Single-cell transcriptomics uncovers cellular architecture and developmental trajectories in hepatoblastoma.

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.

Gestational age-specific hematological features in preterm infants with necrotizing enterocolitis.

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.

Tracking changes in image-defined risk factors during neoadjuvant chemotherapy and their predictive value for surgical outcomes based on the International Neuroblastoma Surgical Report Form.

BACKGROUND: The capacity of presurgical image-defined risk factors (IDRFs) to predict secondary surgical outcomes in patients with neuroblastoma is controversial. METHODS: The International Neuroblastoma Surgical Report Form (INSRF) was employed to retrospectively collect the clinical data of 53 patients diagnosed with neuroblastoma at our hospital from April 2014 to April 2020. IDRFs were identified at the time of diagnosis and reassessed during the course of neoadjuvant chemotherapy. Various statistical tests were used to evaluate the correlation between IDRFs and secondary surgical outcomes. RESULTS: A total of 195 IDRFs were identified. Notably, by two courses of neoadjuvant chemotherapy, the number of "two body compartments," "intraspinal tumor extension," and "trachea-compressing" IDRFs decreased significantly (p = .001). The primary tumor volumes and the number of IDRFs decreased significantly by four courses of neoadjuvant chemotherapy, especially in "intraspinal tumor extension" IDRFs (p = .034). The median number of IDRF per patient was four (interquartile range [IQR]: 1-5) at diagnosis, which diminished to one (IQR: 1-3) subsequent to neoadjuvant chemotherapy. The presence of preoperative IDRFs was not associated with surgical complications (p = .286) or the extent of surgery (p = .188). However, the number of preoperative IDRFs linked to the extent of surgery (p = .002), not to operative complications (p = .669). Specifically, presurgery "renal vessel contact" IDRFs were predictive of surgical complications, while presurgery "infiltration of vital structures" IDRFs were associated with the extent of surgery. CONCLUSION: The number of IDRFs decreased significantly by four courses of neoadjuvant chemotherapy. The number and type of presurgery IDRFs may predict secondary surgical outcomes, surpassing the mere consideration of their presence or absence.

Endoscopic Balloon Dilatation-Based Membrane Resection for Membranous Duodenal Stenosis: A Feasibility and Safety Study (With Video).

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.

DRG1 Maintains Intestinal Epithelial Cell Junctions and Barrier Function by Regulating RAC1 Activity in Necrotizing Enterocolitis.

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.

Role of image-defined risk factors in predicting surgical complications of localized neuroblastoma.

PURPOSE: To explore the relationship between image-defined risk factors and surgical complications of localized neuroblastoma. METHODS: We retrospectively evaluated 84 patients who met the inclusion criteria at our hospitals between June 2014 and June 2019. Patients' clinic data were collected and the common terminology criteria for adverse events were used to categorize complications as major (grade 3-4) or minor (grade 1-2). RESULTS: Four (11.8%) out of 34 stage L1 patients and 15 (30.0%) out of 50 stage L2 patients had surgical complications (P < 0.05). Seventy patents underwent primary surgery, including all stage L1 patients and 36 stage L2 patients. There were no significant differences between the two groups regarding surgical complications or major surgical complications. Among stage L2 patients, 2 (5.6%) out of 36 who underwent primary surgery and 2 (14.3%) out of 14 who underwent secondary surgery had major surgical complications (P < 0.05). Complete tumor resection was achieved in 18 (50%) and 7 (50%) patients in each group (P > 0.05). The mean numbers of IDRFs were 2.06 and 4.29, respectively (P < 0.05). CONCLUSIONS: Localized neuroblastoma patients with IDRFs have a greater surgical risk. And the number of IDRFs is not ignorable, especially in predicting major surgical complications.

Reoperation After Cyst Excision with Hepaticojejunostomy for Choledochal Cysts: Our Experience in 18 Cases.

