Experimental Neurology最新文献

{"title":"Preferential motor reinnervation is modulated by both repair site and distal nerve environments.","authors":"C Li, N Rassekh, A O'Daly, F Kebaisch, R Wolinsky, A Vyas, R Skolasky, A Hoke, T Brushart","doi":"10.1016/j.expneurol.2024.115066","DOIUrl":"10.1016/j.expneurol.2024.115066","url":null,"abstract":"<p><p>To restore function after nerve injury, axons must regenerate from the injury site to the periphery, then reinnervate appropriate end organs when they arrive. Only 10 % of adults who suffer nerve injury will regain normal function, often because axons regenerate to functionally inappropriate targets (Brushart, 2011). The peripheral destination of these axons is largely determined by the pathways they enter at the site of nerve repair. To improve clinical outcomes, it is thus critical to improve the accuracy of axon pathfinding. In rodents, motor axons regenerating in mixed nerve preferentially reinnervate pathways leading to muscle, a process termed preferential motor reinnervation (PMR). Previous experiments have shown that PMR can be enhanced by predegenerating nerve grafts to enhance growth factor production and remove inhibitory factors (Abdullah et al., 2013). The current experiments explore the relative contributions of motor pathways, sensory pathways, and the repair environment to this enhancement. Sensory and/or motor pathways within rat femoral nerve grafts were predegenerated for 3 weeks to optimize growth factor production (Brushart et al., 2013) or for 12 weeks to deplete it. Optimizing the environment within previously motor Schwann cell tubes promoted PMR, regardless of whether adjacent sensory pathways were optimized or chronically denervated. However, this positive effect was abolished when sensory pathways were undergoing acute Wallerian degeneration immediately after nerve repair. The repair environment thus precluded motor axon pathfinding in spite of an optimized distal motor pathway. When sensory pathways were optimized and motor pathways were chronically denervated, not only was PMR abolished, but motoneurons failed to respond to the greater volume of growth factors in the sensory nerve. Small sensory neurons, however, selectively reinnervated cutaneous nerve under these conditions. These experiments thus strengthen the concept that, in adult rats, sensory and motor pathways have unique identities capable of influencing both sensory and motor axon regeneration. Furthermore, they demonstrate that, in the rat, delaying nerve repair for 3 weeks to enhance growth factor production and clear the products of acute Wallerian degeneration can enhance regeneration specificity without the need for exogenous treatments.</p>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":" ","pages":"115066"},"PeriodicalIF":4.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695328","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":"Enhancing cognitive function after traumatic brain injury in male mice: The benefits of running regardless of intervention timing","authors":"Liron Tseitlin ,&nbsp;Shaul Schreiber ,&nbsp;Bar Richmond-Hacham ,&nbsp;Lior Bikovski ,&nbsp;Chaim G. Pick","doi":"10.1016/j.expneurol.2024.115069","DOIUrl":"10.1016/j.expneurol.2024.115069","url":null,"abstract":"<div><div>The significant benefits of physical activity are well-documented in academic literature, with growing evidence highlighting its positive effects (among others) on memory and cognitive function. Exercise, particularly aerobic activities, has been shown to mitigate neuroinflammatory processes, promote neuronal regeneration, facilitate recovery from cerebral trauma, and reduce the risk of neurodegenerative diseases. Among neurological conditions, traumatic brain injury (TBI) is the most common in individuals under 50, with 80–90 % of cases categorized as mild traumatic brain injury (mTBI).</div><div>This study investigates the impact of exercise on visual and spatial memory deficits in mice following mTBI. ICR mice were subjected to a seventeen-day treadmill training protocol initiated at four different time intervals post-mTBI (2, 7, 13, and 30 days). A battery of specific behavioral tests was used to assess anxiety-like behaviors, motor skills, and visual and spatial memory.</div><div>Our results indicate that running positively affected mTBI in both novel object recognition (<em>p</em> &lt; 0.001) and Y-maze (p &lt; 0.001) regardless of the running protocol's initiation time, demonstrating that aerobic exercise significantly alleviates cognitive deficits associated with mTBI. Importantly, mTBI did not appear to impact motor abilities or anxiety-like behaviors based on the assessment paradigms utilized. In conclusion, aerobic exercise effectively enhances visual and spatial memory post-mTBI, with promising results observed even when the running protocol is initiated up to one-month post-injury.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"384 ","pages":"Article 115069"},"PeriodicalIF":4.