NPJ Parkinson's Disease最新文献_第2页

A framework for translational therapy development in deep brain stimulation 脑深部刺激转化疗法开发框架

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-11-08 DOI: 10.1038/s41531-024-00829-5

Jia Zhi Chen, Jens Volkmann, Chi Wang Ip

引用次数: 0

Novel tools to quantify total, phospho-Ser129 and aggregated alpha-synuclein in the mouse brain 量化小鼠大脑中总α-突触核蛋白、磷酸化-Ser129α-突触核蛋白和聚集α-突触核蛋白的新工具

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-11-08 DOI: 10.1038/s41531-024-00830-y

Benjamin Guy Trist, Courtney Jade Wright, Alejandra Rangel, Louise Cottle, Asheeta Prasad, Nanna Møller Jensen, Hjalte Gram, Nicolas Dzamko, Poul Henning Jensen, Deniz Kirik

{"title":"Novel tools to quantify total, phospho-Ser129 and aggregated alpha-synuclein in the mouse brain","authors":"Benjamin Guy Trist, Courtney Jade Wright, Alejandra Rangel, Louise Cottle, Asheeta Prasad, Nanna Møller Jensen, Hjalte Gram, Nicolas Dzamko, Poul Henning Jensen, Deniz Kirik","doi":"10.1038/s41531-024-00830-y","DOIUrl":"https://doi.org/10.1038/s41531-024-00830-y","url":null,"abstract":"Assays for quantifying aggregated and phosphorylated (S129) human α-synuclein protein are widely used to evaluate pathological burden in patients suffering from synucleinopathy disorders. Many of these assays, however, do not cross-react with mouse α-synuclein or exhibit poor sensitivity for this target, which is problematic considering the preponderance of mouse models at the forefront of pre-clinical α-synuclein research. In this project, we addressed this unmet need by reformulating two existing AlphaLISA® SureFire® Ultra™ total and pS129 α-synuclein assay kits to yield robust and ultrasensitive (LLoQ ≤ 0.5 pg/mL) quantification of mouse and human wild-type and pS129 α-synuclein protein. We then employed these assays, together with the BioLegend α-synuclein aggregate ELISA, to assess α-synuclein S129 phosphorylation and aggregation in different mouse brain tissue preparations. Overall, we highlight the compatibility of these new immunoassays with rodent models and demonstrate their potential to advance knowledge surrounding α-synuclein phosphorylation and aggregation in synucleinopathies.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"18 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The p.Gly2019Ser is a common LRRK2 pathogenic variant among Egyptians with familial and sporadic Parkinson's disease. p.Gly2019Ser是埃及家族性和散发性帕金森病患者中常见的LRRK2致病变体。

IF 6.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-11-06 DOI: 10.1038/s41531-024-00826-8

Martina B William, Sharifa Hamed, Ali Shalash, Eman M Khedr, Mohamed H Yousef, Shaimaa El-Jaafary, Gharib Fawi, Asmaa Helmy, Eman Hamid, Mohamed Essam, Hamin Lee, Alina Jama, Mohamed Koraym, Doaa M Mahmoud, Sara Elfarrash, Yasmin Elsaid, Asmaa S Gabr, Nourhan Shebl, Nesreen Abdelwahhab, Tamer M Belal, Nehal A B Elsayed, Mohamed El-Gamal, Shimaa Elgamal, Salma Ragab, Jaidaa Mekky, Lobna Aly, Samir Nabhan, Gaafar Ragab, Mohamed A Hussein, Mohamed Tharwat Hegazy, Henry Houlden, Mohamed Salama, Mie Rizig

