1.Expression of chemokine CXCL16 in murine collagen-induced arthritis and the effects on the proliferation of lymphocytes
Lin SUN ; Xiangyuan LIU ; Jinxia ZHAO ; Siliang MAN ; Xia ZHANG
Chinese Journal of Rheumatology 2011;15(3):151-154
Objective To investigate the effect of CXCL16 on the development of murine collageninduced arthritis (CIA). Methods CXCL16 mRNA of the involved synovium and serum CXCL16 protein were determined respectively by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA) in murine collagen-induced arthritis. The proliferation of lymphocytes from murine spleen and the level of RANKL mRNA, stimulated by CXCL16 at different concentrations (0,100, 200, 400, 800 ng/ml), was detected respectively by CCK-8 and RT-PCR, then the level of IL-2 and IFN-γ in culture supernatant was detected by ELISA. Comparisons between groups were tested by t test and one-way ANOVA analysis. Results The serum CXCL16 [(127± 10) vs (72±8) pg/ml, P<0.05] and synovial CXCL16 mRNA (0.214±0.007 vs 0.375±0.009, P<0.01) in CIA were all significantly higher than those in normal controls. The proliferation of CXCL16 (200, 400, 800 ng/ml) in CIA mouse lymphocytes, was significantly higher than that of CXCL16 (0 ng/ml) (0.51±0.06, 0.56±0.05, 0.55±0.04, (0.41±0.04, P<0.05). And CXCL16 on the CIA stimulated lymphocyte proliferation was significantly higher than controls on normal lymphocytes (P<0.05). Compared with blank control group, the expression of IL-2, IFN-γ and RANKL mRNA of CIA CXCL16 (400, 800 ng/ml) groups was higher significantly (P<0.01). Conclusion CXCL16 plays an important role in the development of murine CIA by activating lymphocytes.
2.Detection and clinical significance of blood D-Dimer in rheumatoid arthritis
Jinxia ZHAO ; Lin SUN ; Xia ZHANG ; Xiangyuan LIU
Chinese Journal of Rheumatology 2011;15(3):168-171
Objective To detect D-Dimer in the blood of rheumatoid arthritis (RA) patients and to investigate its clinical significance in RA. Methods Blood samples were obtained from 58 patients with RA,18 patients with systemic lupus erythematosus (SLE), 15 patients with ankylosing spondylitis, 11 patients with osteoarthritis, and 20 patients with other connective tissue diseases. The presence of thrombotic diseases was excluded in all patients. The presence of D-Dimer in the blood was examined by immunoturbidimetry. The following clinical and laboratory data were collected: disease activity index DAS28, rheumatoid factor (RF),erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Mann-Whitney U test, t-test ,Spearman correlation were used for statistical analysis. Results ① The prevalence of high level D-Dimer in RA patients was higher than that of the control group (82.6% vs 21.9%, P<0.01). The titer of D-Dimer in RA was significantly higher than that of the control group [(1.76±1.57) vs (0.32±0.25) mg/L, P<0.01]. ②DAS28 was higher in RA patients with positive D-Dimer than those with negative D-Dimer (5.4±1.0 vs 4.4±0.8,P<0.01). The values of ESR, CRP and RF in RA patients with positive D-Dimer were significantly higher than those in patients with negative D-Dimer (P<0.05). ③ There was positive correlation between D-Dimer and DAS28 (r=0.406, P<0.05), ESR (r=0.355, P<0.01), and RF (r=0.319, P<0.05). Conclusion The level of D-Dimer in the blood of RA patients is significantly higher than other rheumatic diseases, and is positively correlated with disease activities. The results indicated that the activation of coagulation-fibrinolytic systems may play a role in the pathogenesis of rheumatoid arthritis.
