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FUBP3 mediates the amyloid-β-induced neuronal NLRP3 expression

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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Clinical manifestations and spermatogenesis outcomes in Chinese patients with congenital hypogonadotropic hypogonadism caused by inherited or de novo FGFR1 mutations

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Asian Journal of Andrology 2024年第4期26卷 426-432页

作者： Yu-Fan Yang Hai-Lu Ma xi Wang Min Nie Jiang-Feng Mao Xue-Yan wu Department of Endocrinology Peking Union Medical College HospitalChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100730China.

Fibroblast growth factor receptor 1(FGFR1)mutations are associated with congenital hypogonadotropic hypogonadism(CHH)through inheritance or spontaneous *** detected FGFR1 mutations in a Chinese cohort of 210 CHH patients at Peking Union Medical College Hospital(Beijing,China)using next-generation and Sanger *** assessed missense variant pathogenicity using six bioinformatics tools and compared clinical features and treatment outcomes between inherited and de novo mutation *** 19 patients with FGFR1 mutations,three were recurrent,and 16 were novel *** of the novel mutations were likely pathogenic according to the American College of Medical Genetics and Genomics(ACMG)guidelines,with the prevalent P366L *** majority of FGFR1 mutations was inherited(57.9%),with frameshift mutations exclusive to the de novo mutation *** inherited mutation group had a lower incidence of cryptorchidism,short stature,and skeletal *** the inherited mutation group,luteinizing hormone(LH)levels were 0.5 IU l−1,follicle-stimulating hormone(FSH)levels were 1.0 IU l−1,and testosterone levels were 1.3 nmol l−*** contrast,the de novo group had LH levels of 0.2 IU l−1,FSH levels of 0.5 IU l−1,and testosterone levels of 0.9 nmol l−1,indicating milder hypothalamus–pituitary–gonadal axis(HPGA)functional deficiency in the inherited *** inherited mutation group showed a tendency toward higher spermatogenesis *** conclusion,this study underscores the predominance of inherited FGFR1 mutations and their association with milder HPGA dysfunction compared to de novo mutations,contributing to our understanding of the genetic and clinical aspects of FGFR1 mutations.

关键词： congenital hypogonadotropic hypogonadism de novo FGFR1 inherited

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Mechanism of Qili Qiangxin Capsule for Heart Failure Based on miR133a-Endoplasmic Reticulum Stress

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Chinese Journal of Integrative Medicine 2024年第5期30卷 398-407页

作者： JI xiao-di YANG Ding CUI xi-yuan LOU Li-xia NIE Bo ZHAO Jiu-li ZHAO Ming-jing wu Ai-ming Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine Key Laboratory of Chinese Internal Medicine of Ministry of Education and BeijingBeijing 100700China Department of Traditional Chinese Medicine Fuwai HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100037China

Objective:To investigate the pharmacological mechanism of Qili Qiangxin Capsule(QLQX)improvement of heart failure(HF)based on miR133a-endoplasmic reticulum stress(ERS)***:A left coronary artery ligation-induced HF after myocardial infarction model was used in this *** were randomly assigned to the sham group,the model group,the QLQX group[0.32 g/(kg·d)],and the captopril group[2.25 mg/(kg·d)],15 rats per group,followed by 4 weeks of *** function such as left ventricular ejection fraction(EF),fractional shortening(FS),left ventricular systolic pressure(LVSP),left ventricular end diastolic pressure(LVEDP),the maximal rate of increase of left ventricular pressure(+dp/dt max),and the maximal rate of decrease of left ventricular pressure(–dp/dt max)were monitored by echocardiography and *** and eosin(HE)and Masson stainings were used to visualize pathological changes in myocardial *** m RNA expression of mi R133a,glucose-regulated protein78(GRP78),inositol-requiring enzyme 1(IRE1),activating transcription factor 6(ATF6),X-box binding protein1(XBP1),C/EBP homologous protein(CHOP)and Caspase 12 were detected by *** protein expression of GRP78,p-IRE1/IRE1ratio,cleaved-ATF6,XBP1-s(the spliced form of XBP1),CHOP and Caspase 12 were detected by Western *** T-mediated d UTP nick-end labeling(TUNEL)staining was used to detect the rate of ***:QLQX significantly improved cardiac function as evidenced by increased EF,FS,LVSP,+dp/dt max,-dp/dt max,and decreased LVEDP(P<0.05,P<0.01).HE staining showed that QLQX ameliorated cardiac pathologic damage to some *** staining indicated that QLQX significantly reduced collagen volume fraction in myocardial tissue(P<0.01).Results from RT-PCR and Western blot showed that QLQX significantly increased the expression of mi R133a and inhibited the m RNA expressions of GRP78,IRE1,ATF6 and XBP1,as well as decreased the protein expressions of GRP78,cleave

