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X-box binding protein 1 caused an imbalance in pyroptosis and mitophagy in immature rats with di-(2-ethylhexyl)phthalate-induced testis toxicity

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Genes & Diseases 2024年第2期11卷 935-951页

作者： Yifan Hong Xiazhu Zhou Qi Li Jing Chen Yuexin Wei Chunlan Long Lianju Shen Xiangqin Zheng Dinggang Li Xia Wang Chenjun Yu Shengde Wu Guanghui Wei Department of Urology Children's Hospital of Chongqing Medical UniversityChongqing 400014China Pediatric Research Institute Children's Hospital of Chongqing Medical UniversityChongqing 400014China Chongqing Key Laboratory of children Urogenital Development and Tissue Engineering Children's Hospital of Chongqing Medical UniversityChongqing 400014China Chongqing Key Laboratory of Pediatrics Children's Hospital of Chongqing Medical UniversityChongqing 400014China Ministry of Education Key Laboratory of Child Development and disorders Children's Hospital of Chongqing Medical UniversityChongqing 400014China National Clinical Research Center for Child Health and disorders Children's Hospital of Chongqing Medical UniversityChongqing 400014China China International Science and Technology Cooperation Base of Child Development and Critical disorders Children's Hospital of Chongqing Medical UniversityChongqing 400014China

As a widely used plasticizer,di-(2-ethylhexyl)phthalate(DEHP)is known to induce significant testicular ***,the potential mechanism and effects of pubertal exposure to DEHP on testis development remain *** vivo,postnatal day(PND)21 male rats were gavaged with 0,250,and 500 mg/kg DEHP for ten *** to the seminiferous epithelium and disturbed spermatogenesis were observed after DEHP ***,oxidative stress-induced injury and pyroptosis were *** endoplasmic reticulum(ER)stress and mitophagy were involved in this *** phthalate(MEHP)was used as the biometabolite of DEHP in *** GC-1 and GC-2 cell lines were exposed to 0,100μM,200μM,and 400μM MEHP for 24 *** oxygen species(ROS)generation,oxidative stress damage,ER stress,mitophagy,and pyroptosis were significantly increased after MEHP *** ultrastructure of the ER and mitochondria was destroyed.X-box binding protein 1(XBP1)was observed to be activated and translocated into the *** generation was inhibited by *** levels of antioxidative stress,ER stress,mitophagy,and pyroptosis were decreased as *** the administration of the ER stress inhibitor 4-phenyl-butyric acid,both mitophagy and pyroptosis were ***-induced XBP1 down-regulation decreased the levels of mitophagy and *** equilibrium between pyroptosis and mitophagy was disturbed by XBP1 *** summary,our findings confirmed that DEHP induced a ROS-mediated imbalance in pyroptosis and mitophagy in immature rat testes via ***,XBP1 might be the key target in DEHP-related testis dysfunction.

关键词： DEHP Mitophagy Pyroptosis Testicular development XBP1

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A genomic association study revealing subphenotypes of childhood steroid-sensitive nephrotic syndrome in a larger genomic sequencing cohort

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Genes & Diseases 2024年第4期11卷 400-410页

作者： Han Chan Fenfen Ni Bo Zhao Huimin Jiang Juanjuan Ding Li Wang Xiaowen Wang Jingjing Cui Shipin Feng Xiaojie Gao Xueying Yang Huan Chi Hao Lee Xuelan Chen Xiaoqin Li Jia Jiao Daoqi Wu Gaofu Zhang Mo Wang Yupeng Cun Xiongzhong Ruan Haiping Yang Qiu Li Department of Nephrology Children's Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of PediatricsChongqing 400014China Department of Nephrology Shenzhen Children's HospitalShenzhenGuangdong 518034China Department of Nephrology Kunming Children's HospitalKunming Medical UniversityKunmingYunnan 650228China Department of Nephrology Wuhan Children's HospitalTongji Medical College of Huazhong University of Science and TechnologyWuhanHubei 430015China Department of Nephrology Chengdu Women and Children Central HospitalChengduSichuan 610073China Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Department of Nephrology John Moorhead Research LaboratoryUniversity College London Medical SchoolRoyal Free CampusUniversity College LondonLondon NW32PFUnited Kingdom

