Clinica Chimica Acta最新文献

{"title":"Proteomics of neuropsychiatric disorders.","authors":"Afeng Liu, Lina Sun, Wenshu Meng","doi":"10.1016/j.cca.2024.120093","DOIUrl":"https://doi.org/10.1016/j.cca.2024.120093","url":null,"abstract":"<p><p>The pathogenesis of neuropsychiatric disorders (NDs) remains largely unclear due to the lack of objective and reliable biomarkers. Although proteomics is a powerful tool for identification of biomarkers, this approach has been largely ignored in the field of NDs. This review examines recent use of mass spectrometry-based proteomics in characterizing a number of differentially expressed proteins associated with NDs in various biomatrices including blood, urine, saliva, tear and cerebrospinal fluid as well as brain tissue. While preliminary, these early studies appear promising but require comprehensive validation in multi-center and large-scale clinical cohorts. We also discuss the challenges and prospects of proteomics as applied to NDs. These findings may provide a foundation for developing proteomic-based diagnostics and advancing precision medicine in NDs.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120093"},"PeriodicalIF":3.2,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834168","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":"Comprehensive analysis of chromosome abnormalities by chromosome conformation based karyotyping (C-MoKa) in patients with conception failure and pregnancy loss.","authors":"Xiao Bao, Yuxia Yang, Wenbin Niu, Yimin Wang, Hao Shi, Yangyun Zou, Yidong Liu, Cheng Wan, Jun Ren, Sijia Lu, Yingpu Sun","doi":"10.1016/j.cca.2024.120089","DOIUrl":"10.1016/j.cca.2024.120089","url":null,"abstract":"<p><strong>Background: </strong>Chromosome abnormalities are a leading cause of conception failure and pregnancy loss. While traditional cytogenetics technologies like karyotyping have been helpful in identifying structural variations (SVs), they face challenges in detecting complex rearrangements and cryptic structures. In this study, we developed a new method called chromosome conformation based karyotyping (C-MoKa) to comprehensively detect different types of chromosomal abnormalities in patients with conception failure and pregnancy loss.</p><p><strong>Methods: </strong>A total of 70 clinical samples exhibiting known results of SVs, mosaic aneuploidies, copy number variations （CNVs） and uniparental disomy (UPD) were included in our cohort and underwent C-MoKa analysis. The results obtained from different techniques, including karyotyping, CNV-seq, and CMA were compared and analyzed.</p><p><strong>Results: </strong>Distinct chromosomal conformation patterns of various variations were observed and analyzed in clinical samples. Our C-MoKa method not only validated all the findings of karyotyping, CNV-seq and CMA, but also provided more detailed results. It demonstrated superior fragment resolution (<500 Kb) and more precise breakpoints (>100 kb). Moreover, C-MoKa showed higher sensitivity in decoding intricate rearrangements in a single test.</p><p><strong>Conclusions: </strong>Our results highlight the potential utility of C-MoKa in precisely unraveling SVs, mosaic aneuploidies, CNVs, and UPD in clinical settings, which can significantly impact further clinical decision-making.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120089"},"PeriodicalIF":3.2,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823594","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":"Targeted and non-targeted proteomics to identify the urinary protein biomarkers for Wilson disease.","authors":"Simin Dong, Xixi Wang, Huiling Zhou, Huan Xu, Liqian Su, Linshen Xie, Yongxin Li","doi":"10.1016/j.cca.2024.120090","DOIUrl":"https://doi.org/10.1016/j.cca.2024.120090","url":null,"abstract":"<p><strong>Background: </strong>Wilson disease (WD) is a genetic disorder of copper metabolism. Early diagnosis of WD is inherently challenging due to the absence of typical symptoms. This study aimed to identify urinary protein biomarkers for WD using targeted and nontargeted mass spectrometry-based approaches.</p><p><strong>Methods: </strong>Exploratory urinary proteomic research on WD patients was initially conducted and revealed some potential biomarkers (alpha-2-macroglobulin, alpha-1-antitrypsin, complement C3, prothrombin, and complement factor B). A multiple reaction monitoring (MRM) assay was subsequently developed and applied to an independent WD cohort for protein candidate validation. Finally, a Random Forest (RF) model constructed with five proteins was evaluated for its diagnostic capacity.</p><p><strong>Results: </strong>The linear range of the MRM assay extended from 0.025 ng/L to 155 ng/L and the limit of quantification (LOQ) ranged from 0.0095 ng/L to 9.2308 ng/L. Alpha-2-macroglobulin, alpha-1-antitrypsin, and complement C3 exhibited significant increases (p < 0.05) in WD patients compared to the controls, whereas prothrombin and complement factor B only showed variations in concentration. The physiology reference intervals (RIs) for alpha-2-macroglobulin, alpha-1-antitrypsin, complement C3, prothrombin, and complement factor B were estimated as 0-12.50, 0-123.08, 0-5.20, 0-16.59, 0-4.85 ng/mol Cr, while the pathology RIs were 0-114.86, 0-600.98, 0-12.62, 0-22.16, and 0-10.83 ng/mol Cr, respectively. The RF model demonstrated an area under the curve (AUC) of 0.99 for the training data and 0.83 for the testing data.