Acta Pharmaceutica Sinica. B最新文献

{"title":"Microglial APOE4 promotes neuron degeneration in Alzheimer's disease through inhibition of lipid droplet autophagy","authors":"Meng Mao , Xiwen Ma , Xiaochuan Wang , Jianping Ye","doi":"10.1016/j.apsb.2024.10.009","DOIUrl":"10.1016/j.apsb.2024.10.009","url":null,"abstract":"","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 1","pages":"Pages 657-660"},"PeriodicalIF":14.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388373","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":"Natural product mediated mesenchymal–epithelial remodeling by covalently binding ENO1 to degrade m6A modified β-catenin mRNA","authors":"Tianyang Chen ,&nbsp;Guangju Liu ,&nbsp;Sisi Chen ,&nbsp;Fengyuan Zhang ,&nbsp;Shuoqian Ma ,&nbsp;Yongping Bai ,&nbsp;Quan Zhang ,&nbsp;Yahui Ding","doi":"10.1016/j.apsb.2024.07.013","DOIUrl":"10.1016/j.apsb.2024.07.013","url":null,"abstract":"<div><div>The transition of cancer cells from epithelial state to mesenchymal state awarded hepatocellular carcinoma (HCC) stem cell properties and induced tumorigenicity, drug resistance, and high recurrence rate. Reversing the mesenchymal state to epithelial state by inducing mesenchymal–epithelial remodeling could inhibit the progression of HCC. Using high-throughput screening, chrysin was selected from natural products to reverse epithelial-mesenchymal transition (EMT) by selectively increasing CDH1 expression. The target identification suggested chrysin exerted its anti-HCC effect through covalently and specifically binding threonine 205 (Thr205) of alpha-enolase (ENO1). For the first time, we revealed that ENO1 bound <em>β</em>-catenin mRNA, and recruited YTHDF2 to identify the m6A modified <em>β</em>-catenin in the 3′-UTR region to degrade <em>β</em>-catenin mRNA. Eventually, the CDH1 gene expression was improved through the regulation of <em>β</em>-catenin mRNA. ENO1/<em>β</em>-catenin mRNA interaction might be a promising target for cellular plasticity reprogramming. Moreover, chrysin could mediate mesenchymal‒epithelial remodeling through increasing degradation of <em>β</em>-catenin mRNA by promoting the binding of ENO1 and <em>β</em>-catenin mRNA. To the best of our knowledge, chrysin is the first reported small molecule inducing <em>β</em>-catenin mRNA degradation through binding to ENO1. The water-soluble derivative of chrysin may be a natural product-derived lead compound for circumventing metastasis, recurrence, and drug resistance of HCC by mediating mesenchymal‒epithelial remodeling.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 1","pages":"Pages 467-483"},"PeriodicalIF":14.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141696062","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":"Cyclometalated iridium(III) complex based on isoquinoline alkaloid synergistically elicits the ICD response and IDO inhibition via autophagy-dependent ferroptosis","authors":"Yuan Lu ,&nbsp;Shan-Shan Wang ,&nbsp;Meng-Ya Li ,&nbsp;Rong Liu ,&nbsp;Meng-Fan Zhu ,&nbsp;Liang-Mei Yang ,&nbsp;Feng-Yang Wang ,&nbsp;Ke-Bin Huang ,&nbsp;Hong Liang","doi":"10.1016/j.apsb.2024.06.017","DOIUrl":"10.1016/j.apsb.2024.06.017","url":null,"abstract":"<div><div>The development of anticancer drugs to treat triple-negative breast cancer (TNBC) is an ongoing challenge. Immunogenic cell death (ICD) has garnered considerable interest worldwide as a promising synergistic modality for cancer chemoimmunotherapy. However, only few drugs or treatment modalities can trigger an ICD response and none of them exert a considerable clinical effect against TNBC. Therefore, new agents with potentially effective chemoimmunotherapeutic response are required. In this study, five new cyclometalated Ir(III) complexes containing isoquinoline alkaloid CˆN ligands were designed and synthesized. Among them, <strong>Ir-1</strong> exhibited the highest <em>in vitro</em> cytotoxicity. Mechanistically, <strong>Ir-1</strong> could trigger autophagy-dependent ferroptosis and a subsequent ferroptosis-dependent ICD response as well as indoleamine 2,3-dioxygenase (IDO) inhibition <em>via</em> reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress in MDA-MB-231 cells. When immunocompetent BALB/c mice were vaccinated with <strong>Ir-1</strong>-treated dying TNBC cells, antitumor CD8⁺ T-cell response and Foxp3⁺ T-cell depletion were induced, resulting in long-lasting antitumor immunity in TNBC cells. Moreover, combination therapy with <strong>Ir-1</strong> and anti-PD1 could substantially augment <em>in vivo</em> therapeutic effects. Based on these results, <strong>Ir-1</strong> is a promising candidate for chemoimmunotherapy against TNBC and its effects are mediated synergistically <em>via</em> ICD induction and IDO blockage.