Expression of CD28-T-cell subtypes in peripheral blood and synovial fluid of patients with rheumatoid arthritis / 中华风湿病学杂志

ObjectiveTo investigate the expression and significance of CD28- cells, CD4+ and CD8+T lymphocytes in the peripheral blood and synovial fluid in patients with rheumatoid arthritis ( RA ). Methods The expression of CD28, CD4+, CD8+ T lymphocytes and inducible co-stimulator(ICOS) in the peripheral blood and synovial fluid in 45 patients with RA were detected by three-color flow cytometry. Independent sample's t test was used for statistical analysis between the two groups. ResultsSynovial fluid CD4+CD28+ICOS+, CD4+CD28- ICOS+ , CD8 + CD28 + , CD8 + CD28 + 1COS+ T lymphocytes were significantly increased than the peripheral blood in RA patients[(36±19)％ vs (15±8)％, t=-4.234, P＜0.01; (2.1±2.2)％ vs (0.6±1.4)％, t=-3.143, P＜0.01; (62±15)％ vs (47±18)％, t=-2.885, P＜0.01; (9±9)％ vs (3±3)％,t=-2.131, P＜0.05], Synovial fluid CD8+CD28-T lymphoc-ytes were significantly reduced than the peripheral blood[(38±15)％ vs (54±18)％, t=2.975, P＜0.01], Synovial fluid CD8+ CD28-ICOS+, CD4+CD28+and CD4+ CD28- T lymphocytes had no significant difference than the peripheral blood (P＞0.05). Compared with peripheral blood in the same patients with RA, CD4+CD28+ ICOS+, CD8+ CD28+ T lymphocyteswere significantly increased[(38±18)％ vs (16±10)％, t=-4.065, P＜0.01 ; (61±16)％ vs (41±21)％, t=-4.065,P＜0.01], CD8+CD28-T was significantly reduced[(39±16)％ vs (59±21)％, t=2.949, P＜0.01]. The level of CD4+ CD28-, CD8+ CD28-, CD28-ICOS+ T lymphocytes in the active and remission patients with RA was not significantly different (P＞0.05). ConclusionSynovial fluid CD28T lymphocyte subsets disturbance and the abnormal expression of ICOS in patients with RA may play important roles in the mechanism of joint damage.

Adverse events of anti-tumour necrosis factor therapy for ankylosing spondylitis: a retrospective study of 369 Chinese Han population / 中华风湿病学杂志

ObjectiveTo evaluate the adverse events occurred during tumour necrosis factor (TNF)-αblocker treatment in Chinese Han population patients with ankylosing spondylitis (AS).MethodsThis study had enrolled 369 Chinese Han population patients with ankylosing spondylitis.They all received TNF-αblocker treatment in the hospital.All 1011 administration were recorded in total.All of them were evaluated for adverse events 2 hours after injection,126 of them had received long-term TNF-α blocker injection,and they were followed-up at week 8,12,52,104.Mild immediate adverse events and long-term adverse events were all counted.SPSS 10.0 software package was used for Fisher's exact test.ResultsThree hundred and sixty-nine patients had 1011 administrations in total,652 had received rhTNFR:Fc,316 had infliximab,21had etanercept,22 had adalimumab injections.Adverse events 2 hours after injection were:17 (2.6％) for rhTNFR:Fc,12 (3.8％) for infliximab,0 for etanercept,1 (4.5％) for adalimumab.Twenty adverse events were mild(12 for rhTNFR:Fc,9 for infliximab),5 events were moderate(3 for rhTNFR:Fc,1 for infliximab,1 for adalimumab),4 events were severe(2 for rhTNFR:Fc,2 for infliximab).The frequency of adverse events were comparable between rhTNFR:Fc and Infliximab injection in immediate adverse reactions (P=0.31).One hundred and twenty-six (69 rhTNFR:Fc,57 infliximab) patients had long-term usage,and were followed-up at week 8,12,52,104,39 patients had adverse reactions:20 (51.3％) for rhTNFR:Fc,19(48.7％) for infliximab.Thirty-seven patients had infectious events(94.9％ ),1 neurological event(2.6％),and 1 patient had tuberculosis relapse (2.6％).Outcomes were comparable with rhTNFR:Fc and infliximab in long-term usage(P=0.69).ConclusionAttention should be paid to the above events in Chinese Han patients with ankylosing spondylitis who were treated with TNF-α blocker treatment.Special attention should be paid to those patients who are in their third or fourth injection.The occurrence of immediate reaction or long-term adverse events between rhTNFR:Fc and infliximab are comparable.

