基于文献整理和数据挖掘的解痉舒督汤治疗强直性脊柱炎临床研究
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摘要
[背景]
强直性脊柱炎(ankylosing spondylitis, AS)是血清阴性脊柱关节病的一种,是一种慢性进行性炎症性疾病,发病率为0.3%,男女发病比例为2-3：1,多见于青壮年,发病高峰年龄为15-30岁。AS主要累及中轴关节及周围组织、外周关节、关节外组织。主要症状为腰背疼痛、僵直,脊柱及髓关节活动受限,严重者脊柱弯曲畸形,出现“脊以代头、尻以代踵”。本病多为慢性进行性,病程长,易反复发作,西医治疗主要以非甾体类消炎止痛药(nonsteroidal antiinflammatory drugs, NSAIDS)和改善病情抗风湿药(disease modifying anti-rheumatic drugs, DMARDS)为主,但疗程长,副作用大,患者依从性差。目前肿瘤坏死因子a(tumor necrosis factor-alpha, TNF-a)抑制剂在国内逐渐被推广应用,但费用高,副作用大,缺乏远期疗效的循证医学证据。中医治疗可使AS患者病情长期处于缓解期,提高患者生活质量,且安全性好,费用低廉。具有良好的社会效益和经济效益。
[目的]
通过对名老中医诊治AS的文献进行收集整理和计量分析,探讨总结AS的病名、病因病机、证候要素、治则治法、用药规律；整理挖掘导师针对AS的诊治特色、用药经验等,有利于其学术思想推广；通过临床病例观察,评价解痉舒督汤治疗AS的临床疗效和安全性。分析柔肝舒筋、解痉止痛治疗AS的疗效特点。
[方法]
收集公开发表的AS诊疗经验的文献,对文献所涉及的病名、病因病机、辨证分型、治法及主要用药形成固定字段,输入数据表,应用统计软件SPSS16.0进行频数统计,并对证候分型进行证候要素分析,对治法和用药规律进行科学总结；以“人机结合、以人为本”为原则,运用“中国中医科学院西苑医院科研病例采集系统V1.0”、“名老中医学术思想挖掘平台V1.0”和关联规则等数据挖掘方法,结合导师本人指导和跟师体会,全面总结导师治疗AS的临床思维模式、选方用药经验等。采用随机对照临床试验,将90例AS患者随机分为中药组、中西医结合组和西药组,中药组予解痉舒督汤治疗,中西医结合组予解痉舒督汤联合柳氮磺胺吡啶肠溶片治疗,西药组予柳氮磺胺吡啶肠溶片加双氯芬酸钠缓释片治疗,连续用药3个月,选取治疗前、治疗2周,1个月、治疗3个月作为评价时点,从Bath强直性脊柱炎病情活动指数(bath ankylosing spondylitis disease activity index, BASDAI)、Bath强直性脊柱炎功能指数(bath ankylosing spondylitis function index, BASFI)、总体疼痛评分、患者对病情的总体评价评分、中医症状积分五项主要疗效指标和胸廓活动度、指地距、枕墙距、血沉(erythrocyte sedimentation rate, ESR)、C反应蛋白(c-reactive protein, CRP)五项次要疗效指标来评价解痉舒督汤治疗AS的临床疗效。
[结果]
1AS中医病名证候治法用药规律分析
AS涉及的中医病名有29个,其中骨痹、肾痹、痹证(症)是最多见的3个病名。正虚邪侵,内外合邪导致AS的发生,内因包括正气不足,先天禀赋不足,后天失养,情志内伤,饮食失宜,劳倦过度,外因包括感受六淫,外伤。病机为本虚标实,虚实夹杂,但在本虚上,认识不一,认为本虚主要是肾虚的有52位医家(77.6%),肾督亏虚的有35位医家(52.4%),肝肾不足的有18位医家(26.9%)。证候分型有56种,频次大于10次的证候名称有瘀血痹阻、肾督亏虚、湿热痹阻、寒湿痹阻、痰瘀蕴结、肝肾阴虚、风寒湿痹7个。按照所含的病理因素或证候要素的数量进行分类,可分为单因素证候12个、两因素证候33个、多因素证候8个及不便分类证候3个,56种证候包括8个证候要素,有限数量证候要素的应用组合构成了强直性脊柱炎丰富多样的证候类型。将所述及治法分解为单因素治法,频次超过10次的有17个,分别是补肾、除湿、活血化瘀、通络/剔络、清热、壮督/通督、散寒、补肝肾、祛风、止痛、化痰、养血/调营/和血、解毒、补气、壮骨/强筋骨、健脾胃、行气/调气/益卫。出现10位或以上医家共同使用过治疗AS的药物主要分属于补肾药、活血药、祛风湿药、清热燥湿药、利水渗湿药、芳化湿浊药、虫类搜风剔络药、化痰药、补气药、养血药10类。
2导师房定亚教授治疗AS经验总结与数据挖掘
共收集病例105人次,常见症状有腰痛、髋关节痛、胸背僵痛、腰背下肢活动受限、颈项僵痛、背痛、腰骶痛、腰酸、膝关节痛、足跟痛、颈项活动受限、乏力、多汗。主要证型有气虚血瘀型、热毒痹阻型、湿热痹阻型、肾虚血瘀型、风寒湿痹型、肝肾亏虚型。主要治法为柔肝舒筋、解痉止痛、祛风通络、化痰软坚、清热解毒、益气、补肾、活血。常用中药128味,其中葛根、白芍、威灵仙、山慈菇、蜈蚣用药频次比例在80%以上,是解痉舒督汤的君臣药。
3解痉舒督汤治疗AS临床研究
共完成观察病例84例,男性60例(占71.43%),女性24例(占28.57%),男女比例为2.5：1。其中中药组30例,中西医结合组30例,西药组24例。84例AS患者,年龄14-58岁,中药组平均年龄为31.63±6.12,中西医结合组平均年龄为33.13±10.81,西药组33.50±11.45。中药组、中西医结合组、西药组总体疗效分别是80.00%、83.33%、79.17%,经统计学分析无显著性差异。中西医结合组疗效并未因联合使用柳氮磺胺吡啶而增加。在治疗观察过程中,中药组未出现血尿及肝肾功的异常,主要不良反应是消化道不适,如恶心、腹胀、腹泻,但症状轻微,不良反应发生率低于中西医结合组和西药组。
本研究五项主要疗效指标包括BASDAI、BASFI、总体疼痛评分、患者对病情的总体评价评分、中医症状积分。BASDAI在治疗2周,三组开始出现不同程度的下降,但中药组和中西医结合组比西药组改善明显,具有统计学差异(中药组P<0.05,中西医结合组P<0.01)；在治疗1月时,中药组和中西医结合组比西药组改善明显,具有统计学差异(中药组P<0.05,中西医结合组P<0.01)；在治疗3月时,中西医结合组比西药组改善明显,具有统计学差异(P<0.05)。BASFI治疗2周,三组开始出现不同程度的下降,中药组、中西医结合组与西药组比较,改善更为明显,具有统计学差异(中药组P<0.05,中西医结合组P<0.01)；治疗1月时,中药组、中西医结合组比西药组改善明显,具有统计学差异(P<0.05)；治疗3月时,三组间比较无统计学差异(P>0.05)。总体疼痛评分、患者对病情的总体评价治疗前后比较,三组均有下降,但在治疗2周时,中西医结合组比西药组改善明显,具有统计学差异(P<0.05)。中医症状积分在治疗2周时,中药组、中西医结合组分别与治疗前相比有改善,且差异具有显著性(P<0.001),中药组、中西医结合组与西药组相比,改善明显,具有统计学差异(中药组P<0.05,中西医结合组P<0.01),中药组与中西医结合组比较,中西医结合组改善明显,具有统计学差异(P<0.05)；治疗1月和治疗3月时,西药组亦有改善,但没有中药组、中西医结合组改善明显,差异具有显著性(P<0.01)。
次要疗效指标包括胸廓活动度、指地距、枕墙距、ESR、CRP。胸廓活动度三组间同期比较,无统计学差异(P>0.05),在治疗2周时,中西医结合组和西药组与本组治疗前相比,改善具有统计学意义(中西医结合组P<0.001,西药组P<0.05)；在治疗1月、3月时,与本组治疗前相比,三组均有改善,且差异具有显著性。指地距三组间同期比较,无统计学差异(P>0.05),在治疗2周、1月、3月时,与本组治疗前相比,三组均有改善,且差异具有显著性。枕墙距三组间同期比较,无统计学差异(P>0.05)。ESR、CRP三组同期比较,无统计学差异(P>0.05),在治疗1月、3月时,与本组治疗前相比,三组均有改善,且差异具有显著性(P<0.05,P<0.001)。本研究中,中药组、中西医结合组对中医症状积分改善优于西药组,中药组、中西医结合组对BASDAI、BASFI改善在治疗2周、1月优于西药组,中西医结合组对BASDAI改善在治疗3月优于西药组。中西医结合组对总体疼痛评分、患者对病情的总体评价改善在治疗2周优于西药组,中药组和中西医结合组在治疗1月、3月对总体疼痛评分、患者对病情的总体评价改善与西药组相比无差异。中药组和中西医结合组对胸廓活动度、指地距、枕墙距、ESR、CRP的疗效与西药组相比无差异。
[结论]
1AS中医病名证候治法用药规律
当代名老中医对AS的病名认识不统一,多归属于中医骨痹、肾痹、痹证(症)范畴。唯房师将AS归属于“筋痹”范畴。病因有内外两方面,病机主流认识本虚标实,虚实夹杂。房师认为筋痹的主要病机为肝气不疏,肝血不足,筋脉失养,气血痹阻。AS常见证候要素有虚、湿、寒、风、瘀、热、痰、毒。AS常见治法是补肾、除湿、活血、通络。应用补肾药时,要以患者证型的寒热偏性来选择滋肾阴、温肾阳或平补肾阴肾阳。祛风除湿、散寒通络之品仍是目前许多医家治疗强直性脊柱炎的重要组方用药。活血化瘀贯穿整个治疗过程的始终已被多数医家认同。在强直性脊柱炎活动期或晚期,多应用虫类搜风剔络药和动物类的活血化瘀药。房师以柔肝舒筋、解痉止痛为法自拟解痉舒督汤治疗AS。
2导师房定亚教授治疗AS经验总结与数据挖掘
房师认为AS当归属于中医“筋痹”范畴。筋痹是指因人体正虚,风寒湿热之邪客于筋脉,或外伤于筋,或痰湿流注筋脉,气血痹阻,导致以筋急拘挛、抽掣疼痛、关节屈曲不利、腰背弯曲强直、步履艰难等为主要表现的一种病证。病位在筋脉、关节,涉及脏腑主要为肝,基本病机特点为肝气不疏,肝血不充,筋脉失养,气血痹阻。典型证候表现是疼痛拘挛强直。解痉舒督汤是治疗AS的基础方,其组成为葛根、白芍、蜈蚣、威灵仙、山慈菇、生黄芪、鹿衔草、乌蛇、生甘草、薏苡仁。导师倡导辨病与辨证相结合,治疗AS在解痉舒督汤基础上尚需根据分期和兼挟证(症)不同,结合现代生理病理及药理,加减用药。
3解痉舒督汤治疗AS临床研究
解痉舒督汤治疗强直性脊柱炎是有效的,并没有因联合柳氮磺胺吡啶而使总疗效提高,其安全性和依从性要优于西药组或联合柳氮磺胺吡啶。
Background
As a chronic inflammatory disease,ankylosing spondylitis belongs to seronegative spondyloarthropathy.The incidence rate of the disease is0.3%.The incidence ratio of male and female is2-3:1.The disease is more common in young adults, and the peak age of incidence is15-30years old. The central axis joints,peripheral joints and the tissues outside joints are mainly involved in patients of AS.The lower back pain or stiffness,activity limitation of the spine and hip are the main symptoms.In severe cases,the spine deformity may occur.Western medicine includes NSAIDS and DMARDS.However,the patient compliance is poor because of long treatment courses and side effects.Traditional Chinese medicine can keep long-term remission in patients with AS and improve the life quality of patients.Due to security and low cost,TCM treatment of AS have good social and economic benefits.
Objective
To discuss and summarize TCM name of AS,etiology,pathogenesis,TCM syndrome essential factor,therapeutic principle and drug rules,collection and quantitative analysis of literatures concerning the famous TCM doctors'clinical experiences of treating AS were carried out.To collect and mine the tutor's treatment features and medication experiences,principle of man machine integration was used,which was beneficial to extend the tutor's academic thoughts.To evaluate the efficacy and safety of the jiejingshudu decoction,clinical cases of AS were observed.
Method
Published literatures concerning AS diagnosis and treatment experience were collected.Denominations were formed into fixed fields of pathogenesis,syndrome differentiation,treatment method and the main drug that involved in these literatures.A database and frequency statistics were established by aid of SPSS16.0.A variety of data mining methods were used under the principle of man machine integration and people-orientation.The tutor's guidance with personal appreciation was combined,the tutor's clinical experiences was fully summarized.A randomized controlled clinical trial was conducted.90patients with AS were randomly divided into three groups:TCM group,integration of traditional Chinese and western medicine group,western medicine group.The patients of TCM group were treated with jiejingshudu decoction.The patients of integration of traditional Chinese and western medicine group were treated with jiejingshudu decoction and sulfasalazine.The patients of western medicine group were treated with sulfasalazine and diclofenac sodium.There were three months continuous medication for all AS patients.The changes in the five main and the five secondary efficacy indicators were recorded after two weeks,one month and three months of treatment.The five main efficacy indicators included BASDAI,BASFI,total pain score,overall evaluation score of patients with the disease and TCM symptom score.The five secondary efficacy indicators included thoracic mobility,finger-floor distance, occipital head-wall distance,ESR,CRP.
Result
1Literature research
There were29involved TCM names of the disease in the collected literatures. Bone impediment,kidney impediment and impediment syndrome were more common. Pathogen invaded the body in case of healthy qi deficiency,which resulted in the occurrence of AS.Etiology included both internal and external factors.The internal factors refered to healthy qi deficiency,congenital deficiency,acquired dystrophy, emotional trauma,improper diet,and overwork.The external factors refered to six excessive pathogens or wound.The pathogenesis was deficiency-excess complex,that was,deficiency at root and excess at branch.Physicians understund differently the root deficiency.There were52physicians who realised that the root deficiency refered to kidney deficiency(77.6%).There were35physicians who realised that the root deficiency refered to kidney and governor vessel deficiency(52.4%).There were18physicians who realised that the root deficiency refered to liver and kidney deficiency(26.9%).56syndrome types were involved in the literatures.The syndrome names with frequency greater than10times refered to static blood obstruction syndrome,kidney and governor vessel deficiency syndrome,syndrome of dampness-heat impediment,syndrome of cold-dampness impediment,syndrome of phlegm and blood stasis accumulation,syndrome of liver-kidney yin deficiency, syndrome of wind-cold-dampness impediment.According to the quantity of pathological factors or key elements the syndromes were divided into12single-factor syndromes,33two-factor syndromes,8Multi-factor syndromes,3inconvenient category syndromes.8key elements were included in the syndromes.A limited number of key elements were assembled into various types of syndrome of AS.The methods of treatment described in the literatures were decomposed into a single-factor method of treatment.Frequency of 17methods of treatment were greater than10times.These17methods of treatment were composed of tonifying the kidney,eliminating dampness,activating blood and resolving stasis,freeing the collateral vessels,clearing away heat,invigorating or unblocking du,dissipating cold,tonifying the liver and kidney,dispelling wind,relieving pain,resolving phlegm,nourishing blood or harmonizing the nutrient,detoxify,tonifying qi,invigorating bone or nourishing sinew,fortifying the spleen and invigorating the blood,moving qi or tonifying defense qi.The herbs which were applied by10or more physicians belonged to10categories of Chinese medicinal.10categories of Chinese medicinal were composed of kidney-tonifying medicinal,blood-activating medicinal, wind-dampness-dispelling medicinal,heat-clearing and dampness-drying medicinal, dampness-draining diuretic medicinal,dampness-resolving fragrant medicinal,wormy wind-dispelling or collateral vessels-freeing medicinal,phlegm-resolving medicinal, qi-tonifying medicinal and blood-tonifying medicinal.
