emerging therapies

新兴疗法
  • 文章类型: Journal Article
    心律失常包括一系列以异常心律为特征的病症,影响全球数百万人,并显著增加发病率和死亡率。这篇综述提供了在管理心律失常的当前做法和新兴疗法的全面分析。涵盖他们的定义,分类,流行病学,以及有效管理的重要性。它探索了各种心律失常的病理生理学,包括心律失常发生的机制,比如重新进入,自动性,并触发了活动。该评论详细介绍了最新的诊断工具,包括心电图,Holter监测,和电生理研究,并讨论了不同心律失常的临床表现,从室上性到心室型和缓慢性心律失常。我们研究了当前的药理学和非药理学治疗策略,如抗心律失常药物,导管消融,和设备治疗,强调它们的功效和局限性。此外,这篇综述深入研究了新兴的疗法,包括先进的导管消融技术,新型抗心律失常药,基因治疗,和创新的设备技术,如无引线起搏器和皮下植入式心脏复律除颤器(ICD)。在不同人群中管理心律失常的特殊考虑因素,包括儿科,老年人,孕妇,正在讨论。此外,这篇综述探讨了心律失常管理的未来方向,强调个性化医疗,人工智能应用,以及先进技术在诊断和治疗中的集成。通过综合当前的知识和前景,这项审查旨在增进了解并促进该领域的进步,最终改善患者心律失常的预后。
    Cardiac arrhythmias encompass a range of conditions characterized by abnormal heart rhythms, affecting millions globally and significantly contributing to morbidity and mortality. This review provides a comprehensive analysis of the current practices and emerging therapies in managing cardiac arrhythmias, covering their definition, classification, epidemiology, and the critical importance of effective management. It explores the pathophysiology underlying various arrhythmias, including the mechanisms of arrhythmogenesis, such as re-entry, automaticity, and triggered activity. The review details the latest diagnostic tools, including ECG, Holter monitoring, and electrophysiological studies, and discusses the clinical presentation of different arrhythmias, from supraventricular to ventricular types and bradyarrhythmias. We examine current pharmacological and non-pharmacological treatment strategies, such as antiarrhythmic drugs, catheter ablation, and device therapy, highlighting their efficacy and limitations. Furthermore, the review delves into emerging therapies, including advanced catheter ablation techniques, novel antiarrhythmic agents, gene therapy, and innovative device technologies like leadless pacemakers and subcutaneous implantable cardioverter-defibrillators (ICDs). Special considerations for managing arrhythmias in diverse populations, including pediatrics, the elderly, and pregnant women, are discussed. Additionally, the review explores future directions in arrhythmia management, emphasizing personalized medicine, artificial intelligence applications, and the integration of advanced technologies in diagnosis and treatment. By synthesizing current knowledge and prospects, this review aims to enhance understanding and promote advancements in the field, ultimately improving patient outcomes with cardiac arrhythmias.
