Hirschsprung-associated inflammatory bowel disease: A multicenter study from the APSA Hirschsprung disease interest group

Background/PurposeA small number of Hirschsprung disease (HD) patients develop inflammatory bowel disease (IBD)-like symptoms after pullthrough surgery. The etiology and pathophysiology of Hirschsprung-associated IBD (HD-IBD) remains unknown. This study aims to further characterize HD-IBD, to identify potential risk factors and to evaluate response to treatment in a large group of patients.MethodsRetrospective study of patients diagnosed with IBD after pullthrough surgery between 2000 and 2021 at 17 institutions. Data regarding clinical presentation and course of HD and IBD were reviewed. Effectiveness of medical therapy for IBD was recorded using a Likert scale.ResultsThere were 55 patients (78% male). 50% (n = 28) had long segment disease. Hirschsprung-associated enterocolitis (HAEC) was reported in 68% (n = 36). Ten patients (18%) had Trisomy 21. IBD was diagnosed after age 5 in 63% (n = 34). IBD presentation consisted of colonic or small bowel inflammation resembling IBD in 69% (n = 38), unexplained or persistent fistula in 18% (n = 10) and unexplained HAEC >5 years old or unresponsive to standard treatment in 13% (n = 7). Biological agents were the most effective (80%) medications. A third of patients required a surgical procedure for IBD.ConclusionMore than half of the patients were diagnosed with HD-IBD after 5 years old. Long segment disease, HAEC after pull through operation and trisomy 21 may represent risk factors for this condition. Investigation for possible IBD should be considered in children with unexplained fistulae, HAEC beyond the age of 5 or unresponsive to standard therapy, and symptoms suggestive of IBD. Biological agents were the most effective medical treatment.Level of EvidenceLevel 4     

Vaccination evokes gender-dependent protection against tularemia infection in C57BL/6Tac mice

Francisella tularensis (Ft) is a Category A biothreat agent for which there currently is no FDA-approved vaccine. Thus, there is a substantial effort underway to develop an effective tularemia vaccine. While it is well established that gender can significantly impact susceptibility to primary infection, the impact of gender on vaccine efficacy is not well established. Thus, development of a successful vaccine against tularemia will require an understanding of the impact gender has on vaccine-induced protection against this organism. In this study, a role for gender in vaccine-induced protection following Ft challenge is identified for the first time. In the present study, mucosal vaccination with inactivated Ft (iFt) LVS elicited gender-based protection in C57BL/6Tac mice against respiratory challenge with Ft LVS. Specifically, vaccinated male mice were more susceptible to subsequent Ft LVS challenge. This increased susceptibility in male mice correlated with increased bacterial burden, increased tissue inflammation, and increased proinflammatory cytokine production late in post-challenge infection. In contrast, improved survival of iFt-vaccinated female mice correlated with reduced bacterial burden and enhanced levels of Ft-specific Abs in serum and broncho-alveolar lavage (BAL) fluid post-challenge. Furthermore, vaccination with a live attenuated vaccine consisting of an Ft LVS superoxide dismutase (SodB) mutant, which has proven efficacious against the highly virulent Ft SchuS4 strain, demonstrated similar gender bias in protection post-Ft SchuS4 challenge. Of particular significance is the fact that these are the first studies to demonstrate that gender differences impact disease outcome in the case of lethal respiratory tularemia following mucosal vaccination. In addition, these studies further emphasize the fact that gender differences must be a serious consideration in any future tularemia vaccine development studies.     

滋阴清热方治疗对甲状腺功能亢进症阴虚火旺证患者疗效、血浆内皮素-1、炎症因子和免疫功能的影响

目的:研究滋阴清热方治疗对甲状腺功能亢进症阴虚火旺证患者疗效、血浆内皮素-1、炎症因子和免疫功能的影响。方法:将广州市花都区妇幼保健院收治的100例甲状腺功能亢进症阴虚火旺证患者分成观察组和对照组。对照组:给患者使用常规药物治疗;观察组:在对照组的基础上,给予滋阴清热方治疗。干预后,比较两组患者的临床疗效、血浆内皮素-1(Endothelin,ET)、炎症因子[白介素-2(Interleukin-2,IL-2)、白介素-8(Interleukin-8,IL-8)]及肿瘤坏死因子(Tumour Necrosis Factor-α,TNF-α)和免疫功能(CD3^+、CD4^+、CD8^+及CD4^+/CD8^+)。结果:干预前,两组患者IL-2、IL-8及TNF-α无变化,差异无统计学意义(P>0.05);干预后,观察组患者的IL-2比对照组高,且对照组的IL-8及TNF-α比观察组的高,P<0.05,差异有统计学意义;干预前,两组患者的CD3^+、CD4^+、CD8^+及CD4^+/CD8^+与ET无变化;干预后,观察组的CD3^+、CD4^+、CD8+及CD4^+/CD8^+比对照组高,P <0.05,差异有统计学意义,且观察组的ET低于对照组且观察组总有效率明显高于对照组。结论:滋阴清热方治疗降低了血浆内皮素-1,减少炎症的出现,提高免疫功能。     