2The tutor's clinic experiences and data mining
A total of105people cases were collected in the study.The common symptoms included lumbago,pain of hip joints,thoracodorsal stiff and pain,lower extremity and lower back activity limitation,stiff and pain of neck,back pain,lumbosacral pain,mild lumbago,knee pain,heel pain,activity limitation of neck,lack of strength and profuse sweating.The main pattern types included pattern of qi deficiency with blood stasis, pattern of heat toxin impediment,pattern of dampness-heat impediment,pattern of kidney deficiency and blood stasis,pattern of wind-cold-dampness impediment and pattern of liver-kidney deficiency.The main treatment methods included emolliating the liver to relax sinews,arresting convulsions to relieve pain,dispelling wind to free the collateral vessels, resolving phlegm to soften hardness,clearing the heat to detoxify,tonifying qi,tonify the kidney and activating blood.There were128herbs commonly used by the tutor.Herbs of frequency more than80%among them involved Gegen,Baishao,Weilingxian,Shancigu,Wugong.The five herbs were sovereign and minister medicinals of jiejingshudu decoction.
3A clinic trial on jiejingshudu decoction treating AS
Observation of84cases was completed.There were60males(71.43%) and24females(28.57%).The ratio of male to female was2.5:1.Among the three test groups,there were30cases in TCM group,30cases in integration of traditional Chinese and western medicine group,24cases in the western medicine group.The ages of84patients were from14to58years old.The average age was31.63±6.12in TCM group.The average age was33.13±10.81in integration of traditional Chinese and western medicine group.The average age was33.50±11.45in the western medicine group.The total efficacy of TCM group,integration of traditional Chinese and western medicine group,western medicine group was80.00%,83.33%,79.17%.The result was no significant difference in the statistical analysis.The total efficacy of integration of traditional Chinese and western medicine group didn't increase.In the period of clinical observation patients of TCM group did not show abnormal blood and urine test,whose main adverse reaction were mild gastrointestinal discomfort such as nausea, distention,diarrhea.The incidence of adverse reactions in TCM group was less than that in the other two groups.
The five main efficacy indicators included BASDAI,BASFI,total pain score, overall evaluation score of patients with the disease and TCM symptom score. BASDAI began to decrease to different extent in the three groups after two weeks of treatment.It decreased statistically significantly in the other two groups in comparison to the Western medicine group after two weeks or one month of treatment(TCM group P<0.05, integration of traditional Chinese and western medicine group P<0.01). BASDAI decreased statistically and significantly in the integration of traditional Chinese and western medicine group in comparison to the western medicine group after three month of treatment(P<0.05).BASFI began to decrease to varying degrees in the three groups after two weeks of treatment.It decreased statistically significantly in the other two groups in comparison to the western medicine group after two weeks of treatment.(TCM group P<0.05,integration of traditional Chinese and Western medicine group P<0.01).It decreased statistically and significantly in the other two groups in comparison to the western medicine group after one month of treatment(P<0.05).The difference of BASFI among the three groups was not statistically significant after three months of treatment.Contrasted before and after treatment, total pain scores of the three groups decreased.Total pain score and overall evaluation score of patients with the disease improved statistically and significantly in the integration of traditional Chinese and western medicine group in comparison to the western medicine group after two weeks of treatment(P<0.05).Contrasted before and after two weeks of treatment,TCM symptom scores of TCM group and the integration of traditional Chinese and western medicine group improved statistically and significantly(P<0.001).It improved statistically and significantly in the other two groups in comparison to the western medicine group after two weeks of treatment(TCM group P<0.05, integration of traditional Chinese and western medicine group P<0.01).TCM symptom score of the integration of traditional Chinese and western medicine group in comparison to the western medicine group improved statistically and significantly after two weeks of treatment(P<0.05).It improved in the western medicine group after one or three months of treatment,however,it improved statistically and significantly in the other two groups in comparison to the western medicine group(P<0.01).
The five secondary efficacy indicators included thoracic mobility,finger-floor distance,occipital head-wall distance,ESR,CRP.By contemporary comparison, thoracic mobilities of the three groups had no statistically significant difference (P>0.05).After two weeks of treatment thoracic mobilities of TCM group and the integration of traditional Chinese and western medicine group improved statistically and significantly(integration of traditional Chinese and western medicine group P<0.001,TCM group P<0.05).Contrasted before and after one or three months of treatment, thoracic mobilities of the three groups improved statistically and significantly. By contemporary comparison,finger-floor distances of the three groups had no statistically significant difference(P>0.05).Contrasted before treatment with after two weeks,one or three months of treatment, finger-floor distances of the three groups improved statistically and significantly.By contemporary comparison, occipital head-wall distances of the three groups had no statistically significant difference (P>0.05).By contemporary comparison,ESR and CRP of the three groups had no statistically significant difference(P>0.05).Compared with this group before treatment, the two indicators of the three groups improved statistically and significantly afer one or three months of treatment(P<0.05,P<0.001).
Improvement of TCM symptom score in TCM group or the integration of traditional Chinese and western medicine group was better than that in the western medicine group.Improvement of BASDAI and BASFI in the other two groups was better than that in the western medicine group afer two weeks and one month of treatment.Improvement of BASDAI in the integration of traditional Chinese and western medicine group was better than that in the western medicine group afer three months of treatment.Improvement of total pain score and overall evaluation score in the integration of traditional Chinese and western medicine group was better than that in the western medicine group afer two weeks of treatment.With prolonged treatment period,the difference of the two scores in the other groups compared with the western medicine group became not significant.Compared with the western medicine group,the other secondary efficacy indicators,including thoracic mobility,finger-floor distance, occipital head-wall distance,ESR and CRP,had no significant differences.
Conclusion
1Literature research
The contemporary famious TCM doctors did not agree with TCM names of the disease.Most of them regard the disease as bone impediment,kidney impediment and impediment syndrome.Only Professor Fang thinks that AS should be attributated to sinew impediment.Etiology includes both internal and external factors.The main pathogenesis is deficiency-excess complex,that is,deficiency at root and excess at branch.Professor Fang thinks that pathogenesis of AS is sinews dystrophy and qi-blood blockage due to liver qi stagnation or liver blood deficiency.The key syndrome elements refer to deficiency,dampness,cold,wind,stasis,heat,phlegm and toxin.The common methods of treatment include tonifying the kidney,eliminating dampness,activating blood and resolving stasis,freeing the collateral vessels.The herbal drugs of tonifying kidney are selected by heat or cold nature of the syndrome type.Wind-dampness dispelling and cold dispersing medicinal often emerge in many physicians' prescriptions.The majority of doctors agree with usage of blood-activating and stasis-resolving medicine throughout the therapeutic process.Wormy wind-dispelling or collateral vessels-freeing medicine and animal blood-activating or stasis-resolving medicine are more applied to AS patients in active phase or late stage.Professor Fang realized that emolliating the liver to relax sinews and relieving spasm to alleviate pain are the total principles of treating AS.Jiejingshudu decoction is a self-made recipe for AS by Professor Fang.
2The tutor's clinic experiences and data mining
Tutor Professor Fang thinks that AS should be attributated to sinew impediment. Sinew impediment is a group of symptoms including sinew contracture or spasm, pulling pain,joint flexion,lumbar back bending and rigidity,trudge,etc.Either wind-cold-dampness-heat pathogen invades the sinews in the statement of body healthy qi deficiency,or the sinews are injured,or phlegm-dampness binds the sinews, which results in the occurrence of sinew impediment.The disease of sinew impediment is located in sinews and joints.The liver viscus is mainly involved.Basic pathogenesis is characterized by sinews dystrophy and qi-blood blockage due to liver qi stagnaton or liver blood deficiency.Typical symptoms consist of pain,spasm and ankylosis. Jiejingshudu decoction is a basic formula treating AS,which is composed of Gegen,Baishao,Weilingxian,Shancigu,Wugong,Shenghuangqi,Luxiancao,Wushaoshe,S henggancao,Yiyiren.Tutor Professor Fang advocates combination disease identification with syndrome differentiation.According to the stage of disease and accompanying syndrome,the herbal drugs are added or cut down on the basis of Jiejingshudu decoction, with reference to modern physiological,pathological and pharmacological knowledge.
3A clinic trial on jiejingshudu decoction treating AS
Jiejingshudu decoction is a effective formula for treating AS.Efficacy of jiejingshudu decoction does not improve in the case of combination of sulfasalazine. Security and patient compliance of jiejingshudu decoction are superior to sulfasalazine in combination or sulfasalazine plus diclofenac sodium
强直性脊柱炎(ankylosing spondylitis, AS)是血清阴性脊柱关节病的一种,是一种慢性进行性炎症性疾病,发病率为0.3%,男女发病比例为2-3：1,多见于青壮年,发病高峰年龄为15-30岁。AS主要累及中轴关节及周围组织、外周关节、关节外组织。主要症状为腰背疼痛、僵直,脊柱及髓关节活动受限,严重者脊柱弯曲畸形,出现“脊以代头、尻以代踵”。本病多为慢性进行性,病程长,易反复发作,西医治疗主要以非甾体类消炎止痛药(nonsteroidal antiinflammatory drugs, NSAIDS)和改善病情抗风湿药(disease modifying anti-rheumatic drugs, DMARDS)为主,但疗程长,副作用大,患者依从性差。目前肿瘤坏死因子a(tumor necrosis factor-alpha, TNF-a)抑制剂在国内逐渐被推广应用,但费用高,副作用大,缺乏远期疗效的循证医学证据。中医治疗可使AS患者病情长期处于缓解期,提高患者生活质量,且安全性好,费用低廉。具有良好的社会效益和经济效益。
[目的]
通过对名老中医诊治AS的文献进行收集整理和计量分析,探讨总结AS的病名、病因病机、证候要素、治则治法、用药规律；整理挖掘导师针对AS的诊治特色、用药经验等,有利于其学术思想推广；通过临床病例观察,评价解痉舒督汤治疗AS的临床疗效和安全性。分析柔肝舒筋、解痉止痛治疗AS的疗效特点。
[方法]
收集公开发表的AS诊疗经验的文献,对文献所涉及的病名、病因病机、辨证分型、治法及主要用药形成固定字段,输入数据表,应用统计软件SPSS16.0进行频数统计,并对证候分型进行证候要素分析,对治法和用药规律进行科学总结；以“人机结合、以人为本”为原则,运用“中国中医科学院西苑医院科研病例采集系统V1.0”、“名老中医学术思想挖掘平台V1.0”和关联规则等数据挖掘方法,结合导师本人指导和跟师体会,全面总结导师治疗AS的临床思维模式、选方用药经验等。采用随机对照临床试验,将90例AS患者随机分为中药组、中西医结合组和西药组,中药组予解痉舒督汤治疗,中西医结合组予解痉舒督汤联合柳氮磺胺吡啶肠溶片治疗,西药组予柳氮磺胺吡啶肠溶片加双氯芬酸钠缓释片治疗,连续用药3个月,选取治疗前、治疗2周,1个月、治疗3个月作为评价时点,从Bath强直性脊柱炎病情活动指数(bath ankylosing spondylitis disease activity index, BASDAI)、Bath强直性脊柱炎功能指数(bath ankylosing spondylitis function index, BASFI)、总体疼痛评分、患者对病情的总体评价评分、中医症状积分五项主要疗效指标和胸廓活动度、指地距、枕墙距、血沉(erythrocyte sedimentation rate, ESR)、C反应蛋白(c-reactive protein, CRP)五项次要疗效指标来评价解痉舒督汤治疗AS的临床疗效。
[结果]
1AS中医病名证候治法用药规律分析
AS涉及的中医病名有29个,其中骨痹、肾痹、痹证(症)是最多见的3个病名。正虚邪侵,内外合邪导致AS的发生,内因包括正气不足,先天禀赋不足,后天失养,情志内伤,饮食失宜,劳倦过度,外因包括感受六淫,外伤。病机为本虚标实,虚实夹杂,但在本虚上,认识不一,认为本虚主要是肾虚的有52位医家(77.6%),肾督亏虚的有35位医家(52.4%),肝肾不足的有18位医家(26.9%)。证候分型有56种,频次大于10次的证候名称有瘀血痹阻、肾督亏虚、湿热痹阻、寒湿痹阻、痰瘀蕴结、肝肾阴虚、风寒湿痹7个。按照所含的病理因素或证候要素的数量进行分类,可分为单因素证候12个、两因素证候33个、多因素证候8个及不便分类证候3个,56种证候包括8个证候要素,有限数量证候要素的应用组合构成了强直性脊柱炎丰富多样的证候类型。将所述及治法分解为单因素治法,频次超过10次的有17个,分别是补肾、除湿、活血化瘀、通络/剔络、清热、壮督/通督、散寒、补肝肾、祛风、止痛、化痰、养血/调营/和血、解毒、补气、壮骨/强筋骨、健脾胃、行气/调气/益卫。出现10位或以上医家共同使用过治疗AS的药物主要分属于补肾药、活血药、祛风湿药、清热燥湿药、利水渗湿药、芳化湿浊药、虫类搜风剔络药、化痰药、补气药、养血药10类。
2导师房定亚教授治疗AS经验总结与数据挖掘
共收集病例105人次,常见症状有腰痛、髋关节痛、胸背僵痛、腰背下肢活动受限、颈项僵痛、背痛、腰骶痛、腰酸、膝关节痛、足跟痛、颈项活动受限、乏力、多汗。主要证型有气虚血瘀型、热毒痹阻型、湿热痹阻型、肾虚血瘀型、风寒湿痹型、肝肾亏虚型。主要治法为柔肝舒筋、解痉止痛、祛风通络、化痰软坚、清热解毒、益气、补肾、活血。常用中药128味,其中葛根、白芍、威灵仙、山慈菇、蜈蚣用药频次比例在80%以上,是解痉舒督汤的君臣药。
3解痉舒督汤治疗AS临床研究
共完成观察病例84例,男性60例(占71.43%),女性24例(占28.57%),男女比例为2.5：1。其中中药组30例,中西医结合组30例,西药组24例。84例AS患者,年龄14-58岁,中药组平均年龄为31.63±6.12,中西医结合组平均年龄为33.13±10.81,西药组33.50±11.45。中药组、中西医结合组、西药组总体疗效分别是80.00%、83.33%、79.17%,经统计学分析无显著性差异。中西医结合组疗效并未因联合使用柳氮磺胺吡啶而增加。在治疗观察过程中,中药组未出现血尿及肝肾功的异常,主要不良反应是消化道不适,如恶心、腹胀、腹泻,但症状轻微,不良反应发生率低于中西医结合组和西药组。
本研究五项主要疗效指标包括BASDAI、BASFI、总体疼痛评分、患者对病情的总体评价评分、中医症状积分。BASDAI在治疗2周,三组开始出现不同程度的下降,但中药组和中西医结合组比西药组改善明显,具有统计学差异(中药组P<0.05,中西医结合组P<0.01)；在治疗1月时,中药组和中西医结合组比西药组改善明显,具有统计学差异(中药组P<0.05,中西医结合组P<0.01)；在治疗3月时,中西医结合组比西药组改善明显,具有统计学差异(P<0.05)。BASFI治疗2周,三组开始出现不同程度的下降,中药组、中西医结合组与西药组比较,改善更为明显,具有统计学差异(中药组P<0.05,中西医结合组P<0.01)；治疗1月时,中药组、中西医结合组比西药组改善明显,具有统计学差异(P<0.05)；治疗3月时,三组间比较无统计学差异(P>0.05)。总体疼痛评分、患者对病情的总体评价治疗前后比较,三组均有下降,但在治疗2周时,中西医结合组比西药组改善明显,具有统计学差异(P<0.05)。中医症状积分在治疗2周时,中药组、中西医结合组分别与治疗前相比有改善,且差异具有显著性(P<0.001),中药组、中西医结合组与西药组相比,改善明显,具有统计学差异(中药组P<0.05,中西医结合组P<0.01),中药组与中西医结合组比较,中西医结合组改善明显,具有统计学差异(P<0.05)；治疗1月和治疗3月时,西药组亦有改善,但没有中药组、中西医结合组改善明显,差异具有显著性(P<0.01)。
次要疗效指标包括胸廓活动度、指地距、枕墙距、ESR、CRP。胸廓活动度三组间同期比较,无统计学差异(P>0.05),在治疗2周时,中西医结合组和西药组与本组治疗前相比,改善具有统计学意义(中西医结合组P<0.001,西药组P<0.05)；在治疗1月、3月时,与本组治疗前相比,三组均有改善,且差异具有显著性。指地距三组间同期比较,无统计学差异(P>0.05),在治疗2周、1月、3月时,与本组治疗前相比,三组均有改善,且差异具有显著性。枕墙距三组间同期比较,无统计学差异(P>0.05)。ESR、CRP三组同期比较,无统计学差异(P>0.05),在治疗1月、3月时,与本组治疗前相比,三组均有改善,且差异具有显著性(P<0.05,P<0.001)。本研究中,中药组、中西医结合组对中医症状积分改善优于西药组,中药组、中西医结合组对BASDAI、BASFI改善在治疗2周、1月优于西药组,中西医结合组对BASDAI改善在治疗3月优于西药组。中西医结合组对总体疼痛评分、患者对病情的总体评价改善在治疗2周优于西药组,中药组和中西医结合组在治疗1月、3月对总体疼痛评分、患者对病情的总体评价改善与西药组相比无差异。中药组和中西医结合组对胸廓活动度、指地距、枕墙距、ESR、CRP的疗效与西药组相比无差异。
