BackgroundDisease severity, illness perceptions, coping strategies, stress, psychological well-being, and quality of life were reported to have close relationships. According to the Common Sense Model, illness perceptions and coping strategies could mediate the relationship between illness stimuli and illness outcomes such as psychological health and quality of life. Stress was also associated with the individual’s disease severity, anxiety, depression, and quality of life.ObjectivesThe study aimed to explore the influencing factors of illness outcomes, and to what extent illness perceptions, coping strategies, and stress mediate the relationship between disease severity and anxiety, and depression and quality of life.MethodsOur study included 159 patients with Crohn’s disease who were attending a tertiary hospital outpatient clinic or who were hospitalized. Disease severity was measured with the Crohn’s Disease Activity Index. Illness perceptions were measured with the Brief Illness Perceptions Questionnaire. Coping strategies were measured with the Carver Brief Coping Questionnaire. Stress was measured with the Perceived Stress Questionnaire. Anxiety and depression were measured with the Hospital Anxiety and Depression Scale. Quality of life was measured with the Inflammatory Bowel Disease Questionnaire.ResultsDisease severity, illness perceptions, maladaptive coping, stress, anxiety, depression and quality of life were significantly correlated with each other among patients with Crohn’s disease. Using structural equation modeling to describe the inner relationship of the aforementioned variables, an excellent-fitted model was drawn. (χ2[10]=13.83, P=0.18, χ2/N=1.38, standardized root mean square residual [SRMR] <0.05, root mean square error of approximation [RMSEA] <0.05, goodness of fit index [GFI] >0.97, comparative fit index [CFI] >0.99). Disease severity had a direct influence on illness perceptions. Illness perceptions had a direct influence on stress. Both illness perceptions and stress had direct influences on anxiety, depression, and quality of life, while maladaptive coping did not directly influence anxiety, depression, or quality of life. Stress had a direct influence on maladaptive coping. Quality of life was also directly influenced by disease severity and anxiety.ConclusionInterrelationships between disease stimuli, disease perceptions and management and disease outcomes could be found in patients with Crohn’s disease. Illness perceptions and stress mediated an individual’s disease severity and anxiety, depression and quality of life, while coping strategy was not an applicable mediator.

It has been established that mammalian target of Rapamycin (mTOR) inhibitors have anti-inflammatory effects in models of experimental colitis. However, the underlying mechanism is largely unknown. In this research, we investigate the anti-inflammatory effects of AZD8055, a potent mTOR inhibitor, on T cell response in dextran sulfate sodium (DSS)-induced colitis in mice, a commonly used animal model of inflammatory bowel diseases (IBD). Severity of colitis is evaluated by changing of body weight, bloody stool, fecal consistency, histology evaluation and cytokine expression. We find that AZD8055 treatment attenuates DSS-induced body weight loss, colon length shortening and pathological damage of the colon. And AZD8055 treatment decreases colonic expression of genes encoding the pro-inflammatory cytokines interferon-γ, interleukin (IL)-17A, IL-1β,IL-6 and tumor necrosis factor(TNF)-a and increases colonic expression of anti-inflammatory cytokines IL-10. We show that AZD8055 treatment decreases the percentages of CD4+ T cells and CD8+ T cells in spleen, lymph nodes and peripheral blood of mice. We also find that AZD8055 treatment significantly reduces the number of T helper 1(TH1) cells and TH17 cells and increases regulatory T (Treg) cells in the lamina propria and mesenteric lymph nodes. Furthermore, we demonstrates that AZD8055 suppresses the proliferation of CD4+ and CD8+ T cells and the differentiation of TH1/TH17 cells and expands Treg cells in vitro. The results suggest that, in experimental colitis, AZD8055 exerts anti-inflammatory effect by regulating T helper cell polarization and proliferation.

Neddylation, a newly identified post-translational modification, is significant for the activity and stability of target proteins. The exact role of neddylation in the pathogenesis of inflammatory bowel disease, specifically those mediated by dendritic cells (DCs), was still rarely reported. Here, we showed that inhibition of neddylation protected mice from mucosal inflammation. Targeting neddylation also inhibited DC maturation characterized by reduced cytokine production, down-regulated costimulatory molecules and suppressed capacity in allogeneic T cell stimulation. Additionally, inactivation of neddylation promotes caspase dependent apoptosis of DCs. These phenomena were attributed to the inactivation of mTOR, which was caused by Cullin-1 deneddylation induced Deptor accumulation. Together, our findings revealed that neddylation inhibition suppressed DC functions through mTOR signaling pathway and provided a potential therapeutic opportunity in inflammatory bowel diseases.

AIMTo evaluate the usefulness of different parameters to differentiate Crohn’s disease (CD) from primary intestinal lymphoma (PIL).METHODSThe medical records of 85 patients with CD and 56 patients with PIL were reviewed retrospectively. Demographic, clinical, laboratory, endoscopic, and computed tomographic enterography (CTE) parameters were collected. The univariate value of each parameter was analyzed. A differentiation model was established by pooling all the valuable parameters. Diagnostic efficacy was analyzed, and a receiver operating characteristic (ROC) curve was plotted.RESULTSThe demographic and clinical parameters that showed significant values for differentiating CD from PIL included age of onset, symptom duration, presence of diarrhea, abdominal mass, and perianal lesions (P < 0.05). Elevated lactate dehydrogenase and serum β2-microglobulin levels suggested a PIL diagnosis (P < 0.05). The endoscopic parameters that showed significant values for differentiating CD from PIL included multiple-site lesions, longitudinal ulcer, irregular ulcer, and intraluminal proliferative mass (P < 0.05). The CTE parameters that were useful in the identification of the two conditions included involvement of ≤ 3 segments, circular thickening of the bowel wall, wall thickness > 8 mm, aneurysmal dilation, stricture with proximal dilation, “comb sign”, mass showing the “sandwich sign”, and intussusceptions (P < 0.05). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the differentiation model were 91.8%, 96.4%, 93.6%, 97.5%, and 88.5%, respectively. The cutoff value was 0.5. The area under the ROC curve was 0.989.CONCLUSIONThe differentiation model that integrated the various parameters together may yield a high diagnostic efficacy in the differential diagnosis between CD and PIL.