Retrospective assessment of short-term outcomes of robotic- versus laparoscopic-assisted duodenal diamond anastomosis in neonates.

OBJECTIVE: The purpose of this study was to retrospectively compare the short-term outcomes of robotic- (RAD) and laparoscopic-assisted duodenal diamond-shaped anastomosis (LAD) in neonates. METHODS: Neonates who underwent RAD (n = 30) or LAD (n = 38) between January 2019 and December 2022 were analyzed retrospectively. Major patient data were collected, including preoperative, intraoperative, and postoperative information. RESULTS: All patients were neonates below the age of 30 days weighing 4 kg. Thirty (44.1%) neonates underwent RAD and 38 neonates (55.9%) underwent LAD. Compared to the LAD group, the RAD group had a shorter intra-abdominal operation time (RAD, 60.0(50.0 ~ 70.0) min; LAD, 79.9(69.0 ~ 95.3) min; p < 0.001). There were no significant differences in immediate and 30-day complications between the two groups. CONCLUSIONS: RAD is safe and effective in neonates. Compared to traditional LAD, RAD showed comparable results.

Echocardiographic measurements of left ventricular dimensions and function in newborns with omphalocele and pulmonary.

PURPOSE: The purpose of this study was to explore echocardiographic parameters of the left ventricle (LV) in relation to the outcomes of omphalocele neonates with pulmonary hypertension (PH). METHODS: This retrospective study was conducted among omphalocele patients with PH born from 2019 to 2020. Patients in this study did not have additional severe malformations or chromosomal aberrations. Patients who died under palliative care were excluded. The echocardiographic parameters of LV were obtained within 24 h after birth. Clinical and outcomes data were recorded, echocardiograms evaluated for left ventricular internal dimension in end-diastole (LVIDd), end-diastolic volume (EDV), stroke volume (SV) and cardiac output index (CI), among others. RESULTS: There were 18 omphalocele newborns with PH, of whom 14 survived and 4 died. Both groups were comparable in the baseline characteristics. Non-survival was associated with a smaller LV [LVIDd (12.2 mm versus15.7 mm, p < 0.05), EDV (3.5 ml versus 6.8 ml, p < 0.05)] and with worse systolic function [SV (2.3 ml versus 4.2 ml, p < 0.05), and CI (1.7 L/min/m2 versus 2.9 L/min/m2, p < 0.01)]. CONCLUSION: In the cohort of omphalocele patients with PH, lower LVIDd, EDV, SV and CI were associated with mortality. LEVEL OF EVIDENCE: Level III.

Biliary atresia in twins'population: a retrospective multicenter study in mainland China.

AIM: We evaluated the demographic of biliary atresia (BA) children from twins family and aimed to investigated what it can add to the twins' literature and our understanding of the disease. METHODS: This study contains 11 medical centers in mainland China and the medical record of twins with BA was retrospectively analyzed from January 2012 to December 2018. Follow-up was carried out by out-patient review and questionnaire. RESULTS: The study included 19 twin pairs in whom there was discordance for BA. Sixteen (84.2%) affected twin underwent Kasai Procedure (KP); median age at KP was 78 (49-168) days. There were ten affected twins that became jaundice-free at 3 months post-KP, and eight occurred with different degrees of cholangitis post-KP. Six affected twins received Liver Transplantation (LT) successfully. The 2 year native liver survival rate and the 2 year overall survival rate of affected twins were 61.1 and 94.4%, respectively. There were three affected monozygotic (MZ) twins and one healthy co-twin with BA-associated congenital malformations, all of which were cardiac malformations. The number of virus infection of affected MZ twins was significantly more (p = 0.04) than affected dizygotic (DZ) twin. CONCLUSIONS: Discordance for BA in 19 pairs of twins supported that BA may be related to genetic phenotype or penetrance. The difference in genetic background between MZ and DZ affects the susceptibility of the host to virus infection. High acceptance of KP (84.2%) in our study implied a high motivation for treatment for twins with BA. Delays of KP (78 days) in affected twin may be related to the postnatal gradual onset and the late diagnosis.

