Virchows Archiv最新文献

{"title":"Claudin-18.2 immunohistochemical evaluation in pancreatic cancer specimens: review and recommendations for routine testing and scoring.","authors":"Claudio Luchini, Kristina A Matkowskyj, Takeshi Kuwata, Teri A Longacre, Peter Schirmacher, Manabu Takamatsu, Josef Rüschoff, Matteo Fassan","doi":"10.1007/s00428-025-04222-2","DOIUrl":"10.1007/s00428-025-04222-2","url":null,"abstract":"<p><p>The evaluation of claudin-18 (CLDN18) by immunohistochemistry (IHC) has already entered routine diagnostic activity as a predictive biomarker for patients with gastric and gastroesophageal junction adenocarcinomas. Of note, the CLDN18 gene encodes for 2 isoforms, claudin-18.1 (CLDN18.1) and 18.2 (CLD18.2). Recent evidence has shown CLDN18.2 can be expressed in a relatively high rate of cases of pancreatic ductal adenocarcinoma (PDAC). Based on these findings, preclinical research has been conducted, and clinical trials are currently underway testing anti-CLDN18.2 targeted regimens for patients affected by locally advanced unresectable and metastatic PDAC. Notably, the therapeutic strategies with specific antibodies are directed against CLDN18.2, while the antibody for IHC recognizes both isoforms, CLDN18.1 and CLDN18.2. Since CLDN18.1 is not expressed in the stomach or in the pancreas, IHC for CLDN18 in these sites can be considered specific for the isoform CLD18.2. At this time, no specific practical testing or interpretation guidelines have been proposed in this setting. However, there are several preanalytical and analytical variables and key potential pancreas-specific pitfalls, such as the frequently diffuse and strong CLDN18.2 expression in PDAC precursors, which will likely interfere with adequate CLDN18 staining and interpretation. To overcome these issues and steer the standardization of CLDN18 evaluation within the PDAC framework, this manuscript provides practical guidance on CLDN18 testing and scoring. The adoption of a standardized approach will help align all the efforts, both in research and clinical trial settings to optimally guide the most appropriate patients for anti-CLDN18.2 targeted therapies in PDAC.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"487-499"},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small cell carcinoma with rhabdomyosarcomatous differentiation of the urinary bladder: an integrated clinicopathological and molecular characterization of five cases.","authors":"Ming Zhao, Ping Zhang, Jiayun Xu, Suying Wang, Yinzhou Shi, Lin Ye, Xiaomin Xu, Xiaodong Teng","doi":"10.1007/s00428-025-04174-7","DOIUrl":"10.1007/s00428-025-04174-7","url":null,"abstract":"<p><p>This study delineates the clinicopathological and molecular features of five rare cases of small cell carcinoma (SmCC) of the urinary bladder with rhabdomyosarcomatous differentiation, distinguishing them from alveolar rhabdomyosarcoma (ARMS). All patients were adult males (median age: 67 years) presenting with hematuria and solitary exophytic bladder masses (mean size: 2.9 cm). Histologically, tumors exhibited predominant SmCC morphology with focal anaplastic features. Focal area showing features suggesting rhabdomyosarcomatous differentiation included scattered cells with eosinophilic cytoplasm and eccentric nuclei resembling rhabdoid or immature skeletal muscle (2/5), and pseudoglandular/alveolar growth patterns mimicking ARMS (2/5). All tumors had coexisting urothelial carcinoma components (accounting for 5-15% of tumor volume). Immunohistochemistry revealed epithelial (AE1/AE3, CAM5.2), neuroendocrine (synaptophysin and/or chromogranin A, INSM1, CD56), and myogenic (desmin, MyoD1, myogenin) marker co-expression within SmCC. Molecular profiling demonstrated universal TP53/RB1 inactivation (5/5), recurrent TERT promoter mutations (4/5), and high tumor mutational burden (mean: 27.4 muts/Mb), while fluorescence in situ hybridization demonstrated the absence of ARMS-defining rearrangements involving PAX3, PAX7, and FOXO1 in all cases. Among four patients with available follow-up (5-19 months), one died of disease at 5 months, one developed multiple bone metastases by 5 months, while two showed no tumor recurrence or metastatic progression (both were treated with radical cystectomy followed by adjuvant etoposide-cisplatin chemotherapy). This study provides the first integrated clinicopathological and molecular characterization of SmCC with rhabdomyosarcomatous differentiation in the bladder. The presence of SmCC-specific alterations (TP53/RB1/TERT) and absence of ARMS-defining fusions support classification as a unique SmCC subtype with divergent rhabdomyosarcomatous differentiation.