3.Expression of CXCL16 /CXCR6 in fibroblast-like synoviocytes in rheumatoid arthritis and its role in synoviocyte proliferation
Xia ZHANG ; Jinxia ZHAO ; Lin SUN ; Xiangyuan LIU
Journal of Peking University(Health Sciences) 2017;49(4):663-668
Objective:It has been found that serum CXCL16 concentration in rheumatoid arthritis (RA) patients are significantly higher than those in osteoarthritis (OA) and normal subjects, and are positively correlated with disease activity and bone erosion.However, how is CXCL16 involved in the pathogenesis of RA is unclear.To evaluate the expression of CXCL16 and its receptor CXCR6 in fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) patients, and to explore the role of CXCL16 in the proliferation of RA-FLS.Methods: FLS were isolated from knee synovial tissues obtained from 8 patients of RA, 7 osteoarthritis (OA) and 3 normal controls.The diagnosis of RA was in line with the 1987 American Rheumatology Association (ACR) RA classification criteria, osteoarthritis met the 1996 ACR revised knee osteoarthritis classification criteria.Control synovium were obtained from trauma caused knee joint injury in healthy individuals who required surgery.Human knee FLS were cultured by tissue explants adherent method.FLS between passages 3 and 5 were used in the experiment.Expression of CXCL16 and its receptor CXCR6 were performed in Western blot analysis.FLS proliferation follo-wing stimulation with TNF-α and different concentrations of CXCL16 was examined by cell counting kit-8 (CCK-8).Expression of phosphorylated AKT (pAKT) in RA-FLS stimulated by CXCL16 was quantified by Western blot.Different concentrations of recombinant human CXCL16 were added to the culture medium of RA-FLS.After 48 h culture, supernantants were collected, and TNF-α, IL-6, RANKL and MMP3 in culture supernatants of RA-FLS were determined by enzyme-linked immunosorbent assays (ELISA) operated following the kit instructions.Results: Expression of CXCL16 and CXCR6 in RA-FLS was significantly higher than that of OA and controls (P<0.05), but no significant difference was found between OA-FLS and control FLS.Proliferation of RA-FLS was markedly up-regulated after stimulation of CXCL16 (P <0.05).In the case of the CXCL16 stimulated OA-FLS and control FLS, the FLS proliferation remained basically unchanged.Expression of phosphorylated AKT in RA-FLS increased remarkably in condition of CXCL16 (50,100, 200 μg/L) stimulation.The levels of IL-6 and RANKL in culture supernatants of RA-FLS were obviously increased under CXCL16 (200 μg/L) stimulation, while TNF-α and MMP-3 levels in the culture supernatants remained unchanged after CXCL16 (200 μg/L) stimulation.Conclusion: This study shows that the expression of CXCL16 and its receptor was highly elevated in RA-FLS.Recombinant CXCL16 promoted RA-FLS proliferation and activation in vitro.All these indicate that CXCL16 play an important role in the pathogenesis of RA, anti-CXCL16 treatment may help to relieve inflammation and bone damage of RA patients.However, due to the limitations of this study, the role of CXCL16 and its receptors in RA-FLS remains to be elucidated by further research.
4.Colquhounia root tablet inhibits the expression of adhesion molecule in acute lung injury of rats
Xigang MA ; Xiangyuan CAO ; Zhenxiang ZHANG ; Yongjian XU
Chinese Journal of Pathophysiology 2000;0(12):-
AIM:To study the effects of colquhounia root tablet on the expression of adhesion molecule in acute lung injury of rats. METHODS: The rats were divided into 3 groups: ALI group, colquhounia root tablet+ALI group and control group . ALI animal model was performed by treatment with oleic acid. The positive expression rates of CD11a, CD11b and CD18 in polymorphonuclear neutrophils and monocytes were analyzed by flow cytometry. ICAM-1 expression in lung tissue was determined by immunohistochemistry, histopathological examination and biological markers were measured from lung specimens.RESULTS: Colquhounia root tablet decreased the expression of CD11a, CD11b and CD18 in polymorphonuclear neutrophils and monocytes, and ICAM-1 in lung tissue (P
5.The investigation and multivariable statistical analysis of hyperuricemia in 1500 elderly people
Xiangyuan LIU ; Yulan XIAO ; Suqin REN ; Lijun TANG ; Liyun ZHANG
Chinese Journal of Rheumatology 2001;0(05):-
Objective To explore the prevalence and clinical features of hyperuricemia in elderly people and to analyze the influencing factors of hyperuricemia in elderly people. Methods Serum uric acid (SUA) levels in 1500 elderly people were examined by the uricase-peroxidase enzymatic method .Clinical parameters of hyperuricemia group and normal SUA group were comparatively analyzed. Logistic regression was used to analyze the influencing factors of SUA in elderly people. Results In 264 out of 1500 (17.6%) the SUA level were increased. The ratio of male to female in the hyperuricemia group was 256:8. The proportion of the patients with increased SUA levels, mean level of SUA, serum urea nitrogen, serum creatinine and serum triglyceride were all increased with age. As compared with the normal SUA group, the hyperuricemia group were more prone to have adiposis hepatica (P
6.Significance of antibodies of IgG, IgA and IgM isotypes against peptidylarginine deiminase 4 in early rheumatoid arthritis
Jinxia ZHAO ; Yingjian ZHANG ; Lin SUN ; Changhong LI ; Xiangyuan LIU
Chinese Journal of Rheumatology 2014;18(11):734-737
Objective To evaluate the prevalence and clinical significance of IgG,IgA and IgM isotypes of anti-peptidylarginine deiminase 4 (anti-PAD4) antibodies in early rheumatoid arthritis (RA).Methods IgG,IgA and IgM isotypes of anti-PAD4 antibodies were measured in the sera of 88 RA patients with disease duration less than 2 years,62 patients with other rheumatic diseases and 57 healthy subjects.The diagnostic performance of IgG,IgA and IgM isotypes of anti-PAD4 antibodies and their relationship with disease duration,DAS28,ESR,CRP,anti-CCP antibodies and rheumatoid factor (RF) were evaluated.Data analysis were performed using t test,U test and Spearman's association analysis.Results ① The sensitivities of IgG,IgA,and IgM isotypes for early RA were 28.41%,36.36% and 9.09% respectively.The specificities of IgG,IgA and IgM isotypes were 94.12%,93.28% and 95.80% respectively.② IgA isotype was positively correlated with age (r=0.234,P=0.028),DAS28 (r=0.309,P=0.007),ESR (r=0.382,P=0.000) and CRP (r=0.291,P=0.008),while negatively correlated with disease duration (r=-0.295,P=0.006).③ IgA isotype was positively correlated with IgG isotype (r=0.451,P<0.01).In the IgG negative patients,the positivity of IgA isotype was 29%(18/63),which indicated that the IgA isotype might be helpful in diagnosing RA in IgG isotype negative patients.Conclusion Anti-PAD4 antibodies can be detected in early RA,primarily with IgA and IgG isotypes.IgA isotype has negative correlation with disease duration,indicating that IgA isotype of anti-PAD4 antibody may play a role in the very early stage RA.
