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A retrospective analysis of plasma exchange com bined with glucocorticosteroids in the treatment of systemic lupus erythematosus associated with acute pancreatitis

Yikai YU ; Ju LI ; Xiaowei HUANG ; Yecheng FENG ; Linli DONG ; Shaoxian HU ; Xiaomei LEI

Chinese Journal of Rheumatology.2015;(6):410-413. doi:10.3760/cma.j.issn.1007-7480.2015.06.013

Objective To investigate the clinical features and mechanism and feasibility of plasma exchange (PE) in treating systemic lupus erythematosus (SLE) complicated with acute pancreatitis (AP). Methods A retrospective analysis of SLE associated with AP was done based on the HIS in Tongji Hospital. Totally 24 SLEAP patients were admitted to Tongji hospital from March 2006 to May 2014. Patientsˊ serum amylase, lipase and interleukin (IL)-6 concentration were measured before and after plasma exchange. According to different therapy strategy, patients were divided into two groups. Fifteen patients treated with plasma exchange combination with glucocorticosteroid (GC) were classified as Group A, the other 9 patients who were treated with GC only were classified as group B. At baseline and after treatment, the serum lipid concentration, average daily glucocorticosteroid dosage between group A and B were compared with ANOVA and serum IL-6 concentration between roup A and B were compared with Wilcoxon rank test. Results SLEDAI score in group A patients at baseline (16 ±5) was no statistically different from that in group B (18 ±4) (t=1.31, P=0.320). Average daily GC dosage in group A 31.0 (20.50, 30.08)mg/d was significantly less than that in group B 47.85 (45.58, 59.23) mg/d (Z=35.50, P= 0.002). Serum IL-6 levels in group A and B at baseline was not significantly different 13.14 (11.12,16.57) mg/L vs 14.63 (11.37, 16.37) mg/L (Z=12.20, P=0.300), after 2 weeks treatment, IL-6 level, which was 9.16 (7.93, 10.75) mg/L, decreased significantly in group A while it didnˊt show tendency of decrease in group B, which was 13.62(9.29, 17.63) mg/L (Z=28.50, P=0.039). Serum lipid concentration after 2 weeks therapy in Group A [TC=(5.02 ±0.53) mmol/L, TG=(1.46 ±0.44) mmol/L] decreased significantly compared to baseline [TC=(6.11±0.50) mmol/L, TG=(2.14±0.65) mmol/L] (F=4.46, P=0.010; F=6.09, P=0.002), while similar tendency wasnˊt observed in group B (F=1.57, P>0.05). Conclusion PE combined with GC could lower serum IL-6 levels, reduce the amount of GC and lower serum lipid to improve prognosis. Therefore it might be a safe and effective way and is worthy of continuing to explore its feasibility.

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Clinical analysis of 9 cases of thymoma in sy stemic lupus erythematosus

Jie LI ; Lijun SONG ; Xiao YU ; Qiang SHU ; Huaxiang LIU ; Feng DING ; Xingfu LI

Chinese Journal of Rheumatology.2015;(6):407-410. doi:10.3760/cma.j.issn.1007-7480.2015.06.012

Objective Thymoma is associated with autoimmune diseases. We retrospectively analyzed the clinical characteristics of thymoma complicated systemic lupus erythematosus (SLE). Methods Patients were from Qilu Hospital Shandong University between June 2004 and June 2014, and satisfied classification criteria of American College of Rheumatology (ACR) classification criteria 1997 for SLE. Thymoma was diagnosed by chest CT scan. Results Nine cases were of thymoma complicated with SLE, with the male:female ratio of 1∶8. The age of SLE onset was (48±19) years, age of thymoma discovery was (47±19) years. The follow-up period was 3 to 10 years. Three cases (33%) were benign thymoma and underwent thymectomy and verified by histopa-thology test. One case presented thymoma 9 years after SLE, 5 cases (56%) presented SLE and thymoma simultaneously, 3 cases (33%) presented SLE after thymectomy. Clinical manifestations of SLE included 4(44%) skin lesions, 8(89%) polyarthritis, 5(56%) nephritis, 3(33%) leukocytopenia, 3(33%) throm-bocytopenia, 2 (22%) of interstitial pneumonia, 4 (44%) pleural effusion, no neuropsychiatric systemic lupus erythematosus. Nine cases (100%) were ANA positive, 7 (78%) were anti-dsDNA positive. Conclusion SLE complicated thymoma usually occurs in relatively older age, tend to present with multi-systemic presentations, and high percentage of anti-dsDNA positivity.