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  • 文章类型: Journal Article
    心房颤动(AF)是一种以心房电活动不规则为特征的常见心律失常,对全球的患者管理和医疗保健系统构成重大挑战。非风湿性房颤,与风湿性心脏病引起的房颤不同,包括一系列病因,包括高血压,冠状动脉疾病,和结构性心脏异常。这篇综述探讨了管理非风湿性房颤的最新进展,包括诊断方法,药物治疗,创新的非药物干预措施。从传统心电图到高级成像模式的诊断策略与新兴的生物标志物和可穿戴技术一起进行了探索,以促进早期检测和管理。药理学管理选项,包括新型抗凝剂和节律控制剂,根据现行指南和最近的临床试验进行评估。非药物干预措施,如导管消融和基于器械的治疗,讨论了他们不断发展的技术和结果。针对不同患者人群的特殊考虑,包括老年人和运动员,被解决,强调个性化的方法来优化治疗结果。本综述以对未来AF管理方向的见解为结尾,强调基因治疗的有希望的途径,再生医学,和精准医学方法。通过综合最近的研究发现和临床创新,这篇综述提供了非风湿性房颤管理的动态景观的全面概述,为临床医生提供见解,研究人员,和医疗保健利益相关者。
    Atrial fibrillation (AF) is a prevalent cardiac arrhythmia characterized by irregular atrial electrical activity, posing significant challenges to patient management and healthcare systems worldwide. Non-rheumatic AF, distinct from AF due to rheumatic heart disease, encompasses a spectrum of etiologies, including hypertension, coronary artery disease, and structural heart abnormalities. This review examines the latest advancements in managing non-rheumatic AF, encompassing diagnostic approaches, pharmacological therapies, and innovative non-pharmacological interventions. Diagnostic strategies ranging from traditional electrocardiography to advanced imaging modalities are explored alongside emerging biomarkers and wearable technologies facilitating early detection and management. Pharmacological management options, including novel anticoagulants and rhythm control agents, are evaluated in light of current guidelines and recent clinical trials. Non-pharmacological interventions, such as catheter ablation and device-based therapies, are discussed regarding their evolving techniques and outcomes. Special considerations for diverse patient populations, including elderly individuals and athletes, are addressed, emphasizing personalized approaches to optimize therapeutic outcomes. The review concludes with insights into future directions for AF management, highlighting promising avenues in gene therapy, regenerative medicine, and precision medicine approaches. By synthesizing recent research findings and clinical innovations, this review provides a comprehensive overview of the dynamic landscape of non-rheumatic AF management, offering insights for clinicians, researchers, and healthcare stakeholders.
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  • 文章类型: Journal Article
    眼部表现通常是潜在系统性疾病的关键指标,提供有价值的诊断和预后信息。这篇综合综述旨在阐明眼部症状和全身状况之间复杂的相互作用。强调早期识别和跨学科合作在患者管理中的重要性。该综述涵盖了各种系统性疾病,包括心血管,自身免疫,传染性,神经学,内分泌,血液学,遗传,皮肤病学,胃肠,肝,肾,和结缔组织疾病,突出他们的具体眼部表现。诊断方法,包括眼科检查技术,成像模式,和实验室测试,进行了讨论,以提高诊断准确性。此外,审查概述了当前的管理和治疗策略,强调需要多学科的护理方法。还探讨了新兴疗法和未来的研究方向,强调在这一领域不断创新的必要性。这篇综述旨在改善临床实践,促进综合医疗保健,并通过提供全身性疾病中眼部表现的详细概述,最终提高患者的预后。
    Ocular manifestations often serve as critical indicators of underlying systemic diseases, providing valuable diagnostic and prognostic information. This comprehensive review aims to elucidate the complex interplay between ocular symptoms and systemic conditions, emphasising the importance of early recognition and interdisciplinary collaboration in patient management. The review encompasses various systemic diseases, including cardiovascular, autoimmune, infectious, neurological, endocrine, hematologic, genetic, dermatologic, gastrointestinal, hepatic, renal, and connective tissue disorders, highlighting their specific ocular manifestations. Diagnostic approaches, including ophthalmologic examination techniques, imaging modalities, and laboratory tests, are discussed to enhance diagnostic accuracy. Furthermore, the review outlines current management and treatment strategies, emphasising the need for a multidisciplinary approach to care. Emerging therapies and future research directions are also explored, underscoring the necessity of continued innovation in this field. This review aims to improve clinical practices, promote integrative healthcare, and ultimately enhance patient outcomes by providing a detailed overview of ocular manifestations in systemic diseases.
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  • 文章类型: Journal Article
    非结核分枝杆菌(NTM)感染由于其固有的多药耐药性和现有治疗的有限功效而成为重要的临床挑战。这些感染越来越普遍,需要新的和有效的治疗策略。
    这篇综述讨论了NTM感染的几个关键方面:i)发病机理和流行病学;ii)当前治疗方案的局限性和挑战;iii)新兴和替代治疗策略;iv)先进的药物递送系统,如纳米颗粒和外排泵抑制剂;v)创新的抗菌替代品,如抗菌肽,噬菌体疗法,和植物化学物质;和vi)其他潜在的治疗方式,如吸入一氧化氮,小分子,外科清创术,光疗,和免疫调节疗法。
    个性化医疗,先进的药物输送系统,和替代疗法为NTM治疗的未来带来了希望。早期准确鉴定NTM物种,通过改进的诊断方法,对于定制治疗方案至关重要。新兴疗法显示出对抗耐药NTM菌株的前景,但是克服临床试验等障碍,监管障碍,高生产成本至关重要。持续的研究和创新对于改善治疗效果和患者预后至关重要。
    UNASSIGNED: Nontuberculous mycobacteria (NTM) infections have emerged as a significant clinical challenge due to their intrinsic multidrug resistance and the limited efficacy of existing treatments. These infections are becoming increasingly prevalent, with a need for new and effective therapeutic strategies.
