Drug Resistance Updates最新文献

{"title":"Autophagy in cancer development, immune evasion, and drug resistance","authors":"Xuegang Niu ,&nbsp;Qi You ,&nbsp;Kaijian Hou ,&nbsp;Yu Tian ,&nbsp;Penghui Wei ,&nbsp;Yang Zhu ,&nbsp;Bin Gao ,&nbsp;Milad Ashrafizadeh ,&nbsp;Amir Reza Aref ,&nbsp;Alireza Kalbasi ,&nbsp;Israel Cañadas ,&nbsp;Gautam Sethi ,&nbsp;Vinay Tergaonkar ,&nbsp;Lingzhi Wang ,&nbsp;Yuanxiang Lin ,&nbsp;Dezhi Kang ,&nbsp;Daniel J. Klionsky","doi":"10.1016/j.drup.2024.101170","DOIUrl":"10.1016/j.drup.2024.101170","url":null,"abstract":"<div><div>Macroautophagy/autophagy is a highly conserved evolutionary mechanism involving lysosomes for the degradation of cytoplasmic components including organelles. The constitutive, basal level of autophagy is fundamental for preserving cellular homeostasis; however, alterations in autophagy can cause disease pathogenesis, including cancer. The role of autophagy in cancer is particularly complicated, since this process acts both as a tumor suppressor in precancerous stages but facilitates tumor progression during carcinogenesis and later stages of cancer progression. This shift between anti-tumor and pro-tumor roles may be influenced by genetic and environmental factors modulating key pathways such as those involving autophagy-related proteins, the PI3K-AKT-MTOR axis, and AMPK, which often show dysregulation in tumors. Autophagy regulates various cellular functions, including metabolism of glucose, glutamine, and lipids, cell proliferation, metastasis, and several types of cell death (apoptosis, ferroptosis, necroptosis and immunogenic cell death). These multifaceted roles demonstrate the potential of autophagy to affect DNA damage repair, cell death pathways, proliferation and survival, which are critical in determining cancer cells’ response to chemotherapy. Therefore, targeting autophagy pathways presents a promising strategy to combat chemoresistance, as one of the major reasons for the failure in cancer patient treatment. Furthermore, autophagy modulates immune evasion and the function of immune cells such as T cells and dendritic cells, influencing the tumor microenvironment and cancer’s biological behavior. However, the therapeutic targeting of autophagy is complex due to its dual role in promoting survival and inducing cell death in cancer cells, highlighting the need for strategies that consider both the beneficial and detrimental effects of autophagy modulation in cancer therapy. Hence, both inducers and inhibitors of autophagy have been introduced for the treatment of cancer. This review emphasizes the intricate interplay between autophagy, tumor biology, and immune responses, offering insights into potential therapeutic approaches that deploy autophagy in the cancer suppression.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"78 ","pages":"Article 101170"},"PeriodicalIF":15.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721174","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":"Modeling the epidemiologic impact of age-targeted vaccination for drug-resistant tuberculosis","authors":"Pei-Yao Zhai ,&nbsp;Zhi-Xian Chen ,&nbsp;Ting Jiang ,&nbsp;Jian Feng ,&nbsp;Bin Zhang ,&nbsp;Xiao Zang ,&nbsp;Yan-Lin Zhao ,&nbsp;Gang Qin","doi":"10.1016/j.drup.2024.101172","DOIUrl":"10.1016/j.drup.2024.101172","url":null,"abstract":"<div><div>This study used a calibrated mathematical model to evaluate age-specific tuberculosis (TB) vaccination strategies, for drug-resistant (DR)-TB management in China. Prioritizing elderly vaccination significantly reduced multidrug-resistant or rifampicin-resistant TB incidence and mortality, while avoiding the need for second-line treatment, offering a promising approach to mitigate DR-TB burden by 2050.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"78 ","pages":"Article 101172"},"PeriodicalIF":15.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632053","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":"Zebrafish patient-derived xenograft system for predicting carboplatin resistance and metastasis of ovarian cancer","authors":"Feifeng Song ,&nbsp;Xiaofen Yi ,&nbsp;Xiaowei Zheng ,&nbsp;Zhentao Zhang ,&nbsp;Linqian Zhao ,&nbsp;Yan Shen ,&nbsp;Ye Zhi ,&nbsp;Ting Liu ,&nbsp;Xiaozhen Liu ,&nbsp;Tong Xu ,&nbsp;Xiaoping Hu ,&nbsp;Yiwen Zhang ,&nbsp;Huafeng Shou ,&nbsp;Ping Huang","doi":"10.1016/j.drup.2024.101162","DOIUrl":"10.1016/j.drup.2024.101162","url":null,"abstract":"<div><h3>Aims</h3><div>Ovarian cancer (OC) remains a significant challenge in oncology due to high rates of drug resistance and disease relapse following standard treatment with surgery and platinum-based chemotherapy. Despite the widespread use of these treatments, no effective biomarkers currently exist to identify which patients will respond favorably to therapy. This study introduces a zebrafish patient-derived xenograft (PDX) system, capable of replicating both the carboplatin response and metastatic behavior observed in OC patients, within a rapid 3-day assay period.