BACKGROUND Complete cyst excision with biliary reconstruction is the treatment of choice for choledochal cyst (CC). The aim of this article is to review our experience in patients who underwent reoperation between January 1995 and December 2014. MATERIAL AND METHODS The records of 18 patients (female/male, 15/3) were retrospectively analyzed including age, sex, cyst type, initial procedure, lab and imaging findings, indications for reoperation, intraoperative findings, and results of reoperation. The median follow-up period was 6 years. RESULTS The rate of reoperation in this study was about 6.8%. Eighteen patients (7 type Ia, 2Ic, 9 IV-A) developed severe postoperative complications and required surgical intervention. The median time interval from primary surgery to reoperation was 19.5 months (range, 3 days to 8 years). Two early complications required surgery due to anastomotic bile leakage and intussusception. Sixteen late complications occurred, including 3 intrahepatic bile duct stenosis with calculi, 5 anastomotic strictures with/without stones, 4 intrapancreatic cyst remnants, 3 adhesive bowel obstructions, and 1 internal hernia. For patients with persistent dilatation of the intrahepatic bile duct or anastomotic stricture, removal of stones and revision of hepaticojejunostomy were performed, with additional hepatic ductoplasty when necessary. Radical excision of the dilated cystic remnant in the head of pancreas was performed in 4 patients, with 1 needing additional pancreaticojejunostomy procedure. No deaths occurred. Sixteen patients recovered uneventfully after reoperation, and 2 wound infections developed. CONCLUSIONS A wide hepaticojejunostomy with/without ductoplasty is essential to prevent cholangitis, anastomotic stricture, and calculi formation. Complete cyst excision, including the intrapancreatic portion, should be meticulously pursued.

Fn14 hepatic progenitor cells are associated with liver fibrosis in biliary atresia.

PURPOSE: The liver in biliary atresia (BA) is characterized by progressing fibrosis which is promoted by unclear reasons. We aimed to understand the factors influencing liver fibrosis. This study hypothesized that HPCs (hepatic progenitor cells) are activated and associated with liver fibrosis in biliary atresia. METHODS: Liver samples from biliary atresia patients are as BA group, and the normal liver derived from hepatoblastoma infants during operation are control group. The extent of fibrosis in liver samples was blindly evaluated by two experienced pathologists depending on Ishak system. The BA liver samples were divided into mild liver fibrosis group (grade I-IV, BAa) and severe liver fibrosis group (grade V-VI, BAb) to detect Fn14 protein expression. RESULTS: In mRNA level, Fn14 expression was 21.23 ± 8.3 vs. 1.00 ± 0.17, p = 0.023 < 0.05 and CD133 expression was 6.02 ± 2.16 vs. 1.14 ± 0.75, p = 0.008 < 0.01 between BA group and control group. Fn14 cells co-expressed the progenitor marker CD133 in liver, and activated in BA. Fn14 andα-SMA were co-location in fibrous area in liver. Compared to the control group, Fn14, CD133, and α-SMA protein expression were 2.10 ± 0.53 vs. 0.97 ± 0.2, p = 0.001, 2.23 ± 0.57 vs. 1.00 ± 0.03, p = 0.000, 4.96 ± 2.4 vs. 1.00 ± 0.22, p = 0.001. The Fn14 protein expression was 2.60 ± 0.35 vs. 1.86 ± 0.42, p = 0.012, between BAb and BAa group. CONCLUSION: Fn14 cells, which co-express the progenitor marker CD133 in liver, are HPCs and activated in BA. Fn14 + HPCs are associated with liver fibrosis in BA.

Human ß-defensin-3 promotes intestinal epithelial cell migration and reduces the development of necrotizing enterocolitis in a neonatal rat model.

BACKGROUND: The aim of this study was to investigate the effects of human ß-defensin-3 (hBD3) on intestinal wound healing and in a neonatal rat model of necrotizing enterocolitis (NEC). METHODS: Enterocyte migration and proliferation were detected in vitro and in vivo. The role of chemokine receptor CCR6 and its downstream signaling pathway was assessed. Newborn Sprague-Dawley rats were randomly divided into four groups: Control+NS, Control+hBD3, NEC+NS, and NEC+hBD3. Body weight, histological score, survival time, cytokines expression, and mucosal integrity were evaluated. RESULTS: hBD3 could stimulate enterocyte migration, but not proliferation, both in cultured enterocytes and in the NEC model. Neutralizing antibody and small interfering RNA confirmed this stimulatory effect was mediated by CCR6. Furthermore, hBD3 induced Rho activation, myosin light chain 2 phosphorylation, and F-actin accumulation. The bactericidal activity of hBD3 was maintained throughout a broad pH range. Strikingly, hBD3 administration decreased the incidence of NEC, increased the survival rate, and reduced the severity of NEC. Moreover, hBD3 reduced the proinflammatory cytokines expression in ileum and serum and preserved the intestinal barrier integrity. CONCLUSION: This study provided evidence that the antimicrobial peptide hBD3 might participate in intestinal wound healing by promoting enterocyte migration and show beneficial effects on newborn rats with NEC.

