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Energetic Stress-Induced Metabolic Regulation by Extracellular Vesicles. 细胞外囊泡对能量应激诱导的代谢调节。
IF 5.8 2区 医学 Q1 PHYSIOLOGY Pub Date : 2023-06-26 DOI: 10.1002/cphy.c230001
Clair Crewe

Recent studies have demonstrated that extracellular vesicles (EVs) serve powerful and complex functions in metabolic regulation and metabolic-associated disease, although this field of research is still in its infancy. EVs are released into the extracellular space from all cells and carry a wide range of cargo including miRNAs, mRNA, DNA, proteins, and metabolites that have robust signaling effects in receiving cells. EV production is stimulated by all major stress pathways and, as such, has a role in both restoring homeostasis during stress and perpetuating disease. In metabolic regulation, the dominant stress signal is a lack of energy due to either nutrient deficits or damaged mitochondria from nutrient excess. This stress signal is termed "energetic stress," which triggers a robust and evolutionarily conserved response that engages major cellular stress pathways, the ER unfolded protein response, the hypoxia response, the antioxidant response, and autophagy. This article proposes the model that energetic stress is the dominant stimulator of EV release with a focus on metabolically important cells such as hepatocytes, adipocytes, myocytes, and pancreatic β-cells. Furthermore, this article will discuss how the cargo in stress-stimulated EVs regulates metabolism in receiving cells in both beneficial and detrimental ways. © 2023 American Physiological Society. Compr Physiol 13:5051-5068, 2023.

最近的研究表明,细胞外囊泡(EVs)在代谢调节和代谢相关疾病中具有强大而复杂的功能,尽管这一研究领域仍处于起步阶段。电动汽车从所有细胞释放到细胞外空间,并携带广泛的货物,包括mirna, mRNA, DNA,蛋白质和代谢物,在接收细胞中具有强大的信号传导作用。所有主要的应激途径都能刺激EV的产生,因此,它在应激状态下恢复体内平衡和使疾病持续存在方面都有作用。在代谢调节中,主要的应激信号是由于营养缺乏或营养过剩造成的线粒体损伤而导致的能量缺乏。这种应激信号被称为“能量应激”,它触发了一种强大的、进化上保守的反应,包括主要的细胞应激途径、内质网未折叠蛋白反应、缺氧反应、抗氧化反应和自噬。本文提出了能量应激是EV释放的主要刺激物的模型,重点是代谢重要细胞,如肝细胞、脂肪细胞、肌细胞和胰腺β细胞。此外,本文将讨论应力刺激电动汽车中的货物如何以有益和有害的方式调节接收细胞的代谢。©2023美国生理学会。中国生物医学工程学报(英文版),2023。
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引用次数: 1
Kidney Lymphatics. 肾淋巴管。
IF 5.8 2区 医学 Q1 PHYSIOLOGY Pub Date : 2023-06-26 DOI: 10.1002/cphy.c220029
Peter S Russell, Max Itkin, John A Windsor, Anthony R J Phillips

Following significant advances in lymphatic biology, the important role of kidney lymphatics in kidney function and dysfunction is now being more fully appreciated. Kidney lymphatics begin in the cortex as blind-ended lymphatic capillaries and then coalesce into larger lymphatics that follow the main blood vessels out through the kidney hilum. Their function in draining interstitial fluid, macromolecules, and cells underpins their important role in kidney fluid and immune homeostasis. This article provides a comprehensive overview of recent and more established research findings on kidney lymphatics and the implications of these findings for kidney function and disease. The use of lymphatic molecular markers has greatly expanded our knowledge of the development, anatomy, and pathophysiology of kidney lymphatics. Significant recent discoveries include the diverse embryological source of kidney lymphatics, the hybrid nature of the ascending vasa recta, and the effects of lymphangiogenesis on kidney diseases such as acute kidney injury and renal fibrosis. On the basis of these recent advances, there is now an opportunity to link information from across multiple research disciplines to drive a new era of lymphatic-targeted therapies for kidney disease. © 2023 American Physiological Society. Compr Physiol 13:4945-4984, 2023.