    UNASSIGNED: This review addresses several key aspects of NTM infections: i) pathogenesis and epidemiology; ii) the limitations and challenges of current treatment options; iii) emerging and alternative therapeutic strategies; iv) advanced drug delivery systems such as nanoparticles and efflux pump inhibitors; v) innovative antibacterial alternatives like antimicrobial peptides, bacteriophage therapy, and phytochemicals; and vi) other potential treatment modalities such as inhaled nitric oxide, small molecules, surgical debridement, phototherapy, and immunomodulatory therapy.
    UNASSIGNED: Personalized medicine, advanced drug delivery systems, and alternative therapies hold promise for the future of NTM treatment. Early and accurate identification of NTM species, enabled by improved diagnostic methods, is critical for tailoring treatment regimens. Emerging therapies show promise against drug-resistant NTM strains, but overcoming barriers like clinical trials, regulatory hurdles, and high production costs is crucial. Continued research and innovation are essential to improve treatment efficacy and patient outcomes.
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  • 文章类型: Journal Article
    心血管疾病(CVDs),包括缺血性心脏病和中风,是全世界死亡的主要原因,每年造成近两千万人死亡。传统疗法,虽然有效,没有遏制人口老龄化和生活方式因素导致的心血管疾病患病率上升。这篇综述重点介绍了创新的治疗策略,这些策略在改善患者预后和改变心血管护理方面显示出希望。新兴的药物治疗,例如前蛋白转化酶枯草杆菌蛋白酶/kexin9型(PCSK9)抑制剂和钠-葡萄糖共转运蛋白2(SGLT2)抑制剂,引入新的机制来补充现有的治疗方法,显著降低心血管事件和死亡率。这些进步强调了正在进行的临床试验和研究以发现新的治疗靶标的必要性。先进的生物疗法,包括基因疗法,干细胞疗法,和基于RNA的治疗,为修复和再生受损的心血管组织提供开创性的潜力。尽管处于不同的临床验证阶段,早期结果很有希望,这表明这些疗法可以从根本上改变心血管疾病的治疗前景。创新的医疗设备和技术,如植入式设备,微创手术,和可穿戴技术,正在彻底改变CVD管理。这些进步有助于早期诊断,连续监测,有效的治疗,将护理带出医院进入家庭,改善患者预后并降低医疗成本。个性化医疗,由遗传分析和生物标志物鉴定驱动,允许定制的疗法,提高治疗效果和减少不良反应。然而,采用这些新兴疗法面临重大挑战,包括监管障碍,成本和可访问性问题,和道德考虑。解决这些障碍和促进跨学科合作对于加速创新治疗的开发和实施至关重要。在心血管护理中整合新兴的治疗策略具有改变CVD管理的巨大潜力。通过优先考虑未来的研究并克服现有的挑战,一个个性化的新时代,有效,并且可以实现可获得的心血管护理。
    Cardiovascular diseases (CVDs), including ischemic heart disease and stroke, are the leading cause of mortality worldwide, causing nearly 20 million deaths annually. Traditional therapies, while effective, have not curbed the rising prevalence of CVDs driven by aging populations and lifestyle factors. This review highlights innovative therapeutic strategies that show promise in improving patient outcomes and transforming cardiovascular care. Emerging pharmacological treatments, such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and sodium-glucose co-transporter 2 (SGLT2) inhibitors, introduce novel mechanisms to complement existing therapies, significantly reducing cardiovascular events and mortality. These advancements emphasize the necessity of ongoing clinical trials and research to discover new therapeutic targets. Advanced biological therapies, including gene therapy, stem cell therapy, and RNA-based treatments, offer groundbreaking potential for repairing and regenerating damaged cardiovascular tissues. Despite being in various stages of clinical validation, early results are promising, suggesting these therapies could fundamentally change the CVD treatment landscape. Innovative medical devices