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 1","pages":"Pages 424-437"},"PeriodicalIF":14.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141528644","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":"Caffeic acid-vanadium nanozymes treat skin flap ischemia-reperfusion injury through macrophage reprogramming and the upregulation of X-linked inhibitors of apoptotic proteins","authors":"Xinyu Zhao ,&nbsp;Jie Shan ,&nbsp;Hanying Qian ,&nbsp;Xu Jin ,&nbsp;Yiwei Sun ,&nbsp;Jianghao Xing ,&nbsp;Qingrong Li ,&nbsp;Xu-Lin Chen ,&nbsp;Xianwen Wang","doi":"10.1016/j.apsb.2024.08.022","DOIUrl":"10.1016/j.apsb.2024.08.022","url":null,"abstract":"<div><div>Ischemia-reperfusion (I/R) injury following skin flap transplantation is a critical factor leading to flap necrosis and transplant failure. Antagonizing inflammatory responses and oxidative stress are regarded as crucial targets for mitigating reperfusion injury and enhancing flap survival. In this study, caffeic acid-vanadium metal polyphenol nanoparticles (CA-V NPs) were prepared for the treatment of skin flap ischemia and reperfusion. This study was conducted using a one-step method to prepare new types of CA-V NPs with uniform sizes and stable structures. <em>In vitro</em>, the CA-V NPs exhibited CAT-like and SOD-like activities and could effectively scavenge ROS, generate oxygen, and alleviate oxidative stress. In the H₂O₂-induced cellular oxidative stress model, CA-V NPs effectively reduced ROS levels and inhibited apoptosis through the XIAP/Caspase-3 pathway. In the cellular inflammation model induced by LPS combined with IFN-<em>γ</em>, CA-V NPs reprogrammed macrophage polarization toward the M2 phenotype and reduced inflammatory responses by reducing the expression of the chemokines CCL4 and CXCL2. In addition, animal experiments have shown that CA-V NPs can alleviate oxidative stress in skin flap tissues, inhibit apoptosis, promote angiogenesis, and ultimately improve the survival rate of skin flaps. CA-V NPs provide a new target and strategy for the treatment of flap I/R injury.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 1","pages":"Pages 592-610"},"PeriodicalIF":14.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142186904","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":"Unlocking the role of wound microbiome in diabetic, burn, and germ-free wound repair treated by natural and synthetic scaffolds","authors":"Zeyu Xu ,&nbsp;Lixiang Zhang ,&nbsp;Qinghan Tang ,&nbsp;Chenxi Yang ,&nbsp;Xiaotong Ding ,&nbsp;Ziyu Wang ,&nbsp;Rizhong Huang ,&nbsp;Ruihan Jiang ,&nbsp;Joannake Maitz ,&nbsp;Huaikai Shi ,&nbsp;Xin Yan ,&nbsp;Mei Dong ,&nbsp;Jun Chen ,&nbsp;Yiwei Wang","doi":"10.1016/j.apsb.2024.08.024","DOIUrl":"10.1016/j.apsb.2024.08.024","url":null,"abstract":"<div><div>In current clinical practice, various dermal templates and skin substitutes are used to enhance wound healing. However, the role of wound commensal microbiome in regulating scaffold performance and the healing process remains unclear. In this study, we investigated the influence of both natural and synthetic scaffolds on the wound commensal microbiome and wound repair in three distinct models including diabetic wounds, burn injuries, and germ-free (GF) wounds. Remarkably, synthetic electrospun polycaprolactone (PCL) scaffolds were observed to positively promote microbiome diversity, leading to enhanced diabetic wound healing compared to the natural scaffolds Integra® (INT) and MatriDerm® (MAD). In contrast, both natural and synthetic scaffolds exhibited comparable effects on the diversity of the microbiome and the healing of burn injuries. In GF wounds with no detectable microorganisms, a reversed healing rate was noted showing natural scaffold (MAD) accelerated wound repair compared to the open or the synthetic scaffold (PCL) treatment. Furthermore, the response of the wound commensal microbiome to PCL scaffolds appears pivotal in promoting anti-inflammatory factors during diabetic wound healing. Our results emphasize that the wound commensal microbiome, mediated by different scaffolds plays an important role in the wound healing process.