Drug Resistance Updates最新文献

{"title":"CYP1B1 promotes PARPi-resistance via histone H1.4 interaction and increased chromatin accessibility in ovarian cancer","authors":"Yite Xue ,&nbsp;Taotao Yin ,&nbsp;Shuo Yuan ,&nbsp;Lingfang Wang ,&nbsp;Hui Lin ,&nbsp;Tianzhe Jin ,&nbsp;Ruiyi Xu ,&nbsp;Jiaxin Gu ,&nbsp;Shizhen Shen ,&nbsp;Xiaojing Chen ,&nbsp;Zhuoye Chen ,&nbsp;Ni Sima ,&nbsp;Lifeng Chen ,&nbsp;Weiguo Lu ,&nbsp;Xiao Li ,&nbsp;Xiaodong Cheng ,&nbsp;Hui Wang","doi":"10.1016/j.drup.2024.101151","DOIUrl":"10.1016/j.drup.2024.101151","url":null,"abstract":"<div><h3>Introduction</h3><div>Ovarian cancer is the most lethal gynecological cancer and presents significant therapeutic challenges. The discovery of synthetic lethality between PARP inhibitors (PARPi) and homologous recombination deficiency marked a new era in treating BRCA1/2-mutated tumors. However, PARPi resistance remains a major clinical challenge.</div></div><div><h3>Methods</h3><div>RNA sequencing was used to identify genes altered by PARPi treatment and LC-MS was used to detect proteins interacting with CYP1B1. Resistance mechanisms were explored through ATAC-seq and gene expression manipulation. Additional techniques, including micrococcal nuclease digestion assays, DAPI staining, and fluorescence microscopy, were used to assess changes in nuclear morphology and chromatin accessibility.</div></div><div><h3>Results</h3><div>The gradual exposure of Olaparib has developed a PARPi-resistant cell line, A2780-OlaR, which exhibits significant upregulation of CYP1B1 at both RNA and protein levels. Down-regulating CYP1B1 expression or using specific inhibitors decreased the cellular response to Olaparib. Linker histone H1.4 was identified as associated with CYP1B1. ATAC-seq showed differential chromatin accessibility between A2780-OlaR and parental cells, indicating that the downregulation of H1.4 was associated with increased chromatin accessibility and higher cell viability after Olaparib treatment.</div></div><div><h3>Conclusion</h3><div>Our findings reveal a novel role for CYP1B1 in driving PARPi resistance through distinct molecular mechanisms in A2780-OlaR. This study highlights the importance of chromatin accessibility in PARPi efficacy and suggests the CYP1B1/H1.4 axis as a promising therapeutic target for overcoming drug resistance in ovarian cancer, offering potentially therapeutic benefits.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101151"},"PeriodicalIF":15.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142416322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RGS5+ lymphatic endothelial cells facilitate metastasis and acquired drug resistance of breast cancer through oxidative stress-sensing mechanism","authors":"Caixin Qiu ,&nbsp;Chaoyi Tang ,&nbsp;Yujun Tang ,&nbsp;Ka Su ,&nbsp;Xiao Chai ,&nbsp;Zexu Zhan ,&nbsp;Xing Niu ,&nbsp;Jiehua Li","doi":"10.1016/j.drup.2024.101149","DOIUrl":"10.1016/j.drup.2024.101149","url":null,"abstract":"<div><h3>Aims</h3><div>Oxidative stress reflected by elevated reactive oxygen species (ROS) in the tumor ecosystem, is a hallmark of human cancers. The mechanisms by which oxidative stress regulate the metastatic ecosystem and resistance remain elusive. This study aimed to dissect the oxidative stress-sensing machinery during the evolvement of early dissemination and acquired drug resistance in breast cancer.</div></div><div><h3>Methods</h3><div>Here, we constructed single-cell landscape of primary breast tumors and metastatic lymph nodes, and focused on RGS5⁺ endothelial cell subpopulation in breast cancer metastasis and resistance.</div></div><div><h3>Results</h3><div>We reported on RGS5 as a master in endothelial cells sensing oxidative stress. RGS5⁺ endothelial cells facilitated tumor-endothelial adhesion and transendothelial migration of breast cancer cells. Antioxidant suppressed oxidative stress-induced RGS5 expression in endothelial cells, and prevented adhesion and transendothelial migration of cancer cells. RGS5-overexpressed HLECs displayed attenuated glycolysis and oxidative phosphorylation. Drug-resistant HLECs with RGS5 overexpression conferred acquired drug resistance of breast cancer cells. Importantly, genetic knockdown of RGS5 prevented tumor growth and lymph node metastasis.</div></div><div><h3>Conclusions</h3><div>Our work demonstrates that RGS5 in lymphatic endothelial cells senses oxidative stress to promote breast cancer lymph node metastasis and resistance, providing a novel insight into a potentially targetable oxidative stress-sensing machinery in breast cancer treatment.