Mann C, Gooberman-Hill R. Health care provision for osteoarthritis: concordance between what patients would like and what health professionals think they should have. Arthritis Care Res (Hoboken) 2011;63:963–972. doi: 10.1002/acr.20459. The orally administered, selective inhibitor of Janus Kinase 1 (JAK1), filgotinib (FIL), is currently being investigated for the treatment of rheumatoid arthritis (RA) in Phase 3 studies and in other inflammatory diseases.

Gomez-Sanchez R, Yakhine-Diop SM, Bravo-San Pedro JM, Pizarro-Estrella E, Rodriguez-Arribas M, Climent V, et al. PINK1 deficiency enhances autophagy and mitophagy induction. Mol Cell Oncol. 2016;3:e1046579. Wang K, Zhou LY, Wang JX, Wang Y, Sun T, Zhao B, et al. E2F1-dependent miR-421 regulates mitochondrial fragmentation and myocardial infarction by targeting Pink1. Nat Commun. 2015;6:7619. Chen Y, Dorn GW 2nd. PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria. Science (New York, NY). 2013;340:471–5. Galluzzi L, Pedro JM, Demaria S, Formenti SC, Kroemer G. Activating autophagy to potentiate immunogenic chemotherapy and radiation therapy. Nat Rev Clin Oncol. 2016;14:247–58.Rougerie P, Largeteau Q, Megrelis L, Carrette F, Lejeune T, Toffali L, et al. Fam65b is a new transcriptional target of FOXO1 that regulates RhoA signaling for T lymphocyte migration. J Immunol (Baltimore, MD: 1950). 2013;190:748–55. Pasman Z, Been MD, Garcia-Blanco MA. Exon circularization in mammalian nuclear extracts. RNA (New Y, NY). 1996;2:603–10. Conventional electron microscopy was performed as described previously [ 41]. In brief, cells were fixed with 2.5% glutaraldehyde and then postfixed with 1% osmium tetraoxide, dehydrated in a graded series of ethanol concentrations, and embedded in Embed812 resin. The ultrathin sections were mounted on copper grids and then double-stained with uranyl acetate and lead citrate. The number of autophagic vacuoles was determined for a minimum of 100 cells. Heart ultrastructural analysis was also performed. The samples were examined and photographed with a FEI Tecnai spirit transmission electron microscope. Echocardiographic assessment

Autophagy is a well-established conserved mechanism that delivers the intracellular constituents and organelles to lysosomes for degradation [ 1]. More and more studies suggest that autophagic death is an important process that is distinct from apoptosis [ 2]. Autophagy has been demonstrated to have a critical role in many physiological and pathological processes. Dysregulation of autophagy is associated with a number of cardiac diseases including dilated cardiomyopathy, ischemic heart disease, and heart failure [ 3, 4, 5]. Although the regulation of autophagy is important in cardiovascular diseases, there is no effective treatment for the autophagy-related cardiac diseases and heart failure. Exploring and revealing the molecular mechanisms underlying the regulation of autophagy will provide a potential interventional strategy for treating cardiovascular diseases. Lin Z, Murtaza I, Wang K, Jiao J, Gao J, Li PF. miR-23a functions downstream of NFATc3 to regulate cardiac hypertrophy. Proc Natl Acad Sci USA. 2009;106:12103–8. Odding E, Valkenburg HA, Algra D, Vandenouweland F, Grobbee D, Hofman A. Association of locomotor complaints and disability in the Rotterdam study. Ann Rheum Dis. 1995;54:721–725. doi: 10.1136/ard.54.9.721. Li Z, Huang C, Bao C, Chen L, Lin M, Wang X, et al. Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct. 2015;22:256–64.Of the participants with hip complaints, 63% (n = 370) were classified as having HOA at baseline according to the ACR criteria. Of those not classified with HOA at baseline, 40% developed HOA according to the clinical or combined clinical/radiographic ACR criteria after 2 and/or 5 years. Up to 92% of participants (n = 829) with knee complaints were classified as having KOA at baseline; of those not classified with KOA at baseline, 55% developed KOA according to the clinical ACR criteria or the clinical/radiographic ACR criteria after 2 and/or 5 years. The following factors were associated with development of HOA: morning stiffness (OR 2.39; 95% CI 1.14-4.98), painful internal rotation (OR 2.53; 95% CI 1.23-5.19), hip flexion < 115° (OR 2.33; 95% CI 1.17-4.64) and erythrocyte sedimentation rate (ESR) < 20 mm/h (OR 2.94; 95% CI 1.13-7.61). No variables were associated with development of KOA at 2-year and/or 5-year follow up. Stable Internet Connection: Users will be required to have a stable and strong internet connection for streaming videos and programs. For circRNA microarrays, total RNAs were extracted from the sham-treated mice and I/R-treated mouse heart tissues. The fluorescent cRNA was obtained using random primers according to Arraystar Super RNA Labeling protocol (Arraystar Super RNA Labeling Kit; Arraystar). Then the labeled cDNA was hybridized to Arraystar mouse circRNA Array. The microarray hybridization and the collection of data were performed by Kang Chen Bio-tech, Shanghai, China. For the transcriptome microarray, total RNA was extracted from cardiomyocytes by using Trizol reagent and then the isolated mRNAs were reverse transcribed and hybridized to mouse Genome Array (CapitalBio Corp.). Transmission electron microscopy Beilina A, Van Der Brug M, Ahmad R, Kesavapany S, Miller DW, Petsko GA, et al. Mutations in PTEN-induced putative kinase 1 associated with recessive parkinsonism have differential effects on protein stability. Proc Natl Acad Sci USA. 2005;102:5703–8. Huttlin EL, Jedrychowski MP, Elias JE, Goswami T, Rad R, Beausoleil SA, et al. A tissue-specific atlas of mouse protein phosphorylation and expression. Cell. 2010;143:1174–89.