随着淋巴生物学的重大进展,肾淋巴在肾脏功能和功能障碍中的重要作用现在得到了更充分的认识。肾淋巴管开始于皮质,作为盲端淋巴毛细血管,然后合并成更大的淋巴管,跟随主血管穿过肾门。它们在引流间质液、大分子和细胞方面的功能支撑了它们在肾液和免疫稳态中的重要作用。这篇文章提供了一个全面的概述最近和更成熟的研究发现肾淋巴和这些发现对肾功能和疾病的影响。淋巴分子标记的使用极大地扩展了我们对肾淋巴的发育、解剖和病理生理学的认识。最近的重大发现包括肾淋巴的不同胚胎学来源,上升直血管的杂交性质,以及淋巴管生成对肾脏疾病(如急性肾损伤和肾纤维化)的影响。在这些最新进展的基础上,现在有机会将来自多个研究学科的信息联系起来,以推动肾脏疾病淋巴靶向治疗的新时代。©2023美国生理学会。[j] .物理学报(英文版),2009(3):444 - 444。
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引用次数: 1
Extracellular Vesicle MicroRNA in the Kidney. 肾脏中的细胞外囊泡 MicroRNA
IF 4.2 2区 医学 Q1 PHYSIOLOGY Pub Date : 2023-06-26 DOI: 10.1002/cphy.c220023
Sekyung Oh, Chang M Lee, Sang-H Kwon

Most cells in our body release membrane-bound, nano-sized particles into the extracellular milieu through cellular metabolic processes. Various types of macromolecules, reflecting the physiological and pathological status of the producing cells, are packaged into such so-called extracellular vesicles (EVs), which can travel over a distance to target cells, thereby transmitting donor cell information. The short, noncoding ribonucleic acid (RNA) called microRNA (miRNA) takes a crucial part in EV-resident macromolecules. Notably, EVs transferring miRNAs can induce alterations in the gene expression profiles of the recipient cells, through genetically instructed, base-pairing interaction between the miRNAs and their target cell messenger RNAs (mRNAs), resulting in either nucleolytic decay or translational halt of the engaged mRNAs. As in other body fluids, EVs released in urine, termed urinary EVs (uEVs), carry specific sets of miRNA molecules, which indicate either normal or diseased states of the kidney, the principal source of uEVs. Studies have therefore been directed to elucidate the contents and biological roles of miRNAs in uEVs and moreover to utilize the gene regulatory properties of miRNA cargos in ameliorating kidney diseases through their delivery via engineered EVs. We here review the fundamental principles of the biology of EVs and miRNA as well as our current understanding of the biological roles and applications of EV-loaded miRNAs in the kidney. We further discuss the limitations of contemporary research approaches, suggesting future directions to overcome the difficulties to advance both the basic biological understanding of miRNAs in EVs and their clinical applications in treating kidney diseases. © 2023 American Physiological Society. Compr Physiol 13:4833-4850, 2023.

人体内的大多数细胞都会通过细胞代谢过程向细胞外环境释放与膜结合的纳米级微粒。反映生产细胞生理和病理状态的各类大分子被包装进这种所谓的细胞外囊泡 (EV),这些囊泡可以远距离到达靶细胞,从而传递供体细胞的信息。被称为微小核糖核酸(miRNA)的短小非编码核糖核酸(RNA)在EV驻留大分子中起着至关重要的作用。值得注意的是,转移了 miRNA 的 EV 可通过 miRNA 与靶细胞信使 RNA(mRNA)之间的基因指示、碱基配对相互作用,诱导改变受体细胞的基因表达谱,从而导致参与的 mRNA 核溶解衰变或翻译停止。与其他体液一样,尿液中释放的 EVs(称为尿 EVs(uEVs))也携带特定的 miRNA 分子集,这些 miRNA 表明肾脏(uEVs 的主要来源)处于正常或患病状态。因此,研究的方向是阐明uEVs中miRNA的内容和生物学作用,以及利用miRNA载体的基因调控特性,通过工程化EVs递送来改善肾脏疾病。我们在此回顾了 EVs 和 miRNA 生物学的基本原理,以及我们目前对 EV 载体 miRNA 在肾脏中的生物学作用和应用的理解。我们进一步讨论了当代研究方法的局限性,提出了克服困难的未来方向,以推进对 EV 中 miRNA 的基础生物学理解及其在治疗肾脏疾病中的临床应用。© 2023 美国生理学会。Compr Physiol 13:4833-4850, 2023.
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引用次数: 0
Spatial Single-Cell Technologies for Exploring Gastrointestinal Tissue Transcriptome. 探索胃肠道组织转录组的空间单细胞技术。
IF 4.2 2区 医学 Q1 PHYSIOLOGY Pub Date : 2023-06-26 DOI: 10.1002/cphy.c210053
Hyun Min Kang, Jun Hee Lee

