[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.

[Clinical effect of sirolimus in treatment of blue rubber bleb nevus syndrome in children: a report of 2 cases and literature review].

To study the clinical effect of oral sirolimus in the treatment of children with blue rubber bleb nevus syndrome (BRBNS) in the gastrointestinal tract, a retrospective analysis was performed on the clinical data and follow-up results of two children with BRBNS treated by sirolimus. The two children with BRBNS had gastrointestinal bleeding and anemia and were treated with sirolimus at a dose of 1 mg/day as part of treatment. The plasma concentration of the drug was maintained between 2.5-12.0 ng/mL. The children showed disappearance of gastrointestinal bleeding and improvements in anemia and coagulation function, and blood transfusion could be stopped during treatment, with no obvious adverse drug reactions. PubMed, Wanfang Data, and CNKI were searched for related articles on sirolimus in the treatment of BRBNS. A total of 26 cases of children with BRBNS, aged 0-18 years, were obtained. With the addition of the 2 cases in this study, sirolimus treatment achieved a satisfactory clinical effect in all 28 cases. Sirolimus may be effective and safe in the treatment of children with BRBNS, and further prospective studies are needed to evaluate the long-term efficacy of this drug.

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.

Runt-related Transcription Factor 1 (RUNX1) Binds to p50 in Macrophages and Enhances TLR4-triggered Inflammation and Septic Shock.

An appropriate inflammatory response plays critical roles in eliminating pathogens, whereas an excessive inflammatory response can cause tissue damage. Runt-related transcription factor 1 (RUNX1), a master regulator of hematopoiesis, plays critical roles in T cells; however, its roles in Toll-like receptor 4 (TLR4)-mediated inflammation in macrophages are unclear. Here, we demonstrated that upon TLR4 ligand stimulation by lipopolysaccharide (LPS), macrophages reduced the expression levels of RUNX1 Silencing of Runx1 attenuated the LPS-induced IL-1ß and IL-6 production levels, but the TNF-α levels were not affected. Overexpression of RUNX1 promoted IL-1ß and IL-6 production in response to LPS stimulation. Moreover, RUNX1 interacted with the NF-κB subunit p50, and coexpression of RUNX1 with p50 further enhanced the NF-κB luciferase activity. Importantly, treatment with the RUNX1 inhibitor, Ro 5-3335, protected mice from LPS-induced endotoxic shock and substantially reduced the IL-6 levels. These findings suggest that RUNX1 may be a new potential target for resolving TLR4-associated uncontrolled inflammation and preventing sepsis.

[Therapeutic effects of zinc supplement as adjunctive therapy in infants and young children with rotavirus enteritis].

OBJECTIVE: To investigate the therapeutic effects of oral zinc supplement in infants and young children with rotavirus enteritis, and its preventive effects against diarrhea recurrence within 3 months after treatment. METHODS: A total of 103 infants and young children with rotavirus enteritis were randomly divided into zinc supplement group (n=51) and conventional treatment group (n=52). Both groups were equally treated with a comprehensive therapy, besides which the zinc supplement group received zinc gluconate granules for 10 days. The treatment outcomes were examined at 72 hours after treatment, and the time required for the disappearance of positive symptoms and the recovery of injured extra-intestinal organs were determined. In addition, these patients were followed up for 3 months to determine the incidence of diarrhea recurrence after treatment. RESULTS: The overall response rate in the zinc supplement group was significantly higher than that in the conventional treatment group (90% vs 75%; P<0.05). The durations of diarrhea, high fever, and vomiting in the zinc supplement group were significantly shorter than that in the conventional treatment group (P<0.05). In addition, the recurrence rate of diarrhea and the incidence of severe diarrhea within 3 months after treatment in the zinc supplement group were significantly lower than in the conventional treatment group (P<0.05). CONCLUSIONS: Oral zinc supplement as adjunctive therapy is effective in treating infants and young children with rotavirus enteritis, and reducing the incidence and severity of diarrhea recurrence in the subsequent 3 months.

Corrigendum: Efficacy and Safety of Shenqu Xiaoshi Oral Liquid Compared With Domperidone Syrup in Children With Functional Dyspepsia.