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692854","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":"Inhibition of PAD4-mediated neutrophil extracellular traps formation attenuates hypoxic–ischemic brain injury in neonatal mice","authors":"Xiaoping Yu ,&nbsp;Zhaoyan Chen ,&nbsp;Fei Ruan ,&nbsp;Yaqing Jiang ,&nbsp;Wei Bao ,&nbsp;Di Wu ,&nbsp;Lishuo Chao ,&nbsp;Rui Wu ,&nbsp;Kai Le","doi":"10.1016/j.expneurol.2024.115065","DOIUrl":"10.1016/j.expneurol.2024.115065","url":null,"abstract":"<div><div>Neonatal hypoxic–ischemic encephalopathy (HIE) is the primary cause of neonatal mortality and severe neurological sequelae. The interaction of neuroinflammation with the immune system represents a significant pathological mechanism underlying the development of HIE. Neutrophil extracellular traps (NETs) are a recently identified antimicrobial mechanism utilized by neutrophils. NETs can act as damage-associated molecular patterns, thereby amplifying the immune response and exerting proinflammatory effects. However, further research is needed to elucidate their role in the pathogenesis of HIE. In this study, we investigated the role of NETs in a hypoxic–ischemic brain injury (HIBI) model. We first reported that a pharmacological intervention to inhibit peptidylarginine deiminase type IV (PAD4) may constitute an effective strategy for reducing HI insult-induced neuroinflammation, neuronal apoptosis, and brain tissue destruction while also enhancing long-term neurobehavioral function in mice. These results support a pathological role for NETs in HIBI, and targeting PAD4 is a potential direction for the treatment of HIE.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"384 ","pages":"Article 115065"},"PeriodicalIF":4.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681176","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":"Mechanism of effect and therapeutic potential of NLRP3 inflammasome in spinal cord injury","authors":"Hou-yun Gu ,&nbsp;Ning Liu","doi":"10.1016/j.expneurol.2024.115059","DOIUrl":"10.1016/j.expneurol.2024.115059","url":null,"abstract":"<div><div>Spinal cord injury (SCI) is a serious and disabling central nervous system injury that can trigger various neuropathological conditions, resulting in neuronal damage and release of various pro-inflammatory mediators, leading to neurological dysfunction. Currently, surgical decompression, drugs and rehabilitation are primarily used to relieve symptoms and improve endogenous repair mechanisms; however, they cannot directly promote nerve regeneration and functional recovery. SCI can be divided into primary and secondary injuries. Secondary injury is key to determining the severity of injury, whereas inflammation and cell death are important pathological mechanisms in the process of secondary SCI. The activation of the inflammasome complex is thought to be a necessary step in neuro-inflammation and a key trigger for neuronal death. The NLRP3 inflammasome is a cytoplasmic multiprotein complex that is considered an important factor in the development of SCI. Once the NLRP3 inflammasome is activated after SCI, NLRP3 nucleates the assembly of an inflammasome, leading to caspase 1-mediated proteolytic activation of the interleukin-1β (IL-1β) family of cytokines, and induces an inflammatory, pyroptotic cell death. Inhibition of inflammasomes can effectively inhibit inflammation and cell death in the body and promote the recovery of nerve function after SCI. Therefore, inhibition of NLRP3 inflammasome activation may be a promising approach for the treatment of SCI. In this review, we describe the current understanding of NLRP3 inflammasome activation in SCI pathogenesis and its subsequent impact on SCI and summarize drugs and other potential inhibitors based on NLRP3 inflammasome regulation. The objective of this study was to emphasize the role of the NLRP3 inflammasome in SCI, and provide a new therapeutic strategy and theoretical basis for targeting the NLRP3 inflammasome as a therapy for SCI.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"384 ","pages":"Article 115059"},"PeriodicalIF":4.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686479","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":"Diminished lactate utilization in LDHB-deficient neurons leads to impaired long-term memory retention","authors":"Jin Soo Lee ,&nbsp;Bok Seon Yoon ,&nbsp;Songmi Han ,&nbsp;Yihyang Kim ,&nbsp;Chan Bae Park","doi":"10.1016/j.expneurol.2024.115064","DOIUrl":"10.1016/j.expneurol.2024.115064","url":null,"abstract":"<div><div>Neurons' high energy demands for processing, transmitting, and storing information in the brain necessitate efficient energy metabolism to maintain normal neuronal function. The astrocyte-neuron lactate shuttle (ANLS) hypothesis suggests neurons preferentially use lactate from astrocytes over glucose for energy. This study investigated lactate dehydrogenase B (LDHB), which preferentially converts lactate to pyruvate, in neuronal energy metabolism and cognitive function. LDHB-deficient neurons showed reduced lactate-driven energy metabolism in culture, while LDHB-deficient brains accumulated lactate, both indicating decreased lactate utilization. This reduced lactate utilization was