Objective:To explore the multidisciplinary management that centred on gastroenterology department, and follow-up study of children with Alagille syndrome(ALGS).Methods:The clinical data of 19 children diagnosed with ALGS in Pediatric Gastroenterology Department, Shengjing Hospital of China Medical University since June 2013 to December 2022 was retrospectively analyzed, and the clinical manifestations of various systems of the body were followed up and evaluated, and then developed the personalised management strategies.Results:Among the 19 confirmed patients, 18 cases were confirmed by genetic testing.Eighteen cases(94.7%) had characteristic facial features.To follow-up node, 8 cases(42.1%) had cholestasis, with alanine aminotransferase(210.20±110.50)U/L, aspartate aminotransferase(187.86±96.70)U/L, and direct bilirubin(110.93±108.15)μmol/L.Eighteen cases(94.7%) had pruritus.Eighteen cases(94.7%) of the patients had a high risk of malnutrition, and the level of total bilirubin[(76.17±107.34)μmol/L] and total bile acid[(100.18±83.78)μmol/L] were significantly increased in the children with obvious growth retardation.Thirteen cases(68.42%) had diffuse liver injury.The clinical opinions on genetic counseling, application of new drugs, liver transplantation, cardiac medicine and surgery follow-up, spine and oral surgery orthodontics were given by multiple disciplines.Conclusion:ALGS children have a high risk of long-term malnutrition and are associated with the severity of liver injury, and pruritus and jaundice are the main clinical manifestations.The management of ALGS patients should be centered around liver disease doctors, combined with multiple disciplines, paying attention to changes in various related organs of ALGS patients, and improving their quality of life.

Inflammatory bowel disease is a chronic recurrent inflammatory disease of the intestine of unknown origin.It is currently thought to be mediated by a combination of susceptibility genes, intestinal microecology and immune involvement, with all three interacting and influencing each other.This leads to a disruption of the intestinal microenvironment, which affects the host′s immune tolerance, and ultimately induces intestinal inflammation.In this review, we summarized the mechanisms of intestinal microbiota in children with inflammatory bowel disease and discussed new ideas of microecological agents for individualized treatment of children with inflammatory bowel disease.

Henoch Schonlein purpura(HSP), also known as immunoglobulin A vasculitis, is the most common vasculitis in children, which involves skin, gastrointestinal tract, joints and kidney.Glucocorticoid is the conventional treatment for HSP patients with digestive system symptoms.Antacids, including H 2-receptor antagonists and proton pump inhibitors, are often used in combination with glucocorticoids in order to avoid the adverse reactions of glucocorticoids therapy.Antacids may play a role in the treatment of HSP patients by alleviating gastrointestinal symptoms, adjuvant treatment of secondary acute pancreatitis, inhibiting Helicobacter pylori and reducing the adverse reactions of glucocorticoids.However, there are few studies and more exploration is needed.

Inflammatory bowel disease(IBD)is a group of chronic intestinal inflammatory diseases with unknown etiology and pathogenesis.It usually presents chronic diarrhea, mucous bloody stool, recurrent abdominal pain and other non-specific intestinal manifestations, and it is also accompanied by recurrent fever, growth delay.More studies show that IBD not only affects the intestinal function, but also involves the external organs of the body.The most involved organs include the mouth, joints, skin and eyes.Its pathogenesis is related to genetic susceptibility, immune system disorder and the influence of intestinal microbiota.In addition, the extraintestinal manifestations of inflammatory bowel disease can occur several years before and after diagnosis, which can easily cause delay in diagnosis.Therefore, clinicians should be aware of the various manifestations of inflammatory bowel disease and develop a treatment plan.This review will state the recent progress of extraintestinal manifestations of inflammatory bowel disease in children.

