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BACKGROUND@#Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control.@*METHODS@#The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months.@*RESULTS@#Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group.@*CONCLUSION@#Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state.@*TRIAL REGISTRATION@#Chictr.org, ChiCTR2000039799.
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Humans , Quality of Life , China , Arthritis, Rheumatoid/drug therapy , Piperidines/therapeutic use , Treatment Outcome , Antirheumatic Agents/therapeutic use , Pyrroles/therapeutic useABSTRACT
Objective:To explore the impact of clinical features, serological indicators, and pulmonary function test (PFT) on the prognosis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD).Methods:Clinical data of RA-ILD patients who were diagnosed by HRCT and were followed up in Changhai Hospital or Yancheng First People's Hospital from 2011 to 2021 were collected Respiratory functional impairment of the patients was evaluated according to the changes of HRCT score and PFT, and the patients were divided into progressive group and stable group. COX survival analysis and ROC curve were used to determine the factors related to the progression of RA-ILD.Results:Finally 98 RA-ILD patients were included. The mean age of ILD onset was (62.9±12.1) years old, the median course of RA was 7.0 (1.0, 15.3)years, and the median follow-up time was 36.5 months (14.0, 79.5). There were 49 cases in the progressive group, and the clinical characteristics and laboratory tests of the two groups were compared. The results showed that: progressive time [(23(8.5,43.0)months vs 63(32.5,90.9) months, Z=-4.55, P=0.001)], HRCT score [(115(109,135) vs 111(105,116), Z=-2.70, P=0.007)], forced vital capacity(FVC) predicted [(70.1±15.7)% vs (80.8±19.7)%, t=2.12, P=0.039)], diffusing capacity of the lungs for CO(DLCO) predicted [(57.5±16.3)% vs (83.4±18.8)%, t=4.87, P=0.001)], male [(44.9% vs 18.4%, χ2=7.97, P=0.005)], UIP pattern [(36(73.5%) vs 9(18.4%), χ2=29.96, P<0.001)], RF>200 U/ml[(21(65.6%) vs 18(41.9%), χ2=4.15, P=0.042)], anti-CCP>75 U/ml [(42(91.3%) vs 35(71.4%), χ2=6.10, P=0.013], all had significantly different between the two groups. In multivariate analyses, UIP[ HR(95% CI)=3.25(1.62,6.50), P<0.001], anti-CCP antibody >75 U/ ml[ HR(95% CI)=3.85 (1.20,12.33), P=0.023] and smoking [ HR (95% CI): 5.74(1.10, 30.13), P=0.039] were significantly correlated with the progression of pulmonary fibrosis in RA-ILD patients. PFT was performed in only 44 patients with RA-ILD. The univariate analyses and ROC curve suggested that DLCO predicted [ HR (95% CI)=1.04 (1.02,1.06), P<0.001] was a significant risk factor for the progression of RA-ILD, and the area under curve (AUC) of DLCO was 0.845 [95% CI=(0.729,0.961)]. Conclusion:UIP pattern, high titer of anti-CCP antibody, smoking, and reduced DLCO predicted % may be potential predictors for poor prognosis of RA-ILD patients.
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Systemic sclerosis (SSc) is an autoimmune rheumatic disease that is characterized by skin fibrosis with multi-organ involvement. In China, the standardized diagnosis and treatment for SSc is still lacking. Based on the diagnosis criteria and guidelines from China and abroad, Chinese Rheumatology Association developed the current standardization of diagnosis and treatment for SSc. The purposes of this guideline are to standardize clinical management for SSc in China, to interpret the key evaluation tools for SSc, and to recommend therapeutic principle and strategies.
