Laboratory Investigation最新文献

{"title":"Mild Duodenal Mucosal Injury and Increased Type I Interferon Signaling Are Preludes to Celiac Disease","authors":"Changqing Ma ,&nbsp;Adina K. Bard ,&nbsp;Eric Tycksen ,&nbsp;Brian D. Muegge ,&nbsp;Phillip I. Tarr ,&nbsp;Lori R. Holtz ,&nbsp;Ta-Chiang Liu","doi":"10.1016/j.labinv.2025.104170","DOIUrl":"10.1016/j.labinv.2025.104170","url":null,"abstract":"<div><div>Celiac disease (CeD) is an immune-mediated chronic enteropathy caused by gluten exposure in genetically susceptible individuals. The characteristic histologic features of CeD include increased intraepithelial lymphocytes and villous atrophy. Clinically, a subset of individuals with elevated concentrations of serum tissue transglutaminase (TTG) antibodies have intact duodenal villous architecture at initial endoscopy and biopsy but then progress to CeD over time while on gluten-containing foods. We hypothesized that these rare potential CeD cases with progression can allow us to interrogate histologic and molecular signatures to predict those who subsequently develop CeD and to study the final cascade into the overt lesions of CeD. We retrospectively identified 16 children over a 10-year period with elevated serum TTG antibody concentrations but without significant villous atrophy at index duodenal biopsies, in whom subsequent biopsies confirmed CeD while consuming gluten-containing foods. Their clinical and histologic features were compared with age-, race-, and gender-matched controls including active CeD (n = 28) and non-CeD children (negative TTG antibody, normal histology, n = 35). Transcriptomic analysis was performed on a subset of the index biopsies of potential CeD cases with progression and controls. None of the 16 children with potential CeD with progression had a family history of CeD or presented with poor growth or anemia or had commenced a gluten-free diet at the time of index biopsy. The index biopsies of children with potential CeD with progression had significantly greater prevalence of intraepithelial lymphocytes (81% vs 12%, <em>P</em> = .002) and mild villous atrophy (94% vs 22%, <em>P</em> = .006) compared with non-CeD biopsies; none had severe villous atrophy (<em>P</em> = .002). Transcriptomic analysis demonstrated upregulated type I interferon signaling, Janus kinase (JAK)/signal transducer and activator (STAT) pathway of transcription activation and innate and adaptive immunity in duodenum of potential CeD with progression was comparable to non-CeD but preserved signaling in brush border absorption, transporter functions, and epithelial metabolic functions, compared with active CeD. Our results show for the first time that mild mucosal injury in the duodenum of children with potential CeD with progression is accompanied by upregulation of pathways also activated in CeD. Mild mucosal injury and type I interferon signaling may be the initiating cellular and molecular biomarkers in identifying the subset of potential CeD individuals who would progress to CeD while consuming gluten-containing foods.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 7","pages":"Article 104170"},"PeriodicalIF":5.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878765","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}

{"title":"Comparison of Fluorescence In Situ Hybridization, Next-Generation Sequencing, and DNA Methylation Microarray for Copy Number Variation Assessment in Gliomas","authors":"Jiao Wang ,&nbsp;Yang Lan ,&nbsp;Hao-Yue Qi ,&nbsp;Li-Hong Wang ,&nbsp;Sen Wei ,&nbsp;Ye Yuan ,&nbsp;Jia Ge ,&nbsp;Ai-Ling Li ,&nbsp;Ze-Xuan Yan ,&nbsp;Lei Li ,&nbsp;Peng-Yu Ming ,&nbsp;Tian-Ran Hu ,&nbsp;Xiu-Wu Bian ,&nbsp;Xiao-Hong Yao ,&nbsp;Tao Luo","doi":"10.1016/j.labinv.2025.104168","DOIUrl":"10.1016/j.labinv.2025.104168","url":null,"abstract":"<div><div>Gene-level and chromosomal copy number variation (CNV) assessments are critical in the integrated diagnosis of gliomas. Whereas fluorescence in situ hybridization (FISH) has been traditionally employed for CNV detection, emerging technologies such as next-generation sequencing (NGS) and DNA methylation microarray (DMM) are available in clinical practice. Nevertheless, the comparative performance of these 3 assays and the concordance of them remain unclear. A retrospective cohort study comprising 104 patients diagnosed with gliomas was conducted at our hospital. We systematically compared FISH, NGS, and DMM for detecting the following 6 CNV-related diagnostic or prognostic parameters: epidermal growth factor receptor (<em>EGFR</em>), cyclin-dependent kinase inhibitor 2A/B (<em>CDKN2A/B</em>), 1p, 19q, chromosome 7, and chromosome 10. All the 3 methods showed high consistency in <em>EGFR</em> assessment; however, FISH demonstrated relatively low concordance with NGS/DMM in detecting other parameters. In contrast, NGS and DMM exhibited strong concordance in the assessment of all the 6 parameters. Notably, discordant cases were associated with high-grade gliomas (grade 3/4; <em>P</em> &lt; .05) and a high fraction of genome altered (<em>P</em> &lt; .01), indicating high malignancy and genomic instability of discordant cases. This study elucidated the discrepancies and limitations of conventional FISH compared with NGS/DMM in CNV assessments. The discrepancies were associated with high-grade gliomas and genomic instability. We propose a process with recommendations on methods, highlighting the importance of integrated multiplatform assays in accurate clinical diagnosis.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 7","pages":"Article 104168"},"PeriodicalIF":5.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882501","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}

