Duodenal web is rare in children, and reports of symptomatic cases with delayed presentation are even scarcer. This paper reports a 19-month-old female toddler admitted to hospital due to recurrent vomiting. Imaging examinations suggested duodenal obstruction, with an initial consideration of superior mesenteric artery syndrome or space-occupying lesion of the duodenum. In this case, circumferential thickening of the muscular layer of the duodenal wall was detected by endoscopic ultrasound (EUS), and pathological biopsy was performed simultaneously. Neoplastic lesions were systematically excluded, and the diagnosis of delayed-presentation duodenal web was established. The toddler successfully underwent endoscopic web incision eventually, avoiding open surgery. Postoperatively, the vomiting symptom was completely relieved without any complications. EUS clearly delineates the layered structure of the duodenal wall, thereby helping to elucidate the etiology of the obstruction and rule out neoplasms. This provides a direct basis for informed clinical decision-making regarding minimally invasive treatment of atypical, delayed-presentation duodenal obstruction.

To investigate the association between cholangitis and portal hypertension (PH) risk, and the efficacy of UDCA in native liver survivors after successful Kasai portoenterostomy (KPE). A multicenter, retrospective cross-sectional study was conducted at nine Chinese pediatric centers. Patient grouping was based on cumulative cholangitis episodes and UDCA regimens. After a median follow-up of 56 months, the overall incidence of PH was 23.63

BACKGROUND:The enteric nervous system (ENS), which arises from enteric neural crest cells (ENCCs), plays important roles in many aspects of gastrointestinal tract function, including motility, secretions, blood flow and hormone release. Defects in ENS development could lead to a broad range of disorders, including Hirschsprung's disease (HSCR), which is characterized by missing nerve cells in the distal segment of the colon. Here, we identify EMB as an evolutionarily conserved regulator of ENS development. METHODS:We first examined EMB expression in human and mouse intestines using scRNA-seq data and immunofluorescence staining. To investigate its role in ENS development, we constructed Emb-knockout zebrafish and mouse models. To explore the underlying mechanisms, we focused on ENCCs and analyzed their proliferation and migration using migration assays in explant guts and organoid cultures. Finally, we assessed rare EMB variants in a cohort of HSCR patients. RESULTS:In zebrafish, loss of emb leads to a decrease number of enteric neurons and impaired intestinal transit ability. In mice, knockout of Emb causes HSCR-like phenotypes and defects. In vitro experiments, including explant mouse gut and organoid cultures, show that EMB is required for both the proliferation and migration of ENCCs. Mechanistically, EMB binds to and recruits the phosphatase complex PP2A to the cellular membrane to facilitate the activation of PI3K-AKT pathway, thereby promoting ENCCs development. Indeed, application of PI3K or AKT agonists partially restores the ENS developmental defects in zebrafish emb mutants. Furthermore, rare variants of EMB may potentially contribute to the pathology of HSCR in humans. CONCLUSIONS:EMB is required for ENS development by regulating the proliferation and migration of the ENCCs. Mechanistically, EMB recruits PP2A to the cell membrane, reducing cytoplasmic dephosphorylation activity and promoting the activation of the PI3K signaling pathway.

