Alanine aminotransferase as a risk marker for new-onset metabolic dysfunction-associated fatty liver disease.

In this editorial, we comment on the article by Chen et al. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a global public health burden whose incidence has risen concurrently with overweight and obesity. Given its detrimental health impact, early identification of at-risk individuals is crucial. MAFLD diagnosis is based on evidence of hepatic steatosis indicated by liver biopsy, imaging, or blood biomarkers, and one of the following conditions: Overweight/ obesity, type 2 diabetes mellitus, or metabolic dysregulation. However, in large-scale epidemiological studies, liver biopsies are not feasible. The application of techniques such as ultrasonography, computed tomography, magnetic resonance imaging, and magnetic resonance spectroscopy is restricted by their limited sensitivity, low effectiveness, high costs, and need for specialized software. Blood biomarkers offer several advantages, particularly in large-scale epidemiological studies or clinical scenarios where traditional imaging techniques are impractical. Analysis of cumulative effects of excess high-normal blood alanine aminotransferase (ALT) levels of blood ALT levels could facilitate identification of at-risk patients who might not be detected through conventional imaging methods. Accordingly, investigating the utility of blood biomarkers in MAFLD should enhance early detection and monitoring, enabling timely intervention and management and improving patient outcomes.

Comprehensive characterization of the genetic landscape of familial Hirschsprung's disease.

BACKGROUND: Hirschsprung's disease (HSCR) is one of the most common congenital digestive tract malformations and can cause stubborn constipation or gastrointestinal obstruction after birth, causing great physical and mental pain to patients and their families. Studies have shown that more than 20 genes are involved in HSCR, and most cases of HSCR are sporadic. However, the overall rate of familial recurrence in 4331 cases of HSCR is about 7.6%. Furthermore, familial HSCR patients show incomplete dominance. We still do not know the penetrance and genetic characteristics of these known risk genes due to the rarity of HSCR families. METHODS: To find published references, we used the title/abstract terms "Hirschsprung" and "familial" in the PubMed database and the MeSH terms "Hirschsprung" and "familial" in Web of Science. Finally, we summarized 129 HSCR families over the last 40 years. RESULTS: The male-to-female ratio and the percentage of short segment-HSCR in familial HSCR are much lower than in sporadic HSCR. The primary gene factors in the syndromic families are ret proto-oncogene (RET) and endothelin B receptor gene (EDNRB). Most families show incomplete dominance and are relevant to RET, and the RET mutation has 56% penetrance in familial HSCR. When one of the parents is a RET mutation carrier in an HSCR family, the offspring's recurrence risk is 28%, and the incidence of the offspring does not depend on whether the parent suffers from HSCR. CONCLUSION: Our findings will help HSCR patients obtain better genetic counseling, calculate the risk of recurrence, and provide new insights for future pedigree studies.

Diaphyseal and Metaphyseal Modeling Defects-Clinical Findings and Identification of WRAP53 Deficiency in Craniometadiaphyseal Dysplasia.

Background: Diaphyseal and metaphyseal modeling defects lead to severe changes in bone mass and shape, which are common features in osteoporosis that linked to non-vertebral fractures. Original mechanism of diaphyseal and metaphyseal modeling defects has proved elusive. Studying rare syndromes can elucidate mechanisms of common disorders and identify potential therapeutic targets. Methods: We evaluated a family pedigree with craniometadiaphyseal dysplasia (CRMDD, OMIM 269300), a genetic disorder that is characterized by cortical-bone thinning, limb deformity, and absent of normal metaphyseal flaring and diaphyseal constriction. Systemic radiographic examination and serum hormone test were made for this rare disease. One patient and her two normal parents were examined by means of whole-exome sequencing (WES) to identify the candidate pathogenic gene and rule out mucopolysaccharidosis and Prader-Willi Syndrome by means of Sanger sequencing. Results: There are several conspicuous radiographic characteristics: (1) bullet-shaped phalanges, (2) long and narrow pelvic inlet, absent of supra-acetabular constriction, (3) round rod-shaped long tubular bones, (4) prominent aiploic mastoid, (5) bending-shaped limb, genua varus and genu varum, and (6) congenital dislocation of elbow. Here, we did not find any wormian bones, and there are several typical clinical characteristics: (1) macrocephaly and wide jaw, (2) Avatar elf-shaped ears, pointed and protruding ears, (3) hypertrophy of limbs, (4) flat feet and giant hand phenomenon, (5) nail dystrophy, (6) limb deformity, (7) high-arched palate, (8) superficial hemangiomas, (9) tall stature, and intellectual disability. In this patient, we found biallelic frameshift deletion mutations in WRAP53, and those two mutations were transmitted from her parents respectively. Conclusions: We describe her clinical and radiological findings and presented a new subtype without wormian bones and with a tall stature. Our study showed that craniometadiaphyseal dysplasia was caused by a deficiency of WRAP53 with autosomal recessive inheritance.

