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Objective:To investigate the clinical characteristics of patients with rheumatic diseases and abnormal liver function, as well as determine the proportion and severity of liver function abnormalities.Methods:Cross-sectional study. Data were collected from patients registered in the Chinese Rheumatism Date Center from 2011 to 2021. The rheumatic diseases analyzed in this study were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren syndrome (SS), ankylosing spondylitis (AS), and gout. Patient data, including demographic characteristics [ such as age, sex, body mass index,(BMI), and smoking history], liver function test results [including alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase(ALP), and total bilirubin], and use of anti-rheumatic immune drugs and liver-protective drugs, were collected and compared between groups with normal and abnormal liver functions. In addition, the proportions of abnormal liver function were compared between sex and age groups.Results:A total of 116 308 patients were included in this study, including 49 659 with RA, 17 597 with SLE, 9 039 with SS, 11 321 with AS, and 28 692 with gout. The lowest proportion of liver function abnormalities was observed in patients with RA[11.02% (5 470/49 659)], followed by those with SS[17.97% (1 624/9 039)] and AS [18.22% (2 063/11 321) ], whereas patients with SLE [21.14% (3 720/17 597) ] and gout [28.73% (8 242/28 692)] exhibited the highest proportion of these abnormalities. Elevated ALT, mostly classified as grade 1, was the most commonly noted liver function abnormality, whereas elevated ALP was the least common. Some patients who took liver-protective drugs had normal liver function, with the lowest percentage observed in patients with gout [7.45% (36/483) ] and ranging from 21.7% to 30.34% in patients with RA, SLE, SS, and AS. The proportion of liver function abnormalities was higher in males than in females for all disease types [RA: 13.8%(1 368/9 906) vs. 10.3%(4 102/39 753); SLE: 33.6% (479/1 424) vs. 20.0% (3 241/16 173); SS: 25.4%(111/437) vs. 17.6%(1 513/8 602); AS: 20.1%(1 629/8 119) vs. 13.6% (434/3 202); and gout: 29.3% (8 033/27 394) vs. 16.1% (209/1 298)]. In RA, SLE, and AS, the proportions of liver function abnormalities were similar across all age groups. In SS, the proportion of liver function abnormalities increased with age [<40 years: 14.9%(294/1 979); 40-59 years: 18.1%(858/4 741); ≥60 years: 20.4%(472/2 319)], whereas a reversal of this trend was observed in gout [<40 years: 34.9%(4 294/12 320); 40-59 years: 25.5%(2 905/11 398);≥60 years: 21.0%(1 042/4 971)].Conclusions:The proportions of combined liver function abnormalities in patients with rheumatologic diseases were high, and the utilization rates of liver-protective drugs were low. It is necessary to pay more attention to monitoring patients′ liver function, timely administer liver-protective drugs, and optimize liver-protective regimens during the treatment of rheumatic diseases.
