谷氨酰胺强化肠内营养对炎症性肠病幼鼠模型结肠黏膜细胞凋亡作用的研究

目的 探讨谷氨酰胺强化肠内营养对炎症性肠病（IBD）幼鼠模型肠黏膜细胞凋亡的调控及促进黏膜愈合的作用。方法 将80只4~5周龄Sprague-Dawley雄性大鼠随机分为空白对照组、IBD模型组、短肽组和短肽+谷氨酰胺（Gln）组,每组20只。采用一次性结肠灌注三硝基苯磺酸建立IBD模型,造模3 d后,短肽组给予短肽制剂（100 mL/kg）,短肽+Gln组给予短肽制剂（100 mL/kg）+Gln（0.5 g/kg）,干预1周。实验结束后观察幼鼠的一般情况,并留取肠黏膜,苏木素-伊红（HE）染色观察肠黏膜组织病理情况;RTPCR法检测肠黏膜凋亡调控基因（bax、bcl-2）及凋亡信号转导因子（Caspase-3、Caspase-9）的表达;Westernblot法检测结肠黏膜IGF-1表达水平。结果 IBD模型组一般情况均较其他组差,短肽+Gln组一般情况优于IBD模型组和短肽组。模型组bax mRNA表达水平高于空白对照组、短肽组和短肽+Gln组（P < 0.05）;bcl-2、Caspase-3、Caspase-9 mRNA水平在各组比较差异均无统计学意义（P > 0.05）。短肽组IGF-1水平明显高于短肽+Gln组、空白对照组及IBD模型组（P < 0.05）。结论 Gln强化肠内营养能有效改善IBD模型幼鼠的一般营养状况,但在抑制结肠黏膜细胞凋亡及刺激结肠黏膜IGF-1合成方面并未优于专一肠内营养。     

Differential effects of cadmium administration on peripheral blood granulocytes in rats

Infiltration of circulatory inflammatory cells is a common histopathological finding in target organs following cadmium administration, but there is paucity of data concerning their activity. In this study, the effects of sublethal (1 mg/kg) cadmium on peripheral blood polymorphonuclear (PMN) cells were examined 48 h following administration in rats, when tissue (liver and lung) infiltration of these cells was observed. Cadmium administration resulted in systemic inflammatory cytokine and acute phase response with an increase in circulatory neutrophil numbers and cells that express CD11b molecules. Rise in basic aspects of oxidative activity including intracellular myeloperoxidase (MPO), reactive oxygen (nitroblue tetrazolium/NBT cytochemical assay) and nitrogen (Griess assay) species production was observed in PMNs from cadmium-administered rats. A decrease in levels of mRNA for IL-1β, TNF-α and IL-6 was noted, but production of these cytokines was affected differentially. Described effects of cadmium on PMNs add further to the understanding of inflammatory potential of this environmental contaminant.     

炎症因子用于早期预测妊娠期糖尿病的研究进展

妊娠期糖尿病(gestational diabetes mellitus,GDM)是指在妊娠期发生或首次发现的不同程度的糖耐量异常或糖尿病,对母亲及胎儿的危害很大,早期发现其危险因子,并进行早期诊断和干预,来预防、减少GDM及其并发症的发生值得关注和研究。炎症因子在GDM发生中的作用一直是研究的热点之一,本文将综述用炎症因子指标对GDM进行早期预测的研究进展。     

Hepatocellular adenoma: Classification,variants and clinical relevance

Hepatocellular adenomas are benign tumors with two major complications, bleeding and malignant transformation. The overall narrative of hepatocellular adenoma has evolved over time. Solitary or multiple hepatocellular developing in the normal liver of women of child bearing age exposed to oral contraceptives still represents the most frequent clinical context, however, new associations are being recognized. Hepatocellular adenoma is discovered on a background of liver diseases such as non-alcoholic steatohepatitis, vascular diseases, and alcoholic cirrhosis. Hepatocellular adenoma is also reported in men, young or older adults, and even in infants. On the morpho-molecular side, the great leap forward was the discovery that hepatocellular adenoma was not a single entity and that at least 3 different subtypes exist, with specific underlying gene mutations. These mutations affect the HNF1A gene, several genes leading to JAK/STAT3 pathway activation and the CTNNB1 gene. All of them are associated with more or less specific histopathological characteristics and can be recognized using immunohistochemistry either with specific antibodies or with surrogate markers. Liver pathologists and radiologists are the key actors in the identification of the different subtypes of hepatocellular adenoma by the recognition of their specific morphological features. The major impact of the classification of hepatocellular adenoma is to identify subjects who are at higher risk of malignant transformation. With the development of new molecular technologies, there is hope for a better understanding of the natural history of the different subtypes, and, particularly for their mechanisms of malignant transformation.     

