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Objective:To explore clinical factors of poor prognosis in patients with anti-melanoma differentiation-associated gene 5 andtibody positive dermatomyositis (MDA5-DM).Methods:One hundred and twenty-six enrolled adults with MDA5-DM were divided into the survival group and the deceased group according to the outcomes. Survival time, clinical manifestations, laboratory tests, pulmonary function tests, myositis antibodies and treatments were collected for statistical analysis. Serum concentrations of IL-15, HMGB1, and sCD163 were measured by ELISA in MDA5-DM patients and healthy controls. Mann-Whitney U nonparametric test and Student′s t-test were used to compare the continuous variables between the two groups, and χ2 or Fisher′s exact test were used for comparison of categorical variables. Cox regression analysis was used to assess the survival predictors in MDA5-DM patients. The cumulative survival rate was calculated by Kaplan-Meier curve analysis, and Log-rank tests were used to examine differences in survival curves. P<0.05 was considered statistically significant. Results:Cox multivariate regression analysis revealed that age > 57 years [ HR (95% CI)=3.05 (1.20, 7.80), P=0.020], RP-ILD [ HR (95% CI)=25.07 (5.42, 115.98), P<0.001], and levels of anti-Ro52 antibody [ HR (95% CI)=3.41 (1.36, 8.53), P=0.009] were important prognostic factors independent of multiple clinical parameters. The ELISA test results showed that the levels of serum IL-15[0.91 (0.66, 2.00)pg/ml vs. 0.51(0.39, 0.72)pg/ml, Z=-4.57, P<0.001] and HMGB1 [230.53(90.40, 394.31)ng/ml vs. 32.66 (17.82, 46.21)ng/ml, Z=-6.52, P<0.001] in MDA5-DM patients were significantly higher than those in healthy controls, but there were no significant differences in the level of serum IL-15 [1.21(0.63, 2.12)pg/ml vs. 0.91(0.68, 1.66)pg/ml, Z=-0.30, P=0.766], HMGB1[267.61(167.03, 444.23)ng/ml vs. 228.35(74.74, 344.32)ng/ml, Z=0.82, P=0.413], and sCD163 [112.70(93.45, 148.51)ng/ml vs. 132.72(96.79, 203.18)ng/ml, Z=-0.62, P=0.536] between the survival group and the deceased group. Conclusion:Older age, RP-ILD, and high levels of anti-Ro52 antibody significantly increase the risk of death in MDA5-DM patients. Intensive follow-up of patients with the above factors in the early stages may help to improve the prognosis.
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To investigate clinical characteristics of muscular sarcoidosis presenting muscle mass as initial symptom. The clinical data of 10 patients diagnosed with muscular sarcoidosis and admitted in the Second Affiliated Hospital of Zhejiang University School of Medicine from May 2014 to October 2020 were collected and retrospectively analyzed. All patients were female, including 2 patients with unilateral involvement of lower extremities, 7 patients with bilateral involvement of lower extremities, and 1 patient with bilateral involvement of upper and lower extremities. Lung lesions were presented in all patients, and 9 cases had mediastinal lymphadenopathy. Serum angiotensin-converting enzyme (sACE) was 57-118 IU/ml. No specific characteristics were found by ultrasound. Typical “dark-star” sign and “three-stripe” sign were shown in the magnetic resonance imaging (MRI). The pathology of striated muscle was non-necrotizing granulomatous inflammation. Three patients were not treated. In 7 patients treated with prednisone 0.5-1 mg ·kg -1·d -1, immunosuppressants were combined in 3 patients at initial and the other 4 patients later on. During the follow-up of 7-62 months, 1 patient was stable, 6 improved and 3 relapsed. Till now, 5 patients are still on the treatment of glucocorticoid and immunosuppressant.
