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Pyroptosis is a kind of programmed cell death accompanied by inflammatory responses, which is mainly induced by the Caspase-1/4/5/11 activated mediated via inflammasomes or lipopolysaccharide.Pyroptosis causes the cleavage of various Gasdermin family members, including Gasdermin D, in which a large number of pro-inflammatory factors are released to cause inflammatory responses in various diseases.At present, pyroptosis has not been extensively analyzed in pediatric surgical diseases.This review summarizes the research progress of pyroptosis in pediatric surgical diseases like Hirschsprung′s disease, biliary atresia, neonatal necrotizing enterocolitis, and tumors.It is found that pyroptosis is involved in the occurrence and development of pediatric surgical diseases.The research on the specific mechanism of pyroptosis in pediatric surgical disease and involved signaling pathways contributes to the early diagnosis and treatment of some pediatric surgical diseases.
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Objective:To evaluate the diagnostic value of intestinal regional oxygen saturation（rSO 2）and fecal calprotectin in the occurrence and severity of necrotizing enterocolitis（NEC）in premature infants. Methods:A prospective observational study was conducted among premature infants admitted to Quanzhou Children's Hospital from October 2019 to December 2022. Intestinal rSO 2 was monitored within two hours of diagnosis of NEC，and fecal calprotectin was measured. Results:A total of 60 patients were included, including 30 cases with NEC and 30 cases without NEC, 14 cases of medical NEC, 16 cases of surgical NEC, and eight infants died due to NEC. Infants with NEC had lower intestinal rSO 2 [49（30，60）% vs. 66（60，69）%] and higher calprotectin levels [479（297，886）μg/g vs. 203（113，275）μg/g] than those in infants without NEC ( P<0.01). The levels of intestinal rSO 2 were lower in surgical NEC than those in medical NEC，and were lower in the death group than that in the survival group ( P<0.01)，but no similar difference was found in the levels of calprotectin. ROC curve analysis showed that intestinal rSO 2 combined with calprotectin had a sensitivity of 73%，a specificity of 100%，and the largest area under curve of 0.91 in the diagnosis of NEC. Intestinal rSO 2 had an optimal cut-off value of 31% in predicting death in infants with NEC，with a sensitivity of 100%，a specificity of 95%，and an area under curve of 0.99. Conclusion:Intestinal rSO 2 and fecal calprotectin can effectively identify the presence of NEC，and their combined detection can improve the diagnostic efficiency. Intestinal rSO 2 is a good predictor of the severity of NEC，but not fecal calprotectin.
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Objective:To determine the predictive value of high-frequency ultrasonography for necrotizing enterocolitis (NEC) requiring surgical treatment in neonates.Methods:From January 2018 to December 2021, neonates diagnosed with NEC (Bell stage Ⅱ and above) in our hospital were retrospectively analyzed. The neonates were assigned into surgical group and non-surgical group according to the treatment. The following ultrasonography results were compared between the two groups: intestinal motility, gastrointestinal (GI) wall perfusion, pneumatosis intestinalis (PI), portal vein gas, peritoneal effusion translucency, depth of ascites fluid and GI wall thickness. Logistic regression was used to determine risk factors of surgical treatment for NEC. ROC curve was drawn to calculate the predictive value of combined and individual factors for NEC requiring surgical treatment.Results:A total of 40 neonates were enrolled, including 18 in the surgical group and 22 in the non-surgical group. No significant differences existed between the two groups in PI and depth of ascites fluid ( P>0.05). The surgical group had higher incidences of decreased intestinal motility, portal vein gas, reduced GI wall perfusion, poor peritoneal effusion translucency and thinner GI wall than the non-surgical group (all P<0.05). Logistic regression analysis showed that poor translucency of peritoneal effusion, thinning of GI wall, reduced GI wall perfusion and decreased intestinal motility were risk factors for surgical treatment of NEC. ROC curve showed that the cut-off value predicting surgical treatment based on GI wall thickness was 1.2 mm, with an area under the curve (AUC) of 0.746, sensitivity of 87.5% and specificity of 65.6%. The AUC of the combined factors predicting surgical treatment was 0.867, with sensitivity of 96.9% and specificity of 75.8%. Conclusions:Decreased intestinal motility and GI wall perfusion, thinning of GI wall and poor peritoneal effusion translucency on high-frequency ultrasonography have high predictive efficacy for the need of surgical treatment in the acute phase of NEC.
