2016年PANLAR共识建议——骨关节炎 Recommendations and Level of Evidence Relating to Hand OA Nonpharmacological treatment modalities 1. Education with regard to joint protection together with an exercise regimen including muscle strengthening and range of motion exercises .(IC) 2. The combination of an orthosis (splint) with an exercise regimen to improve pain and functionality in the short and long term.(IIaB) Pharmacological treatment modalities 3. Topical NSAIDs are indicated as being effective and safe for mild to moderate pain in patients with few affected joints and in elderly patients with mild to moderate persistent pain.(IA) 4. Acetaminophen/paracetamol (up to 3 g/day) is the preferred oral analgesic for the long-term treatment particularly in elderly patients because of its relative safety in comparison with NSAIDs. (IB) 5. Oral NSAIDs are recommended at the lowest effective dose and for the shortest time possible if patients present inadequate response to acetaminophen/paracetamol . The high risk associated with gastrointestinal and cardiovascular events should be considered. (IA) 6. The use of chondroitin sulfate for pain relief and function is recommended as it has a good safety profile.(IA) 7. Glucosamine and chondroitin sulfate are supported in the treatment of hand and knee OA. (IB) 8. Steroids or intra-articular hyaluronic acid may be considered for use in the treatment of OA of the symptomatic TMC joint. (IIaB) 9. Intramuscular steroid is not recommended for patients with symptomatic hand OA. (IIIC) 10. The use of diacerein is not recommended as its effectiveness and the risk/benefits profile has not been established. (IIIC) 11. Adalimumab or infliximab are not recommended in patients with secondary or erosive hand . (IIIB) 12. Bisphosphonates (clodronate) is not recommended.(IIIB) 13. Hydroxychloroquine is not recommended for the symptomatic treatment of erosive hand OA. (IIIC) Surgical treatment modalities 14. Trapeziectomia, arthroplasty with ligament reconstruction and tendon interposition , or arthrodesis may be considered for severe OA of the base of the first finger (rhizarthrosis) if severe pain and/or disability and after conservative treatment have failed.(IIbB) 15. Ligament reconstruction is recommended for stage I. Hemitrapeziectomy, TM joint arthrodesis, implant, or arthroplasty is recommended for stages II and III. Complete removal of the trapezium with or without ligament reconstruction is recommended for stage IV. (IIbB） Recommendations and Level of Evidence Relating to Hip OA Nonpharmacological treatment modalities 1. Information and education regarding the therapeutic objectives and the importance of changes in lifestyle, which include an exercise regimen, weight reduction, use of walking aids (walking stick and crutches) and shoe adjustments and other measures to prevent the progression of joint damage. (IB) 2. Strengthening the extensors and abductors improves functionality and can be used to prepare the patient before a hip implant.(IB) 3. The use of orthoses is recommended to prevent the progression of degenerative changes and improve hip function.(IIbB) 4. Thermotherapy can be performed to relieve pain.(IB) 5. Transcutaneous electrical nerve stimulation (TENS) should also be used for pain relief and to reduce stiffness.(IIbB) 6. Aerobic exercise performed on a regular basis and muscle stretching and strengthening and joint mobility exercises are recommended.(IB) 7. The use of a walking stick in the contralateral hand is also recommended. The handle should be at the level of the greater trochanter of the femur .(IIbB) 8. A neuromuscular bandage may be beneficial as it aids analgesia, stimulates circulation, and reduces pressure. Consequently,the patient’s posture is improved.(IIaB) Pharmacological treatment modalities 9. The use of acetaminophen/paracetamol is recommended in mild to moderate pain, owing to its safety profile.(IB) 10. NSAIDs (ibuprofen, naproxen, diclofenac, meloxicam) or selective COX-2 inhibitors (celecoxib, etoricoxib) may be indicated higher than usual doses in more severe pain.(IB) 11. Naproxen could be used in patients with cardiovascular risk. It should be administered in conjunction with a proton-pump inhibitor owing to the high gastrointestinal risk. (IA) 12. Weak opioids such as tramadol may be beneficial if there is no response to NSAIDs or COX-2 inhibitors, no toleration, or are contraindicated.(IIbB) 13. The use of hyaluronic acid may be beneficial and, thus, could help to reduce the NSAID use.(IIbB) 14. Intra-articular corticosteroid injection (ultrasound-guided) may be beneficial to provide fast pain relief in patients who suffer painful relapses and who do not respond to analgesics and NSAIDs.(IIaB) 15. Avocado and soybean unsaponifiable may play a useful role, and recent studies have provided the evidence that they may slow the progression of OA.(IIA) 16. The use of diacerein has reported a high rate of adverse effects, such as diarrhea and risk of liver damage.(IIIB) Surgical treatment modalities 17. Total hip arthroplasty is indicated when OA is accompanied by pain and walking difficulty and when the quality of life is impaired. It improves not only these factors but also patient survival. A variety of models and metal implants are available and different approaches can be chosen such as the use of a cemented, uncemented, or hybrid prosthesis. Recommendations and Level of Evidence Relating to Knee OA Nonpharmacological treatment modalities 1. Information and education regarding treatment goals and the importance of lifestyle changes to reduce the degenerative damage of the knee joint should be provided.(IA) 2. Hydrotherapy in a therapeutic tank may be indicated in mild knee pain without swelling or stiffness; it is especially beneficial for elderly patients.A program of exercises for flexibility, mobilization, and stretching can be included.(IIaA) 3. Mechanotherapy, including flexibility programs and mobilization and stretching exercises, can reduce pain and improve the range of motion of the knee.(IIbA) 4. Thermotherapy (heat and cold) may help to improve the symptoms of knee OA.(IIaA) 5. The use heat to reduce pain and stiffness before performing flexion exercises in moderate and persistent pain is recommended.(IB) 6. A program of flexibility, stretching, and strengthening exercises for symptomatic knee OA is recommended as this reduces pain during walking and climbing stairs and improves the strength of the quadriceps femoris.(IA) 7. A daily walk is recommended as this improves muscle strength, aerobic capacity, and endurance; facilitates a good night’s sleep; and reduces knee pain.(IA) 8. Aerobic exercise can be implemented gradually and progressively according to each patient’s level of fitness at a frequency of three or more times per week, with a minimum duration of 20 to 30 minutes per session.(IA) 9. Exercises for concentric contraction of the flexor and extensor muscles of the knee are indicated as these have been shown to reduce pain both at rest and during activity.