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BACKGROUND Infantile-onset inflammatory bowel disease (IO-IBD) occurs in very young children and causes severe clinical manifestations, which has poor responses to traditional inflammatory bowel disease (IBD) treatments. At present, there are no simple and reliable laboratory indicators for early screening IO-IBD patients, especially those in whom the disease is caused by monogenic diseases. AIM To search for valuable indicators for early identifying IO-IBD patients, especially those in whom the disease is caused by monogenic diseases. METHODS A retrospective analysis was performed in 73 patients with IO-IBD admitted to our hospital in the past 5 years. Based on the next-generation sequencing results, they were divided into a monogenic IBD group (M-IBD) and a non-monogenic IBD group (NM-IBD). Forty age-matched patients with allergic proctocolitis (AP) were included in a control group. The clinical manifestations and the inflammatory factors in peripheral blood were evaluated. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were used to identify the screening factors and cut-off values of IO-IBD as well as monogenic IO-IBD, respectively. RESULTS Among the 44 M-IBD patients, 35 carried IL-10RA mutations, and the most common mutations were c.301C>T (p.R101W, 30/70) and the c.537G>A (p.T179T, 17/70). Patients with higher serum tumor necrosis factor (TNF)-α value were more likely to have IBD [odds ratio (OR) = 1.25, 95% confidence interval (CI): 1.05-1.50, P = 0.013], while higher serum albumin level was associated with lower risk of IBD (OR = 0.86, 95%CI: 0.74-1.00, P = 0.048). The cut-off values of TNF-α and albumin were 17.40 pg/mL (sensitivity: 0.78; specificity: 0.88) and 36.50 g/L (sensitivity: 0.80; specificity: 0.90), respectively. The increased ferritin level was indicative of a genetic mutation in IO-IBD patients. Its cut-off value was 28.20 ng/mL (sensitivity: 0.93; specificity: 0.92). When interleukin (IL)-10 level was higher than 33.05 pg/mL (sensitivity: 1.00; specificity: 0.84), or the onset age was earlier than 0.21 mo (sensitivity: 0.82; specificity: 0.94), the presence of disease-causing mutations in IL-10RA in IO-IBD patients was strongly suggested. CONCLUSION Serum TNF-α and albumin level could differentiate IO-IBD patients from allergic proctocolitis patients, and serum ferritin and IL-10 levels are useful indicators for early diagnosing monogenic IO-IBD.

BACKGROUND Interleukin 10 receptor alpha subunit (IL10RA) dysfunction is the main cause of very early-onset inflammatory bowel disease (VEO-IBD) in East Asians. AIM To identify disease-causing gene mutations in four patients with VEO-IBD and verify functional changes related to the disease-causing mutations. METHODS From May 2016 to September 2020, four young patients with clinically diagnosed VEO-IBD were recruited. Before hospitalization, using targeted gene panel sequencing and trio-whole-exome sequencing (WES), three patients were found to harbor a IL10RA mutation (c.301C>T, p.R101W in one patient; c.537G>A, p.T179T in two patients), but WES results of the fourth patient were not conclusive. We performed whole-genome sequencing (WGS) on patients A and B and reanalyzed the data from patients C and D. Peripheral blood mononuclear cells (PBMCs) from patient D were isolated and stimulated with lipopolysaccharide (LPS), interleukin 10 (IL-10), and LPS + IL-10. Serum IL-10 levels in four patients and tumor necrosis factor-α (TNF-α) in the cell supernatant were determined by enzyme-linked immunosorbent assay. Phosphorylation of signal transducer and activator of transcription 3 (STAT3) at Tyr705 and Ser727 in PBMCs was determined by western blot analysis. RESULTS The four children in our study consisted of two males and two females. The age at disease onset ranged from 18 d to 9 mo. After hospitalization, a novel 333-bp deletion encompassing exon 1 of IL10RA was found in patients A and B using WGS and was found in patients C and D after reanalysis of their WES data. Patient D was homozygous for the 333 bp deletion. All four patients had elevated serum IL-10 levels. In vitro, IL-10-stimulated PBMCs from patient D failed to induce STAT3 phosphorylation at Tyr705 and only minimally suppressed TNF-α production induced by LPS. Phosphorylation at Ser727 in PBMCs was not affected by LPS or LPS + IL-10 in both healthy subjects and in patient D. CONCLUSION WGS revealed a novel 333-bp deletion of IL10RA in four patients with VEO-IBD, whereas the WES results were inconclusive.

Summary Emerging evidence has linked the exosomes to many immunological disorders, including infectious diseases. However, knowledge regarding the role of exosomes in Helicobacter pylori infection is limited. Here, we show that serum exosomes from chronic gastritis patients with H. pylori infection (Hp exosomes) stimulate the expression of the soluble interleukin (IL)-6 receptor (sIL-6R), which is involved in IL-6 trans-signalling in gastric epithelial cells. Interestingly, sIL-6R up-regulates expression of the proinflammatory cytokine IL-1α, and the neutralization of sIL-6R suppresses IL-1α secretion. Thus, Hp exosomes regulate IL-1α expression via sIL-6R-mediated IL-6 trans-signaling. Altogether, this study reveals a novel perspective in which exosomes play a vital role in immunological mechanisms during H. pylori infection.

To evaluate the effectiveness and complications of tension-free vaginal tape (TVT), transobturator tape (TOT), and tension-free vaginal tape-obturator (TVT-O) in a medium- to long-term follow up.We searched PubMed, EMBASE, Cochrane database, ClinicalTrials.gov, Google Scholar, and the International Continence Society (ICS) website from August to December 2012 in Guangzhou First People's Hospital, Guangzhou, China. Randomized controlled trials (RCTs) comparing the effectiveness and complications of TVT, TOT, and TVT-O were selected.Forty RCTs were included. The TVT and TOT had similar subjective (risk ratio [RR]: 0.99; 95% confidence interval [CI]: 0.93-1.04), and objective cure rates (RR: 0.96; 95% CI: 0.70-1.32). However, TVT had a reduced risk of groin/thigh pain (RR: 0.33; 95% CI: 0.18-0.59). The subjective (RR: 1.02; 95% CI: 0.97-1.06) and objective cure rates (RR: 1.02; 95% CI: 0.99-1.06) of TVT-O were similar to TVT, but TVT had a higher risk of bladder perforations (RR: 2.29; 95% CI: 1.18-4.45). The TVT-O and TOT had similar subjective (RR: 0.99; 95% CI: 0.93-1.06), and objective cure rates (RR: 1.01; 95% CI: 0.95-1.07). However, TVT-O had a lower risk of vaginal erosion rates (RR: 0.16; 95% CI: 0.03-0.89).The subjective and objective cure rates of stress urinary incontinence were similar among TVT, TOT, and TVT-O in a medium- to long-term follow up. The TVT had a higher risk of bladder perforation than TVT-O, and a lower risk of groin/thigh pain than TOT, and TVT-O had a lower risk of vaginal erosion rates than TOT.