摘要： Mutations and single base pair polymorphisms in various genes have been associated with increased susceptibility to inflammatory bowel disease (IBD). We have created a series of rat strains carrying targeted genetic alterations within three IBD susceptibility genes: Nod2, Atg16l1, and Il23r, using CRISPR/Cas9 genome editing technology. Knock-out alleles and alleles with known human susceptibility polymorphisms were generated on three different genetic backgrounds: Fischer, Lewis and Sprague Dawley. The availability of these rat models will contribute to our understanding of the basic biological roles of these three genes as well as provide new potential IBD animal models.

关键词： consensus   diagnosis   inflammatory bowel diseases   treatment  

关键词： NLRP3   Inflammatory bowel disease   Small molecule inhibitor   Targeted therapy  

摘要： The incidence and prevalence of inflammatory bowel disease (IBD) are increasing worldwide. Current approved medication for IBD treatment in the clinic mainly includes corticosteroids and neutralization antibodies to proinflammatory cytokines. However, drug resistance and severe side effect hinder long-term efficacy of these agents. The NOD-like receptor family pyrin domain containing protein 3 (NLRP3) is exclusively expressed in several inflammatory and autoimmune diseases. Excessive expression, aberrant activation, polymorphism, and gain-of-function mutation of the NLRP3 inflammasome contribute to IBD pathogenesis. In this article, we summarize the regulatory factors to NLRP3, and review recently developed NLRP3 inhibitors and their preclinical and clinical applications in treating inflammatory and autoimmune diseases. We present our views on the therapeutic potential of NLRP3 inhibitors as emerging therapeutic avenue for IBD.

关键词： anorectal diseases   functional constipation   irritable bowel syndrome   transcutaneous acupoint elect  

摘要： In recent years, transcutaneous electrical stimulation of apical apex (TAES) has received more and more attention and has been gradually applied to various anorectal diseases to treat postoperative pain relief, postoperative urinary retention, functional constipation, irritable bowel syndrome, etc. Is easy to operate, low in cost and worthy of clinical promotion. However, in the future research, the frequency setting and acupoint selection during the treatment should be scientifically standardized, so that the technology can better serve the clinical practice.

摘要： Inflammatory bowel disease (IBD) that presents in children <6 years of age is known as very early-onset IBD (VEO-IBD). Extraintestinal manifestations in IBD, such as erythema nodosum (EN), pyoderma gangrenosum (PG), and, less likely, leukocytoclastic vasculitis (LV), are more commonly present in Crohn's disease. Association between LV and ulcerative colitis (UC) is not commonly seen. We report a case of a 6-year-old female with a VEO-IBD UC phenotype presenting with multiple episodes of leukocytoclastic vasculitis, each preceded by streptococcal pharyngitis. Prior to the diagnosis of VEO-IBD, a skin biopsy was obtained and had shown leukocytoclastic vasculitis with a negative IgA stain. Initial laboratory results were remarkable for leukocytosis and increased anti-strep O and anti-DNase B titers. Gastrointestinal panel PCR demonstrated Clostridium difficile toxin A/B. Treatment for LV consisted of methylprednisolone IV 20 mg for four days with a weaning schedule of prednisolone for two weeks and naproxen 250 mg BID for three days. Clostridium difficile was treated with metronidazole 250 mg TID for ten days. She remained stable for three years until she presented with continuous bloody stools, newly onset chest pain, and shortness of breath. Computed tomography angiogram (CTA) was normal. Stool calprotectin was elevated at 658 mcg/gm. Abdominal magnetic resonance enterography (MRE), esophagogastroduodenoscopy, and colonoscopy confirmed a VEO-IBD ulcerative colitis phenotype. She was started on infliximab 10 mg/kg every four weeks after infliximab titers, and antibodies were obtained. Currently, the patient remains on clinical and biochemical remission, with no recent LV episodes or recurrence of streptococcal pharyngitis. Our patient is unique as no case report has been published with multiple episodes of leukocytoclastic vasculitis in association with a VEO-IBD UC phenotype.

