Clinical Features and Genetic Analysis of Pediatric Patients with Alagille Syndrome Presenting Initially with Liver Function Abnormalities / 华中科技大学学报（医学）（英德文版）

Alagille syndrome (AGS) is a multisystem disorder and caused by mutations in JAG1 or NOTCH2 gene.The diagnosis of AGS is hampered by its highly variable clinical manifestations.We performed a retrospective analysis on 16 children diagnosed as having AGS in recent five years in our hospital.Cholestasis was seen in 15 patients (93.8％),heart disease in 12 (75％),characteristic facies in 7 (43.8％),and butterfly vertebrae in 7 (43.8％).Ophthalmology examination was not performed on all the patients.Further,serum biochemical parameters were compared between AGS and 16 biliary atresia (BA) patients who were confirmed by surgery.Elevated liver enzymes were seen in all the patients.Serum total cholesterol (TC) (P=0.0007),alanine aminotransferase (ALT) (P=0.0056),aspartate aminotransferase (AST) (P=0.0114),gamma-glutamyl transferase (GGT) (P=0.035) and total bile acid (TBA) levels (P=0.042) were significantly elevated in AGS patients compared to those in BA cases.However,there were no significant differences in serum total bilirubin (TB),conjugated bilirubin (CB) and albumin (ALB) between the two groups.We identified 14 different JAG1 gene variations and 1 NOTCH2 gene mutation in 16 Chinese AGS patients.Our study suggested clinical features of AGS are highly variable and not all patients meet the classical diagnostic criteria.It was suggested that hypercholesterolaemia and significantly elevated GGT,TBA and ALT may be helpful to diagnose AGS.Genetic testing is integral in the diagnosis of AGS.

Clinical Features and Genetic Analysis of Pediatric Patients with Alagille Syndrome Presenting Initially with Liver Function Abnormalities / 华中科技大学学报（医学）（英德文版）

Alagille syndrome (AGS) is a multisystem disorder and caused by mutations in JAG1 or NOTCH2 gene.The diagnosis of AGS is hampered by its highly variable clinical manifestations.We performed a retrospective analysis on 16 children diagnosed as having AGS in recent five years in our hospital.Cholestasis was seen in 15 patients (93.8％),heart disease in 12 (75％),characteristic facies in 7 (43.8％),and butterfly vertebrae in 7 (43.8％).Ophthalmology examination was not performed on all the patients.Further,serum biochemical parameters were compared between AGS and 16 biliary atresia (BA) patients who were confirmed by surgery.Elevated liver enzymes were seen in all the patients.Serum total cholesterol (TC) (P=0.0007),alanine aminotransferase (ALT) (P=0.0056),aspartate aminotransferase (AST) (P=0.0114),gamma-glutamyl transferase (GGT) (P=0.035) and total bile acid (TBA) levels (P=0.042) were significantly elevated in AGS patients compared to those in BA cases.However,there were no significant differences in serum total bilirubin (TB),conjugated bilirubin (CB) and albumin (ALB) between the two groups.We identified 14 different JAG1 gene variations and 1 NOTCH2 gene mutation in 16 Chinese AGS patients.Our study suggested clinical features of AGS are highly variable and not all patients meet the classical diagnostic criteria.It was suggested that hypercholesterolaemia and significantly elevated GGT,TBA and ALT may be helpful to diagnose AGS.Genetic testing is integral in the diagnosis of AGS.

Novel Insights into the Pathogenesis of Hirschsprung's-associated Enterocolitis / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To systematically summary the updated results about the pathogenesis of Hirschsprung's-associated enterocolitis (HAEC). Besides, we discussed the research key and direction based on these results.</p><p><b>DATA SOURCES</b>Our data cited in this review were obtained mainly from PubMed from 1975 to 2015, with keywords "Hirschsprung enterocolitis", "Hirschsprung's enterocolitis", "Hirschsprung's-associated enterocolitis", "Hirschsprung-associated enterocolitis", "HAEC", and "EC".</p><p><b>STUDY SELECTION</b>Articles regarding the pathogenesis of HAEC were selected, and the articles mainly regarding the diagnosis, surgical approach, treatment, and follow-up were excluded.</p><p><b>RESULTS</b>Several factors, mainly including mucus barrier, intestinal microbiota, and immune function, as well as some other factors such as genetic variations and surgical reasons, have been found to be related to the pathogenesis of HAEC. Changed quantity and barrier property of mucus, different composition of microbiota, and an abnormal immune state work together or separately trigger HAEC.</p><p><b>CONCLUSIONS</b>The maintenance of intestinal homeostasis is due to a well cooperation of microbiota, mucus barrier, and immune system. If any part presents abnormal, intestinal homeostasis will be broken. Meanwhile, for patients with Hirschsprung's disease or HAEC, dysfunction of these parts has been found. Thus, the happening of HAEC may be mainly attributed to the disorders of intestinal microbiota, mucus barrier, and immune system.</p>

