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The Traf2 and NcK interacting kinase inhibitor NCB-0846 suppresses seizure activity involving the decrease of GRIA1

Genes & Diseases 2024年第3期11卷 452-467页

作者： Min Wang Yixue Gu Qiubo Li Bangzhe Feng Xinke Lv Hao Zhang Qingxia Kong Zhifang Dong Xin Tian Yanke Zhang department of Neurology Affiliated Hospital of Jining Medical UniversityJiningShandong 272000China department of Neurology The First Affiliated Hospital of Chongqing Medical UniversityChongqing Key Laboratory of NeurologyChongqing 400016China department of pediatrics Affiliated Hospital of Jining Medical UniversityJiningShandong 272000China department of Neurosurgery Affliated Hospital of Jining Medical UniversityJiningShandong 272000China Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai 200031China

Epilepsy,one of the most common neurological disorders,is characterized by spon-taneous recurrent *** lobe epilepsy(TLE)is one of the most common medically intractable seizure ***2-and NcK-interacting kinase(TNIK)has recently attracted attention as a critical modulation target of many neurological and psychiatric disorders,but its role in epilepsy remains *** this study,we hypothesized the involvement of TNIK in epilepsy and investigated TNIK expression in patients with intractable TLE and in a pilocarpineinduced rat model of epilepsy by western blotting,immunofluorescence,and immunohistochemistry.A pentylenetetrazole(PTZ)-induced epilepsy rat model was used to determine the effect of the TNIK inhibitor NCB-0846 on behavioral manifestations of ***(Co-IP)/mass spectrometry(MS)was used to identify the potential *** Co-IP,we detected and confirmed the main potential TNIK *** fractionation was used to establish the effect of NCB-0846 on the expression of the main interactors in postsynaptic density(PSD)*** found that TNIK was primarily located in neurons and decreased significantly in epilepsy model rats and TLE patients compared with ***-0846 delayed kindling progression and decreased seizure ***-IP/MS identified 63 candidate TNIK interactors in rat hippocampi,notably ***-IP showed that TNIK might correlate with endogenous GRIA1,SYN2,PSD-95,CaMKIV,GABRG1,and *** addition,the significant decrease in GRIA1 in hippocampal total lysate and PSDs after NCB-0846 treatment might help modify the progression of PTZ *** results suggest that TNIK contributes to epileptic pathology and is a potential antiepileptic drug target.

关键词： Epilepsy NCB-0846 Rat TLE TNIK Traf2-and NcK-interacting kinase

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Function and dysfunction of GEMIN5:understanding a novel neurodevelopmental disorder

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Neural Regeneration Research 2024年第11期19卷 2377-2386页

作者： Charles H.Nelson Udai B.Pandey department of pediatrics Division of Child NeurologyChildren’s Hospital of PittsburghUniversity of Pittsburgh Medical CenterPittsburghPAUSA Children’s Neuroscience Institute Children’s Hospital of PittsburghUniversity of Pittsburgh Medical CenterPittsburghPAUSA

The recent identification of a neurodevelopmental disorder with cerebellar atrophy and motor dysfunction(NEDCAM)has resulted in an increased interest in GEMIN5,a multifunction RNA-binding *** the largest member of the survival motor neuron complex,GEMIN5 plays a key role in the biogenesis of small nuclear ribonucleoproteins while also exhibiting translational regulatory functions as an independent *** many questions remain regarding both the pathogenesis and pathophysiology of this new disorder,considerable progress has been made in the brief time since its *** this review,we examine GEMIN5 within the context of NEDCAM,focusing on the structure,function,and expression of the protein specifically in regard to the disorder ***,we explore the current animal models of NEDCAM,as well as potential molecular pathways for treatment and future directions of *** review provides a comprehensive overview of recent advances in our understanding of this unique member of the survival motor neuron complex.

