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2.
Pediatr Res ; 2024 Jan 04.
Article En | MEDLINE | ID: mdl-38177247

BACKGROUND: This study aimed to investigate gestational age-specific hematological features in preterm infants with necrotizing enterocolitis (NEC) and identify predictive hematological biomarkers for surgical NEC. METHODS: We conducted a retrospective study comparing gestational age (GA)-specific clinical data between medical NEC (m-NEC) and surgical NEC (s-NEC) subgroups, stratified by GA as <28 weeks, 28 ≤ GA < 32 weeks, and 32 ≤ GA < 37 weeks. Multivariate logistic analysis and receiver operating characteristic curve were used to identify the independent predictors of s-NEC. RESULTS: In comparison to m-NEC at NEC onset, s-NEC infants exhibited the following findings: In GA < 28 weeks, s-NEC infants had lower platelet counts. In 28 ≤ GA < 32 weeks, lower absolute lymphocyte counts, and significant percent drop in platelets, lymphocytes, and monocytes were observed. In 32 ≤ GA < 37 weeks, lower absolute lymphocyte counts and significant percent drop in lymphocytes were found. Independent predictors were able to distinguish s-NEC from m-NEC. The area under the curve (AUC) for platelet counts in GA < 28 weeks was 0.880, while C-reactive protein in 28 ≤ GA < 32 weeks had an AUC of 0.889. The AUC for lymphocyte counts in 32 ≤ GA < 37 weeks was 0.892. CONCLUSION: This study identified hematological abnormalities in the development of NEC based on gestational age. Independent predictors may help clinicians distinguish surgical NEC from medical NEC. IMPACT: Necrotizing enterocolitis (NEC) patients with different gestational ages (GA) exhibit different hematological features and independent predictors of surgical NEC differ among different GAs. Our research made the current studies about peripheral hematological features with NEC more complete by analyzing peripheral data collected within 24 h of birth, at day 5-7, day 3-4, day 1-2 before NEC onset, at the time of NEC onset, day 1, day 2, day 3, day 4-5, day 6-7 after NEC onset. Our study is helpful to clinicians in developing a more detailed diagnostic strategy based on GA for the early identification of surgical NEC.

3.
J Pediatr Gastroenterol Nutr ; 77(2): e36-e41, 2023 08 01.
Article En | MEDLINE | ID: mdl-37285839

OBJECTIVES: Surgery is generally considered as the first-line therapy for membranous duodenal stenosis (MDS) in children. However, abdominal surgery leaves permanent scars and may even cause intestinal adhesion. Therefore, an effective, safe, and minimally invasive method is urgently needed. This study aimed to evaluate the safety, efficacy, and feasibility of endoscopic balloon dilatation-based membrane resection (EBD-MR) to treat MDS in children. METHODS: We retrospectively reviewed patients with MDS treated with EBD-MR in Shanghai Children's Hospital from May 2016 to August 2021. Primary study outcome was clinical success, defined as weight gain and complete remission of vomiting, without the need for repeat endoscopic or surgical intervention during follow-up. Secondary outcomes included technical success, diameter changes of the membrane opening, and adverse events. RESULTS: Nineteen children (9 females, mean age 14.5 ± 11.2 months) received endoscopic treatment for MDS, and clinical success was achieved in 18 of 19 patients (94.7%). No bleeding, perforation, and jaundice occurred. Diameters of the membrane opening increased from 2.97 ± 2.87 mm to 9.78 ± 1.27 mm after the treatment, symptoms of vomiting did not reappear during 10-73 months of follow-up, and body mass index of the children increased from 14.9 ± 2.2 kg/m 2 (pre-operation) to 16.2 ± 3.7 kg/m 2 (6 months after operation). One patient required surgical revision because of existence of a second web; three patients received 2-3 sessions of endoscopic treatment to obtain the final remission. CONCLUSIONS: The EBD-MR technique is safe, effective, and feasible for MDS, which provided an excellent alternative to surgical management for the disease in pediatric patients.