correlated with impaired long-term memory in LDHB-deficient mice, while short-term memory remained unaffected and overall neuropathology was only mildly disturbed. Unexpectedly, LDHB-deficient neurons maintain stable energy metabolism under physiological glucose conditions, indicating the presence of lactate dehydrogenase (LDH) activity in LDHB-deficient neurons. The observation of lactate dehydrogenase A (LDHA), which preferentially converts pyruvate to lactate but can also catalyze the reverse reaction less efficiently, in LDHB-deficient neurons may explain their stable energy metabolism and reduced lactate utilization. This study challenges the established concept of strict LDH isoform compartmentalization in brain cells, questioning the exclusive presence of LDHB in neurons and suggesting a more flexible neuronal metabolic profile than previously assumed by the ANSL hypothesis.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"384 ","pages":"Article 115064"},"PeriodicalIF":4.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681172","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":"Time of day dependent reduction in stroke infarct volume by the Reverb agonist SR9009 in mice","authors":"Pradip K. Kamat ,&nbsp;Mohammad Badruzzaman Khan ,&nbsp;Shahneela Siddiqui ,&nbsp;Tyler Grace Hattaway ,&nbsp;Affan Anas ,&nbsp;R. Daniel Rudic ,&nbsp;Babak Baban ,&nbsp;Krishnan M. Dhandapani ,&nbsp;David C. Hess","doi":"10.1016/j.expneurol.2024.115067","DOIUrl":"10.1016/j.expneurol.2024.115067","url":null,"abstract":"<div><div>Ischemic stroke leads to disability and death worldwide and evidence suggests that stroke severity is affected by the time dimension of the stroke. Rev-Erbα regulates the core circadian clock through repression of the positive clock element Bmal1. However, it remains unclear if a Rev-Erbα agonist (SR9009) alleviates stroke pathology in mice. We found that stroke reduces the level of Rev-Erbα and elevates neuroinflammation and stroke severity at zeitgeber time (ZT) ZT06. Therefore, we hypothesized that SR9009 treatment may reduce neuroinflammation and stroke severity in a mouse suture occlusion model. At 12 to 14 weeks, C57BL/6 J (Wild Type, <em>n</em> = 5–10 mice/group) mice were randomly assigned to undergo MCAO stroke for 60 min at either zeitgeber time ZT06 (MCAO-ZT06-sleep phase) or ZT18 (MCAO-ZT18-awake phase). Stroked mice were treated with SR9009 (100 mg/kg) or vehicle at 1 h and 24 h after MCAO. After forty-eight hours of stroke, TTC staining, Western blot, and qRT-PCR were performed. We found that SR9009 treatment alleviates neuroinflammation and infarct volume by Rev-Erb remodeling in ZT06 stroke mice but not in ZT18 stroke mice. Additionally, monocytic and neutrophilic NLRP3 as well as brain NLRP3 levels were reduced by SR9009 treatment in ZT06 stroke though no effects were observed at ZT18 stroke. SR9009 also reduced TNFα expression and increased IL-10 expression in blood and brain in ZT06 stroke mice and no differences were observed at ZT18. There were no significant effects of SR9009 on neurological deficit score and sensorimotor function at ZT06 or ZT18 at 48 h. Our study demonstrates that SR9009 treatment reduces stroke volume, circulating immune response, circadian expression, and that the protection was circadian- and treatment time-dependent.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"384 ","pages":"Article 115067"},"PeriodicalIF":4.6,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667592","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":"Protein arginine methyltransferases as regulators of cellular stress","authors":"Julia Zaccarelli-Magalhães,&nbsp;Cristiane Teresinha Citadin,&nbsp;Julia Langman,&nbsp;Drew James Smith,&nbsp;Luiz Henrique Matuguma,&nbsp;Hung Wen Lin,&nbsp;Mariana Sayuri Berto Udo","doi":"10.1016/j.expneurol.2024.115060","DOIUrl":"10.1016/j.expneurol.2024.115060","url":null,"abstract":"<div><div>Arginine modification can be a “switch” to regulate DNA transcription and a post-translational modification via methylation of a variety of cellular targets involved in signal transduction, gene transcription, DNA repair, and mRNA alterations. This consequently can turn downstream biological effectors “on” and “off”. Arginine methylation is catalyzed by protein arginine methyltransferases (PRMTs 1‐9) in both the nucleus and cytoplasm, and is thought to be involved in many disease processes. However, PRMTs have not been well-documented in the brain and their function as it relates to metabolism, circulation, functional learning and memory are understudied. In this review, we provide a comprehensive overview of PRMTs relevant to cellular stress, and future directions into PRMTs as therapeutic regulators in brain pathologies.