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

Genetic variants in RET and risk of Hirschsprung's disease in Southeastern Chinese: a haplotype-based analysis

<p>Abstract</p> <p>Background</p> <p>Hirschsprung's disease (HSCR) is a classic oligogenic disorder. Except inactivating mutations of RET, some single nucleotide polymorphisms (SNPs) are identified to be associated with the risk of HSCR. This study was conducted to examine the impact of the haplotypes profile of the reported associated SNPs of RET on the risk of HSCR in a Southeastern Chinese population.</p> <p>Methods</p> <p>Genotypes of -5G > A (rs10900296), -1A > C (rs10900297), c135G > A (rs1800858), c1296A > G (rs1800860), and c2307T > G (rs1800861) were analyzed in 123 HSCR patients and 168 controls by polymerase chain reaction amplification and direct sequencing. Associations with risk of HSCR were estimated by odds ratio (OR) and their 95% confidence intervals (95% CI) using logistic regression.</p> <p>Results</p> <p>We observed a significantly increased risk of HSCR associated with the RET -5AA (OR = 17.75, 95% CI = 7.34-42.92), -1CC (OR = 10.89, 95% CI = 3.13-37.85), 135AA (OR = 13.61, 95% CI = 6.14-30.14), 1296GG (OR = 2.40, 95% CI = 1.38-4.18) or 2307GG (OR = 9.79, 95% CI = 4.28-22.43) respectively. The five SNPs were in strong linkage disequilibrium. The haplotype A-C-A-G-G (OR = 5.06, 95% CI = 1.97-12.99) and diplotype A-C-A-G-G/A-C-A-G-G (OR = 21.08, 95% CI = 5.28-84.09) was also associated with the increased risk of HSCR, indicating a cumulative effect of these SNPs on the susceptibility of HSCR.</p> <p>Conclusion</p> <p>These results support the hypothesis that common variations in RET pathway might play an important role in development of HSCR.</p

An improved joint non-negative matrix factorization for identifying surgical treatment timing of neonatal necrotizing enterocolitis

Neonatal necrotizing enterocolitis is a severe neonatal intestinal disease. Timely identification of surgical indications is essential for newborns in order to seek the best time for treatment and improve prognosis. This paper attempts to establish an algorithm model based on multimodal clinical data to determine the features of surgical indications and construct an auxiliary diagnosis model. The proposed algorithm adds hypergraph constraints on the two modal data based on Joint Nonnegative Matrix Factorization (JNMF), aiming to mine the higher-order correlations of the two data features. In addition, the adjacency matrix of the two kinds of data is used as a network regularization constraint to prevent overfitting. Orthogonal and L1-norm regulations were introduced to avoid feature redundancy and perform feature selection, respectively, and confirmed 14 clinical features. Finally, we used three classifiers, random forest, support vector machine, and logistic regression, to perform binary classification of patients requiring surgery. The results show that when the features selected by the proposed algorithm model are classified by random forest, the area under the ROC curve is 0.8, which has high prediction accuracy

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

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

Abstract 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

The role of the 5-hydroxytryptamine pathway in reflux-induced esophageal mucosal injury in rats

<p>Abstract</p> <p>Background</p> <p>Dysfunction of the 5-hydroxytryptamine (5-HT) signaling pathway can lead to gastrointestinal motility and secretion abnormalities and to visceral hypersensitivity. The aim of this study is to investigate the role of 5-HT in reflux-induced esophageal mucosal injury.</p> <p>Methods</p> <p>Fifty 8-week-old male Sprague-Dawley (SD) rats were randomly divided into a gastroesophageal reflux (GER) model group (30 rats) and a sham surgery control group (20 rats). Four weeks after surgery, the esophageal mucosa was collected for histological evaluation, 5-HT concentrations, and 5-HT selective reuptake transporter (SERT) mRNA and 5-HT₄ receptor (5-HT₄R) protein expressions.</p> <p>Results</p> <p>Twenty-seven rats in the GER model group survived, and three rats died. Histologically, in the GER model group, 20 rats had reflux esophagitis (RE group), and 7 rats had non-erosive reflux disease (NERD group). The 5-HT levels in the esophageal tissue from the RE group were significantly higher than those from the control and NERD groups. Both the RE and NERD groups showed significant increases in SERT mRNA expression of the esophageal mucosa than that of the controls, and the SERT mRNA level in the RE group was significantly higher than that in the NERD group. The 5-HT₄R protein level of the esophageal mucosa in the RE group was significantly lower than that in the controls and the NERD group.</p> <p>Conclusions</p> <p>We conclude that a 5-HT signaling pathway disorder could be a major factor in the pathogenesis of GER and RE.</p

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

Abstract 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