A narrative review on the role of genetics in children with acute recurrent pancreatitis and chronic pancreatitis.

The incidence of pancreatitis in children has increased over the past two decades. With advances in molecular biological techniques and clinical research, genetic variations have emerged as a pivotal etiological factor in pediatric pancreatitis. This review aims to summarize recent clinical research advancements in understanding pediatric pancreatitis caused by various gene mutations. As of the year 2020, researchers had identified 12 genes implicated in the pathogenesis of pancreatitis. These genes primarily contributed to the development of pancreatitis through three mechanisms. Pancreatitis resulting from these gene mutations exhibits several distinct characteristics, including early onset, a heightened risk of developing pancreatic duct stones, rapid disease progression, and a significantly increased risk of pancreatic endocrine and exocrine dysfunction, as well as pancreatic cancer in the future. Genetic sequencing is recommended for children with pancreatitis based on six indications. The sequencing not only assists in the clinical diagnosis but also enhances our understanding of the pathophysiology of pancreatitis.

[Association between drug trough concentration and disease outcome before infliximab maintenance treatment in children with Crohn's disease]. / å ‹ç½—æ©ç— æ‚£å„¿è‹±å¤«åˆ©è¥¿å•æŠ—ç»´æŒæ²»ç–—å‰è¡€è¯æµ“åº¦ä¸Žç–¾ç— è½¬å½’çš„å ³ç³».

OBJECTIVES: To study the association between infliximab trough level (IFX-TL) prior to maintenance treatment and disease outcome in children with Crohn's disease (CD). METHODS: A retrospective analysis was performed on 35 children with CD who received induction therapy with infliximab (IFX) and the measurement of IFX-TL before maintenance treatment from August 2018 to November 2021. Clinical data and laboratory markers at baseline and before maintenance treatment were collected, and the association between outcome and IFX-TL was analyzed. RESULTS: The clinical remission group, endoscopic remission group, and combined remission group had a significantly higher IFX-TL level than the corresponding non-remission groups (P<0.05), and there was no significant difference in the IFX-TL level between the biological remission and non-biological remission groups (P>0.05). The receiver operating characteristic (ROC) curve showed that IFX-TL had an area under the ROC curve of 0.959 (95%CI: 0.894-1) in predicting clinical remission, with a sensitivity of 90% and a specificity of 100% at the optimal cutoff value of 2.3 µg/mL (P<0.001). CONCLUSIONS: Among children with CD receiving infliximab induction therapy, the children achieving clinical and endoscopic remission before maintenance treatment tend to have a higher level of IFX-TL. IFX-TL has a certain predictive value for clinical remission.

Rapamycin regulates osteogenic differentiation through Parkin-mediated mitophagy in rheumatoid arthritis.

Varying degrees of bone destruction and bone loss occur in the development of rheumatoid arthritis (RA). Nevertheless, the mechanism underlying osteoporosis in the development of RA is not completely elucidated. Recent evidence indicates that mitophagy may play a vital role in regulating the differentiation and function of preosteoblast. Parkin is associated with mitophagy and various inflammatory diseases, but the precise role of Parkin in the treatment of osteoporosis in RA is unclear. In the present study, we found that the abnormal bone metabolism of RA is related to the activation of the mechanistic targets of mTORC1 pathway, and chronic inflammation which regulates the differentiation of preosteoblast through mitophagy. In this study, we found that Parkin was upregulated, and the mitochondrion was damaged in tumor necrosis factor alpha (TNF-α) stimulated preosteoblasts. Rapamycin (RAPA, an mTORC1 pathway blocker) upregulation of Parkin-mediated mitophagy tends to attenuate mitochondrial impairment caused by TNF-α in preosteoblasts. Theexperimentinvivo demonstrated that the combination therapy with TNF-α neutralizing antibody and RAPA significantly reduced osteoporosis in AIA mice. Drug inhibition of this pathway can be a potential treatment for osteoporosis in patients with RA.

Magnetically Guided Capsule Endoscopy and Magnetic Resonance Enterography in Children With Crohn's Disease: Manifestations and the Value of Assessing Disease Activity.

