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Expression and clinical significance of matrix metailoproteinase-13 and insulin-like growth factor-1 in the synovial lesion of Kashin-Beck disease

Guohua CHEN ; Genyuan CHEN

Chinese Journal of Rheumatology.2010;14(10):690-693. doi:10.3760/cma.j.issn.1007-7480.2010.10.009

Objective To discuss the matrix metalloproteinase ( MMP- 13 ) and insulin-like growth factor (IGF)-1 in knee osteoarthritis (OA) and Kashin-Beck disease (KBD) and to explore the mechanism of synovial lesions and their similarities and differences are compared. Methods Synovial fluid of 18 OA patients, 13 KBD patients, 6 normal controls were collected and their synovium were obtained at the same time.The synovium MMP-13 and IGF-1 were examined by immunohistochemistry, while those of the synovial fluid were tested by enzyme-linked immunosorbent assay (ELISA). One way ANOVA and LSD-t test were used for statistical analysis. Results The results of these 37 synovial tissue and synovial fluid samples showed that: ① The average optical density of the positive staining of the KBD synovial tissue (692±131,354±101, 415±62) was not statistically significant from that of the OA group (452±57, 366±65, 652±86)(P＞0.05) and the control group (541±98, 524±202, 379±94, P＜0.05). ②There was significant different between the expression of IGF-1 of synovial tissue in the KBD group (311±174, 235±95, 412±109) and the OA group (452±57, 652±75, 544±64) as well as the control group (251±29, 336±54, 388±76)(P＜0.05).③ Compared with the concentration of MMP-13 in the synovial fluid of the OA group (0.93±0.51), there was no significant difference between the OA and the KBD group (2.02±1.12) (P＞0.05); but, there was significant differences when compared with the control group (2.33 ±0.29, P＜0.05). ④ When compared the the concentration of IGF-1 in the synovial fluid in the KBD group [ (2.87±1.48) and the OA group (1.27±0.33)as well as that of the eontrol group (0.93±1.07)] the difference was significant. Conclusions ① Cartilagedegeneration and joint damage may be a part of the articular synovial lesions in KBD patients, just like that of the OA, and the may exist as a part of the pathogenesis. ② MMP-13 may be involved in the synovial damage,and is the major degenerating factors in cartilage extracellular matrix (ECM) in OA patients and KBD patients. ③ As one of the ECM synthesis factors, IGF-1 may play an important role in the synovial damage of OA and KBD disease, but the repair mechanism may be different between the two diseases.

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Expression of NLRP3 inflammasome mRNA in peripheral blood monocytes of patients with gouty arthritis

Qibin YANG ; Jingguo ZHOU ; Yufeng QING ; Wenguang XIE ; Mingcai ZHAO ; Min LI

Chinese Journal of Rheumatology.2010;14(10):686-689. doi:10.3760/cma.j.issn.1007-7480.2010.10.008

Objective To study the expression level of NLRP3 (NLR family, pyrin domain containing3) inflammasome (NLRP3, ASC, caspase-1 ) mRNA in peripheral blood monocytes (PBMCs) from patients with gout arthritis (GA) and to explore the pathogenesis of GA. Methods NLRP3 inflammasome mRNA was measured using quantitative real-time PCR in PBMCs. The expression of NLRP3 inflammasome mRNA in PBMCs was compared between patients with GA (n=24) and healthy controls (n=24). β-actin was selected as the internal control. Students' t-test was used in two independent samples and Spearman's correlation was used to evaluate the relationship between mRNA level and inflammatory parameters. Results The expression of ASC mRNA in GA increased significantly when compared to healthy controls [(0.029±0.021 ) vs (0.009±0.007 ), P＜0.01 ], and the expression of NLRP3 and caspase-1 mRNA was significantly lower in patients with GA compared to healthy controls [(0.062±0.084) vs (0.133±0.106), P＜0.05; (0.025±0.014) vs (0.117±0.156), P＜0.01]. Moreover, the expression of ASC mRNA was found to correlate significantly with globulin (r=-0.547, P＜0.05) and very low density lipoprotein cholesterol (r=-0.540, P＜0.05) in GA patients,and caspase-1 was correlated to globulin(r= -0.773. P＜0.01) and very low density lipoprotein cholesterol (r=-0.465. P＜0.05). Furthermore, the ASC mRNA in GA patients was associated significantly with NLRP3 mRNA(r=-0.450, P＜0.05) and caspase-1 (r=0.604, P＜0.01 ). Conclusion Dysregulated expression of the NLRP3inflammasome is involved in the inflammatory response and plays a key role in the pathogenesis of GA.

