ABSTRACT
Objective:To analyze the clinical features of MDA5 antibody positive dermatomyositis (MDA5-DM) and to provide evidence for early diagnosis and treatment.Methods:From March 2019 to June 2021, 272 patients with anti-MDA5-DM from the Nanjing Medical University myositis-associated interstitial lung disease cohort were enrolled, with 76 patients with anti-synthetase syndrome (ASS) as the control group. The clinical characteristics and the occurrence of interstitial lung disease were analyzed. T-test was used for normally distributed and variance-homogeneous independent samples, Mann-Whitney U test for non-normally distributed data, and chi-square test or Fisher′s exact test for dichotomous variables. Results:Among the 272 anti-MDA5-DM patients, 88.6% (241/272) developed interstitial lung disease (ILD), and 33.8% (92/272) developed rapidly progressive ILD (RP-ILD). The six-month all-cause mortality rate of anti-MDA5-DM patients was 16.9% (46/272), and it was as high as 47.8% (44/92) for those with RP-ILD. Compared with ASS patients, anti-MDA5-DM patients had a significantly higher proportion of males, arthritis, Gottron's sign, heliotrope rash, V-sign, periungual erythema, and skin ulcers ( P<0.05). The levels of ALT, AST, and ferritin were significantly increased ( P<0.05). Compared with non-RP-ILD patients, RP-ILD patients had a significantly higher proportion of males [35.9%(33/92) vs. 23.3%(42/180), χ2=4.79, P=0.029], higher levels of LDH [387 (276, 547) U/L vs. 310 (245, 400) U/L, Z=-3.67, P<0.001], ESR [45.5 (29.25, 63.25) mm/1 h vs. 31.2 (20, 51) mm/1 h, Z=-3.71, P<0.001], CRP [10.9 (4.1, 25.2) mg/L vs. 4.54 (2.58, 9.08) mg/L, Z=-4.97, P<0.001], ferritin [1 340 (650, 2 000) ng/ml vs. 556 (203, 1 186) ng/ml, Z=-4.40, P<0.001], and a higher proportion of anti-Ro52 antibody and anti-MDA5 antibody co-positivity [87.0%(80/92) vs. 52.2%(94/180), χ2=31.87, P<0.001]. Conclusion:Anti-MDA5-DM patients are prone to develop RP-ILD and have poor prognosis.
ABSTRACT
Objective:To investigate the clinical features and prognosis of male with anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody.Methods:The clinical data of 246 patients with DM and anti-MDA5 autoantibodies hospitalized by Jiangsu Myositis Cooperation Group from 2017 to 2020 were collected and retrospectively analyzed. Chi-square test was performed to compared between counting data groups; Quantitative data were expressed by M ( Q1, Q3), and rank sum test was used for comparison between groups; Single factor survival analysis was performed by Kaplan-Meier method and Log rank test; Cox regression analysis were used for multivariate survival analysis. Results:①The male group had a higher proportion of rash at the sun exposure area [67.1%(47/70) vs 52.8%(93/176), χ2=4.18, P=0.041] and V-sign [50.0%(35/70) vs 30.7%(54/176), χ2=8.09, P=0.004] than the female group. The male group had higher levels of creatine kinase [112(18, 981)U/L vs 57 (13.6, 1 433)U/L, Z=-3.50, P<0.001] and ferritin [1 500 (166, 32 716)ng/ml vs 569 (18, 14 839)ng/ml, Z=-5.85, P<0.001] than the female group. The proportion of ILD [40.0%(28/70) vs 59.7%(105/176), χ2=7.82, P=0.020] patients and the red blood cell sedimentation rate[31.0(4.0, 101.5)mm/1 h vs 43.4(5.0, 126.5)mm/1 h, Z=-2.22, P=0.026] in the male group was lower than that of the female group, but the proportion of rapidly progressive interstitial lung disease (PR-ILD) [47.1%(33/70) vs 31.3%(55/176), χ2=5.51, P=0.019] was higher than that of the female group. ②In male patients with positive anti-MDA5 antibodies,the death group had a shorter course of disease[1.0(1.0, 3.0) month vs 2.5(0.5,84) month, Z=-3.07, P=0.002], the incidence of arthritis [16.7%(4/24) vs 42.2%(19/45), χ2=4.60, P=0.032] were low than those in survival group,while aspartate aminotransferase (AST)[64(22.1, 565)U/L vs 51(14,601)U/L, Z=-2.42, P=0.016], lactate dehydrogenase (LDH) [485(24,1 464)U/L vs 352(170, 1 213)U/L, Z=-3.38, P=0.001], C-reactive protein (CRP) [11.6(2.9, 61.7) mg/L vs 4.95(0.6, 86.4) mg/L, Z=-1.96, P=0.050], and ferritin levels [2 000(681, 7 676) vs 1 125 (166, 32 716)ng/ml, Z=-3.18, P=0.001] were higher than those in the survival group, and RP-ILD [95.8%(23/24) vs 22.2%(10/45), χ2=33.99, P<0.001] occurred at a significantly higher rate. ③Cox regression analysis indicated that the course of disease LDH level, and RP-ILD were related factors for the prognosis of male anti-MDA5 antibodies [ HR (95% CI)=0.203(0.077, 0.534), P=0.001; HR (95% CI)=1.002(1.001, 1.004), P=0.003; HR (95% CI)=95.674 (10.872, 841.904), P<0.001]. Conclusion:The clinical manifestations of male anti-MDA5 antibody-positive patients are different from those of female. The incidence of ILD is low, but the proportion of PR-ILD is high. The course of disease, serum LDH level, and RP-ILD are prognostic factors of male anti-MDA5 antibody-positive patients.
ABSTRACT
Objective:To investigate the role of HIS (hyperinflammatory syndrome) score in predicting the prognosis of anti-melanoma differentiation associated gene 5(MDA5) antibody-positive dermatomyositis (DM) patients with interstitial lung disease (ILD).Methods:A total of 43 patients with anti-MDA5 antibody-positive dermatomyositis and 228 connective tissue disease (CTD) patients with ILD hospitalized in the First Affiliated Hospital of Nanjing Medical University from January 2018 to April 2021 were enrolled into this study. All patients were complicated with ILD and their HIS score were assessed. Non-parametric Mann-Whitney U test, Chi-squared test, Fisher exact probability and receiver operating characteristic (ROC) curve were used for data analysis. Results:The HIS score of 43 patients with anti-MDA5 antibody-positive dermat-omyositis were collected. Among 228 CTD-ILD patients in the control groups, the primary disease consisted of 33(14.5%) anti-synthetase antibody syndrome (ASS), 44(19.3%) rheumatoid arthritis (RA), 65(28.5%) Sj?gren's syndromes (SS), 43 (18.9%) systemic sclerosis (SSc) and 43 (18.9%) systemic lupus erythematosus(SLE). The HIS score of anti-MDA5-positive DM-ILD patients [2(1, 3)] was higher than those in ASS patients [1(0, 2), Z=-2.06, P<0.05] and significantly higher than those in RA-ILD [1(0, 2), Z=-2.87, P<0.01], SS-ILD [0(0,1), Z=-5.78, P<0.01], SSC-ILD [1(0, 1), Z=-3.84, P<0.01] and SLE-ILD [1(0, 2), Z=-3.81, P<0.01]. Comparing HIS score of anti-MDA5-positive DM-ILD patients, the 3-months mortality rate in the low, medium and high groups was 0(0/15), 38.1%(8/21) and 85.7%(6/7). The area under ROC curve (95% CI) was 0.857[(0.747, 0.967), P<0.001] for HIS score in predicting 3-months mortality probability of anti-MDA5-positive DM-ILD. Conclusion:HIS score of anti-MDA5-positive DM-ILD is higher than that in CTD-ILD patients and the baseline level is related to the 3-months mortality rate.
