Journal of Physiology-London最新文献

{"title":"Ventilator-induced diaphragm dysfunction: phenomenology and mechanism(s) of pathogenesis.","authors":"Scott K Powers","doi":"10.1113/JP283860","DOIUrl":"https://doi.org/10.1113/JP283860","url":null,"abstract":"<p><p>Mechanical ventilation (MV) is used to support ventilation and pulmonary gas exchange in patients during critical illness and surgery. Although MV is a life-saving intervention for patients in respiratory failure, an unintended side-effect of MV is the rapid development of diaphragmatic atrophy and contractile dysfunction. This MV-induced diaphragmatic weakness is labelled as 'ventilator-induced diaphragm dysfunction' (VIDD). VIDD is an important clinical problem because diaphragmatic weakness is a risk factor for the failure to wean patients from MV. Indeed, the inability to remove patients from ventilator support results in prolonged hospitalization and increased morbidity and mortality. The pathogenesis of VIDD has been extensively investigated, revealing that increased mitochondrial production of reactive oxygen species within diaphragm muscle fibres promotes a cascade of redox-regulated signalling events leading to both accelerated proteolysis and depressed protein synthesis. Together, these events promote the rapid development of diaphragmatic atrophy and contractile dysfunction. This review highlights the MV-induced changes in the structure/function of diaphragm muscle and discusses the cell-signalling mechanisms responsible for the pathogenesis of VIDD. This report concludes with a discussion of potential therapeutic opportunities to prevent VIDD and suggestions for future research in this exciting field.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142114294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conjunctive processing of spatial border and locomotion in retrosplenial cortex during spatial navigation.","authors":"Hao Sun, Ruolan Cai, Rui Li, Mingxuan Li, Lixia Gao, Xinjian Li","doi":"10.1113/JP286434","DOIUrl":"https://doi.org/10.1113/JP286434","url":null,"abstract":"<p><p>Spatial information and dynamic locomotor behaviours are equally important for achieving locomotor goals during spatial navigation. However, it remains unclear how spatial and locomotor information is integrated during the processing of self-initiated spatial navigation. Anatomically, the retrosplenial cortex (RSC) has reciprocal connections with brain regions related to spatial processing, including the hippocampus and para-hippocampus, and also receives inputs from the secondary motor cortex. In addition, RSC is functionally associated with allocentric and egocentric spatial targets and head-turning. So, RSC may be a critical region for integrating spatial and locomotor information. In this study, we first examined the role of RSC in spatial navigation using the Morris water maze and found that mice with inactivated RSC took a longer time and distance to reach their destination. Then, by imaging neuronal activity in freely behaving mice within two open fields of different sizes, we identified a large proportion of border cells, head-turning cells and locomotor speed cells in the superficial layer of RSC. Interestingly, some RSC neurons exhibited conjunctive coding for both spatial and locomotor signals. Furthermore, these conjunctive neurons showed higher prediction accuracy compared with simple spatial or locomotor neurons in special navigator scenes using the border, turning and positive-speed conjunctive cells. Our study reveals that the RSC is an important conjunctive brain region that processes spatial and locomotor information during spatial navigation. KEY POINTS: Retrosplenial cortex (RSC) is indispensable during spatial navigation, which was displayed by the longer time and distance of mice to reach their destination after the inactivation of RSC in a water maze. The superficial layer of RSC has a larger population of spatial-related border cells, and locomotion-related head orientation and speed cells; however, it has few place cells in two-dimensional spatial arenas. Some RSC neurons exhibited conjunctive coding for both spatial and locomotor signals, and the conjunctive neurons showed higher prediction accuracy compared with simple spatial or locomotor neurons in special navigation scenes. Our study reveals that the RSC is an important conjunctive brain region that processes both spatial and locomotor information during spatial navigation.