Histopathology最新文献

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HMGA2-positive salivary gland neoplasms with prominent trabecular/canalicular morphology: a focus on carcinomas arising within this phenotype HMGA2 阳性唾液腺肿瘤具有突出的小梁/针状形态:重点研究这种表型中出现的癌。
IF 3.9 2区 医学
Histopathology Pub Date : 2024-10-03 DOI: 10.1111/his.15334
Melad N Dababneh, Elizabeth M Azzato, Joy Nakitandwe, Vincent Cracolici, Akeesha A Shah
{"title":"HMGA2-positive salivary gland neoplasms with prominent trabecular/canalicular morphology: a focus on carcinomas arising within this phenotype","authors":"Melad N Dababneh,&nbsp;Elizabeth M Azzato,&nbsp;Joy Nakitandwe,&nbsp;Vincent Cracolici,&nbsp;Akeesha A Shah","doi":"10.1111/his.15334","DOIUrl":"10.1111/his.15334","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Pleomorphic adenoma (PA) with a prominent trabecular/canalicular morphology has consistent HMGA2 protein expression, and association with <i>HMGA2</i> fusions. We report our experience with this subtype, with emphasis on the carcinomas that can arise in this context.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>A retro- and prospective review (2013–2024) of major salivary gland tumours with prominent trabecular/canalicular morphology was performed. Twenty-one parotid tumours met the criteria: 14 benign (66.7%), six carcinomas (28.6%), and one of uncertain behaviour (4.7%). HMGA2 immunohistochemistry (IHC) was performed on all cases. Next-generation sequencing was successfully performed on 18. Seven benign cases had a conventional PA component. In all cases, the tumour cells in these trabecular/canalicular areas demonstrated variable papillary thyroid carcinoma-like nuclear changes, including chromatin clearing, overcrowding, membrane irregularities, and intranuclear pseudoinclusions. Benign tumours were well-demarcated, whereas carcinomas demonstrated either a multinodular pattern of invasion or subtle infiltration. Two carcinomas showed increased cytologic atypia and architectural complexity and one had perineural invasion. By IHC, all were positive for HMGA2. In the trabecular/canalicular areas, there was consistent strong expression of CAM5.2, S-100, and SOX-10 and variable expression of p63 but negative p40. <i>HMGA2</i> alterations were detected in 16 of 18 cases (89%). Follow-up was available on two carcinomas, with one being locally recurrent.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>While most HMGA2-positive salivary gland neoplasms with a prominent trabecular/canalicular growth pattern are benign, they, like traditional PAs, may give rise to carcinomas that can locally recur. These carcinomas can be deceptively bland, subtly infiltrative, or have a multinodular pattern of invasion.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"86 3","pages":"385-396"},"PeriodicalIF":3.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365105","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}
引用次数: 0
Histopathology and determining the viability of infectious agents 组织病理学和确定传染性病原体的生存能力。
IF 3.9 2区 医学
Histopathology Pub Date : 2024-10-02 DOI: 10.1111/his.15314
Sebastian Lucas
{"title":"Histopathology and determining the viability of infectious agents","authors":"Sebastian Lucas","doi":"10.1111/his.15314","DOIUrl":"10.1111/his.15314","url":null,"abstract":"","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"85 6","pages":"853-856"},"PeriodicalIF":3.9,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361457","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}
引用次数: 0
Importance of the criteria used for assessment of lymphovascular space invasion in endometrial carcinoma 子宫内膜癌淋巴管间隙侵犯评估标准的重要性。
IF 3.9 2区 医学
Histopathology Pub Date : 2024-09-26 DOI: 10.1111/his.15329
Jutta Huvila
{"title":"Importance of the criteria used for assessment of lymphovascular space invasion in endometrial carcinoma","authors":"Jutta Huvila","doi":"10.1111/his.15329","DOIUrl":"10.1111/his.15329","url":null,"abstract":"","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"86 2","pages":"308-311"},"PeriodicalIF":3.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345812","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}