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 1","pages":"Pages 611-626"},"PeriodicalIF":14.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263633","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":"Cerebral endothelial 3-mercaptopyruvate sulfurtransferase improves ischemia-induced cognitive impairment via interacting with protein phosphatase 2A","authors":"Li Zhu ,&nbsp;Yi Huang ,&nbsp;Jing Jin ,&nbsp;Rongjun Zou ,&nbsp;Rui Zuo ,&nbsp;Yong Luo ,&nbsp;Ziqing Song ,&nbsp;Linfeng Dai ,&nbsp;Minyi Zhang ,&nbsp;Qiuhe Chen ,&nbsp;Yunting Wang ,&nbsp;Wei Wang ,&nbsp;Rongrong He ,&nbsp;Yang Chen","doi":"10.1016/j.apsb.2024.11.015","DOIUrl":"10.1016/j.apsb.2024.11.015","url":null,"abstract":"<div><div>The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H₂S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H₂S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Ac<em>α</em> in the brain endothelium. Mice with endothelium-specific null PP2A (PP2A^EC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing <em>Ppp2ca</em> rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST–H₂S signaling pathway. A robust reduction in endothelial MPST-dependent H₂S production followed PP2A deficiency. Exogenous H₂S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2A^EC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H₂S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 1","pages":"Pages 314-330"},"PeriodicalIF":14.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388190","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":"Real-time platelet P2Y12 receptor occupancy as a promising pharmacodynamics biomarker for bridging the gap between PK/PD of clopidogrel therapy","authors":"Haipeng Li ,&nbsp;Yueming Gu ,&nbsp;Yumeng Zhao ,&nbsp;Aiyun Xu ,&nbsp;Dong Sun ,&nbsp;Jingkai Gu","doi":"10.1016/j.apsb.2024.08.008","DOIUrl":"10.1016/j.apsb.2024.08.008","url":null,"abstract":"<div><div>Clopidogrel effectively inhibits platelet aggregation in response to ADP by irreversibly binding to the platelet P2Y₁₂ receptor through its active metabolite. However, the observed discrepancies between the pharmacokinetics (PK) and pharmacodynamics (PD) of clopidogrel present substantial challenges in individualizing of antiplatelet therapy. To address these challenges, a robust liquid chromatography–tandem mass spectrometry method has been developed to facilitate the real-time assessment of platelet P2Y₁₂ receptor occupancy. This method has been validated in animal models, providing a reliable link between individual PK profiles and PD effects. Target receptor occupancy offers a comprehensive overview of interindividual variations in clopidogrel metabolism, regulation of P2Y₁₂ receptor expression, and platelet turnover. Moreover, it directly correlates with the inhibitory effect on platelet aggregation. The levels of platelet P2Y₁₂ occupancy accurately reflect the extent of clinical factors influencing the PD of clopidogrel, including dosage, drug–drug interactions (DDI), and type 2 diabetes mellitus (T2DM). As a normalized metric, platelet P2Y₁₂ occupancy not only serves potential as a diagnostic tool for personalized clopidogrel therapy but also aids in elucidating the role of the P2Y₁₂ signaling pathway in cases of abnormal on-treatment platelet reactivity.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 1","pages":"Pages 484-493"},"PeriodicalIF":14.