多层螺旋CT口服小肠造影（MSCTE）对克罗恩病的诊断价值
|
摘要
背景：
克罗恩病(Crohn's Disease, CD)属于炎症性肠病(Inflammatory Bowel Disease, IBD)的一种,是病因不明的胃肠道慢性炎性肉芽肿性疾病,呈节段或跳跃式分布,从口腔至肛门各段消化道均可受累,病变多见于末段回肠和邻近右侧结肠。治疗CD的药物选择需基于病变范围、病变程度、患者对治疗的反应以及不同个体的情况而定,不同部位不同活动程度的CD在药物选择上有很大差别,明确疾病累及部位以及活动程度对治疗CD有重要指导意义。目前有多种临床方法协助诊断CD及其病变程度、范围和评估有无其他并发症等,如结肠镜、小肠镜、消化道钡餐造影,各自存在其优缺点及局限性,随着影像学技术的发展,多层螺旋CT口服小肠造影(Multi-slice Computer Tomography Enterography, MSCTE)作为新的非侵入性诊断CD工具逐渐广泛应用于临床,但目前对其诊断价值尚未有统一的定论。
目的：
探讨MSCTE对诊断CD病变范围的敏感度及特异度；探讨MSCTE表现与CD患者C-反应蛋白(C-Reactive Protein, CRP)及红细胞沉降率(Erythrocyte Sedimentation Rate, ESR)的关联性；探讨MSCTE表现与CD患者临床疾病活动度的关联性；探讨MSCTE与小肠镜的联系。
方法：
(1)选取2010.6-2012.2在我院消化科临床上拟诊或确诊为CD并行MSCTE患者共50例入选A组,收集患者相关病史、辅助检查结果,计算Harvey-Bradshaw指数(Harvey-Bradshaw Index, HBI)并得出患者疾病活动等级,应用SPSS15.0软件计算患者MSCTE对于探查结直肠病变的准确性和可靠性；计算患者各MSCTE表现(包括肠系膜血管改变、肠壁增厚、肠壁粘膜强化、淋巴结增大、肠腔狭窄或扩张、瘘道形成)与CRP、ESR及患者疾病活动等级的相关系数R及其假设检验。
(2)选取2009.4-2012.2在我院行MSCTE检查并在MSCTE检查前后1月内行小肠镜的患者(包括门诊患者及住院患者)共81例入选B组,收集患者病史资料、辅助检查结果,分析统计患者就诊原因、MSCTE影像学诊断及小肠镜诊断,应用SPSS15.0软件计算患者MSCTE探查肠道炎性病变的准确性及可靠性,计算其中诊断为CD患者各MSCTE表现所占的比例。
结果：
A组：(1)50例患者中5例单独累及结直肠(10.0%),19例单独累及小肠(38.0%),22例同时累及结直肠、小肠(44.0%),1例仅累及胃窦区(2.0%),3例未有异常发现(6.0%)。MSCTE对于探查结直肠病变的敏感度为12/15(80.0%),特异度为4/7(57.1%),假阴性率为3/15(20.0%),假阳性率为3/7(42.9%),约登指数为0.371,粗一致率为72.7%。Kappa值为0.371(P>0.05)；(2)50例患者中有14例显示肠系膜血管改变,43例显示有肠段肠壁增厚(超过4mm),39例显示有肠壁粘膜强化,29例显示肠系膜根部淋巴结增大,25例显示肠腔狭窄或扩张,3例发现瘘道形成；(3)CRP可能与MSCTE表现中淋巴结增大以及肠腔狭窄或扩张相关(R>0.2,P>0.05),ESR可能与MSCTE表现中肠系膜血管改变、淋巴结增大相关(R>0.2,P>0.05)；(4)患者疾病活动等级可能与MSCTE表现中肠系膜血管改变相关(R>0.2,P>0.05)。
B组：(1)81例患者就诊原因中消化道出血及腹痛原因待查所占比例最高,分别为30.9%及25.9%,MSCTE诊断为炎性病变者比例最高,为46.9%,肠道占位或肿瘤次之,为23.5%,小肠镜诊断为炎性病变比例最高,为51.9%,肠道肿瘤次之,为19.8%；(2)MSCTE对探查肠道炎性病变的敏感度为30/42(71.4%),特异度为31/39(79.5%),假阴性率为12/42(28.6%),假阳性率为8/39(20.5%),约登指数为0.509,粗一致率为75.3%,Kappa值为0.507(P>0.05)；(3)MSCTE显示存在炎性病变患者最后诊断为CD者为57.9%,对于显示炎性病变累及小肠患者最后诊断为CD占62.9%；(4)B组患者中最后诊断为CD者共29例,这些患者MSCTE表现中肠壁增厚及肠壁粘膜强化所占比例最高,分别为79.3%及72.4%,肠系膜血管改变占13.8%,不存在瘘道形成的病例。
结论：
(1)CD大多累及小肠,亦可累及结直肠,MSCTE在反映小肠病变方面有其优越性,亦能在一定程度上反映结直肠病变。(2)MSCTE能在一定程度上反映CD的疾病活动程度,但不能完全替代内镜检查,可作为CD患者长期随访的工具。(3)MSCTE中显示存在炎性病变特别是累及小肠时需首先考虑CD。(4)MSCTE与CRP及ESR之间的相关性仍缺乏统一的说法,将来需进行更多前瞻性研究及大样本研究以明确。
Background:
Crohn's disease (CD) is a chronic inflammatory granulomatous disease with unknown etiology. It can affect any portion of the gastrointestinal tract, such as the esophagus, stomach, duodenum, the small bowel, colon, while the terminal ileum and proximal colon are most commonly affected. The treatment of CD depends on not only the extent and the severity of the disease, but also patient's responsiveness to previous treatments and the condition of individual patient. So it is important to identify the affected portion and evaluate the activity of CD. So far lots of diagnostic tools can help to diagnose CD such as ileocolonoscopy, barium enema examination, double balloon enteroscopy (DBE). They have their own advantages and disadvantages. Nowadays multi-slice computer tomography enterography (MSCTE) becomes the common non-invasive diagnostic tool. However its diagnostic value is still controversial.
Aim:
To explore the sensitivity and specificity of the MSCTE in diagnosing the extent of CD, the relationship between MSCTE and CRP/ESR of CD patients, the relationship between MSCTE and the activity of CD, and the relationship between MSCTE and DBE.
Methods:
50patients with known or suspected CD undergoing MSCTE in Zhongshan Hospital from June2010to February2012were chosen as group A. Clinical data included history, physical exam, laboratory tests, colonoscopy and MSCTE findings (abnormal mucosal vascularity, bowel wall thickening, mucosal enhancement, intestinal stenosis or distension, lymph node enlargement, fistula formation) were collected. We analyzed the accuracy and reliability of MSCTE in detecting colorectal lesions. SPSS15.0was used for the statistical analysis of the correlation between MSCTE findings and CRP/ESR in CD and the correlation between MSCTE findings and the activity of CD.
81patients undergoing MSCTE and DBE in Zhongshan Hospital from April2009to February2012were chosen as group B. Clinical data included history, MSCTE findings and DBE findings were collected. We analyzed the accuracy and reliability of MSCTE in detecting inflammatory lesions. SPSS15.0was used for the statistical analysis of the MSCTE findings and DBE findings in CD patients.
Results:
Group A:(1) MSCTE findings showed5patients (5/50) were affected only in colorectum,19patients (19/50) were affected only in small intestine,22patients (22/50) were affected both in colorectum and small intestine, and one patient (1/50) was affected in gastric antrum. The sensitivity of MSCTE in detecting colorectal lesions in CD was12/15, while the specificity was4/7. Kappa value was0.371(P>0.05).(2)MSCTE findings showed14patients (14/50) were with abnormal mucosal vascularity,43patients (43/50) were with bowel wall thickening (above4millimeter),39patients (39/50) were with mucosal enhancement,29patients (29/50) were with lymph node enlargement,25patients (25/50) were with intestinal stenosis or distension and3patients (3/50) were with fistula formation.(3)CRP may be correlated with lymph node enlargement and intestinal stenosis or distension (R>0.2, P>0.05). ESR may be correlated with abnormal mucosal vascularity and lymph node enlargement (R>0.2, P>0.05).(4) The activity of CD may be correlated with abnormal mucosal vascularity (R>0.2, P>0.05).
Group B:(1)30.9percent of the patients were suspected intestinal hemorrhage and25.9percent were with abdominal pain.46.9percent of the patients showed inflammatory lesions and23.5percent showed intestinal tumor in their MSCTE findings.51.9percent of the patients showed inflammatory lesions and19.8percent showed intestinal tumor in their DBE findings.(2) The sensitivity of MSCTE in detecting inflammatory lesions was30/42, while the specificity was31/39. Kappa value was0.507(P>0.05).(3)22patients (22/38) who showed inflammatory lesions in MSCTE findings were ultimately diagnosed with CD.(4)29patients were ultimately diagnosed with CD in group B. MSCTE findings showed4patients (4/29) were with abnormal mucosal vascularity,23patients (23/29) were with bowel wall thickening,21patients (21/29) were with mucosal enhancement,11patients (11/29) were with lymph node enlargement and14patients (14/29) were with intestinal stenosis or distension.