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Objective:To study the effects of endoplasmic reticulum stress (ERS) and autophagy mechanisms in the pathogenesis of necrotizing enterocolitis (NEC).Methods:A total of 39 newborn SD rats were randomly assigned into 3 groups: the NEC group (NEC model: artificial feeding+hypoxic stimulation+intragastric injection of lipopolysaccharides), the ERS antagonist group (NEC model+intraperitoneal injection of 4-phenylbutyric acid) and the ERS inducer group (NEC model+intraperitoneal injection of tunicamycin). After successful modeling, the rats were sacrificed and intestinal tissues were obtained. The intestinal pathology was observed using electronic microscope. Intestinal fatty acid binding protein (I-FABP) was detected using ELISA. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to examine mRNA levels of glucose-regulated protein 78 (GRP78) and oxygen-regulated protein 150 (ORP150). Western-blot was used to detect p62 and autophagy-related proteins (microtubule-associated protein 1 light chain 3 (LC3)Ⅱ and LC3Ⅰ) and LC3Ⅱ/LC3Ⅰ ratio was calculated.Results:(1) For all 3 groups, the pathological scores of rat intestines were≥2. (2) The ERS inducer group showed significantly higher clinical score, pathological score, I-FABP level, GRP78 and ORP150 mRNA levels and LC3Ⅱ/ LC3Ⅰ ratio than the NEC group and ERS antagonist group, and the NEC group higher than the ERS antagonist group ( P<0.05). The p62 level in the ERS inducer group was significantly lower than the NEC group and the ERS antagonist group, and the NEC group lower than the ERS antagonist group ( P<0.05). (3) The LC3Ⅱ/ LC3Ⅰ ratio was positively correlated with clinical score, pathological score and I-FABP level ( P<0.05). The p62 level was negatively correlated with clinical score, pathological score and I-FABP level ( P<0.05). The mRNA levels of GRP78 and ORP150 were positively correlated with clinical score, pathological score and I-FABP level ( P<0.05). LC3Ⅱ/ LC3Ⅰ ratio was positively correlated with the mRNA levels of GRP78 and ORP150 ( P<0.05). The p62 level was negatively correlated with the mRNA levels of GRP78 and ORP150 ( P<0.05). Conclusions:ERS is associated with the pathogenesis of NEC. Inhibition of ERS can reduce autophagy and improve intestinal barrier function and clinical symptoms of NEC.
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Objective:To construct prediction models of necrotizing enterocolitis (NEC) using machine learning (ML) methods.Methods:From January 2015 to October 2021, neonates with suspected NEC symptoms receiving abdominal ultrasound examinations in our hospital were retrospectively analyzed. The neonates were assigned into NEC group (modified Bell's staging≥Ⅱ) and non-NEC group for diagnostic prediction analysis (dataset 1). The NEC group was subgrouped into surgical NEC group (staging≥Ⅲ) and conservative NEC group for severity analysis (dataset 2). Feature selection algorithms including extremely randomized trees, elastic net and recursive feature elimination were used to screen all variables. The diagnostic and severity prediction models for NEC were established using logistic regression, support vector machine (SVM), random forest, light gradient boosting machine and other ML methods. The performances of different models were evaluated using area under the receiver operating characteristic curve (AUC), sensitivity, specificity, negative predictive value and positive predictive value.Results:A total of 536 neonates were enrolled, including 234 in the NEC group and 302 in the non-NEC group (dataset 1).70 were in the surgical NEC group and 164 in the conservative NEC group (dataset 2). The variables selected by extremely randomized trees showed the best predictive performance in two datasets. For diagnostic prediction models, the SVM model had the best predictive performance, with AUC of 0.932 (95% CI 0.891-0.973) and accuracy of 0.844 (95% CI 0.793-0.895). A total of 11 predictive variables were determined, including portal venous gas, intestinal dilation, neutrophil percentage and absolute monocyte count at the onset of illness. For NEC severity prediction models, the SVM model showed the best predictive performance, with AUC of 0.835 (95% CI 0.737-0.933) and accuracy of 0.787 (95% CI 0.703-0.871). A total of 25 predictive variables were identified, including age of onset, C-reactive protein and absolute neutrophil count at clincial onset. Conclusions:NEC prediction model established using feature selection algorithm and SVM classification model in ML is helpful for the diagnosis of NEC and grading of disease severity.
