Journal of Molecular Neuroscience最新文献

{"title":"Molecular Mechanisms of Epilepsy: The Role of the Chloride Transporter KCC2","authors":"Giorgio Belperio,&nbsp;Claudia Corso,&nbsp;Carlos B. Duarte,&nbsp;Miranda Mele","doi":"10.1007/s12031-022-02041-7","DOIUrl":"10.1007/s12031-022-02041-7","url":null,"abstract":"<div><p>Epilepsy is a neurological disease characterized by abnormal or synchronous brain activity causing seizures, which may produce convulsions, minor physical signs, or a combination of symptoms. These disorders affect approximately 65 million people worldwide, from all ages and genders. Seizures apart, epileptic patients present a high risk to develop neuropsychological comorbidities such as cognitive deficits, emotional disturbance, and psychiatric disorders, which severely impair quality of life. Currently, the treatment for epilepsy includes the administration of drugs or surgery, but about 30% of the patients treated with antiepileptic drugs develop time-dependent pharmacoresistence. Therefore, further investigation about epilepsy and its causes is needed to find new pharmacological targets and innovative therapeutic strategies. Pharmacoresistance is associated to changes in neuronal plasticity and alterations of GABA_A receptor-mediated neurotransmission. The downregulation of GABA inhibitory activity may arise from a positive shift in GABA_A receptor reversal potential, due to an alteration in chloride homeostasis. In this paper, we review the contribution of K⁺-Cl⁻-cotransporter (KCC2) to the alterations in the Cl^– gradient observed in epileptic condition, and how these alterations are coupled to the increase in the excitability.\u0000</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"72 7","pages":"1500 - 1515"},"PeriodicalIF":3.1,"publicationDate":"2022-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4496836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Analysis and Identification of CSF-Derived Risk miRNAs and Pivotal Genes in Multiple Sclerosis","authors":"Yingchao Su,&nbsp;Zhihui Li,&nbsp;Xinming Rang,&nbsp;Yifei Wang,&nbsp;Jin Fu","doi":"10.1007/s12031-022-02007-9","DOIUrl":"10.1007/s12031-022-02007-9","url":null,"abstract":"<div><p>Multiple sclerosis (MS) is a common chronic autoimmune disorder of the central nervous system that predominantly affects young adults. Mounting evidence indicates that deregulation of microRNAs (miRNAs) in cerebrospinal fluid (CSF) has been implicated in MS as a potential biomarker. However, comprehensive assessments of CSF miRNAs and their target genes are lacking. Here, aberrantly expressed CSF miRNAs of MS patients were obtained from numerous studies by manual search. With detailed information on these miRNAs, we utilized online databases to screen out immune-related target genes and further performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. To identify MS high-risk pathways and pivotal genes, pathway crosstalk and pathway-gene networks were constructed, followed by the establishment of a protein–protein interaction (PPI) network. The datasets collected from ArrayExpress were used to assess pivotal genes. Overall, 21 MS-related CSF miRNAs were included in this study. Subsequently, we identified 469 MS-related genes and 14 high-risk pathways. In the pathway-gene network, 27 critical MS-related genes participated in at least half of the high-risk pathways, and these genes were used to identify pivotal genes. Finally, miR-150, miR-328, and miR-34c-5p were determined to be risk miRNAs via the regulation of the pivotal risk genes MAPK1, AKT1, and VEGFA. Among them, VEGFA was validated to be significantly decreased in the CSF cells of MS patients by transcriptomic datasets. These findings may provide potential biomarkers or therapeutic targets and help elucidate the molecular mechanisms underlying the pathogenesis of MS.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"72 9","pages":"1916 - 1928"},"PeriodicalIF":3.1,"publicationDate":"2022-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4464530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astrocyte Activation, but not Microglia, Is Associated with the Experimental Mouse Model of Schizophrenia Induced by Chronic Ketamine","authors":"Ying Wei,&nbsp;Li Xiao,&nbsp;Weihao Fan,&nbsp;Jing Zou,&nbsp;Hong Yang,&nbsp;Bo Liu,&nbsp;Yi Ye,&nbsp;Di Wen,&nbsp;Linchuan Liao","doi":"10.1007/s12031-022-02046-2","DOIUrl":"10.1007/s12031-022-02046-2","url":null,"abstract":"<div><p>Ketamine is a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors. Many experimental studies have shown that ketamine can induce cognitive impairments and schizophrenia-like symptoms. While much data have demonstrated that glial cells are associated with the pathophysiology of psychiatric disorders, including schizophrenia, the response of glial cells to ketamine and its significance to schizophrenia are not clear. The present study was intended to explore whether chronic ketamine treatment would induce behavioral and glial changes in mice. First, ketamine was used to stimulate behavioral abnormalities similar to