Phalangeal Intra-Articular Osteochondroma Caused a Rare Clinodactyly Deformity in Children: Case Series and Literature Review.

Background: Various factors are discovered in the development of clinodactyly. The purpose of this retrospective study was to present a group of children with a rare clinodactyly deformity caused by phalangeal intra-articular osteochondroma and evaluate the efficacy of various treatment methods. Methods: All child patients that were treated for finger problems in our center between Jan 2017 and Dec 2020 were reviewed. A detailed analysis was made of the diagnosis and treatment methods in eight rare cases. X-rays and histopathology were applied. Results: A preliminary analysis of 405 patients in total was performed, and we included eight cases in our final analysis. This cohort consisted of 2 girls and 6 boys, with a mean age of 5.74 ± 3.22 years (range: 2y5m to 11y). Overall, four patients had their right hand affected and four patients had their left hand affected. One patient was diagnosed as having hereditary multiple osteochondroma (HMO) while the other seven patients were all grouped into solitary osteochondroma. Osteochondroma was proven in all of them by histopathology examination. Preoperative X-rays were used to allow identification and surgery planning in all cases. All osteochondromas were intra-articular and in the distal end of the phalanges, which is located opposite the epiphyseal growth area. All of the osteochondromas developed in half side of the phalanges. The angulation in the finger long axis was measured, and resulted in a mean angulation of 34.63 ± 24.93 degree (range: 10.16-88.91 degree). All of them received surgery, resulting in good appearance and fingers straightening. No recurrence was recorded. Conclusions: This retrospective analysis indicates that 10 degrees can be selected as the angulation level for diagnosis of clinodactyly deformities. What's more important, the abnormal mass proven by X-rays should be included as the classical direct sign for diagnosis. The first choice of treatment is surgery in symptomatic osteochondromas.

Prenatal low-dose endotoxin exposure prolongs intestinal epithelial activation after birth and contributes to necrotizing enterocolitis.

PURPOSE: To investigate the effects of low dose endotoxin on transcriptional activity in intestinal epithelium, and its role in necrotizing enterocolitis (NEC). METHODS: Lipopolysaccharides (LPS) were injected into the amniotic cavity of pregnant mice under ultrasound guidance. The effects of LPS on fetal and neonatal intestines were determined. Mouse pups were exposed to low dose LPS (0.01 µg per fetus) prenatally and subjected to experimental NEC after birth. The incidence and severity of NEC, as well as intestinal permeability, NF-κB activation, and IL-6 expression were studied. The signaling pathways in the intestinal epithelial cells (IECs) that were activated by LPS were also investigated. RESULTS: Low dose LPS did not increase apoptosis, myeloperoxidase activity, histological injury or NF-κB activity in fetal intestines. However, prenatal low dose LPS exposure disturbed the transient and self-limited activation of NF-κB in neonatal intestines after birth. Importantly, it increased the incidence and severity of experimental NEC in neonatal mice. In primary IECs, low dose LPS induced IRAK-1 expression via activation of GSK3ß. Elevated IRAK-1 levels prolonged the activation of IECs upon stimulation by high dose LPS. CONCLUSION: Prenatal low dose endotoxin exposure disturbs self-limited postnatal epithelial cell activation and predisposes the neonatal intestine to NEC. LEVEL OF EVIDENCE: Not applicable (experimental animal study).

Dual roles of commensal bacteria after intestinal ischemia and reperfusion.

