Experimental Neurology最新文献

{"title":"Suppression of cGAS/STING pathway-triggered necroptosis in the hippocampus relates H₂S to attenuate cognitive dysfunction of Parkinson's disease.","authors":"Xin-Le Huang, Yu Hu, Wu Jiang, Jia-Mei Jiang, Wei Zou, Ping Zhang, Xiao-Qing Tang","doi":"10.1016/j.expneurol.2024.115093","DOIUrl":"10.1016/j.expneurol.2024.115093","url":null,"abstract":"<p><strong>Background: </strong>Cognitive dysfunction is the most severe non-motor symptom of Parkinson's disease (PD). Our previous study revealed that hydrogen sulfide (H₂S) ameliorates cognitive dysfunction in PD, but the underlying mechanisms remain unclear. Hippocampal necroptosis plays a vital role in cognitive dysfunction, while the cGAS/STING pathway triggers necroptosis. To understand the mechanism underlying the inhibitory role of H₂S in cognitive dysfunction of PD, we explored whether H₂S reduces the enhancement of necroptosis and the activation of the cGAS/STING pathway in the hippocampus of the rotenone (ROT)-induced PD rat model.</p><p><strong>Method: </strong>Adult Sprague-Dawley (SD) rats were pre-treated with NaHS (30 or 100 μmol/kg/d, i.p.) for 7 days and then co-treated with ROT (2 mg/kg/d, s.i.) for 35 days. The Y-maze and Morris water maze (MWM) tests were used to assess the cognitive function. Hematoxylin-eosin (H&E) staining was used to detect the hippocampal pathological morphology. Western blotting analysis was used to measure the expressions of proteins. Enzyme-linked immunosorbent assay was used to determine the levels of inflammatory factors.</p><p><strong>Result: </strong>NaHS (a donor of H₂S) mitigated cognitive dysfunction in ROT-exposed rats, according to the Y-maze and MWM tests. NaHS treatment also markedly down-regulated the expressions of necroptosis-related proteins (RIPK1, RIPK3, and MLKL) and decreased the levels of necroptosis-related inflammatory factors (IL-6 and IL-1β) in the hippocampus of ROT-exposed rats. Furthermore, NaHS treatment reduced the expressions of cGAS/STING pathway-related proteins (cGAS, STING, p-TBK1^Ser172, p-IRF3^Ser396, and p-P65^Ser536) and decreased the contents of pro-inflammation factors (INF-β and TNF-α) in the hippocampus of ROT-exposed rats.</p><p><strong>Conclusion: </strong>H₂S attenuates the cGAS/STING pathway-triggered necroptosis in the hippocampus, which is related to H₂S to attenuate cognitive dysfunction in PD.</p>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":" ","pages":"115093"},"PeriodicalIF":4.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785022","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":"Optical coherence tomography enables longitudinal evaluation of cell graft-directed remodeling in stroke lesions.","authors":"Honour O Adewumi, Matthew G Simkulet, Gülce Küreli, John T Giblin, Arnaldo Bisbal Lopez, Şefik Evren Erdener, John Jiang, David A Boas, Timothy M O'Shea","doi":"10.1016/j.expneurol.2024.115117","DOIUrl":"https://doi.org/10.1016/j.expneurol.2024.115117","url":null,"abstract":"<p><p>Stem cell grafting can promote glial repair of adult stroke injuries during the subacute wound healing phase, but graft survival and glial repair outcomes are perturbed by lesion severity and mode of injury. To better understand how stroke lesion environments alter the functions of cell grafts, we employed optical coherence tomography (OCT) to longitudinally image mouse cortical photothrombotic ischemic strokes treated with allogeneic neural progenitor cell (NPC) grafts. OCT angiography, signal intensity, and signal decay resulting from optical scattering were assessed at multiple timepoints across two weeks in mice receiving an NPC graft or an injection of saline at two days after stroke. OCT scattering information revealed pronounced axial lesion contraction that naturally occurred throughout the subacute wound healing phase that was not modified by either NPC or saline treatment. By analyzing OCT signal intensity along the coronal plane, we observed dramatic contraction of the cortex away from the imaging window in the first week after stroke which impaired conventional OCT angiography but which enabled the detection of NPC graft-induced glial repair. There was moderate, but variable, NPC graft survival at photothrombotic strokes at two weeks which was inversely correlated with acute stroke lesion sizes as measured by OCT prior to treatment, suggesting a prognostic role for OCT imaging and reinforcing the dominant effect of lesion size and severity on graft outcome. Overall, our findings demonstrate the utility of OCT imaging for both tracking and predicting natural and treatment-directed changes in ischemic stroke lesion cores.