Tumor Biology最新文献_第2页

Combined use of CYFRA 21-1 and CA 125 predicts survival of patients with metastatic NSCLC and stable disease in IMpower150. 联合使用 CYFRA 21-1 和 CA 125 预测转移性 NSCLC 患者的生存率和 IMpower150 中疾病的稳定性。

Tumor Biology Pub Date : 2024-01-01 DOI: 10.3233/TUB-230001

Anika Mang, Wei Zou, Vinzent Rolny, Martin Reck, Daniel Cigoianu, Katja Schulze, Stefan Holdenrieder, Mark A Socinski, David S Shames, Birgit Wehnl, Namrata S Patil

{"title":"Combined use of CYFRA 21-1 and CA 125 predicts survival of patients with metastatic NSCLC and stable disease in IMpower150.","authors":"Anika Mang, Wei Zou, Vinzent Rolny, Martin Reck, Daniel Cigoianu, Katja Schulze, Stefan Holdenrieder, Mark A Socinski, David S Shames, Birgit Wehnl, Namrata S Patil","doi":"10.3233/TUB-230001","DOIUrl":"10.3233/TUB-230001","url":null,"abstract":"Background: Patients with non-small cell lung cancer (NSCLC) and stable disease (SD) have an unmet clinical need to help guide early treatment adjustments.Objective: To evaluate the potential of tumor biomarkers to inform on survival outcomes in NSCLC SD patients.Methods: This post hoc analysis included 480 patients from the IMpower150 study with metastatic NSCLC, treated with chemotherapy, atezolizumab and bevacizumab combinations, who had SD at first CT scan (post-treatment initiation). Patients were stratified into high- and low-risk groups (overall survival [OS] and progression-free survival [PFS] outcomes) based on serum tumor biomarker levels.Results: The CYFRA 21-1 and CA 125 biomarker combination predicted OS and PFS in patients with SD. Risk of death was ~4-fold higher for the biomarker-stratified high-risk versus low-risk SD patients (hazard ratio [HR] 3.80; 95% confidence interval [CI] 3.02-4.78; p < 0.0001). OS in patients with the low- and high-risk SD was comparable to that in patients with the CT-defined partial response (PR; HR 1.10; 95% CI 0.898-1.34) and progressive disease (PD) (HR 1.05; 95% CI 0.621-1.77), respectively. The findings were similar with PFS, and consistent across treatment arms.Conclusions: Biomarker testing shows potential for providing prognostic information to help direct treatment in NSCLC patients with SD. Prospective clinical studies are warranted.ClinicalTrials.gov: NCT02366143.","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":"S177-S190"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9946782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lung cancer tumor markers in serous effusions and other body fluids. 浆液性渗出物和其他体液中的肺癌肿瘤标记物。

Tumor Biology Pub Date : 2024-01-01 DOI: 10.3233/TUB-220024

Jaume Trapé, Silvia Bérgamo, Laura González-Garcia, Carolina González-Fernández

引用次数: 0

Prognostic value of tumor markers ProGRP, NSE and CYFRA 21-1 in patients with small cell lung cancer and chemotherapy-induced remission. 肿瘤标志物ProGRP、NSE和CYFRA 21-1对小细胞肺癌癌症和化疗诱导的缓解患者的预后价值。

Tumor Biology Pub Date : 2024-01-01 DOI: 10.3233/TUB-230016

Thomas Muley, Felix J Herth, Claus Peter Heussel, Mark Kriegsmann, Michael Thomas, Michael Meister, Marc A Schneider, Birgit Wehnl, Anika Mang, Stefan Holdenrieder