</div></div><div><h3>Methods</h3><div>Two OC cell lines: carboplatin-sensitive (A2780) and resistant (OVCAR8) were used to assess differential responses to treatment in murine and zebrafish xenograft models. Tumor tissues from 16 OC patients were implanted into zebrafish embryos to test carboplatin responses and predict metastasis. Additionally, eight clinical OC samples were directly implanted into zebrafish embryos as part of a proof-of-concept demonstration.</div></div><div><h3>Results</h3><div>The zebrafish xenografts accurately reflected the carboplatin sensitivity and resistance patterns seen in <em>in vitro</em> and murine models. The zebrafish PDX model demonstrated a 67 % success rate for implantation and a 100 % success rate for engraftment. Notably, the model effectively distinguished between metastatic and non-metastatic disease, with an area under the ROC curve (AUC) of 0.818. Furthermore, the zebrafish PDX model showed a high concordance with patient-specific responses to carboplatin.</div></div><div><h3>Conclusions</h3><div>This zebrafish PDX model offers a fast, accurate, and clinically relevant platform for evaluating carboplatin response and predicting metastasis in OC patients. It holds significant potential for advancing personalized medicine, allowing for more precise therapeutic outcome predictions and individualized treatment strategies.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"78 ","pages":"Article 101162"},"PeriodicalIF":15.8,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689134","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":"TMOD3 accelerated resistance to immunotherapy in KRAS-mutated pancreatic cancer through promoting autophagy-dependent degradation of ASCL4","authors":"Zhiwei He ,&nbsp;Dijie Zheng ,&nbsp;Futang Li ,&nbsp;Liwen Chen ,&nbsp;Changhao Wu ,&nbsp;Zhirui Zeng ,&nbsp;Chao Yu","doi":"10.1016/j.drup.2024.101171","DOIUrl":"10.1016/j.drup.2024.101171","url":null,"abstract":"<div><div>The high prevalence of KRAS mutations in pancreatic cancer (PC) is widely acknowledged and results in the resistance of targeted ferroptosis therapy and immunotherapy. Herein, via a CRISPR/Cas9 library screen, the effects of ferroptosis agonists were increased in KRAS-mutant PC cells upon knockout of tropomodulin 3 (TMOD3), while these effects were not observed in KRAS-wild-type cells. Increased levels of TMOD3 were found in PC tissues, particularly in those with KRAS mutations. The increase in TMOD3 expression was facilitated by KRAS via the ETS transcription factor ELK1. Liquid chromatography–mass spectrometry (LC/MS) showed that TMOD3 increased acyl-CoA synthetase long chain family member 4 (ACSL4) protein expression and fatty acid metabolism. Mechanistically, TMOD3 promoted F-actin polymerization, thereby facilitating the fusion of autophagosomes with lysosomes, increasing the degradation of the ACSL4 protein, and augmenting the ferroptosis-inducing effects of RSL3. These effects of TMOD3 were counteracted by the administration of cytochalasin, the removal of the α2 domain of TMOD3, or the introduction of a mutation at S71. Cangrelor, an FDA-approved drug, can target TMOD3. In a mouse model, the suppression of TMOD3 using cangrelor or gene silencing technology resulted in increased infiltration of CD8+ T cells into tumor tissues with KRAS mutations and exhibited a synergistic effect with the PD-1 antibody. In conclusion, TMOD3 was found to inhibit ferroptosis and induced the resistance to PD-1 antibody by facilitating the fusion of autophagosomes and lysosomes through the promotion of F-actin polymerization in KRAS-mutant PC. TMOD3 was identified as a novel target for PC therapy.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"78 ","pages":"Article 101171"},"PeriodicalIF":15.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632056","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":"Revolutionising infection control: building the next generation of phage banks","authors":"Braira Wahid,&nbsp;Muhammad Salman Tiwana,&nbsp;Akhtar Ali","doi":"10.1016/j.drup.2024.101143","DOIUrl":"10.1016/j.drup.2024.101143","url":null,"abstract":"<div><div>The escalating global burden of antimicrobial resistance (AMR) represents a critical public health challenge. This rise in antibiotic resistance is concomitant with heightened antibiotic consumption, with an estimated annual usage of 100,000 to 200,000 tons. A recent systematic review, which analysed data from 204 countries, reported that AMR was responsible for 4.95 million deaths in 2019 (<span><span>Murray et al., 2022</span></span>). The growing threat of AMR is imposing a significant financial burden on the global economy, with the CDC reporting an additional annual cost of $20 billion in the U.S. and €9 billion in Europe. The emerging field of bacteriophage therapy offers promising potential as a game-changer in the era of AMR. However, existing literature reveals numerous research gaps and technological challenges, including insufficient information on phage pharmacology, genomics, and a lack of preclinical and clinical data. In addition to conducting further research to address existing knowledge gaps, establishing phage banks in clinical facilities could be a transformative advancement in the fight against AMR.