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Sjögren's syndrome （SS）， a disorder of immune system， is one of the dominant diseases treated by traditional Chinese medicine （TCM）. China Association of Chinese Medicine organized experts in the field of TCM and western medicine rheumatology and pharmacology to discuss the advantages and optimal regimens of TCM for the treatment of SS. The experts generally agreed on the low early diagnosis rate of SS and the lack of targeted therapeutic drugs. In addition， autoimmune abnormality is the key factor in the occurrence of SS and deficiency of both Qi and Yin is the core pathogenesis. SS has unique tongue manifestations， which is expected to allow for the early diagnosis and treatment with integrated traditional Chinese and western medicine. TCM has advantages in treating SS in terms of alleviating clinical symptoms and systemic involvement， individualized treatment， relieving sleep and mood disorders， preventing the occurrence in the early stage， and enhancing the effectiveness and reducing toxicity in the treatment by integrated TCM and western medicine. In general， TCM has advantages in different stages of SS. Internal and external use of TCM， acupuncture， and acupotome are all available options. The optimal regimens should be determined on the basis of pattern identification， stage of disease， and the advantages of TCM. Clinical characteristics and biomarkers of SS should be studied to classify patients， so as to design precision evidence-based TCM regimens for SS. On the basis of unique tongue manifestations of SS， models for early diagnosis and poor prognosis identification of SS should also be established to achieve early prevention and treatment and to improve the prognosis. In the future， we should vigorously carry out high-quality evidence-based medical research on the treatment of SS by TCM and integrated traditional Chinese and western medicine and develop relevant guidelines to optimize and standardize current diagnosis and treatment， thereby laying a basis for clarifying and explaining the advantages of TCM in treating SS.
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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 explore the effect of massive blood transfusion on inflammatory factors, islet B cell function, incidence and mortality of multiple organ dysfunction syndrome (MODS) in patients with severe traumatic hemorrhage. 【Methods】 214 traumatic hemorrhage patients who received blood transfusion and were hospitalized in the Third People′s Hospital of Xingtai from January 2015 to June 2019 were enrolled and divided into the routine blood transfusion group (n=118) and massive blood transfusion group (n=96) according to the amount and method of blood transfusion. The changes of the inflammatory factors such as TNF α and IL-6, the functional indexes of Islet B cells such as HOMA-B and Δ INS30 / Δ GLU30, and the incidence and mortality of MODS in two groups 3 d after blood transfusion were observed. 【Results】 The level of TNF α(ng/L), IL-6(ng/L), HOMA-B and Δ INS30 / Δ GLU30 were (64.21±8.41) vs (30.75±5.26), (216.52±17.99) vs (152.45±16.26) (58.55±10.23) vs (103.47±17.48) and (2.95±0.69) vs (5.87±1.30) in the massive transfusion group and routine transfusion group, respectively (P<0.01). The incidence of MODS was 63.54%(61/96) vs 40.07%(52/118)(P<0.01) while the mortality of MODS was 46.88%(40/118) vs 33.90% (P>0.05). 【Conclusion】 The massive blood transfusion could increase the incidence of MODS in patients with severe traumatic hemorrhage by promoting inflammatory reaction and dysfunction of islet B cells.