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Objective:In general, patients with seropositive rheumatoid arthritis (RA) are considered to show an aggressive disease course. However, the relationship between the two subgroups in disease severity is controversial. Our study is aimed to compare the clinical characteristics and prognosis of double-seropositive and seronegative RA in China through a real-world large scale study.Methods:RA patients who met the 1987 American College of Rheumatology (ACR) classification criteria or the 2010 ACR/European Anti-Rheumatism Alliance RA classification criteria, and who attended the 10 hospitals across the country from September 2015 to January 2020, were enrolled. According to the serological status, patients were divided into 4 subgroups [rheumatoid factor (RF)(-) anti-cyclic citrullinated peptide (CCP) antibody (-), RF(+), RF(+) anti-CCP antibody(+), anti-CCP antibody(+)] and compared the disease characteristics and treatment response. One-way analysis of variance was used for measurement data that conformed to normal distribution, Kruskal-Wallis H test was used for measurement data that did not conform to normal distribution; paired t test was used for comparison before and after treatment within the group if the data was normally distributed else paired rank sum test was used; χ2 test was used for count data. Results:① A total of 2 461 patients were included, including 1 813 RF(+) anti-CCP antibody(+) patients (73.67%), 129 RF(+) patients (5.24%), 245 RF(-) anti-CCP antibody(-) patients (9.96%), 74 anti-CCP antibody(+) patients (11.13%). ② Regardless of the CCP status, RF(+) patients had an early age of onset [RF(-) anti-CCP antibody(-) (51±14) years old, anti-CCP antibody(+) (50±15) years old, RF(+) anti-CCP antibody(+) (48±14) years old, RF(+)(48±13) years old, F=3.003, P=0.029], longer disease duration [RF(-) anti-CCP antibody(-) 50 (20, 126) months, anti-CCP antibody(+) 60(24, 150) months, RF(+) anti-CCP antibody(+) 89(35, 179) months, RF(+) 83(25, 160) months, H=22.001, P<0.01], more joint swelling counts (SJC) [RF(-) anti-CCP antibody(-) 2(0, 6), Anti-CCP antibody(+) 2(0, 5), RF(+) anti-CCP antibody(+) 2(0, 7), RF(+) 2(0, 6), H=8.939, P=0.03] and tender joint counts (TJC) [RF(-) anti-CCP antibody(-) 3(0, 8), anti-CCP antibody(+) 2(0, 6), RF(+) anti-CCP antibody(+) 3(1, 9), RF(+) 2(0, 8), H=11.341, P=0.01] and the morning stiff time was longer [RF(-) anti-CCP antibody(-) 30(0, 60) min, anti-CCP antibody(+) 20(0, 60) min, RF(+) anti-CCP antibody(+) 30(10, 60) min, RF(+) 30(10, 60) min, H=13.32, P<0.01]; ESR [RF(-) anti-CCP antibody(-) 17(9, 38) mm/1 h, anti-CCP antibody(+) 20(10, 35) mm/1 h, RF(+) anti-CCP antibody(+) 26(14, 45) mm/1 h, RF(+) 28(14, 50) mm/1 h, H=37.084, P<0.01] and CRP [RF(-) anti-CCP antibody(-) 2.3 (0.8, 15.9) mm/L, Anti-CCP antibody(+) 2.7(0.7, 12.1) mm/L, RF(+) anti-CCP antibody(+) 5.2(1.3, 17.2) mm/L, RF (+) 5.2(0.9, 16.2) mm/L, H=22.141, P<0.01] of the RF(+)patients were significantly higher than RF(-) patients, and RF(+) patients had higher disease severity(DAS28-ESR) [RF(-) anti-CCP antibody(-) (4.0±1.8), anti-CCP antibody(+) (3.8±1.6), RF(+) anti-CCP antibody(+) (4.3±1.8), RF(+) (4.1±1.7), F=7.269, P<0.01]. ③ The RF(+) anti-CCP antibody(+) patients were divided into 4 subgroups, and it was found that RF-H anti-CCP antibody-L patients had higher disease severity [RF-H anti-CCP antibody-H 4.3(2.9, 5.6), RF-L anti-CCP antibody-L 4.5(3.0, 5.7), RF-H anti-CCP antibody-L 4.9(3.1, 6.2), RF-L anti-CCP antibody-H 2.8(1.8, 3.9), H=20.374, P<0.01]. ④ After 3-month follow up, the clinical characteristics of the four groups were improved, but there was no significant difference in the improvement of the four groups, indicating that the RF and anti-CCP antibody status did not affect the remission within 3 months. Conclusion:Among RA patients, the disease activity of RA patients is closely related to RF and the RF(+) patients have more severe disease than RF(-) patients. Patients with higher RF titer also have more severe disease than that of patients with low RF titer. After 3 months of medication treatment, the antibody status does not affect the disease remission rate.
