Laboratory Investigation最新文献

{"title":"Liquid Biopsy in Lung Cancer: Nano-Flow Cytometry Detection of Non-Small Cell Lung Cancer in Blood.","authors":"Andong Zhang, Qiqi Gao, Chen Tian, Wentao Chen, Catherine Pan, Ling Wang, Jie Huang, Jing Zhang","doi":"10.1016/j.labinv.2024.102151","DOIUrl":"https://doi.org/10.1016/j.labinv.2024.102151","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) remains a leading cause of global mortality, with current screening and diagnostic methods often lacking in sensitivity and specificity. In our endeavor to develop precise, objective, and easily accessible diagnostic biomarkers for NSCLC, this study aimed to leverage rapidly evolving liquid biopsy techniques in the field of pathology to differentiate NSCLC patients from healthy controls by isolating peripheral blood samples and enriching extracellular vesicles (EVs) containing lung-derived proteins (TTF-1 and SFTPB), along with the cancer-associated protein CD151⁺ EVs. Additionally, for practical applications, we established a nano-flow cytometry assay to detect plasma EVs readily. NSCLC patients demonstrated significantly reduced counts of TTF-1⁺ EVs and CD151⁺ EVs in plasma compared to healthy controls (P<0.0001), while SFTPB⁺ EVs showed no significant difference (P>0.05). Integrated analysis of TTF-1⁺, CD151⁺ and SFTPB⁺ EVs yielded area under the curve (AUC) values of 0.913 and 0.854 in the discovery and validation cohorts, respectively. Thus, while further validation is essential, the newly developed technologies are of great significance for the robust detection of NSCLC biomarkers.</p>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468982","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":"Assessing the Tumor Immune Landscape Across Multiple Spatial Scales to Differentiate Immunotherapy Response in Metastatic Non-Small Cell Lung Cancer","authors":"","doi":"10.1016/j.labinv.2024.102148","DOIUrl":"10.1016/j.labinv.2024.102148","url":null,"abstract":"<div><div>Although immune checkpoint inhibitor-based therapy has shown promising results in non-small cell lung cancer patients with high programmed death-ligand 1 expression, not all patients respond to therapy. The tumor microenvironment (TME) is complex and heterogeneous, making it challenging to understand the key agents and features that influence response to therapies. In this study, we leverage multiplex fluorescent immunohistochemistry to quantitatively assess interactions between tumor and immune cells in an effort to identify patterns occurring at multiple spatial levels of the TME. To do so, we introduce several computational methods novel to a data set of 1,269 multiplex fluorescent immunohistochemistry images from a cohort of 52 patients with metastatic non-small cell lung cancer. With the spatial G-cross function, we quantify the degree of cell interaction at an entire image level, where we see significantly increased activity of cytotoxic T cells and helper T cells with epithelial tumor cells in responders to immune checkpoint inhibitor-based (<em>P</em> = .022 and <em>P &lt; .</em>001, respectively) and decreased activity of T-regulatory cells with epithelial tumor cells compared with nonresponders (<em>P</em> = .010). By leveraging spatial overlap methods, we define tumor subregions (which we call the tumor “periphery,” “edge.” and “center”) and discover more localized immune-immune interactions influencing positive response, including those between cytotoxic T cells and helper T cells with antigen presenting cells in these subregions specifically. Finally, we trained an interpretable deep learning model that identified key cellular regions of interest that most influenced response classification (area under the curve = 0.71 ± 0.02). Assessing spatial interactions within these subregions further revealed new insights that were not significant at the whole image level, particularly the elevated association of antigen presenting cells and T-regulatory cells with one another in responder groups (<em>P</em> = .024). Altogether, we demonstrate that elucidating patterns of cell composition and interplay across multiple levels of spatial analyses can improve our understanding of the TME and better differentiate patient responses to immunotherapy.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400678","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":"Peptidomics and machine-learning-based evaluation of ncRNA-derived micropeptides in breast cancer: Expression patterns and functional/therapeutic insights.","authors":"Alexandre Luiz Korte de Azevedo, Talita Helen Bombardelli Gomig, Michel Batista, Jaqueline Carvalho de Oliveira, Iglenir João Cavalli, Daniela Fiori Gradia, Enilze Maria de Souza Fonseca Ribeiro","doi":"10.1016/j.labinv.2024.102150","DOIUrl":"https://doi.org/10.1016/j.labinv.2024.102150","url":null,"abstract":"<p><p>Breast cancer is a highly heterogeneous disease characterized by different subtypes arising from molecular alterations that give the disease different phenotypes, clinical behaviors, and prognostic. The ncRNA-derived micropeptides (MPs) represent a novel layer of complexity in cancer study once they can be biologically active and can present