Medicinal Research Reviews最新文献

{"title":"Opportunities and Challenges in Clinical and Preclinical Drug Development for Mycobacterium marinum.","authors":"Qian-Qian Jing, Wen-Hui Wang, Qun Zhang, Tong-Yi Xu, Mei-Yan Wei, Chang-Lun Shao","doi":"10.1002/med.70126","DOIUrl":"https://doi.org/10.1002/med.70126","url":null,"abstract":"<p><p>Over recent decades, non-tuberculous mycobacterial infections have increased significantly. Mycobacterium marinum, a widely distributed environmental pathogen, can cause cutaneous and invasive diseases in humans and aquatic animals. Over the past century, our understanding of this pathogen has evolved from early descriptions of \"swimming pool granuloma\" to recognition of its intracellular lifestyle, granulomatous host responses, and genetic and functional similarities to Mycobacterium tuberculosis. Despite these advances, clinical management remains challenging. Current regimens are largely extrapolated from anti-tuberculous therapy. These regimens show variable efficacy and require prolonged treatment durations, and there is a near-total absence of randomized controlled trials specifically for M. marinum. The emergence of intrinsic and acquired resistance further complicates treatment decisions. On the preclinical front, drug screening using M. marinum as a surrogate model for tuberculosis has increased substantially over the past two decades, yet the translation of candidate compounds to clinical use remains slow. This Review examines the opportunities and persistent challenges in drug development for M. marinum over the past century, tracing the evolutionary trajectory from empirical combination therapy to mechanism‑based drug discovery. It outlines the pathogenic mechanisms of M. marinum, evaluates the resistance profiles of current clinical drugs and treatment regimens under clinical investigation, and introduces promising small‑molecule compounds. We also highlight critical knowledge gaps, including the near-total absence of dedicated clinical trials for M. marinum, the lack of predictive animal models, poorly defined compound targets, and insufficient surveillance of drug resistance. Addressing these gaps is essential to translate preclinical progress into tangible clinical benefit and to close the long‑standing translational gap in this field.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149356984","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":"Metal-Organic Frameworks for Cancer Therapy: From Therapeutic Intervention to Monitoring and Efficacy Feedback.","authors":"Zikang Hu, Ping Wang, Cheng Yang, Senyao Meng, Yibin Hou, Huawei Li, Hongrun Gao, Zhenxing Li, Lumin Wang","doi":"10.1002/med.70125","DOIUrl":"https://doi.org/10.1002/med.70125","url":null,"abstract":"<p><p>Metal-organic frameworks (MOFs) can form a multifunctional platform for cancer therapy due to their tunable metal nodes, designable organic ligands, large surface areas, and controllable pore architectures. These features enable MOFs not only to serve as carriers for drugs, nucleic acids, and diverse therapeutic agents, but also to participate directly in local therapeutic processes through photodynamic, photothermal, and chemodynamic effects. MOF-based platforms contribute to improved loading capacity, microenvironment responsiveness, catalytic activity, and local therapeutic efficacy, which have been widely explored in drug delivery, photodynamic therapy, photothermal therapy, chemodynamic therapy, and combination therapy recently. MOFs can also achieve tumor localization, in vivo distribution tracking, tumor marker identification, microenvironment monitoring, and treatment effect evaluation through imaging and biosensing functions. This review systematically summarizes recent advances of MOFs in cancer treatment, focusing on their roles in major therapeutic strategies and their potential as a comprehensive treatment platform that integrates treatment, monitoring, and feedback. The current challenges restricting their clinical translation are also comprehensively discussed, including issues related to the complex in vivo mechanism of action, stability, safety, and the consistency of material large-scale preparation. Furthermore, future perspectives and development directions of advanced MOF-based therapeutic platforms are prospected.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316503","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":"Advances in Traditional Chinese Medicine for Diabetic Glaucoma: A Systematic Review From Holistic Pathogenesis to Multi-Target Interventions.","authors":"Jinshen Liu, Yujia Yu, Chen Hu, Feng Cheng, Chunhan Feng, Jie Bao, Xiangqu Yu, Zhao Xia, Rao Ding, Zhonghui Li, Jiaqi Chen, Jiamin Zhou, Hui Zhang, Xiang Li","doi":"10.1002/med.70085","DOIUrl":"10.1002/med.70085","url":null,"abstract":"<p><p>Diabetic glaucoma, a severe microvascular and neurodegenerative complication of diabetes, involves complex pathological mechanisms including chronic hyperglycemia‑induced oxidative stress, inflammatory responses, microcirculatory disturbances, and retinal ganglion cell (RGC) apoptosis. While conventional Western medicine has achieved significant success in intraocular pressure (IOP) control, it faces challenges in providing long‑term neuroprotection and delaying disease progression. Traditional Chinese Medicine (TCM), guided by its holistic