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"523-533"},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angiomatoid fibrous histiocytoma occurring at distal/acral extremity sites: clinicopathological and molecular study of 26 cases highlighting frequent myxoid histology and site-dependent genotypic variation.","authors":"Abbas Agaimy, Jeremy Molligan, Fatimah I Alruwaii, Cristina R Antonescu, Elizabeth G Demicco, Brendan C Dickson, John Gross, Michael Michal, Kyle Perry, Lars Tögel, Robert Stoehr, Nasir Ud Din, Andrew L Folpe","doi":"10.1007/s00428-025-04199-y","DOIUrl":"10.1007/s00428-025-04199-y","url":null,"abstract":"<p><p>Angiomatoid fibrous histiocytoma (AFH) is a rare mesenchymal neoplasm of borderline malignancy (locally recurring, rarely metastasizing), most often involving the limbs, trunk, and head/neck. Rarely, AFH may involve unusual locations. Herein, we characterize the clinicopathologic features of 26 AFH of the distal extremities, including acral sites. The tumors occurred in 19 females and 7 males ranging in age from 12 to 76 years (median, 23 years). Tumors involved the upper (n = 19) and lower (n = 6) distal extremity; one affected an unspecified digital site. Twenty-two cases occurred in acral locations (hands and feet). Subsets of cases showed the following morphologic features: multinodular architecture (26/26), lymphoid cuffs (23/26), prominent stromal myxoid change (11/25), angiomatoid features (9/26), and cytologic pleomorphism (8/26). The average mitotic count was 1/10 HPF; 3 cases showed brisk mitotic activity (> 10 mitoses/10 HPF). Immunohistochemistry revealed variable expression of desmin (16/25), EMA (14/21) and ALK (5/8). Molecular testing revealed EWSR1 rearrangements in 17/18 cases (94%). Among 12 tumors with known fusion partners, the fusions partner was CREB1 in 6 cases (50%), CREM in 4 tumors (33%), ATF1 in one tumor (8%) and PBX3 (8%) in another tumor. Prominent myxoid features were noted in 75% CREM versus 33% of CREB1 versus 0% of ATF1-fused tumors. AFH occurring in distal extremity/acral locations have a predilection for females, upper extremity locations, frequent unusual (solid, non-angiomatoid and myxoid) morphology and higher frequency of CREM over ATF1 fusions. Awareness of the morphologic spectrum of these rare neoplasms is essential for correct classification.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"587-595"},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144761386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acantholytic squamous cell carcinoma of the lung with pseudoglandular features: clinicopathologic study of 14 cases.","authors":"David I Suster, A Craig Mackinnon, Haider A Mejbel, Saul Suster","doi":"10.1007/s00428-025-04149-8","DOIUrl":"10.1007/s00428-025-04149-8","url":null,"abstract":"<p><p>Squamous cell carcinoma of the lung with an acantholytic pseudoglandular pattern of growth is a rare presentation of pulmonary squamous cell carcinoma that can pose difficulties for diagnosis. We have studied 14 lung tumors showing striking pseudoglandular features that led to confusion with adenocarcinoma or adenosquamous carcinoma. The patients were six women, and eight men aged 64-88 years (median = 74.5 years). The tumors measured from 1.4 to 8.5 cm (mean = 4.6 cm); five cases were peripherally located and nine were hilar. The tumors were characterized by squamous cell carcinoma histology with admixed pseudoglandular areas composed of irregular islands of large round to polygonal tumor cells with abundant cytoplasm and closely apposed cell borders that showed central gland-like or tubular spaces lined by atypical cells; in many cases, tumor cells could be seen projecting into the lumen displaying an acantholytic pattern with dyskeratosis. Immunohistochemical stains showed nuclear positivity of the tumor cells for p40 and CK5/6, and negative staining for napsin-A and TTF1. Next-generation sequencing was performed in 12 cases and showed point mutations in 8/12 (66%) of patients, most commonly involving the TP53 gene, and copy number variations in 4/12 (33%) of cases, involving 11 different genes. Seven patients died of tumor between 3 months and 7 years (median = 4.0 years); three patients were alive and free of disease from 4 to 5 years, and 1 patient was alive with tumor at 4 years and then lost to follow-up. Squamous cell carcinoma of lung with acantholytic and pseudoglandular features is an unusual histologic presentation of lung squamous cell carcinoma that can cause diagnostic difficulties; awareness of this presentation and application of immunohistochemical stains is of importance for correct diagnosis.