Retrospective Studies , Female , Humans , Child , Infant , Child, Preschool , Dilatation/methods , Feasibility Studies , China , Treatment Outcome
4.
J Pediatr (Rio J) ; 99(5): 449-455, 2023.
Article En | MEDLINE | ID: mdl-37015323

OBJECTIVE: Necrotizing enterocolitis (NEC) is characterized by a rich infiltration of macrophages in the intestines, which is derived from monocytes in the blood. The authors aimed to explore the changing trend of absolute monocyte counts (AMC) over time in NEC infants and to verify whether the reduction of AMC correlates with the severity of NEC and whether it can be used to identify infants who need surgery. METHOD: The authors collected the clinical data of 66 control and 222 NEC infants. The NEC infants were divided into medical NEC (M-NEC) and surgical NEC (S-NEC). The counting of monocyte and their percentage change were compared at the time of birth, before NEC (baseline), the onset of NEC and after NEC (recovery). In addition, the same comparison was made among stages 1, 2 and 3 of Bell's staging, respectively. RESULTS: The authors found that the AMC in NEC infants decreased sharply at the onset. Further comparison was made between 172 cases of M-NEC and 50 cases of S-NEC. It was discovered that the AMC reduced more in S-NEC infants at onset, but it increased more at recovery. In addition, the authors found that among stage 1,2 and 3, stage 3 had the lowest AMC and the largest percentage decrease at the onset. CONCLUSION: The AMC decreases sharply in NEC infants at onset, and the degree of decline is associated with the severity of NEC. AMC is expected to be a marker of NEC and provide a reference for clinicians in the diagnosis and treatment of NEC.


Enterocolitis, Necrotizing , Infant, Newborn, Diseases , Infant , Infant, Newborn , Humans , Infant, Premature , Monocytes , Enterocolitis, Necrotizing/diagnosis , Enterocolitis, Necrotizing/surgery , Leukocyte Count , Retrospective Studies
5.
Hepatology ; 77(6): 1911-1928, 2023 06 01.
Article En | MEDLINE | ID: mdl-36059151

BACKGROUND AND AIMS: Hepatoblastoma (HB) is the predominant type of childhood liver cancer. Treatment options for the clinically advanced HB remain limited. We aimed to dissect the cellular and molecular basis underlying HB oncogenesis and heterogeneity at the single-cell level, which could facilitate a better understanding of HB at both the biological and clinical levels. APPROACH AND RESULTS: Single-cell transcriptome profiling of tumor and paired distal liver tissue samples from five patients with HB was performed. Deconvolution analysis was used for integrating the single-cell transcriptomic profiles with the bulk transcriptomes of our HB cohort of post-neoadjuvant chemotherapy tumor samples. A single-cell transcriptomic landscape of early human liver parenchymal development was established for exploring the cellular root and hierarchy of HB oncogenesis. As a result, seven distinct tumor cell subpopulations were annotated, and an effective HB subtyping method was established based on their compositions. A HB tumor cell hierarchy was further revealed to not only fit with the classical cancer stem cell (CSC) model but also mirror the early human liver parenchymal development. Moreover, FACT inhibition, which could disrupt the oncogenic positive feedback loop between MYC and SSRP1 in HB, was identified as a promising epigenetic-targeted therapeutic strategy against the CSC-like HB1-Pro-like1 subpopulation and its related high-risk "Pro-like1" subtype of HB. CONCLUSIONS: Our findings illustrate the cellular architecture and developmental trajectories of HB via integrative bulk and single-cell transcriptome analyses, thus establishing a resourceful framework for the development of targeted diagnostics and therapeutics in the future.


