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Antiphospholipid syndrome (APS) is a systemic autoimmune disorder with vascular, obstetric, and hematological manifestations associated with thrombotic and inflammatory mechanisms orchestrated by antiphospholipid (aPLs) antibodies. Current clinical practice in APS is highly variable duo to lack of high quality of evidence. Here, Chinese Rheumatology Association developed recommendations for management of APS in China. The recommendations cover the early diagnosis, disease evaluation, thrombotic risk assessment, and treatment.
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Objective:To explore the expression and predictive value of serum CD36 level in cardio-vascular risk in patients with rheumatoid arthritis (RA) and to provide a new theoretical basis for clinical iden-tification and prediction of patients at moderate and high cardiovascular risk in RA patients.Methods:Eighty-four RA patients hospitalized to the Department of Rheumatology and Immunology of the second hospital of Lanzhou University in Gansu Province were selected as the study subjects, and 34 healthy people were selected as the controls. All RA patients were divided into low cardiovascular risk groups and medium and high cardiovascular risk groups according to prediction for ASCVD risk in China (China-PAR) cardiovascular risk assessment. At the same time, they were tested for serological indicators at admission. Statistical Product and Service Solutions (SPSS)) 26.0 software was used for the statistical data analysis. T-test and nonparametric test were used for comparison of the measurement data. The Chi-square test and Fisher's exact test were used for the comparison of classified data. Variables with P<0.05 in univariate analysis were included into the Logistic regression model. Results:Compared with the healthy control group, the number of patients with medium and high cardiovascular risk in RA[8 cases (23.5)% and 38 cases (45.2)%, χ2=4.80, P=0.029] was significantly higher and was negatively correlated with serum CD36 ( r=-0.27, P<0.05). Logistic regression analysis showed that age [ OR(95% CI)=1.654(1.157, 2.365), P=0.006] and diastolic blood pressure [ OR(95% CI)=1.225(1.040, 1.442) , P=0.015] were independent risk factors for medium and high cardiovascular risk in RA patients, and serum CD36 level [ OR(95% CI)=0.569(0.352, 0.922) , P=0.022] was the protective factor of medium and high cardiovascular risk in RA patients according to the results of Logistic regression analysis. The area under the receiver operating characteristic (ROC) area under the curve (AUC) was 0.691, the cut-off value was 4.27 pg/ml, and the sensitivity and specificity were 89.7% and 41.0% respectively. Conclusion:The serum CD36 level decreases with the increase of cardiovascular risk in RA patients. A higher serum CD36 level is a protective factor of cardiovascular risk in RA patients, and CD36 has a certain predictive value for cardiovascular risk in RA patients and is a potential predictor.
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Objective:To explore the clinical application and long-term safety of hydroxychloroquine sulfate (HCQ) in the treatment of rheumatic diseases.Methods:A multi-center cross-sectional study was conducted between August 2017 and August 2018 in a random sample of eleven medical institutions of rheumatology and immunology in China. Patients who took HCQ for more than 3 months were enrolled into this study. The cumulative dose and long-term side effects of HCQ were recorded. The changes of laboratory indexes before and after treatment with HCQ were analyzed. Categorical variables were presented with counts and proportions, and evaluated by Chi-square test. Continuous parametric data were presented as Mean±standard deviation, and evaluated by Student's t test or Mann-Whitney U test. P-values less than 0.05 were considered statistically significant. Results:A total of 886 patients with rheumatic diseases were enrolled into this study, including 505 cases with systemic lupus erythematosus (57.0%), 210 cases with rheumatoid arthritis (23.7%), 80 cases with Sj?gren's syndrome (9.0%), 57 cases with undifferentiated connective tissue disease (6.4%), 12 cases of systemic vasculitis (1.4%), 10 cases of mixed connective tissue disease (1.1%), 7 cases of myositis (0.8%) and 5 cases with systemic sclerosis (0.6%). The most common long-term side effects of HCQ was skin or mucous lesions (12.4%) and vision problems (8.0%). Other adverse reactions included problems of digestive system (3.0%), nervous system (2.1%), musculoskeletal system (1.1%) and cardiovascular system (0.9%). 140 cases (15.8%) had stopped taking HCQ during the treatment. More than half of them decided to stop taking medicine by themselves. Fifty-four patients (6.1%) stopped using HCQ due to side effects while 24 of them took it again, and another 12 patients (1.4%) stopped the drug due to remission of illness. Patients were divided into three groups according to the cumulative dose of HCQ: less than 500 g, 500-1 000 g and more than 1 000 g respectively. There was significant difference in the incidence of long-term side effects among the three groups ( χ2=6.382, P=0.041). The last group (more than 1 000 g) suffered the highest incidence of long-term adverse reactions (37.1%). No severe adverse drug reactions were observed in this study. Conclusion:Hydroxychloroquine is widely used in the treatment of rheumatic diseases. The incidence of long-term side effects is 20.4%, is 6.1% lead to drug withdrawal, which are especially related to the cumulative doses. It should be adjusted properly according to the clinical application.
