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Effects of home-based telerehabilitation-assisted inspiratory muscle training in patients with idiopathic pulmonary fibrosis: A randomized controlled trial. 家庭远程康复辅助吸气肌训练对特发性肺纤维化患者的影响:随机对照试验
IF 5.3 2区 材料科学 Q2 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2024-12-01 Epub Date: 2024-08-11 DOI: 10.1111/resp.14810
Rıdvan Aktan, Kemal Can Tertemiz, Salih Yiğit, Sevgi Özalevli, Aylin Ozgen Alpaydin, Eyüp Sabri Uçan

Background and objective: There are few studies that have used inspiratory muscle training (IMT) as an intervention for patients with isolated idiopathic pulmonary fibrosis (IPF). This study aimed to investigate and interpret the effects of home-based telerehabilitation-assisted IMT in patients with IPF.

Methods: Twenty-eight participants with IPF took part in the study. Lung function tests, functional exercise capacity by 6-min walk distance (6MWD), dyspnoea perception by modified medical research council dyspnoea scale (mMRC), and inspiratory muscle strength by maximal inspiratory pressure (MIP) were assessed. IMT was performed twice a day, 7 days/week, for 8 weeks. The intervention group (n = 14) performed IMT at 50% of their baseline MIP while the control group (n = 14) performed IMT without applied resistance. Loading intensity was progressed by keeping the load at 4-6 on a modified Borg scale for the highest tolerable perceived respiratory effort for each patient.

Results: Dyspnoea based on mMRC score (p < 0.001, η2 effect size = 0.48) significantly decreased within the intervention group compared with the control group. There were significant increases in the intervention group compared to the control group based on 6MWD (p < 0.001, η2 effect size = 0.43), MIP (p = 0.006, η2 effect size = 0.25) and MIP % predicted (p = 0.008, η2 effect size = 0.25).

Conclusion: The findings of this study suggest that an 8-week home-based telerehabilitation-assisted IMT intervention produced improvements in inspiratory muscle strength, leading to improvements in functional exercise capacity and dyspnoea.

背景和目的:将吸气肌训练(IMT)作为孤立性特发性肺纤维化(IPF)患者干预措施的研究很少。本研究旨在调查和解释家庭远程康复辅助吸气肌训练对 IPF 患者的影响:28名 IPF 患者参加了研究。方法:28 名 IPF 患者参加了这项研究,他们接受了肺功能测试、6 分钟步行距离(6MWD)功能锻炼能力、改良医学研究委员会呼吸困难量表(mMRC)呼吸困难感知和最大吸气压力(MIP)吸气肌力评估。IMT 每天进行两次,每周 7 天,为期 8 周。干预组(n = 14)以基线 MIP 的 50%进行 IMT,而对照组(n = 14)则在不施加阻力的情况下进行 IMT。每个患者的负荷强度保持在改良博格量表的 4-6 级,以达到可承受的最高呼吸强度:结果:与对照组相比,干预组患者根据 mMRC 评分得出的呼吸困难评分(p 2效应大小=0.48)明显降低。干预组与对照组相比,6MWD(p 2 效应量=0.43)、MIP(p = 0.006,η2 效应量=0.25)和 MIP 预测百分比(p = 0.008,η2 效应量=0.25)均有明显增加:本研究结果表明,为期 8 周的家庭远程康复辅助 IMT 干预可改善吸气肌力,从而提高功能锻炼能力和呼吸困难。
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引用次数: 0
Multi-shell gold nanoparticles functionalized with methotrexate: a novel nanotherapeutic approach for improved antitumoral and antioxidant activity and enhanced biocompatibility. 甲氨蝶呤功能化多壳金纳米粒子:一种提高抗肿瘤和抗氧化活性以及生物相容性的新型纳米治疗方法。
IF 6.5 2区 材料科学 Q2 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2024-12-01 Epub Date: 2024-08-17 DOI: 10.1080/10717544.2024.2388624
Denisse-Iulia Bostiog, Natalia Simionescu, Adina Coroaba, Ioana C Marinas, Mariana C Chifiriuc, Gratiela Gradisteanu Pircalabioru, Stelian S Maier, Mariana Pinteala

