Aim To investigate the relationship between oxidative stress and the aortic endothelial cells injury in type 2 diabetes rats,as well as the effect of valsartan. Methods The type 2 diabetic models were induced by low dose of streptozotocin (STZ) with high-energy diet.12 weeks after injecting STZ, rats were randomly divided into three groups: normal control, diabetes control and valsartan (24 mg?kg-1?d-1, 8 weeks, ig.) treated diabetes. At the 12th and 20thweek end, such indices as the endothelium-dependent vasodilation and the shape of aorta endothelium, the serum contents of SOD, GSH-Px , MDA and NO, and the level of NOS gene expression in aorta were measured. Results ① At the 12th weekend,in the diabetes group, the relaxation of aortic rings to low concentration of Ach declined, the aortic endothelial cells intumesced, contents of serum SOD, GSH-Px, MDA and NO significantly increased, the expression of iNOS mRNA in aorta obviously up-regulated while the expression of eNOS mRNA showed no change. ② At the 20th weekend,in the diabetes control group, the dilatory reactivity of aortic rings decreased to each concentration of Ach, the aortic endothelium appeared degenerative and necrotic, activities of SOD and GSH-Px decreased as well as the content of NO, the content of MDA increased continuously, and the iNOS mRNA expression up-regulated while eNOSmRNA expression down-regulated. Valsartan could regress the aggravation and improve contents of serum SOD, GSH-Px, MDA, NO and NOS mRNA of the aorta. Conclusion The oxidative stress and abnormality of NO participate the process of aortic endothelial cell injury. Valsartan plays a protective role partially through enhancing antioxidation effect and adjusting NO production.

Objective To study the expression of aspartic proteinase cathepsin D in the germinal center of follicular lymphoma and follicular hyperplasia. Methods Immunohistochemical staining was performed to detect the expression of cathepsin D in paraffin sections of 10 cases of follicular lymphoma and 9 cases of follicular hyperplasia. Results Cathepsin D was weakly expressed in the plasma of dendritic cells and histiocytes in the germinal centers of 9 out of 10 cases of follicular hyperplasia. The number of positive cells were smaller in the center of follicles, but larger in the periphery. It was more strongly expressed in the plasma of dendritic cells and histiocytes located predominantly in the peripheral areas of germinal centers of follicular lymphoma in 10 patients. Some germinal centers were surrounded by T lymphocytes in 4 cases of follicular lymphoma, and cathepsin D positive cells in these germinal centers were more in number than that in the germinal centers without being surrounded by T cells in other 6 cases of follicular lymphoma, in which positive sign even absent in some germinal centers. Conclusion Cathepsin D is a good marker for the dendritic cells and histiocytes, and its differential expression in follicular lymphoma and follicular hyperplasia is helpful for differential diagnosis of the diseases. Based on the former reports of cathepsin D with its important roles in antigen processing, we suppose that lower expression of this protease is probably due to the decreased ability of immunological response to tumor in follicular lymphoma patients.

Objective To study the relation between the expression of drug-resistance gene and in vitro drug sensitivity test in ovarian carcinoma and clinical biological behavior.Methods In 60 primarily treated patients with epithelial ovarian carcinoma,the expression of COX-2,Connexin43(CX43)and P-gp was detected using flow cytometry.Sensitivity of cells of short term in vitro culture to anticancer drugs was also examined by the game techniques.Remits The expression level of COX-2 was higher in tissue with DDP-resistance patients than those with sensitivity patients but the expression level of CX43 was lower in tissue with DDP-resistance and Taxol-resistanee patients than those with sensitivity patients.The expression level of P-gp was higher in tissue with VP16-resistance patients than those with sensitivity patients.The sensitivity of DDP,Taxol and VP16 was lower in tissue with higher expression of COX-2 and P-gp than those with lower expression of COX-2 and P-gp.The sensitivity of DDP and Taxol was higher in tissue with higher expression of CX43 than those with lower expression of CX43.Conclusion The in vitro sensitivity of some of the drugs is effected by tissues with expression of COX-2,P-gp and CX43.It is not only useful but also individualized treatment for application of sensitive drug test and detecting the expression of COX-2,P-gP and CX43 to increase the response rate of chemotherapy in patients with epithelial ovarian carcinoma.

Objective To construct the short hairpin RNA recombinant plasmids targeting mdr1 gene which expresses highly in ovarian cancer resistance strain SKOV3/TAXOL to silence endogenefic mdr1 gene expression and investigate the role of mdr1 gene in the development of resistant ovarian cancer. Methods The pGPU6/GFP/Neo-mdr1 were constructed by gene clone technology. The influence on proliferation and apoptosis were investigated by CCK-8 in SKOV3/TAXOL after transfected pGPU6/GFP/Neo-mdr1. Results The expression against mdr1 proteins were inhibited by pGPU6/GFP/Neo-mdr1. The cell proliferation were inhibited after transfected pGPU6/GFP/Neo-mdr1 by CCK-8. The apoptosis were observed in DAB experiments and the apoptosis rate increased. Conclusion mdr1 plays an important role in proliferation of resistant ovarian cancer and the short hairpin RNA of mdr1 can efficiently suppress mdr1 expression and enhance the apoptosis in SKOV3/ATAXOL.

