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.     

The effect of appendectomy on the course of ulcerative colitis: a systematic review

Aim Previous studies have shown significantly lower appendectomy rates in ulcerative colitis (UC) patients compared with healthy controls. Evidence indicating that the appendix has an immunomodulatory role in UC has been accumulating. To examine the latest evidence on the effect of appendectomy on the disease course of UC. Method PubMed, The Cochrane Library and EMBASE were searched. Primary end‐points were number of relapses, use of steroids, number of hospital admissions and number of colectomies. Results The search resulted in six observational studies (five case–control studies and one cohort study) totalling 2532 patients. Owing to clinical heterogeneity, no meta‐analysis could be conducted. One study found lower relapse rates in patients appendectomized before the onset of UC [absolute risk reduction (ARR) = 21.5%; 95% CI: 1.71–45.92%]. Another two studies found a reduced requirement for immunosuppression in appendectomized patients (ARR = 20.2%; 95% CI: 9.67–30.46% in the first study and ARR = 21.4%; 95% CI: 10.32–32.97% in the second study). In addition, one study found lower colectomy rates in nonappendectomized patients (ARR = 8.7%; 95% CI: 1.29–18.66%) and two studies found lower colectomy rates in appendectomized patients (ARR = 21.4%; 95% CI: 13.17–28.79% in the first study and ARR = 18.7%; 95% CI: 7.50–29.97% in the second study). Conclusion There are limited and conflicting data available regarding the effect of appendectomy on the disease course of UC. Most studies suggest a beneficial effect and the minority find no, or a negative, effect.     

Genomic profiling of inflammatory breast cancer: A review

Inflammatory breast cancer (IBC) is a rare but aggressive form of breast cancer. Despite efforts in the past decade to delineate the molecular biology of IBC by applying high-throughput molecular profiling technologies to clinical samples, IBC remains insufficiently characterized. The reasons for that include limited sizes of the study population, heterogeneity with respect to the composition of the IBC and non-IBC control groups and technological differences across studies. In 2008, the World IBC Consortium was founded to foster collaboration between research groups focusing on IBC. One of the initial projects was to redefine the molecular profile of IBC using an unprecedented number of samples and search for gene signatures associated with survival and response to neo-adjuvant chemotherapy. Here, we provide an overview of all the molecular profiling studies that have been performed on IBC clinical samples to date.     

干细胞疗法治疗炎症性肠病的应用

炎症性肠病是一种慢性炎症性疾病,主要包括克罗恩病和溃疡性结肠炎,其发病原因尚不清楚。干细胞疗法在治疗炎症性肠病方面可能是非常有价值的,近年来,干细胞疗法的研究也更加突出而显著,本文就干细胞疗法治疗炎症性肠病的应用作一概述。     

How will insights from genetics translate to clinical practice in inflammatory bowel disease?

Inflammatory bowel disease, consisting of Crohn's disease and ulcerative colitis, is a chronic inflammatory disease of the gut, which arises through an excessive immune response to the normal gut flora in a genetically susceptible host. The disease affects predominantly young adults and due to its chronic and relapsing nature gives rise to a high disease burden both financially, physically and psychologically. Current therapy still cannot prevent the need for surgical intervention in more than half of IBD patients. Consequently, advances in IBD therapy are of high importance. Recently, several new forms of targeted therapy have been introduced, which should improve surgery-free prognosis of IBD patients. Recent identification of genetic risk variants for IBD has led to new insights into the biological mechanisms of the disease, which will, in the future, lead to new targeted therapy. In the meantime repositioning of drugs from biologically similar diseases towards IBD might lead to new IBD therapies.     

Post-infectious irritable bowel syndrome:Mechanistic insights into chronic disturbances following enteric infection

Irritable bowel syndrome(IBS)is a commonly encountered chronic functional gastrointestinal(GI)disorder.Approximately 10%of IBS patients can trace the onset of their symptoms to a previous a bout of infectious dysentery.The appearance of new IBS symptoms following an infectious event is defined as post-infectiousIBS.Indeed,with the World Health Organization estimating between 2 and 4 billion cases annually,infectious diarrheal disease represents an incredible international healthcare burden.Additionally,compounding evidence suggests many commonly encountered enteropathogens as unique triggers behind IBS symptom generation and underlying pathophysiological features.A growing body of work provides evidence supporting a role for pathogen-mediated modifications in the resident intestinal microbiota,epithelial barrier integrity,effector cell functions,and innate and adaptive immune features,all proposed physiological manifestations that can underlie GI abnormalities in IBS.Enteric pathogens must employ a vast array of machinery to evade host protective immune mechanisms,and illicit successful infections.Consequently,the impact of infectious events on host physiology can be multidimensional in terms of anatomical location,functional scope,and duration.This review offers a unique discussion of the mechanisms employed by many commonly encountered enteric pathogens that cause acute disease,but may also lead to the establishment of chronic GI dysfunction compatible with IBS.     