Background and objectives:Biliary atresia (BA) with concurrent cytomegalovirus (CMV) is a distinct subtype that is linked to a poorer prognosis. Currently, there are no standardized criteria for the diagnosis or antiviral treatment (AVT) of this condition. It has a high prevalence in China. The aim was to investigate the infection, diagnosis and treatment of CMV infection in infants with BA through a multicenter questionnaire survey conducted in China. Methods:A multicenter investigation was performed through online questionnaire survey. It investigated the diagnosis and treatment of infants with CMV-infected BA in tertiary-level pediatric centers from January 1st, 2018, to January 1st, 2020. The centers were categorized into low and high-volume groups based on number of infants with BA (≤50 or >50) and were also grouped geographically into south and north groups. Afterward, 100 cases were randomly selected from these infants for a retrospective analysis. Results:A total of 22 questionnaires were collected, and 20 were included in the analysis. The questionnaire survey encompassed 1,276 infants with type III BA. 31.3% of the infants of BA had CMV detected. According to the survey results, a large proportion of centers preferred using CMV-DNA (75.0%) and CMV-IgM (95.0%) as their preferred methods for CMV detection. In the high-volume group, more centers opted for CMV-DNA detection (100.0% vs. 66.7%) and administered AVT (87.5%). In the retrospective analysis of 100 infants with BA, 39 were found to be CMV-positive and among these, 74.4% received AVT. Conclusion:Among the 1,276 infants with BA in this cohort, 31.3% (399 cases) had concomitant CMV infection, representing a decrease compared to previous data. CMV-IgM played a crucial role in the detection of the infection. The retrospective analysis indicated that AVT had a beneficial impact on the prognosis of infants with BA who were infected with CMV.

Background: Biliary atresia (BA) is a severe pediatric biliary disorder characterized by the progressive obstruction of liver bile ducts. In the absence of treatment, fibrosis advances rapidly in most affected children. In recent years, there has been significant progress in the management of BA, but many challenges remain. This guideline provides expert opinions on the screening, diagnosis, treatment, and follow-up of BA, aiming to assist and guide clinical practice. Methods: The guideline steering group, guideline development group, and guideline review group were formed to formulate clinical questions, develop recommendations, and draft guidelines using the GRADE Grid method, nominal group technique (NGT), and Delphi voting method. Three offline meetings were held on November 5, 2022, June 10, 2023, November 10, 2023, and October 27, 2024, respectively, to vote on the recommendations and solicit comments and suggestions from all participating experts. All experts from the United States, Europe, and Asia contributed significantly to this consensus guideline. Results: After summarizing high-quality literature on clinically encountered issues such as early screening, complementary checkup, treatments, follow-up, vaccinations, growth, development, and neurocognition, 23 observations were made and strength of recommendations were given. Conclusions: International guidelines for BA can guide surgeons, patients, medical societies, hospital administrators, and relevant community groups in their current practice. The diagnosis and treatment of BA remains controversial internationally and more research evidence is needed.

Evaluate clinical efficacy of ursodeoxycholic acid (UDCA) in biliary atresia (BA) infants post-Kasai portoenterostomy (KPE) using real-world data. Retrospective analysis of 698 BA patients from eight Chinese pediatric centers (2020–2025). Age-stratified analyses used propensity score matching (PSM) and inverse probability treatment weighting (IPTW) to adjust baseline differences. Primary outcomes were UDCA utilization and effects on bilirubin (TBil, DBil) and total bile acid (TBA) levels. The median follow-up duration for the cohort was 49 months (IQR: 25–74), with male patients accounting for 54.2

ObjectiveThis study aims to analyze and summarize the clinical characteristics of small intestinal adenomyosis.MethodsA retrospective study was conducted on children with small intestinal adenomyosis at our center from 2014 to 2024. The age of onset, gender, clinical symptoms, auxiliary examination results, treatment plans, and pathological characteristics of the tumors were recorded and analyzed.ResultsSix cases of small intestinal adenomyosis were analyzed. The male-to-female ratio was 5:1. The median age was 19 months, with two-thirds of the affected children being under 2 years old. Two cases were identified in newborns during the treatment of intestinal malrotation. The remaining patients developed symptoms of intussusception. Preoperative ultrasound identified pathological lead points in two cases. Among the six cases, one case's adenomyoma was located in the jejunum, while the rest was located in the ileum, with tumors ranging from 25 to 140 cm from the ileocecal region. All six patients underwent resection of the tumor segments in the small intestine followed by anastomosis; postoperative prognosis was favorable. Of the six pathological results, glandular-like structures were found in five tumors, with three cases lined with cuboidal or columnar epithelium and one case lined with stratified or squamous epithelium.ConclusionsSmall intestinal adenomyosis is observed to be more prevalent in male, with onset ages ranging from six days to four years. It frequently coexists with recurrent intussusception, making reduction with air or water enema challenging. Abdominal ultrasound typically shows tumors at the leading edge of the intussusception, with compromised blood flow signals and multiple small cystic or honeycomb-like anechoic structures. Surgery is the primary treatment and generally results in a favorable prognosis.

