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Improving neuroblastoma risk prediction through a polygenic risk score derived from genome-wide association study-identified loci

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Chinese Journal of Cancer Research 2025年第01期 1-13页

作者： Wenli Zhang Jinhong Zhu Mengzhen Zhang Jiaming Chang Jiabin Liu Liping Chen Xinxin Zhang Haiyan Wu Chunlei Zhou Jing He Department of Pediatric surgery Guangzhou Institute of Pediatrics Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease Guangzhou Women and Children's Medical Center Guangzhou Medical University Department of Clinical Laboratory Biobank Harbin Medical University Cancer Hospital Department of Pathology Children's Hospital of Nanjing Medical University

Objective: Neuroblastoma is the most common extracranial solid tumor in children and has complex genetic underpinnings. Previous genome-wide association studies(GWAss) have identified many loci associated with neuroblastoma susceptibility; however, their application in risk prediction for Chinese children has not been systematically explored. This study seeks to enhance neuroblastoma risk prediction by validating these loci and evaluating their performance in polygenic risk ***: We validated 35 GWAs-identified neuroblastoma susceptibility loci in a cohort of Chinese children,consisting of 402 neuroblastoma patients and 473 healthy controls. Genotyping these polymorphisms was conducted via the TaqMan method. Univariable and multivariable logistic regression analyses revealed the genetic loci significantly associated with neuroblastoma risk. We constructed polygenic risk models by combining these loci and assessed their predictive performance via area under the curve(AUC) analysis. We also established a polygenic risk scoring(PRs) model for risk prediction by adopting the PLINK ***: Fourteen loci, including ten protective polymorphisms from CAsC15, BARD1, LMO1, HsD17B12, and HACE1, and four risk variants from BARD1, RsRC1, CPZ and MMP20 were significantly associated with neuroblastoma risk. Compared with single-gene model, the 8-gene model(AUC=0.72) and 13-gene model(AUC=0.73) demonstrated superior predictive performance. Additionally, a PRs incorporating six significant loci achieved an AUC of 0.66, effectively stratifying individuals into distinct risk categories regarding neuroblastoma susceptibility. A higher PRs was significantly associated with advanced International Neuroblastoma staging system(INss) stages, suggesting its potential for clinical risk ***: Our findings validate multiple loci as neuroblastoma risk factors in Chinese children and demonstrate the utility of polygenic risk models, particularly the PRs, in

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FUBP3 mediates the amyloid-β-induced neuronal NLRP3 expression

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Neural Regeneration Research 2025年第7期20卷 2068-2083页

作者： Jing Yao Yuan Li Xi Liu Wenping Liang Yu Li Liyong Wu Zhe Wang Weihong song The National Clinical Research Center for Geriatric Disease Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina Department of Neurosurgery Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Pediatrics The Second Affiliated Hospital and Yuying Children’s HospitalKey Laboratory of Alzheimer’s Disease of Zhejiang ProvinceInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang ProvinceChina Oujiang Laboratory(Zhejiang Laboratory for Regenerative Medicine Visionand Brain Health)WenzhouZhejiang ProvinceChina

Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangles,in the *** NLRP3 inflammasome may play a role in the transition from amyloid-βdeposition to tau phosphorylation and *** NLRP3 is primarily found in brain microglia,and tau is predominantly located in neurons,it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory ***,we found that neurons also express NLRP3 in vitro and in vivo,and that neuronal NLRP3 regulates tau *** biochemical methods,we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in *** primary neurons and the neuroblastoma cell line Neuro2A,FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-βis *** the brains of aged wild-type mice and a mouse model of Alzheimer's disease,FUBP3 expression was markedly increased in cortical *** analysis suggested that FUBP3 plays a role in neuron-mediated immune *** also found that FUBP3 trimmed the 5′end of DNA fragments that it bound,implying that FUBP3 functions in stress-induced *** findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-β-to–phospho-tau transition than microglial NLRP3,and that amyloid-βfundamentally alters the regulatory mechanism of NLRP3 expression in *** that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice,FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.

关键词： 5′end trimming Alzheimer's disease amyloid-beta amyloid-β-dependent transcription FUBP3 inflammasome inflammation neuron NLRP3 tau transcription factor

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Inhibition of the NLRP3 inflammasome attenuates spiral ganglion neuron degeneration in aminoglycoside-induced hearing loss

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Neural Regeneration Research 2025年第10期20卷 3025-3039页