Identification of Genes Associated With Hirschsprung Disease, Based on Whole-Genome Sequence Analysis, and Potential Effects on Enteric Nervous System Development.

BACKGROUND & AIMS: Hirschsprung disease, or congenital aganglionosis, is believed to be oligogenic-that is, caused by multiple genetic factors. We performed whole-genome sequence analyses of patients with Hirschsprung disease to identify genetic factors that contribute to disease development and analyzed the functional effects of these variants. METHODS: We performed whole-genome sequence analyses of 443 patients with short-segment disease, recruited from hospitals in China and Vietnam, and 493 ethnically matched individuals without Hirschsprung disease (controls). We performed genome-wide association analyses and gene-based rare-variant burden tests to identify rare and common disease-associated variants and study their interactions. We obtained induced pluripotent stem cell (iPSC) lines from 4 patients with Hirschsprung disease and 2 control individuals, and we used these to generate enteric neural crest cells for transcriptomic analyses. We assessed the neuronal lineage differentiation capability of iPSC-derived enteric neural crest cells using an in vitro differentiation assay. RESULTS: We identified 4 susceptibility loci, including 1 in the phospholipase D1 gene (PLD1) (P = 7.4 × 10-7). The patients had a significant excess of rare protein-altering variants in genes previously associated with Hirschsprung disease and in the ß-secretase 2 gene (BACE2) (P = 2.9 × 10-6). The epistatic effects of common and rare variants across these loci provided a sensitized background that increased risk for the disease. In studies of the iPSCs, we observed common and distinct pathways associated with variants in RET that affect risk. In functional assays, we found variants in BACE2 to protect enteric neurons from apoptosis. We propose that alterations in BACE1 signaling via amyloid ß precursor protein and BACE2 contribute to pathogenesis of Hirschsprung disease. CONCLUSIONS: In whole-genome sequence analyses of patients with Hirschsprung disease, we identified rare and common variants associated with disease risk. Using iPSC cells, we discovered some functional effects of these variants.

[Clinical analysis of annular pancreas in neonates].

OBJECTIVE: To analyze clinical manifestations, diagnosis and treatment of annular pancreas in neonates. METHODS: Clinical data of 114 neonates with annular pancreas admitted in the Children's Hospital of Zhejiang University from January 2009 to December 2018 were reviewed. The demographic parameters (gestational age, birth weight), clinical manifestations, onset time, results of antenatal examination, associated anomalies, radiological findings, operations, postoperative complications were analyzed. RESULTS: One hundred and two cases were examined by abdominal echography, in which 68 cases showed duodenal obstruction, 4 cases showed annular pancreas. Plain abdomen X-ray examination performed in 113 cases before operation, 76 cases presented double-bubble sign, 12 cases presented single-bubble sign and 5 cases had high-position intestinal obstruction. Upper gastrointestinal radiography (UGI) was performed in 103 cases, which suggested duodenal obstruction in 102 cases. Operations were performed in all cases, of which 69 cases were operated under laparoscopy including 1 case converted to open laparotomy. The mean fasting time after surgery was (7.8±2.7) d, and the mean length of hospital stay was (16.9±10.1) d. Five patients had postoperative complications. The incidence of postoperative complications in antenatal abnormal group was lower than that in the antenatal non-abnormal group (P<0.05); the average fasting time in laparoendscopic surgery group was shorter than that in traditional laparotomy group (P<0.05). CONCLUSIONS: Neonates with recurrent vomiting early after birth should be highly suspected to have annular pancreas. The fetal chromosome examination should be performed with abnormal antenatal screening. Surgery is the only effective way to diagnose and treat annular pancreas, and laparoscopic surgery could be the first choice for experienced doctors.

[Therapeutic experience of type â ¢-b congenital intestinal atresia].