(IA) 10. Support devices may be useful for reducing pain and stiffness and improving the functionality of the knee.Insoles and knee braces have been shown to decrease valgus or varus and knee pain.(IIaA) 11. The use of bandage tape may help to reduce pain in patients with joint instability knee OA.(IIaB) 12. The use of assistive devices such as a walking stick, walker, or crutches is suggested as a preventive measure.A walking stick must be used in the contralateral hand and the height must be adjusted to the level of the greater trochanter, with the elbow bent at an angle of 25 to 30 degrees.(IIaB) Pharmacological treatment modalities 13. Acetaminophen/paracetamol is recommended at a dose of up to 3 g/day for the treatment of mild pain resulting from knee OA. Moderate gastrolesive effects may occur and patients should be monitored for possible hepatic complications.(IB) 14. NSAIDs such as diclofenac, ibuprofen, and naproxen, and selective NSAIDs including celecoxib and etoricoxib are indicated in moderate pain.In all cases, gastric protection, such as a proton-pump inhibitor, is required and naproxen is recommended in patients with cardiovascular risk.(IA) 15. Topical NSAIDs may be indicated in patients with gastrointestinal risk, even though the analgesic response decreases after 1 year of use.(IA) 16. The use of tramadol in the case of severe pain in its various administration forms is recommended .(IA) 17. Capsaicin gel was shown to be an effective treatment for knee OA accompanied by mild to moderate pain.(IIB) 18. Intra-articular corticosteroid injection (ultrasound-guided) may be beneficial to provide fast pain relief.(IIaB) 19. Chondroitin sulfate has shown to have a beneficial effect on symptoms in patients with knee OA and a high safety profile.It has been proven that its effect persists for 3 months after stopping the treatment (carryover effect). Recent studies have provided evidence that chondroitin sulfate use may delay OA progression.(IA) 20. The combined use of glucosamine and chondroitin sulfat e is indicated in patients with knee OA and moderate to severe pain.(IA) 21. Glucosamine may be beneficial for pain relief and for improving joint function in patients.(IA) 22. Avocado soybean unsaponifiable may help to slow the progression of joint damage associated with knee OA.(IIbA) 23. The administration of intra-articular steroids may be reasonable for knee OA accompanied by inflammation.(IIbB) 24. Intra-articular injection of hyaluronic acid of different molecular weights has proven to be beneficial in the treatment of knee OA.(IIaB) 25. Oral administration of hyaluronic acid may have a beneficial therapeutic effect in patients with symptomatic knee OA and may possibly have an even greater effect in relatively young patients.(IIbC) 26. The use of strontium ranelate may be beneficial for the treatment of knee pain.(IIbB) 27. Duloxetine may be helpful for knee OA accompanied by chronic pain. (IIbC) 28. The administration of low-dose oral steroids for a maximum of 12 weeks could be considered in patients older than 65 years.(IIbC) 29. Intra-articular injection of platelet-rich plasma may help to relieve pain associated with knee OA; however, our recommendation is to conduct better quality studies.(IIbC) 30. The use of a supplement containing omega-3 and omega-6 fatty acids, zinc and vitamin E could be considered to reduce pain and stiffness and improve joint function, and also to reduce the intake of NSAIDs/analgesics.(IIB)
EULAR类风湿性关节炎DMARDs治疗指南 The management of rheumatoid arthritis (RA) has changed dramatically over the past 30 years. Few therapeutic agents existed then, which were either minimally or not efficacious, because of toxicity and the fact that optimal dosing and onset of action had not yet been elucidated for some agents.Available therapies were started late rather than early in the course of the disease. Early arthritis clinics were emerging,and their successes fuelled reappraisal of the classification criteria then available that focused primarily on longstanding disease. A therapeutic target had not yet been defined, because relief of symptoms appeared to be the most important goal and the concept of aiming at disease states like remission or low disease activity was at best aspirational. Recommendation 1. Glossary and definitions 2. Overarching principles A. Treatment of patients with RA should aim at the best care and must be based on a shared decision between the patient and the rheumatologist . B. Treatment decisions are based on disease activity and other patient factors, such as progression of structural damage,comorbidities and safety issues . C. Rheumatologists are the specialists who should primarily care for patients with RA. D. RA incurs high individual, medical and societal costs, all of which should be considered in its management by the treating rheumatologist. 3. Recommendations General aspects Individual recommendations 1. Therapy with DMARDs should be started as soon as the diagnosis of RA is made. 2. Treatment should be aimed at reaching a target of sustained remission or low disease activity in every patient. 3. Monitoring should be frequent in active disease (every 1–3 months); if there is no improvement by at most 3 months after the start of treatment or the target has not been reached by 6 months, therapy should be adjusted. 4. MTX should be part of the first treatment strategy. 5. In patients with a contraindication to MTX (or early intolerance), leflunomide or sulfasalazine should be considered as part of the (first) treatment strategy. 6. Short-term GC should be considered when initiating or changing csDMARDs, in different dose regimens and routes of administration, but should be tapered as rapidly as clinically feasible. 7. If the treatment target is not achieved with the first csDMARD strategy, in the absence of poor prognostic factors,other csDMARDs should be considered. 8. If the treatment target is not achieved with the first csDMARD strategy, when poor prognostic factors are present,addition of a bDMARD* or a tsDMARD* should be considered;current practice would be to start a bDMARD§ . 9. bDMARDs* and tsDMARDs# should be combined with a csDMARD; in patients who cannot use csDMARDs as comedication, IL-6 pathway inhibitors and tsDMARDs may have some advantages compared with other bDMARDs . 10. If a bDMARD* or tsDMARD§ has failed, treatment with another bDMARD or a tsDMARD should be considered; if one TNF-inhibitor therapy has failed, patients may receive another TNF-inhibitor or an agent with another mode of action. 11. If a patient is in persistent remission after having tapered GC, one can consider tapering bDMARDs , especially if this treatment is combined with a csDMARD . 12. If a patient is in persistent remission, tapering the csDMARD could be considered . 4. The 2016 EULAR updated recommendations 5. Algorithm based on the 2016 European League Against Rheumatism (EULAR) recommendations on rheumatoid arthritis (RA) management.
