ObjectivesTo explore the pathogenesis of rheumatoid arthritis (RA), the different metabolites were screened in synovial fluid by metabolomics.MethodsSynovial fluid from 25 RA patients and 10 normal subjects were analyzed by GC/TOF MS analysis so as to give a broad overview of synovial fluid metabolites. The metabolic profiles of RA patients and normal subjects were compared using multivariate statistical analysis. Different proteins were verified by qPCR and western blot. Different metabolites were verified by colorimetric assay kit in 25 inactive RA patients, 25 active RA patients and 20 normal subjects. The influence of hypoxia-inducible factor (HIF)-1α pathway on catabolism was detected by HIF-1α knockdown.ResultsA subset of 58 metabolites was identified, in which the concentrations of 7 metabolites related to energy metabolism were significantly different as shown by importance in the projection (VIP) (VIP≥1) and Student’s t-test (p<0.05). In the 7 metabolites, the concentration of glucose was decreased, and the concentration of lactic acid was increased in the synovial fluid of RA patients than normal subjects verified by colorimetric assay Kit. Receiver operator characteristic (ROC) analysis shows that the concentration of glucose and lactic acid in synovial fluid could be used as dependable biomarkers for the diagnosis of active RA, provided an AUC of 0.906 and 0.922. Sensitivity and specificity, which were determined by cut-off points, reached 84% and 96% in sensitivity and 95% and 85% in specificity, respectively. The verification of different proteins identified in our previous proteomic study shows that the enzymes of anaerobic catabolism were up-regulated (PFKP and LDHA), and the enzymes of aerobic oxidation and fatty acid oxidation were down-regulated (CS, DLST, PGD, ACSL4, ACADVL and HADHA) in RA patients. The expression of HIF-1α and the enzymes of aerobic oxidation and fatty acid oxidation were decreased and the enzymes of anaerobic catabolism were increased in FLS cells after HIF-1α knockdown.ConclusionIt was found that enhanced anaerobic catabolism and reduced aerobic oxidation regulated by HIF pathway are newly recognized factors contributing to the progression of RA, and low glucose and high lactic acid concentration in synovial fluid may be the potential biomarker of RA.

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BackgroundThe clinical pathology of gastric signet-ring cell carcinoma (SRC) is still unclear. This meta-analysis was performed to evaluate the difference in biological behavior and prognosis between SRC and non-signet ring cell carcinoma (NSRC).MethodsA total of 58 eligible studies were analyzed using RevMan and other auxiliary software. Biological behaviors were compared based on odds ratio (OR) and mean difference (MD). Hazards ratio (HR) was calculated for prognosis based on Kaplan–Meier curves.ResultsTotally, 28,946 SRC patients were compared with 81,917 NSRC patients. Compared with NSRC patients, lower male: female ratio (OR = 0.53, P &lt; 0.01), younger age (MD = −4.89, P &lt; 0.01), more middle location (OR = 1.64, P &lt; 0.01), more depressed type at early stage (OR = 1.31, P &lt; 0.05), higher incidence of Borrmann type IV (OR = 1.96, P &lt; 0.01), less lymph node metastasis at early stage (OR = 0.78, P &lt; 0.05), better prognosis at early stage (HR = 0.59, P &lt; 0.01), and worse prognosis at advanced stage (HR = 1.19, P &lt; 0.01) were associated with SRC patients.ConclusionThe prognosis of SRC at early stage is better than other types of gastric cancer, while that of SRC at advanced stage is relatively poorer.

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