BackgroundHepatoblastoma is the most prevalent primary hepatic malignancy in children, comprising 80% of pediatric hepatic malignancies and 1% of all pediatric malignancies. However, traditional treatments have proven inadequate in effectively curing hepatoblastoma, leading to a poor prognosis.MethodsA literature search was conducted on multiple electronic databases (PubMed and Google Scholar). A total of 86 articles were eligible for inclusion in this review.ResultThis review aims to consolidate recent developments in hepatoblastoma research, focusing on the latest advances in cancer-associated genomics, epigenetic studies, transcriptional programs and molecular subtypes. We also discuss the current treatment approaches and forthcoming strategies to address cancer-associated biological challenges.ConclusionTo provide a comprehensive summary of the molecular mechanisms associated with hepatoblastoma occurrence, this review highlights three key aspects: genomics, epigenetics, and transcriptomics. Our review aims to facilitate the exploration of novel molecular mechanisms and the development of innovative clinical treatment strategies for hepatoblastoma.

Children diagnosed with advanced hepatoblastoma (HB) generally have a poor prognosis and are in urgent need of effective treatment strategies. Long non-coding RNAs (lncRNAs) have been found to play crucial roles in various malignant tumors and can be potential targets for tumor diagnosis, treatment and prognosis. However, the role of most lncRNAs in HB pathogenesis is still not well understood. In this study, we investigated the expression of Linc01124 and its effect in HB. Clinical samples of HB patients were collected, and differentially expressed lncRNAs in HB were screened by quantitative real-time polymerase chain reaction (qRT-PCR). The Cell Counting kit-8 and 5-ethynyl-2′-deoxyuridine assay were used to detect cell proliferation in HB cells. The HB cells' apoptosis was assessed by the flow cytometry and terminaldeoxynucleotidyl transferase-mediated nick-end labeling assay. Then micro-RNAs and messenger RNAs targeted by Linc01124 were selected according to miRanda and miRTarbase. The gene pathways regulated by Linc01124 were predicted through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. The prediction results were subsequently validated using qRT-PCR and Western blotting (WB). A Pearson's correlation analysis was conducted to examine the correlation between hsa-miR-24-3p and Linc01124, IL4, PDGFRB, BRCA1, and NOS3. In addition, HB cells were treated with a Linc01124 inhibitor and PI3K-Akt pathway activator to evaluate the involvement of miR-24-3p/PI3K/AKT in the regulation of HB cell function by Linc01124. Linc01124 was up-regulated in HB cells and tissues. Knockdown of Linc01124 can reduce cell proliferation and increase apoptosis. Bioinformatics analysis predicted that hsa-miR-24-3p could target Linc01124 and 8 genes involved in the PI3K-Akt pathway. qRT-PCR and WB experiments also demonstrated that disrupting Linc01124 expression could increase miR-24-3p expression and inhibit the PI3K/AKT pathway. Meanwhile, the target genes IL4, PDGFRB, BRCA1 and NOS3 expression were also down-regulated by silencing Linc01124. Hsa-miR-24-3p was found to have a negative association with Linc01124, IL4, PDGFRB, BRCA1 and NOS3. PI3K/AKT activator could rescue the decreased proliferation and increased apoptosis induced by Linc01124 knockdown. Linc01124 plays an oncogenic role by improving the activity of the PI3K/AKT pathway, which provides a theoretical basis for future research on the pathogenesis and progression mechanism of HB.