In the gastrointestinal (GI) system, like in other organ systems, the histological structure is a key determinant of physiological function. Tissues form multiple layers in the GI tract to perform their specialized functions in secretion, absorption, and motility. Even at the single layer, the heterogeneous cell population performs a diverse range of digestive or regulatory functions. Although many details of such functions at the histological and cell biological levels were revealed by traditional methods such as cell sorting, isolation, and culture, as well as histological methods such as immunostaining and RNA in situ hybridization, recent advances in spatial single-cell technologies could further contribute to our understanding of the molecular makeup of GI histological structures by providing a genome-wide overview of how different genes are expressed across individual cells and tissue layers. The current minireview summarizes recent advances in the spatial transcriptomics field and discusses how such technologies can promote our understanding of GI physiology. © 2023 American Physiological Society. Compr Physiol 13:4709-4718, 2023.

在胃肠道(GI)系统中,与其他器官系统一样,组织学结构是决定生理功能的关键因素。组织在胃肠道中形成多层,以发挥其分泌、吸收和蠕动的专门功能。即使在单层组织中,异质细胞群也能发挥多种消化或调节功能。尽管细胞分选、分离和培养等传统方法以及免疫染色和 RNA 原位杂交等组织学方法揭示了组织学和细胞生物学层面上此类功能的许多细节,但空间单细胞技术的最新进展可以提供不同基因如何在单个细胞和组织层之间表达的全基因组概览,从而进一步促进我们对消化道组织学结构的分子构成的理解。本期小视图总结了空间转录组学领域的最新进展,并讨论了此类技术如何促进我们对消化道生理学的理解。© 2023 美国生理学会。Compr Physiol 13:4709-4718, 2023.
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引用次数: 0
Issue Information. 问题的信息。
IF 5.8 2区 医学 Q1 PHYSIOLOGY Pub Date : 2023-06-26 DOI: 10.1002/cphy.cv13i03
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引用次数: 0
Exercise and Experiments of Nature. 大自然的锻炼和实验。
IF 4.2 2区 医学 Q1 PHYSIOLOGY Pub Date : 2023-06-26 DOI: 10.1002/cphy.c220027
Michael J Joyner, Chad C Wiggins, Sarah E Baker, Stephen A Klassen, Jonathon W Senefeld

In this article, we highlight the contributions of passive experiments that address important exercise-related questions in integrative physiology and medicine. Passive experiments differ from active experiments in that passive experiments involve limited or no active intervention to generate observations and test hypotheses. Experiments of nature and natural experiments are two types of passive experiments. Experiments of nature include research participants with rare genetic or acquired conditions that facilitate exploration of specific physiological mechanisms. In this way, experiments of nature are parallel to classical "knockout" animal models among human research participants. Natural experiments are gleaned from data sets that allow population-based questions to be addressed. An advantage of both types of passive experiments is that more extreme and/or prolonged exposures to physiological and behavioral stimuli are possible in humans. In this article, we discuss a number of key passive experiments that have generated foundational medical knowledge or mechanistic physiological insights related to exercise. Both natural experiments and experiments of nature will be essential to generate and test hypotheses about the limits of human adaptability to stressors like exercise. © 2023 American Physiological Society. Compr Physiol 13:4879-4907, 2023.

