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Nicotinamide adenine dinucleotide treatment confers resistance to neonatal ischemia and hypoxia:effects on neurobehavioral phenotypes

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Neural Regeneration Research 2024年第12期19卷 2760-2772页

作者： Xiaowen Xu Xinxin Wang Li Zhang Yiming Jin Lili Li Meifang Jin Lianyong Li Hong Ni Division of Brain science Institute of Pediatric ResearchChildren’s Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina department of pediatric Orthopedics Shengjing Hospital of China Medical UniversityShenyangLiaoning ProvinceChina

Neonatal hypoxic-ischemic brain injury is the main cause of hypoxic-ischemic encephalopathy and cerebral ***,there are few effective clinical treatments for neonatal hypoxic-ischemic brain ***,we investigated the neuroprotective and molecular mechanisms of exogenous nicotinamide adenine dinucleotide,which can protect against hypoxic injury in adulthood,in a mouse model of neonatal hypoxic-ischemic brain *** this study,nicotinamide adenine dinucleotide(5 mg/kg)was intraperitoneally administered 30 minutes befo re surgery and every 24 hours *** results showed that nicotinamide adenine dinucleotide treatment improved body weight,brain structure,adenosine triphosphate levels,oxidative damage,neurobehavioral test outcomes,and seizure threshold in experimental *** mass tag proteomics revealed that numerous proteins were altered after nicotinamide adenine dinucleotide treatment in hypoxic-ischemic brain injury *** reaction monitoring and western blotting confirmed changes in the expression levels of proteins including serine(or cysteine)peptidase inhibitor,clade A,member 3N,fibronectin 1,5'-nucleotidase,cytosolic IA,microtubule associated protein 2,and complexin *** analyses showed that nicotinamide adenine dinucleotide ameliorated hypoxic-ischemic injury through inflammation-related signaling pathways(e.g.,nuclear factor-kappa B,mitogen-activated protein kinase,and phosphatidylinositol 3 kinase/protein kinase B).These findings suggest that nicotinamide adenine dinucleotide treatment can improve neurobehavioral phenotypes in hypoxic-ischemic brain injury mice through inflammation-related pathways.

关键词： brain injury cerebral palsy hypoxia hypoxic-ischemic brain injury inflammation neuroprotection nicotinamide adenine dinucleotide neonate nicotinamide adenine dinucleotide proteomics

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Characteristics and Risk Factors for pediatric Sepsis

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Current medical science 2024年第3期44卷 648-656页

作者： Yong-bing ZHU Tong-lin LIU Qi DAI Shu-fan LIU Peng XIONG Hao HUANG Yi YUAN Tian-nan ZHANG Yu CHEN department of pediatric Intensive Care Unit Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Objective Sepsis is considered a major cause of health loss in children and had high mortality and ***,there is no reliable model for predicting the prognosis of pediatric patients with *** study aimed to analyze the clinical characteristics of sepsis in children and assess the risk factors associated with poor prognosis in pediatric sepsis patients to identify timely interventions and improve their *** This study analyzed the clinical indicators and laboratory results of septic patients hospitalized in the pediatric Intensive Care Unit of Tongji Hospital,Tongji medical College,Huazhong University of science and Technology,China,from January 1,2019,to December 31,*** factors for sepsis were identified by logistic regression *** A total of 355 children with sepsis were enrolled,with 333 children(93.8%)in the good prognosis group,and 22 children(6.2%)in the poor prognosis *** them,there were 255 patients(71.8%)in the sepsis group,and 100 patients(28.2%)in the severe sepsis *** length of hospital stay in the poor prognosis group was longer than that in the good prognosis group(P0.05),and the platelet(PLT),albumin(ALB),and hemoglobin(Hb)levels were lower in the poor prognosis group(P<0.01).The IL-8 levels in the severe sepsis group were higher than those in the sepsis group(P<0.05).Multiple logistic regression analysis suggested that lower Hb levels,ALB levels,peak PLT counts,and higher IL-1βlevels were independent risk factors for poor prognosis in children with *** Lower Hb,ALB,and PLT counts and elevated IL-1βare independent risk factors for poor prognosis in children with sepsis.