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Objective:This study explored the correlation between Cardiovascular metabolic index (CMI) and hyperuricemia (HUA) in non-obese Chinese population.Methods:73 150 non-obese people who received routine physical examination between January 2014 to December 2017 were included in this cross-sectional study (from Jingjiang People's Hospital of Jiangsu Province, Hangzhou Aeronautical Sanatorium of Chinese Air Force, and Shanghai Changhai Hospital). The anthropometric indexes, lipid parameters including triglycerides, and high-density lipoprotein cholesterol, uric acid, and other clinical parameters were collected, and the CMI values were calculated from the waist-to-body ratio (WHtR). The correlation between CMI and HUA was analyzed by Logistic regression model.Results:Among 39 443 non-obese women, 5 825 patients were HUAs with a prevalence rate of 14.7%; among 33 707 non-obese men, 7 720 were HUAs with a prevalence rate of 22.9%. HUA had no significant association with Waist-to-Hip Ratio (WHR) and WHtR, but only with CMI. The highest quartile of women in CMI was 6.311(5.734, 6.947) and 6.785(6.092, 7.557) in male, P<0.01. Conclusion:CMI is significantly associated with HUA in non-obese Chinese population and is expected to become a new monitoring parameter for the prevention and management of HUA and gout.
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Objective:The aim of this study was to compare the efficacy and safety of iguratimod (IGU) or leflnomide (LEF) in combination with methotrexate (MTX) in patients with active rheumatoid arthritis (RA).Methods:This was a multicenter, randomized, double-blinded, double dummy and controlled clinical trial. Patients with moderate or high active RA were randomized in a 1∶1 ratio to receive IGU+MTX (Group A) or LEF+MTX (Group B) treatment. The efficacy and safety were assessed at week 12, 24 and 52, respectively. The primary endpoint was the American Colleague of Rheumatology 20 (ACR20) response rates at the 52th week. Pearson chi square test and two-way Analysis of Variance (ANOVA) were used to compare the improve- ment of ACR20 and DAS28 at 52 weeks. Pearson chi square test or Fisher exact probability test were used to compare the ACR 20 and ACR70 rate between the two groups after treatment. The measurement data of the two groups were compared by independent sample t-test or nonparametric test. Results:A total of 240 RA patients were enrolled in the present study. As a result, 84.1% and 81.0% of patients achieved ACR20 criteria at the 52th week in Group A and Group B, respectively ( χ2=0.35, P=0.56). And the ACR50/70 response rates, disease activity score 28 (DAS28), simplified disease activity index (SDAI) and the absolute decrease of DAS28 from baseline were not statistically different between the two groups at week 12, 24 and 52. The rates of adverse events were lower in Group A than those in Group B (60.0% vs 79.0%, P<0.01). The elevations of glutamic pyruvic transaminase/glutamic oxalacetic transaminase levels, concomitant use of hepatinica and white blood cell decrease were more common in Group B ( P<0.05). Conclusion:IGU in combination with MTX is an efficacious and safe treatment regimen, which is comparable in efficacy in control active RA but superior in safety to LEF combined with MTX.
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Objective:To explore the clinical teaching effect of case-based learning combined with diagnosis and treatment guidelines in standardized residency training in the department of rheumatology and immunology.Methods:Forty standardized trainees were randomized into two groups. One was the observation group, which adopted case-based learning combined with diagnosis and treatment guidelines. The other one was the control group, which performed the traditional clinical teaching mode. After 4 weeks, the assessment and satisfaction evaluation were carried out among the two groups. SPSS 19.0 was used for t test and Mann-Whitney test. Results:Students in observation group showed significantly better ability of physical examination and case analysis than those in the control group. The satisfaction degree of the students in the observation group was significantly higher in terms of diagnosis and treatment standard, clinical thinking, problem solving ability, self-learning ability and personal profession benefits than that in the control group.Conclusion:Case-based learning with diagnosis and treatment guidelines is an ideal teaching method combining theory with practice perfectly, which can significantly improve the effect of clinical teaching of standardized residency training in the department of rheumatology and immunology.
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Objective:To explore the role of tutorial system combined with TBL teaching method in standardized residency training of the department of rheumatology and immunology.Methods:Sixty residents who participated in standardized training in the department of rheumatology and immunology of our hospital from July 2017 to July 2018 were divided into experimental and control groups according to the period of training. The experimental group adopted the tutorial responsibility system and TBL teaching method, and the control group adopted the traditional residency training mode. The clinical and scientific research abilities of the two groups were compared, and the questionnaires of satisfaction were compared. The statistical analysis was carried out by SPSS 19.0 software.Results:The examination results, scientific research ability and questionnaire survey satisfaction of the tutorial responsibility system combined with TBL teaching method group were higher than those of the traditional teaching group, with statistical significance ( P<0.05 or P<0.01). Conclusion:The tutorial responsibility system combined with TBL teaching method can effectively improve the diagnosis and treatment thinking ability, practical operation skills, clinical scientific research ability, self-study ability and team consciousness, and provide new ideas and methods for improving the quality of standardized residency training.