</p>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":" ","pages":"115117"},"PeriodicalIF":4.6,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853620","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":"Insight into cerebral microvessel endothelial regulation of cognitive impairment: A systematic review of the causes and consequences.","authors":"Chang Liu, Xiaoyu Chen, Shaojie Yang, Xuncui Wang, Peiyang Sun, Jingji Wang, Guoqi Zhu","doi":"10.1016/j.expneurol.2024.115116","DOIUrl":"10.1016/j.expneurol.2024.115116","url":null,"abstract":"<p><p>Research on cognitive impairment (CI) has increasingly focused on the central nervous system, identifying numerous neuronal targets and circuits of relevance for CI pathogenesis and treatment. Brain microvascular endothelial cells (BMECs) form a barrier between the peripheral and central nervous systems, constituting the primary component of the blood-brain barrier (BBB) and playing a vital role in maintaining neural homeostasis. Stemming from the recognition of the close link between vascular dysfunction and CI, in recent years intense research has been devoted to characterize the pathological changes and molecular mechanisms underlying BMEC dysfunction both during normal aging and in disorders of cognition such as Alzheimer's disease and vascular dementia. In this review, keywords such as \"dementia\", \"cognitive impairment\", and \"endothelium\" were used to search PubMed and Web of Science. Based on the literature thus retrieved, we first review some common triggers of CI, i.e., amyloid beta and tau deposition, chronic cerebral hypoperfusion, hyperglycemia, viral infections, and neuroinflammation, and describe the specific mechanisms responsible for endothelial damage. Second, we review molecular aspects of endothelial damage leading to BBB disruption, neuronal injury, and myelin degeneration, which are crucial events underlying CI. Finally, we summarize the potential targets of endothelial damage in the development of cognitive dysfunction associated with Alzheimer's disease, vascular dementia, type 2 diabetes mellitus, and physiological aging. A thorough understanding of the induction mechanism and potential outcomes of microvascular endothelial damage is of great significance for the study of CI, to guide both diagnostic and therapeutic approaches for its prevention and treatment.</p>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":" ","pages":"115116"},"PeriodicalIF":4.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827947","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":"Microglial suppression by myeloperoxidase inhibitor does not delay neurodegeneration in a mouse model of progressive multiple sclerosis.","authors":"Alessandra Pistolesi, Giuseppe Ranieri, Maura Calvani, Daniele Guasti, Alberto Chiarugi, Daniela Buonvicino","doi":"10.1016/j.expneurol.2024.115095","DOIUrl":"10.1016/j.expneurol.2024.115095","url":null,"abstract":"<p><p>Drugs able to efficiently counteract the progression of multiple sclerosis (MS) are still an unmet need. Numerous preclinical evidence indicates that reactive oxygen-generating enzyme myeloperoxidase (MPO), expressed by neutrophils and microglia, might play a key role in neurodegenerative disorders. Then, the MPO inhibition has been evaluated in clinical trials in Parkinson's and multiple system atrophy patients, and a clinical trial for the treatment of amyotrophic lateral sclerosis is underway. The effects of MPO inhibition on MS patients have not yet been explored. In the present study, by adopting the NOD mouse model of progressive MS (PMS), we evaluated the pharmacological effects of the MPO inhibitor verdiperstat (also known as AZD3241) on functional, immune, and mitochondrial parameters during disease evolution. We found that daily treatment with verdiperstat did not affect the pattern of progression as well as survival, despite its ability to reduce mitochondrial reactive oxygen species and microglia activation in the spinal cord of immunized mice. Remarkably, verdiperstat did not affect adaptive immunity, neutrophils invasion as well as mitochondrial derangement in the spinal cords of immunized mice. Data suggest that microglia suppression is not sufficient to prevent disease evolution, corroborating the hypothesis that immune-independent components drive neurodegeneration in progressive MS.