{"title":"Prognostic value of tumor markers ProGRP, NSE and CYFRA 21-1 in patients with small cell lung cancer and chemotherapy-induced remission.","authors":"Thomas Muley, Felix J Herth, Claus Peter Heussel, Mark Kriegsmann, Michael Thomas, Michael Meister, Marc A Schneider, Birgit Wehnl, Anika Mang, Stefan Holdenrieder","doi":"10.3233/TUB-230016","DOIUrl":"10.3233/TUB-230016","url":null,"abstract":"Background: Despite successful response to first line therapy, patients with small-cell lung cancer (SCLC) often suffer from early relapses and disease progression.Objective: To investigate the relevance of serum tumor markers for estimation of prognosis at several time points during the course of disease.Methods: In a prospective, single-center study, serial assessments of progastrin-releasing peptide (ProGRP), neuron-specific enolase (NSE), cytokeratin-19 fragments (CYFRA 21-1) and carcino-embryogenic antigen (CEA) were performed during and after chemotherapy in 232 SCLC patients, and correlated with therapy response and overall survival (OS).Results: ProGRP, NSE and CYFRA 21-1 levels decreased quickly after the first chemotherapy cycle and correlated well with the radiological response. Either as single markers or in combination they provided valuable prognostic information regarding OS at all timepoints investigated: prior to first-line therapy, after two treatment cycles in patients with successful response to first-line therapy, and prior to the start of second-line therapy. Furthermore, they were useful for continuous monitoring during and after therapy and often indicated progressive disease several months ahead of radiological changes.Conclusions: The results indicate the great potential of ProGRP, NSE and CYFRA 21-1 for estimating prognosis and monitoring of SCLC patients throughout the course of the disease.","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":"S219-S232"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41238983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparing modeling strategies combining changes in multiple serum tumor biomarkers for early prediction of immunotherapy non-response in non-small cell lung cancer. 比较结合多种血清肿瘤生物标记物变化的建模策略，以早期预测非小细胞肺癌免疫疗法无应答情况。

Tumor Biology Pub Date : 2024-01-01 DOI: 10.3233/TUB-220022

Frederik A van Delft, Milou M F Schuurbiers, Mirte Muller, Sjaak A Burgers, Huub H van Rossum, Maarten J IJzerman, Michel M van den Heuvel, Hendrik Koffijberg

{"title":"Comparing modeling strategies combining changes in multiple serum tumor biomarkers for early prediction of immunotherapy non-response in non-small cell lung cancer.","authors":"Frederik A van Delft, Milou M F Schuurbiers, Mirte Muller, Sjaak A Burgers, Huub H van Rossum, Maarten J IJzerman, Michel M van den Heuvel, Hendrik Koffijberg","doi":"10.3233/TUB-220022","DOIUrl":"10.3233/TUB-220022","url":null,"abstract":"Background: Patients treated with immune checkpoint inhibitors (ICI) are at risk of adverse events (AEs) even though not all patients will benefit. Serum tumor markers (STMs) are known to reflect tumor activity and might therefore be useful to predict response, guide treatment decisions and thereby prevent AEs.Objective: This study aims to compare a range of prediction methods to predict non-response using multiple sequentially measured STMs.Methods: Nine prediction models were compared to predict treatment non-response at 6-months (n = 412) using bi-weekly CYFRA, CEA, CA-125, NSE, and SCC measurements determined in the first 6-weeks of therapy. All methods were applied to six different biomarker combinations including two to five STMs. Model performance was assessed based on sensitivity, while model training aimed at 95% specificity to ensure a low false-positive rate.Results: In the validation cohort, boosting provided the highest sensitivity at a fixed specificity across most STM combinations (12.9% -59.4%). Boosting applied to CYFRA and CEA achieved the highest sensitivity on the validation data while maintaining a specificity >95%.Conclusions: Non-response in NSCLC patients treated with ICIs can be predicted with a specificity >95% by combining multiple sequentially measured STMs in a prediction model. Clinical use is subject to further external validation.","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":"S269-S281"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9987013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cervical cancer risk in association with TNF-alpha gene polymorphisms in Bangladeshi women. 孟加拉妇女患宫颈癌的风险与 TNF-α 基因多态性的关系。

Tumor Biology Pub Date : 2024-01-01 DOI: 10.3233/TUB-240002

Zasia Hossain Tishe, Sanjana Shawkat, Meherun Nessa Popy, Sadia Biswas Mumu, Annur Ferdous, Munira Jahan Raisa, Mehedi Hasan, Taposhi Nahid Sultana, Nusrat Islam Chaity, Mohd Nazmul Hasan Apu, Md Shaki Mostaid

