Objective To study the effect of cholecystokinin-octapeptide(CCK-8) on the proliferation of fibroblast-like synovial cell line RSC-364 and p38 MAPK activity induced by TNF-? in rat.Methods The proliferation of RSC-364 cells was measured by monotetrazolium(MTT) colourmetric assay and the level of activation of p38 MAPK was deteced by Western blot.Results An increase in p38 MAPK phosphorylation was detected 5 min after TNF-?((50 ?g/L))addition,and reached a plateau at(15 min),finally returned to the basic level at(2 h).TNF-?(10,25,(50 ?g/L)) increased p38 MAPK phosphorylation in a dose dependent manner at 15 min.CCK-8((10~(-10))～(10~(-6)mol/L))could inhibit the proliferation and the level of phosphorylation of p38 MAPK in a dose dependent manner.Moreover the inhibitory effects were partly reversed by CCK-A receptor specific antagonist CR1409 or CCK-B receptor specific antagonist CR2945.SB203580 inhibited TNF-?-stimulated RSC-364 proliferation.Conclusion CCK-8 inhibited TNF-?-stimulated proliferation by decreasing p38 MAPK phosphorylation in RSC-364 cells,which was mediated through CCK-A receptor or CCK-B receptor.

Pregnancy and the puerperium have been recognized to increase the risk of stroke, particularly from late pregnancy and through the puerperium. The reported incidences of stroke during pregnancy and the puerperium varied widely, but when it occurs, there may be implications for management of the patient and delivery of the child. Important causes of stroke during pregnancy and the puerperium include preeclampsia and eclampsia, cardioembolism, rapture of cerebral vascular anomaly, cerebral aneurysm rupture and antiphospholipid syndrome, thrombotic thrombocytopenic purpura. Management of patients with pregnancy-related stroke is largely the same as that of nonpregnant patients, including thrombolysis, atntiplatelets and anticoagulants, with more consideration on maternal and fetal risks.

Objective To analyze the etiological changes of atrial fibrillation(AF) in Zhanjiang. Methods The etiology of 592 AF cases during 1990～1997 were analyzed, and 610 cases during 2000～2007 were analyzed as comparison. Results Rheumatic heart disease(36.8%) was main etiology of AF during 1990～1997. But coronary artery disease(33.1%) has surpassed rheumatic heart disease recently, and the hyperthyroidism and undetermined-e-tiology of atrial fibrillation were decreasing. The etiology of atrial fibrillation in different age groups was significantly different(P <0.05 or P <0.01). Conclusion The etiology of atrial fibrillation changes every year,and age is a pre-dictable factor to the etiology of atrial fibrillation.

Objective To discuss the influence of μ-opioid receptor ( OPRM1) and CYP3A gene polymor-phism on analgesic effect of fentanyl for abdominal hysterectomy patients .Methods 198 cases of gynecologic anes-thesia patients who were treated by elective abdominal hysterectomy surgery ,were selected in the hospital .The rela-tionship between the fentanyl consumption of intravenous analgesia and OPRMI and CYP 3A gene polymorphisms was detected by using polymerase chain reaction-restriction fragment length polymorphism detection .Results In 198 pa-tients,OPRM1 genotyping was 186 cases,the other 10 patients failed to typing were excluded ,including 89 cases of type A/A,type A/G 76 cases,type G/G 21 cases,OPRM1 the frequency of A118G allele was 31.7%.No statistically significant differences were found in mean VAS score of CYP 3A4*1/*1,CYP3A4*1/*1G,CYP3A4*1G/*1G instantly after operation in the three groups and 24h postoperation.By using analysis of variance with body mass ,age and intraoperative volume as a covariate factors after first 24h fentanyl consumption ,the difference was statistically sig-nificant among the three groups (P<0.05),CYP3A4*1G/*1G group was significantly lower than that in CYP3A4*1/*1G group and CYP3A4*1/*1 group,there was no significant difference between CYP 3A4*1/*1G group and CYP3A4*1/*1 group (P>0.05).In addition,because the OPRM1 A118G interacts with CYP3A4*1G, reducedthe quantity of expression of opioid receptor carrying CYP 3A4*1 and OPRM1 A118G/G,and thus more fent-anyl was needed postoperation to achieve the same effect .Conclusion It provided a theoretical basis and reference for clinical application of personalized medicine by analyzing the gynecological patients μopioid receptor gene A118G and CYP3A4*1G polymorphism.

