Current gene therapy最新文献

{"title":"Novel Perspective of Regulating P53/Bcl2/Caspase-3 via In vitro Targeted AFP Gene Knocks Out in HepG2 Cells Using CRISPR/Cas9 Editing Tool.","authors":"Fatma Khorshed, Amina M Medhat, Germine M Hamdy, Ehab El-Dabaa, Hanaa Hammad, Heba A H Abd Elhameed, Mohamed Saber","doi":"10.2174/0115665232366303250529164610","DOIUrl":"https://doi.org/10.2174/0115665232366303250529164610","url":null,"abstract":"<p><strong>Introduction: </strong>Hepatocellular carcinoma (HCC) is a major health burden worldwide, with a persistent need for molecular target drugs. Alpha-fetoprotein (AFP) is a major concern during HCC, as it has an incompletely solved action. CRISPR/Cas9 is a gene editing tool that aids in cancer treatment research; thus, this study evaluated the effect of in vitro knockout of AFP on HCC using CRISPR/Cas9 technique.</p><p><strong>Methods: </strong>Two sgRNAs targeting specific sites in AFP exon 2 were separately cloned to the mammalian expression vector pSpCas9 (BB)-2a-GFP (PX458). HepG2 cells were transfected with CRISPR constructs I and II, and a pool of the two constructs (M) for 6 -, 24- and 39 hours using liopfectamine3000. AFP editing was evaluated regarding genomic DNA sequence, RNA, and protein expression levels. In addition, the effect of AFP knocking out on HepG2 viability, and apoptotic genes mRNA and protein expression levels were evaluated using crystal violet assay, real-time PCR, and western blot analysis respectively.</p><p><strong>Results: </strong>The results revealed efficient delivery of the AFP/CRISPR constructs to HepG2 cells. Insertion and deletion mutations introduced to the AFP genomic sequence were analyzed using TIDE software analysis and the Expasy translation tool. The viability of the HepG2 cells was reduced 39 hours post-transfection with significant modulation in the expression of the apoptotic markers P53, BAX, Bcl2, and caspase-3.</p><p><strong>Conclusion: </strong>This study succeeded in developing AFP/CRISPR constructs that could disrupt the AFP genomic sequence, reduce its expression, and restore the activity of cell-specific apoptotic factors, demonstrating the potential inhibitory effect of AFP downregulation on HCC progression.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Extrachromosomal DNA (ecDNA) in Cancer: A New Era of CHK1 Inhibition and Personalized Treatments.","authors":"Komal, Lovekesh Singh, Subramanyam Sarma Ganti","doi":"10.2174/0115665232390083250526072441","DOIUrl":"https://doi.org/10.2174/0115665232390083250526072441","url":null,"abstract":"","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-Generation Nucleic Acid Delivery: A Review of Nanobiosystem Design and Applications.","authors":"Ashish Kumar Parashar, Anu Hardenia, Sunil Kumar Dwivedi, Gaurav Kant Saraogi, Shiv Hardenia","doi":"10.2174/0115665232367377250519114910","DOIUrl":"https://doi.org/10.2174/0115665232367377250519114910","url":null,"abstract":"<p><p>The increasing approval of nucleic acid therapeutics has led to a significant advancement in medicines, demonstrating their potential to revolutionize the prevention and treatment of numerous diseases. However, challenges like nuclease degradation and difficult cellular delivery hinder their use as therapeutic agents. The rising demand for precise gene therapy delivery has positioned nanobiosystems as a groundbreaking solution, with their customizable properties enabling targeted and efficient delivery. Nucleic Acid therapeutics, encompassing antisense DNA, mRNA, small interfering RNA (siRNA), and microRNA (miRNA), have been rigorously investigated for their capacity to modulate gene expression. Notably, integrating these gene therapies with nanoscale delivery platforms has significantly broadened their scope, facilitating sophisticated advancements in bioanalysis, gene silencing, protein replacement therapies, and the development of vaccines. This review provides a thorough review of recent advancements in nanobiosystems for therapeutic nucleic acid delivery. We explore the unique characteristics of various nanobiosystems, including gene therapy-based delivery, nanoparticles, stimuli-responsive systems, smart nanocarriers, and extracellular vesicle-based delivery. We offer a detailed overview of their applications in nucleic acid delivery. Furthermore, we address biological barriers and strategies for the therapeutic delivery of nucleic acids. Ultimately, this review provides critical insights into the strategic development of nextgeneration delivery vectors for nucleic acid therapeutics.