引用次数: 0
Inflammatory spindle cell PEComa of the lung with YAP1::TFE3 fusion: a report of two cases and a potential relationship with clear cell stromal tumour 伴有 YAP1::TFE3 融合的肺部炎性纺锤形细胞 PEC 瘤:两例病例报告及与透明细胞间质瘤的潜在关系。
IF 3.9 2区 医学
Histopathology Pub Date : 2024-09-26 DOI: 10.1111/his.15328
Naoki Kojima, Shogo Nishino, Yukiko Sasahara, Tetsuro Taki, Hiroki Imada, Tomohiro Miyoshi, Shun-ichi Watanabe, Genichiro Ishii, Yasushi Yatabe, Taisuke Mori, Akihiko Yoshida
{"title":"Inflammatory spindle cell PEComa of the lung with YAP1::TFE3 fusion: a report of two cases and a potential relationship with clear cell stromal tumour","authors":"Naoki Kojima,&nbsp;Shogo Nishino,&nbsp;Yukiko Sasahara,&nbsp;Tetsuro Taki,&nbsp;Hiroki Imada,&nbsp;Tomohiro Miyoshi,&nbsp;Shun-ichi Watanabe,&nbsp;Genichiro Ishii,&nbsp;Yasushi Yatabe,&nbsp;Taisuke Mori,&nbsp;Akihiko Yoshida","doi":"10.1111/his.15328","DOIUrl":"10.1111/his.15328","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The PEComa family of tumours is defined by spindle/epithelioid cells with myomelanocytic differentiation. A small subset harbours <i>TFE3</i> fusion; however, <i>YAP1::TEE3</i> has not been reported. Clear cell stromal tumour of the lung (CCST-L) is an emerging entity characterized by spindle to epithelioid cells with focal cytoplasmic clearing, inflammatory infiltrates, no myomelanocytic differentiation, and <i>YAP1::TFE3</i> fusion. Herein, we report two cases of lung tumours with myomelanocytic differentiation that showed inflammatory spindle cell histology, focal epithelioid clear cells, as well as <i>YAP1::TFE3</i> fusion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>The patients were both men, aged 61 and 68 years. The tumours in both cases presented as well-circumscribed solid masses involving the lung hilum. After lobectomy, no recurrence was observed at 7 and 32 months. Both tumours shared storiform to short fascicular growth of long spindle cells, with a minor component of epithelioid cells showing clear cytoplasm in the background of substantial intratumoral chronic inflammation and dilated blood vessels. One tumour showed focal melanin deposition. Both tumours were immunohistochemically positive for HMB45, Melan A, and h-caldesmon. Fluorescence <i>in situ</i> hybridization assays indicated the presence of <i>YAP1::TFE3</i> fusions, which was confirmed by RNA sequencing in one case tested, and by immunohistochemical TFE3 expression and loss of YAP1 C-terminus staining.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We present two cases of inflammatory spindle to epithelioid cell tumours of the lungs with myomelanocytic differentiation and <i>YAP1::TFE3</i> fusion. This unique morphology and gene fusion suggest that these tumours may constitute a distinct subset of lung PEComa. Furthermore, morphological and molecular overlap with CCST-L gives rise to a hypothesis of a potential inherent relationship between PEComa and CCST-L.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"86 3","pages":"365-372"},"PeriodicalIF":3.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345813","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}
引用次数: 0
MTAP protein status is highly concordant with CDKN2A fluorescent in situ hybridization and allows stratification of the luminal subtype in muscle-invasive bladder cancer MTAP 蛋白状态与 CDKN2A 荧光原位杂交高度吻合,可对肌肉浸润性膀胱癌的管腔亚型进行分层。
IF 3.9 2区 医学
Histopathology Pub Date : 2024-09-26 DOI: 10.1111/his.15324
Ekaterina Olkhov-Mitsel, Alexander Oberc, Kenneth J Craddock, Christopher Sherman, Elzbieta Slodkowska, Michelle R Downes