Objective: To investigate the value of magnetically guided capsule endoscopy (MGCE) and magnetic resonance enterography (MRE) in assessing the activity of pediatric Crohn's disease. Methods: Clinical data from 82 subjects with pediatric Crohn's disease, who underwent MGCE and MRE from October 2018 to March 2021 were analyzed retrospectively. Pairwise comparisons of several indexes, including MaRIA, CECDAI, PCDAI, and SES-CD, were performed by Spearman's rank correlation test and kappa consistency analysis. CECDAI and MaRIA values predicted whether patients were moderately or severely active (PCDAI ≥30) clinically by logistic regression analysis. The area under the receiver operating characteristic curve (AUC) quantified the evaluation value of moderate to severe activity of pediatric CD. Results: In judging the severity of CD in the small intestine, the correlation coefficient between CECDAI and MaRIA was 0.406 (p < 0.05), and the kappa value of the consistency analysis was 0.299 (p < 0.05). MaRIA was weakly correlated with PCDAI (r = 0.254, p < 0.05), and they were weakly consistent in assessing the activity of Crohn's disease (kappa = 0.135, p < 0.05). For predicting clinically moderate to severe activity, the fitted AUC based on CECDAI and MarRIA was 0.917, which was higher than applying a single parameter (CECDAI = 0.725, MarRIA = 0.899, respectively). MaRIA and serum albumin were significantly and negatively correlated (r = -1.064, p < 0.05). The consistency of the detection rate of gastric ulcers by MGCE and gastroscopy was moderate (kappa = 0.586, p < 0.05), and the detection rate of ulcers in the terminal ileum between MGCE and colonoscopy showed high consistency (kappa = 0.609, p < 0.05). Conclusions: MGCE and MRE are valuable, non-invasive methods for evaluating small bowel lesions in children with CD. The combined application of MGCE and MRE can better characterize the disease activity.

Autosomal recessive 333 base pair interleukin 10 receptor alpha subunit deletion in very early-onset inflammatory bowel disease.

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.

ERp29 forms a feedback regulation loop with microRNA-135a-5p and promotes progression of colorectal cancer.

Expression of endoplasmic reticulum (ER) stress-associated genes is often dysregulated in cancer progression. ER protein 29 (ERp29) is abnormally expressed in many neoplasms and plays an important role in tumorigenesis. Here, we showed ERp29 is a novel target for microRNA-135a-5p (miR-135a-5p) to inhibit the progression of colorectal cancer (CRC); correspondingly, ERp29 acts as an oncoprotein in CRC by promoting proliferation and metastasis of CRC cells, and suppressing apoptosis of the cells. More importantly, we found that miR-135a-5p expression is reversely upregulated by ERp29 through suppressing IL-1ß-elicited methylation of miR-135a-5p promoter region, a process for enterocyte to maintain a balance between miR-135a-5p and ERp29 but dysregulated in CRC. Our study reveals a novel feedback regulation loop between miR-135a-5p and ERp29 that is critical for maintaining appropriate level of each of them, but partially imbalanced in CRC, resulting in abnormal expression of miR-135a-5p and ERp29, which further accelerates CRC progression. We provide supporting evidence for ERp29 and miR-135a-5p as potential biomarkers for diagnosis and treatment of CRC.

Crohn's disease with pulmonary granuloma in a child: a case report and review of the literature.

Crohn's disease (CD) is a chronic granulomatous disease that affects the gastrointestinal system. Additionally, CD has multiple extraintestinal manifestations, and bronchopulmonary manifestations are extremely rare. Pulmonary lesions can occur before the diagnosis of CD; thus, pulmonary manifestations are often overlooked, which leads to misdiagnoses. Herein, we present a case with pulmonary nodules being exhibited before the patient was diagnosed with CD. To the best of our knowledge, only a few cases concerning this phenomenon have been reported. We describe an 11-year-old boy with a two-year history of anemia and without any gastrointestinal symptoms. He did not receive any thorough inspection until arthralgia occurred. Multiple nodules were found in his bilateral lungs via computed tomography scan. Combined with the child's medical history, physical examinations, and all of the investigations, the final diagnosis was CD with pulmonary nodules and arthritis. After 2 months of treatment, the patient's symptoms had significantly improved. To summarize the clinical manifestations, auxiliary examination features, and treatments of CD in children with pulmonary involvement, we also review the relevant characteristics of pulmonary involvement in CD patients. This case indicates the importance of recognizing the pulmonary manifestations of CD. Clinicians should be aware of the possibility of CD when their patients have lung nodules, even in children with no typical manifestations of CD.