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating the Predominant Role of AEBP1 in Different Types of Cancers with a Focus on Glioblastoma Progression - A Review.","authors":"Rangaraj Kaviyaprabha, Sridhar Muthusami, Thandaserry Vasudevan Miji, Palanisamy Arulselvan, Muruganantham Bharathi","doi":"10.2174/0115665232365878250503091118","DOIUrl":"https://doi.org/10.2174/0115665232365878250503091118","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Glioblastoma multiforme (GBM) is a highly deleterious lesion with an increased recurrence rate even after radiotherapy and chemotherapy. In this context, additional biomarkers are needed to curb chemoresistance. Computational approaches help us process the RNA-seq and identify the Differentially Expressed Genes (DEGs) in tumors and adjacent normal regions to identify the diagnostic and therapeutic biomarkers.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and materials: &lt;/strong&gt;In this study, we extensively reviewed the role of AEBP1 in different types of cancer, highlighting its significance as a novel target to prevent collagen deposition. Specifically, the underlying mechanisms of AEBP1 in Glioblastoma were analyzed extensively using computational approaches that include Gene Expression Omnibus (GEO), GEPIA to obtain the TCGA-GBM dataset, and Glioma-BioDP to identify the survival rate in the context of AEBP1 expression associated with patients' age. Meanwhile, Tumor Immune Single-cell Hub 2 was implemented to identify the expression of AEBP1 in immunologically lineaged, cancerous, and stromal cells. In addition to that, the miRNA regulation associated with the AEBP1 expression was predicted by implementing NetworkAnalyst, TarBase v8.0, and CancerMIRNome. We identified the DEGs by examining the GSE121723, GSE184643, and GSE14824 datasets with P-values ≤ 0.05 as statistically significant. Furthermore, we predicted and analyzed the highly expressed genes and identified the survival rate, which significantly stated that the overexpression of AEBP1 was associated with decreased survival rates in GBM patients. The Protein-Protein Interaction network was constructed to identify the correlated gene expression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results and discussion: &lt;/strong&gt;We identified 3695, 37001, and 8855 significantly differentially expressed genes (DEGs). The DEGs were filtered by applying a log2 fold-change cut-off of ≥2.0. Finally, 139 common genes were mapped with the identified DEGs (1338 genes) and SDEs (500 genes) estimated from the TCGA-GBM dataset. The analysis revealed that 155 genes are commonly upregulated, and survival analyses were performed that described the AEBP1 significantly reduced the GBM patients' survival rate among other genes. The constructed PPI network and correlated expression analysis associated with the AEBP1 expression revealed that COL6A2 and THBS2 might play a significant role in the GBM stage advancements by depositing collagens in the matrix environment. Also, the miRNA analysis revealed that the hsa-miR-128-3p and hsa-miR-512-3p could be targeted as a miRNA marker gene to prevent the GBM progression associated with the AEBP1 expression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;AEBP1 is a multi-cancer drug target, underscoring its diagnostic and prognostic value in different types of cancer preventive medicine. It influences tumor growth, metastasis, and immune evasion in cancers like adrenocortical, oral, breast, bladder, ga","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Gene Therapy for X-Linked Myotubular Myopathy: Current Progress and Future Challenges.","authors":"Md Sadique Hussain, Gyas Khan, Gaurav Gupta","doi":"10.2174/0115665232388661250430062849","DOIUrl":"https://doi.org/10.2174/0115665232388661250430062849","url":null,"abstract":"","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and Validation of Amino Acid Metabolism-Related Biomarkers and Investigation of their Potential Mechanisms in Lung Adenocarcinoma.","authors":"Xu Zhu, Ying Zhang, Peiying Pan, Xinlei Liu, Jian Zhang, Xiaojun Du, Tao Wang, Yin Teng, Chao Fan, Jianglun Li, Jieheng Wu, Zhu Zeng, Siyuan Yang","doi":"10.2174/0115665232364091250203090710","DOIUrl":"https://doi.org/10.2174/0115665232364091250203090710","url":null,"abstract":"<p><strong>Background: </strong>In lung adenocarcinoma (LUAD), the metabolism of amino acids (AAs) plays a crucial role in the growth, infiltration, and metastasis of tumor cells. Nevertheless, the potential of AA metabolism-associated genes (AAMRGs) to serve as prognostic indicators in LUAD remains ambiguous. Thus, this study sought to evaluate the prognostic value of AAMRGs in LUAD patients.</p><p><strong>Methods: </strong>Herein, we extracted LUAD transcriptomic information from two key repositories, namely The Cancer Genome Atlas Program (TCGA) and Gene Expression Omnibus. The non-negative matrix factorization (NMF) clustering technique was used to categorize the LUAD cases based on their AAM profiles before assessing the survival rates and composition of immune cells. Using limma software, shared dysregulated transcripts were identified across subgroups before functional annotation via DAVID, which comprised exploration of gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathway. The prognostic framework was developed using five prognostic indicators through TCGA-derived LUAD specimens. We performed the analysis using singlevariable Cox, least absolute shrinkage and selection operator regression, and multi-factorial Cox regression. Molecular pathways between cohorts were compared with gene set enrichment analysis (GSEA). Real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical (IHC) analysis were utilized to validate the key genetic components of the model.