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Objective:To analyze the clinical characteristics of anti-cyclic citrullinated peptide (CCP) antibody-negative rheumatoid arthritis (RA) patients.Methods:To retrospectively analyze the medical records of RA patients hospitalized in the department of rheumatology and immunity of Peking University Third Hospital from January 2013 to December 2018, we collected the baseline characteristics, joint manifestations, extra-articular manifestations, and laboratory parameters of RA patients, and compared the differences between anti-CCP antibody-negative patients and anti-CCP antibody-positive patients by U test and chi-square test. Results:A total of 486 RA patients were included in this study, including 153 anti-CCP antibody-negative patients (31.5%) and 333 anti-CCP antibody-positive patients (68.5%). Compared with anti-CCP antibody-positive group, anti-CCP antibody-negative group had shorter disease course ( U=-4.750, P<0.01) and the pro-portion of morning stiffness, shoulder or elbow joint involvement, and hand arthritis ( P<0.05) was lower, while the incidence of phlebothrombosis of leg ( χ2=4.100, P=0.043) was higher, as well as thrombocytosis ( U=-2.179, P=0.029) and elevation of CRP ( U=-2.154, P=0.03). Subgroup analysis based on RF showed that CCP RF + group had higher percentage of women ( P=0.042) and higher incidence of interstitial lung disease ( χ2=5.652, P=0.017) and secondary Sj?gren's syndrome ( χ2=11.211, P=0.001), compared with CCP RF - group. Conclusion:anti-CCP antibody-negative-patients have similar clinical char-acteristics with anti-CCP antibody-positive group, but the involvement of shoulder or elbow joint and hand arthritis are less common in anti-CCP antibody-negative group. Meanwhile the incidence of phlebothrombosis of leg is higher, and the level of platelet(PLT) and C-reactive protein (CRP) is higher, suggesting that anti-CCP antibody-negative RA may have more vident inflammatory response.
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Objective:To investigate the effects of oxidized low density lipoprotein (Ox-LDL) on cell proliferation and mRNA expression of inflammatory factors in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA).Methods:Tissue culture was used to isolate and 4-6 generation cultured RA-FLS cells were used for subsequent experiments. RA-FLS were stimulated for 24 hours with different con-centr-ations of human Ox-LDL, then the MTS cell proliferation and toxicity test kit were used to detect the prolifer-ation of RA-FLS. Real time-polymerase chain reaction (RT-PCR) was used to test the expression of inflamm- atory factors like interleukin (IL)-6, transforming growth factor (TGF)-β, IL-8, tumor necrosis factor (TNF)-α and receptors like CD36 and scavenger receptor binds phosphatidylsed neoxidized lipoprotein (SR-PSOX) inRA-FLS. T test and F test were used in this study. Results:Ox-LDL (10, 25, 50 μg/ml) could obviously promote the proliferation of RA-FLS, and theabsorbance values (490 nm) were (1.04±0.15), (1.05±0.14), and (1.00±0.10), respectively, all higher than the control group (0.81±0.04) and the difference was statistically significant ( F=4.737, P<0.01). In addition, 50 μg/ml and 100 μg/ml Ox-LDL also promoted the expression of IL-6 mRNA ( F=14.709, P<0.01) and inhi-bited the expression of TGF-β mRNA ( F=299.074, P<0.01), but there was no obvious effect on the expression of IL-8 and TNF-α. Ox-LDL stimulation could obviously promote the expression of SR-PSOX receptor on RA-FLS ( F=68.636, P<0.01) and inhibit the expression of CD36( F=18.085, P<0.01). After the transfection of siRNA, SR-PSOX mRNA level was significantly inhibited and the mRNA expression of IL-6 was significantly decreased after Ox-LDL stimulation of RA-FLS ( t=3.875, P<0.01), while TGF-β mRNA expres-sion was not significantly changed( t=-0.193, P>0.05). Conclusion:Ox-LDL may play a role in promoting the activation of RA-FLS proliferation and the expression of IL-6 mRNA by increasing the SR-PSOX receptor of RA-FLS, suggesting that Ox-LDL is involved in the synovial inflammation of RA.
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Fibrosis is the common pathological basis of various lesions. It is mainly manifested as excess collagen deposition and fibrous connective tissue in tissues with destructed structures and impaired function. At present, the pathogenesis of fibrosis is still unclear, and no effective treatment or prevention for fibrosis is available. In recent years, numerous studies have shown that chemokine CXCL16 and its receptor CXCR6 play an important role in the development of fibrosis. This paper summarizes the biological character-istics of CXCL16/CXCR6 axis and its role in fibrosis.