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Analysis on the survey of risk factors of symptomatic osteoarthritis in Shanxi rural community

Ruiping ZHANG ; Fangchao LIU ; Junfeng ZHANG ; Haiyuan DONG ; Guifen LIU

Chinese Journal of Rheumatology.2015;(6):404-406. doi:10.3760/cma.j.issn.1007-7480.2015.06.011

Objective To investigate the factor that affecting the prevalence of osteoarthritis in rural areas of Shanxi, China. Methods All the residents above 16-year-old from the villages chosen by multi-stage stratified cluster sampling in Yangcheng County and Pianguan County in Shanxi Province were investigated by COPCORD procedure of WHO. All respondents signed the informed consent forms. Chi-square test and multivariable logistic regression analysis were used for the risk factor analysis. Results Seven thousand one hundred and twenty-six permanent residents in the two counties were investigated, of which 1734 cases of patients with osteoarthritis were identified. Take with or without osteoarthritis as response variables, statistically significant variables in the univariate analysis were substituted into the logistic regression model. Forward method was used for the variable selection. The inclusion criteria set as 0.10. The results showed that, age, room heating and ventilation, marital status, occupation, education, engaged in coal mine work, accompanied cardiovascular disease were the risk factors for osteoarthritis disease. Conclusion There were many factors that affect the prevalence of osteoarthritis in Shanxi rural communities, in which lifestyle may play an important role. Early intervention on risk factors may have a significant effect on reducing the prevalence.

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The side-effects of cyclop hosphamide in the treatment of systemic autoimmune diseases

Jing XU ; Dan ZHANG ; Zhuoli ZHANG

Chinese Journal of Rheumatology.2015;(6):392-395. doi:10.3760/cma.j.issn.1007-7480.2015.06.008

Objective To understand the side-effects of cyclophosphamide (CTX) in the treatment of systemic autoimmune diseases and the possible risk factors. Methods Two hundred and forty-one patients with systemic autoimmune diseases were recruited from the Rheumatology Division of Peking University First Hospital during January 1st, 2009 and March 31, 2012. All the patients received oral or intravenous cyclopho-sphamide. The data were collected by medical record review as well as telephone follow-up. Logistic regression analyses were used for statistical analysis. Results Statistical analysis for age, sex, disease, cumulative dose, treatment duration and mode of administration were included in the factor analysis that would impact the CTX related side-effects. Age ( x2=14.8, P=0.002), gender ( x2=11.2, P=0.001), the underlying disease ( x2=26.1, P<0.01), cumulative dose ( x2=9.8, P=0.007) and mode of administration of CTX ( x2=19.5, P<0.01) were all correlated with the incidence of CTX side-effects. Multivariate analysis showed that women [OR=2.32, 95%CI (1.15, 4.70), P=0.02], intravenous-oral sequential use of CTX [OR=5.25, 95%CI (2.30, 11.97), P<0.01] and systemic lupus erythematosus [OR=4.02, 95%CI (2.24, 7.21), P<0.01] as the underlying disease were independent risk factors for CTX side-effects. Conclusion Alopecia, gastrointestinal discomfort and gonads toxicity ware com-monly seen in Chinese patients with systemic autoimmune diseases receiving CTX. Hemor-rhagic cystitis is very rare. Women, intravenous-oral sequential use of CTX and the systemic lupus erythematosus are indepen-dent risk factors for CTX side-effects.

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Analysis of the relationship between anti-mitochondrial antibody subtypeⅡIgM and anti-centromere antibody IgG in primary biliary cirrhosis patients

Naining YIN ; Yanrui FENG ; Wenshuang WU

Chinese Journal of Rheumatology.2015;(6):389-391. doi:10.3760/cma.j.issn.1007-7480.2015.06.007

