Translational Neurodegeneration最新文献

{"title":"Biases in α-synuclein immuno-quantitation: a core problem for basic and ancillary studies of Parkinson's disease and multiple system atrophy.","authors":"Florent Laferrière, Ludivine Sabatier, Stéphane Claverol, Francesca De Giorgi, François Ichas","doi":"10.1186/s40035-024-00408-x","DOIUrl":"10.1186/s40035-024-00408-x","url":null,"abstract":"","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"13 1","pages":"15"},"PeriodicalIF":12.6,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10962071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140289087","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}

{"title":"Putative novel CSF biomarkers of Alzheimer's disease based on the novel concept of generic protein misfolding and proteotoxicity: the PRAMA cohort.","authors":"Alessandra Bigi, Giulia Fani, Valentina Bessi, Liliana Napolitano, Silvia Bagnoli, Assunta Ingannato, Lorenzo Neri, Roberta Cascella, Paolo Matteini, Sandro Sorbi, Benedetta Nacmias, Cristina Cecchi, Fabrizio Chiti","doi":"10.1186/s40035-024-00405-0","DOIUrl":"10.1186/s40035-024-00405-0","url":null,"abstract":"","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"13 1","pages":"14"},"PeriodicalIF":12.6,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10924410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140065963","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}

{"title":"LRRK2 kinase inhibition reverses G2019S mutation-dependent effects on tau pathology progression","authors":"Noah Lubben, Julia K. Brynildsen, Connor M. Webb, Howard L. Li, Cheryl E. G. Leyns, Lakshmi Changolkar, Bin Zhang, Emily S. Meymand, Mia O’Reilly, Zach Madaj, Daniella DeWeerd, Matthew J. Fell, Virginia M. Y. Lee, Dani S. Bassett, Michael X. Henderson","doi":"10.1186/s40035-024-00403-2","DOIUrl":"https://doi.org/10.1186/s40035-024-00403-2","url":null,"abstract":"Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson’s disease (PD). These mutations elevate the LRRK2 kinase activity, making LRRK2 kinase inhibitors an attractive therapeutic. LRRK2 kinase activity has been consistently linked to specific cell signaling pathways, mostly related to organelle trafficking and homeostasis, but its relationship to PD pathogenesis has been more difficult to define. LRRK2-PD patients consistently present with loss of dopaminergic neurons in the substantia nigra but show variable development of Lewy body or tau tangle pathology. Animal models carrying LRRK2 mutations do not develop robust PD-related phenotypes spontaneously, hampering the assessment of the efficacy of LRRK2 inhibitors against disease processes. We hypothesized that mutations in LRRK2 may not be directly related to a single disease pathway, but instead may elevate the susceptibility to multiple disease processes, depending on the disease trigger. To test this hypothesis, we have previously evaluated progression of α-synuclein and tau pathologies following injection of proteopathic seeds. We demonstrated that transgenic mice overexpressing mutant LRRK2 show alterations in the brain-wide progression of pathology, especially at older ages. Here, we assess tau pathology progression in relation to long-term LRRK2 kinase inhibition. Wild-type or LRRK2G2019S knock-in mice were injected with tau fibrils and treated with control diet or diet containing LRRK2 kinase inhibitor MLi-2 targeting the IC50 or IC90 of LRRK2 for 3–6 months. Mice were evaluated for tau pathology by brain-wide quantitative pathology in 844 brain regions and subsequent linear diffusion modeling of progression. Consistent with our previous work, we found systemic alterations in the progression of tau pathology in LRRK2G2019S mice, which were most pronounced at 6 months. Importantly, LRRK2 kinase inhibition reversed these effects in LRRK2G2019S mice, but had minimal effect in wild-type mice, suggesting that LRRK2 kinase inhibition is likely to reverse specific disease processes in G2019S mutation carriers. Additional work may be necessary to determine the potential effect in non-carriers. This work supports a protective role of LRRK2 kinase inhibition in G2019S carriers and provides a rational workflow for systematic evaluation of brain-wide phenotypes in therapeutic development.","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"2012 1","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140025783","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}