PURPOSE: The roles of commensal bacteria after intestinal ischemia and reperfusion (IIR) are unclear. In current study, we aim to investigate the effects and underlying mechanisms of commensal bacteria in injury and epithelial restitution after IIR. METHODS: Commensal gut bacteria were deleted by broad-spectrum antibiotics in mice. IIR was induced by clamping superior mesenteric artery. Intestinal injury, permeability, epithelial proliferation, and proinflammatory activity of mesenteric lymph were investigated. RESULTS: Commensals deletion improved mice survival in the early phase, but failed to improve the overall survival at 96 h after IIR. Commensals deletion reduced proliferation of intestinal epithelial cells (IEC) and augmented proinflammatory activity of mesenteric lymph after IIR. Lipopolysaccharides (LPS) supplement promoted IEC proliferation and improved survival in mice with commensals deletion after IIR. LPS induced production of prostaglandin E2 (PGE2) in mucosa via toll-like receptor 4-NFκB-cyclooxygenase 2 pathway. PGE2 enhanced IEC proliferation in vivo, which was preceded by activation of Akt and extracellular signal-regulated kinase (ERK) 1/2. Blocking of EGFR, PI3K/Akt activity abolished LPS-induced IEC proliferation. CONCLUSIONS: Commensal bacteria are essential for epithelial restitution after IIR, which enhance IEC proliferation via induction of PGE2.

Clinical Features and Genetic Analysis of Pediatric Patients with Alagille Syndrome Presenting Initially with Liver Function Abnormalities.

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.

Ex utero intrapartum treatment for giant congenital omphalocele.

BACKGROUND: To determine whether ex utero intrapartum treatment (EXIT) is an appropriate approach for managing fetuses antenatally diagnosed with giant congenital omphaloceles. METHODS: We retrospectively reviewed patients with omphaloceles who underwent either an EXIT procedure or a traditional repair surgery. Basic and clinical parameters including gender, gestational age, birth weight, maternal blood loss, operative times and operative complications were analyzed. During the 6-12-month follow-ups, postoperative complications including bowel obstruction, abdominal infections, postoperative abdominal distension were monitored, and survival rate was analyzed. RESULTS: A total of seven patients underwent the EXIT procedure and 11 patients underwent the traditional postnatal surgery. We found no differences in maternal age, gestational age at diagnosis, gestational age at delivery and birth weight between the two groups. In the EXIT group, the average operation time for mother was 68.3 ± 17.5 minutes and the average maternal blood loss was 233.0 ± 57.7 mL. The operation time in the EXIT group (22.0 ± 4.5 minutes) was shorter than that in the traditional group (35 ± 8.7 minutes), but the length of hospital stay in the EXIT group (20.5 ± 3.1 days) was longer than that in the traditional group (15.7 ± 2.5 days, P < 0.05). During the follow-up, one patient in the EXIT group had an intestinal obstruction, one developed abdominal compartment syndrome and one died in the traditional group. CONCLUSIONS: In our experience, EXIT is a safe and effective procedure for the treatment of giant congenital omphaloceles. However, more experience is needed before this procedure can be widely recommended.

Two-incision laparoscopic appendectomy for a severe hemophilia A child patient with coagulation factor VII deficiency: Case report and review of literature.

RATIONALE: The main complication of patients with severe hemophilia is recurrent bleeding events that usually affected musculoskeletal contractures. And replacement therapy methods were continuously improved to minimize adverse impacts brought by those complications. However, only several cases reported about the appendectomy for hemophilia A. We report a case of acute appendicitis treated by two-incision laparoscopy in a boy with hemophilia A and coagulation factor VII deficiency for the first time. PATIENT CONCERNS: An 8y7m-old Chinese boy presented with half a day of right sided abdominal pain, fever, nausea, and vomiting. DIAGNOSES: He received a computed tomography (CT) scan which revealed an enlarged appendix, thickened wall and appendiceal fecalith, and had received a conservative anti-bacterial treatment for his acute appendicitis but failed. He was diagnosed with hemophilia A and coagulation factor VII deficiency. INTERVENTIONS: Two-incision laparoscopic appendectomy was made in success with a careful management of perioperative period. We monitored the clotting factor FVIII level and gave him a replacement therapy. OUTCOMES: The patient had an uneventful recovery. LESSONS: It is important to exclude intraabdominal or retroperitoneal hemorrhage in patients suffering from hemophilia and acute abdominal pain. Pre-operative evaluation of validity of the FVIII replacement therapy is another effective strategy to assess the safety and feasibility of applying an operation procedure. The two-incision laparoscopic appendectomy is an effective treatment for this kind of patients for its minimal trauma and fast recovery characteristics. Our report shows that laparoscopic appendectomy is feasible in a child suffering from hemophilia after adequate blood clotting factor replacement treatment.