[结论]
1AS中医病名证候治法用药规律
当代名老中医对AS的病名认识不统一,多归属于中医骨痹、肾痹、痹证(症)范畴。唯房师将AS归属于“筋痹”范畴。病因有内外两方面,病机主流认识本虚标实,虚实夹杂。房师认为筋痹的主要病机为肝气不疏,肝血不足,筋脉失养,气血痹阻。AS常见证候要素有虚、湿、寒、风、瘀、热、痰、毒。AS常见治法是补肾、除湿、活血、通络。应用补肾药时,要以患者证型的寒热偏性来选择滋肾阴、温肾阳或平补肾阴肾阳。祛风除湿、散寒通络之品仍是目前许多医家治疗强直性脊柱炎的重要组方用药。活血化瘀贯穿整个治疗过程的始终已被多数医家认同。在强直性脊柱炎活动期或晚期,多应用虫类搜风剔络药和动物类的活血化瘀药。房师以柔肝舒筋、解痉止痛为法自拟解痉舒督汤治疗AS。
2导师房定亚教授治疗AS经验总结与数据挖掘
房师认为AS当归属于中医“筋痹”范畴。筋痹是指因人体正虚,风寒湿热之邪客于筋脉,或外伤于筋,或痰湿流注筋脉,气血痹阻,导致以筋急拘挛、抽掣疼痛、关节屈曲不利、腰背弯曲强直、步履艰难等为主要表现的一种病证。病位在筋脉、关节,涉及脏腑主要为肝,基本病机特点为肝气不疏,肝血不充,筋脉失养,气血痹阻。典型证候表现是疼痛拘挛强直。解痉舒督汤是治疗AS的基础方,其组成为葛根、白芍、蜈蚣、威灵仙、山慈菇、生黄芪、鹿衔草、乌蛇、生甘草、薏苡仁。导师倡导辨病与辨证相结合,治疗AS在解痉舒督汤基础上尚需根据分期和兼挟证(症)不同,结合现代生理病理及药理,加减用药。
3解痉舒督汤治疗AS临床研究
解痉舒督汤治疗强直性脊柱炎是有效的,并没有因联合柳氮磺胺吡啶而使总疗效提高,其安全性和依从性要优于西药组或联合柳氮磺胺吡啶。
Background
As a chronic inflammatory disease,ankylosing spondylitis belongs to seronegative spondyloarthropathy.The incidence rate of the disease is0.3%.The incidence ratio of male and female is2-3:1.The disease is more common in young adults, and the peak age of incidence is15-30years old. The central axis joints,peripheral joints and the tissues outside joints are mainly involved in patients of AS.The lower back pain or stiffness,activity limitation of the spine and hip are the main symptoms.In severe cases,the spine deformity may occur.Western medicine includes NSAIDS and DMARDS.However,the patient compliance is poor because of long treatment courses and side effects.Traditional Chinese medicine can keep long-term remission in patients with AS and improve the life quality of patients.Due to security and low cost,TCM treatment of AS have good social and economic benefits.
Objective
To discuss and summarize TCM name of AS,etiology,pathogenesis,TCM syndrome essential factor,therapeutic principle and drug rules,collection and quantitative analysis of literatures concerning the famous TCM doctors'clinical experiences of treating AS were carried out.To collect and mine the tutor's treatment features and medication experiences,principle of man machine integration was used,which was beneficial to extend the tutor's academic thoughts.To evaluate the efficacy and safety of the jiejingshudu decoction,clinical cases of AS were observed.
Method
Published literatures concerning AS diagnosis and treatment experience were collected.Denominations were formed into fixed fields of pathogenesis,syndrome differentiation,treatment method and the main drug that involved in these literatures.A database and frequency statistics were established by aid of SPSS16.0.A variety of data mining methods were used under the principle of man machine integration and people-orientation.The tutor's guidance with personal appreciation was combined,the tutor's clinical experiences was fully summarized.A randomized controlled clinical trial was conducted.90patients with AS were randomly divided into three groups:TCM group,integration of traditional Chinese and western medicine group,western medicine group.The patients of TCM group were treated with jiejingshudu decoction.The patients of integration of traditional Chinese and western medicine group were treated with jiejingshudu decoction and sulfasalazine.The patients of western medicine group were treated with sulfasalazine and diclofenac sodium.There were three months continuous medication for all AS patients.The changes in the five main and the five secondary efficacy indicators were recorded after two weeks,one month and three months of treatment.The five main efficacy indicators included BASDAI,BASFI,total pain score,overall evaluation score of patients with the disease and TCM symptom score.The five secondary efficacy indicators included thoracic mobility,finger-floor distance, occipital head-wall distance,ESR,CRP.
Result
1Literature research
There were29involved TCM names of the disease in the collected literatures. Bone impediment,kidney impediment and impediment syndrome were more common. Pathogen invaded the body in case of healthy qi deficiency,which resulted in the occurrence of AS.Etiology included both internal and external factors.The internal factors refered to healthy qi deficiency,congenital deficiency,acquired dystrophy, emotional trauma,improper diet,and overwork.The external factors refered to six excessive pathogens or wound.The pathogenesis was deficiency-excess complex,that was,deficiency at root and excess at branch.Physicians understund differently the root deficiency.There were52physicians who realised that the root deficiency refered to kidney deficiency(77.6%).There were35physicians who realised that the root deficiency refered to kidney and governor vessel deficiency(52.4%).There were18physicians who realised that the root deficiency refered to liver and kidney deficiency(26.9%).56syndrome types were involved in the literatures.The syndrome names with frequency greater than10times refered to static blood obstruction syndrome,kidney and governor vessel deficiency syndrome,syndrome of dampness-heat impediment,syndrome of cold-dampness impediment,syndrome of phlegm and blood stasis accumulation,syndrome of liver-kidney yin deficiency, syndrome of wind-cold-dampness impediment.According to the quantity of pathological factors or key elements the syndromes were divided into12single-factor syndromes,33two-factor syndromes,8Multi-factor syndromes,3inconvenient category syndromes.8key elements were included in the syndromes.A limited number of key elements were assembled into various types of syndrome of AS.The methods of treatment described in the literatures were decomposed into a single-factor method of treatment.Frequency of 17methods of treatment were greater than10times.These17methods of treatment were composed of tonifying the kidney,eliminating dampness,activating blood and resolving stasis,freeing the collateral vessels,clearing away heat,invigorating or unblocking du,dissipating cold,tonifying the liver and kidney,dispelling wind,relieving pain,resolving phlegm,nourishing blood or harmonizing the nutrient,detoxify,tonifying qi,invigorating bone or nourishing sinew,fortifying the spleen and invigorating the blood,moving qi or tonifying defense qi.The herbs which were applied by10or more physicians belonged to10categories of Chinese medicinal.10categories of Chinese medicinal were composed of kidney-tonifying medicinal,blood-activating medicinal, wind-dampness-dispelling medicinal,heat-clearing and dampness-drying medicinal, dampness-draining diuretic medicinal,dampness-resolving fragrant medicinal,wormy wind-dispelling or collateral vessels-freeing medicinal,phlegm-resolving medicinal, qi-tonifying medicinal and blood-tonifying medicinal.
2The tutor's clinic experiences and data mining
A total of105people cases were collected in the study.The common symptoms included lumbago,pain of hip joints,thoracodorsal stiff and pain,lower extremity and lower back activity limitation,stiff and pain of neck,back pain,lumbosacral pain,mild lumbago,knee pain,heel pain,activity limitation of neck,lack of strength and profuse sweating.The main pattern types included pattern of qi deficiency with blood stasis, pattern of heat toxin impediment,pattern of dampness-heat impediment,pattern of kidney deficiency and blood stasis,pattern of wind-cold-dampness impediment and pattern of liver-kidney deficiency.The main treatment methods included emolliating the liver to relax sinews,arresting convulsions to relieve pain,dispelling wind to free the collateral vessels, resolving phlegm to soften hardness,clearing the heat to detoxify,tonifying qi,tonify the kidney and activating blood.There were128herbs commonly used by the tutor.Herbs of frequency more than80%among them involved Gegen,Baishao,Weilingxian,Shancigu,Wugong.The five herbs were sovereign and minister medicinals of jiejingshudu decoction.
3A clinic trial on jiejingshudu decoction treating AS
Observation of84cases was completed.There were60males(71.43%) and24females(28.57%).The ratio of male to female was2.5:1.Among the three test groups,there were30cases in TCM group,30cases in integration of traditional Chinese and western medicine group,24cases in the western medicine group.The ages of84patients were from14to58years old.The average age was31.63±6.12in TCM group.The average age was33.13±10.81in integration of traditional Chinese and western medicine group.The average age was33.50±11.45in the western medicine group.The total efficacy of TCM group,integration of traditional Chinese and western medicine group,western medicine group was80.00%,83.33%,79.17%.The result was no significant difference in the statistical analysis.The total efficacy of integration of traditional Chinese and western medicine group didn't increase.In the period of clinical observation patients of TCM group did not show abnormal blood and urine test,whose main adverse reaction were mild gastrointestinal discomfort such as nausea, distention,diarrhea.The incidence of adverse reactions in TCM group was less than that in the other two groups.
The five main efficacy indicators included BASDAI,BASFI,total pain score, overall evaluation score of patients with the disease and TCM symptom score. BASDAI began to decrease to different extent in the three groups after two weeks of treatment.It decreased statistically significantly in the other two groups in comparison to the Western medicine group after two weeks or one month of treatment(TCM group P<0.05, integration of traditional Chinese and western medicine group P<0.01). BASDAI decreased statistically and significantly in the integration of traditional Chinese and western medicine group in comparison to the western medicine group after three month of treatment(P<0.05).BASFI began to decrease to varying degrees in the three groups after two weeks of treatment.It decreased statistically significantly in the other two groups in comparison to the western medicine group after two weeks of treatment.(TCM group P<0.05,integration of traditional Chinese and Western medicine group P<0.01).It decreased statistically and significantly in the other two groups in comparison to the western medicine group after one month of treatment(P<0.05).The difference of BASFI among the three groups was not statistically significant after three months of treatment.Contrasted before and after treatment, total pain scores of the three groups decreased.Total pain score and overall evaluation score of patients with the disease improved statistically and significantly in the integration of traditional Chinese and western medicine group in comparison to the western medicine group after two weeks of treatment(P<0.05).Contrasted before and after two weeks of treatment,TCM symptom scores of TCM group and the integration of traditional Chinese and western medicine group improved statistically and significantly(P<0.001).It improved statistically and significantly in the other two groups in comparison to the western medicine group after two weeks of treatment(TCM group P<0.05, integration of traditional Chinese and western medicine group P<0.01).TCM symptom score of the integration of traditional Chinese and western medicine group in comparison to the western medicine group improved statistically and significantly after two weeks of treatment(P<0.05).It improved in the western medicine group after one or three months of treatment,however,it improved statistically and significantly in the other two groups in comparison to the western medicine group(P<0.01).
The five secondary efficacy indicators included thoracic mobility,finger-floor distance,occipital head-wall distance,ESR,CRP.By contemporary comparison, thoracic mobilities of the three groups had no statistically significant difference (P>0.05).After two weeks of treatment thoracic mobilities of TCM group and the integration of traditional Chinese and western medicine group improved statistically and significantly(integration of traditional Chinese and western medicine group P<0.001,TCM group P<0.05).Contrasted before and after one or three months of treatment, thoracic mobilities of the three groups improved statistically and significantly. By contemporary comparison,finger-floor distances of the three groups had no statistically significant difference(P>0.05).Contrasted before treatment with after two weeks,one or three months of treatment, finger-floor distances of the three groups improved statistically and significantly.By contemporary comparison, occipital head-wall distances of the three groups had no statistically significant difference (P>0.05).By contemporary comparison,ESR and CRP of the three groups had no statistically significant difference(P>0.05).Compared with this group before treatment, the two indicators of the three groups improved statistically and significantly afer one or three months of treatment(P<0.05,P<0.001).
Improvement of TCM symptom score in TCM group or the integration of traditional Chinese and western medicine group was better than that in the western medicine group.Improvement of BASDAI and BASFI in the other two groups was better than that in the western medicine group afer two weeks and one month of treatment.Improvement of BASDAI in the integration of traditional Chinese and western medicine group was better than that in the western medicine group afer three months of treatment.Improvement of total pain score and overall evaluation score in the integration of traditional Chinese and western medicine group was better than that in the western medicine group afer two weeks of treatment.With prolonged treatment period,the difference of the two scores in the other groups compared with the western medicine group became not significant.Compared with the western medicine group,the other secondary efficacy indicators,including thoracic mobility,finger-floor distance, occipital head-wall distance,ESR and CRP,had no significant differences.