{"title":"Therapeutics for neurodegenerative diseases by targeting the gut microbiome: from bench to bedside","authors":"Yuan-Yuan Ma, Xin Li, Jin-Tai Yu, Yan-Jiang Wang","doi":"10.1186/s40035-024-00404-1","DOIUrl":"https://doi.org/10.1186/s40035-024-00404-1","url":null,"abstract":"The aetiologies and origins of neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD), are complex and multifaceted. A growing body of evidence suggests that the gut microbiome plays crucial roles in the development and progression of neurodegenerative diseases. Clinicians have come to realize that therapeutics targeting the gut microbiome have the potential to halt the progression of neurodegenerative diseases. This narrative review examines the alterations in the gut microbiome in AD, PD, ALS and HD, highlighting the close relationship between the gut microbiome and the brain in neurodegenerative diseases. Processes that mediate the gut microbiome–brain communication in neurodegenerative diseases, including the immunological, vagus nerve and circulatory pathways, are evaluated. Furthermore, we summarize potential therapeutics for neurodegenerative diseases that modify the gut microbiome and its metabolites, including diets, probiotics and prebiotics, microbial metabolites, antibacterials and faecal microbiome transplantation. Finally, current challenges and future directions are discussed.","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"62 1","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139977954","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}

{"title":"α-Synuclein oligomers potentiate neuroinflammatory NF-κB activity and induce Ca_v3.2 calcium signaling in astrocytes.","authors":"Emmanouela Leandrou, Ioanna Chalatsa, Dimitrios Anagnostou, Christina Machalia, Maria Semitekolou, Vicky Filippa, Manousos Makridakis, Antonia Vlahou, Ema Anastasiadou, Kostas Vekrellis, Evangelia Emmanouilidou","doi":"10.1186/s40035-024-00401-4","DOIUrl":"10.1186/s40035-024-00401-4","url":null,"abstract":"<p><strong>Background: </strong>It is now realized that Parkinson's disease (PD) pathology extends beyond the substantia nigra, affecting both central and peripheral nervous systems, and exhibits a variety of non-motor symptoms often preceding motor features. Neuroinflammation induced by activated microglia and astrocytes is thought to underlie these manifestations. α-Synuclein aggregation has been linked with sustained neuroinflammation in PD, aggravating neuronal degeneration; however, there is still a lack of critical information about the structural identity of the α-synuclein conformers that activate microglia and/or astrocytes and the molecular pathways involved.</p><p><strong>Methods: </strong>To investigate the role of α-synuclein conformers in the development and maintenance of neuroinflammation, we used primary quiescent microglia and astrocytes, post-mortem brain tissues from PD patients and A53T α-synuclein transgenic mice that recapitulate key features of PD-related inflammatory responses in the absence of cell death, i.e., increased levels of pro-inflammatory cytokines and complement proteins. Biochemical and -omics techniques including RNAseq and secretomic analyses, combined with 3D reconstruction of individual astrocytes and live calcium imaging, were used to uncover the molecular mechanisms underlying glial responses in the presence of α-synuclein oligomers in vivo and in vitro.</p><p><strong>Results: </strong>We found that the presence of SDS-resistant hyper-phosphorylated α-synuclein oligomers, but not monomers, was correlated with sustained inflammatory responses, such as elevated levels of endogenous antibodies and cytokines and microglial activation. Similar oligomeric α-synuclein species were found in post-mortem human brain samples of PD patients but not control individuals. Detailed analysis revealed a decrease in Iba1^Low/CD68^Low microglia and robust alterations in astrocyte number and morphology including process retraction. Our data indicated an activation of the p38/ATF2 signaling pathway mostly in microglia and a sustained induction of the NF-κB pathway in astrocytes of A53T mice. The sustained NF-κB activity triggered the upregulation of astrocytic T-type Ca_v3.2 Ca²⁺ channels, altering the astrocytic secretome and promoting the secretion of IGFBPL1, an IGF-1 binding protein with anti-inflammatory and neuroprotective potential.</p><p><strong>Conclusions: </strong>Our work supports a causative link between the neuron-produced α-synuclein oligomers and sustained neuroinflammation in vivo and maps the signaling pathways that are stimulated in microglia and astrocytes. It also highlights the recruitment of astrocytic Ca_v3.2 channels as a potential neuroprotective mediator against the α-synuclein-induced neuroinflammation.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"13 1","pages":"11"},"PeriodicalIF":12.6,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139913569","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}

{"title":"Emerging role of senescent microglia in brain aging-related neurodegenerative diseases","authors":"Chan Rim, Min-Jung You, Minyeop Nahm, Min-Soo Kwon","doi":"10.1186/s40035-024-00402-3","DOIUrl":"https://doi.org/10.1186/s40035-024-00402-3","url":null,"abstract":"Brain aging is a recognized risk factor for neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), but the intricate interplay between brain aging and the pathogenesis of these conditions remains inadequately understood. Cellular senescence is considered to contribute to cellular dysfunction and inflammaging. According to the threshold theory of senescent cell accumulation, the vulnerability to neurodegenerative diseases is associated with the rates of senescent cell generation and clearance within the brain. Given the role of microglia in eliminating senescent cells, the accumulation of senescent microglia may lead to the acceleration of brain aging, contributing to inflammaging and increased vulnerability to neurodegenerative diseases. In this review, we propose the idea that the senescence of microglia, which is notably vulnerable to aging, could potentially serve as a central catalyst in the progression of neurodegenerative diseases. The senescent microglia are emerging as a promising target for mitigating neurodegenerative diseases.","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"13 1","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139910130","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}