作者： Jia Fang Zhuangzhuang Li Pengjun Wang Xiaoxu Zhang song Mao Yini Li Dongzhen Yu Xiaoyan Li Yazhi Xing Haibo shi shankai Yin Department of Otolaryngology Head and Neck surgery Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineOtolaryngology Institute of Shanghai Jiao Tong UniversityShanghai Key Laboratory of Sleep Disordered BreathingShanghaiChina Department of Otorhinolaryngology-Head and Neck surgery Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial ***,their use leads to irreversible hearing damage by causing apoptosis of hair cells as their direct *** addition,the hearing damage caused by aminoglycosides involves damage of spiral ganglion neurons upon *** investigate the mechanisms underlying spiral ganglion neuron degeneration induced by aminoglycosides,we used a C57BL/6J mouse model treated with *** found that the mice exhibited auditory deficits following the acute loss of outer hair *** ganglion neurons displayed hallmarks of pyroptosis and exhibited progressive degeneration over *** profiling of these neurons showed significant upregulation of genes associated with inflammation and immune response,particularly those related to the NLRP3 *** of the canonical pyroptotic pathway in spiral ganglion neurons was observed,accompanied by infiltration of macrophages and the release of proinflammatory *** intervention targeting NLRP3 using Mcc950 and genetic intervention using NLRP3 knockout ameliorated spiral ganglion neuron degeneration in the injury *** findings suggest that NLRP3 inflammasome-mediated pyroptosis plays a role in aminoglycoside-induced spiral ganglion neuron *** of this pathway may offer a potential therapeutic strategy for treating sensorineural hearing loss by reducing spiral ganglion neuron degeneration.

关键词： degeneration hearing loss macrophages Mcc950 neuroinflammation NLRP3 inflammasome ototoxicity pyroptosis sensorineural hearing loss spiral ganglion neuron

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Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

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Neural Regeneration Research 2025年第4期20卷 1135-1152页

作者： Yisheng Chen Zhongcheng Fan Zhiwen Luo Xueran Kang Renwen Wan Fangqi Li Weiwei Lin Zhihua Han Beijie Qi Jinrong Lin Yaying sun Jiebin Huang Yuzhen Xu shiyi Chen Department of sport Medicine Huashan HospitalFudan UniversityShanghaiChina Department of Orthopedic surgery Hainan Province Clinical Medical CenterHaikou Affiliated Hospital of Central South University Xiangya School of MedicineHaikouHainan ProvinceChina Department of Basic Medicine Shanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Neurosurgery Second Affiliated Hospital of Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina Department of Orthopedics Shanghai General HospitalSchool of Medicine Shanghai Jiao Tong UniversityShanghaiChina Department of Infectious Diseases Children’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghaiChina Department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina

Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural *** role of the small ubiquitin-like modifier(sUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of *** used machine learning to create the exercise and sUMO-related gene signature(EsLRs).This signature shows how physical activity might help improve the outlook for low-grade glioma and other *** demonstrated the prognostic and immunotherapeutic significance of EsLRs markers,specifically highlighting how murine double minute 2(MDM2),a component of the EsLRs,can be targeted by *** underscores the intricate relationship between natural compounds such as nutlin-3 and immune *** comprehensive CRIsPR screening,we validated the effects of specific EsLRs genes on low-grade glioma *** also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic ***-3a inhibited glioma cell proliferation and activated the p53 *** efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or *** using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway ***,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing *** results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma *** research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.

关键词： exercise and sUMO-related gene signatures(EsLRs) glioblastoma management low-grade glioma natural bioactives neural regeneration physical exercise

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CT whole lung radiomic nomogram:a potential biomarker for lung function evaluation and identification of COPD

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Military Medical Research 2025年第1期12卷 36-47页

作者： Tao-Hu Zhou Xiu-Xiu Zhou Jiong Ni Yan-Qing Ma Fang-Yi Xu Bing Fan Yu Guan Xin-Ang Jiang Xiao-Qing Lin Jie Li Yi Xia Xiang Wang Yun Wang Wen-Jun Huang Wen-Ting Tu Peng Dong Zhao-Bin Li shi-Yuan Liu Li Fan Department of Radiology the Second Affiliated Hospital of Naval Medical UniversityShanghai 200003China school of Medical Imaging Shandong Second Medical UniversityWeifang 261053ShandongChina Department of Radiology School of MedicineTongji HospitalTongji UniversityShanghai 200065China Department of Radiology Zhejiang Province People’s HospitalAffiliated People’s Hospital of Hangzhou Medical CollegeHangzhou 310014China Department of Radiology Sir Run Run Shaw HospitalZhejiang 310018China Jiangxi Provincial People’s hospital the First Affiliated Hospital of Nanchang Medical CollegeNanchang 330006China College of Health sciences and Engineering University of Shanghai for Science and TechnologyShanghai 200093China Department of Radiology the Second People’s Hospital of DeyangDeyang 618000SichuanChina Department of Radiation Oncology Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai 200233China