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In recent years, osteoporosis (OP) has become one of the main diseases affecting the health of middle-aged and elderly people in China, and the prevalence of OP has increased significantly. The clinical diagnosis and treatment guidelines for this disease are also constantly updated. The overall principles speciallyemphasise that doctors and patients need to work together to negotiate the details of the diagnosis and treatment guidelines, in order to improve the OP clinical diagnosis and treatment rate. Therefore, patients′ knowledge of the disease, understanding of clinical guidelines, and cooperation with doctors to implement diagnosis and treatment plans are very important. In this study, from the most concerned issues of the patients, we established the OP patient practice guideline working group. 14 recommendations, as the OP patient practice guidelines, are proposed in accordance with the relevant principles of the "World Health Organization guidelines development manual" and the international normative process.
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Objective To explore the effects of ring finger protein 43 (RNF43) on fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA).Methods Synovial tissues from patients with RA treated by knee arthroplasty were used to isolate FLSs by type 2 collagenase.RNF43 lentivirus overexpressing plasmid was constructed and transfected in to RA-FLS.After successful transfection,RNA and super natant of RA-FLS were extracted.QRT-polymerase chain reaction (PCR) and enzyme linked immunosorbent assay (ELISA) were used to detect the mRNA and protein expression levels of matrix metalloproteinase (MMP)-1,MMP-3 and MMP-13.Data were analyzed with Student's t test.Results Transfection efficiency could meet the test requirements when the multiplicity of infection was 40 and was in conjunction with appropriate concentration of polybrene.The mRNA of RNF43 increased for 26158-fold than the control group.In vitro,compared with the control group,RNF43 could significantly inhibit the mRNA of MMP-1,MMP-3 and MMP-13 and MMP-13 [(0.19±0.06),t=28.314,P＜0.05;(0.28±0.07),t=23.413,P＜0.05;(0.21±0.09),t=18.365,P＜0.05]and the protein of MMP-1,MMP-3 and MMP-13 and MMP-13 [(31.0±9.4) pg/ml,(17.1±2.1) pg/ml,t=3.198,P=0.029],MMP-3 [(38.7±8.1) pg/ml,(24.9±3.5) pg/ml,t=3.514,P=0.015],MMP-13 [(35.9±5.4) pg/ml,(20.6±2.9) pg/ml,t=5.632,P=0.001].Conclusion The results of study suggest that RNF43 could inhibit the secretion of MMPs in RA-FLS by suppressing the activity of Wnt signal pathway.