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Objective:To study the patterns of tocilizumab (TCZ) use, its efficacy and safety in patients with rheumatoid arthritis (RA) in routine clinical practice.Methods:A total of 407 patients with RA were enrolled from 23 centers and treated with TCZ within 8 weeks prior to the enrollment visit, and were followed for 6-month. The patterns of TCZ treatment at 6 months, the effectiveness and safety outcomes were recorded. Statistical analysis was performed using SAS version 9.4.Results:A total of 396 patients were included for analysis, in which 330 (83.3%) patients received TCZ combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and 16.7%(66/396) received TCZ monotherapy. At baseline, TCZ was initiated in 56.6%(224/396) and 9.6%(38/396) of patients after failure of DMARDs and other biological agents (bDMARDs) respectively. During the 6-month follow-up period, the mean frequency of TCZ administration was (3.7±1.6), the mean TCZ dosage was (7.4±1.2) mg/kg, and the mean interval between doses was (40±13) days. 120(25.8%) patients were on TCZ treatment at the end of the study. Improvements in disease activity, systemic symptoms and patient report outcomes were observed at the end of the study. 22.7%(90/396) patients experienced at least one treatment related adverse event, and 8 patients experienced at least one serious adverse event.Conclusion:This study demonstrates that TCZ treatment is effective in patients with RA when being treated for 6 months with an acceptable safety profile. The duration of TCZ treatment needs to be extended.
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Objective To explore the efficacy and safety of umbilical cord mesenchymal stem cells(UC-MSCs) infusion in treating refractory rheumatoid arthritis(RA).Methods Four cases of refractory RA and invalid by improving disease condition and anti-rheumatic drugs in this hospital from December 2014 to November 2015 underwent once UC-MSCs suspension intravenous infusion after signing the informed consent.The cells number was 1 × 106 per kg.We evaluated the tender and swollen joints number,erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),28-joint disease activity score(DAS28),visual analog scale(VAS)pain score and related safety indices were compared between before and after infusion.Results After infusion treatment in 3 cases,the tender and swollen joints number,ESR and DAS28(4) score were significantly improved,but another case was ineffective.No anaphylaxis,rejection reaction or adverse events occurred in all cases and no abnormal change was found in routine blood,liver and kidney function.Conclusion The UC-MSCs infusion is has good safe for treating refractory RA and improves the disease condition to some extent.
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Objective To investigate the plasma protein concentration of S100B protein,hyperphosphorylated tau protein (P-tau) and β-amyloid (Aβ1-42) of rheumatoid arthritis (RA) patients with mild cognitive impairment (MCI) and to provide a reference for clinical diagnosis and prevention of cognitive dysfunction of RA patients.Methods The subjects were consisted of three groups:RA patients with MCI,RA patients with normal cognitive function (NC) and healthy controls.The Montreal Cognitive Assessment (MoCA)was used to test patients' cognitive function,generalized anxiety disorder scale-7 (GAD-7) scale and 9-item patient health questionnaire-9 (PHQ-9) were used to exclude anxiety and depression of RA patients.The concentration of S100B protein,P-tau protein and Aβ1-42 protein in plasma was detected by enzyme-linked immunosorbent assay (ELISA),and the correlation among the concentration of S100B protein,P-tau protein and MoCA scores was analyzed by Pearson's chi-squared test.Results ① Cognitive scores showed that some RA patients had MCI.② The plasma levels of S100B (F=11.81,P＜0.05),P-tau (F=3.3,P＜0.05) protein in RA patients with MCI were higher than that in NC RA patients and the control group (P＜0.05).③ The clinical index analysis showed that the concentration of C reactive protein (CRP) in RA patients with MCI was higher than that in NC RA patients and healthy control,the difference was statistically significant (t=6.44,P＜0.05).④The levels of plasma P-tau (r=-0.539,P＜0.05),S100B (r=-0.346,P＜0.05),CRP (r=-0.358,P＜0.05) protein were negatively correlated with cognitive scores (P＜0.05).Conclusion CRP,S100B protein and P-tau protein are associated with the pathogenesis of RA patients with MCI.The consequences of plasma concentration test can be com-bined with cognitive assessment questionnaire to provide reference for clinical diagnosis of RA patients with MCI.