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Objective To observe the efficacy and safety of tocilizumab combined with methotrexate (MTX) in the treatment of refractory adult-onset Still's disease (AOSD), and to explore whether it is possible to reduce the dose of tocilizumab when disease is under control. Methods Twenty-eight patients with refractory AOSD received the treatment of tocilizumab (8 mg/kg, Intravenous infusion every 4 weeks, and reduced to 8 mg/kg every 8 weeks after 6 months of remission) combined with MTX (12.5 mg oral intake per week). The clinical efficacy, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), ferritin level and dose change of glucocorticoid (GC) were observed prior to treatment initiation and 2, 4, 8, 12, 24, 36, 48 weeks after treatment. All adverse reactions were recorded. The Chi-square test and repetitive measure analysis of variance were used for statistical analysis. Results Compared with the baseline levels, our results showed that after 8-weeks of treatment with tocilizumab all patients had normal body temperature, while skin rash, joint swelling and pain disappeared. CRP [(125.4 ±48.3) mg/L, (6.1 ±2.5) mg/L vs (4.9 ±1.8) mg/L , F=77.034, P<0.01], ESR [(103±31) mm/1 h, (17±7) mm/1 h vs (16±4) mm/1 h, F=55.73, P<0.01], white blood cells count [(18.1± 5.3)×109/L, (8.2±2.9)×109/L vs (7.2±2.1)×109/L, F=24.71, P<0.01], neutrophils count [(16.7±4.9)×109/L, (6.1± 2.2)×109/L vs(4.9±2.3)×109/L, F=35.295, P<0.01], blood platelets [(312±83)×109/L, (199±40)×109/L vs (204± 47)×109/L, F=7.139, P<0.01], hemoglobin [(100±9) g/L, (116±9) g/L vs (277±102) g/L, F=9.852, P<0.01], ferritin level [(3542±1313) ng/ml, (2342±923) ng/ml vs (277±102) ng/ml), F=34.232, P<0.01] were improved significantly, clinical symptoms and laboratory tests continued to improve at week 12, 24, 36 and 48, the doseof prednisone was reduced from (71.4±20.7) mg/d to (55.0±11.1) mg/d (P<0.05) After 2 weeks, and the dosage was gradually reduced to 3.3±2.1 mg/d (P<0.05) at the end of 48 weeks. Five (17.9％) patients discontinued prednisone after 36 weeks, and 7 (25％) patients at week 48, no serious adverse events were found during the treatment. Conclusion Tocilizumab can rapidly and significantly improve clinical symptoms and laboratory tests of patients with refractory AOSD and it also can help with the reduction of GC dosage. In addition, the disease remains stable after the dose reduction of tombuzumab. The safety profile is good.