{"title":"Cervical cancer risk in association with TNF-alpha gene polymorphisms in Bangladeshi women.","authors":"Zasia Hossain Tishe, Sanjana Shawkat, Meherun Nessa Popy, Sadia Biswas Mumu, Annur Ferdous, Munira Jahan Raisa, Mehedi Hasan, Taposhi Nahid Sultana, Nusrat Islam Chaity, Mohd Nazmul Hasan Apu, Md Shaki Mostaid","doi":"10.3233/TUB-240002","DOIUrl":"10.3233/TUB-240002","url":null,"abstract":"Background: Tumor necrosis factor-alpha (TNF-α) is among the vital pro-inflammatory cytokines that potentially exerts a significant influence on the immune response, hence potentially regulating the advancement of cervical lesions.Objective: Our study objective was to examine the relationship between two single nucleotide polymorphisms (SNPs) (rs1799724 and rs1800629) of TNF-α and the risk of cervical cancer in women from Bangladesh.Methods: We recruited 133 patients with cervical cancer and 126 healthy individuals for this study. Genotyping was performed using real-time PCR SNP genotyping assay. Multivariate logistic regression analysis was used to determine the odds ratio (OR) along with 95% confidence intervals (CI) and p-values.Results: For rs1799724 (C > T) polymorphism, TT mutant homozygous genotype carried 3.26 times increased risk of developing cervical cancer (OR = 3.26, 95% CI = 1.15-9.28, p = 0.027). Polymorphism of rs1800629 (G > A) was also related to an elevated risk of cervical cancer. Individuals with the AG heterozygous genotype (OR = 2.85, 95% CI = 1.20-6.74, p = 0.017) and AA mutant homozygous genotype (OR = 4.55, 95% CI = 1.24-16.60, p = 0.022) also had a higher likelihood of having cervical cancer. Moreover, we found that injectable contraceptives increase the risk of cervical cancer. Individuals who smoked and/or had first-degree relatives with cancer were more likely to carry the risk allele, which increases the likelihood of developing cervical cancer.Conclusion: TNF-α polymorphisms in rs1799724 and rs1800629 increase the susceptibility of developing cervical cancer in women from Bangladesh.","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":"46 1","pages":"13-24"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Blood platelet RNA profiles do not enable for nivolumab response prediction at baseline in patients with non-small cell lung cancer. 在非小细胞肺癌患者基线时，血小板 RNA 图谱无法预测 nivolumab 的反应。

Tumor Biology Pub Date : 2024-01-01 DOI: 10.3233/TUB-220037

Mirte Muller, Myron G Best, Vincent van der Noort, T Jeroen N Hiltermann, Anna-Larissa N Niemeijer, Edward Post, Nik Sol, Sjors G J G In 't Veld, Tineke Nogarede, Lisanne Visser, Robert D Schouten, Daan van den Broek, Karlijn Hummelink, Kim Monkhorst, Adrianus J de Langen, Ed Schuuring, Egbert F Smit, Harry J M Groen, Thomas Wurdinger, Michel M van den Heuvel