Hepatoblastoma , Liver Neoplasms , Humans , Hepatoblastoma/drug therapy , Transcriptome , Liver Neoplasms/pathology , Gene Expression Profiling , DNA-Binding Proteins , High Mobility Group Proteins/therapeutic use , Transcriptional Elongation Factors
6.
J. pediatr. (Rio J.) ; 99(5): 449-455, 2023. tab, graf
Article En | LILACS-Express | LILACS | ID: biblio-1514455

Abstract Objective: Necrotizing enterocolitis (NEC) is characterized by a rich infiltration of macrophages in the intestines, which is derived from monocytes in the blood. The authors aimed to explore the changing trend of absolute monocyte counts (AMC) over time in NEC infants and to verify whether the reduction of AMC correlates with the severity of NEC and whether it can be used to identify infants who need surgery. Method: The authors collected the clinical data of 66 control and 222 NEC infants. The NEC infants were divided into medical NEC (M-NEC) and surgical NEC (S-NEC). The counting of mono-cyte and their percentage change were compared at the time of birth, before NEC (baseline), the onset of NEC and after NEC (recovery). In addition, the same comparison was made among stages 1, 2 and 3 of Bell's staging, respectively. Results: The authors found that the AMC in NEC infants decreased sharply at the onset. Further comparison was made between 172 cases of M-NEC and 50 cases of S-NEC. It was discovered that the AMC reduced more in S-NEC infants at onset, but it increased more at recovery. In addition, the authors found that among stage 1,2 and 3, stage 3 had the lowest AMC and the largest percentage decrease at the onset. Conclusion: The AMC decreases sharply in NEC infants at onset, and the degree of decline is associated with the severity of NEC. AMC is expected to be a marker of NEC and provide a reference for clinicians in the diagnosis and treatment of NEC.

7.
Front Surg ; 9: 990101, 2022.
Article En | MEDLINE | ID: mdl-36338646

Aim: To detect the composition of the gut microbiota in biliary atresia after Kasai surgery. Methods: Infants within six months after the Kasai operation who were diagnosed by cholangiography at Shanghai Children's Hospital were enrolled in the study. Fecal samples were collected from diapers, placed into sterile tubes in the inpatient department or outpatient department and frozen at -80°C within half an hour. The gut microbiota was detected by 16S rRNA sequences. Then, the patients that were followed up to one year after the Kasai operation who suffered from cholangitis at least one time were grouped into the BAcho group, and the others were grouped into the BAnoncho group. Results: Nine of 18 BA patients were grouped into the BAcho group, and the others were grouped into the BAnoncho group. In the BAcho group, AST, ALT and GGT were significantly increased compared to the BAnoncho group. The number of total OTUs (operational taxonomic units) in feces was more elevated in the BAnoncho group than in the BAcho group. In the BAnoncho group, the Chao index at the OTU level was significantly increased compared to that in the BAcho group (66.37 ± 21.5 vs. 45.64 ± 11.25, p = 0.02 < 0.05). Bifidobacterium was the most abundant genus in the BAnoncho group, accounting for 22.14%, and Klebsiella accounted for 22.74% in the BAcho group. Compared with the BAnoncho group, Bacteroides was significantly decreased in the BAcho group (p = 0.037). Conclusion: The composition of the gut microbiota was different between BA with cholangitis and BA without cholangitis.

8.
Front Pediatr ; 10: 966839, 2022.
Article En | MEDLINE | ID: mdl-36147812

Purpose: We aim to see incidental appendectomy (IA) was worth or not during the laparoscopic treatment of intussusception. Methods: This study included forty-eight patients who underwent a laparoscopic procedure for idiopathic intussusception without intestinal resection between April 2014 and April 2021. The Chi-square or Fisher's exact tests for categorical variables and the Student t-test for continuous variables were used to analyze and compare patient characteristics. Results: IA was performed on 63% (30/48) of patients after surgical reduction, while 18 (37%), did not. Patients who underwent IA had a higher total cost (16,618 ± 2,174 vs.14,301 ± 5,206, P = 0.036), and a longer mean operation duration (59 ± 19 vs.45 ± 21, P = 0.025). The distribution of the PO time, length of hospital stay, PCs, and RI did not differ significantly. The histopathological evaluation of the 30 resected appendices revealed five (17%) with signs of acute inflammation, 20 (66%) with chronic signs of inflammation, and five (17%) with inconspicuous appendices. Conclusion: IA is linked to a longer average operation time and a higher total cost. There is insufficient evidence to recommend IA during laparoscopic intussusception treatment. The risks and benefits of IA need further study.