{"title":"MTAP protein status is highly concordant with CDKN2A fluorescent in situ hybridization and allows stratification of the luminal subtype in muscle-invasive bladder cancer","authors":"Ekaterina Olkhov-Mitsel,&nbsp;Alexander Oberc,&nbsp;Kenneth J Craddock,&nbsp;Christopher Sherman,&nbsp;Elzbieta Slodkowska,&nbsp;Michelle R Downes","doi":"10.1111/his.15324","DOIUrl":"10.1111/his.15324","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Loss of heterozygosity in chromosome 9p21, common in urothelial carcinoma (UC), typically involves deletion of <i>CDKN2A</i> and <i>MTAP</i> genes. MTAP loss is emerging as a promising therapeutic target and predictive biomarker in UC. This single-centrre retrospective study examined the incidence of <i>CDKN2A</i> deletions and MTAP loss in muscle-invasive bladder cancer (MIBC) and metastatic urothelial carcinoma (mUC), investigating their correlations with clinical, pathological, and genomic features, as well as patient outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Fluorescence <i>in situ</i> hybridization (FISH) and immunohistochemistry (IHC) were performed on 302 MIBC specimens and 63 biopsy-proven metachronous urothelial metastases to assess <i>CDKN2A</i> deletions and MTAP protein expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>CDKN2A</i> homozygous deletion (HD), identified in 30.3% of MIBCs, and MTAP loss, found in 28.8% of MIBCs, were both significantly associated with the luminal-URO subtype, <i>FGFR3</i> mutations, and normal/wildtype p53 IHC (<i>P</i> &lt; 0.05). Loss of MTAP expression was significantly correlated with <i>CDKN2A</i> HD, with 84.0% sensitivity, 92.3% negative predictive value (NPV), 96.3% specificity, and 91.9% positive predictive value (PPV). MTAP expression was 100% concordant between primary tumours and nodal metastases. Patients with MTAP loss had a higher incidence of visceral metastases (50%) compared to bone/soft tissue (35.7%) and nodes (14.3%). Mean progression-free survival and overall survival were shorter for patients with MTAP loss, although not statistically significant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings highlight <i>CDKN2A</i> HD and MTAP loss as prevalent genetic alterations in MIBC and mUC, particularly within the luminal-URO subtype and <i>FGFR3</i>-mutated, p53-normal/wildtype tumours. MTAP IHC can serve as a surrogate marker for 9p21.3 HD, highlighting its clinical relevance and potential as a therapeutic target and predictive biomarker in MIBC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"86 3","pages":"352-364"},"PeriodicalIF":3.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345814","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}
引用次数: 0
Characterisation of Kürsteiner canals of parathyroid: imparting relevance to a one-and-a-quarter-century-old concept 甲状旁腺Kürsteiner管的特征:赋予一个已有四分之一世纪历史的概念以现实意义。
IF 3.9 2区 医学
Histopathology Pub Date : 2024-09-24 DOI: 10.1111/his.15326
Haley Corbin, Linwah Yip, Sally E Carty, Miguel Reyes-Múgica, Raja R Seethala
{"title":"Characterisation of Kürsteiner canals of parathyroid: imparting relevance to a one-and-a-quarter-century-old concept","authors":"Haley Corbin,&nbsp;Linwah Yip,&nbsp;Sally E Carty,&nbsp;Miguel Reyes-Múgica,&nbsp;Raja R Seethala","doi":"10.1111/his.15326","DOIUrl":"10.1111/his.15326","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Kürsteiner canals (KC) were described at least 125 years ago as pharyngeal pouch embryological remnants of parathyroid and thymic development. While considered precursors for a subset of parathyroid cysts and salivary heterotopias (SH), they remain enigmatic. We now define a comprehensive phenotype of KC remnants and investigate their role in a spectrum of parathyroid lesions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>`Sixty-two cystic and 22 non-cystic parathyroid lesions (73 patients) were retrieved from our institutional archive (2011–23) and evaluated for the presence of KC and prevalence of KC phenotype in parathyroid hormone (PTH)-positive and PTH-negative cysts. KC phenotype was defined as: cysts and tubules with surrounding sclerosis; bland, unilayered lining with frequent nuclear indentation of lumina; vesicular chromatin relative to chief cells; attenuated eosinophilic to ‘hyper-cleared’ cytoplasm; and staining pattern PTH-negative, SOX-10-positive, CK7-positive, GATA-3-positive and PAX-9 dim, a subset with oestrogen/progesterone receptor (ER/PR) positivity. Thirty PTH-negative cysts were identified in the neck/mediastinum; 14 of this group also showed SH. Thirty-two PTH-positive cysts included: 11 cystic parathyroid adenomas, 17 hyperplastic parathyroids, and four carcinomas. KC showed two distinct subtypes and were often found near PTH-negative cysts. PTH-negative cysts were associated with inferior parathyroids, SOX-10 positivity, fibrosclerosis, vesicular nuclei indenting cyst lumina and hyper-cleared or attenuated eosinophilic cytoplasm.