{"title":"Blood platelet RNA profiles do not enable for nivolumab response prediction at baseline in patients with non-small cell lung cancer.","authors":"Mirte Muller, Myron G Best, Vincent van der Noort, T Jeroen N Hiltermann, Anna-Larissa N Niemeijer, Edward Post, Nik Sol, Sjors G J G In 't Veld, Tineke Nogarede, Lisanne Visser, Robert D Schouten, Daan van den Broek, Karlijn Hummelink, Kim Monkhorst, Adrianus J de Langen, Ed Schuuring, Egbert F Smit, Harry J M Groen, Thomas Wurdinger, Michel M van den Heuvel","doi":"10.3233/TUB-220037","DOIUrl":"10.3233/TUB-220037","url":null,"abstract":"Background: Anti-PD-(L)1 immunotherapy has emerged as a promising treatment approach for non-small cell lung cancer (NSCLC), though the response rates remain low. Pre-treatment response prediction may improve patient allocation for immunotherapy. Blood platelets act as active immune-like cells, thereby constraining T-cell activity, propagating cancer metastasis, and adjusting their spliced mRNA content.Objective: We investigated whether platelet RNA profiles before start of nivolumab anti-PD1 immunotherapy may predict treatment responses.Methods: We performed RNA-sequencing of platelet RNA samples isolated from stage III-IV NSCLC patients before treatment with nivolumab. Treatment response was scored by the RECIST-criteria. Data were analyzed using a predefined thromboSeq analysis including a particle-swarm-enhanced support vector machine (PSO/SVM) classification algorithm.Results: We collected and processed a 286-samples cohort, separated into a training/evaluation and validation series and subjected those to training of the PSO/SVM-classification algorithm. We observed only low classification accuracy in the 107-samples validation series (area under the curve (AUC) training series: 0.73 (95% -CI: 0.63-0.84, n = 88 samples), AUC evaluation series: 0.64 (95% -CI: 0.51-0.76, n = 91 samples), AUC validation series: 0.58 (95% -CI: 0.45-0.70, n = 107 samples)), employing a five-RNAs biomarker panel.Conclusions: We concluded that platelet RNA may have minimally discriminative capacity for anti-PD1 nivolumab response prediction, with which the current methodology is insufficient for diagnostic application.","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":"S327-S340"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9572307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Serum tumor markers for response prediction and monitoring of advanced lung cancer: A review focusing on immunotherapy and targeted therapies. 用于晚期肺癌反应预测和监测的血清肿瘤标志物：以免疫疗法和靶向疗法为重点的综述。

Tumor Biology Pub Date : 2024-01-01 DOI: 10.3233/TUB-220039

Michel van den Heuvel, Stefan Holdenrieder, Milou Schuurbiers, Daniel Cigoianu, Inga Trulson, Huub van Rossum, David Lang

{"title":"Serum tumor markers for response prediction and monitoring of advanced lung cancer: A review focusing on immunotherapy and targeted therapies.","authors":"Michel van den Heuvel, Stefan Holdenrieder, Milou Schuurbiers, Daniel Cigoianu, Inga Trulson, Huub van Rossum, David Lang","doi":"10.3233/TUB-220039","DOIUrl":"10.3233/TUB-220039","url":null,"abstract":"Background: The value of serum tumor markers (STMs) in the current therapeutic landscape of lung cancer is unclear.Objective: This scoping review gathered evidence of the predictive, prognostic, and monitoring value of STMs for patients with advanced lung cancer receiving immunotherapy (IT) or targeted therapy (TT).Methods: Literature searches were conducted (cut-off: May 2022) using PubMed and Cochrane CENTRAL databases. Medical professionals advised on the search strategies.Results: Study heterogeneity limited the evidence and inferences from the 36 publications reviewed. While increased baseline levels of serum cytokeratin 19 fragment antigen (CYFRA21-1) and carcinoembryonic antigen (CEA) may predict IT response, results for TT were less clear. For monitoring IT-treated patients, STM panels (including CYFRA21-1, CEA, and neuron-specific enolase) may surpass the power of single analyses to predict non-response. CYFRA21-1 measurement could aid in monitoring TT-treated patients, but the value of CEA in this context requires further investigation. Overall, baseline and dynamic changes in individual or combined STM levels have potential utility to predict treatment outcome and for monitoring of patients with advanced lung cancer.Conclusions: In advanced lung cancer, STMs provide additional relevant clinical information by predicting treatment outcome, but further standardization and validation is warranted.","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":"S233-S268"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9895334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Missing prognostic value of soluble PD-1, PD-L1 and PD-L2 in lung cancer patients undergoing chemotherapy - A CEPAC-TDM biomarker substudy. 可溶性 PD-1、PD-L1 和 PD-L2 在接受化疗的肺癌患者中缺失的预后价值--CEPAC-TDM 生物标志物子研究。

