The current drug non-clinical safety evalua-tion has been highly systematized and standardized, but the standard toxicology model is still some inade-quacies, need to consider other animal models of safety evaluation. This paper will expound the need of animal disease models using in safety evaluation from the as-pect of scientific theories, data requirements and the need of clinical. Then recognizing on the perspective of drug regulatory agencies to explore the feasibility of u-sing animal disease models for safety evaluation and the deficiencies, in order to predict as accurately as possi-ble of the adverse drug reactions in clinical, applied to reduce the risk of clinical patients ( patients benefit ) , and reduce the risk of drug development failures ( pharmaceutical companies benefit ) . All in all we should attach great importance to the applications of animal disease models in non-clinical safety evalua-tion.

The goal of radiologic intervention in patients with membranous or segmental ob struction of inferior vena cava(Budd-Chiari Syndrome)is to relieve the major venous obstruction, control portal hypertension and prevent further hepatocellular damage until collateral hepatic venous outflow channels can develop.Percutaneous balloon angioplasty(PTA)was used to treat 15 patients with this syndrome who were followed up for an average of 30.57?13.57 months(range,8～48 months).In occlusion,PTA can be considered a safe and effective treatment at least patency of one hepatic vein.The therapy is not definitive,multiple treatment are required for the long-term care of the ptients who all hepatic vein are obliterated.

Geminin is a multifunctional protein which localizes in nucleus,it has complicated structural and functional domains.Geminin plays very important roles in cell proliferation,embryonic development,tumorigenesis and so on.Geminin affects cell proliferation through influence on the important events in cell cycle phases.There are many mechanisms by which Geminin can control DNA replication,inhibit centrosome over-duplication,promote G2/M phase progression,maintain proper cytokinesis.At different development stages,Geminin acts as an inhibitor or inducer in regulating embryonic development,especially in nervous system formation.Geminin also plays a regulative role in eye development and embryonic development through the interactions with homeobox genes or proteins Six3 and Hox,Geminin functions as a coordinator of cell proliferative and differentiative control.Recently,Geminin was found to have relationship with cancer,the study on the function of Geminin in cancer has been a meaningful aspect.Geminin can act as a marker to evaluate progression and prognosis in cancer.It may be a novel molecular target in therapy of cancer.The activity of Geminin is regulated by transcription level and post-transcription level,the post-transcriptional regulation of Geminin protein may take the main position.

Objective To study the morphology and the effect of bovine lactoferricin (LfcinB) for Jurkat T leukemia cells and HFL-I cell and further validate and analyze the signal transduction passage way of LfcinB-induced apoptosis. Method The Jurkat T leukemia cells and fibroblasts stained with Hoechst 33258 after in vitro treatment with LfcinB were observed through fluorescence microscope, compared with positive and negative control groups to analyze the difference between the effect of LfcinB on Jurkat T leukemia cells and HFL-I cell with gel electrophoresis analysis of DNA fragmentation. Early apoptosis and mitochondrial membrane potential of Jurkat T leukemia cells were analyzed by flow cytometry, and the changes of caspase-3, caspase-8, caspase-9 and cytochrome C in endochylema of Jurkat T leukemia cells after exposed to LfcinB during 4, 6 and 8 h were detected by Western blotting. Results DNA Ladder was shown by gel electrophoresis analysis of DNA fragmentation in Jurkat T leukemia cells following treatment with LfcinB, which was not found in HFL-I cell. Through fluorescence microscope, we found that nucleus of LfcinB-exposed Jurkat T leukemia cells stained with Hoechst 3325 became condense, but the nucleus of HFL-I cell was not changed. The results of flow cytometry analysis indicated that apoptosis rates of Jurkat T leukemia cells exposed to LfcinB for 2, 4 h were 11.5% and 17.8% respectively, with decline of mitochondria membrane potential. Immunoblot analysis showed that LfcinB could increase the content of cytochrome C, with the activated caspase-3 and caspase-9 increase gradually in endochylema of Jurkat T leukemia cells, however there was no effect of LfcinB on caspase-8. Conclusion LfcinB induced apoptosis of Jurkat T lenkemia cells, but not affected fibroblasts. After Jurkat T leukemia cells, contacted with LfcinB for more than 2 h, the contents of caspase-3, caspase-9 and cytochrome C in the cells were cumulatively increasing, which further validated that LfcinB induced Jurkat apoptosis by intra-cellular signal pathway depending on caspase family.