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"619-628"},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary tenosynovial giant cell tumor arising in the nasal cavity with molecular confirmation: the first reported case.","authors":"Wenyi Jing, Lalai Ainiwaer, Xin He","doi":"10.1007/s00428-025-04221-3","DOIUrl":"10.1007/s00428-025-04221-3","url":null,"abstract":"<p><p>Tenosynovial giant cell tumors (TGCT) arising in the head and neck region are rare, and to date, no primary TGCT originating in the nasal cavity has been reported. Here, we report an extremely rare primary TGCT in the nasal cavity in a 28-year-old female. Computed tomography scan revealed a soft tissue density nodule measuring 1.6 × 1.4 cm in the left nasal cavity. Histologically, the tumor is mainly composed of mononuclear cells with round to oval nuclei, mild to moderate atypia. Scattered multinucleated giant cells and nests of foamy histiocytes were also identified. FISH analysis detected CSF1 gene rearrangement. Next-generation sequencing identified a CBL gene missense mutation (c. 1250C > G/ p.P417R). To the best of our knowledge, this is the first example of genetically confirmed TGCT in the nasal cavity. Our study broadens the anatomical spectrum of TGCT and highlights the inclusion of TGCT in the differential diagnosis of nasal cavity lesions.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"713-717"},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation between TP53 mutational status and digital quantification of p53 immunohistochemistry in mantle cell lymphoma.","authors":"Mingfei Yan, Shenon Sethi, Zachary Epstein-Peterson, Anita Kumar, Ahmet Dogan, Pallavi Galera","doi":"10.1007/s00428-025-04227-x","DOIUrl":"10.1007/s00428-025-04227-x","url":null,"abstract":"<p><p>TP53 mutation is a significant negative prognostic factor in mantle cell lymphoma (MCL). While p53 immunohistochemical (IHC) staining is frequently used to evaluate TP53 mutation status, specific cut-offs correlating with mutations remain undefined and largely empirical. This study analyzed tumor specimens from 172 patients with MCL with both p53 IHC and TP53 mutation data, categorizing p53 nuclear expression into four groups (0 + , 1 + , 2 + , and 3 +) using digital image analysis. We established IHC cut-offs with 100% specificity for identifying TP53 non-truncating mutations: 5% for 3 + nuclei, 50% for combined 2 + and 3 + nuclei, and an H-score of 150. The combined 2 + and 3 + nuclei percentage showed the highest sensitivity and negative predictive value. Notably, p53 IHC expression did not significantly correlate with the variant allele frequencies (VAFs) of TP53 missense mutations. However, patients with both TP53 missense and ATM mutations displayed lower p53 expression compared to those with only TP53 missense mutations. TP53 truncating mutations affecting the DNA-binding domain were associated with null p53 staining, while truncating mutations in the tetramerization domain showed weak to moderate staining. Cases with single nucleotide substitutions involving TP53 splice sites showed weak to moderate p53 staining and lacked 3 + nuclei. In cases where multiple types of TP53 mutations coexisted, the clonally dominant mutation influenced the overall p53 expression level. Finally, we observed significantly worse overall survival in patients demonstrating p53 overexpression by using the above mentioned IHC cut-offs. This study provides essential evidence for interpreting p53 IHC staining and may potentially guide rapid risk stratification of patients with MCL, especially in limited resource settings.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"659-670"},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coccoid Helicobacter pylori in patients with obesity: an immunohistochemical study.","authors":"Chen Mayer, Daniel Hillel, Iris Barshack, Michael Schvimer","doi":"10.1007/s00428-025-04042-4","DOIUrl":"10.1007/s00428-025-04042-4","url":null,"abstract":"<p><p>Helicobacter pylori (HP) is a Gram-negative bacterium that infects approximately fifty percent (50%) of individuals worldwide. The coccoid form of HP, a dormant state with altered morphology, has been associated with persistent infections and antibiotic resistance. This study aimed to investigate the prevalence of the coccoid form of HP in patients living with obesity. Sleeve gastrectomy specimens from obese patients and gastric biopsies from non-obese individuals were analyzed. Immunohistochemistry (IHC) staining and histopathological examination were performed to identify and quantify the coccoid forms of HP. Statistical analysis was conducted to compare the results between the two groups. The study included 53 obese patients and 62 non-obese individuals. The percentage of coccoid forms of HP was significantly higher in obese patients compared to non-obese individuals (median 50% vs. 10%, p < 0.001). Type of gastritis was also significantly different between the groups. Obese patients exhibited a higher prevalence of the coccoid form of HP in their gastric mucosa. This finding suggests that the gastric microenvironment in obesity may favor the formation of the coccoid form, potentially impacting the colonization and pathogenicity of HP. The higher prevalence of the coccoid form in obese patients has important clinical implications, as it is more resistant to antibiotics and difficult to eradicate. Alternative treatment strategies may be necessary to effectively manage HP infections in this population. Furthermore, the presence of the coccoid form may increase the risk of HP-associated diseases in obese individuals. Further research is needed to elucidate the underlying mechanisms and explore novel treatment approaches for HP infection in the context of obesity.