{"title":"The p.Gly2019Ser is a common LRRK2 pathogenic variant among Egyptians with familial and sporadic Parkinson's disease.","authors":"Martina B William, Sharifa Hamed, Ali Shalash, Eman M Khedr, Mohamed H Yousef, Shaimaa El-Jaafary, Gharib Fawi, Asmaa Helmy, Eman Hamid, Mohamed Essam, Hamin Lee, Alina Jama, Mohamed Koraym, Doaa M Mahmoud, Sara Elfarrash, Yasmin Elsaid, Asmaa S Gabr, Nourhan Shebl, Nesreen Abdelwahhab, Tamer M Belal, Nehal A B Elsayed, Mohamed El-Gamal, Shimaa Elgamal, Salma Ragab, Jaidaa Mekky, Lobna Aly, Samir Nabhan, Gaafar Ragab, Mohamed A Hussein, Mohamed Tharwat Hegazy, Henry Houlden, Mohamed Salama, Mie Rizig","doi":"10.1038/s41531-024-00826-8","DOIUrl":"10.1038/s41531-024-00826-8","url":null,"abstract":"The impact of LRRK2 variants on the risk of Parkinson's disease in Egyptians remains unknown. We examined 1210 Egyptians (611 PD patients and 599 controls) from 16 governorates across Egypt for 12 LRRK2 pathogenic variants. The p.Gly2019Ser was the only variant detected, with a prevalence of 4.1% in sporadic cases, 6.5% in familial cases, and 0.68% in controls. Among p.Gly2019Ser carriers, all were heterozygous bar one homozygous patient, and all shared the common haplotype 1. Demographics and UPDRS scores did not differ between carriers and non-carriers, with most patients being males and developed PD in their fifties. Young and Early-onset PD prevalence was 37.5% in carriers and 33% in non-carriers. Familial cases were 16.6% in carriers and 11.5% in non-carriers. This study affirms that like other Mediterranean populations, Egyptians with PD have a higher prevalence of the p.Gly2019Ser variant compared to the global average. LRRK2 inhibitors could be promising therapeutic options for further exploration in this population.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"10 1","pages":"215"},"PeriodicalIF":6.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcranial direct current stimulation for Parkinson’s disease: systematic review and meta-analysis of motor and cognitive effects 经颅直流电刺激治疗帕金森病：运动和认知效果的系统回顾和荟萃分析

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-11-06 DOI: 10.1038/s41531-024-00821-z

Zhuo Duan, Chencheng Zhang

引用次数: 0

Systemic inflammation accelerates neurodegeneration in a rat model of Parkinson's disease overexpressing human alpha synuclein. 在过度表达人α突触核蛋白的帕金森病大鼠模型中，全身炎症会加速神经退行性变。

IF 6.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-11-05 DOI: 10.1038/s41531-024-00824-w

Mariangela Massaro Cenere, Marta Tiberi, Emanuela Paldino, Sebastian Luca D'Addario, Mauro Federici, Cecilia Giacomet, Debora Cutuli, Alessandro Matteocci, Francesca Cossa, Beatrice Zarrilli, Nicolas Casadei, Ada Ledonne, Laura Petrosini, Nicola Berretta, Francesca Romana Fusco, Valerio Chiurchiù, Nicola B Mercuri

{"title":"Systemic inflammation accelerates neurodegeneration in a rat model of Parkinson's disease overexpressing human alpha synuclein.","authors":"Mariangela Massaro Cenere, Marta Tiberi, Emanuela Paldino, Sebastian Luca D'Addario, Mauro Federici, Cecilia Giacomet, Debora Cutuli, Alessandro Matteocci, Francesca Cossa, Beatrice Zarrilli, Nicolas Casadei, Ada Ledonne, Laura Petrosini, Nicola Berretta, Francesca Romana Fusco, Valerio Chiurchiù, Nicola B Mercuri","doi":"10.1038/s41531-024-00824-w","DOIUrl":"10.1038/s41531-024-00824-w","url":null,"abstract":"Increasing efforts have been made to elucidate how genetic and environmental factors interact in Parkinson's disease (PD). In the present study, we assessed the development of symptoms on a genetic PD rat model that overexpresses human α-synuclein (Snca+/+) at a presymptomatic age, exposed to a pro-inflammatory insult by intraperitoneal injection of lipopolysaccharide (LPS), using immunohistology, high-dimensional flow cytometry, constant potential amperometry, and behavioral analyses. A single injection of LPS into WT and Snca+/+ rats triggered long-lasting increase in the activation of pro-inflammatory microglial markers, monocytes, and T lymphocytes. However, only LPS Snca+/+ rats showed dopaminergic neuronal loss in the substantia nigra pars compacta (SNpc), associated with a reduction in the release of evoked dopamine in the striatum. No significant changes were observed in the behavioral domain. We propose our double-hit animal as a reliable model to investigate the mechanisms whereby α-synuclein and inflammation interact to promote neurodegeneration in PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"10 1","pages":"213"},"PeriodicalIF":6.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The effect of pallidal stimulation on sleep outcomes and related brain connectometries in Parkinson’s disease 刺激苍白球对帕金森病患者睡眠结果及相关脑连接测量的影响

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-11-04 DOI: 10.1038/s41531-024-00800-4

Zhaoting Zheng, Defeng Liu, Houyou Fan, Hutao Xie, Quan Zhang, Guofan Qin, Yin Jiang, Fangang Meng, Zixiao Yin, Anchao Yang, Jianguo Zhang