</p><p><strong>Results: </strong>NMF clustering analysis was performed to categorize 497 LUAD patients into three distinct subgroups with obvious variations in the survival rates. The subtypes exhibited substantial disparities in immune cell populations, particularly in monocytes and mast cells. Analysis of 176 shared differentially expressed genes (DEGs) revealed enrichment in T lymphocyte stimulation, immunological reactions, and extra immune-related processes within the subgroups. The prognostic framework was constructed using biomarkers, such as ERO1LB, HPGDS, LOXL2, TMPRSS11E, and SLC34A2. Moreover, GSEA demonstrated a correlation between elevated risk and cell cycle processes, but lower risk was linked with arachidonic acid metabolic pathways. Analysis of 1128 DEGs revealed enrichment in various physiological processes, including cellular division, p53 signaling cascades, immunological responses, and additional pathways upon the comparison of high and low-risk cohorts. The RT-qPCR analysis confirmed elevated expression levels of ERO1LB and TMPRSS11E in LUAD specimens. Consistent with RT-qPCR analysis, the IHC results affirmed that the expression levels of ERO1LB and TMPRSS11E were increased in LUAD specimens.</p><p><strong>Conclusion: </strong>The five identified AAMRGs in LUAD were validated and appropriately utilized to construct a risk assessment model that could potentially act as prognostic biomarkers for LUAD patients.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaged Capillary Isoelectric Focusing (icIEF) Platform for Characterization of Charge Variants of Adeno-Associated Virus (AAV) Capsids and Impact on Their Transduction Efficiency.","authors":"Brandon Hoyle, Dhimiter Bello, Jonathan Hill, Soumita Das, Jonghan Kim","doi":"10.2174/0115665232369708250327081305","DOIUrl":"https://doi.org/10.2174/0115665232369708250327081305","url":null,"abstract":"<p><strong>Objective: </strong>Adeno-Associated Virus (AAV) vectors are comprised of a capsid protein encapsulating a Deoxyribonucleic Acid (DNA) transgene that has been used in the gene therapy field showing potential to treat a range of genetic diseases. Methods in the field of gene therapy should be optimized or enhanced to deepen understanding of AAVs, specifically around charge heterogeneity of capsid species.</p><p><strong>Methods: </strong>In this study, a versatile approach was presented for investigating the charge heterogeneity of Adeno-Associated Virus (AAV) capsid proteins of a variety of serotypes. This method employs Imaged Capillary Isoelectric Focusing (icIEF) coupled with native fluorescence imaging detection and has undergone exhaustive validation.</p><p><strong>Results: </strong>Demonstrating its platform nature, this method analyzed seven different AAV serotypes from multiple manufacturing platforms. The distinctive profiles generated for each AAV serotype serve as valuable indicators for both identity confirmation and stability assessment. It was shown that thermal stress and pH conditions play a role in increasing acidic charged variants over time, affecting the charge heterogeneity of AAVs, which can be serotype-specific. Reverse phase LC-MS was used to identify and confirm the increased presence of Post-Translational Modifications (PTMs) that are linked to increasing acidic species variants relative to non-stressed AAVs.</p><p><strong>Conclusion: </strong>These PTMs have biological consequences reflected in the diminished expression of the protein of interest in vitro. This cIEF method successfully analyzed a variety of AAV serotypes, and increasing trends of acidic variants led to reduced in vitro potency.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-Generation Whole-Exome Pattern: Advanced Methods and Clinical Significance.","authors":"Sumel Ashique, Anas Islam, Navjot Kaur Sandhu, Bhavinee Sharma, Rashmi Pathak, Himanshu Sharma","doi":"10.2174/0115665232356780250331181436","DOIUrl":"https://doi.org/10.2174/0115665232356780250331181436","url":null,"abstract":"<p><p>NGS (Next-generation sequencing) has emerged as the primary approach for gene finding in uncommon hereditary disorders. Targeted gene panels, whole genome sequencing (WGS), and whole exome sequencing (WES) are uses of next-generation sequencing and other related technologies. It is possible to explain personal or individual genome sequencing using NGS technology, as well as to detect disease-causing mutations using NGS