关键词： heart failure Qili Qiangxin Capsule miR133a endoplasmic reticulum stress apoptosis

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Decarboxylative cyanation and thiocyanation via catalytic electron donor-acceptor complex with copper catalysis

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Science China Chemistry 2024年第9期67卷 3019-3028页

作者： Hongping Zhao xiaoxiang xi Tianbao wu Zimin Chen Minyan Wang Weiming Yuan Key Laboratory of Material Chemistry for Energy Conversion and Storage Ministry of Education Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica School of Chemistry and Chemical Engineering Huazhong University of Science and Technology (HUST) State Key Laboratory of Coordination Chemistry School of Chemistry and Chemical Engineering Nanjing University Shenzhen Huazhong University of Science and Technology Research Institute

A new catalytic decarboxylative cyanation and thiocyanation via a synergistic Na I/Cu catalysis is developed. The photoexcited electron donor-acceptor complex by assembly of Na I, R3P, and N-acyloxy-phthalimide ester(NHPI ester) triggers the generation of alkyl radical species, which then engages in Cu-catalyzed radical coupling process. Key to success of this dual catalytic transformation is the reliable charge transfer between I· and Cu(I). This dual catalytic platform can eliminate the use of expensive iridium-based photocatalyst or synthetically elaborate organic dyes. A series of primary, secondary, and tertiary alkyl nitriles and thiocyanates are easily synthesized. Moreover, an asymmetric decarboxylative cyanation by applying a chiral Cu catalyst is also developed to afford chiral nitriles in high enantioselectivity. The mechanistic details and the origin of the high enantioselectivity are further investigated by the mechanistic experiments and the density functional theory calculations.

关键词： electron donor-acceptor catalysis copper catalysis cyanation thiocyanation asymmetric synthesis

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Development and validation of a novel non-invasive test for diagnosing nonalcoholic fatty liver disease in Chinese children

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World Journal of Pediatrics 2024年第4期20卷 413-421页

作者： Zhe-Wen Qin Qian-Nan Ren Hong-xi Zhang Ya-Ru Liu Ke Huang Wei wu Guan-Ping Dong Yan Ni Jun-Fen Fu Division of Endocrinology National Clinical Research Center for Child HealthNational Children’s Regional Medical CenterThe Children’s HospitalDepartment of EndocrinologyNational Clinical Research Center for Child HealthNational Children’s Regional Medical CenterThe Children’s HospitalZhejiang University School of MedicineHangzhou310052China

With the exploding prevalence of obesity,many children are at risk of developing nonalcoholic fatty liver *** anthropometric and laboratory parameters,our study aimed to develop a model to quantitatively evaluate liver fat content(LFC)in children with *** A well-characterized cohort of 181 children between 5 and 16 years of age were recruited to the study in the Endocrinology Department as the derivation *** external validation cohort comprised 77 *** assessment of liver fat content was performed using proton magnetic resonance *** and laboratory metrics were measured in all subjects.B-ultrasound examination was carried out in the external validation *** Kruskal-Wallis test,Spearman bivariate correlation analyses,univariable linear regressions and multivariable linear regression were used to build the optimal predictive *** The model was based on indicators including alanine aminotransferase,homeostasis model assessment of insulin resistance,triglycerides,waist circumference and Tanner *** adjusted R^(2)of the model was 0.589,which presented high sensitivity and specificity both in internal[sensitivity of 0.824,specificity of 0.900,area under curve(AUC)of 0.900 with a 95%confidence interval:0.783–1.000]and external validation(sensitivity of 0.918 and specificity of 0.821,AUC of 0.901 with a 95%confidence interval:0.818–0.984).Conclusions Our model based on five clinical indicators was simple,non-invasive,and inexpensive;it had high sensitivity and specificity in predicting LFC in ***,it may be useful for identifying children with obesity who are at risk for developing nonalcoholic fatty liver disease.

关键词： Biochemical markers Children Magnetic resonance spectroscopy Nonalcoholic fatty liver disease Pediatric obesity

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Torque effect on vibration behavior of high-speed train gearbox under internal and external excitations

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Railway Engineering Science 2024年第2期32卷 229-243页

作者： Yue Zhou xi Wang Hongbo Que Rubing Guo xinhai Lin Siqin Jin Chengpan wu Yu Hou School of Mechanical Electronic and Control EngineeringBeijing Jiaotong UniversityBeijing 100044China CRRC Qishuyan Institute Co. Ltd.No.258Wuyi RoadQishuyanChangzhou 213011China Frontiers Science Center for Smart High-Speed Railway System Beijing Jiaotong UniversityBeijing 100044China