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Objective To detect the levels of procalcitonin in multiple genes autoinflammatory disease (adult Still disease,systemic juvenile idiopathic arthritis,crohn's Crohn's disease),and to explore the relationship between erythrocyte sedimentation rate (ESR),C-reactive protein (CRP),ESR/CRP and disease or complicated infection combined disease.Methods One hundred and fifty-three patients were en-rolled,88 patients with multiple genes autoinflammatory disease,including 32 cases of adult Still disease,27 cases of systemic juvenile idiopathic arthritis,29 cases of Crohn's disease.In addition,30 cases of healthy controls,35 patients with systemic lupus erythematosus (SLE) were included into this study.Electroche-miluminescence was used to test the value of serum PCT,erythrocyte sedimentation rate was tested by blood sedimentation instrument method,the CRP level was tested by lmmunoturbidimetry,and the data was handed managed and analysised by matlab software and One-way analysis of variance (ANOVA) was used to compare the differences of PCTs between groups.Results ① In the non-infection condition,the PCT value of the autoimmune inflammatory diseases [(0.36±0.74) μg/L,95％confidence interval (CI) (0.174 9,0.550 9) μg/L)] was signifieantly higher than that of the healthy control group [(0.06±0.06) μg/L,95％CI (0.035 1,0.081 7 μg/L)],the difference was statistically significant (F=5.03,P=0.027 4),but there was no statistically significant (F=1.03,P=0.475 5) when comparing with SLE group.② The PCT level of the non-infected inflammatory enteric arthritis [(0.20±0.32),95％CI(0.042 7,0.364 3) μg/L] was different compared with the healthy group,the difference was statistically significant (F=5.77,P=0.020 4),at the same time,the difference was not statistically significant when comparing with the SLE group (F=0.22,P=0.647 6).When the PCT value in non-infected adults Still disease [(0.60±1.02) 95％CI(0.048 4,1.153 6) μg/L] compared with the healthy group,the difference was statistically significant (F=7.22,P=0.01) but the difference was not statistically different when compared with the SLE group (F=2.65,P=0.114 3).The PCT level difference was statistically significant (F=2.23,P＜0.01)when comparing infection-free juvenile idiopathic arthritis [(1.52±2.02) μg/L,95％CI(0.054 8,4.591 9) μg/L] and the healthy group,the difference was statistically significantly different (F=8.34,P=0.004 7) when compared with the PCT of the non-infected SLE group.③ In the case of autoinflammatory diseases without infection,the 95％CI of ESR/CRP ratio was between 1.121 2 and 3.589 4.In the case of co-infection,the 95％ CI of ESR/CRP ratio was between 1.502 2 and 8.718 8,so we considered autoimmune inflammatory diseases might had a high possibility of co-infection when the ESR/CRP ratio was higher than 3.5.Conclusion ① The multiple genes autoinflammatory disease group has a higher value of PCT level than healthy controls even without infection.② The mean and 95％CI range of PCT of the inflammatory bowel disease arthritis,adult Still disease and the juvenile id-iopathic arthritis is significantly higher than the healthy controls,partially higher than SLE group.In addition,the PCT level in the juvenile idiopathic arthritis is the highest.③ In clinical,to estimate whether the multiple genes autoinflammatory disease has bacterial infection,we can't just simply rely on PCT to estimate whether the multiple genes autoinflammatory disease has bacterial infection,we may consider the ratio of the ESR/CRP,when the value is higher than 3.5,we may consider patients has strong probability with infection.
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Objective To explore the potential effects of neutrophil extracellular traps (NETs) on rheumatoid arthritis synovial fibroblasts (RA-FLSs).Methods The synovial tissues of RA patients were isolated and cultured in vitro.Peripheral blood neutrophils were extracted from healthy volunteers and used to stimulate NETs' formation,following with NETs' extraction.MTS proliferation assay was used to evaluate the effect of NETs on the proliferation of RA-FLSs.QRT-polymerase chain reaction (q-PCR) was used to determine the expression of connective tissue growth factor (CTGF) mRNA in cells treated with NETs-stimulated RA-FLSs for 60 h.The results were processed using paired sample t-test and one-way analysis of variance (ANOVA).Results The isolated and purified neutrophils could form NETs by in vitro stimulation.The concentration of extracted NETs-DNA was 58.5 ng/μl (1×106 cells).Compared with the control group (0 μl NETs),NETs could promote the proliferation of RA-FLSs.With the increase of NETs' concentration,the proliferation of RA-FLSs was also enhanced (F=99.519,P＜0.05).Compared with the control group (0 μl NETs),10 μl NETs could significandy promote the proliferation of RA-FLSs (t=-12.226,P＜0.01).Pretreatment of NETs with DNase Ⅰ inhibited its effect on promoting the proliferation of RA-FLSs (t=-2.376,P=0.049),NETs stimulated the upre-gulation of CTGF mRNA expression in RA-FLSs [(30.7±0.5),t=12.13,P＜0.01].Conclusion NETs can promote the proliferation of RA-FLSs and stimulate the up-regulation of CTGF mRNA in RA-FLSs in vitro.