</p>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":" ","pages":"115095"},"PeriodicalIF":4.6,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824077","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 PTP1B inhibition rescues motor learning, neuroinflammation, and hyperglycaemia in a mouse model of Alzheimer's disease.","authors":"Zara Franklin, Claire Hull, Mirela Delibegovic, Bettina Platt","doi":"10.1016/j.expneurol.2024.115115","DOIUrl":"10.1016/j.expneurol.2024.115115","url":null,"abstract":"<p><strong>Background: </strong>Patients with Alzheimer's Disease (AD) frequently suffer from comorbidities such as type 2 diabetes mellitus (T2DM), accompanied by shared common pathologies such as increased inflammation and impaired glucose homeostasis. Beta-secretase 1 (BACE1), the rate limiting enzyme in AD associated beta-amyloid (Aβ) production, is also implicated in metabolic dysfunction and can increase central and peripheral protein levels of protein tyrosine phosphatase 1B (PTP1B). PTP1B is a validated target in diabetes and obesity, and is a neuroinflammatory regulator involved in degenerative processes. This study investigated the effects of the PTP1B inhibitor, trodusquemine (MSI-1436) on the cognitive and metabolic phenotypes of the neuronal human BACE1 knock-in (PLB4) mouse, a co-morbidity model of AD and T2DM, and their wild-type (PLB_WT) controls.</p><p><strong>Methods: </strong>Five-month-old male PLB4 and PLB_WT mice received PTP1B inhibitor treatment (1 mg/kg intraperitoneal injection; 5 weeks). Activity and spatial habituation (Phenotyper), motor learning (RotaRod), glucose tolerance, and brain and liver molecular analyses were analysed following treatment.</p><p><strong>Results: </strong>Inhibition of PTP1B improved motor learning alongside glucose tolerance in PLB4 mice, without affecting body weight/adiposity. MSI-1436 treatment led to lower protein levels of amyloid precursor protein (APP), reduced astrogliosis and restoration of the endoplasmic chaperone immunoglobulin heavy chain binding protein (BIP) in the brain, alongside decreased insulin receptor substrate-1 (IRS1) and dipeptidyl peptidase-4 (DPP4) proteins in the liver.</p><p><strong>Conclusion: </strong>We provide evidence that neuronal BACE1 contributes to neuroinflammation and hyperglycaemia in PLB4 mice, and this can be partially rescued by PTP1B inhibition. Targeting PTP1B may therefore offer an attractive therapeutic approach to ameliorate co-morbidity associated pathologies in AD and T2DM.</p>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":" ","pages":"115115"},"PeriodicalIF":4.6,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822037","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":"Glial scarring limits recovery following decompressive surgery in rats with syringomyelia.","authors":"Shengyu Cui, Jinze Li, Can Zhang, Qian Li, Chuan Jiang, Xinyu Wang, Xiaoxu Yu, Kang Li, Yuxin Feng, Fengzeng Jian","doi":"10.1016/j.expneurol.2024.115113","DOIUrl":"10.1016/j.expneurol.2024.115113","url":null,"abstract":"<p><p>Syringomyelia is a neurological disease that is difficult to cure, and treatments often have limited effectiveness. In this study, a rat model of syringomyelia induced by epidural compression was used to investigate the factors that limit the prognosis of syringomyelia. After we treated syringomyelia rats with surgical decompression alone, MRI revealed that the syringomyelia rats did not show the expected therapeutic effect. Through cerebrospinal fluid (CSF) tracing experiments, we found that the CSF flow in the subarachnoid space (SAS) of rats was restored after decompression. This shows that the poor