关键词： pediatric sepsis inflammation severity prognosis risk factors

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Alanine aminotransferase as a risk marker for new-onset metabolic dysfunction-associated fatty liver disease

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World Journal of Gastroenterology 2024年第25期30卷 3132-3139页

作者： Di Wang Bing-Yan Zhou Lei Xiang Xu-Yong Chen Jie-Xiong Feng department of pediatric Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030Hubei ProvinceChina

In this editorial,we comment on the article by Chen et *** dysfunction-associated fatty liver disease(MAFLD)is a global public health burden whose incidence has risen concurrently with overweight and *** its detri-mental health impact,early identification of at-risk individuals is *** diagnosis is based on evidence of hepatic steatosis indicated by liver biopsy,imaging,or blood biomarkers,and one of the following conditions:Overweight/obesity,type 2 diabetes mellitus,or metabolic ***,in large-scale epidemiological studies,liver biopsies are not *** application of techniques such as ultrasonography,computed tomography,magnetic resonance imaging,and magnetic resonance spectroscopy is restricted by their limited sensitivity,low effectiveness,high costs,and need for specialized *** biomarkers offer several advantages,particularly in large-scale epidemiological studies or clinical scenarios where traditional imaging techniques are *** of cumulative effects of excess high-normal blood alanine aminotrans-ferase(ALT)levels of blood ALT levels could facilitate identification of at-risk patients who might not be detected through conventional imaging ***,investigating the utility of blood biomarkers in MAFLD should enhance early detection and monitoring,enabling timely inter-vention and management and improving patient outcomes.

关键词： Nonalcoholic fatty liver disease Metabolic dysfunction-associated fatty liver disease Alanine aminotransferase Screening Risk marker

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Mechanism of Endogenous Peptide PDYBX1 and Precursor Protein YBX1 in Hirschsprung’s Disease

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Neuroscience Bulletin 2024年第6期40卷 695-706页

作者： Qiaochu Sun Zhengke Zhi Chenglong Wang Chunxia Du Jie Tang Hongxing Li Weibing Tang department of pediatric Surgery Children’s Hospital of Nanjing Medical UniversityNanjing210008China

Endogenous peptides,bioactive agents with a small molecular weight and outstanding absorbability,regulate various cellular processes and ***,their role in the occurrence of Hirschsprung’s disease(HSCR)remains ***,we found that the expression of an endogenous peptide derived from YBX1(termed PDYBX1 in this study)was upregulated in the aganglionic colonic tissue of HSCR patients,whereas its precursor protein YBX1 was *** shown by Transwell and cytoskeleton staining assays,silencing YBX1 inhibited the migration of enteric neural cells,and this effect was partially reversed after treatment with ***,immunoprecipitation and immunofluorescence revealed that ERK2 bound to YBX1 and *** of YBX1 blocked the ERK1/2 pathway,but upregulation of PDYBX1 counteracted this effect by binding to ERK2,thereby promoting cell migration and *** together,the endogenous peptide PDYBX1 may partially alleviate the inhibition of the ERK1/2 pathway caused by the downregulation of its precursor protein YBX1 to antagonize the impairment of enteric neural ***1 may be exploited to design a novel potential therapeutic agent for HSCR.