关键词： cerebellar atrophy GEMIN5 neurodevelopmental disorder neurological disease SMN complex

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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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Advancements in nutritional diagnosis and support strategies during the perioperative period for patients with liver cancer

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World Journal of Gastrointestinal Surgery 2024年第8期16卷 2409-2425页

作者： Xiao-Qin Li Yun Liang Chen-Feng Huang Sui-Ning Li Lei Cheng Chuan You Yao-Xia Liu Tao Wang department of Hepatobiliary Surgery The Affiliated Hospital of North Sichuan Medical CollegeNanchong 637000Sichuan ProvinceChina department of Paediatric Surgery The Affiliated Hospital of North Sichuan Medical CollegeNanchong 637000Sichuan ProvinceChina department of Cardiovascular Surgery The First Affiliated HospitalJinan UniversityGuangzhou 510632Guangdong ProvinceChina department of Geriatric Endocrinology Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610072Sichuan ProvinceChina department of Pediatric Cardiology West China Second University HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina department of pediatrics Key Laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University)Ministry of EducationChengdu 610041Sichuan ProvinceChina

Liver cancer represents a grave hepatic condition and constitutes a significant global health *** resection remains the principal therapeutic modality for liver ***,perioperative malnutrition exerts a notable impact on patients with liver cancer,emerging as an independent risk factor for disease mortality and adverse ***,precise nutritional diagnosis and timely nutritional support hold the potential to enhance therapeutic efficacy and quality of life for liver cancer *** study represents a meticulous foray into the literature,extracting data from PubMed,Web of Science,and EMBASE databases,with a focus on the past 5 *** scrutinizes the impact of malnutrition on patients undergoing liver cancer surgery,the etiological underpinnings of malnutrition within this patient cohort,the critical assessment of perioperative nutritional status,and the strategic approaches to nutritional *** rigorous inclusion and exclusion criteria,the amassed scholarly works are meticulously synthesized,methodically organized,and categorically elaborated ***,the authors propose the incorporation of a multidisciplinary nutrition management team during the perioperative period,comprising nutritionists,pharmacists,physicians,nurses,psychologists,and rehabilitation therapists,among other specialized ***,they collaborate to devise and implement personalized nutritional support plans,monitor patients’nutritional status,and make necessary adjustments as *** comprehensive management and intervention,improvements in the nutritional status of liver cancer patients can be achieved,thereby enhancing surgical success rates and facilitating postoperative *** is believed that this manuscript will offer valuable insights to advance the nutritional management during the perioperative phase of liver cancer,aiding in ameliorating patients'nutritional status and treatment outcomes.

关键词： Liver cancer Nutritional diagnosis Nutritional support Perioperative period Genetic testing Immunonutrition Probiotics and gut microbiota

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Clinical characteristics and genetic mutations of 10 Chinese children with cystic fibrosis or cystic frbrosis transmembrane conductance regulator-related disorders

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中华医学杂志(英文版) 2024年第14期137卷 1753-1755页

作者： Tan Shanshan Cao Ling department of Pulmonology The Children’s Hospital Affiliated to the Capital Institute of Pediatrics Beijing China

To the Editor: Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. To date, over 2000 CFTR mutations have been identified. CF mostly occurs in the Caucasian population, and its incidence is approximately 1/25,000 to 1/1800. However, the number of CF cases in China is small. To discover the gene mutations and clinical characteristics of Chinese children with CF, as well as their correlation, the clinical data of 10 children with CF or CFTR-related disorders (CFTR-RD) were retrospectively analyzed in this study.

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Implementation of an international medical student pen-pal club:survey outcomes of perceptions in cultural competency and global health

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Global Health Journal 2024年第1期8卷 11-15页

作者： Max J.Goodman Jennifer Livschitz Ji Won Kim Megan L.Schultz Medical College of Wisconsin MilwaukeeWI 53226USA department of pediatrics Division of Emergency MedicineMedical College of WisconsinMilwaukeeWI53226USA