Conclusion
1Literature research
The contemporary famious TCM doctors did not agree with TCM names of the disease.Most of them regard the disease as bone impediment,kidney impediment and impediment syndrome.Only Professor Fang thinks that AS should be attributated to sinew impediment.Etiology includes both internal and external factors.The main pathogenesis is deficiency-excess complex,that is,deficiency at root and excess at branch.Professor Fang thinks that pathogenesis of AS is sinews dystrophy and qi-blood blockage due to liver qi stagnation or liver blood deficiency.The key syndrome elements refer to deficiency,dampness,cold,wind,stasis,heat,phlegm and toxin.The common methods of treatment include tonifying the kidney,eliminating dampness,activating blood and resolving stasis,freeing the collateral vessels.The herbal drugs of tonifying kidney are selected by heat or cold nature of the syndrome type.Wind-dampness dispelling and cold dispersing medicinal often emerge in many physicians' prescriptions.The majority of doctors agree with usage of blood-activating and stasis-resolving medicine throughout the therapeutic process.Wormy wind-dispelling or collateral vessels-freeing medicine and animal blood-activating or stasis-resolving medicine are more applied to AS patients in active phase or late stage.Professor Fang realized that emolliating the liver to relax sinews and relieving spasm to alleviate pain are the total principles of treating AS.Jiejingshudu decoction is a self-made recipe for AS by Professor Fang.
2The tutor's clinic experiences and data mining
Tutor Professor Fang thinks that AS should be attributated to sinew impediment. Sinew impediment is a group of symptoms including sinew contracture or spasm, pulling pain,joint flexion,lumbar back bending and rigidity,trudge,etc.Either wind-cold-dampness-heat pathogen invades the sinews in the statement of body healthy qi deficiency,or the sinews are injured,or phlegm-dampness binds the sinews, which results in the occurrence of sinew impediment.The disease of sinew impediment is located in sinews and joints.The liver viscus is mainly involved.Basic pathogenesis is characterized by sinews dystrophy and qi-blood blockage due to liver qi stagnaton or liver blood deficiency.Typical symptoms consist of pain,spasm and ankylosis. Jiejingshudu decoction is a basic formula treating AS,which is composed of Gegen,Baishao,Weilingxian,Shancigu,Wugong,Shenghuangqi,Luxiancao,Wushaoshe,S henggancao,Yiyiren.Tutor Professor Fang advocates combination disease identification with syndrome differentiation.According to the stage of disease and accompanying syndrome,the herbal drugs are added or cut down on the basis of Jiejingshudu decoction, with reference to modern physiological,pathological and pharmacological knowledge.
3A clinic trial on jiejingshudu decoction treating AS
Jiejingshudu decoction is a effective formula for treating AS.Efficacy of jiejingshudu decoction does not improve in the case of combination of sulfasalazine. Security and patient compliance of jiejingshudu decoction are superior to sulfasalazine in combination or sulfasalazine plus diclofenac sodium
引文
1.Geirsson AJ,Eyjolfsdottir H,Bjornsdottir Qet al.Prevalence and clinical characteristics of ankylosing spondylitis in Iceland-a nationwide study[J].Clin Exp Rheumatol,2010,28(3):333-340
2.Hanova P,Pavelka K,Holcatova I,et al.Incidence and prevalence of psoriatic arthritis, ankylosing spondylitis and reactive arthritis in the first descriptive population-based study in the Czech Republic[J].Scand J Rheumatol,2010,39(4): 310-317
3.陈仁忠.强直性脊柱炎在福建的发病情况调查[J].中国现代药物应用,2008,2(2)：124
4.王丽.强直性脊柱炎在吉林省发病情况调查[J].中国现代医生,2008,46(33)：115
5.Tam LS,Gu J,Yu D.Pathogenesis of ankylosing spondylitis[J].Nat Rev Rheumatol,2010,6(7):399-405
6.Erdes Sh.Some aspects of pathogenesis of ankylosing spondylitis[J].Ter Arkh, 2011,83(5):51-56
7.Seip MT,Erali M,Wies RL,et al.HLA-B27 typing:evaluation of an allele-specfic PCR melting assay and two flow cytometric antigen assays[J].Cytometry B Clin Cytom,2005,63(1):10-15
8.Kasifoglu T,Calisir C,Cansu DU,et al.The frequency of sacroiliitis in familial Mediterranean fever and the role of HLA-B27 and MEFV mutations in the development of sacroiliitis[J].Clin Rheumatol,2009,28(1):41-46
9.陈晓明.HLA-B27抗原检测在强直性脊柱炎诊断中的价值[J].中国现代医生,2011,49(4)：129-130
10.金明威,陈哲,陈颖.流式细胞术检测HLA—B27及其临床意义[J].中国优生与遗传杂志,2011,19(5)：32-35
11.Reveille JD,Maganti RM.Subtypes of HLA-B27:history and implications in the pathogenesis of ankylosing spondylitis[J].Adv Exp Med Biol,2009,64(9):159-176
12.Carica Fernandez S,Gonzalez S,Mina Blanco A,et al.New insights regarding HLA-B27 diversity in the Asian population[J].Tissue Antigens,2001,58(4):259-262
13.Hou T Y,Chen H C,Chen C H,et al.Usefulness of humanleucocyte antigen-B27 subtypes in predicting ankylosing spondylitis:Taiwan experience[J].Intern Med J,2007, 37(11):749-752
14.喻霞云,顾国浩,高纯,等.HLA—B27亚型与强直性脊柱炎相关性分析[J].苏州大学学报,2006,26(4)：607-609
15.Reveille J D.Major histocompatibility genes and ankylosing spondylitis[J].Best Pract Res Clin Rheumatol,2006,20(3):601-609
16.李维,黄霞.HLA—B27亚型与强直性脊柱炎的相关性研究[J].临床血液学杂志,2007,4(5)：218-220
17.刘波,邱萌.HLA-B27表达阴性的早中期强直性脊柱炎患者调查[J].中国医药导报,2011,8(12)：63-64
18.Wang X,Lin Z,Wei Q,et al.Expression of IL-23 and IL-17 and effect of IL-23 on IL-17 production in ankylosing spondylitis[J].Rheumatol Int,2009,29(11):1343-1347
19.Bowness P,Ridley A,Shaw J,et al.Th17 cells expressing KIR3DL2+ and responsive to HLA-B27 homodimers are increased in ankylosing spondylitis[J].J Immunol,2011,186(4):2672-2680
20.Chen CH,Lin KC,Yu DT,et al.Serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in ankylosing spondylitis:MMP-3 is areproducibly sensitive and specific biomarker of disease activity[J].Rheumatology(Oxford),2006, 45(4):414-420
21.Bal A,Unlu E,Bahar G,et al.Comparison of serum IL-1 beta. SIL-2R. IL-6 and TNF-alpha levels with disease activity parameters in ankylosing spondylitis[J].Clin Rheumatol,2007,26(2):211-215
22.Braun J,Davis J,Dougados M,et al.First update of the international AS consensus statement for the use of anti-TNF agents in patients with ankylosing spondylitis[J].Ann Rheum Dis,2006,65(3):316-320
23.Wendling D,Toussirot E.AntiTNF-alpha therapy in ankylosing spondylitis[J]. Expert Oping Pharmacother,2004,5(7):1497-1507
24.Lai E,Teodoro T,Volchuk A.Endoplasmic reticulum stress:signaling the unfolded protein response[J].Physiology(Betesda),2007,22:193-201
25.May E,Dorris ML,Satumtira N,et al.CD8 alpha beta t cells are not essential to the pathogenesis of arthritis or colitis in HLA-B27 transgenic rats[J].J Immunol,2003, 170(2):1099-1105
26.Saleki K,Hartigan N,Lith M,et al.Differential oxidation of HLA-B2704 and HLA-B*2705 in lymphoblastoid and transfected adherent cells[J]. Antioxid Redox Signal,2006,8(3-4):292-299
27.Galocha B,de Castro JA.Folding of HLA-B27 subtypes is determined by the global effect of polymorphic residues and shows incomplete correspondence to ankylosing spondylitis[J].Arthritis Rheum,2008,58(2):401-412
28.Gensler LS,Ward MM,Reveille JD,et al.Clinical, radiographic, and functional differences between juvenile-onset and adult-onset ankylosing spondylitis:results from the PSOAS cohort[J].Ann Rheum Dis,2008,67(2):233-237
29.Chen HA,Chen CH,Liao HT,et al.Factors associated with radiographic spinal involvement and hip involvement in ankylosing spondylitis[J].Semin Arthritis Rheum, 2011,40(6):552-558
30.Vosse D,de Vlam K.Osteoporosis in rheumatoid arthritis and ankylosing spondylitis[J].Clin Exp Rheumatol,2009,27(55):62-67
31.van der Horst-Bruinsma IE,Lems WF,Dijkmans BA.A systematic comparison of rheumatoid arthritis and ankylosing spondylitis[J].Clin Exp Rheumatol,2009,27(55): 43-49
32.Quismorio FP Jr.Pulmonary involvement in ankylosing spondylitis[J].Curr Opin Pulm Med,2006,12:342
33.Altin R,Ozdolap S,Savranlar A,et al.Comparison of early and late pleuropulmonary findings of ankylosing spondylitis by high-resolution computed tomography and effects on patients' daily life[J].Clin Rheumatol,2005,24:22
34.Bremander A,Petersson IF,Bergman S,et al.Population-based estimates of common comorbidities and cardiovascular disease in ankylosing spondylitis[J].Arthritis Care Res (Hoboken),2011,63(4):550-556
35.Dik VK,Peters MJ,Dijkmans PA,et al.The relationship between disease-related characteristics and conduction disturbances in ankylosing spondylitis[J].Scand J Rheumatol,2010,39(1):38-41
36.Bodnar N,Kerekes G,Seres I,et al.Assessment of subclinical vascular disease associated with ankylosing spondylitis[J].J Rheumatol,2011,38(4),723-729
37.Mathieu S,Gossec L,Dougados M,et al.Cardiovascular profile in ankylosing spondylitis:a systematic review and meta-analysis[J].Arthritis Care Res (Hoboken), 2011,63(4):557-563
38.Roussou E,Sultana S,Spondyloarthritis in women:differences in disease onset、 clinical presentation and Bath Ankylosing Spondylitis Disease Activity and Functional indices(BASDAI and BASFI) between men and women with spondyloarthritides[J]. Clin Rheumatol,2011,30(1):121-127
39.方玲,樊晓海,叶夏云,等.93例女性强直性脊柱炎的诊断特点[J].军医进修学院学报,2010,31(5)：418-419
40.晋瑞,王惠芳.儿童强直性脊柱炎的临床特点及鉴别诊断[J].临床误诊误治,2005(18)7：491-492
41.Ostensen M,Forger F,Nelson JL,et al.Pregnancy in patients with rheumatic disease:anti-inflammatory cytokines increase in pregnancy and decrease post partum[J]. Ann Rheum Dis,2005,64:839-844
42.方玲,钟建庭.强直性脊柱炎的诊治现状[J].中国医师进修杂志,2006,29(7)：69-71
43.赵丽珂,黄慈波.强直性脊柱炎的诊断治疗进展[J].临床药物治疗杂志,2010,8(1)：14-18
44.Wanders A,Vander Heijde D,Landewe R,et al.Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis:a randomized clinical trial[J].Arthritis Rheum,2005,52:1756-1765
45.Ward MM.Prospects for disease modification in ankylosing spondylitis:do nonsteroidal antiinflammatory drugs do more than treat symptoms[J].Arthritis Rheum, 2005,52:1634
46.Vander Heijde D,Baraf HS,Ramos-Remus C,et al.Undifferentiated spondyloarthritis: anosological missing link[J].Arthritis Rheum,2005,52(4):1205-1215
47.American College of Rheumatology Ad Hoc Group on Recommendations for use of selective and nonselective nonsteroidal antiinflammatory drugs:an American College of Rheumatology white paper[J].Arhtritis Rheum(Arhtritis Care Res), 2008,59(8):1058-1073
48.Scott D.Solomon,John J.V.McMurray,Marc A.Pfeffer,et al.Cardiovascular Risk Associated with Celecoxib in a Clinical Trial for Colorectal Adenoma Prevention[J].N Engl J Med,2005,352:1071-1080
49.Loren Laine,Sean P Curtis,Byron Cryer,et al.Assessment of upper gastrointestinal safety of etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term(MEDAL) programme:a randomised comparison[J].Lancet,2007,369:465-473
50.Christopher P Cannon,Sean P Curtis,Garret A FitzGerald,Henry Krum,et al.Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term(MEDAL)programme:a randomised comparison[J].Lancet 2006;368: 1771-81.