Conclusions:
CD most commonly affects colorectum and small intestine. MSCTE examination has excellent potential to discover small intestinal and colorectal lesions. MSCTE findings can help to evaluate the clinical activity of CD. CD should always be suspected when the patient shows inflammatory lesions in MSCTE findings. The relationship between MSCTE findings and CRP/ESR is still controversial and further studies are necessary.
克罗恩病(Crohn's Disease, CD)属于炎症性肠病(Inflammatory Bowel Disease, IBD)的一种,是病因不明的胃肠道慢性炎性肉芽肿性疾病,呈节段或跳跃式分布,从口腔至肛门各段消化道均可受累,病变多见于末段回肠和邻近右侧结肠。治疗CD的药物选择需基于病变范围、病变程度、患者对治疗的反应以及不同个体的情况而定,不同部位不同活动程度的CD在药物选择上有很大差别,明确疾病累及部位以及活动程度对治疗CD有重要指导意义。目前有多种临床方法协助诊断CD及其病变程度、范围和评估有无其他并发症等,如结肠镜、小肠镜、消化道钡餐造影,各自存在其优缺点及局限性,随着影像学技术的发展,多层螺旋CT口服小肠造影(Multi-slice Computer Tomography Enterography, MSCTE)作为新的非侵入性诊断CD工具逐渐广泛应用于临床,但目前对其诊断价值尚未有统一的定论。
目的：
探讨MSCTE对诊断CD病变范围的敏感度及特异度；探讨MSCTE表现与CD患者C-反应蛋白(C-Reactive Protein, CRP)及红细胞沉降率(Erythrocyte Sedimentation Rate, ESR)的关联性；探讨MSCTE表现与CD患者临床疾病活动度的关联性；探讨MSCTE与小肠镜的联系。
方法：
(1)选取2010.6-2012.2在我院消化科临床上拟诊或确诊为CD并行MSCTE患者共50例入选A组,收集患者相关病史、辅助检查结果,计算Harvey-Bradshaw指数(Harvey-Bradshaw Index, HBI)并得出患者疾病活动等级,应用SPSS15.0软件计算患者MSCTE对于探查结直肠病变的准确性和可靠性；计算患者各MSCTE表现(包括肠系膜血管改变、肠壁增厚、肠壁粘膜强化、淋巴结增大、肠腔狭窄或扩张、瘘道形成)与CRP、ESR及患者疾病活动等级的相关系数R及其假设检验。
(2)选取2009.4-2012.2在我院行MSCTE检查并在MSCTE检查前后1月内行小肠镜的患者(包括门诊患者及住院患者)共81例入选B组,收集患者病史资料、辅助检查结果,分析统计患者就诊原因、MSCTE影像学诊断及小肠镜诊断,应用SPSS15.0软件计算患者MSCTE探查肠道炎性病变的准确性及可靠性,计算其中诊断为CD患者各MSCTE表现所占的比例。
结果：
A组：(1)50例患者中5例单独累及结直肠(10.0%),19例单独累及小肠(38.0%),22例同时累及结直肠、小肠(44.0%),1例仅累及胃窦区(2.0%),3例未有异常发现(6.0%)。MSCTE对于探查结直肠病变的敏感度为12/15(80.0%),特异度为4/7(57.1%),假阴性率为3/15(20.0%),假阳性率为3/7(42.9%),约登指数为0.371,粗一致率为72.7%。Kappa值为0.371(P>0.05)；(2)50例患者中有14例显示肠系膜血管改变,43例显示有肠段肠壁增厚(超过4mm),39例显示有肠壁粘膜强化,29例显示肠系膜根部淋巴结增大,25例显示肠腔狭窄或扩张,3例发现瘘道形成；(3)CRP可能与MSCTE表现中淋巴结增大以及肠腔狭窄或扩张相关(R>0.2,P>0.05),ESR可能与MSCTE表现中肠系膜血管改变、淋巴结增大相关(R>0.2,P>0.05)；(4)患者疾病活动等级可能与MSCTE表现中肠系膜血管改变相关(R>0.2,P>0.05)。
B组：(1)81例患者就诊原因中消化道出血及腹痛原因待查所占比例最高,分别为30.9%及25.9%,MSCTE诊断为炎性病变者比例最高,为46.9%,肠道占位或肿瘤次之,为23.5%,小肠镜诊断为炎性病变比例最高,为51.9%,肠道肿瘤次之,为19.8%；(2)MSCTE对探查肠道炎性病变的敏感度为30/42(71.4%),特异度为31/39(79.5%),假阴性率为12/42(28.6%),假阳性率为8/39(20.5%),约登指数为0.509,粗一致率为75.3%,Kappa值为0.507(P>0.05)；(3)MSCTE显示存在炎性病变患者最后诊断为CD者为57.9%,对于显示炎性病变累及小肠患者最后诊断为CD占62.9%；(4)B组患者中最后诊断为CD者共29例,这些患者MSCTE表现中肠壁增厚及肠壁粘膜强化所占比例最高,分别为79.3%及72.4%,肠系膜血管改变占13.8%,不存在瘘道形成的病例。
结论：
(1)CD大多累及小肠,亦可累及结直肠,MSCTE在反映小肠病变方面有其优越性,亦能在一定程度上反映结直肠病变。(2)MSCTE能在一定程度上反映CD的疾病活动程度,但不能完全替代内镜检查,可作为CD患者长期随访的工具。(3)MSCTE中显示存在炎性病变特别是累及小肠时需首先考虑CD。(4)MSCTE与CRP及ESR之间的相关性仍缺乏统一的说法,将来需进行更多前瞻性研究及大样本研究以明确。
Background:
Crohn's disease (CD) is a chronic inflammatory granulomatous disease with unknown etiology. It can affect any portion of the gastrointestinal tract, such as the esophagus, stomach, duodenum, the small bowel, colon, while the terminal ileum and proximal colon are most commonly affected. The treatment of CD depends on not only the extent and the severity of the disease, but also patient's responsiveness to previous treatments and the condition of individual patient. So it is important to identify the affected portion and evaluate the activity of CD. So far lots of diagnostic tools can help to diagnose CD such as ileocolonoscopy, barium enema examination, double balloon enteroscopy (DBE). They have their own advantages and disadvantages. Nowadays multi-slice computer tomography enterography (MSCTE) becomes the common non-invasive diagnostic tool. However its diagnostic value is still controversial.
Aim:
To explore the sensitivity and specificity of the MSCTE in diagnosing the extent of CD, the relationship between MSCTE and CRP/ESR of CD patients, the relationship between MSCTE and the activity of CD, and the relationship between MSCTE and DBE.
Methods:
50patients with known or suspected CD undergoing MSCTE in Zhongshan Hospital from June2010to February2012were chosen as group A. Clinical data included history, physical exam, laboratory tests, colonoscopy and MSCTE findings (abnormal mucosal vascularity, bowel wall thickening, mucosal enhancement, intestinal stenosis or distension, lymph node enlargement, fistula formation) were collected. We analyzed the accuracy and reliability of MSCTE in detecting colorectal lesions. SPSS15.0was used for the statistical analysis of the correlation between MSCTE findings and CRP/ESR in CD and the correlation between MSCTE findings and the activity of CD.
81patients undergoing MSCTE and DBE in Zhongshan Hospital from April2009to February2012were chosen as group B. Clinical data included history, MSCTE findings and DBE findings were collected. We analyzed the accuracy and reliability of MSCTE in detecting inflammatory lesions. SPSS15.0was used for the statistical analysis of the MSCTE findings and DBE findings in CD patients.
Results:
Group A:(1) MSCTE findings showed5patients (5/50) were affected only in colorectum,19patients (19/50) were affected only in small intestine,22patients (22/50) were affected both in colorectum and small intestine, and one patient (1/50) was affected in gastric antrum. The sensitivity of MSCTE in detecting colorectal lesions in CD was12/15, while the specificity was4/7. Kappa value was0.371(P>0.05).(2)MSCTE findings showed14patients (14/50) were with abnormal mucosal vascularity,43patients (43/50) were with bowel wall thickening (above4millimeter),39patients (39/50) were with mucosal enhancement,29patients (29/50) were with lymph node enlargement,25patients (25/50) were with intestinal stenosis or distension and3patients (3/50) were with fistula formation.(3)CRP may be correlated with lymph node enlargement and intestinal stenosis or distension (R>0.2, P>0.05). ESR may be correlated with abnormal mucosal vascularity and lymph node enlargement (R>0.2, P>0.05).(4) The activity of CD may be correlated with abnormal mucosal vascularity (R>0.2, P>0.05).