Methotrexate (MTX) is a folic acid antagonist routinely used in cancer treatment, characterized by poor water solubility and low skin permeability. These issues could be mitigated by using drug delivery systems, such as functionalized gold nanoparticles (AuNPs), known for their versatility and unique properties. This study aimed to develop multi-shell AuNPs functionalized with MTX for the improvement of MTX antitumoral, antioxidant, and biocompatibility features. Stable phosphine-coated AuNPs were synthesized and functionalized with tailored polyethylene glycol (PEG) and short-branched polyethyleneimine (PEI) moieties, followed by MTX covalent binding. Physicochemical characterization by UV-vis and Fourier-transform infrared spectroscopy (FTIR) spectroscopy, dynamic light scattering (DLS), scanning transmission electron microscopy (STEM), and X-ray photoelectron spectroscopy (XPS) confirmed the synthesis at each step. The antioxidant activity of functionalized AuNPs was determined using DPPH radical scavenging assay, ferric ions' reducing antioxidant power (FRAP), and cupric reducing antioxidant capacity (CUPRAC) assays. Biocompatibility and cytotoxicity were assessed using MTT and LDH assays on HaCaT human keratinocytes and CAL27 squamous cell carcinoma. MTX functionalized AuNPs demonstrated enhanced antioxidant activity and a pronounced cytotoxic effect on the tumoral cells compared to their individual components, highlighting their potential for improving cancer therapy.

甲氨蝶呤(MTX)是一种叶酸拮抗剂,常用于癌症治疗,其特点是水溶性差、皮肤渗透性低。利用功能化金纳米粒子(AuNPs)等药物递送系统可以缓解这些问题。本研究旨在开发具有 MTX 功能的多壳 AuNPs,以提高 MTX 的抗肿瘤、抗氧化和生物相容性。研究人员合成了稳定的膦包被 AuNPs,并用定制的聚乙二醇(PEG)和短支链聚乙烯亚胺(PEI)分子进行功能化,然后与 MTX 共价结合。通过紫外-可见光光谱、傅立叶变换红外光谱、动态光散射、扫描透射电子显微镜和 X 射线光电子能谱等方法进行的物理化学表征证实了每一步的合成过程。利用 DPPH 自由基清除试验、铁离子还原抗氧化能力(FRAP)和铜离子还原抗氧化能力(CUPRAC)试验测定了功能化 AuNPs 的抗氧化活性。在 HaCaT 人角质细胞和 CAL27 鳞状细胞癌上使用 MTT 和 LDH 试验评估了生物相容性和细胞毒性。与单个成分相比,MTX 功能化 AuNPs 表现出更强的抗氧化活性和对肿瘤细胞的明显细胞毒性作用,凸显了其改善癌症治疗的潜力。
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引用次数: 0
Development of a novel SupraChoroidal-to-Optic-NervE (SCONE) drug delivery system. 开发新型脉络膜上-视神经(SCONE)给药系统。
IF 6.5 2区 材料科学 Q2 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2024-12-01 Epub Date: 2024-07-15 DOI: 10.1080/10717544.2024.2379369
Bryce Chiang, Kathleen Heng, Kyeongwoo Jang, Roopa Dalal, Yaping Joyce Liao, David Myung, Jeffrey L Goldberg

Purpose: Targeted drug delivery to the optic nerve head may be useful in the preclinical study and later clinical management of optic neuropathies, however, there are no FDA-approved drug delivery systems to achieve this. The purpose of this work was to develop an optic nerve head drug delivery technique.

Methods: Different strategies to approach the optic nerve head were investigated, including standard intravitreal and retroorbital injections. A novel SupraChoroidal-to-Optic-NervE (SCONE) delivery was optimized by creating a sclerotomy and introducing a catheter into the suprachoroidal space. Under direct visualization, the catheter was guided to the optic nerve head. India ink was injected. The suprachoroidal approach was performed in New Zealand White rabbit eyes in vivo (25 animals total). Parameters, including microneedle size and design, catheter design, and catheter tip angle, were optimized ex vivo and in vivo.

Results: Out of the candidate optic nerve head approaches, intravitreal, retroorbital, and suprachoroidal approaches were able to localize India ink to within 2 mm of the optic nerve. The suprachoroidal approach was further investigated, and after optimization, was able to deposit India ink directly within the optic nerve head in up to 80% of attempts. In eyes with successful SCONE delivery, latency and amplitude of visual evoked potentials was not different than the naïve untreated eye.

Conclusions: SCONE delivery can be used for targeted drug delivery to the optic nerve head of rabbits without measurable toxicity measured anatomically or functionally. Successful development of this system may yield novel opportunities to study optic nerve head-specific drug delivery in animal models, and paradigm-shifting management strategies for treating optic neuropathies.

Translational relevance: Here we demonstrate data on a new method for targeted delivery to the optic nerve head, addressing a significant unmet need in therapeutics for optic neuropathies.

