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.

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.

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.

Accurate prediction of biliary atresia with an integrated model using MMP-7 levels and bile acids.

BACKGROUND: Biliary atresia (BA) is a rare fatal liver disease in children, and the aim of this study was to develop a method to diagnose BA early. METHODS: We determined serum levels of matrix metalloproteinase-7 (MMP-7), the results of 13 liver tests, and the levels of 20 bile acids, and integrated computational models were constructed to diagnose BA. RESULTS: Our findings demonstrated that MMP-7 expression levels, as well as the results of four liver tests and levels of ten bile acids, were significantly different between 86 BA and 59 non-BA patients (P < 0.05). The computational prediction model revealed that MMP-7 levels alone had a higher predictive accuracy [area under the receiver operating characteristic curve (AUC) = 0.966, 95% confidence interval (CI): 0.942, 0.989] than liver test results and bile acid levels. The AUC was 0.890 (95% CI 0.837, 0.943) for liver test results and 0.825 (95% CI 0.758, 0.892) for bile acid levels. Furthermore, bile levels had a higher contribution to enhancing the predictive accuracy of MMP-7 levels (AUC = 0.976, 95% CI 0.953, 1.000) than liver test results. The AUC was 0.983 (95% CI 0.962, 1.000) for MMP-7 levels combined with liver test results and bile acid levels. In addition, we found that MMP-7 levels were highly correlated with gamma-glutamyl transferase levels and the liver fibrosis score. CONCLUSION: The innovative integrated models based on a large number of indicators provide a noninvasive and cost-effective approach for accurately diagnosing BA in children. Video Abstract (MP4 142103 KB).

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.

Severity assessment to guide empiric antibiotic therapy for cholangitis in children after Kasai portoenterostomy: a multicenter prospective randomized control trial in China.

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

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.

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.

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.

A Nomogram for Predicting Surgical Timing in Neonates with Necrotizing Enterocolitis.

OBJECTIVE: To explore the surgical risk variables in patients with necrotizing enterocolitis (NEC) and develop a nomogram model for predicting the surgical intervention timing of NEC. METHODS: Infants diagnosed with NEC were enrolled in our study. We gathered information from clinical data, laboratory examinations, and radiological manifestations. Using LASSO (least absolute shrinkage and selection operator) regression analysis and multivariate logistic regression analysis, a clinical prediction model based on the logistic nomogram was developed. The performance of the nomogram model was evaluated using the receiver operating characteristic (ROC) curve, calibration curves, and decision curve analysis (DCA). RESULTS: A surgical intervention risk nomogram based on hypothermia, absent bowel sounds, WBC > 20 × 109/L or < 5 × 109/L, CRP > 50 mg/L, pneumatosis intestinalis, and ascites was practical, had a moderate predictive value (AUC > 0.8), improved calibration, and enhanced clinical benefit. CONCLUSIONS: This simple and reliable clinical prediction nomogram model can help physicians evaluate children with NEC in a fast and effective manner, enabling the early identification and diagnosis of children at risk for surgery. It offers clinical revolutionary value for the development of medical or surgical treatment plans for children with NEC.

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.

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.

Expression and possible role of Smad3 in postnecrotizing enterocolitis stricture.

Objective: To investigate the expression of Smad3 (mothers against decapentaplegic homolog 3) protein in postnecrotizing enterocolitis stricture and its possible mechanism of action. Methods: We used immunohistochemistry to detect the expression characteristics of Smad3 and nuclear factor kappa B (NF-κB) proteins in human postnecrotizing enterocolitis stricture. We cultured IEC-6 (crypt epithelial cells of rat small intestine) in vitro and inhibited the expression of Smad3 using siRNA technique. Quantitative PCR, western blotting, and ELISA were used to detect the changes in transforming growth factor-ß1 (TGF-ß1), NF-κB, tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and zonula occludens-1 (ZO-1) messenger RNA (mRNA) and protein expressions in IEC-6 cells. CCK8 kit and Transwell cellular migration were used to detect cell proliferation and migration. Changes in epithelial-mesenchymal transition (EMT) markers (E-cadherin and vimentin) in IEC-6 cells were detected by immunofluorescence technique. Results: The results showed that Smad3 protein and NF-κB protein were overexpressed in narrow intestinal tissues and that Smad3 protein expression was positively correlated with NF-κB protein expression. After inhibiting the expression of Smad3 in IEC-6 cells, the mRNA expressions of NF-κB, TGF-ß1, ZO-1, and VEGF decreased, whereas the mRNA expression of TNF-α did not significantly change. TGF-ß1, NF-κB, and TNF-α protein expressions in IEC-6 cells decreased, whereas ZO-1 and intracellular VEGF protein expressions increased. IEC-6 cell proliferation and migration capacity decreased. There was no significant change in protein expression levels of EMT markers E-cadherin and vimentin and also extracellular VEGF protein expression. Conclusions: We suspect that the high expression of Smad3 protein in postnecrotizing enterocolitis stricture may promote the occurrence and development of secondary intestinal stenosis. The mechanism may be related to the regulation of TGF-ß1, NF-κB, TNF-α, ZO-1, and VEGF mRNA and protein expression. This may also be related to the ability of Smad3 to promote epithelial cell proliferation and migration.