[This corrects the article DOI: 10.3389/fphar.2022.831912.].

Efficacy and Safety of Shenqu Xiaoshi Oral Liquid Compared With Domperidone Syrup in Children With Functional Dyspepsia.

Background: Treatment of functional dyspepsia (FD) in children is generally symptomatic and unsatisfactory. Traditional Chinese medicines, such as Shenqu Xiaoshi Oral Liquid (SXOL), have been recommended to alleviate dyspeptic symptoms. However, evidence of their safety and efficacy remains limited to date. AIM: To assess whether 2 weeks of therapy with SXOL was non-inferior to domperidone syrup in children with FD. Methods: In this randomized, double-blind, double-simulated, non-inferiority, multi-center clinical trial, we recruited children (3-14 years) with FD according to the Rome IV criteria from 17 tertiary medical centers across China. Patients were randomly allocated (1:1) to receive SXOL or domperidone syrup for 2 weeks. We compared the participants' clinical scores from both groups based on the severity and frequency of dyspepsia symptoms according to Rome IV criteria (0, 1, 2, and 4 weeks after randomization). The primary endpoint was the total response rate, which was defined as the proportion of patients with a decrease of 30% or more in the FD symptoms clinical score from baseline, at the end of the 2-weeks treatment. A non-inferiority margin of -10% was set. Secondary endpoints and adverse events were assessed. This trial is registered with www.Chictr.org.cn, number ChiCTR1900022654. Results: Between February 2019 and March 2021, a total of 373 patients were assessed for eligibility, and 356 patients were enrolled and randomized. The clinical response rate at week two was similar for SXOL [118 (83.10%) of 142] and domperidone [128 (81.01%) of 158]; difference 2.09; 95% CI -6.74 to 10.71, thereby establishing non-inferiority. The total FD symptom scores were significantly improved in the two groups at 1-, 2-, and 4-weeks follow-up periods (p < 0.005). The decrease in symptom score compared with the baseline were similar between these two groups. Over the total study period, 10 patients experienced at least one treatment-related adverse event [six (3.37%)] in the SXOL group, four [(2.25%) in the domperidone group], although no serious adverse event was noted. Conclusion: Treatment with SXOL effectively improves dyspeptic symptoms and is well tolerated. In addition, it is not inferior to domperidone syrup and leads to sustained improvement in Chinese children with FD.

Celiac disease in children with diarrhea in 4 cities in China.

OBJECTIVE: The aim of the study was to investigate whether celiac disease (CD) could be the cause of chronic diarrhea in Chinese patients. PATIENTS AND METHODS: During the period of January 2005 to December 2008, patients with chronic diarrhea in pediatric hospitals from 4 major cities (Shanghai, Wuhan, Jinan, and Chengdu) in China were included in the study. The clinical history, physical findings, and laboratory data were collected and analyzed. RESULTS: Among 199 patients with chronic diarrhea, 118 were enrolled in the study. Fourteen (11.9%) were diagnosed as being affected by CD. CONCLUSIONS: The 14 patients are the first reported cases of CD in Chinese patients with chronic diarrhea.

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.

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.