Objective The aim of this study is to analyze the association between IgM anti-mitochon-drial antibody subtypeⅡ(AMA-M2-IgM) and the anti-centromere antibody IgG (ACA-IgG) in primary biliary cirrhosis (PBC) patients, and to investigate the clinical significance of M2-IgM and ACA-IgG in the diagnosis of PBC. Methods We selected 36 cases of PBC patients as research subjects whose AMA-IgG and AMA-M2-IgG were both negative. The M2-IgM positive rate in the ACA-IgG positive group and negative group was compared. We also analyzed the course of disease, pathological changes and the positive conversion rate of M2-IgG between the M2-IgM positive group and negative group. Results There were 9 cases of M2-IgM positive patients (64%) and 5 cases of M2-IgM negative patients (36%) in the ACA-IgG positive group. In the ACA-IgG negative group we found 3 cases of M2-IgM positive patients (14%) and 19 cases of M2-IgM negative patients (86%). So the M2-IgM positive rate in the ACA-IgG positive group was significantly higher than that of the ACA-IgG negative group (P=0.003). According to the tracking detection results, the M2-IgG positive conversion rate in the M2-IgM positive group was 67% (8 patients), which was significantly higher than the M2-IgM negative group 8%, (2 patients) (P=0.001). Conclusion M2-IgM is a specific antibody for PBC in the early stage, which presents earlier than M2-IgG. In the PBC patients whose AMA-IgG and AMA-M2-IgG antibodies are both negative, the M2-IgM positive rate is closely related to the ACA-IgG, so the ACA-IgG detection is very important in the early diagnosis of PBC. Therefore, we speculated that patients with ACA-IgG antibody are more susceptible to PBC.

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The ABCG2 gene rs2231142 polymorphism contributes to the increased risk for gout:a meta-analysis

Ya QIU ; Hua LIU ; Jingguo ZHOU ; Yufeng QING ; Mingcai ZHAO ; Wenguang XIE ; Wantai DANG

Chinese Journal of Rheumatology.2015;(6):384-388. doi:10.3760/cma.j.issn.1007-7480.2015.06.006

Objective This study is aimed to evaluate the association between the ABCG2 gene rs2231142 variant and gout using meta-analysis. Methods Related studies were identified by searching extensively in Chinese and foreign language databases such as Pubmed, EMBASE, Cochrane Library, CBMdisc databases and so on. The quality of included studies was assessed by using the Newcastle-Ottawa Scale (NOS). The odds ratio (OR) was calculated using a random-effects or fixed-effects model. A Q statistic was used to evaluate the heterogeneity, and Eggerˊs test and funnel plot were used to assess publication bias. Sub-group analyses on ethnicities and sex were also performed. Results A total of 10 studies, including 3 478 gout patients and 10,089 controls from 6 countries or regions, were included and identified for the current metaan-alysis. It was found that the A allele or AA genotype of the ABCG2 rs2231142 polymorphism had an increased risk for gout in the general population [A allele: OR=2.03, 95%CI (1.77, 2.34), P<0.01 and AA genotype: OR=3.01, 95%CI (2.34, 3.88), P<0.01, respectively]. Similar results were found in sub-group analyses of different gender and races. Conclusion Existing evidence indicate that rs2231142 polymorphism (the A allele and AA genotype) is associated with increased risk of gout.

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The mechanism of tumor necrosis factor-alpha participating in the osteoporosis of MRL/lpr mice by inhibiting osteoblast differentitation of BMMSCs in vivo

Dongming SONG ; Ting CUI ; Yingying QIU ; Jinbin RUI ; Xiaoming FEI ; Xinxin XU ; Jing LI ; Yu TANG

Chinese Journal of Rheumatology.2015;(6):364-368. doi:10.3760/cma.j.issn.1007-7480.2015.06.002