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Objective:To study the clinical characteristics and risk factors of necrotizing enterocolitis (NEC) in one of the premature twins.Methods:A retrospective study was conducted on twin premature infants who were admitted to the Department of Neonatology at the Third Affiliated Hospital of Zhengzhou University from January 2017 to December 2022 and only one got NEC. The twins were divided into NEC group and control group, the clinical data were collected and analyzed by SPSS 26.0 statistical software.Results:This study enrolled 109 pairs of premature twins, 109 cases in the NEC group, and 109 cases in the control group. Univariate analysis showed that birth weight, pre NEC white blood cell count were lower in NEC group than those in the control group, while the proportion of smaller than gestational age (SGA), donor of twin-to-twin transfusion syndrome, feeding intolerance, incomplete enteral feeding, start feeding time >48 h, red blood cell transfusion 72 h before NEC onset and the neutrophils ratio were higher in the NEC group than that of the control group, the difference was statistically significant ( P<0.05). Multivariate logistic analysis showed that low birth weight ( OR=1.558, 95% CI1.197-2.142), SGA ( OR=1.721, 95% CI 1.217-2.536), feeding intolerance ( OR=3.798, 95% CI 1.347-10.706), and incomplete enteral feeding ( OR=4.319, 95% CI 1.673-11.149) were independent risk factors for NEC ( P<0.05). Conclusions:Low birth weight, small for gestational age, feeding intolerance, and incomplete enteral feeding are independent risk factors for NEC in one of the premature twins.
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Objective To investigate the effect of inhibiting autophagy induced by endoplasmic reticulum stress(ERS)on necrotiz-ing enterocolitis(NEC)in neonatal rats.Methods First,the NEC model of neonatal rats was established.Then,the intestinal epitheli-al cells were isolated and divided into three groups:control group,inhibition group and induction group.The control group was cultured normally,the inhibition group was added with 4-phenylbutyric acid,and the induction group was added with tunicamycin for 24hours.Enzyme-linked immunosorbent assay(ELISA)was used to detect the expression of the cellular inflammatory cytokines tumor necrosis factor-α(TNF-α)and intestinal fatty acid binding protein(I-FABP)in each group.Real-time quantitative polymerase chain reac-tion(RT-qPCR)was used to detect the mRNA expression level of the markers of ERS glucose regulated protein 78(GRP78)and oxy-gen-regulated protein 150(ORP150).Western blot was used to detect the expression of autophagy related proteins LC3 Ⅱ/Ⅰ and p62.Results Compared with the control group,the expression of p62 in the inhibition group increased significantly,the expression of TNF-α,I-FABP,GRP78,ORP150,LC3 Ⅱ/Ⅰ in the inhibition group was significantly decreased,while the expression of p62 in the induc-tion group was significantly decreased,the expressions of TNF-α,Ⅰ-FABP,GRP78,ORP150,LC3 Ⅱ/Ⅰ were significantly increased,and the differences were statistically significant(P＜0.05).Conclusion Inhibition of ERS induced autophagy activation can alleviate intestinal mucosal injury and inflammatory response in neonatal rats with NEC and improve intestinal barrier function.