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Clinical analysis of 100 patients with Wegener's granulomatosis

Guohua ZHANG ; Qingjun WU ; Limin ZHANG ; Xiaofeng ZENG

Chinese Journal of Rheumatology.2010;14(10):677-681. doi:10.3760/cma.j.issn.1007-7480.2010.10.006

Objective To investigate the clinical features of 100 cases with Wegener's granulomatosis (WG). Methods One hundred patients with WG admitted to our center in recent 11 years were retrospectively analyzed. Results The ratio of male to female was 1.04:1. The average age was (39±17) years (ranging from 4 to 72 years). The upper respiratory tract (86%), lung (82%), kidney (70%) and ocular (53%) were the major affected organs, followed by neurological system ( 12% ) and cardiovascular system ( 11% ). cANCA was positive in 77% of patients, while ANCA was negative in 8%. Images mostly showed multiple nodules/mass with/without cavity in lung (59%) and sinusitis (57%). The pathologic features were necrotic granulomatosis and/or microvasculitis,which was 78% in nasal mucosa/mass biopsy and 75% in lung.Focal segmental necrotic glomerulonephritis ( 59% ) was an important feature for confirming the diagnosis. Of the WG groups, 49% of patients were in generalized subgroup followed by localized (22%), early systemic ( 15% ), severe renal (9%) and refractory group (5%). The patients were treated with corticosteroid and cyclophosphamide. The remission rate in the induction phase was 78%, while the mortality rate was 4%. The follow-up duration ranged from 1 to 145 months. Complications included infection (22%), chronic renal failure( 12% ), deep venous thrombosis( 11% ). Five patients died(8% ), in which 2 patients died of infection.Conclusion The clinical manifestations of Wegener's granulomatosis are complicate. ANCA testing, images of sinus and lung and histological biopsy have played important roles in early diagnosis, which is significant to initiate appropriate and prompt treatment in order to reduce complications and improve prognosis.

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Expression and clinical significance of interleukin-17 and Th17 cells in the peripheral blood of patients with systemic lupus erythematosus

Xue XU ; Yu XUE ; Lin LV

Chinese Journal of Rheumatology.2010;14(10):672-676. doi:10.3760/cma.j.issn.1007-7480.2010.10.005

Objective To determine the protein and mRNA levels ofinterleukin-17 (IL-17) and the proportion of Th17 cells in the peripheral blood of patients with systemic lupus erythematosus (SLE) and their clinical significance is analyzed. Methods Twenty-five hospitalized SLE patients were recruited and twentytwo healthy volunteers were enrolled as normal controls. Plasma protein and mRNA of IL-17 in the peripheral blood were measured by enzyme-linked immunosorbent assay and real time-PCR respectively. Flow cytometric assay was used to analyze the percentage of Th17 cells in SLE patients. The relationship between IL-17/Th17 cells and clinical or laboratory parameters of SLE patients was explored. Students' t-test and Spearman's correlation was used to evaluate the relationship between mRNA level and inflammatory parameters. Results The plasma concentration and mRNA level of IL-17 was significantly elevated in SLE patients as compared to the normal controls (P＜0.05). The percentage of Th17 cells in patients with SLE was higher than that of normal controls and was significantly increased in more active SLE patients and SLE with nephritis than less active SLE and SLE without nephritis (P＜0.05). Both plasma levels of IL-17 and the proportion of Th17 cells were positively correlated with SLEDAI (r=0.681, P＜0.01; r=0.426, P=0.034). Conclusion Plasma IL-17 protein and mRNA expression level and the percentage of Th17 cells in SLE patients are all significantly elevated and the close relationship between IL-17/Th17 cells and disease activity suggests that IL-17/Th17 may play an important role in the pathogenesis of SLE.