有影响力的研究，免费获取 - 阅读，分享，引用 这里有骨质疏松和关节炎的顶级研究 还有发表于核心期刊的新观点和突破性研究： Risk Factors for Hip Fracture in Older Men: The Osteoporotic Fractures in Men Study (MrOS) 这项前瞻性研究基于 5,994 位从美国 6 个临床机构招募到的 65 岁以上的研究对象（主要是高加索人），本次研究全面评估了老年男性髋部骨折的风险因素 Targeting VEGF and its Receptors for the Treatment of Osteoarthritis and Associated Pain 这篇评论强调了 OA 病理学中的血管内皮生长因子（ VEGF ）的潜在重要性和将抑制 VEGF 及其受体作为 OA 治疗的潜在益处。 Mortality After Atypical Femoral Fractures: A Cohort Study FGF23 Regulates Bone Mineralization in a 1,25(OH) 2 D 3 and Klotho-Independent Manner Short-Term Effect of Estrogen on Human Bone Marrow Fat 此外还有： New eCompendium on Rare Bone Diseases eCompendia 汇总了近期发表在专题期刊上的 JBMR 文章。我们会为每一期 eCompendium 选定一个主题，以期为读者提供最新且易于获取的特定领域的原创性研究文章。 注册获取免费内容提醒 下载 JBMR App Effects of high heel wear and increased weight on the knee during walking 本研究通过测试，即增加高跟鞋的高度和增加 20% 的重量来测试膝盖运动学和动力学的变化，从而解释妇女的膝盖骨关节炎发病率。 Mechanisms of tendon injury and repair 本文介绍了三种最常见的腱末端病 - 屈肌腱撕裂，跟腱断裂，肩袖疾病的受伤及恢复知识的现状，尤其侧重于利用动物模型理解肌腱愈合。 Spotlight on the 2015 Journal of Orthopaedic Research Excellence in Basic, Clinical, and Translational Science Award Tendon Functional Extracellular Matrix 注册免费获取内容提醒 下载 App - iOS 下 载 App - Android 骨质疏松和关节炎的跨学科研究 Annals of the New York Academy of Sciences Questioning the association between bisphosphonates and atypical femoral fractures / 质疑： 双膦酸盐和非典型股骨骨折之间的关联 Arthritis Rheumatology 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis 2015 美国大学风湿病指南中 类风湿 性 关节炎的治疗 Biotechnology and Bioengineering Combining 3D human in vitro methods for a 3Rs evaluation of novel titanium surfaces in orthopaedic applications 结合体外方法的 3D 人体的新型钛表面的整形外科应用的 3R 评价 Clinical and Experimental Pharmacology and Physiology Curcumin alleviates glucocorticoid-induced osteoporosis by protecting osteoblasts from apoptosis in vivo and in vitro 姜黄素通过体内和体外保护成骨细胞凋亡减轻糖皮质激素诱导的骨质疏松症 FEBS Open Bio A comparative proteomics study of a synovial cell line stimulated with TNF-α TNF- α 刺激下的 滑膜细胞系的比较蛋白质组学研究 Journal of Physiology Exercise: The lifelong supplement for healthy ageing and slowing down the onset of frailty 锻炼：健康的老龄化和防止体弱的有效途径 Journal of the American Geriatrics Society Is Self-Reported Sleep Duration Associated with Osteoporosis? Data from a 4-Year Aggregated Analysis from the National Health and Nutrition Examination Survey 自我报告的睡眠时间与骨质疏松症 有关系吗 ？ 4 年 的 全国健康和营养调查数据 汇总分析 WIREs Nanomedicine and Nanobiotechnology Osteogenic growth peptide and its use as a bio‐conjugate in regenerative medicine applications 骨生长胎及其作为生物缀合物在再生医学中的应用 WIREs Systems Biology and Medicine Bringing computational models of bone regeneration to the clinic 骨再生计算模型在临床中的应用 ▲ Return to top 生理学王牌期刊 Physical exercise increases adult hippocampal neurogenesis in male rats provided it is aerobic and sustained Brown adipose tissue activation as measured by infrared thermography by mild anticipatory psychological stress in lean healthy females Journal of Physiology 期待您的投稿 点击下方查看更多内容: K+ Channels and Cardiac Electrophysiology The Biomedical Basis of Elite Performance Advances in Calcium Signalling Physiological Reports Contrasting effects of afferent and efferent vagal nerve stimulation on insulin secretion and blood glucose regulation Physiological Reports has released its latest podcast! 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More New Research in Physiology Comprehensive Physiology Regulation of the Hypothalamic‐Pituitary‐Adrenocortical Stress Response Acta Physiologica Myostatin in relation to physical activity and dysglycaemia and its effect on energy metabolism in human skeletal muscle cells ▲ Return to top 解剖学热门期刊 The Anatomical Record Modeling Ancient Egyptian Mummification on Fresh Human Tissue: Macroscopic and Histological Aspects The Nasal Complex of Neanderthals: An Entry Portal to their Place in Human Ancestry 注册免费获取内容提醒 下载 A pp - iOS 下载 A pp - Android Anatomical Sciences Education The production of anatomical teaching resources using three-dimensional (3D) printing technology Developing medical students as teachers: An anatomy-based student-as-teacher program with emphasis on core teaching competencies 注册免费获取内容提醒 下载 App - iOS 下载 App - Android Developmental Dynamics Developmental Dynamics is seeking a new Editor-in-Chief. 注册免费获取内容提醒 下载 App - iOS 下载 App -Android ▲ Return to top 更多特刊内容 Journal of Anatomy Symposium issue on Primate Ecomorphology Ecomorphology （生态形态学）主要研究动物的形态和栖息地与它们的行为反应之间的关联性。