prognosis of syringomyelia rats in this study is not caused by CSF circulation disorders, suggesting the existence of other factors. Further, immunofluorescence revealed that there were extensive glial scars characterized by increased expression of glial fibrillary acidic protein (GFAP) and chondroitin sulfate proteoglycans (CSPGs) around the syrinx in the non-improved group compared to the improved group. To verify the limiting role of glial scarring in the prognosis of syringomyelia, we intervened with the selective astrocyte inhibitor fluorocitrate (FC). Intrathecal injection of FC significantly inhibited the formation of glial scar after decompression in syringomyelia rats and promoted the reduction of syrinx. This scar-inhibiting effect significantly improved neuronal survival, promoted axonal and myelin recovery, and showed better recovery in sensory function and fine motor control functions. These findings suggest that glial scarring around syrinx is a key factor limiting recovery of syringomyelia. By inhibiting glial scar formation, the prognosis of syringomyelia can be significantly improved, which provides a new strategy for improving clinical treatment effects.</p>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":" ","pages":"115113"},"PeriodicalIF":4.6,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817720","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":"The role of the CCL5-CCR5 axis in microglial activation leading to postoperative cognitive dysfunction.","authors":"Yuanyuan An, Yu Yao, Huan Liu, Yuqing Xi, Mengying Pi, Rui Xu, Yulin Huang, Shuming Li, Xiaoping Gu","doi":"10.1016/j.expneurol.2024.115114","DOIUrl":"10.1016/j.expneurol.2024.115114","url":null,"abstract":"<p><p>Postoperative cognitive dysfunction (POCD) is a common complication following surgeries involving general anesthesia. Although the CCL5-CCR5 axis is implicated in various neurological conditions, its role in POCD remains unclear. In our POCD model, we observed an increase in CCL5 and CCR5 levels concurrent with microglial activation and significant upregulation of inflammatory cytokines IL-6 and IL-1β. Administration of MVC, a CCR5 antagonist, alleviated neuroinflammation, prevented dendritic spine loss, and improved cognitive deficits by inhibiting the CCR5/CREB/NLRP1 pathway. However, the cognitive benefits of MVC were reversed by the CREB inhibitor 666-15. Our findings highlight the potential of targeting the CCL5-CCR5 axis as a therapeutic strategy for preventing and treating POCD.</p>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":" ","pages":"115114"},"PeriodicalIF":4.6,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817722","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":"Epidural electrical stimulation combined with photobiomodulation restores hindlimb motor function in rats with thoracic spinal cord injury.","authors":"Xiao-Jun Guo, Le-Wei He, Jia-Qi Chang, Wen-Nan Su, Ting Feng, Yi-Meng Gao, Yuan-Yuan Wu, Can Zhao, Jia-Sheng Rao","doi":"10.1016/j.expneurol.2024.115112","DOIUrl":"https://doi.org/10.1016/j.expneurol.2024.115112","url":null,"abstract":"<p><p>Epidural electrical stimulation (EES) could restore motor function of paralyzed limbs of patients with spinal cord injury (SCI). However, its invasiveness limits its application in early stage of injury. Photobiomodulation (PBM) utilizes infrared light for percutaneous irradiation of the spinal cord to protect nerve tissue, delay muscle atrophy, and can be applied in early stage of SCI due to its non-invasiveness. This study tested the effect of the combination of EES and PBM on promoting motor function recovery in SCI rats. Severe contusion was induced at the T9 spinal segment in female rats, EES (applied to the L2 and S1 spinal cord segments) with treadmill training was conducted one week after the injury, and PBM percutaneous irradiation started at the injured segment on the day of surgery. In the third week post-injury, electromyographic and gait performance during training were recorded. Besides, the muscles of the hind limbs and the spinal cord on the caudal side of the injured segment were extracted. The results demonstrate that compared to the EES- or PBM-only group, this combined therapy led to several indicators returning to intact levels, including behavioral and electrophysiological, the gait patterns was also closer to intact rats. Additionally, the combined treatment group showed minimal muscle atrophy and maximal preservation of the injured spinal cord on the caudal side, with this histological improvement correlated with motor function recovery. Taken together, our results showed that this combined therapy was a more effective treatment for improving motor dysfunction after SCI which could protect the damaged spinal cord and promote the recovery of motor function in rats with SCI.