Dissecting the genetic components that contribute to the two main subphenotypes of steroid-sensitive nephrotic syndrome(SSNS)using genome-wide association studies(GWAS)strategy is important for understanding the *** conducted a multicenter cohort study(360 patients and 1835 controls)combined with a GWAS strategy to identify susceptibility var-iants associated with the following two subphenotypes of ssNS:steroid-sensitive nephrotic syn-drome without relapse(SSNswR,181 patients)and steroid-dependent/frequent relapse nephrotic syndrome(SDNS/FRNS,179 patients).The distribution of two single-nucleotide poly-morphisms(SNPs)in ANKRD36 and ALPG was significant between SSNSWR and healthy controls,and that of two SNPs in GAD1 and HLA-DQA1 was significant between SDNS/FRNS and healthy ***,rs1047989 in HLA-DQA1 was a candidate locus for SDNS/FRNS but not for *** significant SNPs were observed between SSNSWR and SDNS/***,chromosome 2:171713702 in GAD1 was associated with a greater steroid dose(>0.75 mg/kg/d)upon relapse to first remission in patients with SDNS/FRNS(odds ratio=3.14;95%confidence interval,0.97-9.87;P=0.034).rs117014418 in APOL4 was significantly associated with a decrease in eGFR of greater than 20%compared with the baseline in SDNS/FRNS patients(P=0.0001).Protein-protein intersection network construction suggested that HLA-DQA1 and HLA-DQB1 function together through ***,SSNSWR belongs to non-HLA region-dependent nephropathy,and the HLA-DQA/DQB region is likely strongly associated with dis-ease relapse,especially in SDNS/*** study provides a novel approach for the GWAS strategy of SsNS and contributes to our understanding of the pathological mechanisms of SSNSWRandSDNS/FRNS.

关键词： Frequentrelapse Genome-wide association study Human leukocyte antigen region Steroid-sensitive nephrotic syndrome

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Comments on the editorial by Riggio&Ageloni on the ascitic fluid analysis

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World Journal of Gastroenterology 2009年第48期15卷 6137-6138页

作者： Anastasios Koulaouzidis day Case & Endoscopy Unit Centre of Liver and Digestive DisordersRoyal Infirmary of Edinburgh

Angeloni et al published a landmark study on the use of Coulter counters in spontaneous bacterial peritonitis(SBP)*** and Angeloni have recently published an editorial on the ascitic fluid analysis in diagnosis and mo... 详细信息

关键词： Peritonitis Reagent Dipstick Paracentesis Guidelines Ascites

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Sirolimus can promote the disappearance of renal angiomyolipoma associated with tuberous sclerosis complex:a prospective cohort study

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World Journal of Pediatrics 2024年第6期20卷 602-610页

作者： Shuo Dun Yang-Yang Wang Lin Wan Qiu-Hong Wang Qian Lu Xiao-Yan Yang Qi Zhang Hui-Min Chen Lu-Peng Qiu Li-Ping Zou Medical School of Chinese PLA Beijing 100853China Department of Pediatrics The First Medical CenterChinese PLA General HospitalBeijing 100853China Center of Epilepsy Beijing Institute for Brain DisordersBeijing 100069China

Background Renal angiomyolipoma(RAML)is the most common kidney lesion in patients with tuberous sclerosis complex(TSC),affecting about 80%of *** is a benign tumor that grows over time,usually bilaterally,and can easily lead to kidney complications such as acute ***,we investigated the efficacy and safety of sirolimus in children with TSC-associated RAML and explored the factors affecting tumor disappearance under sirolimus treatment through subgroup *** A prospective cohort study was *** was initiated at 1 mg/(m^(2)×day),and dose adjustments were made by a 2-week titration period to attain a trough blood concentration of 5-10 ng/*** disappearance of RAML in chil-dren after sirolimus treatment was observed,and Cox regression was used to screen the factors affecting tumor *** One hundred and twenty-six patients who met the criteria were *** 3 months,6 months,12 months,and 24 months of follow-up,tumors disappeared in 18(14.3%),30(23.8%),39(31.0%),and 42(33.3%)children,*** disappeared in 50(39.7%)children by the last visit of each individual,and 30(60%)of them occurred within 6 *** multivariate Cox regression analysis showed that patients with a smaller maximum tumor diameter at baseline had a higher tumor disappearance ***-six(29%)patients had stomatitis during the entire treatment period,and no serious *** Sirolimus could promote the disappearance of TSC-related *** disappearance rate was correlated with the maximum diameter at baseline,and the smaller the tumor was,the higher the disappearance *** is well tolerated in the treatment of RAML associated with TSC.

关键词： Angiomyolipoma mTOR inhibitor Sirolimus Tuberous sclerosis

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Longitudinal Study of High and Low Functioning Preschoolchildren with ASD and the Progress Made FollowingTherapeutic Intervention

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Psychology Research 2017年第4期7卷 205-218页

作者： Kotsopoulou Angelique Georgiou Anastasia Gyftogianni Aikaterini Gyftogianni Maria Florou Irene Palaiodimou Eleonora Troupou Antigoni Koumanioti EfthimiaDay Centre for Children with Developmental Disorders Messolonghi Greece

The present study addresses three problem areas among preschool children with ASD （Autism Spectrum Disorder）：co-occurring psychiatric problems, speech-language and feeding difficulties, and progress of low functioning（globally retarded） children in most areas of development. Fifty children with ASD （mean age 3 years） were studiedThree therapists of different disciplines （the first to see and treat the children） examined carefully the files of thechildren.