，并介导它的行为反应之间的关联的研究。本期的论文为生态形态学提供了优秀的框架性介绍。 Journal of Neuroscience Research The Amygdala: Dysfunction, Hyperfunction, and Connectivity 本期内容着重介绍了扁桃体在健康和疾病中的作用，并描述了扁桃体的生理特征和结构变化如何表现出不同的疾病。 Journal of Fish Biology Metabolic Rate in Fishes. 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骨关节炎是一种自身免疫病，其特征是膝关节骨骼及软骨组织的自我消化、修复、畸形和疼痛，占关节炎总病例的10%-15%。自身免疫病的病因尚不完全清楚，但通常认为与身体某个部位的慢性炎症有关。这种慢性炎症可能来自肠道菌群失调，也可能来自身体疾病，如癌症患者常伴有骨关节炎。 与其说肥胖是骨关节炎的后遗症，不如说二者都是慢性炎症的并发症。因此，骨关节炎的严重程度并不完全取决于患者的体重是多少，而是也取决于患者所吃的食物是什么。刚刚在《风湿病年报》上发表的一篇文章证实了这个观点。 在小鼠关节炎模型中发现，饲喂饱和脂肪（动物油）的小鼠骨关节炎更严重，饲喂欧米伽6不饱和脂肪酸（植物油）的小鼠骨关节炎有所缓解，而饲喂欧米伽3不饱和脂肪酸（深海鱼油）的小鼠骨关节炎基本康复。 不同种类油脂影响骨关节炎的深层原因在于饱和脂肪酸能促炎，而不饱和脂肪酸能抗炎，其中多不饱和脂肪酸（多个双键）的抗炎能力强于单不饱和脂肪酸（一个双键）。欧米伽6植物油含2-4个双键，欧米伽3深海鱼油含3-6个双键，前者的抗炎活性弱于后者。 因此，从小鼠实验推测，骨关节炎患者吃深海鱼油有助于康复，而吃动物油则会加剧病情，但仍需通过人体试验加以证实。 Omega 3 fatty acids lessen severity of osteoarthritis in mice Date: July 11, 2014 Source: Duke Medicine Summary: Mice consuming a supplement of omega 3 fatty acids had healthier joints than those fed diets high in saturated fats and omega 6 fatty acids, according to researchers. “Our results suggest that dietary factors play a more significant role than mechanical factors in the link between obesity and osteoarthritis,” said the study's senior author. Microcomputed tomography (3D X-ray) images (top) and histology images (bottom) of the knees of mice fed a very high fat diet containing omega 3 fatty acid supplement (left) or only omega 6 fatty acids (right) after a knee injury. The omega 6 diet showed abnormal bone remodeling and calcified tissue formation in the joint (white arrow). The omega 6 diet also showed significant loss of cartilage (red staining, yellow arrowhead) and increased joint inflammation. Credit: Duke Orthopaedic Research Laboratories Mice consuming a supplement of omega 3 fatty acids had healthier joints than those fed diets high in saturated fats and omega 6 fatty acids, according to Duke Medicine researchers. The findings, published in the Annals of the Rheumatic Diseases , suggest that unhealthy dietary fats – not just obesity – may contribute to worsening osteoarthritis. “Our results suggest that dietary factors play a more significant role than mechanical factors in the link between obesity and osteoarthritis,” said Farshid Guilak, Ph.D., Laszlo Ormandy Professor of Orthopaedic Surgery at Duke and the study’s senior author. Obesity is one of the primary risk factors for osteoarthritis, although the mechanisms linking these conditions are not fully understood. It has been assumed that increased weight wears the joints out, but this doesn’t explain why arthritis is also found in hands and other joints that don’t bear weight. Guilak and his colleagues began studying systemic factors other than body weight to determine their effect on arthritis, and in an earlier study in obese mice, found that the lack of appetite hormone leptin predicted whether the mice had arthritis. “This made us think that maybe it’s not how much weight you gain, but what you eat,” Guilak said. In this study, the researchers focused on mice with osteoarthritis of the knee caused by injury to the joint. Arthritis resulting from trauma or injury is thought to account for 10 to 15 percent of all cases of arthritis. The mice were fed one of three high-fat diets: one rich in saturated fat, one rich in omega 6 fatty acids, and one rich in omega 6 fatty acids but supplemented with a small amount of omega 3 fatty acids. Saturated fat, which usually comes from animal sources, is known to raise cholesterol levels. Omega 6 fatty acids, often found in corn oil, soybean oil, nuts and seeds, are thought to be a healthier source of fat. Omega 3 fatty acids, commonly found in fish or fish oil supplements, are often touted as “healthy fat” given their heart-healthy and anti-inflammatory properties. Unfortunately, most Americans eat significantly more saturated fat and omega 6 fatty acids than omega 3 fatty acids. “A healthy diet would include roughly equal ratios of these fats, but we’re way off the scale in the Western diet,” Guilak said. The researchers found that arthritis was significantly associated with the mice’s diets, but not with body weight. The mice that ate diets high in saturated fat or omega 6 fatty acids experienced significant worsening of their arthritis, while mice consuming a small supplement of omega 3 fatty acids had healthier joints. “While