ABSTRACT
Objective:To investigate the changes of intestinal mucosal barrier function related indexes [diamine oxidase and secretory immunoglobulin A (sIgA)] in peripheral blood of patients with rheumatoid arthritis (RA) and their correlation with peripheral immune function.Methods:A total of 40 patients with RA who admitted to the Rheumatology and Immunology department of the Second Hospital of the Shanxi Medical University were enrolled. We collected their clinical and laboratory data, and selected 20 age and gender matched people as the control group. Enzyme-linked immunosorbnent assay (ELISA) was used to detect the level of DAO and sIgA in the peripheral blood, the lymphocytes and CD4 + T subsets were detected by flow cytometry. Then t-test, rank sum test and correlation analysis were conducted for statistical analysis. Results:① The level of DAO in patients with RA was higher than that of healthy controls [205(164, 251) ng/ml vs 364 (276, 483) ng/ml, Z=-4.48, P<0.001], while the level of sIgA was decreased [3.64 (2.76, 4.83)×10 5 ng/ml vs 6.83 (4.80, 9.44)×10 5, Z=-3.84, P<0.001]. ② The absolute number of B and CD4 + T cells were increased in RA, the difference were statistically significant, but the absolute number of T, natural killer cells (NK) and CD8 + T cells were not significantly different between the two groups. For CD4 + T subsets, the absolute number of T helper cells (Th)1 and Treg cells in RA group were significantly decreased than healthy controls, but there were no statistical significant difference in the number of Th2 and Th17 cells. ③ The level of DAO was positively correlated with absolute number of Th17 cells in patients with RA ( r=0.36 P=0.038), and positively correlated with age and white blood cell count ( r=0.40, P=0.021; r=0.40, P=0.020), but no significant correlation among other indicators were found. ④ The serum sIgA level of RA patients in antimutated citrullinated vimentin antibody (MCV), antiperinuclear factor (APF) and antikeratin antibody (AKA) positive group were higher than those in the negative group [3.99(2.99, 5.58)×10 5 ng/ml vs 2.73(2.29, 3.05)×10 5 ng/ml, Z=-2.55, P=0.011; 5.49 (3.26, 5.70)×10 5 ng/ml vs 3.12 (2.29, 4.04)×10 5 ng/ml, Z=-2.28, P=0.023; 4.07 (3.19, 5.65)×10 5 ng/ml vs 2.88 (2.24, 3.86)×10 5 ng/ml, Z=-2.42, P=0.016], while there was no significant difference in DAO level between groups. ⑤ The DAO level of RA patients with pulmonary interstitial fibrosis was significantly higher than that in the group without pulmonary interstitial fibrosis [421 (216, 528) ng/ml vs 191 (150, 223) ng/ml, Z=-2.81, P=0.005], while there were no significant differences in DAO and sIgA levels among other groups. Conclusion:In RA patients with inte-stinal mucosal barrier impairment, the DAO level is increased, while the sIgA is decreased, and in addition, elevated peripheral blood Th17 may be involved in the process of intestinal mucosal barrier impairment.
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Objective We investigated the correlation between inflammatory cytokines and drugresi-stant proteins. Methods Fourteen DBA1 mice were successfully induced by collagen and Freund's adjuvant. According to the scores of synovial pathology, the collagen-induced arthritis (CIA) group was divided into mild, moderate-severe groups, another four mice were selected as controls. The mRNA expressions of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), multidrug resistance protein 1 (MRP1) in splenic lymphocyte cells were measured by reverse transcription-polymerase chain reaction (RT-PCR). The concentrations of inter-leukin (IL)-1β, IL-2, IL-6, IL-10, umor necrosis factor (TNF)-α, IL-17 in serum were detected by Cytometric Bead Array (CBA). The correlation between different inflammatory cytokines and these proteins were analyzed, then one of the proteins which were most related with cytokines by immunohisto-chemical (IHC) in the synovium was studied. Data were analyzed by the Mann-Whitney U test, Kruskal-Wallis H test and spearman analysis. Results ①Compared with normal controls, the levels of IL-6 and TNF-α in the serum of mild CIA group, moderate-severe CIA group were significantly increased {IL-6 controls: [7.75 (5.14, 9.17) pg/ml];mild CIA: [25.31 (15.15, 29.27) pg/ml]; modeate-severe CIA: [45.03 (38.87, 64.02) pg/ml]. TNF-α: controls: [22.81 (20.84, 28.17) pg/ml]; mild CIA: [45.00(32.76, 58.51) pg/ml]; modeate-severe CIA: [45.00(39.78, 8.95) pg/ml]}(Z=14.383, P<0.05; Z=8.375, P<0.05). Compared with the mild CIA group, the level of IL-6 in serum was significantly increased in the moderate-to-severe CIA group (P<0.05), but there was no signigicant difference in the TNF-α level (P>0.05). ② In the spleen lymphocytes, there was no significant difference in the mRNA expression level of P-gp and BCRP among the groups, but the mRNA expression level of MRP1 was significantly increased (Z=12.634, P<0.05). Compared with the mild CIA group, the MRP1 mRNA in the moderate-severe CIA group was higher, the difference was significant (Z=12.634, P<0.05). There was a correlation between mRNA expression of MRP1 and P-gp (r=0.635, P=0.015). ③ The mRNA expression of MRP1 was positively correlated with IL-6 level (r=0.711, P=0.004). ④ The expression of MRP1 in normal group, low-level IL-6 group and high- IL-6 level group were as follows: [1.08 (0.65, 1.30)], [1.32 (1.08, 1.49)], [2.07 (1.77, 2.22)] respectively.⑤Compared with the controls, the cytoplasm/membrane of the knee and ankle joint synovial tissue in the CIA group was yellowish-brown, which indicated that MRP1 expression was positive. Conclusion In the CIA arthritis model, synovial tissue lesion is not only related to inflammatory cytokines, but also related to MRP1 expression in the ATP-binding cassette (ABC) transport protein family, and it is proved that IL-6 is highly correlated to MRP1.
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Objective To investigate the correspond of microsatellite instability (MSI) on the prognosis and the effect of chemotherapy for colorectal cancer.Methods The publications about the MSI of colorectal cancer from January 2011 to October 2012 were searched.The Web of Knowledge and MEDLINE (PubMed) databases were used for searching English articles.The CNKI and WanFang databases were used for searching Chinese articles.Statistical analysis and graphics were performed with Comprehensive Meta Analysis V2 software.Results Thirty papers were included in this study.For the prognostic Meta-analysis,MSI-H was a protective factor for the overall survival of patients (OR =0.634,0.558-0.720; P ＜ 0.001).Simultaneously,MSI-H was a protective factor for the disease-free survival of patients (OR =0.571,0.479-0.681; P ＜ 0.001).After using of 5-Fu,the survival rate of MSS/MSI-L patients could be significantly elevated (OR =0.515,0.433-0.611; P ＜ 0.001).However,the survival rate of MSI-H patients did not increase significantly (0.631,0.302-1.318; P =0.220).Conclusions Both the overall survival and disease-free survival of MSI-H patients were significantly better than that of MSS/MSI-L patients.For MSS/MSI-L patients,the chemotherapy effect was remarkable.However,for MSI-H patients,there was no statistics difference between chemotherapy and no-chemotherapy group.