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Small extracellular vesicles from hypoxia-preconditioned bone marrow mesenchymal stem cells attenuate spinal cord injury via miR-146a-5p-mediated regulation of macrophage polarization

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Neural Regeneration Research 2024年第10期19卷 2259-2269页

作者： Zeyan Liang Zhelun Yang Haishu Xie Jian Rao Xiongjie Xu Yike Lin Chunhua Wang Chunmei Chen Department of Neurosurgery Fujian Medical University Union HospitalFuzhouFujian ProvinceChina fujian Neurosurgical institute FuzhouFujian ProvinceChina

Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)help mediate the beneficial effects conferred by MSC transplantation following spinal cord injury.Strikingly,hypoxia-preconditioned bone marrow mesenchymal stem cell-derived SEVs(HSEVs)exhibit increased therapeutic potency.We thus explored the role of HSEVs in macrophage immune regulation after spinal cord injury in rats and their significance in spinal cord repair.SEVs or HSEVs were isolated from bone marrow MSC supernatants by density gradient ultracentrifugation.HSEV administration to rats via tail vein injection after spinal cord injury reduced the lesion area and attenuated spinal cord inflammation.HSEVs regulate macrophage polarization towards the M2 phenotype in vivo and in vitro.Micro RNA sequencing and bioinformatics analyses of SEVs and HSEVs revealed that mi R-146a-5p is a potent mediator of macrophage polarization that targets interleukin-1 receptor-associated kinase 1.Reducing mi R-146a-5p expression in HSEVs partially attenuated macrophage polarization.Our data suggest that HSEVs attenuate spinal cord inflammation and injury in rats by transporting mi R-146a-5p,which alters macrophage polarization.This study provides new insights into the application of HSEVs as a therapeutic tool for spinal cord injury.

关键词： bone marrow mesenchymal stem cells hypoxia preconditioning interleukin-1 receptor-associated kinase 1 macrophages mesenchymal stem cells small extracellular vesicles spinal cord injury

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Pien Tze Huang Inhibits Proliferation of Colorectal Cancer Cells through Suppressing PNO1 Expression and Activating p53/p21 Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第6期30卷 515-524页

作者： CAO Liu-jing LIU Li-ya CHEN You-qin HAN Yu-ying WEI Li-hui YAO Meng-ying FANG Yi WU Mei-zhu CHENG Ying Thomas J.Sferra LIU Hui-xin LI Li PENG Jun SHEN A-ling Clinical Research institute the Second Affiliated Hospital&Academy of Integrative MedicineFujian University of Traditional Chinese MedicineFuzhou350122China fujian Key Laboratory of Integrative Medicine in geriatrics Fujian University of Traditional Chinese MedicineFuzhou350122China Department of Pediatrics Case Western Reserve University School of MedicineUH Rainbow Babies and Children’s HospitalClevelandOH44106USA Innovation and Transformation Center Fujian University of Traditional Chinese MedicineFuzhou350122China Department of Health Management Fujian Provincial HospitalShengli Clinical College of Fujian Medical UniversityFuzhou000000China

ObjectiveTo explore the regulatory effect of Pien Tze Huang (PZH) on targeting partner of NOB1 (PNO1) and it’s down-stream mediators in colorectal cancer (CRC) cells.MethodsQuantitative polymerase chain reaction was performed to determine mRNA levels of PNO1, TP53, and CDKN1A. Western blotting was performed to determine protein levels of PNO1, p53, and p21. HCT-8 cells were transduced with a lentivirus over-expressing PNO1. Colony formation assay was used to detect cell survival in PNO1 overexpression of HCT-8 cells after PZH treatment. Cell-cycle distribution, cell viability and cell apoptosis were performed to identify the effect of PNO1 overexpression on cell proliferation and apoptosis of HCT-8 cells after PZH treatment. Xenograft BALB/c nude mice bearing HCT116 cells transduced with sh-PNO1 or sh-Ctrl lentivirus were evaluated. Western blot assay was performed to detect PNO1, p53, p21 and PCNA expression in tumor sections. Terminal deoxynucleotidyl transferase dUTP nick end labling (TUNEL) assay was used to determine the apoptotic cells in tissues.ResultsPZH treatment decreased cell viability, down-regulated PNO1 expression, and up-regulated p53 and p21 expressions in HCT-8 cells (P<0.05). PNO1 overexpression attenuated the effects of PZH treatment, including the expression of p53 and p21, cell growth, cell viability, cell cycle arrest and cell apoptosis in vitro (P<0.05). PNO1 knockdown eliminated the effects of PZH treatment on tumor growth, inhibiting cell proliferation inhibition and apoptosis induction in vivo (P<0.05). Similarly, PNO1 knockdown attenuated the effects of PZH treatment on the down-regulation of PNO1 and up-regulation of p53 and p21 in vivo (P<0.05).ConclusionThe mechanism by which PZH induces its CRC anti-proliferative effect is at least in part by regulating the expression of PNO1 and its downstream targets p53 and p21.