{"title":"The effect of pallidal stimulation on sleep outcomes and related brain connectometries in Parkinson’s disease","authors":"Zhaoting Zheng, Defeng Liu, Houyou Fan, Hutao Xie, Quan Zhang, Guofan Qin, Yin Jiang, Fangang Meng, Zixiao Yin, Anchao Yang, Jianguo Zhang","doi":"10.1038/s41531-024-00800-4","DOIUrl":"https://doi.org/10.1038/s41531-024-00800-4","url":null,"abstract":"Sleep difficulties affect up to 98% of Parkinson’s disease (PD) patients and are often not well treated. How globus pallidus internus (GPi)-DBS could help is less understood. We retrospectively analyzed sleep outcomes in 32 PD patients after GPi-DBS with a two-year follow-up. We observed high heterogeneity in sleep response to pallidal stimulation: 16 patients showed clinically meaningful improvement, 9 had minor changes, and 7 experienced worsened sleep quality, with no overall significant change on the Parkinson’s Disease Sleep Scale-2 (P = 0.19). Further analysis revealed that stimulation of the left sensorimotor GPi was significantly associated with sleep improvement. Fiber tracts from the left sensorimotor GPi to the bilateral sensorimotor cortex, right GPi, brainstem, and bilateral cerebellum were linked to better sleep, while projections to the left hippocampus correlated with worsened sleep. These findings may guide personalized GPi-DBS lead placement to optimize sleep outcomes in PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"17 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Subthalamic stimulation causally modulates human voluntary decision-making to stay or go. 刺激丘脑下部可调节人类的去留自主决策。

IF 6.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-11-02 DOI: 10.1038/s41531-024-00807-x

Yichen Wang, Linbin Wang, Luis Manssuer, Yi-Jie Zhao, Qiong Ding, Yixin Pan, Peng Huang, Dianyou Li, Valerie Voon

{"title":"Subthalamic stimulation causally modulates human voluntary decision-making to stay or go.","authors":"Yichen Wang, Linbin Wang, Luis Manssuer, Yi-Jie Zhao, Qiong Ding, Yixin Pan, Peng Huang, Dianyou Li, Valerie Voon","doi":"10.1038/s41531-024-00807-x","DOIUrl":"10.1038/s41531-024-00807-x","url":null,"abstract":"The voluntary nature of decision-making is fundamental to human behavior. The subthalamic nucleus is important in reactive decision-making, but its role in voluntary decision-making remains unclear. We recorded from deep brain stimulation subthalamic electrodes time-locked with acute stimulation using a Go/Nogo task to assess voluntary action and inaction. Beta oscillations during voluntary decision-making were temporally dissociated from motor function. Parkinson's patients showed an inaction bias with high beta and intermediate physiological states. Stimulation reversed the inaction bias highlighting its causal nature, and shifting physiology closer to reactive choices. Depression was associated with higher alpha during Voluntary-Nogo characterized by inaction or inertial status quo maintenance whereas apathy had higher beta-gamma during voluntary action or impaired effortful initiation of action. Our findings suggest the human subthalamic nucleus causally contributes to voluntary decision-making, possibly through threshold gating or toggling mechanisms, with stimulation shifting towards voluntary action and suggest biomarkers as potential clinical predictors.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"10 1","pages":"210"},"PeriodicalIF":6.7,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biomarkers for cognitive impairment in alpha-synucleinopathies: an overview of systematic reviews and meta-analyses. α-突触核蛋白病认知障碍的生物标志物：系统综述和荟萃分析概述。

IF 6.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-11-02 DOI: 10.1038/s41531-024-00823-x

Elisa Mantovani, Alice Martini, Alessandro Dinoto, Chiara Zucchella, Sergio Ferrari, Sara Mariotto, Michele Tinazzi, Stefano Tamburin

{"title":"Biomarkers for cognitive impairment in alpha-synucleinopathies: an overview of systematic reviews and meta-analyses.","authors":"Elisa Mantovani, Alice Martini, Alessandro Dinoto, Chiara Zucchella, Sergio Ferrari, Sara Mariotto, Michele Tinazzi, Stefano Tamburin","doi":"10.1038/s41531-024-00823-x","DOIUrl":"10.1038/s41531-024-00823-x","url":null,"abstract":"Cognitive impairment (CI) is common in α-synucleinopathies, i.e., Parkinson's disease, Lewy bodies dementia, and multiple system atrophy. We summarize data from systematic reviews/meta-analyses on neuroimaging, neurophysiology, biofluid and genetic diagnostic/prognostic biomarkers of CI in α-synucleinopathies. Diagnostic biomarkers include atrophy/functional neuroimaging brain changes, abnormal cortical amyloid and tau deposition, and cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers, cortical rhythm slowing, reduced cortical cholinergic and glutamatergic and increased cortical GABAergic activity, delayed P300 latency, increased plasma homocysteine and cystatin C and decreased vitamin B12 and folate, increased CSF/serum albumin quotient, and serum neurofilament light chain. Prognostic biomarkers include brain regional atrophy, cortical rhythm slowing, CSF amyloid biomarkers, Val66Met polymorphism, and apolipoprotein-E ε2 and ε4 alleles. Some AD/amyloid/tau biomarkers may diagnose/predict CI in α-synucleinopathies, but single, validated diagnostic/prognostic biomarkers lack. Future studies should include large consortia, biobanks, multi-omics approach, artificial intelligence, and machine learning to better reflect the complexity of CI in α-synucleinopathies.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"10 1","pages":"211"},"PeriodicalIF":6.7,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