关键词： Hirschsprung’s disease YBX1 Endogenous peptide PDYBX1 Enteric neural cell

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Clinical characteristics of postoperative necrotizing enterocolitis in patients with congenital jejunoileal atresia and its risk factors

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World Journal of pediatric Surgery 2024年第1期7卷 42-46页

作者： Xiaofeng Xiong Wei Lu Fuzhong Xing Yuan Cai Jixin Yang Yuhang Yuan Jiexiong Feng Xuyong Chen department of pediatric Surgery Tongji Hospital of Tongji Medical College of Huazhong University of Science and TechnologyWuhanHubeiChina department of Neonate Surgery Wuhan Children's HospitalHuazhong University of Science and TechnologyWuhanHubeiChina department of pediatric Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina

Objective To review postoperative necrotizing enterocolitis(NEC)in patients with jejunoileal atresia(JIA)and to explore the potential risk factors related to the concurrence *** Patients diagnosed with JIA who received surgical treatment from January 2016 to June 2021 were ***,viral infection of the fetus,transfusion within 48 hours before NEC,sepsis before JIA repair,pathological and anatomical classification of JIA,combined malformation,occurrence time of NEC after the operation,treatment,and prognosis of patients were *** were divided into NEC group and non-NEC group,and all patients were followed up for 3-6 months to observe for *** A total of 180 patients with JIA were included,of whom 12 were diagnosed with NEC after surgery and 1 patient with NEC died during *** average age,birth weight,gestational age,proportion of premature infants,proportion of preoperative infections,and pathological classification of JIA did not significantly differ between the two *** probability of patients with proximal jejunal atresia(PJA)in the NEC group(58.3%)was higher than that in the non-NEC group(22.6%)(p=0.011),and patients with PJA had longer parenteral nutrition time than patients without PJA(26.64±9.21 days vs 15.11±6.58 days,p<0.001).Conclusion PJA was more likely to be associated with concurrent NEC after surgery,which is a highly NEC-related risk factor inherent in JIA.

关键词： patients postoperative transfusion

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Chinese expert consensus statement on the diagnosis and treatment of Hirschsprung disease

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Chinese medical Journal 2024年第5期137卷 505-507页

作者： Tianqi Zhu Weibing Tang Jiexiong Feng the Chinese Research Group of Hirschsprung Disease department of pediatric Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyHubei Clinical Center of Hirschsprung’s Disease and Allied DisordersWuhanHubei 430030China department of Neonatal Surgery Children’s Hospital of Nanjing Medical UniversityNanjingJiangsu 210008China 不详

Hirschsprung disease(HSCR)is a congenital anomaly of the intestine caused by the developmental absence of the enteric nervous system,which results in variable lengths of intestinal dysfunction and requires surgical intervention.^([1])Due to the complex etiology,multiple surgical procedures and postoperative complications,the diagnosis and treatment strategies of HSCR have always been the focus of pediatric surgeons around the *** pediatric surgical experts with rich clinical experience from almost all national and provincial children’s medical centers in China constituted the Chinese Research Group of Hirschsprung disease(CRGHSCR).

关键词： diagnosis intestine treatment

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Nucleotide excision repair gene polymorphisms and hepatoblastoma susceptibility in Eastern Chinese children:A five-center case-control study

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Chinese Journal of Cancer Research 2024年第3期36卷 298-305页

作者： Huimin Yin Xianqiang Wang Shouhua Zhang Shaohua He Wenli Zhang Hongting Lu Yizhen Wang Jing He Chunlei Zhou department of pediatric Surgery Guangzhou Institute of PediatricsGuangdong Provincial Key Laboratory of Research in Structural Birth Defect DiseaseGuangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhou 510623China department of pediatric Surgery Senior Department of Pediatricsthe Seventh Center of Chinese People’s Liberation Army(PLA)General HospitalBeijing 100000China department of General Surgery Jiangxi Provincial Children’s HospitalNanchang 330006China department of pediatric Surgery Shengli Clinical Medical College of Fujian Medical UniversityFuzhou 350001China department of pediatric Surgery Qingdao Women and Children’s HospitalQingdao 266000China department of Pathology Anhui Provincial Children’s HospitalHefei 230051China department of Pathology Children’s Hospital of Nanjing Medical UniversityNanjing 210008China