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101149"},"PeriodicalIF":15.8,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasmid-borne tigecycline resistance gene tet(X4) in Salmonella enterica and Escherichia coli isolates from a pediatric patient with diarrhea","authors":"Zelin Yan ,&nbsp;Yan Li ,&nbsp;Yingling Ni,&nbsp;Xiaoni Xia,&nbsp;Yanyan Zhang,&nbsp;Yuchen Wu,&nbsp;Jing Zhang,&nbsp;Gongxiang Chen,&nbsp;Ruichao Li,&nbsp;Rong Zhang","doi":"10.1016/j.drup.2024.101145","DOIUrl":"10.1016/j.drup.2024.101145","url":null,"abstract":"","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101145"},"PeriodicalIF":15.8,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142122726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of staphylococcal resistance to clinically relevant antibiotics","authors":"Daniela Brdová,&nbsp;Tomáš Ruml,&nbsp;Jitka Viktorová","doi":"10.1016/j.drup.2024.101147","DOIUrl":"10.1016/j.drup.2024.101147","url":null,"abstract":"<div><p><em>Staphylococcus aureus</em>, a notorious pathogen with versatile virulence, poses a significant challenge to current antibiotic treatments due to its ability to develop resistance mechanisms against a variety of clinically relevant antibiotics. In this comprehensive review, we carefully dissect the resistance mechanisms employed by <em>S. aureus</em> against various antibiotics commonly used in clinical settings. The article navigates through intricate molecular pathways, elucidating the mechanisms by which <em>S. aureus</em> evades the therapeutic efficacy of antibiotics, such as β-lactams, vancomycin, daptomycin, linezolid, <em>etc</em>. Each antibiotic is scrutinised for its mechanism of action, impact on bacterial physiology, and the corresponding resistance strategies adopted by <em>S. aureus</em>. By synthesising the knowledge surrounding these resistance mechanisms, this review aims to serve as a comprehensive resource that provides a foundation for the development of innovative therapeutic strategies and alternative treatments for <em>S. aureus</em> infections. Understanding the evolving landscape of antibiotic resistance is imperative for devising effective countermeasures in the battle against this formidable pathogen.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101147"},"PeriodicalIF":15.8,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1368764624001055/pdfft?md5=12f715097caabdafe7529ca70e6a87b4&pid=1-s2.0-S1368764624001055-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142128769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the resistance to therapies in pancreatic ductal adenocarcinoma","authors":"Ashu Shah ,&nbsp;Koelina Ganguly ,&nbsp;Sanchita Rauth ,&nbsp;Shamema S. Sheree ,&nbsp;Imran Khan ,&nbsp;Apar K. Ganti ,&nbsp;Moorthy P. Ponnusamy ,&nbsp;Sushil Kumar ,&nbsp;Maneesh Jain ,&nbsp;Surinder K. Batra","doi":"10.1016/j.drup.2024.101146","DOIUrl":"10.1016/j.drup.2024.101146","url":null,"abstract":"<div><p>Despite the ongoing advances in interventional strategies (surgery, chemotherapy, radiotherapy, and immunotherapy) for managing pancreatic ductal adenocarcinoma (PDAC), the development of therapy refractory phenotypes remains a significant challenge. Resistance to various therapeutic modalities in PDAC emanates from a combination of inherent and acquired factors and is attributable to cancer cell-intrinsic and -extrinsic mechanisms. The critical determinants of therapy resistance include oncogenic signaling and epigenetic modifications that drive cancer cell stemness and metabolic adaptations, CAF-mediated stromagenesis that results in ECM deposition altered mechanotransduction, and secretome and immune evasion. We reviewed the current understanding of these multifaceted mechanisms operating in the PDAC microenvironment, influencing the response to chemotherapy, radiotherapy, and immunotherapy regimens. We then describe how the lessons learned from these studies can guide us to discover novel therapeutic regimens to prevent, delay, or revert resistance and achieve durable clinical responses.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101146"},"PeriodicalIF":15.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Un-methylation of NUDT21 represses docosahexaenoic acid biosynthesis contributing to enzalutamide resistance in prostate cancer","authors":"Shin-Chih Lin ,&nbsp;Ya-Chuan Tsai ,&nbsp;Ying-Lan Chen ,&nbsp;Hui-Kuan Lin ,&nbsp;Yun-Chen Huang ,&nbsp;Yi-Syuan Lin ,&nbsp;Yu-Sheng Cheng ,&nbsp;Hsing-Yi Chen ,&nbsp;Chia-Jung Li ,&nbsp;Tsung-Yen Lin ,&nbsp;Shih-Chieh Lin","doi":"10.1016/j.drup.2024.101144","DOIUrl":"10.1016/j.drup.2024.101144","url":null,"abstract":"<div><h3>Aims</h3><p>The recent approval of enzalutamide for metastatic castration-sensitive prostate cancer underscores its growing clinical significance, raising concerns about emerging resistance and limited treatment options. While the reactivation of the androgen receptor (AR) and other genes plays a role in enzalutamide resistance, identifications of novel underlying mechanism with therapeutic potential in enzalutamide-resistant (EnzaR) cells remain largely elusive.