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101143"},"PeriodicalIF":15.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100765","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":"Targeting NQO1 induces ferroptosis and triggers anti-tumor immunity in immunotherapy-resistant KEAP1-deficient cancers","authors":"Zhennan Yuan ,&nbsp;Xueying Wang ,&nbsp;Boyu Qin ,&nbsp;Rulong Hu ,&nbsp;Rui Miao ,&nbsp;Yang Zhou ,&nbsp;Lei Wang ,&nbsp;Tong Liu","doi":"10.1016/j.drup.2024.101160","DOIUrl":"10.1016/j.drup.2024.101160","url":null,"abstract":"<div><div>Immunotherapy has revolutionized cancer treatment, yet the efficacy of immunotherapeutic approaches remains limited. Resistance to ferroptosis is one of the reasons for the poor therapeutic outcomes in tumors with Kelch-like ECH-associated protein 1 (KEAP1) mutations. However, the specific mechanisms by which KEAP1-mutant tumors resist immunotherapy are not fully understood. In this study, we showed that the loss of function in KEAP1 results in resistance to ferroptosis. We identified NAD(P)H Quinone Dehydrogenase 1 (NQO1) as a transcriptional target of nuclear factor erythroid 2–related factor 2 (NRF2) and revealed that inducing NQO1-mediated ferroptosis in KEAP1-deficient tumors triggers an antitumor immune cascade. Additionally, it was found that NQO1 protein levels could serve as a candidate biomarker for predicting sensitivity to immunotherapy in clinical tumor patients. We validated these findings in several preclinical tumor models. Overall, KEAP1 mutations define a unique disease phenotype, and targeting its key downstream molecule NQO1 offers new hope for patients with resistance to immunotherapy.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101160"},"PeriodicalIF":15.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142552011","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":"Ning Li ,&nbsp;Ya-Jie Sun ,&nbsp;Li-Yun Huang ,&nbsp;Rong-Rong Li ,&nbsp;Jun-Sheng Zhang ,&nbsp;Ai-Hua Qiu ,&nbsp;Jing Wang ,&nbsp;Lu Yang","doi":"10.1016/j.drup.2024.101161","DOIUrl":"10.1016/j.drup.2024.101161","url":null,"abstract":"<div><h3>Aims</h3><div>Acquired resistance to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) frequently emerges, and CDK4/6i-containing therapies in triple-negative breast cancer (TNBC) remain to be determined.</div></div><div><h3>Methods</h3><div>RNA-sequencing, cell viability analysis, immunoblotting, siRNA transfection et al. were used to investigate and verify the resistance mechanism. BALB/c nude mice xenograft models and spontaneous MMTV-PyMT models were used to explore in vivo efficacy.</div></div><div><h3>Results</h3><div>The mTOR pathway was activated in acquired CDK4/6i-resistant cells and inhibition of mTORC1 restored the sensitivity. While fasting-mimicking diet (FMD) enhances the activity of anticancer agents by inhibiting the mTORC1 signaling, we assessed FMD and found that FMD restored the sensitivity of CDK4/6i-resistant cells to abemaciclib and potentiated the anti-tumor activity of CDK4/6i in TNBC. The anti-tumor effects of FMD and/or CDK4/6i were accompanied by the downregulation of S6 phosphorylation. FMD cooperated with CDK4/6i to suppress the levels of IGF1 and RAS. The combination of FMD and abemaciclib also led to a potent inhibition of tumor growth in spontaneous transgenic MMTV-PyMT mouse models.</div></div><div><h3>Conclusions</h3><div>Our data demonstrate that FMD overcomes resistance and potentiates the anti-tumor effect of CDK4/6i by inhibiting mTORC1 signaling via lowering the levels of IGF1 and RAS, providing the rationale for clinical investigation of a potential FMD-CDK4/6i strategy in breast cancer.