Group B:(1)30.9percent of the patients were suspected intestinal hemorrhage and25.9percent were with abdominal pain.46.9percent of the patients showed inflammatory lesions and23.5percent showed intestinal tumor in their MSCTE findings.51.9percent of the patients showed inflammatory lesions and19.8percent showed intestinal tumor in their DBE findings.(2) The sensitivity of MSCTE in detecting inflammatory lesions was30/42, while the specificity was31/39. Kappa value was0.507(P>0.05).(3)22patients (22/38) who showed inflammatory lesions in MSCTE findings were ultimately diagnosed with CD.(4)29patients were ultimately diagnosed with CD in group B. MSCTE findings showed4patients (4/29) were with abnormal mucosal vascularity,23patients (23/29) were with bowel wall thickening,21patients (21/29) were with mucosal enhancement,11patients (11/29) were with lymph node enlargement and14patients (14/29) were with intestinal stenosis or distension.
Conclusions:
CD most commonly affects colorectum and small intestine. MSCTE examination has excellent potential to discover small intestinal and colorectal lesions. MSCTE findings can help to evaluate the clinical activity of CD. CD should always be suspected when the patient shows inflammatory lesions in MSCTE findings. The relationship between MSCTE findings and CRP/ESR is still controversial and further studies are necessary.
引文
1. Baumgart DC. The Diagnosis and Treatment of Crohn's Disease and Ulcerative Colitis [J]. Dtsch Arztebl Int.2009,106:123-133.
2. Brazilian Study Group of Inflammatory Bowel Diseases. Consensus guidelines for the management of inflammatory bowel disease [J]. Arq Gastroenterol.2010, 7(3):313-325.
3. Wold PB, Fletcher JG, Johnson CD, et al. Assessment of small bowel Crohn disease: noninvasive peroral CT enterography compared with other imaging methods and endoscopy-feasibility study [J]. Radiology.2003,229(1):275-281.
4. MacDonald JK, McDonald JW. Natalizumab for induction of remission in Crohn's disease [J]. Cochrane Database Syst Rev.2007,24(1):CD006097.
5. Guidi L, Minordi LM, Semeraro S, et al. Clinical correlations of small bowel CT and contrast radiology findings in Crohn's disease [J]. Eur Rev Med Pharmacol Sci. 2004,8(5):215-217.
6. Higgins PD, Caoili E, Zimmermann M, et al. Computed tomographic enterography adds information to clinical management in small bowel Crohn's disease [J]. Inflamm Bowel Dis.2007,13(3):262-268.
7. Yamamoto H, Kita H, Sunada K, et al. Clinical outcomes of double-balloon endoscopy for the diagnosis and treatment of small-intestinal diseases [J]. Clin Gastroenterol Hepatol.2004,2(11):1010-1016.
8. Sunada K, Yamamoto H, Kita H, et al. Clinical outcomes of enteroscopy using the double-balloon method for strictures of the small intestine [J]. World J Gastroenterol. 2005,11(7):1087-1089.
9. Yang SK, Yun S, Kim JH, et al. Epidemiology of inflammatory bowel disease in the Songpa-Kangdong district, Seoul, Korea,1986-2005:a KASID study [J]. Inflamm Bowel Dis.2008,14(4):542-549.
10. Wang YF, Ouyang Q, Hu RW. Progression of inflammatory bowel disease in China [J]. J Dig Dis.2010,11 (2):76-82.
11. Biancone L, De Nigris F, Del Vecchio Blanco G, et al. Review article:monitoring the activity of Crohn's disease [J]. Aliment Pharmacol Ther.2002,16 Suppl 4:29-33.
12. Sostegni R, Daperno M, Scaglione N, et al. Review article:Crohn's disease: monitoring disease activity [J]. Aliment Pharmacol Ther.2003,17 Suppl 2:11-17.
13. Paulsen SR, Huprich JE, Fletcher JG, et al. CT enterography as a diagnostic tool in evaluating small bowel disorders:review of clinical experience with over 700 cases [J]. Radiographics.2006,26(3):641-662.
14. Lakatos L, Kiss LS, David G, et al. Incidence, disease phenotype at diagnosis, and early disease course in inflammatory bowel diseases in Western Hungary,2002-2006 [J]. Inflamm Bowel Dis.2011,17(12):2558-2565.
15.沈志坤.中国大陆克罗恩病病变累及部位的汇总分析[J].中国临床康复,2006,10(48)：185-187.
16. Bodily KD, Fletcher JG, Solem CA, et al. Crohn Disease:mural attenuation and thickness at contrast-enhanced CT Enterography--correlation with endoscopic and histologic findings of inflammation [J]. Radiology.2006,238(2):505-516.
17. Turetschek K, Schober E, Wunderbaldinger P, et al. Findings at helical CT-enteroclysis in symptomatic patients with crohn disease:correlation with endoscopic and surgical findings [J]. J Comput Assist Tomogr.2002,26(4):488-492.
18. Knollmann FD, Dietrich T, Bleckmann T, et al. Magnetic resonance imaging of inflammatory bowel disease:evaluation in a rabbit model [J]. J Magn Reson Imaging. 2002,15(2):165-173.
19. Lee SS, Kim AY, Yang SK, et al. Crohn disease of the small bowel:comparison of CT enterography, MR enterography, and small-bowel follow-through as diagnostic techniques [J]. Radiology.2009,251(3):751-761.
20. Solem CA, Loftus EV, Tremaine WJ, Correlation of C-reactive protein with clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease [J]. Inflamm Bowel Dis.2005, 11(8):707-712.
21. Colombel JF, Solem CA, Sandborn WJ, et al. Quantitative measurement and visual assessment of ileal Crohn's disease activity by computed tomography enterography:correlation with endoscopic severity and C reactive protein [J]. Gut. 2006,55(11):1561-1567.
22. Summers RW, Switz DM, Sessions JT, et al. National Cooperative Crohn's Disease Study:results of drug treatment [J]. Gastroenterology.1979,77(4):847-869.
23. Harvey RF, Bradshaw JM. A simple index of Crohn's disease activity [J]. Lancet. 1980,1(8167):514.
24. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement [J]. Lancet.1986, 1(8476):307-310.
25. Best WR. Predicting the Crohn's disease activity index from the Harvey-Bradshaw Index [J]. Inflamm Bowel Dis.2006,12(4):304-310.
26. Minordi LM, Vecchioli A, Guidi L, et al. CT findings and clinical activity in Crohn's disease[J]. Clin Imaging.2009,33(2):123-129.
27. Nagamata H, Inadama E, Arihiro S, et al. The usefulness of MDCT in Crohn's disease[J]. Nihon Shokakibyo Gakkai Zasshi.2002,99(11):1317-1325.
28. Adler J, R Punglia D, Dillman JR, et al. Computed tomography enterography findings correlate with tissue inflammation, not fibrosis in resected small bowel Crohn's disease [J]. Inflamm Bowel Dis.2011,24.
29. Ozturk E, Cakir O, Mutlu H, et al. Diagnostic value of CTE in patients with Crohn's disease [J]. Clin Imaging.2007,31(3):185-188.
30. Choi D, Jin Lee S, Ah Cho Y, et al. Bowel wall thickening in patients with Crohn's disease:CT patterns and correlation with inflammatory activity [J]. Clin Radiol.2003, 58(1):68-74.
31. Marmo R, Rotondano G, Piscopo R, et al. Meta-analysis:capsule enteroscopy vs. conventional modalities in diagnosis of small bowel diseases [J]. Aliment Pharmacol Ther.2005,22(7):595-604.
32. Leighton JA, Legnani P, Seidman EG. Role of capsule endoscopy in inflammatory bowel disease:where we are and where we are going [J]. Inflamm Bowel Dis.2007, 13(3):331-337.
33. Marmo R, Rotondano G, Piscopo R, et al. Capsule endoscopy versus enteroclysis in the detection of small-bowel involvement in Crohn's disease:a prospective trial [J]. Clin Gastroenterol Hepatol.2005,3(8):772-776.
34.朱林林,王一平CTE、CE、SBFT、MRE对小肠克罗恩病的诊断性系统评价[J].解放军医学杂志,2011,36(8)：848-851.
35. Cave D, Legnani P, de Franchis R, et al. ICCE consensus for capsule retention [J]. Endoscopy.2005,37(10):1065-1067.
36. Oshitani N, Yukawa T, Yamagami H, et al. Evaluation of deep small bowel involvement by double-balloon enteroscopy in Crohn's disease [J]. Am J Gastroenterol.2006,101 (7):1484-1489.
37. Akahoshi K, Kubokawa M, Matsumoto M, et al. Double-balloon endoscopy in the diagnosis and management of GI tract diseases:Methodology, indications, safety, and clinical impact [J]. World J Gastroenterol.2006,12(47):7654-7659.
38. Pohl J, May A, Nachbar L, et al. Diagnostic and therapeutic yield of push-and-pull enteroscopy for symptomatic small bowel Crohn's disease strictures [J]. Eur J Gastroenterol Hepatol.2007,19(7):529-534.
39. Semrad CE. Role of double balloon enteroscopy in Crohn's disease [J]. Gastrointest Endosc.2007,66(3 Suppl):S94-95.
1. Yang SK, Yun S, Kim JH, et al. Epidemiology of inflammatory bowel disease in the Songpa-Kangdong district, Seoul, Korea,1986-2005:a KASID study [J]. Inflamm Bowel Dis.2008,14(4):542-549.