Novel Insights into the Pathogenesis of Hirschsprung's-associated Enterocolitis.

OBJECTIVE: 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. DATA SOURCES: 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". STUDY SELECTION: Articles regarding the pathogenesis of HAEC were selected, and the articles mainly regarding the diagnosis, surgical approach, treatment, and follow-up were excluded. RESULTS: 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. CONCLUSIONS: 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.

Antibody blockade of mucosal addressin cell adhesion molecule-1 attenuates proinflammatory activity of mesenteric lymph after hemorrhagic shock and resuscitation.

BACKGROUND: The current study was designed to determine the effects of antibody blockade of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) on the proinflammatory activity of mesenteric lymph after hemorrhagic shock and resuscitation (HS/R). METHODS: Rats were subjected to HS/R with or without treatment with MAdCAM-1 polyclonal antibody. MAdCAM-1 expression and lymphocyte infiltration in rats were examined. Post-shock mesenteric lymph was collected, filtered to remove lymphocytes, and transfused into recipient mice to induce systemic inflammation and intestinal injury. The proinflammatory activity of post-shock lymph in mice was determined by examining intestinal permeability, enterocyte apoptosis, intestinal lactate levels, lung myeloperoxidase (MPO) activity, and serum cytokine levels. Survival of recipient mice was determined over a 1-week time period. RESULTS: Rats subjected to HS/R had increased MAdCAM-1 expression and lymphocyte infiltration in the intestine. Antibody blockade of MAdCAM-1 attenuated the increased lymphocyte infiltration after HS/R (P < .05). Post-shock mesenteric lymph transfusion significantly increased mortality accompanied by increases in gut permeability, enterocyte apoptosis, intestinal lactate levels, lung MPO activity, and serum levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, IL-10, and transforming growth factor-ß (all P < .05). Antibody blockade of MAdCAM-1 in rats subjected to HS/R attenuated the proinflammatory activity of post-shock mesenteric lymph, with abrogation of lymph transfusion-induced increases in mortality, gut permeability, epithelial cell apoptosis, intestinal lactate levels, lung MPO activity, and serum levels of IL-1ß, IL-6, and TNF-α (all P < .05). CONCLUSION: These findings demonstrate that antibody blockade of MAdCAM-1 attenuates the proinflammatory activity of mesenteric lymph after HS/R.

Comparison of different noninvasive diagnostic methods for biliary atresia: a meta-analysis.

BACKGROUND: This study was undertaken to retrospectively analyze the accuracy of different methods in differentiating biliary atresia from neonatal jaundice. METHODS: A search was made in MEDLINE, and the Web of Science for relevant original articles published in English; methodological quality of the included studies was also assessed. Two reviewers extracted data independently. Studies were pooled, summary receiver operating characteristics curve and diagnostic odds ratio (DOR) with corresponding confidence intervals were calculated. RESULTS: For diagnosis of biliary atresia, ultrasonography (US), hepatic scintigraphy (HBS), and magnetic resonance cholangiography (MRCP) had a pooled sensitivity of 74.9% (range: 70.4%-79.1%), 93.4% (range: 90.3%-95.7%) and 89.7% (range: 84.8%-93.4%), a specificity of 93.4% (range: 91.4%-95.1%), 69.2% (range: 65.1%-73.1%) and 64.7% (range: 58.0%-71.0%), a positive likelihood ratio of 12.16 (range: 6.41-23.08), 3.01 (range: 2.15-4.20) and 3.10 (range: 1.59-6.06), a negative likelihood ratio of 0.23 (range: 0.13-0.38), 0.13 (range: 0.06-0.25) and 0.16 (range: 0.06-0.44), DOR of 72.56 (range: 27.34-192.58), 29.88 (range: 12.82-69.64) and 32.48 (range: 8.22-128.29), with an area under the curve of 0.96, 0.91, and 0.92, and Q value of 0.90, 0.85, and 0.85, respectively. CONCLUSIONS: US, HBS and MRCP can be very useful for the diagnostic work-up of neonatal cholestasis. To improve the sensitivity and specificity, several additional measures can be used.