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142114287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myosin ATPase inhibition fails to rescue the metabolically dysregulated proteome of nebulin-deficient muscle.","authors":"Jenni Laitila, Robert A E Seaborne, Natasha Ranu, Justin S Kolb, Carina Wallgren-Pettersson, Nanna Witting, John Vissing, Juan Jesus Vilchez, Edmar Zanoteli, Johanna Palmio, Sanna Huovinen, Henk Granzier, Julien Ochala","doi":"10.1113/JP286870","DOIUrl":"https://doi.org/10.1113/JP286870","url":null,"abstract":"<p><p>Nemaline myopathy (NM) is a genetic muscle disease, primarily caused by mutations in the NEB gene (NEB-NM) and with muscle myosin dysfunction as a major molecular pathogenic mechanism. Recently, we have observed that the myosin biochemical super-relaxed state was significantly impaired in NEB-NM, inducing an aberrant increase in ATP consumption and remodelling of the energy proteome in diseased muscle fibres. Because the small-molecule Mavacamten is known to promote the myosin super-relaxed state and reduce the ATP demand, we tested its potency in the context of NEB-NM. We first conducted in vitro experiments in isolated single myofibres from patients and found that Mavacamten successfully reversed the myosin ATP overconsumption. Following this, we assessed its short-term in vivo effects using the conditional nebulin knockout (cNeb KO) mouse model and subsequently performing global proteomics profiling in dissected soleus myofibres. After a 4 week treatment period, we observed a remodelling of a large number of proteins in both cNeb KO mice and their wild-type siblings. Nevertheless, these changes were not related to the energy proteome, indicating that short-term Mavacamten treatment is not sufficient to properly counterbalance the metabolically dysregulated proteome of cNeb KO mice. Taken together, our findings emphasize Mavacamten potency in vitro but challenge its short-term efficacy in vivo. KEY POINTS: No cure exists for nemaline myopathy, a type of genetic skeletal muscle disease mainly derived from mutations in genes encoding myofilament proteins. Applying Mavacamten, a small molecule directly targeting the myofilaments, to isolated membrane-permeabilized muscle fibres from human patients restored myosin energetic disturbances. Treating a mouse model of nemaline myopathy in vivo with Mavacamten for 4 weeks, remodelled the skeletal muscle fibre proteome without any noticeable effects on energetic proteins. Short-term Mavacamten treatment may not be sufficient to reverse the muscle phenotype in nemaline myopathy.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142114289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Propagation of sharp wave-ripple activity in the mouse hippocampal CA3 subfield in vitro.","authors":"Natalie Schieferstein, Ana Del Toro, Roberta Evangelista, Barbara Imbrosci, Aarti Swaminathan, Dietmar Schmitz, Nikolaus Maier, Richard Kempter","doi":"10.1113/JP285671","DOIUrl":"https://doi.org/10.1113/JP285671","url":null,"abstract":"<p><p>Sharp wave-ripple complexes (SPW-Rs) are spontaneous oscillatory events that characterize hippocampal activity during resting periods and slow-wave sleep. SPW-Rs are related to memory consolidation - the process during which newly acquired memories are transformed into long-lasting memory traces. To test the involvement of SPW-Rs in this process, it is crucial to understand how SPW-Rs originate and propagate throughout the hippocampus. SPW-Rs can originate in CA3, and they typically spread from CA3 to CA1, but little is known about their formation within CA3. To investigate the generation and propagation of SPW-Rs in CA3, we recorded from mouse hippocampal slices using multi-electrode arrays and patch-clamp electrodes. We characterized extracellular and intracellular correlates of SPW-Rs and quantified their propagation along the pyramidal cell layer of CA3. We found that a hippocampal slice can be described by a speed and a direction of propagation of SPW-Rs. The preferred propagation direction was from CA3c (the subfield closer to the dentate gyrus) toward CA3a (the subfield at the boundary to CA2). In patch-clamp recordings from CA3 pyramidal neurons, propagation was estimated separately for excitatory and inhibitory currents associated with SPW-Rs. We found that propagation speed and direction of excitatory and inhibitory currents were correlated. The magnitude of the speed of propagation of SPW-Rs within CA3 was consistent with the speed of propagation of action potentials in axons of CA3 principal cells. KEY POINTS: Hippocampal sharp waves are considered important for memory consolidation; therefore, it is of interest to understand the mechanisms of their generation and propagation. Here, we used two different approaches to study the propagation of sharp waves in mouse CA3 in vitro: multi-electrode arrays and multiple single-cell recordings. We find a preferred direction of propagation of sharp waves from CA3c toward CA3a - both in the local field potential and in sharp wave-associated excitatory and inhibitory synaptic activity. The speed of sharp wave propagation is consistent with the speed of action potential propagation along the axons of CA3 pyramidal neurons. These new insights into the dynamics of sharp waves in the CA3 network will inform future experiments and theoretical models of sharp-wave generation mechanisms.