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System analysis based on the T cell exhaustion‑related genes identifies CD38 as a novel therapy target for ovarian cancer

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Oncology Research 2023年第4期31卷 591-604页

作者： TIANMING SHI RONGRONG YAN MI HAN Department of Gynecologic Oncology The International Peace Maternity and Child Health HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Shanghai Key Laboratory of Embryo Original Diseases School of MedicineShanghai Jiao Tong UniversityShanghaiChina

Ovarian cancer(OV)is highly heterogeneous tumor with a very poor *** increasingly show that T cell exhaustion is prognostically relevant in *** aim of this study was to dissect the heterogeneity of T cell subclusters in OV through single cell transcriptomic *** single RNA-sequencing(scRNA-seq)data of five OV patients were analyzed,and six major cell clusters were identified after threshold *** clustering of T cell-associated clusters revealed four *** related to oxidative phosphorylation,G2M checkpoint,JAK-STAT and MAPK signaling were significantly activated,while the p53 pathway was inhibited in the CD8+exhausted T *** standard marker genes of CD8+T cell exhaustion were screened to develop a T-cell related gene score(TRS)based on random forest plots in TCGA *** patients with low TRS have better prognosis compared to the patients with high TRS in both TCGA and *** addition,most genes included in the TRS showed significant differences in expression levels between the high-and low-risk *** cell infiltration was analyzed using the MCPcounter and xCell algorithms,which revealed significant differences between the two risk groups,indicating that the different prognoses may stem from the respective immune *** addition,CD38 knockdown in OV cell lines increased apoptosis and inhibited invasion in ***,we performed a drug sensitivity analysis and identified six potential drug candidates for *** summarize,we identified the heterogeneity and clinical significance of T cell exhaustion in OV and built a superior prognostic model based on T cell exhaustion genes,which can contribute to the development of more precise and effective therapies.

关键词： CD8+T exhausted Ovarian cancer Prognostic model Single cell sequencing

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Cardiac troponin I R193H mutant interacts with HDAC1 to repress phosphodiesterase 4D expression in cardiomyocytes

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Genes & Diseases 2021年第4期8卷 569-579页

作者： Weian Zhao Qian lu Jing Luo Bo Pan Ling-Juan Liu Jie Tian Department of Anesthesiology The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong Province510080PR China Department of Cardiology Children’s Hospital of Chongqing Medical UniversityMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of PediatricsChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing401122PR China

Cardiac Troponin I(cTnI)is a subunit of the thin filament involved in regulation of heart *** cTnI accounts for most genetic mutations associated with restric-tive cardiomyopathy(RCM).We previously found phosphodiesterase 4D(PDE4D)decreased in RCM mice with cTnIR193H mutation and the mutant cTnI might be involved in PDE4D *** study aims to elucidate a novel role of cTnIR193H mutant as a gene ***-sion of cTnIR193H mutant in cardiomyocytes showed decrease in PDED4D protein expression,while the enrichment of histone deacetylase 1(HDAC1)was increased along with decreases in acetylated lysine 4(acH3K4)and 9(acH3K9)levels in the PDE4D ***1 overex-pression could also downregulate PDE4D via reducing acH3K4 and acH3K9 ***-IP assays showed that cTnIR193H mutant owed increased binding ability to HDAC1 compared with wild type *** as a HDAC1 inhibitor could diminish the strength of cTnIR193H-HDAC1 inter-actions and alleviate the reduction in PDE4D ***,our data indicated that cTnIR193H mutant could repress PDE4D expression in cardiomyocytes through HDAC1 associ-ated histone deacetylation *** the typical function of cTnI in cytoplasm,our study suggested a novel role of cTnI mutants in nuclei in regulating gene expression.