9.
Am J Transl Res ; 14(7): 4830-4837, 2022.
Article En | MEDLINE | ID: mdl-35958473

OBJECTIVE: To explore and analyze the risk factors for postoperative complications in patients with Hirschsprung's disease (HD). METHODS: Patients with HD admitted to the hospital from 2015 to 2020 were reviewed in this retrospective study. Follow-up data collected included constipation, fecal incontinence, anastomotic fistula, Hirschsprung's-associated enterocolitis (HAEC), and readmission. The putative risk factors for postoperative complications in patients with HD were as follows: clinical classification, gender, operative age, hemoglobin and serum albumin levels and preoperative HAEC. A follow-up survey was conducted for all patients by telephone. Data were analyzed statistically using SPSS version 23.0. RESULTS: A total of 154 patients were included in the study, of whom 119 patients were followed up successfully. 53 patients who had complications postoperatively were compared to 66 patients who had no related complications. Among patients with complications: 8 had constipation, 22 had fecal incontinence and 33 had HAEC. The gender, operative age, hemoglobin levels and preoperative HAEC did not differ significantly between the two groups. However, significant differences were observed between the 2 groups in clinical classification, surgical method, serum albumin level, and whether or not a one-stage operation was performed (P<0.05). CONCLUSION: Clinical classification, surgical method, preoperative albumin level and whether or not a one-stage operation was performed emerged as risk factors affecting the postoperative complications of patients with HD. Therefore, the prognosis in HD can be improved by strengthening the preoperative nutritional support and selecting appropriate surgical methods according to the clinical subtype.

10.
Cell Biosci ; 12(1): 3, 2022 Jan 04.
Article En | MEDLINE | ID: mdl-34983626

BACKGROUND: Neonates possess an immature and plastic immune system, which is a major cause of some diseases in newborns. Necrotizing enterocolitis (NEC) is a severe and devastating intestinal disease that typically affects premature infants. However, the development of intestinal immune cells in neonates and their roles in the pathological process of NEC have not been elucidated. RESULTS: We examined the ontogeny of intestinal lamina propria lymphocytes in the early life of mice and found a high percentage of RORγt+ cells (containing inflammatory Th17 and ILC3 populations) during the first week of life. Importantly, the proportion of RORγt+ cells of intestinal lamina propria further increased in both NEC mice and patients tissue than the control. Furthermore, the application of GSK805, a specific antagonist of RORγt, inhibited IL-17A release and ameliorated NEC severity. CONCLUSIONS: Our data reveal the high proportion of RORγt+ cells in newborn mice may directly contribute to the development of NEC.

11.
Front Pediatr ; 10: 1101163, 2022.
Article En | MEDLINE | ID: mdl-36699312

Background: The presence of intrahepatic foreign bodies is a rare occurrence at the emergency department. Normally, foreign bodies reach the liver through migration. Incidence is lower among children than among adults, and the circumstances of children are often different. We report a 19-month-old boy with a sewing needle in the liver and review the previous reports of intrahepatic sewing needle in the PubMed database from the last three decades. Case presentation: A 19-month-old boy was transferred to our center from a local hospital presenting intermittent cough and rhinorrhea. A chest radiograph to exclude pulmonary disease revealed an incidental finding of a high-density shadow in the hepatic region. On admission, the boy had no gastrointestinal symptoms. Abdominal physical examinations were unremarkable. His mother, a worker in a textile factory, denied any history of trauma. Abuse was excluded based on investigation. Preoperative routine test results were normal. Contrast-enhanced computed tomography (CT) revealed that the sewing needle was located in hepatic segment IV and the tip had close relationship with intrahepatic portal vein. Initially, laparoscopy was performed without success. We eventually converted to laparotomy to completely remove the rusty sewing needle. The patient resumed feeding soon after the operation and was discharged in a few days. Conclusions: Intrahepatic sewing needle has high incidence among boys and developing countries. Combined with contrast-enhanced CT, knowledge of the pediatric patient's family background and medical history would help judge the route of entry and determine the management and surgical strategy. Laparoscopic procedure is not suitable for rusty sewing needles.