omega 3 fatty acids aren’t reversing the injury, they appear to slow the progression of arthritis in this group of mice,” Guilak said. “In fact, omega 3 fatty acids eliminated the detrimental effects of obesity in obese mice.” The researchers also looked at the mice’s ability to heal wounds, which may help them to understand the relationships between arthritis and wound healing. In mice consuming omega 3 fatty acids, a small ear punch typically used to differentiate mice healed much more quickly than it did in animals that did not receive the supplement. “We found that independent of body weight, dietary fatty acids regulate ear wound healing and severity of osteoarthritis following joint injury in obese mice,” said Chia-Lung Wu, a biomedical engineering graduate student in the Duke Orthopaedic Research Laboratories and the study’s lead author. The researchers are working to translate their findings to humans. “A great next step would be to do a clinical study to look at effect of omega 3 fatty acids post-injury,” Guilak said. Story Source: The above story is based on materials provided by Duke Medicine . Note: Materials may be edited for content and length. Journal Reference : Farshid Guilak et al. Dietary fatty acid content regulates wound repair and the pathogenesis of osteoarthritis following joint injury . Annals of the Rheumatic Diseases , July 2014 DOI: 10.1136/annrheumdis-2014-205601
类风湿性关节炎（ rheumatoid arthritis ）是一种以关节滑膜炎为特征的慢性全身性自身免疫性疾病。类风湿性关节炎 是一类自身免疫性疾病，滑膜炎持久反复发作，可导致关节内软骨和骨的破坏，关节功能障碍，甚至残废。尽管这个疾病不是恶性肿瘤，但由于患者病情反复发作，并最终导致关节畸形，功能丧失，会给患者和家庭带来沉重负担。 类风湿性关节炎又称类风湿（ RA ），是一种病因尚未明了的慢性全身性炎症性疾病，以慢性、对称性、多滑膜关节炎和关节外病变为主要临床表现，属于自身免疫炎性疾病。该病好发于手、腕、足等小关节，反复发作，呈对称分布。早期有关节红肿热痛和功能障碍，晚期关节可出现不同程度的僵硬畸形，并伴有骨和骨骼肌的萎缩，极易致残。 从病理改变的角度来看，类风湿性关节炎是一种主要累及关节滑膜，以后可波及到关节软骨、骨组织、关节韧带和肌键，其次为浆膜、心、肺及眼等结缔组织的广泛性炎症性疾病。除关节病变外，类风湿性关节炎的全身性表现还有发热、疲乏无力、心包炎、皮下结节、胸膜炎、动脉炎、周围神经病变等。 类风湿性关节炎病因尚未完全明确，是与环境、细胞、病毒、遗传、性激素及神经精神状态等因素密切相关的疾病。其发病机理也未完全明确，但是属于自身免疫性疾病已被普遍承认。类风湿性关节为病变的组织变化虽可因部位而略有变异，但基本变化相同。有三个特点：弥漫或局限性组织中的淋巴或浆细胞浸润、血管炎和类风湿性肉芽肿形成。 类风湿性关节炎目前属于无法治愈的疾病，治疗目的仅在于：①控制炎症，缓解症状；②保持关节功能和防止畸形；③修复受损关节以减轻疼痛和恢复功能。药物治疗包括三类，一类是“改善病情抗风湿性药物”，这类药物包括咪唑硫嘌呤、环孢霉素、 D-penicillamine 、 gold salts 、 hydroxychloroquine 、 leflunomide 、 methotrexate (MTX) 、 minocycline 和 sulfasalazine 。第二类是抗炎症生物制剂，例如肿瘤坏死因子、白细胞介素 1 和 6 的阻断剂等。第三类就是抗炎药物和镇痛药物。 氢气的抗炎症作用至少可以有理由尝试氢气是否对类风湿具有治疗价值。最近来自日本的一项研究表明，氢气对类风湿，特别是早期类风湿具有显著的治疗作用。该研究是一项非双盲小规模的临床研究，结论的可信度有限。 研究选择 20 名 类风湿关节炎 患者，治疗手段是让患者每天饮用高浓度氢气水 530 ml 。高浓度氢气水是因为该研究采用 4-5 ppm （质量比）氢气浓度，而一般情况下，氢气的最大溶解度不超过 2 ppm ，本研究中作者采用一种特殊的氢气溶液制备方法。整个治疗周期为 12 周。治疗先采用每天饮用氢气水连续 4 周，然后停止 4 周，再每天饮用氢气水连续 4 周。用血液和尿液中 8 羟基鸟嘌呤作为氧化损伤的指标，用 C 反应蛋白作为炎症反应的指标。结果发现，经过治疗 4 周后，尿液氧化指标和炎症反应指标都显著下降，在间隔 4 周后，上述指标继续下降（原因？）。在第 2 个 4 周治疗后，尿液氧化指标进一步下降，尿液氧化指标尽管没有显著下降，但低于正常水平。最令人称奇的是， 5 名早期（发病低于 12 月）患者全部都明显缓解，其中 4 名患者在整个治疗结束后症状完全消失。 该研究说明，作为一种抗氧化物质，氢气具有治疗人类类风湿关节炎的作用，这是非常让人激动的研究结果。当然这一研究仍需要更大规模的临床研究进一步证实。可以继续联想，类风湿关节炎是一种自身免疫性疾病，那么其他自身免疫性疾病的类型有许多，例如血管炎、多发性硬化、系统性红斑狼疮、银屑病等，这些疾病目前都没有用氢气治疗的尝试，无论是动物实验，还是临床研究。不过有人声称氢水对某些银屑病患者有效果，法国卢尔德的氢气水主要对一些因多发性硬化而瘫痪的患者有特殊效果，希望这些不仅仅是一种巧合。本研究采用增加氢气溶解的方法使用氢气，其实能提高人体利用氢气的手段有很多，只要有治疗效果，给药量、给方法和途径并非制约因素。 本文章发表在 Medical Gas Research 上，全文可以免费阅读。 Consumption of water containing a high concentration of molecular hydrogen reduces oxidative stress and disease activity in patients with rheumatoid arthritis: an open-label pilot study Ishibashi T, Sato B, Rikitake M, Seo T, Kurokawa R, Hara Y, Naritomi Y, Hara H, Nagao T Medical Gas Research 2012, 2 :27 (2 October 2012)
http://life.scichina.com:8082/sciC/CN/abstract/abstract508807.shtml 青蒿素和雷帕霉素阻遏一氧化氮爆发性缺氧 激发的小鼠急性关节滑膜炎 吴佩①†, 鲍飞②†, 郑青③, 肖娜①, 汪大婷①, 曾庆平①* ① 广州中医药大学热带医学研究所, 广州 510405; ② 中山大学附属第一医院放射治疗科, 广州 510080; ③ 暨南大学药学院, 广州 510632 † 同等贡献 * 联系人, E-mail: qpzeng@gzhtcm.edu.cn 投稿日期: 2012-03-31; 接受日期: 2012-08-15 广东省自然科学基金(批准号: 9145624536-4000003)和广东省高校师资队伍建设专项经费(2008)资助项目 doi: 10.1360/052012-148 摘要 为探讨类风湿性关节炎(RA)的发病原因并揭示青蒿素及雷帕霉素抗RA的作用机理, 本研究建立了完全弗氏佐剂(CFA)诱导的急性关节炎(CIAA)小鼠模型. 从炎症形态学及组织病理学上与经典的胶原诱导关节炎(CIA)的比较表明, CIAA能完全模拟CIA的关节红肿、滑膜增生和炎性浸润, 而且造模时间大大缩短(从28天缩短到3天). 关节腔CFA注射使促炎症细胞因子基因全面上调, 一氧化氮(NO)急剧爆发, 缺氧诱导因子-1(HIF-1)和血管内皮生长因子(VEGF)过表达, 最终导致滑膜血管新生及细胞增殖. 用NO供体化合物硝普钠(SNP)注射小鼠关节腔也能引起关节红肿, 而CFA与NO合成抑制剂NG-单甲基-L-精氨酸(L-NMMA)共同给药则无关节炎症发生. SNP先激活促炎症细胞因子表达, 然后阻遏诱导型NO合酶表达, 再进一步促进HIF-1和VEGF表达. 在CIAA小鼠造模前后注射青蒿琥酯和/或雷帕霉素, 可逆转缺氧诱导的HIF-1和VEGF表达、滑膜血管形成、肿瘤样增生和淋巴细胞炎性浸润. 青蒿琥酯不能完全抑制CFA诱导的免疫激活, 而雷帕霉素可显著下调CFA激发的促炎症细胞因子表达, 二者均能抑制NO合成, 可见NO是RA发病的重要媒介因素. 