and technologies, such as implantable devices, minimally invasive procedures, and wearable technology, are revolutionizing CVD management. These advancements facilitate early diagnosis, continuous monitoring, and effective treatment, driving care out of hospitals and into homes, improving patient outcomes and reducing healthcare costs. Personalized medicine, driven by genetic profiling and biomarker identification, allows for tailored therapies that enhance treatment efficacy and minimize adverse effects. However, the adoption of these emerging therapies faces significant challenges, including regulatory hurdles, cost and accessibility issues, and ethical considerations. Addressing these barriers and fostering interdisciplinary collaboration are crucial for accelerating the development and implementation of innovative treatments. Integrating emerging therapeutic strategies in cardiovascular care holds immense potential to transform CVD management. By prioritizing future research and overcoming existing challenges, a new era of personalized, effective, and accessible cardiovascular care can be achieved.
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  • 文章类型: Journal Article
    这篇叙述性综述提供了对泌乳素瘤的简洁探索,最常见的垂体腺瘤,专注于其流行病学,临床表现,和治疗干预措施。从其患病率和病因的概述开始,本综述探讨了泌乳素腺瘤的性别分布和家族性关联.临床表现,包括内分泌干扰,生殖健康问题,和代谢紊乱,被检查,强调它们对荷尔蒙调节和心血管健康的影响。然后叙述通过药物治疗,手术干预,和放射治疗,突出它们的功效,副作用,和长期管理挑战。讨论了减轻副作用和优化治疗结果的策略,强调多学科合作在泌乳素瘤管理中的重要性。这篇综述是为医疗保健专业人员和研究人员提供的简明而全面的资源,提供对催乳素瘤的临床复杂性和治疗细微差别的见解,以指导最佳的患者护理策略。
    This narrative review provides a succinct exploration of prolactinoma, the most common pituitary adenoma, focusing on its epidemiology, clinical manifestations, and therapeutic interventions. Beginning with an overview of its prevalence and aetiology, the review delves into the gender distribution and familial associations of prolactinoma. Clinical presentations, including endocrine disruptions, reproductive health issues, and metabolic disturbances, are examined, emphasizing their impact on hormonal regulation and cardiovascular health. The narrative then navigates through pharmacological treatments, surgical interventions, and radiation therapy, highlighting their efficacy, side effects, and long-term management challenges. Strategies to mitigate side effects and optimize treatment outcomes are discussed, emphasizing the importance of multidisciplinary collaboration in prolactinoma management. This review is a concise yet comprehensive resource for healthcare professionals and researchers, providing insights into prolactinoma\'s clinical complexities and therapeutic nuances to guide optimal patient care strategies.
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  • 文章类型: Journal Article
    自1900年代初被发现以来,镰状细胞病(SCD)对血红蛋白和血红蛋白病的科学理解做出了重要贡献。尽管如此,现在将近一个世纪后,最佳的医疗管理,甚至治疗选择仍然有限。令人鼓舞的是,在过去的十年里,人们一直在推动对SCD患者的护理,并对治疗该疾病的选择产生了多样化的兴趣.
    这里,我们回顾了SCD包括胎儿血红蛋白诱导剂在内的疾病改善疗法的现状,单克隆抗体,抗炎调节剂,和酶活化剂。我们还讨论了目前对转化基因疗法有特殊兴趣的治疗策略。
    SCD是一种慢性疾病,尽管有一个世纪的临床描述,直到现在,在改善SCD患者的寿命和生活质量的治疗选择方面才出现增长和进步。我们预计新设计的,甚至是重新利用的疗法,可以作为单一药物或组合药物来解决SCD的进展。绝大多数患有SCD的人不太可能接受基因疗法,因此,即使对于那些最终可能选择寻求潜在治愈策略的患者,改善疾病管理也是至关重要的.