2. Wang YF, Ouyang Q, Hu RW. Progression of inflammatory bowel disease in China [J]. J Dig Dis.2010, 11(2):76-82.
3. Baumgart DC. The diagnosis and treatment of Crohn's disease and ulcerative colitis [J]. Dtsch Arztebl Int.2009,106(8):123-133.
4. Brazilian Study Group of Inflammatory Bowel Diseases. Consensus guidelines for the management of inflammatory bowel disease [J]. Arq Gastroenterol.2010, 7(3):313-325.
5. Lakatos L, Kiss LS, David G, et al. Incidence, disease phenotype at diagnosis, and early disease course in inflammatory bowel diseases in Western Hungary,2002-2006 [J]. Inflamm Bowel Dis.2011,17(12):2558-2565.
6.沈志坤.中国大陆克罗恩病病变累及部位的汇总分析[J].中国临床康复,2006,10(48)：185-187.
7.成芳,钟唬.炎症性肠病的影像学诊断[J].诊断学理论与实践,2008,7(1)：89-92.
8. Cirillo LC, Camera L, Della Noce M, et al. Accuracy of enteroclysis in Crohn's disease of the small bowel:a retrospective study [J]. Eur Radiol.2000, 10(12):1894-1898.
9.王吉耀,廖二元.内科学(上册)[M].北京,人民卫生出版社.2005,451.
10. Maglinte DD, Kelvin FM, O'Connor K, et al. Current status of small bowel radiography [J]. Abdom Imaging.1996,21(3):247-257.
11. Malatjalian DA. Pathology of inflammatory bowel disease in colorectal mucosal biopsies [J]. Dig Dis Sci.1987,32(12 Suppl):5S-15S.
12. Maglinte DD, Chernish SM, Kelvin FM, et al. Crohn disease of the small intestine: accuracy and relevance of enteroclysis [J]. Radiology.1992,184(2):541-545.
13. Paulsen SR, Huprich JE, Fletcher JG, et al. CT enterography as a diagnostic tool in evaluating small bowel disorders:review of clinical experience with over 700 cases [J]. Radiographics.2006,26(3):641-662.
14. Wold PB, Fletcher JG, Johnson CD, et al. Assessment of small bowel Crohn disease:noninvasive peroral CT enterography compared with other imaging methods and endoscopy--feasibility study [J]. Radiology.2003,229(1):275-281.
15. Higgins PD, Caoili E, Zimmermann M, et al. Computed tomographic enterography adds information to clinical management in small bowel Crohn's disease [J]. Inflamm Bowel Dis.2007,13(3):262-268.
16. Turetschek K, Schober E, Wunderbaldinger P, et al. Findings at helical CT-enteroclysis in symptomatic patients with crohn disease:correlation with endoscopic and surgical findings [J]. J Comput Assist Tomogr.2002,26(4):488-492.
17. Knollmann FD, Dietrich T, Bleckmann T, Magnetic resonance imaging of inflammatory bowel disease:evaluation in a rabbit model [J]. J Magn Reson Imaging. 2002,15(2):165-173.
18. Lee SS, Kim AY, Yang SK, et al. Crohn disease of the small bowel:comparison of CT enterography, MR enterography, and small-bowel follow-through as diagnostic techniques [J]. Radiology.2009,251(3):751-761.
19. Vogel J, da Luz Moreira A, Baker M, et al. CT enterography for Crohn's disease: accurate preoperative diagnostic imaging [J]. Dis Colon Rectum.2007, 50(11):1761-1769.
20. Zissin R, Gayer G, Kots E, et al. Iliopsoas abscess:a report of 24 patients diagnosed by CT [J]. Abdom Imaging.2001,26(5):533-539.
21. Choi D, Jin Lee S, Ah Cho Y, et al. Bowel wall thickening in patients with Crohn's disease:CT patterns and correlation with inflammatory activity [J]. Clin Radiol.2003, 58(1):68-74.
22. Minordi LM, Vecchioli A, Guidi L, et al. CT findings and clinical activity in Crohn's disease[J]. Clin Imaging.2009,33(2):123-129.
23. Nagamata H, Inadama E, Arihiro S, et al. The usefulness of MDCT in Crohn's disease[J]. Nihon Shokakibyo Gakkai Zasshi.2002,99(11):1317-1325.
24. Adler J, R Punglia D, Dillman JR, et al. Computed tomography enterography findings correlate with tissue inflammation, not fibrosis in resected small bowel Crohn's disease [J]. Inflamm Bowel Dis.2011,24.
25. Ozturk E, Cakir O, Mutlu H, et al. Diagnostic value of CTE in patients with Crohn's disease [J]. Clin Imaging.2007,31(3):185-188.
26. Chiorean MV, Sandrasegaran K, Saxena R, et al. Correlation of CT enteroclysis with surgical pathology in Crohn's disease [J]. Am J Gastroenterol.2007, 102(11):2541-2550.
27. Papanikolaou N, Prassopoulos P, Grammatikakis J, et al. Optimization of a contrast medium suitable for conventional enteroclysis, MR enteroclysis, and virtual MR enteroscopy [J]. Abdom Imaging.2002,27(5):517-522.
28. Masselli G, Vecchioli A, Gualdi GF. Crohn disease of the small bowel:MR enteroclysis versus conventional enteroclysis [J]. Abdom Imaging.2006, 31(4):400-409.
29. Prassopoulos P, Papanikolaou N, Grammatikakis J, et al. MR enteroclysis imaging of Crohn disease [J]. Radiographics.2001,21 Spec No:S161-172.
30. Gourtsoyiannis NC, Grammatikakis J, Papamastorakis G, et al. Imaging of small intestinal Crohn's disease:comparison between MR enteroclysis and conventional enteroclysis [J]. Eur Radiol.2006,16(9):1915-1925.
31. Florie J, Horsthuis K, Hommes DW, et al. Magnetic resonance imaging compared with ileocolonoscopy in evaluating disease severity in Crohn's disease [J]. Clin Gastroenterol Hepatol [J].2005,3(12):1221-1228.
32. Sempere GA, Martinez Sanjuan V, Medina Chulia E, et al. MRI evaluation of inflammatory activity in Crohn's disease [J]. AJR Am J Roentgenol.2005, 184(6):1829-1835.
33. Schmidt S, Lepori D, Meuwly JY, et al. Prospective comparison of MR enteroclysis with multidetector spiral-CT enteroclysis:interobserver agreement and sensitivity by means of "sign-by-sign" correlation [J]. Eur Radiol.2003, 13(6):1303-1311.
34. Zimmermann EM, Al-Hawary MM. MRI of the small bowel in patients with Crohn's disease [J]. Curr Opin Gastroenterol.2011,27(2):132-138.
35. Stacy MR, Maxfield MW, Sinusas AJ. Targeted Molecular Imaging of Angiogenesis in PET and SPECT:A Review [J]. Yale J Biol Med.2012,85(1):75-86.
36. Louis E, Ancion G, Colard A, et al. Noninvasive assessment of Crohn's disease intestinal lesions with (18)F-FDG PET/CT [J]. J Nucl Med.2007,48(7):1053-1059.
37. Meisner RS, Spier BJ, Einarsson S, et al. Pilot study using PET/CT as a novel, noninvasive assessment of disease activity in inflammatory bowel disease [J]. Inflamm Bowel Dis.2007,13(8):993-1000.
38. Spier BJ, Perlman SB, Jaskowiak CJ, et al. PET/CT in the evaluation of inflammatory bowel disease:studies in patients before and after treatment [J]. Mol Imaging Biol.2010,12(1):85-88.
39. Groshar D, Bernstine H, Stern D, et al. PET/CT enterography in Crohn disease: correlation of disease activity on CT enterography with 18F-FDG uptake [J]. J Nucl Med.2010,51(7):1009-1014.
40. Lapp RT, Spier BJ, Perlman SB, et al. Clinical utility of positron emission tomography/computed tomography in inflammatory bowel disease [J]. Mol Imaging Biol.2011,13(3):573-576.
1.高云峰,蔡红慧.炎症性肠病免疫学研究进展[J].绍兴文理学院学报,2003,23(8)：22-24.
2. Gershon RK, Kondo K. Cell interactions in the induction of tolerance:the role of thymic lymphocytes [J]. Immunology.1970,18(5):723-737.
3. Sakaguchi S, Sakaguchi N, Asano M, et al.Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases [J]. J Immunol.1995,155(3):1151-1164.
4. Bluestone JA, Abbas AK. Natural versus adaptive regulatory T cells [J]. Nat Rev Immunol.2003,3(3):253-257.
5. Sakaguchi S. Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses [J]. Annu Rev Immunol. 2004,22:531-562.
6. Itoh M, Takahashi T, Sakaguchi N, et al. Thymus and autoimmunity:production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance [J]. J Immunol.1999, 162(9):5317-5326.
7. Tai X, Cowan M, Feigenbaum L, et al. CD28 costimulation of developing thymocytes induces Foxp3 expression and regulatory T cell differentiation independently of interleukin 2 [J]. Nat Immunol.2005,6(2):152-162.
8. Jiang H, Chess L. The specific regulation of immune responses by CD8+T cells restricted by the MHC class Ib molecule, Qa-1 [J]. Annu Rev Immunol.2000, 18:185-216.