OBJECTIVE: To summarize the clinical characteristics and treatment of type Ⅲ-b congenital intestinal atresia (CIA). METHODS: The clinical data of 12 type Ⅲ-b CIA treated in the Children's Hospital of Zhejiang University School of Medicine from January 2015 to December 2017 were analyzed retrospectively. RESULTS: Of the 12 patients diagnosed as type Ⅲ-b CIA in operation, treatment was refused during operation by their parents in 2 cases. For one child, only the proximal intestine was partly resected in the first operation, dilatation and dysplasia of the duodenum was diagnosed and total duodenum was resected and sutured in the second operation, as the child had postoperative intestinal obstruction. For one child, due to the long distal normal intestine, distal apple-peel like intestine was partly resected without mesenteric reformation. For the rest 8 children total duodenum resection and mesenteric reformation were performed. During the postoperative follow-up, one case was early rejected for further treatment by parents, one case died from complex congenital heart disease, 5 cases had the complication of short bowel syndrome. All 8 survival children received parenteral nutrition support after operation, 5 of whom received parenteral nutrition support for more than 42 days, and they were followed up for 1-3 years after discharge. The short-time efficacy was satisfactory. CONCLUSIONS: For children with type Ⅲ-b CIA, the distal apple-peel like intestine should be preserved as much as possible, the mesenteric reformation should be performed and the proximal dilated bowel should be partly resected and sutured. Postoperative nutritional support and early intestinal rehabilitation contribute to the compensation for rest intestines.

Clinical characteristic comparison of low birth weight and very low birth weight preterm infants with neonatal necrotizing enterocolitis: a single tertiary center experience from eastern China.

PURPOSE: This study aims to understand the clinical characteristics of preterm neonatal necrotizing enterocolitis (NEC) to improve the medical management level. METHODS: The clinical characteristics of preterm NEC infants with low birth weight (LBW, ≥ 1500 g) and very low birth weight (VLBW, < 1500 g) were compared. Then, clinical information, including demographics, surgical interventions and morbidity, were collected. RESULTS: A total of 149 preterm NEC infants (60 with VLBW and 89 with LBW) were enrolled. Their median birth weight and gestational age were 1600 g and 31 weeks, respectively. Respiratory support and surfactant therapy were more frequent in VLBW infants (90% vs. 38% and 75% vs. 21.3%) than in LBW infants. In addition, 70.5% of these infants were fed by formula before the NEC occurred. Prematurity-associated morbidities were significantly higher in VLBW infants. Furthermore, 12.8% of all NEC infants died at discharge, and mortality was more prevalent in VLBW infants (21.7% vs. 6.7%). The most frequently received surgeries were enterostomy (n = 58), primary anastomosis (n = 42), and peritoneal drainage (n = 2). Multifocal, localized and pan-intestinal disease occurred in 77.5%, 19.6% and three infants, respectively. Furthermore, postoperative complications occurred more frequently in VLBW infants. CONCLUSION: The overall mortality was 12.8% for infants who had a larger mean gestational age and birth weight, when compared to that in developed countries. Higher rate of formula feeding might be an important risk factor for NEC development. Furthermore, mortality and morbidities, especially nutrition-associated complications, were more frequent in VLBW infants.

[Transumbilical single-site laparoscopic surgery for congenital duodenal obstruction in neonates].

OBJECTIVE: To evaluate the efficacy and safety of transumbilical single-site laparoscopic surgery for congenital duodenal obstruction (CDO) in neonates. METHODS: A retrospective analysis of clinical data of 15 patients with CDO undergoing transumbilical single-site laparoscopic treatment during November 2017 and January 2018 (single-site group), and 20 patients with CDO undergoing conventional three-hole laparoscopic treatment during August 2017 and October 2017 (three-hole group) was performed. All patients were from the Children's Hospital, Zhejiang University School of Medicine. The operation time, time of initial feeding, time of adequate feeding, length of hospital stay after operation and postoperative complications were compared between two groups. RESULTS: The operations were completed in all patients. No patient converted to laparotomy, and no massive hemorrhage was observed during operation. The operation time of single-site group was (90±10) min for patients with duodenal diamond-shaped anastomosis and (81±15) min for patients with Ladd operation, while those of three-hole group were (85±9) min and (72±11) min, respectively. Postoperative initial feeding time of single-site group was (5.0±1.0) d, and that of the three-hole group was (4.8±0.8) d. The adequate feeding time was (9.0±1.2) d in the single-site group, and (9.3±0.8) d in the three-hole group. The length of hospital stay after operation was (11.2±2.5) d in the single-site group, and (11.5±2.8) d in the three-hole group. There was no significant difference in operation time, postoperative initial feeding time, adequate feeding time and length of hospital stay after operation between two groups (all P>0.05). CONCLUSIONS: Transumbilical single-site laparoscopic surgery for CDO in neonates is safe and effective, and the postoperative abdominal scar is more hidden.