关键词：心理学研究医学

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Therapeutic Potential of Thunbergia laurifolia *** in Gestational Diabetes Mellitus:Insights from a Rat Model

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Chinese Journal of Integrative Medicine 2024年第9期30卷 788-798页

作者： Sasitorn Kerdsuknirund Arreeya Kosinan Panida Khunkaewla Pakanit Kupittayanant Ratchadaporn Oonsivilai Pattama Tongdee Porntip Nimkuntod Susan Wray Sajeera Kupittayanant School of Preclinical Sciences Institute of ScienceSuranaree University of TechnologyNakhon Ratchasima30000Thailand Biochemistry-Electrochemistry Research Unit School of BiochemistryInstitute of ScienceSuranaree University of TechnologyNakhon Ratchasima30000Thailand School of Animal Technology and Innovation Institute of Agricultural TechnologySuranaree University of TechnologyNakhon Ratchasima30000Thailand School of Food Technology Institute of Agricultural TechnologySuranaree University of TechnologyNakhon Ratchasima30000Thailand School of Obstetrics and Gynecology Institute of MedicineSuranaree University of TechnologyNakhon Ratchasima30000Thailand School of Internal Medicine Institute of MedicineSuranaree University of TechnologyNakhon Ratchasima30000Thailand Harris-Wellbeing Preterm Birth Research centre Department of Women and Children’s Healththe Institute of Lifecourse and Medical SciencesUniversity of LiverpoolLiverpoolUK

Objective:To assess the effects of Thunbergia laurifolia ***(TLE)on gestational diabetes mellitus(GDM)in a rat ***:Thunbergia laurifolin *** were subjected to ethanolic *** vivo study,50 pregnant rats were randomly divided into 5 groups(10 for each):non-GDM group,GDM induced by streptozotocin(STZ,60 mg/kg i.p.),metformin(MET)100 mg/kg,TLE 50,and 500 mg/kg *** was performed on gestation day 7 until term(day 21).The effects of TLE on blood glucose,insulin levels,lipid profiles,liver enzymes,and maternal performances were *** in vitro study,the effect of TLE was examined using the organ bath for uterine force ***:In in vivo study,TLE significantly reduced blood glucose as compared to GDM(P<0.05)with gradually increased insulin *** effect was consistent with islets of Langerhans ***,the uterine muscular layer displayed a marked increase in fiber area in response to both doses as compared to GDM(P<0.05).Additionally,TLE significantly reduced total cholesterol,triglyceride,and alanine transaminase levels(P<0.05).Intriguingly,TLE also led to a notable augmentation in gravid uterus size,live fetuses count,and implantation numbers,while significantly reducing the post-implantation loss rate associated with fetal classification(P<0.05).Thus,GDM improvements were close to those produced by *** in vitro study,TLE exerted a concentration-dependent inhibition of spontaneous uterine contractility(half-maximal inhibition concentration=1.2 mg/L).This inhibitory effect extended to potassium chloride depolarization and oxytocin-mediated *** combined with its major constituent,rosmarinic acid,TLE produced an enhanced inhibitory effect(P<0.05).Conclusions:TLE ameliorated blood glucose levels,enhanced uterine muscular structure,and improved maternal and fetal performance in *** also displayed tocolytic *** findings underscore the need for further explor

关键词： myometrium gestational diabetes mellitus tocolytic oxytocin Thunbergia laurifolia L.

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Molecular mechanisms of congenital heart disease in down syndrome

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Genes & Diseases 2019年第4期6卷 372-377页

作者： Hui Zhang Lingjuan Liu Jie Tian Department of Cardiology Heart CentreChildren’s Hospital of Chongqing Medical UniversityChongqing 400014China Ministry of Education Key Laboratory of Child Development and disorders Key Laboratory of Pediatrics in ChongqingChongqing International Science and Technology Cooperation Center for Child Development and DisordersChongqing 400014China

Down syndrome(DS),as a typical genomic aneuploidy,is a common cause of various birth defects,among which is congenital heart disease(CHD).40e60%neonates with DS have some kinds of ***,the molecular pathogenic mechanisms of DS associated CHD are still not fully *** review summarizes available studies on DS associated CHD from seven aspects so as to provide a crucial and updated overview of what we known so far in this domain.