Objective To observe the effect of Saccharomyces boulardii(SB) on interleukin-17, interleukin-10 and transforming growth factor-β1 of inflammatory bowel disease ( IBD ) rats which were induced by trinitro-benzene-sulfonic acid( TNBS) . Methods Balb/c female rats were randomly divided into three groups,normal group,TNBS group and TNBS+SB group. TNBS method was used to set up IBD rat models. TNBS group:the mice were injected by 5％ TNBS 0. 1 ml+50％ ethanol 0. 1 ml per mouse from rectum for 5 days,and then were filled in stomach by normal saline 0. 1 ml on the 2nd day for 2 weeks;TNBS+SB group:the mice were injected by 5％ TNBS 0. 10 ml+50％ ethanol 0. 10 ml per mouse from rectum for 5 days,and then were filled in stomach by SB (SB no less than 109 CFU/ml) 0. 1 ml on the 2nd day for 2 weeks;the normal group:the mice were injected by 50％ ethanol 0. 2 ml per mouse from rectum for 5 days, and then were filled in stomach by normal saline 0. 1 ml on the 2nd day for 2 weeks. At the 15th day,the general situation of mice were observed,serum and colon tissue was collected. Alterations of colon inflamma-tion were observed by means of haematoxylin-eosin ( HE);the level of IL-17,IL-10 and TGF-β1 in serum were evaluated by enzyme linked immunosorbent assay (ELISA). The level of IL-17,IL-10 and TGF-β1 in colon tissue was evaluated by immunohistochemistry. Results The IL-17 level of serum and colon tissue in-creased(P<0. 05),but IL-10(P<0. 05) and TGF-β1(P<0. 05)decreased in TNBS group compared with those in the normal group. The level of IL-17 in TNBS+SB group was lower than that in TNBS group( P<0. 05),but the levels of IL-10(P<0. 05) and TGF-β1(P<0. 05)were higher than those in TNBS group. Compared with the normal group,the level of IL-17 in TNBS+SB group increased ( P<0. 05 ) , but IL-10 (P<0.05) and TGF-β1(P <0.05)decreased. Conclusion The expression of cytokine IL-17 increase, IL-10 and TGF-β1 decrease in peripheral blood and colon tissue of IBD. SB may ameliorate the intestinal inflammatory response of IBD by balancing the expression of IL-17,IL-10 and TGF-β1.

Objective To establish the inflammatory bowel disease model of mice by Trinitro-benzenesulfonic acid(TNBS).To investigate the correlation between the IBD and SIgA level and the effect of Clostridium butyricum,Bifidobacterium infantis single or combined on sIgA expression.Methods BABL/c mice were randomly divided into:WT group,TNBS group,CB group,BB group and CB + BB group.After 2 weeks,the general situation and weight change of mice was evaluated.Then the mice were sacrificed to collect colon tissue.The inflammation of each group was observed by HE staining.The expression of sIgA were respectively located and measured by immunohistochemistry and Western blotting.Results TNBS group showed more pathological changes in the colon than the WT group,CB group,BB group and CB + BB group;the expressions of sIgA in colon were mainly located in intestinal lumen and lamina propria of intestinal villus;the level of sIgA in colon and tissue decreased in the TNBS group compared with WT group(P ＜ 0.01;P ＜ 0.01);the level of sIgA in colon and tissue increased ín the CB group and BB group compared with TN-BS group(P ＜0.01;P ＜0.01;P ＜0.01;P ＜ 0.01).There is no significant difference between CB group and BB group(P ＞ 0.05).The level of sIgA in colon and tissue increased in the CB +BB group compared with CB group or BB group(P ＜0.01;P ＜0.01).Conclusion The change of sIgA content is related to the occurrence of IBD.CB and BB can both promote sIgA production in IBD mice and reduce the inflammatory reaction.The combination of the two probiotics shows stronger effect than single one.

