Frontiers in Cellular Neuroscience最新文献

{"title":"Cycloastragenol promotes dorsal column axon regeneration in mice.","authors":"Tao Zihan, Teng Wenwen, Ma Yanxia, Saijilafu","doi":"10.3389/fncel.2024.1424137","DOIUrl":"https://doi.org/10.3389/fncel.2024.1424137","url":null,"abstract":"<p><strong>Introduction: </strong>Cycloastragenol (CAG) has a wide range of pharmacological effects, including anti-inflammatory, antiaging, antioxidative, and antitumorigenic properties. In addition, our previous study showed that CAG administration can promote axonal regeneration in peripheral neurons. However, whether CAG can activate axon regeneration central nervous system (CNS) remains unknown.</p><p><strong>Methods: </strong>Here, we established a novel mouse model for visualizing spinal cord dorsal column axon regeneration involving the injection of AAV2/9-Cre into the lumbar 4/5 dorsal root ganglion (DRG) of Rosa-tdTomato reporter mice. We then treated mice by intraperitoneal administration of CAG.</p><p><strong>Results: </strong>Our results showed that intraperitoneal CAG injections significantly promoted the growth of <i>vitro</i>-cultured DRG axons as well as the growth of dorsal column axons over the injury site in spinal cord injury (SCI) mice. Our results further indicate that CAG administration can promote the recovery of sensory and urinary function in SCI mice.</p><p><strong>Conclusion: </strong>Together, our findings highlight the therapeutic potential of CAG in spinal cord injury repair.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1424137"},"PeriodicalIF":4.2,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case report: Atypical young case of MV1 Creutzfeldt-Jakob disease with unusually long survival.","authors":"Lucie Yeongran Ahn, Mark L Cohen, Ignazio Cali, Tia Russell, Jessica Ludwig, Xun Jia, Alberto Bizzi, Lawrence B Schonberger, Ryan A Maddox, Rohini Paul, Tania C Ghazarian, Jaspreet Garcha, Mostafa Hammoudi, Brian Stephen Appleby","doi":"10.3389/fncel.2024.1518542","DOIUrl":"https://doi.org/10.3389/fncel.2024.1518542","url":null,"abstract":"<p><p>Creutzfeldt-Jakob disease (CJD) is a rare, fatal, rapidly progressive neurodegenerative disease resulting from an accumulation of misfolded prion proteins (PrP). CJD affects 1-2 new individuals per million each year, and the sporadic type accounts for 90% of those cases. Though the median age at onset and disease duration vary depending on the subtype of sporadic CJD (sCJD), the disease typically affects middle-aged to elderly individuals with a median survival of 4-6 months. sCJD in younger individuals is extremely rare. Here, we present a 21-year-old female who died with a sporadic prion disease. She presented with psychiatric symptoms followed by a rapidly progressive neurocognitive and motor decline. EEG was negative for periodic sharp wave complexes; however, brain MRI was suggestive of prion disease. The cerebrospinal fluid (CSF) real-time quaking-induced conversion (RT-QuIC) assay was indeterminate. Neuropathologic examination at autopsy revealed severe neuronal loss and gliosis with secondary white matter degeneration but minimal spongiform changes and PrP deposits in the cerebellum and neocortex by immunohistochemistry. Absence of pathogenic mutations and methionine/valine heterozygosity at codon 129 of the prion protein gene (PRNP), atypical type 1 protease-resistant PrP that lacks or shows underrepresentation of the diglycosylated PrP isoform by western blot analysis, and no acquired prion disease risk factors resulted in a final diagnosis of atypical sCJD. Very young onset sCJD often has atypical clinical presentations and disease progression, neuropathological examination results, and/or laboratory test results that may confound diagnosis. It is critical to perform thorough, comprehensive evaluations to make an accurate diagnosis, which includes autopsy confirmation with histology, prion protein typing and prion gene sequencing.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1518542"},"PeriodicalIF":4.2,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STZ-induced hyperglycemia differentially influences mitochondrial distribution and morphology in the habenulointerpeduncular circuit.","authors":"Mohammad Jodeiri Farshbaf, Taelor A Matos, Kristi Niblo, Yacoub Alokam, Jessica L Ables","doi":"10.3389/fncel.2024.1432887","DOIUrl":"10.3389/fncel.2024.1432887","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetes is a metabolic disorder of glucose homeostasis that is a significant risk factor for neurodegenerative diseases, such as Alzheimer's disease, as well as mood disorders, which often precede neurodegenerative conditions. We examined the medial habenulainterpeduncular nucleus (MHb-IPN), as this circuit plays crucial roles in mood regulation, has been linked to the development of diabetes after smoking, and is rich in cholinergic neurons, which are affected in other brain areas in Alzheimer's disease.