Background Hepatic stellate cell (HSC) activation and hepatic fibrosis mediated biliary atresia (BA) development, but the underlying molecular mechanisms are poorly understood. This study aimed to investigate the roles of circRNA hsa_circ_0009096 in the regulation of HSC proliferation and hepatic fibrosis. Methods A cellular hepatic fibrosis model was established by treating LX-2 cells with transforming growth factor β (TGF-β1). RNaseR and actinomycin D assays were performed to detect hsa_circ_0009096 stability. Expression of hsa_circ_0009096, miR-370-3p, and target genes was detected using reverse transcription-qPCR. Direct binding of hsa_circ_0009096 to miR-370-3p was validated using dual luciferase reporter assay. Cell cycle progression and apoptosis of LX-2 cells were assessed using flow cytometry. The alpha-smooth muscle actin (α-SMA), collagen 1A1 (COL1A1), and TGF beta receptor 2 (TGFBR2) protein levels in LX-2 cells were analyzed using immunocytochemistry and western blotting. Results Hsa_circ_0009096 exhibited more resistance to RNase R and actinomycinD digestion than UTRN mRNA. Hsa_circ_0009096 expression increased significantly in LX-2 cells treated with TGF-β1, accompanied by elevated α-SMA and COL1A1 expression. Hsa_circ_0009096 siRNAs effectively promoted miR-370-3p and suppressed TGFBR2 expression in LX-2 cells, mediated by direct association of hsa_circ_0009096 with miR-370-3p. Hsa_circ_0009096 siRNA interfered with the cell cycle progression, promoted apoptosis, and reduced α-SMA and COL1A1 expression in LX-2 cells treated with TGF-β1. MiR-370-3p inhibitors mitigated the alterations in cell cycle progression, apoptosis, and α-SMA, COL1A1, and TGFBR2 expression in LX-2 cells caused by hsa_circ_0009096 siRNA. In conclusion, hsa_circ_0009096 promoted HSC proliferation and hepatic fibrosis during BA pathogenesis by accelerating TGFBR2 expression by sponging miR-370-3p.

Children diagnosed with advanced hepatoblastoma (HB) generally have a poor prognosis and are in urgent need of effective treatment strategies. Long non-coding RNAs (lncRNAs) have been found to play crucial roles in various malignant tumors and can be potential targets for tumor diagnosis, treatment and prognosis. However, the role of most lncRNAs in HB pathogenesis is still not well understood. In this study, we investigated the expression of Linc01124 and its effect in HB. Clinical samples of HB patients were collected, and differentially expressed lncRNAs in HB were screened by quantitative real-time polymerase chain reaction (qRT-PCR). The Cell Counting kit-8 and 5-ethynyl-2 '-deoxyuridine assay were used to detect cell proliferation in HB cells. The HB cells' apoptosis was assessed by the flow cytometry and terminaldeoxynucleotidyl transferase-mediated nick-end labeling assay. Then micro-RNAs and messenger RNAs targeted by Linc01124 were selected according to miRanda and miRTarbase. The gene pathways regulated by Linc01124 were predicted through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. The prediction results were subsequently validated using qRT-PCR and Western blotting (WB). A Pearson's correlation analysis was conducted to examine the correlation between hsa-miR-24-3p and Linc01124, IL4, PDGFRB, BRCA1, and NOS3. In addition, HB cells were treated with a Linc01124 inhibitor and PI3K-Akt pathway activator to evaluate the involvement of miR-243p/PI3K/AKT in the regulation of HB cell function by Linc01124. Linc01124 was up-regulated in HB cells and tissues. Knockdown of Linc01124 can reduce cell proliferation and increase apoptosis. Bioinformatics analysis predicted that hsa-miR-24-3p could target Linc01124 and 8 genes involved in the PI3K-Akt pathway. qRT-PCR and WB experiments also demonstrated that disrupting Linc01124 expression could increase miR-24-3p expression and inhibit the PI3K/AKT pathway. Meanwhile, the target genes IL4, PDGFRB, BRCA1 and NOS3 expression were also down-regulated by silencing Linc01124. Hsa-miR-24-3p was found to have a negative association with Linc01124, IL4, PDGFRB, BRCA1 and NOS3. PI3K/AKT activator could rescue the decreased proliferation and increased apoptosis induced by Linc01124 knockdown. Linc01124 plays an oncogenic role by improving the activity of the PI3K/AKT pathway, which provides a theoretical basis for future research on the pathogenesis and progression mechanism of HB.