关键词： colorectal cancer Pien Tze Huang Chinese medicine partner of NOB1 proliferation p53/p21 pathway

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Exosomes derived from microglia overexpressing miR-124-3p alleviate neuronal endoplasmic reticulum stress damage after repetitive mild traumatic brain injury

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Neural Regeneration Research 2024年第9期19卷 2010-2018页

作者： Yan Wang Dai Li Lan Zhang Zhenyu Yin Zhaoli Han Xintong Ge Meimei Li Jing Zhao Shishuang Zhang Yan Zuo Xiangyang Xiong Han Gao Qiang Liu Fanglian Chen Ping Lei Department of geriatrics Tianjin Medical University General HospitalTianjinChina Tianjin geriatrics institute Tianjin Medical University General HospitalTianjinChina Tianjin Neurological institute Tianjin Medical University General HospitalTianjinChina

We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains unclear.In this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of miR-124-3p.We found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum stress.Furthermore,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured neurons.Finally,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly reduced.These findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress.Therefore,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.

关键词： apoptosis C/EBP homologous protein endoplasmic reticulum stress exosome inositol-requiring enzyme 1α microglia miR-124-3p neuron repetitive mild traumatic brain injury X-box binding protein 1

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Efficient Spin-Flip between Charge-Transfer States for High-Performance Electroluminescence, without an Intermediate Locally Excited State

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Research 2024年第1期2023卷 339-349页

作者： Donghai Zhang Shanshan Jiang Xiaodong Tao Fulin Lin Lingyi Meng Xu-Lin Chen Can-Zhong Lu State Key Laboratory of Structural Chemistry Fujian Institute of Research on the Structure of MatterChinese Academy of SciencesFuzhouFujian 350002China fujian Science and Technology Innovation Laboratory for Optoelectronic Information of China FuzhouFujian 350108China Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials Xiamen Institute of Rare Earth MaterialsHaixi InstitutesChinese Academy of SciencesXiamenFujian 361021China University of Chinese Academy of Sciences Beijing 100049China

Thermally activated delayed fluorescence(TADF)materials with both high photoluminescence quantum yield(PLQY)and fast reverse intersystem crossing(RISC)are strongly desired to realize efficient and stable organic light-emitting diodes(OLEDs).Control of excited-state dynamics via molecular design plays a central role in optimizing the PLQY and RISC rate of TADF materials but remains challenging.Here,3 TADF emitters possessing similar molecular structures,similar high PLQYs(89.5%to 96.3%),and approximate energy levels of the lowest excited singlet states(S_(1)),but significantly different spin-flipping RISC rates(0.03×10^(6) s^(−1) vs.2.26×10^(6) s^(−1))and exciton lifetime(297.1 to 332.8μs vs.6.0μs)were systematically synthesized to deeply investigate the feasibility of spin-flip between charge-transfer excited states(^(3)CT–^(1)CT)transition.

关键词： transition lifetime desired

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Alterations in nasal microbiota of patients with amyotrophic lateral sclerosis

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Chinese Medical Journal 2024年第2期137卷 162-171页

作者： Kaixiong Liu Qifu Guo Ying Ding Li Luo Jianchai Huang Qijie Zhang Department of Respiratory and Critical Care Medicine The First Affiliated HospitalFujian Medical UniversityFuzhouFujian 350005China Department of Respiratory and Critical Care MedicineNational Regional Medical CenterBinhai Campus of The First Affiliated HospitalFujian Medical UniversityFuzhouFujian 350212China Department of Neurology Fujian Institute of NeurologyThe First Affiliated HospitalFujian Medical UniversityFuzhouFujian 350005China Department of NeurologyNational Regional Medical CenterBinhai Campus of The First Affiliated HospitalFujian Medical UniversityFuzhouFujian 350212China