关键词： Down syndrome Congenital heart disease Molecular mechanisms

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Parents of children with Autistic Spectrum Disorder (ASD) as Co-therapists: The Therapists’ View

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Psychology Research 2021年第2期11卷 44-55页

作者： Angelique Kotsopoulou Ermioni Papadaki Irene Florou Antigoni Troupou Dimitra Kolosioni Anastasia Georgiou Maria Gyftogianni Aikaterini Gyftogianni Athina Iliopoulou Eleonora Paleodimou Marigo Sakellari Efthimia Koumanioti day centre for children with developmental disorders MessolonghiGreece

Studies on the evaluation by therapists of parental behavior towards their children with Autistic Spectrum Disorder(ASD)and towards the therapists of their children are *** are necessary,however,for enabling parents to become *** present study’s purpose was the evaluation by therapists of the behavior of parents towards their children,of their relationship to therapists,and therapy *** sample consisted of 178 parents of 89 children(72 boys)with ASD,who underwent intensive early intervention at a day centre for developmental *** professional team completed a questionnaire,separately for the mother and father,evaluating the parental attitude towards their children and towards the *** behavior of parents was less satisfactory than *** fathers had difficulties in understanding their child’s problems,and had unrealistic expectations;mothers’behavior towards their children and therapists was better than the fathers’.Mothers had difficulty mostly in the management of the child’s behavior,and did not do well with *** might be difficult for every parent to become *** the child’s difficulties by the mother,adequate handling of feeding and homework,were statistically significant in the good outcome of therapy.

关键词： Autistic Spectrum Disorder(ASD) parents co-therapists stress expectations collaboration homework

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A Tool for Setting Therapeutic Goals by the Multidisciplinary Team for the Preschool Child With ASD （Autism Spectrum Disorder）

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Psychology Research 2014年第5期4卷 354-363页

作者： Kotsopoulou Angelique Georgiou Anastasia Gyftogianni Maria Gyftogianni Kataerina Sakellari Marigo Troupou Antigoni Florou Irene day centre for children with developmental disorders Messolonghi Greece

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Dedifferentiated human umbilical cord mesenchymal stem cell reprogramming of endogenous hSDF-1a expression participates in neural restoration in hypoxic-ischemic brain damagerats

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Genes & Diseases 2021年第3期8卷 331-343页

作者： Zhou Xiaoqin Liu Jia Dai Mengjie Gu Jialu Bi Yang Wang Yuting Hu Huajian Liu Bo Zhang Xiaojun Li Zhongyue Chen Jie Li Tingyu Zhan Xue Department of Gastroenterology Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and Disorders(Chongqing)401122PR China International Science and Technology Cooperation Base of Child Development and Critical disorders Children’sHospital of Chongqing Medical UniversityChongqing401122PR China Department of Pediatric Research Institute Chongqing Key Laboratory of Child Health and NutritionChildren’s Hospital of Chongqing Medical UniversityChongqing401122PR China Department of Neonatology Chongqing Health Center for Womenand Children400021PR China Child Health centre of Northwest Women and children’s Hospital USA

The transplantation of human umbilical cord mesenchymal stem cells(hUC-MSCs)can promote hypoxic-ischemic brain damage(HIBD)nerve repair,but finding suitable seed cells to optimize transplantation and improve treatment efficiency is an urgent problem to be *** this study,we induced hUC-MSCs into dedifferentiated hUC-MSCs(De-hUC-MSCs),and the morphology,stem cell surface markers,proliferation and tri-directional differentiation ability of the De-hUC-MSCs and hUC-MSCs were detected.A whole-gene chip was utilized for genome cluster,gene ontology and KEGG pathway analyses of differentially expressed ***-hUC-MSCs were transplanted into HIBD rats,and behavioral experiments and immunofluorescence assays were used to assess the therapeutic effect.A lentivirus vector for human stromal cell-derived factor-1(hSDF-1a)was constructed,and the role of hSDF-1a in the neuroprotective effect and mechanism of De-hUC-MSCs was ***-hUC-MSCs displayed similar cell morphology,stem cell surface marker expression,cell proliferation and even three-dimensional differentiation ability as hUC-MSCs but exhibited greater treatment potential in *** reprogramming mechanism of hSDF-1a participated in the dedifferentiation *** successfully constructing a stable hSDF-1a cell line,we found that De-hUC-MSCs might participate in nerve repair through the hSDF-1a/CXCR4/PI3K/Akt ***-hUC-MSCs reprogramming of endogenous hSDF-1a expression may mediate the hSDF-1a/CXCR4/PI3K/Akt pathway involved in nerve repair in HIBD rats.

关键词： Dediffer entiation Human umbilicalcord mesenchymal stem cells Hypoxic-ischemic brain damage Neurorestoration Reprogramming Stromal cell-derived factor-1

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