[Complications after laparoscopic Ladd operation for intestinal malrotation in neonates].

OBJECTIVE: To analyze complications after laparoscopic Ladd operation for intestinal malrotation, related causes and possible solutions. METHODS: Clinical data of 81 neonates who underwent laparoscopic Ladd operations for intestinal malrotation in the Children's Hospital, Zhejiang University School of Medicine between January 2015 and January 2018 were reviewed. The abdominal complications and findings during operation and reoperation were analyzed. RESULTS: Operations were successfully completed in all patients, and there was no patient converted to open surgery. The annular pancreas in 6 cases and duodenal diaphragm in 4 cases were confirmed during the operation. The recurrent volvulus developed in 3 patients (3.7%), of whom 2 cases were confirmed to have midgut necrosis during open surgery 1 week and 3 months after laparoscopic Ladd operation, and both finally died; 1 case was corrected by second laparoscopic operation. Cecal perforation occurred in 1 patient (1.2%), which was caused by intensive high frequency coagulation of the appendiceal stump. One patient (1.2%) developed chylous ascites and improved after conservative treatment. Adhesive small bowel obstruction was observed in 3 cases (3.7%), and all relieved after conservative treatment. CONCLUSIONS: Laparoscopic Ladd operation for intestinal malrotation in neonates was effective, and the incidence of abdominal complications may be minimized by experienced skills and strict perioperative management.

Splenic hamartomas in two children.

Hamartomas are extremely rare splenic benign tumours in children. We present two cases, both in boys (6 and 8 years old), with left upper quadrant abdominal pain that were otherwise asymptomatic. Both patients showed a splenic mass on preoperative ultrasonography and magnetic resonance imaging (MRI). One patient had a focal splenic mass that was identified preoperatively with contrasted computed tomography (CT) scans. Both patients underwent a total splenectomy. Although multi-modality imaging findings were described preoperatively, the final diagnosis in each case was splenic hamartoma based on histology and immunohistochemistry. The postoperative courses were uneventful.

A nomogram for predicting hemorrhagic shock in pediatric patients with multiple trauma.

The timely detection and management of hemorrhagic shock hold paramount importance in clinical practice. This study was designed to establish a nomogram that may facilitate early identification of hemorrhagic shock in pediatric patients with multiple-trauma. A retrospective study was conducted utilizing a cohort comprising 325 pediatric patients diagnosed with multiple-trauma, who received treatment at the Children's Hospital, Zhejiang University School of Medicine, Zhejiang, China. For external validation, an additional cohort of 144 patients from a children's hospital in Taizhou was included. The model's predictor selection was optimized through the application of the Least Absolute Shrinkage and Selection Operator (LASSO) regression. Subsequently, a prediction nomogram was constructed using multivariable logistic regression analysis. The performance and clinical utility of the developed model were comprehensively assessed utilizing various statistical metrics, including Harrell's Concordance Index (C-index), receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis (DCA). Multivariate logistic regression analysis identified systolic blood pressure (ΔSBP), platelet count, activated partial thromboplastin time (APTT), and injury severity score (ISS) as independent predictors for hemorrhagic shock. The nomogram constructed using these predictors demonstrated robust predictive capabilities, as evidenced by an impressive area under the curve (AUC) value of 0.963. The model's goodness-of-fit was assessed using the Hosmer-Lemeshow test (χ2 = 10.023, P = 0.209). Furthermore, decision curve analysis revealed significantly improved net benefits with the model. External validation further confirmed the reliability of the proposed predictive nomogram. This study successfully developed a nomogram for predicting the occurrence of hemorrhagic shock in pediatric patients with multiple trauma. This nomogram may serve as an accurate and effective tool for timely and efficient management of children with multiple trauma.