51.中华医学会风湿病学分会.强直性脊柱炎诊疗指南(草案)[J].中华风湿病学杂志,2003,7(10)
52.中华医学会风湿病学分会.强直性脊柱炎诊疗指南[J].中华风湿病学杂志,2010,14(8)：557-559
53.Furst De,Breedveld Fc,Kalden Jr,et al.Updated consensus statement on biological agents specifically tumor necrosis factor blocking agents and interleukin-1 receptor antagonist(IL-1ra), for the treatment of rheumatic diseases[J].Ann Rheum Dis,2005,64(Suppl):2-14
54.Davis Jc Jr.Understanding the role of tumor necrosis factor inhibition in ankylosing spondylitis[J].Semin Arthritis Rheum,2005,34(4):668-677
55.Zochling J,Van Der Heijde D,Dougados M,et al.Current evidence for the management of ankylosing spondylitis:a systematic literature review for the ASAS/EULAR management recommendations in ankylosing spondylitis[J].Ann Rheum Dis,2006,65(4):423-432
56.J Zochling,D van der Heijde,R Burgos-Vargas,et al.ASAS/EULAR recommendations for the management of ankylosing spondylitis[J].Ann Rheum Dis,2006,65:442-452
57.L.Goh,A.Samanta.A systematic medline analysis of therapeutic approaches in ankylosing spondylitis[J].Rheumatol Int,2009,29:1123-1135
58.Nurullah Akkoc,Sjef van der Linden,Muhammad Asim Khan.Ankylosing spondylitis and symptom-modifying vs disease-modifying therapy[J].Best Practice& Research Clinical Rheumatology.2006,20(3):539-557
59.Brandt J,Listing J,Haibel H,et al.Methotrexate in the treatment of ankylosing spondylitis [J]. Rheumatology(Oxford),2005,44(3):342-348
60.Martin-Mola E,Sieper J,Leirisalo-Repo M.Sustained efficacy and safety, including patient-reported outcomes, with etanercept treatment over 5 years in patients with ankylosing spondylitis[J].Clin Exp Rheumatol,2010,28(2):238-245
61.Inman RD,Maksymowych WP.A double-blind,placebo-controlled trial of low dose infliximab in ankylosing spondylitis[J].J Rheumatol.2010,37(6):1203-1210
62.Van der Heijde D,Kivitz A,Schiff Mh,et al.Efficacy and safety of adalimumab in patients with ankylosing spondylitis:results of a multicenter,randomized,double-blind, placebo-controlled trial[J].Arthritis Rheum,2006,54(7):2136-2146
63.Van der Heijde D,Revicki D,Gooch K,el al.Physical function,disease activity, and health-related quality-of-life outcomes after 3 years of adalimumab treatment in patients with ankylosing spondylitis[J].Arthritis Res Tiler,2009,11(4):124
64.Rudwaleit M,Claudepierre P, Wordsworth P,et al.Effectiveness,safety,and predictors of good clinical response in 1250 patients treated with adalimumab for active ankylosing spondylitis[J].J Rheumatol,2009,36(4):801-808
65.Rudwaleit M,Olivieri I,Boki KA,et al.Adalimumab is effective and well tolerated in treating patients with ankylosing spondylitis who have advanced spinal fusion[J].Rheumatology(Oxford),2009,48(5):551-557
66.Rudwaleit M,Gooch K,Michel B,et al.Adalimumab improves sleep and sleep quality in patients with active ankylosing spondylitis[J].J Rheumatol,2011,38(1):79-86
67.Kukar M,Petryna O.Eflhimiou E Biological targets in the treatment of rheumatoid arthritis:a comprehensive review of current and in-development biological disease modifying anti-rheumatic drugs[J].Biologics,2009,3(3):443-457
68.Mazumdar S,Greenw aid D,Golimumab[J].Mabs,2009,1(5):422-431
69.Shealy D,Cai A,Staquet K.Characterization of golimumab,a human monoclonal antibody specific for human tumor necrosis factor alpha[J].Mabs,2010,2(4):331-352
70.张卓莉,董怡.辅刺激因子调节剂——类风湿关节炎治疗的新途径[J].中国新药杂志,2006,15(11)：845-848
71.Song IH,Heldmann F,Rudwaleit M,et al.Treatment of active ankylosing spondylitis with abatacept:an open-label,24-week pilot study[J].Ann Rheum Dis, 2011,7(6):1108-1110
72.Lekpa FK,Farrenq V,Canoui-Poitrine F,et al.Lack of efficacy of abatacept in axial spondylarthropathies refractory to tumor-necrosis-factor inhibition[J].Joint Bone Spine,2011,78(4),302-312
73.Zochling J,Van der Heijde D,Dougados M,et al.Current evidence for the management of ankylosing spondylitis:A systematic literature review for the ASAS/EULAR management recommendations in ankylosing spondylitis[J].Ann Rheum Dis,2006,65:423-432
74.Zochling J,Van der Heijde D,Burgos-Vargas R,et al.ASAS/EULAR recommendations for the management of ankylosing spondylitis[J].Ann Rheum Dis,2006,65:444-452
75.左晓霞,陶立坚,高洁生主译.凯利风湿病学[M].2006,北京,人民卫生出版社,第一版,971
76.栗占国,唐福林主译.凯利风湿病学[M].北京大学医学出版社,北京,2011,第版,1252-1253
77.Dagfinrud H,Kvien TK,Hagen KB.Physiotherapy interventions for ankylosing spondylitis.Cochrane Database of Systematic Reviews 4,2004,pub2.DOI.art.no. cd002822
78.杨岫岩.强直性脊柱炎的疗效评价[J].实用医学杂志,2002,18(2)：118-120
79.Anderson JJ,Baron G,van der Heijde D,et al.ASAGpreliminary definition of short term improvement in ankylosing spondylitis[J].Arthritis Rheum,2001,44(8): 1876-1886
80.Doward LC,Spoorenberg A,Cook SA,et al:Development of the ASDoL:A quality of life instrument specific to ankylosing spondylitis[J].Ann Rheum Dis,2003,62: 20-26
1.战国·佚名撰.黄帝内经素问[M].北京：中医古籍出版社,1997
2.隋·杨上善撰,王洪图重校.黄帝内经太素[M].北京：科学技术文献出版社,2000
3.元·朱丹溪著.脉因证治[M].山西：山西科学技术出版社,
4.明·楼英著.医学纲目[M].北京：中国中医药出版社,1996
5.汉·华佗著.杨金生重校.华佗神方[M].北京：中国古籍出版社,1997
6.清·李用粹编撰.证治汇补[M].北京：中国中医药出版社,2008
7.清·罗美编撰.古今名医汇粹[M].北京：中国古籍出版社,1999
8.清·张璐著.张氏医通[M].北京：中国中医药出版社,1995
9.明·秦景明撰.症因脉治[M].北京：中国中医药出版社,1998
10.隋·巢元方撰,中华中医药学会编.诸病源候论[M].北京：华夏出版社,1998
11.宋·杨士瀛撰.仁斋直指方[M].上海：第二军医大学出版社,2006
12.汉·华佗撰,农汉才点校.中藏经[M].北京：学苑出版社,2007
13.唐·王焘撰.外台秘要[M].北京：人民卫生出版社,1987
14.清·罗东逸著.内经博议[M].北京：学苑出版社,2010
15.明·王肯堂著.证治准绳[M].北京：人民卫生出版社,2001
16.晋·皇甫谧著.针灸甲乙经[M].北京：中国医药科技出版社,2011
17.明·张介宾著.类经[M].北京：学苑出版社,2005
18.曹颖甫著,鲍艳举陶有强校注.金匮发微[M].北京：学苑出版社,2008
19.清·薛雪撰,洪丕谟 姜玉珍点校.医经原旨[M].上海：上海中医学院出版社,1991
20.金·张元素原著.医学启源[M].北京：人民军医出版社,2009
21.明·孙志宏撰.简明医彀[M].北京：人民卫生出版社,1984
22.清·汪宏著.望诊遵经[M].北京：中国中医药出版社,2009
23.清·章虚谷著.灵素节注类编[M].浙江：浙江科学技术出版社,1984
24.宋·严用和撰.严氏济生方[M].北京：人民卫生出版社,1980
25.唐·孙思邈著.备急千金要方[M].山西：山西科技出版社,2010
26.宋·王怀隐,陈昭遇等编.太平圣惠方[M].北京：人民卫生出版社,1958
27.清·叶天士著.临证指南医案[M].北京：人民卫生出版社,2006
28.宋·许叔微撰.普济本事方[M].北京：中国中医药出版社,2007
29.清·尤怡著,张印生等校注.金匮翼[M].北京：中医古籍出版社,2003
30.元·危亦林撰.世医得效方[M].北京：中国中医药出版社,2009
31.明·徐春甫辑.古今医统大全[M].北京：人民卫生出版社,2000
32.清·喻嘉言著,丁侃校.医门法律[M].北京：中国医药科技出版社,2011
33.清·林佩琴著.类证治裁[M].山西：山西科学技术出版社,2010
34.清·吴谦等编.医宗金鉴[M].北京：人民卫生出版社,1992
35.清·何梦瑶著.医碥[M].北京：中国中医药出版社,2009
36.金·李东垣著.脾胃论[M].北京：中国医药科技出版社,2011
37.明·李梃编撰,田代华等整理.医学入门[M].北京：人民卫生出版社,2006
38.清·潘楫著.医灯续焰[M].北京：中国中医药出版社,1999
39.明·朱棣等编.普济方[M].北京：人民卫生出版社,1959
40.元·朱震亨撰,王英等整理.丹溪心法[M].北京：人民卫生出版社,2005
41.明·董宿辑录,方贤续补.奇效良方[M].天津：天津科学技术出版社,2003
42.宋·赵估编.圣济总录[M].北京：人民卫生出版社,2004
43.清·张秉成著.本草便读[M].北京：学苑出版社,2010
44.战国·佚名著.黄帝内经灵枢[M].山西：山西科学技术出版社,2011
45.明·高武撰.针灸素难要旨[M].上海：上海科技出版社,1959
46.明·杨继洲原著.针灸大成[M].北京：人民卫生出版社,2006
47.清·黄元御著,孙国中方向红注.素问悬解[M].北京：学苑出版社,2008
48.明·高武编撰.针灸聚英[M].北京：人民卫生出版社,2006
49.明·张介宾撰.类经图翼[M].北京：人民卫生出版社,1980
50.金·张子和撰.儒门事亲[M].北京：人民卫生出版社,2006
1.蔡余力,陈德强,张兴彩.曹贻训教授治疗强直性脊柱炎经验[J].中国误诊学杂志,2011,11(6)：1381
2.林昌松,刘晓玲,关彤等.陈纪藩教授治疗强直性脊柱炎经验[J].新中医,2001,33(2)：0-11.
3.王政.陈湘君治疗强直性脊柱炎经验[J].辽宁中医杂志,2000,27(5)：196
4.罗汉文,李逸群.陈志维教授治疗强直性脊柱炎经验介绍[J].新中医,2010,42(1)：35-36
5.崔儒涛.崔学增治疗强直性脊柱炎经验[J].中医杂志,1999,40(11)：655-656
6.丁锷.临床心得举隅[J].安徽中医临床杂志,2003,15(2)：81-82
7.杜秀兰.雷公藤复方治疗强直性脊椎炎62例[J].山东中医杂志,1995,14(12)：544-545
8.马芳,周彩云.房定亚治疗强直性脊柱炎经验[J].中医杂志,2009,50(8)：685-686
9.马从孝.冯兴华治疗强直性脊柱炎经验[J].山东中医杂志,2007,26(7)：487-488
10.梁慧英,冯兴华.冯兴华教授对强直性脊柱炎病因病机认识的探析[J].中华中医药杂志,2011,26(9)：2012-2014
11.冯兴华.强直性脊柱炎证候规范之我见[J].中国中医骨伤科杂志,2009,11(17)：179-181
12.许凤全.冯兴华辨治强直性脊柱炎经验集要[J].辽宁中医杂志,2008,35(10)：1478-1479
13.张海波,傅禹砜.傅警龙治疗强直性脊柱炎经验[J].长春中医药大学学报,2008,24(6)：639
14.胡荫奇,常志遂.痹病古今名家验案全析[M].科学技术文献出版社,北京,2003,第-版,446-447
15.王英俊.高明利强直性脊柱炎中医辨治规律[J].辽宁中医药大学硕士学位论文,2011,5
16.岳月.高明利教授运用补肾通督法治疗强直性脊柱炎经验总结.辽宁中医药大学硕士学位论文,2006,5
17.张梅红、谷万里等.谷越涛治疗强直性脊柱炎经验[J].四川中医,2004,22(8)：5-6.
18.郭艳幸.郭维淮治疗强直性脊柱炎经验[J].中国中医骨伤科杂志,1997,5(5)：59-61
19王义军.胡荫奇治疗强直性脊柱炎经验[J].中国中医药信息杂志,2004,11(12)：1102-1103.
20.夏璇.黄清春中西医结合治疗强直性脊柱炎经验[J].中国中医药信息杂志,2011,18(3)：96
21.田黎.黄仰模教授治疗痹证经验介绍[J].中华中医药学刊,2008,26(12)：2553-2554
22.焦树德.强直性脊柱炎的治疗经验[J].河北中医,2004,26(10)：725-726
23.项红.焦树德治疗强直性脊柱炎的临床经验[J].北京中医,2004,23(3)：142-143
24.刘继刚.焦树德教授治疗强直性脊柱炎的经验介绍[J].贵阳中医学院学报,2002,24(3)：14-15
25.刘树权.金明秀治疗强直性脊柱炎经验[J].辽宁中医杂志,2003,30(4)：248
26.韩善夯.金实教授治疗强直性脊柱炎经验[J].四川中医,2005,23(11)：1-2
27.赵岩松,陈嘉苹,许镫尹等.孔光一治疗强直性脊柱炎经验介绍[J].北京中医药,2010,29(1)：21-22
28.袁普卫.李堪印治疗强直性脊柱炎的经验介绍[J].国际中医中药杂志,2010,32(2)：186
29.魏玲玲,黄飞,李秋贵.李文瑞论强直性脊柱炎证治[J].辽宁中医杂志,2009,36(2)：175-176
30.林昌松,续青.中医治疗强直性脊柱炎经验[J].河北中医,2001,23(2)：115-116
31.王桂珍,黄传兵,汪元等.刘健治疗强直性脊柱炎经验[J].安徽中医学院学报,2010,29(6)：38-39
32.曹玉举,娄伯恩,秦涛等.娄多峰教授治疗痹证用药经验[J].中医研究,2010,23(4)：59-61
33.曹玉举,李娜,秦涛.娄多峰教授治疗痹证经验[J].中医研究,2010,23(1)：63-65
34.曹玉举.娄多峰教授论风湿病病因病机[J].中医研究,2011,24(10)：64-67
35.赵敏.娄玉钤治疗强直性脊柱炎经验[J].中医杂志,2010,51(11)：980-981
36.袁怡.鲁贤昌教授治疗强直性脊柱炎经验介绍[J].新中医,2009,41(2)：18-19
37.章天寿.路志正治疗强直性脊柱炎经验[J].中医杂志,2002,43(7)：499-503
38.周慧敏,万莹,岳滞滢.吕文亮教授辨治杂病验案举隅[J].国医论坛,2008,23(6)：9-10
39.朱辉.莫成荣治疗强直性脊柱炎的经验[J].辽宁中医杂志,2004,31(3)：184-185
40.刘欢,庞学丰.庞学丰辨治风湿病临床经验掇萃[J].吉林中医药,2008,28(10)：711-712
41.张营光.曲淑琴教授运用活血化瘀法为主治疗强直性脊柱炎经验总结.辽宁中医药大学硕士学位论文,2011,4
42.张建力.任建华运用益肾通督法治疗强直性脊柱炎经验[J].甘肃中医,2009,22(4)：21-22
43.商阿萍,潘广博.辨证治疗强直性脊柱炎经验[J].河北中医,2008,(30)6：599-601
44.汪东涛.沈鹰治疗强直性脊柱炎经验[J].山东中医药大学学报,2008,32(4)：306-307
45.李具宝,王拥军,周泉等.施杞从痹论治强直性脊柱炎经验初探[J].上海中医药杂志,2010,(44)12：1-2
46.高翔,吴弢,叶秀兰等.施杞从痹论治强直性脊柱炎经验举隅[J].上海中医药杂志,2010,(44)7：16-18
47.徐慧媛,齐贺彬.治疗强直性脊柱炎的经验介绍.首届国际中西医结合风湿病学术会议论文汇编,2004,159-160
48.舒尚义.舒尚义老师治疗强直性脊柱炎经验举要[J].云南中医药杂志,2008,29(6)：1
49.宋欣伟.宋欣伟教授治疗强直性脊柱炎的经验[J].云南中医药杂,2009,30(1)：21
50.周伟平.苏励主任治疗强直性脊柱炎的经验[J].福建中医药,2007,38(3)：16
51.葛瑞彩.孙素平教授治疗强直性脊柱炎经验[J].甘肃中医学院学报, 2010,27(4)：12-13
52.胡刚明,万彬彬.田玉美治疗强直性脊柱炎的临床经验[J].湖北中医杂志,2010,32(1)：33-34
53.陈月月.汪悦教授治疗强直性脊柱炎经验[J].现代中医药,2010,30(1)：39-40
54.冯皓,周腊梅,廖华军.汪悦教授治疗强直性脊柱炎经验分析[J].中国民族民间医药,2010,(14)：30-34
55.张静,牛臻洁.王素芝治疗尪痹的经验[J].辽宁中医杂志,2003,30(11)：870-871
56.王北.王为兰教授治疗强直性脊柱炎的临床经验[J].北京中医药大学学报(中医临床版),2008,15(5)：23-24
57.矫健鹏,刘煊.魏品康从痰论治强直性脊柱炎经验探析[J].中华中医药杂志,2011,26(8)：1759-1761
58.杨敏.吴启富教授中西医结合治疗强直性脊柱炎经验.全国中西医结合强直性脊柱炎专题研讨会论文汇编,2007,181-184
59.肖泓,吴咏昕.吴生元浅谈导师治疗强直性脊柱炎的经验[J].云南中医中药杂志,2002,23(5)：8-9
60.卢勤妹.吴旭教授通督温阳法临床应用[J].辽宁中医药大学学报2011,13(11)：16-17
61.谢海洲.治疗风湿病的经验体会[J].中国中医药信息杂志,2000,7(12)：1-2
62.张俊莉,陈爱琳.徐玲主任医师治疗强直性脊柱炎经验[J].陕西中医,2005,26(11)：1200-1201
63.高积粮.阎小萍治疗强直性脊柱炎经验管窥[J].中医药临床杂志,2007,19(2)：108-109
64.孔维萍,阎小萍.阎小萍教授治疗强直性脊柱炎的学术思想及其临床经验[J].中医正骨,2008(20)6：64-65
65.李强,王莉莉.阎小萍治疗强直性脊柱炎经验[J].中医杂志,2010,51(增刊2)：148-150
66.杨仓良.从毒邪致病辨治强直性脊柱炎[J].新中医,2007,39(8)：1-3
67.李航.杨少山主任医师应用滋阴法治疗疑难病验案举隅[J].新中医,2010,42(7)：152-153
68.卢思俭.尹玉茹诊治强直性脊柱炎经验[J].山东中医杂志,1997,16(6)：272-273.
