Objective To investigate the effect of combination low-dose of methotrexate (MTX) and cy-clophosphamide (CTX) intermittent therapy on the synovial cell p53 expression of collagen-indued arthritis Rats. The possible synergistic effect is examined and the possible meehaniams are evaluated. Methods Models of CIA were successfully established in 75 female Wistar rats. The CIA rats were then randomized into controls. At the end of this 24-week study the synovium of ankle joints were obtained, fixed, decalcified, wrapped and cut into slices. The intensity of p53 mutations expressions was examined by immunohistochemi-stry method. Results The intensity of p53 mutations expression of synoviocytes in CIA model group was significantly higher than that in the controls. In addition, the p53 mutations expressions in the synoviocytes of the treatment groups were decreased markedly, which did not return to the baseline level. The improvement of p53 mutations in the combination treatment group was higher than the single treatment groups and the difference was statistically significant (P<0.05). However, the difference between the combination treatment group and high-dose MTX treatment group was not significant. Conclusion Low-dose of MTX combined with CTX has the same efficacy comparing to high-dose of MTX in inhibiting p53 expression of CIA rats synoviocytes, but it is superior to low-dose single drug group. The results suggest that the combination of MTX and CTX may be synergistic in the treatment of RA.

Objective To explore effects and possible mechanisms of combination therapy with methotrexate (MTX) and low dose cyclophosphamide (CTX) intermittently on the cyclin D 1 expression in the synovium of collagen induced arthritis rats.The outcome is analyzed.Methods After CIA experimental models were successfully established in female Wistar rats,they were randomly divided into CIA model group,low-dose MTX treatment group (0.9 mg·kg-1·W-1),high-dose MTX treatment group (2.7 mg·kg-1·W-1),Jowdose CTX treatment group [24 mg·kg-1·(3W)-1],and" low-dose MTX + low-dose CTX treatment group (MTX 0.9 mg·kg-1·W-1,CTX [24 mg·kg-1·(3W)-1].All of the rats were sacrificed 24 weeks after the first immunization,the specimens of ankle joints were exposed,fixed,decalcified,wrapped and cut into slices.The Cyclin D1 mRNA levels were examined by situ hybridization.Results The mRNA level of cyelin D1 in CIA synovial lining layer was significantly higher than that of normal controls,which suggested that in situ proliferation of synoviocytes might contribute to the thickening of rheumatoid synovial lining layer.The synovial expression intensity of the mRNA level of cyclin D1 in the treatment groups was decreased evidently.The mRNA level of cyclin D1 of the combination treatment group was higher than other groups,which was statistically significant (P＜0.05).Conclusion This is the first research on the effects of MTX combined with CTX intermittently based on cell cycles in CIA animal model.Combination therapy seems to be more effective than single-agent therapy.The results suggest that combining cell cycle stage specific agent MTX with cell cycle stage nonspecific agent CTX may be synergistic in the treatment of RA.Inhibition of the increased expression of the synovial cyclin D1 mRNA maybe an important mechanism of the MTX and CTX combination treatment for RA.

Objective To evaluate the triage value of high-risk human papillomavirus (HR-HPV)detection in women with atypical squamous cells of undetermined significance (ASCUS).Methods Two huandred women with atypical squamous cells of undetermined significance (ASCUS) were selected by thinprep cell test(TCT) simultaneously using HPV DNA testing by hybrid capture Ⅱ (HC) and biopsy under the colposcopy,compared the HR-HPV DNA testing with final pathological diagnosis.CIN (cervical intraepithelial neoplasia) means cervical biopsy positive.Results The positive rate of cervical biopsy in HPV positive patients was 60.38％(96/159),and in HPV negative patients was 21.95％(9/41),the difference was obviously (P ＜ 0.05).Conclusion HR-HPV detection is a good triage approach for the patients with ASCUS.