青蒿琥酯和雷帕霉素通过阻断NO产生的连锁效应展示了预防及治疗RA的潜在应用前景. 关键词 类风湿性关节炎 一氧化氮 缺氧 病因学 发病机理 Artemisinin and Rapamycin Compromise Nitric Oxide-driven and Hypoxia-triggered Acute Articular Synovitis in Mice WU Pei1, BAO Fei2, ZHENG Qing3, XIAO Na1, WANG DaTing1 ZENG QingPing1 1 Tropical Medicine Institute, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; 2 Department of Radiotherapy, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; 3 College of Pharmacology, Jinan University, Guangzhou 510632, China To investigate the etiological cause of rheumatoid arthritis (RA) and reveal the mechanism underlying the artemisinin and rapamycin against RA, the present work has established a mouse model of the complete Freund's adjuvant (CFA)-induced acute arthritis (CIAA). The inflammation morphological and histopathological comparisons of CIAA with the classic collagen-induced arthritis (CIA) indicated that CIAA perfectly simulates CIA in articular erythema and edema, synovial hyperplasia, and inflammatory infiltration in a substantially shortened modeling time (from 28 to 3d). Intra-articular injection with CFA allows global up-regulation of pro-inflammatory cytokine genes, dramatic burst of nitric oxide (NO), overexpression of hypoxia inducible factor 1 alpha (HIF-1) and vascular epithelial growth factor (VEGF), and synovial angiogenesis and hyperplasia. Aticular injection of mice with the NO donor compound sodium nitroprusside (SNP) also causes articular erythema and edema, whereas co-administration of CFA with the NO synthetic inhibitor NG-monomethyl-L-arginine (L-NMMA) abrogates articular inflammation. SNP activates pro-inflammatory cytokines but suppresses inducible NO synthase within three days, and upregulates HIF-1 and VEGF within two weeks. Pre- and post-injection of modeling CIAA mice with artesunate and/or rapamycin reverses hypoxia-induced expression of HIF-1 and VEGF, synovial angiogenesis, tumor-like hyperplasia, and lymphocytic inflammatory infiltration. While artesunate fails to completely repress CFA-induced immune activation, rapamycin down-regulates CFA-triggered expression of pro-inflammatory cytokines. Nevertheless, both artesunate and rapamycin are able to inhibit NO production. Conclusively, NO serves as a pivotal mediator of RA pathogenesis, and artemisinin and rapamycin, by blocking NO generation, hold potential promise in prophylactic and therapeutic interventions of RA patients. rheumatoid arthritis, nitric oxide, hypoxia, etiology, pathogenesis 724.pdf
Start A-Literature C-Literature B-list Filter Literature A-query: matrix metalloproteinase 13 C-query: articular chondrocytes and osteoarthrit... The B-list contains title words and phrases (terms) that appeared in both the A and the C literature. 172 articles appeared in both literatures and were not included in the process of computing the B-list but can be viewed here . The results of this search are saved under id # 1678 and can be accessed from the start page after you leave this session. There are 333 terms on the current B-list (发现遗传基因相关知识概念94个，对科研选题和进行中的科研工作有一定启发作用和参考价值 are predicted to be relevant) , which is shown ranked according to predicted relevance. The list can be further trimmed down using the filters listed in the left margin. To assess whether there appears to be a biologically significant relationship between the AB and BC literatures for specific B-terms, please select one or more B-terms and then click the button to view the corresponding AB and BC literatures. Use Ctrl to select multiple B-terms. http://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/edit_b.cgi job id # 1678 started Mon Jul 9 21:52:31 2012 Max_citations: 50000 Stoplist: /var/www/arrowsmith_uic/data/stopwords_pubmed Ngram_max: 3 A_query_raw: matrix metalloproteinase 13Mon Jul 9 21:52:39 2012 A query = matrix metalloproteinase 13 started Mon Jul 9 21:52:47 2012 A query resulted in 1578 titles C_query_raw: matrix metalloproteinase 13 Mon Jul 9 21:53:14 2012 C: matrix metalloproteinase 13 1578 A: pubmed_query_A 1578 AC: ( matrix metalloproteinase 13 ) AND ( matrix metalloproteinase 13 ) 1578 C_query_raw: articular chondrocytes and osteoarthritis Mon Jul 9 21:54:00 2012 C: articular chondrocytes and osteoarthritis 2398 A: pubmed_query_A 1578 AC: ( matrix metalloproteinase 13 ) AND ( articular chondrocytes and osteoarthritis ) 172 C_query_raw: articular chondrocytes and