IntroductionFinding non-invasive methods to predict the degree of liver fibrosis is very important in managing children with biliary atresia. Therefore, we explored the predictive value of APRI, FIB-4, and serological markers for liver fibrosis in children with biliary atresia.MethodsThis study retrospectively reviewed data from children diagnosed with BA between March and December 2022. Liver tissue pathology specimens were obtained during surgery. The serum markers were measured within 2 days before the Kasai procedure or liver transplantation. The aspartate aminotransferase-to-platelet ratio index (APRI) and the four-factor-based fibrosis index (FIB-4) were calculated. The outcome was the diagnosis of progressive liver fibrosis.ResultsThis study reviewed the data from 41 children with biliary atresia. APRI had 52% sensitivity and 83% specificity for progressive liver fibrosis, while FIB-4 had 83% sensitivity and 67% specificity. Their areas under the curve were not significantly different from those of conventional markers.ConclusionAlthough they were not better than conventional markers, APRI and FIB-4 can be used as follow-up markers for progressive liver fibrosis in patients with biliary atresia, but their predictive value was moderate. Additional studies are necessary to determine whether they could be combined with other markers to improve their predictive value.

Summary: Extensive remodeling of the female mammary epithelium during development and pregnancy has been linked to cancer susceptibility. The faithful response of mammary epithelial cells (MECs) to hormone signaling is key to avoiding breast cancer development. Here, we show that lactogenic differentiation of murine MECs requires silencing of genes encoding ribosomal RNA (rRNA) by the antisense transcript PAPAS. Accordingly, knockdown of PAPAS derepresses rRNA genes, attenuates the response to lactogenic hormones, and induces malignant transformation. Restoring PAPAS levels in breast cancer cells reduces tumorigenicity and lung invasion and activates many interferon-regulated genes previously linked to metastasis suppression. Mechanistically, PAPAS transcription depends on R-loop formation at the 3′ end of rRNA genes, which is repressed by RNase H1 and replication protein A (RPA) overexpression in breast cancer cells. Depletion of PAPAS and upregulation of RNase H1 and RPA in human breast cancer underpin the clinical relevance of our findings.

Circular RNAs (circRNAs) serve an essential role in the occurrence and development of cholangiocarcinoma, but the expression and function of circRNA in biliary atresia (BA) is not clear. In the present study, circRNA expression profiles were investigated in the liver tissues of patients with BA as well as in the choledochal cyst (CC) tissues of control patients using RNA sequencing. A total of 78 differentially expressed circRNAs (DECs) were identified between the BA and CC tissues. The expression levels of eight circRNAs (hsa_circ_0006137, hsa_circ_0079422, hsa_circ_0007375, hsa_circ_0005597, hsa_circ_0006961, hsa_circ_0081171, hsa_circ_0084665 and hsa_circ_0075828) in the liver tissues of the BA group and control group were measured using reverse transcription-quantitative polymerase chain reaction. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis demonstrated that the identified DECs are involved in a variety of biological processes, including apoptosis and metabolism. In addition, based on the GO and KEGG pathway enrichment analyses, it was revealed that target genes that can be affected by circRNAs regulatory network were enriched in the TGF-β signaling pathway, EGFR tyrosine kinase inhibitor resistance pathway and transcription factor regulation pathway as well as other pathways that may be associated with the pathogenesis of BA. The present study revealed that circRNAs are potentially implicated in the pathogenesis of BA and could help to find promising targets and biomarkers for BA.