Background:Pen-pal clubs(PPC)are used worldwide for students to learn about different cultures and other skillsets without the need for *** medical students are interested in global health opportunities abroad but costs,scheduling,and other barriers allow few to participate in such *** is important that medical students have nuanced global medical perspectives and can contribute to the global medical ***:The purpose of this study is to demonstrate that an international medical student PPC improves medical students'perspectives of cultural competency and global health ***:In 2021,a novel medical student PPC was established that began between an American and Japanese medical *** a shareholders meeting,it was decided that the number of medical schools involved globally be expanded through previous institutional affiliations and online *** total,the club connected 50 American medical students and 52 medical students from 17 high-and middle-income *** primary form of communication was online;pen-pals were encouraged to communicate monthly using provided topics,although frequency and way of communication was their *** February 2022,American PPC members were emailed a qualitative survey to assess the PPC's ***:The survey was completed by 42%of American PPC members,95%of which were 22-26 *** were preclinical medical students,60%whom were female and the majority either white(47%)or Asian(43%).Overall,the PPC positively influenced American medical students'perception of global medicine,medical education,and their cultural competency after joining the PPC compared to prior(P=0.004).Conclusion:PPCs encourage medical students to think from a global perspective and foster open-mindedness within varying social and cultural *** a global communication platform for students during medical school education may be an additional way to train aspiring global l

关键词： Pen-pals Medical student Global health Cultural competency

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Resistant Pulmonary TB-HIV Co-Infection in an Infant: About a Case

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Open Journal of pediatrics 2024年第2期14卷 420-425页

作者： Mariam Maiga Pierre Togo Tati Simaga Mariam Traoré Moussa Konaté Mamadou Diallo Alou Samaké Mamadou Keïta Korotoumou Wélé Diallo Djibril Kassogué pediatrics department Distric VI Reference Health Center Bamako Mali Paediatrics department Gabriel Touré Teaching Hospital Bamako Mali pediatrics department Mali Hospital Bamako Mali Paediatrics department Timbuktu Regional Hospital Bamako Mali

Diagnosis of childhood tuberculosis (TB) is difficult, especially in resource-limited countries where the number of reported cases of TB-HIV co-infection continues to rise. This co-infection poses a diagnostic and therapeutic problem for caregivers. We report a case of rifampicin-resistant HIV-TB pulmonary coinfection in a 19-month-old infant.

关键词： Tuberculosis Rifampicin Resistance HIV Infants

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Relationship between sleep quality and blood pressure level in nurses performing shift work

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Frontiers of Nursing 2024年第1期11卷 77-84页

作者： Antonina Tsipkalo Kateryna Kozak Mariya Marushchak department of Functional and Laboratory Diagnostics I.Horbachevsky Ternopil National Medical UniversityTernopil 46001Ukraine department of pediatrics No.2 I.Horbachevsky Ternopil National Medical UniversityTernopil 46001Ukraine

Objective:The aim of the study was to evaluate the quality of sleep in nurses performing shift work in therapeutic and surgical depar tments and to establish possible relationships between level of blood pressure(BP)and quality of ***:A total of 20 nurses of the therapeutic depar tments and 20 nurses of the surgical depar tments were enrolled in the *** quality was assessed using the Pittsburgh Sleep Quality Index(PSQI).BP was measured according to the standard protocol using the Korotkoff method;a sphygmomanometer was used for this twice with an interval of 2 min between 10:00 *** 10:30 *** average value for the 2 indicators was *** diagnosis of essential ar terial hyper tension(AH)was established according to the recommendations of the European Association of Cardiology and the European Association of Hypertension(2018).Results:The overall assessment of the sleep quality of the nurses involved in shift work indicates poor sleep quality;this was true in respondents of both the surgical and therapeutic ***,it was observed that the quality of sleep was significantly lower in nurses of the therapeutic ***,poor sleep quality was associated with AH,which was diagnosed in 65%of the nurses of the therapeutic departments and 45%of the nurses of the surgical departments,that is,in almost all of the ***,in the nurses of the therapeutic departments,the level of systolic BP exceeded that of the nurses of the surgical ***:Poor sleep quality is a significant risk factor for AH development and is relevant to nurses performing shift *** clinical studies should be conducted to better understand the mechanisms underlying such adverse cardiometabolic outcomes associated with sleep disorders in the health-sector shift workers.

