关键词： Risk assessment  

摘要： Inflammatory bowel disease (IBD) is a term used to describe disorders that involve chronic inflammation in the gastrointestinal tract, affecting more than 6.8 million people worldwide. Biological therapy is used in the most severe cases of IBD where anti-tumour necrosis factor-alpha (TNF-alpha) antibodies are the first choice for a biological treatment. When administrated to patients, these antibodies interact with TNF-alpha, usually overexpressed in these diseases, neutralizing its biological activity. Because of the chronic nature of these diseases, a recurring administration of the therapeutic antibodies is required, thus making therapy monitorization essential for the correct management of these diseases. The aim of this work is the development of an enzyme-linked immunosorbent assay (ELISA) microfluidic biosensor to quantify the therapeutic antibodies in IBD patient plasma samples, where the commercial monoclonal antibody Infliximab (IFX) is used as a model target. By providing a faster and more accurate measurement of IFX, the proposed method leads to improved therapy scheduling and a reduced risk of endogenous anti-drug antibodies (ADAs) reducing the efficacy of the treatment. The time needed between sample insertion and result output for the microfluidic ELISA (mELISA) is 24 minutes, drastically shorter than the time required by the conventional ELISA (cELISA). The mELISA presented in this work has a LoD of 0.026 mu g mL(-1), while commercially available solutions provide a LoD of 0.15 mu g mL(-1). Results acquired by the mELISA are highly correlated with the results obtained from the cELISA (r = 0.998;R-2 = 0.996;p < 0.0001), demonstrating the validity of the microfluidic approach for the quantification of IFX from patient plasma and its potential for use at the point-of-care (POC).

关键词： 手术室护理   肛肠   切口愈合   并发症   发生率   最大收缩压  

摘要： 目的:探究手术室护理在肛肠疾病手术患者中的应用效果.方法:本次纳入86例患者,时间2018年4月至2020年6月,随机数表法分为对照组(行常规护理)与观察组(行手术室护理).比较两组护理效果.结果:观察组切口愈合时间(13.19±1.75)d、切口肉芽生长(0.72±0.08)分、VAS(2.34±0.34)分均低于对照组(17.68±2.34)d、(1.24±0.27)分、(4.11±0.59)分(P<0.05);护理后,观察组肛管静息压(11.27±1.35)kPa低于对照组(12.31±1.78)kPa、对照组最大收缩压(18.19±2.47)kPa低于观察组(21.68±3.14)kPa(P<0.05);观察组并发症发生率6.51％低于对照组23.91％(P<0.05).结论:手术室护理在该疾病患者中效果显著.

关键词： Oxygen  

摘要： Inflammatory bowel disease (IBD) is related to excessive reactive oxygen species (ROS) and high expression of proinflammatory cytokines. An enzymatically active drug carrier that can simultaneously scavenge excessive ROS and deliver anti-inflammatory drugs to inhibit the production of inflammatory cytokines may lead to improved therapeutic effects. Herein, nanoparticles (NPs) that can target activated macrophages, remove ROS and release anti-inflammatory drugs are fabricated by loading budesonide (Bud) into dextran sulfate sodium (DSS)-coated hollow mesoporous manganese dioxide (hMnO(2)) NPs. This strategy can treat IBD better through the synergistic effect of the ROS-scavenging hMnO(2) carriers and anti-inflammatory drug by blocking the amplification effect of inflammation. In addition, compared with free Bud, the drug delivery system can reduce side effects of Bud and improve its treatment outcome at the same dosage. Therefore, this study provides a new method for the design of highly effective synergistic anti-inflammatory nanomedicines.

关键词： Liver   Elastase   Duodenum   Inflammatory bowel disease  

摘要： Elastase, a serine protease, plays important roles in our body in food digestion and defence against pathogens. Particularly, the elastase present in neutrophils is directly associated with inflammatory bowel disease (IBD). Through a rational approach, we have developed a fluorescent elastase probe that has multiple advantages for biological applications including two-photon ratiometric imaging capability. Using the probe, which is capable of detecting intracellular elastase activity associated with inflammation, we have investigated elastase level changes in various mouse organs under an IBD condition for the first time. The results reveal notably higher elastase levels in the liver and duodenum of the healthy mice than in the other investigated organs. Under the IBD condition, we observed significant elastase level changes in the liver, duodenum, colon, and lung. The downregulation of elastase in the liver under the IBD condition suggests migration of neutrophils into the upregulated organs. The notable upregulation of elastase in the duodenum is explained by self-production of elastase, in addition to the neutrophil migration from the liver. We have observed little elastase level changes in selected organs of immune-deficient mice raised under the normal and IBD conditions, which supports the neutrophil migration as the reason for perturbed elastase activity in the healthy mice. The results also suggest an important role of the liver in maintaining the immune response associated with the inflammation-induced elastase level changes. The probe offers an ideal tool for mapping neutrophil migration in body. Further understanding of the elastase-associated biology and diagnosis of IBD by monitoring affected organs are anticipated using the probe.