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Early/late onset sepsis(EOS/LOS)and necrotizing enterocolitis(NEC)are common diseases during the neonatal period,with poor prognosis in severe cases.The early clinical manifestations are not specific,the diag-nosis is difficult,currently-used non-specific laboratory tests(C-reactive protein,procalcitonin,etc.)have disad-vantages,which may lead to missed diagnosis or misdiagnosis.Serum amyloid A(SAA)is a novel acute phase re-actant that increases significantly in the early stage of EOS/LOS and NEC,and lasts for a long time,it is related to the severity of the disease and can reflect the therapeutic effect,thus it can be used as a biomarker for diagnosis and treatment of these two diseases.This paper reviews SA A and its value in the early diagnosis of EOS/LOS and NEC,providing new references for the diagnosis and treatment of such diseases.
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ABSTRACT Objective: To describe the long-term health outcomes of neonates affected by necrotizing enterocolitis (NEC) and its implications for quality of life. Data source: This is an integrative review, conducted by searching the literature in the following databases: Virtual Health Library (BVS), Latin American and Caribbean Health Sciences Literature (LILACS), Medical Literature Analysis and Retrieval System Online (MEDLINE), and PubMed, using Health Sciences Descriptors (DeCS): "necrotizing enterocolitis," "quality of life," and "prognosis" combined with the Boolean operators AND and OR: "quality of life" OR "prognosis." Inclusion criteria were: publication period between 2012 and 2022. Data synthesis: A total of 1,010 studies were located, of which ten were selected to comprise the bibliographic sample of this review. Children with NEC are prone to exhibit cognitive neurological impairment, especially those who undergo surgical procedures due to more severe conditions. Motor development was considered below average when compared to healthy children, with more noticeable delays in fine and gross motor function development. The search for the relationship between NEC and quality of life revealed that this condition has a negative impact on the well-being of affected individuals. Conclusions: NEC has proven to be a serious condition contributing to high rates of morbidity and mortality in newborns, potentially leading to a reduction in the quality of life of affected patients.
RESUMO Objetivo: Descrever os desfechos em longo prazo na saúde de neonatos acometidos com enterocolite necrosante (ECN) e suas repercussões na qualidade de vida. Fontes de dados: Trata-se de uma revisão integrativa, realizada com base no levantamento da bibliografia nas bases de dados: Biblioteca Virtual em Saúde (BVS), Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs), Medical Literature Analysis and Retrieval System Online (Medline) e PubMed por meio dos Descritores em Ciências da Saúde (DeCS): "necrotizing enterocolitis", "quality of life" e "prognosis" combinados com os operadores booleanos AND e OR: "quality of life" OR "prognosis". Os critérios de inclusão foram: período de publicação entre 2012 e 2022; Síntese dos dados: Foram localizados 1.010 estudos, dos quais dez foram selecionados para compor a amostra bibliográfica desta revisão. As crianças com ECN são propensas a apresentar comprometimento neurológico cognitivo, principalmente aquelas submetidas a procedimentos cirúrgicos em razão de quadros mais graves. O desenvolvimento motor foi considerado abaixo da média se comparado ao de crianças saudáveis, com atraso mais perceptível no desenvolvimento de funções motoras finas e grossas. A busca pela relação entre enterocolite necrosante e qualidade vida trouxe como resultado que essa condição tem impacto negativo sobre o bem-estar dos indivíduos acometidos. Conclusões: A enterocolite necrosante mostrou-se como uma condição grave que contribui para altas taxas de morbimortalidade em recém-nascidos, sendo uma potencial causa para a redução da qualidade de vida dos pacientes acometidos.