NLRP3 activation in macrophages promotes acute intestinal injury in neonatal necrotizing enterocolitis.

BACKGROUND: Macrophages are involved in various immune inflammatory disease conditions. This study aimed to investigate the role and mechanism of macrophages in regulating acute intestinal injury in neonatal necrotizing enterocolitis (NEC). METHODS: CD68, nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing 3 (NLRP3), cysteine aspartate-specific protease-1 (caspase-1), and interleukin-1ß (IL-1ß) in paraffin sections of intestinal tissues from NEC and control patients were detected with immunohistochemistry, immunofluorescence, and western blot. Hypertonic pet milk, hypoxia and cold stimulation were used to establish a mouse (wild type and Nlrp3-/-) model of NEC. The mouse macrophage (RAW 264.7) and rat intestinal epithelial cell-6 lines were also cultured followed by various treatments. Macrophages, intestinal epithelial cell injuries, and IL-1ß release were determined. RESULTS: Compared to the gut "healthy" patients, the intestinal lamina propria of NEC patients had high macrophage infiltration and high NLRP3, caspase-1, and IL-1ß levels. Furthermore, in vivo, the survival rate of Nlrp3-/- NEC mice was dramatically improved, the proportion of intestinal macrophages was reduced, and intestinal injury was decreased compared to those of wild-type NEC mice. NLRP3, caspase-1, and IL-1ß derived from macrophages or supernatant from cocultures of macrophages and intestinal epithelial cells also caused intestinal epithelial cell injuries. CONCLUSIONS: Macrophage activation may be essential for NEC development. NLRP3/caspase-1/IL-1ß cellular signals derived from macrophages may be the underlying mechanism of NEC development, and all these may be therapeutic targets for developing treatments for NEC.

Macrophage α7nAChR alleviates the inflammation of neonatal necrotizing enterocolitis through mTOR/NLRP3/IL-1ß pathway.

BACKGROUND: Neonatal necrotizing enterocolitis (NEC) is one of the most prevalent and severe intestinal emergencies in newborns. The inflammatory activation of macrophages is associated with the intestinal injury of NEC. The neuroimmune regulation mediated by α7 nicotinic acetylcholine receptor (α7nAChR) plays an important role in regulating macrophage activation and inflammation progression, but in NEC remains unclear. This study aims to explore the effect of macrophage α7nAChR on NEC. METHODS: Mice NEC model were conducted with high-osmolarity formula feeding, hypoxia, and cold stimulation. The α7nAChR agonist PNU-282987 and mTOR inhibitor rapamycin were treated by intraperitoneal injections in mice. The expression and distribution of macrophages, α7nAChR, and phospho-mammalian target of rapamycin (p-mTOR) in the intestines of NEC patients and mice was assessed using immunohistochemistry, immunofluorescence, and flow cytometry. The expression of NLRP3, activated caspase-1 and IL-1ß in mice intestines was detected by flow cytometry, western blot or ELISA. In vitro, the mouse RAW264.7 macrophage cell line was also cultured followed by various treatments. Expression of p-mTOR, NLRP3, activated caspase-1, and IL-1ß in macrophages was determined. RESULTS: Macrophages accumulated in the intestines and the expression of α7nAChR in the mucosal and submucosal layers of the intestines was increased in both the NEC patients and mice. The p-mTOR and CD68 were increased and co-localized in intestines of NEC patients. In vitro, α7nAChR agonist PNU-282987 significantly reduced the increase of NLRP3, activated caspase-1, and IL-1ß in macrophages. PNU-282987 also significantly reduced the increase of p-mTOR. The effect was blocked by AMPK inhibitor compound C. The expression of NLRP3, activated caspase-1, and IL-1ß was inhibited after mTOR inhibitor rapamycin treatment. In NEC model mice, PNU-282987 reduced the expression of p-mTOR, NLRP3, activated caspase-1, and IL-1ß in the intestine. Meanwhile, rapamycin significantly attenuated NLRP3 activation and the release of IL-1ß. Moreover, the proportion of intestinal macrophages and intestinal injury decreased after PNU-282987 treatment. CONCLUSION: Macrophage α7nAChR activation mitigates NLRP3 inflammasome activation by modulating mTOR phosphorylation, and subsequently alleviates intestinal inflammation and injury in NEC.