Nursing Intervention for Outpatient Rehabilitation in Pediatric Patients with Hirschsprung Disease after Colectomy.

OBJECTIVE: The present study was designed to evaluate the effectiveness of a nursing intervention program for outpatient rehabilitation of children with Hirschsprung-associated enterocolitis (HAEC) after radical colectomy for Hirschsprung disease (HD). BACKGROUND: Postoperative outcomes severely affect the quality of life in pediatric HD patients after operation. The improvement in defecation function is regarded as one of the most useful parameters to evaluate the quality of life in HD patients after radical intestinal resection. A close attention should also be paid to the patients' ability of social adaptation. METHODS: This prospective, randomized control trial enrolled 85 pediatric patients with HAEC after colectomy. They were randomly divided into the control and intervention groups. All the patients were followed up for 6 to 12 months after initial HAEC treatment. RESULTS: The intervention group had a lower enterocolitis recurrence rate than the control group, with a better ability to control defecation and their parents had better rehabilitation nursing knowledge (p < 0.05). The degree of parents' satisfaction regarding the outcome was significantly better in the intervention group than that in the control group (p < 0.05). CONCLUSION: A systemic rehabilitation nursing program could decrease enterocolitis recurrence, improve the recovery of anorectal functions, and enhance the quality of life in the pediatric patients after radical colectomy.

Review of the molecular pathogenesis of osteosarcoma.

Treating the osteosarcoma (OSA) remains a challenge. Current strategies focus on the primary tumor and have limited efficacy for metastatic OSA. A better understanding of the OSA pathogenesis may provide a rational basis for innovative treatment strategies especially for metastases. The aim of this review is to give an overview of the molecular mechanisms of OSA tumorigenesis, OSA cell proliferation, apoptosis, migration, and chemotherapy resistance, and how improved understanding might contribute to designing a better treatment target for OSA.

Intestinal microcirculatory dysfunction and neonatal necrotizing enterocolitis.

OBJECTIVE: 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. DATA SOURCES: 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". STUDY SELECTION: Mainly original milestone articles and critical reviews written by major pioneer investigators in the field were selected. RESULTS: 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. CONCLUSION: 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.

A new diagnostic scoring system to differentiate Hirschsprung's disease from Hirschsprung's disease-allied disorders in patients with suspected intestinal dysganglionosis.

PURPOSE: To create a simple diagnostic scoring system to differentiate Hirschsprung's disease (HD) from Hirschsprung's disease-allied disorders (HAD) in patients with suspected intestinal dysganglionosis (IDs). METHODS: Between 1998 and 2008, 967 patients with suspected intestinal dysganglionosis underwent surgical treatment at the pediatric surgery department of Tongji Hospital. The diagnosis of HD or HAD was confirmed by postoperative pathological examination. All patients underwent preoperative work-up including barium enema, anorectal manometry, and histochemical acetylcholinesterase staining of rectal mucosa. Known risk factors for IDs were recorded. The predicting score was calculated by summing the scores of the risk factors and three preoperative tests. The sensitivity, specificity, accuracy, positive predictive values, negative predictive values, positive likelihood ratios, and negative likelihood ratios of the predicting score were calculated. The cutoff score for predicting HD was determined using receiver operating characteristic (ROC) analysis. The accuracy of the predicting score was measured by the area under the ROC curve. RESULTS: Failed or delayed passage of meconium, age <3 years and male gender were risk factors associated with HD. The area under the ROC curve of the predicting score was 0.927 (95 % confidence interval, 0.910-0.944). A predicting score of more than 5 was used as a cutoff for predicting HD. The scoring system achieved 83.1 % sensitivity, 89.5 % specificity, and 85.9 % accuracy in predicting HD. CONCLUSION: Patients with a predicting score of more than 5 are more likely to be diagnosed with HD, whereas a score less than 5 are mostly indicative of HAD.

[Transumbilical laparoscopic pull-through for children with hypoganglionosis].

OBJECTIVE: To investigate the surgical outcomes after on transumbilical laparoscopic pull-through procedure for pediatric hypoganglionosis(HYP). METHODS: 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. RESULTS: 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. CONCLUSION: It is safe and effective for children with hypoganglionosis to undergo transumbilical laparoscopic pull-through procedure.