7.Detection of BRAF in the synovial fluid and its clinical significance in rheumatoid arthritis
Jinxia ZHAO ; Lin SUN ; Yingjian ZHANG ; Xia ZHANG ; Ru LI ; Xiangyuan LIU
Chinese Journal of Rheumatology 2013;(7):446-449
Objective To detect v raf murine sarcoma viral oncogene homologue B1 (BRAF) in the synovial fluid of rheumatoid arthritis (RA) and to investigate its clinical significance in RA.Methods Synovial fluid samples were obtained from patients with RA and osteoarthritis (OA).Serum samples were obtained from patients with RA,OA and heathy controls.The presence of BRAF in the synovial fluid and sera were examined by enzyme-linked immunosorbent assay (ELISA).Western blotting was used to detect the expression of BRAF protein in the synovial tissue of RA and OA.The associations between the BRAF and the clinical features and laboratory parameters of RA were evaluated.Data analysis were performed using t test and Spearman's association analysis.Results ① The level of BRAF in the synovial fluid of RA [(84±59) ng/ml] was significantly higher than OA [(38±41) ng/ml] (t=3.290,P=0.002).② The level of BRAF in the sera of RA patients [(22.0±12.5) ng/ml] was also higher than OA [(6.8±7.5) ng/ml,t=3.882,P<0.01] and healthy controls [(4.8±2.2) ng/ml,t=6.766,P<0.01].③ In RA patients,the BRAF protein level in the synovial fluid [(102±52) ng/ml] was significantly higher than that in the serum [(21±12) ng/ml] (t=-4.316,P=0.003).④The expression level of BRAF in the synovial tissue of RA (0.284±0.045) was higher than that in OA patients (0.191±0.013,t=3.169,P=0.034).⑤ The level of BRAF in the synovial fluid had a negative correlation with disease duration (r=-0.40,P=0.019) and a positive correlation with rheumatoid factor (RF) levels (r=0.37,P=0.03).Conclusion The presence of BRAF in the synovial fluid and synovium of RA indicates that BRAF may play a role in the pathogenesis of RA,especially in the early stage.
8.Significance of antibodies of IgG, IgA and IgM subtypes antibodies against cyclic citrullinated peptide in early rheumatoid arthritis
Yingjian ZHANG ; Jinxia ZHAO ; Lin SUN ; Changhong LI ; Guiye LI ; Xiangyuan LIU ; Zhanguo LI
Chinese Journal of Rheumatology 2013;(1):5-9
Objective To evaluate the prevalence and clinical values of anti-cyclic citrullinated peptide (anti-CCP) antibodies of IgG,IgA and IgM subtypes in individuals with early rheumatoid arthritis (RA).Methods IgG,IgA and IgM subtypes of anti-CCP antibodies were measured in the sera of 87 RA patients with disease duration shorter than 2 years,61 patients with other rheumatic diseases and 49 healthy subjects.We analyzed the diagnostic value of IgG,IgA and IgM subtypes of anti-CCP antibodies and their relationship with disease duration,DAS28,ESR,CRP,and rheumatoid factor (RF).Chi-square test,t test and Spearman's correlation analysis were used for statistical analysis.Results ① The diagnostic sensitivity of IgG,and IgA subtype for early RA was 75.9% and 67.8% respectively,which was higher than IgM subtype (14%,P<0.01 each).The specificity of IgG,IgA and IgM subtype was 96.4%,91.8% and 93.6% respectively.② IgG and IgA subtypes were correlated with CRP (r=0.278,P=0.01; r=0.217,P=0.047) and RF (r=0.430,P=0.000; r=0.271,P=0.012),while IgM subtype was positively correlated with disease duration (r=0.279,P=0.014).③ Patients who had IgG-and IgA subtype had a shorter disease course (3.3±2.3) than those patients who had IgA-and IgG+ (9.5±8.4) and who had IgG+ and IgA+ (8.2±7.0) (P<0.05).④ IgA subtype was positive in 19.0% of the IgG negative patients.When combining IgG,and antibodies of IgA subtypes together,the sensitivity and specificity was 63.2% and 100%,while the sensitivity and specificity was 80.5% and 85.2% when either one was positive.Conclusion Both the IgG,and IgA subtypes of anti-CCP antibodies have a good sensitivity for early RA.They are related to disease activity.Measuring IgA subtype of anti-CCP antibody in RA patients with negative IgG subtype may help to identify early RA.IgA subtype of anti-CCP antibody may play a role in very early RA.
