Brain Pathology最新文献

{"title":"SPI1 activates TGF-β1/PI3K/Akt signaling through transcriptional upregulation of FKBP12 to support the mesenchymal phenotype of glioma stem cells","authors":"Yifu Song,&nbsp;Yaochuan Zhang,&nbsp;Xiaoliang Wang,&nbsp;Xiaodi Han,&nbsp;Mengwu Shi,&nbsp;Ling Xu,&nbsp;Juanhan Yu,&nbsp;Li Zhang,&nbsp;Sheng Han","doi":"10.1111/bpa.13217","DOIUrl":"10.1111/bpa.13217","url":null,"abstract":"<p>Glioma stem cells (GSCs) exhibit diverse molecular subtypes with the mesenchymal (MES) population representing the most malignant variant. The oncogenic potential of <i>Salmonella</i> pathogenicity island 1 (SPI1), an oncogenic transcription factor, has been established across various human malignancies. In this study, we explored the association between the SPI1 pathway and the MES GSC phenotype. Through comprehensive analysis of the Cancer Genome Atlas and Chinese Glioma Genome Atlas glioma databases, along with patient-derived GSC cultures, we analyzed SPI1 expression. Using genetic knockdown and overexpression techniques, we assessed the functional impact of SPI1 on GSC MES marker expression, invasion, proliferation, self-renewal, and sensitivity to radiation in vitro, as well as its influence on tumor formation in vivo. Additionally, we investigated the downstream signaling cascades activated by SPI1. Our findings revealed a positive correlation between elevated SPI1 expression and the MES phenotype, which in turn, correlated with poor survival. SPI1 enhanced GSC MES differentiation, self-renewal, and radioresistance in vitro, promoting tumorigenicity in vivo. Mechanistically, SPI1 augmented the transcriptional activity of both TGF-β1 and FKBP12 while activating the non-canonical PI3K/Akt pathway. Notably, inhibition of TGF-β1/PI3K/Akt signaling partially attenuated SPI1-induced GSC MES differentiation and its associated malignant phenotype. Collectively, our results underscore SPI1's role in activating TGF-β1/PI3K/Akt signaling through transcriptional upregulation of FKBP12, thereby supporting the aggressive MES phenotype of GSCs. Therefore, SPI1 emerges as a potential therapeutic target in glioma treatment.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 3","pages":""},"PeriodicalIF":6.4,"publicationDate":"2023-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13217","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49688789","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":"Society News","authors":"","doi":"10.1111/bpa.13095","DOIUrl":"https://doi.org/10.1111/bpa.13095","url":null,"abstract":"","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"33 6","pages":""},"PeriodicalIF":6.4,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50136414","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":"Poly-GA immunohistochemistry is a reliable tool for detecting C9orf72 hexanucleotide repeat expansions","authors":"Jordan Carroll,&nbsp;Heather McCann,&nbsp;Glenda M. Halliday,&nbsp;John B. Kwok,&nbsp;Carol Dobson-Stone,&nbsp;Claire E. Shepherd","doi":"10.1111/bpa.13216","DOIUrl":"10.1111/bpa.13216","url":null,"abstract":"<p>Poly-GA immunohistochemistry (A) on formalin fixed paraffin embedded cerebellum sections shows a similar distribution to p62 antibody (B) and reliably identifies neuronal cytoplasmic inclusions and neurites in cases with known <i>C9orf72</i> repeat expansion. This is useful in the research setting where genetic testing has not been performed in life or suitable tissue is not avilable post-mortem.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13216","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41191949","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":"Colocalization of TDP-43 and stress granules at the early stage of TDP-43 aggregation in amyotrophic lateral sclerosis","authors":"Fumiaki Mori,&nbsp;Hina Yasui,&nbsp;Yasuo Miki,&nbsp;Tomoya Kon,&nbsp;Akira Arai,&nbsp;Hidekachi Kurotaki,&nbsp;Masahiko Tomiyama,&nbsp;Koichi Wakabayashi","doi":"10.1111/bpa.13215","DOIUrl":"10.1111/bpa.13215","url":null,"abstract":"<p>TDP-43 aggregates (skeins and round inclusions [RIs]) are frequent histopathological features of amyotrophic lateral sclerosis (ALS). We have shown that diffuse punctate cytoplasmic staining (DPCS) is the earliest pathologic manifestation of TDP-43 in ALS, corresponding to nonfibrillar TDP-43 located in the rough endoplasmic reticulum. Previous in vitro studies have suggested that TDP-43 inclusions may be derived from stress granules (SGs). Therefore, we investigated the involvement of SGs in the formation of TDP-43 inclusions. Formalin-fixed spinal cords of six ALS patients with a disease duration of less than 