12.
Am J Transl Res ; 14(12): 8782-8787, 2022.
Article En | MEDLINE | ID: mdl-36628252

Mesenchymal hamartoma of the liver (MHL) often presents as a painless right upper abdominal mass in young children. However, MHL is rarely reported in the neonatal period. We presented the case of a preterm newborn with a huge MHL. The boy was delivered at 30 weeks weighing 1750 g. Abdominal distention was the initial presentation. Ultrasound and computed tomography showed a highly vascularized mass originating from the left lobe. Liver hemangioma was initially suspected and oral propranolol was administered. However, the tumor was rapidly enlarging, resulting in compromised respiratory status and severe anemia. Surgical resection and neonatal management were successful. The patient required cardiopulmonary resuscitation in the operating room and received packed red blood cells. The histopathological result was mesenchymal hamartoma. The baby recovered well after one-year follow-up. We also reviewed the clinical courses and treatment strategies of preterm MHL cases in published English literature from 1990 to 2021.

13.
Front Pediatr ; 9: 710382, 2021.
Article En | MEDLINE | ID: mdl-34869093

Background: Hydrogen is protective against intestinal injury in necrotizing enterocolitis (NEC), mainly through to alleviate inflammation response. The M1 macrophages can promote inflammation. We hypothesized that hydrogen would promote the M1 macrophages conversion during the polarization and reduce the inflammatory factors in NEC. Methods: We used M1 and M2 macrophages induced from RAW264.7 cells and bone marrow-derived macrophages, models of NEC and macrophages derived from spleens, abdominal lymph nodes and lamina propria in model mice. Cytokines, CD16/32 and CD206 were measured by quantitative PCR, flow cytometry. Nuclear factor-κB (NF-κB) p65 were determined by western blot. Histology staining were used to assess the severity of NEC. Results: Macrophages were successfully polarized to M1 or M2 by assessing the expression of inflammatory factors. Pro-inflammatory factors and CD16/32 in M1 macrophages were decreased, and the expression of CD16/32 in lamina propria were inhibited after treatment with hydrogen, but the changes has no effects in other tissues. Hydrogen inhibited the NF-κB p65 in M1 macrophages nucleus and distal ileum of NEC. HE staining showed hydrogen could attenuate the severity of NEC. Conclusion: Hydrogen could attenuate the severity of NEC through promoting M1 macrophages conversion by inhibited the expression of NF-κB p65 in the nucleus.

14.
Front Cell Dev Biol ; 9: 655703, 2021.
Article En | MEDLINE | ID: mdl-34422793

Hepatoblastoma (HB) is a rare disease but nevertheless the most common hepatic tumor in the pediatric population. For patients with advanced HB, the prognosis is dismal and there are limited therapeutic options. Multiple microRNAs (miRNAs) were reported to be involved in HB development, but the miRNA-mRNA interaction network in HB remains elusive. Through a comparison between HB and normal liver samples in the GSE131329 dataset, we detected 580 upregulated differentially expressed mRNAs (DE-mRNAs) and 790 downregulated DE-mRNAs. As for the GSE153089 dataset, the first cluster of differentially expressed miRNAs (DE-miRNAs) were detected between fetal-type tumor and normal liver groups, while the second cluster of DE-miRNAs were detected between embryonal-type tumor and normal liver groups. Through the intersection of these two clusters of DE-miRNAs, 33 upregulated hub miRNAs, and 12 downregulated hub miRNAs were obtained. Based on the respective hub miRNAs, the upstream transcription factors (TFs) were detected via TransmiR v2.0, while the downstream target genes were predicted via miRNet database. The intersection of target genes of respective hub miRNAs and corresponding DE-mRNAs contributed to 250 downregulated candidate genes and 202 upregulated candidate genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses demonstrated the upregulated candidate genes mainly enriched in the terms and pathways relating to the cell cycle. We constructed protein-protein interaction (PPI) network, and obtained 211 node pairs for the downregulated candidate genes and 157 node pairs for the upregulated candidate genes. Cytoscape software was applied for visualizing the PPI network and respective top 10 hub genes were identified using CytoHubba. The expression values of hub genes in the PPI network were subsequently validated through Oncopression database followed by quantitative real-time polymerase chain reaction (qRT-PCR) in HB and matched normal liver tissues, resulting in six significant downregulated genes and seven significant upregulated genes. The miRNA-mRNA interaction network was finally constructed. In conclusion, we uncover various miRNAs, TFs, and hub genes as potential regulators in HB pathogenesis. Additionally, the miRNA-mRNA interaction network, PPI modules, and pathways may provide potential biomarkers for future HB theranostics.