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>KC are common in parathyroids and show a distinct histological and immunohistochemical profile, with an inferior predilection favouring branchial cleft III distribution. Diagnostically, the high prevalence of this phenotype in PTH-negative cysts and salivary heterotopia supports derivation of non-functioning cysts from KC. Conversely, PTH-positive cysts are more compatible with cystic change within hyperfunctioning glands.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"86 3","pages":"341-351"},"PeriodicalIF":3.9,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307660","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}
引用次数: 0
WHO Classification of Tumours: moving towards the sixth edition 世界卫生组织肿瘤分类:迈向第六版
IF 6.4 2区 医学
Histopathology Pub Date : 2024-09-19 DOI: 10.1111/his.15325
Christine Giesen, Gabrielle Goldman‐Levy, Ian A Cree, Ramon Cierco Jimenez, Alberto Machado, Dilani Lokuhetty
{"title":"WHO Classification of Tumours: moving towards the sixth edition","authors":"Christine Giesen, Gabrielle Goldman‐Levy, Ian A Cree, Ramon Cierco Jimenez, Alberto Machado, Dilani Lokuhetty","doi":"10.1111/his.15325","DOIUrl":"https://doi.org/10.1111/his.15325","url":null,"abstract":"","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"48 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263501","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}
引用次数: 0
JAK2-mutated abnormal megakaryocytic proliferation without thrombocytosis: a diagnostic challenge JAK2突变的巨核细胞异常增殖而无血小板增多:诊断难题
IF 3.9 2区 医学
Histopathology Pub Date : 2024-09-17 DOI: 10.1111/his.15321
Triantafyllia Koletsa, Kassiani Boulogeorgou, Sofia Chatzileontiadou, Amalia Fola, Maria Florou, Maria Papaioannou, Evdoxia Hatjiharissi
{"title":"JAK2-mutated abnormal megakaryocytic proliferation without thrombocytosis: a diagnostic challenge","authors":"Triantafyllia Koletsa,&nbsp;Kassiani Boulogeorgou,&nbsp;Sofia Chatzileontiadou,&nbsp;Amalia Fola,&nbsp;Maria Florou,&nbsp;Maria Papaioannou,&nbsp;Evdoxia Hatjiharissi","doi":"10.1111/his.15321","DOIUrl":"10.1111/his.15321","url":null,"abstract":"","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"85 6","pages":"963-965"},"PeriodicalIF":3.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263504","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}
引用次数: 0
Time requirements for diagnosing mesothelioma in situ 诊断原位间皮瘤的时间要求
IF 3.9 2区 医学
Histopathology Pub Date : 2024-09-16 DOI: 10.1111/his.15322
Andrew Churg
{"title":"Time requirements for diagnosing mesothelioma in situ","authors":"Andrew Churg","doi":"10.1111/his.15322","DOIUrl":"10.1111/his.15322","url":null,"abstract":"","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"85 6","pages":"963"},"PeriodicalIF":3.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263503","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}
引用次数: 0
Cellular congenital mesoblastic nephroma with focal anaplasia, report of a case 细胞性先天中胚层肾瘤伴局灶性无细胞增生,一例报告
IF 3.9 2区 医学
Histopathology Pub Date : 2024-09-13 DOI: 10.1111/his.15286
Ashlie Rubrecht, Nilay Shah, Jennifer H. Aldrink, Kathleen M. Schieffer, Laura E Biederman
{"title":"Cellular congenital mesoblastic nephroma with focal anaplasia, report of a case","authors":"Ashlie Rubrecht,&nbsp;Nilay Shah,&nbsp;Jennifer H. Aldrink,&nbsp;Kathleen M. Schieffer,&nbsp;Laura E Biederman","doi":"10.1111/his.15286","DOIUrl":"10.1111/his.15286","url":null,"abstract":"","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"85 5","pages":"826-829"},"PeriodicalIF":3.9,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263505","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}
引用次数: 0
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