Biliary atresia (BA) is a rare neonatal cholestatic disease that presents with a marked bile duct reaction and rapid fibrotic development. Our earlier research has shown that circUTRN24 is highly elevated in BA, but the exact molecular mechanism is still unknown. This study attempted to investigate whether circUTRN24 induces BA liver fibrosis through regulation of autophagy and to elucidate its molecular mechanism. Using TGF-β-treated hepatic stellate cells (HSC) LX-2, we created a liver fibrosis model. qRT-PCR was used to analyze the expression of circUTRN24, miR-483-3p, and IGF-1. Western blot analysis was used to assess the expression of IGF-1, HSC activation-related proteins, and autophagy-related proteins. The TGF-β-induced LX-2 cell fibrosis model was then supplemented with circUTRN24 siRNA, miR-483-3p mimics, and the autophagy activator Rapamycin, and functional rescue tests were carried out to investigate the role of circUTRN24, miR-483-3p, and autophagy in BA liver fibrosis. Using a luciferase reporter assay, a direct interaction between miR-483-3p and circUTRN24 or IGF-1 was discovered. With the increase of TGF-β treatment concentration, circUTRN24 expression also gradually increased, as did HSC activation and autophagy-related protein. si-circUTRN24 significantly decreased circUTRN24 expression and inhibited HSC activation and autophagy, which was reversed by Rapamycin. Through bioinformatics prediction and validation, we found circUTRN24 might act through miR-483-3p targeting IGF-1 in the autophagy-related mTOR pathway. Furthermore, miR-483-3p mimics significantly increased miR-483-3p expression and inhibited HSC activation and autophagy, which were reversed by Rapamycin. Functional rescue experiments showed that si-circUTRN24 inhibited circUTRN24 and IGF-1 expressions and promoted miR-483-3p expression, while the miR-483-3p inhibitor abolished these effects. These findings imply that circUTRN24/miR-483-3p/IGF-1 axis mediated LX-2 cell fibrosis by regulating autophagy.

Here, we present a case with genetically confirmed SCN. The main symptom of the child was recurring fever. The combination of antibiotics combined with G-CSF injection was proved to be insufficient, and the patient developed ''solid'' liver abscess. After undergoing surgical anatomical hepatic lobectomy, the child's infection symptoms showed improvement. The postoperative culture of the purulent material from the liver infection lesion revealed an infection with Staphylococcus aureus. Our case raises the possibility of pathogen sources and routes of infection, clinical characteristics, and effective treatment for SCN patients with concomitant liver abscess.

BACKGROUND:Cholangitis is common in patients with biliary atresia following Kasai portoenterostomy (KPE). The prompt use of empiric antibiotics is essential due to the lack of identified microorganisms. The authors aimed to validate a severity grading system to guide empiric antibiotic therapy in the management of post-KPE cholangitis.MATERIALS AND METHODS:This multicenter, prospective, randomized, open-label study recruited patients with post-KPE cholangitis and was conducted from January 2018 to December 2019. On admission, patients were categorized into mild, moderate, and severe cholangitis according to the severity grading system. Patients in the mild cholangitis group were randomized to receive cefoperazone sodium tazobactam sodium (CSTS) or meropenem (MEPM). Patients with severe cholangitis were randomized to treatment with MEPM or a combination of MEPM plus immunoglobulin (MEPM+IVIG). Patients with moderate cholangitis received MEPM.RESULTS:The primary endpoint was duration of fever (DOF). Secondary outcomes included blood culture, length of hospital stay, incidence of recurrent cholangitis, jaundice clearance rate, and native liver survival (NLS). For mild cholangitis, DOF, and length of hospital stay were similar between those treated with CSTS or MEPM (all P >0.05). In addition, no significant difference in recurrence rate, jaundice clearance rate, and NLS was observed between patients treated with CSTS and MEPM at 1-month, 3-month, and 6-month follow-up. In patients with moderate cholangitis, the DOF was 36.00 (interquartile range: 24.00-48.00) h. In severe cholangitis, compared with MEPM, MEPM+IVIG decreased DOF and improved liver function by reducing alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and direct bilirubin at 1-month follow-up. However, recurrence rate, jaundice clearance rate, and NLS did not differ significantly between MEPM+IVIG and MEPM at 1-month, 3-month, and 6-month follow-up.CONCLUSIONS:In patients with post-KPE cholangitis, MEPM is not superior to CSTS for the treatment of mild cholangitis. However, MEPM+IVIG treatment was associated with better short-term clinical outcomes in patients with severe cholangitis.