Molecular confocal laser endomicroscopy:A novel technique for in vivo cellular characterization of gastrointestinal lesions

While flexible endoscopy is essential for macroscopic evaluation,confocal laser endomicroscopy(CLE)has recently emerged as an endoscopic method enabling visualization at a cellular level.Two systems are currently available,one based on miniprobes that can be inserted via a conventional endoscope or via a needle guided by endoscopic ultrasound.The second system has a confocal microscope integrated into the distal part of an endoscope.By adding molecular probes like fluorescein conjugated antibodies or fluorescent peptides to this procedure(either topically or systemically administered during on-going endoscopy),a novel world of molecular evaluation opens up.The method of molecular CLE could potentially be used for estimating the expression of important receptors in carcinomas,subsequently resulting in immediate individualization of treatment regimens,but also for improving the diagnostic accuracy of endoscopic procedures by identifying otherwise invisible mucosal lesions.Furthermore,studies have shown that fluorescein labelled drugs can be used to estimate the affinity of the drug to a target organ,which probably can be correlated to the efficacy of the drug.However,several of the studies in this research field have been conducted in animal facilities or in vitro,while only a limited number of trials have actually been carried out in vivo.Therefore,safety issues still needs further evaluations.This review will present an overview of the implications and pitfalls,as well as future challenges of molecular CLE in gastrointestinal diseases.     

Treatment of Crohn’s disease in pregnant women: Drug and multidisciplinary approaches

Inflammatory bowel disease affects a substantial number of women in their reproductive years. Pregnancy presents a number of challenges for clinicians and patients; the health of the baby needs to be balanced with the need to maintain remission in the mother. Historically, treatments for Crohn’s disease (CD) were often discontinued during the pregnancy, or nursing period, due to concerns about teratogenicity. Fortunately, observational data has reported the relative safety of many agents used to treat CD, including 5-aminosalicylic acid, thiopurines, and tumor necrosis factor. Data on the long-term development outcomes of children exposed to these therapies in utero are still limited. It is most important that physicians educate the patient regarding the optimal time to conceive, discuss the possible risks, and together decide on the best management strategy.     

Síndrome antissintetase: anti-PL-7, anti-PL-12 e anti-EJ

ObjectivesDue to the scarcity of studies in the literature, we conducted an analysis of a series of patients with the anti-PL-7, PL-12 and EJ types of antisynthetase syndrome (ASS).MethodsWe conducted a retrospective cohort study of 20 patients with ASS (8 with anti- PL-7, 6 with PL-12, 6 with EJ) monitored in our department between 1982 and 2012.ResultsThe mean patient age at disease onset was 38.5 ± 12.9 years, and the disease duration was 4.5 ± 6.4 years. Of all the patients, 70% were white and 85% were female. Constitutional symptoms occurred in 90% of cases. All patients presented objective muscle weakness in the limbs; in addition, 30% were bedridden and 65% demonstrated high dysphagia at diagnosis. Joint and pulmonary involvement and Raynaud's phenomenon occurred in 50%, 40% and 65% of cases, respectively, with more than half of the patients presenting incipient pneumopathy, ground-glass opacity and/or pulmonary fibrosis. There were no cases of neurological and/or cardiac involvement. All patients received prednisone or other immunosuppressants depending on tolerance, side effects and/or disease refractoriness. Importantly, patients with the anti-EJ type of ASS demonstrated higher rates of recurrence. Two patients died during follow-up, and 1 patient had breast cancer at the time of diagnosis.ConclusionsASS (anti-PL-7, PL-12 and EJ) was found to predominantly affect white women. Although the autoantibodies described in the present study are more related to pulmonary than joint involvement, our patients showed a significant percentage of both types of involvement and a high percentage of myopathy. We also observed a low mortality rate.