Valuable clinical indicators for identifying infantile-onset inflammatory bowel disease patients with monogenic diseases.

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.

Study of disease phenotype and its association with prognosis of paediatric inflammatory bowel disease in China.

BACKGROUND: To investigate the unique features of inflammatory bowel disease (IBD) in children, we wanted to identify whether there might be a strong correlation between the disease phenotype and its prognosis at various ages in paediatric patients. METHODS: We collected data from patients diagnosed with IBD (ulcerative colitis (UC) or Crohn's disease (CD)) from 2002 to 2016. The diagnosis was made according to the Porto criteria and Paris Classification. Patient characteristics, clinical manifestations and treatments were collected. Risk factors for surgery, mortality and relapse were analysed by Cox proportional hazard models. RESULTS: Of the 143 patients, 113 had CD, and 30 had UC; there were 89 males and 54 females with a median age of 9 years (y). Thirteen patients in the 0-2 y group were identified as having mutations in IL-10 receptor A, and this mutation was significantly more common in this age group than in 3-9 and 10-16 y patients. The risk factor for surgery was the B3 phenotype; risk factors for death were age 0-2 y and B3 phenotype; 0-2 y, B3 phenotype and steroid dependency were risk factors for early relapse. CONCLUSIONS: Clinical manifestations of the onset of IBD in infants and toddlers were extensive and aggressive and were closely associated with early relapse and death. It is of particular interest that some of these patients developed IBD due to monogenic disorders; thus, introduction of genetic testing is essential for these patients.

Comprehensive analysis of differentially expressed non-coding RNAs and mRNAs in gastric cancer cells under hypoxic conditions.

Hypoxia commonly occurs in solid cancers, especially in gastric cancer due to its rapid growth. The ability of gastric cancer cells to survive and progress under hypoxic conditions has been known for decades, but the mechanisms underlying this characteristic remain poorly understood. As cancer cells undergo changes in their genetic profile under certain conditions, we investigated the expression profile of non-coding RNAs (circRNAs, lncRNAs, and miRNAs) and mRNAs in gastric cancer MKN-28 cells under hypoxic conditions via sequencing and subsequent bioinformatic analyses. In addition, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the results. We identified a number of significantly differentially expressed circRNAs, lncRNAs, miRNAs, and mRNAs in hypoxia-exposed MKN-28 cells relative to the normoxia control, and results of qRT-PCR were consistent with sequencing data. Pathway enrichment analyses revealed the principal functions of the significantly deregulated genes. Furthermore, examination of co-expression and competing endogenous RNA (ceRNAs) networks illustrated the complex regulatory pathways among non-coding RNAs and mRNAs, implicating these pathways in gastric cancer. In conclusion, our findings provide a novel perspective on non-coding RNAs and mRNAs and lay the foundation for future research on the potential roles of non-coding RNAs in gastric cancer under hypoxic conditions.

ERp29 inhibits tumorigenicity by suppressing epithelial mesenchymal transition in gastric cancer.

ERp29 is a novel endoplasmic reticulum (ER) protein that plays an important role in protein unfolding and secretion. Recently, it has been reported to be widely implicated in control of tumorigenesis in some tumors. However, the potential function of ERp29 in gastric cancer remains poorly understood. In this study, we found that the positive rate of ERp29 in gastric cancer tissues was significantly lower than that in adjacent non-tumor tissues. And tumor with high ERp29 expression had inclinations towards smaller tumor size and earlier TNM stage. The in vitro experiments indicated that over-expression of ERp29 in gastric cancer cells significantly suppressed the proliferation and migration of tumor cells, which is consistent with the result of the in vivo animal experiments. Furthermore, our mechanistic investigations revealed that ERp29 reversed EMT process in gastric carcinoma, and its effect was related to the inactivation of ERK1/2 and AKT phosphorylation. Thus, we conclude that ERp29 acts as a tumor suppressor gene in gastric cancer, and is expected to become a novel target of the treatment of GC.

Targeted Gene Next-Generation Sequencing in Chinese Children with Chronic Pancreatitis and Acute Recurrent Pancreatitis.