Protection of human osteoprotegerin mediated by adeno-associated virus on joint destruction in collagen-induced arthritis / 中华风湿病学杂志

Objective Using an in vivo adeno-associated virus(AAV)-mediated gene transfer technique,this study was designed to evaluate the protective effects of human osteoprotegerin(OPG)transgene against joint destruction in collagen induced arthritis(CIA)model.MethodsAfter CIA was established in the Sprague-Dawley rats,the experimental animals were treated with PBS or rAAV-EGFP or rAAV-hOPG (100μl/d)intra-articular injection 25 days after arthritis induction for 10 days.Paraffin-embedded joints were then analyzed histologically.The joint destruction was evaluated by Larsen Score.The protein expression of OPG,IL-1,MMP-3 was identified by enzyme-linked immunosorbent assay(ELISA).Results Suecessful trans-gene expression was confirmed by the detection of OPG by ELISA and positive fluorescence of the frozen joint section. Image analysis revealed that the expression of OPG significantly protected against joint destruction by 30% compared with the CIA group. Conclusion OPG gene transfer mediated by rAAV effectively protects against bone destruction induced by CIA model. Those data suggest that gene transferring using rAAV-OPG may be a feasible and effective therapeutic approach to treat or prevent joint destruction in inflammatory arthritis.

A multicenter,random,open,parallel controlled study on the efficacy and safety of ibuprofen arginate in treating rheumatoid arthritis and knee osteoarthritis / 中华风湿病学杂志

Objective To compare the clinical efficacy of ibuprofen arginate,a new nonsteroidal antiinflammatory drug,with that of ibuprofen,in patients with rheumatoid arthritis or knee osteoarthritis and to evaluate the safety and tolerability of ibuprofen argihate.Methods This is a muhicenter,random,open,active comparator-controlled,parallel clinical trail in which 171 patients with rheumatoid arthritis or knee osteoarthritis were enrolled.Patients were randomized to 2 groups:400 mg of ibuprofen arginate three times daily and 400 mg of ibuprofen three times daily respectively.Clinical efficacy and safety were evaluated after 4-week treatment.Results Ibuprofen arginate,at dosages of 400 mg three times daily,had shown significant efficacy in relieving pain,tenderness and swelling of joints and there was no significant difference when compared to that of ibuprofen.There was no difference in clinical adverse effects between the two groups and no serious adverse effects were repofled.But ibuprofen arginate could initiate effectiveness more rapidly than ibuprofen in both rheumatoid arthritisand osteoarthritis patients.Conclusion Ibuprofen arginate has the same clinical efficacy and safety profiles as itmprofen in treating rheumatoid arthritis and osteoarthritis.However,its onset is more rapid than ibuprofen.

Effect of intra-articular usteoprotegerin gene transduction on the expression of tartrate-resistant acid phosphatase and vascular endothelial growth factor mRNA in collagen induced arthritis / 中华风湿病学杂志

Objective This study was designed to investigate the expression changes of osteopro-tegerin (OPG), tartrate-resistant acid phosphatase (TRAP) and vascular endothelial growth factor (VEGF) mRNA in collagen induced arthritis(CIA) rats. Methods After CIA was induced in Sprague-Dawley rats, the experimental animals were treated with PBS or rAAV-EGFP or rAAV-hOPG (100 μl/day) intra-articular injection for 10 days. Messenger RNAs (mRNAs) were obtained from CIA synovium 40days after first immun-ization. Reverse transcriptase-polymerase chain reactions (RT-PCR) were carried out to detect the mRNA encoding OPG, TRAP, VEGF and β-actin, which acted as inner control. The genes detected clearly by RT-PCR were quantified using real-time PCR. Results The expression of all genes was confirmed by specific single bands in RT-PCR. Real-time PCR showed that the expression levels of TRAP and VEGF were increased, whereas those of OPG mRNA were decreased in CIA group compared with normal controls. The intra-articular gene transduction markedly increased the gene copies of OPG by 128.21% (P<0.01). The expression change of OPG in synovium also caused the decrease of the expression levels of TRAP and VEGF by 58.79% (P<0.01)and 17.85% (P>0.05) respectively, however, the expression change of VEGF was not statistically significant. Conclusion OPG gene mediated by rAAV can be successfully tranfered to knee joint synovium in vivo. The results of this study suggest that gene transfer using rAAV-OPG may be a feasible and effective therapeutic approach to treat or prevent joint destruction in inflammatory arthritis.