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142114290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Timely interventions: aerobic exercise and microvascular health post-menopause.","authors":"Adam Mustapha Khay, Gabrielle Gilmer, Hirotaka Iijima","doi":"10.1113/JP287073","DOIUrl":"10.1113/JP287073","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142114293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new sympathetic understanding of exercise blood flow regulation in heart failure with preserved ejection fraction.","authors":"Giorgio Manferdelli, Denis J Wakeham","doi":"10.1113/JP287108","DOIUrl":"https://doi.org/10.1113/JP287108","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142114284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A proline-tyrosine motif, endocytosis and low salt – how to link protein functions to organ physiology","authors":"Christoph Fahlke","doi":"10.1113/JP287335","DOIUrl":"https://doi.org/10.1113/JP287335","url":null,"abstract":"&lt;p&gt;Physiology studies the functioning of the human body and aims at a comprehensive understanding of the physical and chemical processes that define the function of organs and their cooperation in a healthy body. An important application of physiology is – via improved understanding of disease pathophysiology and disease compensatory processes – the development of novel and improved treatment options for human diseases. It is obvious that such goals can only be achieved by studying cell and organ functions at a molecular level. Proteins direct virtually all cell functions, and rational treatment options will either have to correct protein dysfunctions as the disease cause or to stimulate or inhibit other proteins that may compensate for the disease-causing dysfunction.&lt;/p&gt;&lt;p&gt;In the last decades, we have witnessed amazing progress in molecular physiology: structural biology has allowed identification of primary, secondary and tertiary structures from a large number of proteins; and biochemistry, cell physiology and computer-based simulation have clarified the mechanisms of their function at almost atomistic resolution. This breath-taking success almost made us forget the difficulties of the next step – to link detailed molecular understanding of single protein function to cell and organ behaviour. In this issue of &lt;i&gt;The Journal of Physiology&lt;/i&gt; Clara Mayayo-Vallverdú and colleagues provide an example of scientific work that exactly addresses this important task (Mayayo-Vallverdú et al., &lt;span&gt;2024&lt;/span&gt;)&lt;/p&gt;&lt;p&gt;The authors study a particular anion channel, ClC-K–barttin, which is predominantly expressed in the kidney and in the inner ear. ClC-K–barttin channels contribute to NaCl resorption in the loop of Henle and to K&lt;sup&gt;+&lt;/sup&gt; secretion by the stria vascularis. They are assembled as multi-subunit complexes, consisting of the pore-forming ClC-K subunit and the accessory barttin subunit. Although neither the stoichiometry nor the architecture of the complex is known, its formation is obligatory for channel function. ClC-K is non-conducting without barttin (Fischer et al., &lt;span&gt;2010&lt;/span&gt;) and cannot traffic to the surface membrane. Barttin allows ClC-K to exit from the endoplasmic reticulum and insert into the plasma membrane and changes its function by modifying voltage-dependent gating processes (Fischer et al., &lt;span&gt;2010&lt;/span&gt;). ClC-K proteins cannot be detected in cells lacking barttin (Rickheit et al., &lt;span&gt;2010&lt;/span&gt;), most likely because barttin is required for complex glycosylation and thus protein stability of ClC-K subunits (Janssen et al., &lt;span&gt;2009&lt;/span&gt;). Mutations in the gene encoding barttin, &lt;i&gt;BSND&lt;/i&gt;, cause Bartter syndrome IV, with impaired urinary concentration and sensory deafness, with clear correlation between barttin dysfunction and clinical symptoms (Janssen et al., &lt;span&gt;2009&lt;/span&gt;).&lt;/p&gt;&lt;p&gt;This latest paper by the Estevez group is based on a barttin point mutation, Y98A, that was identified decades ago to i","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1113/JP287335","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to 'Neuronal activity patterns in microcircuits of the cerebellar cortical C3 zone during reaching'.","authors":"","doi":"10.1113/JP287525","DOIUrl":"https://doi.org/10.1113/JP287525","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142114288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Jun-activated SOCS1 enhances ubiquitination and degradation of CCAAT/enhancer-binding protein β to ameliorate cerebral ischaemia/reperfusion injury.","authors":"Chuan He, Tie Wang, Yanwu Han, Changyang Zuo, Guangming Wang","doi":"10.1113/JP285673","DOIUrl":"https://doi.org/10.1113/JP285673","url":null,"abstract":"<p><p>This study investigates the molecular mechanisms behind ischaemia/reperfusion (I/R) injury in the brain, focusing on neuronal apoptosis. It scrutinizes the role of the Jun proto-oncogene in apoptosis, involvement of SOCS1 in neural precursor cell accumulation in ischaemic