OBJECTIVE: To identify causal mutations in certain genes in children with acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP). STUDY DESIGN: After patients were enrolled (CP, 55; ARP, 14) and their clinical characteristics were investigated, we performed next-generation sequencing to detect nucleotide variations among the following 10 genes: cationic trypsinogen protease serine 1 (PRSS1), serine protease inhibitor, Kazal type 1 (SPINK1), cystic fibrosis transmembrane conductance regulator gene (CFTR), chymotrypsin C (CTRC), calcium-sensing receptor (CASR), cathepsin B (CTSB), keratin 8 (KRT8), CLAUDIN 2 (CLDN2), carboxypeptidase A1 (CPA1), and ATPase type 8B member 1 (ATP8B1). Mutations were searched against online databases to obtain information on the cause of the diseases. Certain novel mutations were analyzed using the SIFT2 and Polyphen-2 to predict the effect on protein function. RESULTS: There were 45 patients with CP and 10 patients with ARP who harbored 1 or more mutations in these genes; 45 patients had at least 1 mutation related to pancreatitis. Mutations were observed in the PRSS1, SPINK1, and CFTR genes in 17 patients, the CASR gene in 5 patients, and the CTSB, CTRC, and KRT8 genes in 1 patient. Mutations were not found in the CLDN, CPA1, or ATP8B1 genes. We found that mutations in SPINK1 may increase the risk of pancreatic duct stones (OR, 11.07; P = .003). The patients with CFTR mutations had a higher level of serum amylase (316.0 U/L vs 92.5 U/L; P = .026). CONCLUSION: Mutations, especially those in PRSS1, SPINK1, and CFTR, accounted for the major etiologies in Chinese children with CP or ARP. Children presenting mutations in the SPINK1 gene may have a higher risk of developing pancreatic duct stones.

DC-SIGN and Toll-like receptor 4 mediate oxidized low-density lipoprotein-induced inflammatory responses in macrophages.

The regulation of inflammatory responses by innate immune receptors is recognized as a crucial step in the development of atherosclerosis, although the precise molecular mechanisms remain to be elucidated. This study focused on illustrating the roles of dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN)- and Toll-like receptor 4 (TLR4)-regulated inflammatory responses in macrophages. We found that DC-SIGN expression levels were increased in macrophages of atherosclerotic plaques. Oxidized low-density lipoprotein (oxLDL) significantly enhanced DC-SIGN protein expression levels after a short-term exposure. Knockdown of DC-SIGN decreased expression and secretion of interleukin 1-ß (IL1-ß), monocyte chemo-attractant protein 1 (MCP-1), tumor necrosis factor-α (TNFα) and matrix metalloproteinase-9 (MMP-9). Immunofluorescence studies demonstrated that DC-SIGN and TLR4 co-localized in regions of the plaques. Moreover, DC-SIGN was co-expressed with TLR4 on the plasma membrane after oxLDL stimulation. The presence of an endogenous interaction and the results of the in vitro pull-down assays revealed that DC-SIGN binds directly with TLR4. We also present evidence that DC-SIGN mediates TLR4-regulated NFκB activation but not activation of p38 and JNK. Our results suggest an essential role of DC-SIGN/TLR4 signaling in macrophages in the pathogenesis of atherosclerosis.

Comprehensive mutation screening for 10 genes in Chinese patients suffering very early onset inflammatory bowel disease.

AIM: To perform sequencing analysis in patients with very early-onset inflammatory bowel disease (VEO-IBD) to determine the genetic basis for VEO-IBD in Chinese pediatric patients. METHODS: A total of 13 Chinese pediatric patients with VEO-IBD were diagnosed from May 2012 and August 2014. The relevant clinical characteristics of these patients were analyzed. Then DNA in the peripheral blood from patients was extracted. Next generation sequencing (NGS) based on an Illumina-Miseq platform was used to analyze the exons in the coding regions of 10 candidate genes: IL-10, IL-10RA, IL-10RB, NOD2, FUT2, IL23R, GPR35, GPR65, TNFSF15, and ADAM30. The Sanger sequencing was used to verify the variations detected in NGS. RESULTS: Out of the 13 pediatric patients, ten were diagnosed with Crohn's disease, and three diagnosed with ulcerative colitis. Mutations in IL-10RA and IL-10RB were detected in five patients. There were four patients who had single nucleotide polymorphisms associated with IBD. Two patients had IL-10RA and FUT2 polymorphisms, and two patients had IL-10RB and FUT2 polymorphisms. Gene variations were not found in the rest four patients. Children with mutations had lower percentile body weight (1.0% vs 27.5%, P = 0.002) and hemoglobin (87.4 g/L vs 108.5 g/L, P = 0.040) when compared with children without mutations. Although the age of onset was earlier, height was shorter, and the response to treatment was poorer in the mutation group, there was no significant difference in these factors between groups. CONCLUSION: IL-10RA and IL-10RB mutations are common in Chinese children with VEO-IBD. Patients with mutations have an earlier disease onset, lower body weight and hemoglobin, and poorer prognosis.