</p><p><strong>Methods: </strong>This study aimed to investigate the impact of streptozotocin (STZ)-induced hyperglycemia, a type 1 diabetes model, on mitochondrial and lipid homeostasis in 4% paraformaldehyde-fixed sections from the MHb and IPN of C57BL/6 J male mice, using a recently developed automated pipeline for mitochondrial analysis in confocal images. We examined different time points after STZ-induced diabetes onset to determine how the brain responded to chronic hyperglycemia, with the limitation that mitochondria and lipids were not examined with respect to cell type or intracellular location.</p><p><strong>Results: </strong>Mitochondrial distribution and morphology differentially responded to hyperglycemia depending on time and brain area. Six weeks after STZ treatment, mitochondria in the ventral MHb and dorsal IPN increased in number and exhibited altered morphology, but no changes were observed in the lateral habenula (LHb) or ventral IPN. Strikingly, mitochondrial numbers returned to normal dynamics at 12 weeks. Both blood glucose level and glycated hemoglobin (HbA1C) correlated with mitochondrial dynamics in ventral MHb, whereas only HbA1C correlated in the IPN. We also examined lipid homeostasis using BODIPY staining for neutral lipids in this model given that diabetes is associated with disrupted lipid homeostasis. BODIPY staining intensity was unchanged in the vMHb of STZ-treated mice but increased in the IPN and VTA and decreased in the LHb at 12 weeks. Interestingly, areas that demonstrated changes in mitochondria had little change in lipid staining and vice versa.</p><p><strong>Discussion: </strong>This study is the first to describe the specific impacts of diabetes on mitochondria in the MHb-IPN circuit and suggests that the cholinergic MHb is uniquely sensitive to diabetesinduced hyperglycemia. Further studies are needed to understand the functional and behavioral implications of these findings.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1432887"},"PeriodicalIF":4.2,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11700986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acceleration of spontaneous visual recovery by voluntary physical exercise in adolescent amblyopic rats.","authors":"Irene Di Marco, Gabriele Sansevero, Nicoletta Berardi, Alessandro Sale","doi":"10.3389/fncel.2024.1519197","DOIUrl":"https://doi.org/10.3389/fncel.2024.1519197","url":null,"abstract":"<p><p>Abnormal visual experience during development resulting from an imbalance in the activity of the two eyes can lead to permanent severe visual deficits, a pathology called amblyopia (lazy eye). While this condition is extremely difficult to treat in adults, current interventions can elicit significant amounts of visual recovery when performed in juveniles before the end of the critical period, even if the achievable results can be unsatisfactory due to the progressive decline in visual cortical plasticity. Similarly to human subjects, rodents becoming amblyopic due to early visual deprivation can display spontaneous functional recovery if the deprivation ends within the critical period time window. With the aim to investigate the impact of non-invasive strategies able to increase this spontaneous potential for plasticity, we wondered whether physical exercise could speed up spontaneous recovery of visual functions in juvenile amblyopic rats. Our results show that physical exercise accelerates visual recovery in adolescent rats, encouraging application of behavioral plasticizing treatments to promote recovery in young individuals.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1519197"},"PeriodicalIF":4.2,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synaptic microarchitecture: the role of spatial interplay between excitatory and inhibitory inputs in shaping dendritic plasticity and neuronal output.","authors":"Dario Cupolillo, Vincenzo Regio, Andrea Barberis","doi":"10.3389/fncel.2024.1513602","DOIUrl":"https://doi.org/10.3389/fncel.2024.1513602","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1513602"},"PeriodicalIF":4.2,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the SARS-CoV-2 spike protein long-term effect on neuro-PASC.","authors":"Filipe Menezes, Julys da Fonseca Palmeira, Juliana Dos Santos Oliveira, Gustavo Adolfo Argañaraz, Carlos Roberto Jorge Soares, Otávio Toledo Nóbrega, Bergmann Morais Ribeiro, Enrique Roberto Argañaraz","doi":"10.3389/fncel.2024.1481963","DOIUrl":"10.3389/fncel.2024.1481963","url":null,"abstract":"<p><p>The persistence or emergence of long-term symptoms following resolution of primary SARS-CoV-2 infection is referred to as long COVID or post-acute sequelae of COVID-19 (PASC). PASC predominantly