concept and treatment based on syndrome differentiation, demonstrates unique advantages through multi-component, multi‑target, and multi‑pathway synergistic regulation. This review systematically elucidates the TCM pathogenesis evolution pattern of \"deficiency leading to stasis, ocular collateral damage\" in diabetic glaucoma and establishes correlation networks between TCM syndrome types and modern pathological mechanisms. Integrating epidemiological evidence, we analyze the core mechanisms of representative Chinese herbs and formulas-including Ginkgo biloba extract, indirubin‑related components, and the Si‑Hua formula-in exerting antioxidant, anti‑inflammatory, microcirculation‑improving, and direct neuroprotective effects through regulation of key signaling pathways such as PI3K/AKT, Nrf2, and NF‑κB. Importantly, this article employs network pharmacology methods to visually present the synergistic \"component‑target‑pathway\" interaction network of the Si‑Hua formula, and introduces a quantitative comparison of the regulatory intensity of key herbal components on signaling pathways. We also discuss the chemical structures of major secondary metabolites from these herbs and the principles of reverse pharmacology that connect TCM to modern drug discovery. By quantitatively evaluating the regulatory intensity of key herbal components on signaling pathways and exploring the interventional potential of TCM in emerging mechanisms like ferroptosis (Figure 9), this review aims to establish a comprehensive scientific framework for TCM prevention and treatment of diabetic glaucoma, providing solid academic support for the modernization and internationalization of TCM.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":"1990-2012"},"PeriodicalIF":13.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468012","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":"Beyond Bioenergetics: Moonlighting Functions of F₁F_O-ATPase From ATP Synthesis to an ATP-Wasting Death Switch.","authors":"Salvatore Nesci","doi":"10.1002/med.70088","DOIUrl":"10.1002/med.70088","url":null,"abstract":"<p><p>Mitochondrial F₁F_O-ATPase is classically viewed as the \"splendid\" rotary nanomachine that sustains life by converting the proton-motive force (pmf) into ATP. Yet this same complex can adopt a second, context-dependent function that links bioenergetics to cell fate. When oxygen becomes limiting during ischemia, stroke, hypoxia, or anoxia, respiratory chain activity declines, pmf collapses, and the enzyme reverses direction: ATP hydrolysis drives rotor turnover and pumps H⁺ across the inner mitochondrial membrane to partially restore pmf. This reverse mode can be protective by preserving membrane potential and basic mitochondrial homeostasis, but it also imposes a severe energetic burden on the cell. A key determinant of whether F₁F_O-ATPase acts as an energy-conserving or energy-dissipating machine is the identity of the catalytic divalent cation. Under physiological conditions, Mg²⁺ supports efficient, reversible ATP synthesis/hydrolysis. In pathology, mitochondrial Ca²⁺ overload may replace Mg²⁺ at catalytic sites, shifting catalysis toward ATP hydrolysis and promoting an ATP-wasting state that triggers mitochondrial permeability transition pore (mPTP) formation and regulated cell death. Thus, ATP hydrolysis by F₁F_O-ATPase beyond regulation by pmf and inhibitory proteins such as IF1, cation cofactor selection emerges as a decisive switch that repurposes the enzyme from \"enzyme of life\" to \"enzyme of death.\" Here, this cofactor-dependent reversibility is framed as a moonlighting role of F₁F_O-ATPase, integrating energy conversion with death signaling. Conceptual questions are outlined to resolve current debate and to exploit this switch for therapeutic insight.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":"2013-2016"},"PeriodicalIF":13.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429432","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":"SHP2 in Cancer: From Tumor Biology to Therapeutic Targeting.","authors":"Maryam Jama, Michael Overduin, Khaled H Barakat","doi":"10.1002/med.70119","DOIUrl":"10.1002/med.70119","url":null,"abstract":"<p><p>SHP2 is a tyrosine phosphatase that mediates intracellular signaling downstream of transmembrane receptors regulated by a pair of src homology 2 (SH2) domains. Its overexpression and mutation are pivotal in driving tumor progression by influencing various cancer's fundamental characteristics, such as metastasis, DNA repair, angiogenesis, immunosuppression, and telomere extension. SHP2 acts as a convergent node of oncogenic signaling pathways including MAPK, PI3K-AKT, VEGF, JAK-STAT making it an attractive target for cancer therapeutics. Preclinical studies demonstrate that SHP2 allosteric inhibitors in combination with EGFR, PD-1, KRAS, or MEK inhibitors, show potent antitumour activity and effectively overcome adaptive resistance beyond conventional therapies. Multiple SHP2 allosteric inhibitors are currently in clinical trials to assess their effectiveness, safety, and tolerability in treating various malignancies. Despite these advancements, SHP2's complex role presents challenges for the efficacy of SHP2 monotherapy and in the context of SHP2 mutants. Current allosteric inhibitors lack a well-defined mode of action for selectively targeting hyperactive SHP2 in malignancies. Moreover, a deeper understanding of SHP2's regulatory mechanisms and its interactions within the tumor microenvironment is needed to optimize SHP2-directed therapies. This review highlights these challenges, with a focus on SHP2 regulation, disease-associated mutants, its role in cancer cells and the tumor microenvironment, current and future therapeutic prospects.