在这篇文章中,我们强调了被动实验的贡献,这些实验解决了生理学和医学综合中与运动相关的重要问题。被动实验与主动实验的不同之处在于,被动实验涉及有限或没有主动干预来产生观察结果和检验假设。自然实验和自然实验是被动实验的两种类型。自然实验包括具有罕见遗传或后天条件的研究参与者,这些条件有助于探索特定的生理机制。通过这种方式,自然实验与人类研究参与者中的经典“敲除”动物模型类似。自然实验是从数据集中收集的,这些数据集可以解决基于人群的问题。这两种类型的被动实验的优点是,人类可能会更极端和/或更长时间地暴露于生理和行为刺激。在这篇文章中,我们讨论了一些关键的被动实验,这些实验产生了与运动相关的基础医学知识或机制生理见解。自然实验和自然实验对于产生和测试关于人类对运动等压力源的适应性极限的假设至关重要。©2023美国生理学会。Compr Physiol 13:4879-49072023。
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引用次数: 0
Insulin Regulation of Hepatic Lipid Homeostasis. 胰岛素对肝脂平衡的调节
IF 4.2 2区 医学 Q1 PHYSIOLOGY Pub Date : 2023-06-26 DOI: 10.1002/cphy.c220015
Kahealani Uehara, Dominic Santoleri, Anna E Garcia Whitlock, Paul M Titchenell

The incidence of obesity, insulin resistance, and type II diabetes (T2DM) continues to rise worldwide. The liver is a central insulin-responsive metabolic organ that governs whole-body metabolic homeostasis. Therefore, defining the mechanisms underlying insulin action in the liver is essential to our understanding of the pathogenesis of insulin resistance. During periods of fasting, the liver catabolizes fatty acids and stored glycogen to meet the metabolic demands of the body. In postprandial conditions, insulin signals to the liver to store excess nutrients into triglycerides, cholesterol, and glycogen. In insulin-resistant states, such as T2DM, hepatic insulin signaling continues to promote lipid synthesis but fails to suppress glucose production, leading to hypertriglyceridemia and hyperglycemia. Insulin resistance is associated with the development of metabolic disorders such as cardiovascular and kidney disease, atherosclerosis, stroke, and cancer. Of note, nonalcoholic fatty liver disease (NAFLD), a spectrum of diseases encompassing fatty liver, inflammation, fibrosis, and cirrhosis, is linked to abnormalities in insulin-mediated lipid metabolism. Therefore, understanding the role of insulin signaling under normal and pathologic states may provide insights into preventative and therapeutic opportunities for the treatment of metabolic diseases. Here, we provide a review of the field of hepatic insulin signaling and lipid regulation, including providing historical context, detailed molecular mechanisms, and address gaps in our understanding of hepatic lipid regulation and the derangements under insulin-resistant conditions. © 2023 American Physiological Society. Compr Physiol 13:4785-4809, 2023.

肥胖、胰岛素抵抗和 II 型糖尿病(T2DM)的发病率在全球范围内持续上升。肝脏是胰岛素反应性代谢的中心器官,掌管着全身代谢平衡。因此,明确肝脏中胰岛素的作用机制对于我们了解胰岛素抵抗的发病机制至关重要。在禁食期间,肝脏会分解脂肪酸和储存的糖原,以满足机体的代谢需求。在餐后状态下,胰岛素向肝脏发出信号,将多余的营养物质储存为甘油三酯、胆固醇和糖原。在胰岛素抵抗状态下,如 T2DM,肝脏胰岛素信号继续促进脂质合成,但无法抑制葡萄糖生成,从而导致高甘油三酯血症和高血糖。胰岛素抵抗与心血管疾病、肾脏疾病、动脉粥样硬化、中风和癌症等代谢性疾病的发生有关。值得注意的是,非酒精性脂肪肝(NAFLD)是包括脂肪肝、炎症、纤维化和肝硬化在内的一系列疾病,与胰岛素介导的脂质代谢异常有关。因此,了解胰岛素信号在正常和病理状态下的作用可为代谢性疾病的预防和治疗提供洞察力。在此,我们将对肝脏胰岛素信号传导和脂质调节领域进行综述,包括提供历史背景、详细的分子机制,并探讨我们对肝脏脂质调节和胰岛素抵抗条件下的失调的认识差距。© 2023 美国生理学会。Compr Physiol 13:4785-4809, 2023.
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引用次数: 0
Gallstone and Gallbladder Disease: Biliary Tract and Cholangiopathies. 胆结石和胆囊疾病:胆道和胆管疾病。
IF 5.8 2区 医学 Q1 PHYSIOLOGY Pub Date : 2023-06-26 DOI: 10.1002/cphy.c220028
Ludovica Ceci, Yuyan Han, Kelsey Krutsinger, Leonardo Baiocchi, Nan Wu, Debjyoti Kundu, Konstantina Kyritsi, Tianhao Zhou, Eugenio Gaudio, Heather Francis, Gianfranco Alpini, Lindsey Kennedy