{"title":"APOBEC-Driven Hypermutation in the Lymphocyte-Predominant Group of Triple-Negative Breast Cancer","authors":"Miseon Lee ,&nbsp;Ahwon Lee ,&nbsp;Tae-Kyung Yoo ,&nbsp;Byung Joo Chae ,&nbsp;Sung Gwe Ahn ,&nbsp;Byung-Ock Choi ,&nbsp;Woo-Chan Park ,&nbsp;Sung Hun Kim ,&nbsp;Jieun Lee ,&nbsp;Jun Kang","doi":"10.1016/j.labinv.2025.104165","DOIUrl":"10.1016/j.labinv.2025.104165","url":null,"abstract":"<div><div>This study aimed to evaluate the clinicopathologic and genomic characteristics of triple-negative breast cancer subclassification. Triple-negative breast cancer was classified into the luminal androgen receptor (LAR) subtype and the tumor-infiltrating lymphocytes (TILs) groups of the non-LAR subtype—lymphocyte predominant (LP), lymphocyte intermediate, and lymphocyte depleted—based on androgen receptor immunohistochemistry and TILs. Clinicopathologic and genomic characteristics were evaluated for these triple-negative breast cancer subclasses. The LP group was associated with a histologic type of carcinoma with medullary features, a higher tumor mutation burden, and increased APOBEC activity, indicative of APOBEC-driven hypermutation. The LAR subtype was characterized by a higher prevalence of <em>PIK3CA</em> mutations, lower homologous recombination deficiency scores, and associations with histologic types of invasive lobular carcinoma, and carcinoma with apocrine differentiation. This study demonstrated the distinct clinicopathologic and genomic characteristics of triple-negative breast cancer subclassifications. APOBEC activity–related hypermutation is a defining characteristic of the LP group.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 7","pages":"Article 104165"},"PeriodicalIF":5.1,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811568","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}

{"title":"Hidden in the Absence: Clinicopathologic Insights on Kidney Diseases Associated With Selective IgA Deficiency","authors":"Bangchen Wang ,&nbsp;Harpreet Singh ,&nbsp;Matthew Ellis ,&nbsp;Laura Barisoni ,&nbsp;David N. Howell","doi":"10.1016/j.labinv.2025.104163","DOIUrl":"10.1016/j.labinv.2025.104163","url":null,"abstract":"<div><div>Selective IgA deficiency (sIgAD) is the most common type of primary immunodeficiency. The diagnosis of sIgAD has occasionally been suggested when a complete absence of background IgA immunofluorescent staining on renal biopsies was observed, but such findings have been described in only 2 patients to date. In this study, the clinical, demographic, and renal biopsy findings of 15 patients with suspected sIgAD, based on a total lack of immunofluorescence for IgA, were collected. In our cohort, most patients presented with acute kidney injury, with or without proteinuria, and had clinical histories consistent with sIgAD, including recurrent infections, autoimmune diseases, allergic disorders, and cancer. However, only 1 patient had a known history of sIgAD. Immunoglobulin testing was available in 10 of 15 patients, 9 of whom showed findings consistent with a diagnosis of sIgAD. Renal biopsies in most patients revealed immune-related glomerular diseases, with lupus nephritis being the most common diagnosis. Recognizing the total absence of IgA staining indicative of sIgAD is important because it can be associated with recurrent infections, autoimmune diseases, allergic disorders, anaphylactic transfusion reactions, and, rarely, malignancies.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 7","pages":"Article 104163"},"PeriodicalIF":5.1,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811702","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}

{"title":"Cover","authors":"","doi":"10.1016/S0023-6837(25)00042-X","DOIUrl":"10.1016/S0023-6837(25)00042-X","url":null,"abstract":"","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 4","pages":"Article 104132"},"PeriodicalIF":5.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829954","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}