Application and prospects of robotic surgery in children: a scoping review.

As an innovative minimally invasive surgical technology, robot-assisted surgery (RAS) has greatly improved the accuracy and safety of surgery through the advantages of three-dimensional magnification, tremor filtering, precision and flexibility, and has been carried out by an increasing number of surgeries. In recent years, robots have been gradually applied to children, bringing new ideas and challenges to pediatric surgeons. This review will describe the advantages and limitations of robotic surgery in children, summarize its application in pediatric surgery, and provide an outlook. It is believed that clinicians should actively carry out RAS under the premise of rigorously ensuring surgical indications and strive to improve the efficacy of surgical treatment for children.

The role and mechanisms of miRNA in neonatal necrotizing enterocolitis.

Neonatal necrotizing enterocolitis (NEC), the most significant causes of neonatal mortality, is a disease of acute intestinal inflammation. At present, it is not clear exactly how the disease is caused, but it has been suggested that this disorder is a result of a complex interaction among prematurity, enteral feeding and inappropriate pro-inflammation response and bacterial infection of the intestine. A microRNA (miRNA) is a class of endogenous non-coding single-stranded RNA that is about 23 nucleotides long engaging in the regulation of the gene expression. Recently, numerous studies have determined that abnormal miRNA expression plays important roles in various diseases, including NEC. Here, we summarized the role of miRNAs in NEC. We introduce the biosynthetic and function of miRNAs and then describe the possible mechanisms of miRNAs in the initiation and development of NEC, including their influence on the intestinal epithelial barrier's function and regulation of the inflammatory process. Finally, this review aids in a comprehensive understanding of the current miRNA to accurately predict the diagnosis of NEC and provide ideas to find potential therapeutic targets of miRNA for NEC. In conclusion, our aims are to highlight the close relationship between miRNAs and NEC and to summarize the practical value of developing diagnostic biomarkers and potential therapeutic targets of NEC.

Case Report: Novel JAG1 gene mutations in two infants with alagille syndrome characterized by cholestasis.

Background: Infants with Alagille syndrome (ALGS) need to be promptly differentiated from biliary atresia (BA) at an early stage. ALGS is an autosomal, dominant, multisystem disorder with variable phenotypic penetrance caused by heterozygous mutations in JAG1 or NOTCH2, which encode the Notch signaling pathway. Case presentation: We report two cases, both with cholestatic jaundice as the main manifestation, in which BA was excluded and finally diagnosed as ALGS based on characteristic facial features, serological tests, imaging, laparoscopic cholangiography, pathology and genetic findings. Both cases are novel mutant genes on chromosome 20 that have not been reported in the literature. The mutation in patient 1 was a novel heterozygous nonsense mutation (NM_000214 exon20, c.2419G > T, p.E807Ter), which was a spontaneous mutation. Followed up to 1 year and 6 months, the symptoms resolved with ursodeoxycholic acid and cholestyramine, and the jaundice has now subsided. Patient 2 was a novel heterozygous frameshift mutation (NM_000214 exon19, c.2367-2368dupTC, p.P790Lfs*31), which was inherited from his mother. This patient was followed up to 9 months and is currently awaiting liver transplantation. Conclusion: Both cholestatic infants reported combined to exclude BA, avoid Kasai portoenterostomy (KPE), and definitively diagnose ALGS. Broadening the spectrum of JAG1 gene mutations.

Meconium Peritonitis, Intestinal Atresia Combined With Biliary Atresia: A Case Report.

Meconium peritonitis (MP) combined with intestinal atresia (IA) is a rare neonatal condition, and it is even rarer in combination with biliary atresia (BA). We describe a case of an infant who developed short bowel syndrome after partial intestinal resection due to MP and IA, along with a Santullienterostomy. During continuous enteral and parenteral nutrition, the stool color became paler. BA was identified by elevated direct bilirubin (DBIL), gamma-glutamyltransferase (GGT), serum matrix metalloproteinase-7 (MMP-7), and hepatobiliary ultrasound; then, Kasai portoenterostomy (KPE) was performed promptly. The Roux-en-Y limb was adjusted intraoperatively to preserve the maximum length of the small intestine while closing the enterostomy. After the operation, the infant gradually adapted to enteral nutrition, his bilirubin level returned to normal, and his weight gradually caught up to the normal range. Although rare, BA should be suspected when MP is combined with IA and when the stool becomes paler in color in the enterostomy state.