The Correlation Between Decreased Ornithine Level and Alleviation of Rheumatoid Arthritis Patients Assessed by a Randomized,Placebo-Controlled,Double-Blind Clinical Trial of Sinomenine

Sinomenine(SIN)is commonly used as part of rheumatoid arthritis(RA)therapy in China,but there is still no published evidence of the efficacy of SIN monotherapy.This work investigates the efficacy and safety of SIN in treating RA patients and analyzes the correlation between ornithine level and the alleviation of disease activity in RA patients.In this 24 week,randomized,placebo-controlled,double-blind clinical trial,people with mild to moderate RA were randomly assigned(1:1:1,stratified by hospital)to receive SIN(120 mg,twice daily),methotrexate(MTX)(10 mg per week),or SIN+MTX therapy.The primary outcome was the proportion of patients who achieved a 50%improvement in the American College of Rheumatology(ACR50)criteria at week 24 and who showed improvement according to the clinical disease activity index(CDAI).In this prospective subgroup analysis,we also assessed whether the 24-week alterations of disease activity in the treatment group were significantly correlated to the levels of blood ornithine.Of the 135 enrolled participants,38,39,and 36 patients were treated with SIN,MTX,and SIN+MTX,respectively.In the SIN-treated group,52.63%of patients achieved ACR50 after 24-weeks of treatment,which was comparable to the results in the MTX-treated and SIN+MTX-treated groups.Hepatic and gastrointestinal disorders were the main adverse events;however,the ratio of patients suffering from hepatic disorder in the SIN group(1/38)was much lower than that in the MTX(10/39)and SIN+MTX(8/36)groups.A total of 221 serum samples were collected at the four follow-up time points in the three treatments,and the levels of ornithine,citrulline,and arginine were obtained through ultrahigh performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF/MS).The serum ornithine level decreased after the 24-week treatment along with a decrease in disease activity,and may reflect therapeutic responses with a sensitivity value of 80%.In conclusion,SIN revealed a comparable efficacy to MTX for treating RA patients,but with fewer side effects.In addition,the serum ornithine level was found for the first time to have a close correlation with the alleviation of RA,which shows the value of this measure as an assessment indicator of drugs in treating RA.

Proteome Analysis of Neisseria meningitidis Serogroup Strains C Associated with Outbreaks in China

Objective During 2003-2005, an outbreak of meningitis due to Neisseria meningitidis serogroup C occurred in China. With the aim to find strain clues result in the final epidemics, the ancestral strain 053442, a clinical isolate, and a carrier strain 053426 with different gene type were analyzed. Methods Clinical strain 053442 and carrier strain 053426 were cultured on GC agar plates under the same condition. Two-dimensional electrophoresis was performed using the pH 3–10 nonlinear IPG strips of 24 cm length, and all the protein spots were identified by matrix-assisted laser desorption/ionization time of flight spectrometry. Results 502 and 380 protein spots were identified in 053426 and 053442 respectively, relating to 266 and 202 different genes covering a wide range of cellular functions. The express volume and number of proteins involved in energy metabolism, protein synthesis and amino acid biosynthesis in 053426 were higher than in 053442. Virulence factor Opa, Opc and a series of proteins involved in pilus assembly and retraction were identified in 053442, which appear to be of primary importance in colonization and invasion of human cells. Compared to 053442, virulence protein species were less in 053426, with lower express volumes too. No Opa and Opc were detected in 053426. Conclusion The different protein expression profiles of the clinical strain 053442 and carrier strain 053426 in the present study provide some clues of the different pathogenicity of the two strains, which may account for result in the final epidemics.

Anti-cyclic citrullinated peptide antibody predicts the development of rheumatoid arthritis in patients with undifferentiated arthritis

Background:Clinical outcomes of undifferentiated arthritis(UA)are diverse,and only 40%of patients with UA develop rheumatoid arthritis(RA)after 3 years.Discovering predictive markers at disease onset for further intervention is critical.Therefore,our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.Methods:We performed a prospective,multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals.Clinical and serological parameters were obtained at recruitment.Follow-up was undertaken in all patients every 12 weeks for 2 years.Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.Results:A total of 234 patients were recruited in this study,and 17(7.3%)patients failed to follow up during the study.Among the 217 patients who completed the study,83(38.2%)patients went into remission.UA patients who developed RA had a higher rheumatoid factor(RF)-positivity(42.9%vs.16.8%,χ^2=8.228,P=0.008),anti-cyclic citrullinated peptide(CCP)antibodypositivity(66.7%vs.10.7%,χ^2=43.897,P<0.001),and double-positivity rate of RF and anti-CCP antibody(38.1%vs.4.1%,χ^2=32.131,P<0.001)than those who did not.Anti-CCP antibody but not RF was an independent predictor for RA development(hazard ratio 18.017,95%confidence interval:5.803–55.938;P<0.001).Conclusion:As an independent predictor of RA,anti-CCP antibody should be tested at disease onset in all patients with UA.