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Objective To study the function of interleukin (IL)-25 for rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) differentiation as well as on the expression of extracellular regulating protein kinase (ERK) and matrix metalloproteinases-3 (MMP-3).Methods The differences on ERK1/2 and MMP-3 protein levels were tested in RA-FLS of RA patients and healthy controls,then IL-17A (10 ng/ml) was tested when the RA-FLS were co-stimulated with different concentrations of IL-25 (0.01,0.1,1 and 10 ng/ml) and IL-17A(10 ng/ml) for 24 hours respectively.The expression of ERK1/2 and MMP-3 protein was detected by the Western blot.T test was used for the comparison between different groups.Results The expression of ERK1/2 (1.71±0.17) and MMP-3 (0.50±0.13) proteins in RA-FLS was higher than the healthy controls (0.50±0.15,0.17±0.05) (t=-9.13,P＜0.01 and t=-4.10,P＜0.05),after stimulated with IL-17A,the expression of ERK1/2 (0.77±0.22) and MMP-3 (0.59±0.13) proteins in RA-FLS were increased compared with the untreated groups (0.18±0.35,0.04±0.03) (t=-4.69,P＜0.01 and t=-7.47,P＜0.01).With increase of the concentration on IL-25,the level of ERK1/2 (0.54±0.26,0.48±0.18,0.48±0.23,0.23±0.06) and MMP-3 (0.58±0.09,0.59±0.14,0.21±0.04,0.04±0.02) in RA-FLS which were stimulated by IL-17A was decreased slowly (t=4.22,P＜0.05 and t=4.95,P＜0.01 and t=7.47,P＜0.01).Conclusion IL-25 can inhibit the stimulation of IL-17A on ERK1/2 and MMP-3 fractionally,which implies that it may take part in the development of RA through this pathway and may be a target for the RA treatment.
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Objective To investigate the possible differences in safety and efficacy between re-use and initial use in patients with ankylosing spondylitis (AS) treated with tumor necrosis factor inhibitors (TNFi). Methods From October 2016 to October 2017, 82 patients with AS who were admitted to the Second Hospital of Lanzhou University were studied. Among them, 57 patients used TNFi for the first time and 25 patients reuse it after the interruption. After 3 months of standardized use of TNF-inhibitor, we compared the efficacy indicators [visual analogue scale/score (VAS), morning stiffness, bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), Bath ankylosing spondylitis metroloty index (BASMI), ankylosing spondylitis disease activity score (ASDAS), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) 0 and safety events between the two groups. T test and covariance analysis were used. Results The efficacy indexes of the two groups after treatment were significantly improved, the difference was statistically significant (P<0.05) compared with the baseline [Before and after treatment in the first treatment group: ESR: (40±31) mm/1 h, (8±8) mm/1 h, CRP: (28±35) mg/L, (5±9) mg/L, VAS: (6.5±1.6), (2.0 ±1.7), Morning stiff time: (0.6 ±0.4) h, (0.1 ±0.2) h, BASDAI: (5.0 ±1.3) h, (1.6 ±1.2) h, BASFI: (4.1 ±2.3), (1.3±1.3), BASMI: (2.6±2.0), (0.8±1.0), ASDAS: (3.5±0.8), (1.2±0.7); Before and after treatment in the re-use group: ESR: (39 ±33) mm/1 h, (9 ±10) mm/1 h, CRP: (28 ±28) mg/L, (5 ±6) mg/L, VAS: (6.6 ±1.9), (1.6 ±1.0), Morning stiff time:(0.6±0.4) h, (0.1±0.1) h, BASDAI:(5.1±0.8), (1.4±1.4), BASFI (5.1±2.2), (1.3±1.4), BASMI:(3.4 ±1.8), (1.0 ±0.9), ASDAS: (3.6 ±0.8), (1.2 ±0.4)]. But there was no statistical significant difference between the two groups in patients after treatment (P>0.05). Conclusion Patients with AS who re-uses TNFi after discontinuation could achieve the same safety and efficacy as they first use it.