9. Levings MK, Sangregorio R, Sartirana C, et al. Human CD25+CD4+ T suppressor cell clones produce transforming growth factor beta, but not interleukin 10, and are distinct from type 1 T regulatory cells [J]. J Exp Med.2002,196(10):1335-1346.
10. Weiner HL. Induction and mechanism of action of transforming growth factor-beta-secreting Th3 regulatory cells [J]. Immunol Rev.2001,182:207-214.
11. Coffer PJ, Burgering BM. Forkhead-box transcription factors and their role in the immune system [J]. Nat Rev Immunol.2004,4(11):889-899.
12. Morgan ME, van Bilsen JH, Bakker AM, et al. Expression of FOXP3 mRNA is not confined to CD4+CD25+ T regulatory cells in humans [J]. Hum Immunol.2005, 66(1):13-20.
13. Brunkow ME, Jeffery EW, Hjerrild KA, et al. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse [J]. Nat Genet.2001,27(1):68-73.
14. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3 [J]. Science.2003,299(5609):1057-1061.
15. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells [J]. Nat Immunol.2003,4(4):330-336.
16. Khattri R, Cox T, Yasayko SA, et al. An essential role for Scurfin in CD4+CD25+ T regulatory cells [J]. Nat Immunol.2003,4(4):337-342.
17. Verhasselt V, Vosters O, Beuneu C, et al. Induction of FOXP3-expressing regulatory CD4pos T cells by human mature autologous dendritic cells [J]. Eur J Immunol.2004,34(3):762-772.
18. Zheng SG, Wang JH, Stohl W, et al. TGF-beta requires CTLA-4 early after T cell activation to induce FoxP3 and generate adaptive CD4+CD25+regulatory cells [J]. J Immunol.2006,176(6):3321-3329.
19. Josefowicz SZ, Wilson CB, Rudensky AY. Cutting edge:TCR stimulation is sufficient for induction of Foxp3 expression in the absence of DNA methyltransferase 1 [J]. J Immunol.2009,182(11):6648-6652.
20. Lal G, Bromberg JS. Epigenetic mechanisms of regulation of Foxp3 expression [J]. Blood.2009,114(18):3727-3735.
21. Kim HP, Leonard WJ. CREB/ATF-dependent T cell receptor-induced FoxP3 gene expression:a role for DNA methylation [J]. J Exp Med.2007,204(7):1543-1551.
22. Haxhinasto S, Mathis D, Benoist C. The AKT-mTOR axis regulates de novo differentiation of CD4+Foxp3+ cells [J]. J Exp Med.2008,205(3):565-574.
23. Janikashvili N, Bonnotte B, Katsanis E, et al. The dendritic cell-regulatory T lymphocyte crosstalk contributes to tumor-induced tolerance [J]. lin Dev Immunol. 2011,2011:430394.
24. Suffia IJ, Reckling SK, Piccirillo CA, et al. Infected site-restricted Foxp3+ natural regulatory T cells are specific for microbial antigens [J]. J Exp Med.2006, 203(3):777-788.
25. Takahashi T, Kuniyasu Y, Toda M, et al. Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells:induction of autoimmune disease by breaking their anergic/suppressive state [J]. Int Immunol.1998, 10(12):1969-1980.
26. Hontsu S, Yoneyama H, Ueha S, et al. Visualization of naturally occurring Foxp3+ regulatory T cells in normal and tumor-bearing mice [J]. Int Immunopharmacol.2004, 4(14):1785-1793.
27. Asseman C, Mauze S, Leach MW, et al. An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation [J]. J Exp Med.1999, 190(7):995-1004.
28. Marie JC, Letterio JJ, Gavin M, et al. TGF-betal maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells [J]. J Exp Med.2005, 201(7):1061-1067.
29. Becker C, Fantini MC, Neurath MF. TGF-beta as a T cell regulator in colitis and colon cancer [J]. Cytokine Growth Factor Rev.2006,17(1-2):97-106.
30. Fallarino F, Grohmann U, Hwang KW, et al. Modulation of tryptophan catabolism by regulatory T cells [J]. Nat Immunol.2003,4(12):1206-1212.
31. Liang B, Workman C, Lee J, et al. Regulatory T cells inhibit dendritic cells by lymphocyte activation gene-3 engagement of MHC class Ⅱ [J]. J Immunol.2008, 180(9):5916-5926.
32. Maul J, Loddenkemper C, Mundt P, et al. Peripheral and intestinal regulatory CD4+ CD25(high) T cells in inflammatory bowel disease [J]. Gastroenterology.2005, 128(7):1868-1878.
33. Boschetti G, Nancey S, Sardi F, et al. Therapy with anti-TNFa antibody enhances number and function of Foxp3 (+) regulatory T cells in inflammatory bowel diseases [J]. Inflamm Bowel Dis.2011,17(1):160-170.
34. Yu QT, Saruta M, Avanesyan A, et al. Expression and functional characterization of FOXP3+ CD4+ regulatory T cells in ulcerative colitis [J]. Inflamm Bowel Dis. 2007,13(2):191-199.
35. Takahashi M, Nakamura K, Honda K, et al. An inverse correlation of human peripheral blood regulatory T cell frequency with the disease activity of ulcerative colitis [J]. Dig Dis Sci.2006,51(4):677-686.
36. Harrington LE, Hatton RD, Mangan PR, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages [J]. Nat Immunol.2005,6(11):1123-1132.
37. Bettelli E, Carrier Y, Gao W, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells [J]. Nature.2006, 441(7090):235-238.
38. Bettelli E, Korn T, Oukka M, et al. Induction and effector functions of T(H)17 cells [J]. Nature.2008,453(7198):1051-1057.
39. Izcue A, Hue S, Buonocore S, et al. Interleukin-23 restrains regulatory T cell activity to drive T cell-dependent colitis [J]. Immunity.2008,28(4):559-570.
40. Weaver CT, Murphy KM. The central role of the Th17 lineage in regulating the inflammatory/autoimmune axis [J]. Semin Immunol.2007,19(6):351-352.
41. Izcue A, Hue S, Buonocore S, et al. Interleukin-23 restrains regulatory T cell activity to drive T cell-dependent colitis [J].Immunity.2008,28(4):559-570.
42. Huang W, Na L, Fidel PL, et al. Requirement of interleukin-17A for systemic anti-Candida albicans host defense in mice [J]. J Infect Dis.2004,190(3):624-631.
43. Hymowitz SG, Filvaroff EH, Yin JP, et al. IL-17s adopt a cystine knot fold: structure and activity of a novel cytokine, IL-17F, and implications for receptor binding [J]. EMBO J.2001,20(19):5332-5341.
44. Bamba S, Andoh A, Yasui H, et al. Matrix metalloproteinase-3 secretion from human colonic subepithelial myofibroblasts:role of interleukin-17 [J]. J Gastroenterol. 2003,38(6):548-554.
45. Fujino S, Andoh A, Bamba S, et al. Increased expression of interleukin 17 in inflammatory bowel disease [J]. Gut.2003,52(1):65-70.
46. Frosali F, Giudici F, Romagnani P, et al. Phenotypic and functional features of human Th 17 cells [J]. J Exp Med.2007,204(8):1849-1861.
47. Monteleone G, Pallone F, MacDonald TT. Interleukin-21:a critical regulator of the balance between effector and regulatory T-cell responses [J]. Trends Immunol.2008, 29(6):290-294.
48. Monteleone G, Monteleone I, Fina D, et al. Interleukin-21 enhances T-helper cell type I signaling and interferon-gamma production in Crohn's disease [J]. Gastroenterology.2005,128(3):687-694.
49 Monteleone G, Caruso R, Fina D, et al. Control of matrix metalloproteinase production in human intestinal fibroblasts by interleukin 21 [J]. Gut.2006, 55(12):1774-1780.
50. Uhlig HH, Powrie F. Dendritic cells and the intestinal bacterial flora:a role for localized mucosal immune responses [J]. J Clin Invest.2003,112(5):648-651.
51.冯百岁,罗杰,刘占举.IL-23受体在炎症性肠病患者外周血淋巴细胞中的表达及意义[J].西安交通大学学报(医学版),2009,30：96-98.
52. Kobayashi T, Okamoto S, Hisamatsu T, et al. IL23 differentially regulates the Thl/Th17 balance in ulcerative colitis and Crohn's disease [J]. Gut.2008, 57(12):1682-1689.
53. Mosmann TR, Cherwinski H, Bond MW, et al. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins [J]. J Immunol.1986,136(7):2348-2357.
54. Mangan PR, Harrington LE, O'Quinn DB, et al. Transforming growth factor-beta induces development of the T(H)17 lineage [J]. Nature.2006,441 (7090):231-234.
55. Bettelli E, Carrier Y, Gao W, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells [J]. Nature.2006, 441(7090):235-238.
56. Deknuydt F, Bioley G, Valmori D, et al. IL-1beta and IL-2 convert human Treg into T(H)17 cells [J]. Clin Immunol.2009,131(2):298-307.
57. Afzali B, Lombardi G, Lechler RI, et al. The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease [J]. Clin Exp Immunol.2007,148(1):32-46.
