Background and purpose:P38 mitogen-activated protein kinase (P38MAPK) signal transduction pathway is involved in occurrence, development and transfer process in a wide variety of tumors. Urokinase-type plasminogen activator (uPA) plays an important role in tumor invasion and metastasis. This study aimed to explore the clinical signiifcance of the P38MAPK signaling pathway and the expression of uPA in ovarian cancer.Methods:The expressions of uPA, P38MAPK, ERK and AKT were detected in 49 cases of cervical adenocarcinoma by immunohistochemistry. The expressions of uPA and P38MAPK were detected by Western blot in ovarian cancer cell lines HO8910, HO-8910PM, SKOV3 and CAOV3. The changes of uPA and P38MAPK were detected by SB203580, a speciifc inhibitor of P38MAPK signal transduction pathway.Results:The result of immunohistochemical method showed that positive expression rates for uPA, P38MAPK, ERK and AKT were 61.22%, 57.14%, 53.06% and 55.10%, respectively. The expression of the uPA was positively correlated with the P38MAPK (r=0.865,P=0.001), and related with clinicopathologic stage, differentiated degree, lymph node metastasis, but not related with age and histologic type (P>0.05). The expressions of AKT and ERK were related with the lymph node metastasis and greater omentum metastasis(P<0.05), but not related with age and histologic type (P>0.05). The expression of uPA in HO-8910PM was higher than that in ovarian cancer cell lines HO8910, SKOV3 and CAOV3, and the expression of uPA reduced when the P38MAPK signal transduction pathway was cut off by the SB203580. The expressions of P38MAPK and uPA were negatively correlated with the prognosis of ovarian cancer (Log-rank=3.897 and 11.044,P=0.048 and 0.001). Conclusion:The P38MAPK signal transduction pathway was activated in ovarian cancer. The activated P38MAPK signal transduction pathway can raise the expression of uPA, which may contribute to the development of ovarian cancer. The result indicates that the P38MAPK signal transduction pathway and uPA might play an important role in the invasion and metastasis of ovarian cancer. P38MAPK and uPA might be useful markers for evaluating prognosis of ovarian cancer.

Objective To investigate the inhibitory effects of IL-18 gene on HCC growth in vivo. MethodsThe recombinant adenovirus vector containing IL-18 gene was constructed and cotransfected into 293 cells together with EcoT22 I-digested Ad5 DNA-TPC, the recombinant adenoviruses were generated, and injected into a rat model bearing HCC. Results The recombinant adenovirus vector containing IL-18 gene inhibited the proliferation of HCC cell line CBRH 3. The rats receiving IL-18 gene injection within 3 days after inoculation of CBRH 3 all had long term survival, while those injected at day 5 or 7 survived a limited longer period than control groups (P

OBJECTIVE: To investigate the effects of resveratrol on the expression of SIRT1,the activity of eNOS and the secretion of NO of highlipid cultured primary human umbilical vein endothelial cells(HUVEC).METHODS: HUVEC were divided into normal control group,highlipid group and highlipid+resveratrol group,cultured for 24 hours.The expression of SIRT1 mRNA and protein were analyzed by RT-PCR and Western blot methods.Supernatant were used to analyze the nitric oxide(NO) content and activity of endothelial nitric oxide synthase(eNOS).RESULTS: Compared with highlipid group,resveratrol group increased the expression of SIRT1 mRNA and protein,the activity of eNOS and the secretion of NO(P

