-3 plays a crucial role in the apoptosis of RTE cells induced by ONOO -.

AIM:To study the effect of ONOO- on the airway epithelial injury. METHODS: The mitochondrial respiration, the amount of lactate dedydrogenase (LDH) release into the cell culture medium, the levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), and the cellular apoptosis were examined after exposure of cultured rat tracheal epithelial (RTE) cells to ONOO-. RESULTS: Exposure of RTE cells to 0.25, 0.5 and 1 mmol/L ONOO- caused a dose-dependent suppression of the mitochondrial respiration . ONOO- also caused a dose-dependent increase in the percentage of LDH release. Exposure of RTE cells to ONOO- resulted in an increased generation of 8-OHdG in a dose-dependent manner. ONOO- caused an increase in apoptotic percentage in RTE cells in a time-dependent manner at different concentrations. CONCLUSION: ONOO- could cause necrosis and apoptosis in cultured RTE cells. Low concentration of ONOO- caused apoptosis in a time-dependent manner. Whereas exposure to high concentration of ONOO- resulted in cell necrosis, ONOO- caused a dose-dependent increase in the percentage of LDH release. Suppression of mitochondrial respiration and oxidative DNA damage by ONOO- may be the major cause of cellular injury induced by ONOO-.

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 investigate the inhibitory effect of four and a half LIM protein 2(FHL2) on inhibitor of differentiation 1(Id1)-mediated suppression of transcriptional regulation activity and Id1-promoted invasive growth of human breast cancer cells MCF-7.Methods The effect of FHL2 on Id1-mediated transcriptional repression in MCF-7 cells was determined by cotransfection and relative biluciferase assay.The cell proliferation was determined by MTT assay,and the invasive capacity of MCF-7 cells was determined by Transwell assay.Results The transcriptional repression effect of Id1 on basic helix-loop-helix(bHLH) factor E47-mediated transcription activity in MCF-7 cells,and Id1-promoted proliferation and invasive growth of MCF-7 cells were significantly suppressed by FHL2.Conclusion FHL2 can inhibit the proliferation and invasive growth of human breast cancer cells via repressing Id1-mediated functional activity.The results provide a basis for further investigating the functional roles of FHL2-Id1 signal pathway in the carcinogenesis and development of human breast cancer.