</p></div><div><h3>Methods</h3><p>Drug-resistant prostate cancer cell lines, animal models, and organoids were utilized to examine NUDT21 function by transcriptomic and metabolomic analyses through loss-of-function and gain-of-function assays. Notably, a mono-methylation monoclonal antibody and conditional-knockin transgenic mouse model of NUDT21 were generated for evaluating its function.</p></div><div><h3>Results</h3><p>NUDT21 overexpression acts as a crucial alternative polyadenylation (APA) mediator, supported by its oncogenic role in prostate cancer. PRMT7-mediated mono-methylation of NUDT21 induces a shift in 3’UTR usage, reducing oncogenicity. In contrast, its un-methylation promotes cancer growth and cuproptosis insensitivity in EnzaR cells by exporting toxic copper and suppressing docosahexaenoic acid (DHA) biosynthesis. Crucially, NUDT21 inhibition or DHA supplementation with copper ionophore holds therapeutic promise for EnzaR cells.</p></div><div><h3>Conclusions</h3><p>The un-methylation of NUDT21-mediated 3’UTR shortening unveils a novel mechanism for enzalutamide resistance, and our findings offer innovative strategies for advancing the treatment of prostate cancer patients experiencing enzalutamide resistance.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101144"},"PeriodicalIF":15.8,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S136876462400102X/pdfft?md5=8d5415fa3df7d10f5e75ab1ffb7c812f&pid=1-s2.0-S136876462400102X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142087300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR-AMRtracker: A novel toolkit to monitor the antimicrobial resistance gene transfer in fecal microbiota","authors":"Gong Li ,&nbsp;Teng-Fei Long ,&nbsp;Shi-Ying Zhou ,&nbsp;Li-Juan Xia ,&nbsp;Ang Gao ,&nbsp;Lei Wan ,&nbsp;Xiao-Yuan Diao ,&nbsp;Yu-Zhang He ,&nbsp;Ruan-Yang Sun ,&nbsp;Jin-Tao Yang ,&nbsp;Sheng-Qiu Tang ,&nbsp;Hao Ren ,&nbsp;Liang-Xing Fang ,&nbsp;Xiao-Ping Liao ,&nbsp;Ya-Hong Liu ,&nbsp;Liang Chen ,&nbsp;Jian Sun","doi":"10.1016/j.drup.2024.101142","DOIUrl":"10.1016/j.drup.2024.101142","url":null,"abstract":"<div><p>The spread of antibiotic resistance genes (ARGs), particularly those carried on plasmids, poses a major risk to global health. However, the extent and frequency of ARGs transfer in microbial communities among human, animal, and environmental sectors is not well understood due to a lack of effective tracking tools. We have developed a novel fluorescent tracing tool, CRISPR-AMRtracker, to study ARG transfer. It combines CRISPR/Cas9 fluorescence tagging, fluorescence-activated cell sorting, 16S rRNA gene sequencing, and microbial community analysis. CRISPR-AMRtracker integrates a fluorescent tag immediately downstream of ARGs, enabling the tracking of ARG transfer without compromising the host cell's antibiotic susceptibility, fitness, conjugation, and transposition. Notably, our experiments demonstrate that <em>sfGFP</em>-tagged plasmid-borne <em>mcr-1</em> can transfer across diverse bacterial species within fecal samples. This innovative approach holds the potential to illuminate the dynamics of ARG dissemination and provide valuable insights to shape effective strategies in mitigating the escalating threat of antibiotic resistance.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101142"},"PeriodicalIF":15.8,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142098635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fusion event mediated by IS903B between chromosome and plasmid in two MCR-9- and KPC-2-co-producing Klebsiella pneumoniae isolates","authors":"Ruishan Liu ,&nbsp;Yingying Chen ,&nbsp;Hao Xu ,&nbsp;Huanran Zhang ,&nbsp;Yi Liu ,&nbsp;Xiaojing Liu ,&nbsp;Haowei Ye ,&nbsp;Mantao Chen ,&nbsp;Beiwen Zheng","doi":"10.1016/j.drup.2024.101139","DOIUrl":"10.1016/j.drup.2024.101139","url":null,"abstract":"<div><p>Herein, we first isolated two MCR-9- and KPC-2-co-producing <em>K. pneumoniae</em> isolates. Notably, we observed a fusion event between the chromosome and plasmid, mediated by IS<em>903B</em>, in these two strains. This cointegration of chromosomes and plasmids introduces a new mode of transmission for antimicrobial resistance genes.