Drug Resistance Updates最新文献

{"title":"5-methylcytosine methylation of MALAT1 promotes resistance to sorafenib in hepatocellular carcinoma through ELAVL1/SLC7A11-mediated ferroptosis.","authors":"Chuan-Jian Shi, Feng-Xiang Pang, Yu-He Lei, Li-Qiang Deng, Fu-Zhen Pan, Zhi-Qing Liang, Tian Xie, Xian-Lin Wu, Yu-Yan Wang, Yan-Fang Xian, Wei-Qiang Zeng, Han-Li Lin, Jin-Fang Zhang","doi":"10.1016/j.drup.2024.101181","DOIUrl":"10.1016/j.drup.2024.101181","url":null,"abstract":"<p><p>Emerging evidence demonstrates that long non-coding RNAs (lncRNAs) play a crucial role in sorafenib resistance in hepatocellular carcinoma (HCC), and lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a dysregulated lncRNA in sorafenib-resistant HCC cells. However, the underlying regulatory mechanisms of MALAT1 in sorafenib-resistant HCC cells remain unclear. In the present study, we demonstrated that 5-methylcytosine (m⁵C) methylation catalyzed by NSUN2 and ALYREF contributed to the RNA stability and upregulation of MALAT1. The NSUN2/ALYREF/MALAT1 signaling axis was activated in sorafenib-resistant cells, and the upregulation of MALAT1 inhibited sorafenib-induced ferroptosis to drive sorafenib resistance. Mechanistically, MALAT1 maintained the mRNA stability of SLC7A11 by directly binding to ELAVL1 and stimulating its cytoplasmic translocation. Furthermore, we explored a new synergetic strategy for the treatment of HCC by combining MALAT1 inhibitor MALAT1-IN1 with sorafenib. The results demonstrated that MALAT1-IN1 significantly enhanced sorafenib efficacy for the treatment of HCC both in vitro and in vivo. Collectively, our work brings new insights into the epigenetic mechanisms of sorafenib resistance and offers an alternative therapeutic strategy targeting ferroptosis for sorafenib-resistant HCC patients.</p>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"78 ","pages":"101181"},"PeriodicalIF":15.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808390","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":"Global phylogeography and antibiotic resistance characteristics of Morganella: An epidemiological, spatial, comparative genomic study.","authors":"Qian Liu, Hong Shen, Ming Wei, Xi Chen, Li Gu, Wentao Zhu","doi":"10.1016/j.drup.2024.101180","DOIUrl":"10.1016/j.drup.2024.101180","url":null,"abstract":"<p><p>Morganella morganii has been recognized as an important opportunistic pathogen that is becoming increasingly prevalent worldwide. However, the current global evolutionary dynamics and emergence of ARGs remain obscure. The present study determined the global distribution, genomic classification, phylogeny, and monitor longitudinal resistome changes. During 1900-2024, a total of 1027 non-duplicate Morganella genomes have been reported from 49 countries. The countries with the highest number were China (433), the USA (143), and France (74). Through ANI distance analysis and core genome phylogeny, Morganella was reclassified into six species: M. morganii, M. sibonii, M. chanii, M. laugraudii, M. kristinii, M. psychrotolerans. Further analysis using cgMLST identified 87 distinct genetic clusters and 737 singleton strains, indicating a high level of multi-locus sequence type diversity and local clonal outbreaks. Bayesian evolutionary analysis revealed the most recent common ancestor year and potential global transmission routes. A total of 195 ARGs were carried by Morganella isolates, with each genome containing between 2 and 544 ARGs. The most common ARGs were associated with resistance to the following drug-classes: aminoglycosides, beta-lactam, chloramphenicol, sulfamides, and tetracycline. Twenty-one carbapenemase-encoding genes were identified in 22 countries, with bla_NDM-1, bla_KPC-2, bla_IMP-27, bla_OXA-48, bla_NDM-5, bla_NDM-7, and bla_VIM-1 being the most prevalent. Positive correlations were observed between ARGs and mobile genetic elements, like plasmids, ISs, and Tns, indicating frequent mobilization of certain ARGs by different mobile genetic elements (p < 0.05). In conclusion, Morganella isolates that are showing an upward trend in resistance and infection rates warrant a reclassification of their taxonomy and continuous monitoring for resistance.</p>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"78 ","pages":"101180"},"PeriodicalIF":15.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808475","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":"Reshaping the battlefield: A decade of clonal wars among Staphylococcus aureus in China.","authors":"Wangxiao Zhou, Ye Jin, Pan Chen, Qi Ge, Xu Dong, Yunbo Chen, Minghua Jiang, Yonghong Xiao","doi":"10.1016/j.drup.2024.101178","DOIUrl":"10.1016/j.drup.2024.101178","url":null,"abstract":"<p><strong>Background: </strong>Long-term comprehensive studies on the genomic epidemiology of both methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) isolates are limited in China. Here, we aimed to assess the genomic epidemiological characteristics and population dynamics of S. aureus in China.