osteoarthritis Mon Jul 9 21:54:31 2012 C: articular chondrocytes and osteoarthritis 2398 A: pubmed_query_A 1578 AC: ( matrix metalloproteinase 13 ) AND ( articular chondrocytes and osteoarthritis ) 172 C query = articular chondrocytes and osteoarthritis started Mon Jul 9 21:54:47 2012 C query resulted in 2398 titles A AND C query resulted in 172 titles 2873 B-terms ready on Mon Jul 9 21:56:35 2012 Sem_filter: Genes Molecular Sequences, and Gene Protein Names 333 B-terms left after filter executed Mon Jul 9 21:59:52 2012 B-list on Mon Jul 9 22:00:51 2012 1 cox-2 2 jnk 3 akt 4 vegf 5 erk1 6 beta catenin 7 smad 8 aggrecan 9 toll receptor 10 wnt 11 synovial fibroblast 12 smad3 13 map kinase 14 mmp-2 15 timp-1 16 leptin 17 signal regulated kinase 18 tissue inhibitor metalloproteinase 19 oncostatin m 20 c jun 21 adiponectin 22 promoter polymorphism 23 fibromodulin 24 matrix metalloproteinase 25 adamts-4 26 timp 27 mmp-9 28 cdna 29 jak stat 30 matrix gene 31 c fos 32 endostatin 33 p38 34 collagen induced arthritis 35 chemokine 36 nf kappab 37 cd44 38 bone morphogenetic protein 39 il-1beta 40 caspase-3 41 rankl 42 il-6 43 il-1 44 ap-1 45 promoter region 46 cathepsin k 47 gadd45beta 48 sox9 49 transcription factor 50 mmp-1 51 metalloproteinase gene 52 mmp-13 53 igf i 54 matrix metalloproteinase gene 55 rheumatoid synovial 56 leukemia inhibitory factor 57 erk 58 tgf beta1 59 caspase-8 60 ccn2 61 tgf beta 62 acl 63 human synovial 64 igf 65 interleukin 66 mmp-3 67 protein kinase c 68 jun 69 timp-2 70 bcl-2 71 pthrp 72 estrogen receptor 73 ctgf 74 endo180 75 fibroblast growth factor 76 bmp 77 mmp 78 disintegrin 79 collagen gene 80 tnf alpha 81 glucocorticoid receptor 82 hyaluronan synthase 83 mmp13 84 tlr4 85 cathepsin b 86 p53 87 bmp-2 88 hip 89 pth 90 proteoglycan 91 related oncogene alpha 92 metalloprotease 93 catabolic gene 94 estrogen receptor alpha http://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/view_b_txt.cgi?ID=1678 研究实例： Start A-Literature C-Literature B-list Filter Literature AB literature B-term BC literature matrix metalloproteinase 13 cox-2 articular chondrocytes and os... 1: Differential down-regulation of COX-2 and MMP-13 in human skin fibroblasts by glucosamine-hydrochloride.2009 Add to clipboard 2: The effects of selective COX-2 inhibitor/celecoxib and omega-3 fatty acid on matrix metalloproteinases, TIMP-1, and laminin-5gamma2-chain immunolocalization in experimental periodontitis.2008 Add to clipboard 1: TAK1 mediates the collagen-II-dependent induction of the COX-2 gene and PGE2 release in primary human chondrocytes.2010 Add to clipboard 2: Dynamic compression inhibits fibronectin fragment induced iNOS and COX-2 expression in chondrocyte/agarose constructs.2009 Add to clipboard 3: COX-2 and iNOS are critical in advanced glycation end product-activated chondrocytes in vitro.2009 Add to clipboard 4: Effects of advanced glycation end products on the expression of COX-2 , PGE2 and NO in human osteoarthritic chondrocytes.2008 Add to clipboard 5: Long-term NSAID treatment directly decreases COX-2 and mPGES-1 production in the articular cartilage of patients with osteoarthritis.2008 Add to clipboard 6: Avocado soybean unsaponifiables (ASU) suppress TNF-alpha, IL-1beta, COX-2 , iNOS gene expression, and prostaglandin E2 and nitric oxide production in articular chondrocytes and monocyte/macrophages.2007 Add to clipboard 7: NF-kappaBp65-specific siRNA inhibits expression of genes of COX-2 , NOS-2 and MMP-9 in rat IL-1beta-induced and TNF-alpha-induced chondrocytes.2006 Add to clipboard 8: Selective COX-2 inhibitor regulates the MAP kinase signaling pathway in human osteoarthritic chondrocytes after induction of nitric oxide.2005 Add to clipboard 9: Cross talk between COX-2 inhibitor and hyaluronic acid in osteoarthritic chondrocytes.2004 Add to clipboard 10: COX-2 , NO, and cartilage damage and repair.2000 Add to clipboard 11: Tetracycline up-regulates COX-2 expression and prostaglandin E2 production independent of its effect on nitric oxide.1999 Add to clipboard http://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/show_sentences.cgi 研究动态文献： 关节炎中的表观遗传学基因开关 http://www.ebiotrade.com/newsf/2012-7/201279105548935.htm