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OBJECTIVE@#To investigate the expression of leukocyte immunoglobulin-like receptor A3 (LILRA3) in CD14 monocytes of patients with rheumatoid arthritis (RA).@*METHODS@#Fifty three RA patients admitted in the Second Affiliated Hospital of Zhejiang University School of Medicine from February 2017 to August 2017, and 21 healthy subjects were enrolled in the study. The expression of LILRA3 in CD14 monocyte subset was determined by flow cytometry, and its correlations with clinical features, laboratory examination results, antibodies and disease activity were analyzed.@*RESULTS@#LILRA3 percentage in the CD14 monocyte subset of RA patients was higher than that in the healthy controls (0.05). In addition, the percentages of LILRA3 in the monocytes of rheumatoid factor (RF)-positive or anti-cyclic citrullinated peptide (CCP) antibody-positive patients were significantly higher than those of the RF-or anti-CCP antibody-negative patients (all 5.1 was higher than that in patients with DAS28 ≤ 5.1 (<0.05).@*CONCLUSIONS@#The expression of LILRA3 is up-regulated in CD14 monocyte subset isolated from RA patients, and it is correlated with disease activity.
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Humans , Arthritis, Rheumatoid , Blood , Autoantibodies , Blood , Biomarkers , Blood , Flow Cytometry , Monocytes , Metabolism , Receptors, Immunologic , Genetics , Up-RegulationABSTRACT
Objective To investigate the clinical significance of soluble Semaphorin 5A(Sema 5A) in patients of rheumatoid arthritis(RA) and the effect of Sema 5A on osteoclastogenesis in RAW264.7 cells.Methods (1)Soluble Sema 5A was detected in the serum of 62 RA patients,30 osteoarthritis(OA) patients and 48 healthy controls(HC) by enzyme-linked immunosorbent assay(ELISA).The relationships between serum Sema 5A and disease activity,radiographic severity and laboratory parameters were investigated in RA patients.(2)RAW264.7 cells were treated with different concentrations of Sema 5A(0,0.5,1,2.5,5 μg/ml).After 7 days,tartrate-resistant acid phosphate(TRAP) staining was performed.The mRNA levels of TRAP,cathepsin-K and matrix metallopeptidase 9(MMP-9) were tested using real-time polymerase chain reaction (RT-PCR).(3)Bone resorption area of dentine slides cultured with RAW264.7 cells was calculated after Sema 5A (5μg/ml) treatment.Results (1)The serum Sema 5A in RA patients[(5.24±0.59)μg/L] was significantly higher than those in healthy controls[(2.93±0.34)μg/L,P<0.01] and OA patients[(2.68±0.47)μg/L,P<0.05].The Sema 5A level in RA patients was positively correlated with disease activity score with 28 joint using C-reactive protein(DAS28-CRP),clinical disease activity index (CDAI),C-reactive protein(CRP) and sharp scores(P<0.05 or P<0.01).In addition,the serum Sema 5A in RA patients with positive anti-cyclic citrullinated peptide(CCP) antibody was significantly greater than that of anti-CCP antibody-negative patients (P<0.05).(2)After RAW264.7 cells were treated with Sema 5A,the number of TRAP positive osteoclasts increased according to the increase of Sema 5A concentration with maximal effect at 5 μg/ml.Meanwhile,Sema 5A promoted mRNA expression of TRAP,Cathepsin-K and MMP-9.(3)Bone resorption area increased when RAW264.7 cells were treated with Sema 5A(5 μg/ml).Conclusions Serum Sema 5A is elevated in RA patients and correlated with disease activity and radiographic severity.Sema 5A promotes osteoclastogenesis of RAW264.7 cells.