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Objective To evaluate the clinical performance of chemiluminescent immunoassay (CLIA) on anti-nuclear antibody(ANA) specific autoantibodies testing.Methods A multi-center clinical study A total of 811 Sera samples were collected from 6 collaborating hospitals during the period of April to July 2016, and tested with CLIA and line immunoassay (LIA) in parallel for autoantibodies to ribonucleoprotein(RNP), smith antigen(Sm), SSA/Ro60,SSB/La, centromere protein B(CENPB), double-stranded DNA(dsDNA), nucleosome(Nuc), and ribosome P protein(Rib-P).The positive rate,specificity and qualitative coincidence rate for each antibody between CLIA and LIA methods were analyzed.All discrepant samples for systemic lupus erythematosus (SLE) highly specific autoantibodies (including anti-Sm, dsDNA, Nuc and Rib-P) were retested by enzyme linked immunosorbent assay (ELISA) and further analyzed with SLE disease cohort using McNemar test.Results The positive rate and specificity of CLIA and LIA for antibodies to ANA specific antigens were comparable.Excellent qualitative coincidence were found between CLIA and LIA for the detection of anti-RNP, SSA/Ro60, SSB/La and CENPB (Kappa>0.75), while the coincidence rate foranti-Sm, dsDNA, Nuc and Rib-P detection were moderate (0.4
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Objective To observe the effects of S100A4 siRNA on the expression of serum TNF‐α,IL‐1βand VEGF in adjuvant arthritis rats .Methods Adjuvant arthritis rat models were established and were randomly divided into model group and interfere group .On Day 11 ,rats in interfere group were injected with S100A4 siRNA fragment in articular cavity .Arthritis index (AI) chan‐ges and pathological changes of ankle joint were observed .The levels of serum TNF‐α and IL‐1β ,VEGF were detected by ELISA . Results Compared with that of model group ,the levels of serum TNF‐ α ,IL‐1β and VEGF were reduced significantly in interfere group (P< 0 .05) ;variances of AI and pathological scores in interfere group were diminished significantly (P< 0 .05) .Conclusion Inhibition of the expression of S100A4 gene can significantly reduce the expression of inflammatory factor TNF‐α ,IL‐1 β and angio‐genesis factor VEGF ,and improve the pathological injury of synovial membrane .
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Objective To evaluate the efficacy and safety of two forms of preparations of dexamethasone palmitate in the treatment of rheumatoid arthritis (RA).Methods A multicenter,double-blind,randomized,parallel-group clinical trial was carried out according to good clinical practice (GCP).A total of 237cases of RA patients with mild to moderate knee swelling were randomly divided into the treatment group (n=118 ) or the control group (n=119) and were treated with two kinds of dexamethasone palmitate 8 mg injection respectively.The primary efficacy endpoints were the circumference of the knee joint at the upper and the lower edge after the intra-articular injection.The secondary efficacy endpoints were joint tenderness index and patients general assessment.The adveme events were recorded.Analysis of covariance,t test or Wilcoxon test,x2 test or Fisher exact test were used for statistical analysis.Results The upper edges of the treatment group and the control group after treatment were (37.2±3.3) cm and (36.4±3.9) cm respectively,and the lower edges of the two groups were (34.4±2.9) cm and (33.9±3.4) cm respectively.They were all significantly smaller than the edges before treatment [(38.1± 3.3) cm and (37.3±4.0) cm of the upper edges,(35.1±3.0)cm and (34.6±3.6) cm of the lower edges respectively ) (P＜0.O1)].After treatment,the joint tenderness index were improved (P＜0.01).A total ratio of great improvement and improvement of patients general assessment of the two group patients were 67.5％ (79/117) and 74.8％ (86/115) respectively.No statistical significant difference was found in all primary and secondary efficacy endpoints between the two groups (P＞0.05).During the clinical trial,the incidence of adverse events related to the treatment of two groups were 4.2％ and 6.8％,without any significant difference (P＞0.05).Conclusion New preparation of dexamethasone palmitate has the same efficacy and safety as the imported producted in the treatment of RA.The circumference of the knee joints at the upper and the lower edge may be used to assess the effects of intra-articular injections.