The efficacy evaluation of etanercept in patients with Behcet's disease / 中华风湿病学杂志

Objective To evaluate the therapeutic effect of etanercept in patients with Behcet's disease (BD). Methods Twenty six patients with active BD were eligible for anti-TNF-α treatment, which failed previously to commonly used drugs. All the patients were stopped previous therapy and treated with etanercept 25 mg twice a week. The clinical responses and laboratory parameters were evaluated at the baseline, week 2, 4, 8, 12 and 24, and week 12 of etanercept withdrawal. Results Etanercept was effective in several clinical lesions and lab. parameters at all time points. Especially at week 2, including oral ulcers, genital ulcers, erythema nodosum, pseudofolliculitis and swollen joints (P<0.01). Two of four cases of uveitis were contro-lled with addition of topical corticosteroids; The ileocecal junction ulcer of 1 patient healed after 2 months etanercept therapy; four cases of epididymitis reached complete remission at week 4. ESR(P=0.012) and CRP (P=0.013) were also rapidly decreased at week 2. Most patients were relapsed at week 12 of etanercept withdrawal compared with baseline except for swollen joints (0.65±1.09 vs 0.31±0.60, P<0.01) after etanercept withdrawal, in which the typical rebound was CRP from (481±312) mg/L to (549±267) mg/L (P=0.013).Conclusion Etanereept has rapid efficacy onset for most of the mucocutaneous disorders and possibly effective for arthritis, ophthalmitis, epididymitis and colonic ulcer of BD.

The clinical characteristics of interstitial lung disease in patients with dermatomyositis and polymyositis / 中华风湿病学杂志

Objective To analyze the clinical features,and prognosis of the interstitial lung disease (ILD) in patients with dermatomyositis (DM) and polymyositis (PM) by chest X-ray,chest high-resolution CT scan (HRCT) and pulmonary lung function.Methods Thirty-three patients hospitalized with DM/PM associated ILD were retrospectively analyzed.Results Thirty-three patients with ILD were confirmed by HRCT.Abnormal pulmonary function tests were available in 82% of patients.Clinical-imaging analysis revealed that the pathological features of ILD were non-specific interstitial pneumonia (NSIP,57%) and unusual interstitial pneumonia (UIP,25%).UIP types showed a poor prognosis and high mortality (70%).Conclusion This study shows that HRCT is more sensitive for the diagnosis of ILD than lung function tests and chest X-ray.Combined HRCT and chest X-ray with lung function tests and blood gas analysis have shown that the major pathological types of ILD are NSIP and UIP,in which UIP are associated with high mortality and poor prognosis.

Association of the CTLA-4 gene with rheumatoid arthritis in Chinese Han population.

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is important for downregulation of T-cell activation, and CTLA-4 gene polymorphisms have been implicated as risk factors for rheumatoid arthritis (RA). Previous studies of the association between the +49 polymorphism of the CTLA-4 gene in RA have provided conflicting results. In order to determine association of the CTLA-4 gene with RA in Chinese Han population, we used denaturing gradient gel electrophoresis (DGGE) to genotype polymorphisms of four SNPs (MH30, +49, CT60 and JO31) of the CTLA-4 gene in 326 RA patients and 250 healthy controls. Furthermore, meta-analysis of all available studies relating +49 polymorphism to the risk of RA was performed to confirm the disease association. Among the SNPs examined, the genotype frequencies of CTLA-4 +49 and CT60 in RA patients differed significantly from controls (P=0.028 and 0.007). In addition, the distribution of four haplotypes constructed by these two SNPs was significantly different between patients and controls (chi(2)=10.58, d.f. =3, P=0.014). The meta-analysis also revealed that in both European and Asian populations, the CLTA-4 +49 G allele was associated with the risk of RA. These results suggested that the CTLA-4 gene might be involved in the susceptibility to RA in the Chinese Han population and both +49 and CT60 of CTLA-4 gene might be the causal variants in RA disease.

