OBJECTIVETo understand the clinical features of gastrointestinal cow's milk allergy in children, and to assess the importance of cow's milk challenge.

METHODAn analysis was performed on the clinical manifestations and the challenge results of 50 children who received cow's milk challenges after admission to the department of gastroenterology, Children' s Hospital of Zhejiang University School of Medicine from January,2009 to December, 2012. The value of immunoglobulin E antibody was also analyzed among the 50 children, 25 cases were male and the other 25 were female. The youngest subject was 1. 6 months old, and the oldest was 20 months, most of the cases were younger than 6 months (36 cases).

RESULT(1) Diarrhea (27 cases, 54%) and hematochezia (25 cases, 50%) were the most common clinical features, vomiting, hematemesis and abdominal distention were rare. (2) Cow's milk challenges failed in 58% of the cases, 90% of whom showed delayed allergy. Diarrhea (19 cases, 73%) was the major later presentation, whereas the immediate hypersensitivity showed angio-edema, gastrointestinal symptom and rash. (3) The neutrophil count ((3.8 ± 2.8) x 10(9)/L vs. (2.5 ± 1.3) x 10(9)/L) was higher after challenge among children who failed the challenge. The change in the count of blood cell, neutrophil and platelet was studied, however, there were no statistical differences between the challenge-failed children and the passed ones. (4) Forty-seven cases had milk specific immunoglobulin E antibody test, and 5 showed positive results, 4 of whom were seen among the challenge-failed children.

CONCLUSIONDiarrhea and hematochezia was the most common clinical manifestation, and cow's milk protein induced proctocolitis was the most common disease in practice. It is important and necessary to perform cow's milk challenge.

Animals ; Female ; Gastrointestinal Diseases ; etiology ; Gastrointestinal Hemorrhage ; etiology ; Hematemesis ; etiology ; Humans ; Hypersensitivity, Immediate ; immunology ; Infant ; Infant, Newborn ; Male ; Milk ; Milk Hypersensitivity ; immunology ; Vomiting ; etiology

Objective:To investigate the effect and mechanism of 6-formylindolo[3,2-b]carbazole (FICZ) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.Methods:Male C57BL/6J mice aged 8-12 weeks were divided into 4 groups with 8 mice in each group, according to the method of simple random sampling. Sepsis-induced ALI mice model was established by intraperitoneal injection of LPS 5 mg/kg (LPS group), and phosphate buffer saline (PBS) control group (PBS group) was injected with equal volume of PBS. The LPS+FICZ group was intervened by intraperitoneal injection of 1 μg FICZ 1 hour after LPS stimuli, while the FICZ control group (FICZ group) was given the same amount of FICZ 1 hour after intraperitoneal injection of PBS. Serum and lung tissue were collected 24 hours after LPS stimuli, and the pathological changes of lung tissue were analyzed by hematoxylin-eosin (HE) staining and wet/dry weight (W/D) ratio of lung tissue. The concentrations of inflammatory factors in serum and lung tissue were detected by enzyme linked immunosorbent assay (ELISA). The expression levels of endoplasmic reticulum stress signaling pathway related molecules were detected by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) and Western blotting.Results:Compared with PBS group, inflammatory cell infiltration, alveolar collapse and obvious alveolar exudative lesions had increased, lung tissue W/D ratio was significantly increased, serum interleukin-6 (IL-6) level, lung tissue IL-6 mRNA expression, and the mRNA expressions of glucose-regulated protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), CCAAT/EBP homologous protein (CHOP), and the protein expressions of GRP78, PERK, activating transcription factor 6 (ATF6), CHOP in lung tissue were significantly increased in LPS group. However, the indexes of FICZ group were not affected. Compared with LPS group, LPS+FICZ group had less inflammatory cell infiltration, relatively intact alveolar structure. Lung W/D weight ratio in LPS+FICZ group was significantly decreased (5.38±0.10 vs. 6.60±0.30, P < 0.01), so as serum IL-6 (ng/L: 15.55±3.77 vs. 32.22±3.84) and lung IL-6 mRNA expression (2 -ΔΔCt: 0.79±0.21 vs. 6.89±0.92, both P < 0.01). The mRNA expressions of GRP78, PERK and CHOP were also significantly decreased [GRP78 mRNA (2 -ΔΔCt): 1.90±0.16 vs. 7.55±1.29, PERK mRNA (2 -ΔΔCt): 1.68±0.20 vs. 4.54±0.89, CHOP mRNA (2 -ΔΔCt): 1.13±0.24 vs. 4.44±1.13, all P < 0.05], and the protein expressions of GRP78, PERK, ATF6 and CHOP were significantly decreased (GRP78/GAPDH: 0.59±0.02 vs. 0.77±0.01, PERK/GAPDH: 0.48±0.03 vs. 1.04±0.05, ATF6/GAPDH: 0.51±0.03 vs. 0.65±0.01, CHOP/GAPDH: 0.91±0.05 vs. 1.11±0.07, all P < 0.05). Conclusion:FICZ protects LPS-induced ALI possibly via suppressing endoplasmic reticulum stress and reducing IL-6 expression in blood and lung tissue.