Background:Links between alterations in gut microbiota composition and amyotrophic lateral sclerosis(ALS)have previously been reported.This study aimed to examine the microbiota in the nasal cavity of ALS.Methods:Sixty-six ALS patients and 40 healthy caregivers who live in close proximity with patients were enrolled.High throughput metagenomic sequencing of the 16S ribosomal deoxyribonucleic acid(rDNA)gene V3-V4 region of nasal microbiota was used to characterize the alpha and beta diversity and relative abundance of bacterial taxa,predict function,and conduct correlation analysis between specific taxa and clinical features.Results:The nasal microbiome of ALS patients showed lower alpha diversity than that of corresponding healthy family members.Genera Gaiella,Sphingomonas,Polaribacter_1,Lachnospiraceae_NK4A136_group,Klebsiella,and Alistipes were differentially enriched in ALS patients compared to controls.Nasal microbiota composition in ALS patients significantly differed from that in healthy subjects(unweighted UniFrac P=0.001),while Linear discriminant analysis Effect Size(LEfSe)analysis indicated that Bacteroidetes and Firmicutes dominated healthy nasal communities at the phylum level,whereas Actinobacteria was the predominant phylum and Thermoleophilia was the predominant class in ALS patients.Genus Faecalibacterium and Alistipes were positively correlated with ALS functional rating scale revised(ALSFRS-R;r_(s)=0.349,P=0.020 and r_(s)=0.393,P=0.008),while Prevotella-9 and Bacteroides operational taxonomic units(OTUs)were positively associated with lung function(FVC)in ALS patients(r_(s)=0.304,P=0.045,and r_(s)=0.300,P=0.048,respectively).Prevotella-1 was positively correlated with white blood cell counts(WBC,r_(s)=0.347,P=0.021),neutrophil percentage(Neu%,r_(s)=0.428,P=0.004),and neutrophil-to-lymphocyte ratio(NLR,r_(s)=0.411,P=0.006),but negatively correlated with lymphocyte percentage(Lym%,r_(s)=-0.408,P=0.006).In contrast,Streptococcus was negatively associated with Neu%(r_(s)=-0.445,P=0.003)and NLR(r_(s)

关键词： Amyotrophic lateral sclerosis Nasal microbiota Dysbiosis Inflammation

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Artificial intelligence for the detection of glaucoma with SD-OCT images:a systematic review and Meta-analysis

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International Journal of Ophthalmology(English edition) 2024年第3期17卷 408-419页

作者： Nan-Nan Shi Jing Li Guang-Hui Liu Ming-Fang Cao Department of Ophthalmology Affiliated People’s Hospital(Fujian Provincial People’s Hospital)Fujian University of Traditional Chinese MedicineFuzhou 350004Fujian ProvinceChina Eye institute of Integrated Chinese and Western Medicine Fujian University of Traditional Chinese MedicineFuzhou 350004Fujian ProvinceChina

●AIM:To quantify the performance of artificial intelligence(AI)in detecting glaucoma with spectral-domain optical coherence tomography(SD-OCT)images.●METHODS:Electronic databases including PubMed,Embase,Scopus,ScienceDirect,ProQuest and Cochrane Library were searched before May 31,2023 which adopted AI for glaucoma detection with SD-OCT images.All pieces of the literature were screened and extracted by two investigators.Meta-analysis,Meta-regression,subgroup,and publication of bias were conducted by Stata16.0.The risk of bias assessment was performed in Revman5.4 using the QUADAS-2 tool.●RESULTS:Twenty studies and 51 models were selected for systematic review and Meta-analysis.The pooled sensitivity and specificity were 0.91(95%CI:0.86–0.94,I2=94.67%),0.90(95%CI:0.87–0.92,I2=89.24%).The pooled positive likelihood ratio(PLR)and negative likelihood ratio(NLR)were 8.79(95%CI:6.93–11.15,I2=89.31%)and 0.11(95%CI:0.07–0.16,I2=95.25%).The pooled diagnostic odds ratio(DOR)and area under curve(AUC)were 83.58(95%CI:47.15–148.15,I2=100%)and 0.95(95%CI:0.93–0.97).There was no threshold effect(Spearman correlation coefficient=0.22,P>0.05).●CONCLUSION:There is a high accuracy for the detection of glaucoma with AI with SD-OCT images.The application of AI-based algorithms allows together with“doctor+artificial intelligence”to improve the diagnosis of glaucoma.

关键词： artificial intelligence spectral-domain optical coherence tomography glaucoma Meta-analysis

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Exploring device physics of perovskite solar cell via machine learning with limited samples

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Journal of Energy Chemistry 2024年第7期94卷 441-448页

作者： Shanshan Zhao Jie Wang Zhongli Guo Hongqiang Luo Lihua Lu Yuanyuan Tian Zhuoying Jiang Jing Zhang Mengyu Chen Lin Li Cheng Li School of Electronic Science and Engineering Xiamen UniversityXiamen 361005FujianChina Future Display institute of Xiamen Xiamen 361005FujianChina