15.
Am J Cancer Res ; 11(5): 1982-2004, 2021.
Article En | MEDLINE | ID: mdl-34094665

Hepatoblastoma (HB) is the most frequent pediatric liver malignancy. However, the treatment outcome for patients with advanced-stage HB remains unsatisfactory. Accumulating evidence indicates that ßKlotho (KLB) acts as an oncogene or a tumor-suppressor gene in a context-dependent manner. Despite this, the expression profile and effects of KLB on the growth of HB are still elusive. This study aimed to explore the effect of miR-206/KLB axis on HB growth. The expression of KLB was explored in HB cells (HepG2 and HuH6) and tissues using quantitative polymerase chain reaction (qPCR), Western blot analysis, and immunohistochemistry. Besides, miR-206 expression was determined in HB cells and tissues using qPCR and fluorescence in situ hybridization. The prognostic value of KLB or miR-206 in our patients with HB was investigated using the Kaplan-Meier method. The biological effects of KLB or miR-206 on HB cells were identified in vitro. The proliferative effects of KLB on HuH6 cells were also investigated in vivo. Moreover, the mechanical signaling of KLB in HB was determined through bioinformatics analysis followed by experimental validation. The results showed a significant upregulation of KLB in HB tissues and cells. Elevated level of KLB was found to be significantly correlated with the aggressive phenotype and poor overall survival for children with HB. The in vitro function assay demonstrated that KLB knockdown promoted apoptosis and suppressed the proliferation, migration, and invasion of HB cells. Besides, KLB knockdown inhibited the proliferation of HuH6 cells in vivo, while KLB overexpression had the opposite effect. Furthermore, KLB was proved to be the direct target of miR-206. Low level of miR-206 served as an independent risk factor for poor prognosis in children with HB. The overexpression of miR-206 negatively regulated the aggressive biological behaviors of HB cells, which was partially rescued by KLB overexpression. Mechanically, the miR-206/KLB axis played a vital role in HB growth through augmenting the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling. In conclusion, the data demonstrated that the miR-206/KLB axis might serve as an important biomarker/therapeutic target for HB.

16.
Cell Biosci ; 11(1): 20, 2021 Jan 19.
Article En | MEDLINE | ID: mdl-33482929

BACKGROUND: Intestinal dysbiosis is believed to be one of the factors inducing neonatal necrotizing enterocolitis (NEC). Probiotics have been employed to treat NEC in a number of animal experiments and clinical trials, and some significant benefits of utilizing probiotics for the prevention or alleviation of NEC have been confirmed. However, the mechanism underlying the efficacy of probiotics in treating NEC has not been elucidated. RESULTS: Impairment of the intestinal barrier, which was characterized by the decreased expression of tight junction components, was observed in the pathogenesis of NEC. The probiotic mixture alleviated this intestinal damage by enhancing the function of the barrier. Meanwhile, the probiotics remodeled the composition of the intestinal microbiota in NEC mice. Furthermore, increased expression of the pregnane X receptor (PXR) was observed after treatment with the probiotic mixture, and PXR overexpression in Caco-2 cells protected the barrier from lipopolysaccharide (LPS) damage. Further research showed that PXR could inhibit the phosphorylation of c-Jun N-terminal kinase (JNK) and could increase the expression of tight junction components. CONCLUSIONS: Our study confirmed that probiotics could ameliorate intestinal lesions by enhancing the function of the mucosal barrier. Specifically, probiotics may target PXR, which may subsequently enhance the expression of tight junction components by inhibiting the phosphorylation of JNK and enhance the function of the barrier.