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Objective To study the proliferation and inflammatory phenotypes of human fibroblast-like synoviocytes (FLS) induced by tumor necrosis factor-α(TNF-α). Methods The rheumatoid arthritis (RA)-FLS were cultured in vitro, then treated with different concentrations of diallyl trisulfide (DATS). The proliferation activity was detected by CCK-8 method. Then TNF-α was used to stimulate the RA-FLS, mRNA and protein expression of interleukin (IL)-6, matrix metalloproteinases (MMP)-1 and vascular endothelial growth factor (VEGF) were detected by quantitative real time polymerase chain reaction (qPCR) and enzyme linked immunosorbent assay (ELISA). Differences among groups were determined by one-way analysis of variance (ANOVA), LSD-t test was used for comparison between 2 groups. Results RA-FLS was successfully is-olated and cultured in vitro. The positive rate of CD90 and CD29 in the RA-FLS was more than 90％. The proli-feration activity of RA-FLS treated with 100 μmoL/L, 200 μmol/L and 300 μmol/L DATS was (98.92 ± 0.40)％, (95.91±0.32)％, (94.05±0.24)％, respectively. As Compared with the normal control group, the pro-liferation activity of RA-FLS was lower, and the statistically significant difference is between normal control group 200 μmol/L and 300 μmol/L DATS (t=-4.46, P<0.05; t=-7.98, P<0.05). After TNF-α stimulation, the expression of IL-6's mRNA in experiment group (100μmol/L DATS) is higher compared with the model control group (t=5.74, P<0.05), but the change of IL-6's protein is no significant difference (t=-0.49, P=0.627). The differences of mRNA and protein expression levels of MMP-1 and VEGF between the experiment group (100μmol/L DATS) and the model control group were not statistically significant. The relative mRNA level [(0.42 ± 0.06), t=-23.47, P<0.05;(0.14±0.039), t=-36.59, P<0.05;(0.36±0.09), t=-13.1, P<0.05)] and the protein levels [(108.0±4.7) ng/L, t=-63.79, P<0.05, (26.0±1.0) ng/L, t=-9.68, P<0.05;(57.9±0.7), t=-34.59, P<0.05] of IL-6, MMP-1, VEGF in experiment group (200μmol/L DATS) were significantly decreased. And the relative mRNA level [(0.041 ±0.027), t=-38.48, P<0.05; (0.027 ±0.027), t=-41.22, P<0.05; (0.131 ±0.047), t=-17.74, P<0.05] and the protein levels [(24.2 ±2.3) ng/L , t=-88.69, P<0.05; (22.7 ±1.0) ng/L , t=-14.13, P<0.05; (34.5 ±1.7), t=-48.45, P<0.05] of IL-6, MMP-1, VEGF in the experiment group (300 μmol/L DATS) were also significantly decreased. The difference between the two groups was significant (t=-24.89, P<0.05; t=-4.45, P<0.05; t=-13.87, P<0.05). Conclusion DATS can inhibit the proliferation and the effect of TNF-αinduced secretion of IL-6, MMP-1 and VEGF in RA-FLS. The effect is dose-dependent.
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Objective To explore the molecular pathological mechanism of gout, and to explore the mechanism of how interleukin (IL)-37 influencing PDZK1 protein in gout through nuclear factor κB (NF-κB) pathway. Methods HK-2 cells were stimulated with inflammatory signal IL-37. The expression of PDZK1 and its subcellular localization were detected by real-time fluorescence quantitative polymerase chain reaction (real-time PCR) at different concentrations of IL-37 (defined as group A), PDTC+IL-37 (defined as group B), Wortmannin+IL-37 (defined as group C), respectively.The changes of PDZK1 protein expression in HK-2 cells were detected by adding inhibitor PDTC (NF-κB pathway inhibitor) or Wortmannin (PI3K pathway inhibitor) and inflammatory signal stimulating protein imprinting method. The comparative t test was used for statistical analysis between groups A, B and A and C. Results The average levels of PDZK1 mRNA were as follows:(group A: 28.71 ±0.35, 28.57 ±0.31, 28.78 ±0.28, 28.63 ±0.29, 28.62 ±0.19; group B: 28.71 ±0.31, 28.83 ±0.27, 28.58±0.26, 28.73±0.36, 28.68±0.35;group C:28.81±0.32, 28.91±0.29, 28.72±0.24, 28.59±0.18, 28.58±0.22). There was no significant change in PDZK1 mRNA level in group A and B. The same IL-37 was found in group A and B. The values of T were 5.73, 4.72, 4.69, 5.86 and 6.79, respectively. The P values were all greater than 0.05, and there was no significant difference between the two groups. The values of T were 6.78, 7.13, 7.47, 6.38 and 5.98 in the same IL-37 concentration groups of A and C, respectively, and the P values were all greater than 0.05, with no significant difference. The levels of PDZK1 protein in the three groups by Western blot analysis were as follows: (group A: 0.200±0.082, 0.412±0.032, 0.723±0.063, 1.202±0.021, 1.222±0.023;group B: 0.124±0.064, 0.303±0.081, 0.325±0.062, 0.223±0.071, 0.343±0.052; group C: 0.017±0.022, 0.204± 0.015, 0.187±0.053, 0.302±0.051, 0.404±0.051), The levels of PDZK1 protein in group A treated with different concentrations of IL-37 followed by the concentration of IL-37. The level of PDZK1 protein in group B increased with the increase of IL-37 concentration, but the level of PDZK1 protein in group B was lower than that in the group treated with IL-37 only, and decreased when the concentration of IL-37 was 40 ng/ml.The level of PDZK1 protein in group C increased with the increase of IL-37 concentration, but the level of PDZK1 protein in group C was lower than that in the group treated with IL-37 only, and the same concentration of IL-37 in group A and B. The values of T were 1.83, 1.37, 1.64, 1.57 ,1.49, with P values greater than 0.05. There was no significant difference between the two groups. The values of T were 1.28, 1.37, 1.26, 1.42, 1.39 in the same concentration of IL-37 in group A and C, with P values greater than 0.05, with no significant difference.The results of immunofluorescence analysis showed that the trend of the three groups was basically consistent with that of Western-Blot. Conclusion The pathogenesis of gout induced by IL-37 through PDZK1 protein may not occur at the transcriptional level, but may occur at the level of protein translation.