{"title":"Neoadjuvant Therapy–Associated CDX2 Expression and Its Prognostic Implication in Esophageal Adenocarcinoma","authors":"Heong Ahn ,&nbsp;Madhurya Ramineni ,&nbsp;Hangchuan Shi ,&nbsp;Rena X. Li ,&nbsp;Moises Velez ,&nbsp;Yansheng Hao","doi":"10.1016/j.labinv.2025.104135","DOIUrl":"10.1016/j.labinv.2025.104135","url":null,"abstract":"<div><div>Neoadjuvant chemoradiotherapy followed by surgery is the standard care for locally advanced esophageal adenocarcinoma. However, reliable postoperative prognostic biomarkers are still needed to stratify patients with different clinical outcomes. This study aimed to investigate postneoadjuvant expression changes of CDX2 and its association with histopathological features, biomarkers for targeted therapy, distant metastasis, and survival status. A total of 62 esophagogastrectomy specimens from one institution were evaluated. A tissue microarray was constructed, and IHC staining was performed. CDX2 expression was found in 27 (43.5%) cases with well-to-poor differentiation. Compared with preoperative biopsies, 68.8% of cases demonstrated induced or enhanced CDX2 expression. There were no significant differences in age, tumor location, histologic grade, lymph node metastasis, tumor stage, and treatment response between CDX2-positive and CDX2-negative groups. Neuroendocrine and Paneth cell differentiation induced by neoadjuvant therapy were more commonly seen in CDX2-positive cases. CDX2 expression was associated with higher multidrug resistance-1 and HER-2 expression. Patients with CDX2-positive diseases showed a higher risk of distant metastasis and a worse prognosis than those with CDX2-negative diseases.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 6","pages":"Article 104135"},"PeriodicalIF":5.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730730","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}

{"title":"Systematic Analysis of Factors Affecting Human Epidermal Growth Factor Receptor 2 Interpretation Consistency: Staining Protocols, Artificial Intelligence–Based Image Standardization, and Classification Criteria","authors":"Chen Jiang ,&nbsp;Mei Li ,&nbsp;Chengyou Zheng ,&nbsp;Shumei Yan ,&nbsp;Lingzhi Kong ,&nbsp;Yu Wu ,&nbsp;Jinhui Zhang ,&nbsp;Xue Chao ,&nbsp;Xi Cai ,&nbsp;Wentai Feng ,&nbsp;Jiehua He ,&nbsp;Rongzhen Luo ,&nbsp;Shuoyu Xu ,&nbsp;Yuanzhong Yang ,&nbsp;Peng Sun","doi":"10.1016/j.labinv.2025.104134","DOIUrl":"10.1016/j.labinv.2025.104134","url":null,"abstract":"<div><div>The efficacy of human epidermal growth factor receptor 2 (HER2)–targeting antibody-drug conjugates has underscored the critical need for precise HER2 diagnostics in breast cancer treatment. Despite the clinical importance, variability in immunohistochemical (IHC) staining protocols and interobserver inconsistencies challenge the reliability of HER2 status assessment, which is critical for guiding patient treatment strategies. To investigate the factors affecting HER2 interpretation consistency, tissue microarrays from 1063 breast carcinoma cases underwent 3 distinct IHC protocols, and a novel artificial intelligence (AI) model was developed to standardize HER2-stained images. A total of 5 sets of tissue microarrays (Nordi QC, protocol 1, protocol 2, protocol 1 AI, and protocol 2 AI) were independently reviewed by 8 pathologists. The Fleiss Kappa value and overall agreement rate measured interobserver agreement, with logistic regression analyzing the impact of variables on diagnostic accuracy. Our results showed that the Nordi QC protocol had the highest interobserver agreement (Kappa 0.754). AI-based image normalization notably enhanced consistency, particularly for HER2 low cases, aligning scores toward the Nordi QC standard. Logistic regression analysis indicated that both staining protocol and AI-based image standardization significantly influenced diagnostic accuracy (<em>P</em> &lt; .001). The American Society of Clinical Oncology/College of American Pathologists 2018 binary criteria demonstrated the highest HER2 interobserver consistency (Kappa &gt; 0.95). Compared with the American Society of Clinical Oncology/College of American Pathologists 2023 criteria, the newly proposed null, ultra-low/low, positive criteria, merging HER2 low and ultra-low categories, demonstrated improved reliability and agreement, especially in distinguishing the challenging HER2–ultra-low cases, which showed an exceedingly low interobserver agreement (Kappa &lt; 0.20) across all protocols. Overall, variability in IHC staining protocols and HER2 classification criteria significantly affect the diagnostic consistency among pathologists. The integration of an AI model for image standardization and the adoption of the null, ultra-low/low, positive criteria may refine diagnostic precision and bolster clinical decision-making in breast cancer treatment.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 6","pages":"Article 104134"},"PeriodicalIF":5.1,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710491","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}