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A survey and analysis of quality of life and its affecting factors of elderly patients with rheumatoid arthritis

Ping LI

Chinese Journal of Rheumatology.2010;14(10):694-697. doi:10.3760/cma.j.issn.1007-7480.2010.10.010

Objective To explore an effective way to improve the quality of life of elderly rheumatoid arthritis (RA) patients by a survey about their present living conditions and analyze the effect of some related factors. Methods This was a descriptive study and convenient sampling survey were adopted. Seventyfive elder patients with RA were investigated with self-developed questionnaire, self-mana-gement scale,family function questionnaire, DAS28, 36 question scale health survey questionnaire (SF-36). The demographic data, elderly RA related knowledge and attitudes, self-management, family function and quality of life were also investigated. Univariate analysis was used to analyze the relationship between the quality of life of elderly RA and the affecting factors. Results The score of SF-36 was (66±12). The SF-36 scores was associated with joint function (r=0.705, P＜0.01 ), and DAS28 (r=-0.712, P＜0.01 ). The SF-36 score was positively associated with the understanding of the deterioration of symptoms, the attitude of patients towards their diseases, satisfactory to the help from their families, the access to medical care and the degree of selfmanagement (r=0.515, 0.485, 0.540, 0.575, 0.545, P＜0.01); while it was negatively associated with the duration of disease course (r=-0.312, P＜0.01 ). In addition, this study also discovered that the quality of life declined with the decline of their economic status, but tended to improve with the increase of education level.Conclusion The life quality of elderly RA patients is not ideal. It is associated with DAS 28 score, the duration of disease course, the understanding of their diseases, the attitude towards their disease, selfmanagement, family support and other facotrs

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The immunomodulatory effect of allogenic mesenchymal stem cell transplantation on rats with collagen induced arthritis

Fang LI ; Xiaofeng LI ; Jieting JIA ; Liyun ZHANG ; Lihui MA ; Ke XU

Chinese Journal of Rheumatology.2010;14(10):682-685. doi:10.3760/cma.j.issn.1007-7480.2010.10.007

Objective To observe the immunologic effect of transplantation of MSCs by studying the early and later period of collagen induced arthritis. Methods Rats MSCs were isolated and expanded from bone marrow cells by density gradient centrifugation and adhering to the culture plastic bottle, and the phenotypes were assessed by flow cytometry. We established collagen induced arthritis rats model. MSCs wereinjected from tail veins. We observed the expression of Foxp3 mRNA using RT-PCR, and the level of CD4+CD25+ T cell was tested by flow cytometry. One-way ANOVA and LSD-t test were used for statistical analysis.Results The percentage of CD4+ CD25+ T cells in early and later CIA groups was lower than that of normal control group and treatment groups, which showed statistically significant difference (P＜0.05). The level of CD4+ CD25+ T cell in early MSCs treatment group was higher than the later MSNs treatment group, which showed statistically significant difference (P＜0.05). Compared to the normal group and treatment groups, the expression level of Foxp3 mRNA in the early and later CIA groups was decreased markedly, while the early MSNs treatment group versus the later treatment group showed no statistically significant difference (P＞0.05).The intensity of Foxp3 mRNA in the treatment groups was similar to normal control group. Conclusion In this study, MSCs has shown significant immune-modulatory effects. It up-regulates the level of CD4+ CD25+ T cell in CIA rats, accelerate the expression of Foxp3 mRNA. The early treatment group is more effective than the late treatment group.