9.Clinical and radiographic analysis of patients with cervical subluxations in rheumatoid arthritis
Lin SUN ; Biying ZHANG ; Rui LIU ; Jinxia ZHAO ; Xiaoli DENG ; Xiangyuan LIU
Chinese Journal of Rheumatology 2015;19(11):745-749
Objective To investigate the clinical and radiographic features of rheumatoid arthritis (RA) patients with cervical subluxations.Methods The clinical, laboratory and imaging data of 68 RA patients who were hospitalized to our hospital because of cervical syndrome were retrospectively reviewed.The patients were divided into two groups depend based on whether cervical spine subluxations presented or not.Mann-Whitney U test, t test and Person correlation, x2 test were used for statistical analysis.Results This study confirmed the high frequency (11.6%, 39/335) of radiological cervical subluxations in RA patients.The nNeck pain was a common symptom, accounting for 87% (34/39).Other symptoms included limb numbness 59% (23/39).The rate of positive C-reactive protein (CRP) in the subluxation group was both significantly higher than that of the non-subluxation group [89%(24/27) vs 59%(16/27),x2=6.17, P<0.01].Anterior atlantoaxial subluxation (AAS) was the most common form, accounting for 95%(37/39) of all cervical subluxations,followed by vertical subluxation (VS), accounting for 18% (7/39).Subaxial subluxation (SAS) of the lower cervical vertebrae was less common (5.1%).The ratio of bone destruction, spinal stenosis, spinal cord compression in image findings of the subluxation group was significantly higher than that of the non-subluxation group (x2=7.96, x2=6.12, x2=4.89, P<0.05).But more hyperostosis and osteosclerosis feature of the non-subluxation group could be observed more hyperostosis and osteosclerosis feature (x2=6.21, P<0.05).PADI correlated with ADI (r=-0.588, P=0.015).Conclusion This study confirms the high frequency of radiological cervical involvement in patients with RA.AAS is the most common form of cervical involvement and may occur either independently or concomitantly with cranial settling and subaxial subluxation.
10.Meta-analysis of insertion/deletion genetic variation of ACE gene and onset riskof type 2 diabetic nephropathy in Chinese population
Chunhua BEI ; Ying ZHANG ; Linyuan QIN ; Lin YANG ; Jieying DUAN ; Nian LIU ; Hongping YU ; Xiangyuan YU
Chongqing Medicine 2017;46(24):3362-3365
Objective To systematically assess the relation between angiotensin-I converting enzyme(ACE) gene insertion/deletion (I/D) variation and type 2 diabetic nephropathy (T2DN) onset risk among Chinese population.Methods The related literatures were retrieved from the China National Knowledge Infrastructure (CNKI) and Wanfang Data until June 1st,2016.The RevMan 5.0 was used to conduct the statistical analysis.The merge OR value and corresponding 95% confidence interval(95%CI) were used to assess ACE gene I/D polymorphism and T2DN onset risk.Results Totally 29 papers with 4 357 subjects were included according to the inclusion and exclusion standard,including 2 208 cases of DN and 2 149 cases of T2DM without DN.Meta analysis showed that compared with ACE gene I/D polymorphism I allele,D allele could significantly increase the risk of T2DM patients suffering from DN,the OR value and corresponding 95%CI were 1.44(1.25,1.66);the gene analysis showed that ACE gene I/D polymorphism loci were significantly correlated with DN onset risk in the Asian population.The corresponding relative onset risk OR and 95%CI were 1.42(1.15,1.76) and 1.75(1.46,2.10) in the dominant and recessive genetic model.The Begg′s test showed that the included data had no obvious publication bias existence.Conclusion ACE gene I/D polymorphism is closely correlated with the onset risk of T2DN,and D allele might be a risk genetic factor for DN occurrence in the patients with T2DM.