    UNASSIGNED: Since its discovery in the early 1900s, sickle cell disease (SCD) has contributed significantly to the scientific understanding of hemoglobin and hemoglobinopathies. Despite this, now almost a century later, optimal medical management and even curative options remain limited. Encouragingly, in the last decade, there has been a push toward advancing the care for individuals with SCD and a diversifying interest in options to manage this disorder.
    UNASSIGNED: Here, we review the current state of disease modifying therapies for SCD including fetal hemoglobin inducers, monoclonal antibodies, anti-inflammatory modulators, and enzyme activators. We also discuss current curative strategies with specific interest in transformative gene therapies.
    UNASSIGNED: SCD is a chronic, progressive disease that despite a century of clinical description, only now is seeing a growth and advance in therapeutic options to improve the lifespan and quality of life for individuals with SCD. We anticipate newly designed and even repurposed therapies that may work as a single agent or combination agents to tackle the progression of SCD. The vast majority of individuals living with SCD are unlikely to receive gene therapy, therefore improved disease management is critical even for those that may ultimately chose to pursue a potentially curative strategy.
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  • 文章类型: Journal Article
    进行性核上性麻痹(PSP)是一种神经退行性疾病,其特征是4R-tau蛋白聚集体在各个大脑区域积累。PSP导致神经元丢失,胶质增生,和tau阳性夹杂物,如神经原纤维缠结,簇状星形胶质细胞,和盘绕的身体。这些病理变化主要影响脑干和基底节,导致独特的MRI特征,如蜂鸟和牵牛花标志。PSP显示临床异质性,表现为不同的表型,其中最经典的是理查森综合征(PSP-RS)。受累区域和萎缩扩散方式可以进一步区分PSP的亚型。PSP患者会出现各种体征和症状,比如姿势不稳定,核上眼肌麻痹,低振幅快速手指敲击,和不规则的睡眠模式。PSP最常见的症状是姿势不稳,falls,垂直凝视麻痹,运动迟缓,和认知障碍。这些特征通常与帕金森病(PD)和其他帕金森病综合征的特征重叠,使诊断具有挑战性。PSP是一个重要的临床课题的研究,因为它是一种毁灭性的和不可治愈的疾病。然而,关于其病理生理学的知识仍然存在许多空白,诊断,和治疗。几项临床试验正在进行中,以测试以各种方式针对tau的新型疗法,例如调节其翻译后修饰,稳定其与微管的相互作用,或通过免疫疗法增强其清除能力。这些方法可能为减缓PSP的进展提供新的希望。在这次审查中,我们的目标是提供有关PSP的当前知识的概述,从发病机理到管理。我们还讨论了PSP研究的最新进展和未来方向。
    Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by the accumulation of 4R-tau protein aggregates in various brain regions. PSP leads to neuronal loss, gliosis, and tau-positive inclusions, such as neurofibrillary tangles, tufted astrocytes, and coiled bodies. These pathological changes mainly affect the brainstem and the basal ganglia, resulting in distinctive MRI features, such as the hummingbird and morning glory signs. PSP shows clinical heterogeneity and presents as different phenotypes, the most classical of which is Richardson\'s syndrome (PSP-RS). The region of involvement and the mode of atrophy spread can further distinguish subtypes of PSP. PSP patients can experience various signs and symptoms, such as postural instability, supranuclear ophthalmoplegia, low amplitude fast finger tapping, and irregular sleep patterns. The most common symptoms of PSP are postural instability, falls, vertical gaze palsy, bradykinesia, and cognitive impairment. These features often overlap with those of Parkinson\'s disease (PD) and other Parkinsonian syndromes, making the diagnosis challenging. PSP is an essential clinical topic to research because it is a devastating and incurable disease. However, there are still many gaps in knowledge about its pathophysiology, diagnosis, and treatment. Several clinical trials are underway to test noveltherapies that target tau in various ways, such as modulating its post-translational modifications, stabilizing its interaction with microtubules, or enhancing its clearance by immunotherapy. These approaches may offer new hope for slowing down the progression of PSP. In this review, we aim to provide an overview of the current knowledge on PSP, from its pathogenesis to its management. We also discuss the latest advances and future directions in PSP research.