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149293523","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":"Is the Adipose Tissue Vascular System a Therapeutic Target in the Era of Precision Medicine?","authors":"Daniela Rosendo-Silva, Diana Sousa, Carina C Magalhães, Paulo Matafome","doi":"10.1002/med.70121","DOIUrl":"https://doi.org/10.1002/med.70121","url":null,"abstract":"<p><p>Changes in adipose tissue function, morphology, and secretome during obesity impair endothelial cell function and lead to persistent hypoxia and unresolved inflammation, which will contribute to whole-body endothelial dysfunction and chronic low-grade inflammation. Indeed, visceral fat dysfunction is more associated with insulin resistance than body mass index. Understanding the molecular landscape of visceral adipose tissue is pivotal to better comprehending an individual's metabolic health and even predicting future health outcomes. Single-cell studies are showing that the heterogeneity of the adipose depots relies not only on the diversity of cellular types, but also on the differential gene expression and secretome (even within the same cellular type). Adipose tissue cells respond in an orchestrated manner to adequate tissue plasticity to the current energetic needs, either by expanding or retracting. This response relies on coordinated regulation of adipocyte metabolism, angiogenesis, extracellular matrix remodeling, and short-term inflammation and oxidative stress. In this review, we look closely at cell intercommunication in the fat depot and discuss the main events occurring in adipose tissue associated with the progressive tissue dysfunction that happens in obesity: adipocyte metabolism, angiogenesis, and extracellular matrix remodeling. Furthermore, we discuss the modulation of angiogenesis as a potential therapeutic target in obesity by gathering relevant recent research and collectively discuss the metabolic implications of inhibiting or promoting angiogenesis at different stages of the metabolic sequelae of obesity.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149284273","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":"Recent Progress on Limonoids: The Potential, Challenges, and Insights of Chemistry and Biology.","authors":"Tianze Li, Min Lv, Hui Xu","doi":"10.1002/med.70120","DOIUrl":"https://doi.org/10.1002/med.70120","url":null,"abstract":"<p><p>Limonoids are an important class of highly oxygenated triterpenoids containing a distinctive 4,4,8-trimethyl-17-furanylsteroid skeleton. To date, over 2700 members, including azadirachtin, toosendanin, limonin, obacunone, nomilin, harrisonin, nimbolide, gedunin, salannin, nimbin, khayanolide, xylocarpin, swietenine, rocaglamide, trichilin, vilasinin, etc., have been isolated from citrus fruits and the plants of the Rutaceae and Meliaceae families. They play a significant role in the discovery of novel drug and pesticide candidates owing to their wide range of biological activities, such as protective, anti-inflammatory, anti-cancer, antimicrobial, and insecticidal properties. Therefore, their potential, challenges, and insights into the chemistry and biology of triterpenoid-type limonoids have recently garnered much attention. The focus of this review is not only to summarize the isolation, total synthesis, and structural modifications of limonoid-type natural products as potential therapeutic and pesticidal agents, but also to highlight the underlying mechanisms of their pharmacological effects from 2017 to 2025. Noteworthily, perspectives were given on the limonoid-type compounds as leads for further development of novel drugs and agrochemicals, and their applications in the future. Hopefully, this review can serve as a comprehensive reference for future research on limonoids and their derivatives in the pharmaceutical and agricultural fields.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149284267","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 Landscape of Radiopharmaceutical Innovation: Emerging Targets and Molecules.","authors":"Can Liu, Siqi Zhang, Xuekai Song, Jieting Shen, Linger Li, Tongtong Zhang, Xindan Hu, Quan Zuo, Qichen Hu, Jie Yan, Rui Wang, Kuan Hu","doi":"10.1002/med.70115","DOIUrl":"https://doi.org/10.1002/med.70115","url":null,"abstract":"<p><p>Following the recent commercial success of FDA‑approved targeted radiopharmaceuticals, an increasing number of pipeline candidates have advanced into clinical trials. Analyzing their development timelines, study durations, and clinical outcomes enables researchers to discern current trends and identify agents with promising commercial potential. This review provides a global overview of radiopharmaceutical development, with a focus on disease targets, radionuclides, ligand platforms, and clinical indications. Our analysis reveals that, alongside established targets such as PSMA and SSTR, emerging targets-including CAIX, GPC3, and DLL3-are broadening the spectrum of cancers amenable