Objective To investigate the mechanism of tumor necrosis factor-α (TNF)-α inhibiting osteo blastdifferentiation of mesenchymal stem cells (BMMSCs) in the pathogenesis of osteoporosis in the mouse model of systemic lupus erythematosus (MRL/lpr). Methods The femurs of MRL / lpr and C3He/HeJ mice were isolated, the bone structure were examined by hematoxylin-eosin (HE) staining. The proteins of TNF-α, NF-κB P50, bone morphogenetic protein -2 (BMP-2) and PSmad1/5/8 were measured by immunohistochemical stain. Bone marrow mesenchymal stem cells (BMMSCs) were isolated. After BMMSCs grew on the cover slips, the proteins on top of it were evaluated by immunohistochemistry stain. Moreover, the alkaline phosphatase (ALP) staining was employed for the measurement of the early osteogenic differentiation. BMMSCs together with hydroxyapatite were embedded subcutaneously in the nude mice and eight weeks later, the ectopic bone formation was evaluated. The recombinant human tumor necrosis factor receptor type Ⅱantibody fusion protein (etanercept) or normal saline was subcutaneous injected to the mice with lupus. After four weeks, the expression of these proteins was observed and the ectopic bone formation was investigated. Image-Pro plus 6.0 software was employed for imagine analysis, and Studentˊs t-test was used to test the differences between 2 independent groups. Results MRL/lpr mice showed decreased volume of cortex and the percentage of cortex to the volume of bone of MRL/lpr mice was significantly lower compared to control groups and with C3He/HeJ mice (13.96±0.25 vs 23.61±0.71, n=3, P<0.01). The protein levels of both TNF-αand NF-κB P50 on the femur of MRL/lprl mice were higher than those of the control group (0.643±0.051 vs 0.405±0.022, 0.917±0.023 vs 0.650±0.032, n=3, P<0.01). The expressions of BMP-2 on the femur of MRL/lpr mice were lower than those of the C3He/HeJ mice (0.52 ±0.03 vs 0.72 ±0.03, n=3, P<0.01). There was no difference in the expression of PSmad1/5/8 on the femur between the two groups by immunohistochemistry detection (1.264 ±0.021 vs 1.301± 0.044, n=3, P>0.05). The expressions of TNF-α and NF-κB P50 in BMMSCs of MRL/lprl mice were higher than those of the C3He/HeJ (0.184±0.021 vs 0.136±0.013, 0.132±0.021 vs 0.097± 0.014, n=3, P<0.01), while BMP-2 and PSmad were lower than those of the control group (0.128±0.013 vs 0.216±0.221, 0.115±0.023 vs 0.196±0.034, n=3, P<0.01). After 7 days of BMP-2 stimulation, the activities of ALP of BMMSCs from MRL/lprl mice were reduced detected by ALP staining and the osteoblast differentiation of these cells were decreased than BMMSCs from the control mice by HE and Masson staining. The percentage of the cortex to the volume of bone of the etanercept injection MRL/lpr mice was higher than that of the control group (21.8±1.0 vs 14.3 ±0.6, n=3, P<0.01). Moreover, the proteins of TNF-α and NF-κB P50 on the femurs of such injected mice were lower than those of the control group (0.540±0.024 vs 0.682±0.031, 0.857±0.023 vs 1.098±0.044, n=3, P<0.05), while the expressions of BMP-2 were higher than the control group (0.99±0.04 vs 0.85±0.04, n=3, P<0.05). There was no difference in the PSmad1/5/8 expression on the bone of the two group of lupus mice (0.88 ±0.08 vs 0.84 ±0.04, n=3, P>0.05). The ectopic bone formation of BMMSCs of the etanercept injected MRL/lpr mice was higher than that of the normal saline injected mice, however, it was lower than that of the C3He/HeJ mice. Conclusion TNF-α inhibits osteoblast differentiation of mesenchymal stem cells by depressing Smad signaling which may contribute to the osteoporosis of the lupus mice.

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Expression of the poly (ADP-ribose) polymerase and its relationship with apoptosis on peripheral blood mononuclear cells in patients with systemic lupus erythematosus

Dongyu CHEN ; Fang LI ; Qiang SHU

Chinese Journal of Rheumatology.2015;(6):401-403. doi:10.3760/cma.j.issn.1007-7480.2015.06.010

Objective Poly (ADP-ribose) polymerase (PARP) have been demonstrated to play an important role in systemic lupus erythematosus (SLE). In this study we assessed the expression of PARP on peripheral blood mononuclear cells with active or inacte SLE and tried to investigate the relationship between PARP and cell apoptosis on SLE. Methods Thirty definitive SLE patients and 10 healthy controls were enrolled. PBMC were separated from the peripheral blood samples. Western blot technique was applied to analyze the expression of PARP. Flow cytometry were applied to analyze the cell apoptosis. T test were used. Results The cell apoptosis in active patients with SLE was significantly higher than that of inactive patients with SLE and normal controls (the t values were 4.83 and 5.05 respectively, P<0.05). The level of PARP expression was significantly decreased in active patients with SLE as compared with controls and inactive patients with SLE (the t values were 7.66 and 7.07 respectively, P<0.05). At the same time, the cleavage fragment of PARP increased in active patients. Conclusion The results suggest that PARP may be involved in the pathogenesis of SLE and the expression level may be a good indicator for disease activity of SLE . Decrease of PARP may promote the occurrence and development of SLE. In addition, PARP may play a certain role in adjusting cell apoptosis in patients with SLE.