Upper Gastrointestinal Bleeding in Chinese Children: A Multicenter 10-Year Retrospective Study.

Objective This study aims to analyze the clinical and endoscopic presentations of upper gastrointestinal bleeding (UGIB) in the Chinese children. Methods A 10-year retrospective study was made on children with UGIB and undertaken esophagogastroduodenoscopy (EGD) from 4 tertiary referral centers in China. Results Of the 1218 children studied, the bleeding source was found in 76.4%. Erosive gastritis was the most common endoscopic finding (33.5%), followed by duodenal ulcer (23.2%). The proportion of erosive gastritis decreased with age (correlation coefficient = -0.787), and duodenal ulcer increased with age (correlation coefficient = 0.958). The bleeding source was more likely to be determined in children having EGDs within 48 hours (80.6% vs 67.9%). Conclusions In Chinese children with UGIB, erosive gastritis and duodenal ulcer were the leading causes, and their proportions varied with age. EGDs performed within 48 hours may improve the possibility of finding the source of bleeding.

ERp19 contributes to tumorigenicity in human gastric cancer by promoting cell growth, migration and invasion.

ERp19, a mammalian thioredoxin-like protein, plays a key role in defense against endoplasmic reticulum stress. It belongs to the protein disulfide isomerize (PDI) family, whose members have been implicated in development of breast, ovarian and gastrointestinal cancers. However, the role of ERp19 in gastric cancer (GC) remains undefined. Therefore, we sought to investigate the expression and prognostic value of ERp19 in GC patients, and to explore the role of ERp19 in tumorigenicity. Expression of ERp19 in gastric tissues was assessed by immunohistochemical staining and real-time PCR in clinical samples of GC patients. Statistical analysis of clinical cases revealed that the expression levels of ERp19 were higher in tumor tissues than non-tumor tissues. And the level of ERp19 expression was correlated with tumor size, lymph node involvement and poor clinical prognosis. Furthermore, ERp19 knockdown dramatically suppressed gastric cancer cell growth, inhibited cellular migration/invasion and down regulated the phosphorylation of FAK and paxillin, whereas ERp19 over-expression reversed these changes. We conclude that ERp19 contributes to tumorigenicity and metastasis of GC by activating the FAK signaling pathway, and may function as an oncogene in GC. ERp19 may represent a new diagnostic and prognostic marker and a novel target for the treatment of GC.

Enterocyte dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin expression in inflammatory bowel disease.

AIM: To investigate dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) expression in intestinal epithelial cells (IECs) in inflammatory bowel disease (IBD). METHODS: The expression of DC-SIGN in IECs was examined by immunohistochemistry of intestinal mucosal biopsies from 32 patients with IBD and 10 controls. Disease activity indices and histopathology scores were used to assess the tissue lesions and pathologic damage. Animal studies utilized BALB/c mice with dextran sodium sulfate (DSS)-induced colitis treated with anti-P-selectin lectin-EGF domain monoclonal antibody (PsL-EGFmAb). Controls, untreated and treated mice were sacrificed after 7 d, followed by isolation of colon tissue and IECs. Colonic expression of DC-SIGN, CD80, CD86 and MHC II was examined by immunohistochemistry or flow cytometry. The capacity of mouse enterocytes or dendritic cells to activate T cells was determined by co-culture with naïve CD4(+) T cells. Culture supernatant and intracellular levels of interleukin (IL)-4 and interferon (IFN)-γ were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively. The ability of IECs to promote T cell proliferation was detected by flow cytometry staining with carboxyfluorescein diacetate succinimidyl ester. RESULTS: Compared with controls, DC-SIGN expression was significantly increased in IECs from patients with Crohn's disease (P < 0.01) or ulcerative colitis (P < 0.05). DC-SIGN expression was strongly correlated with disease severity in IBD (r = 0.48; P < 0.05). Similarly, in the DSS-induced colitis mouse model, IECs showed upregulated expression of DC-SIGN, CD80, CD86 and MHC, and DC-SIGN expression was positively correlated with disease activity (r = 0.62: P < 0.01). IECs from mouse colitis stimulated naïve T cells to generate IL-4 (P < 0.05). Otherwise, dendritic cells promoted a T-helper-1-skewing phenotype by stimulating IFN-γ secretion. However, DC-SIGN expression and T cell differentiation were suppressed following treatment of mice with DSS-induced colitis with PsL-EGFmAb. The proliferation cycles of CD4(+) T cells from mice with DSS-induced colitis appeared as five cycles, which was more than in the control and treated groups. These results suggest that IECs can promote T cell proliferation. CONCLUSION: IECs regulate tissue-associated immune compartments under the control of DC-SIGN in IBD.