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Objective To compare the clinical response with etoricoxib 60 mg once daily with diclofenac sodium tablet 75 mg two times daily in the treatment of osteoarthritis of the knee or hip joint.Methods A 4-week multicenter,randomized,double-blinded and active comparator-controlled clinical trial was performed during January 2005 and June 2005 in 6 medical centers in China.Eligible patients (≥40 years old Chinese patients with osteoarthritis of the knee and hip) were randomized (1:1 ratio) to receive etoricoxib 60 mg once daily (n=90),or diclofenac sodium 75 mg twice daily (n=90).Primary efficacy end point is the change of WOMAC (Western Ontario and McMaster Universities osteoarthritis index) pain subscale from baseline to 4 weeks; non-inferiority bounds were pre-defined [if the upper bound of 95% confidence interval (CI) for the difference is less than 10 mm on a 100-mm VAS WOMAC pain subscale] for the comparison of the change between the two groups.The secondary efficacy endpoints include WOMAC physical function subscale,WOMAC stiffness subscale,patient's global assessment of response to therapy (PGART),investigator's global assessment of disease status (IGADS),discontinuation due to lack of efficacy and rescue paracetamol tablet count.Safety was assessed by physical examination,adverse experience reported,and laboratory safety data.Results C6mpared to baseline,the changes of WOMAC pain subscale after 4 weeks treatment were statistically significant (P<0.01) in both groups (etoricoxib group:51±16 vs 21± 19; diclofenac sodium group:53±16 vs 22±19).There was no difference in the change of WOMAC pain subscale between the two groups.The change in WOMAC stiffness subscale,WOMAC physical function subscale,PGART and IGADS in both groups were statistically significant (P<0.01),but there was no difference between treatment groups according to the pre-defined non-inferiority criteria.No drug related serious adverse events were observed during the study.The difference in drug-related adverse event incidence between the two groups was not statistically significant.Etoricoxib and diclofenac sodium were generally safe and well tolerated.Conclusion Etoricoxib 60 mg administered once daily is efficacious and shows clinical efficacy notinferior to that of diclofenac sodium 75 mg administered twice daily for the treatment of osteoarthritis.Etoricoxib 60 mg administered once daily for 4 weeks is generally safe and well tolerated.
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Objective To investigate the clinical efficacy and safety of low-dose rituximab (RTX) for patients in primary Sj(..o)gren's syndrome (pSS) with thrombocytopenia.Methods Four pSS patients,2 with refractory thrombocytopenia and 2 with glucocorticoid-dependent thrombocytopenia,were treated with rituximab at 100 mg,intravenous,weekly for a total of two cycles,together with prednisone 1-2 mg · kg-1 ·d-1,and the counts of platelets and B-cells were evaluated.Results Efficacy of treatment was observed in all patients.The counts of platelets,at (3-39) x 109/L baseline,incleased in 1-2 weeks,and went up to ( 107-241 ) × 109/L in 3-8 weeks.Sustained remission had been achieved for 27-52 weeks.The doses of prednisone were tappered to 3.75-7.50 mg/day in 12 weeks.One patient who relapsed at the 27th week (platelet count 47 x 109/L),was retreated with 100 mg of RTX and still had good efficacy.The counts of B-cells reduced to (0.007-0.010) × 109/L,but they did not achieved the depletion.There were no severe adverse events during RTX therapy.Conclusions Our study has shown good efficacy and tolerability of lowdose RTX for pSS with thrombocytopenia.Low-dose RTX allows for reduction in corticosteroid doses and B-cells,while large-scale randomized double-blind controlled trials are needed to confirm the results.