69.曹奕,李佩芳,陈幸生.张道宗教授通督调神学术思想浅析[J].中国针灸, 2006,26(10)：741-743
70.罗丽彬.张凤山教授治疗风湿病经验介绍[J].新中医,2009,41(12)：9
71.王振宇.张凤山教授中西医结合诊治风湿病的经验总结.第四届全国中西医结合风湿类疾病学术会议论文汇编,2000,33-35
72.何庆勇.张吉针药并用治疗强直性脊柱炎的经验[J].中华中医药杂志,2006,21(9)：544-546
73.潘秋.张吉教授针药并用治疗强直性脊柱炎验案1则[J].北京中医药大学学报(中医临床版),2005,12(6)：36
74.张蓓莉.张镜人临证经验拾掇[J].辽宁中医杂志,2002,29(2)：65-66
75.邓长财,鞠中斌.张鸣鹤治疗活动期强直性脊柱炎经验探讨[J].山东中医药大学学报,2006,30(5)：372-373
76.王福林.张延昌主任医师治疗风湿病临床验案3则[J].中医研究,2011,24(1)：57-60
77.张鹏.张志刚治疗强直性脊柱炎经验[J].山东中医杂志,2005,24(8)：503-504
78.潘文萍,周丽萍.周翠英治疗强直性脊柱炎的经验[J].四川中医,2002,20(11)：1-3
79.陈爱萍.周乃玉教授益肾强督治疗强直性脊柱炎[J].甘肃中医,2010,23(9)：11-12
80.邱志济,朱建平,马璇卿.朱良春治疗强直性脊柱炎用药特色选析[J].辽宁中医杂志,2001,28(11)：656-657
81.蒋恬,顾冬梅.朱良春教授治疗风湿病学术思想和诊疗技术简介[J].新中医,2011,43(6)：150-151
82.顾冬梅,蒋恬,朱婉华.朱婉华益肾蠲痹法治疗强直性脊柱炎临床经验[J].中国中医基础医学杂志,2011,17(8)：872-874
83.夏俊杰.朱晓鸣治疗强直性脊柱炎经验[J].湖北中医杂志,1997,19(6)：10-11
84.娄玉钤.风湿病命名与分类的规范化研究[J].中华中医药杂志,2008,23(9)：840-844
85.张显彬,王海隆.强直性脊柱炎中医辨证分型文献分析[J].湖南中医杂志,2006,22(6)：71-72
86.李坚,李满意,娄玉钤.强直性脊柱炎中医证型分布规律研究[J].世界中西医结合杂志,2011,6(1)：6-10
1.Tang X,Zhu X,Liu S,et al.Phytoestrogens induce differential estrogen receptor beta-mediated responses in transfected MG-63 cells [J]. Endocrine,2008,34(3):29-35
2.陈珍旭,吴蓉易,张淑玉,等.葛根素对实验性大鼠肺纤维化影响[J].临床肺科杂志,2006,11(4)：423-426
3.Chang Y,Hsieh CY,Peng ZA,et al.Neuroprotective mechanisms of puerarin in middle cerebral artery occlusion-induced brain infarction in rats [J].Journal of Biomedical Science,2009,16(1):9
4.Wan H,Zhu H,Tian M,et al.Protective effect of chuanxiongzine-puerarin in a rat model of transient middle cerebral artery occlusion-induced focal cerebral ischemia [J].Nuclear Medicine Communications,2008,29(12):1113-1122
5.Zhuang Z,Jiang G.Thirty cases of the blood-stasis type prolapse of lumbar intervertebral disc treated by acupuncture at the xi (cleft) point plus herbal intervention injection [J] Journal of Traditional Chinese Medicine,2008,28(3):178-182
6.姜晓晓,李勇,吴永宾,等.葛根素预处理对体外循环围手术期细胞因子的影响[J].中国中西医结合杂志,2009,29(12)：1089-1091
7.邓兆智,钟秋生,吴月芹,等.白芍总苷、甲氨喋呤和柳氮磺吡啶治疗强直性脊柱炎的疗效和安全性研究[J].实用中医内科杂志,2005,19(4)：328-329
8.刘晖,龚瑶,库尔班江,等.联合白芍总苷治疗强直性脊柱炎的临床观察[J].新疆医学,2004,34：79-80
9.吴东红,赵育松.帕夫林治疗强直性脊柱炎临床疗效观察[J].哈尔滨医科大学学报,2002,36(5)：381-384
10.褚婕,张金芝,沈大跃等.中药蜈蚣对小鼠免疫功能的影响[J].天津药学,1994,6(2)：23-25
11.夏伦祝,徐先祥,张睿.威灵仙总皂苷对小鼠免疫功能的影响[J].安徽医药,2009,13(5)：496-497
12.吴青业,鞠学鹏,关业枝,等.威灵仙水煎液对佐剂性关节炎模型小鼠的作用及机理研究[J].中药药理与临床,2011,27(1)：68-70
13.张蕴毅,张宏伟,李佩芬,等.威灵仙的解痉抗炎镇痛作用[J].中成药,2001,23(11)：808-811
14.Shim JS, Kim JH, Lee J,et al.Anti-angiogenic activity of a ho2moisoflavanone from Cremastra appendiculata[J].Planta Med,2004,70(2):171-173
15.杨璐,沈洪.黄芪及其主要成分抗肿瘤免疫机制研究进展[J].山东中医药大学学报,2011,35(3)：281-285
16.李秀萍,孙树凯,魏军等.白花蛇舌草对肝损伤小鼠T细胞亚群、TNF-a和IL-6的影响[J].宁夏医学杂志,2010,32(6)：495-497
17.孟玮,刘志强,邱志翠,等.中医白花蛇舌草对小鼠免疫功能影响的初步研究[J].现代中西医结合杂志,2005,14(2)：163
18.杨凌,崔晓燕,张许等.黄芩提取物的抗炎免疫作用研究[J].中国药房,2007,18(24)：1856-1857
19.李谷才,任凤莲.超临界流体萃取百合中的秋水仙碱.湖南：中南大学,2004
20.苗明三.百合多糖抗氧化作用研究[J].中药药理与临床,2001,17(2)：12-13
21.曾明,李守汉,曾爽,等.兰州百合抗运动性疲劳的实验研究[J].山西师大体育学院学报,2005,20(1)：110-112
1.路志正,焦树德.实用中医风湿病学[M].人民卫生出版社,北京,1996,第一版,2
2.娄玉钤.风湿病命名与分类的规范化研究[J].中华中医药杂志,2008,23(9)：840-844
3.马芳,周彩云.房定亚治疗强直性脊柱炎经验[J].中医杂志,2009,50(8)：685-686
4.谢文彦.健胃愈疡胶囊治疗消化性溃疡40例临床观察[J].长春中医药大学学报,2011,27(6)：432
5.王建.解痉镇痛方免煎颗粒剂治疗偏头痛[J].湖北中医学院学报,2007,9(2)：54
6.毛树文,赵鹏.解痉止痛推拿法治疗慢性盆腔炎[J].吉林中医药,2011,31(4)：352-353
7.卫德龙,虞陆祥,李国进.急性胆囊炎胆石症中西医结合治疗[J].浙江中西医结合杂志,2006,16(7)：437-438
8.李仁顺,汪少开,荣丽红.补肾益气活血通络解痉止痛法治疗冠心病心绞痛的临床研究[J].中医药学报,2006,34(1)：49-51
9.田志丽,林亚琳.解痉止痛汤治疗小儿再发性腹痛的疗效观察[J].河北中 医,2005,27(7)：511
10.刘宏潇,冯兴华,何夏秀,等.补肾强脊颗粒治疗强直性脊柱炎疗效与安全性评价[J].中国中西医结合杂志,2006,26(5)：403-406
11.纪伟,宋亚楠.腰痹通胶囊治疗强直性脊柱炎临床观察[J].实用临床医药杂志,2010,14(21)：60-61
12.方翼,黄烽.抗强直性脊柱炎药物的研究进展[J].解放军药学学报,2008,24(6)：521-524
13.黄烽.脊柱关节炎的发病机制与治疗新进展[J].基础医学与临床,2005,25(9)：780-784
14.栗占国,唐福林主译.凯利风湿病学[M].北京大学医学出版社,北京,2011,第一版,1252-1253
2.Hanova P,Pavelka K,Holcatova I,et al.Incidence and prevalence of psoriatic arthritis, ankylosing spondylitis and reactive arthritis in the first descriptive population-based study in the Czech Republic[J].Scand J Rheumatol,2010,39(4): 310-317
3.陈仁忠.强直性脊柱炎在福建的发病情况调查[J].中国现代药物应用,2008,2(2)：124
4.王丽.强直性脊柱炎在吉林省发病情况调查[J].中国现代医生,2008,46(33)：115
5.Tam LS,Gu J,Yu D.Pathogenesis of ankylosing spondylitis[J].Nat Rev Rheumatol,2010,6(7):399-405
6.Erdes Sh.Some aspects of pathogenesis of ankylosing spondylitis[J].Ter Arkh, 2011,83(5):51-56
7.Seip MT,Erali M,Wies RL,et al.HLA-B27 typing:evaluation of an allele-specfic PCR melting assay and two flow cytometric antigen assays[J].Cytometry B Clin Cytom,2005,63(1):10-15
8.Kasifoglu T,Calisir C,Cansu DU,et al.The frequency of sacroiliitis in familial Mediterranean fever and the role of HLA-B27 and MEFV mutations in the development of sacroiliitis[J].Clin Rheumatol,2009,28(1):41-46
9.陈晓明.HLA-B27抗原检测在强直性脊柱炎诊断中的价值[J].中国现代医生,2011,49(4)：129-130
10.金明威,陈哲,陈颖.流式细胞术检测HLA—B27及其临床意义[J].中国优生与遗传杂志,2011,19(5)：32-35
11.Reveille JD,Maganti RM.Subtypes of HLA-B27:history and implications in the pathogenesis of ankylosing spondylitis[J].Adv Exp Med Biol,2009,64(9):159-176
12.Carica Fernandez S,Gonzalez S,Mina Blanco A,et al.New insights regarding HLA-B27 diversity in the Asian population[J].Tissue Antigens,2001,58(4):259-262
13.Hou T Y,Chen H C,Chen C H,et al.Usefulness of humanleucocyte antigen-B27 subtypes in predicting ankylosing spondylitis:Taiwan experience[J].Intern Med J,2007, 37(11):749-752
14.喻霞云,顾国浩,高纯,等.HLA—B27亚型与强直性脊柱炎相关性分析[J].苏州大学学报,2006,26(4)：607-609
15.Reveille J D.Major histocompatibility genes and ankylosing spondylitis[J].Best Pract Res Clin Rheumatol,2006,20(3):601-609
16.李维,黄霞.HLA—B27亚型与强直性脊柱炎的相关性研究[J].临床血液学杂志,2007,4(5)：218-220
17.刘波,邱萌.HLA-B27表达阴性的早中期强直性脊柱炎患者调查[J].中国医药导报,2011,8(12)：63-64
18.Wang X,Lin Z,Wei Q,et al.Expression of IL-23 and IL-17 and effect of IL-23 on IL-17 production in ankylosing spondylitis[J].Rheumatol Int,2009,29(11):1343-1347
19.Bowness P,Ridley A,Shaw J,et al.Th17 cells expressing KIR3DL2+ and responsive to HLA-B27 homodimers are increased in ankylosing spondylitis[J].J Immunol,2011,186(4):2672-2680
20.Chen CH,Lin KC,Yu DT,et al.Serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in ankylosing spondylitis:MMP-3 is areproducibly sensitive and specific biomarker of disease activity[J].Rheumatology(Oxford),2006, 45(4):414-420
21.Bal A,Unlu E,Bahar G,et al.Comparison of serum IL-1 beta. SIL-2R. IL-6 and TNF-alpha levels with disease activity parameters in ankylosing spondylitis[J].Clin Rheumatol,2007,26(2):211-215
22.Braun J,Davis J,Dougados M,et al.First update of the international AS consensus statement for the use of anti-TNF agents in patients with ankylosing spondylitis[J].Ann Rheum Dis,2006,65(3):316-320
23.Wendling D,Toussirot E.AntiTNF-alpha therapy in ankylosing spondylitis[J]. Expert Oping Pharmacother,2004,5(7):1497-1507
24.Lai E,Teodoro T,Volchuk A.Endoplasmic reticulum stress:signaling the unfolded protein response[J].Physiology(Betesda),2007,22:193-201
25.May E,Dorris ML,Satumtira N,et al.CD8 alpha beta t cells are not essential to the pathogenesis of arthritis or colitis in HLA-B27 transgenic rats[J].J Immunol,2003, 170(2):1099-1105
26.Saleki K,Hartigan N,Lith M,et al.Differential oxidation of HLA-B2704 and HLA-B*2705 in lymphoblastoid and transfected adherent cells[J]. Antioxid Redox Signal,2006,8(3-4):292-299
27.Galocha B,de Castro JA.Folding of HLA-B27 subtypes is determined by the global effect of polymorphic residues and shows incomplete correspondence to ankylosing spondylitis[J].Arthritis Rheum,2008,58(2):401-412
28.Gensler LS,Ward MM,Reveille JD,et al.Clinical, radiographic, and functional differences between juvenile-onset and adult-onset ankylosing spondylitis:results from the PSOAS cohort[J].Ann Rheum Dis,2008,67(2):233-237
29.Chen HA,Chen CH,Liao HT,et al.Factors associated with radiographic spinal involvement and hip involvement in ankylosing spondylitis[J].Semin Arthritis Rheum, 2011,40(6):552-558
30.Vosse D,de Vlam K.Osteoporosis in rheumatoid arthritis and ankylosing spondylitis[J].Clin Exp Rheumatol,2009,27(55):62-67
31.van der Horst-Bruinsma IE,Lems WF,Dijkmans BA.A systematic comparison of rheumatoid arthritis and ankylosing spondylitis[J].Clin Exp Rheumatol,2009,27(55): 43-49
32.Quismorio FP Jr.Pulmonary involvement in ankylosing spondylitis[J].Curr Opin Pulm Med,2006,12:342
33.Altin R,Ozdolap S,Savranlar A,et al.Comparison of early and late pleuropulmonary findings of ankylosing spondylitis by high-resolution computed tomography and effects on patients' daily life[J].Clin Rheumatol,2005,24:22
34.Bremander A,Petersson IF,Bergman S,et al.Population-based estimates of common comorbidities and cardiovascular disease in ankylosing spondylitis[J].Arthritis Care Res (Hoboken),2011,63(4):550-556
35.Dik VK,Peters MJ,Dijkmans PA,et al.The relationship between disease-related characteristics and conduction disturbances in ankylosing spondylitis[J].Scand J Rheumatol,2010,39(1):38-41
36.Bodnar N,Kerekes G,Seres I,et al.Assessment of subclinical vascular disease associated with ankylosing spondylitis[J].J Rheumatol,2011,38(4),723-729
37.Mathieu S,Gossec L,Dougados M,et al.Cardiovascular profile in ankylosing spondylitis:a systematic review and meta-analysis[J].Arthritis Care Res (Hoboken), 2011,63(4):557-563
38.Roussou E,Sultana S,Spondyloarthritis in women:differences in disease onset、 clinical presentation and Bath Ankylosing Spondylitis Disease Activity and Functional indices(BASDAI and BASFI) between men and women with spondyloarthritides[J]. Clin Rheumatol,2011,30(1):121-127
39.方玲,樊晓海,叶夏云,等.93例女性强直性脊柱炎的诊断特点[J].军医进修学院学报,2010,31(5)：418-419
40.晋瑞,王惠芳.儿童强直性脊柱炎的临床特点及鉴别诊断[J].临床误诊误治,2005(18)7：491-492
41.Ostensen M,Forger F,Nelson JL,et al.Pregnancy in patients with rheumatic disease:anti-inflammatory cytokines increase in pregnancy and decrease post partum[J]. Ann Rheum Dis,2005,64:839-844
42.方玲,钟建庭.强直性脊柱炎的诊治现状[J].中国医师进修杂志,2006,29(7)：69-71
43.赵丽珂,黄慈波.强直性脊柱炎的诊断治疗进展[J].临床药物治疗杂志,2010,8(1)：14-18
44.Wanders A,Vander Heijde D,Landewe R,et al.Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis:a randomized clinical trial[J].Arthritis Rheum,2005,52:1756-1765
45.Ward MM.Prospects for disease modification in ankylosing spondylitis:do nonsteroidal antiinflammatory drugs do more than treat symptoms[J].Arthritis Rheum, 2005,52:1634
46.Vander Heijde D,Baraf HS,Ramos-Remus C,et al.Undifferentiated spondyloarthritis: anosological missing link[J].Arthritis Rheum,2005,52(4):1205-1215
47.American College of Rheumatology Ad Hoc Group on Recommendations for use of selective and nonselective nonsteroidal antiinflammatory drugs:an American College of Rheumatology white paper[J].Arhtritis Rheum(Arhtritis Care Res), 2008,59(8):1058-1073
48.Scott D.Solomon,John J.V.McMurray,Marc A.Pfeffer,et al.Cardiovascular Risk Associated with Celecoxib in a Clinical Trial for Colorectal Adenoma Prevention[J].N Engl J Med,2005,352:1071-1080
49.Loren Laine,Sean P Curtis,Byron Cryer,et al.Assessment of upper gastrointestinal safety of etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term(MEDAL) programme:a randomised comparison[J].Lancet,2007,369:465-473
50.Christopher P Cannon,Sean P Curtis,Garret A FitzGerald,Henry Krum,et al.Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term(MEDAL)programme:a randomised comparison[J].Lancet 2006;368: 1771-81.