Association between Helicobacter pylori infection and pathological changes in the gastric mucosa in Chinese children.

OBJECTIVE: H. pylori infection in children has a high prevalence worldwide. The disease can cause progressive gastric mucosal inflammation, as verified in animal models. However, data from large-scale clinical studies are limited. METHODS: We examined 1,634 Chinese children with upper gastrointestinal discomfort using endoscopy. The clinical and pathological data of the patients were analyzed. RESULTS: A total of 524 (32.1%) patients were infected with H. pylori, and the prevalence of H. pylori infection increased with age. The H. pylori-infected patients exhibited a significantly higher prevalence of active inflammation (26.9% vs. 4.1%), lymphoid follicle formation (18.5% vs. 4.6%) and marked lymphocyte infiltration (19.7% vs. 5.6%). The H. pylori-infected patients also exhibited a significantly higher prevalence of moderate to marked chronic superficial gastritis (41.9% vs. 9.2%) and moderate chronic atrophic gastritis (21.7% vs. 2.6%) than the uninfected patients (p<0.01). CONCLUSION: H. pylori infection is associated with the degree of gastric mucosal inflammation and the severity of different types of chronic gastritis.

Role of DC-SIGN in Helicobacter pylori infection of gastrointestinal cells.

H. pylori causes gastritis and increases the risk of gastric ulcer and gastric cancer. However, it was recently shown that H. pylori provides protection against inflammatory bowel diseases. To assess the molecular mechanism of such functions, we studied the role of DC-SIGN in H. pylori-infected gastrointestinal epithelial cells. DC-SIGN was found to be over-expressed in the gastric epithelial cells infected with H. pylori and mediated Th1 differentiation, which may be involved in H. pylori-induced gastric mucosal injury. In addition, DC-SIGN was also up-regulated in the intestinal epithelial cells derived from colitis mouse model, but the expression levels were blocked upon H. pylori infection, indicating that H. pylori infection may reduce both local and systemic inflammatory responses. In conclusion, we propose that gastrointestinal epithelial cells infected with H. pylori may lead to acquiring of immune properties via a trans-differentiation process, and regulate tissue-associated immune compartments under the control of DC-SIGN.

Inflammatory bowel disease in Chinese children: a multicenter analysis over a decade from Shanghai.

BACKGROUND: The purpose was to estimate the incidence and characteristics of childhood inflammatory bowel disease (IBD) during 2000-2010 in Shanghai, China. METHODS: IBD patients between the ages of 0 and 18 years old were identified by survey of computerized medical information. Relevant data were extracted from their corresponding medical records. RESULTS: A total of 153 IBD cases were included in the study. Among them, 107 were males and 46 were females (male/female ratio, 2.3:1.0). Eighty-two had Crohn's disease (CD) and 71 had ulcerative colitis (UC). The peak prevalence of IBD was observed in the 10-14-year-old age group. The annual incidence of IBD in the 0 to 14 years age group of Shanghai residents steadily increased from 2000 to 2010. The most common symptoms of IBD were diarrhea (68.6%), bloody stool (68.6%), and abdominal pain (61.4%). More CD than UC patients had anemia and raised erythrocyte sedimentation rate and C-reactive protein levels. Ileocolonic type disease was more common in CD patients, and left-side colon involvement was more common in UC. Of all CD patients, 33 had mild active disease and 49 had moderate/severe disease. In UC patients, 34 were mild and 37 were moderate/severe disease. CONCLUSIONS: This retrospective, multicenter hospital-based study over a decade shows a steadily increasing trend of childhood IBD in China. This suggests a need for population-based epidemiological studies to explore the risk factors.