目的:向视神经头靶向给药可能有助于视神经病变的临床前研究和日后的临床治疗,但目前还没有经美国食品及药物管理局批准的给药系统可实现这一目标。这项工作的目的是开发一种视神经头给药技术:方法:研究了接近视神经头的不同策略,包括标准的玻璃体内注射和眶后注射。通过开硬膜外切口并将导管引入脉络膜上腔,优化了一种新颖的脉络膜上腔至视神经头(SCONE)给药方法。在直视下,导管被引导至视神经头。注入印度墨水。脉络膜上腔方法在新西兰白兔眼中进行了活体实验(共 25 只)。对包括微针尺寸和设计、导管设计和导管顶端角度在内的参数进行了体内外优化:结果:在候选的视神经头入路中,玻璃体内入路、眶后入路和脉络膜上入路能够将印度墨水定位在视神经2毫米以内。我们进一步研究了脉络膜上途径,经过优化后,80% 的尝试都能将印度墨水直接注入视神经头。在成功注射 SCONE 的眼球中,视觉诱发电位的潜伏期和振幅与未经治疗的新眼球没有差异:结论:SCONE 给药可用于向兔子的视神经头靶向给药,从解剖学或功能学角度测量都不会产生明显的毒性。该系统的成功开发可能会为研究动物模型中视神经头特异性给药带来新的机遇,并为治疗视神经病变提供改变模式的管理策略:在此,我们展示了一种向视神经头靶向给药新方法的数据,解决了视神经病变治疗中尚未满足的重大需求。
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引用次数: 0
Improving anti-oxidant stress treatment of subarachnoid hemorrhage through self-assembled nanoparticles of oleanolic acid. 通过齐墩果酸自组装纳米颗粒改善蛛网膜下腔出血的抗氧化治疗。
IF 6.5 2区 材料科学 Q2 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2024-12-01 Epub Date: 2024-08-21 DOI: 10.1080/10717544.2024.2388735
Youdong Zhou, Hengyu Wang, Xinyi Zhu, Qingyu Zhao, Gang Deng, Yong Li, Qianxue Chen

Subarachnoid hemorrhage (SAH) is a life-threatening acute hemorrhagic cerebrovascular disease, with early brain injury (EBI) being the main cause of high mortality and severe neurological dysfunction. Oxidative stress plays a crucial role in the pathogenesis of EBI. In this study, we synthesized antioxidant stress nanoparticles based on self-assembled oleanolic acid (OA) using the solvent volatilization method. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM) techniques were employed to analyze and understand the self-assembly mechanism of oleic acid nanoparticles (OA NPs). The TUNEL assay, Nissl staining, and brain water content measurements were conducted to investigate the impact of OA NPs on cortical neuronal injury. Additionally, Western blot analysis was performed to investigate the antioxidant stress mechanism of OA NPs. The result showed that OA NPs exhibited a spherical structure with an average diameter of 168 nm. The application of OA NPs in SAH has been found to contribute to the reduction of keap1 protein levels and an increase in the nuclear level of Nrf2. As a result, the transcription of antioxidant stress proteins, including HO1 and NQO1, is triggered. The activation of the antioxidant stress pathway by OA NPs ultimately leads to a decrease in neuron damage and an improvement in neurological dysfunction. In conclusion, we successfully designed and synthesized OA NPs that can efficiently target the site of SAH. These nanoparticles have demonstrated their potential as antioxidants for the treatment of SAH, offering significant clinical applications.