Objective:Nucleotide excision repair(NER)plays a vital role in maintaining genome stability,and the effect of NER gene polymorphisms on hepatoblastoma susceptibility is still under *** study aimed to evaluate the relationship between NER gene polymorphisms and the risk of hepatoblastoma in Eastern Chinese Han ***:In this five-center case-control study,we enrolled 966 subjects from East China(193 hepatoblastoma patients and 773 healthy controls).The TaqMan method was used to genotype 19 single nucleotide polymorphisms(SNPs)in NER pathway genes,including ERCC1,XPA,XPC,XPD,XPF,and ***,multivariate logistic regression analysis was performed,and odds ratios(ORs)and 95%confidence intervals(95%CIs)were utilized to assess the strength of ***:Three SNPs were related to hepatoblastoma *** rs2229090 and XPD rs3810366 significantly contributed to hepatoblastoma risk according to the dominant model(adjusted OR=1.49,95%CI=1.07−2.08,P=0.019;adjusted OR=1.66,95%CI=1.12−2.45,P=0.012,respectively).However,XPD rs238406 conferred a significantly decreased risk of hepatoblastoma under the dominant model(adjusted OR=0.68,95%CI=0.49−0.95;P=0.024).Stratified analysis demonstrated that these significant associations were more prominent in certain ***,there was evidence of functional implications of these significant SNPs suggested by online expression quantitative trait loci(eQTLs)and splicing quantitative trait loci(sQTLs)***:In summary,NER pathway gene polymorphisms(XPC rs2229090,XPD rs3810366,and XPD rs238406)are significantly associated with hepatoblastoma risk,and further research is required to verify these findings.

关键词： Nucleotide excision repair polymorphisms hepatoblastoma susceptibility

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Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies

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Signal Transduction and Targeted Therapy 2024年第1期9卷 173-210页

作者： Md Entaz Bahar Hyun Joon Kim Deok Ryong Kim department of Biochemistry and Convergence medical sciences and Institute of medical science Gyeongsang National UniversityCollege of MedicineJinjuSouth Korea department of Anatomy and Convergence medical sciences and Institute of medical science Gyeongsang National UniversityCollege of MedicineJinjuSouth Korea

Metastatic dissemination of solid tumors,a leading cause of cancer-related mortality,underscores the urgent need for enhanced insights into the molecular and cellular mechanisms underlying metastasis,chemoresistance,and the mechanistic backgrounds of individuals whose cancers are prone to *** most prevalent signaling cascade governed by multi-kinase inhibitors is the mitogen-activated protein kinase(MAPK)pathway,encompassing the RAS–RAF–MAPK kinase(MEK)–extracellular signal-related kinase(ERK)*** kinase is a primary mediator of the MAPK pathway,responsible for the sequential activation of downstream targets,such as MEK and the transcription factor ERK,which control numerous cellular and physiological processes,including organism development,cell cycle control,cell proliferation and differentiation,cell survival,and *** in this signaling cascade are associated with diseases such as *** inhibitors(RAFi)combined with MEK blockers represent an FDAapproved therapeutic strategy for numerous RAF-mutant cancers,including melanoma,non-small cell lung carcinoma,and thyroid ***,the development of therapy resistance by cancer cells remains an important ***,an intracellular lysosome-dependent catabolic recycling process,plays a critical role in the development of RAFi resistance in ***,targeting RAF and autophagy could be novel treatment strategies for RAF-mutant *** this review,we delve deeper into the mechanistic insights surrounding RAF kinase signaling in tumorigenesis and ***,we explore and discuss the ongoing development of next-generation RAF inhibitors with enhanced therapeutic ***,this review sheds light on the functional interplay between RAF-targeted therapies and autophagy in cancer.