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Objective To investigate the expression level of oxidized low density lipoprotein (ox-LDL) and its scavenger receptor scavenger receptor that binds phosphatidylserine and oxidized lipoprotein (SRPSOX) in patients with rheumatoid arthritis (RA),and to explore the relationship between ox-LDL and disease activity.Methods The serum ox-LDL in RA patients and healthy control group were detected by enzymelinked immunosorbent assay (ELISA),as well as the fluidox-LDL in RA,osteoarthritis (OA) and inflammatory arthritis (IA).The expression of SR-PSOX in mixed cells of RA and IApatients was detected by western blot.The expression of serum ox-LDL between RA groupand the control group was analyzed by t-test and non-parametric test.The correlation of serum ox-LDL expression levels in RA patients with C-reactive protein (CRP),erythrocyte sedimentation rate (ESR) and other inflammatory factors and disease activitywas analyzed by Pearson linear regression.Results The expression of ox-LDL in the serum of RA patients was significantly higher than that of normal control group [(3 076±131) mU/ml,(2 334±84) mU/ml,t=4.242,P＜0.01].The expression of ox-LDL in synovial fluid of RA patients was significantly higher than that of the OA group [(4 963±354) mU/ml],(3 956±347) mU/ml,t=2.372,P＜0.05).The expression of SR-PSOX in synovial fluid mixed cells of RA patients was higher than that of the IA group [(4.92±0.18) vs (0.24±0.04),t=33.53,P＜0.01].The expression of ox-LDL in serum of RA patients was negatively correlated with ESR,CRP and overall disease activity DAS28 (r=-9.42,P=0.009;r=-0.35,P=0.029 7;r=0.42,P=0.008 4).The expression of ox-LDL in the serum of RA patients with moderate disease activity was significantly higher than those patients with high disease activity [(3 302±138) mU/ml vs (2 464±228) mU/ml,t=3.335,P＜0.01],however,those with low disease activity and disease remission had higher serum ox-LDL expression but without statistical significant differences.After treated with anti-rheumatic drugs (DMARDs),serum ox-LDL of RA patients had a trend of slight increasing butwithout sign-ificant difference.The ox-LDL/LDL-C or ox-LDL/HDL-C was negatively not correlated with disease activity score in 28 (DAS28),ESR,CRP.Conclusion In RA patients,the expression of ox-LDL in the serum and synovial fluid is high and the SR-PSOX expressionin synovial fluid is also high.The serum ox-LDL levels are negatively correlated with ESR,CRP and DAS28,which are related to disease activity of RA.These findings suggest that the ox-LDL and the receptor SR-PSOX may play a role in RA pathogenesis,but needs further study.
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Objective To investigate the expression of miRNA-31 in peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA) patients,and the relationship between miRNA-31 and disease activity of RA.Methods After obtaining the informed consent,peripheral blood samples of 56 RA patients,12 systemic lupus erythematosus (SLE) patients,6 Sj(o)gren's syndrome (SS) patients and 30 healthy controls were collected from the Department of Rheumatology,Peking University Third Hospital.RNA was extracted from the PBMCs which were separated by Ficoll-Paque PLUS.The expression of miRNA-31 in the PBMCs of RA patients,SLE patients,SS patients and healthy controls was detected by real-time Polymerase Chain Reaction (PCR).Furthermore,according to the RA disease activity score (DAS28),RA patients were divided into high,moderate and low disease activity groups and remission group,and miRNA-31 expression was compared between different groups.Data were analyzed using t test or Mann-Whitney U test.Results The expression of miRNA-31 in PBMCs of RA patients was 7.25 times (P=0.003 8) higher when compared with that of the control group.To be specific,the expression of miRNA-31 was 10.63 times in PBMCs of high activity RA group (P=0.01) and 8.95 times in moderate activity RA group (P=0.000 3) when compared with that of the control group,and there was no significant difference between low activity,remission groups and control groups in terms of miRNA-31 expression.Furthermore,the expression of miRNA-31 in PBMCs of SLE patients was not significantly different from the control and miRNA-31 expression in PBMCs of SS patients was 1.64 times (P=0.02) higher than that of the RA patients,but the average level of miRNA-31 was much less than that of RA patients.The increased miRNA-31 may serve as a diagnostic marker for disease activity of RA.