摘要： Inflammatory bowel disease (IBD) is a chronic inflammatory condition of gastrointestinal (GI) tract with dysregulated mucosal immune functions and disturbed commensal ecosystem of the intestinal lumen. IBD is categorized into two major subsets: Crohn's disease (CD) and ulcerative colitis (UC). Though advent of biologics has shifted the treatment with relatively longer remission compared to small molecule pharmaceuticals, patients still suffer from long-term complications. Since gut-microbiome is now accepted as another human organ holding potential for long-lasting human health, probiotics, and its engineering hold great promises to treat several previously untreatable chronic inflammatory conditions including IBD. Several emerging biological engineering tools have unlimited potential to manipulate probiotic bacterial system. These can produce useful therapeutic biologics with a goal to either ameliorate and/or treat previously untreatable chronic inflammatory conditions. As gut-microbiome is diverse and vary in different ethnic, geographic, and cultural human population, it will be important to develop vision for personalized probiotic treatment and develop the technology thereof to make personalized probiotic options a reality. The aim of this review paper is to present an overview of the current knowledge on both pharmacological and nonpharmacological IBD treatment modalities with a special emphasis on probiotic strains that are developed through the probiotic engineering. These engineered probiotics contain the most anti-inflammatory cytokines found within the human immune response and are currently being used to treat the intestinal inflammation in IBD for the IBD treatment.

关键词： Assays   Rodent models   Inhibitors   Inhibition   Peptides and proteins  

摘要： Inflammatory bowel disease (IBD) is a multifactorial autoimmune disease, representing a major clinical challenge. Herein, a strategy of dual-targeting approach employing retinoic acid receptor-related orphan receptor gamma-t (ROR gamma t) and dihydroorotate dehydrogenase (DHODH) was proposed for the treatment of IBD. Dual ROR gamma t/DHODH inhibitors are expected not only to reduce ROR gamma t-driven Th17 cell differentiation but also to mitigate the expansion and activation of T cells, which may enhance anti-inflammatory effects. Starting from 2-aminobenzothiazole hit 1, a series of 2-aminotetrahydrobenzothiazoles were discovered as potent dual ROR gamma t/DHODH inhibitors. Compound 14d stands out with IC50 values of 0.110 mu M for ROR gamma t and of 0.297 mu M for DHODH. With acceptable mouse pharmacokinetic profiles, 14d exhibited remarkable in vivo anti-inflammatory activity and dose-dependently alleviated the severity of dextran sulfate sodium (DSS)-induced acute colitis in mice. Taken together, the present study provides a novel framework for the development of therapeutic agents for the treatment of IBD.

关键词： Life expectancy   Medication   Inflammatory bowel disease   Elderly   Mortality   Pharmacoepidemiology   Health administrative data  

摘要： Background Life expectancy in people with inflammatory bowel disease (IBD) has increased but remains shorter than in people without IBD. We describe the life expectancy associated with IBD therapies among the growing number of older adults living with IBD. Methods Older adults (>= 65 years) with IBD were identified from population-based health administrative data using a validated algorithm. Life expectancy on patients' 65th birthday, stratified by sex, was calculated using a period life table approach from age- and sex-specific mortality rates among patients receiving immunomodulator monotherapy, biologic monotherapy, combination therapy, mesalamine, systemic steroids, and no therapy. Results Among 28,260 older adults with IBD (239,125 person-years of follow-up), life expectancy at 65 years was longest for patients taking mesalamine (females: 22.1 years, 95% CI 21.8-22.5;males: 19.6 years, 95% CI 19.3-20.0) and shortest for patients taking steroids (females: 11.7 years, 95% CI 11.0-12.4;males 10.3 years, 95% CI 9.7-10.8). Life expectancy was similar for patients receiving immunomodulator monotherapy and biologic monotherapy. Immunomodulator monotherapy was associated with a reduction in life expectancy compared to combination therapy by 5.1 (95% CI 2.3-7.8) in females and 2.8 years (95% CI 0.1-5.5) in males. Conclusions Life expectancy varies across therapies used for IBD, with differences likely arising from a combination of medication effectiveness, safety profiles, disease severity, and comorbid conditions. These considerations should be balanced when deciding on a therapeutic approach for the management of IBD in older adults.

关键词： Inflammatory bowel disease   Depression   Neuroinflammation   Gut-brain axis  

摘要： Patients with inflammatory bowel disease (IBD) suffer from depression at higher rates than the general population. An etiological trigger of depressive symptoms is theorised to be inflammation within the central nervous system. It is believed that heightened intestinal inflammation and dysfunction of the enteric nervous system (ENS) contribute to impaired intestinal permeability, which facilitates the translocation of intestinal enterotoxins into the blood circulation. Consequently, these may compromise the immunological and physiological functioning of distant non-intestinal tissues such as the brain. In vivo models of colitis provide evidence of increased blood-brain barrier permeability and enhanced central nervous system (CNS) immune activity triggered by intestinal enterotoxins and blood-borne inflammatory mediators. Understanding the immunological, physiological, and structural changes associated with IBD and neuroinflammation may aid in the development of more tailored and suitable pharmaceutical treatment for IBD-associated depression.