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"384 ","pages":"Article 115060"},"PeriodicalIF":4.6,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647231","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":"Pharmacological inhibition of P2RX4 receptor as a potential therapeutic strategy to prevent intracranial aneurysm formation","authors":"Isao Ono ,&nbsp;Masahiko Itani ,&nbsp;Akihiro Okada ,&nbsp;Kimiko Yamamoto ,&nbsp;Akitsugu Kawashima ,&nbsp;Yoshiki Arakawa ,&nbsp;Tomohiro Aoki","doi":"10.1016/j.expneurol.2024.115061","DOIUrl":"10.1016/j.expneurol.2024.115061","url":null,"abstract":"<div><div>Intracranial aneurysms (IA) affect 1–5 % of the population and are a major cause of subarachnoid hemorrhage. Thus, preventing IA development and progression is crucial for public health. IA has been considered a non-physiological, high shear stress-induced chronic inflammatory disease affecting the bifurcation site of the intracranial arteries. Therefore, factors that sense high shear stress and induce IAs by triggering inflammation could potentially act as therapeutic targets. P2RX4 is a member of the purinoreceptor family that converts the strength of shear stress into intracellular signals. To verify its therapeutic potential, we investigated the effects of P2RX4 and a selective antagonist on the formation of IAs. Results showed that P2RX4 deficiency significantly suppressed the formation of IAs. Consistently, the selective P2RX4 antagonist NC-2600, which potently inhibited Ca²⁺ influx in response to shear-stress loading in endothelial cells <em>in vitro</em>, significantly suppressed the formation of IAs. The results of the present study contribute to our understanding of the pathogenesis of IAs and may provide benefits to society through the future development of medical therapies targeting P2RX4.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"384 ","pages":"Article 115061"},"PeriodicalIF":4.6,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647230","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":"Mitochondrial stress and inflammation in neurological disorders","authors":"Qing Wang ,&nbsp;John H. Zhang","doi":"10.1016/j.expneurol.2024.115063","DOIUrl":"10.1016/j.expneurol.2024.115063","url":null,"abstract":"","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"383 ","pages":"Article 115063"},"PeriodicalIF":4.6,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681180","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":"Gut microbiota-derived 3-indoleacetic acid confers a protection against sepsis-associated encephalopathy through microglial aryl hydrocarbon receptors","authors":"Zhi-Bin Huang ,&nbsp;Guo-Pan Zhang ,&nbsp;Chen-Xin Lu ,&nbsp;Cansheng Gong ,&nbsp;Xiaotan Gao ,&nbsp;Yanqi Lin ,&nbsp;Ping Su ,&nbsp;Wenyan Xu ,&nbsp;Yongbao Lin ,&nbsp;Na Lin ,&nbsp;Xuyang Wu ,&nbsp;Xiaohui Chen ,&nbsp;Ting Zheng ,&nbsp;Xiaochun Zheng","doi":"10.1016/j.expneurol.2024.115055","DOIUrl":"10.1016/j.expneurol.2024.115055","url":null,"abstract":"<div><h3>Background</h3><div>The gut microbiota significantly contributes to the pathogenesis of central nervous system disorders. Among the bioactive molecules produced by the gut microbiota, 3-indoleacetic acid (IAA) has been shown to attenuate oxidative stress and inflammatory responses. This experiment aimed to determine the impacts of IAA on sepsis-associated encephalopathy (SAE) and the underlying mechanisms.</div></div><div><h3>Methods</h3><div>A total of 34 septic patients and 24 healthy controls were included in the analysis of the clinical correlation between fecal IAA and septic encephalopathy. Fecal microbiota transplantation was used to verify the role of the gut microbiota and its metabolites in SAE. Male C57BL/6 mice aged six to eight weeks, pre-treated with IAA via oral gavage, were subjected to the cecal ligation and puncture (CLP) procedures. This treatment was administered either in combination with an aryl hydrocarbon receptor (AhR) antagonist, CH223191, or a CSF1R inhibitor, PLX3397, to eliminate microglia. Both immunofluorescence staining and enzyme-linked immunosorbent assays were used to evaluate microglia activation and inflammatory cytokine secretion. Behavioral assessments were conducted to quantify neurological deficits.</div></div><div><h3>Results</h3><div>A decreased fecal level of IAA was observed in the patients with sepsis-associated delirium (SAD), a manifestation of SAE. A reduced IAA level was significantly associated with worsen clinical outcomes. Fecal microbiota transplantation from the SAD patients induced an SAE-like phenotype in mice, but supplementing exogenous IAA improved the SAE-like phenotype, mediated by microglia. IAA effectively binded with the aryl hydrocarbon receptor (AhR). Furthermore, IAA increased the nuclear activity of AhR in the lipopolysaccharide (LPS)-treated microglial cells, leading to reduced secretion of inflammatory cytokines. The AhR inhibitor CH223191 counteracted the protective effect of IAA against SAE in mice.</div></div><div><h3>Conclusions</h3><div>Gut microbiota-derived IAA confers a protection against SAE by activating AhR in microglia, improving neuronal and cognitive impairments. Thus, IAA holds the promise as a potential therapeutic agent for managing SAE.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"384 ","pages":"Article 115055"},"PeriodicalIF":4.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638447","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}