To explore the inhibitory effect of ginkgolide B (GB) on MH7A human fibroblast-like synoviocytes (FLS) and its potential mechanism. Firstly, 20 μg/L tumor necrosis factor-α (TNF-α) was pretreated with MH7A to establish a cell model of arthritis. After incubation of MH7A cells with various concentrations of GB, CCK-8 assay, Transwell assay, and flow cytometry (FCM) were separately used to detect cell viability, cell invasion, and cell apoptosis rate and cell cycle; Real-time quantitative PCR and Western blot assay were performed to detect the apoptosis- and cycle-related gene transcriptions and protein expressions, respectively. The results showed that compared with the control group, GB dose- and time-dependently suppressed cell viability to a greater extent; GB significantly reduced cell invasive ability and increased cell apoptosis rate and proportion of G0/G1 phase in MH7A cells, along with increased transcription levels of Bcl-2-associated X protein (Bax) and p21 mRNA and decreased transcription levels of Bcl-2, myeloid cell leukemia 1(Mcl-1), protein kinase B (PKB; AKT), IP3K, Cyclin D1 and cyclin-dependent kinase 4 (CDK4) mRNA; GB remarkably increased expression levels of Bax, p21, and cleaved-Caspase 3 protein and decreased expression levels of Bcl-2, Mcl-1, p-AKT, p-PI3K, Cyclin D1, and CDK4 protein, with decreased ratios of p-PI3K/PI3K, p-AKT/AKT, and Bcl-2/Bax. In conclusion, GB blocks the G1-to-S cell cycle transition, suppresses cell viability and cell invasion and induces cell apoptosis of MH7A human RA-FLS via suppressing the PI3K/AKT signaling pathway.

OBJECTIVE To explore the synergistic effect of clorgiline and voriconazole on inhibition of bacteria and formation of biofilms in vitro so as to provide experiment bases for clinical treatment of drug-resistant Candida albicans infection.METHODS Minimum inhibitory concentrations(MICs)of voriconazole and clorgiline against two strains of C.albicans were explored by broth microdilution method.The synergistic effect of the two drugs on inhibition of bacteria were evaluated by chessboard method,and the fractional inhibitory concentration index(FICI)was calculated.The potential mechanisms of clorgiline for synergistically boost the effect of voriconazole were studied by rhodamine 6G(R6G)efflux pump test;the effects of the single and combined use of the two drugs on inhibition of the biofilms were explored by crystal violet staining method.RESULTS The MICs of the sin-gle voriconazole against the 2 strains of C.albicans were 0.25 μg/ml and 8 μg/ml,respectively;the MICs were decreased to 0.0625 μg/ml and 0.5 μg/ml,respectively,after its combination with clorgiline.The FICIs of the combined use of the two drugs against the two strains were both less than 0.5,showing synergistic antibacterial effect.The result of R6G efflux pump experiment indicated that clorgiline inhibited the efflux of R6G within 2 hours.The biofilm formation experiment showed that the single use of voriconazole or clorgiline had limited effect on inhibition of biofilm formation,and the combined use of the two drugs could inhibit the biofilm formation.CONCLUSIONS Clorgiline can enhance the antibacterial activity of voriconazole by inhibiting the efflux pump func-tion of the C.albicans strains.The two drugs show remarkable synergistic effect on inhibition of the biofilm for-mation,which may provide novel strategies for combined use of drugs and theoretical bases for treatment of the drug-resistant C.albicans infection.

OBJECTIVE To explore the synergistic effect of clorgiline and voriconazole on inhibition of bacteria and formation of biofilms in vitro so as to provide experiment bases for clinical treatment of drug-resistant Candida albicans infection.METHODS Minimum inhibitory concentrations(MICs)of voriconazole and clorgiline against two strains of C.albicans were explored by broth microdilution method.The synergistic effect of the two drugs on inhibition of bacteria were evaluated by chessboard method,and the fractional inhibitory concentration index(FICI)was calculated.The potential mechanisms of clorgiline for synergistically boost the effect of voriconazole were studied by rhodamine 6G(R6G)efflux pump test;the effects of the single and combined use of the two drugs on inhibition of the biofilms were explored by crystal violet staining method.RESULTS The MICs of the sin-gle voriconazole against the 2 strains of C.albicans were 0.25 μg/ml and 8 μg/ml,respectively;the MICs were decreased to 0.0625 μg/ml and 0.5 μg/ml,respectively,after its combination with clorgiline.The FICIs of the combined use of the two drugs against the two strains were both less than 0.5,showing synergistic antibacterial effect.The result of R6G efflux pump experiment indicated that clorgiline inhibited the efflux of R6G within 2 hours.The biofilm formation experiment showed that the single use of voriconazole or clorgiline had limited effect on inhibition of biofilm formation,and the combined use of the two drugs could inhibit the biofilm formation.CONCLUSIONS Clorgiline can enhance the antibacterial activity of voriconazole by inhibiting the efflux pump func-tion of the C.albicans strains.The two drugs show remarkable synergistic effect on inhibition of the biofilm for-mation,which may provide novel strategies for combined use of drugs and theoretical bases for treatment of the drug-resistant C.albicans infection.

Objective:To determine the value of lung function, cannula diameter and swallowing function in predicting the success of tube blocking in patients with severe neurological diseases so as to standardize the tracheal decannulation procedure.Methods:The tracheotomy tube blocking of 28 neurological disease patients was studied retrospectively. Before their tracheotomy tubes were blocked the patients′ lung function and swallowing function had been evaluated, and sputum volume and endotracheal tube diameter had been recorded.Results:The five most useful predictors of success in tracheotomy tube blocking were FVC, FVC%, FEV1 (L), FEV1 (L), FEV1 (L) and PEF(L/S). Their OR values were all greater than 1, indicating good predictive power. FEV1 and PEF showed the best predictive power, with OR values of 81.70 and 27.77, respectively. There was no significant difference between the two groups in terms of the other indicators. FEV1 predicted that the best truncation value for tracheotomy tube blocking success is 0.42L, achieving a sensitivity was 100% a specificity of 63.64%, and a correction index of 0.636.Conclusion:FEV1 values can be a useful predictor of successful tracheotomy tube blocking. Using it should improve the success rate of tube decannulation.