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Objective To study the expression of dishevelled-2 (DVL2) in rheumatoid arthritis cartilage and its effect on cartilage destruction.Methods Cartilage DVL2 expression in rat models of rheumatoid arthritis (RA),osteoarthritis(OA) and collagen-induced arthritis(CIA) were tested by Western blotting.DVL2 overexpressed lentivirus was transfected into the knee of CIA rats.Primary chondrocytes were extracted from RA patients by knee arthroplasty and transfected with DVL2 overexpressed lentivirus.Gene expression of related inflammation related cytokines was detected by real-time polymerase chain reaction (PCR).Results Compared with knee articular cartilage in OA patients and normal rats,DVL2 protein was highly expressed in knee cartilage of RA patients and CIA rats (P values 0.041 and 0.032,respectively).DVL2 did not significantly affect the destruction of knee cartilage in CIA rats (P=0.885).DVL2 overexpression in chondrocytes enhanced gene expression of cyclo-oxygenase-2 (COX-2),inducible nitric oxide synthase (NOS),matrix metalloproteinase (MMP) 2,MMP-3,and MMP-9,which could be more pronounced when tumor necrosis factor alpha was added.Conclusions DVL2 is highly expressed in RA articular cartilage and promotes the expression of inflammatory cytokines and MMP gene in chondrocytes by activating Wnt/β-catenin pathway,which involves in the destruction of articular cartilage in RA.
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Objective This study aims to investigate the frequency and characteristics of vascular involvement in Beh(c)et's disease (BD).Methods We enrolled patients who were hospitalized at Changhai Hospital affiliated Naval Medical University and who had been diagnosed with BD at discharge from January 1999 to July 2017.Patientswere divided into two groups,Vascular Beh(c)et's disease (VBD) group and non-VBD group,according to vascular involvement or not.We recorded and compared the demographicinformation,disease activity scores Beh(c)et’s Disease Current Activity Form (BDCAF),other systemic involvement and laboratory test results between the two groups.The clinical features of vascular involvement were analyzed.The measureddata were statistically analyzed with Student's t/t’ test or Mann-Whitney U test.The numerical data were statistically analyzed with x2 test or continuity correction x2 test.Results The total numbers of BD patients were 224,including 120 males and 104 females.Vascular involvements were found in 41 (18.3％) cases,including 34 males and 7 females.VBD was more common in males (28.3％ vs 6.7％,x2=17.388,P＜0.01).Of 41 VBD patients,11 cases (26.8％) had single vascular lesions,and 30 cases (73.2％) had multiple vascular lesions.Moreover,24 cases (58.5％) had arterial lesions,and 25 cases (61.0％) had venous lesions.Eight (19.5％) patients had both arterial and venous lesions.Compared to the non-VBD group,the VBD group had a higher frequency of cardiac involvement (22.0％ vs 3.8％,x2=16.592,P＜0.01),a higher disease activity index score (BDCAF) [3.0(2.0,4.0) score vs 2.0(2.0,3.0) score,U=2 609.5,P=0.001],higher levels of C-reactiveprotein (CRP) (14.45(4.97,64.08) mg/L vs 9.02(3.16,26.53) mg/L,U=2 809,P=0.046) and plasma homocysteine (Hcy) [(17.6±7.7) μmol/L vs (7.1±2.1) μmol/L,t'=7.894,P＜0.01].Conclusion VBD mainly affectsmales.It mainly presentsas multiple lesions.Moreover,patients in the VBD group havehigher frequency of cardiac complications,higher disease activity index scores (BDCAF),higher levels of CRP and Hcy than the non-VBD group.These results may have great valueto predict and diagnoseof VBD.
