大家好，我是吧里的一名病友，我决定间断性地更新一些关于克罗恩病病理机制（不是治疗手段）上的文献的摘要（非全文）。
目的是增加大家对克罗恩病的认识，提高大家对疾病的掌控感，从而提高对它的信心。
另一方面，有可能的话，希望能被相关的临床工作者和科研工作者看见，节省他们阅读文献的时间。
我在本帖中更新的内容基本上会和副结核分歧杆菌有关。
吧里有几位吧友和我一样，认为副结核分歧杆菌可能是导致克罗恩病的罪魁祸首。理由如下：
（1）尽管有研究表明克罗恩病与基因存在一定程度的相关，但是基于国外人群的样本的，中国人的发病率一直是低于西方的，然而近年来中国发病几率呈现的飞速增加的趋势，难道是中国人的基因在这几年发生了突变？显然不是，所以我认为肯定是有外部原因的。
（2）副结核分歧杆菌和结合分歧杆菌同属一个菌群家族，来这个吧半年以上的吧友相比对结核病的肠内表现已经非常了解了，它与克罗恩病非常难以区分。我个人推测，克罗恩病和肠结核病可能就是亲戚，生物学里有句话，叫做结构决定功能，副结核分歧杆菌和结核杆菌作为同家族菌种，其基本结构存在相似之处，必然在功能上可能也有近似的地方。因此，副结核分歧杆菌导致克罗恩病的假设是合理的。
（3）副结核分歧杆菌之所以出名，是因为它在牛羊等牲畜上会导致“约翰病”，其表现和克罗恩病及其类似。
下面进入正题，下面这篇应该是会议摘要，不像是什么突破性的研究进展，但标题很有意思：
MYCOBACTERIUM AVIUM SSP. PARATUBERCULOSIS (MAP) CAN BE RELIABLY DETECTED AND CULTURED FROM PERIPHERAL BLOOD OF 100% OF PATIENTS WITH RECENT ONSET CROHN'S DISEASE
副结核分歧杆菌在100%的近期发作的克罗恩病患者外周血液中能够被轻易地检测并培养出来。
作者：Adrienne L. McNees, Najah R. Zayyani, Diane Markesich, David Y. Graham
背景： 副结核分歧杆菌(Mycobacterium avium ssp. Paratuberculosis, MAP)在很长一段时间内都被认为是导致克罗恩病的病理机制。时不时地能从克罗恩患者外周血液巨噬细胞中检测到MAP的DNA。我们评估了是否这种“时灵时不灵”的情况是由于其含量过低，或是MAP间歇性地进入血液。巴林（一个国家）最近经历了一场克罗恩病大爆发，因此有充足地实验对象。
方法：我们假设，是否MAP进入血液是间歇性的，或是低水平的，因此当采样更大、更频繁时，检测出MAP的几率会随之增加。我们从病史小于5年的110个巴林的克罗恩病患者中每个采集了1-4管样品（也就是采血），同时选取了217非炎症性肠病患者作为对照组。从静脉血中分离出外周血单核细胞(Peripheral blood mononuclear cells, PBMCs)，并检测了MAP（用PCR）。一部分PBMC样品被用于培养MAP菌群。
结果：MAP的DNA在对照组没检测出来。而在110个克罗恩患者中，有80.9%的患者检测出了MAP的DNA。而增加了样本量曾逐步提高了检测出MAP的几率：每个患者取样一次，检出MAP几率68%；每个患者两次，检出率84%；每个患者三次，检出率96%；4次及以上，检出率100%！！！
而从49个病人中取样并培养菌群，其中26个样品培养菌种检测出了MAP (53%)。同样的，测试多次血液样本（这部分没看懂，到底是多测几次还是加大量，但不影响理解结果）增加了培养出MAP的几率：1样本=43%；2样本=42%；3样本=75%；4或更多=100%。（后面那句话太难翻译了我就不翻了，大家自己看吧）。
结论：该结果符合了假设，即之前出现MAP检测几率变化大可能是因为MAP本身密度低或间歇性进入血液。
原文：
Background: Mycobacterium avium ssp. paratuberculosis (MAP) has long been considered a possible etiologic agent for Crohn's disease. MAP DNA has been detected with variable frequency in peripheral blood macrophages from patients with Crohn's disease. We evaluated whether the variability related to the presence of low level or intermittent MAP shedding into the blood. Bahrain has experienced a recent outbreak of Crohn's disease thus contains a population enriched with recent onset disease. Methods: We hypothesized that if MAP
shedding was either intermittent or low level, then the detection rate should increase with more samples being tested from a patient. We tested 1 to 4 blood samples from 110 Bahrain Crohn's disease patients with IBD symptoms for <5 years (mean age of 34.5 years), and 217 samples from non-IBD controls. Peripheral blood mononuclear cells (PBMCs) were separated from venous blood using centrifugation separation of buffy coat and red cell lysis and tested for MAP using a validated nested PCR for MAP IS900. A proportion of PBMC samples