58. Eastaff-Leung N, Mabarrack N, Barbour A, et al. Foxp3+ regulatory T cells, Th17 effector cells, and cytokine environment in inflammatory bowel disease [J]. J Clin Immunol.2010,30(1):80-89.
59.牛倩,黄卓春,蔡蓓等.类风湿性关节炎患者外周血Th17/Treg细胞比率失衡的研究[J].细胞与分子免疫学杂志,2010,26(3)：267-269,272.
2. Brazilian Study Group of Inflammatory Bowel Diseases. Consensus guidelines for the management of inflammatory bowel disease [J]. Arq Gastroenterol.2010, 7(3):313-325.
3. Wold PB, Fletcher JG, Johnson CD, et al. Assessment of small bowel Crohn disease: noninvasive peroral CT enterography compared with other imaging methods and endoscopy-feasibility study [J]. Radiology.2003,229(1):275-281.
4. MacDonald JK, McDonald JW. Natalizumab for induction of remission in Crohn's disease [J]. Cochrane Database Syst Rev.2007,24(1):CD006097.
5. Guidi L, Minordi LM, Semeraro S, et al. Clinical correlations of small bowel CT and contrast radiology findings in Crohn's disease [J]. Eur Rev Med Pharmacol Sci. 2004,8(5):215-217.
6. Higgins PD, Caoili E, Zimmermann M, et al. Computed tomographic enterography adds information to clinical management in small bowel Crohn's disease [J]. Inflamm Bowel Dis.2007,13(3):262-268.
7. Yamamoto H, Kita H, Sunada K, et al. Clinical outcomes of double-balloon endoscopy for the diagnosis and treatment of small-intestinal diseases [J]. Clin Gastroenterol Hepatol.2004,2(11):1010-1016.
8. Sunada K, Yamamoto H, Kita H, et al. Clinical outcomes of enteroscopy using the double-balloon method for strictures of the small intestine [J]. World J Gastroenterol. 2005,11(7):1087-1089.
9. Yang SK, Yun S, Kim JH, et al. Epidemiology of inflammatory bowel disease in the Songpa-Kangdong district, Seoul, Korea,1986-2005:a KASID study [J]. Inflamm Bowel Dis.2008,14(4):542-549.
10. Wang YF, Ouyang Q, Hu RW. Progression of inflammatory bowel disease in China [J]. J Dig Dis.2010,11 (2):76-82.
11. Biancone L, De Nigris F, Del Vecchio Blanco G, et al. Review article:monitoring the activity of Crohn's disease [J]. Aliment Pharmacol Ther.2002,16 Suppl 4:29-33.
12. Sostegni R, Daperno M, Scaglione N, et al. Review article:Crohn's disease: monitoring disease activity [J]. Aliment Pharmacol Ther.2003,17 Suppl 2:11-17.
13. Paulsen SR, Huprich JE, Fletcher JG, et al. CT enterography as a diagnostic tool in evaluating small bowel disorders:review of clinical experience with over 700 cases [J]. Radiographics.2006,26(3):641-662.
14. Lakatos L, Kiss LS, David G, et al. Incidence, disease phenotype at diagnosis, and early disease course in inflammatory bowel diseases in Western Hungary,2002-2006 [J]. Inflamm Bowel Dis.2011,17(12):2558-2565.
15.沈志坤.中国大陆克罗恩病病变累及部位的汇总分析[J].中国临床康复,2006,10(48)：185-187.
16. Bodily KD, Fletcher JG, Solem CA, et al. Crohn Disease:mural attenuation and thickness at contrast-enhanced CT Enterography--correlation with endoscopic and histologic findings of inflammation [J]. Radiology.2006,238(2):505-516.
17. Turetschek K, Schober E, Wunderbaldinger P, et al. Findings at helical CT-enteroclysis in symptomatic patients with crohn disease:correlation with endoscopic and surgical findings [J]. J Comput Assist Tomogr.2002,26(4):488-492.
18. Knollmann FD, Dietrich T, Bleckmann T, et al. Magnetic resonance imaging of inflammatory bowel disease:evaluation in a rabbit model [J]. J Magn Reson Imaging. 2002,15(2):165-173.
19. Lee SS, Kim AY, Yang SK, et al. Crohn disease of the small bowel:comparison of CT enterography, MR enterography, and small-bowel follow-through as diagnostic techniques [J]. Radiology.2009,251(3):751-761.
20. Solem CA, Loftus EV, Tremaine WJ, Correlation of C-reactive protein with clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease [J]. Inflamm Bowel Dis.2005, 11(8):707-712.
21. Colombel JF, Solem CA, Sandborn WJ, et al. Quantitative measurement and visual assessment of ileal Crohn's disease activity by computed tomography enterography:correlation with endoscopic severity and C reactive protein [J]. Gut. 2006,55(11):1561-1567.
22. Summers RW, Switz DM, Sessions JT, et al. National Cooperative Crohn's Disease Study:results of drug treatment [J]. Gastroenterology.1979,77(4):847-869.
23. Harvey RF, Bradshaw JM. A simple index of Crohn's disease activity [J]. Lancet. 1980,1(8167):514.
24. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement [J]. Lancet.1986, 1(8476):307-310.
25. Best WR. Predicting the Crohn's disease activity index from the Harvey-Bradshaw Index [J]. Inflamm Bowel Dis.2006,12(4):304-310.
26. Minordi LM, Vecchioli A, Guidi L, et al. CT findings and clinical activity in Crohn's disease[J]. Clin Imaging.2009,33(2):123-129.
27. Nagamata H, Inadama E, Arihiro S, et al. The usefulness of MDCT in Crohn's disease[J]. Nihon Shokakibyo Gakkai Zasshi.2002,99(11):1317-1325.
28. Adler J, R Punglia D, Dillman JR, et al. Computed tomography enterography findings correlate with tissue inflammation, not fibrosis in resected small bowel Crohn's disease [J]. Inflamm Bowel Dis.2011,24.
29. Ozturk E, Cakir O, Mutlu H, et al. Diagnostic value of CTE in patients with Crohn's disease [J]. Clin Imaging.2007,31(3):185-188.
30. Choi D, Jin Lee S, Ah Cho Y, et al. Bowel wall thickening in patients with Crohn's disease:CT patterns and correlation with inflammatory activity [J]. Clin Radiol.2003, 58(1):68-74.
31. Marmo R, Rotondano G, Piscopo R, et al. Meta-analysis:capsule enteroscopy vs. conventional modalities in diagnosis of small bowel diseases [J]. Aliment Pharmacol Ther.2005,22(7):595-604.
32. Leighton JA, Legnani P, Seidman EG. Role of capsule endoscopy in inflammatory bowel disease:where we are and where we are going [J]. Inflamm Bowel Dis.2007, 13(3):331-337.
33. Marmo R, Rotondano G, Piscopo R, et al. Capsule endoscopy versus enteroclysis in the detection of small-bowel involvement in Crohn's disease:a prospective trial [J]. Clin Gastroenterol Hepatol.2005,3(8):772-776.
34.朱林林,王一平CTE、CE、SBFT、MRE对小肠克罗恩病的诊断性系统评价[J].解放军医学杂志,2011,36(8)：848-851.
35. Cave D, Legnani P, de Franchis R, et al. ICCE consensus for capsule retention [J]. Endoscopy.2005,37(10):1065-1067.
36. Oshitani N, Yukawa T, Yamagami H, et al. Evaluation of deep small bowel involvement by double-balloon enteroscopy in Crohn's disease [J]. Am J Gastroenterol.2006,101 (7):1484-1489.
37. Akahoshi K, Kubokawa M, Matsumoto M, et al. Double-balloon endoscopy in the diagnosis and management of GI tract diseases:Methodology, indications, safety, and clinical impact [J]. World J Gastroenterol.2006,12(47):7654-7659.
38. Pohl J, May A, Nachbar L, et al. Diagnostic and therapeutic yield of push-and-pull enteroscopy for symptomatic small bowel Crohn's disease strictures [J]. Eur J Gastroenterol Hepatol.2007,19(7):529-534.
39. Semrad CE. Role of double balloon enteroscopy in Crohn's disease [J]. Gastrointest Endosc.2007,66(3 Suppl):S94-95.
1. Yang SK, Yun S, Kim JH, et al. Epidemiology of inflammatory bowel disease in the Songpa-Kangdong district, Seoul, Korea,1986-2005:a KASID study [J]. Inflamm Bowel Dis.2008,14(4):542-549.
2. Wang YF, Ouyang Q, Hu RW. Progression of inflammatory bowel disease in China [J]. J Dig Dis.2010, 11(2):76-82.
3. Baumgart DC. The diagnosis and treatment of Crohn's disease and ulcerative colitis [J]. Dtsch Arztebl Int.2009,106(8):123-133.
4. Brazilian Study Group of Inflammatory Bowel Diseases. Consensus guidelines for the management of inflammatory bowel disease [J]. Arq Gastroenterol.2010, 7(3):313-325.