ABSTRACT
Objective To investigate the expression and clinical significance of transcription factor SOX5 in peripheral blood mononuclear cells (PBMCs) and serum in patients with rheumatoid arthritis (RA). Methods The relative expression of representative genes of the SOX gene family in the PBMCs from RA patients were detected by Real-Time Polymerase Chain Reaction (RT-PCR), and serum levels of SOX5 expression were measured by enzyme-linked immunosorbent assay (ELISA) in 30 RA patients, 27 osteoarthritis (OA) patients and 30 healthy controls (HC). The expression levels of SOX5 in PBMCs were detected by RT-PCR after stimulated with IL-6, TNF-α, IL-1β and IL-17 for 24 hours. The relationship between SOX5 and receptor activator of nuclear factor κB ligand (RANKL) was detected by co-Immunoprecipitation (co-IP). The formation of TRAP-positive cells after silence SOX5 in osteoclast precursor cell treated with RANKL was observed by Tartrate-resistant acid phasphate stain (TRAP). The differences were tested using one-way ANOVA followed by Student-Newman-Keuls post hoc analysis Correlations were analyzed using Pearson's analysis. Results SOX5 was predominantly expressed in the PBMCs of RA as compared with other SOX family genes in PBMC. PBMC levels of SOX5 in RA patients (21±19) were higher than the OA patients (10±8) and healthy control group (5±4)(F=8.343, P<0.01). While, Serum levels of SOX5 in RA patients [(19132±12054) pg/ml were higher than the OA patients [(9065±15172) pg/ml] and healthy control group [(3242±1251) pg/ml] (F=15.31, P<0.01). IL-6, TNF-α, IL-1β and IL-17 led to the up-regulation of SOX5 expression in PBMCs. IL-6, TNF-α, IL-1β promoted the interaction of SOX5 and RANKL in PBMCs. Silencing SOX5 reduced the formation of TRAP-positive cells in osteoclast precursor cell treated with RANKL. Conclusion Our results have proven that transcriptional factor SOX5 regulates the expression of RANKL and participates in the process of RA bone erosion. Inhibition of SOX5 expression may be a new therapy target of RA.
ABSTRACT
Objective To investigate the serum level of calcium-binding protein A9(S100A9)in patients with rheumatoid arthritis and explore its potential clinical significance. Methods The serum level of S100A9 was measured by ELISA in 79 rheumatoid arthritis (RA) patients and 20 healthy controls (HC). The correlation of S100A9 level and relevant clinical parameters were analyzed. Results The serum level of S100A9 was significantly increase in RA patients than those in HC. The serum level of S100A9 was higher in high disease activity than that in moderate and low disease activity in the RA group. There was a positive correlation in serum S100A9 level and DAS28 score,Rheumatoid factor,tender joint count and swollen joint count. Conclusion The serum level of S100A9 increases in RA patients and correlates with RA activity.
ABSTRACT
Objective To investigate the prevalence and risk factors of hyperuricemia (HUA) in rural residents of Gaoyou City,Jiangsu Province.Methods A total of 4504 rural residents were investigated in a cross-sectional study.Questionarre survey and physical examination were used for the stndy.Fatsing venous blood samples were collected for biochemical examination.T-test,chi-square test for multiple-group data comparison and logistic regression analysis were used for statistical analysis.Results The prevalence of HUA was 11.9%,15.7% in male,which was significantly higher than 8.6% in the female (P<0.01),the risks of HUA in male was 1.98 times higher than in female.The average value of serum uric acid in this population was higher than.that of female.The prevalence of HUA in female increased with age.Non-conditional logistic regression analysis showed WHR,Cr,Tg,hypertension were the independent risk factors of male patients with HUA.Age,BMI,Cr,Tg,hypertension were independent risk factors of HUA in female.Conclusion The prevalence of HUA can be affected by age and sex.Weight control,keeping blood pressure and blood lipid profiles in normals levels are important for the prevention of HUA.
ABSTRACT
Objective To explore the potential role of high levels of adiponectin (AD) in the inflammatory joint of rheumatoid arthritis (RA). Methods ELISA was used to measure the levels of AD, IL-Iβ,IL-6, IL-8, TNF-α, MCP-1 and MMP-9 in the synovial fluids of RA and osteroarthritis (OA), the levels of these cytokines were tested after the synovial fibroblasts (SFLs) were stimulated with AD. Doublelabeling immunohistochemistry was used to analyze the expression of AD in RA synovium. Cytokines were measured by ELISA after SFLs were stimulated with AD. The expression of RANKL was detected by real-time PCR after MH7A were treated with AD and IL-6 ANOVA, Student's t-test, Mann-Whitney U-tese, Spearman's-test were used for statistical analysis. Results High levels of AD in RA synovial fluids were correlated with IL-6 levels. Double labeling immunohistochemistry showed that AD was localized in fibroblasts. MCP-1 and IL-6 were dramatically increased in human synovial fibroblasts following incubation with recombinant AD for 24 h. RANKL mRNA was significantly increased in MH7A after treated with AD and IL-6. Conclusion High levels of AD in the inflammatory joints of RA are likely to contribute to the high expression of IL-6, MCP-1 and RANKL, which may play an important role in the chronic inflammation, osteoclasts activation and bone erosion in RA.