schizophrenia evaluated by the open field test, elevated plus-maze test, Y maze test, novel object recognition test, and tail suspension test. Secondly, histopathology and Nissl staining were performed. Meanwhile, immunofluorescence was used to evaluate the expression levels of IBA-1 (a microglial marker) and GFAP (an astrocyte marker) in the mouse hippocampus for any change. Then, ELISA was used to analyze proinflammatory cytokine levels for any change. Our results showed that ketamine (25 mg/kg, i.p., qid, 12 days) induced anxiety, recognition deficits, and neuronal injury in the hippocampus. Moreover, chronic ketamine treatment enhanced GFAP expression in CA1 and DG regions of the hippocampus but did not influence the expression of IBA-1. Ketamine also increased the levels of IL-1β, IL-6, and TNF-α in the mouse hippocampus. Our study created a new procedure for ketamine administration, which successfully induce negative symptoms and cognitive-behavioral defects in schizophrenia by chronic ketamine. This study further revealed that an increase in astrocytosis, but not microglia, is associated with the mouse model of schizophrenia caused by ketamine. In summary, hippocampal astrocytes may be involved in the pathophysiology of ketamine-induced schizophrenia-like phenotypes through reactive transformation and regulation of neuroinflammation.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"72 9","pages":"1902 - 1915"},"PeriodicalIF":3.1,"publicationDate":"2022-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-022-02046-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4345017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From the Desk of the Editor‑in‑Chief: Excerpts from the Society for Neurochemistry (ESN) Future Perspectives for European Neurochemistry Highlighting the Symposium Asking “Autism, Epilepsy, Intellectual Disability Where Do These All Meet?”","authors":"Illana Gozes","doi":"10.1007/s12031-022-02045-3","DOIUrl":"10.1007/s12031-022-02045-3","url":null,"abstract":"","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"72 7","pages":"1527 - 1529"},"PeriodicalIF":3.1,"publicationDate":"2022-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4300211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network Biology Approaches to Uncover Therapeutic Targets Associated with Molecular Signaling Pathways from circRNA in Postoperative Cognitive Dysfunction Pathogenesis","authors":"Piplu Bhuiyan,&nbsp;GS Chuwdhury,&nbsp;Zhaochu Sun,&nbsp;Yinan Chen,&nbsp;Hongquan Dong,&nbsp;Fee Faysal Ahmed,&nbsp;Li Nana,&nbsp;Md Habibur Rahman,&nbsp;Yanning Qian","doi":"10.1007/s12031-022-02042-6","DOIUrl":"10.1007/s12031-022-02042-6","url":null,"abstract":"<div><h2>Abstract\u0000</h2><div><p>Postoperative cognitive dysfunction (POCD) is a cognitive deterioration and dementia that arise after a surgical procedure, affecting up to 40% of surgery patients over the age of 60. The precise etiology and molecular mechanisms underlying POCD remain uncovered. These reasons led us to employ integrative bioinformatics and machine learning methodologies to identify several biological signaling pathways involved and molecular signatures to better understand the pathophysiology of POCD. A total of 223 differentially expressed genes (DEGs) comprising 156 upregulated and 67 downregulated genes were identified from the circRNA microarray dataset by comparing POCD and non-POCD samples. Gene ontology (GO) analyses of DEGs were significantly involved in neurogenesis, autophagy regulation, translation in the postsynapse, modulating synaptic transmission, regulation of the cellular catabolic process, macromolecule modification, and chromatin remodeling. Pathway enrichment analysis indicated some key molecular pathways, including mTOR signaling pathway, AKT phosphorylation of cytosolic targets, MAPK and NF-κB signaling pathway, PI3K/AKT signaling pathway, nitric oxide signaling pathway, chaperones that modulate interferon signaling pathway, apoptosis signaling pathway, VEGF signaling pathway, cellular senescence, RANKL/RARK signaling pathway, and AGE/RAGE pathway. Furthermore, seven hub genes were identified from the PPI network and also determined transcription factors and protein kinases. Finally, we identified a new predictive drug for the treatment of SCZ using the LINCS L1000, GCP, and P100 databases. Together, our results bring a new era of the pathogenesis of a deeper understanding of POCD, identified novel therapeutic targets, and predicted drug inhibitors in POCD.