Objective This study aims to analyze the clinical characteristics of idiopathic inflammatory myopathy (IIM) associated interstitial lung disease (ILD) with positive anti melanoma differentiation-associated gene 5 (MDA5) antibody. Methods The clinical data of 91 patients with IIM in Shanxi Bethune Hospital from Jan 2019 to Mar 2022 were collected. Then various comparisons and analyzed retrospectively in the clinical symptoms, laboratory indicators and imaging characteristics between the negative MDA5-IIM and the positive anti-MDA5-IIM. ResultsCompared with the negative anti-MDA5-IIM patients, the significantly higher incidences of Gottron sign (71.0% vs. 38.3%), ulcerative rash (45.2% vs.16.7%), dyspnea (64.5% vs. 36.7%), and ILD (71.0% vs. 43.3%), in the positive anti-MDA5-IIM patients (P<0.05). Compared with the negative anti-MDA5-IIM patients, the more ground-glass opacification (GGO) in the positive anti-MDA5-IIM patients on high resolution computed tomography (81.8% vs.53.8%, P<0.05). Compared with the positive anti-MDA5-IIM patients without ILD, the positive anti-MDA5-IIM patients with ILD had significantly higher incidence of Gottron sign (77.3% vs. 33.3%), the increased levels of lactate dehydrogenase [(525.20±203.09) IU/L vs. (321.73±188.88) IU/L], Krebs von den Lungen-6 [(1399.55±869.64) U/mL vs. (371.56±128.92) U/mL], and D-dimer [(1226.65±902.31) U/L vs. (703.73±160.11) U/L], as well as higher positive rate of anti-Ro-52 antibody (68.2% vs. 22.2%) and the higher case fatality rate (54.5% vs. 0.0%), with all P<0.05. The triple treatment of high-dose glucocorticoid (GC) combined with intravenous cyclophosphamide (IVCY) and another immunosuppressive agent (tacrolimus or tofacitinib) was found to be effective in the MDA5-IIM associated ILD group, with a lower case fatality rate (28.6%) than high-dose GC combined with IVCY group (47.1%). Conclusions The positive anti-MDA5-IIM with ILD of patients have the higher incidence of rash and dyspnea, with GGO as the most common imaging manifestation. When rapidly progressive interstitial lung disease (RPILD) is combined, the case fatality rate higher. Meanwhile, early intensive immunosuppressive therapy may improve the survival rate of RPILD patients with positive anti-MDA5 antibody.
Objective To investigate the feasibility of fabricating an oriented scaffold combined with chondrogenic-induced bone marrow mesenchymal stem cells (BMSCs) for enhancement of the biomechanical property of tissue engineered cartilage in vivo. Methods Temperature gradient-guided thermal-induced phase separation was used to fabricate an oriented cartilage extracellular matrix-derived scaffold composed of microtubules arranged in parallel in vertical section. No-oriented scaffold was fabricated by simple freeze-drying. Mechanical property of oriented and non-oriented scaffold was determined by measurement of compressive modulus. Oriented and non-oriented scaffolds were seeded with chondrogenic-induced BMSCs, which were obtained from the New Zealand white rabbits. Proliferation, morphological characteristics, and the distribution of the cells on the scaffolds were analyzed by MTT assay and scanning electron microscope. Then cell-scaffold composites were implanted subcutaneously in the dorsa of nude mice. At 2 and 4 weeks after implantation, the samples were harvested for evaluating biochemical, histological, and biomechanical properties. Results The compressive modulus of oriented scaffold was significantly higher than that of non-oriented scaffold (t=201.099, P=0.000). The cell proliferation on the oriented scaffold was significantly higher than that on the non-oriented scaffold from 3 to 9 days (P lt; 0.05). At 4 weeks, collagen type II immunohistochemical staining, safranin O staining, and toluidine blue staining showed positive results in all samples, but negative for collagen type I. There were numerous parallel giant bundles of densely packed collagen fibers with chondrocyte-like cells on the oriented-structure constructs. Total DNA, glycosaminoglycan (GAG), and collagen contents increased with time, and no significant difference was found between 2 groups (P gt; 0.05). The compressive modulus of the oriented tissue engineered cartilage was significantly higher than that of the non-oriented tissue engineered cartilage at 2 and 4 weeks after implantation (P lt; 0.05). Total DNA, GAG, collagen contents, and compressive modulus in the 2 tissue engineered cartilages were significantly lower than those in normal cartilage (P lt; 0.05). Conclusion Oriented extracellular matrix-derived scaffold can enhance the biomechanical property of tissue engineered cartilage and thus it represents a promising approach to cartilage tissue engineering.