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The effects of mycophenolic acid on the endotheline-1 induced proliferation, contraction and migration of pulmonary arterial smooth muscle cells: in vitro study

Yi ZHENG ; Xuhua SHI

Chinese Journal of Rheumatology.2010;14(10):664-667. doi:10.3760/cma.j.issn.1007-7480.2010.10.003

Objective To investigate the effect of mycophenolic acid (MPA) on the endotheline-1 (ET-1) induced proliferation, contraction and migration of pulmonary arterial smooth muscle cells (PASMCs)and to explore the mechanism of MPA on pulmonary arterial hypertension (PAH), and the effect of exogenous guanosine nucleotide reversing anti-proliferative effect of MPA. Paired-samples t-test was used for statistical analysis. Methods MTT test, scarification test, Millicell cell culture insertion and the length of PASMCs mcasured under microscope were used. Results The A values of group ET-1 + low concentration MPA decreased when compared with group ET-1 (0.348±0.036 vs 0.447±0.013, t=6.357, P=0.000) and the A values of group ET-1 + high concentration MPA was further decreased. The A values of group ET-1 + low concentration MPA + guanosine was higher than that of group ET-1 + low concentration MPA (0.390±0.018 vs 0.348 ±0.036, t=2.573, P=0.028). The average migration distance and the average migration numbers of PASMCs of groups MPA was decreased than that of group ET-1. The average cell length of PASMCs of groups MPA was increas ed than that of group ET-1. Conclusion MPA can effectively inhibit the proliferation,contraction and migration of PASMCs by ET-1 induction. The IMPDH may play a role in anti-proliferative effect of MPA on PASMCs, but is unnecessary to be the sole mechanism. These findings has provide new insight into the mechanisms of mycophenolate mofetil in the treatment of PAH.

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The clinical significance of anti-saccharomyces cerevisia antibody in primary biliary cirrhosis

Chaojun HU ; Shulan ZHANG ; Renfang ZHOU ; Xi LI ; Ping LI ; Lijun LI ; Xiaojuan DONG ; Fengchun ZHANG ; Yongzhe LI

Chinese Journal of Rheumatology.2010;14(10):659-663. doi:10.3760/cma.j.issn.1007-7480.2010.10.002

Objective To explore the prevalence of the anti-saccharomyces cerevisiae antibody (ASCA) in patients with primary biliary cirrhosis and evaluate it's clinical significance. Methods The subtypes of ASCA including IgA and IgG in blood samples from 162 patients with PBC, 44 patients with AIH,4-1 patients with other non-autoimmune liver diseases controls (LDC), 144 patients with inflammatory bowel disease (IBD) and 35 healthy controls were measured by ELISA. Chi-square test and Mann Whitney U test were used for statistical analysis. Results The positive rate of ASCA-IgA in PBC was 24.1%, which was higher than that in ulcerative colitis (UC) group ( 11.6%,χ2=5.5, P＜0.05 ) and healthy controls (0, χ2=10.5,P＜0.01 ). Compared with the AIH group (20.5%) or LDC group ( 14.6% ) or Crohn's disease (CD) (34.5%),there was no statistically significant difference (P＞0.05). The prevalence of ASCA-IgG in PBC was 11.1%,lower than the CD group (27.6%, χ2=8.9, P＜0.01 ), but higher than that in the healthy controls (0, χ2=10.5,P＜0.01 ). There was no statistically significant difference (P＞0.05) between PBC and the AIH group (15.9%)or LDC group (7.3%) or UC group (8.1% ). The positive rate of both ASCA-IgA and ASCA-IgG in PBC was only 6.2%, statistically lower than that of the CD group ( 17.2%, χ2=6.3, P＜0.05). The prevalence of ASCA-IgA or ASCA-IgG in PBC was 29.0%, which was statistically lower than that of the CD group (44.8%, χ2=4.8,P＜0.05), but higher than that of the UC group (χ2=5.9, P＜0.05) or healthy controls (χ2=13.3, P＜0.01).ASCA was detected more frequently in PBC patients with positive anti-GP210 antibody than in anti-GP210 antibody negative PBC patients (38.6% vs 23.8%,χ2=3.9, P＜0.05). The positive rate of ASCA between AMA positive and negative patients with PBC or anti-SP100 antibodies positive and negative patients with PBC was not significantly different. PBC patients with positive ASCA-IgA had higher level of TBIL, DBIL, TBA, LD,IgA, IgM, ESR and lower level of ALB, A/G, CHE than patients with negative ASCA-IgA. There was no statistically significant difference in liver injury indicators and immune function parameters between patients with positive ASCA-IgG and negative ASCA-IgG. Conclusion ASCA is not an IBD-specific antibody. There is a high prevalence of ASCA in patients with PBC, especially the subtype of ASCA-IgA. ASCA-IgA is found to be associated with the severity of liver damage and immune activity whereas ASCA-IgG is not associated with them.