Objective:To investigate the improvement effects of duodenal-jejunal bypass (DJB)on the blood glucose homeostasis,insulin resistance and inflammation of the obese type 2 diabetic (T2DM)ZDF rats,and to discuss its possible mechanism.Methods:A total of 20 ZDF rats were randomly divided into DJB operation group and sham operation group (n = 10).There were 8 rats survived in each group after operation.The level of blood glucose (FBG)was detected by Roche glucose meter at 1 week before operation,2 weeks,4 weeks and 6 weeks after operation;the fasting serum insulin level of the rats was measured by ELISA kit;the insulin sensitivity index (HOMA-ISI)and insulin resistance index (HOMA-IR)were calculated.The rats were executed 6 weeks after operation.HE staining was used to observe the morphology of the inflammatory cells in BP limb of the rats;the expression levels of AMPK and pAMPK in BP lamb of the rats were observed by immunohistochemical staining;the expression levels of interleukin 1β(IL-1β),interleukin 6 (IL-6),tumor necrosis factorα(TNF-α),nuclear factorκB (NF-κB),and interleukin 10 (IL-10)mRNA of the rats were detected by QRT-PCR method.Results:From the 2nd week after operation,compared with before operation,the FBG levels of the rats in DJB operation group were decreased (t=3.798,P <0.05);compared with sham operation group,the FBG level of the rats in DJB operation group was decreased (t=3.205,P <0.05).Six weeks after operation,compared with sham operation group,the HOMA-IR of the rats in DJB operation group was significantly decreased (t=4.441,P <0.05)and the HOMA-ISI was significantly increased (t=-8.65,P < 0.05).The HE staining results showed that compared with sham operation group,the morphology of the inflammatory cells in BP limb of the rats in DJB operation group was significantly improved.The QRT-PCR results showed that the expression levels of IL-1β,IL-6,TNF-αand NF-κB of the rats in DJB operation group was significantly decreased compared with sham operation group (P < 0.05), while the expression level of IL-10 was significantly increased (P < 0.05).The immunohistochemical test results showed that the expression levels of AMPK and pAMPK in BP lamb of the rats in DJB operation group were increased compared with sham operation group.Conclusion:DJB can significantly improve the blood glucose homeostasis and insulin resistance in the T2DM rats,and its mechanism may be related to the decreased expressions of inflammatory factors and the activation of AMPK molecules in BP lamb of the T2DM rats.

Objective: To evaluate the efficacy and safety of Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea (AAD) in infants and young children. Method: From November 2012 to September 2013, ten research units of large teaching hospitals or children′s hospitals participated in this multicenter randomized controlled clinical trial. Hospitalized young children aged between 1 month and 3 years (nongastrointestinal infection and antibiotic therapy required)were involved in our study. The children were randomly divided into control group and prevention group by means of block random allocation method. The control group received antibiotic therapy and other conventional treatment. The prevention group was given additional Saccharomyces boulardii (250 mg/d) orally. Diarrhea rates of two groups were compared both during the usage of antibiotics and within 14 days after the antibiotics withdrawal. The adverse reactions of Saccharomyces boulardii were observed all through this study. The results were analyzed by χ² test or Kruskal-Wallis test or t test. Result: Totally 408 cases (213 cases in prevention group and 195 cases in control group) were enrolled. The age ranged from 1 month to 3 years, with an average age of 1.14 years. The basic diseases were parenteral infections: 368 cases with different kinds of respiratory tract infections or pneumonia, 10 cases of bacterial meningitis, 9 cases with septicemia or sepsis, 6 cases with pertussis or pertussis like syndrome, 5 cases with urinary infection, 5 cases with skin or subcutaneous tissue infections, 3 cases of Kawasaki disease, one with scarlet fever and one with congenital syphilis. During the administration of antibiotics, the incidence of AAD in prevention group was 10.3% (22 cases), which was significantly lower than that of control group (57 cases, 29.2%, χ²=23.296, P<0.05). Within 14 days after the discontinuation of antibiotics, the percent of new diarrhea cases in prevention group (2.4%, 5/213) was also significantly lower than that in control group (16.4%, 32/195, χ²=23.4, P<0.05). Further analysis revealed that the rate of AAD in children less than or equal to 1 year old (25.1%, 52/207) was significantly higher than that of over 1 year old (13.4%, 27/201, χ²=8.922, P<0.05). The incidence of AAD in children treated with antibiotics for more than 5 days was 22.2%(60/270), which was significantly higher than that of less than or equal to 5 days (13.8%, 19/138, χ²=4.180, P<0.05). Although no significant difference was observed, the AAD rate of patients with combined use of two antibiotics was higher than that of using one. During the antibiotic therapy, compared with the control group, the risk of AAD in children under 1 year old was reduced by 52% (χ²=9.217, P<0.05), and 91% (χ²=20.35, P<0.05) in the children over 1 year old in prevention group. The risk of AAD of prevention group decreased by 66% (χ²=13.67, P<0.05) in patients treated with one antibiotics, and 65% in children with combined use of antibiotics (χ²=10.57, P<0.05). In patients treated with antibiotics for less than or equal to 5 days, the risk of AAD decreased by 74% in prevention group (χ²=7.38, P<0.05); and 63% if the course lasted for over 5 days (χ²=16.87, P<0.05). Within 14 days after the withdrawal of antibiotics, compared with the control group, the risk of diarrhea in the prevention group decreased by 82% (χ²=13.35, P<0.05) in infants (≤1 year old) and 93% (χ²=12.00, P<0.05) in children (>1 year old); the risk of diarrhea was reduced by 86% (χ²=9.57, P<0.05) and 87% (χ²=17.71, P<0.05) respectively in prevention group with single and combined use of antibiotics. In patients treated with antibiotics for more than 5 days, the risk of diarrhea in prevention group was reduced by 63% (χ²=22.79, P<0.05), while there was no significant difference if the antibiotics course was less than or equal to 5 days (χ²=2.97, P>0.05). No adverse effects related with Saccharomyces boulardii were observed in our study. Conclusion Saccharomyces boulardii is effective and safe to prevent AAD of infants and young children both during the usage of antibiotics and up to 14 days after drug discontinuance. It can be one of the drugs of for choice prevention of AAD in infants and young children. Trial registration Chinese Clinical Trial Tegister, ChiECRCT-2012-25.