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Objective To investigate the clinical characteristics of Macrophage activation syndrome (MAS) in patients with rheumatoid arthritis (RA), so as to reduce misdiagnosis. The objective of this paper was to improve the comprehensive and systematic understanding of rheumatoid arthritis complicated with macrophage activation syndrome. Methods The clinical data of one patient with macrophage activation syndrome secondary to RA were analyzed retrospectively, and the related literatures were reviewed. Results The patient was a 65 year old male with ahistory of RA for 14 years. The patient presented with symmetrical multi-joint pain aggravated with stiffness for 14 years and was admitted because of aggravation for 2 weeks. He failed many drugs for the treatment of rheumatoid arthritis was ineffective accompanied with intermittent leukocytopenia. After bone marrow aspiration and biopsy, the phenomenon of phagocytosis of macrophages was clearly diagnosed. He was treatment with high dose corticosteroid +CsA+ human immunoglobulin and his condition wasimproved. Literature was searched in PubMed, Wan Fang medical network database, RA+MAS. Finally, 12 related articles was yielded, and a total of 14 patients, including 8 males, 6 females. Four patients were adults and 10 were children. The shortest duration was 0.5 months, the longest was 24 months. Fever, skin rash, arthritis, enlargement of the liver or spleen, decreased of blood cells count, elevation of liver transaminase, increase of triglyceride, and a series of symptoms and laboratory parameters were observed in the course of the disease. Conclusion When rheumatoid arthritis patients show decreased blood leukocytes and can not be explained by other causes, the differential diagnosis should be carefully performed to rule out secondary macrophage activation syndrome. Always be awake of the risks and dangers of rheumatoid arthritis complicated with macrophage activation syndrome. Early diagnosis and timely are important to improve prognosis.
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Objective To investigate the clinical characteristics of Macrophage activation syndrome (MAS) in patients with rheumatoid arthritis (RA), so as to reduce misdiagnosis. The objective of this paper was to improve the comprehensive and systematic understanding of rheumatoid arthritis complicated with macrophage activation syndrome. Methods The clinical data of one patient with macrophage activation syndrome secondary to RA were analyzed retrospectively, and the related literatures were reviewed. Results The patient was a 65 year old male with ahistory of RA for 14 years. The patient presented with symmetrical multi-joint pain aggravated with stiffness for 14 years and was admitted because of aggravation for 2 weeks. He failed many drugs for the treatment of rheumatoid arthritis was ineffective accompanied with intermittent leukocytopenia. After bone marrow aspiration and biopsy, the phenomenon of phagocytosis of macrophages was clearly diagnosed. He was treatment with high dose corticosteroid +CsA+ human immunoglobulin and his condition wasimproved. Literature was searched in PubMed, Wan Fang medical network database, RA+MAS. Finally, 12 related articles was yielded, and a total of 14 patients, including 8 males, 6 females. Four patients were adults and 10 were children. The shortest duration was 0.5 months, the longest was 24 months. Fever, skin rash, arthritis, enlargement of the liver or spleen, decreased of blood cells count, elevation of liver transaminase, increase of triglyceride, and a series of symptoms and laboratory parameters were observed in the course of the disease. Conclusion When rheumatoid arthritis patients show decreased blood leukocytes and can not be explained by other causes, the differential diagnosis should be carefully performed to rule out secondary macrophage activation syndrome. Always be awake of the risks and dangers of rheumatoid arthritis complicated with macrophage activation syndrome. Early diagnosis and timely are important to improve prognosis.