Objective To observe the effects of glucagon like peptide-1 (GLP-1) analogues liraglutide on expressions of nitric oxide synthase (NOS) and cyclo-oxygen-ase (COX)2 in renal medulla of type 2 diabetes rats, and the mechanism of its lowering blood pressure and promoting excretion of water and salt in kidney. Methods Type 2 diabetes model rats were generated by high-fat and high-sugar feeding for 8 weeks followed by intraperitoneal injection of streptozotocin (STZ). Subse?quently, eighteen type 2 diabetes rats were divided into two groups: liraglutide treatment group (DMT) and diabetes group (DM). Twelve normal rats were divided into two groups: liraglutide treatment wild type group (WTT) and wild type group (WT). DMT and WTT groups were given liraglutide (200μg/kg) by subcutaneous injection, DM and WT groups were given equivalent normal saline by the same way. The levels of blood glucose and blood pressure were detected at 0, 2, 4 and 6 weeks after treatment in groups of rats. Samples of urine were collected for detecting ion concentrations (K+, Na+and Cl-) af?ter treatment for six weeks. Rats were sacrificed and blood samples were collected for detecting ion concentrations (K+, Na+and Cl-). The expression levels of NOS and COX2 mRNA and protein in renal medulla were detected by real-time PCR and Western blot assay. Results After treating with liraglutide, the values of blood glucose (F=5.933, P<0.05) and blood pres?
sure (F=22.070, P<0.05) were gradually decreased in DMT group. After treatment with liraglutide for 6 weeks, the values of blood glucose (mmol/L:12.78 ± 3.82 vs. 18.75 ± 1.68) and blood pressure (mmHg:119.98 ± 4.43 vs. 136.42 ± 4.48) were signifi?cantly decreased (P<0.05) in DMT group than those of DM group (P<0.05). There were no significant differences in the concentrations of K+, Na+and Cl-between the two groups. There were higher levels of K+(mmol/L:46.55 ± 6.43 vs. 33.13 ± 9.71), Na+(mmol/L:56.33±8.83 vs. 41.20±7.25) and Cl-(mmol/L:159.81±25.06 vs. 71.44±12.99) in urine in DMT group than those of DM group (P<0.05). The mRNA levels and protein expressions of NOS and COX2 in renal medulla were significant?ly increased in DMT group than those of DM group (P<0.05). Conclusion GLP-1 analogues liraglutide may enhance the expression of COX2 by increasing the expression of NOS to excrete water and salt, and decrease blood pressure.

Objective To explore the role of liver X receptor (LXR) agonist T0901317 on thrombomodulin (TM) expression in human glomerular endothelial cells and the possible mechanisms.Methods Different concentrations of T0901317 were used to stimulate human glomerular endothelial cells for different time,then LXRα,LXRβ expression were detected by using Western blotting analysis;the roles of T0901317 on TM mRNA and TM protein expression were observed by using real-time PCR,Western blotting and immunofluorescence assay.LXRα,LXRβ gene interference segment Si-hLXRα,Si -hLXRβ were transfected into human glomerular endothelial cells with the concentration of 100 nmol/L respectively,then the roles of Si-hLXRα,Si-hLXRβ on the TM protein and TM mRNA expression were assayed by Western blotting and real time PCR.Results Human glomerular endothelial cells expressed LXRα and LXRβ.Compared to the normal cells and DMSO group,T0901317 could significantly promote TM expression in human glomerular endothelial cells (P ＜ 0.05) and showed a time -and dose-dependent manner.TM expression in Si-hLXRα transfected group was significantly lower than that in the control group (P ＜ 0.05),while TM expression in Si-hLXRβ transfected group had no significant difference compared to the control group.Conclusions Human glomerular endothelial cells express LXRα and LXRβ.LXR agonist T0901317 promotes TM expression in human glomerular endothelial cells,which may be mainly through activating LXRa.

To study the cognitive effects of diterpene ginkgolides (DG), transient middle cerebral artery occlusion (tMCAO)-induced rats were established. tMCAO-rats induced by suture method were divided into sham operation group, solvent control group, NBP group, DG group. The animal experiments in the present study were performed in accordance with the Ethical Guidelines of the Laboratory Animal Welfare Ethical Committee of Peking Union Medical College (00000646, 00000635). The effects of DG on tMCAO rats were evaluated by neurological severity score, cerebral infarction volume measurement, step-down and Morris water maze test. In the acute tMCAO rat model, 100 mg·kg^-1 DG improved the neural score and infarction volume. In the chronic tMCAO rat model, DG 100 mg·kg^-1 significantly improved the survival rate of tMCAO-induced rats. The Morris water maze results showed 100 mg·kg^-1 DG decreased the latency of tMCAO-induced rats to find the platform, while the effect was weaker than the NBP. However, DG 30 mg·kg^-1 did not show a significant effect. In conclusion, DG exerted a therapeutic effect on transient middle cerebral artery occlusion.