Objective To explore the effects of Nimodipine on oncogene c-fos and c-jun mRNA expressions in dorsal root ganglia of rats following acute sciatic nerve injury.Methods Nimodipine at a dose of 10 mg/kg at 5,15,30,60 and 120 min and at a different dose of 2.5,5 and 10 mg/kg at 60 min was given to each rat through intraperitoneal injection before transection of sciatic nerve.Using reverse transcription PCR(RT-PCR) technique,the c-fos and c-jun mRNA expressions were detected at 5,15,30,60 and 120 min after injection of Nimodipine and following acute sciatic nerve injury.Results Compared with control group,the expressions of c-fos mRNA in injury group were obviously increased at 30,60 and 120 min after injury(all P

Aim To observe the influence of CCK-8 on expression of MMPs/TIMP-1 in TNF-α-induced rat fibroblast-like synovial cell line RSC-364.Methods The secretion levels of MMP-1, MMP-3, MMP-9 and TIMP-1 were determined using ELISA;MMP-3 and MMP-9 mRNA expressions were detected by RT-PCR.Results MMP-3 and MMP-9 could not be examined in RSC-364 incubated with CCK-8 and unstimulated RSC-364, which was able to product a little MMP-1, TIMP-1 and express even less MMP-3,-9 mRNA.CCK-8 inhibited the increase in MMP-1, MMP-3, MMP-9 secretion and MMP-3,-9 mRNA expression in TNF-α-induced RSC-364.TIMP-1 production was also increased in TNF-α-induced RSC-364.CCK-8 had no effect on TIMP-1 production in TNF-α-induced RSC-364, but was able to reduce the ratios of MMP-1, MMP-3, MMP-9 to TIMP-1.Conclusion The inhibitory effect of CCK-8 on MMPs activity may be related to the decrease of MMPs mRNA expression, MMPs secretion and the ratios of MMPs to TIMP-1 in TNF-α-induced RSC-364, which indicates that CCK-8 might be a possible regulator in the pathogenesis of rheumatoid arthritis.

AIM: To investigate the inhibitory effects of cholecystokinin octapeptide(CCK-8) on nuclear factor-?B(NF-?B) activities stimulated by lipopolysaccharide(LPS) by using forskolin,the activator of adenylate cyclase,and PKA inhibitor H-89 in rat pulmonary interstitial macrophages(PIMs).METHODS: PIMs were isolated and purified.EMDA was applied to detect NF-?B activities and Western blotting was used to analyze the I?B-? protein level in rat PIMs.RESULTS: The NF-?B activity was not detected in normal control rat PIMs.The NF-?B activity in LPS-treated rat PIMs was obviously higher than that in control group(P0.05).The NF-?B activity in CCK+LPS group and LPS+Fsk group were obviously lower than that in LPS group(P

ObjectiveTo explore the effect of TLR4,PI3K and NF-κB on the migration of asthmatic airway smooth muscle cell(ASMCs) induced by airway epithelial cells.MethodsPrimary ASMCs were cultured by the method of cell digestion.Cell culture supernatant of RTE cells were collected by TNF-α stimulation of epithelial cells.Detected the IL-8 and RANTES levels in the supernatant.The effect of TLR4/PI3K-related signaling molecules on the migration of asthmatic ASMCs induced by epithelial cells were detected by Modified Boyden chemotaxis chamber with anti-TLR4 antibody,Wortmannin and PDTC drugs as a tool.ResultsThe levels of IL-8 and RANTES in the supernatant of TNF-αgroups were significantly increased,and that in the 20 ng/ml group was significantly higher than other groups ( P＜0.01 ).Compared with control group,the transmembrane migration of asthmatic ASMCs from other groups was significantly increased (P＜0.01 ).The transmembrane migration of asthmatic ASMCs from treated groups was significantly increased than asthma group (P＜0.01).The migration of asthmatic ASMCs from TNF-α+anti-TLR4 antibody group,TNF-α+Wortmannin group and TNF-α+Wortmannin+PDTC were significantly decreased than that of TNF-αgroup( P＜0.01 ).The migration of asthmatic ASMCs from TNF-α+Wortmannin+PDTC were significantly decreased than that of TNF-α+Wortmannin group (P＜0.05).ConclusionTLR4/PI3K-related signaling molecules involved in the transmembrane migration of asthmatic ASMCs induced by airway epithelial cells and may be one of the mechanisms of airway remodeling of asthma.