{"title":"Monoclonal Antibodies From Children With Acute Kawasaki Disease Identify a Common Antigenic Target in Fatal Cases Over 5 Decades","authors":"Anne H. Rowley ,&nbsp;Robert Byrd ,&nbsp;David Arrollo ,&nbsp;Amornrat O’Brien ,&nbsp;Stanford Shulman ,&nbsp;Masaru Terai ,&nbsp;Kwang-Youn Kim ,&nbsp;Kassandra Mercado ,&nbsp;Kristine Wylie ,&nbsp;Robert Fialkowski ,&nbsp;Susan C. Baker","doi":"10.1016/j.labinv.2025.104131","DOIUrl":"10.1016/j.labinv.2025.104131","url":null,"abstract":"<div><div>Kawasaki disease (KD) is a unique febrile illness of young children that can result in coronary artery aneurysms, myocardial infarction, aneurysm rupture, and sudden death. The epidemiologic features, including the young age group affected, the rarity of recurrence, and the presence of epidemics and outbreaks, point to a single infectious causative agent. The recent decrease in KD cases worldwide during pandemic mitigation supports transmission of the agent via a respiratory route. However, substantial research over decades has shown that KD etiology cannot be linked to any currently known infectious agent. We previously identified the presence of intracytoplasmic inclusion (ICI) bodies in the bronchial epithelium in children with fatal KD and a convergent plasmablast-derived antibody response to a specific protein epitope, supporting 1 predominant respiratory causative agent. Here, we report immunohistochemistry and epitope binding using an expanded pool of KD monoclonal antibodies prepared from single peripheral blood plasmablasts from 12 children with acute KD. We identified 1 or more monoclonal antibodies from each of the 12 patients that recognized ICI bodies in KD bronchial epithelium. Using a representative monoclonal antibody, ICI bodies were detected in 20 of 20 children with fatal KD across 5 decades, 10 from the United States and 10 from Japan, and were absent in 19 of 20 infant controls (<em>P</em> &lt; .001). We also found that all 12 children with acute KD generated plasmablast(s) recognizing the previously reported peptide antigen. Taken together, these results point to 1 predominant causative agent of KD across many decades and geographic areas and should direct future KD research studies.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 6","pages":"Article 104131"},"PeriodicalIF":5.1,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692689","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}

{"title":"Erratum to “Virtual Tissue Microarrays for Validating Digital Biomarker Analysis in Colorectal Carcinoma” (Lab Invest 105(2025) 104098)","authors":"Margarita Melnikova Jørgensen ,&nbsp;Stephen Jacques Hamilton-Dutoit ,&nbsp;Jesper Bertram Bramsen ,&nbsp;Claus Lindbjerg Andersen ,&nbsp;Ida Elisabeth Holm","doi":"10.1016/j.labinv.2025.104122","DOIUrl":"10.1016/j.labinv.2025.104122","url":null,"abstract":"","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 5","pages":"Article 104122"},"PeriodicalIF":5.1,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143685405","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":"Spatial Correlation of the Extracellular Matrix to Immune Cell Phenotypes in the Tumor Boundary of Clear Cell Renal Cell Carcinoma Revealed by Cyclic Immunohistochemistry","authors":"Grigor Andreev ,&nbsp;Tino Vollmer ,&nbsp;Max Zirngibl ,&nbsp;Martin Werner ,&nbsp;Markus Grabbert ,&nbsp;Oliver Schilling ,&nbsp;Manuel Rogg ,&nbsp;Christoph Schell","doi":"10.1016/j.labinv.2025.104130","DOIUrl":"10.1016/j.labinv.2025.104130","url":null,"abstract":"<div><div>The significance of the tumor microenvironment (TME) in predicting immunotherapy efficacy is increasingly acknowledged. However, the complexity of the TME necessitates novel technological approaches for the precise characterization of individual cell types, functional phenotypes, and heterocellular spatial interactions. This study utilizes a streamlined multiplex cyclic immunohistochemistry (cycIHC) protocol for detailed TME annotation. Unlike proprietary methods, cycIHC relies on iterative cycles of conventional immunohistochemistry, using off-the-shelf antibodies and reagents, followed by digitalization, chromogen removal, and antibody stripping. The method was combined with open-source tools for the coregistration of individual staining cycles. Using clear cell renal cell carcinoma (ccRCC) as a model, the protocol was applied for granular annotation of cellular and acellular structures in the tumor boundary zone. Our results demonstrate that the tumor periphery, particularly the pseudocapsule of ccRCC, is homogeneously organized across the 3D scale, yet exhibits distinct cellular distribution gradients of T and B cells. These patterns correspond to deposited extracellular matrix proteins, especially collagen types I and VI. Our findings indicate an instructive impact of extracellular matrix proteins on defining the spatial organization of immune cells in the TME of ccRCC. The developed cycIHC method facilitates detailed characterization of the TME and may enhance the understanding of tumor-immune cell interactions.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 6","pages":"Article 104130"},"PeriodicalIF":5.1,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692690","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}