Infliximab induces remission in cryptogenic multifocal ulcerous stenosing enteritis:First case

We present the case of a 29-year-old patient with a history of abdominal pain and vomiting.Based on wireless video capsule findings he was previously diagnosed with ileal Crohn’s disease at a different institution,although the clinical and radiological picture was not typical and the response to corticosteroids was poor.We performed a single-balloon enteroscopy showing a short,ulcerous stenosis 50 cm proximal from Bauhin’s valve.The endoscopic and clinical histopathological findings were compatible with cryptogenic multifocal ulcerous stenosing enteritis(CMUSE).High dose corticosteroids were again started,without effect.The monoclonal tumor necrosis factor-α(TNF-α) antibody infliximab was added to the medical therapy.After induction therapy,both clinical and endoscopic amelioration was obtained.Larger case studies are needed to confirm the efficacy of TNF-α inhibition in steroid refractory CMUSE.     

炎症调控介质:保护素D1的研究进展

背景 保护素D1 (protectin D1,PD1)是近期发现的由二十二碳六烯酸(docosahexenoic acid,DHA)衍生的生物活性分子,是机体一种重要的内源性脂质抗炎及促炎症消退介质. 目的 深入认识这个新的家族有助于探讨多种疾病的发病机制,并为其治疗提供新的靶点. 内容 大量研究表明,PD1对多种炎性细胞的功能和多种炎症相关基因的表达有广泛的调节作用,能促进炎症反应及时消退,可改善多种疾病的转归.现就PD1的生物学活性、对炎性细胞及炎症相关疾病的作用作一综述. 趋向 随着研究的深入,必将全面地揭示PD1的病理生理意义、详细地阐明其效应机理,并最终研制出具有临床应用价值的新型抗炎药物.     

Does perioperative biological therapy increase 30-day post-operative complication rates in inflammatory bowel disease patients undergoing intra-abdominal surgery? A systematic review

BackgroundBiopharmaceuticals revolutionised inflammatory bowel disease (IBD) treatment. However, it is postulated they compromise immunity, collagen production and angiogenesis resulting in infective post-operative complications and altered wound/anastomotic healing. Research has failed to agree on risks associated with perioperative biologics therefore it was anticipated that a systematic review may provide a consensus and contribute recommendations for clinical practice.MethodsA systematic review conducted as per PRISMA guidelines included a methodical search of PubMed, Google Scholar, EMBASE/Ovid and Cochrane Library using MeSH and/or keywords for papers published between 01/01/1998 and 04/02/2019.The population analysed included adult ulcerative colitis, Crohn's disease, Indeterminate Colitis or IBD unclassified patients. The intervention was intra-abdominal surgery in patients treated with biological therapy in the preceding 12 weeks compared to patients who had intra-abdominal surgery without biological therapy within the defined timeframe. The primary outcome was surgical site infection (SSI) with secondary outcomes including wound dehiscence, intra-abdominal sepsis/abscess, systemic infection and anastomotic breakdown within 30 days post-procedure. Papers were evaluated by two independent reviewers and those included were assessed for quality/bias using the Newcastle–Ottowa scale.Results2064 UC, Crohn's and IC patients were analysed across 8 included studies. Several studies' multivariate analyses demonstrated corticosteroids to be independent predictors of morbidity. There are no increased complications associated with anti-TNFα exposure while vedolizumab increased SSI and small bowel obstruction.ConclusionProspective studies and randomised control trials are required to clarify study outcomes and recommendations published to date. Presently, biologics should continue to be used and considered beneficial in this population.     

Therapeutic drug monitoring with biologic agents in immune mediated inflammatory diseases

ABSTRACT

Introduction: Biologic therapy has revolutionized the treatment of immune mediated inflammatory diseases (IMID), such as inflammatory bowel disease (IBD), rheumatoid and psoriatic arthritis, ankylosing spondylitis and psoriasis. Nevertheless, some patients exhibit primary nonresponse (PNR) or secondary loss of response (SLR) to biologics.

Areas covered: This collaborative review provides data on the role of therapeutic drug monitoring (TDM) in IMID for optimizing biologic therapy including infliximab, adalimumab, certolizumab pegol etanercept and golimumab vedolizumab, secukinumab and ustekinumab.

Expert opinion: Most exposure-response relationship studies show a positive correlation between biologic drug concentrations and favorable therapeutic outcomes in IMID with higher drug concentrations typically associated with more objective outcomes. Clinically, reactive TDM rationalizes the management of PNR and SLR to anti-tumor necrosis factor therapy and is emerging as the new standard of care in IBD as it is also more cost-effective than empiric dose escalation. Preliminary data suggest that proactive TDM with the goal to achieve a threshold drug concentration is associated with better therapeutic outcomes when compared to empiric drug optimization and/or reactive TDM of infliximab and adalimumab in IBD. However, more data from well-designed prospective studies are needed to prove the benefit of TDM-based algorithms in real life clinical practice in IMID.