</p><p><strong>Methods: </strong>We performed whole-genome sequencing and resistance phenotyping on 3848 S. aureus isolates from bloodstream infections across 72 hospitals in 22 provinces, from 2011 to 2020 in China. We explored the dynamic trends in the resistance/virulence genes and mobile genetic element profiles across lineages, and conducted time-scaled phylogenetic investigation for prevalent lineages.</p><p><strong>Findings: </strong>The results revealed 315 different sequence types (STs) among all strains, 205 of which were novel. Significant shifts in MRSA population structure were observed, with ST59 replacing ST239 as the dominant lineage, exhibiting widespread inter-hospital transmission and increasing lineage diversity. In contrast, the composition of predominant MSSA lineages, ST188 (11.21 %), ST7 (9.79 %), ST22 (9.10 %), ST5 (8.56 %) and ST398 (7.91 %), remained relatively stable over time, with the diversity among MSSA strains consistently preserved at the population level. Phylogenetic reconstruction showed that ST59, ST398, ST22 and ST188 MSSA could evolve into corresponding MRSA lineages through the acquisition of staphylococcal cassette chromosome mec (SCCmec) elements. Moreover, the distribution patterns of resistance and virulence genes closely correlated with different lineages, where the proportion of PVL⁺ isolates in MRSA is rising. Concurrently, changes in the MRSA population structure led to an overall decrease in the number of resistance and virulence genes, significantly increased antimicrobial sensitivity.</p><p><strong>Interpretation: </strong>The shifting genomic landscape of S. aureus in China underscores the need for tailored antimicrobial stewardship and enhances understanding of its epidemiological trends over the past decade.</p>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"78 ","pages":"101178"},"PeriodicalIF":15.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774229","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":"Fasting-mimicking diet potentiates anti-tumor effects of CDK4/6 inhibitors against breast cancer by suppressing NRAS- and IGF1-mediated mTORC1 signaling.","authors":"Sebastian Brandhorst, Valter D Longo","doi":"10.1016/j.drup.2024.101182","DOIUrl":"10.1016/j.drup.2024.101182","url":null,"abstract":"<p><p>Fasting-mimicking diet (FMD) cycles, defined as 3-5 day periods of a calorie-restricted, low-protein, low-carbohydrate, and high-fat diet, have emerged as a dietary approach to delay cancer initiation and progression in both autograft and xenograft mouse models and as a safe and feasible approach to decrease risk factors for cancer and other age-related pathologies in humans. A substantial number of pre-clinical studies focused on various tumor types have shown that fasting/FMDs can potentiate the efficacy of various standard-of-care cancer therapies but also modulate the immune system to promote a T cell-dependent attack of tumor cells. Importantly, combining drug treatment with fasting/FMDs can overcome acquired drug resistance which frequently emerges and reduces long-term treatment benefits. However, the mechanisms by which the FMD reverts resistance to CDK4/6i remain poorly understood. Here, Li and colleagues provide evidence that FMD cycles act as a wild card to reduce the activity of a signaling network that includes IGF-1, RAS, AKT, and mTOR-S6K to delay cancer progression and reverse the acquisition of drug resistance. These findings expand the mechanistic understanding of the FMD-mediated increase in drug efficacy and provide further evidence to support trials combining hormone therapy, CDK4/6 inhibitors, and FMD in breast cancer treatment. These new results on FMD cycles add an optimistic outlook to extend the efficacy of standard-of-care drugs that eventually become ineffective because of acquired resistance.</p>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":" ","pages":"101182"},"PeriodicalIF":15.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814603","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":"Association of idealized amphiphiles and protease inhibitors: Conferring antimicrobial peptides with stable antibacterial activity under physiological conditions to combat multidrug-resistant bacteria.","authors":"Yongjie Zhu, Bowen Li, Wanying Xu, Yuanmengxue Wang, Guoyu Li, Chongpeng Bi, Changxuan Shao, Anshan Shan","doi":"10.1016/j.drup.2024.101183","DOIUrl":"https://doi.org/10.1016/j.drup.2024.101183","url":null,"abstract":"<p><strong>Aims: </strong>The unstable antimicrobial activity of antimicrobial peptides (AMPs) under physiological conditions (especially the degradation instigated proteases) seems to be a persistent impediment for their successful implementation in clinical trials. Consequently, our objective was to devise AMP engineering frameworks that could sustain robust antibacterial efficacy within physiological environments.</p><p><strong>Methods: </strong>In this work, we harvested AMPs with stable antimicrobial activity under the physiological barriers through the combination of idealized amphiphiles and trypsin inhibitors.