were used to attempt to culture MAP. Results: MAP DNA was not detected by PCR in any of the 217 control patient samples. MAP DNA was detected in 89 patients (80.9%) tested from 110 Crohn's disease patients. Increasing the number of blood draws per patient tested by PCR increased MAP- positive results (1 sample = 68%; 2 samples = 84%; 3 samples = 96%; 4 or more samples = 100% MAP positive). Samples from 49 patients
were tested for MAP growth in culture and 26 gave positive results (53%). Similarly, testing multiple blood draw samples from 49 Crohn's disease patients in culture for MAP growth increased the detection rate of cultivable, slow growing Mycobacteria (1 sample = 43%; 2 samples = 42%; 3 samples = 75%; 4 or more samples = 100% MAP positive). The culture slants that produced required longer than 6 months to appear and appeared as tiny cream colored, slightly rough colonies. Conclusions: These results are consistent with the notion that MAP are circulating in the peripheral blood of patients with Crohn's disease either at low level or intermittently. Carefully designed clinical trials in Crohn's patients that specifically confirm the presence of MAP and relate the responses to treatment and recurrence are required to establish a causal zoonotic link between the pathogen, a major food industry and a devastating chronic human gastrointestinal illness.
目的是增加大家对克罗恩病的认识，提高大家对疾病的掌控感，从而提高对它的信心。
另一方面，有可能的话，希望能被相关的临床工作者和科研工作者看见，节省他们阅读文献的时间。
我在本帖中更新的内容基本上会和副结核分歧杆菌有关。
吧里有几位吧友和我一样，认为副结核分歧杆菌可能是导致克罗恩病的罪魁祸首。理由如下：
（1）尽管有研究表明克罗恩病与基因存在一定程度的相关，但是基于国外人群的样本的，中国人的发病率一直是低于西方的，然而近年来中国发病几率呈现的飞速增加的趋势，难道是中国人的基因在这几年发生了突变？显然不是，所以我认为肯定是有外部原因的。
（2）副结核分歧杆菌和结合分歧杆菌同属一个菌群家族，来这个吧半年以上的吧友相比对结核病的肠内表现已经非常了解了，它与克罗恩病非常难以区分。我个人推测，克罗恩病和肠结核病可能就是亲戚，生物学里有句话，叫做结构决定功能，副结核分歧杆菌和结核杆菌作为同家族菌种，其基本结构存在相似之处，必然在功能上可能也有近似的地方。因此，副结核分歧杆菌导致克罗恩病的假设是合理的。
（3）副结核分歧杆菌之所以出名，是因为它在牛羊等牲畜上会导致“约翰病”，其表现和克罗恩病及其类似。
下面进入正题，下面这篇应该是会议摘要，不像是什么突破性的研究进展，但标题很有意思：
MYCOBACTERIUM AVIUM SSP. PARATUBERCULOSIS (MAP) CAN BE RELIABLY DETECTED AND CULTURED FROM PERIPHERAL BLOOD OF 100% OF PATIENTS WITH RECENT ONSET CROHN'S DISEASE
副结核分歧杆菌在100%的近期发作的克罗恩病患者外周血液中能够被轻易地检测并培养出来。
作者：Adrienne L. McNees, Najah R. Zayyani, Diane Markesich, David Y. Graham
背景： 副结核分歧杆菌(Mycobacterium avium ssp. Paratuberculosis, MAP)在很长一段时间内都被认为是导致克罗恩病的病理机制。时不时地能从克罗恩患者外周血液巨噬细胞中检测到MAP的DNA。我们评估了是否这种“时灵时不灵”的情况是由于其含量过低，或是MAP间歇性地进入血液。巴林（一个国家）最近经历了一场克罗恩病大爆发，因此有充足地实验对象。
方法：我们假设，是否MAP进入血液是间歇性的，或是低水平的，因此当采样更大、更频繁时，检测出MAP的几率会随之增加。我们从病史小于5年的110个巴林的克罗恩病患者中每个采集了1-4管样品（也就是采血），同时选取了217非炎症性肠病患者作为对照组。从静脉血中分离出外周血单核细胞(Peripheral blood mononuclear cells, PBMCs)，并检测了MAP（用PCR）。一部分PBMC样品被用于培养MAP菌群。
结果：MAP的DNA在对照组没检测出来。而在110个克罗恩患者中，有80.9%的患者检测出了MAP的DNA。而增加了样本量曾逐步提高了检测出MAP的几率：每个患者取样一次，检出MAP几率68%；每个患者两次，检出率84%；每个患者三次，检出率96%；4次及以上，检出率100%！！！