来自中南大学的一篇通讯，发表在 African Journal of Pharmacy and Pharmacology 。作者根据氢气的抗氧化、抗炎症作用报道，提出可以用氢气治疗骨关节炎的看法。虽然氢气治疗疾病的研究目前已经很多，但仍没有关于关节炎方面的报道。相信氢气对类风湿等关节炎应该有不错的治疗效果。 活性氧和骨关节炎的关系非常密切。氢气作为一种选择性抗氧化物质，可以中和强毒性自由基。根据最近的研究，本文提出氢气作为一种新的治疗手段可以用于治疗骨关节炎的假说。根据文献检索，本文回顾分析了 2011 年 7 月前发表的关于活性氧、骨关节炎和氢气相关的同行评议英文论文。骨关节炎的的病理生理因素非常多，其中活性氧在该疾病的启动和发展中具有重要地位，特别是在软骨细胞坏死和骨质破坏中发挥重要调节作用。由于在许多动物模型和临床疾病中证明氢气的显著治疗价值。本文提出氢气可以通过抗氧化抗炎症治疗骨关节炎的假说。当然要证明该假说，需要许多基础和临床研究来证明。 全文： http://www.academicjournals.org/ajpp/PDF/pdf2012/8%20Feb/Li%20and%20Wang.pdf Can hydrogen retard the progression of osteoarthritis? Ding Li and WanChun Wang* Department of Orthopaedics, the Second Xiangya Hospital of Central South University, Middle Ren-Min Road No. 139, Changsha, Hunan 410011, China. Accepted 17 January, 2012 There is a direct relationship between reactive oxygen species (ROS) and the progression of osteoarthritis (OA). Hydrogen is considered as a selective antioxidant, which can neutralize the superfluous ROS. This investigation aimed to describe whether hydrogen can be used as a new treatment to retard the progression of OA based on recent studies. The peer-reviewed literature published prior to July, 2011 in the PubMed database was searched using pre-defined search criteria. Articles, published in English, were selected for their relevance to ROS, hydrogen or OA. The pathogenesis of OA is multifactor. Studies have revealed that ROS can contribute to the onset and progression of OA by inducing indispensable chondrocyte death and matrix degradation. Meanwhile, hydrogen is considered to be a selective antioxidant and can be used as a kind of therapeutic medical gas which has recently been explored in animal model and in clinic. We propose a hypothesis that hydrogen may be a new treatment to retard the progression of OA, although further researches need to be carried out in vivo or clinical studies
目前国际上常用的膝关节评分标准，包括Lysholm评分 ，美国特种外科医院膝关节评分(hospital for special surgery knee score，简称HSS评分) 、美国膝关节协会评分(American knee society knee score，简称KSS评分) 、国际膝关节文献委员会膝关节评估表(the international knee documentation committee knee uation form，简称IKDC评分) 、美国西部Ontario和McMaster大学骨关节炎指数评分(the western Ontario and McMaster universities osteoarthritis index，简称WOMAC骨关节炎指数评分) 、美国骨科协会膝关节评分(the American academy of orthopaedic surgeons，简称AAOS评分) 、膝关节损伤和骨关节炎评分(the knee injury and osteoarthritis score，简称KOOS) 、辛辛那提评分系统(the Cincinnati knee rating system)等. 1．Lysholm评分：由Lysholm 和Gillqui在1982年提出，是评价膝关节韧带损伤的条件特异性评分，它也被广泛地运用于其他各种膝关节疾病，如半月板损伤、软骨退变或软化。从评分内容上看，跛行、交锁、疼痛、支持、不稳定、肿胀、上楼困难、下蹲受限都是膝关节相关韧带和半月板损伤以及膝软骨疾病所出现的症状，Lysholm评分简单、明了、直接、全面地评述了患者的局部功能，而且询问方式简便，占用患者时间短，不具有创伤性，易于被患者所接受。Lysholm评分不仅能评价患者最为重要的日常活动的功能感知，而且对于患者不同强度的运动功能等级也能做出初步评估。它通过数字式的评分和患者活动级别的联系，对于患者功能障碍的程度做出清楚的划分，从而使评估系统中每一个内容参数都能反映治疗过程。 2．AKS评分：AKS评分系统是1989年由美国膝关节协会(the American knee society)提出的另一膝关节综合评分标准。从内容上分析，AKS评分分为膝评分和功能评分两大部分。膝评分又分为疼痛、活动度和稳定性；功能评分包括行走能力和上下楼能力的评价。AKSS评分全面评估了膝关节整体功能和形态，更精确地评价了关节自身条件。自1989年提出以来被广泛运用于全膝置换患者术前、术后评分。它还有效地解决了HSS评分中年龄相关疾病引起评分下降的问题，在患者长期随访的过程中避免了更大的偏倚。通过KSS评分，我们能了解到术后患者长期的恢复情况。有研究表明，患者在术后l0～l2年中，在无并发症的情况下，AKS评分能非常显著地检测出随着年限的增长人工关节的损耗程度，这无疑为改良人工关节材料和手术方式提供了依据。还有研究表明，连续随访的患者膝关节功能比同年限不连续随访的患者要好，这说明评分在指导患者康复和功能锻炼方面也有一定的作用。因此，AKS评分在近年已逐渐取代HSS评分，成为评估TKA最为有效的评分。 3．HSS评分：1976年美国特种外科医院(the hospital for special surgery)提出的一个总分为100分的评分系统。与AKS评分相比，HSS评分在近年来使用率逐渐下降，也就是说，逐渐被AKS评分所取代。即便如此，它在TKA手术前后关节功能的恢复及手术前后的比较仍然具有相当高的正确性，尤其是手术后近期的评分，可以全面评价髌股关节及股胫关节的运动情况。HSS评分内容中，包括了膝关节置换术后局部情况和机体的整体功能，这样对于老年或身体其他部位病变影响整体功能的患者，评分价值会受到影响。这些患者即使术后膝关节无疼痛，但随着年龄的增长或其他疾病的影响而使身体活动功能受到限制时，评分值会自行下降，从而不能反映手术的实际情况(比如类风湿病患者由于是多关节受累，其术后评分相对较低)，所以当对手术治疗的患者远期疗效评估偏倚相对较大。而且，HSS评分只能比较手术前、后患者功能恢复情况，不能对手术存在的风险做出正确评估。正是因为存在这些不足，才使HSS评分在近年来逐渐被AKS评分所取代。 4．IKDC评分：目前国际上公认IKDC对于韧带损伤尤其是前交叉韧带损伤、缺损的评估有着比较高的可靠性、有效性和敏感性。为IKDC评分可运用于各种条件的膝关节，它并不是专门针对运动或膝关节不稳定的评分，而是全面评价了膝关节系统的主观症状和客观体征，但是他同时指出，此评分的缺点是不能反映患者的基本生活环境。国际膝关节文献委员会指出目前的IKDC评分还不是最完善的，他们的最终目标是设计出一个简单但是能精确反映各种膝关节功能紊乱包括韧带损伤、髌股关节疾病、半月板疾病和骨关节炎的评估系统。 WOMAC骨关节炎指数评分：WOMAC骨关节炎指数评分是由Bellamy等于1988年首先提出，此评分是根据患者相关症状和体征来评价膝关节炎的严重程度及其治疗疗效。从统计资料可以看出，WOMAC评分在OA及RA的文献中使用频率相对较高。从内容上看，此评分从疼痛、僵硬和关节功能三大方面来评价膝关节的结构和功能，覆盖了整个骨关节炎的基本症状和体征。WOMAC评分的有效性体现在能准确地反映出患者治疗前后的一些情况，如患者对治疗的满足程度。相对而言，此评分对于骨关节炎的评估还有着较高的可靠性。但是，它对于韧带和半月板等膝关节损伤非凡是急性损伤的评估不及Lysholm、IKDC评分来的准确和有效。
今天听到一位在美国大学做研究的教授朋友说她在国际杂志 Arthritis and Rheumatism 上发了一篇文章，题目是太极拳治疗骨关节炎有效，称把太极拳带入了美国的主流医学。 读后颇感兴趣，便与其探讨，问：第八套广播体操如何？是不是也能治疗关节炎？回答是也可能，但太极拳除了有生理体质的锻炼功效，还有心理的疗效。身、心双疗，效果更佳。 于是我想到了烧香拜佛，建议她下一篇文章的题目是烧香拜佛治疗百病有效。也建议各位平常没事打打太极拳，不会打的做做广播体操，周末上山烧烧香。同时也想到了一个新学科，叫 CCM （ Chinese Culture Medicine ）。 不要误解我这里是讽刺中国文化和哲学。我更想强调中国文化和哲学对人的心理健康和生理健康之间关系的的深刻认识和广泛应用。这也是我们中医理论的精萃。
标签: 关节炎