Endoscopic retrograde cholangiopancreatography in children with symptomatic pancreaticobiliary maljunction: A retrospective multicenter study.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) has been widely used in pediatric patients with cholangiopancreatic diseases. AIM: To evaluate the efficacy, safety, and long-term follow-up results of ERCP in symptomatic pancreaticobiliary maljunction (PBM). METHODS: A multicenter, retrospective study was conducted on 75 pediatric patients who were diagnosed with PBM and underwent therapeutic ERCP at three endoscopy centers between January 2008 and March 2019. They were divided into four PBM groups based on the fluoroscopy in ERCP. Their clinical characteristics, specific ERCP procedures, adverse events, and long-term follow-up results were retrospectively reviewed. RESULTS: Totally, 112 ERCPs were performed on the 75 children with symptomatic PBM. Clinical manifestations included abdominal pain (62/75, 82.7%), vomiting (35/75, 46.7%), acholic stool (4/75, 5.3%), fever (3/75, 4.0%), acute pancreatitis (47/75, 62.7%), hyperbilirubinemia (13/75, 17.3%), and elevated liver enzymes (22/75, 29.3%). ERCP interventions included endoscopic sphincterotomy, endoscopic retrograde biliary or pancreatic drainage, stone extraction, etc. Procedure-related complications were observed in 12 patients and included post-ERCP pancreatitis (9/75, 12.0%), gastrointestinal bleeding (1/75, 1.3%), and infection (2/75, 2.7%). During a mean follow-up period of 46 mo (range: 2 to 134 mo), ERCP therapy alleviated the biliary obstruction and reduced the incidence of pancreatitis. The overall effective rate of ERCP therapy was 82.4%; seven patients (9.3%) were lost to follow-up, eight (11.8%) re-experienced pancreatitis, and eleven (16.2%) underwent radical surgery, known as prophylactic excision of the extrahepatic bile duct and hepaticojejunostomy. CONCLUSION: ERCP is a safe and effective treatment option to relieve biliary or pancreatic obstruction in symptomatic PBM, with the characteristics of minor trauma, fewer complications, and repeatability.

Chinese clinical practice guidelines for acute infectious diarrhea in children.

BACKGROUND: The guidelines addressed the evidence-based indications for the management of children with acute infectious diarrhea in Chinese pediatric population. DATA SOURCES: The experts group of evidence development put forward clinical problems, collects evidence, forms preliminary recommendations, and then uses open-ended discussions to form recommendations. The literature review was done for developing this guideline in databases including PubMed, Cochrane, EMBASE, China Biomedical Database, and Chinese Journal Full-text Database up to June 2013. Search the topic "acute diarrhea" or "enteritis" and "adolescent" or "child" or "Pediatric patient" or "Baby" or "Infant". RESULTS: For the treatment of mild, moderate dehydration, hypotonic oral rehydration solutions (ORS) are strongly recommended. Intravenous (IV) rehydration is recommended for severe dehydration, with a mixture of alkali-containing dextrose sodium solution. Nasogastric feeding tube rehydration is used for children with severe dehydration without IV infusion conditions with ORS solution. Regular feeding should resume as soon as possible after oral rehydration or IV rehydration. The lactose-free diet can shorten the diarrhea duration. Zinc supplements are recommended in children with acute infectious diarrhea. Saccharomyces boulardii and Lactobacillus Rhamnus are recommended to be used in acute watery diarrhea. Saccharomyces boulardii is recommended in children with antibiotic-associated diarrhea as well. Montmorillonite and Racecadotril (acetorphan) can improve the symptoms of diarrhea or shorten the course of acute watery diarrhea. Antibiotics are recommended with dysenteric-like diarrhea, suspected cholera with severe dehydration, immunodeficiency, and premature delivery children with chronic underlying disease; otherwise, antibiotics are not recommended. CONCLUSION: The principles of the most controversial treatments with of acute infectious disease are reaching to a consensus in China.

[Forlax in the treatment of childhood constipation: a randomized, controlled, multicenter clinical study].

OBJECTIVE: To determine the therapeutic effectiveness and safety of polyethylene glycol 4000 (forlax) in the treatment of constipation in children over 8 years old. METHODS: This study was designed as a randomized, positive medicine (lactulose) controlled multicenter trial. A total of 216 children with constipation from 8-18 years old from 7 hospitals across China who were matched with a uniform entry criteria were enrolled in this study. The 216 patients were randomized to receive either oral forlax (20 g/d, n=105) or lactulose (15 mL/d, n=111) for 2 weeks. The therapeutic effects, including bowel movement frequency, stool consistency, clinical complete remission rate of constipation and abdominal symptoms, and the safety of forlax and lactulose were evaluated at 1 and 2 weeks of treatment. RESULTS: The median weekly frequency of bowel movement in the forlax group increased by 4 and 5 times respectively after 1 and 2 weeks of treatment, and increased by 3 and 4 times in the lactulose group (P < 0.05). The stool consistency of the two groups was both improved significantly after treatment. The Bristol score of stool consistency of the forlax and lactulose groups were 3.41+/-1.11 and 3.64+/-1.33 respectively (P < 0.05) after 1 week of treatment, and were 4.26+/-0.89 and 3.63+/-1.33 respectively (P < 0.05) after 2 weeks of treatment. The clinical complete remission rate of constipation in the forlax and lactulose groups was 70% and 40% respectively (P < 0.05) by week 1 of treatment, and that was 72% and 41% respectively (P < 0.05) by week 2 of treatment. Abdominal pain disappeared in 75% of patients in the forlax group but in only 57% in the lactulose group by week 2 of treatment (P < 0.05). No serious adverse events happened and no abnormalities were found in laboratory tests and physical examinations in the two groups after medication. CONCLUSIONS: Forlax is safe and effective in the treatment of constipation in children over 8 years old.