RNF31-mediated IKKα ubiquitination aggravates inflammation and intestinal injury through regulating NF-κB activation in human and mouse neonates.

AIMS: Neonatal necrotizing enterocolitis (NEC) is a leading cause of intestine inflammatory disease, and macrophage is significantly activated during NEC development. Posttranslational modifications (PTMs) of proteins, particularly ubiquitination, play critical roles in immune response. This study aimed to investigate the effects of ubiquitin-modified proteins on macrophage activation and NEC, and discover novel NEC-related inflammatory proteins. MATERIALS AND METHODS: Proteomic and ubiquitin proteomic analyses of intestinal macrophages in NEC/healthy mouse pups were carried out. In vitro macrophage inflammation model and in vivo NEC mouse model, as well as clinical human samples were used for further verification the inhibitor of nuclear factor-κB kinase α (IKKα) ubiquitination on NEC development through Western blot, immunofluorescence, quantitative real-time polymerase chain reaction (qRT-PCR) and flow cytometry. KEY FINDINGS: We report here that IKKα was a new ubiquitin-modified protein during NEC through ubiquitin proteomics, and RING finger protein 31 (RNF31) acted as an E3 ligase to be involved in IKKα degradation. Inhibition of IKKα ubiquitination and degradation with siRNF31 or proteasome inhibitor decreased nuclear factor-κB (NF-κB) activation, thereby decreasing the expression of pro-inflammatory factors and M1 macrophage polarization, resulting in reliving the severity of NEC. SIGNIFICANCE: Our study suggests the activation of RNF31-IKKα-NF-κB axis triggering NEC development and suppressing RNF31-mediated IKKα degradation may be therapeutic strategies to be developed for NEC treatment.

Common genetic variants regulating ADD3 gene expression alter biliary atresia risk.

BACKGROUND & AIMS: Biliary atresia (BA) is a rare and most severe cholestatic disease in neonates, but the pathogenic mechanisms are unknown. Through a previous genome wide association study (GWAS) on Han Chinese, we discovered association of the 10q24.2 region encompassing ADD3 and XPNPEP1 genes, which was replicated in Chinese and Thai populations. This study aims to fully characterize the genetic architecture at 10q24.2 and to reveal the link between the genetic variants and BA. METHODS: We genotyped 107 single nucleotide polymorphisms (SNPs) in 10q24.2 in 339 Han Chinese patients and 401 matched controls using Sequenom. Exhaustive follow-up studies of the association signals were performed. RESULTS: The combined BA-association p-value of the GWAS SNP (rs17095355) achieved 6.06×10(-10). Further, we revealed the common risk haplotype encompassing 5 tagging-SNPs, capturing the risk-predisposing alleles in 10q24.2 [p=5.32×10(-11); odds ratio, OR: 2.38; confidence interval, CI: (2.14-2.62)]. Through Sanger sequencing, no deleterious rare variants (RVs) residing in the risk haplotype were found, dismissing the theory of "synthetic" association. Moreover, in bioinformatics and in vivo genotype-expression investigations, the BA-associated potentially regulatory SNPs correlated with ADD3 gene expression (n=36; p=0.0030). Remarkably, the risk haplotype frequency coincides with BA incidences in the population, and, positive selection (favoring the derived alleles that arose from mutations) was evident at the ADD3 locus, suggesting a possible role for the BA-associated common variants in shaping the general population diversity. CONCLUSIONS: Common genetic variants in 10q24.2 can alter BA risk by regulating ADD3 expression levels in the liver, and may exert an effect on disease epidemiology and on the general population.