potential as biomarkers and also in therapeutics. However, few large-scale studies address the expression of these peptides at the peptidomics level or evaluate their functions and potential in peptide-based therapeutics for breast cancer. In this study, we propose deepening the landscape of ncRNA-derived MPs in breast cancer subtypes and advance the comprehension of the relevance of these molecules to the disease. Firstly, we constructed a 16,349 unique putative MP sequence dataset by integrating two previously published lists of predicted ncRNA-derived MPs. We evaluated its expression on high-throughput mass spectrometry data of breast tumor samples from different subtypes. Next, we applied several machine and deep learning tools, such as AntiCP 2.0, MULocDeep, PEPstrMOD, Peptipedia, and PreAIP, to predict its functions, cellular localization, tertiary structure, physicochemical features, and other properties related to therapeutics. We identified 58 peptides expressed on breast tissue, including 27 differentially expressed MPs in tumor compared to non-tumor samples and MPs exhibiting tumor or subtype specificity. These peptides presented physicochemical features compatible with the canonical proteome and were predicted to influence the tumor immune environment and participate in cell communication, metabolism, and signaling processes. Also, some MPs presented potential as anti-cancer, anti-inflammatory, and anti-angiogenic molecules. Our data demonstrate that MPs derived from ncRNAs have expression patterns associated with specific breast cancer subtypes and tumor specificity, thus highlighting their potential as biomarkers for molecular classification. We also reinforce the relevance of MPs as biologically active molecules that play a role in breast tumorigenesis, besides their potential in peptide-based therapeutics.</p>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406582","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":"Role of the Crosstalk B:Neoplastic T Follicular Helper Cells in the Pathobiology of Nodal T Follicular Helper Cell Lymphomas","authors":"","doi":"10.1016/j.labinv.2024.102147","DOIUrl":"10.1016/j.labinv.2024.102147","url":null,"abstract":"<div><div>Angioimmunoblastic T-cell lymphoma (AITL), the most common form of peripheral T-cell lymphoma, originates from follicular helper T (Tfh) cells and is notably resistant to current treatments. The disease progression and maintenance, at least in early stages, are driven by a complex interplay between neoplastic Tfh and clusters of B-cells within the tumor microenvironment, mirroring the functional crosstalk observed inside germinal centers. This interaction is further complicated by recurrent mutations, such as <em>TET2</em> and <em>DNMT3A</em>, which are present in both Tfh cells and B-cells. These findings suggest that the symbiotic relationship between these 2 cell types could represent a therapeutic vulnerability. This review examines the key components and signaling mechanisms involved in the synapses between B-cells and Tfh cells, emphasizing their significant role in the pathobiology of AITL and potential as therapeutic targets.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400679","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":"Enhancing Biomarker Detection in Cancer: A Comparative Analysis of Preanalytical Reverse Transcription Enzymes for Liquid Biopsy Application","authors":"","doi":"10.1016/j.labinv.2024.102142","DOIUrl":"10.1016/j.labinv.2024.102142","url":null,"abstract":"<div><div>Circulating tumor cells and liquid biopsy-based biomarkers might one day play a crucial role in the treatment decision process for patients of several cancer entities. However, clinical studies on liquid biopsy approaches revealed distinct detection rates and thus, different risk scoring for patients. This study delves into the comparison of 2 utilized reverse transcription enzymes, namely, SuperScript IV VILO (VILO) and Sensiscript (SS), aiming to understand their impact on biomarker detection rates. Prostate cancer cell lines were used to assess detection limits, followed by an investigation of biomarker status in clinical liquid biopsy samples of distinct tumor entities. Our findings highlight the superior reverse transcription efficacy of VILO over SS, commonly used in studies employing the AdnaTest platform. The enhanced efficacy of VILO results in a significantly higher number of patients positive for biomarkers. Clinically, the use of a less-sensitive enzyme system may lead to the misclassification of genuinely biomarker-positive patients, potentially altering their prognosis due to inadequate clinical monitoring or inappropriate treatment strategies.