</p><p><strong>Conclusions: </strong>Based on the proteomic results, the quantitative method was successfully applied for the validation of protein candidates in WD. Using supervised machine learning, the five-protein panel exhibited excellent accuracy in non-invasive diagnosis of WD.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120090"},"PeriodicalIF":3.2,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821981","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":"A model based on chitinase 3-like protein for expecting liver severity of hepatitis B virus infections in the immune tolerance phase.","authors":"Jia-Lan Wang, Su-Wen Jiang, Ai-Rong Hu, Xiao-Jun Shi, Ai-Wu Zhou, Ken Lin, Ying Fan, Meng-Han Jin, Hao-Jin Zhang","doi":"10.1016/j.cca.2024.120085","DOIUrl":"10.1016/j.cca.2024.120085","url":null,"abstract":"<p><strong>Background: </strong>The question of whether to treat patients with chronic hepatitis B (CHB) during the immune tolerance (IT) period is a matter of ongoing debate, as it is difficult to discern different levels of liver disease severity. We created and assessed a novel diagnostic model for identifying significant liver tissue damage in individuals with CHB in IT phase.</p><p><strong>Methods: </strong>From November 2018 to December 2022, a cross-sectional study of 311 patients with chronic hepatitis B virus infection (HBV DNA > 30 IU/mL) at Ningbo No. 2 Hospital, Ningbo, China, who underwent liver biopsy, including 44 patients in IT phase. Utilizing univariate regression analyses and logistics analysis, and model was developed and validated to predict the severity of hepatic inflammatory and fibrosis in CHB patients and in IT phase.</p><p><strong>Results: </strong>Chitinase 3-like Protein (CHI3L1), albumin (ALB), alanine transaminase (ALT) / aspartate aminotransferase (AST) were identified as independent predictors of liver lesion severity in CHB patients with IT. The three were combined to build the model (named as CAA index), which demonstrated good performance. The CAA index achieved an area under the receiver operating characteristic curve (AUC) of 0.916 (95 % CI, 0.820-1.000) and AUC of validation group was 0.875 (95 % CI, 0.683-1.000).</p><p><strong>Conclusions: </strong>CHI3L1 serves as an independent measure of liver fibrosis and inflammation in CHB. This diagnostic model has some value in assessing the severity of the patient's liver lesion severity and may be a reliable non-invasive diagnostic model helping determine whether treatment is necessary among CHB patients in IT phase.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120085"},"PeriodicalIF":3.2,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817469","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":"Harmonization of anti-nuclear antibody testing (ANA) by indirect immunofluorescence assay: Results from ten years of UK NEQAS external quality assessment.","authors":"Maria Infantino, Teresa Carbone, Dina Patel, Ravishankar Sargur, Carol Stanley, Amina Bhayat-Cammack, Emirena Garrafa, Silvia Pancani, Mariangela Manfredi, Luis E C Andrade, Nicola Bizzaro","doi":"10.1016/j.cca.2024.120088","DOIUrl":"10.1016/j.cca.2024.120088","url":null,"abstract":"<p><p>External quality assurance (EQA) programs play a pivotal role in monitoring laboratory practices, allowing each laboratory to evaluate the consistency of results across different methods as well the ability of individual laboratories to compare and improve over time their own performance. The objective of our study was to analyze the UK NEQAS EQA reports for the \"Antibodies to Nuclear and Related Antigens\" program from 2013 to 2023, to assess the overall level of harmonization of the responses for anti-nuclear antibody (ANA) testing by indirect immunofluorescence (IIF), in terms of both pattern and titer consensus. As a second aim, we analyzed the impact of the introduction in UK NEQAS EQA reports of the International Consensus on ANA Patterns (ICAP) nomenclature and of digital image recognition on the harmonization of the ANA HEp-2 IIF test. The percentage of consensus for positive/negative results was significantly higher (90.9 ± 1.4) in 2023 than in 2013 (64.0 ± 7.8, p < 0.001). Common to all years in the investigated period, consensus on pattern recognition was significantly lower for the homogenous pattern (70.5 ± 16.0) compared to the centromere (84.9 ± 14.9), the speckled (90.3 ± 12.3), and the negative (84.5 ± 18.6, p < 0.001) samples, while it was significantly higher for titers 1:80-1:320 than for titers > 1:320 (p < 0.001). The difference between manual reading and digital reading was not significant (93.8 % vs. 92.4 %; p = 0.078), but it was significant between the pre- and post-use of the ICAP nomenclature (82.6 % vs. 93.8 %; p < 0.001). This study shows that the variability in ANA recognition and reporting is pattern (homogeneous > speckled > centromere) and titer (high titer > low titer) dependent. While we did not find any difference between the use of manual reading compared to digital reading, the adoption of the ICAP nomenclature greatly improved the harmonization of ANA reporting.