Objective To explore the efficacy and safety of the application of enteral nutrition (EN) in gastrointestinal disease in children,and to explore the possibility of the implementation of family EN.Method Retrospective analysis of disease spectrum,EN approach,preparation,speed and time as well as adverse reactions and outcomes in 47 pediatric patients with gastrointestinal disease underwent EN therapy during July 2014 to March 2015.The nutrition indicators before and after EN therapy were compared by paired t-test.Result A total of 47 patients were selected,27 male (57％) and 20 female (43％),aged 0.8 (0.3,4.0) years,9 with mechanical or chemical damage to the esophagus,7 with inflammatory bowel disease (including ulcerative colitis and Crohn's disease),6 with chronic diarrhea,5 with acute pancreatitis,3 with acute diarrhea and severe malnutrition,3 with short bowel syndrome,3 with improper feeding,3 with feeding difficulties,3 with protein losing enteropathy,2 with post-enterostomy,2 with enterocolitis,1 with gastroesophageal reflux,were diagnosed.Of 47 cases,22 were given oral nutrition,28 were fed with nasogastric tube and 4 with nasojejunal tube feeding,2 with percutaneous endoscopic gastrojejunostomy tube feeding for each.In these tube-feeding cases,20 cases were treated with continuous infusion and 21 cases with intermittent infusion.Eleven cases were fed with amino acid formula;21 cases took the choice of peptide formulations;16 cases chose whole protein formula,including six cases who chose 3.3-4.2 kJ/ml higher energy density formula,10 cases selected common energy density formula including breast milk.Twenty-one cases suffered from different degrees of adverse reactions,including vomiting in 7 cases,abdominal pain and bloating in 3,diarrhea in 12,secondary respiratory infections in 5.Five patients were discharged after giving up of treatment by parents due to poor efficacy on primary disease;3 cases were transferred to other departments for further treatment;15 cases were discharged with a feeding tube for family nutrition and specialist out-patient treatment.The rest 24 cases were all improved and discharged.There were significant differences in nutrition indicators before and after EN,weight-for-age Z score (WAZ)(-2.3 ± 1.9 vs.-1.9 ± 1.8,t =4.156,P =0.000),weight-for-height Z score (WHZ) (-1.9 ± 1.7 vs.-1.2±1.5,t=3.714,P=0.001),albumin ((35 ±9)g/L vs.(39 ±6) g/L,t=3.017,P=0.005) and prealbumin ((0.11 ±0.05)g/L vs.(0.18 ±0.07)g/L,t=5.144,P=0.000).Conclusion EN is suitable for a variety of children's digestive diseases,which can improve the nutritional status of the patients and was safe for clinical application.As the implementation of EN is simple and has good compliance,family EN is proven to be feasible.

Objective: To explore the clinical features and complications of foreign bodies in the upper gastrointestinal tract in children and to investigate the effectiveness of endoscopic management. Methods: Data of patients with foreign bodies in upper gastrointestinal tract were collected retrospectively at Endoscopy Center, the Children's Hospital, Zhejiang University School of Medicine, from January 2011 to December 2016. Clinical characteristics, the types of foreign bodies, the location and duration of foreign body impaction were summarized. The risk factors of complications and endoscopic removal failure were analyzed by using Logistic regression analysis. Results: A total of 1 334 patients (825 males and 509 females) were enrolled. The median age was 2.5 years, with a range from 0.25 to 15 years and peak age 1-3 years. Twenty patients had esophageal diseases. The most common foreign body ingested was coin (n=964, 72.3%). Foreign bodies were most commonly located in the esophagus (n=1 002, 75.1%), especially in the upper esophagus (n=857, 85.5%). The duration of foreign body impaction ranged from 3 hours to 5 years. Among 1 334 patients, 252 patients (18.9%) developed complications, including ulcers (n=101, 40.0%) and perforations(n=13, 5.2%). The success rate of endoscopic removal was 96.6% (n=1 288). By Logistic regression analysis, sharp foreign body ingestion (OR=6.893, 95%CI: 4.421-10.746) , esophageal impaction (OR=5.253, 95%CI:3.352-8.233) and foreign body impaction longer than 24 hours (OR=4.336, 95%CI:3.091-6.082) were risk factors of complications. Sharp foreign body ingestion was the risk factor of endoscopic failure (OR=5.372, 95%CI:2.773-10.406) . Conclusions Coin is the most common foreign body in upper gastrointestinal tract. Sharp foreign bodies impacted in the esophagus over 24 hours increase the risk of complications. Endoscopic removal of foreign bodies from the upper gastrointestinal tract in children has a high success rate. Sharp foreign body ingestion increases the risk of failure in endoscopic removing.