to radiopharmaceutical intervention. Concurrently, the adoption of therapeutic radionuclides with potent antitumor efficacy, particularly ²²⁵Ac, ²¹²Pb, and ¹⁶¹Tb, is gaining momentum. Examination of unsuccessful cases highlights persistent challenges, notably radionuclide supply constraints and in vivo toxicity. Encouragingly, regulatory frameworks are becoming more flexible to expedite development, and first‑in‑human studies offer an early opportunity to eliminate poor‑performing candidates before large‑scale trials. Nevertheless, there remains an urgent need for standardized clinical trial protocols to bridge the gap between clinical investigation and regulatory evaluation. Overall, this review aims to bridge the informational and technological gaps among laboratory-based basic research, hospital-based clinical trials, and industrial development, thereby offering insights for future progress and assisting in overcoming the obstacles facing radiopharmaceutical discovery.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149284322","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":"Chemical Modulation of the cGAS-STING-ENPP1 Axis: Medicinal Chemistry and Clinical Perspective.","authors":"Akash U Shinde, Sandip B Bharate","doi":"10.1002/med.70118","DOIUrl":"https://doi.org/10.1002/med.70118","url":null,"abstract":"<p><p>The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway plays a fundamental role in innate immune signaling and has emerged as a therapeutically relevant pathway across cancer, inflammatory, and autoimmune diseases. Herein, we provide a comprehensive medicinal chemistry-focused overview of both activation and inhibition of the cGAS-STING pathway, focusing on three druggable therapeutic targets, cGAS, STING, and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). The translational maturity of these targets differs substantially, with STING being the most clinically advanced, whereas cGAS and ENPP1 remain emerging targets supported predominantly by preclinical evidence, with the advancement of a few inhibitors into early-stage clinical trials. The biological rationale for pathway modulation, along with modulators, is discussed with emphasis on active site interactions, scaffold diversity, their activity profiles, structure-activity relationships, species selectivity, and in vivo efficacy. The particular focus is on patent literature and advanced-stage molecules, discussing their ADME properties, pharmacokinetics, and clinical development status. Although STING agonists have achieved a larger reach in clinical trials within this pathway, recent developments suggest that cGAS inhibitors and ENPP1 inhibitors hold a greater promise for future clinical success. In summary, this review provides insights into medicinal chemistry and translational challenges and future opportunities for rational drug design to guide next-generation modulators of the cGAS-STING-ENPP1 axis.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149260138","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":"Landscape of Endocytic Effectors for Extracellular Targeted Protein Degradation.","authors":"Yuxin Liang, Shiqun Shao, Yuping Chen, Jingxing Si, Youqing Shen","doi":"10.1002/med.70112","DOIUrl":"https://doi.org/10.1002/med.70112","url":null,"abstract":"<p><p>Extracellular targeted protein degradation (eTPD) has emerged as a new strategy for regulating the abundance and activity of extracellular and membrane proteins, with prominent potential to address traditionally undruggable targets in oncology, autoimmune diseases, and neurodegenerative disorders. Most eTPD platforms employ heterobifunctional chimeras that link proteins of interest (POIs) to specific endocytic effectors (EEs), either lysosome-targeting receptors (LTRs) or membrane-bound E3 ubiquitin ligases, to direct POIs to lysosomes for degradation. Since EE engagement dictates cellular uptake, intracellular trafficking route, recycling kinetics, tissue specificity, and overall degradation efficacy, one compelling topic in the eTPD community is to identify effective EEs for developing new eTPD tools. To inform new EE discovery, here we review the current landscape of EEs utilized in eTPD. We categorize LTRs based on their ligand specificity and discuss representative receptors including the cation-independent mannose-6-phosphate receptor (CI-M6PR) and the asialoglycoprotein receptor (ASGPR), with emphasis on their internalization and trafficking characteristics. For each category, we highlight representative degrader designs and assess how degrader attributes such as ligand format, valency, molecular size, linker chemistry, and linker length influence trafficking properties and degradation efficacy. We further discuss cell-surface E3 ligase-based degraders and emerging EE-independent strategies-receptor-independent membrane-interacting modalities exemplified by cell-penetrating peptides-that exploit alternative endocytic pathways without relying on specific effector expression. Finally, we discuss key challenges and future opportunities for integrating effector biology with degrader engineering to advance eTPD toward therapeutic drug discovery.</p>","PeriodicalId":207,"journal":{"name":"Medicinal Research Reviews","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149236322","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}