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The experimental gene therapy with lentiviral-mediated RNA interference targeting tumor necrosis factor-α

Yingjie ZHAO ; Jibo WANG ; Lei ZHAO ; Dawei WEN ; Lin PAN ; Kun YANG ; Aihua SUI

Chinese Journal of Rheumatology.2015;(6):396-400. doi:10.3760/cma.j.issn.1007-7480.2015.06.009

Objective To investigate the effects of lentiviral-mediated RNA interference (RNAi) targeting tumor necrosis factor-α(TNF)-αgene on the expression of TNF-α, interleukin (IL)-1β, IL-6 of murine macrophages RAW264.7, and the efficiency of RNAi experimental gene therapy for the murine collagen-induced arthritis (CIA). Methods The RAW264.7 macrophages were infected by lentivirus-RNAi particles, then stimulated by Lipopolysaccharides (LPS). The TNF-α, IL-1β, IL-6 expression of RAW264.7 macrophages were measured with real-time polymerase chain reaction (PCR) and enzyme linked immunosorbent assay (ELISA). CIA models were esta-blished in DBA/1 mice using bovine type Ⅱ collagen. The treatment effect of lentivirus-RNAi on CIA were observed through arthritis scores, serum TNF-α measurement and hind paw paraffin section hematoxylin/eosin staining after lentivirus-RNAi particles tail vein injection. Results The TNF-αmRNA relative expression level of lentiviral RNAi group was 0.291 ±0.021, significantly lower than that of negative control group 0.925±0.013 (t=25.4, P<0.01). The inhibition rate in mRNA levels was 68.5%. The serum TNF-α level of lentiviral RNAi group was [(249 ±11) ng/ml], significantly lower than that of negative control [(382±6) ng/ml] (t=10.31, P<0.05). The inhibition rate of protein levels was 34.7%. It had no effect on the IL-1β and IL-6 mRNA expression. On the 8th day after systemic administration, the arthritis score of lentivirus-RNAi group was 2.50±0.19, which was significantly lower than that of blank controls (3.63 ±0.18) and negative controls (3.75 ±0.16) (F=42.8, P<0.01). From now on, arthritis score of lentivirus-RNAi group and positive control decreased slowly to at least 2 weeks after treatment induction. The serum TNF-α levels of lentivirus-RNAi group and positive controls were [(35±6) pg/ml] and [(32±7) pg/ml] significantly lower than that of negative controls [(47±3) pg/ml] (t=3.03, 4.11, P<0.01) respectively. Morphological examination showed that the lentivirus-RNAi decreased CIA pathological manifestations. Conclusion Lentiviral-mediated RNAi targeting murine TNF-α gene can effectively inhibit TNF-α expression both in vitro and in vivo, which also effectively improve the CIA arthritis score. Lentiviral-mediated RNAi targeting TNF-αgene provides a potential strategy for rheumatoid arthritis (RA) treatment.

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Study on the peri-puerperium outcome and associated factors of patients with primary Sj?grenˊs syndrome

Cheng CHEN ; Xuan XUAN ; Xinping TIAN

Chinese Journal of Rheumatology.2015;(6):380-383. doi:10.3760/cma.j.issn.1007-7480.2015.06.005

Objective To analyze the peripartum complications,frequency of neonatal abnormalities and the associated factors in patients with primary Sj?grenˊs syndrome (SS). Methods The chart of 39 patients with primary SS who were admitted to the hospital for delivery were retrospectively reviewed. The clinical data, obstetrical outcome and the frequency of neonatal abnormalities as well as the possible associated factors were analyzed. Results There were 76 pregnancies and 41 deliveries among these 39 patients. Two patients (5%) had pregnancy-related hypertension, 1 (3%) had gestational diabetes and 1 (3%) had eclampsia. Twenty-eight(72%) patients had at least one episode of complication. In which, 27(68%) were induced abortion, 2 (5%) were premature birth, 6 (21%) were amniotic fluid volume abnormalities, 2 (5%) were post-partum bleeding, 5 (13%) were premature rupture of membrane, 6 (21%) were intra-uterine distress and 3 (8%) had intra-uterine growth retardation. Fetal abnormality was detected in 7(18%) patients, in which 3 fetus (8%) died before delivery, 2 fetus (5%) were small than gestational age and 2 (5%) had fetal deformity. Compared to the reports in the literature, the rate of abortion and fetal death was higher, but the rate of growth retardation , induced abortion was lower. Conclusion The frequency of peri-partum complication and fetal abnormality is increased in patients with primary SS. Pregnancies in patients with primary SS should beclosely monitored by rheumatologists.

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