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OBJECTIVE:To investigate the reliability and validity of the Chinese version Morisky Medication Adherence Scales-8 in assessing medication compliance of the patients with rheumatoid arthritis.METHODS:The Chinese version of MMAS-8 was used to evaluate the compliance of 200 rheumatoid arthritis patients who responded to the WeChat public issue from the public forum of China rheumatism.Item analysis,homogeneity test,reliability analysis,and validity analysis were all conducted.RESULTS:The eight items showed significant difference between the two extreme groups as head and tail 27％ of the total score in Levene method F test (P＜0.001).t test of variance inequality was adopted,with significant difference (P＜0.001).Correlation coefficient between the 7 items and the total score was higher than 0.400,and the 8 items were significantly correlated with the total score (P＜0.001).Internal consistency reliability coefficient Cronbach's α was 0.657,and standardized Cronbach's α was 0.662.For construct validity,KMO was 0.638,Bartlett's sphericity test was 246.278,factor analysis method was adopted to extract 3 common factors,and explainable total variance was 58.846％.Pearson correlation coefficient was 0.435 between MMAS-8 total score and MA-VAS score (P＜0.001).CONCLUSIONS:Reliability and validity of the Chinese version MMAS-8 for the determination of medication compliance in patients with rheumatoid arthritis are good.
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Objective:It has been found that serum CXCL16 concentration in rheumatoid arthritis (RA) patients are significantly higher than those in osteoarthritis (OA) and normal subjects, and are positively correlated with disease activity and bone erosion.However, how is CXCL16 involved in the pathogenesis of RA is unclear.To evaluate the expression of CXCL16 and its receptor CXCR6 in fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) patients, and to explore the role of CXCL16 in the proliferation of RA-FLS.Methods: FLS were isolated from knee synovial tissues obtained from 8 patients of RA, 7 osteoarthritis (OA) and 3 normal controls.The diagnosis of RA was in line with the 1987 American Rheumatology Association (ACR) RA classification criteria, osteoarthritis met the 1996 ACR revised knee osteoarthritis classification criteria.Control synovium were obtained from trauma caused knee joint injury in healthy individuals who required surgery.Human knee FLS were cultured by tissue explants adherent method.FLS between passages 3 and 5 were used in the experiment.Expression of CXCL16 and its receptor CXCR6 were performed in Western blot analysis.FLS proliferation follo-wing stimulation with TNF-α and different concentrations of CXCL16 was examined by cell counting kit-8 (CCK-8).Expression of phosphorylated AKT (pAKT) in RA-FLS stimulated by CXCL16 was quantified by Western blot.Different concentrations of recombinant human CXCL16 were added to the culture medium of RA-FLS.After 48 h culture, supernantants were collected, and TNF-α, IL-6, RANKL and MMP3 in culture supernatants of RA-FLS were determined by enzyme-linked immunosorbent assays (ELISA) operated following the kit instructions.Results: Expression of CXCL16 and CXCR6 in RA-FLS was significantly higher than that of OA and controls (P<0.05), but no significant difference was found between OA-FLS and control FLS.Proliferation of RA-FLS was markedly up-regulated after stimulation of CXCL16 (P <0.05).In the case of the CXCL16 stimulated OA-FLS and control FLS, the FLS proliferation remained basically unchanged.Expression of phosphorylated AKT in RA-FLS increased remarkably in condition of CXCL16 (50,100, 200 μg/L) stimulation.The levels of IL-6 and RANKL in culture supernatants of RA-FLS were obviously increased under CXCL16 (200 μg/L) stimulation, while TNF-α and MMP-3 levels in the culture supernatants remained unchanged after CXCL16 (200 μg/L) stimulation.Conclusion: This study shows that the expression of CXCL16 and its receptor was highly elevated in RA-FLS.Recombinant CXCL16 promoted RA-FLS proliferation and activation in vitro.All these indicate that CXCL16 play an important role in the pathogenesis of RA, anti-CXCL16 treatment may help to relieve inflammation and bone damage of RA patients.However, due to the limitations of this study, the role of CXCL16 and its receptors in RA-FLS remains to be elucidated by further research.