affects the cardiovascular, neurological, respiratory, gastrointestinal, reproductive, and immune systems. Among these, the central nervous system (CNS) is significantly impacted, leading to a spectrum of symptoms, including fatigue, headaches, brain fog, cognitive impairment, anosmia, hypogeusia, neuropsychiatric symptoms, and peripheral neuropathy (neuro-PASC). However, the risk factors and pathogenic mechanisms responsible for neuro-PASC remain unclear. This review hypothesis discusses the leading hypotheses regarding the pathophysiological mechanisms involved in long COVID/PASC, focusing on neuro-PASC. We propose vascular dysfunction mediated by activation of astrocytes and pericytes followed by blood-brain barrier (BBB) disruption as underlying pathophysiological mechanisms of neurological manifestations. Additionally, we provide insights into the role of spike protein at the blood-brain interface. Finally, we explore the potential pathogenic mechanisms initiated by the interaction between the spike protein and cellular receptors at the brain endothelial and tissue levels.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1481963"},"PeriodicalIF":4.2,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain organoid methodologies to explore mechanisms of disease in progressive multiple sclerosis.","authors":"Madalena B C Simões-Abade, Marlene Patterer, Alexandra M Nicaise, Stefano Pluchino","doi":"10.3389/fncel.2024.1488691","DOIUrl":"10.3389/fncel.2024.1488691","url":null,"abstract":"<p><p>Multiple sclerosis (MS), a debilitating autoimmune disorder targeting the central nervous system (CNS), is marked by relentless demyelination and inflammation. Clinically, it presents in three distinct forms: relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS). While disease-modifying therapies (DMTs) offer some relief to people with RRMS, treatment options for progressive MS (pMS) remain frustratingly inadequate. This gap highlights an urgent need for advanced disease modeling techniques to unravel the intricate pathology of pMS. Human induced pluripotent stem cell (iPSC) technologies and brain organoids are emerging as promising tools for disease modeling in both 2D and 3D <i>in vitro</i> environments. These innovative approaches enable the study of disease mechanisms that closely mimic human pathophysiology and offer new platforms for screening therapeutic compounds, surpassing the limitations of traditional animal models. However, deploying brain organoids in disease modeling presents challenges, especially in the context of non-monogenic disorders. This review delves into cutting-edge brain organoid techniques that hold the potential to revolutionize our understanding of pMS, offering a pathway to disentangle its underlying mechanisms and drive transformative discoveries.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1488691"},"PeriodicalIF":4.2,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Tet2</i>-mediated clonal hematopoiesis modestly improves neurological deficits and is associated with inflammation resolution in the subacute phase of experimental stroke.","authors":"Megan A Evans, Nicholas W Chavkin, Soichi Sano, Hanna Sun, Taneesha Sardana, Ramya Ravi, Heather Doviak, Ying Wang, Yoshimitsu Yura, Ariel H Polizio, Keita Horitani, Hayato Ogawa, Karen K Hirschi, Kenneth Walsh","doi":"10.3389/fncel.2024.1487867","DOIUrl":"10.3389/fncel.2024.1487867","url":null,"abstract":"<p><strong>Introduction: </strong>Recent work has revealed that clonal hematopoiesis (CH) is associated with a higher risk of numerous age-related diseases, including ischemic stroke, however little is known about whether it influences stroke outcome independent of its widespread effects on cardiovascular disease. Studies suggest that leukocytes carrying CH driver mutations have an enhanced inflammatory profile, which could conceivably exacerbate brain injury after a stroke.</p><p><strong>Methods: </strong>Using a competitive bone marrow transplant model of <i>Tet2</i>-mediated CH, we tested the hypothesis that CH would lead to a poorer outcome after ischemic stroke by augmenting brain inflammation. Stroke was induced in mice by middle cerebral artery occlusion and neurological outcome was assessed at acute (24 h) and subacute (14 d) timepoints. Brains were collected at both time points for histological, immunofluorescence and gene expression assays.</p><p><strong>Results: </strong>Unexpectedly, <i>Tet2</i>-mediated CH had no effect on acute stroke outcome but led to a reduction in neurological deficits during the subacute phase. This improved neurological outcome was associated with lower levels of brain inflammation as evidenced by lower transcript levels of various inflammatory molecules alongside reduced astrogliosis.