</p>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":" ","pages":"115112"},"PeriodicalIF":4.6,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817642","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":"Electrical impedance myography detects progressive pathological alterations in the hindlimb muscle of the PMP22-C3 mice, an animal model of CMT1A.","authors":"Atsuki Taruta, Tetsuaki Hiyoshi, Akina Harada, Masato Nakashima","doi":"10.1016/j.expneurol.2024.115111","DOIUrl":"10.1016/j.expneurol.2024.115111","url":null,"abstract":"<p><p>Charcot-Marie-Tooth type 1A (CMT1A) is the most common inherited peripheral dysmyelinating neuropathy. Although lower limb muscle weakness is the most important factor affecting the quality of life of patients with CMT1A, existing clinical measures for its evaluation have limitations, including low sensitivity in detecting disease progression. Electrical impedance myography (EIM) is a newer tool that enables noninvasive evaluation of muscle state by measuring muscle composition, and potentially supports the evaluation of neuromuscular disease progression and treatment effects. To determine the potential of EIM as a CMT1A biomarker, we obtained natural history data for EIM from the gastrocnemius muscle of the PMP22-C3 mice, an animal model of CMT1A. Alterations in the EIM parameters, weak hindlimb grip strength, decreased muscle fiber size, and changes in the mRNA expression of genes related to neuromuscular junction dysfunction were found. These changes were more pronounced at later stages (12 and 18 weeks of age) than at earlier stage (6 weeks of age), indicating that EIM can detect disease progression in PMP22-C3 mice. Our preclinical findings support the use of EIM as a potential translational biomarker for assessing progressive changes in the pathological muscle state in CMT1A.</p>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":" ","pages":"115111"},"PeriodicalIF":4.6,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817706","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":"hPSCs-derived brain organoids for disease modeling, toxicity testing and drug evaluation.","authors":"Na Xie, Jinrong Bai, Ya Hou, Jia Liu, Yi Zhang, Xianli Meng, Xiaobo Wang","doi":"10.1016/j.expneurol.2024.115110","DOIUrl":"10.1016/j.expneurol.2024.115110","url":null,"abstract":"<p><p>Due to the differences and variances in genetic background, in vitro and animal models cannot meet the modern medical exploration of real human brain structure and function. Recently, brain organoids generated by human pluripotent stem cells (hPSCs) can mimic the structure and physiological function of human brain, being widely used in medical research. Brain organoids generated from normal hPSCs or patient-derived induced pluripotent stem cells offer a more promising approach for the study of diverse human brain diseases. More importantly, the use of the established brain organoid model for drug evaluation is conducive to shorten the clinical transformation period. Herein, we summarize methods for the identification of brain organoids from cellular diversity, morphology and neuronal activity, brain disease modeling, toxicity testing, and drug evaluation. Based on this, it is hoped that this review will provide new insights into the pathogenesis of brain diseases and drug research and development, promoting the rapid development of brain science.</p>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":" ","pages":"115110"},"PeriodicalIF":4.6,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817721","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}