Objective To evaluate the protection of combined clostridium butyricum and bifidobac-terium living powders for antibiotic-associated diarrhea ( AAD ) with all kinds of infections in hospitalized children,and to compare the therapeutic effect with saccharomyces boulardii. Methods This study was a prospective,randomized case-control clinical trial which collected the data of the hospitalized children with all kinds of infections in Pediactric Department of Shengjing Hospital of China Medical University between May 2011 to May 2012. A total of 552 cases were enrolled and 480 cases completed the study. A total of 240 chil-dren were in experimental group,80 cases received combined clostridium butyricum and bifidobacterium liv-ing powders 840 mg per time,twice a day and the other 160 cases received saccharomyces boulardii 250 mg per time,twice a day,for one week; the control group took none of probiltics. Two groups received routine antibiotic therapy. Everyday′s defecate frequency was recorded, the traits of excrement according to bristol stool assessment scale were evaluated,the incidence of diarrhea and drug related adverse reactions were coun-ted. Results During the studied 7 days,the AAD incidence was 4. 2%(10/240) in experimental group and 20. 4%(49/240) in control group,there was significant difference between two groups. The risk of AAD in experimental group decreased 58. 5%. Compared to saccharomyces boulardii,combined clostridium butyricum and bifidobacterium living powders decreased 38. 2% (RR=0. 728, 95%CI 0. 257~0. 784, P=0. 009). Compared to control group,the average defecate frequency decreased in experimental group,diarrhea duration contracted,there was statistic difference between two groups ( P<0. 01 ) . No drug related adverse reactions happened during the trial. Conclusion Both combined clostridium butyricum and bifidobacterium living powders and saccharomyces boulardii could effectively reduce the risk of AAD in hospitalized children with bacterial infection,relieve diarrhea symptoms,short the duration of diarrhea,and did not find the adverse reac-tions. Combined clostridium butyricum and bifidobacterium living powders and saccharomyces boulardii had the same protective effect for AAD of northern China children.

Human cytomegalovirus (HCMV) infection is very common in the population. The form of infection usually presents silent or latent infection in the persons with normal immune function, but it can lead to a high mortality in the fetuses and the patients with immune deficiency. At present,the pathogenesis of the congenital infection by HCMV is not very clear. In the α chemokine homologue encoded by HCMV UL146, the variation of the nucleotide and amino acid sequences and the highly conservative domain suggests that this domain is important for HCMV in biological significance. And the study on the gene polymorphism and the function of its encoding protein will play an important role to reveal the pathogenesis of HCMV.