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"78 ","pages":"Article 101161"},"PeriodicalIF":15.8,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578202","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":"Comprehensive metabolomic analysis identifies key biomarkers and modulators of immunotherapy response in NSCLC patients","authors":"Se-Hoon Lee ,&nbsp;Sujeong Kim ,&nbsp;Jueun Lee ,&nbsp;Yunjae Kim ,&nbsp;Yanghyun Joo ,&nbsp;Jun-yeong Heo ,&nbsp;Heeyeon Lee ,&nbsp;Charles Lee ,&nbsp;Geum-Sook Hwang ,&nbsp;Hansoo Park","doi":"10.1016/j.drup.2024.101159","DOIUrl":"10.1016/j.drup.2024.101159","url":null,"abstract":"<div><div>Although immune checkpoint inhibitors (ICIs) have revolutionized immuno-oncology with effective clinical responses, only 30 to 40% of patients respond to ICIs, highlighting the need for reliable biomarkers to predict and enhance therapeutic outcomes. This study investigated how amino acid, glycolysis, and bile acid metabolism affect ICI efficacy in non-small cell lung cancer (NSCLC) patients. Through targeted metabolomic profiling and machine learning analysis, we identified amino acid metabolism as a key factor, with histidine (His) linked to favorable outcomes and homocysteine (HCys), phenylalanine (Phe), and sarcosine (Sar) linked to poor outcomes. Importantly, the His/HCys+Phe+Sar ratio emerges as a robust biomarker. Furthermore, we emphasize the role of glycolysis-related metabolites, particularly lactate. Elevated lactate levels post-immunotherapy treatment correlate with poorer outcomes, underscoring lactate as a potential indicator of treatment efficacy. Moreover, specific bile acids, glycochenodeoxycholic acid (GCDCA) and taurolithocholic acid (TLCA), are associated with better survival and therapeutic response. Particularly, TLCA enhances T cell activation and anti-tumor immunity, suggesting its utility as a predictive biomarker and therapeutic agent. We also suggest a connection between gut microbiota and TLCA levels, with the Eubacterium genus modulating this relationship. Therefore, modulating specific metabolic pathways—particularly amino acid, glycolysis, and bile acid metabolism—could predict and enhance the efficacy of ICI therapy in NSCLC patients, with potential implications for personalized treatment strategies in immuno-oncology.</div></div><div><h3>One sentence summary</h3><div>Our study identifies metabolic biomarkers and pathways that could predict and enhance the outcomes of immune checkpoint inhibitor therapy in NSCLC patients</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101159"},"PeriodicalIF":15.8,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142416324","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":"Novel mobile colistin resistance gene mcr-4.9 in Vibrio cholerae from migratory birds","authors":"Weishuai Zhai ,&nbsp;Hanzhang Cai ,&nbsp;Dongyan Shao,&nbsp;Xiaojie Yu,&nbsp;Xiong Zhu,&nbsp;Dejun Liu,&nbsp;Zhangqi Shen,&nbsp;Shaolin Wang,&nbsp;Jijun Kang,&nbsp;Congming Wu,&nbsp;Jianzhong Shen,&nbsp;Yang Wang,&nbsp;Lu Liu","doi":"10.1016/j.drup.2024.101157","DOIUrl":"10.1016/j.drup.2024.101157","url":null,"abstract":"","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101157"},"PeriodicalIF":15.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142407193","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":"Acetate utilization promotes hormone therapy resistance in prostate cancer through neuroendocrine differentiation","authors":"Dajun Gao ,&nbsp;Yanting Shen ,&nbsp;Lingfan Xu ,&nbsp;Yi Sun ,&nbsp;Hailiang Hu ,&nbsp;Bin Xu ,&nbsp;Zhong Wang ,&nbsp;Huan Xu","doi":"10.1016/j.drup.2024.101158","DOIUrl":"10.1016/j.drup.2024.101158","url":null,"abstract":"<div><h3>Aims</h3><div>Tumor fatty acid (FA) metabolic plasticity plays a pivotal role in resistance to therapy and poses limitations to anticancer strategies. In this study, our aim is to uncover the role of acetate metabolism in neurodifferentiation (NED)-mediated castration-resistant prostate cancer (CRPC).</div></div><div><h3>Methods</h3><div>We conducted analyses using LC-MS/MS on clinical prostate cancer tissue before and after hormone therapy. We established tumor xenograft mouse models, primary tumor cells, and human-derived organoids to detect the novel mechanism of NED and to identify potential therapies.</div></div><div><h3>Results</h3><div>The hormone therapy-induced upregulation of acetate metabolism was mediated by acyl-CoA synthetase short-chain family member 2 (ACSS2), which increased c-MYC expression for NED induction. Notably, combined treatment with an ACSS2 inhibitor and enzalutamide significantly reduced the xenograft tumor volume.</div></div><div><h3>Conclusion</h3><div>Our findings uncovered the critical role of acetate metabolism in NED-mediated CRPC and suggest that ACSS2 inhibitors may represent a novel, low-toxicity strategy when combined with hormone therapy for treating patients with NED-mediated CRPC.</div></div>","PeriodicalId":51022,"journal":{"name":"Drug Resistance Updates","volume":"77 ","pages":"Article 101158"},"PeriodicalIF":15.8,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142416323","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}