Tumor necrosis factor alpha gene polymorphisms in ankylosing spondylitis: associations with clinical disease progression and disease susceptibility / 中国组织工程研究

BACKGROUND: The association of tumor necrosis factor alpha (TNF-α) gene polymorphisms with the onset and development of ankylosing spondylitis (AS) has been the focus of studies on AS in the field of genetics.OBJECTIVE: To explore the association of the polymophisms of TNF-α promoter gene at positions-308 and -238 with AS susceptibility and clinical pathological changes.DESIGN: A case-control study.SETTING:The Rheumatic Immunology Department of Changhai Hospital of the Second Military Medical University of Chinese PLA.PARTICIPANTS: Totally, 108 AS patients were recruited from Rheumatic Immunology Department of Changhai Hospital, Second Military Medical University of Chinese PLA from January 1999 to December 2003 ,they had no kinship. The ratio of men to women was 5.3: 1. They aged from 13 to 71 (30-± 12) years old, and AS was divided into Ⅰ- Ⅳ radiographic stages according to the sacro-iliac joint damage. A total of 100 healthy controls were randomly selected from the blood donators(Shanghai Hospital) who were aged from 19 -56 (33 ±9) years old, and the ratio of men to women was 4.9: 1. Informed consent was obtained from all the subjects.ti-coagulated with EDTA. Polymerase chain reaction amplification and purification of the TNF-α promoter region was made and the sequence of polymerase chain reaction products was examined and displayed by Chromas 1.62 softcorresponding radiographic stage of sacro-iliac joint damage was assessed to investigate the influence of gene polymorphisms on AS.MAIN OUTCOME MEASURES: DNA direct sequencing method was used to detect -238 and -308 allele phenotypes for investigating the association with clinical presentations.G and -238G/A allele was 98.1% (106 cases) and1. 9% (2 cases) respectively in AS group and 95.0% (95 cases) and 5.0% (5 cases) respecquency of TNF-α promoter gene at positions -308. 1.1(G/G) and - 308.1.2(G/A) alleles was 82.4% (89 cases) and 17.6% (192 cases) respectively in AS group, which was not significantly different compared respectively with 85.0% (85 cases) and 14.0% (14 cases) of the control of sacro-iliac joint damage and the frequency of TNF-α promoter gene at the position of - 308 (G/G) and (G/A): AS patients with(G/G) phenotype who were confirmed of radiographic stage Ⅰ, Ⅱ, Ⅲ, and Ⅳ were observed in 3/35/40/11cases,compared with (G/A) phenotype of 1/12/6/0 cases.The difference was statistically significant (χ2GMH = 4.77, P ＜ 0.05 ).CONCLUSION: Our data suggest that the polymorphisms of TNF-α promoter gene at positions of - 238 and - 308 allele has no association with AS susceptibility, but the polymorphisms of TNF - α promoter gene at the position of -308 might exert great influence on AS according to the radiographic stage of sacro-iliac joint damage.

To demonstrate the change in peripheral blood T lymphocyte subgroups and cytokines of Behet′s syndrome / 中华风湿病学杂志

Objective To demonstrate the change in peripheral blood T lymphocyte subgroup and cytokines of Beh?et′s disease (BD). Methods T lymphocyte subgroup was detected by flow cytometry and serum interleukin (IL)-8, sIL-2R, IL-1?, IL-2, IL-6 and TNF-? were assayed by RIA. Results CD4, CD4/CD8, NK of BD decreased evidently and CD8 incrdased. Serum IL-8, sIL-2R increased compared to normal controls. Change of IL-2, IL-6, tumor necrosing factor (TNF)-? , IL-1? showed no statistical significance compared to normal group. Conclusion Change in peripheral blood T lymphocyte subgroup and serum IL-8, sIL-2R can be one of the activity index of BD.