regions, and the upregulation of C-EBPβ in the hippocampus following I/R. Key to the study is understanding how Jun controls C-EBPβ degradation via SOCS1, potentially offering new clinical treatment avenues for I/R. Techniques such as mRNA sequencing, KEGG enrichment analysis and protein-protein interaction (PPI) in mouse models have indicated involvement of Jun (AP-1) in I/R-induced cerebral damage. The study employs middle cerebral artery occlusion in different mouse models and oxygen-glucose deprivation/reoxygenation in cortical neurons to examine the impacts of Jun and SOCS1 manipulation on cerebral I/R injury and neuronal damage. The findings reveal that I/R reduces Jun expression in the brain, but its restoration lessens cerebral I/R injury and neuron death. Jun activates SOCS1 transcriptionally, leading to C-EBPβ degradation, thereby diminishing cerebral I/R injury through the SOCS1/C-EBPβ pathway. These insights provide a deeper understanding of post-I/R cerebral injury mechanisms and suggest new therapeutic targets for cerebral I/R injury. KEY POINTS: Jun and SOCS1 are poorly expressed, and C-EBPβ is highly expressed in ischaemia/reperfusion mouse brain tissues. Jun transcriptionally activates SOCS1. SOCS1 promotes the ubiquitination-dependent C-EBPβ protein degradation. Jun blunts oxygen-glucose deprivation/reoxygenation-induced neuron apoptosis and alleviates neuronal injury. This study provides a theoretical basis for the management of post-I/R brain injury.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142086396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of the peripheral chemoreceptors in cardiovascular and metabolic control in type 2 diabetes.","authors":"Jacqueline K Limberg, Elizabeth P Ott, Aubrey M Pipkins, Eric C Lis, Anna M Gonsalves, Jennifer L Harper, Camila Manrique-Acevedo","doi":"10.1113/JP286975","DOIUrl":"https://doi.org/10.1113/JP286975","url":null,"abstract":"<p><p>Preclinical work supports a role for the peripheral chemoreceptors in the progression of cardiovascular and metabolic pathologies. In the present study, we examined peripheral chemosensitivity in adults with type 2 diabetes (T2D) and the contribution of the peripheral chemoreceptors to resting cardiovascular and metabolic control. We hypothesized that: (1) adults with T2D exhibit exaggerated peripheral chemoreflex sensitivity; (2) the peripheral chemoreceptors contribute to cardiovascular dysfunction in T2D; and (3) attenuation of peripheral chemoreceptor activity improves glucose tolerance in T2D. Seventeen adults with diagnosed T2D [six males/11 females; aged 54 ± 11 years; glycated haemoglobin (HbA1c) 7.6 ± 1.5%] and 20 controls without T2D (9 males/11 females; aged 49 ± 13 years, HbA1c 5.2 ± 0.4%) participated in the study. The hypoxic ventilatory response (HVR) was assessed as an index of peripheral chemosensitivity. Resting heart rate, blood pressure and minute ventilation were measured when breathing normoxic followed by hyperoxic air (1.0 <math> <semantics><msub><mi>F</mi> <mrow><mi>I</mi> <msub><mi>O</mi> <mn>2</mn></msub> </mrow> </msub> <annotation>${{F}_{{mathrm{I}}{{{mathrm{O}}}_{mathrm{2}}}}}$</annotation></semantics> </math> ) to acutely attenuate peripheral chemoreceptor activity. A subset of participants (n = 9 per group) completed two additional visits [normoxia (0.21 <math> <semantics><msub><mi>F</mi> <mrow><mi>I</mi> <msub><mi>O</mi> <mn>2</mn></msub> </mrow> </msub> <annotation>${{F}_{{mathrm{I}}{{{mathrm{O}}}_{mathrm{2}}}}}$</annotation></semantics> </math> ), hyperoxia (1.0 <math> <semantics><msub><mi>F</mi> <mrow><mi>I</mi> <msub><mi>O</mi> <mn>2</mn></msub> </mrow> </msub> <annotation>${{F}_{{mathrm{I}}{{{mathrm{O}}}_{mathrm{2}}}}}$</annotation></semantics> </math> )] where glucose and insulin were measured for 2 h following an oral glucose challenge. HVR was augmented in adults with T2D (-0.84 ± 0.49 L min^-1/%) vs. control (-0.48 ± 0.40 L min^-1/%, P = 0.021). Attenuation of peripheral chemoreceptor activity decreased heart rate (P < 0.001), mean blood pressure (P = 0.009) and minute ventilation (P = 0.002); any effect of hyperoxia did not differ between groups. There was no effect of hyperoxia on the glucose (control, P = 0.864; T2D, P = 0.982), nor insulin (control, P = 0.763; T2D, P = 0.189) response to the oral glucose challenge. Peripheral chemoreflex sensitivity is elevated in adults with T2D; however, acute attenuation of peripheral chemoreflex activity with hyperoxia does not restore cardiometabolic function. KEY POINTS: Preclinical work supports a role for the peripheral chemoreceptors in the progression of cardiovascular and metabolic pathologies. In the present study, we examined peripheral chemosensitivity in adults with type 2 diabetes and the contribution of the peripheral chemoreceptors to resting cardiovascular control and glucose tolerance. We observed elevated peripheral chemo","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142086331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}