Our study expands the current knowledge on the genotype-correlated phenotypes with a defect of IL10 signaling. B-cell lymphoma was more frequent than would be expected in patients with IL10RB mutations. There may be a unique genetic architecture among Eastern Asia compared with other populations. Although allogeneic HSCT represents a causal therapeutic approach for IL10-and IL10R-deficient patients, a word of caution is warranted.
Backgrounds Due to the decreasing eradication rate of Helicobacter pylori, some novel alternatives have been developed, such as bismuth‐containing quadruple therapy and non‐bismuth‐containing quadruple therapy (sequential and concomitant treatment). Little is known about whether a success rate above 90% can be achieved with these regimens in Chinese children. Methods In this prospective, open, comparative cross‐sectional study, we recruited treatment‐naïve children (aged between 6 and 18 years) with H pylori infection. The patients were assigned either standard triple therapy, sequential therapy, bismuth‐based quadruple therapy, or concomitant therapy at the discretion of the prescribing physician. H pylori infection was evaluated at least 4 weeks after the completion of the treatment. A negative urea breath test (UBT) indicated successful eradication. The primary endpoint was the eradication frequency of H pylori in the full analysis set (FAS), which included all children who received at least one dose of the treatment and with available follow‐up data. Results Between September 2017 and December 2018, 228 patients were finally included in the FAS analyses. The eradication rates were 74.1% for standard triple therapy (43/58, [95% CI: 62.8%‐85.5%]), 69.5% for sequential therapy (41/59, [95% CI: 57.8%‐81.2%]), 89.8% for bismuth‐based quadruple therapy (53/59, [95% CI: 82.1%‐97.5%]), and 84.6% for concomitant therapy (44/52, [95% CI: 74.8%‐94.4%]). Bismuth‐based therapy was superior to triple therapy, while sequential therapy and concomitant therapy were not superior to triple therapy. The frequency of adverse events was 12.1% (7/58) in standard triple therapy, 6.8% (4/59) in sequential therapy, 15.3% (9/59) in bismuth‐based therapy, and 15.4% (8/52) in concomitant therapy. The rate of adverse events was similar among the four groups. Conclusion Bismuth quadruple therapy can achieve an eradication rate of 89.8% as first‐line treatment and is safe and well tolerated. Bismuth could be a promising alternative as a first‐line regimen in Chinese children.
AIMTo determine whether cell division cycle (Cdc)42 is regulated by microRNA (miR)-15a in the development of pediatric inflammatory bowel disease (IBD).METHODSWe cultured 293T cells, used plasmids and performed dual-luciferase assay to determine whether Cdc42 is a miR-15a target gene. We cultured Caco-2 cells, and stimulated them with tumor necrosis factor (TNF)-α. We then employed lentiviruses to alter the expression of miR-15a and Cdc42. We performed quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunofluorescence to determine whether Cdc42 is regulated by miR-15a in Caco-2 cells. Finally, we collected ileocecal tissue by endoscopy from patients and performed qRT-PCR to examine the expression of miR-15a and Cdc42 in pediatric IBD patients.RESULTSTarget Scan and dual-luciferase assay revealed that Cdc42 was a miR-15a target gene. MiR-15a expression increased (P = 0.0038) and Cdc42 expression decreased (P = 0.0013) in cells stimulated with TNF-α, and the expression of the epithelial junction proteins zona occludens (ZO)-1 (P < 0.05) and E-cadherin (P < 0.001) decreased. Cdc42 levels decreased in miR-15a-mimic cells (P < 0.001) and increased in miR-15a inhibitor cells (P < 0.05). ZO-1 and E-cadherin decreased in miR-15a-mimic cells (P < 0.001) but not in the miR-15a inhibitor + TNF-α cells. In Lv-Cdc42 + TNF-α cells, ZO-1 and E-cadherin expression increased compared to the Lv-Cdc42-NC + TNF-α (P < 0.05) or miR-15a-mimic cells (P < 0.05). Fifty-four pediatric IBD patients were included in this study, 21 in the control group, 19 in the Crohn’s disease (CD) active (AC) group, seven in the CD remission (RE) group, and seven in the ulcerative colitis (UC) group. MiR-15a increased and Cdc42 decreased in the CD AC group compared to the control group (P < 0.05). miR-15a decreased and Cdc42 increased in the CD RE group compared to the CD AC group (P < 0.05). miR-15a was positively correlated with the Pediatric Crohn’s disease Activity Index (PCDAI) (P = 0.006), while Cdc42 was negatively correlated with PCDAI (P = 0.0008). Finally, miR-15a expression negatively correlated with Cdc42 in pediatric IBD patients (P = 0.0045).CONCLUSIONMiR-15a negatively regulates epithelial junctions through Cdc42 in Caco-2 cells and pediatric IBD patients.
Patients with infantile-onset IBD had severe phenotype and early onset. Medical, surgical interventions with supportive care are essential. High-throughput sequencing ensures appropriate treatment. Hematopoietic stem cell transplantation can be performed in selected patients with IL10RA mutations (see Video Abstract, Supplemental Digital Content 1, http://links.lww.com/IBD/B657).
Background:The aim of this study was to prospectively study the effect of exclusive enteral nutrition (EEN) treatment on Chinese pediatric Crohn's disease (CD) patients. Methods: Thirty-one newly diagnosed CD patients were enrolled in this study and treated with EEN for 8 weeks. Twelve healthy controls (HCs) donated their fecal samples. Statistical methods were used to compare the differences. Results: According to the Simple Endoscopic Score for CD (SES-CD) at the end of the EEN treatment, 21 patients with SES-CD ≤4 were classified into the remission group (CD-RE), and 10 patients with SES-CD >4 were classified into the nonremission group (CD-NRE). After EEN therapy, there was a significant decrease in the SES-CD, the weighted Pediatric Crohn's Disease Activity Index (wPCDAI), and fecal calprotectin (FCP) in the CD-RE group (all P < .001). The wPCDAI and FCP also decreased in the CD-NRE group (both P < .05). In terms of nutrition improvement, the CD-RE group patients showed more improvement in weight gain, hemoglobin, and serum albumin level than the CD-NRE group patients (all P < .05). For the microbiota, the CD patients had a lower bacterial diversity and different bacterial community compared with HCs. EEN increased overall diversity and was able to shift the dysbiosis in CD patients toward a healthier state. Absence of improvement in wPCDAI and Shannon index at 2 weeks predicts poor response at the end of EEN. Conclusion: EEN can be used in most Chinese pediatric CD patients to induce remission and improve nutrition.
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