Intestinal microcirculatory dysfunction and neonatal necrotizing enterocolitis / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>Based on the observation that coagulation necrosis occurs in the majority of neonatal necrotizing enterocolitis (NEC) patients, it is clear that intestinal ischemia is a contributing factor to the pathogenesis of NEC. However, the published studies regarding the role of intestinal ischemia in NEC are controversial. The aim of this paper is to review the current studies regarding intestinal microcirculatory dysfunction and NEC, and try to elucidate the exact role of intestinal microcirculatory dysfunction in NEC.</p><p><b>DATA SOURCES</b>The studies cited in this review were mainly obtained from articles listed in Medline and PubMed. The search terms used were "intestinal microcirculatory dysfunction" and "neonatal necrotizing enterocolitis".</p><p><b>STUDY SELECTION</b>Mainly original milestone articles and critical reviews written by major pioneer investigators in the field were selected.</p><p><b>RESULTS</b>Immature regulatory control of mesentery circulation makes the neonatal intestinal microvasculature vulnerable. When neonates are subjected to stress, endothelial cell dysfunction occurs and results in vasoconstriction of arterioles, inflammatory cell infiltration and activation in venules, and endothelial barrier disruption in capillaries. The compromised vasculature increases circulation resistance and therefore decreases intestinal perfusion, and may eventually progress to intestinal necrosis.</p><p><b>CONCLUSION</b>Intestinal ischemia plays an important role through the whole course of NEC. New therapeutic agents targeting intestinal ischemia, like HB-EGF, are promising therapeutic agents for the treatment of NEC.</p>

Changes of glucagon-like peptide-2 expression in serum and ileum after colectomy in rats / 中华实用儿科临床杂志

Objective To explore the effect of colectomy on the expression of glucagon-like peptide-2 (GLP-2) in serum and ileum and compare the changes of GLP-2 after different colectomy in rats.Methods Eighty male or female rats,aging 3-4 months old,were recruited in this study.The rats weight 180-250 g.The 80 rats were evenly and randomly distributed into 4 groups according to the surgical procedures they underwent:control group,in which the rats were not performed any procedures; sham surgery group,in which the rats underwent laparotomy ;left hemicolectomy group,in which the rats were performed left hemicolectomy;and subtotal colectomy group,in which the rats were performed subtotal colectomy.According to execution time,each group had 4 subgroups,including 0 day group,10 day group,20 day group and 30 day group,and 5 rats were included in each subgroup.The whole blood was collected through cardiac puncture.Serum was collected and GLP-2 in serum was determined by enzyme-linked immunosorbent assay.The GLP-2 in ileum was studied by immunohistochemistry staining.The length of villus of ileum was also measured by HE staining.Results The protein of GLP-2 was found in fibroblasts,epithelium and endocrine cells in ileum.Compared with control group and sham surgery group,the expressions of GLP-2 in serum and ileum increased significantly in the rats that underwent left hemicolectomy after surgery(all P ＜ 0.05),and it was increasing with time.The villus length of the rats underwent left hemicolectomy also increased significantly compared with the control group and sham surgery groups 20 days and 30 days after surgery(all P ＜ 0.05).The expressions of GLP-2 in serun and ileum and villus length of the rats with subtotal colectomy were not significantly different from those of the control group and sham surgery group(all P ＞ 0.05).Conclusions The expressions of GLP-2 in serum and ileum are elevated after left hemicolectomy but not in subtotal colectomy,which may be related to the delayed intestinal adaption after colectomy.

Comparison of embryonic nature orifice transumbilical endoscopic surgery with conventional laparoscopic surgery treatmenting Hirschsprung disease / 中华实用儿科临床杂志

Objective To compare the therapeutic effects of embryonic nature orifice transumbilical endoscopic surgery(ENOTES) with conventional laparoscopic(CL) surgery in Hirschsprung disease(HD).Methods A total of 111 children from Sep.2009 to Dec.2010 were included in the retrospective study.The patients were divided into 2groups:ENOTES group (66 cases) and CL group (45 cases).The general conditions of children were reviewed operative situation,postoperative complications and defecation 1 year after operation.Results In the left colectomy,there was no difference between 2 groups in age,weight,operative blood loss and postoperative stay (all P ＞ 0.05),but ENOTES took up less time than CL(P ＜ 0.05) ;in the subtotal colectomy,no significant difference existed in all series.All children underwent primary radical surgery,neither transfer to open surgery nor dead case.In ENOTES group,there were 9 cases suffering from enterocolitis postoperatively (13.6％),while 7 cases (15.6％) in CL group.Twenty-eight patients in ENOTES group and 12 in CL group were followed up for 1 year.Less abdominal distension postoperatively was noted in ENTOES group than CL group(P ＜ 0.05),but no other difference in other available data.In addition,no obvious operative scar was noted on the abdomen in ENOTES group,what meant better cosmetic benefit than CL.Conclusion HD treated with ENOTES can gain the same outcomes with CL with better cosmetic effect.