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Objective To evaluate the efficacy and safety of etoricoxib and meloxicam in the treatment of patients with acute gout. Methods A randomized,active comparator study was conducted at outpatients and inpatients in our hospital from January 2009 to July 2010.A total of 84patients aged (63.7± 11.0) years with an acute attack of gout were treated with etoricoxib 120 mg/d (n =48),or meloxicam 15 mg/d (n =36) for 7 d.The patient's assessment of joint pain (0- 4 point Likert scale) at drug treatment for 2-5 d was considered as the primary efficacy end point,4 h after firstly takiug the drug and 2-8 d after treatment as the secondary efficacy end point.The starting efficacy was determined until pain relieved by patient himself. The safety was assessed by adverse experiences and indexes including leucocyte, platelet,crcatinine, uric acid,alanine transaminase (ALT),aspartate transaminase (AST) and mean artery pressure(MAP). Results In 84 patients,3cases (8.3%) in meloxicam treatment and 15 cases (31.2%) in etoricoxib treatment (among which 13 cases finished treatment) discontinued therapy.The improvement scores of joint pain were (-0.41 ±0.35 vs.-0.19±0.30,P=0.005) at4 h after firstly taking the drug,(-1.66±0.58 vs. 1.38±0.44,P=0.018)at drug treatment for 2 -5 d,( - 1.83 ± 0.60 vs.- 1.85 ± 0.53,P=0.9) at 2 8 d after treatment,and (-2.64±0.45 vs. - 2.38±0.37,P=0.000) post-treatment higher than pre treatment.The starting time of pain relieving were (4.0 ± 4.6) h in etoricoxib treatment and (12.1±5.7) h in meloxicam treatment. The levels of leucocyte were decreased after treatment as compared with before treatment in both two drug treatments(P<0.05),while no differences were found in platelet.creatinine,uric acid,ALT and AST.MAP after etoricoxib treatment was increased compared with pretreatment ( P < 0.05 ). Drug related adverse experiences appeared in 15 cases (31.2 % ) in etoricoxib treatment and 12 cases(33.3 % ) in meloxicam treatment(P=1.000).The ratio of gastrointestinal tract-related adverse effects in meloxicam treatment was higher than in etoricoxib (22.2% vs.6.2%,P< 0.05),while adverse effects on cardiovascular in etoricoxib treatment were comparable to that of meloxicam (16.7 % and 11.1 %,P>0.05). Conclusions Etoricoxib at a dose of 120 mg once daily may be more effective than meloxicam for acute gout in aspects of safety and tolerance.
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Objective To investigate the clinical characteristics of bronchopulmonary amyloidosis secondmy to primary Sj(0)gren's syndrome (pSS).Methods One patient in our series and 42 patients in the literatures were analyzed.The clinical manifestations,imaging features,diagnosis,treatments and prognosis of these patients were described respectively.Results Among the 43 cases,42 patients were female (98%).The median age was 57 (range 29-79) years.The diagnosis of bronchopulmonary amyloidosis was made subsequently to that of pSS with a median delay of 8.9 (range 0-30) years.Thirty-eight cases (88%) were localized amyloidosis.Most cases were related to AL amyloidosis (21/28,75% ).The main clinical manifestations included cough (18/38,47%),short of breath (13/38,34% ),sputum (9/38,24%) and hemoptysis (5/38,13% ).Nine patients (9/38,24% ) had no clinical symptoms.The most common patterns of radiological manifestations included multiple nodules (40/43,93%),multiple cysts or bullae (16/43,37%),interstitial lung disease (16/43,37% ),irregular luminal narrowing and airway wall thickening (8/43,19% ).The pulmonary function test was done in 17 patients,which revealed moderate to severe reduced diffusion capacity for carbon monoxide (8/17,47% ).The diagnosis of amyloidosis was made based on pathological findings in all cases.Pathologic examination showed diffuse deposits of amorphous,eosinophilic,Congo-red positive staining material.The treatments were symptomatic.The prognosis of most patients was good.The median follow-up time was 26.5 (range 2-96) months,only 2 patients died during the follow-up.Conclusion The bronchopulmonary amyloidosis secondary to pSS is localized amyloidosis in most cases.Clinical manifestations depend on the location and extent of airway lesions.The appearance of multiple lung nodules with calcified or cysts in chest images should be considered as secondary amyloidosis.No specific therapy is available for these cases,however,this condition in majority of patients progresses slowly.