51.中华医学会风湿病学分会.强直性脊柱炎诊疗指南(草案)[J].中华风湿病学杂志,2003,7(10)
52.中华医学会风湿病学分会.强直性脊柱炎诊疗指南[J].中华风湿病学杂志,2010,14(8)：557-559
53.Furst De,Breedveld Fc,Kalden Jr,et al.Updated consensus statement on biological agents specifically tumor necrosis factor blocking agents and interleukin-1 receptor antagonist(IL-1ra), for the treatment of rheumatic diseases[J].Ann Rheum Dis,2005,64(Suppl):2-14
54.Davis Jc Jr.Understanding the role of tumor necrosis factor inhibition in ankylosing spondylitis[J].Semin Arthritis Rheum,2005,34(4):668-677
55.Zochling J,Van Der Heijde D,Dougados M,et al.Current evidence for the management of ankylosing spondylitis:a systematic literature review for the ASAS/EULAR management recommendations in ankylosing spondylitis[J].Ann Rheum Dis,2006,65(4):423-432
56.J Zochling,D van der Heijde,R Burgos-Vargas,et al.ASAS/EULAR recommendations for the management of ankylosing spondylitis[J].Ann Rheum Dis,2006,65:442-452
57.L.Goh,A.Samanta.A systematic medline analysis of therapeutic approaches in ankylosing spondylitis[J].Rheumatol Int,2009,29:1123-1135
58.Nurullah Akkoc,Sjef van der Linden,Muhammad Asim Khan.Ankylosing spondylitis and symptom-modifying vs disease-modifying therapy[J].Best Practice& Research Clinical Rheumatology.2006,20(3):539-557
59.Brandt J,Listing J,Haibel H,et al.Methotrexate in the treatment of ankylosing spondylitis [J]. Rheumatology(Oxford),2005,44(3):342-348
60.Martin-Mola E,Sieper J,Leirisalo-Repo M.Sustained efficacy and safety, including patient-reported outcomes, with etanercept treatment over 5 years in patients with ankylosing spondylitis[J].Clin Exp Rheumatol,2010,28(2):238-245
61.Inman RD,Maksymowych WP.A double-blind,placebo-controlled trial of low dose infliximab in ankylosing spondylitis[J].J Rheumatol.2010,37(6):1203-1210
62.Van der Heijde D,Kivitz A,Schiff Mh,et al.Efficacy and safety of adalimumab in patients with ankylosing spondylitis:results of a multicenter,randomized,double-blind, placebo-controlled trial[J].Arthritis Rheum,2006,54(7):2136-2146
63.Van der Heijde D,Revicki D,Gooch K,el al.Physical function,disease activity, and health-related quality-of-life outcomes after 3 years of adalimumab treatment in patients with ankylosing spondylitis[J].Arthritis Res Tiler,2009,11(4):124
64.Rudwaleit M,Claudepierre P, Wordsworth P,et al.Effectiveness,safety,and predictors of good clinical response in 1250 patients treated with adalimumab for active ankylosing spondylitis[J].J Rheumatol,2009,36(4):801-808
65.Rudwaleit M,Olivieri I,Boki KA,et al.Adalimumab is effective and well tolerated in treating patients with ankylosing spondylitis who have advanced spinal fusion[J].Rheumatology(Oxford),2009,48(5):551-557
66.Rudwaleit M,Gooch K,Michel B,et al.Adalimumab improves sleep and sleep quality in patients with active ankylosing spondylitis[J].J Rheumatol,2011,38(1):79-86
67.Kukar M,Petryna O.Eflhimiou E Biological targets in the treatment of rheumatoid arthritis:a comprehensive review of current and in-development biological disease modifying anti-rheumatic drugs[J].Biologics,2009,3(3):443-457
68.Mazumdar S,Greenw aid D,Golimumab[J].Mabs,2009,1(5):422-431
69.Shealy D,Cai A,Staquet K.Characterization of golimumab,a human monoclonal antibody specific for human tumor necrosis factor alpha[J].Mabs,2010,2(4):331-352
70.张卓莉,董怡.辅刺激因子调节剂——类风湿关节炎治疗的新途径[J].中国新药杂志,2006,15(11)：845-848
71.Song IH,Heldmann F,Rudwaleit M,et al.Treatment of active ankylosing spondylitis with abatacept:an open-label,24-week pilot study[J].Ann Rheum Dis, 2011,7(6):1108-1110
72.Lekpa FK,Farrenq V,Canoui-Poitrine F,et al.Lack of efficacy of abatacept in axial spondylarthropathies refractory to tumor-necrosis-factor inhibition[J].Joint Bone Spine,2011,78(4),302-312
73.Zochling J,Van der Heijde D,Dougados M,et al.Current evidence for the management of ankylosing spondylitis:A systematic literature review for the ASAS/EULAR management recommendations in ankylosing spondylitis[J].Ann Rheum Dis,2006,65:423-432
74.Zochling J,Van der Heijde D,Burgos-Vargas R,et al.ASAS/EULAR recommendations for the management of ankylosing spondylitis[J].Ann Rheum Dis,2006,65:444-452
75.左晓霞,陶立坚,高洁生主译.凯利风湿病学[M].2006,北京,人民卫生出版社,第一版,971
76.栗占国,唐福林主译.凯利风湿病学[M].北京大学医学出版社,北京,2011,第版,1252-1253
77.Dagfinrud H,Kvien TK,Hagen KB.Physiotherapy interventions for ankylosing spondylitis.Cochrane Database of Systematic Reviews 4,2004,pub2.DOI.art.no. cd002822
78.杨岫岩.强直性脊柱炎的疗效评价[J].实用医学杂志,2002,18(2)：118-120
79.Anderson JJ,Baron G,van der Heijde D,et al.ASAGpreliminary definition of short term improvement in ankylosing spondylitis[J].Arthritis Rheum,2001,44(8): 1876-1886
80.Doward LC,Spoorenberg A,Cook SA,et al:Development of the ASDoL:A quality of life instrument specific to ankylosing spondylitis[J].Ann Rheum Dis,2003,62: 20-26
1.战国·佚名撰.黄帝内经素问[M].北京：中医古籍出版社,1997
2.隋·杨上善撰,王洪图重校.黄帝内经太素[M].北京：科学技术文献出版社,2000
3.元·朱丹溪著.脉因证治[M].山西：山西科学技术出版社,
4.明·楼英著.医学纲目[M].北京：中国中医药出版社,1996
5.汉·华佗著.杨金生重校.华佗神方[M].北京：中国古籍出版社,1997
6.清·李用粹编撰.证治汇补[M].北京：中国中医药出版社,2008
7.清·罗美编撰.古今名医汇粹[M].北京：中国古籍出版社,1999
8.清·张璐著.张氏医通[M].北京：中国中医药出版社,1995
9.明·秦景明撰.症因脉治[M].北京：中国中医药出版社,1998
10.隋·巢元方撰,中华中医药学会编.诸病源候论[M].北京：华夏出版社,1998
11.宋·杨士瀛撰.仁斋直指方[M].上海：第二军医大学出版社,2006
12.汉·华佗撰,农汉才点校.中藏经[M].北京：学苑出版社,2007
13.唐·王焘撰.外台秘要[M].北京：人民卫生出版社,1987
14.清·罗东逸著.内经博议[M].北京：学苑出版社,2010
15.明·王肯堂著.证治准绳[M].北京：人民卫生出版社,2001
16.晋·皇甫谧著.针灸甲乙经[M].北京：中国医药科技出版社,2011
17.明·张介宾著.类经[M].北京：学苑出版社,2005
18.曹颖甫著,鲍艳举陶有强校注.金匮发微[M].北京：学苑出版社,2008
19.清·薛雪撰,洪丕谟 姜玉珍点校.医经原旨[M].上海：上海中医学院出版社,1991
20.金·张元素原著.医学启源[M].北京：人民军医出版社,2009
21.明·孙志宏撰.简明医彀[M].北京：人民卫生出版社,1984
22.清·汪宏著.望诊遵经[M].北京：中国中医药出版社,2009
23.清·章虚谷著.灵素节注类编[M].浙江：浙江科学技术出版社,1984
24.宋·严用和撰.严氏济生方[M].北京：人民卫生出版社,1980
25.唐·孙思邈著.备急千金要方[M].山西：山西科技出版社,2010
26.宋·王怀隐,陈昭遇等编.太平圣惠方[M].北京：人民卫生出版社,1958
27.清·叶天士著.临证指南医案[M].北京：人民卫生出版社,2006
28.宋·许叔微撰.普济本事方[M].北京：中国中医药出版社,2007
29.清·尤怡著,张印生等校注.金匮翼[M].北京：中医古籍出版社,2003
30.元·危亦林撰.世医得效方[M].北京：中国中医药出版社,2009
31.明·徐春甫辑.古今医统大全[M].北京：人民卫生出版社,2000
32.清·喻嘉言著,丁侃校.医门法律[M].北京：中国医药科技出版社,2011
33.清·林佩琴著.类证治裁[M].山西：山西科学技术出版社,2010
34.清·吴谦等编.医宗金鉴[M].北京：人民卫生出版社,1992
35.清·何梦瑶著.医碥[M].北京：中国中医药出版社,2009
36.金·李东垣著.脾胃论[M].北京：中国医药科技出版社,2011
37.明·李梃编撰,田代华等整理.医学入门[M].北京：人民卫生出版社,2006
38.清·潘楫著.医灯续焰[M].北京：中国中医药出版社,1999
39.明·朱棣等编.普济方[M].北京：人民卫生出版社,1959
40.元·朱震亨撰,王英等整理.丹溪心法[M].北京：人民卫生出版社,2005
41.明·董宿辑录,方贤续补.奇效良方[M].天津：天津科学技术出版社,2003
42.宋·赵估编.圣济总录[M].北京：人民卫生出版社,2004
43.清·张秉成著.本草便读[M].北京：学苑出版社,2010
44.战国·佚名著.黄帝内经灵枢[M].山西：山西科学技术出版社,2011
45.明·高武撰.针灸素难要旨[M].上海：上海科技出版社,1959
46.明·杨继洲原著.针灸大成[M].北京：人民卫生出版社,2006
47.清·黄元御著,孙国中方向红注.素问悬解[M].北京：学苑出版社,2008
48.明·高武编撰.针灸聚英[M].北京：人民卫生出版社,2006
49.明·张介宾撰.类经图翼[M].北京：人民卫生出版社,1980
50.金·张子和撰.儒门事亲[M].北京：人民卫生出版社,2006
1.蔡余力,陈德强,张兴彩.曹贻训教授治疗强直性脊柱炎经验[J].中国误诊学杂志,2011,11(6)：1381
2.林昌松,刘晓玲,关彤等.陈纪藩教授治疗强直性脊柱炎经验[J].新中医,2001,33(2)：0-11.
3.王政.陈湘君治疗强直性脊柱炎经验[J].辽宁中医杂志,2000,27(5)：196
4.罗汉文,李逸群.陈志维教授治疗强直性脊柱炎经验介绍[J].新中医,2010,42(1)：35-36
5.崔儒涛.崔学增治疗强直性脊柱炎经验[J].中医杂志,1999,40(11)：655-656
6.丁锷.临床心得举隅[J].安徽中医临床杂志,2003,15(2)：81-82
7.杜秀兰.雷公藤复方治疗强直性脊椎炎62例[J].山东中医杂志,1995,14(12)：544-545
8.马芳,周彩云.房定亚治疗强直性脊柱炎经验[J].中医杂志,2009,50(8)：685-686
9.马从孝.冯兴华治疗强直性脊柱炎经验[J].山东中医杂志,2007,26(7)：487-488
10.梁慧英,冯兴华.冯兴华教授对强直性脊柱炎病因病机认识的探析[J].中华中医药杂志,2011,26(9)：2012-2014
11.冯兴华.强直性脊柱炎证候规范之我见[J].中国中医骨伤科杂志,2009,11(17)：179-181
12.许凤全.冯兴华辨治强直性脊柱炎经验集要[J].辽宁中医杂志,2008,35(10)：1478-1479
13.张海波,傅禹砜.傅警龙治疗强直性脊柱炎经验[J].长春中医药大学学报,2008,24(6)：639
14.胡荫奇,常志遂.痹病古今名家验案全析[M].科学技术文献出版社,北京,2003,第-版,446-447
15.王英俊.高明利强直性脊柱炎中医辨治规律[J].辽宁中医药大学硕士学位论文,2011,5
16.岳月.高明利教授运用补肾通督法治疗强直性脊柱炎经验总结.辽宁中医药大学硕士学位论文,2006,5
17.张梅红、谷万里等.谷越涛治疗强直性脊柱炎经验[J].四川中医,2004,22(8)：5-6.