关键词： cTnIR93H EGCG HDAC1 Histone modifications PDE4D reduction

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Retinoic acid can improve autophagy through depression of the PI3K-Akt-mTOR signaling pathway via RARαto restore spermatogenesis in cryptorchid infertile rats

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Genes & Diseases 2022年第5期9卷 1368-1377页

作者： Chunlan Long Yu Zhou Lianju Shen Yihang Yu Dong Hu Xing Liu Tao Lin Dawei He Tao Xu Deying Zhang Jing Zhu Guanghui Wei Chongqing Key Laboratory of children Urogenital Development and Tissue Engineering 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 PediatricsChongqing 400014PR China Department of Urology Children’s Hospital of Chongqing Medical UniversityChongqing 400014PR China Bio-manufacturing Center Department of Mechanical EngineeringTsinghua UniversityBeijing 100084PR China

Cryptorchidism-caused adult infertility is a common component of idiopathic reasons for male *** acid(RA)has a vital effect on the spermatogenesis ***,we found that the expression of c-Kit,Stra8,and Sycp3 could be up-regulated via the activation of retinoic acid receptorα(RARα)after RA supplementation in neonatal cryptorchid infertile *** also demonstrated that the protein expression of PI3K,p-Akt/pan-Akt,and p-mTOR/mTOR was higher in cryptorchid than in normal testes,and could be suppressed with RA in *** RA treatment in infertile cryptorchid testis in vivo,the levels of the autophagy proteins LC3 and Beclin1 increased and those of P62 *** tracer indicated that the permeability of blood-testis barrier(BTB)in cryptorchid rats decreased after RA ***,after blocking the RARαwith AR7(an RARαantagonist)in testicle culture in vitro,we observed that compared with normal testes,the PI3K-Akt-mTOR signaling pathway and the autophagy pathway was increased and decreased,respectively,which were coincident with cryptorchisd testes in ***,the appropriate concentrations of RA treatment could depress the PI3K-Akt-mTOR signaling pathway and improve the autophagy *** results confirmed that RA can rehabilitate BTB function and drive key protein levels in spermatogonial differentiation through depressing the PI3K-Akt-mTOR signaling pathway via RARα.

关键词： Cryptorchidism Male infertility Retinoic acid Spermatogenesis Testis

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Incidence characteristics of testicular microlithiasis and its association with risk of primary testicular tumors in children: a systematic review and meta-analysis

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World Journal of Pediatrics 2020年第6期16卷 585-597页

作者： Cheng-Jun Yu Jian-Dong Lu Jie Zhao Yi Wei Tian-Xin Zhao Tao Lin •Da-Wei He Sheng-De Wu Guang-Hui Wei Department of Urology Children's Hospital of Chongqing Medical UniversityChongqingChina Chongqing Key Laboratory of children Urogenital Development and Tissue Engineering ChongqingChina National Clinical Research Center for child Health and Disorders ChongqingChina Chongqing Key Laboratory of Pediatrics Chongqing Room 806.Kejiao Building(No.6)No.136.Zhongshan 2nd RoadYuzhong DistrictChongqing.China China international Science and Technology Cooperation Base of child Development and Critical Disorders ChongqingChina Ministry of Education Key Laboratory of child Development and Disorders ChongqingChina

Background To systematically evaluate the incidence characteristics of testicular microlithiasis(TM)in children and its association with primary testicular tumors(PTT).Methods A systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis(PRISMA)statement.A priori protocol was registered in the PROSPERO database(CRD42018111119),and a literature search of all relevant studies published until February 2019 was ***,retrospective cohort,or cross-sectional studies containing ultrasonography(US)data on the incidence of TM or the association between TM and PTT were eligible for *** Of the 102 identified articles,18 studies involving 58,195 children were included in the final *** overall incidence of TM in children with additional risk factors for FTT was 2.1%.In children,the proportion of left TM in unilateral cases was 55.7%,the frequency of bilateral TM was 69.0%,and proportion of classic TM was 71.8%[95%confidence interval(Cl)62.4-81.1%,P=0.0,72=0.0%].About 93.5%of TM remained unchanged,and newly detected PTT rate was very low(4/296)during *** overall risk ratio of TM in children with a concurrent diagnosis of PTT was 15.46(95%Cl 6.93-34.47,Pchildren is highly ***,TM is usually bilateral,of the classic type,and remains stable or unchanged at *** patients with TM and contributing factors for PTT have an increased risk for PTT;however,there is no evidence to support mandatory US surveillance of children with TM.