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ObjectiveTo evaluate the clinical and radiological efficacy of TNFR Ⅱ -Fc combined with methotrexate( MTX ) in treatment of patients with moderate and severe rheumatoid arthritis.MethodsThree hundred and ninty-six RA patients were randomized into the combined treatment group,the TNFR Ⅱ -Fc only group and MTX only group.All patients were treated for 24 weeks.ACR-N,ACR20,ACR50,ACR70,DAS28-ESR and Sharp score of both hands were measured for efficacy,and the side-effects were analyzed by one-way ANOVA.Results After 24-week therapy,the ACR-N of the combined treatment group [( 12.79±9.24)%-year] was significantly improved than that of the TNFR Ⅱ-Fc only group [(9.56±11.16)%-year,P<0.05] and that of the MTX only group[(5.08±11.10)%-year,P<0.05],and the TNFR Ⅱ-Fc group was significantly improved than that of the MTX group(P<0.05).The ACR20 response rate of the combined group(80.4%) was significantly higher than that of the TNFR Ⅱ -Fc group(71.1%,P<0.05) and the MTX group(56.7%,P<0.01 ).The ACRS0 response rate of the combined group(53.6%) was significantly higher than that of the MTX group(30.8%,P<0.01 ).The ACR70 response rate of the combined group was 27.7%,which was significantly different from that of the TNFR Ⅱ -Fc group (15.8%) and MTX group (7.7%,P<0.05or P<0.01 ).DAS28-ESR in the combination group was significantly reduced than those of the TNFR Ⅱ -Fc group and MTX group,and the DAS28-ESR of the TNFR Ⅱ -Fc group was significantly reduced than MTX group.The average total Sharp score of both hands,which demonstrated the radiographic changes,was significantly reduced in the combination group than the MTX group(P=0.03).The total adverse events in the combined group(40.9%) was significantly high than that of the MTX group(28.8%,P<0.05).Conclusion TNFR Ⅱ -Fc combined with MTX can effectively control the activity of RA and radiological progress.
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ObjectiveTo evaluate the efficacy and safety of etanercept 50 mg once-weekly treatment of Chinese patients with active ankylosing spondylitis ( AS).Methods Four hundred patients with active AS,enrolled in six medical centers,were randomly divided into either the treatment group or the placebo group in a 3∶1 ratio.The total length of the study was 12 weeks.The first 6-week period was a double-blind placebo controlled treatment period and the second 6-week period was an open-labeled treatment period.During the first 6-week period,300 patients in the treatment group received once-weekly subcutaneous injection of etanercept (50 mg),whereas the 100 patients in the placebo group received placebo injection.During the second 6-week period,patients in both groups received etanercept (50 mg once weekly subcutaneous injection).The primary end point was the percentage of patients achieving the Assessments in Ankylosing Spondylitis (ASAS) 20% response ( ASAS 20 ) at week 6.Other outcome measures included the percentage of patients achieving ASAS 5/6,partial remission and Bath AS disease activity index 50 ( BASDAI 50) responses at week 12.ResultsA total of 381 patients completed the trial,including 285 patients in the etanercept group and 96 patients in the placebo group.At week 2,the percentage of patients achieving ASAS 20 in the etanercept group was 55.7%,whereas the placebo group was only 17.0% ( P < 0.001 ).At week 6,77.5% of patients in the etanercept group achieved ASAS 20 as compared with 32.3% in the placebo group ( P < 0.001 ).At the end of 12 weeks,the percentage of patients in the etanercept group achieving the ASAS 20 was 89.5%.Improvements of other measures were also significant in the etanercept group.Etanercept was well tolerated and no malignancy and life-threatening events were observed in this study.Most adverse events observed were mild injection-site reactions.ConclusionEtanercept 50 mg weekly treatment of Chinese patients with active ankylosing spondylitis is convenient,fast-acting,highly effective,and well tolerated.