Objective: To evaluate the effectiveness of enteral nutrition in children with accidental upper gastrointestinal injury. Methods: The medical records of 128 patients with mechanical or chemical gastrointestinal mucosal injury, who were hospitalized in Department of Gastroenterology, Children's Hospital of Zhejiang University School of Medicine from January 1, 2011 to December 30, 2017, were collected. All cases were treated with enteral nutrition. The clinical features and etiologies were retrospectively analyzed. Weight-for-age Z score and lab findings including white blood cells, C-reactive protein, neutrophils, albumin, prealbumin, urea nitrogen and hemoglobin before and after treatment were extracted. The clinical characteristics, the duration of enteral nutrition and gastrointestinal mucosal healing between different etiologies were further analyzed. Normal distribution variables and categorized variables were compared with t test and χ² test respectively, and abnormal distribution data was compared with Wilcoxon test. Results: Among all the cases, 77 were males and 51 were females. The average age was (29±22) months. The mean duration of hospitalization and enteral nutrition were (11±7)d and (27±20)d respectively. Vomiting was the most common clinical presentation (72 cases, 56.3%). In 79 cases the problems were caused by mechanical injury, among which coins were most commonly seen. The rest 49 cases were caused by chemical injury. However, the duration of hospitalization ((13±8) d vs. (10±6)d, t=-3.089, P=0.002) and enteral nutrition ((39±22) vs. (19±14) d, t=-5.365, P=0.000) were longer in children with chemical injury than those with mechanical injury. A total of 112 cases got complete blood count and C-reactive protein both before and after enteral nutrition. Inflammatory markers, including leukocytes ((7.7±2.7) ×10⁹/L vs. (13.7±5.0) ×10⁹/L, t=12.244, P <0.05), neutrophils ((3.4±1.9)×10⁹/L vs. (9.4±4.6) ×10⁹/L, t=13.655, P<0.05), and C-reactive proteins (5.0(3.0,7.8) vs. 13.5(6.0,40.5) mg/L, Z=7.776, P <0.05) were significantly decreased. The nutritional markers, including the weight-for-age z score (-0.1 ± 1.0 vs. 0.0 ± 1.0, t=-2.622, P=0.010) and the prealbumin (0.1 ± 0.1 vs. 0.2 ± 0.0 g/L, t=-3.671, P=0.001) were significantly increased. Fifty-five (82.1%) children in mechanical injury group recovered in 4 weeks, while 27 (79.4%) children in chemical injury group recovered in 7 weeks. Conclusion Enteral nutrition can provide adequate nutritional requirements for children with upper gastrointestinal injury, and may help to decrease imflammation and improve mucosal healing.

Endoscopic retrograde cholangiopancreatography（ERCP）is an important minimally invasive treatment method in adults with biliary and pancreatic diseases. With the development of endoscopic technology and the increasing understanding of pediatric biliary and pancreatic diseases，ERCP technology has gradually become an indispensable diagnostic and treatment method for pediatric patients with biliary and pancreatic diseases. This review mainly elaborated on the indications and surgical points of ERCP in pediatric biliary and pancreatic diseases，in order to promote the application and development of ERCP in children.

Background::Gut-resident macrophages (gMacs) supplemented by monocytes-to-gMacs differentiation play a critical role in maintaining intestinal homeostasis. Activating transcription factor 4 (ATF4) is involved in immune cell differentiation. We therefore set out to investigate the role of ATF4-regulated monocytes-to-gMacs differentiation in sepsis-induced intestinal injury.Methods::Sepsis was induced in C57BL/6 wild type (WT) mice and Atf4-knockdown ( Atf4+/-) mice by cecal ligation and puncture or administration of lipopolysaccharide (LPS). Colon, peripheral blood mononuclear cells, sera, lung, liver, and mesenteric lymph nodes were collected for flow cytometry, hematoxylin and eosin staining, immunohistochemistry, quantitative reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. Results::CD64, CD11b, Ly6C, major histocompatibility complex-II (MHC-II), CX3CR1, Ly6G, and SSC were identified as optimal primary markers for detecting the process of monocytes-to-gMacs differentiation in the colon of WT mice. Monocytes-to-gMacs differentiation was impaired in the colon during sepsis and was associated with decreased expression of ATF4 in P1 (Ly6C hi monocytes), the precursor cells of gMacs. Atf4 knockdown exacerbated the impairment of monocytes-to-gMacs differentiation in response to LPS, resulting in a significant reduction of gMacs in the colon. Furthermore, compared with WT mice, Atf4+/- mice exhibited higher pathology scores, increased expression of inflammatory factor genes ( TNF-α, IL-1β), suppressed expression of CD31 and vascular endothelial-cadherin in the colon, and increased translocation of intestinal bacteria to lymph nodes and lungs following exposure to LPS. However, the aggravation of sepsis-induced intestinal injury resulting from Atf4 knockdown was not caused by the enhanced inflammatory effect of Ly6C hi monocytes and gMacs. Conclusion::ATF4, as a novel regulator of monocytes-to-gMacs differentiation, plays a critical role in protecting mice against sepsis-induced intestinal injury, suggesting that ATF4 might be a potential therapeutic target for sepsis treatment.