Influence of parental age at delivery and birth order on ankylosing spondylitis / 第二军医大学学报

2 in B27 positive groups and X = l. 58

Relationship between serum IL-1?,IL-6,IL-8,TNF-? and sIL-2R levels and disease activity in adult Still disease patients / 第二军医大学学报

Objective:To study the changes of serum IL 1?,IL 6,IL 8,TNF ? and sIL 2R and its relationship with disease activity in adult Still disease patients.Methods:Serum levels of IL 1?,IL 6,IL 8,TNF ? and sIL 2R were assessed by ELISA in 18 adult Still disease patients before and one month after treatment with prednisone.Results: Active adult Still disease patients had significant elevated erythrocyte sedimentation rate (ESR) and serum levels of C reactive protein (CRP),IL 1?,IL 6,IL 8,TNF ? and sIL 2R.After one month treatment with prednisone,ESR and serum levels of CRP,IL 6,TNF ? and sIL 2R significantly decreased.There was a significant correlation between ESR values and serum IL 6,TNF ? and sIL 2R levels,and between serum CRP levels and IL 6,TNF ? and sIL 2R levels.Serum IgG,IgA and IgM levels in active adult Still disease patients were similar to those in healthy controls.Conclusion: There are no changes in serum immunoglobulins but significant increases of serum IL 1?,IL 6,IL 8,TNF ? and sIL 2R levels in active adult Still disease.Serum levels of IL 6,TNF ? and sIL 2R are related to the activity of adult Still disease.

Effects of Intramuscular or Intracerebroventricular Injectionof Pentagastrin on Action Potential Amplitudeof Myocardial Cells and Heart Rate in Rats / 第三军医大学学报

The effects of intramuscular or intracerebroventricular injection of penta-gastrin(PG) on the action potential amplitude (APA) of the myocardial cells and the heart rate(HR) were studied. The results were as follows:1 ) Injection of 10?g/10?l of PG into one of the lateral ventricles of the ratfailed to produce any effect on APA or HR. When the dosage of PG was doubled(20?g/10?l), then HR could be slowed down significantly (P

Misdiagnosis analysis of POEMS syndrome and its early diagnosis / 第二军医大学学报

Objective:To study the causes of misdiagnosis of patients with POEMS syndrome and to discuss the clues for its early diagnosis.Methods:The clinical and laboratory data of 26 inpatients with POEMS syndrome,who were treated in Changhai hospital over the last decade,were retrospectively analyzed.Results:The misdiagnosis rate of our group was 100%. The misdiagnosis was made in(3.31?0.97)hospitals and in(3.31?0.93)clinical departments;the misdiagnosis period was (19.42?10.86)months and it had been misdiagnosed as 18 other diseases.The initial symptoms included polyneuropathy in 21 (80.8%)cases,edema of lower extremity in 22(84.6%)cases,and body weight loss in 8(30.8%)cases.The typical clinical symptoms included polyneuropathy in 26(100%)cases and organomegaly in 24(92.3%).Two cases had newly-identified uterine hypertrophy,one had adrenal gland hypertrophy,and one had gastric wall thickening mimicking advanced gastric cancer.Hypothyroidism,impotence,skin pigmentation and sclerosis occurred in 76.9%(20/26),60%(6/10),92.3%(24/ 26)and 65.4%(17/26)cases,respectively.Monoclonal plasma cell proliferation was documented in 18(81.8%);M proteins were positive in 14(63.6%)cases by serum immunofixation,and only 2(9.1%)cases also positive by serum protein electrophoresis.One patient was positive of M protein by urine immunofixation and one had abnormal infiltration of plasma cells in the gastric wall.Lymph node biopsy were performed in 8 patients and 3 were found to have Castleman disease;the other 5 cases had lymphocyte infiltration,with 3 complicated with plasma cell proliferation.Nerve biopsy in 4 cases all revealed axonal degeneration and one patient complicated with demyelination.Bone marrow biopsy in 5 cases revealed plasmacytosis in 2 cases and myeloma in one.Excessive radioactivity resorption was found in 10 of the 16 cases(62.5%)and abnormal plasma cells were detected in 2 cases by bone aspiration guided by radioisotope bone scan.Conclusion:Misdiagnosis of POEMS syndrome is very common.Polyneuropathy,edema of lower extremity and body weight loss are the common early symptoms of POEMS syndrome. Early diagnosis can be made by having an intimate knowledge of the progression of the disease and by detecting M protein through various approaches.

Study on transplantation of cartilage and articular cartilage tissue engineering / 第二军医大学学报

The repair of articular cartilage defects has been a dif ficult problem. Presently cartilaginous autograft and allograft, periosteal and perichondral graft and transplantation of chondrocytes had been widely applied t o repair cartilaginous defects. The application of tissue engineering might be a method of hope. This article reviewed the progression of cartilage transplantation and the tissue engineering.