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142186941","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":"Nanoengineered cargo with targeted in vivo Foxo3 gene editing modulated mitophagy of chondrocytes to alleviate osteoarthritis","authors":"Manyu Chen ,&nbsp;Yuan Liu ,&nbsp;Quanying Liu ,&nbsp;Siyan Deng ,&nbsp;Yuhan Liu ,&nbsp;Jiehao Chen ,&nbsp;Yaojia Zhou ,&nbsp;Xiaolin Cui ,&nbsp;Jie Liang ,&nbsp;Xingdong Zhang ,&nbsp;Yujiang Fan ,&nbsp;Qiguang Wang ,&nbsp;Bin Shen","doi":"10.1016/j.apsb.2024.12.008","DOIUrl":"10.1016/j.apsb.2024.12.008","url":null,"abstract":"<div><div>Mitochondrial dysfunction in chondrocytes is a key pathogenic factor in osteoarthritis (OA), but directly modulating mitochondria <em>in vivo</em> remains a significant challenge. This study is the first to verify a correlation between mitochondrial dysfunction and the downregulation of the <em>FOXO3</em> gene in the cartilage of OA patients, highlighting the potential for regulating mitophagy <em>via FOXO3</em> gene modulation to alleviate OA. Consequently, we developed a chondrocyte-targeting CRISPR/Cas9-based <em>FOXO3</em> gene-editing tool (FoxO3) and integrated it within a nanoengineered ‘truck’ (NETT, FoxO3-NETT). This was further encapsulated in injectable hydrogel microspheres (FoxO3-NETT@SMs) to harness the antioxidant properties of sodium alginate and the enhanced lubrication of hybrid exosomes. Collectively, these FoxO3-NETT@SMs successfully activate mitophagy and rebalance mitochondrial function in OA chondrocytes through the <em>Foxo3</em> gene-modulated PINK1/Parkin pathway. As a result, FoxO3-NETT@SMs stimulate chondrocytes proliferation, migration, and ECM production <em>in vitro</em>, and effectively alleviate OA progression <em>in vivo</em>, demonstrating significant potential for clinical applications.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 1","pages":"Pages 571-591"},"PeriodicalIF":14.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388018","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":"“Relative symmetry with electronegativity of different key-groups” strategy for MRGPRX2 antagonist design and its effect on antigen-induced pulmonary inflammation","authors":"Jiayu Lu ,&nbsp;Zhaomin Xia ,&nbsp;Yongjing Zhang ,&nbsp;He Wang ,&nbsp;Wen Yang ,&nbsp;Siqi Wang ,&nbsp;Nan Wang ,&nbsp;Yun Liu ,&nbsp;Huaizhen He ,&nbsp;Cheng Wang ,&nbsp;Langchong He","doi":"10.1016/j.apsb.2024.11.023","DOIUrl":"10.1016/j.apsb.2024.11.023","url":null,"abstract":"<div><div>MRGPRX2 antagonists possess the potential for the treatment of allergic rhinitis, atopic dermatitis, and chronic urticaria. Previously, we identified a class of diaryl urea (DPU) MRGPRX2 antagonists with sub-micromolar IC₅₀ values <em>in vitro</em>. However, the structure–activity relationship remains unclear. Herein, we adopted a “relative symmetry with electronegativity of different key-groups” strategy for further modification of DPUs to achieve a promising MRGPRX2 antagonist with higher activity and safety. Electrostatic potential energy analysis and biological evaluation revealed that B-1023 and B-5023, that possess relatively symmetric electron-withdrawing substituents, remarkable inhibited mast cell degranulation at a sub-micromolar IC₅₀ <em>in vitro</em> and alleviated anaphylactic symptoms. Furthermore, B-1023, mitigated antigen-induced pulmonary inflammation (AIPI) in mice and competitively bonded to MRGPRX2. In summary, the “relative symmetry with electronegativity of different key-groups” strategy provided a drug design pattern for MRGPRX2 antagonists and identified promising antiallergic precursors for AIPI treatment.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 1","pages":"Pages 494-507"},"PeriodicalIF":14.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388194","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":"DiPTAC: A degradation platform via directly targeting proteasome","authors":"Yutong Tu ,&nbsp;Qian Yu ,&nbsp;Mengna Li ,&nbsp;Lixin Gao ,&nbsp;Jialuo Mao ,&nbsp;Jingkun Ma ,&nbsp;Xiaowu Dong ,&nbsp;Jinxin Che ,&nbsp;Chong Zhang ,&nbsp;Linghui Zeng ,&nbsp;Huajian Zhu ,&nbsp;Jiaan Shao ,&nbsp;Jingli Hou ,&nbsp;Liming Hu ,&nbsp;Bingbing Wan ,&nbsp;Jia Li ,&nbsp;Yubo Zhou ,&nbsp;Jiankang Zhang","doi":"10.1016/j.apsb.2024.09.003","DOIUrl":"10.1016/j.apsb.2024.09.003","url":null,"abstract":"","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 1","pages":"Pages 661-664"},"PeriodicalIF":14.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263510","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}