关键词： blood pressure nurses shift work sleep quality Pittsburgh Sleep Quality Index

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Emerging role of cellular senescence in normal lung development and perinatal lung injury

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Chinese Medical Journal Pulmonary and Critical Care Medicine 2024年第1期2卷 10-16页

作者： Phyllis A.Dennery Hongwei Yao department of Molecular Biology Cell Biology&BiochemistryDivision of Biology and MedicineBrown UniversityProvidenceRI 02912USA department of pediatrics Warren Alpert Medical School of Brown UniversityProvidenceRI 02903USA

Cellular senescence is a status of irreversible growth arrest,which can be triggered by the p53/p21cip1 and p16INK4/Rb pathways via intrinsic and external *** cells are typically enlarged and flattened,and characterized by numerous molecular *** latter consists of increased surfaceome,increased resid-ual lysosomal activity at pH 6.0(manifested by increased activity of senescence-associated beta-galactosidase[SA-𝛽-gal]),senescence-associated mitochondrial dysfunction,cytoplasmic chromatin fragment,nuclear lamin b1 exclusion,telomere-associated foci,and the senescence-associated secretory *** features vary depending on the stressor leading to senescence and the type of *** senescence plays pivotal roles in organismal aging and in the pathogenesis of aging-related ***,senescence can also both promote and inhibit wound healing *** recently report that senescence as a programmed pro-cess contributes to normal lung *** senescence is also observed in Down Syndrome,as well as in premature infants with bronchopulmonary dysplasia and in a hyperoxia-induced rodent model of this ***,this senescence results in neonatal lung *** this review,we briefly discuss the molecular features of *** then focus on the emerging role of senescence in normal lung development and in the pathogenesis of bronchopulmonary dysplasia as well as putative signaling pathways driving ***,we discuss potential therapeutic approaches targeting senescent cells to prevent perinatal lung diseases.

关键词： Senescence Normal lung development Bronchopulmonary dysplasia Down syndrome Senolytics

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A Proposal on the Novel Method to Estimate Optimal Sleep Duration Based on Self-Reported Survey Data

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Journal of Behavioral and Brain Science 2024年第8期14卷 227-239页

作者： Jun Kohyama department of pediatrics Tokyo Bay Urayasu Ichikawa Medical Center Chiba Japan

Background: Many adolescents have a sleep debt. Individuals sleeping for their optimal sleep duration are expected to experience no sleepiness. Then, it is important to recognize one’s optimal sleep duration to reduce sleep debt. However, there is no simple method to determine this value. Since body mass index and sleep duration exhibit a U-shaped association, it is expected that a person taking optimal sleep duration would show no marked deviation from the mean body mass index value for the population evaluated. By using self-reported sleepiness and standardized body mass index, this study aimed to estimate individual optimal sleep duration. Methods: Data from 2540 grade 5 - 11 students were used. Students who declared no sleepiness during class and also had a gender- and grade-standardized body mass index of ±1.5 were termed ideal students. The average sleep durations of ideal students were compared with those of non-ideal students. The differences of sleep duration between ideal and no-ideal students were added to habitual sleep duration of each non-ideal student to obtain assumed optimal sleep duration. A multiple regression line to predict assumed optimal sleep duration was calculated using the least squares method. Results: The mean sleep duration of 666 ideal students exceeded the lower limit of daily sleep duration proposed as “may be appropriate” for children aged 6 - 17 years by National Sleep Foundation of the USA, being longer than those of non-ideal students. Significant regression formula for assumed optimal sleep duration was obtained (adjusted R2 = 0.996, p Conclusions: No contradiction was identified in the sleep duration obtained from ideal students as with optimal sleep duration. Although further studies to confirm the current estimation are needed, a simple formula to estimate individual optimal sleep duration through easily obtainable parameters was proposed.

关键词： Body Mass Index Catch-Up Sleep Insufficient Sleep Syndrome Optimal Sleep Duration Sleepiness

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