Laparoscopic-assisted sclerotherapy in pediatric retroperitoneal lymphatic malformations.

Background: Retroperitoneal lymphatic malformations (LMs) are rare. Currently, the treatment of retroperitoneal LMs remains challenging. This study aimed to examine the safety and efficacy of laparoscopic-assisted sclerotherapy for retroperitoneal LMs in pediatric patients. Methods: We retrospectively reviewed patients treated with laparoscopic-assisted sclerotherapy for retroperitoneal LMs in a single tertiary medical center between July 2020 and February 2023. Doxycycline was prepared into a solution with a concentration of 10 mg/ml for use in sclerotherapy. Demographic data, clinical features, details of management, and outcomes were collected and analyzed. Results: A total of six patients, comprising three males and three females, were identified. The LMs were categorized into four macrocystic and two mixed-cystic types. The mean age and weight were 52.2 months (range, 11-108 months) and 20 kg (range, 12.5-27.5 kg), respectively. Three patients presented with abdominal pain or distension, while the other three patients were asymptomatic. All six patients underwent a total of eight sclerotherapy sessions. Two patients experienced intra-cystic hemorrhage and required a second sclerotherapy session. Only one patient presented with vomiting after sclerotherapy, which resolved spontaneously. Five patients met the complete response criteria, and one patient met the effective criteria. The mean reduction in lesion size was 92.3% (range, 69.9%-99.6%). No further complications or recurrence were recorded during follow-up. Conclusion: Laparoscopic-assisted sclerotherapy is a safe and effective approach for treating retroperitoneal LMs. This technique is applicable for both macrocystic and mixed-cystic retroperitoneal LMs.

Reduction of absolute monocyte counts is associated with the severity of preterm necrotizing enterocolitis.

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.

Re-operation for Hirschsprung's disease: experience in 24 patients from China.

PURPOSE: The aim of this study is to review the authors' 12-year experience with re-operative surgery for Hirschsprung's disease (HD) including indications of re-operation and surgical technique. METHODS: We retrospectively reviewed the data of 24 patients who underwent re-operation from 1998 to 2010. The type of initial procedure, clinical presentations, indications and details of redo surgery, and the functional results were analyzed. RESULTS: The primary operations performed on these patients included Duhamel (nine cases), Soave (12 cases), Swenson (one case) and Rehbein (two cases). The indications for re-operation were recurrent constipation due to severe anastomotic stricture (five cases), residual aganglionic segments (five cases) and gate syndrome after Duhamel procedure (five cases); fistula formation including rectocutaneous fistula (six cases), rectovaginal fistula (one case), complex fistula (two cases). The redo procedure ranged from posterior sagittal approach combined with laparotomy (seven cases), Soave procedure (seven cases, six conventional Soave + one transanal Soave), Duhamel procedure (one case), Rehbein procedure (three cases), re-using the stapling device (five cases), repairing the rectovaginal fistula via laparotomy (one case). We have followed up the patients for 7 months to 6 years (mean 2.5 years). After re-operation, in 22 patients older than 3 years, 19 (86.4%) have normal or near normal bowel habits with a stool frequency of 1-5 times per day, two have voluntary bowel movements but occasional soiling (once or twice per week) and without significant incontinence, one presented rectosacral fistula due to careless dilatation. There were no deaths. CONCLUSION: Re-operation can work out the anatomical or pathological problems resulted from failed initial procedure and improve the patient's quality of life. Posterior sagittal approach, Soave and Duhamel are all safe and effective, but we still need to try our best to diminish the necessity of re-operation.

Clinical outcomes and risk factors for postoperative complications in children with Hirschsprung's disease.

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.

The composition of the gut microbiota is altered in biliary atresia with cholangitis.

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.

Case report and literature review: An intrahepatic sewing needle in a child.

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.

Giant hepatic mesenchymal hamartoma in a preterm newborn: a case report and literature review.

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.

A retrospective study about incidental appendectomy during the laparoscopic treatment of intussusception.

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.

Ontogeny of RORγt+ cells in the intestine of newborns and its role in the development of experimental necrotizing enterocolitis.

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.

ßKlotho, a direct target of miR-206, contributes to the growth of hepatoblastoma through augmenting PI3K/Akt/mTOR signaling.

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.