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.

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.

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.

Frequency of cytochrome P450 2C9 allelic variants in the Chinese and French populations.

Cytochrome P450 2C9 (CYP2C9) is a polymorphic enzyme responsible for the metabolism of different drugs with low therapeutic index such as oral anticoagulants. CYP2C9*2 and CYP2C9*3 are two single nucleotide polymorphic allelic variants. The frequency of these alleles in different ethnic populations is extremely variable. In this study, we compared the frequencies of CYP2C9 allelic variants among 394 Chinese living in Shanghai to 151 French Caucasians living in Paris. The allelic frequencies of CYP2C9 variants of the Chinese and the French subjects were 0.963, 0.001, 0.036 and 0.77, 0.15, 0.08 for CYP2C9*1, CYP2C9*2, CYP2C9*3, respectively. Chinese CYP2C9*3 allelic frequency was twice as lower as the French subjects, but three times higher than Korean (0.036 vs. 0.011). The CYP2C9*2 allele could be detected in only one Chinese subject, whereas it represented the major allelic variant in French Caucasians. The low frequency of the CYP2C9*2 and CYP2C9*3 allelic variants in Chinese subjects does not justify their detection in clinical practice, unlike French Caucasians.

Effects of epidermal growth factor on the growth of human gastric cancer cell and the implanted tumor of nude mice.

AIM: Epidermal growth factor (EGF) plays an important role in the regulation of gastrointestinal tissue growth and development, and it can stimulate epithelial proliferation, cell differentiation and growth. It has been established that the EGF can promote gastric cytoprotection and ulcer healing. But the potential ability of EGF to regulate the gastric cancer growth is unknown. This study is to investigate the influence of EGF on human gastric cancer cell and the implanted tumor growth of nude mice. METHODS: The cell growth rates of human gastric adenocarcinoma cell lines MKN-28, MKN-45, SGC-7901 and normal human gastric epithelial cells 3T3 were assessed when incubated with recombinant human EGF (rhEGF, 0.05, 0.1, 0.5, 1.0, 10, 50, 100 mg.L(-1)) using MTT method. The cells of MKN-28, MKN-45, SGC-7901 (gastric cancer tissue 1.5mm(3)) were implanted in the BALB/cA nude mice for 10 days. The EGF was given intraperitoneally (15, 30, 60 microg.kg(-1)) for 3 weeks. The body weights of the tumor-bearing animals and their tumor mass were measured afterwards to assess the mitogenic effect of rhEGF in the nude mice. RESULTS: Within the concentration range of 0.05-100mg.L(-1), rhEGF could increase the cell growth of normal 3T3 cells (cell growth rate 100% vs 102.8%, P<0.05), but partially restrain the gastric cancer cell growth. The latter effect was related to cell differentiation. In 15-60 microg/kg rhEGF groups, the mean implanted tumor mass of MKN-28 cell were 1.75 g, 1.91 g, 2.08 g/NS group 1.97 g (P>0.05), the mean tumor mass of SGC-7901 cell were 1.53 g, 1.07 g, 1.20 g/NS group 1.07 g (P>0.05), and for MKN-45 cell, the tumor mass were respectively 1.92 g, 1.29 g, 1.77 /NS group 1.82 g (P>0.05). So rhEGF had no obvious effect on implanted MKN-28, SGC-7901 and MKN-45 tumor growth. CONCLUSION: EGF has no stimulating effect on the human gastric cancer cell growth neither in vitro nor in vivo.

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.