Perovskite solar cells(PsCs)have developed tremendously over the past decade.However,the key factors influencing the power conversion efficiency(PCE)of PSCs remain incompletely understood,due to the complexity and coupling of these structural and compositional parameters.In this research,we demon-strate an effective approach to optimize PSCs performance via machine learning(ML).To address chal-lenges posed by limited samples,we propose a feature mask(FM)method,which augments training samples through feature transformation rather than synthetic data.Using this approach,squeeze-and-excitation residual network(SEResNet)model achieves an accuracy with a root-mean-square-error(RMSE)of 0.833%and a Pearson's correlation coefficient(r)of 0.980.Furthermore,we employ the permu-tation importance(PI)algorithm to investigate key features for PCE.Subsequently,we predict PCE through high-throughput screenings,in which we study the relationship between PCE and chemical com-positions.After that,we conduct experiments to validate the consistency between predicted results by ML and experimental results.In this work,ML demonstrates the capability to predict device performance,extract key parameters from complex systems,and accelerate the transition from laboratory findings to commercialapplications.

关键词： Perovskite solar cell Machine learning Device physics Performance prediction Limited samples

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CGG repeat expansion in LOC642361/NUTM2B-AS1 typically presents as oculopharyngodistal myopathy

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Journal of Genetics and Genomics 2024年第2期51卷 184-196页

作者： Yan Shi Chunyan Cao Yiheng Zeng Yuanliang Ding Long Chen Fuze Zheng Xuejiao Chen Fanggui Zhou Xiefeng Yang Jinjing Li Liuqing Xu Guorong Xu Minting Lin Hiroyuki Ishiura Shoji Tsuji Ning Wang Zhiqiang Wang Wan-Jin Chen Kang Yang Department of Neurology and institute of Neurology of First Affiliated Hospital Institute of NeuroscienceFujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian 350005China Department of Neurology National Regional Medical CenterBinhai Campus of the First Affiliated HospitalFujian Medical UniversityFuzhouFujian 350212China The First Affiliated Hospital College of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan 471000China Department of Neurology Zhangzhou Municipal Hospital of Fujian Province and Zhangzhou Affiliated Hospital of Fujian Medical UniversityZhangzhouFujian 363000China Department of Neurology Jian'ou Municipal Hospital of Fujian ProvinceJian'ouFujian 353100China Department of Radiology First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian 350005China Department of Neurology Graduate School of MedicineThe University of TokyoTokyo 113-8655Japan Department of Neurology Okayama University Graduate School of MedicineDentistry and Pharmaceutical SciencesOkayama 700-8558Japan institute of Medical Genomics International University of Health and WelfareChiba 286-0048Japan

CGG repeat expansions in LOC642361/NUTM2B-AS1 have recently been identified as a cause of oculopharyngeal myopathy with leukoencephalopathy.However,since only three patients from a single family were reported,it remains unknown whether their clinicopathological features are typical for CGG repeat expansions in LOC642361/NUTM2B-AS1.Here,using repeat-primed-polymerase chain reaction and long-read sequencing,we identify 12 individuals from 3 unrelated families with CGG repeat expansions in LOC642361/NUTM2B-AS1,typically presenting with oculopharyngodistal myopathy.The CGG repeat expansions range from 161 to 669 repeat units.Most of the patients present with ptosis,restricted eye movements,dysphagia,dysarthria,and diffuse limb muscle weakness.Only one patient shows T2-weighted hyperintensity in the cerebellar white matter surrounding the deep cerebellar nuclei on brain magnetic resonance imaging.Muscle biopsies from three patients show a myopathic pattern and rimmed vacuoles.Analyses of muscle biopsies suggest that CGG repeat expansions in LOC642361/NUTM2B-AS1 may deleteriously affect aggrephagic capacity,suggesting that RNA toxicity and mitochondrial dysfunction may contribute to pathogenesis.Our study thus expands the phenotypic spectrum for the CGG repeat expansion of LOC642361/NUTM2B-AS1 and indicates that this genetic variant typically manifests as oculopharyngodistal myopathy with chronic myopathic changes with rimmed vacuoles and filamentous intranuclear inclusions in muscle fibers.