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Objective To analyze the death causes of of dermatomyositis(DM)and polymyositis(PM)patients with interstitial pneumonia.Methods A retrospectively analysis of the clinical and laboratory characteristics of 15 dead DM and PM patients with interstitial pneumonia was carried out,and 23 survivors served as controls.Results The age of the dead group was(50.1?12.0)years old,and 12(80%)patients died within the six months after onset.The mortality was higher in the acute or subacute interstitial pneumonia patients than that in the chronic patients.With longer course of the disease,lung infections became the major cause of death.Significantly higher serum lactate dehydrogenase,glutamate- pyruvate transaminase,glutamic-oxalacetic transaminase levels were found in the dead group.The dead group had higher incidence of dyspnea and“Velcro”-like crackles and louer arterial oxygen pressure.The elevation of lactate dehydrogenase indicated worse prognosis.The elevation of creatine kinase and anti Jo-1 antibody werent the death causes. Conclusion The early onset of interstitial lung disease and lung infection were the major death causes in dermatomyositis and polymyositis patients.The earlier treatment of pneumonia-may improve the prognosis and reduce mortality.
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Objectives To assess the presence of autoantibodies directed against the epitopes of SmB and SmD in systemic lupus erythemotosus(SLE) as well as other different connective tissue diseases(CTDs) and analyze the clinical significance of them.Methods Polypeptides of SmB and SmD were designed with the animo acids sequence by the biologic technical software.The sera from different patients including 102 SLE,153 other CTDs and 54 controls were detected by ELISA with thesynthetic polypeptides.Results The positive percentage of anti-SmB and antiSm-D epitopes were higher in SLE than in other groups (P
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Objective To investigate the plasma level of free radicals and antioxidative activity in elderly patients with type 2 diabetes mellitus and relation to microvascular complication. Methods The concentration of erythrocyte lipoperoxides(LPO), plasma vitamin E(VE), plasma vitamin C(VC), plasma betacarotene(? CAR), whole blood glutathione(GSH) and the activity of erythrocyte superoxide dismutase(SOD), erythrocyte catalase (CAT), erythrocyte glutathione peroxidase(GSH PX) in 65 elderly patients with type 2 diabetes and 65 healthy patients were measured. Meanwhile, fasting glucose, 2 hours post meal glucose, glycated hemoglobin, fasting and post meal C peptide, triglycerides, cholesterol, urine albumin excretion rate, electromyogram were measured. Results Compared with the healthy patients, the average value of LPO(42 97?6 99)nmol/g and (31 59?7 44)nmol/g, VC (40 98?10 51)?mol/L and (52 23?10 51)?mol/L, VE (16 44?2 45)?mol/L and (23 04?5 38)?mol/L, ? CAR (1 19?0 23)?mol/L and (1 63?0 40)?mol/L and GSH(0 98?0 16 vs 1 25?0 20) in elderly patients with type 2 diabetes were significantly increased, while the activities of SOD(1712 44?157 04)U/L and (1 928 38?143 44)U/L, CAT(217 01?29 36)?g/g vs (264 40?63 55)?g/g, GSH PX(21 01?3 38)?10 -10 U/RBC vs (25 16?6 41)?10 -10 U/RBC were obviously decreased. The change was more obvious in the patients with microvascular complication compared with those without microvascular complication. Plasma level of LPO were correlated positively with age(r=0 310, P
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Objective:Measured the soluble forms of intercellular adhesive molecule 1 (sICAM 1), soluble vascular cell adhesion molecule ( sVCAM 1) and interleukin 1(IL 1),tumor necrosis factor(TNF), interferon ?(IFN ?),study the role of sICAM 1 and sVCAM 1 in rheumatoid arthritis(RA).Methods:A sandwich ELISA technique was used to measure the serums levels of sICAM 1, sVCAM 1 ,IL 1,TNF,IFN ? in 30 patients with active RA and 30 normal control subjects.Results:The levels of sICAM 1 and sVCAM 1 in patients with RA were significantly higher than that in control subjects(P