Osteoarthritis (OA) is a chronic degenerative joint disorder. Previous studies have shown abnormally increased apoptosis of chondrocytes in patients and animal models of OA. TNF-α and nitric oxide have been reported to induce chondrocyte ageing; however, the mechanism of chondrocyte apoptosis induced by IL-1β has remained unclear. The aim of this study is to identify the role of the c-Jun N-terminal kinase (JNK) - c-Jun pathway in regulating induction of Bim, and its implication in chondrocyte apoptosis. This study showed that Bim is upregulated in chondrocytes obtained from the articular cartilage of OA patients and in cultured mouse chondrocytes treated with IL-1β. Upregulation of Bim was found to be critical for chondrocyte apoptosis induced by IL-1β, as revealed by the genetic knockdown of Bim, wherein apoptosis was greatly reduced in the chondrocytes. Moreover, activation of the JNK-c-Jun pathway was observed under IL-1β treatment, as indicated by the increased expression levels of c-Jun protein. Suppression of the JNK-c-Jun pathway, using chemical inhibitors and RNA interference, inhibited the Bim upregulation induced by IL-1β. These findings suggest that the JNK-c-Jun pathway is involved in the upregulation of Bim during OA and that the JNK-c-Jun-Bim pathway is vital for chondrocyte apoptosis.
BackgroundAutoimmune diseases (AID) are often treated with glucocorticoids. Glucocorticoids have a number of substantial side effects in human body, including hyperglycemia and osteoporosis.ObjectivesOur study was to investigate the use of glucocorticoid in patients with autoimmune diseases and its negative influence on blood glucose and osteoporosis in the patients who receiving glucocorticoid treatment.MethodsPatients with autoimmune diseases were enrolled from July to December in 2017 in rheumatology department of the Third Affiliated Hospital of Sun Yat-sen University. Demographic information, family history, past medical history, and clinical information were collected by two rheumatologists, including years of having glucocorticoids for treatment, largest dose of methylprednisolone, current dose of glucocorticoids. Blood glucose, glycosylated haemoglobin, and bone mineral density was required. The Statistical Package for Social Sciences (SPSS) software version 21 was used for all data management and analysis.ResultsOf all the 75 patients, 15 (20%) were male patients. 14.7% had primary education, while 26.6% received education in university. Numbers of the patients were stated as follows. Lupus, 29; rheumatoid arthritis, 4; Sjogren’s syndrome, 10; systemic sclerosis, 10; myositis, 4; mixed connective tissue disease, 1; autoimmune hepatitis, 1; vasculitis, 5; other diseases, 11. Mean age was 40.29±14.64 years. Mean disease duration was 4.74±6.62 years. 3 (4%) patients had family history of diabetes. 3 (4%) patients had past medical history of diabetes. Mean duration of taking glucocorticoids was 3.30±4.40 years. 13 (17.3%) of the patients underwent high dose of glucocorticoid intravenous pulse (120 mg to 1000 mg of methylprednisolone). Current dose of glucocorticoids was 5.30±3.96 tablets of methylprednisolone. Mean blood glucose was 4.61±0.92 mmol/L. Mean glycosylated haemoglobin was 5.46±0.84. 2 patients were found to have diabetes in this study. 5 other patients were found to have higher blood sugar than normal range (3.9–6.1 mmol/L, according to our laboratory). 14 (18.7%) of the patients had osteoporosis according to BMD scores. In 17 patients who had receiving glucocorticoids for more than five years, 3 (17.6%) patients were found to have higher blood sugar than normal range and 5 (29.4%) patients were found to have osteoporosis.ConclusionsGlucocorticoids have substantial side effects in hyperglycemia and osteoporosis in the patient receiving glucocorticoid treatment. More years of taking glucocorticoids could lead to more hyperglycemia and osteoporosis. We should evaluate side effects of glucocorticoids in the patients with AIDs.Disclosure of InterestY. Jiang: None declared, G. Du: None declared, X. Wu: None declared, Y. Xie: None declared, M. Zhao: None declared, Z. Liao Grant/research support from: National Natural Sciences Foundation of China [grant number 81201372], J. Gu Grant/research support from: the 5010 Subject of Sun Yat-sen University (2007023)
The use of blisk is essential for improving the performance of aviation engines, and the cutting of blade curved surface is the core of the blisk CNC machining. In response to the problem of traditional ball end milling cutter and barrel milling cutter that is difficult to take into account the quality and efficiency of curved blade machining, this article proposes a barrel-taper-ball milling cutter. The contour of the new cutter's barrel taper area is more fit with the blade curved surface, which is conducive to obtaining a larger cutting step and a tiny scallop height. Further, for the problem of weak-rigidity thin-wall curved surface machining chatter, the cutting dynamics model of the five-axis machining of the barrel-taper-ball milling cutter is established. Through the determination of the material contact criterion of the cutting edge micro element, the cutting geometry analysis algorithm of the five-axis processing of the blade curved surface is proposed. By deducing the forces in oblique cutting of the barrel taper area and the ball end area, the time-varying characteristics of the blade modes are explored, and the multiple frequently method theory is extended to the five-axis machining of the blade curved surface with barrel-taper-ball milling cutter. Finally, the stable state cutting parameter domain is constructed. Experiments and simulation indicate that the cutting step of the new cutter under the same surface roughness can increase by 7 times, the error of the cutting geometry solution of the blade curved surface is only 0.5%, the average error of the predicted three-dimensional cutting force is about 4.95%, and the optimized stable state cutting parameter can achieve machining without cutting chatter.
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