17.
Dig Dis Sci ; 66(12): 4237-4250, 2021 12.
Article En | MEDLINE | ID: mdl-33471252

BACKGROUND: An immature intestine is a high-risk factor for necrotizing enterocolitis (NEC), which is a serious intestinal disease in newborns. The regulation of developmentally regulated GTP-binding protein 1 (DRG1) during organ development suggests a potential role of DRG1 in the maturation process of the intestine. AIM: To illustrate the function of DRG1 during the pathogenesis of NEC. METHODS: DRG1 expression in the intestine was measured using immunohistochemistry and q-PCR. Immunoprecipitation coupled with mass spectrometry was used to identify the interacting proteins of DRG1. The biological functions of the potential interactors were annotated with the Database for Annotation, Visualization and Integrated Discovery. Caco2 and FHs74Int cells with stable DRG1 silencing or overexpression were used to investigate the influence of DRG1 on cell junctions and intestinal barrier permeability and to elucidate the downstream mechanism. RESULTS: DRG1 was constitutively expressed during the intestinal maturation process but significantly decreased in the ileum in the context of NEC. Protein interaction analysis revealed that DRG1 was closely correlated with cell junctions. DRG1 deficiency destabilized the E-cadherin and occludin proteins near the cell membrane and increased the permeability of the epithelial cell monolayer, while DRG1 overexpression prevented lipopolysaccharide-induced disruption of E-cadherin and occludin expression and cell monolayer integrity. Further investigation suggested that DRG1 maintained cell junctions, especially adherens junctions, by regulating RAC1 activity, and RAC1 inhibition with NSC23766 attenuated intestinal injury and led to improved barrier integrity in experimental NEC. CONCLUSIONS: Our findings illustrate the mechanism underlying the effect of DRG1 deficiency on epithelial cell permeability regulation and provide evidence supporting the application of RAC1 inhibitors for protection against NEC.


Enterocolitis, Necrotizing/enzymology , Epithelial Cells/enzymology , GTP-Binding Proteins/metabolism , Intercellular Junctions/enzymology , Intestinal Mucosa/enzymology , rac1 GTP-Binding Protein/metabolism , Aminoquinolines/pharmacology , Animals , Antigens, CD/metabolism , Caco-2 Cells , Cadherins/metabolism , Electric Impedance , Enterocolitis, Necrotizing/drug therapy , Enterocolitis, Necrotizing/genetics , Enterocolitis, Necrotizing/pathology , Enzyme Inhibitors/pharmacology , Epithelial Cells/drug effects , Epithelial Cells/pathology , GTP-Binding Proteins/genetics , HEK293 Cells , Humans , Intercellular Junctions/drug effects , Intercellular Junctions/genetics , Intercellular Junctions/pathology , Intestinal Mucosa/drug effects , Intestinal Mucosa/pathology , Mice , Occludin/metabolism , Permeability , Pyrimidines/pharmacology , rac1 GTP-Binding Protein/analysis
18.
J Pediatr Surg ; 56(4): 800-804, 2021 Apr.
Article En | MEDLINE | ID: mdl-32709530

BACKGROUND: Pyriform sinus fistula (PSF) is a rare congenital anomaly, and the preferred definitive treatment is yet to be verified. In this study, we investigated the treatment outcomes of PSF specifically comparing endoscopic-assisted surgery and endoscopic radiofrequency ablation (RA). METHODS: The medical records of patients treated for PSF at the Shanghai Children's Hospital between October 2016 and September 2019 were retrospectively evaluated. RESULTS: There were 93 girls and 98 boys. The median age at onset and operation was 3 years and 5 years, respectively. Endoscopic-assisted surgery was performed in 143 patients. During the same period, RA was performed in 48 patients, and 10 of them concurrently underwent incision and drainage of neck abscesses. Longer hospital stay was found in the endoscopic-assisted surgery group than in the RA group (10.50 ±â€¯3.93 vs. 5.02 ±â€¯3.30 days, P < 0.001). Postoperative complications were not significantly different between the two groups, except for neck infection (0 vs. 8.3%, P = 0.004). After a median follow-up period of 21 months, no significant difference was found between the two groups in terms of recurrence (1.4% vs. 0, P = 0.560). CONCLUSION: Patients treated with RA had a significantly shorter hospital stay than those treated with endoscopic-assisted surgery. Outcomes of endoscopic-assisted surgery and RA were not significantly different for the management of PSF and treatment method should be tailored to the patient. LEVEL OF EVIDENCE: IV.