5. Lakatos L, Kiss LS, David G, et al. Incidence, disease phenotype at diagnosis, and early disease course in inflammatory bowel diseases in Western Hungary,2002-2006 [J]. Inflamm Bowel Dis.2011,17(12):2558-2565.
6.沈志坤.中国大陆克罗恩病病变累及部位的汇总分析[J].中国临床康复,2006,10(48)：185-187.
7.成芳,钟唬.炎症性肠病的影像学诊断[J].诊断学理论与实践,2008,7(1)：89-92.
8. Cirillo LC, Camera L, Della Noce M, et al. Accuracy of enteroclysis in Crohn's disease of the small bowel:a retrospective study [J]. Eur Radiol.2000, 10(12):1894-1898.
9.王吉耀,廖二元.内科学(上册)[M].北京,人民卫生出版社.2005,451.
10. Maglinte DD, Kelvin FM, O'Connor K, et al. Current status of small bowel radiography [J]. Abdom Imaging.1996,21(3):247-257.
11. Malatjalian DA. Pathology of inflammatory bowel disease in colorectal mucosal biopsies [J]. Dig Dis Sci.1987,32(12 Suppl):5S-15S.
12. Maglinte DD, Chernish SM, Kelvin FM, et al. Crohn disease of the small intestine: accuracy and relevance of enteroclysis [J]. Radiology.1992,184(2):541-545.
13. Paulsen SR, Huprich JE, Fletcher JG, et al. CT enterography as a diagnostic tool in evaluating small bowel disorders:review of clinical experience with over 700 cases [J]. Radiographics.2006,26(3):641-662.
14. Wold PB, Fletcher JG, Johnson CD, et al. Assessment of small bowel Crohn disease:noninvasive peroral CT enterography compared with other imaging methods and endoscopy--feasibility study [J]. Radiology.2003,229(1):275-281.
15. Higgins PD, Caoili E, Zimmermann M, et al. Computed tomographic enterography adds information to clinical management in small bowel Crohn's disease [J]. Inflamm Bowel Dis.2007,13(3):262-268.
16. Turetschek K, Schober E, Wunderbaldinger P, et al. Findings at helical CT-enteroclysis in symptomatic patients with crohn disease:correlation with endoscopic and surgical findings [J]. J Comput Assist Tomogr.2002,26(4):488-492.
17. Knollmann FD, Dietrich T, Bleckmann T, Magnetic resonance imaging of inflammatory bowel disease:evaluation in a rabbit model [J]. J Magn Reson Imaging. 2002,15(2):165-173.
18. Lee SS, Kim AY, Yang SK, et al. Crohn disease of the small bowel:comparison of CT enterography, MR enterography, and small-bowel follow-through as diagnostic techniques [J]. Radiology.2009,251(3):751-761.
19. Vogel J, da Luz Moreira A, Baker M, et al. CT enterography for Crohn's disease: accurate preoperative diagnostic imaging [J]. Dis Colon Rectum.2007, 50(11):1761-1769.
20. Zissin R, Gayer G, Kots E, et al. Iliopsoas abscess:a report of 24 patients diagnosed by CT [J]. Abdom Imaging.2001,26(5):533-539.
21. Choi D, Jin Lee S, Ah Cho Y, et al. Bowel wall thickening in patients with Crohn's disease:CT patterns and correlation with inflammatory activity [J]. Clin Radiol.2003, 58(1):68-74.
22. Minordi LM, Vecchioli A, Guidi L, et al. CT findings and clinical activity in Crohn's disease[J]. Clin Imaging.2009,33(2):123-129.
23. Nagamata H, Inadama E, Arihiro S, et al. The usefulness of MDCT in Crohn's disease[J]. Nihon Shokakibyo Gakkai Zasshi.2002,99(11):1317-1325.
24. Adler J, R Punglia D, Dillman JR, et al. Computed tomography enterography findings correlate with tissue inflammation, not fibrosis in resected small bowel Crohn's disease [J]. Inflamm Bowel Dis.2011,24.
25. Ozturk E, Cakir O, Mutlu H, et al. Diagnostic value of CTE in patients with Crohn's disease [J]. Clin Imaging.2007,31(3):185-188.
26. Chiorean MV, Sandrasegaran K, Saxena R, et al. Correlation of CT enteroclysis with surgical pathology in Crohn's disease [J]. Am J Gastroenterol.2007, 102(11):2541-2550.
27. Papanikolaou N, Prassopoulos P, Grammatikakis J, et al. Optimization of a contrast medium suitable for conventional enteroclysis, MR enteroclysis, and virtual MR enteroscopy [J]. Abdom Imaging.2002,27(5):517-522.
28. Masselli G, Vecchioli A, Gualdi GF. Crohn disease of the small bowel:MR enteroclysis versus conventional enteroclysis [J]. Abdom Imaging.2006, 31(4):400-409.
29. Prassopoulos P, Papanikolaou N, Grammatikakis J, et al. MR enteroclysis imaging of Crohn disease [J]. Radiographics.2001,21 Spec No:S161-172.
30. Gourtsoyiannis NC, Grammatikakis J, Papamastorakis G, et al. Imaging of small intestinal Crohn's disease:comparison between MR enteroclysis and conventional enteroclysis [J]. Eur Radiol.2006,16(9):1915-1925.
31. Florie J, Horsthuis K, Hommes DW, et al. Magnetic resonance imaging compared with ileocolonoscopy in evaluating disease severity in Crohn's disease [J]. Clin Gastroenterol Hepatol [J].2005,3(12):1221-1228.
32. Sempere GA, Martinez Sanjuan V, Medina Chulia E, et al. MRI evaluation of inflammatory activity in Crohn's disease [J]. AJR Am J Roentgenol.2005, 184(6):1829-1835.
33. Schmidt S, Lepori D, Meuwly JY, et al. Prospective comparison of MR enteroclysis with multidetector spiral-CT enteroclysis:interobserver agreement and sensitivity by means of "sign-by-sign" correlation [J]. Eur Radiol.2003, 13(6):1303-1311.
34. Zimmermann EM, Al-Hawary MM. MRI of the small bowel in patients with Crohn's disease [J]. Curr Opin Gastroenterol.2011,27(2):132-138.
35. Stacy MR, Maxfield MW, Sinusas AJ. Targeted Molecular Imaging of Angiogenesis in PET and SPECT:A Review [J]. Yale J Biol Med.2012,85(1):75-86.
36. Louis E, Ancion G, Colard A, et al. Noninvasive assessment of Crohn's disease intestinal lesions with (18)F-FDG PET/CT [J]. J Nucl Med.2007,48(7):1053-1059.
37. Meisner RS, Spier BJ, Einarsson S, et al. Pilot study using PET/CT as a novel, noninvasive assessment of disease activity in inflammatory bowel disease [J]. Inflamm Bowel Dis.2007,13(8):993-1000.
38. Spier BJ, Perlman SB, Jaskowiak CJ, et al. PET/CT in the evaluation of inflammatory bowel disease:studies in patients before and after treatment [J]. Mol Imaging Biol.2010,12(1):85-88.
39. Groshar D, Bernstine H, Stern D, et al. PET/CT enterography in Crohn disease: correlation of disease activity on CT enterography with 18F-FDG uptake [J]. J Nucl Med.2010,51(7):1009-1014.
40. Lapp RT, Spier BJ, Perlman SB, et al. Clinical utility of positron emission tomography/computed tomography in inflammatory bowel disease [J]. Mol Imaging Biol.2011,13(3):573-576.
1.高云峰,蔡红慧.炎症性肠病免疫学研究进展[J].绍兴文理学院学报,2003,23(8)：22-24.
2. Gershon RK, Kondo K. Cell interactions in the induction of tolerance:the role of thymic lymphocytes [J]. Immunology.1970,18(5):723-737.
3. Sakaguchi S, Sakaguchi N, Asano M, et al.Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases [J]. J Immunol.1995,155(3):1151-1164.
4. Bluestone JA, Abbas AK. Natural versus adaptive regulatory T cells [J]. Nat Rev Immunol.2003,3(3):253-257.
5. Sakaguchi S. Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses [J]. Annu Rev Immunol. 2004,22:531-562.
6. Itoh M, Takahashi T, Sakaguchi N, et al. Thymus and autoimmunity:production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance [J]. J Immunol.1999, 162(9):5317-5326.
7. Tai X, Cowan M, Feigenbaum L, et al. CD28 costimulation of developing thymocytes induces Foxp3 expression and regulatory T cell differentiation independently of interleukin 2 [J]. Nat Immunol.2005,6(2):152-162.
8. Jiang H, Chess L. The specific regulation of immune responses by CD8+T cells restricted by the MHC class Ib molecule, Qa-1 [J]. Annu Rev Immunol.2000, 18:185-216.
9. Levings MK, Sangregorio R, Sartirana C, et al. Human CD25+CD4+ T suppressor cell clones produce transforming growth factor beta, but not interleukin 10, and are distinct from type 1 T regulatory cells [J]. J Exp Med.2002,196(10):1335-1346.
10. Weiner HL. Induction and mechanism of action of transforming growth factor-beta-secreting Th3 regulatory cells [J]. Immunol Rev.2001,182:207-214.