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Objective To investigate the clinical efficacy of white mustard seed moxibustion on four flower points [bilateral points Geshu(BL 17) and Danshu(BL 19)] in treating night sweat.Method One hundred and twenty patients with night sweat were randomly allocated to groups A, B and C, 40 cases each. Group A received white mustard seed moxibustion on four flower points; group B, oral administration of zuogui pills; group C, application of millet paste to four flower points. After 22 days of treatment, pre-treatment and post-treatment TCM symptoms and signs of hyperhidrosis scores were compared in the three groups and the clinical therapeutic effects were compared between the three groups.ResultThere was a statistically significant pre-/post-treatment difference in the TCM symptoms and signs of hyperhidrosis score in the three groups (P<0.05). The cure rate and the total efficacy rate were 50.0% and 92.5%, respectively, in group A; 27.5% and 75.0%, respectively, in group B; 12.5% and 50.0%, respectively, in group C. There were statistically significant differences in the cure rate and the total efficacy rate, and the TCM symptoms and signs of hyperhidrosis score between group A and group B or C (P<0.05) and between groups B and C (P<0.05).Conclusion White mustard seed moxibustion on four flower points is an effective way to treat night sweat and can markedly improve its symptoms in the patients.
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Objective To analyze the clinical and laboratory manifestations of primary Sj(o)gren's syndrom (pSS) with neurological involvement.Methods One hundred and forty eight patients fulfilling the 2002 American-European pSS classification criteria were retrospectively analyzed.Neurological manifestations were diagnosed based on the clinical,biological,electrophysiological,and imaging findings.Biographical,clinical,and laboratory data were compared between patients with and without neurological manifestations.Statistical methods used were Mann-Whitney U test,Chi-square test and Fisher exact probability.Results The prevalence of neurological involvement in pSS was 20.3％ (30/148),and the incidence of peripheral neuropathy,the central neuropathy and combination of the central neuropathy with peripheral neuropathy were 10.1％(15/148),9.5％(14/148) and 0.7％(1/148),respectively.The clinical spectrum of peripheral neuropathies encountered in Sj(o)gren's syndrome (SS) patients varied,with the pure sensory neuropathies being the most common,followed by sensorimotor neurophathies.Motor neuron disease was the most common type of central neurophathies.Compared with those without neurological manifestations,the duration of peripheral nerve system/central nerve system (PNS/CNS)-pSS patients was relatively short [(55±76) months vs (100±108) months,Z=-2.682,P＜0.05],and the antinuclear antibody (ANA) titer and RF titer were lower [(234±248) vs (377±339),Z=-2.008,P＜0.05;(126±279) U/ml vs (359±1 445) U/ml,Z=-2.243,P＜0.05].In PNS/CNS-pSS patients,the most common clinical manifestations included numbness (50％),pain (23％),and muscle weakness (63％).Conclusion The prevalence of neurological involvement in pSS is high.The duration is relatively short and the disease activity is high,but the disease features are atypical and may be neglected by rheumatologists.
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Objective To analyze the prevalence and clinical features of cytomegalovirus (CMV)infection in patients with systemic lupus erythematosus (SLE).Methods Patients with SLE in Peking University Third Hospital from 2013 to 2015 and age and sex matched healthy controls were enrolled.All patients were detected for CMV antibody,CMV DNA and CMV PP65 in the blood.The prevalence of CMV infection and the clinical characteristics were analyzed using Chi-square test.Results Altogether 349 SLE patients and 209 healthy controls were enrolled.In SLE group,the positive rate of CMV IgG was 90.3％ (315/349),which was similar to that of the control group,while the positive rate of CMV IgM was 8.0％ (28/349),which wassignificantly higher than controls 1.4％(3/209) (x2=10.811,P=0.001),and the active CMV infection rate was 69.1％(241/349).Those in the active phase of SLE were more likely to have active CMV infection when compared with those in remission [75.4％(93/256) vs 51.6％(48/93),x2=18.049,P＜0.01].The percentage [43.2％(104/241)] of severe patients in those with active CMV infection was much higher than that in those without CMV infection 9.2％(10/108) (x2=38.953,P＜0.01).Those SLE patients had active CMV infection were clinically more severe and the most common clinical manifestation were proteinuria/hemoturia,cytopenia and fever.Conclusion In SLE patients,the positive rate of CMV IgM is significantly higher than healthy control and the prevalence of active CMV infection is high,especially in those at active disease.Those with active CMV infection are clinically more severe but have no features of active CMV infection,which indicates that the CMV infection might be a trigger of SLE activity.
