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     

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。     

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。     

核因子-κB与创伤的关系及其在法医病理学中的应用

损伤时间推断是法医病理学的一个研究热点和难点。核因子-κB(NF-κB)是一种核转录调节蛋白,参与多种炎性介质的转录和调控。近年来研究发现NF-κB与机体创伤后的反应密切相关,其在损伤后的时序性表达可望在法医病理学用于损伤时间推断。     

Potency variation of small-molecule chymase inhibitors across species

Chymases (EC 3.4.21.39) are mast cell serine proteinases that are variably expressed in different species and, in most cases, display either chymotryptic or elastolytic substrate specificity. Given that chymase inhibitors have emerged as potential therapeutic agents for treating various inflammatory, allergic, and cardiovascular disorders, it is important to understand interspecies differences of the enzymes as well as the behavior of inhibitors with them. We have expressed chymases from humans, macaques, dogs, sheep (MCP2 and MCP3), guinea pigs, and hamsters (HAM1 and HAM2) in baculovirus-infected insect cells. The enzymes were purified and characterized with kinetic constants by using chromogenic substrates. We evaluated in vitro the potency of five nonpeptide inhibitors, originally targeted against human chymase. The inhibitors exhibited remarkable cross-species variation of sensitivity, with the greatest potency observed against human and macaque chymases, with K_i values ranging from ∼0.4 to 72 nM. Compounds were 10-300-fold less potent, and in some instances ineffective, against chymases from the other species. The X-ray structure of one of the potent phosphinate inhibitors, JNJ-18054478, complexed with human chymase was solved at 1.8 Å resolution to further understand the binding mode. Subtle variations in the residues in the active site that are already known to influence chymase substrate specificity can also strongly affect the compound potency. The results are discussed in the context of selecting a suitable animal model to study compounds ultimately targeted for human chymase.     

Mucosal features and granulocyte–monocyte-apheresis in steroid-dependent/refractory ulcerative colitis

BACKGROUND: Mucosa-infiltrated granulocyte neutrophils are an early characteristic of inflammation and the main histological feature of active ulcerative colitis. Mucosal healing has recently been indicated as an important tool in the evaluation of response to treatment. While several studies have stressed the efficacy of granulocyte-monocyte-apheresis in inducing clinical remission in active ulcerative colitis, few data are available on mucosal features. AIM: Aim of this study was to assess the effects of granulocyte-monocyte-apheresis on clinical and mucosal features in patients with ulcerative colitis, dependent upon or refractory to steroids. MATERIAL AND METHODS: From April 2004 to April 2005, 12 patients (5 females, 7 males, mean age 49 years, range 33-71 years), with mild-moderate ulcerative colitis (six left colitis, six pancolitis) dependent/refractory upon steroids were enrolled. Each patient was treated for a 5-week period with five cycles of granulocyte-monocyte-apheresis. Patients were evaluated at baseline and 1 week after the last apheresis by means of Global Physician Assessment, quality of life features, laboratory tests (erythrocyte sedimentation rate, CRP, full blood count, faecal calprotectine), endoscopy and histology. RESULTS: At week 6 of follow-up, complete mucosal healing was observed in 3 out of 12 patients, partial mucosal healing in 8 patients and no change in 1 patient. Clinical response was complete in 8 out of 12 patients. CONCLUSIONS: These data suggest that granulocyte-monocyte-apheresis induces an improvement both in clinical and mucosal lesions in steroid-dependent/refractory ulcerative colitis. Of note, the reduction in granulocyte infiltration and the improvement in mucosal lesions are accompanied by a reduction in faecal calprotectine.     

炎症性肠病危险因素的流行病学调查研究

目的通过病例调查，筛选IBD的危险因素。方法采用问卷方式，对72例确诊IBD患者及72例配对的健康个体调查，对结果进行COX回归分析，筛选出IBD的致病危险因素。结果COX回归分析提示紧张度、牛奶和油炸食品在IBD致病因素中具有统计学意义。结论紧张度、牛奶和油炸食品可能是IBD的致病危险因素。     

对大肠癌术后早期炎性肠梗阻诊治的探讨

目的：探讨大肠癌术后早期炎性肠梗阻的特点及治疗方法；方法：分析10例大肠癌术后出现早期炎性肠梗阻的临床表现并进行综合保守治疗；结果：10例患者保守治疗全部成功；结论：术后早期炎性肠梗阻是一种非细菌性炎性肠梗阻，以发生在术后早期，腹胀、呕吐明显，腹痛轻或无为主要临床特点，治疗应采用保守治疗。     

A Case Report of Inflammatory Pseudosarcoma of the Urinary Bladder

A case of inflammatory pseudosarcoma of the urinary bladder in a 35 year-old Japanese male is presented. This benign lesion can easily be mistaken for spindle cell sarcoma since it consists of rhabdomyoblast like elongated strap cells showing infiltrative growth, and whether it is benign or malignant is difficult to determine by microscopic examination. In this case, spindle cell proliferation extended among bundles of the superficial muscle layer. However, no abnormal mitoses, severe nuclear atypia or cellular pleomorphism could be seen, thus indicating inflammatory pseudosarcoma. Although the lesion was not completely resected, no recurrent disease has been clinically observed for two years following transurethral resection. Urologists and surgical pathologists must be able to detect this lesion in order to avoid unnecessary surgical procedures. Acta Pathol Jpn 42: 760 765,1992.     

大鼠急性脊髓损伤时IκBα的表达及其意义

目的 研究大鼠急性脊髓损伤时抑制蛋白α(IkBa)表达变化规律。方法 将60只SD大鼠随机分为两组：损伤组48只大鼠，行脊柱椎板切除及脊髓打击术。对照组12只大鼠，仅行椎板切除术。应用免疫组织化学及Western blot分别测定脊髓细胞浆内IkBα的表达变化情况。免疫组织化学以细胞浆出现棕黄色颗粒为阳性结果，Western blot以醋酸纤维素膜上出现棕色条带为阳性结果。结果 在损伤后1h，IkBα表达开始下降，12h降到最低点，损伤后24h表达开始回升，5d逐步恢复正常。结论 IkBα活性变化可作为急性创伤性脊髓损伤时炎症反应程度的一项观测指标，通过抑制IkBα磷酸化降解环节，成为抑制炎症反应的新途径。