关键词： children Incidence Primary testicular tumors Testicular microlithiasis

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NLRP3 inflammasome as a novel therapeutic target for Alzheimer’s disease

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2098-2099页

作者： Yun Zhang Zhifang Dong Weihong Song Townsend Family Laboratories Department of PsychiatryThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada 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 UniversityChongqingChina

In a recent publication in Nature,Ising et *** the effect of the NLRP3 inflammasome on Aβ-induced tau pathology in Alzheimer’s disease(AD).The findings indicate that NLRP3 may be a novel target for the treatment of AD.

关键词： Alzheimer Aβ tau

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众脑之力:通过开放神经影像数据和大规模协作催化神经精神疾病的创新发现

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Science Bulletin 2024年第10期69卷 1536-1555页

作者：鲁彬陈骁 Francisco Xavier Castellanos Paul M.Thompson 左西年臧玉峰严超赣 CAS Key Laboratory of Behavioral Science Institute of PsychologyBeijing 100101China Department of Psychology University of Chinese Academy of SciencesBeijing 100101China Department of child and Adolescent Psychiatry NYU Grossman School of MedicineNew York 10016USA d Nathan Kline Institute for Psychiatric Research Orangeburg 10962USA Imaging Genetics Center Mark&Mary Stevens Institute for Neuroimaging&InformaticsKeck School of MedicineUniversity of Southern CaliforniaLos Angeles 90033USA Developmental Population Neuroscience Research Center IDG/McGovern Institute for Brain ResearchBeijing Normal UniversityBeijing 100875China National Basic Science Data Center Beijing 100190China Centre for Cognition and Brain Disorders The Affiliated Hospital of Hangzhou Normal UniversityHangzhou 310004China Institute of Psychological Science Hangzhou Normal UniversityHangzhou 310030China Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairment Hangzhou 311121China international Big-Data Center for Depression Research Institute of PsychologyChinese Academy of SciencesBeijing 100101China Magnetic Resonance Imaging Research Center Institute of PsychologyChinese Academy of SciencesBeijing 100101China

Recent advances in open neuroimaging data are enhancing our comprehension of neuropsychiatric *** pooling images from various cohorts,statistical power has increased,enabling the detection of subtle abnormalities and robust associations,and fostering new research *** collaborations in imaging have furthered our knowledge of the neurobiological foundations of brain disorders and aided in imaging-based prediction for more targeted ***-scale magnetic resonance imaging initiatives are driving innovation in analytics and supporting generalizable psychiatric *** also emphasize the significant role of big data in understanding neural mechanisms and in the early identification and precise treatment of neuropsychiatric ***,challenges such as data harmonization across different sites,privacy protection,and effective data sharing must be *** proper governance and open science practices,we conclude with a projection of how large-scale imaging resources and collaborations could revolutionize diagnosis,treatment selection,and outcome prediction,contributing to optimal brain health.

关键词： Magnetic resonance imaging Neuropsychiatric disorders Big data Open science Artificial intelligence

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Phenotypic characterization of patients with activated PI3Kδ syndrome 1 presenting with features of systemic lupus erythematosus

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Genes & Diseases 2021年第6期8卷 907-917页

作者： Yanping Wang Qiuyun Yang Xuemei Chen Wenjing Tang Lina Zhou Zhi Chen Yunfei An Zhiyong Zhang Xuemei Tang Xiaodong Zhao National Clinical Research Center for child Health and Disorders(Chongqing) Children’s Hospital ofChongqing Medical UniversityChongqing400014PR China China international Science and Technology Cooperation Base of child Development and Critical Disorders Children’s Hospital of Chongqing Medical UniversityChongqing400014PR China Chongqing Key Laboratory of child Infection and Immunity Children’s Hospital of Chongqing Medical UniversityChongqing400014PR China Division of Rheumatology and Immunology Children’s Hospital of Chongqing Medical UniversityChongqing400014PR China