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120088"},"PeriodicalIF":3.2,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817471","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":"Standardization of hemoglobin A₂ and hemoglobin F: Achievements and perspectives.","authors":"Andrea Mosca, Cristian Arsene, Renata Paleari, Patricia Kaiser, Kees Harteveld, Yvonne Daniel, Chie Amano, Atsushi Murakami, Guy Auclair","doi":"10.1016/j.cca.2024.120087","DOIUrl":"10.1016/j.cca.2024.120087","url":null,"abstract":"<p><p>The establishment of reference systems for the standardization of hemoglobin A₂ (HbA₂) and fetal hemoglobin (HbF), both critical for improving diagnostic accuracy in conditions such as β-thalassemia and sickle cell disease, are described. Efforts were led by the IFCC and other groups to address and reduce the variability in laboratory measurements of these hemoglobins. This document outlines the production of certified reference materials (CRMs) for HbA₂ and the development of a reference measurement procedure using isotope dilution mass spectrometry. Similarly, standardizing HbF is essential for supporting diagnostic and therapeutic strategies, particularly in managing sickle cell disease. HbF levels can predict disease outcomes and guide treatment plans. Significant challenges remain in achieving consistent measurement across laboratories, and the process for standardization for this minor hemoglobin has just begun. We are confident that the implementation of these reference systems will provide improved accuracy and traceability in the future.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120087"},"PeriodicalIF":3.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812222","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":"Artificial intelligence aided serum protein electrophoresis analysis of Finnish patient samples: Retrospective validation.","authors":"Tapio Lahtiharju, Lassi Paavolainen, Janne Suvisaari, Pasi Nokelainen, Emmi Rotgers, Mikko Anttonen, Outi Itkonen","doi":"10.1016/j.cca.2024.120086","DOIUrl":"10.1016/j.cca.2024.120086","url":null,"abstract":"<p><strong>Background and aims: </strong>Serum protein electrophoresis interpretation requires a substantial amount of manual work. In 2020, Chabrun et al. created a machine learning method called SPECTR for the task. We aimed to validate and test the SPECTR method against our results of more precise immunofixation electrophoresis.</p><p><strong>Materials and methods: </strong>We gathered 34 625 patients and their first serum protein electrophoresis sample in Helsinki University Hospital. We trained three neural network models: (1) a fractionation model to fractionate electropherograms; (2) a classification model to classify samples to normal, ambiguous, and abnormal (i.e. containing paraprotein); (3) an integration model to predict concentration and location of paraproteins.</p><p><strong>Results: </strong>The fractionation model demonstrated an error rate of ≤0.33 g/L in 95 % samples. The classification model achieved an area under the curve of 97 % in receiver operating characteristic analysis. The integration model demonstrated a coefficient of determination (R²) of 0.991 and a root-mean-square error of 1.37 g/L in linear regression.</p><p><strong>Conclusion: </strong>The neural network models proved to be suitable for partial automation in serum protein electrophoresis reporting, i.e. classification of normal electropherograms. Furthermore, the models can accurately suggest the location and concentration of paraproteins.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120086"},"PeriodicalIF":3.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812221","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":"MicroRNA biosensors for detection of chronic kidney disease.","authors":"Mohammad Reza Balali, Mohammad Taghizadeh, Mehdi Alizadeh, Yousof Karami, Farzaneh Karimi, Seyyed Hossein Khatami, Mortaza Taheri-Anganeh, Sajad Ehtiati, Ahmad Movahedpour, Reza Mahmoudi, Hassan Ghasemi","doi":"10.1016/j.cca.2024.120081","DOIUrl":"10.1016/j.cca.2024.120081","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) is a prevalent health condition characterized by gradual kidney function loss. Early detection is crucial for the effective management and treatment of CKD. A promising biomarker for various diseases, including chronic kidney disease, is microRNAs (miRNAs), which are becoming increasingly important due to their stability and differential expression in various disease-related states, including CKD. Recent developments in microRNA biosensors have made it possible to detect miRNAs associated with CKD in a sensitive and specific manner. This review article discusses the current state of microRNA biosensors for detecting CKD and highlights their potential applications in clinical settings. Various microRNA biosensors, including electrochemical, optical, and nanomaterial-based sensors, are explored for their ability to detect specific miRNAs linked to CKD progression. The advantages and limitations of these biosensors are evaluated, focusing on factors such as sensitivity, specificity, and ease of use. Overall, microRNA biosensors are promising diagnostic tools for early detection of CKD. However, challenges such as standardizing protocols, validating in large cohorts, and translating to clinical practice remain to be addressed. Future research efforts should aim to overcome these limitations to fully realize the potential of microRNA biosensors in improving the diagnosis and management of CKD.