Background:Computed tomography(CT)plays a great role in characterizing and quantifying changes in lung structure and function of chronic obstructive pulmonary disease(COPD).This study aimed to explore the performance of CT-based whole lung radiomic in discriminating COPD patients and non-COPD ***:This retrospective study was performed on 2785 patients who underwent pulmonary function examination in 5 hospitals and were divided into non-COPD group and COPD *** radiomic features of the whole lung volume were *** absolute shrinkage and selection operator(LAssO)logistic regression was applied for feature selection and radiomic signature construction.A radiomic nomogram was established by combining the radiomic score and clinical *** operating characteristic(ROC)curve analysis and decision curve analysis(DCA)were used to evaluate the predictive performance of the radiomic nomogram in the training,internal validation,and independent external validation ***:Eighteen radiomic features were collected from the whole lung volume to construct a radiomic *** area under the curve(AUC)of the radiomic model in the training,internal,and independent external validation cohorts were 0.888[95%confidence interval(CI)0.869–0.906],0.874(95%CI 0.844–0.904),and 0.846(95%CI 0.822–0.870),*** were higher than the clinical model(AUC were 0.732,0.714,and 0.777,respectively,Pstrated that the nomogram constructed by combining radiomic score,age,sex,height,and smoking status was superior to the clinical factor ***:The intuitive nomogram constructed by CT-based whole-lung radiomic has shown good performance and high accuracy in identifying COPD in this multicenter study.

关键词： Chronic obstructive pulmonary disease(COPD) Computed tomography(CT) Radiomic

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TMED3 promotes prostate cancer via FOXO1a and FOXO3a phosphorylation

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Oncology Research 2025年第1期33卷 161-169页

作者： XIUWANG WEI JIANBO LIANG HUANWEN HUANG DAMING YANG XINXIN WANG XIUJIA WANG CHANGsHENG CHEN KAIQIANG LI TAIsEN PANG BIN HU FENGNING WU Department of Urology The People’s Hospital of Guangxi Zhuang Autonomous RegionNanning530000China Department of Rehabilitation The People’s Hospital of Guangxi Zhuang Autonomous RegionNanning530000China

Background:Transmembrane emp24 trafficking protein 3(TMED3)is associated with the development of several tumors;however,whether TMED3 regulates the progression of prostate cancer remains *** and Methods:short hairpin RNA was performed to repress TMED3 in prostate cancer cells(DU145 cells)and in a prostate cancer mice model to determine its function in prostate cancer in vitro and in ***:In the present study,we found that TMED3 was highly expressed in prostate cancer *** vitro,shTMED3 treatment suppressed the proliferation,invasion,and migration and promoted the apoptosis of DU145 ***,the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed a strong correlation between TMED3 and forkhead box O transcription factor(FOXO)***,TMED3 inhibition efficiently decreased FOXO1a and FOXO3a *** vivo,TMED3 downregulation suppressed the apoptosis,growth,and metastasis of prostate cancer cells via FOXO1a and ***:The present findings show that TMED3 participates in the regulation of prostate cancer progression via FOXO1a and FOXO3a phosphorylation,thereby revealing a novel mechanism underlying prostate cancer development and suggesting that TMED3 inhibition may serve as a novel strategy for prostate cancer treatment.

关键词： Prostate cancer Transmembrane emp24 trafficking protein 3(TMED3) forkhead box O transcription factor(FOXO) Proliferation Apoptosis

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Tilting homeostatic and dyshomeostatic microglial balance in health and disease:transforming growth factor-beta1 as a critical protagonist

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Neural Regeneration Research 2025年第10期20卷 2895-2897页

作者： Nicolas Hugues Yu Luo Department of Molecular and Cellular Biosciences University of CincinnatiCincinnatiOHUSA Neuroscience Graduate Program University of CincinnatiCincinnatiOHUSA Division of Immunobiology Cincinnati Children’s Hospital Medical CenterUniversity of Cincinnati College of MedicineCincinnatiOHUSA

Adult microglia,by continuously sensing changes in their environment and communicating with nearly all brain cell types,are considered to be the immune sentinels of the *** the healthy central nervous system(CNs),microglia display a unique molecular homeostatic signature(i.e.,Tmem119,P2ry12,sall1,siglech,Gpr34,and Hexb)(Figure 1A).