Activated phosphoinositide 3-kinase d syndrome 1(APDS1)is a primary immunode-ficiency disease caused by gain-of-function mutations in *** features of autoimmune disease have been reported in patients with *** this study,we reported three patients with APDS1 presenting with systemic lupus erythematosus(SLE)*** clinical manifestations included recurrent respiratory tract infection,lymphoproliferation,Coombs-positive hemolytic anemia,decreased complement fractions,positive antinuclear antibodies,renal complications related to SLE associated diseases,which met the clinical spectrum of APDS1 and the classification criteria of *** immunological phenotype included an inversion in the CD4:CD8 ratio,an increase in both non-circulating Tfh CD4^(+)memory T and circulating Tfh populations,a low level of recent thymic emigrant T cells,overexpression of CD57 on T cells,and a decrease in B cells with fewer antibody class switch *** phenotypes detected in patients with APDS1 presenting with SLE were resemble that in patients with APDS1 presenting without ***,we described the effect of glucocorticoids and rapamycin therapy on patients with *** phosphorylation of S6 at Ser235/236 was inhibited in patients with APDS1 who underwent glucocorticoids therapy,including two who presented with SLE *** phosphorylation of AKT at Ser473 and phosphorylation of S6 at Ser235/236 were inhibited in other patients with APDS1 who underwent rapamycin ***,we showed the coexistence of immunodeficiency and SLE phenotype in APDS1,and the inhibition of rapamycin in activated Akt-mTOR signaling pathway.

关键词： Activated phosphoinositide 3-kinase dsyndrome 1 Autoimmune disease Immunosuppressive therapy PIK3CD Systemic lupus erythematosus

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Clinical and socioeconomic factors associated with delayed orchidopexy in cryptorchid boys in China: a retrospective study of 2423 cases

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Asian Journal of Andrology 2019年第3期21卷 304-308页

作者： Tian-Xin Zhao Bin Liu Yue-Xin Wei Yi Wei Xiang-Liang Tang Lian-Ju Shen Chun-Lan Long Tao Lin Sheng-De Wu Guang-Hui Wei Department of Urology Children's Hospital of Chongqing Medical University Chongqing 400014 China Chongqing Key Laboratory of children Urogenital Development and Tissue Engineering Chongqing 400014 China Ministry of Education Key Laboratory of child Development and Disorders Chongqing 400014 China China international Science and Technology Cooperation Base of child Development and Critical Disorders Chongqing 400014 China Chongqing Key Laboratory of Pediatrics Chongqing 400014 China

We investigated the associations of clinical and socioeconomic factors with delayed orchidopexy for cryptorchidism in China. A retrospective study was conducted on cryptorchid boys who underwent orchidopexy at children's Hospital at Chongqing Medical University in China from January 2012 to December 2017. Of 2423 patients, 410 (16.9%) received timely repair by 18 months of age, beyond which surgery was considered delayed. Univariate analysis suggested that the laterality of cryptorchidism (P = 0.001), comorbidities including inguinal hernia/scrotal hydrocele (P < 0.001) or urinary tract disease (P = 0.016), and whether patients lived in a poverty county (P < 0.001) could influence whether orchidopexy was timely or delayed. Logistic regression analysis suggested that the following factors were associated with delayed repair: unilateral rather than bilateral cryptorchidism (odds ratio [OR]= 1.752, P < 0.001), absence of inguinal hernia or hydrocele (OR = 2.027, P = 0.019), absence of urinary tract disease (OR = 3.712, P < 0.001), and living in a poverty county (OR = 2.005, P < 0.001). The duration of postoperative hospital stay and hospital costs increased with the patient's age at the time of surgery.