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This article reports one hepatic echinococcosis patient complicated with systemic sclerosis. His clinical manifesta?tions were the progressive fibrosis of the skin,sour regurgitation,and belching. The blood examination showed that eosinophils was reduced,and antinuclear antibody(ANA)was positive at 1∶100 in cytoplasm particle type. He was given prednisone ace?tate 25 mg,q. d.,aspirin 100 mg,q. d.,centella triterpenes cream 12 mg t. i. d.,esomeprazole 40 mg q. d.,and domperidone 10 mg t. i. d. After one week,the Rodnan skin score reduced from 27 to 17. The liver hydatid cyst resection was performed,and the follow?up showed that his clinical manifestations improved and the Rodnan skin score reduced further.
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Objective To observe clinical effect of treating diabetic peripheral neuropathy with Shuxuetong injection combined herbal oral administration. Methods A total of 51 patients with diabetic peripheral neuropathy were randomly recruited into a control group and a treatment group. The control group was treated with western medicine, and the treatment group was treated with Shuxuetong injection combined with Buyang Huanwu decoction. The clinical effect was observed in both groups after the treatment. Results The total effective rate was 88.5% and 68.0% in the treatment group and the control group respectively. The clinical effect in the treatment group was significantly higher than that of the control group (P＜0.05). Conclusion The effects of Shuxuetong injection combined herbal oral administration on diabetic peripheral neuropathy was better than western medicine.
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Objective To investigate the role of astroglial glutamate-glutamine shuttle in the development of neuropathic pain (NP) in rats. Methods Forty-eight adult male SD rats weighing 200-230 g were randomly divided into 8 groups (n =6 each): Ⅰ control group (group C);Ⅱ sham operation group (group S);group ⅢNP;Ⅳ-Ⅶ 0.01, 0.03, 0.05 and 0.10 mmol/L methionine sulfoximine (MSO, an inhibitor of glutamine synthetase (GS)) group (group M1-4 );Ⅷ MSO + glutaminate group (group MG). In group C no operation was performed. In group S the sciatic nerve was only exposed but not ligated. NP was induced by ligation of the tibial nerve and commom peroneal nerve according to the technique described by Dixon. After the establishment of the model, intrathecal PBS 50 μl was injected in group NP, IT 0.01, 0.03, 0.05 and 0.10 mmol/L MSO 50 μl was injected intrathecally in group M1-4, and 0.05 mmol/L MSO 50 μl was injected intrathecally and then 0.25 mmol/L glutamine 50 μl was injected intrathecally 15 min later in group MG. Mechanical pain threshold was measured 1 week before ligation (T0 , baseline), 1 week after ligation (T1) and 15, 30, 45 and 60 min after injection of MSO (T2-5). Then rats were killed and the lumbar segment of the spinal cord was removed for determination of the expression of glial fibrillary acidic protein (GFAP) and GS and the co-expression (GFAP/GS) in the dorsal horn.Results Mechanical pain threshold was significantly lower at T1-5 in group MG and NP and at T2-4 in group M3.4 ,and the expression of GFAP, GS and GFAP/GS was significantly higher in group MG,NP and M3 than in group S and C ( P ＜ 0.05) .Conclusion Astroglial glutamate-glutamine shuttle in the spinal cord is involved in the development of neuropathic pain in rats.