关键词： RAF insight mechanism

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Multiple thoracic and abdominal foregut duplication cysts:A case report

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World Journal of Clinical Cases 2024年第8期12卷 1504-1509页

作者： Tuqa Adil Alsinan Tariq Ibrahim Altokhais department of pediatric Surgery Prince Sultan Military Medical CityRiyadh 12233Saudi Arabia Devision of pediatric Surgery Department of SurgeryCollege of MedicineKing Saud UniversityRiyadh 4545Saudi Arabia

BACKGROUND Congenital enteric duplication cysts are tubular or cystic structures that normally lie alongside the gastrointestinal(GI)*** duplication cysts are typically solitary lesions that occur anywhere near the GI tract from the neck to the rectum,but having multiple duplication cysts is rare,and presentation within the pancreas is extremely *** SUMMARY We herein demonstrate a case of esophageal,gastric,and gastric-type duplication cyst of the pancreas in a seventeen-month-old girl who presented with failure to thrive,abdominal pain,vomiting,hematemesis,and melena since the age of three *** cysts were excised by thoracoscopy and laparoscopy in the same *** our knowledge,no such case has been *** Enteric duplications can occur throughout the entire alimentary *** they occur in the pancreas,they present a formidable challenge in both diagnosis and *** to the risk of complications and malignant transformation,surgical removal is the recommended treatment of all duplication cysts.

关键词： Congenital Duplication cyst Foregut duplication Gastric duplication Pancreas Case report

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Oncogenic β-catenin-driven liver cancer is susceptible to methotrexate-mediated disruption of nucleotide synthesis

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Chinese medical Journal 2024年第2期137卷 181-189页

作者： Fangming Liu Yuting Wu Baohui Zhang Shuhui Yang Kezhuo Shang Jie Li Pengju Zhang Weiwei Deng Linlin Chen Liang Zheng Xiaochen Gai Hongbing Zhang department of Physiology State Key Laboratory of Common Mechanism Research for Major DiseasesHaihe Laboratory of Cell EcosystemInstitute of Basic Medical Sciences and School of Basic MedicineChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China department of Physiology Institute of Basic Medical Sciences and School of Basic MedicineGraduate School of Peking Union Medical CollegeChinese Academy of Medical SciencesBeijing100005China department of Physiology School of Life ScienceChina Medical UniversityShenyangLiaoning 110122China School of Life sciences Westlake UniversityHangzhouZhejiang 310024China Key Laboratory of pediatric Hematology and Oncology Ministry of HealthInstitute of Pediatric Translational MedicineShanghai Children’s Medical CenterShanghai Jiao Tong School of MedicineShanghai 200127China

Background:Liver cancer is largely resistant to *** study aimed to identify the effective chemotherapeutics forβ-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1(CTNNB1),the most frequently altered proto-oncogene in hepatic ***:Constitutiveβ-catenin-activated mouse embryonic fibroblasts(MEFs)were established by deleting exon 3(β-catenin^(Δ(ex3)/+)),the most common mutation site in CTNNB1 gene.A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibitedβ-catenin^(Δ(ex3)/+)but not for wild-type *** metabolomics was carried out to examine the alterations of metabolites in nucleotide *** efficacy and selectivity of methotrexate(MTX)onβ-catenin-activated human liver cancer cells were determined in ***-deficient nude mice subcutaneously inoculated withβ-catenin wild-type or mutant liver cancer cells and hepatitis B virus(HBV);β-catenin^(lox(ex3)/+)mice were used,respectively,to evaluate the efficacy of MTX in the treatment ofβ-catenin mutant liver ***:MTX was identified and validated as a preferential agent against the proliferation and tumor formation ofβ-catenin-activated *** nucleotide synthesis was the major metabolic aberration inβ-catenin-active cells,and this alteration was also the target of ***,MTX abrogated hepatocarcinogenesis of HBV;β-catenin^(lox(ex3)/+)mice,which stimulated concurrent Ctnnb1-activated mutation and HBV infection in liver ***:MTX is a promising chemotherapeutic agent forβ-catenin hyperactive liver *** repurposing MTX has the advantages of lower risk,shorter timelines,and less investment in drug discovery and development,a clinical trial is warranted to test its efficacy in the treatment ofβ-catenin mutant liver cancer.

关键词： Liver cancer β-catenin Methotrexate Nucleotide synthesis Chemotherapy

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