而从49个病人中取样并培养菌群，其中26个样品培养菌种检测出了MAP (53%)。同样的，测试多次血液样本（这部分没看懂，到底是多测几次还是加大量，但不影响理解结果）增加了培养出MAP的几率：1样本=43%；2样本=42%；3样本=75%；4或更多=100%。（后面那句话太难翻译了我就不翻了，大家自己看吧）。
结论：该结果符合了假设，即之前出现MAP检测几率变化大可能是因为MAP本身密度低或间歇性进入血液。
原文：
Background: Mycobacterium avium ssp. paratuberculosis (MAP) has long been considered a possible etiologic agent for Crohn's disease. MAP DNA has been detected with variable frequency in peripheral blood macrophages from patients with Crohn's disease. We evaluated whether the variability related to the presence of low level or intermittent MAP shedding into the blood. Bahrain has experienced a recent outbreak of Crohn's disease thus contains a population enriched with recent onset disease. Methods: We hypothesized that if MAP
shedding was either intermittent or low level, then the detection rate should increase with more samples being tested from a patient. We tested 1 to 4 blood samples from 110 Bahrain Crohn's disease patients with IBD symptoms for <5 years (mean age of 34.5 years), and 217 samples from non-IBD controls. Peripheral blood mononuclear cells (PBMCs) were separated from venous blood using centrifugation separation of buffy coat and red cell lysis and tested for MAP using a validated nested PCR for MAP IS900. A proportion of PBMC samples were used to attempt to culture MAP. Results: MAP DNA was not detected by PCR in any of the 217 control patient samples. MAP DNA was detected in 89 patients (80.9%) tested from 110 Crohn's disease patients. Increasing the number of blood draws per patient tested by PCR increased MAP- positive results (1 sample = 68%; 2 samples = 84%; 3 samples = 96%; 4 or more samples = 100% MAP positive). Samples from 49 patients
were tested for MAP growth in culture and 26 gave positive results (53%). Similarly, testing multiple blood draw samples from 49 Crohn's disease patients in culture for MAP growth increased the detection rate of cultivable, slow growing Mycobacteria (1 sample = 43%; 2 samples = 42%; 3 samples = 75%; 4 or more samples = 100% MAP positive). The culture slants that produced required longer than 6 months to appear and appeared as tiny cream colored, slightly rough colonies. Conclusions: These results are consistent with the notion that MAP are circulating in the peripheral blood of patients with Crohn's disease either at low level or intermittently. Carefully designed clinical trials in Crohn's patients that specifically confirm the presence of MAP and relate the responses to treatment and recurrence are required to establish a causal zoonotic link between the pathogen, a major food industry and a devastating chronic human gastrointestinal illness.