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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.
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BACKGROUND: Sinomenine is an alkaloid monomer extracted from a Chinese medicinal herb sinomenium acutum stem. It is used in the therapy of the rheumatoid arthritis and has clear and definite therapeutic effects, but the therapeutic mechanism is unclear.OBJECTIVE: To observe the effect of sinomenine at different doses in vitro on the activity of nuclear factor-κB(NF-κβ) and mRNA expressions of the tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) andinterleukin-10 (IL-10) in the synovial cells of the rats with adjuvant arthritis(AA) to explore the probable mechanism of sinomenine in the treatment of rheumatoid arthritis(RA).DESIGN: A controlled repeated measuring study based on the cells.SETTING: Department of traditional chinese medicine and the institute of burn research of a military medical university.MATERIALS: This study was finished at the Laboratory of the Institute of Burn Research of Chinese PLA. The experimental animals were 25 healthy male Wistar rats of clean grade. The AA model rats were made and the synovial cells were collected and grouped as follows: normal control group, AA group,AA + sinomenine 30 mg/L group, AA + sinomenine 60 mg/L group, AA + sinomenine 120 mg/L group. The activity of the NF-κB was measured by the electrophoresis mobility shift assay(EMSA) . The mRNA expressions of the TNF-α, IL-1β and IL-10 were measured by reverse transcription-PCR assay.MAIN OUTCOME MEASURES: The results of the changes of the activity of the NF-κB and the mRNA expressions of the TNF-α, IL-1β and IL-10 in the synovial cells of the rats with adjuvant arthritis after the treatment with sinomenine at different doses.RESULTS: Compared with the normal control group, the activity of the NF-κB and the mRNA expressions of the TNF-α, IL-1β and IL-10 in the synovial cells in the AA group all increased significantly and the outcomes were 17±6, 0.570±0.047, 0.730±0.093, 0. 683 ±0.081 (t= 2.71 -4.07, P < 0.05). After the administration of sinomenine, the activity of NF-κB showed a good correlation with mRNA expressions of the TNF-αandIL-13(r=0.810, P <0.001; r=0.562, P <0.05), but no statistical relevance with mRNA expression of IL-10 was established. Sinomenine showed a dose-dependent inhibition on the activity of the NF-κB and the mRNA expressions of the TNF-α and IL-1β in a certain range of concentrations(30-120 mg/L), but no dose-dependent inhibition on mRNA expression of the IL-10 was observed.CONCLUSION: Through the inhibition of the activity of the NF-κB,sinomenine decreased the mRNA expressions of the TNF-α and the IL-1β in the synovial membrane cells.