18.郭艳幸.郭维淮治疗强直性脊柱炎经验[J].中国中医骨伤科杂志,1997,5(5)：59-61
19王义军.胡荫奇治疗强直性脊柱炎经验[J].中国中医药信息杂志,2004,11(12)：1102-1103.
20.夏璇.黄清春中西医结合治疗强直性脊柱炎经验[J].中国中医药信息杂志,2011,18(3)：96
21.田黎.黄仰模教授治疗痹证经验介绍[J].中华中医药学刊,2008,26(12)：2553-2554
22.焦树德.强直性脊柱炎的治疗经验[J].河北中医,2004,26(10)：725-726
23.项红.焦树德治疗强直性脊柱炎的临床经验[J].北京中医,2004,23(3)：142-143
24.刘继刚.焦树德教授治疗强直性脊柱炎的经验介绍[J].贵阳中医学院学报,2002,24(3)：14-15
25.刘树权.金明秀治疗强直性脊柱炎经验[J].辽宁中医杂志,2003,30(4)：248
26.韩善夯.金实教授治疗强直性脊柱炎经验[J].四川中医,2005,23(11)：1-2
27.赵岩松,陈嘉苹,许镫尹等.孔光一治疗强直性脊柱炎经验介绍[J].北京中医药,2010,29(1)：21-22
28.袁普卫.李堪印治疗强直性脊柱炎的经验介绍[J].国际中医中药杂志,2010,32(2)：186
29.魏玲玲,黄飞,李秋贵.李文瑞论强直性脊柱炎证治[J].辽宁中医杂志,2009,36(2)：175-176
30.林昌松,续青.中医治疗强直性脊柱炎经验[J].河北中医,2001,23(2)：115-116
31.王桂珍,黄传兵,汪元等.刘健治疗强直性脊柱炎经验[J].安徽中医学院学报,2010,29(6)：38-39
32.曹玉举,娄伯恩,秦涛等.娄多峰教授治疗痹证用药经验[J].中医研究,2010,23(4)：59-61
33.曹玉举,李娜,秦涛.娄多峰教授治疗痹证经验[J].中医研究,2010,23(1)：63-65
34.曹玉举.娄多峰教授论风湿病病因病机[J].中医研究,2011,24(10)：64-67
35.赵敏.娄玉钤治疗强直性脊柱炎经验[J].中医杂志,2010,51(11)：980-981
36.袁怡.鲁贤昌教授治疗强直性脊柱炎经验介绍[J].新中医,2009,41(2)：18-19
37.章天寿.路志正治疗强直性脊柱炎经验[J].中医杂志,2002,43(7)：499-503
38.周慧敏,万莹,岳滞滢.吕文亮教授辨治杂病验案举隅[J].国医论坛,2008,23(6)：9-10
39.朱辉.莫成荣治疗强直性脊柱炎的经验[J].辽宁中医杂志,2004,31(3)：184-185
40.刘欢,庞学丰.庞学丰辨治风湿病临床经验掇萃[J].吉林中医药,2008,28(10)：711-712
41.张营光.曲淑琴教授运用活血化瘀法为主治疗强直性脊柱炎经验总结.辽宁中医药大学硕士学位论文,2011,4
42.张建力.任建华运用益肾通督法治疗强直性脊柱炎经验[J].甘肃中医,2009,22(4)：21-22
43.商阿萍,潘广博.辨证治疗强直性脊柱炎经验[J].河北中医,2008,(30)6：599-601
44.汪东涛.沈鹰治疗强直性脊柱炎经验[J].山东中医药大学学报,2008,32(4)：306-307
45.李具宝,王拥军,周泉等.施杞从痹论治强直性脊柱炎经验初探[J].上海中医药杂志,2010,(44)12：1-2
46.高翔,吴弢,叶秀兰等.施杞从痹论治强直性脊柱炎经验举隅[J].上海中医药杂志,2010,(44)7：16-18
47.徐慧媛,齐贺彬.治疗强直性脊柱炎的经验介绍.首届国际中西医结合风湿病学术会议论文汇编,2004,159-160
48.舒尚义.舒尚义老师治疗强直性脊柱炎经验举要[J].云南中医药杂志,2008,29(6)：1
49.宋欣伟.宋欣伟教授治疗强直性脊柱炎的经验[J].云南中医药杂,2009,30(1)：21
50.周伟平.苏励主任治疗强直性脊柱炎的经验[J].福建中医药,2007,38(3)：16
51.葛瑞彩.孙素平教授治疗强直性脊柱炎经验[J].甘肃中医学院学报, 2010,27(4)：12-13
52.胡刚明,万彬彬.田玉美治疗强直性脊柱炎的临床经验[J].湖北中医杂志,2010,32(1)：33-34
53.陈月月.汪悦教授治疗强直性脊柱炎经验[J].现代中医药,2010,30(1)：39-40
54.冯皓,周腊梅,廖华军.汪悦教授治疗强直性脊柱炎经验分析[J].中国民族民间医药,2010,(14)：30-34
55.张静,牛臻洁.王素芝治疗尪痹的经验[J].辽宁中医杂志,2003,30(11)：870-871
56.王北.王为兰教授治疗强直性脊柱炎的临床经验[J].北京中医药大学学报(中医临床版),2008,15(5)：23-24
57.矫健鹏,刘煊.魏品康从痰论治强直性脊柱炎经验探析[J].中华中医药杂志,2011,26(8)：1759-1761
58.杨敏.吴启富教授中西医结合治疗强直性脊柱炎经验.全国中西医结合强直性脊柱炎专题研讨会论文汇编,2007,181-184
59.肖泓,吴咏昕.吴生元浅谈导师治疗强直性脊柱炎的经验[J].云南中医中药杂志,2002,23(5)：8-9
60.卢勤妹.吴旭教授通督温阳法临床应用[J].辽宁中医药大学学报2011,13(11)：16-17
61.谢海洲.治疗风湿病的经验体会[J].中国中医药信息杂志,2000,7(12)：1-2
62.张俊莉,陈爱琳.徐玲主任医师治疗强直性脊柱炎经验[J].陕西中医,2005,26(11)：1200-1201
63.高积粮.阎小萍治疗强直性脊柱炎经验管窥[J].中医药临床杂志,2007,19(2)：108-109
64.孔维萍,阎小萍.阎小萍教授治疗强直性脊柱炎的学术思想及其临床经验[J].中医正骨,2008(20)6：64-65
65.李强,王莉莉.阎小萍治疗强直性脊柱炎经验[J].中医杂志,2010,51(增刊2)：148-150
66.杨仓良.从毒邪致病辨治强直性脊柱炎[J].新中医,2007,39(8)：1-3
67.李航.杨少山主任医师应用滋阴法治疗疑难病验案举隅[J].新中医,2010,42(7)：152-153
68.卢思俭.尹玉茹诊治强直性脊柱炎经验[J].山东中医杂志,1997,16(6)：272-273.
69.曹奕,李佩芳,陈幸生.张道宗教授通督调神学术思想浅析[J].中国针灸, 2006,26(10)：741-743
70.罗丽彬.张凤山教授治疗风湿病经验介绍[J].新中医,2009,41(12)：9
71.王振宇.张凤山教授中西医结合诊治风湿病的经验总结.第四届全国中西医结合风湿类疾病学术会议论文汇编,2000,33-35
72.何庆勇.张吉针药并用治疗强直性脊柱炎的经验[J].中华中医药杂志,2006,21(9)：544-546
73.潘秋.张吉教授针药并用治疗强直性脊柱炎验案1则[J].北京中医药大学学报(中医临床版),2005,12(6)：36
74.张蓓莉.张镜人临证经验拾掇[J].辽宁中医杂志,2002,29(2)：65-66
75.邓长财,鞠中斌.张鸣鹤治疗活动期强直性脊柱炎经验探讨[J].山东中医药大学学报,2006,30(5)：372-373
76.王福林.张延昌主任医师治疗风湿病临床验案3则[J].中医研究,2011,24(1)：57-60
77.张鹏.张志刚治疗强直性脊柱炎经验[J].山东中医杂志,2005,24(8)：503-504
78.潘文萍,周丽萍.周翠英治疗强直性脊柱炎的经验[J].四川中医,2002,20(11)：1-3
79.陈爱萍.周乃玉教授益肾强督治疗强直性脊柱炎[J].甘肃中医,2010,23(9)：11-12
80.邱志济,朱建平,马璇卿.朱良春治疗强直性脊柱炎用药特色选析[J].辽宁中医杂志,2001,28(11)：656-657
81.蒋恬,顾冬梅.朱良春教授治疗风湿病学术思想和诊疗技术简介[J].新中医,2011,43(6)：150-151
82.顾冬梅,蒋恬,朱婉华.朱婉华益肾蠲痹法治疗强直性脊柱炎临床经验[J].中国中医基础医学杂志,2011,17(8)：872-874
83.夏俊杰.朱晓鸣治疗强直性脊柱炎经验[J].湖北中医杂志,1997,19(6)：10-11
84.娄玉钤.风湿病命名与分类的规范化研究[J].中华中医药杂志,2008,23(9)：840-844
85.张显彬,王海隆.强直性脊柱炎中医辨证分型文献分析[J].湖南中医杂志,2006,22(6)：71-72
86.李坚,李满意,娄玉钤.强直性脊柱炎中医证型分布规律研究[J].世界中西医结合杂志,2011,6(1)：6-10
1.Tang X,Zhu X,Liu S,et al.Phytoestrogens induce differential estrogen receptor beta-mediated responses in transfected MG-63 cells [J]. Endocrine,2008,34(3):29-35
2.陈珍旭,吴蓉易,张淑玉,等.葛根素对实验性大鼠肺纤维化影响[J].临床肺科杂志,2006,11(4)：423-426
3.Chang Y,Hsieh CY,Peng ZA,et al.Neuroprotective mechanisms of puerarin in middle cerebral artery occlusion-induced brain infarction in rats [J].Journal of Biomedical Science,2009,16(1):9
4.Wan H,Zhu H,Tian M,et al.Protective effect of chuanxiongzine-puerarin in a rat model of transient middle cerebral artery occlusion-induced focal cerebral ischemia [J].Nuclear Medicine Communications,2008,29(12):1113-1122
5.Zhuang Z,Jiang G.Thirty cases of the blood-stasis type prolapse of lumbar intervertebral disc treated by acupuncture at the xi (cleft) point plus herbal intervention injection [J] Journal of Traditional Chinese Medicine,2008,28(3):178-182
6.姜晓晓,李勇,吴永宾,等.葛根素预处理对体外循环围手术期细胞因子的影响[J].中国中西医结合杂志,2009,29(12)：1089-1091
7.邓兆智,钟秋生,吴月芹,等.白芍总苷、甲氨喋呤和柳氮磺吡啶治疗强直性脊柱炎的疗效和安全性研究[J].实用中医内科杂志,2005,19(4)：328-329
8.刘晖,龚瑶,库尔班江,等.联合白芍总苷治疗强直性脊柱炎的临床观察[J].新疆医学,2004,34：79-80
9.吴东红,赵育松.帕夫林治疗强直性脊柱炎临床疗效观察[J].哈尔滨医科大学学报,2002,36(5)：381-384
10.褚婕,张金芝,沈大跃等.中药蜈蚣对小鼠免疫功能的影响[J].天津药学,1994,6(2)：23-25
11.夏伦祝,徐先祥,张睿.威灵仙总皂苷对小鼠免疫功能的影响[J].安徽医药,2009,13(5)：496-497
12.吴青业,鞠学鹏,关业枝,等.威灵仙水煎液对佐剂性关节炎模型小鼠的作用及机理研究[J].中药药理与临床,2011,27(1)：68-70
13.张蕴毅,张宏伟,李佩芬,等.威灵仙的解痉抗炎镇痛作用[J].中成药,2001,23(11)：808-811
14.Shim JS, Kim JH, Lee J,et al.Anti-angiogenic activity of a ho2moisoflavanone from Cremastra appendiculata[J].Planta Med,2004,70(2):171-173
15.杨璐,沈洪.黄芪及其主要成分抗肿瘤免疫机制研究进展[J].山东中医药大学学报,2011,35(3)：281-285
16.李秀萍,孙树凯,魏军等.白花蛇舌草对肝损伤小鼠T细胞亚群、TNF-a和IL-6的影响[J].宁夏医学杂志,2010,32(6)：495-497
17.孟玮,刘志强,邱志翠,等.中医白花蛇舌草对小鼠免疫功能影响的初步研究[J].现代中西医结合杂志,2005,14(2)：163
18.杨凌,崔晓燕,张许等.黄芩提取物的抗炎免疫作用研究[J].中国药房,2007,18(24)：1856-1857
19.李谷才,任凤莲.超临界流体萃取百合中的秋水仙碱.湖南：中南大学,2004
20.苗明三.百合多糖抗氧化作用研究[J].中药药理与临床,2001,17(2)：12-13
21.曾明,李守汉,曾爽,等.兰州百合抗运动性疲劳的实验研究[J].山西师大体育学院学报,2005,20(1)：110-112
1.路志正,焦树德.实用中医风湿病学[M].人民卫生出版社,北京,1996,第一版,2
2.娄玉钤.风湿病命名与分类的规范化研究[J].中华中医药杂志,2008,23(9)：840-844
3.马芳,周彩云.房定亚治疗强直性脊柱炎经验[J].中医杂志,2009,50(8)：685-686
4.谢文彦.健胃愈疡胶囊治疗消化性溃疡40例临床观察[J].长春中医药大学学报,2011,27(6)：432
5.王建.解痉镇痛方免煎颗粒剂治疗偏头痛[J].湖北中医学院学报,2007,9(2)：54
6.毛树文,赵鹏.解痉止痛推拿法治疗慢性盆腔炎[J].吉林中医药,2011,31(4)：352-353
7.卫德龙,虞陆祥,李国进.急性胆囊炎胆石症中西医结合治疗[J].浙江中西医结合杂志,2006,16(7)：437-438
8.李仁顺,汪少开,荣丽红.补肾益气活血通络解痉止痛法治疗冠心病心绞痛的临床研究[J].中医药学报,2006,34(1)：49-51
9.田志丽,林亚琳.解痉止痛汤治疗小儿再发性腹痛的疗效观察[J].河北中 医,2005,27(7)：511
10.刘宏潇,冯兴华,何夏秀,等.补肾强脊颗粒治疗强直性脊柱炎疗效与安全性评价[J].中国中西医结合杂志,2006,26(5)：403-406
11.纪伟,宋亚楠.腰痹通胶囊治疗强直性脊柱炎临床观察[J].实用临床医药杂志,2010,14(21)：60-61
12.方翼,黄烽.抗强直性脊柱炎药物的研究进展[J].解放军药学学报,2008,24(6)：521-524
13.黄烽.脊柱关节炎的发病机制与治疗新进展[J].基础医学与临床,2005,25(9)：780-784
14.栗占国,唐福林主译.凯利风湿病学[M].北京大学医学出版社,北京,2011,第一版,1252-1253