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"681-686"},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indirect clinical validation for predictive biomarkers in oncology: International Quality Network for Pathology (IQN Path) Position Paper.","authors":"Emina E Torlakovic, Raed Al Dieri, Tony Badrick, Zongming Eric Chen, Carol C Cheung, Zandra Deans, Andrew Dodson, Francesca Fenizia, Hiroshi Kijima, Joerg Maas, Antonio Martinez, Søren Nielsen, Simon Patton, Etienne Rouleau, Peter Schirmacher, Tanuja Shet, Tracy Stockley, Nicola Normanno","doi":"10.1007/s00428-025-04169-4","DOIUrl":"10.1007/s00428-025-04169-4","url":null,"abstract":"<p><p>Validation of biomarker assays is mandatory not only for their applications in clinical trials but also for their subsequent transfer to clinical laboratories in routine clinical care. There are two critical components relevant to their transfer to clinical practice: regulatory oversight and methodology transfer. Both aspects are simplified where companion diagnostic (CDx) assays relevant to a given indication are being implemented in clinical laboratories. However, when laboratory developed tests (LDTs) are being used either because CDx is not available or because LDT is preferred, both aspects need special consideration from regulatory agencies as well as clinical laboratories. The key component that links these two aspects is evidence of validation of the new LDTs. For predictive and prognostic biomarkers in oncology, clinical validation is feasible only in clinical trials. This approach is not available or feasible to clinical laboratories that develop LDTs. While clinical laboratories routinely perform technical/analytical validation, depending on the type of biomarker, this may not be sufficient to provide evidence of the LDT's clinical relevance. Laboratories must perform and document their assessment for the need for indirect clinical validation. When indirect clinical validation is required, it must be performed according to existing guidelines for this purpose. This paper provides expert consensus guidance and recommendations on how to assess for the need for indirect clinical validation and how to perform indirect clinical validation where required. This paper also provides a conceptual framework to regulatory agencies for determining requirements for validation of predictive and prognostic biomarkers in oncology.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"565-572"},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perforin-2 is overexpressed in Kikuchi-Fujimoto disease.","authors":"Kirill A Lyapichev, L Jeffrey Medeiros, Narittee Sukswai, Siok Bian Ng, Salwa S Sheikh, Samir Amr, Noula D Shembade, Joseph D Khoury","doi":"10.1007/s00428-025-04046-0","DOIUrl":"10.1007/s00428-025-04046-0","url":null,"abstract":"<p><p>Kikuchi-Fujimoto disease (KFD) is a self-limited lymphadenopathy characterized by subcortical necrosis and paracortical proliferation of lymphocytes, histiocytes and plasmacytoid dendritic cells with abundant apoptosis. The etiology of KFD remains unknown. Perforin-2 is a highly conserved transmembrane molecule capable of forming pores following intercellular interaction with bacteria and erythrocytes. Perforin-2 is also essential for the activation of type I interferon-induced JAK/STAT signaling and elimination of virus infection. Herein, we hypothesized that perforin-2 or macrophage-expressed gene 1 (MPEG1) protein function is dysregulated in KFD, resulting in an exaggerated immune response, possibly following exposure to an unknown infectious agent. Twelve cases of KFD were the study group. We isolated total RNA from fixed, paraffin-embedded whole tissue sections. We also assessed primary human B-cells and 4 cases of reactive follicular hyperplasia as controls. Perforin-2 mRNA levels were assessed by quantitative real-time PCR (qRT-PCR). We found that perforin-2 mRNA expression was significantly upregulated in 11 of 12 (92%) KFD cases as compared with control samples. These results suggest that expression of perforin-2 is dramatically upregulated in KFD cases. Increased levels of perforin-2 likely explain the abundant apoptosis in KFD. These data also support the hypothesis that upregulation of perforin-2 may be part of the host immune reaction to an unknown infectious agent that is the trigger for KFD.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"535-541"},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"37^th European Congress of Pathology - Abstracts.","authors":"","doi":"10.1007/s00428-025-04179-2","DOIUrl":"10.1007/s00428-025-04179-2","url":null,"abstract":"","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":"1-563"},"PeriodicalIF":3.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}