关键词： Oculopharyngeal myopathy with leukoencephalopathy Oculopharyngodistal myopathy CGG repeat expansion Rimmed vacuoles

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The Magnaporthe oryzae effector Avr-PikD suppresses rice immunity by inhibiting an LSD1-like transcriptional activator

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The Crop Journal 2024年第2期12卷 482-492页

作者： Jiayuan Guo Yiling Wu Jianqiang Huang Kaihui Yu Meilian Chen Yijuan Han Zhenhui Zhong Guodong Lu Yonghe Hong Zonghua Wang Xiaofeng Chen fujian Universities Engineering Research Center of Marine Biology and Drugs Fuzhou Institute of OceanographyCollege of Geography and OceanographyMinjiang UniversityFuzhou 350108FujianChina Rice Research institute Fujian Academy of Agricultural SciencesFuzhou 350018FujianChina Ministerial and Provincial Joint Innovation Center for Safety Production of Cross-Strait Crops Minjiang UniversityFuzhou 350108FujianChina State Key Laboratory of Ecological Pest Control for fujian and Taiwan Crops College of Plant ProtectionFujian Agriculture and Forestry UniversityFuzhou 350002FujianChina

Avirulence effectors(Avrs),encoded by plant pathogens,can be recognized by plants harboring the corresponding resistance proteins,thereby initiating effector-triggered immunity(ETI).In susceptible plants,however,Avrs can function as effectors,facilitating infection via effector-triggered susceptibility(ETS).Mechanisms of Avr-mediated ETS remain largely unexplored.Here we report that the Magnaporthe oryzae effector Avr-PikD enters rice cells via the canonical cytoplasmic secretion pathway and suppresses rice basal defense.Avr-PikD interacts with an LSD1-like transcriptional activator AKIP30 of rice,and AKIP30 is also a positive regulator of rice immunity,whereas Avr-PikD impedes its nuclear localization and suppresses its transcriptional activity.In summary,M.oryzae delivers Avr-PikD into rice cells to facilitate ETS by inhibiting AKIP30-mediated transcriptional regulation of immune response against M.oryzae.

关键词： Magnaporthe oryzae Avirulence effector Avr-PikD Effector-triggered susceptibility Rice immunity Transcriptional activator

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T2-weighted imaging-based radiomic-clinical machine learning model for predicting the differentiation of colorectal adenocarcinoma

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 819-832页

作者： Hui-Da Zheng Qiao-Yi Huang Qi-Ming Huang Xiao-Ting Ke Kai Ye Shu Lin Jian-Hua Xu Department of Gastrointestinal Surgery The Second Affiliated Hospital of Fujian Medical UniversityQuanzhou 362000Fujian ProvinceChina Department of Gynaecology and Obstetrics The Second Affiliated Hospital of Fujian Medical UniversityQuanzhou 362000Fujian ProvinceChina Department of Computed Tomography/Magnetic Resonance Imaging The Second Affiliated Hospital of Fujian Medical UniversityQuanzhou 362000Fujian ProvinceChina Centre of Neurological and Metabolic Research The Second Affiliated Hospital of Fujian Medical UniversityQuanzhou 362000Fujian ProvinceChina Group of Neuroendocrinology Garvan Institute of Medical ResearchSydneyNSW 2010Australia

BACKGROUND The study on predicting the differentiation grade of colorectal cancer(CRC)based on magnetic resonance imaging(MRI)has not been reported yet.Developing a non-invasive model to predict the differentiation grade of CRC is of great value.AIM To develop and validate machine learning-based models for predicting the differ-entiation grade of CRC based on T2-weighted images(T2WI).METHODS We retrospectively collected the preoperative imaging and clinical data of 315 patients with CRC who underwent surgery from March 2018 to July 2023.Patients were randomly assigned to a training cohort(n=220)or a validation cohort(n=95)at a 7:3 ratio.Lesions were delineated layer by layer on high-resolution T2WI.Least absolute shrinkage and selection operator regression was applied to screen for radiomic features.Radiomics and clinical models were constructed using the multilayer perceptron(MLP)algorithm.These radiomic features and clinically relevant variables(selected based on a significance level of P<0.05 in the training set)were used to construct radiomics-clinical models.The performance of the three models(clinical,radiomic,and radiomic-clinical model)were evaluated using the area under the curve(AUC),calibration curve and decision curve analysis(DCA).RESULTS After feature selection,eight radiomic features were retained from the initial 1781 features to construct the radiomic model.Eight different classifiers,including logistic regression,support vector machine,k-nearest neighbours,random forest,extreme trees,extreme gradient boosting,light gradient boosting machine,and MLP,were used to construct the model,with MLP demonstrating the best diagnostic performance.The AUC of the radiomic-clinical model was 0.862(95%CI:0.796-0.927)in the training cohort and 0.761(95%CI:0.635-0.887)in the validation cohort.The AUC for the radiomic model was 0.796(95%CI:0.723-0.869)in the training cohort and 0.735(95%CI:0.604-0.866)in the validation cohort.The clinical model achieved an AUC of 0.751(95%CI:0.661-0.842)in the training cohort and

关键词： Radiomics Colorectal cancer Differentiation grade Machine learning T2-weighted imaging

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