α-synuclein overexpression and the microbiome shape the gut and brain metabolome in mice α-突触核蛋白过表达和微生物组塑造了小鼠的肠道和大脑代谢组

IF 8.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-10-30 DOI: 10.1038/s41531-024-00816-w

Livia H. Morais, Joseph C. Boktor, Siamak MahmoudianDehkordi, Rima Kaddurah-Daouk, Sarkis K. Mazmanian

{"title":"α-synuclein overexpression and the microbiome shape the gut and brain metabolome in mice","authors":"Livia H. Morais, Joseph C. Boktor, Siamak MahmoudianDehkordi, Rima Kaddurah-Daouk, Sarkis K. Mazmanian","doi":"10.1038/s41531-024-00816-w","DOIUrl":"https://doi.org/10.1038/s41531-024-00816-w","url":null,"abstract":"Pathological forms of α-synuclein contribute to synucleinopathies, including Parkinson’s disease (PD). Most cases of PD arise from gene-environment interactions. Microbiome composition is altered in PD, and gut bacteria are causal to symptoms in animal models. We quantitatively profiled nearly 630 metabolites in the gut, plasma, and brain of α-synuclein-overexpressing (ASO) mice, compared to wild-type (WT) animals, and comparing germ-free (GF) to specific pathogen-free (SPF) animals (n = 5 WT-SPF; n = 6 ASO-SPF; n = 6 WT-GF; n = 6 ASO-GF). Many differentially expressed metabolites in ASO mice are also dysregulated in human PD patients, including amine oxides, bile acids and indoles. The microbial metabolite trimethylamine N-oxide (TMAO) strongly correlates from the gut to the plasma to the brain in mice, notable since TMAO is elevated in the blood and cerebrospinal fluid of PD patients. These findings uncover broad metabolomic changes that are influenced by the intersection of host genetics and microbiome in a mouse model of PD.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"15 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural basis of epitope recognition by anti-alpha-synuclein antibodies MJFR14-6-4-2. 抗α-突触核蛋白抗体 MJFR14-6-4-2 表位识别的结构基础。

IF 6.7 1区医学

NPJ Parkinson's Disease Pub Date : 2024-10-27 DOI: 10.1038/s41531-024-00822-y

Ilva Liekniņa, Lasse Reimer, Teodors Panteļejevs, Alons Lends, Kristaps Jaudzems, Aadil El-Turabi, Hjalte Gram, Anissa Hammi, Poul Henning Jensen, Kaspars Tārs

{"title":"Structural basis of epitope recognition by anti-alpha-synuclein antibodies MJFR14-6-4-2.","authors":"Ilva Liekniņa, Lasse Reimer, Teodors Panteļejevs, Alons Lends, Kristaps Jaudzems, Aadil El-Turabi, Hjalte Gram, Anissa Hammi, Poul Henning Jensen, Kaspars Tārs","doi":"10.1038/s41531-024-00822-y","DOIUrl":"10.1038/s41531-024-00822-y","url":null,"abstract":"Alpha-synuclein (α-syn) inclusions in the brain are hallmarks of so-called Lewy body diseases. Lewy bodies contain mainly aggregated α-syn together with some other proteins. Monomeric α-syn lacks a well-defined three-dimensional structure, but it can aggregate into oligomeric and fibrillar amyloid species, which can be detected using specific antibodies. Here we investigate the aggregate specificity of monoclonal MJFR14-6-4-2 antibodies. We conclude that partial masking of epitope in unstructured monomer in combination with a high local concentration of epitopes is the main reason for MJFR14-6-4-2 selectivity towards aggregates. Based on the structural insight, we produced mutant α-syn that when fibrillated is unable to bind MJFR14-6-4-2. Using these fibrils as a tool for seeding cellular α-syn aggregation, provides superior signal/noise ratio for detection of cellular α-syn aggregates by MJFR14-6-4-2. Our data provide a molecular level understanding of specific recognition of toxic amyloid oligomers, which is critical for the development of inhibitors against synucleinopathies.","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"10 1","pages":"206"},"PeriodicalIF":6.7,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0