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  • 文章类型: Journal Article
    膜性肾病(MN)是成人肾病综合征的最常见原因之一。磷脂酶A2受体(PLA2R)作为靶抗原的发现导致了对MN的理解和管理的范式转变。目前,血清PLA2R抗体用于诊断,预测,指导治疗。现在,随着20多种新型靶抗原的发现,抗原作图几乎完成。某些抗原的临床关联为临床医生提供线索,如神经表皮生长因子样1与恶性肿瘤和本土药物的关联。血清抗体检测大多数靶抗原,除了外植骨素1和2以及转化生长因子β受体3,但它们的临床效用尚待确定。全基因组关联研究和调查环境因素的研究,比如空气污染,进一步阐明了MN的基础。在过去的几十年中,MN的标准疗法从环状环磷酰胺和类固醇多样化,包括利妥昔单抗和钙调磷酸酶抑制剂。这里,我们提供了对MN的前沿审查,专注于遗传学,免疫系统和环境因素,新型靶抗原及其临床特征,以及目前在MN中可用的和新兴的新疗法。
    Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults. The discovery of phospholipase A2 receptor (PLA2R) as a target antigen has led to a paradigm shift in the understanding and management of MN. At present, serum PLA2R antibodies are used for diagnosis, prognostication, and guiding treatment. Now, with the discovery of more than 20 novel target antigens, antigen mapping is almost complete. The clinical association of certain antigens provides clues for clinicians, such as the association of nerve epidermal growth factor-like 1 with malignancies and indigenous medicines. Serum antibodies are detected for most target antigens, except exostosin 1 and 2 and transforming growth factor-beta receptor 3, but their clinical utility is yet to be defined. Genome-wide association studies and studies investigating environmental factors, such as air pollution, shed more light on the underpinnings of MN. The standard therapy of MN diversified from cyclical cyclophosphamide and steroids to include rituximab and calcineurin inhibitors over the past decades. Here, we provide a cutting-edge review of MN, focusing on genetics, immune system and environmental factors, novel target antigens and their clinical characteristics, and currently available and emerging novel therapies in MN.
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  • 文章类型: Journal Article
    Kirsten大鼠肉瘤病毒(KRAS)是人类癌症中最常见的癌基因,包括非小细胞肺癌(NSCLC)。多年来,由于其结构和难以定位,KRAS被认为是“不可用的”。然而,KRAS-G12C突变蛋白中开关II区的发现,随着新型直接KRAS-G12C抑制剂的设计和开发,改变了治疗领域.Sotorasib和adagrasib是FDA批准的靶向药物,用于KRAS-G12C突变的NSCLC患者。尽管结果很有希望,这些新型抑制剂的功效受到耐药机制的限制。正在进行的研究正在评估克服阻力的组合策略。在这次审查中,我们总结了KRAS蛋白的生物学特性和KRAS突变的特点。然后,我们提出了针对KRAS突变亚型的当前和新兴治疗方法,旨在为具有这种挑战性的驱动突变的肺癌提供个性化治疗。
    Kirsten rat sarcoma virus (KRAS) is the most frequently found oncogene in human cancers, including non-small-cell lung cancer (NSCLC). For many years, KRAS was considered \"undruggable\" due to its structure and difficult targeting. However, the discovery of the switch II region in the KRAS-G12C-mutated protein has changed the therapeutic landscape with the design and development of novel direct KRAS-G12C inhibitors. Sotorasib and adagrasib are FDA-approved targeted agents for pre-treated patients with KRAS-G12C-mutated NSCLC. Despite promising results, the efficacy of these novel inhibitors is limited by mechanisms of resistance. Ongoing studies are evaluating combination strategies for overcoming resistance. In this review, we summarize the biology of the KRAS protein and the characteristics of KRAS mutations. We then present current and emerging therapeutic approaches for targeting KRAS mutation subtypes intending to provide individualized treatment for lung cancer harboring this challenging driver mutation.
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