Background Hepatoblastoma (HB) is the most common liver malignancy in childhood with poor prognosis and lack of effective therapeutic targets. Single-cell transcriptome sequencing technology has been widely used in the study of malignant tumors, which can understand the tumor microenvironment and tumor heterogeneity. Materials and methods Two children with HB and a healthy child were selected as the research subjects. Peripheral blood and tumor tissue were collected for single-cell transcriptome sequencing, and the sequencing data were compared and analyzed to describe the differences in the immune microenvironment between children with HB and normal children. Results There were significant differences in the number and gene expression levels of natural killer cells (NK cells) between children with HB and normal children. More natural killer cells were seen in children with HB compared to normal control. KIR2DL were highly expressed in children with HB. Conclusion Single-cell transcriptome sequencing of peripheral blood mononuclear cells (PBMC) and tumor tissue from children with HB revealed that KIR2DL was significantly up-regulated in NK cells from children with HB. HLA-C molecules on the surface of tumor cells interact with inhibitory receptor KIR2DL on the surface of NK cells, inhibiting the cytotoxicity of NK cells, resulting in immune escape of tumors. Inhibitors of related immune checkpoints to block the interaction between HLA-C and KIR2DL and enhance the cytotoxicity of NK cells, which may be a new strategy for HB treatment.

Background: Choledochal cysts (CCs) are characterized by dilations of the extra- and/or intrahepatic bile ducts. Surgery (cyst excision and Roux-en-Y hepaticojejunostomy) remains the gold standard for treatment. However, delayed hemorrhage can occur postoperatively, and although rare, it can be life-threatening. This study aimed to determine the risk factors and corresponding prevention of delayed hemorrhage after radical CC surgery, and to apply a technique to lower its incidence.Materials and Methods: This retrospective study enrolled 267 patients who received CC surgery between June 2016 and December 2020 at Shenzhen Children's Hospital. Univariate and multivariate logistic regression analyses were performed to identify risk factors for delayed hemorrhage.Results: Eleven (4.1%) patients had delayed hemorrhage after laparoscopic radical surgery. The most common hemorrhage site was the dissected surface between the cyst and adjacent structures with chronic severe adhesions, postoperatively. The occurrence of recurrent CC-associated complication and excessive total blood loss during surgery were risk factors for delayed hemorrhage after CC radical surgery. Length of disease course, operation when cholangitis/pancreatitis still existed, cyst diameter, and application of trypsin inhibitor after the surgery were not significantly different between the two groups.Conclusion: For patients without adhesions, complete cyst resection is the gold standard. However, for those with intensive adhesions, in cases of delayed hemorrhage on the dissection surface and malignancy transformation risk, the Lilly's technique with Roux-en-Y hepaticojejunostomy could be an alternative.

Maternal seeding of the microbiome in neonates promotes a long-lasting biological footprint, but how it impacts disease susceptibility in early life remains unknown. We hypothesized that feeding butyrate to pregnant mice influences the newborn's susceptibility to biliary atresia, a severe cholangiopathy of neonates. Here, we show that butyrate administration to mothers renders newborn mice resistant to inflammation and injury of bile ducts and improves survival. The prevention of hepatic immune cell activation and survival trait is linked to fecal signatures of Bacteroidetes and Clostridia and increases glutamate/glutamine and hypoxanthine in stool metabolites of newborn mice. In human neonates with biliary atresia, the fecal microbiome signature of these bacteria is under-represented, with suppression of glutamate/glutamine and increased hypoxanthine pathways. The direct administration of butyrate or glutamine to newborn mice attenuates the disease phenotype, but only glutamine renders bile duct epithelial cells resistant to cytotoxicity by natural killer cells. Thus, maternal intake of butyrate influences the fecal microbial population and metabolites in newborn mice and the phenotypic expression of experimental biliary atresia, with glutamine promoting survival of bile duct epithelial cells.