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Objective To investigate the traditional Chinese medicine ( TCM) syndromes of rheumatoid arthritis ( RA) by studying the Chinese medical patterns,and analyze the correlations of different indicators and related syndromes. Methods The questionnaires were designed according to clinical epidemiological theories. The data were collected and analyzed by multivariate statistical methods. Results The TCM symptoms of the 401 cases of RA were concluded into 3 common factors,that is,cold,heat and deficient. Their syndromes were sub-classified as 6 groups: cold syndrome,heat syndrome,deficiency,cold heat complex,deficient cold and asthenic fever. Statistical analysis showed that there were significant differences in health assessment questionnaire ( HAQ) ,platelet ( PLT) ,rheumatoid factor ( RF) ,anti-keratin antibody ( AKA) among these 6 TCM syndromes ( P
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Objective To observe the effect of sinomenine(SN) in vitro on nuclear factor-?B(NF-?B) DNA binding activity and nuclear translocation of synoviocytes in collagen-induced arthritis(CIA) rats and explore its antiinflammatory mechanisms.Methods The experimental model of CIA rats was used and synoviocytes were collected.Cells were divided into five groups:normal control,CIA,CIA+10 ?mol/L methotrexate(MTX),CIA+50 ?mol/L SN,CIA+500 ?mol/L SN.Nuclear translocation of NF-?B p65 subunit and NF-?B DNA binding activity of synoviocytes were investigated by fluorescence labelling laser confocal scanning microscopy and electrophoretic mobility shift assay(EMSA) respectively.Results Compared to normal control,significant nuclear translocation of NF-?B p65 subunit was observed and NF-?B DNA binding activity was increased in synoviocytes of CIA rats(P
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Objective To find the different plasma-associated proteins of rheumatoid arthritis (RA) by using two-dimensional gel electrophoresis for understanding the pathogenesis of RA. Methods The total protein from either RA patients or normal ones was prepared by means of immobilized pH gradient based on two-dimensional gel electrophoresis. After silver staining, gel-image analysis was performed by using PDQuest. The differentially expressed proteins were identified by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF-MS). Results 2-DE patterns of plasma from controls and RA patients were presented. The results showed that average number of protein spots was 592 and 563 respectively, and the corresponding average matching rate was 89% and 87% respectively. Gel-image analysis revealed that there were 24 differential protein spots. A total of 15 differential protein spots were successfully identified by MALDI-TOF-MS, of which 6 proteins were up-regulated as compared with control. Conclusion The differentially expressed proteins can be observed in plasma from RA and controls, which can be used to elucidate the pathogenesis of RA for further study.
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OBJECTIVE:To utilize computer to give better service to clinical practice METHODS:About 4 000 prescriptions of Chinese patent medicines,derived from phamacon criteria:the Chinese traditional patent medicine volume 1～20 published by Ministry Health P R China,were logged into computer and corresponding database was established by using Microsoft Access database By searching the
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Objective To study the expressions of co stimulatory factors CD28 and CTLA 4 on CD3 + T cells in peripheral blood lymphocytes (PBMC) and synovial fluid lymphocytes (SFMC) in patients with rheumatoid arthritis (RA) and the relationship of these molecules with the activity of RA. Methods The lymphocytes were collected from the peripheral blood and synovial fluid in RA patients. The CD3 +CD28 + and CD3 +CTLA 4 + molecules on these cells were measured by dual color fluorescence cytometry. The correlation of the expressions of CD3+CD28+ and CD3 +CTLA 4 + molecules with the activity of RA was statistically analyzed by Spearman. Results ① The level of CD3 +CD28 + in PBMC of RA patients was significantly lower than that of the control group and SFMC ( P
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ObjectiveTo understand the possible role of some proteins expressed by human synovial fibroblasts(SFs)in the pathogenesis of rheumatoid arthritis.MethodsThe expression difference of synovial fibroblast proteins between rheumatoid arthritis(RA)patients and healthy controls was analyzed by 2-DE.The differential expression spots were identified by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry(MALDI-TOF-MS),followed by bioinformatics analysis,some of which were validated by Western blot.ResultsUsing 12% SDS-PAGE following pH 4-7 IPG strips in IEF,averagely 837 and 852 protein spots were detected in RA patients and normal subjects,respectively.Gel image analysis revealed that there were 49 differential protein spots.By peptide mass fingerprinting strategy,we identified 40 protein spots derived from gels of SFs in RA patients among differential spots and 23 valid proteins were obtained.Western blot analysis showed that expressions of Enolase ?,Annexin I,Cathepsin D,SOD2,Peroxiredoxin 2 were significantly higher in SFs from RA patients than those from normal subjects,which was consistent with proteome analysis.ConclusionThe differential proteins might be involved in inflammation of synovitis in RA.