1 year (short duration), eight patients with a disease duration of 2–5 years (standard duration), and five normal controls were subjected to histopathological examination using antibodies against an SG marker, HuR. In normal controls, the cytoplasm of anterior horn cells was diffusely HuR-positive. In short-duration and standard-duration ALS, the number of HuR-positive anterior horn cells was significantly decreased relative to the controls. DPCS and RIs were more frequent in short-duration ALS than in standard-duration ALS. The majority of DPCS areas and a small proportion of RIs, but not skeins, were positive for HuR. Immunoelectron microscopy showed that ribosome-like granular structures in DPCS areas and RIs were labeled with anti-HuR, whereas skeins were not. These findings suggest that colocalization of TDP-43 and SGs occurs at the early stage of TDP-43 aggregation.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 2","pages":""},"PeriodicalIF":6.4,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13215","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41111595","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":"LATE-NC in Alzheimer's disease: Molecular aspects and synergies","authors":"Sandra O. Tomé,&nbsp;Klara Gawor,&nbsp;Dietmar Rudolf Thal","doi":"10.1111/bpa.13213","DOIUrl":"10.1111/bpa.13213","url":null,"abstract":"<p>Alzheimer's disease (AD) is classically characterized by senile plaques and neurofibrillary tangles (NFTs). However, multiple copathologies can be observed in the AD brain and contribute to the development of cognitive decline. Limbic-predominant age-related TDP-43 encephalopathy neuropathological changes (LATE-NC) accumulates in the majority of AD cases and leads to more severe cognitive decline compared with AD pathology alone. In this review, we focus on the synergistic relationship between LATE-NC and tau in AD, highlighting the aggravating role of TDP-43 aggregates on tau pathogenesis and its impact on the clinical picture and therapeutic strategies. Additionally, we discuss to what extent the molecular patterns of LATE-NC in AD differ from frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP) neuropathological changes. Thus, we highlight the importance of tau and TDP-43 synergies for subtyping AD patients, which may respond differently to therapeutic interventions depending on the presence of comorbid LATE-NC.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13213","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41094357","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":"Enhanced Creutzfeldt-Jakob disease surveillance in the older population: Assessment of a protocol for screening brain tissue donations for prion disease","authors":"Alexander H. Peden,&nbsp;Adriana Libori,&nbsp;Diane L. Ritchie,&nbsp;Helen Yull,&nbsp;Colin Smith,&nbsp;Lovney Kanguru,&nbsp;Anna Molesworth,&nbsp;Richard Knight,&nbsp;Marcelo A. Barria","doi":"10.1111/bpa.13214","DOIUrl":"10.1111/bpa.13214","url":null,"abstract":"<p>Human prion diseases, including Creutzfeldt-Jakob disease (CJD), occur in sporadic, genetic, and acquired forms. Variant Creutzfeldt-Jakob disease (vCJD) first reported in 1996 in the United Kingdom (UK), resulted from contamination of food with bovine spongiform encephalopathy. There is a concern that UK national surveillance mechanisms might miss some CJD cases (including vCJD), particularly in the older population where other neurodegenerative disorders are more prevalent. We developed a highly sensitive protocol for analysing autopsy brain tissue for the misfolded prion protein (PrP^Sc) associated with prion disease, which could be used to screen for prion disease in the elderly. Brain tissue samples from 331 donors to the Edinburgh Brain and Tissue Bank (EBTB), from 2005 to 2022, were analysed, using immunohistochemical analysis on fixed tissue, and five biochemical tests on frozen specimens from six brain regions, based on different principles for detecting PrP^Sc. An algorithm was established for classifying the biochemical results. To test the effectiveness of the protocol, several neuropathologically confirmed prion disease controls, including vCJD, were included and blinded in the study cohort. On unblinding, all the positive control cases had been correctly identified. No other cases tested positive; our analysis uncovered no overlooked prion disease cases. Our algorithm for classifying cases was effective for handling anomalous biochemical results. An overall analysis suggested that a reduced biochemical protocol employing only three of the five tests on only two brain tissue regions gave sufficient sensitivity and specificity. We conclude that this protocol may be useful as a UK-wide screening programme for human prion disease in selected brains from autopsies in the elderly. Further improvements to the protocol were suggested by enhancements of the in vitro conversion assays made during the course of this study.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 2","pages":""},"PeriodicalIF":6.4,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13214","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41119403","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":"Tumor-associated astrocytes promote tumor progression of Sonic Hedgehog medulloblastoma by secreting lipocalin-2","authors":"Haishuang Li,&nbsp;Yuqing Liu,&nbsp;Yantao Liu,&nbsp;Luzheng Xu,&nbsp;Ziwen Sun,&nbsp;Danfeng Zheng,&nbsp;Xiaodan Liu,&nbsp;Chen Song,&nbsp;Yu Zhang,&nbsp;Hui Liang,&nbsp;Bao Yang,&nbsp;Xinxia Tian,&nbsp;Jianyuan Luo,&nbsp;Qing Chang","doi":"10.1111/bpa.13212","DOIUrl":"10.1111/bpa.13212","url":null,"abstract":"<p>Sonic Hedgehog (SHH) subgroup of medulloblastoma (MB) accounts for about 25% of all subgroups of MB. Tumor microenvironment (TME) may play a key role in the tumor progression and therapeutic resistance. Tumor-associated astrocytes (TAAs) are reshaped to drive tumor progression through multiple paracrine signals. However, the mechanism by which TAAs modulate MB cells remains elusive. Here, we illuminated that TAAs showed a specific and dynamic pattern during SHH-MB development. Most TAAs gathered to the tumor margin during the tumor progression, rather than evenly distributed in the early-stage tumors. We further demonstrated that lipocalin-2 (LCN2) secreted by TAAs could promote the tumor growth and was correlated with the poor prognosis of MB patients. Knocking down LCN2 in TAAs in vitro impeded the proliferation and migration abilities of MB cells. In addition, we identified that TAAs accelerated the tumor growth by secreting LCN2 via STAT3 signaling pathway. Accordingly, blockade of STAT3 signaling by its inhibitor WP1066 and AAV-<i>Lcn2</i> shRNA, respectively, in TAAs abrogated the effects of LCN2 on tumor progression in vitro and in vivo. In summary, we for the first time clarified that LCN2, secreted by TAAs, could promote MB tumor progression via STAT3 pathway and has potential prognostic value. Our findings unveiled a new sight in reprogramming the TME of SHH-MB and provided a potential therapeutic strategy targeting TAAs.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2023-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13212","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10652950","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":"Frontal lobe mass in a 46-year-old woman","authors":"Kevin Y. Zhang,&nbsp;Bharat Ramlal,&nbsp;Karisa C. Schreck,&nbsp;Charles G. Eberhart,&nbsp;Calixto-Hope G. Lucas","doi":"10.1111/bpa.13211","DOIUrl":"10.1111/bpa.13211","url":null,"abstract":"&lt;p&gt;A 46-year-old woman presented with new onset seizures. Magnetic resonance imaging (MRI) revealed a 4 cm heterogeneously enhancing mass centered in the right posterior frontal lobe with mild perilesional edema and effacement of the adjacent sulci (Figure 1A). The mass was restricted to cortex and hemispheric white matter, with no involvement of deep grey matter or other midline structures. A retrospective review of MRI studies from 3 years prior demonstrated mild FLAIR signal abnormality in the same location.&lt;/p&gt;&lt;p&gt;The patient underwent craniotomy for resection. Postoperative MRI showed near gross total resection of the mass. The patient declined adjuvant chemotherapy or radiotherapy and was instead treated with intravenous vitamin therapy, hyperbaric oxygen, and additional nutritional supplements. Postoperative imaging at 6 and 12 months demonstrated an enlarging enhancing component at the resection margin (Figure 1B). Re-resection at 12 months following initial surgery confirmed tumor recurrence.&lt;/p&gt;&lt;p&gt;Histologic sections from the initial surgery revealed a moderately cellular glial neoplasm composed of tumor cells with irregular and hyperchromatic nuclei (Box 1, Figure 2, top row). Foci of microvascular proliferation and necrosis were also seen. The mitotic rate reached up to 6 mitotic figures per 10 high-power fields. Synaptophysin staining highlighted entrapped axons, consistent with an infiltrative growth pattern (Figure 2, middle row). By immunohistochemistry, the neoplastic cells expressed GFAP and OLIG2 but were negative for IDH1 R132H or BRAF V600E mutant protein immunostains. ATRX expression was retained, and p53 labeled only scattered tumor cells.