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290306","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":"Impact of Keratins 8 and 18 Genetic Variants on the Severity of Alcoholic Liver Disease","authors":"","doi":"10.1016/j.labinv.2024.102133","DOIUrl":"10.1016/j.labinv.2024.102133","url":null,"abstract":"<div><div>Alcohol-related liver disease (ALD) affects ∼30% of heavy drinkers and is characterized by liver steatosis, fibrosis, and steatohepatitis. The aggregation of keratins 8 (KRT8) and 18 (KRT18) plays a key role in the formation of Mallory–Denk bodies, a hallmark of ALD. Circulating levels of KRT18 fragments are elevated during ALD, and several <em>KRT8/18</em> genetic variants have been linked to an increased risk of liver disease. In this study, we explored the relationship between the histologic features of ALD and genetic variants of <em>KRT8/18</em> in 106 severe patients with ALD from the Hôpitaux Universitaires de Genève. We found a significant over-representation of several <em>KRT8</em> (rs2070910, rs137898974, rs1065306) and <em>KRT18</em> (rs17120866, rs1492241) variants located in the noncoding regions of these genes. Increased circulating level of keratins 18 fragments were associated with rs17120866 and alcoholic hepatitis. The combination of several <em>KRT18</em> variants appeared associated with a poorer prognosis. These results highlight the possible role of <em>KRT18</em> variants in ALD.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290307","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":"The Tree Shrew Model of Parkinson Disease: A Cost-Effective Alternative to Nonhuman Primate Models","authors":"","doi":"10.1016/j.labinv.2024.102145","DOIUrl":"10.1016/j.labinv.2024.102145","url":null,"abstract":"<div><div>The surge in demand for experimental monkeys has led to a rapid increase in their costs. Consequently, there is a growing need for a cost-effective model of Parkinson disease (PD) that exhibits all core clinical and pathologic phenotypes. Evolutionarily, tree shrews (<em>Tupaia belangeri</em>) are closer to primates in comparison with rodents and could be an ideal species for modeling PD. To develop a tree shrew PD model, we used the 1-methyl-4-phenylpyridinium (MPP⁺), a metabolite derived from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, to induce lesions in dopaminergic neurons of the unilateral substantia nigra. The induced tree shrew model consistently exhibited and maintained all classic clinical manifestations of PD for a 5-month period. The symptoms included bradykinesia, rest tremor, and postural instability, and ∼50% individuals showed apomorphine-induced rotations, a classic phenotype of unilateral PD models. All these are closely resembled the ones observed in PD monkeys. Meanwhile, this model was also sensitive to L-dopa treatment in a dose-dependent manner, which suggested that the motor deficits are dopamine dependent. Immunostaining showed a significant loss of dopaminergic neurons (∼95%) in the lesioned substantia nigra, which is a crucial PD pathological marker. Moreover, a control group of nigral saline injection did not show any motor deficits and pathological changes. Cytomorphologic analysis revealed that the size of nigral dopaminergic neurons in tree shrews is much bigger than that of rodents and is close to that of macaques. The morphologic similarity may be an important structural basis for the manifestation of the highly similar phenotypes between monkey and tree shrew PD models. Collectively, in this study, we have successfully developed a PD model in a small animal species that faithfully recapitulated the classic clinical symptoms and key pathological indicators of PD monkeys, providing a novel and low-cost avenue for evaluation of PD treatments and underlying mechanisms.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349360","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":"Lymphocyte Function in Tertiary Lymphoid Structures Predicts Hepatocellular Carcinoma Outcome","authors":"","doi":"10.1016/j.labinv.2024.102144","DOIUrl":"10.1016/j.labinv.2024.102144","url":null,"abstract":"<div><div>An increasing number of studies have revealed a correlation between tertiary lymphoid structures (TLSs) and the outcome of hepatocellular carcinoma (HCC). Nevertheless, the associations between the heterogeneity of cellular composition and the overall survival (OS) in HCC remain unexplored. Here, we evaluated the cancer tissues from 150 HCC individuals using multiplex immunofluorescence to determine the presence and characteristics of TLS and to investigate the relationship between intra-TLS immunologic activity, TLS maturation, and intratumoral immune cell infiltration. Prognostic factors influencing the outcome were identified through both univariate and multivariate analyses. Additionally, the levels of cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death 1, programmed death-ligand 1, and lymphocyte activation gene-3 were determined, as well as their relationship with TLS features were determined. TLS was detected in 71 (47.3%) of the 150 HCC cases and was related to higher intratumoral infiltration levels of lymphocytes. Additionally, intra-TLS lymphocyte proliferation correlated with that of intratumoral lymphocytes, and the presence of TLS and a high proportion of mature TLS demonstrated a significant correlation with better prognosis (<em>P</em> = .013 and <em>P</em> = .03, respectively). Among TLS-positive tumors, a high proportion of B cells expressing activation-induced cytidine deaminase and a high proportion of CD8⁺ T cells expressing CD45RO were significantly related to improved OS (<em>P</em> = .01 and <em>P</em> &lt; .001, respectively). Comparatively, a high proportion of CD21⁺CD20⁺ B cells demonstrated a significant correlation with poorer OS (<em>P</em> &lt; .001). A markedly reduced number of CTLA-4⁺ cells in the stromal regions in TLS-negative tumors was observed compared with TLS-positive tumors (<em>P</em> = .01). These findings reveal a correlation between TLS presence and improved OS in HCC patients. However, TLS exhibited significant variation in maturation state, T- and B-cell proliferation, and expression of markers related to B- and T-cell function. Notably, these characteristics were also found to possess prognostic significance, indicating that certain TLS might hinder tumor immunity by inhibiting immune cells, whereas others may foster antigen-driven immune responses, likely influenced by the composition and functional status of intra-TLS lymphocytes.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349358","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":"Spatial Heterogeneity of PD-1/PD-L1 Defined Osteosarcoma Microenvironments at Single-Cell Spatial Resolution","authors":"","doi":"10.1016/j.labinv.2024.102143","DOIUrl":"10.1016/j.labinv.2024.102143","url":null,"abstract":"<div><div>Osteosarcoma, predominantly affecting children and adolescents, is a highly aggressive bone cancer with a 5-year survival rate of 65% to 70%. The spatial dynamics between tumor-associated macrophage (TAM) and other cellular subtypes, including T cells, osteoblasts, and osteoclasts, are critical for understanding the complexities of the osteosarcoma tumor microenvironment (TME) and can provide insights into potential immunotherapeutic strategies. Our study employs a pioneering approach that combines deep learning-based digital image analysis with multiplex fluorescence immunohistochemistry to accurately implement cell detection, segmentation, and fluorescence intensity measurements for the in-depth study of the TME. We introduce a novel algorithm for TAM/osteoclast differentiation, crucial for the accurate characterization of cellular composition. Our findings reveal distinct heterogeneity in cell composition and spatial orchestration between PD-1 (−/+) and PD-L1 (−/+) patients, highlighting the role of T-cell functionality in this context. Furthermore, our analysis demonstrates the efficacy of nivolumab in suppressing tumor growth and enhancing lymphocyte infiltration without altering the M1/M2-TAM ratio. This study provides critical insights into the spatial orchestration of cellular subtypes within the PD-1/PD-L1 defined osteosarcoma TME. By leveraging advanced multiplex fluorescence immunohistochemistry and artificial intelligence, we underscore the critical role of TAMs and T-cell interactions, proposing new therapeutic avenues focusing on TAM repolarization and targeted immunotherapies, thus underscoring the study’s potential impact on improving osteosarcoma treatment.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349359","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":"Involvement of BRD4 in Alcoholic Liver Injury: Autophagy Modulation via Regulation of the SIRT1/Beclin1 Axis","authors":"","doi":"10.1016/j.labinv.2024.102134","DOIUrl":"10.1016/j.labinv.2024.102134","url":null,"abstract":"<div><div>Alcoholic liver disease (ALD) caused by chronic alcohol abuse involves complex processes from steatosis to fibrosis, cirrhosis, and hepatocellular carcinoma, posing a global health issue. Bromodomain protein 4 (BRD4) typically serves as a “reader” modulating the functions of transcription factors involved in various biological processes and disease progression. However, the specific mechanisms underlying alcoholic liver injury remain unclear. In this study, we detected aberrant BRD4 expression in the alcohol-induced ALD mouse model of chronic and binge ethanol feeding developed by the National Institute on Alcohol Abuse and Alcoholism, consistent with the in vitro results in Aml-12 mouse hepatocytes. Blocking and inhibiting BRD4 restored the impaired autophagic flux and lysosomal functions in alcohol-treated Aml-12 cells, whereas BRD4 overexpression reduced the expression levels of autophagy marker and lysosomal genes. Furthermore, mouse <em>BRD4</em> knockdown, mediated by a short hairpin RNA carried by the adeno-associated virus serotype 8, significantly attenuated the alcohol-induced hepatocyte damage, including lipid deposition and inflammatory cell infiltration. Mechanistically, BRD4 overexpression in alcoholic liver injury inhibited the expression of sirtuin (SIRT)1 in Aml-12 cells. Chromatin immunoprecipitation and dual-luciferase reporter assays revealed that BRD4 functions as a transcription factor and suppressor, actively binding to the SIRT1 promoter region and inhibiting its transcription. SIRT1 activated autophagy, which was suppressed in alcoholic liver injury via Beclin1 deacetylation. In conclusion, our study revealed that BRD4 negatively regulated the SIRT1/Beclin1 axis and that its deficiency alleviated alcohol-induced liver injury in mice, thus providing a new strategy for ALD treatment.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290308","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}