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Objective To explore the diagnostic and differential diagnostic points of patients with rheumatoid arthritis (RA) complicated with fever.Methods Full clinical analysis was performed for a 62-year old patient with RA and fever.Results Hemophagocytes were found in bone marrows smear.Significantly increased ferritin level (74 299 ng/ml),decreased hemoglobin (67 g/L) and platelet (33×109/L),decreased fibrinogen,increased serum soluble CD25 (sCD25),positive cytomegalovirus (CMV) DNA,positive CMV-PP65 antigen,were found by laboratory examination.Decreased activity of NK cells was detected by flow cytometry.Positron emission computed tomography (PET-CT) revealed splenomegaly and pulmonary inflammations.The clinical conditions were recovered with the treatment of corticosteroid,VP16,cyclosporine,anti-CMV virus therapy.Ferritin level was significantly decreased and platelet was normal.The patient was diagnosed as hemophagocytic syndrome associated with CMV infection.Conclusion The possibility of hemophagocytic syndrome should be considered in RA patients presented with fever.
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Objective To investigate the clinical and radiographic features of rheumatoid arthritis (RA) patients with cervical subluxations.Methods The clinical, laboratory and imaging data of 68 RA patients who were hospitalized to our hospital because of cervical syndrome were retrospectively reviewed.The patients were divided into two groups depend based on whether cervical spine subluxations presented or not.Mann-Whitney U test, t test and Person correlation, x2 test were used for statistical analysis.Results This study confirmed the high frequency (11.6％, 39/335) of radiological cervical subluxations in RA patients.The nNeck pain was a common symptom, accounting for 87％ (34/39).Other symptoms included limb numbness 59％ (23/39).The rate of positive C-reactive protein (CRP) in the subluxation group was both significantly higher than that of the non-subluxation group [89％(24/27) vs 59％(16/27),x2=6.17, P＜0.01].Anterior atlantoaxial subluxation (AAS) was the most common form, accounting for 95％(37/39) of all cervical subluxations,followed by vertical subluxation (VS), accounting for 18％ (7/39).Subaxial subluxation (SAS) of the lower cervical vertebrae was less common (5.1％).The ratio of bone destruction, spinal stenosis, spinal cord compression in image findings of the subluxation group was significantly higher than that of the non-subluxation group (x2=7.96, x2=6.12, x2=4.89, P＜0.05).But more hyperostosis and osteosclerosis feature of the non-subluxation group could be observed more hyperostosis and osteosclerosis feature (x2=6.21, P＜0.05).PADI correlated with ADI (r=-0.588, P=0.015).Conclusion This study confirms the high frequency of radiological cervical involvement in patients with RA.AAS is the most common form of cervical involvement and may occur either independently or concomitantly with cranial settling and subaxial subluxation.