The high-speed train transmission system,experiencing both the internal excitation originating from gear meshing and the external excitation originating from the wheel-rail interaction,exhibits complex dynamic behavior in the actual service *** paper focuses on the gearbox in the high-speed train to carry out the bench test,in which various operat-ing conditions(torques and rotation speeds)were set up and the excitation condition covering both internal and external was *** responses on multiple positions of the gearbox were acquired in the test and the vibration behavior of the gearbox was ***,a stochastic excitation modal test was also carried out on the test bench under different torques,and the modal parameter of the gearbox was ***,the sweep frequency response of the gearbox under gear meshing excitation was analyzed through dynamic *** results showed that the torque has an attenuating effect on the amplitude of gear meshing frequency on the gearbox,and the effect of external excitation on the gearbox vibration cannot be ignored,especially under the rated operating *** was also found that the torque affects the modal param-eter of the gearbox *** torque has a great effect on both the gear meshing stiffness and the bearing stiffness in the transmission system,which is the inherent reason for the changed modal characteristics observed in the modal test and affects the vibration behavior of the gearbox consequently.

关键词： High-speed train Gearbox Bench test Vibration behavior Modal identification

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Cath-KP,a novel peptide derived from frog skin,prevents oxidative stress damage in a Parkinson’s disease model

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Zoological Research 2024年第1期45卷 108-124页

作者： Huanpeng Lu Jinwei Chai Zijian Xu Jiena wu Songzhe He Hang Liao Peng Huang xiaowen Huang xi Chen Haishan Jiang Shaogang Qu Xueqing Xu Department of Neurology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhouGuangdong 510515China Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence GuangzhouGuangdong 510515China Key Laboratory of Mental Health of the Ministry of Education Southern Medical UniversityGuangzhouGuangdong 510515China Department of Dermatology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China Department of Neurology Ganzhou Hospital-Nanfang HospitalSouthern Medical UniversityGanzhouJiangxi 341001China

Parkinson’s disease(PD)is a neurodegenerative condition that results in dyskinesia,with oxidative stress playing a pivotal role in its *** peptides may thus present therapeutic potential for *** this study,a novel cathelicidin peptide(Cath-KP;GCSGRFCNLF NNRRPGRLTLIHRPGGDKRTSTGLIYV)was identified from the skin of the Asiatic painted frog(Kaloula pulchra).Structural analysis using circular dichroism and homology modeling revealed a uniqueαββconformation for *** vitro experiments,including free radical scavenging and ferric-reducing antioxidant analyses,confirmed its antioxidant *** the 1-methyl-4-phenylpyridinium ion(MPP^(+))-induced dopamine cell line and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mice,Cath-KP was found to penetrate cells and reach deep brain tissues,resulting in improved MPP^(+)-induced cell viability and reduced oxidative stress-induced damage by promoting antioxidant enzyme expression and alleviating mitochondrial and intracellular reactive oxygen species accumulation through Sirtuin-1(Sirt1)/Nuclear factor erythroid 2-related factor 2(Nrf2)pathway *** focal adhesion kinase(FAK)and p38 were also identified as regulatory *** the MPTP-induced PD mice,Cath-KP administration increased the number of tyrosine hydroxylase(TH)-positive neurons,restored TH content,and ameliorated *** the best of our knowledge,this study is the first to report on a cathelicidin peptide demonstrating potent antioxidant and neuroprotective properties in a PD model by targeting oxidative *** findings expand the known functions of cathelicidins,and hold promise for the development of therapeutic agents for PD.

关键词： Cath-KP Peptide Parkinson’s disease Oxidative stress Neuroprotection

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Rare variants in FANCJ induce premature ovarian insufficiency in humans and mice

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Journal of Genetics and Genomics 2024年第2期51卷 252-255页

作者： xi Yang Shuting Ren Jialin Yang Yuncheng Pan Zixue Zhou Qing Chen Yunzheng Fang Lingyue Shang Feng Zhang xiaojin Zhang Yanhua wu State Key Laboratory of Genetic Engineering at School of Life Sciences Human Phenome InstituteObstetrics and Gynecology HospitalFudan UniversityShanghai 200438China Obstetrics and Gynecology Hospital Institute of Reproduction and DevelopmentState Key Laboratory of Genetic Engineering at School of Life SciencesFudan UniversityShanghai 200011China Human Phenome Institute Zhangjiang Fudan International Innovation CenterFudan UniversityShanghai 201203China Obstetrics and Gynecology Hospital Institute of Reproduction and DevelopmentFudan UniversityShanghai 200011China State Key Laboratory of Genetic Engineering at School of Life Sciences Obstetrics and Gynecology HospitalFudan UniversityShanghai 200438China National Demonstration Center for Experimental Biology Education School of Life SciencesFudan UniversityShanghai 200433China

Premature ovarian insufficiency(POI)is a severe female reproductive disorder that affects 1%of women in general populations(European Society for Human Reproduction and Embryology[ESHRE]Guideline Group on POI et al.,2016).An increasing prevalence up to 3.7%has been reported in a recent meta-analysis(Golezar et al.,2019).POl can lead to infertility or subfertility,as well as a range of complex complications suffering multi-organ systems,seriously threatening women's health and reducing the life *** contrast,POl is a representative heterogeneous disease with multiple *** more than 70 causative POI genes have been identified,the etiology of more than half of the POI patients is still ambiguous(Jiao et al.,2018).Unreported POI causative genes,therefore,remain to be identified.