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Objective To investigate the effects of Dishevelled (DVL) on apoptosis of diffuse large B-cell lymphoma (DLBCL) cell line OCI-Ly10, and to explore its possible mechanism. Methods Lentivirus plasmid overexpressing DVL2 was constructed, and after virus was packaged, it was transfected into OCI-Ly10 cells. Flow cytometry was used to detect the apoptosis rate of OCI-Ly10 cells with or without the stimulation by TNF-α recombinant protein. Then the gene expression of anti-apoptotic genes, GADD45β and A20, in NF-κB pathway was detected by RT-PCR. Results The virus was sucessfully transfected into OCL-Ly10 cells which overexpressed DVL2. The apoptosis rate of OCL-Ly10 cells overexpressing DVL2 without the stimulation by TNF-α was increased compared with that of the negative control group [(15.46 ±2.37) % vs. (11.72±3.53)%, P=0.03], the A20 mRNA expression level was decreased compared with that of the negative control group [(0.66 ±0.01) vs. 1, P=0.04], and the relative expression level of GADD45β mRNA was not significantly decreased compared with that of the negative control group [(0.79 ±0.15) vs. 1, P=0.642]. The apoptosis rate of DVL2 overexpression OCI-Ly10 cells stimulated by TNF-α was significantly higher than that of the negative control group treated by TNF-α [(22.78±4.56)%vs. (12.79±2.89)%, P=0.007]. The gene expression of A20 and GADD45β in DVL2 overexpression cells stimulated by TNF-α was significantly increased, however, the magnitude of increase in DVL2 overexpression cells was less than that in the negative control group treated by TNF-α [A20: (3.75 ±0.14) times vs. (6.89 ±0.10) times, P=0.008; GADD45β:(4.750±0.21) times vs. (6.14±0.08) times, P=0.03]. Conclusion DVL can promote the apoptosis of OCI-Ly10 cells, and its mechanism may be related with anti-apoptotic genes that inhibits its downstream via NF-κB pathway.
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Objective To explore the metabolic characteristics of rheumatoid arthritis (RA) patients with type 2 diabetes (T2DM) and provide evidence for the management of cardiovascular risk factors. Methods One hundred and four RA patients with T2DM and 100 healthy subjects with matched age and sex were the subjects of study. The metabolic parameters of the two groups was compared and the ratio of metabolic abnormalities in RA with T2DM group was analyzed. Comparisons between groups were analyzed by t-test and Chi-square analysis. Results The average duration of RA and T2DM were (8±6) and (10±5) years respectively; 55.8% patients with CRP>10 mg/L and 72.1% patients with ESR>30 mm/1 h. There was no significant difference in body mass index between the two groups [(23.3 ±3.1) kg/m2 vs (23.4 ±2.8) kg/m2, P=0.991]. The systolic blood and diastolic blood pressures of RA patients with T2DM were significantly higher than those of the control group (P<0.01). There was no significant difference in blood uric acid [(0.27 ± 0.11) mmol/L vs (0.27 ±0.12) mmol/L, P=0.957]. There was no significant difference in the levels of total cholesterol (TC) [(4.6 ±1.0) mmol/L vs (4.5 ±0.5) mmol/L, P=0.547], but the levels of triglyceride (TG), high density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) [TG (1.4±0.8) mmol/L vs (1.1 ±0.3) mmol/L, t=2.871, P=0.005; HDL-C (1.1 ±0.3) mmol/L vs (1.5 ±0.4) mmol/L, t=-7.064, P<0.01;LDL-C (2.6±0.8) mmol/L vs (2.4±0.4) mmol/L, t=2.003, P=0.047] were significantly different in the two groups. 36.5% patients were with hypertension, 17.3% patients were with high TC, 30.7% patients were with high TG, 26.9% patients were with low HDL-C, and 27.8% patients were with high LDL-C. Conclusion High incidence of hypertension, poor blood sugar control, and lipid metabolism disorders are prominent metabolic disorders in RA patients with T2DM. Clinicians, particularly rheumatologists, need to give adequate attention to these conditions.