\u0000</p></div></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"72 9","pages":"1875 - 1901"},"PeriodicalIF":3.1,"publicationDate":"2022-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-022-02042-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4583087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Inflammatory Properties of KLS-13019: a Novel GPR55 Antagonist for Dorsal Root Ganglion and Hippocampal Cultures","authors":"Douglas E. Brenneman,&nbsp;William A. Kinney,&nbsp;Mark E. McDonnell,&nbsp;Pingei Zhao,&nbsp;Mary E. Abood,&nbsp;Sara Jane Ward","doi":"10.1007/s12031-022-02038-2","DOIUrl":"10.1007/s12031-022-02038-2","url":null,"abstract":"<div><p>KLS-13019, a novel devised cannabinoid-like compound, was explored for anti-inflammatory actions in dorsal root ganglion cultures relevant to chemotherapy-induced peripheral neuropathy (CIPN). Time course studies with 3 µM paclitaxel indicated &gt; 1.9-fold increases in immunoreactive (IR) area for cell body GPR55 after 30 min as determined by high content imaging. To test for reversibility of paclitaxel-induced increases in GPR55, cultures were treated for 8 h with paclitaxel alone and then a dose response to KLS-13019 added for another 16 h. This “reversal” paradigm indicated established increases in cell body GPR55 IR areas were decreased back to control levels. Because GPR55 had previously reported inflammatory actions, IL-1β and NLRP3 (inflammasome-3 marker) were also measured in the “reversal” paradigm. Significant increases in all inflammatory markers were produced after 8 h of paclitaxel treatment alone that were reversed to control levels with KLS-13019 treatment. Accompanying studies using alamar blue indicated that decreased cellular viability produced by paclitaxel treatment was reverted back to control levels by KLS-13019. Similar studies conducted with lysophosphatidylinositol (GPR55 agonist) in DRG or hippocampal cultures demonstrated significant increases in neuritic GPR55, NLRP3 and IL-1β areas that were reversed to control levels with KLS-13019 treatment. Studies with a human GPR55-β-arrestin assay in Discover X cells indicated that KLS-13019 was an antagonist without agonist activity. These studies indicated that KLS-13019 has anti-inflammatory properties mediated through GPR55 antagonist actions. Together with previous studies, KLS-13019 is a potent neuroprotective, anti-inflammatory cannabinoid with therapeutic potential for high efficacy treatment of neuropathic pain.\u0000</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"72 9","pages":"1859 - 1874"},"PeriodicalIF":3.1,"publicationDate":"2022-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-022-02038-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4086757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipidomics Analysis Reveals a Protective Effect of Myriocin on Cerebral Ischemia/Reperfusion Model Rats","authors":"Ting Wang,&nbsp;Jingmin Zhang,&nbsp;Meng Yang,&nbsp;Jinxiu Guo,&nbsp;Duolu Li,&nbsp;Ying Li","doi":"10.1007/s12031-022-02014-w","DOIUrl":"10.1007/s12031-022-02014-w","url":null,"abstract":"<div><h2>Abstract\u0000</h2><div><p>Ceramide accumulation has been associated with ischemic stroke. Myriocin is an effective serine palmitoyltransferase (SPT) inhibitor that reduces ceramide levels by inhibiting the de novo synthesis pathway. However, the role of myriocin in cerebral ischemia/reperfusion (I/R) injury and its underlying mechanism remain unknown. The present study established an experimental rat model of middle cerebral artery occlusion (MCAO). We employed ultra-performance liquid chromatograph quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)–based lipidomic analysis to identify the disordered lipid metabolites and the effects of myriocin in cerebral cortical tissues of rats. In this study, we found 15 characterized lipid metabolites involved in sphingolipid and glycerophospholipid metabolism in cerebral I/R-injured rats, and these alterations were significantly alleviated by myriocin. Specifically, the mRNA expression of metabolism-related enzyme genes was detected by real-time quantitative polymerase chain reaction (RT-qPCR). We demonstrated that myriocin could regulate the mRNA expression of ASMase, NSMase, SGMS1, SGMS2, ASAH1, ACER2, and ACER3, which are involved in sphingolipid metabolism and PLA2, which is involved in glycerophospholipid metabolism. Moreover, TUNEL and Western blot assays showed that myriocin plays a key role in regulating neuronal cell apoptosis. In summary, the present work provides a new perspective for the systematic study of metabolic changes in ischemic stroke and the therapeutic applications of myriocin.</p></div></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"72 9","pages":"1846 - 1858"},"PeriodicalIF":3.1,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4031470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Reactive EGCs on Intestinal Motility and Enteric Neurons During Endotoxemia","authors":"Na Li,&nbsp;Jing Xu,&nbsp;Hui Gao,&nbsp;Yuxin Zhang,&nbsp;Yansong Li,&nbsp;Haiqing Chang,&nbsp;Shuwen Tan,&nbsp;Shuang Li,&nbsp;Qiang Wang","doi":"10.1007/s12031-022-02044-4","DOIUrl":"10.1007/s12031-022-02044-4","url":null,"abstract":"<div><p>Paralytic ileus is common in patients with septic shock, causing high morbidity and mortality. Enteric neurons and enteric glial cells (EGCs) regulate intestinal motility. However, little is known about their interaction in endotoxemia. This study aimed to investigate whether reactive EGCs had harmful effects on enteric neurons and participated in intestinal motility disorder in mice during endotoxemia. Endotoxemia was induced by the