findings. NGS, deep sequencing or massively parallel are similar words that describe a method of DNA sequencing leading to revolutionary change in genomic research. Due to its cost-effectiveness, Whole-Exome sequencing (WES) using Next-Generation Sequencing (NGS) is becoming increasingly popular in the field of human genetics. As a diagnostic tool, this technology can reduce the duration of the diagnostic process for several patients and has mostly made a significant contribution to the identification of new genes responsible for causing diseases. Considering the diverse range of phenotypic presentations of the diagnosis, NGS has the potential to uncover causative mutations, including de novo, new, and familial variants, related to epileptic syndromes and significantly enhance molecular diagnosis. The present study centres on the potential applications of next-generation exome sequencing in clinical diagnostics and the challenges encountered in the data processing of such data.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR/Cas9 Technology for Modifying Immune Checkpoint in CAR-T Cell Therapy for Hematopoietic Malignancies.","authors":"Forough Shams, Elham Sharif, Hajar Abbasi-Kenarsari, Nader Hashemi, Masoumeh Sadat Hosseini, Neda Heidari, Effat Noori, Ali Hossein Amini, Maryam Bazrgar, Maryam Rouhani, Yong Teng","doi":"10.2174/0115665232357078250331180413","DOIUrl":"https://doi.org/10.2174/0115665232357078250331180413","url":null,"abstract":"<p><p>Hematologic malignancies, which arise from dysregulation of hematopoiesis, are a group of cancers originating in cells with diminished capacity to differentiate into mature progeny and accumulating immature cells in blood-forming tissues such as lymph nodes and bone marrow. Immune- targeted therapies, such as Immune Checkpoint Blockade (ICB), chimeric antigen receptor T (CAR-T) cell therapy, and the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) system, a precise, popular, and versatile genome engineering tool, have opened new avenues for the treatment of malignancies. Targeting immune checkpoints has revolutionized FDA approval in cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), PD-1 (programmed death-1), and PDL1. According to the ICB and CAR techniques, the production of efficient CAR-T cells depends on the successful genetic modification of T cells, making them less susceptible to immune escape and suppression by cancer cells, which results in reduced off-target toxicity. Therefore, CRISPR/Cas9 has revolutionized the immune checkpoint-based approach for CAR-T cell therapy of hematologic malignancy. Continued research and clinical trials will undoubtedly pave the way for further advances in this field, ultimately benefiting patients and improving outcomes.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transforming RNA-Based Gene Therapy with Innovative Nanocarriers for siRNA and miRNA Delivery.","authors":"Jitendra Singh Chaudhary, Dilip Kumar Chanchal, Kuldeep Singh, Jeetendra Kumar Gupta, Divya Jain, Anubhav Dubey, Mahima Pandey, Shahbaz Khan","doi":"10.2174/0115665232355294250330002630","DOIUrl":"https://doi.org/10.2174/0115665232355294250330002630","url":null,"abstract":"<p><p>The cells have been given precise instructions proprio to the regulation of gene expression by the main genesis of Ryan-based gene therapy, which has revived cancer treatment and other disorders. The difficulty of delivering small interfering RNA (siRNA) and microRNA (miRNA) to a target cell is an enormous task and is often faced by researchers due to characteristic instabilities of these carriers and their poor uptake by the cell membrane. The new developments from nanocarrier technologies offer opportunities for better effectiveness of RNA therapy for its delivery and the effectiveness of the treatment regimen. The objective of this article is to provide an overview of the existing as well as the newest developments in nanocarrier technology, particularly as related to microRNA and small interfering RNA (siRNA) delivery. Their modes of operation and their uses in gene therapies are also examined as principles of their design. We focus on several nanocarrier technologies, which have shown proof of concept in multiple disciplines such as stability, controlled release profiles, and delivery. Lipid-based nanoparticles, polymeric systems, and hybrid nanocarriers are some of the platforms that fall under this category; however, this list is not exhaustive. We also study the idea that certain nanocarriers could have multiple functionalities, which would make it possible to improve cancer treatment by simultaneously carrying chemotherapy and genes. We aim to shed light on the future of RNA-based gene therapy by providing a thorough overview of recent research in the field. This will help us understand how novel nanocarrier technologies can tackle the delivery issues.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}