Fistula , Pyriform Sinus , Radiofrequency Ablation , Child , China/epidemiology , Female , Humans , Male , Pyriform Sinus/surgery , Retrospective Studies
19.
Front Pediatr ; 8: 575812, 2020.
Article En | MEDLINE | ID: mdl-33194907

Background: Diagnostic delay of pyriform sinus fistula (PSF) continues to challenge clinicians, and the preferred imaging modality is yet to be verified. The purpose of this study was to investigate the preferred imaging modality for PSF and the possible risk factors for a longer diagnostic delay. Methods: Medical records of patients with a surgically confirmed PSF from 2014 to 2018 were retrospectively evaluated. A comparison of the first esophagography timing with a true-positive (TP) result and that with a false-negative (FN) result was made. Data of computed tomography (CT) performed immediately after esophagography were also analyzed. In addition, the factors related to diagnostic delay were analyzed using multivariate regression models. Results: A total of 147 patients ranging in age from 0 to 16 years (median: 5.2 years) were included. The mean time since the symptom onset of the first esophagography with TP result was significantly longer than that of the examination with FN result (95.18 ± 79.12 vs. 52.59 ± 42.40 days, P = 0.032). When the time since the symptom onset was less than 12 weeks, the false-negative rate (FNR) of the first esophagography was declining dramatically with a longer time interval. Among 18 cases with an FN result of the first esophagography, the fistulous tract was finally identified in seven cases using an immediate CT. The mean of diagnostic delay was 12.28 months. Besides, rural residency was an independent risk factor for a longer diagnostic delay. Conclusion: Joint examination of esophagography and an immediate CT is the preferred imaging modality for the diagnosis of PSF in children. It is inadvisable to perform the first esophagography when the time since the symptom onset is less than 12 weeks. Besides, the rural residency is an independent risk factor for a longer diagnostic delay.

20.
World J Clin Cases ; 8(20): 4930-4937, 2020 Oct 26.
Article En | MEDLINE | ID: mdl-33195663

BACKGROUND: About 90% of perianal infection is caused by cryptoglandular infection. Only a few cases of peritonitis or intra-abdominal abscesses secondary to perforation of the digestive tract by an ingested foreign body have been reported. The most common sites of impaction and perforation include the appendix, cecum and the terminal ileum. The rectum is an unusual site of foreign body impaction. This report intends to highlight that ingested foreign body impacted in the rectum is an extremely rare cause of perianal abscess and subsequent fistula in infants. CASE SUMMARY: Two cases of perianal abscess and fistula due to ingested jujube pit impacted in the rectum are reported. Both cases are infants with free previous medical history suffered from recurrent perianal infection. The caregivers of the two patients denied ingestion of a foreign body or any history of trauma. Physical examination combined with ultrasound or computed tomography scan established the diagnosis. Both of the patients underwent operation under general anesthesia. In case 1, a jujube pit with sharp ends was discovered embedded within a subcutaneous fistula. The jujube pit was then removed intact along with fistula resection. The wound was successfully laid open to allow healing by secondary intention. In case 2, a jujube pit was found with its sharp end puncturing the rectum, surrounded by pus and necrotic tissue. Subsequent incision and adequate drainage were performed. The whole jujube pit was then removed from the abscess cavity at the same time. Both patients received colonoscopy to rule out inflammatory bowel disease or other potential damages by the ingested jujube pit. The postoperative period was uneventful. At 1.5 year follow-up, no recurrent abscess or fistula were found in either patient. CONCLUSION: An impacted foreign body must not be overlooked as an unusual cause of perianal abscess and fistula, especially in young children.

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