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Objectives: Although colonoscopy remains the gold standard for determining bowel diseases, it's invasive and expensive. New non-invasive diagnostic methods are urgently needed as an initial screening modality. We aimed to investigate the value of fecal calprotectin (FC) and fecal immunochemical test (FIT) in differentiation of significant and non- significant bowel diseases., Methods: In this prospective study, consecutive individuals were included if they underwent colonoscopy for symptoms of lower gastrointestinal (GI) tract, positive fecal occult blood test, surveillance for IBD or colorectal cancer (CRC) screening. Diagnostic value of FC and FIT in discriminating significant bowel diseases (advanced neoplasia, active inflammatory bowel diseases or bowel inflammation due to other causes) and non-significant bowel diseases (normal, asymptomatic diverticulum, non-adenomatous polyp, or non-advanced neoplasia) were evaluated., Results: Among 201 individuals included, 107 patients had significant bowel diseases. FC and FIT had an area under the curve (AUC) of 0.722 (95% confidence interval [CI] 0.653-0.792) and 0.797 (95%CI 0.734-0.860), respectively, for determining significant bowel diseases. Combination of FC and FIT predicted significant bowel diseases with an AUC, sensitivity, specificity, and accuracy of 0.832 (95% CI 0.775-0.890), 77.6%, 74.5%, and 76.1%, respectively. Moreover, combination of FC and FIT was more sensitive among patients with lower GI symptoms than asymptomatic individuals (80.8% vs. 74.1%) to identify significant bowel diseases., Conclusions: A single measurement of FC or FIT is not sufficiently accurate to identify patients with significant bowel disease. However, combination of FC and FIT can help increase the sensitivity, especially in patients with lower GI symptoms.

The proinflammatory effects of IL12p40 had been documented in the literature, and anti-IL12p40 treatment had been proved to be effective in therapy of Crohn disease (CD) in a phase 2b clinical trial. However, the precise role of IL12p40 in the pathogenesis of inflammatory bowel disease (IBD) was still poorly understood. In this study, we investigated the expressions of IL12p40 and its receptor interleukin-12 receptor β 1 both locally and systemically in IBD cases and healthy controls, and the contribution of IL12p40 in IBD pathogenesis. We found that the expression of IL12p40 was elevated both at messenger RNA and protein levels systematically and locally in IBD patients but more significantly in CD patients. Our genetic association study revealed that the polymorphisms of IL12B rs6887695 were associated with both CD and ulcerative colitis (UC) susceptibility in Chinese population, but did not affect the serum IL12p40 level in either CD patients or UC patients. In addition, CD4⁺ T cells isolated from peripheral blood of CD patients secreted the most abundant IL12p40 production, compared with the UC patients and healthy controls. We also found for the first time that neutralizing IL12p40 secretion could inhibit proliferation, enhance apoptosis, induce a G0/G1 arrest, restrain T helper 1 type immune responses, and promote chemokine C-C motif ligand 20-mediated migration of human CD4⁺ T cells, which might be the mechanisms why anti-IL12p40 treatment presented efficacy in CD.

The prevalence of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is increasing markedly in China. The present study performed pedigree analysis of 4 families with a history of IBD and investigated the association of genetic and environmental factors with susceptibility to IBD. A total of 10 IBD patients (8 CD patients and 2 UC patients) and 90 family members were included in the present study. The clinical characteristics of familial subjects were compared with those of patients with sporadic IBD. Previously reported mutations, namely interleukin-10 receptor (IL10R)-A Thr84Ile, IL10RA Gly141Arg, IL10RB Trp159X, X-linked inhibitor of apoptosis (XIAP) Cys203Tyr, nucleotide-binding oligomerization domain-containing protein 2 (NOD2) Arg702Trp, NOD2 Gly908Arg and NOD2 Leu1007fsinsC, were screened in the patients with IBD, and selected demographic factors were compared between the patients and their unaffected family members. It was observed that single-gene and multi-gene inheritance patterns contributed to IBD in Chinese families. Based on data from the registry system, the ratio of patients with a family history of IBD was 1.25%, which was lower than that in the Western population. First-degree relatives were found to be more susceptible to IBD, and siblings were affected more frequently. Furthermore, the median age of diagnosis was younger in familial patients than in sporadic patients (29.0 vs. 36.0 for CD; 35.5 vs. 41.0 for UC). However, none of the 7 susceptibility loci were present in any of the familial patients. Immigration was a significant risk factor of IBD (odds ratio: 4.667; 95% confidence interval: 1.165-18.690; P=0.021). In conclusion, genetic heterogeneity exits between Chinese families with IBD and the Western population. The present findings suggest that genetic background and environmental factors serve a role in the pathogenesis of IBD. [ABSTRACT FROM AUTHOR]