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Hypoxia is a prominent microenvironment feature in a range of disorders including cancer, rheumatoid arthritis (RA), atherosclerosis, inflammatory bowel disease (IBD), infection and obesity. Hypoxia promotes biological functions of fibroblast-like synoviocytes via regulating hypoxia-inducible factor 1α (HIF1α). Dysregulated protein citrullination in RA drives the production of antibodies to citrullinated proteins, a highly specific biomarker of RA. However, the mechanisms promoting citrullination in RA are not yet fully elucidated. In this study, we investigated whether pathophysiological hypoxia as found in the rheumatoid synovium modulates the citrullination in human fibroblast-like synoviocytes (HFLS). Here, we found that peptidylarginine deiminase 2 (PAD2) and citrullinated proteins were increased in HFLS after exposure to hypoxia. Moreover, knocking down HIF1α by HIF1α siRNA ameliorated the expression of PAD2 and citrullinated proteins. Collectively, this study provides a new mechanism involved in generating citrullinated proteins: hypoxia promotes citrullination and PAD production in HFLS. Concurrently, we also proposed a novel hypoxia involved mechanism in RA pathogenesis. This study deepens our understanding of the role of hypoxia in the pathogenesis of RA and provides a potential therapeutic strategy for RA.

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BackgroundChina has no primary medical care and referral system. Patients can choose any hospitals or any doctors they like to seek medical care in China. As a result, most patients with rheumatic diseases rushed to a few large cities.Survey shows more than 40% of the rheumatic disease patients don't need to go to hospital and they only need advices from specialist.Smart System of Disease Management (SSDM) is a series of applications for chronic diseases management, which develop the interaction between doctors and patients. The study shows that, after training, the RA patients can master the SSDM and perform self-management, including DAS28 and HAQ evaluations, as well as medication and lab test data entries.ObjectivesTo evaluate the feasibility and benefit of the medical economics of online consultation based on SSDM by rheumatologist.MethodsThe rheumatologists implemented the education and training programs on using SSDM and assist the patients in downloading SSDM APP.The SSDM includes doctors' application and patients' application. The patient application includes self-assessment (DAS28, HAQ), medication management, adverse events management and laboratory records. After data entry, patients can synchronize data to the authorized doctor. On the basis of understanding of the disease activities, medication and laboratory test results, the rheumatologists can accept consultation request from their patients, and practice consultation in the form of text or telephone call.ResultsBetween February 14, 2015 and January 24, 2016, 11 rheumatologists supplied 76 patients with 58 times free and 45 paid consultations. Paid consultations included 34 times text Q&A and 11 telephone consultations. The consulting fee ranged from RMB 50 to 500 yuan (EUR: RMB =1:7.1) each in average of 272.22 ±90.40 yuan, which is approximate to the registration fee in hospital. The total amount of consultation fee was 12,250 yuan.87% patients receiving online consultation lived in different city with the rheumatologists. If patients seek medical care in hospital, in addition to the registration fees and medical expenses, the mean cost of transportation, accommodation, meals and lost wages was 1320.39±456.10 (300 - 2,800) yuan. The total of cost for all patients would have been 160,450 yuan, which is 13.10 times compared with the cost of online. Through the SSDM system for online consultations, patients can save 92.37% of the cost. Table 1 shows detailed information. Survey shows all patients were satisfied and 64.86% of them were “very satisfied” with the consultations.ConclusionsUsing SSDM system to obtain online consultation, Chinese patients with rheumatic disease can enjoy reduced cost with high satisfaction. In the era lack of primary care system in China, SSDM may serve as a complimentary platform to control medical care cost, as well as relieve the tensions between health care professionals and patients.Disclosure of InterestNone declared

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