NF-kappaB related abnormal hyper-expression of iNOS and NO correlates with the inflammation procedure in biliary atresia livers.

OBJECTIVE: To study the expression of inducible nitric oxide synthase (iNOS) and its related regulators in biliary atresia (BA) livers and exlpore their relationships with the inflammation pathway in BA livers. METHOD: The iNOS expression in livers of 38 cases of BA children, 15 cases of neonatal cholestasis (NC) children, and 18 cases of normal control were, respectively, examined and total nitric oxide (NO) metabolites concentration of all samples were calculated by a colorimetric method based on Griess reaction. The TdT-mediated dupt biotin nick end labeling (TUNEL) method was used to label the apoptotic bile duct epithelial cells and hepatocytes. The western blotting and immunohistochemistry methods to semi-quantitatively analyze the nuclear factor-kappaB (NF-kappaB) expression of each group were also used. RESULTS: The iNOS expression intensity and total NO metabolites concentration of BA group (0.30 +/- 0.08, 90.40 +/- 12.46 micromol/L) were significantly higher than those of NC and normal control groups, P < 0.01. Correlation analysis showed a strong positive correlation between the serum AST level (152.76 +/- 29.59 U/L) and total NO metabolites concentration in BA group. Compared with the NC (32.47 +/- 5.55) and normal control (20.72 +/- 5.63) groups, a significantly higher apoptosis rate of intrahepatic bile duct epithelial cells was found in BA group (54.00 +/- 11.67) that tightly correlated with the iNOS intensity (r = 0.99, P < 0.01). The NF-kappaB intensity of BA group was also significantly higher than that of NC and normal control groups and had a strong positive correlation with the iNOS intensity (r = 0.97, P < 0.01). CONCLUSION: The abnormal hyper-expression of iNOS may play an important role in mediating the inflammation procedure in BA livers. This change perhaps has some relationship with the high expression of NF-kappaB and NO. These regulators can up-regulate the apoptosis of bile duct epithelial cells in BA livers and cause the damage to liver tissues.

Diagnosis and surgical treatment of isolated hypoganglionosis.

BACKGROUND: Some patients suspected with Hirschsprung's disease (HD), however, were diagnosed as having isolated hypoganglionosis according to the updated pathohistologic methods. This study was undertaken to investigate the diagnostic methods and the therapeutic results of isolated hypoganglionosis in children. METHODS: A retrospective analysis was made on 17 patients with isolated hypoganglionosis (hypoganglionosis group) identified pathologically after operation. The data included clinical presentations, barium enema, anorectal manometry, histochemical staining for acetylcholinesterase (AChE) before operation, histological results after operation and follow-up outcomes. The data of hypoganglionosis with HD (HD group) were compared retrospectively. RESULTS: Common complaint of the patients with hypoganglionosis and HD was intractable constipation. Barium enema showed typical narrowing and distended segment of the colon in 9 patients in the hypoganglionosis group (9/16) and in 15 patients in the HD group (15/18). In the hypoganglionosis group, in 15 patients who underwent anorectal manometry only 5 showed absent rectal anal inhibitory reflex, significantly lower than the rate in the HD group (17/18) (P<0.05). From 16 patients in hypoganglionosis group, positive staining for AChE was noted in 3 patients (3/16, 18.8%), significantly lower than that in the HD group (16/18, 88.9%) (P<0.05). Thirteen patients in the hypoganglionosis group received subtotal colectomy, while only 5 patients needed subtotal colectomy in the HD group. In the hypoganglionosis group, except 2 patients who suffered from mild enterocolitis after operation and recovered after conservative therapy, all patients recovered uneventfully without wound dehiscence, intestinal fistula, fecal incontinence or constipation recurrence. In the HD group, one patient suffered from anastomotic leak and got secondary operation, one patient had anastomotic stricture at 1 year after operation and recovered by dilatation, and other three patients suffered from mild enterocolitis after operation and recovered after conservative therapy. CONCLUSIONS: Hypoganglionosis is a common disease, and could be finally confirmed by full-thickness biopsies in different bowel segments. The resection range can be estimated according to barium enema and 24-hour delayed X-ray findings, by which the satisfactory result in short-term follow-up can be obtained.