{"title":"Microstructural integrity of the locus coeruleus and its tracts reflect noradrenergic degeneration in Alzheimer's disease and Parkinson's disease.","authors":"Chen-Pei Lin, Irene Frigerio, John G J M Bol, Maud M A Bouwman, Alex J Wesseling, Martin J Dahl, Annemieke J M Rozemuller, Ysbrand D van der Werf, Petra J W Pouwels, Wilma D J van de Berg, Laura E Jonkman","doi":"10.1186/s40035-024-00400-5","DOIUrl":"10.1186/s40035-024-00400-5","url":null,"abstract":"<p><strong>Background: </strong>Degeneration of the locus coeruleus (LC) noradrenergic system contributes to clinical symptoms in Alzheimer's disease (AD) and Parkinson's disease (PD). Diffusion magnetic resonance imaging (MRI) has the potential to evaluate the integrity of the LC noradrenergic system. The aim of the current study was to determine whether the diffusion MRI-measured integrity of the LC and its tracts are sensitive to noradrenergic degeneration in AD and PD.</p><p><strong>Methods: </strong>Post-mortem in situ T1-weighted and multi-shell diffusion MRI was performed for 9 AD, 14 PD, and 8 control brain donors. Fractional anisotropy (FA) and mean diffusivity were derived from the LC, and from tracts between the LC and the anterior cingulate cortex, the dorsolateral prefrontal cortex (DLPFC), the primary motor cortex (M1) or the hippocampus. Brain tissue sections of the LC and cortical regions were obtained and immunostained for dopamine-beta hydroxylase (DBH) to quantify noradrenergic cell density and fiber load. Group comparisons and correlations between outcome measures were performed using linear regression and partial correlations.</p><p><strong>Results: </strong>The AD and PD cases showed loss of LC noradrenergic cells and fibers. In the cortex, the AD cases showed increased DBH + immunoreactivity in the DLPFC compared to PD cases and controls, while PD cases showed reduced DBH + immunoreactivity in the M1 compared to controls. Higher FA within the LC was found for AD, which was correlated with loss of noradrenergic cells and fibers in the LC. Increased FA of the LC-DLPFC tract was correlated with LC noradrenergic fiber loss in the combined AD and control group, whereas the increased FA of the LC-M1 tract was correlated with LC noradrenergic neuronal loss in the combined PD and control group. The tract alterations were not correlated with cortical DBH + immunoreactivity.</p><p><strong>Conclusions: </strong>In AD and PD, the diffusion MRI-detected alterations within the LC and its tracts to the DLPFC and the M1 were associated with local noradrenergic neuronal loss within the LC, rather than noradrenergic changes in the cortex.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"13 1","pages":"9"},"PeriodicalIF":12.6,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10854137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713145","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}