AIM: To investigate the effect of sulfated cholecystokinin octapeptide (CCK -8 ) on TNF -α induced IL - 6 mRNA expression, NF - κB activation in the rat fibroblast - like synovial cell strain RSC - 364 and its possible receptor mechanisms. METHODS: RSC -364 cells were stimulated with TNF - α( 10 μg/L) in the presence or absence of sCCK- 8( 10-8 - 10-6 mol/L) or/and CCK receptor antagonist proglumide(2 mg/L). IL -6 and CCK receptor A/B (CCK- AR/CCK/BR) mRNA expression were assayed by reverse transcription polymerase chain reaction (RT- PCR) at 3 h after stimulation, and nuclear factor - κB (NF - κB) binding activity was analyzed by electrophoretic mobility shift assay (EMSA) at lh after stimulation. At 30 min of stimulation the IκB protein level in cytoplasma was measured by Western blotting. RESULTS: Both CCK - AR and CCK - BR were constitutively expressed on RSC - 364. sCCK - 8, at concentrations from 10-8 mol/L to 10 -6 mol/L, significantly increased IL - 6 mRNA expression, CCK - AR and CCK - BR mRNA expression, NF - κB binding activity and IκB protein degradation. The effects of sCCK - 8 on NF - κB activity and IκB degradation level were attenuated by CCK receptor antagonist proglumide. CONCLUSION: sCCK - 8 upregulats TNF - α- induced IL - 6 mRNA expression by NF - κB pathway through its receptor on rat synoviocytes, suggesting its possible regulatory role in the pathogenesis of rheumatoid arthritis.

BACKGROUND: There are a lot of researches on the protective action of calcium channel blocker(CCB) on diabetic peripheral neuropathy, but the dosage and the effect on injured nerve need to investigate further in clinical application.OBJECTIVE: To observe the results of electrophysiologic assessment of the effect of CCB flunarizine at different dosages on Bell' s palsy after 1-month treatment.DESIGN: Randomized grouping, blank control and l-month follow up.SETTING: Department of Neurology, First Affiliated Hospital of Nanjing Medical University.PARTICIPANTS: Totally 35 patients with Bell' s palsy, including 19males and 16 females aged from 16 to 58 and the mean age of 32. 8, were selected from Outpatients of the Department of Neurology, the First Affiliated Hospital to Nanjing Medical University from November 1999 to May 2001. The course of disease was ≤ 3 days. Patients were without any treatment, and all of the facial nerve palsy was complete. According to random samplings, all patients were divided randomly into control group (basic treatment group) with 12 cases and treatment groups with 10 cases in first subgroup and 13 in second subgroup.METHODS: Basic treatment: 1 mg/kg per day prednisone(the maximal dosage ≤ 60 mg/day) was taken once every day and reducing dosage by half every 5 days, with a course of therapy for 15 days. 500 μg methycobal was taken orally three times a day and 25 mg fursulthiamine also orally three times a day. Ultrashort wave physiotherapy was taken once a day for 15 days. On the basis of the basic treatment, patients in the first subgroup accepted 5 mg flunarizine once every night, and 10 mg flunarizine once every night was given to the patients in the second subgroup. The latency and amplitude of Blink response were checked before treatment and after 1-month treatment.MAIN OUTCOME MEASURES: The latency and amplitude of Blink response in every group after 1-month treatment.RESULTS: According to the imagery analysis, 35 patients entered the resulting analysis. Before treatment, the 3 groups of blink responses were all efferential blocking in facioplegic side, and in addition, R1 and R2 all disappeared. After treatment for 1 month, Blink response of R1, R2 appeared. The latency of R1 and R2 in the second treatment group was better than that in control group[ (9. 608 ± 0. 575) ms, (31. 869 ± 2. 934) ms,(11.208±1.490) ms and (37. 583 ±5. 408) ms, P ＜0.01], but there were no differences in this respect between the first treatment group and the control group. The ipsilateral amplitudes of Blind response in the three groups were not different after 1-month treatment.CONCLUSION: After 1-month treatment with flunarizine(10 mg/day),the recovery of facial nerve function can be promoted, but the protective effect of flunarizine(5 mg/day) on peripheral nerve is not superior to that with normal treatment. The mechanism and the proper dosage are not observed further in this study.