To compare the neuroprotective and anti-dementia pharmacological effects of chiral oxiracetam, glutamate and calcium ions were used to establish neuronal injury models in vitro, and the protective effects of chiral oxiracetam on primary neurons were assayed by MTT. Permanent bilateral common carotid artery occlusion (2-VO)-induced rats were randomly divided into sham group, model group, galantamine 3 mg‧kg^-1 group, oxiracetam groups (30, 100 and 200 mg‧kg^-1), S-oxiracetam groups (30, 100 and 200 mg‧kg^-1) and R-oxiracetam 200 mg‧kg^-1 group. The animal experiments in the present study were performed in accordance with the Ethical Guidelines of the Laboratory Animal Welfare Ethical Committee of Peking Union Medical College. Morris water maze and step-down test were applied to evaluate the cognitive dysfunction induced by cerebral hypoperfusion in rats. Oxiracetam, S-oxiracetam and R-oxiracetam exerted protective effects on primary neuronal damage caused by various stimuli, and oxiracetam and S-oxiracetam showed better neuro-protective effects. Morris water maze and step-down results showed that oxiracetam, S-oxiracetam and R-oxiracetam improved the cognition of 2-VO rats. In summary, S-oxiracetam exerted a better neuro-protective effect than oxiracetam and R-oxiracetam.

Objective To explore the correlation between adipocyte factors(adiponectin and visfatin)and fetus intrauterine growth.Methods Enzyme immunoassay was used to measure the adiponeetin and visfatin levels in maternal and umbilical serum from 14 women with fetal growth restriction (FGR group),14 women with maerosomia(macrosomia group)and 14 normal pregnant women(control group).The correlations of cord serum adiponectin and visfatin with matemal serum adiponectin and visfatin were analyzed.Results (1)Serum visfatin levels in FGR mothers[(41.4±5.5)]μg/L were significantly higher than that in control women[(34.7±4.9)μg/L and macrosomia mothers[(37.3±4.4)μg/L;P<0.01,P<0.05].Serum adiponectin levels in maerosomia mothers [(4.1±1.3)mg/L]were significantly lower than that in control women [(6.6±1.5)mg/L]and FGR mothers[(6.4±1.3)mg/L;P<0.01].(2)Serum visfatinin levels in FGR babies[(58.1±7.6)μg/L] were significantly increased than that in control newborns[(42.6±7.8)μg/L]and macrosomia babies[(48.5±9.1)μg/L;P<0.01,P<0.05].Serum adiponeetin levels in macrosomia babies[(6.5±1.3)mg/L]were significantly decreased than that in control newborns[(7.7±1.5)mg/L]and FGR babies[(7.7±1.0)mg/L;P<0.05,P<0.05].(3)Maternal serum visfatin levels were positively correlated with umbilical serum visfatin levels(r=0.720.P<0.01).Umbilical serum adiponectin levels were higher than that in maternal serum,but there were no relationship between them(r=0.301,P>0.05).Conclusion The changes of visfatin and adiponeetin levels may be related to the oceurrenee of FGR and fetal macrosomia.

Objective To investigate the morbidity and characteristic of nosocomial infections in end stage renal disease(ESRD) patients undergoing blood purification.Methods Medical records of ESRD patients undergoing blood purification from 2004 to 2005 were enrolled in this retrospective study of hospitalized cases.The clinical data of nosocomial infections in hemodialysis (HD)and peritoneal dialysis(PD)patients were analyzed separately.Results Nosocomial infection was identified in 76 of the 400 enrolled patients.In HD patients,pulmonary infection was the most common nosocomial infection(53.3%),most due to gram-negative microorganisms,followed by bloodstream(16.7%)and urinary tract infection(15%),most of both were due to gram-positive bacteria.Pulmonary infection was usually complicated.Bloodstream infection was associated with the duration of placement of central vein catheters.Asymptomatic bacteriuria accounted for most of the urinary tract infection.In PD patients, most infections were pulmonary infection(65.5%),mainly caused by fungal pathogens,followed by peritonitis(20.7%), mainly due to gram-positive bacteria.Certain proportion of infections in both groups was caused by multiple microorganisms or identified in multiple sites.Conclusions The prevalence of nosocomial infection is high in hospitalized patients undergoing blood purification.The infection is complicated in terms of pathogen and clinical picture.Pulmonary infection is the most common in- fection.The prevalence of fungal infection is increasing.Effective prevention and therapeutic measures should be applied more vigorously in ESRD patients.

Female ; Humans ; Liver Neoplasms ; Middle Aged ; Paraganglioma