intraperitoneal injection of lipopolysaccharide (LPS) in mice. Fluorocitrate (FC) was administered before LPS injection to inhibit the reactive EGCs. The effects of reactive EGCs on intestinal motility were analyzed by motility assays in vivo and colonic migrating motor complexes ex vivo. The number of enteric neurons was evaluated by immunofluorescent staining of HuCD, nNOS, and ChAT in vivo. In addition, we stimulated EGCs with IL-1β and TNF-α in vitro and cultured the primary enteric neurons in the conditioned medium, detecting the apoptosis and morphology of neurons through staining TUNEL, cleaved caspase-3 protein, and anti-β-III tubulin. Intestinal motility and peristaltic reflex were improved by inhibiting reactive EGCs in vivo. The density of the neuronal population in the colonic myenteric plexus increased significantly, while the reactive EGCs were inhibited, especially the nitrergic neurons. In vitro, the enteric neurons cultured in the conditioned medium of reactive EGCs had a considerably higher apoptotic rate, less dendritic complexity, and fewer primary neurites. Reactive enteric glial cells probably participated in paralytic ileus by damaging enteric neurons during endotoxemia. They might provide a novel therapeutic strategy for intestinal motility disorders during endotoxemia or sepsis.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"72 9","pages":"1831 - 1845"},"PeriodicalIF":3.1,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5159400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum Brain-Derived Neurotrophic Factor (BDNF) in COVID-19 Patients and its Association with the COVID-19 Manifestations","authors":"Ali Asgarzadeh,&nbsp;Nasrin Fouladi,&nbsp;Vahid Asghariazar,&nbsp;Shahnaz Fooladi Sarabi,&nbsp;Hamid Afzoun Khiavi,&nbsp;Mahsa Mahmoudi,&nbsp;Elham Safarzadeh","doi":"10.1007/s12031-022-02039-1","DOIUrl":"10.1007/s12031-022-02039-1","url":null,"abstract":"<div><p>COVID-19 is a systematic disease that frequently implies neurological and non-neurological manifestations, predominantly by inducing hypoxia. Brain-derived neurotrophic factor (BDNF) is a key factor in regulating functions of nervous and respiratory systems and has been strongly related to hypoxia. Therefore, this study planned to investigate BDNF association with the COVID-19 manifestations especially neurological impairments and the infection-induced hypoxia. We enrolled sixty-four COVID-19 patients and twenty-four healthy individuals in this study. Patients were divided into two groups, with and without neurological manifestations, and their serum BDNF levels were measured by enzyme-linked immunosorbent assay (ELISA). COVID-19 patients had significantly lower BDNF levels than healthy individuals (<i>p</i> = 0.023). BDNF levels were significantly lower in patients with neurological manifestations compared to healthy individuals (<i>p</i> = 0.010). However, we did not observe a statistically significant difference in BDNF levels between patients with and without neurological manifestations (<i>p</i> = 0.175). BDNF’s levels were significantly lower in patients with CNS manifestations (<i>p</i> = 0.039) and higher in patients with fever (<i>p</i> = 0.03) and dyspnea (<i>p</i> = 0.006). Secondly, BDNF levels have a significant negative association with oxygen therapy requirement (<i>p</i> = 0.015). These results strongly suggest the critical association between dysregulated BDNF and hypoxia in promoting COVID-19 manifestations, particularly neurological impairments.\u0000</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"72 9","pages":"1820 - 1830"},"PeriodicalIF":3.1,"publicationDate":"2022-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-022-02039-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4941817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orthogonal Control of Neuronal Circuits and Behavior Using Photopharmacology","authors":"Rossella Castagna,&nbsp;Dušan Kolarski,&nbsp;Romain Durand-de Cuttoli,&nbsp;Galyna Maleeva","doi":"10.1007/s12031-022-02037-3","DOIUrl":"10.1007/s12031-022-02037-3","url":null,"abstract":"<div><p>Over the last decades, photopharmacology has gone far beyond its proof-of-concept stage to become a bona fide approach to study neural systems in vivo. Indeed, photopharmacological control has expanded over a wide range of endogenous targets, such as receptors, ion channels, transporters, kinases, lipids, and DNA transcription processes. In this review, we provide an overview of the recent progresses in the in vivo photopharmacological control of neuronal circuits and behavior. In particular, the use of small aquatic animals for the in vivo screening of photopharmacological compounds, the recent advances in optical modulation of complex behaviors in mice, and the development of adjacent techniques for light and drug delivery in vivo are described.\u0000</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"72 7","pages":"1433 - 1442"},"PeriodicalIF":3.1,"publicationDate":"2022-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4898648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}