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Presence of antibodies to cyclic citrullinated peptides in juvenile-onset systemic lupus erythematosus

Haiying LIU ; Yunfeng LIU ; Qihong GUAN ; Yanling ZHONG ; Lei PI ; Baidu ZHANG ; Caijiao GUO ; Huasong ZENG

Chinese Journal of Rheumatology.2010;14(10):698-701. doi:10.3760/cma.j.issn.1007-7480.2010.10.011

Objective To determine the prevalence of antibodies to cyclic citrullinated peptides (antiCCP) in patients with juvenile-onset systemic lupus erythematosus (JSLE) and its potential clinical significance. Methods Anti-CCP was measured in sera from patients with JSLE (n=47), juvenile idiopathic arthritis (JIA, n=54) and the sera from age-matched healthy children (n=40) using the third generation of anti-CCP ELISA commercial kit. The association of anti-CCP with other laboratory parameters and clinical features, especially arthritic symptoms in JSLE was also analyzed. T-test, Mann-Whitney U test, Chi-square and Fisher's exact test were used for statistical analysis. Results Out of the 47 JSLE patients, 6 (13%) were anti-CCP positive, which was significantly higher than that of the healthy controls( 13% vs 0, P＜0.05 ), but not different from that of the JIA group (26%, P=0.098). RF was more prevalent in JSLE patients with anti-CCP than patients without (83% vs 15%, P＜0.01 ), but there was no difference in other laboratory parameters and the clinical features ineluding the occurrence of arthritis (67% vs 51%, P＞0.05). As one of the initial symptoms, arthritis was observed in 25 of 47 JSLE patients and no one had developed deforming arthropathy.There was no statistical difference in anti-CCP positivity between JSLE patients with and without articular involvement ( 16% vs 9%, P＞0.05 ). Anti-CCP was not detected in any of the 3 patients with JSLE who had experienced joint pain and limited activity during 3 years follow-up. Conclusion Anti-CCP could be detected in patients with JSLE. It is noteworthy when differentiate from juvenile idiopathic arthritis, but the presence of anti-CCP does not relate with the occurrence of arthritis at presentation and persistence of arthritis in JSLE.

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Comparison of the effect of ibuprofen and glucosamine on synoviocyte proliferation and cartilage oligomeric matrix protein expression in knee osteoarthritis of human

Peng ZHANG ; Yuxin ZHENG ; Yuelong CAO ; Guantong SHI

Chinese Journal of Rheumatology.2010;14(10):668-671. doi:10.3760/cma.j.issn.1007-7480.2010.10.004

Objective To compare the effect of ibuprofen and glucosamine on synoviocyte proliferation and cartilage oligomeric matrix protein (COMP) expression in human knee osteoarthritis. Methods Human synoviocytes were isolated from synovium (earlier stage and late stage of OA) by tissue culture and were cocultured with ibuprofen and glucosamine. The concentration of COMP was determined by MTS/PMS method and hCOMP kit. Two-tailed t-test was used for statistical analysis. Results The observation time of tissue culture was determined at 5～7 day by the MTS/PMS method. The A values of glucosamine [ late stage group (0.054±0.021), early stage group (0.777±0.034)] were less than the normal serum control group (P＜0.05).Both ibuprofen [late stage group (35.4±1.9), early stage group (46.0±2.2)] and glucosamine [late stagegroup (36.6±1.3), early stage group (48.8±1.3) ] could decrease the concentration of COMP in synoviocyte secretion in vitro (P＜0.05). Conclusion Glucosamine can inhibit the synoviocyte proliferation of human knee osteoarthritis (both early stage and late stage) in vitro. Both ibuprofen and glucosamine can inhibit the COMP secretion of synoviocyte in vitro.

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