</p><p><strong>Results: </strong>We screened and identified the lead peptides IK3-A and IK3-S, which showed potent activity against Gram-negative bacteria, including multidrug-resistant (MDR) bacteria, and exhibited promising biocompatibility with mammalian cells. Remarkably, IK3-A and IK3-S maintained sustained antibacterial potency under physiological salts, serum, and protease conditions. Furthermore, both IK3-A and IK3-S kill Gram-negative bacteria by attacking the bacterial cell membrane and inducing oxidative damage (at high concentrations). Crucially, IK3-A and IK3-S have optimal safety and efficacy in mice.</p><p><strong>Conclusions: </strong>This is the first work to compare the effects of different trypsin inhibitors on the resistance of AMPs to protease hydrolysis on the same sequence platform. In conclusion, these findings provide guidance for the molecular design of AMPs with stable antibacterial activity under physiological conditions and facilitates the process of clinical translation of AMPs as antimicrobial biomaterials against MDR bacteria. Moreover, this may stimulate a more general interest in protease inhibitors as molecular scaffolds in the creation of highly stable peptide-based biomaterials.</p>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"79 ","pages":"101183"},"PeriodicalIF":15.8,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820132","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":"CEA-induced PI3K/AKT pathway activation through the binding of CEA to KRT1 contributes to oxaliplatin resistance in gastric cancer","authors":"Yifan Chen, Yulong Mi, Song Tan, Yizhen Chen, Shaolin Liu, Shengtao Lin, Changshun Yang, Weifeng Hong, Weihua Li","doi":"10.1016/j.drup.2024.101179","DOIUrl":"https://doi.org/10.1016/j.drup.2024.101179","url":null,"abstract":"The serum level of carcinoembryonic antigen (CEA) has prognostic value in patients with gastric cancer (GC) receiving oxaliplatin-based chemotherapy. As the molecular functions of CEA are increasingly uncovered, its role in regulating oxaliplatin resistance in GC attracts attention.","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"219 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790068","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":"Acquired resistance to tyrosine kinase targeted therapy: mechanism and tackling strategies","authors":"Defa Wu, Qian Sun, Haolin Tang, Huan Xiao, Jiaxiang Luo, Liang Ouyang, Qiu Sun","doi":"10.1016/j.drup.2024.101176","DOIUrl":"https://doi.org/10.1016/j.drup.2024.101176","url":null,"abstract":"Over the past two decades, tyrosine kinase inhibitors (TKIs) have rapidly emerged as pivotal targeted agents, offering promising therapeutic prospects for patients. However, as the cornerstone of targeted therapies, an increasing number of TKIs have been found to develop acquired resistance during treatment, making the challenge of overcoming this resistance a primary focus of current research. This review comprehensively examines the evolution of TKIs from multiple perspectives, with particular emphasis on the mechanisms underlying acquired resistance, innovative drug design strategies, inherent challenges, and future directions.","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"17 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790126","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":"Why and how citrate may sensitize malignant tumors to immunotherapy","authors":"Philippe Icard ,&nbsp;Mathilde Prieto ,&nbsp;Antoine Coquerel ,&nbsp;Ludovic Fournel ,&nbsp;Joseph Gligorov ,&nbsp;Johanna Noel ,&nbsp;Adrien Mouren ,&nbsp;Anthony Dohan ,&nbsp;Marco Alifano ,&nbsp;Luca Simula","doi":"10.1016/j.drup.2024.101177","DOIUrl":"10.1016/j.drup.2024.101177","url":null,"abstract":"<div><div>Immunotherapy, either alone or in combination with chemotherapy, has demonstrated limited efficacy in a variety of solid cancers. Several factors contribute to explaining primary or secondary resistance. Among them, cancer cells, whose metabolism frequently relies on aerobic glycolysis, promote exhaustion of cytotoxic immune cells by diverting the glucose in the tumor microenvironment (TME) to their own profit, while secreting lactic acid that sustains the oxidative metabolism of immunosuppressive cells. Here, we propose to combine current treatment based on the use of immune checkpoint inhibitors (ICIs) with high doses of sodium citrate (SCT) because citrate inhibits cancer cell metabolism (by targeting both glycolysis and oxidative metabolism) and may active anti-tumor immune response. Indeed, as showed in preclinical studies, SCT reduces cancer cell growth, promoting cell death and chemotherapy effectiveness. Furthermore, since the plasma membrane citrate carrier pmCIC is mainly expressed in cancer cells and low or not expressed in immune and non-transformed cells, we argue that the inhibition of cancer cell metabolism by SCT may increase glucose availability in the TME, thus promoting functionality of anti-tumor immune cells. Concomitantly, the decrease in the amount of lactic acid in the TME may reduce the functionality of immunosuppressive cells. Preclinical studies have shown that SCT can enhance the anti-tumor immune response through an enhancement of T cell infiltration and activation, and a repolarization of macrophages towards a TAM1-like phenotype. Therefore, this simple and cheap strategy may have a major impact to increase the efficacy of current immunotherapies in human solid tumors and we encourage testing it in clinical trials.