Digestive perianastomotic ulcerations after intestinal resection in children.

Digestive perianastomotic ulceration (DPAU) is a rare complication after intestinal resection and anastomosis occurring at or near the anastomosis site. The purpose of this review is to summarize the characteristics of DPAU, including the etiology, diagnosis and differential diagnosis, clinical manifestations, treatment, and future research. All recent literature on DPAU was searched in PubMed, Embase, and Cochrane and then reviewed. The clinical manifestations of DPAU are mainly gastrointestinal symptoms such as bloody stool and chronic anemia. The diagnosis of DPAU is difficult. Specific diseases, such as Crohn's disease, must be ruled out before a diagnosis can be made. In addition, there are no clear treatment guidelines due to the high degree of heterogeneity in response to drugs and surgery. It is recommended to adjust medication in time and combine various treatment methods. In addition, the mechanism that causes DPAU is not well understood; however, several possible mechanisms have been proposed, such as scar tissue ischemia and underlying diseases. Moreover, there is a high risk of relapses, and a long-term follow-up is necessary. Numerous issues remain to be solved in this area; therefore, more randomized controlled trials and studies should be carried out to further understand this disease.

Neuroimmune regulation in Hirschsprung's disease associated enterocolitis.

Neuroimmune pathways are important part of the regulation of inflammatory response. Nerve cells regulate the functions of various immune cells through neurotransmitters, and then participate in the inflammatory immune response. Hirschsprung's disease (HD) is a congenital abnormal development of intestinal neurons, and Hirschsprung-associated enterocolitis (HAEC) is a common complication, which seriously affects the quality of life and even endangers the lives of children. Neuroimmune regulation mediates the occurrence and development of enteritis, which is an important mechanism. However, there is a lack of review on the role of Neuroimmune regulation in enterocolitis associated with Hirschsprung's disease. Therefore, this paper summarizes the characteristics of the interaction between intestinal nerve cells and immune cells, reviews the neuroimmune regulation mechanism of Hirschsprung's disease associated enterocolitis (HAEC), and looks forward to the potential clinical application value.

Survey on surgical treatment of neonatal necrotizing enterocolitis in China 2022.

Objective: The aim of this study was to identify the state of surgical treatment of neonatal necrotizing enterocolitis (NEC) in China. Methods: A total of 246 delegates (88.0% senior surgeons) completed a survey sent by the Neonatal Surgery Group of the Pediatric Surgery Branch of the Chinese Medical Association in 2022. Five centers were eliminated due to lack of experience. Results: Generally, 38.2% of surgeons work in centers where more than 20 cases of surgical NEC are treated per year. A total of 81.3% of surgeons reported the use of ultrasonography; the most used biomarkers were white blood cell count (95.9%), C-reactive protein (93.8%), and procalcitonin (76.3%). Most surgeons (80.9%) used a combination of two (67.2%) antibiotics or single (29.5%) antibiotic for a treatment period of 7-14 days, and most used antibiotics were carbapenems (73.9%), penicillin and cephalosporins (56.0%). Patients are issued the fasting order for 5-7 days by nearly half surgeons (49.8%) for conservative treatment. 70.1% of surgeons deemed that the most difficult decision was to evaluate the optimal timing of surgery. Most surgeons (76.3%) performed diagnostic aspiration of peritoneal fluid. Laparoscopy was performed for the diagnosis and/or treatment of NEC by 40.2% of surgeons. A total of 53.5% of surgeons reported being able to identify localized intestinal necrosis preoperatively. Surgeons relied the most on pneumoperitoneum (94.2%) and failure of conservative treatment (88.8%) to evaluate the surgical indications. At laparotomy, surgical treatments vary according to NEC severity. Infants are fasted for 5-7 days by 55.2% of surgeons postoperatively. Most surgeons (91.7%) followed up with patients with NEC after discharge for up to 5 years (53.8%). Conclusions: The most difficult aspect of surgical NEC is evaluating the timing of surgery, and surgeons in the children's specialized hospitals are experienced. The treatment of NEC totalis is controversial, and the indications for laparoscopy need to be further clarified. More multicenter prospective studies are needed to develop surgical guidelines in the future.