Tumor Biology Pub Date : 2024-01-01 DOI: 10.3233/TUB-230015

Kimberly Geiger, Markus Joerger, Max Roessler, Karina Hettwer, Christoph Ritter, Kirsten Simon, Steffen Uhlig, Stefan Holdenrieder

{"title":"Missing prognostic value of soluble PD-1, PD-L1 and PD-L2 in lung cancer patients undergoing chemotherapy - A CEPAC-TDM biomarker substudy.","authors":"Kimberly Geiger, Markus Joerger, Max Roessler, Karina Hettwer, Christoph Ritter, Kirsten Simon, Steffen Uhlig, Stefan Holdenrieder","doi":"10.3233/TUB-230015","DOIUrl":"10.3233/TUB-230015","url":null,"abstract":"Background: Programmed cell death receptors and ligands in cancer tissue samples are established companion diagnostics for immune checkpoint inhibitor (ICI) therapies.Objective: To investigate the relevance of soluble PD-1, PD-L1 and PD-L2 for estimating therapy response and prognosis in non-small cell lung cancer patients (NSCLC) undergoing platin-based combination chemotherapies.Methods: In a biomarker substudy of a prospective, multicentric clinical trial (CEPAC-TDM) on advanced NSCLC patients, soluble PD-1, PD-L1 and PD-L2 were assessed in serial serum samples by highly sensitive enzyme-linked immunosorbent assays and correlated with radiological response after two cycles of chemotherapy and with overall survival (OS).Results: Among 243 NSCLC patients, 185 achieved response (partial remission and stable disease) and 58 non-response (progression). The distribution of PD-1, PD-L1 and PD-L2 at baseline (C1), prior to staging (C3) and the relative changes (C3/C1) greatly overlapped between the patient groups with response and non-response, thus hindering the discrimination between the two groups. None of the PD markers had prognostic value regarding OS.Conclusions: Neither soluble PD-1, PD-L1 nor PD-L2 did provide clinical utility for predicting response to chemotherapy and prognosis. Studies on the relevance of PD markers in ICI therapies are warranted.","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":"S355-S367"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139566718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lung cancer tumor marker analysis: A clinical laboratory perspective. 肺癌肿瘤标记物分析：临床实验室的视角。

Tumor Biology Pub Date : 2024-01-01 DOI: 10.3233/TUB-240005

Huub H van Rossum, Stefan Holdenrieder

引用次数: 0

A pocket companion to cell-free DNA (cfDNA) preanalytics. 无细胞DNA（cfDNA）预分析的袖珍伴侣。

Tumor Biology Pub Date : 2024-01-01 DOI: 10.3233/TUB-230011

Abel J Bronkhorst, Stefan Holdenrieder

{"title":"A pocket companion to cell-free DNA (cfDNA) preanalytics.","authors":"Abel J Bronkhorst, Stefan Holdenrieder","doi":"10.3233/TUB-230011","DOIUrl":"10.3233/TUB-230011","url":null,"abstract":"The cumulative pool of cell-free DNA (cfDNA) molecules within bodily fluids represents a highly dense and multidimensional information repository. This \"biological mirror\" provides real-time insights into the composition, function, and dynamics of the diverse genomes within the body, enabling significant advancements in personalized molecular medicine. However, effective use of this information necessitates meticulous classification of distinct cfDNA subtypes with exceptional precision. While cfDNA molecules originating from different sources exhibit numerous genetic, epigenetic, and physico-chemical variations, they also share common features that complicate analyses. Considerable progress has been achieved in mapping the landscape of cfDNA features, their clinical correlations, and optimizing extraction procedures, analytical approaches, bioinformatics pipelines, and machine learning algorithms. Nevertheless, preanalytical workflows, despite their profound impact on cfDNA measurements, have not progressed at a corresponding pace. In this perspective article, we emphasize the pivotal role of robust preanalytical procedures in the development and clinical integration of cfDNA assays, highlighting persistent obstacles and emerging challenges.","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":"S297-S308"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41238980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0