关键词： Inflammatory bowel disease   Ulcerative colitis   Crohn's disease   Neurological   Stroke   Cerebral venous thrombosis   Demyelinating   Epilepsy   Neuropathy   Myopathy Anti-TNF-alpha  

摘要： Inflammatory bowel diseases (IBD) are chronic inflammatory conditions affecting the digestive system, comprising two main distinctive entities, ulcerative colitis (UC) and Crohn's disease (CD). Besides gastrointestinal manifestations, IBD causes extraintestinal manifestations in the central and peripheral nervous system. The incidence of neurological complications in IBD ranges from 0.25% to 47.5%. The pathophysiology of neurological manifestations of IBD is mostly immune mediated, but dysfunction of the brain-gut axis, arterial and venous thromboembolism, infections, nutritional deficiencies and side-effects of medications (steroids, metronidazole, sulfasalazine, anti-TNF-alpha, anti-integrin antibodies) are other contributory mechanisms. Patients with IBD have an increased risk of arterial and venous stroke, mainly during periods of exacerbations. Vasculitis is extremely rare. There is a bidirectional association between multiple sclerosis and IBD, with a relative risk for comorbidity of 1.54, being 1.53 for the risk of multiple sclerosis in IBD and 1.55 for the risk of IBD in multiple sclerosis patients. Anti-TNF-alpha therapy is contraindicated in the treatment of patients who have both IBD and multiple sclerosis. Demyelinating disorders can also be a rare complication of anti-TNF-alpha therapy. Optic neuritis, transverse myelitis, progressive myelopathy, central nervous system infections, epilepsy and encephalopathy are among other uncommon neurological complications. Peripheral nervous system manifestations include peripheral neuropathy, either demyelination and axonal, myasthenia gravis and polymyositis/dermatomyositis and localized forms of myositis.

关键词： Linagliptin   Colitis   Inflammation   Oxidative stress   Dipeptidyl peptidase-4  

摘要： Aims: Dipeptidyl peptidase-4 (DPP-4) has been involved in the pathogenesis of inflammatory bowel diseases (IBD), yet the underlying mechanisms remain inconclusive. The present study aimed to investigate the potential of linagliptin, a potent/selective DPP-4 inhibitor with marked anti-inflammatory actions, to attenuate trinitrobenzene sulfonic acid (TNBS)-evoked colitis in rats;an experimental model of IBD, and the implicated molecular mechanisms. This may add to the clinical utility of linagliptin for the management of patients with coexisting IBD and diabetes mellitus. Notably, no former studies have linked JAK2/STAT3, HMGB1/NF kappa B, and Nrf2/HO-1 signaling in TNBS-evoked colitis. Materials and methods: Western blotting and ELISA were used to determine the levels of target signals. Key findings: Administration of linagliptin (1.5 mg/kg;p.o.) mitigated the colitis severity via diminishing the disease activity index, colon weight/length ratio, and macroscopic scores. Linagliptin also lowered the colonic histologic scores and leukocyte invasion. Notably, linagliptin inhibited the colonic DPP-4 activity and upregulated the expression of intestinotrophic GLP-2 without incurring hypoglycemia in animals. Linagliptin curbed inflammation through the suppression of colonic IL-6, TNF-alpha, and myeloperoxidase and upregulation of IL-10. It also inhibited the IL-6/JAK2/STAT3 pathway via downregulating p-JAK2/JAK2 and p-STAT3/STAT3 protein expression and HMGB1/RAGE/NF-kappa B cascade through lowering HMGB1, RAGE, and p-NF-kappa B p65/NF-kappa B p65 protein expression. In the context of mucosal oxidative stress, linagliptin diminished lipid peroxides and augmented GSH, GPx, and total antioxidant capacity. It also activated Nrf2/HO-1 pathway via upregulating Nrf2 and HO-1 protein expression. Significance: Linagliptin shows a promise for the management of IBD via targeting IL-6/JAK2/STAT3, HMGB1/ RAGE/NF-kappa B, and Nrf2/HO-1 pathways.

关键词： Inflammatory bowel disease   Crohn’   s disease   Ulcerative colitis   Emergency surgery   Perianal sepsis   Toxic megacolon   Peritonitis   Perforation   Percutaneous drainage   Abscess   SILS   Laparoscopy   Damage control surgery   Open abdomen  

摘要： Background Despite the current therapeutic options for the treatment of inflammatory bowel disease, surgery is still frequently required in the emergency setting, although the number of cases performed seems to have decreased in recent years. The World Society of Emergency Surgery decided to debate in a consensus conference of experts, the main pertinent issues around the management of inflammatory bowel disease in the emergent situation, with the need to provide focused guidelines for acute care and emergency surgeons. Method A group of experienced surgeons and gastroenterologists were nominated to develop the topics assigned and answer the questions addressed by the Steering Committee of the project. Each expert followed a precise analysis and grading of the studies selected for review. Statements and recommendations were discussed and voted at the Consensus Conference of the 6th World Society of Emergency Surgery held in Nijmegen (The Netherlands) in June 2019. Conclusions Complicated inflammatory bowel disease requires a multidisciplinary approach because of the complexity of this patient group and disease spectrum in the emergency setting, with the aim of obtaining safe surgery with good functional outcomes and a decreasing stoma rate where appropriate.