Dihydromyricetin functions as a tumor suppressor in hepatoblastoma by regulating SOD1/ROS pathway.

Background: Hepatoblastoma has an unsatisfactory prognosis, and traditional chemotherapy has strong side effects. Dihydromyricetin is a flavonoid extracted from a woody vine of the genus Serpentine in the family Vitaceae, with effects such as preventing alcoholic liver and reducing the incidence of liver cancer. However, the effect of DHM on hepatoblastoma and its specific pathway are still unclear. Purpose: The purpose of this study was to investigate the effects of DHM on children's hepatoblastoma and its related mechanisms. Methods: CCK-8 assays were used to measure proliferation. Apoptosis and reactive oxygen species (ROS) were analyzed by flow cytometry. Apoptotic cells were observed using Hoechst 33342 staining and fluorescence microscopy. Protein expression levels in HuH-6 and HepG2 cells were determined by western blotting. Results: We found that DHM was able to inhibit the growth and increase cellular mortality in HuH-6 and HepG2 cells. Furthermore, DHM decreased the intracellular ROS level and increased the expression of SOD1. ROS scavenger NAC promoted apoptosis, while the use of SOD1 inhibitor LCS-1 weakened the ROS scavenging effect of DHM , and to some extent reduced the killing effect of DHM on hepatoblastoma cells. Conclusion: These results suggest that regulating SOD1/ROS pathway to induce apoptosis is one of the potential mechanisms of DHM as a tumor suppressor in hepatoblastoma. Therefore, DHM may be a novel candidate for inhibiting hepatoblastoma growth and deserves further study.

Bioinformatical analysis of the key differentially expressed genes for screening potential biomarkers in Wilms tumor.

Wilms tumor (WT) is the most common pediatric renal malignant tumor in the world. Overall, the prognosis of Wilms tumor is very good. However, the prognosis of patients with anaplastic tumor histology or disease relapse is still poor, and their recurrence rate, metastasis rate and mortality are significantly increased compared with others. Currently, the combination of histopathological examination and molecular biology is essential to predict prognosis and guide the treatment. However, the molecular mechanism has not been well studied. Genetic profiling may be helpful in some way. Hence, we sought to identify novel promising biomarkers of WT by integrating bioinformatics analysis and to identify genes associated with the pathogenesis of WT. In the presented study, the NCBI Gene Expression Omnibus was used to download two datasets of gene expression profiles related to WT patients for the purpose of detecting overlapped differentially expressed genes (DEGs). The DEGs were then uploaded to DAVID database for enrichment analysis. In addition, the functional interactions between proteins were evaluated by simulating the protein-protein interaction (PPI) network of DEGs. The impact of selected hub genes on survival in WT patients was analyzed by using the online tool R2: Genomics Analysis and Visualization Platform. The correlation between gene expression and the degree of immune infiltration was assessed by the Estimation of Stromal and Immune cells in Malignant Tumor tissues using the Expression (ESTIMATE) algorithm and the single sample GSEA. Top 12 genes were identified for further study after constructing a PPI network and screening hub gene modules. Kinesin family member 2C (KIF2C) was identified as the most significant gene predicting the overall survival of WT patients. The expression of KIF2C in WT was further verified by quantitative real-time polymerase chain reaction and immunohistochemistry. Furthermore, we found that KIF2C was significantly correlated with immune cell infiltration in WT. Our present study demonstrated that altered expression of KIF2C may be involved in WT and serve as a potential prognostic biomarker for WT patients.