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Introdução:A enterocolite necrosante é uma doença que pode afetar o trato gastrointestinal de recém-nascidos,cujas manifestações clínicas podem ser caracterizadas por vômitos biliosos, sangue nas fezes, distensão abdominal, além de alterações nos parâmetros hemodinâmicos e instabilidade térmica. As populações mais vulneráveis a essa enfermidade são recém-nascidos de baixo peso,expostos ao ambiente de terapia intensiva neonatal. Objetivos: Identificar o perfil de recém-nascidos e os fatores maternos e neonatais associados à ocorrência de óbitos por enterocolite necrosante, em maternidade de referência do Ceará-Brasil. Metodologia: Trata-se de coorte retrospectiva, estudo que objetiva a descrição da incidência de determinado evento ao longo do tempo, além do estabelecimento de relações causais entre os fatores associados ao acontecimento. Incluíram-serecém-nascidos que tiveram óbitos por enterocolite necrosante entre 2019 e 2021, comficha de investigação de óbitos neonatais preenchida corretamente, não sendo excluído nenhum recém-nascido, totalizando amostra de 29 óbitos.Resultados: Identificou-se que o perfil dos recém-nascidos foi,em maioria, deprematuros e com baixo peso e fatores de risco para outras doenças associadas,como a sepse, o que acarretourealização de procedimentos invasivos e internação em ambiente de terapia intensiva neonatal.Conclusões: A prematuridade e o baixo peso ao nascer foram as variáveis relevantes no estudo e podem estar associadas à piora das condições clínicas do recém-nascido e ao desenvolvimento de enterocolite necrosante (AU).
Introduction: Necrotizing Enterocolitis is a disease that can affect the gastrointestinal tract of newborns, whose clinical manifestations can be characterized by bilious vomiting, blood in stool, abdominal distension, in addition to changes in hemodynamic parameters and thermal instability. The populations most vulnerable to this disease are low birth weight newborns exposed to the neonatal intensive care environment. Objectives: This study aimed to identify the profile of newborns and maternal and neonatal factors associated with the occurrence of deaths from necrotizing enterocolitis in a reference maternity hospital in Ceará, Brazil. Methodology: This is a retrospective cohort study seeking to describe the incidence ofa particular event over time, as well as establish causal relationships between the factors associated with the event. The study population comprised newborns who died from necrotizing enterocolitis between 2019 and 2021, who had neonatal death investigation forms filled out correctly, with no newborns being excluded, totaling a sample of 29 deaths. Results: It was identified that the profile of newborns was mostly premature, of low birth weight and with risk factors for other associated diseases such as sepsis, leading to invasive procedures and hospitalization in a neonatal intensive care environment. Conclusions: Prematurity and low birth weight were relevant variables in the study and may be associated with worsening of the newborn's clinical conditionsand development of necrotizing enterocolitis (AU).
ntroducción:La Enterocolitis Necrotizante es enfermedad que puede afectar el tracto gastrointestinal del recién nacido, cuyas manifestaciones clínicas pueden caracterizarse por vómitos biliosos, sangre en las heces, distensión abdominal, además de cambios en los parámetros hemodinámicos e inestabilidad térmica.Las poblaciones más vulnerables a esta enfermedad son recién nacidos con bajo peso expuestos al entorno de cuidados intensivos neonatales.Objetivos: Identificar el perfil de recién nacidos y los factores maternos y neonatales asociados a la ocurrencia de muertes por enterocolitis necrotizante, en maternidad de referencia en el Ceará-Brasil.Metodología: Estudio de cohorte retrospectivo, para describir la incidencia de determinado evento a lo largo del tiempo, además de establecer relaciones causales entre los factores asociados al evento.Se incluyeron recién nacidos fallecidos por enterocolitis necrotizante entre 2019 y 2021, quienes tuvieron formulario de investigación de muerte neonatal correctamente diligenciado, no excluyéndose ningún recién nacido, totalizando muestra de 29 defunciones.Resultados:El perfil de los recién nacidos fue mayoritariamente prematuro y de bajo peso al nacer y con factores de riesgo para otras enfermedades asociadas, como sepsis, con procedimientos invasivos y hospitalización en ambiente de cuidados intensivosneonatales.Conclusiones:La prematuridad y el bajo peso al nacer fueron variables relevantes en el estudio y pueden estar asociados con empeoramiento de las condiciones clínicas de recién nacidos y desarrollo de enterocolitis necrotizante (AU).