关键词： birth defect children congenital disorder cryptorchidism orchidopexy poverty

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A combination of follicle stimulating hormone, estradiol and age is associated with the pregnancy outcome for women undergoing assisted reproduction: a retrospective cohort analysis

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Science China(Life Sciences) 2019年第1期62卷 112-118页

作者： Ziru Jiang Li Jin Weihui Shi Ji Xi Yulian Hu Xinmei Liu Jianzhong Sheng Guolian Ding Hefeng Huang The international Peace Maternity and child Health Hospital School of Medicine Shanghai Jiao Tong University Institute of Embryo-Fetal Original Adult Disease Shanghai Key Laboratory for Reproductive Medicine School of Medicine Shanghai Jiao Tong University Department of Pathology and Pathophysiology School of Medicine Zhejiang University

To investigate the effect of basal hormone levels including follicle stimulating hormone(FSH) and estradiol(E2) and age on the pregnancy outcomes in women undergoing in vitro fertilization and embryo transfer(IVF-ET), we designed a retrospective cohort analysis and collected information of patients undergoing IVF between January 2014 and April 2017. We found that young women had much better pregnancy outcomes than older women regardless of the hormone levels. The pregnancy outcomes declined in young women with high basal E2, even though they had normal FSH. Older women with higher FSH had a worse outcome of pregnancy, especially with increased E2 level. The results suggest that a combination of FSH, E2 and age could effectively predict the pregnancy outcome for women undergoing IVF-ET, and we should encourage infertile women with diminished ovarian reserve, especially young infertile women, to try the assisted reproduction as early as possible. After 40-yearold, the cost-benefit ratio should be considered according to the ovarian function.

关键词： follicle stimulating hormone estradiol age pregnancy outcome assisted reproduction

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DEHP exposure destroys blood-testis barrier (BTB) integrity of immature testes through excessive ROS-mediated autophagy

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Genes & Diseases 2018年第3期5卷 263-274页

作者： W.E.I.Yi Tang Xiang-Liang Zhou Yu Liu Bin Shen Lian-Ju Long Chun-lan L.I.N.Tao H.E.Da-wei W.U.Sheng-de W.E.I.Guang-hui Department of Urology Children’s Hospital of Chongqing Medical UniversityZhongshan 2RDYuzhong DistrictChongqing400014China Chongqing Key Laboratory of children Urogenital Development and Tissue Engineering China Ministry of Education Key Laboratory of child Development and Disorders China China international Science and Technology Cooperation Base of child Development and Critical Disorders China Chongqing Key Laboratory of Pediatrics Chongqing China

Di-(2-ethylhexyl)phthalate(DEHP),is known to impair testicular functions and ***,its effects on immature testis Blood-testis barrier(BTB)and the underlying mechanisms remain *** constructed a rat model to investigate the roles of autophagy in BTB toxicity induced by *** rats were developmentally exposed to 0,250 and 500 mg/kg DEHP via intragastric administration from postnatal day(PND)1 to PND *** morphology,expressions of BTB junction proteins and autophagy related proteins were *** addition,expressions of oxidative stress markers were also *** results demonstrated that developmental DEHP exposure induced decreasing organ coefficients of immature testes and severe testicular damage in *** expressions of junctional proteins were down-regulated significantly after DEHP ***,DEHP simultaneously increased the number of autophagosomes and the levels of autophagy marker LC3-II and p62,suggesting that the accumulated autophagosomes resulted from impaired autophagy ***,the expressions of HO-1 and SOD levels remarkably decreased after DEHP *** E and C could alleviate the DEHP-induced oxidative stress,reverse the autophagy defect and restore the BTB *** together,DEHP exposure destroys immature testis blood-testis barrier(BTB)integrity through excessive ROSmediated autophagy.

关键词： Autophagy BTB DEHP Immature testis Oxidative stress

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