&lt;/p&gt;&lt;p&gt;Next-generation sequencing studies detected &lt;i&gt;H3F3A&lt;/i&gt; p.K27M (variant allele frequency 42%), &lt;i&gt;NF1&lt;/i&gt; p.E1192* (85%), and &lt;i&gt;TP53&lt;/i&gt; p.E171* (9%) mutations. While the tumor harbored gain of chromosome 7, it lacked chromosome 10 loss, &lt;i&gt;TERT&lt;/i&gt; promoter mutation, or &lt;i&gt;EGFR&lt;/i&gt; amplification. Retrospective immunohistochemical staining showed diffuse immunoreactivity for H3 K27M mutant protein, along with loss of H3K27me3 expression in tumor cells (Figure 2, bottom row). Methylation profiling performed at NIH/NCI demonstrated a high-confidence match to the “diffuse midline glioma, H3 K27-altered” (DMG) class. Uniform manifold approximation and projection dimensionality reduction analysis also placed the tumor in the “DMG, H3 K27-altered” class.&lt;/p&gt;&lt;p&gt;“High-grade glioma (HGG), H3 K27M-mutant, not elsewhere classified (NEC)”&lt;/p&gt;&lt;p&gt;This case represents a rare example of a diffusely infiltrating HGG centered in the cerebral hemisphere harboring &lt;i&gt;H3F3A&lt;/i&gt; p.K27M mutation [&lt;span&gt;1&lt;/span&gt;] and the first to our knowledge demonstrating an epigenetic signature aligning with “DMG, H3 K27-altered.” Midline location is an essential criterion for the diagnosis of DMG according to the 2021 WHO Classification of Tumors of the Central Nervous System. Perplexingly, this case does not involve ","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13211","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10298171","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":"Special Issue: Abstracts of the 20th International Congress of Neuropathology, Berlin, Germany, September 13–16, 2023","authors":"","doi":"10.1111/bpa.13194","DOIUrl":"https://doi.org/10.1111/bpa.13194","url":null,"abstract":"","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"33 S1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2023-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13194","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50135180","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":"The molecular spectrum of amyloid-beta (Aβ) in neurodegenerative diseases beyond Alzheimer's disease","authors":"Shojiro Ichimata,&nbsp;Koji Yoshida,&nbsp;Jun Li,&nbsp;Ekaterina Rogaeva,&nbsp;Anthony E. Lang,&nbsp;Gabor G. Kovacs","doi":"10.1111/bpa.13210","DOIUrl":"10.1111/bpa.13210","url":null,"abstract":"<p>This study investigated the molecular spectrum of amyloid-beta (Aβ) in neurodegenerative diseases beyond Alzheimer's disease (AD). We analyzed Aβ deposition in the temporal cortex and striatum in 116 autopsies, including Lewy body disease (LBD; <i>N</i> = 51), multiple system atrophy (MSA; <i>N</i> = 10), frontotemporal lobar degeneration-TDP-43 (FTLD-TDP; <i>N</i> = 16), and progressive supranuclear palsy (PSP; <i>N</i> = 39). The LBD group exhibited the most Aβ deposition in the temporal cortex and striatum (90/76%, respectively), followed by PSP (69/28%), FTLD-TDP (50/25%), and the MSA group (50/10%). We conducted immunohistochemical analysis using antibodies targeting eight Aβ epitopes in the LBD and PSP groups. Immunohistochemical findings were evaluated semi-quantitatively and quantitatively using digital pathology. Females with LBD exhibited significantly more severe Aβ deposition, particularly Aβ₄₂ and Aβ₄₃, along with significantly more severe tau pathology. Furthermore, a quantitative analysis of all Aβ peptides in the LBD group revealed an association with the <i>APOE-</i>ε4 genotypes. No significant differences were observed between males and females in the PSP group. Finally, we compared striatal Aβ deposition in cases with LBD (<i>N</i> = 15), AD without α-synuclein pathology (<i>N</i> = 6), and PSP (<i>N</i> = 5). There were no differences in the pan-Aβ antibody (6F/3D)-immunolabeled deposition burden among the three groups, but the deposition burden of peptides with high aggregation capacity, especially Aβ₄₃, was significantly higher in the AD and LBD groups than in the PSP group. Furthermore, considerable heterogeneity was observed in the composition of Aβ peptides on a case-by-case basis in the AD and LBD groups, whereas it was relatively uniform in the PSP group. Cluster analysis further supported these findings. Our data suggest that the type of concomitant proteinopathies influences the spectrum of Aβ deposition, impacted also by sex and <i>APOE</i> genotypes.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"34 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13210","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10185219","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}