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101139"},"PeriodicalIF":15.8,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142040454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the secrets: Evolution of resistance mediated by membrane proteins","authors":"Xue Yang ,&nbsp;Min Li ,&nbsp;Zi-Chang Jia ,&nbsp;Yan Liu ,&nbsp;Shun-Fan Wu ,&nbsp;Mo-Xian Chen ,&nbsp;Ge-Fei Hao ,&nbsp;Qing Yang","doi":"10.1016/j.drup.2024.101140","DOIUrl":"10.1016/j.drup.2024.101140","url":null,"abstract":"<div><p>Membrane protein-mediated resistance is a multidisciplinary challenge that spans fields such as medicine, agriculture, and environmental science. Understanding its complexity and devising innovative strategies are crucial for treating diseases like cancer and managing resistant pests in agriculture. This paper explores the dual nature of resistance mechanisms across different organisms: On one hand, animals, bacteria, fungi, plants, and insects exhibit convergent evolution, leading to the development of similar resistance mechanisms. On the other hand, influenced by diverse environmental pressures and structural differences among organisms, they also demonstrate divergent resistance characteristics. Membrane protein-mediated resistance mechanisms are prevalent across animals, bacteria, fungi, plants, and insects, reflecting their shared survival strategies evolved through convergent evolution to address similar survival challenges. However, variations in ecological environments and biological characteristics result in differing responses to resistance. Therefore, examining these differences not only enhances our understanding of adaptive resistance mechanisms but also provides crucial theoretical support and insights for addressing drug resistance and advancing pharmaceutical development.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101140"},"PeriodicalIF":15.8,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1368764624000980/pdfft?md5=f32ad03042bf67bda91992e6b1153808&pid=1-s2.0-S1368764624000980-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142148766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrastructural, metabolic and genetic characteristics of determinants facilitating the acquisition of macrolide resistance by Streptococcus pneumoniae","authors":"Xueqing Wu ,&nbsp;Babek Alibayov ,&nbsp;Xi Xiang ,&nbsp;Santiago M. Lattar ,&nbsp;Fuminori Sakai ,&nbsp;Austin A. Medders ,&nbsp;Brenda S. Antezana ,&nbsp;Lance E. Keller ,&nbsp;Ana G.J. Vidal ,&nbsp;Yih-Ling Tzeng ,&nbsp;D. Ashley Robinson ,&nbsp;David S. Stephens ,&nbsp;Yunsong Yu ,&nbsp;Jorge E. Vidal","doi":"10.1016/j.drup.2024.101138","DOIUrl":"10.1016/j.drup.2024.101138","url":null,"abstract":"<div><h3>Aims</h3><p>To investigate the molecular events associated with acquiring macrolide resistance genes [<em>mefE</em>/<em>mel</em> (Mega) or <em>ermB</em>] in <em>Streptococcus pneumoniae</em> (<em>Spn</em>) during nasopharyngeal colonization.</p></div><div><h3>Methods and results</h3><p>Genomic analysis of 128 macrolide-resistant <em>Spn</em> isolates revealed recombination events in genes of the conjugation apparatus, or the competence system, in strains carrying Tn<em>916</em>-related elements. Studies using confocal and electron microscopy demonstrated that during the transfer of Tn<em>916</em>-related elements in nasopharyngeal cell biofilms, pneumococcal strains formed clusters facilitating their acquisition of resistance determinants at a high recombination frequency (rF). Remarkably, these aggregates comprise both encapsulated and nonencapsulated pneumococci that span extracellular and intracellular compartments. rF assessments showed similar rates regardless Mega was associated with large integrative and conjugative elements (ICEs) (&gt;23 kb) or not (∼5.4 kb). The rF for Mega Class IV(c) insertion region (∼53 kb) was three orders of magnitude higher than the transformation of the capsule locus. Metabolomics studies of the microenvironment created by colonization of human nasopharyngeal cells revealed a link between the acquisition of ICEs and the pathways involving nicotinic acid and sucrose.</p></div><div><h3>Conclusions</h3><p>Pneumococcal clusters, both extracellular and intracellular, facilitate macrolide resistance acquisition, and ICEs were acquired at a higher frequency than the capsule locus. Metabolic changes could serve as intervention targets.</p></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101138"},"PeriodicalIF":15.8,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142012656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}