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Objective To evaluate the prevalence and clinical significance of IgG,IgA and IgM isotypes of anti-peptidylarginine deiminase 4 (anti-PAD4) antibodies in early rheumatoid arthritis (RA).Methods IgG,IgA and IgM isotypes of anti-PAD4 antibodies were measured in the sera of 88 RA patients with disease duration less than 2 years,62 patients with other rheumatic diseases and 57 healthy subjects.The diagnostic performance of IgG,IgA and IgM isotypes of anti-PAD4 antibodies and their relationship with disease duration,DAS28,ESR,CRP,anti-CCP antibodies and rheumatoid factor (RF) were evaluated.Data analysis were performed using t test,U test and Spearman's association analysis.Results ① The sensitivities of IgG,IgA,and IgM isotypes for early RA were 28.41％,36.36％ and 9.09％ respectively.The specificities of IgG,IgA and IgM isotypes were 94.12％,93.28％ and 95.80％ respectively.② IgA isotype was positively correlated with age (r=0.234,P=0.028),DAS28 (r=0.309,P=0.007),ESR (r=0.382,P=0.000) and CRP (r=0.291,P=0.008),while negatively correlated with disease duration (r=-0.295,P=0.006).③ IgA isotype was positively correlated with IgG isotype (r=0.451,P＜0.01).In the IgG negative patients,the positivity of IgA isotype was 29％(18/63),which indicated that the IgA isotype might be helpful in diagnosing RA in IgG isotype negative patients.Conclusion Anti-PAD4 antibodies can be detected in early RA,primarily with IgA and IgG isotypes.IgA isotype has negative correlation with disease duration,indicating that IgA isotype of anti-PAD4 antibody may play a role in the very early stage RA.
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Objective To construct an eukaryotic expression vector of human B-cell translocation gene 2 (BTG2), to express the FLAG-tagged BTG2 protein in HeLa cells,and to supply an experimental tool for investigating the function of BTG2 gene.Methods The full-length BTG2 fragment was obtained by PCR and inserted into the multiple cloning site of pcDNA3.1 (+)vector. Oligo DNA encoding FLAG tag was designed and inserted into pcDNA3.1(+)-BTG2 to construct another vector pcDNA3.1(+)-FLAG-BTG2.The HeLa cells were divided into pcDNA3.1(+)empty vector group,pcDNA3.1(+)-BTG2 group and pcDNA3.1(+)-FLAG-BTG2 group.The HeLa cells were transfected with recombinant plasmids.Western blotting using anti-FLAG antibody was performed to detect the expression of FLAG-BTG2 protein in HeLa cells.Results The sequence of the vector was verified by both BamH Ⅰ endonuclese digestion and DNA sequencing. The Western blotting analysis confirmed that FLAG-fused BTG2 was detected in pcDNA3.1(+)-FLAG-BTG2 group but not in empty vector or pcDNA3.1(+)-BTG2 groups. Conclusion The eukaryotic expression vector pcDNA3.1(+)-FLAG-BTG2 is successfully constructed and FLAG-tagged BTG2 protein is expressed in HeLa cells.
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Objective To detect v raf murine sarcoma viral oncogene homologue B1 (BRAF) in the synovial fluid of rheumatoid arthritis (RA) and to investigate its clinical significance in RA.Methods Synovial fluid samples were obtained from patients with RA and osteoarthritis (OA).Serum samples were obtained from patients with RA,OA and heathy controls.The presence of BRAF in the synovial fluid and sera were examined by enzyme-linked immunosorbent assay (ELISA).Western blotting was used to detect the expression of BRAF protein in the synovial tissue of RA and OA.The associations between the BRAF and the clinical features and laboratory parameters of RA were evaluated.Data analysis were performed using t test and Spearman's association analysis.Results ① The level of BRAF in the synovial fluid of RA [(84±59) ng/ml] was significantly higher than OA [(38±41) ng/ml] (t=3.290,P=0.002).② The level of BRAF in the sera of RA patients [(22.0±12.5) ng/ml] was also higher than OA [(6.8±7.5) ng/ml,t=3.882,P＜0.01] and healthy controls [(4.8±2.2) ng/ml,t=6.766,P＜0.01].③ In RA patients,the BRAF protein level in the synovial fluid [(102±52) ng/ml] was significantly higher than that in the serum [(21±12) ng/ml] (t=-4.316,P=0.003).④The expression level of BRAF in the synovial tissue of RA (0.284±0.045) was higher than that in OA patients (0.191±0.013,t=3.169,P=0.034).⑤ The level of BRAF in the synovial fluid had a negative correlation with disease duration (r=-0.40,P=0.019) and a positive correlation with rheumatoid factor (RF) levels (r=0.37,P=0.03).Conclusion The presence of BRAF in the synovial fluid and synovium of RA indicates that BRAF may play a role in the pathogenesis of RA,especially in the early stage.