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BACKGROUND:Studies have funded that reduced Wnt/β-catenin signaling is involved in the onset and/or progression of bone erosion in rheumatoid arthritis. It can lead to potential new treatment approaches of bone erosion by enhancing Wnt/β-catenin signaling pathway. R-spondin 1 may act as a Wnt agonist, but there is no study in human osteoblasts. OBJECTIVE:To verify the effect of R-spondin 1 on promoting differentiation and maturation of human osteoblasts by inhibiting DKK1. METHODS:S40-transfected human osteoblast lines, hFOB1.19, were treated with R-spondin 1, Wnt-3a and DKK1 to detecting the proliferation, alkaline phoshpatase activity and osteoprotegerin concentration. RESULTS AND CONCLUSION:R-spondin 1 had no effects on hFOB1.19 cel s. Wnt-3a upregulated the activity of alkaline phoshpatase, which could be enhanced by addition of R-spondin 1. R-spondin 1 could reduce the DKK1-mediated inhibition of alkaline phoshpatase activity in hFOB1.19 cel s. R-spondin 1 increased the concentration of osteoprotegerin, and moreover, the promotion of osteoprotegerin by R-spondin 1 alone was stronger than the inhibition by DKK1. These findings suggest that R-spondin 1 can inhibit DKK1 by Wnt/β-catenin signal pathway to promote the differential and maturation of human osteoblasts to excrete osteoprotegerin.
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Objective To analyze the clinical features of eosinophilic granulomatosis with polyangiitis (EGPA).Methods The clinical characteristics,laboratory test,therapeutic regimen,pathology and imaging diagnosis in 23 cases with EGPA from the First Affiliated Changhai Hospital of Second Military Medical University within June 2007 to January 2013 were retrospectively analyzed.Results There were 14 males and 9 females,with the age ranged from 21 to 68 years.The mean age was (42±9) years.The overall prevalence of asthma was 78％(18/23).The allergic rhinitis accounted for 61％(14/23).The maxillary sinuses were the most frequendy involved,which accounted for 57％(13/23).Skin involvement was 57％(13/23),peripheral neuritis was 70％(16/23).Central nervous system involvement presented cerebrovascular event.Cardiac involvement accounted for 48％(11/23),digestive system involvement accounted for 17％(4/23).The outcome of auxiliary laboratory test revealed that 96％(22/23) patients expressed significantly higher levels of IgE and 70％(16/23) patients carried anti-neutrophil cytoplasmic antibodies (ANCA) which were presented as the perinuclear ANCA (p-ANCA).The patchy infiltrates of lung CT scan accounted for 69％ (11/23).EMG showed mononeuritis multiplex and symmetric sensory motor neuropathy.The abnormal ratios of ECG and Echocardiography were 48％(11/23),79％(11/14) respectively.The pathological manifestations were necrotizing vasculitis,eosinophilic tissue infiltration,and extravascular granulomas.Conclusion Our results confirm the heterogenicity in clinical presentation and lack of specificity.Early diagnosis and treatment will be helpful for good prognosis.
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ObjectiveTo understand the difference in characteristics between juvenile dermatomyositis (JDM) and adult dermatomyositis (ADM).Methods Sixty-one cases of JDM were retrospectively analyzed and compared with 30 cases of ADM. Results The rashes were presented as the initial symptom in all expect one JDM patients. Gottron’s papules were presented in 90% JDM patients and 67% ADM patients. Calcium deposition was presented in 7% JDM patients and none of the ADM patients. The cardiovascular system was involved in 7 % JDM patients and 23% ADM patients. Cancer occurred in none of JDM patients and 13% ADM patients. In JDM and ADM patients, the ratio of elevated muscle enzymes from highest to lowest was LDH, hy-droxybutyric acid enzyme, CK-MB, AST, and CK. The positive ratio of magnetic resonance (MRI) all exceeded 80% in JDM and ADM groups. Two cases died in each group.Conclusions The clinical presentation of JDM is basically the same as that of ADM. The most common initial symptoms in JDM are skin rashes and Gottron's papules. Cardiovascular disease and cancer are less in JDM than in ADM. MRI is valuable in the diagnosis of DM.