ObjectiveTo investigate the effect of early intervention on shoulder pain in patients with hemiplegia after stroke. MethodsStroke patients were treated with bedside physical therapy on the shoulder 7 d after onset. They were assessed with short-form McGill pain questionnaire and Fugl-Meyer assessment of upper extremity before and 40 d after treatment. ResultsThe score of MPQ in the treatment group was significantly lower than that in the control group, while the score of FMA was significantly higher(P<0.01). ConclusionEarly intervention can reduce the pain and improve the function of the shoulder in patients with shoulder pain after stroke.

Objective　To analysis the relation of the diameter of continuous curvilinear capsulorhexis and other factors with the capsular block syndrome.Methods　We not only analyzed the etiology and clinical characteristic of six cases in intraoperative,early postoperative and lately postoperative,but also discussed the method of treatment.Results　(1)When the diameter of CCC was smaller than the one of IOL's optic , the CBS easily happened; (2)When the hoops of the hydroview IOL had a smaller anterior angle and larger optic, the CBS easily happened; (3)When the viscoelestic material and cortex were stayed in capsular or anterior chamber, the CBS easily happened.Conclusion　(1)Generaly speaking the size of the CCC should right on the edge of the IOL's optic part; (2)To hydroview IOL, we should choose the one which had a larger anterior angle and a smaller optic; (3)Viscoelastic material which should be cleaned and there was no the rest cortex stayed in the capsular.

OBJECTIVE:To establish a RP-HPLC method for simultaneous determination of chlorapheniramine maleate,furacilin and ephedrine hydrochloride in Puma nose drops.METHODS:The analysis was carried on a XDB C 8 column;the mo?bile phase was composed of methanol(A),acetonitrile(B)and0.02mol/L potassium dihydrogen phosphate solutions(containing0.2%triethylamine and adjusted to pH3.0with phosphoric acid,C)with linear gradient elution(0min～3.5min,A∶B∶C=6∶13∶18,8.5min,A∶B∶C=6∶30∶64)and the flow rate was1.0ml/min;the detection wavelength was254nm and the column temperature was30℃.Chloramphenicol was used as the internal standard.RESULTS:The linear ranges were0.04～0.20mg/ml for chlorapheniramine maleate,0.02～0.10mg/ml for furacilin,0.50～2.50mg/ml for ephedrine hydrochlo?ride.The average recoveries were99.44%(RSD=0.48%,n=3)for chlorapheniramine maleate,101.36%(RSD=0.41%,n=3)for furacilin and99.43%(RSD=0.59%,n=3)for ephedrine hydrochloride.CONCLUSION:The method is reliable,accurate and suitable for quality control of Puma nose drops.

Objective To explore the proliferation of microglia in the frontal cortex,hippocampus and amygdala of the post-stroke depression (PSD) in rats.To understand the role of microglia in the pathogenesis of PSD.Methods The adult female SD rats were divided into four groups(n=5 per group):normal control group,depression group,stroke group and PSD group.In the depression group,the depression model rat were established by chronic unpredictable mild stress (CUMS) combined with separately breeding.In the stroke group,focal cerebral ischemic rat models were established with thread embolization method.In the PSD group,focal cerebral ischemic models rat were established with thread embolization method firstly,and then PSD models rat were established with comprehensive chronic unpredictable mild stress(CUMS) and separately breeding on this basis.After the procedure,rats were subjected to sucrose preference test and open field test.At the postoperative eighth weekend,immunofluorescence technology was used to detect the proliferation changes of OX42 positive cells in the frontal lobe,hippocampus and amygdale.Results At the 29th day after CUMS,the sucrose solution consumption ((23.8±0.8) ％),horizontal movement distance of open field test ((63.0± 1.2) cm) and vertical movement distance ((25.0± 1.0) cm) in PSD group were significantly lower than those in normal group((31.2± 1.9) ％;(69.8±2.3) cm;(31.0± 1.6) cm) and depression group((31.0±1.4) ％;(70.2±2.4) cm;(30.8± 1.1) cm) (P＜0.05).The number of OX42 positive cells of frontal lobe,hippocampus and amygdale in PSD group((20.8±2.6);(20.2±1.3);(19.8±2.6))increased significantly compared with those of normal group((7.4±2.3);(8.0± 1.6);(9.4±2.1)),depression group((8.0±2.0);(7.8 ±2.2);(9.2±1.9))and stroke group((9.6±1.1);(9.4±2.2);(10.2±2.6)) (all P＜0.05).Conclusion The number of microglia in PSD group in the emotional disorders related brain areas(the frontal lobe,hippocampus and amygdale) increases obviously and the increased expression of microglia in the emotional disorders related brain areas may be responsible for the pathogenesis of PSD.