11. Coffer PJ, Burgering BM. Forkhead-box transcription factors and their role in the immune system [J]. Nat Rev Immunol.2004,4(11):889-899.
12. Morgan ME, van Bilsen JH, Bakker AM, et al. Expression of FOXP3 mRNA is not confined to CD4+CD25+ T regulatory cells in humans [J]. Hum Immunol.2005, 66(1):13-20.
13. Brunkow ME, Jeffery EW, Hjerrild KA, et al. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse [J]. Nat Genet.2001,27(1):68-73.
14. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3 [J]. Science.2003,299(5609):1057-1061.
15. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells [J]. Nat Immunol.2003,4(4):330-336.
16. Khattri R, Cox T, Yasayko SA, et al. An essential role for Scurfin in CD4+CD25+ T regulatory cells [J]. Nat Immunol.2003,4(4):337-342.
17. Verhasselt V, Vosters O, Beuneu C, et al. Induction of FOXP3-expressing regulatory CD4pos T cells by human mature autologous dendritic cells [J]. Eur J Immunol.2004,34(3):762-772.
18. Zheng SG, Wang JH, Stohl W, et al. TGF-beta requires CTLA-4 early after T cell activation to induce FoxP3 and generate adaptive CD4+CD25+regulatory cells [J]. J Immunol.2006,176(6):3321-3329.
19. Josefowicz SZ, Wilson CB, Rudensky AY. Cutting edge:TCR stimulation is sufficient for induction of Foxp3 expression in the absence of DNA methyltransferase 1 [J]. J Immunol.2009,182(11):6648-6652.
20. Lal G, Bromberg JS. Epigenetic mechanisms of regulation of Foxp3 expression [J]. Blood.2009,114(18):3727-3735.
21. Kim HP, Leonard WJ. CREB/ATF-dependent T cell receptor-induced FoxP3 gene expression:a role for DNA methylation [J]. J Exp Med.2007,204(7):1543-1551.
22. Haxhinasto S, Mathis D, Benoist C. The AKT-mTOR axis regulates de novo differentiation of CD4+Foxp3+ cells [J]. J Exp Med.2008,205(3):565-574.
23. Janikashvili N, Bonnotte B, Katsanis E, et al. The dendritic cell-regulatory T lymphocyte crosstalk contributes to tumor-induced tolerance [J]. lin Dev Immunol. 2011,2011:430394.
24. Suffia IJ, Reckling SK, Piccirillo CA, et al. Infected site-restricted Foxp3+ natural regulatory T cells are specific for microbial antigens [J]. J Exp Med.2006, 203(3):777-788.
25. Takahashi T, Kuniyasu Y, Toda M, et al. Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells:induction of autoimmune disease by breaking their anergic/suppressive state [J]. Int Immunol.1998, 10(12):1969-1980.
26. Hontsu S, Yoneyama H, Ueha S, et al. Visualization of naturally occurring Foxp3+ regulatory T cells in normal and tumor-bearing mice [J]. Int Immunopharmacol.2004, 4(14):1785-1793.
27. Asseman C, Mauze S, Leach MW, et al. An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation [J]. J Exp Med.1999, 190(7):995-1004.
28. Marie JC, Letterio JJ, Gavin M, et al. TGF-betal maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells [J]. J Exp Med.2005, 201(7):1061-1067.
29. Becker C, Fantini MC, Neurath MF. TGF-beta as a T cell regulator in colitis and colon cancer [J]. Cytokine Growth Factor Rev.2006,17(1-2):97-106.
30. Fallarino F, Grohmann U, Hwang KW, et al. Modulation of tryptophan catabolism by regulatory T cells [J]. Nat Immunol.2003,4(12):1206-1212.
31. Liang B, Workman C, Lee J, et al. Regulatory T cells inhibit dendritic cells by lymphocyte activation gene-3 engagement of MHC class Ⅱ [J]. J Immunol.2008, 180(9):5916-5926.
32. Maul J, Loddenkemper C, Mundt P, et al. Peripheral and intestinal regulatory CD4+ CD25(high) T cells in inflammatory bowel disease [J]. Gastroenterology.2005, 128(7):1868-1878.
33. Boschetti G, Nancey S, Sardi F, et al. Therapy with anti-TNFa antibody enhances number and function of Foxp3 (+) regulatory T cells in inflammatory bowel diseases [J]. Inflamm Bowel Dis.2011,17(1):160-170.
34. Yu QT, Saruta M, Avanesyan A, et al. Expression and functional characterization of FOXP3+ CD4+ regulatory T cells in ulcerative colitis [J]. Inflamm Bowel Dis. 2007,13(2):191-199.
35. Takahashi M, Nakamura K, Honda K, et al. An inverse correlation of human peripheral blood regulatory T cell frequency with the disease activity of ulcerative colitis [J]. Dig Dis Sci.2006,51(4):677-686.
36. Harrington LE, Hatton RD, Mangan PR, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages [J]. Nat Immunol.2005,6(11):1123-1132.
37. Bettelli E, Carrier Y, Gao W, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells [J]. Nature.2006, 441(7090):235-238.
38. Bettelli E, Korn T, Oukka M, et al. Induction and effector functions of T(H)17 cells [J]. Nature.2008,453(7198):1051-1057.
39. Izcue A, Hue S, Buonocore S, et al. Interleukin-23 restrains regulatory T cell activity to drive T cell-dependent colitis [J]. Immunity.2008,28(4):559-570.
40. Weaver CT, Murphy KM. The central role of the Th17 lineage in regulating the inflammatory/autoimmune axis [J]. Semin Immunol.2007,19(6):351-352.
41. Izcue A, Hue S, Buonocore S, et al. Interleukin-23 restrains regulatory T cell activity to drive T cell-dependent colitis [J].Immunity.2008,28(4):559-570.
42. Huang W, Na L, Fidel PL, et al. Requirement of interleukin-17A for systemic anti-Candida albicans host defense in mice [J]. J Infect Dis.2004,190(3):624-631.
43. Hymowitz SG, Filvaroff EH, Yin JP, et al. IL-17s adopt a cystine knot fold: structure and activity of a novel cytokine, IL-17F, and implications for receptor binding [J]. EMBO J.2001,20(19):5332-5341.
44. Bamba S, Andoh A, Yasui H, et al. Matrix metalloproteinase-3 secretion from human colonic subepithelial myofibroblasts:role of interleukin-17 [J]. J Gastroenterol. 2003,38(6):548-554.
45. Fujino S, Andoh A, Bamba S, et al. Increased expression of interleukin 17 in inflammatory bowel disease [J]. Gut.2003,52(1):65-70.
46. Frosali F, Giudici F, Romagnani P, et al. Phenotypic and functional features of human Th 17 cells [J]. J Exp Med.2007,204(8):1849-1861.
47. Monteleone G, Pallone F, MacDonald TT. Interleukin-21:a critical regulator of the balance between effector and regulatory T-cell responses [J]. Trends Immunol.2008, 29(6):290-294.
48. Monteleone G, Monteleone I, Fina D, et al. Interleukin-21 enhances T-helper cell type I signaling and interferon-gamma production in Crohn's disease [J]. Gastroenterology.2005,128(3):687-694.
49 Monteleone G, Caruso R, Fina D, et al. Control of matrix metalloproteinase production in human intestinal fibroblasts by interleukin 21 [J]. Gut.2006, 55(12):1774-1780.
50. Uhlig HH, Powrie F. Dendritic cells and the intestinal bacterial flora:a role for localized mucosal immune responses [J]. J Clin Invest.2003,112(5):648-651.
51.冯百岁,罗杰,刘占举.IL-23受体在炎症性肠病患者外周血淋巴细胞中的表达及意义[J].西安交通大学学报(医学版),2009,30：96-98.
52. Kobayashi T, Okamoto S, Hisamatsu T, et al. IL23 differentially regulates the Thl/Th17 balance in ulcerative colitis and Crohn's disease [J]. Gut.2008, 57(12):1682-1689.
53. Mosmann TR, Cherwinski H, Bond MW, et al. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins [J]. J Immunol.1986,136(7):2348-2357.
54. Mangan PR, Harrington LE, O'Quinn DB, et al. Transforming growth factor-beta induces development of the T(H)17 lineage [J]. Nature.2006,441 (7090):231-234.
55. Bettelli E, Carrier Y, Gao W, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells [J]. Nature.2006, 441(7090):235-238.
56. Deknuydt F, Bioley G, Valmori D, et al. IL-1beta and IL-2 convert human Treg into T(H)17 cells [J]. Clin Immunol.2009,131(2):298-307.
57. Afzali B, Lombardi G, Lechler RI, et al. The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease [J]. Clin Exp Immunol.2007,148(1):32-46.
58. Eastaff-Leung N, Mabarrack N, Barbour A, et al. Foxp3+ regulatory T cells, Th17 effector cells, and cytokine environment in inflammatory bowel disease [J]. J Clin Immunol.2010,30(1):80-89.
59.牛倩,黄卓春,蔡蓓等.类风湿性关节炎患者外周血Th17/Treg细胞比率失衡的研究[J].细胞与分子免疫学杂志,2010,26(3)：267-269,272.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |