Neuropathology最新文献

{"title":"Somatic mutational profiling and clinical impact of driver genes in Latin-Iberian medulloblastomas: Towards precision medicine.","authors":"Letícia Ganem Rillo Paz Barateiro, Rodrigo de Oliveira Cavagna, Mariana Bisarro Dos Reis, Flávia Escremim de Paula, Gustavo Ramos Teixeira, Daniel Antunes Moreno, Murilo Bonatelli, Iara Santana, Fabiano Pinto Saggioro, Luciano Neder, João Norberto Stavale, Suzana Maria Fleury Malheiros, Hernan Garcia-Rivello, Silvia Christiansen, Susana Nunes, Maria João Gil da Costa, Jorge Pinheiro, Carlos Almeida Júnior, Bruna Minniti Mançano, Rui Manuel Reis","doi":"10.1111/neup.12979","DOIUrl":"10.1111/neup.12979","url":null,"abstract":"<p><p>Medulloblastoma (MB) is the most prevalent malignant brain tumor in children, known for its heterogeneity and treatment-associated toxicity, and there is a critical need for new therapeutic targets. We analyzed the somatic mutation profile of 15 driver genes in 69 Latin-Iberian molecularly characterized medulloblastomas using the Illumina TruSight Tumor 15 panel. We classified the variants based on their clinical impact and oncogenicity. Among the patients, 66.7% were MB_SHH, 13.0% MB_WNT, 7.3% MB_Grp3, and 13.0% MB_Grp4. Among the 63 variants found, 54% were classified as Tier I/II and 31.7% as oncogenic/likely oncogenic. We observed 33.3% of cases harboring at least one mutation. TP53 (23.2%, 16/69) was the most mutated gene, followed by PIK3CA (5.8%, 4/69), KIT (4.3%, 3/69), PDGFRA (2.9%, 2/69), EGFR (1.4%, 1/69), ERBB2 (1.4%, 1/69), and NRAS (1.4%, 1/69). Approximately 41% of MB_SHH tumors exhibited mutations, TP53 (32.6%) being the most frequently mutated gene. Tier I/II and oncogenic/likely oncogenic TP53 variants were associated with relapse, progression, and lower survival rates. Potentially actionable variants in the PIK3CA and KIT genes were identified. Latin-Iberian medulloblastomas, particularly the MB_SHH, exhibit higher mutation frequencies than other populations. We corroborate the TP53 mutation status as an important prognostic factor, while PIK3CA and KIT are potential therapeutic targets.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"30-37"},"PeriodicalIF":1.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911032","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":"ASK1 activation in glial cells in post-mortem multiple sclerosis tissue.","authors":"Erika Seki, Xiaoli Guo, Kazuhiko Namekata, Takashi Komori, Hiroyuki Hayashi, Nobutaka Arai, Takayuki Harada","doi":"10.1111/neup.12978","DOIUrl":"10.1111/neup.12978","url":null,"abstract":"<p><p>Multiple sclerosis (MS), the leading cause of disability in young adults, is an inflammatory disease of the central nervous system characterized by localized areas of demyelination. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that has been shown to be implicated in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Interestingly, ASK1 signaling regulates glial cell interactions and drives neuroinflammation in EAE mice. To further investigate its clinical significance, in the present study, we examined the activation of ASK1 in the post-mortem brain of MS patients. ASK1 activation was found in active lesions of the corpus callosum in both microglia/macrophages and astrocytes. Moreover, ASK1 activation in astrocytes was higher than that in microglia/macrophages, which was in line with our findings in EAE mice. Our results suggest an important role of ASK1 in glial cells, indicating that ASK1 might be a good therapeutic target for MS.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"20-29"},"PeriodicalIF":1.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076356","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 assessment of malignancy in IDH-mutant astrocytoma with p16 and methylthioadenosine phosphorylase immunohistochemistry.","authors":"Kenta Masui, Hiromi Onizuka, Yoshihiro Muragaki, Takakazu Kawamata, Yoji Nagashima, Atsushi Kurata, Takashi Komori","doi":"10.1111/neup.13005","DOIUrl":"10.1111/neup.13005","url":null,"abstract":"<p><p>In the fifth edition of the World Health Organization's (WHO) classification of tumors of the central nervous system (CNS), molecular analysis is required for not only determining each tumor type but assessing its prognosis based on malignancy (CNS WHO grade). A notable example is the loss of tumor suppressor gene cyclin-dependent kinase inhibitor 2A (CDKN2A), and CDKN2A homozygous deletion (HD) is a novel CNS WHO grade 4 marker in isocitrate dehydrogenase gene (IDH)-mutant astrocytoma. However, incorporating molecular workup into the \"routine diagnostics\" of each brain tumor type remains a major challenge, especially in resource-limited settings, including low- and middle-income countries. We herein validated the usefulness of p16 and methylthioadenosine phosphorylase (MTAP) immunohistochemistry (IHC) as potential surrogates for the assessment of CDKN2A status in 20 IDH-mutant astrocytoma cases. Of note, loss or retention of p16 and MTAP could accurately predict CDKN2A HD (p16: 87.5%, MTAP: 88.9%) or non-HD (p16: 100%, MTAP: 100%) with a single marker alone. Importantly, we revealed contributing factors to gray-zone IHC results (p16: 5-20%, MTAP: mosaic), including (1) hemizygous deletion of CDKN2A, (2) degenerative findings, and (3) intratumoral CDKN2A HD heterogeneity, the detailed histologic and molecular assessment of which would be a key to achieving integrated assessment of malignancy in IDH-mutant astrocytoma. We characterized the pitfalls of each method and provided for the first time a practical flowchart of astrocytoma grading, contributing to a normalization of WHO2021-based molecular diagnostics in resource-limited settings.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"66-75"},"PeriodicalIF":1.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308226","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":"An autopsy case of progressive supranuclear palsy with severe corticospinal tract degeneration.","authors":"Satoshi Kuru, Motoko Sakai, Hideyuki Moriyoshi, Hiroaki Miyahara, Yasushi Iwasaki","doi":"10.1111/neup.13001","DOIUrl":"10.1111/neup.13001","url":null,"abstract":"<p><p>We report an autopsy case of a 70-year-old man who was clinically diagnosed with atypical progressive supranuclear palsy (PSP). He initially presented with gait ataxia and then showed vertical gaze palsy, rigidity, akinesia, dysphagia, and mild cognitive impairment, followed by prominent upper motor signs later in the course of the disease. Cranial magnetic resonance imaging revealed tegmental atrophy of the midbrain. Autopsy revealed severe neuronal loss and gliosis in the motor cortex and corticospinal degeneration and mild to moderate neuronal loss and gliosis in the basal ganglia, substantia nigra, midbrain, and pons. Tufted astrocytes were primarily found in the motor cortex and basal ganglia. Globose-type neurofibrillary tangles were observed in the locus coeruleus and nucleus olivaris inferior. In the cerebellar cortex, mild Purkinje cell loss and scattered axonal torpedoes were observed with tau-positive Purkinje cells. The dentate nucleus displayed severe neuronal loss and gliosis. The present case showed characteristics of both PSP with prominent cerebellar ataxia (PSP-C) and PSP-primary lateral sclerosis (PSP-PLS).</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"452-458"},"PeriodicalIF":1.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046947","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":"Neuropathologic findings in a patient with hemiparkinsonism and hemiatrophy syndrome.","authors":"Masataka Nakamura, Ayako Tsuge, Kosuke Miyake, Takenobu Kunieda, Hirofumi Kusaka, Yusuke Yakushiji","doi":"10.1111/neup.12994","DOIUrl":"10.1111/neup.12994","url":null,"abstract":"<p><p>The first postmortem neuropathological findings of a hemiparkinsonism and hemiatrophy (HPHA) patient are presented. A 50-year-old man developed resting tremors affecting the right hand and leg, followed by mild clumsiness of the right hand. On examination, he exhibited muscle atrophy of the right leg extremity, accompanied by right-sided parkinsonism. Brain magnetic resonance imaging was normal. Based on the clinical and radiological findings, HPHA syndrome was diagnosed, showing a good response to L-DOPA. He gradually developed muscular atrophy of the right distal upper extremity. Thirteen years after the onset of the disease, left-sided parkinsonism appeared. The patient died of Trousseau's syndrome associated with a rapidly emerging pancreatic tumor. The total duration of the disease was 14 years. Neuropathologically, the substantia nigra showed markedly left-predominant neuronal loss, along with almost symmetrical Lewy body (LB) pathology. These findings indicated that the patient originally had fewer neurons in the left substantia nigra than in the right, probably caused by congenital or childhood cerebral injury, followed by the development of unilateral parkinsonism due to the progression of LB pathology. Despite our extensive neuropathological analysis, we could not specify the etiology or anatomical substrate responsible for the development of right upper and lower extremity atrophy. Further clinicopathological studies are needed to elucidate the pathoanatomical areas causing hemiparkinsonism and hemiatrophy.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"432-439"},"PeriodicalIF":1.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555292","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":"Unveiling primary intracranial eosinophilic angiocentric fibrosis: A rare case report and diagnostic dilemmas.","authors":"Rumela Nayak, Bevinahalli N Nandeesh","doi":"10.1111/neup.12997","DOIUrl":"10.1111/neup.12997","url":null,"abstract":"<p><p>Eosinophilic angiocentric fibrosis (EAF) is a rare, benign fibroinflammatory condition primarily affecting the sinonasal and upper respiratory tract, with a few cases reported beyond these regions. Primary intracranial EAF is rare. To date, only one case of intracranial EAF has been reported; ours is the second. This case report presents a case of EAF in a 55-year-old man, initially misdiagnosed as meningioma based on clinical and radiological features. The patient complained of a persistent dull headache for six months without associated neurological symptoms. Brain magnetic resonance imaging revealed a dural-based lesion with characteristics suggestive of meningioma. However, histopathological examination post-surgical resection revealed a nodular vascular lesion with concentric angiocentric fibrosis, a distinctive onion skin pattern, and an inflammatory infiltrate rich in eosinophils, plasma cells, and histiocytes. Immunohistochemistry ruled out IgG4-related disease, and other systemic disorders were ruled out based on combined clinical and histological features. This case underscores the need for considering EAF in the differential diagnosis of dural-based lesions. Awareness of its potential mimicking of meningioma is crucial for accurate diagnosis and appropriate management, emphasizing the importance of histopathological examination in challenging cases.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"459-463"},"PeriodicalIF":1.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893922","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":"Increase in cathepsin K gene expression in Duchenne muscular dystrophy skeletal muscle.","authors":"Shigemi Kimura, Noriko Miyake, Shiro Ozasa, Hiroe Ueno, Yoshinobu Ohtani, Yutaka Takaoka, Ichizo Nishino","doi":"10.1111/neup.12995","DOIUrl":"10.1111/neup.12995","url":null,"abstract":"<p><p>Dystrophinopathy is caused by alterations in the dystrophin gene. The severe phenotype, Duchenne muscular dystrophy (DMD), is caused by a lack of dystrophin in skeletal muscles, resulting in necrosis and regenerating fibers, inflammatory cells, and muscle fibrosis. Progressive muscle weakness is a characteristic finding of this condition. Here, we encountered a rare case of a 10-year-old patient with asymptomatic dystrophinopathy with no dystrophin expression and investigated the reason for the absence of muscle weakness to obtain therapeutic insights for DMD. Using RNA-seq analysis, gene expression in skeletal muscles was compared among patients with asymptomatic dystrophinopathy, three patients with typical DMD, and two patients without dystrophinopathy who were leading normal daily lives. Cathepsin K (CTSK), myosin heavy chain 3 (MYH3), and nodal modulator 3-like genes exhibited a >8-fold change, whereas crystallin mu gene (CRYM) showed a <1/8-fold change in patients with typical DMD compared with their expression in the patient with asymptomatic dystrophinopathy. Additionally, CTSK and MYH3 expression exhibited a >16-fold change (P < 0.01), whereas CRYM expression showed a <1/16-fold change (P < 0.01) in patients with typical DMD compared with their expression in those without dystrophinopathy. CTSK plays an essential role in skeletal muscle loss, fibrosis, and inflammation in response to muscles injected with cardiotoxin, one of the most common reagents that induce muscle injury. Increased CTSK expression is associated with muscle injury or necrosis in patients with DMD. The lack of muscle weakness in the patient with asymptomatic dystrophinopathy might be attributed to the low CTSK expression in the muscles. To the best of our knowledge, this is the first report to demonstrate that CTSK expression was significantly higher in the skeletal muscles of patients with DMD with a typical phenotype than in those without dystrophinopathy.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"411-421"},"PeriodicalIF":1.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627211","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":"Diffuse leptomeningeal glioneuronal tumor with distinct neuronal and glial components but identical diagnostic molecular and genetic features.","authors":"Andrew J Witten, Carson Dougherty, Chunhai Hao","doi":"10.1111/neup.12996","DOIUrl":"10.1111/neup.12996","url":null,"abstract":"<p><p>The 2021 World Health Organization (WHO) classification of the central nervous system (CNS) tumors has classified diffuse leptomeningeal glioneuronal tumor (DLGNT) as a mixed neuronal and glial tumor. Here, we report a DLGNT with two distinct morphological tumor components but identical molecular features. A four-year-old female child presented with progressive right upper extremity weakness. Magnetic resonance imaging (MRI) revealed the leptomeningeal enhancement over the brain stem and cervicothoracic spine. The histological examination of surgical specimens revealed two distinct tumor components: approximately half of the tumor is composed of oligodendroglioma-like tumor intermingled with nodules of ganglioglioma-like tumor. Immunohistochemistry confirmed the oligodendroglioma and ganglioglioma features. The molecular genetic studies demonstrated the features of DLGNT, including fusion of KIAA1549::BRAF, deletion of chromosome 1p, and absence of isocitrate dehydrogenase 1/2 (IDH1/2) mutation in both tumor components. Interestingly, the genetic studies also revealed the distinct chromosomal abnormalities of the loss of chromosome 4 only in oligodendroglioma-like tumor and copy neutral loss of heterozygosity of 7Q34Q36.3 in the ganglioglioma-like tumor component. This case highlights the critical role of molecular testing in the diagnosis of rare cases of DLGNT with diverse morphological components as well as in the identification of unique molecular alternations responsible for morphological phenotypes of the distinct tumors in DLGNT.