利培酮和齐拉西酮对精神分裂症患者血浆细胞因子的影响

目的:研究抗精神病药对精神分裂症患者细胞因子的影响。方法:符合ICD-10精神分裂症诊断的60名患者,随机分为利培酮组(给予利培酮治疗)和齐拉西酮组(给于齐拉西酮治疗),并以健康对照组比较,对患者在治疗前及治疗8周后测量血浆IL-2、IL-6及TNF-α水平,并对患者进行PANSS量表评定。结果:两组患者治疗前后血浆IL-2、IL-6及TNF-α水平与对照组比较,差异有统计学意义(P0.05)。两组患者治疗后血浆IL-2、IL-6及TNF-α水平较治疗前降低,差异有统计学意义(P0.05)。治疗前IL-2水平与PANSS量表阳性症状评分呈正相关(r=0.54,P0.05)治疗后TNF-α与阴性症状分呈显著正相关(r=0.41,P0.05)。结论:精神分裂症患者存在免疫功能异常,利培酮和齐拉西酮可以降低精神分裂症患者细胞因子水平。细胞因子水平与精神病理存在一定相关性。     

维甲酸调变早幼粒白血病细胞株NB4中G-CSF及其受体表达

目的：进一步研究G－CSF在维甲酸致高白细胞症中的作用。方法：用RT－PCR、Northernblotting方法检测NB4细胞经全反式维甲酸（ATRA）作用后G－CSF mRNA表达的变化，同时用ELISA方法检测细胞培养上清液中G－CSF蛋白水平的变化；采用流式细胞技术检测NB4细胞经ATRA作用后G－CSF受体蛋白表达的变化。结果：ATRA可从基因水平上调NB4细胞中G－CSF表达，并可增加NB4细胞表面G－CSF受体的表达，G－CSF受体表达增加出现的时间虽然稍晚于G－CSF表达增加出现的时间，但仍然在较早期阶段，此时，细胞形态学和NBT实验均证实BN4细胞处于部分分化阶段。结论：在ATRA治疗APL过程中，G－CSF及其受体表达增加可能协同参与了高白细胞症的发生。     

Changes in immune regulation in response to examination stress in atopic and healthy individuals

BACKGROUND: Stress can aggravate the allergic inflammation, but determinants of disturbed immune regulation are largely unknown. OBJECTIVE: To determine systemic immunological, local inflammatory and functional airway responses to stress in healthy and atopic individuals. METHODS: Forty-one undergraduate students, 22 with allergy of whom 16 had asthma, and 19 healthy controls, were studied in a low-stress period and in association with a large exam. Subjects completed questionnaires on stress and health behaviours, underwent lung function tests, bronchial methacholine challenge, measurements of exhaled nitric oxide and urine cortisol. Blood cells were phenotyped, and cytokines from mononuclear blood cells were analysed. RESULTS: Perceived stress and anxiety increased in both groups during the exam period while cortisol increased only in the atopy group. Cytokine production decreased broadly in response to stress in both groups, which was paralleled by an increase in the proportion of regulatory T cells (CD4(+)CD45RO(+)CD25(bright)). Interestingly, atopic individuals, but not controls, reacted with a decreased T-helper type 1/T-helper type 2 (Th1/Th2) ratio and a decrease in natural killer (NK) cell numbers in response to stress. In control subjects only, exhaled nitric oxide decreased and forced expiratory volume in one second increased during stress. CONCLUSION: Atopic and non-atopic subjects shared some immune changes in response to stress, such as a dramatic decline in cytokines and an increase in the number of regulatory T cells in peripheral blood. However, other stress-induced immune changes were unique to atopic individuals, such as a skewed Th1/Th2 ratio and reduced NK cell numbers, indicating that some pathogenic mechanisms in atopics may be more strongly affected by stress than others.     

柔肝消瘢饮对肝硬化大鼠血清和肝组织IL-1β和IL-6含量的影响

目的：观察柔肝消瘕饮对肝硬化大鼠肝组织病理形态学和血清、肝组织IL-1β、IL-6含量的影响。方法：采用复合因素造模法复制肝硬化大鼠模型，以复方鳖甲软肝片为对照，观察柔肝消瘢饮对肝硬化大鼠肝组织病理形态学、血清和肝组织IL-1β、IL-6含量的影响。结果：与正常组比较，模型组大鼠出现肝小叶损害，纤维组织增生，假小叶形成，血清IL-1β、IL-6含量和肝组织IL-6含量均明显升高（P〈0．01或P〈0．05）；与模型组比较，各治疗组肝组织病理损害减轻，血清IL-1β和肝组织IL-6含量均有明显下降，差异有显著性意义（P〈0．01或P〈0．05）；与对照组比较，高剂量组血清IL-6含量明显降低（P〈0．05）。结论：柔肝消瘢饮能显著下调肝硬化大鼠血清IL-1β、IL-6含量和肝组织IL-6含量，具有减轻肝硬化炎症损害，改善肝组织病理形态学作用。     

炎性肠病药物治疗的循证医学研究进展

目的:从循证医学的角度解析炎性肠病药物治疗的相关进展。旨在提高对临床证据的认知,帮助临床医生评估新的治疗,从批判的视角重新看待以往的治疗。方法:收集国外近期相关文献进行评价。结果及结论:炎性肠病(IBD)的发病机制尚不清楚,众多的治疗方案可供选择。因此,循证医学研究结果有非常重要的临床指导意义。IBD的研究方面取得了可喜的进步。但是,有关CD活动指数(CDAI)和临床分型系统仍有待于改进。通过循证医学的研究证据有望确定安全和易于耐受的药物,并能发现目前诊治方面存在的缺陷和问题,更好地解决患者的病痛。