Objective To construct the small hairpinRNA recombinant plasmids targeting mdr-1 gene which expresses highly in ovarian cancer resistance strain SKOV3/TAXOL to silence endogenetic mdr-1 gene expression and investigate the role of mdr-1 gene in the development of resistant ovarian cancer. Methods The pPGPU6/GFP/Neo-mdr-1 were constructed by gene clone technology. The influence on proliferation and apoptosis were investigated by CCK-8 in SKOV3/TAXOL after transfected. pPGPU6/GFP/Neo-mdr-1. Results The expression against mdr-1 proteins were inhibited by pPGPU6/GFP/Neo-mdr-1. The cell proliferation were inhibited after transfected pPGPU6/GFP/Neo-mdr-1 by CCK-8. The apoptosis were observed in DAB experiments and the apoptosis rate incised. Conclusion mdr-1 plays an important role in proliferation of resistant ovarian cancer and the short hairpinRNA of mdr-1 can efficiently suppress mdr-1expression and enhance the apoptosis in SKOV3/TAXOL, which provides a novel method for chemotherapy resistant tumors.

Aim To investigate the effect of irbesartan and spironolactone on expressions of connective tissue growth factor(CTGF),P-p38MAPK proteins during vascular remodeling in renovascular hypertensive rats(RHR).Methods Renovascular hypertension was induced by two kidney one clip(2K1C)operation.8 weeks later,RHRs were given irbesartan or(and)spironolactone for 8 weeks.After 8 weekstreatment,the morphometric measurements were performed in the mesenteric arterioles.Concertration of carboxyterminal propeptide of typeⅠprocollagen(PⅠCP)and N-terminal propeptide of type Ⅲ procollagen(PⅢNP)in blood serum was measured by enzyme linked immunosorbent assay method,and the media collagen area was assessed by collagne-specific Picro-sirius red staining with computerized video processing.Expressions of collagen type I,CTGF,P-p38MAPK proteins were detected using immunohistochemistry respectively.Results The arterial systolic pressure was attenuated significantly after the treatment of irbesartan,and this effect could not be enhanced by spironolactone.The media thickness over lumen ratio,media cross-sectional area over luminal area ratio of mesenteric arterioles,concertration of PⅠCP and PⅢNP,media collagen area,and expression of collagen typeⅠwere significantly increased in RHRs but ameliorated by irbesartan and spironolactone.Meanwhile,the expressions of CTGF,P-p38MAPK proteins were up-regulated in RHRs but blunted significantly after the treatment of irbesartan and spironolactone.The combined treatment had the synergic effects.Conclusions There is a synergistic effect of attenuating extracellular matrix(ECM)producing and amelioration of vascular remodeling(VR)by combined use of irbesartan and spironolactone.It maybe related to the expressions of CTGF and P-p38MAPK proteins down regulated by these two drugs.

AIM: To investigate the alteration of the vascular response to contracting material and the endothelium dependent vascular relaxation (EDVR) at different stages of type Ⅱ diabetes rats. METHODS: Type Ⅱ diabetes rat model was established by high-energy diet and lower dose of STZ. At 12th and 20th weekends after injecting STZ, the vascular reactivities to phenylephrine (PHE) and KCl and the EDVR induced by Ach were measured respectively in the isolated aorta rings. RESULTS: At 12th weekend after injecting STZ, the response to PHE increased, the reactivity to KCl kept unchanged, and the EDVR was damaged lightly. But at the 20 th weekend after injecting STZ, the response to PHE increased further and the reactivity to KCl markedly reinforced, and the EDVR was obviously damaged. CONCLUSION: The response of great vessels to contracting material increased, but the EDVR attenuated at different stages of type Ⅱ diabetes rats. These changes are further reinforced along with the developing of disease duration.

Aim To investigate the alteration of the nitric oxide (NO), the expression of nitric oxide synthase (NOS) mRNA at different stages of the cardiomyopathy in type 2 diabetes rats, and the protective effects of valsartan. Methods Type 2 diabetes model was established by high-energy diet, lower dose of STZ treated SD rat. The treatment period of valsartan was 8 weeks. At 12th and 20th weekend after injection of STZ, cardiac function, heart weight index, concentrations of NO in myocardium and plasma, expressions of iNOSmRNA and eNOSmRNA were measured respectively.Results From 12th week to 20th weekend, the left ventricular systolic and diastolic function was decreased and the heart weight index was increased in diabetes control group (DC group) compared with normal control group (NC group). The levels of the cardic tissue and plasma NO were higher at 12th weekend and lower at 20th weekend in DC group than that in NC group. The expression of iNOSmRNA in cardiac tissue was obviously up-regulated at 12th or 20th weekend while the expression of eNOSmRNA was down-regulated at 20th weekend in diabetes rats. All these abnormalities were partially attenuated by valsartan. Conclusion The abnormal change of the NO and expression of NOSmRNA might be related to the cardiomyopathy in type 2 diabetes. Valsartan might play a protective role in the myocardial disease.