{"title":"Life and disease status of patients with Parkinson's disease during and after zero-COVID in China: an online survey.","authors":"Pei Huang, Yu-Yan Tan, Biao Chen, Hui-Fang Shang, Li-Juan Wang, Chun-Feng Liu, Ling Chen, Ying Chang, Han Wang, Xue-Lian Wang, Xiao-Guang Lei, Li-Fen Yao, Yang Yu, Zheng Ye, Hai-Bo Chen, Sheng-Di Chen","doi":"10.1186/s40035-024-00399-9","DOIUrl":"10.1186/s40035-024-00399-9","url":null,"abstract":"<p><strong>Background: </strong>Little is known about the impact of the COVID-19 pandemic on patients with Parkinson's disease (PD) at different stages of the pandemic. This study aims to assess the lives and disease status of PD patients during the zero-COVID policy period and after ending the zero-COVID policy.</p><p><strong>Methods: </strong>This multicenter cross-sectional study included two online surveys among PD patients in China, from May 30 to June 30 in 2022 and from January 1 to February 28 in 2023, respectively. The survey questionnaires contained four sections: (1) status of COVID-19 infection; (2) impact on motor and non-motor symptoms; (3) impact on daily and social lives; and (4) impact on PD disease management.</p><p><strong>Results: </strong>A total of 1764 PD patients participated in the first online survey, with 200 patients having lockdown experience and 3 being COVID-19-positive (0.17%). In addition, 537 patients participated in the second online survey, with 467 patients having COVID-19 infection (86.96%). (1) During zero-COVID, all of the COVID-19-positive patients had mild symptoms of COVID-19 and no death was reported. After zero-COVID, 83.51% of the COVID-19-positive patients had mild symptoms. The overall death rate and inpatient mortality rate of COVID-19-positive PD patients were 3.21% and 30.00%, respectively. (2) During zero-COVID, 49.43% of PD patients reported worsening of PD-related symptoms (lockdown vs. unlockdown, 60.50% vs. 48.02%, P = 0.0009). After zero-COVID, 54.93% of PD patients reported worsening of PD-related symptoms (COVID-19 positive vs. COVID-19 negative, 59.31% vs. 25.71%, P < 0.0001). (3) During zero-COVID, 62.36% of patients felt worried, and 'limited outdoor activities' (55.39%) was the top reason for mental health problems. After zero-COVID, 59.03% of patients felt worried, with 'poor health' (58.10%) being the top reason. The PD patients tended to change their daily activities from offline to online, and their economic and caregiver burdens increased both during and after zero-COVID. (4) Most PD patients would like to choose online rehabilitation during (69.56%) and after zero-COVID (69.27%). The demand for online medication purchasing also increased during (47.00%) and after zero-COVID (26.63%).</p><p><strong>Conclusions: </strong>The COVID-19 pandemic aggravated the motor and non-motor symptoms of PD patients either during or after the zero-COVID policy period. The PD patients also experienced prominent mental health problems, changes in daily activities, and increases in economic and caregiver burdens. The COVID-19 pandemic has changed ways of PD management with increasing demands for online medication purchasing and rehabilitation.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"13 1","pages":"8"},"PeriodicalIF":12.6,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10845503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139693041","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}

{"title":"The interaction between ageing and Alzheimer's disease: insights from the hallmarks of ageing.","authors":"Yuqing Liu, Yejun Tan, Zheyu Zhang, Min Yi, Lemei Zhu, Weijun Peng","doi":"10.1186/s40035-024-00397-x","DOIUrl":"10.1186/s40035-024-00397-x","url":null,"abstract":"<p><p>Ageing is a crucial risk factor for Alzheimer's disease (AD) and is characterised by systemic changes in both intracellular and extracellular microenvironments that affect the entire body instead of a single organ. Understanding the specific mechanisms underlying the role of ageing in disease development can facilitate the treatment of ageing-related diseases, such as AD. Signs of brain ageing have been observed in both AD patients and animal models. Alleviating the pathological changes caused by brain ageing can dramatically ameliorate the amyloid beta- and tau-induced neuropathological and memory impairments, indicating that ageing plays a crucial role in the pathophysiological process of AD. In this review, we summarize the impact of several age-related factors on AD and propose that preventing pathological changes caused by brain ageing is a promising strategy for improving cognitive health.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"13 1","pages":"7"},"PeriodicalIF":10.8,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10804662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139521993","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}

{"title":"The therapeutic potential of probucol and probucol analogues in neurodegenerative diseases.","authors":"Arazu Sharif, John Mamo, Virginie Lam, Hani Al-Salami, Armin Mooranian, Gerald F Watts, Roger Clarnette, Giuseppe Luna, Ryu Takechi","doi":"10.1186/s40035-024-00398-w","DOIUrl":"10.1186/s40035-024-00398-w","url":null,"abstract":"<p><p>Neurodegenerative disorders present complex pathologies characterized by various interconnected factors, including the aggregation of misfolded proteins, oxidative stress, neuroinflammation and compromised blood-brain barrier (BBB) integrity. Addressing such multifaceted pathways necessitates the development of multi-target therapeutic strategies. Emerging research indicates that probucol, a historic lipid-lowering medication, offers substantial potential in the realm of neurodegenerative disease prevention and treatment. Preclinical investigations have unveiled multifaceted cellular effects of probucol, showcasing its remarkable antioxidative and anti-inflammatory properties, its ability to fortify the BBB and its direct influence on neural preservation and adaptability. These diverse effects collectively translate into enhancements in both motor and cognitive functions. This review provides a comprehensive overview of recent findings highlighting the efficacy of probucol and probucol-related compounds in the context of various neurodegenerative conditions, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and cognitive impairment associated with diabetes.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"13 1","pages":"6"},"PeriodicalIF":10.8,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10802046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139513685","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}