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"440-444"},"PeriodicalIF":1.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788738","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":"Elevated expression of N-myc downstream regulated gene 1 protein in glioblastomas reflects tumor angiogenesis and poor patient prognosis.","authors":"Yasuo Sugita, Takuya Furuta, Kenji Takahashi, Koichi Higaki, Yuichi Murakami, Michihiko Kuwano, Mayumi Ono, Hideyuki Abe, Jun Akiba, Motohiro Morioka","doi":"10.1111/neup.12999","DOIUrl":"10.1111/neup.12999","url":null,"abstract":"<p><p>N-myc downstream regulated gene 1 (NDRG1) is a member of the NDRG family, of which four members (NDRG1, NDRG2, NDRG3, and NDRG4) have been identified. NDRG1 is repressed by c-MYC and N-MYC proto-oncogenes. NDRG1 is translated into a 43 kDa protein that is associated with the regulation of cellular stress responses, proliferation, and differentiation. In this study, we aimed to clarify the relationship between progression of glioblastoma (GB) IDH-wildtype and NDRG1 expression in tumor cells. We assessed the expression of NDRG1 in 41 GBs using immunostaining and evaluated its prognostic significance. NDRG1 expression by GBs was evaluated using Histoscore, which showed high and low scores in 23 and 18 cases, respectively. NDRG1-positive cells were strongly expressed in Ki-67 labeled proliferating tumor cells and CD105 positive proliferating microvessels around the area of palisading necrosis. Statistical analyses showed lower survival rates in the high-score group than the low-score group (P < 0.01). This study indicated that overexpression of NDRG1 by GB reflects tumor angiogenesis and poor patient prognosis.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"422-431"},"PeriodicalIF":1.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893977","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":"Ipsilateral simultaneous multiple hypertensive intracerebral hemorrhages: Analysis of hematoma formation and comparison with distribution of hypertensive mixed-type hematoma.","authors":"Shigeki Takeda, Hitoshi Takahashi, Teruo Miyakawa, Kazunori Yamazaki, Kiyoshi Onda","doi":"10.1111/neup.12998","DOIUrl":"10.1111/neup.12998","url":null,"abstract":"<p><p>A 55-year-old Japanese woman with a history of hypertension and right putaminal hemorrhage developed simultaneous hemorrhages in the left thalamus and putamen and died 24 h later. There were no vascular anomalies in the brain. Synaptophysin immunostaining combined with eosin azure 50 (EA50) staining clearly identified the hematoma and the surrounding brain structures. In the right cerebral hemisphere, a cystic lesion as a sequela of the usual type of hypertensive putaminal hematoma was evident. In the left cerebral hemisphere, two fresh hematomas were evident. One was a thalamic hematoma, which had destroyed the dorsal and medial structures of the thalamus, and the other was an unusual putaminal hematoma, which had destroyed the entire putamen and crossed the internal capsule and caudate nucleus. α-Smooth muscle actin immunostaining combined with EA50 and Victoria bleu staining demonstrated three ruptured arteries associated with fibrin aggregates in the anterior thalamic nucleus and anterior putamen. Some circular structures composed of fibrin, suggesting the presence of ruptured arteries in the neighborhood, were evident in the thalamus and putamen. In the putamen, ruptured arteries and circular structures were present in the lateral to medial areas. Fibrin aggregates in the anterior thalamic nucleus were more numerous than those in the putamen. On the basis of these findings, we concluded that: (i) the artery with numerous fibrin aggregates in the anterior thalamic nucleus had ruptured first, followed by the arteries distributed in other parts of the thalamus and putamen; (ii) the unusual putaminal hematoma was attributable to rupture of the arteries around the center of the putamen, which are not responsible for the usual type of hypertensive putaminal hematoma; and (iii) it is suggested that even if hypertensive hemorrhage occurs simultaneously in the ipsilateral putamen and thalamus, the usual type of hypertensive mixed-type hematoma does not form.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"445-451"},"PeriodicalIF":1.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893921","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}