Cholestatic liver diseases are named primarily due to the blockage of bile flow and buildup of bile acids in the liver. Cholestasis can occur in cholangiopathies, fatty liver diseases, and during COVID-19 infection. Most literature evaluates damage occurring to the intrahepatic biliary tree during cholestasis; however, there may be associations between liver damage and gallbladder damage. Gallbladder damage can manifest as acute or chronic inflammation, perforation, polyps, cancer, and most commonly gallstones. Considering the gallbladder is an extension of the intrahepatic biliary network, and both tissues are lined by biliary epithelial cells that share common mechanisms and properties, it is worth further evaluation to understand the association between bile duct and gallbladder damage. In this comprehensive article, we discuss background information of the biliary tree and gallbladder, from function, damage, and therapeutic approaches. We then discuss published findings that identify gallbladder disorders in various liver diseases. Lastly, we provide the clinical aspect of gallbladder disorders in liver diseases and ways to enhance diagnostic and therapeutic approaches for congruent diagnosis. © 2023 American Physiological Society. Compr Physiol 13:4909-4943, 2023.

胆汁性肝病主要是由于胆汁流动受阻和胆汁酸在肝脏中积聚而得名。胆汁淤积可发生在胆管疾病、脂肪肝疾病和新冠肺炎感染期间。大多数文献评估了胆汁淤积期间肝内胆管树的损伤;然而,肝脏损伤和胆囊损伤之间可能存在关联。胆囊损伤可表现为急性或慢性炎症、穿孔、息肉、癌症和最常见的胆结石。考虑到胆囊是肝内胆管网络的延伸,两种组织都由具有共同机制和特性的胆管上皮细胞排列,因此有必要进一步评估胆管与胆囊损伤之间的关系。在这篇综合性的文章中,我们从功能、损伤和治疗方法等方面讨论了胆道树和胆囊的背景信息。然后,我们讨论了已发表的发现,以确定各种肝病中的胆囊疾病。最后,我们提供了肝脏疾病中胆囊疾病的临床方面,以及增强一致诊断的诊断和治疗方法的方法。©2023美国生理学会。Compr Physiol 13:4909-49432023。
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引用次数: 0
Physiology of the Wildland Firefighter: Managing Extreme Energy Demands in Hostile, Smoky, Mountainous Environments. 野外消防员的生理学:在恶劣的、烟雾弥漫的、多山的环境中管理极端的能量需求。
IF 5.8 2区 医学 Q1 PHYSIOLOGY Pub Date : 2023-03-30 DOI: 10.1002/cphy.c220016
Brent C Ruby, Robert H Coker, Joe Sol, John Quindry, Scott J Montain

Wildland firefighters (WLFFs) are inserted as the front-line defense to minimize loss of natural resources, property, and human life when fires erupt in forested regions of the world. The WLFF occupation is physically demanding as exemplified by total daily energy expenditures that can exceed 25 MJ/day (6000 calories). WLFFs must also cope with complex physical and environmental situations (i.e., heat, altitude, smoke, compromised sleep, elevated stress) which challenge thermoregulatory responses, impair recovery, and increase short- and long-term injury/health risks while presenting logistical obstacles to nutrient and fluid replenishment. The occupation also imposes emotional strain on both the firefighter and their families. The long-term implications of wildfire management and suppression on the physical and mental health of WLFFs are significant, as the frequency and intensity of wildland fire outbreaks as well as the duration of the fire season is lengthening and expected to continue to expand over the next three decades. This article details the physical demands and emerging health concerns facing WLFFs, in addition to the challenges that the U.S. Forest Service and other international agencies must address to protect the health and performance of WLFFs and their ability to endure the strain of an increasingly dangerous work environment. © 2023 American Physiological Society. Compr Physiol 13:4587-4615, 2023.