Transumbilical laparoscopic pull-through for children with hypoganglionosis / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the surgical outcomes after on transumbilical laparoscopic pull-through procedure for pediatric hypoganglionosis(HYP).</p><p><b>METHODS</b>Twelve children with HYP had received transumbilical laparoscopic pull-through procedure from June 2009 to June 2010. Specially designed curved and elongated laparoscopic instruments were used during the procedures. All the patients were followed up over 10 months. Data were collected and analyzed. The diagnosis of hypoganglionsis was pathologically confirmed.</p><p><b>RESULTS</b>No conversions to laparotomy or traditional laparoscopic surgery were required and there were no damages to the abdominal blood vessels, intestine, ductus deferens, or ureters. The average duration of operation was 140 min. The mean intraoperative blood loss was 45 ml. The mean length of specimen was 40 cm. Postoperatively there were no complications such as anastomotic leak, anastomotic stricture, constipation, seepage, or fecal in continence. The average hospital stay after surgery was 9 days. During 10 to 22 months of follow-up(median 16 months), no postoperative recurrence was noticed. No obvious scar was seen 1 months after surgery.</p><p><b>CONCLUSION</b>It is safe and effective for children with hypoganglionosis to undergo transumbilical laparoscopic pull-through procedure.</p>

Study Progress of Ex Utero Intrapartum Treatment / 实用儿科临床杂志

Airway problems in foetus that may cause airway obstruction can be safely managed by using an ex utero intrapartum technique(EXIT).The EXIT procedure maintains a period of uteroplacental circulation for fetal oxygenation during delivery to provide time to explore and secure the airway of the fetus or to perform fetal operations before the umbilical cord is clamped.The common indication for the EXIT procedure is the presence of foetal airway obstruction,which is usually caused by neck mass,congenital diaphragmatic hernia,congenital high way obstruction syndrome,thoracic abnormality,congenital heart and lung dysfunction,conjoined twins,and so on.It avoids the acute airway obstruction in a neonate that has disastrous consequences.

Relationship between Interstitial Cells of Cajal and Gastrointestinal Inflammation in Children / 实用儿科临床杂志

The main function of interstitial cells of Cajal(ICCs) is to produce the gastrointestinal slow-wave electric potential,to impel the propagation of electric potential,and to participate in the transmission of neural signal.The decrease or abnormal distribution of ICCs would lead to gastrointestinal inflammation easily.Meanwhile,as the gastrointestinal inflammation happens,inflammatory cells and mediators also can reduce the number of ICCs.

Clinical Analysis of 20 Children with Ganglioneuroma / 实用儿科临床杂志

Objective To increase the preoperative diagnosis rate,reform the operation and improve the prognosis in children with ganglio -nauroma.Methods Clinical data of 20 children with ganglioneuroma hospitalized in Tongji hospital of Huazhong university of science and technology from Nov.1986 to May.2006 were reviewed(male 9,female 11).The biological,clinical and pathological characteristics of patients were analyzed.Results Among these 20 patients,15 cases were discovered to have no clinical symtom.The B ultrasound showed low-echo in all 16 cases.Under CT scan,20 cases showed low to moderate density shadows,and the distinct enhancement in these tumors was noted with enhanced CT scan.Fourteen cases undergoing MRI all showed low signals in T1W1 and inhomogeneous high signals in T2W1.All patients underwent surgical operations,completely removed in 14 cases,partly in 4 cases, and biopsy was performed only in 2 cases.Fifteen cases were followed up from 7 months to 6 years,tumor recurrence happened only in 1 case.Conclusions Ganglioneuroma is mostly found in chest-abdominal sympathetic chain,it grows up slowly and seems to be innocent.The imaging data of B ultrasound,CT and MRI can give helpful information in the diagnosis of ganglioneuroma.We shall pay attention to the choice of incision and avoidance of injuring the important blood vessels during the operation.Children who have neuroblastoma cells should receive prophylactic chemoprophylaxis treatment and the result of long-time follow up is satisfactory.