关键词： Figure signature critical

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Reconstruction characteristics of gut microbiota from patients with type 1 diabetes affect the phenotypic reproducibility of glucose metabolism in mice

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science China(Life sciences) 2025年第1期68卷 176-188页

作者： Zhiyi Wang Mengxue Gong Yuanyuan Fang Huijuan Yuan Chenhong Zhang state Key Laboratory of Microbial Metabolism School of Life Sciences and BiotechnologyShanghai Jiao Tong UniversityShanghai 200240China Department of Endocrinology Henan Provincial People’s HospitalPeople’s Hospital of Zhengzhou UniversityZhengzhou 450003China

The human microbiota-associated(HMA)mice model,especially the germ-free(GF)-humanized mice,has been widely used to probe the causal relationships between gut microbiota and human diseases such as type 1 diabetes(T1D).However,most studies have not clarified the extent to which the reconstruction of the human donor microbiota in recipient mice correlates with corresponding phenotypic *** this study,we transplanted fecal microbiota from five patients with T1D and four healthy people into GF mice,and microbiota from each donor were transplanted into 10 *** with similar microbiota structure to the donor exhibited better phenotypic *** characteristics of the microbial community assembly of donors also influenced the phenotypic reproducibility in mice,and individuals with a higher proportion of stochastic processes showed more severe *** enriched in patients with T1D had a stronger colonization potential in mice with impaired glucose metabolism,and microbiota functional features related to T1D were better reproduced in these *** indicates that assembly traits and colonization efficacy of microbiota influence phenotypic reproducibility in GF-humanized *** findings provide important insights for using HMA mice models to explore links between gut microbiota and human diseases.

关键词： gut microbiome human microbiota-associated animal model type 1 diabetes

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CAF-derived exosome-miR-3124-5p promotes malignant biological processes in NsCLC via the TOLLIP/TLR4-MyD88-NF-κB pathway

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Oncology Research 2025年第1期33卷 133-148页

作者： TAO sUN QINGHUA sONG HUA LIU Department of Respiratory and Critical Care Medicine Affiliated Hospital of Nantong UniversityMedical School of Nantong UniversityNantong226001China Department of Emergency The People’s Hospital of RugaoNantong226500China Department of Haematology The People’s Hospital of RugaoNantong226500China

Background:Lung cancer is a life-threatening disease that occurs worldwide,but is especially common in *** crucial role of the tumour microenvironment(TME)in non-small cell lung cancer(NsCLC)has attracted recent ***-associated fibroblasts(CAFs)are the main factors that contribute to the TME function,and CAF exosomes are closely linked to ***:The expression levels of miR-3124-5p and Toll-interacting protein(TOLLIP)were analysed by bioinformatics prediction combined with RT-qPCR/Western Blot *** were isolated and identified from clinical NsCLC *** electron microscopy and Western Blot were used to identify exosomes from these *** in proliferation(CCK-8 and clone formation),migration(wound healing),and invasion(transwell)of NsCLC cells were *** Luciferase reporter test was applied to clarify the binding of miR-3124-5p to *** TOLLIP/TLR4/MyD88/NF-κB pathway proteins were determined using Western blot ***:MiR-3124-5p is overexpressed in clinical tissues and cells of ***-3124-5p was dramatically enriched in CAF-derived *** experiments revealed that CAFs delivered miR-3124-5p into NsCLC cells via exosomes,stimulating cancer cell ***-3124-5p acted as a sponge to negatively regulate TOLLIP expression,which activated the TLR4/MyD88/NF-κB axis to promote the occurrence and development of *** salvage tests were performed to determine whether CAF-exosome-derived miR-3124-5p plays a pro-cancer role in NsCLC by affecting the TOLLIP signalling ***:These results provide an interesting direction for the diagnosis and therapy of NsCLC.

关键词： Non-small cell lung cancer(NsCLC) Cancer-associated fibroblasts(CAFs) Exosomes miR-3124-5p Toll-interacting protein(TOLLIP)

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FK506 contributes to peripheral nerve regeneration by inhibiting neuroinflammatory responses and promoting neuron survival

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Neural Regeneration Research 2025年第7期20卷 2108-2115页

作者： Yuhui Kou Zongxue Jin Yusong Yuan Bo Ma Wenyong Xie Na Han Department of Trauma and Orthopedics Peking University People’s HospitalBeijingChina National Center for Trauma Medicine Peking University People’s HospitalBeijingChina Key Laboratory of Trauma and Neural Regeneration(Peking University) Ministry of EducationBeijingChina Trauma Medicine Center Peking University People’s HospitalBeijingChina Department of Orthopedics China-Japan Friendship HospitalBeijingChina

FK506(Tacrolimus)is a systemic immunosuppressant approved by the *** and Drug ***506 has been shown to promote peripheral nerve regeneration,however,its precise mechanism of action and its pathways remain *** this study,we established a rat model of sciatic nerve injury and found that FK506 improved the morphology of the injured sciatic nerve,increased the numbers of motor and sensory neurons,reduced inflammatory responses,markedly improved the conduction function of the injured nerve,and promoted motor function *** findings suggest that FK506 promotes peripheral nerve structure recovery and functional regeneration by reducing the intensity of inflammation after neuronal injury and increasing the number of surviving neurons.

关键词： FK506 inflammation motor neurons nerve regeneration neuron peripheral nerve injury sensory neurons

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