ABSTRACT
Objective To study the expression of Adiponectin (AD) and its receptors Adiponectin receptor 1 (Adipo R1) and Adipo R2 in the synovial fluids and the synovium of rheumatoid arthritis (RA). Methods ELISA was used to determine the levels of AD in 23 RA and 23 osteoarthritis (OA) patients. Real-time PCR and Western blot techniques were employed to study the expression of AD, AdipoR1 and AdipoR2 in the synovium of 10 RA and OA patients. Results It was observed that approximately twice more adiponeetin in the synovial fluids of patients with RA than with OA. Adiponectin and AdipoR1, but not AdipoR2 mRNA, were significantly expressed in synovium of RA patients in comparison with OA. Adiponectin and AdipoR1 protein were wuch more expressed in synovium from RA than those from OA. Conclusion High expression of Adiponectin and AdipoRl is likely to contribute to the formation of inflammatory joints in RA.
ABSTRACT
Objective Through investigating the effect of mesenchymal stem cells (MSCs) on the expression of yon Willebrand factor (vWF) and soluble thrumbomodulin (sTM) of vascular endothelial cells stimulated by serum of systemic lupus erythematosus (SLE) patients to discuss the repairing effect of MSCs on injured endothelium of SLE patients.Methods When human umbilical vein endothelial cell strain ECV-304 was co-cultivated with serum of SLE patients in vitro for twelve hours in order to induce endothelial cells injury,then MSCs were seeded for three days.Enzyme linked immunosorbent assay (ELISA) was used to detect the expression of vWF and sTM in the supernatant.Results When ECV-304 was stimulated by serum of SLE patients,the expression of vWF and sTM in the supernatant was significantly higher than that in the groups not stimulated by serum of SLE patients;When MSCs were seeded ,the expression of vWF in the Lupus serum stimulated group in which MSCs were seeded was significantly lower than that in the lupus serum stimulated group in which MSCs were not seeded,but the expression of sTM between the lupus serum stimulated group which MSCs were seeded and the lupus serum stimulated group in which MSCs were not seeded was not significantly deviatied.Conclusion Serum of lupus patients at active stage can cause injure vascular endothelial cells.MSCs can downregulate the expression of vWF of vascular endothelial cells.These suggest it may participate in the repairing of injured vascular endothelium of SLE patients.
ABSTRACT
Objective To present the experience of surgical treatment of 12 patients with advanced carcinoma of esophagus involving aorta. Methods Resection of esophageal carcinoma and cervical esophago-gastrostomy or supraaortic esophago-gastrostomy were done in 12 patients. In all 12 patients, the resection of limited aortic adventitia was performed in 2 patients, excision of aorta and simple suture in 2 patients and aortoplasty with Gore-Tex patch in 7 patients, the resected segment was replaced with artificial vessel in 1 patient. Results Complete recovery was achieved in 2 weeks in 12 patients, without severe complications such as aortic fistula. Conclusion Surgical treatment expands the operative indications for patients suffering from esophageal carcinoma involving aorta and improves their life quality.
ABSTRACT
Objective To summarize the experience of surgical treatment of ascending aortic aneurysms and aortic dissections. Methods From February 2001 to October 2005, 31 patients including 26 male, 5 female, aged 41.3 years old (range 14-72) received surgical management. Twenty cases were diagnosed as ascending aortic aneurysm and aortic root aneurysm, 8 as Standford A dissection, 3 as Stanford B dissection. Twenty-one patients underwent classic Bentall procedure in which VSD repair was carried out in 1 case, mitral valvoplasty in 2 and mitral valve replacement in 2; Four patients underwent modified Bentall procedure (coronary button technique); Three patients underwent Wheat procedure; The remaining 3 patients with Stanford B dissection underwent graft replacement of descending aorta. Results There was no death during hospital stay that lasted 13-46 d with an average of 16.4 d after operation. The mean clinical follow-up was (21?18.5) months (range 1-63 months). One patient died without describable cause two years later. One patient had ascending aorta-pulmonary artery fistula at color Doppler examination half a year later. One patient was detected rupture of distal anastomoses half a year after operation and underwent stent-graft, SG. Conclusion The surgical treatment of aortic aneurysms and aortic dissections could be carried out safely based on the accurate diagnosis, specific surgical strategy and fine technique.