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"78 ","pages":"Article 101177"},"PeriodicalIF":15.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721172","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":"Blockade of purine metabolism reverses macrophage immunosuppression and enhances anti-tumor immunity in non-small cell lung cancer","authors":"Li Yang ,&nbsp;Aitian Li ,&nbsp;Weina Yu ,&nbsp;Huishang Wang ,&nbsp;Lei Zhang ,&nbsp;Dan Wang ,&nbsp;Ying Wang ,&nbsp;Ru Zhang ,&nbsp;Qingyang Lei ,&nbsp;Zhangnan Liu ,&nbsp;Shanshan Zhen ,&nbsp;Haiming Qin ,&nbsp;Yaqing Liu ,&nbsp;Yang Yang ,&nbsp;Xian-Lu Song ,&nbsp;Yi Zhang","doi":"10.1016/j.drup.2024.101175","DOIUrl":"10.1016/j.drup.2024.101175","url":null,"abstract":"<div><h3>Aims</h3><div>Immune checkpoint blockade therapy is not effective in most patients with non-small cell lung cancer (NSCLC) due to the immunosuppressive tumor microenvironment. Macrophages are key components of tumor-infiltrating immune cells and play a critical role in immunosuppression, which can be mediated by cell-intrinsic metabolism. This study aimed to evaluate whether macrophages regulate NSCLC progression through metabolic crosstalk with cancer cells and affect immunotherapy efficacy.</div></div><div><h3>Methods</h3><div>The macrophage landscape of NSCLC tissues were analyzed by single-cell sequencing and verified through flow cytometry and immunofluorescence. Multiplex assay, single-cell sequencing data, ELISA, immunofluorescence, and RNA-seq et al. were used to investigate and verify the mechanism of macrophage-mediated metabolic regulation on immunosuppression. The tumor-bearing model was established in C57BL/6 J mice to explore in vivo efficacy.</div></div><div><h3>Results</h3><div>We found that tumor tissue-derived macrophages exhibited an anti-inflammatory phenotype and had a prognostic value for NSCLC. NSCLC cell-secreted CXCL8 recruited macrophages from peritumor tissues to tumor sites and promoted programmed death-ligand 1 (PD-L1) expression by activating purine metabolism with increasing xanthine dehydrogenase and uric acid production. Moreover, purine metabolism-mediated macrophage immunosuppression was dependent on NLRP3/caspase-1/IL-1β signaling. Blockade of purine metabolism signaling enhanced anti-tumor immunity and the efficacy of anti-PD-L1 therapy.</div></div><div><h3>Conclusions</h3><div>Collectively, our findings reveal a key role of purine metabolism in macrophage immunosuppression and suggest that blockade of purine metabolism combined with immune checkpoint blockade could provide synergistic effects in NSCLC treatment.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"78 ","pages":"Article 101175"},"PeriodicalIF":15.8,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721164","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":"Post-translational modifications in drug resistance","authors":"Chenggui Miao ,&nbsp;Yurong Huang ,&nbsp;Cheng Zhang ,&nbsp;Xiao Wang ,&nbsp;Bing Wang ,&nbsp;Xinyue Zhou ,&nbsp;Yingqiu Song ,&nbsp;Peng Wu ,&nbsp;Zhe-Sheng Chen ,&nbsp;Yibin Feng","doi":"10.1016/j.drup.2024.101173","DOIUrl":"10.1016/j.drup.2024.101173","url":null,"abstract":"<div><div>Resistance to antitumor drugs, antimicrobial drugs, and antiviral drugs severely limits treatment effectiveness and cure rate of diseases. Protein post-translational modifications (PTMs) represented by glycosylation, ubiquitination, SUMOylation, acetylation, phosphorylation, palmitoylation, and lactylation are closely related to drug resistance. PTMs are typically achieved by adding sugar chains (glycosylation), small proteins (ubiquitination), lipids (palmitoylation), or functional groups (lactylation) to amino acid residues. These covalent additions are usually the results of signaling cascades and could be reversible, with the triggering mechanisms depending on the type of modifications. PTMs are involved in antitumor drug resistance, not only as inducers of drug resistance but also as targets for reversing drug resistance. Bacteria exhibit multiple PTMs-mediated antimicrobial drug resistance. PTMs allow viral proteins and host cell proteins to form complex interaction networks, inducing complex antiviral drug resistance. This review summarizes the important roles of PTMs in drug resistance, providing new ideas for exploring drug resistance mechanisms, developing new drug targets, and guiding treatment plans.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"78 ","pages":"Article 101173"},"PeriodicalIF":15.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721173","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}