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     

烯烃的热力学性质的拓扑研究

目的：寻找一种性能优良的拓扑指数，方法：根据分子图的邻接矩阵和距离矩阵提出一种新的拓扑指数P1^*,P2^*,P3^*,p^4*。结果，拓扑指数P1^*,P2^*,P3^*,p^4*与烯烃的热力学函数－△Hf(g),S(g),△Gf(g)均有相关性，其复相关系数均在99．6％以上。结论：拓扑指数P1^*,P2^*,P3^*,p^4*与烯烃的热力学函的多种物理化学性质均有良好的相关性。     

重质石油中含氮化合物的形态及分布分析Ⅱ．含氦杂环化合物的定性方法

探索了色谱保留值与质谱信息相结合的定性分析方法。用ＳＥ－５４柱代替ＳＥ－５２柱，选用六个多环芳烃化合物作为标准计算保留指数，从而改善了Ｍ．Ｌ．Ｌｅｅ保留指数的应用条件和范围；用文献值转换扩充了Ｌｅｅ的含氮杂环化合物保留指数表，并利用保留时间与沸点的关系作定性佐证。应用该法鉴定了重质石油样品子组分及萘油中的４６个含氮杂环化合物及其异构体，为质谱在异构体鉴定以及缺乏标样所产生的困难提供了可信、简便的定性鉴定方法。     

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。     

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。     

肺炎性假瘤(附52例报告)

目的：分析肺炎性假瘤的临床病理特点，并探讨其诊断问题，方法：回顾性分析52例肺炎性假瘤的临床病理资料。结果：男女发病比为2．25：1，平均年龄50．6岁，平均病程10．8个月，临床主要表现为咳嗽或咳痰，痰中带血或咯血，胸痛或背痛；影像检查见肿块位于肺周边部，单发，圆形或类圆形，病理检查肿块最大平均直径为3．9cm，见于各肺多于左肺，双上肺多于双下肺，44．2％同侧肺门淋巴结因反应性增生而肿大；经系统抗炎，抗结核治疗，肺肿块影均无改变，手术切除可治愈，结论：肺炎性假瘤有其特点，可与肺癌、肺结核、肺炎相区别；确诊仍需病理活检；CT或超声引导经皮活检值得推广，并应重视电视胸腔腔镜在诊治中的作用。