</p><p><strong>Discussion: </strong>These findings suggest that <i>Tet2</i>-mediated CH may have beneficial effects on outcome after stroke, contrasting with the conventional understanding of CH whereby leukocytes with driver mutations promote disease by exacerbating inflammation.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1487867"},"PeriodicalIF":4.2,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of microglia in Neuroinflammation associated with cardiopulmonary bypass.","authors":"Lingda Meng, Tianxiang Gu, Peng Yu, Zhiwei Zhang, Zhijing Wei","doi":"10.3389/fncel.2024.1496520","DOIUrl":"10.3389/fncel.2024.1496520","url":null,"abstract":"<p><p>Cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) are indispensable core techniques in cardiac surgery. Numerous studies have shown that cardiopulmonary bypass and deep hypothermic circulatory arrest are associated with the occurrence of neuroinflammation, accompanied by the activation of microglia. Microglia, as macrophages in the central nervous system, play an irreplaceable role in neuroinflammation. Current research on neuroinflammation induced by microglia activation mainly focuses on neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, neuropathic pain, acquired brain injury, and others. However, there is relatively limited research on microglia and neuroinflammation under conditions of cardiopulmonary bypass and deep hypothermic circulatory arrest. The close relationship between cardiopulmonary bypass, deep hypothermic circulatory arrest, and cardiac surgery underscores the importance of identifying targets for intervening in neuroinflammation through microglia. This could greatly benefit cardiac surgery patients during cardiopulmonary bypass and the perioperative period, significantly improving patient prognosis. This review article provides the first comprehensive discussion on the signaling pathways associated with neuroinflammation triggered by microglia activation, the impact of cardiopulmonary bypass on microglia, as well as the current status and advancements in cardiopulmonary bypass animal models. It provides new insights and methods for the treatment of neuroinflammation related to cardiopulmonary bypass and deep hypothermic circulatory arrest, holding significant importance for clinical treatment by cardiac surgeons, management strategies by cardiopulmonary bypass physicians, and the development of neurologically related medications.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1496520"},"PeriodicalIF":4.2,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SUMO2 rescues neuronal and glial cells from the toxicity of P301L Tau mutant.","authors":"Franca Orsini, Rosaria Pascente, Annacarla Martucci, Sara Palacino, Paul Fraser, Ottavio Arancio, Luana Fioriti","doi":"10.3389/fncel.2024.1437995","DOIUrl":"10.3389/fncel.2024.1437995","url":null,"abstract":"<p><strong>Introduction: </strong>Abnormal intracellular accumulation of Tau aggregates is a hallmark of Alzheimer's disease (AD) and other Tauopathies, such as Frontotemporal dementia (FTD). Tau deposits primarily affect neurons, but evidence indicates that glial cells may also be affected and contribute distinctively to disease progression. Cells can respond to toxic insults by orchestrating global changes in posttranslational modifications of their proteome. Previous studies suggest that SUMOylation, a posttranslational modification consisting of conjugation of SUMO (Small ubiquitin-like modifier) to target proteins, was decreased in the hippocampus of AD patients and in animal model of AD compared with controls. This decrease in SUMOylation was correlated with increased Tau pathology and cognitive decline. Other studies have reported increased levels of SUMO in AD brains. The goal of our study was to evaluate whether SUMO conjugation modifies the neurodegenerative disease pathology associated with the aggregation-prone mutant TauP301L, in neurons and in glial cells.</p><p><strong>Methods: </strong>We used viral approaches to express mutant TauP301L and SUMO2 in the hippocampus of wild-type mice. We assessed Tau distribution by immunostaining and Tau aggregation by insolubility assays followed by western blotting. We assessed neuronal toxicity and performed cell count and shape descriptor analyses on astrocytes and microglial cells.</p><p><strong>Results: </strong>We found that mutant TauP301L, when expressed exclusively in neurons, is toxic not only to neurons but also to glial cells, and that SUMO2 counteracts TauP301L toxicity in neurons as well as in glia.</p><p><strong>Discussion: </strong>Our results uncover an endogenous neuroprotective mechanism, whereby SUMO2 conjugation reduces Tau neuropathology and protects against toxic effects of Tau in glial cells.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1437995"},"PeriodicalIF":4.2,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}