Objective To explore the expression of the CNPase positive oligodendrocytes in the frontal cortex,hippocampus and amygdala of the post-stroke depression (PSD) model rats,and to understand the role of oligodendrocytes in the pathogenesis of PSD.Methods Healthy adult SD rats were randomly divided into normal group,depression group,stroke group,and PSD group (n =5 in each group).In the stroke group,focal cerebral ischemic rat model was made with thread embolization method.In the depression group,the depression model rats were made by chronic unpredictable mild stress(CUMS) combined with separately breeding.In the PSD group,focal cerebral ischemic rat model was made with thread embolization method firstly,and then PSD rat model was established with comprehensive chronic unpredictable mild stress (CUMS) and separately breeding on this basis.After the procedure,rats were subjected to sucrose preference test (SPT) and open field test (OFT).Immunofluorescence staining was used to detect the expression of the CNPase positive oligodendrocytes in the frontal cortex,hippocampus and amygdala at day 29.Results On the 29th day after CUMS,comparing the sucrose solution consumption,horizontal movement distance of open field test and vertical movement distance of the each group,the depression((26.6± 1.1)％,(63.6±2.3)cm,(26.4±1.1)cm) and the PSD groups((23.8±0.8)％,(63.0± 1.2) cm,(25.0± 1.0) cm) were significantlylower than normal ((31.2± 1.9) ％,(69.8± 2.3) cm,(31.0 ± 1.6) cm) and the stroke groups ((31.0± 1.4) ％,(70.2±2.4) cm,(30.8 ± 1.1) cm) (P＜ 0.05).Comparing the expression of the CNPase positive oligodendrocytes in the frontal cortex,hippocampus and amygdala of the each group,the number of the stroke((16.60± 1.82),(14.60±1.82),(15.00±2.12)),depression((16.40±2.07),(14.80±2.17),(15.80±2.28)) and the PSD groups((12.40± 1.52),(11.20± 1.48),(10.80± 1.92)) were significantly less than that in normal group((20.40±3.51),(18.20±2.59),(19.00±2.55)),and the number of expression CNPase positive oligodendrocytes in the PSD group was significantly less than that in stroke and depression groups(all P＜0.05).Conclusion The number of the CNPase positive oligodendrocytes in PSD group in the emotional disorders related brain areas (the frontal lobe,hippocampus and amygdale) reduced obviously,and the oligodendrocytes may play an important role in the pathogenesis of PSD.

Objective To investigate the expressions of glial fibrilary acidic protein (GFAP) in the prefrontal cortex, hippocampus and amygdala in post-stroke depression (PSD) in rats. Methods Healthy adult SD rats w ere randomly divided into a normal group, a depression group, a stroke group, and a PSD group ( n=5 in each group). A model of focal cerebral ischemia w as induced by the intraluminal suture method in the stroke group;a rat chronic stress depression model was induced by using chronic unpredicted mild stress (CUMS) combined w ith single housing in the depression group;a model of focal cerebral ischemia w as induced by the intraluminal suture method in the PSD group. A rat PSD model w as induced by CUMS and single housing at 1 week after operation. The sucrose preference test (SPT) was performed in each group at day 1, 8, 15, and 29 after the first CUMS, and the open-field test ( OFT ) w as used to evaluate the depressive behaviors. Immunofluorescence staining was used to detect the expression of GFAP in the prefrontal cortex, and hippocampus and amygdala at day 29. Results At day 29 after CUMS, the sucrose solution consumption in SPT and the scores of horizontaland vertical movement in OFT in the depression group and PSD group w ere decreased significantly compared w ith the normal group and the stroke group (al P<0.05);the numbers of GFAP immunopositive cel s in the prefrontal cortex, hippocampus, and amygdala in the PSD group w ere significantly less than those in the normal group, depression group and stroke group (al P<0.05), and there w ere no significant differences among the normal group, depression group and stroke group (al P>0.05). Conclusion The decreased expression of GFAP in the prefrontal cortex, hippocampus, and amygdale may play a certain role in the process of PSD.