Aim To explore the molecular mechanism atherosclerosis by network pharmacology and in vitro of Gualou Xiebai Banxia decoction in the treatment of study.Methods All chemical constituents and targets of Gualou Xiehai Banxia decoction were retrieved from TCMSP database.OMIM, DrugBank and TTD databas¬es were searched with "atherosclerosis" as the search term , and the related targets of atherosclerosis were ob¬tained after eliminating duplicate options.DAVID da¬tabase was used for GO and KEGG pathway enrichment analysis of intersection targets.Finally, the analysis results were confirmed in the ox-LDL induced human aortic endothelial cell injury model.Results A total of 30 active compound molecules in Gualou Xiebai Banxia decoction and 78 potential targets for the treat¬ment of atherosclerosis were retrieved.The therapeutic targets were mainly related to inflammatory pathway, apoptosis and so on.(3-sitosterol was chosen as a po¬tential pharmacodynamic molecule for the treatment of atherosclerosis to verify the correctness of the results of network pharmacological analysis.In vitro experiments showed that, (3-sitosterol could prevent ox-LDL in¬duced apoptosis of human aortic endothelial cells and significantly reduce the level of IL-ip, 1L-6 and TNF- cx in cell culture medium, and protein expression of p- NF-kB/NF-kB, 1L-1 p, 1L-6 and TNF-a in cells.Conclusions The treatment effect of Gualou Xiebai Banxia decoction on atherosclerosis is mainly mediated by regulating inflammation, apoptosis and other path¬ways through multi-component effect, multiple targets and multiple pathways.

Objective To investigate the correlation between dynamic contrast-enhanced CT and MRI image findings of intrahepatic mass-forming cholangiocarcinoma(IMCC) and pathologic differentiation.Methods The CT and (or) MRI features of ninety-five patients with IMCC proved by pathologic examination were retrospectively reviewed.Sixty-five patients underwent multiphasic dynamic contrast-enhanced CT scan, twenty-nine underwent multiphasic dynamic contrast-enhanced MRI scan and ten patients underwent multiphasic dynamic contrast-enhanced CT and MRI examination simultaneously.According to the case history and laboratory examination, patients were divided into groups: with chronic hepatitis and without chronic hepatitis and according to the maximum diameter of the tumor, they were divided into＜3 cm, 3 to 6 cm and＞6 cm groups.The imaging features of tumor enhancement were reviewed among groups.The pathologic results and imaging features were compared and patients were divided into well differentiated, moderately differentiated, and poorly differentiated groups.Analyzed by Chi-square test, the difference of tumor enhancement between groups were analyzed.Results The patterns of multiphasic dynamic contrast-enhanced CT and MRI in IMCC patients had five types: type 1:60 cases, peripheral rim and (or) separating enhancement during artery phase, followed by centripetal enhancement progressively and(or) separating enhancement in the equilibrium phase;type 2:11 cases, peripheral rim enhancement in the artery phase and hypointensity (hypoattenuating) during equilibrium phase with central nodular enhancement;type 3:15 cases, no enhancement in the arterial phase and internal heterogeneous enhancement during equilibrium phase;type 4: 6 cases, heterogeneous enhancement in the early phase and wash-out during equilibrium phase;type 5 : 3 cases, no enhancement throughout dynamic enhancement.The results showed that in hepatitis group type1 to 5 had 31, 7, 12, 5 and 1 cases and without hepatitis group had 29, 4, 3, 1 and 2 cases.There was no statistical significance between groups(x2=3.567,P=0.059).The maximum diameter＜3 cm group(28 cases) had 9, 8, 6, 3 and 2 case which showed enhancement type1 to 5;3 to 6 cm group(40 cases) had 27, 2, 7, 3 and 1 cases and＞6 cm group(27 cases) had 24, 1, 2, 0 and 0 cases.There was significant difference in groups(x2=19.582,P＜0.01).Pathological well differentiated and moderately differentiated groups(40 cases) had 24, 7,6, 2 and 1 cases presented enhancement type 1 to 5 and poorly differentiated group(55 cases) had 36, 4, 9, 3 and 3 cases.There was no statistical difference in three differentiated groups(x2=0.296,P=0.586).Conclusions CT and MRI enhancement patterns of IMCC are presented with diversity.The imaging features are associated with focus size and had no relationship with pathological differentiated degree.