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Objective To evaluate the prevalence and clinical values of anti-cyclic citrullinated peptide (anti-CCP) antibodies of IgG,IgA and IgM subtypes in individuals with early rheumatoid arthritis (RA).Methods IgG,IgA and IgM subtypes of anti-CCP antibodies were measured in the sera of 87 RA patients with disease duration shorter than 2 years,61 patients with other rheumatic diseases and 49 healthy subjects.We analyzed the diagnostic value of IgG,IgA and IgM subtypes of anti-CCP antibodies and their relationship with disease duration,DAS28,ESR,CRP,and rheumatoid factor (RF).Chi-square test,t test and Spearman's correlation analysis were used for statistical analysis.Results ① The diagnostic sensitivity of IgG,and IgA subtype for early RA was 75.9％ and 67.8％ respectively,which was higher than IgM subtype (14％,P＜0.01 each).The specificity of IgG,IgA and IgM subtype was 96.4％,91.8％ and 93.6％ respectively.② IgG and IgA subtypes were correlated with CRP (r=0.278,P=0.01； r=0.217,P=0.047) and RF (r=0.430,P=0.000； r=0.271,P=0.012),while IgM subtype was positively correlated with disease duration (r=0.279,P=0.014).③ Patients who had IgG-and IgA subtype had a shorter disease course (3.3±2.3) than those patients who had IgA-and IgG+ (9.5±8.4) and who had IgG+ and IgA+ (8.2±7.0) (P＜0.05).④ IgA subtype was positive in 19.0％ of the IgG negative patients.When combining IgG,and antibodies of IgA subtypes together,the sensitivity and specificity was 63.2％ and 100％,while the sensitivity and specificity was 80.5％ and 85.2％ when either one was positive.Conclusion Both the IgG,and IgA subtypes of anti-CCP antibodies have a good sensitivity for early RA.They are related to disease activity.Measuring IgA subtype of anti-CCP antibody in RA patients with negative IgG subtype may help to identify early RA.IgA subtype of anti-CCP antibody may play a role in very early RA.
ABSTRACT
Objective To establish new classification criteria for early rheumatoid arthritis (E-RA) based on large samples of early inflammatory arthritis patients and to evaluate the value of this criteria in China.Methods Patients who had arthritic complaints with disease duration less than one year were enrolled.They were divided into RA group and non-RA group according to the clinical diagnosis by experienced rheumatologists.The clinical and laboratory parameters were analyzed and those with high sensitivity or specificity were selected as the new classification criteria.Statistical analysis was carried out by using t test,x2 test and Logistic regression.Results ① A total of 803 patients with early inflammatory arthritis were included in this study.Five hundreds and fourteen patients were diagnosed as early RA and 251 were diagnosed as other rheumatic diseases,and the diagnosis of 38 patients remained unestablished by the end of follow-up.② New E-RA classification criteria were established based on the parameters with high sensitivity and/or specificity.The sensitivity of the new E-RA criteria was 84.4％,which was higher than 1987 ACR criteria (58.0％),while the corresponding specificities were similar,which were 87.4％ and 93.6％ respectively.③ Compared with the complex scoring system of 2010 ACR/EULAR criteria,the E-RA criteria was more simple and practical.The diagnostic sensitivity and specificity of E-RA criteria were higher than those of 2010 ACR/EULAR criteria reported in the literatures.④ New classification criteria based on scoring system using Logistic regression analysis was established.The sensitivity of this criteria was 86.4％,which was higher than 1987 ACR criteria (58.0％).Conclusion The diagnostic value of the E-RA criteria developed in this study for early RA is better than 1987 ACR criteria,and is more simple than 2010 ACR/EULAR criteria.It may be used as a new classification criteria for early RA diagnosis.