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120081"},"PeriodicalIF":3.2,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799660","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":"VEGF in psoriatic arthritis: Systematic review and meta-analysis.","authors":"Biagio Di Lorenzo, Stefano Zoroddu, Arduino A Mangoni, Panagiotis Paliogiannis, Gian Luca Erre, Rosanna Satta, Ciriaco Carru, Angelo Zinellu","doi":"10.1016/j.cca.2024.120084","DOIUrl":"10.1016/j.cca.2024.120084","url":null,"abstract":"<p><p>Psoriatic arthritis (PsA), a chronic autoimmune disease of unclear aetiology, is associated with dysregulated angiogenesis due to the proliferation, migration, and differentiation of endothelial cells. Vascular endothelial growth factor (VEGF) plays a key role such that PsA patients exhibit skin and joint symptoms, e.g., pain and stiffness, with morphologic alterations in blood vessels. To more fully examine this phenomenon, a systematic review and meta-analysis compliant with the PRISMA guidelines (PROSPERO CRD42024572653) was conducted using subgroup and meta-regression analyses. Secondary analyses on disease activity and response to treatment were also included. In the twelve selected studies, VEGF was significantly higher in PsA vs healthy controls (SMD = 0.544, 95 % CI 0.253-0.835;p < 0.001) with moderate heterogeneity across studies. Subgroup analysis revealed that the SMD in prospectively conducted studies was significantly higher vs those conducted retrospectively (p = 0.005). Furthermore, methotrexate or sulfasalazine treatment did not affect VEGF which remained significantly higher than controls. Moreover, VEGF was lower in those with inactive disease and in those receiving disease modifying agents in pre-post studies. These findings suggest that VEGF is a promising candidate biomarker in PsA and worthy of further prospective studies to investigate its utility in monitoring disease progress and response to treatment.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120084"},"PeriodicalIF":3.2,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799663","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":"DUPAN-2 in pancreatic cancer: Systematic review and meta-analysis.","authors":"Xiaowen Gong, Yuerong Xuan, Chengshuai Pang, Chenyang Dong, Rui Cao, Zhigang Wei, Chaojie Liang","doi":"10.1016/j.cca.2024.120080","DOIUrl":"https://doi.org/10.1016/j.cca.2024.120080","url":null,"abstract":"<p><strong>Objective: </strong>Pancreatic cancer (PC) is a highly aggressive malignancy with poor prognosis and high mortality rate. Identifying reliable biomarkers for the early diagnosis and treatment is urgently needed. This study aims to comprehensively evaluate the diagnostic and prognostic value of DUPAN-2 in PC through a meta-analysis.</p><p><strong>Methods: </strong>We systematically searched PubMed, Embase, and other databases for studies related to DUPAN-2 and its prognostic and diagnostic relevance in PC, covering publications up to August 2024. We used pooled hazard ratios (HRs) to evaluate the prognostic value of DUPAN-2 in PC, the summary receiver operating characteristic (SROC) curve and the area under the curve (AUC) to assess diagnostic performance, while pooled odds ratios (ORs) analyzed associations with clinicopathological features.</p><p><strong>Results: </strong>A total of 22 studies involving 4765 patients were included in this meta-analysis, with 11 studies focusing on diagnostic analysis, 10 on prognostic analysis, and 3 on clinicopathological features. The diagnostic meta-analysis revealed a pooled sensitivity of 0.63 (95 % CI: 0.56-0.69), a pooled specificity of 0.98 (95 % CI: 0.95-0.99), and an AUC of 0.83 (95 % CI: 0.79-0.86). Subgroup analysis indicated that a DUPAN-2 threshold at 150 U/mL achieved the highest diagnostic performance. The prognostic meta-analysis demonstrated that elevated DUPAN-2 levels were associated with poorer OS (HR = 1.70, 95 % CI: 1.36-2.14) and PFS (HR = 1.33, 95 % CI: 1.14-1.56). Additionally, the clinicopathological features meta-analysis showed that elevated DUPAN-2 levels were associated with vascular invasion (OR = 3.48, 95 % CI: 1.26-9.59), while normalized DUPAN-2 levels were associated with higher resectability (OR = 0.57, 95 % CI: 0.36-0.90) and lower N-stage (OR = 0.39, 95 % CI: 0.24-0.63) CONCLUSION: Serum DUPAN-2 demonstrates significant potential as a biomarker for diagnosis and prognosis in patients with PC.</p>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":" ","pages":"120080"},"PeriodicalIF":3.2,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799653","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}