当世界上的森林地区发生火灾时,野地消防员(WLFFs)被作为第一线防御,以尽量减少自然资源、财产和生命的损失。WLFF职业对身体的要求很高,每天的总能量消耗可能超过25兆焦耳/天(6000卡路里)。wlff还必须应对复杂的物理和环境情况(即高温、高海拔、烟雾、睡眠不足、压力升高),这些情况挑战体温调节反应,损害恢复,增加短期和长期伤害/健康风险,同时给营养和液体补充带来后勤障碍。这个职业也给消防员和他们的家人带来了情感上的压力。由于野火爆发的频率和强度以及火灾季节的持续时间正在延长,并且预计在未来三十年将继续扩大,因此野火管理和扑灭对森林消防员身心健康的长期影响是重大的。本文详细介绍了森林森林消防员所面临的身体需求和新出现的健康问题,以及美国林务局和其他国际机构必须解决的挑战,以保护森林森林消防员的健康和表现,以及他们承受日益危险的工作环境压力的能力。©2023美国生理学会。物理学报(自然科学版),2023。
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引用次数: 0
Pathogenesis of E-Cigarette Vaping Product Use-Associated Lung Injury (EVALI). 电子烟雾化产品使用相关肺损伤(EVALI)的发病机制。
IF 5.8 2区 医学 Q1 PHYSIOLOGY Pub Date : 2023-03-30 DOI: 10.1002/cphy.c220022
Irina Petrache, Arnav Gupta, Patrick S Hume, Tanner Rivera, Kelly S Schweitzer, Hong Wei Chu

EVALI is an acute inflammatory disease in response to lung cell injury induced by electronic cigarettes and vaping devices (EV) frequently containing Vitamin E Acetate or tetrahydrocannabinol additives, in the context of risk factors such as microbial exposure. EVALI resembles a respiratory viral illness that may progress to acute respiratory failure and acute respiratory distress syndrome (ARDS) but can also affect extra pulmonary organs. Manifestations may be severe, leading to death or long-term morbidity and current treatments are largely supportive. While COVID-19 has demanded public and research attention, EVALI continues to affect young individuals and its better understanding via research remains a priority. Although clinical research led to improved recognition of triggers, clinical and pathological manifestations, and natural course of EVALI, important questions remain that require a better understanding of disease pathogenesis. Preclinical models utilizing laboratory animals and cell or tissue culture platforms provide insight into the physiologic and mechanistic consequences of acute and chronic EV exposure, including the characteristics of the respiratory dysfunction and inflammatory response. However, a key limitation in the field is the absence of an established animal model of EVALI. Important areas of research emphasis include identifying triggers and risk factors to understand why only certain vapers develop EVALI, the role of specific lung immune and structural cells in the pathogenesis of EVALI, and the most important molecular mediators and therapeutic targets in EVALI. © 2023 American Physiological Society. Compr Physiol 13:4617-4630, 2023.

EVALI是一种急性炎症性疾病,在微生物暴露等危险因素的背景下,由经常含有维生素E醋酸酯或四氢大麻酚添加剂的电子烟和电子烟设备(EV)引起的肺细胞损伤引起。EVALI类似于一种呼吸道病毒性疾病,可发展为急性呼吸衰竭和急性呼吸窘迫综合征(ARDS),但也可影响肺外器官。表现可能很严重,导致死亡或长期发病,目前的治疗在很大程度上是支持性的。虽然COVID-19引起了公众和研究的关注,但EVALI继续影响着年轻人,通过研究更好地了解它仍然是一个优先事项。尽管临床研究提高了对EVALI的诱因、临床和病理表现以及自然过程的认识,但仍有一些重要问题需要更好地了解疾病的发病机制。利用实验动物和细胞或组织培养平台的临床前模型提供了对急性和慢性EV暴露的生理和机制后果的深入了解,包括呼吸功能障碍和炎症反应的特征。然而,该领域的一个关键限制是缺乏已建立的EVALI动物模型。重要的研究重点领域包括确定触发因素和风险因素,以了解为什么只有某些患者会发生EVALI,特异性肺免疫和结构细胞在EVALI发病机制中的作用,以及EVALI中最重要的分子介质和治疗靶点。©2023美国生理学会。物理学报(自然科学版),2023。
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引用次数: 1
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