关键词： insufficiency fertility

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Regulation of specific abnormal calcium signals in the hippocampal CA1 and primary cortex M1 alleviates the progression of temporal lobe epilepsy

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Neural Regeneration Research 2024年第2期19卷 425-433页

作者： Feng Chen xi Dong Zhenhuan Wang Tongrui wu Liangpeng Wei Yuanyuan Li Kai Zhang Zengguang Ma Chao Tian Jing Li Jingyu Zhao Wei Zhang Aili Liu Hui Shen Laboratory of Neurobiology School of Biomedical EngineeringTianjin Medical UniversityTianjinChina Institute for Translational Neuroscience the Second Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Institute for Translational Brain Research Fudan UniversityShanghaiChina Department of Radiology the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingJiangsu ProvinceChina Innovative Institute of Chinese Medicine and Pharmacy Shandong University of Traditional Chinese MedicineJinanChina Department of Anesthesiology Tianjin Medical University General HospitalTianjinChina Department of Orthopaedics Tianjin Medical University General HospitalTianjinChina Tianjin Eye Hospital Tianjin Eye InstituteTianjin Key Lab of Ophthalmology and Visual ScienceTianjinChina Laboratory of Neurobiology School of Basic Medical SciencesTianjin Medical UniversityTianjinChina

Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence *** pathogenesis of temporal lobe epilepsy is complex and is not fully *** calcium dynamics have been implicated in temporal lobe ***,the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown,and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving *** this study,we used a multichannel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy *** found that calcium signals varied according to the grade of temporal lobe epilepsy *** particular,cortical spreading depression,which has recently been frequently used to represent the continuously and substantially increased calcium signals,was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from gradeⅡto gradeⅤ.However,vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor *** inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to gradeⅠ*** addition,the latency of cortical spreading depression was prolonged,and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly ***,it was possible to rescue the altered intracellular calcium *** simultaneous analysis of calcium signals and epileptic behaviors,we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced,and that the end-point behaviors of temporal lobe epilepsy were *** results indicate that the calcium dynamic between CA1 and M1 may reflect sp

关键词： Ca^(2+) calcium signals chemogenetic methods hippocampus primary motor cortex pyramidal neurons temporal lobe epilepsy

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Intelligent diagnostic model for pterygium by combining attention mechanism and MobileNetV2

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1184-1192页

作者： Mao-Nian wu Kai He Yi-Bei Yu Bo Zheng Shao-Jun Zhu xiang-Qian Hong Wen-Qun xi Zhe Zhang School of Information Engineering Huzhou UniversityHuzhou 313000Zhejiang ProvinceChina Zhejiang Province Key Laboratory of Smart Management and Application of Modern Agricultural Resources Huzhou UniversityHuzhou 313000Zhejiang ProvinceChina School of Mathematical Information Shaoxing UniversityShaoxing 312000Zhejiang ProvinceChina Shenzhen Eye Institute Shenzhen Eye HospitalJinan UniversityShenzhen 518040Guangdong ProvinceChina

AIM:To evaluate the application of an intelligent diagnostic model for ***:For intelligent diagnosis of pterygium,the attention mechanisms—SENet,ECANet,CBAM,and Self-Attention—were fused with the lightweight MobileNetV2 model structure to construct a tri-classification *** study used 1220 images of three types of anterior ocular segments of the pterygium provided by the Eye Hospital of Nanjing Medical *** classification models—VGG16,ResNet50,MobileNetV2,and EfficientNetB7—were trained on the same dataset for *** evaluate model performance in terms of accuracy,Kappa value,test time,sensitivity,specificity,the area under curve(AUC),and visual heat map,470 test images of the anterior segment of the pterygium were ***:The accuracy of the MobileNetV2+Self-Attention model with 281 MB in model size was 92.77%,and the Kappa value of the model was 88.92%.The testing time using the model was 9ms/image in the server and 138ms/image in the local *** sensitivity,specificity,and AUC for the diagnosis of pterygium using normal anterior segment images were 99.47%,100%,and 100%,respectively;using anterior segment images in the observation period were 88.30%,95.32%,and 96.70%,respectively;and using the anterior segment images in the surgery period were 88.18%,94.44%,and 97.30%,***:The developed model is lightweight and can be used not only for detection but also for assessing the severity of pterygium.

关键词： deep learning attention mechanism pterygium intelligent diagnosis

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