蛛网膜下腔出血(SAH)是一种危及生命的急性出血性脑血管疾病,早期脑损伤(EBI)是导致高死亡率和严重神经功能障碍的主要原因。氧化应激在 EBI 的发病机制中起着至关重要的作用。在这项研究中,我们采用溶剂挥发法合成了基于齐墩果酸(OA)自组装的抗氧化应激纳米颗粒。采用X射线衍射(XRD)、傅立叶变换红外光谱(FTIR)和透射电子显微镜(TEM)技术分析和了解了油酸纳米颗粒(OA NPs)的自组装机制。通过TUNEL检测、Nissl染色和脑含水量测量来研究OA NPs对大脑皮层神经元损伤的影响。此外,还进行了 Western 印迹分析,以研究 OA NPs 的抗氧化应激机制。结果表明,OA NPs呈球形结构,平均直径为168 nm。研究发现,在 SAH 中应用 OA NPs 有助于降低 keap1 蛋白水平和提高 Nrf2 的核水平。因此,包括 HO1 和 NQO1 在内的抗氧化应激蛋白的转录被触发。OA NPs 对抗氧化应激途径的激活最终导致神经元损伤的减少和神经功能障碍的改善。总之,我们成功设计并合成了能有效靶向 SAH 病变部位的 OA NPs。这些纳米粒子证明了其作为抗氧化剂治疗 SAH 的潜力,具有重要的临床应用价值。
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引用次数: 0
Statement of Retraction: A convergent synthetic platform for dual anticancer drugs functionalized by reduced graphene nanocomposite delivery for hepatocellular cancer. 撤回声明:用还原石墨烯纳米复合材料递送双抗癌药物治疗肝癌的聚合合成平台
IF 6.5 2区 材料科学 Q2 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2024-12-01 Epub Date: 2024-06-25 DOI: 10.1080/10717544.2024.2368971
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引用次数: 0
Advances in polymeric nano-delivery systems targeting hair follicles for the treatment of acne. 针对毛囊的聚合物纳米给药系统在治疗痤疮方面的进展。
IF 6.5 2区 材料科学 Q2 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2024-12-01 Epub Date: 2024-07-02 DOI: 10.1080/10717544.2024.2372269
Yujing Lei, Wanting Jiang, Cheng Peng, Donghai Wu, Jing Wu, Yiling Xu, Hong Yan, Xinhua Xia

Acne is a common chronic inflammatory disorder of the sebaceous gland in the hair follicle. Commonly used external medications cause skin irritation, and the transdermal capacity is weak, making it difficult to penetrate the cuticle skin barrier. Hair follicles can aid in the breakdown of this barrier. As nanomaterials progress, polymer-based nanocarriers are routinely used for hair follicle drug delivery to treat acne and other skin issues. Based on the physiological and anatomical characteristics of hair follicles, this paper discusses factors affecting hair follicle delivery by polymer nanocarriers, summarizes the common combination technology to improve the targeting of hair follicles by carriers, and finally reviews the most recent research progress of different polymer nanodrug-delivery systems for the treatment of acne by targeting hair follicles.

痤疮是毛囊皮脂腺常见的慢性炎症性疾病。常用的外用药物会刺激皮肤,而且透皮能力较弱,难以穿透角质层皮肤屏障。毛囊可以帮助破坏这一屏障。随着纳米材料的发展,聚合物基纳米载体被常规用于毛囊给药,以治疗痤疮和其他皮肤问题。本文根据毛囊的生理解剖特点,探讨了影响聚合物纳米载体给毛囊给药的因素,总结了提高载体靶向毛囊的常用组合技术,最后综述了不同聚合物纳米给药系统靶向毛囊治疗痤疮的最新研究进展。
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引用次数: 0
An insight into the placental growth factor (PlGf)/angii axis in Covid-19: a detrimental intersection. 洞察 Covid-19 中的胎盘生长因子(PlGf)/angii 轴:有害的交叉点。
IF 6.5 2区 材料科学 Q2 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2024-12-01 Epub Date: 2022-09-12 DOI: 10.1080/02648725.2022.2122291
Hayder M Al-Kuraishy, Ali I Al-Gareeb, Thabat J Al-Maiahy, Athanasios Alexiou, Nobendu Mukerjee, Gaber El-Saber Batiha

Coronavirus disease 2019 (Covid-19) is a recent and current infectious pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Covid-19 may lead to the development of acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and extrapulmonary manifestations in severe cases. Down-regulation of angiotensin-converting enzyme (ACE2) by the SARS-CoV-2 increases the production of angiotensin II (AngII), which increases the release of pro-inflammatory cytokines and placental growth factor (PlGF). PlGF is a critical molecule involved in vasculogenesis and angiogenesis. PlGF is stimulated by AngII in different inflammatory diseases through a variety of signaling pathways. PlGF and AngII are interacted in SARS-CoV-2 infection resulting in the production of pro-inflammatory cytokines and the development of Covid-19 complications. Both AngII and PlGF are interacted and are involved in the progression of inflammatory disorders; therefore, we aimed in this review to highlight the potential role of the PlGF/AngII axis in Covid-19.

冠状病毒病 2019(Covid-19)是由严重急性呼吸系统综合征冠状病毒 2 型(SARS-CoV-2)引起的近期和当前的传染性流行病。Covid-19可能导致急性肺损伤(ALI)、急性呼吸窘迫综合征(ARDS)的发生,严重病例还可能出现肺外表现。SARS-CoV-2 对血管紧张素转换酶(ACE2)的下调增加了血管紧张素 II(AngII)的产生,从而增加了促炎细胞因子和胎盘生长因子(PlGF)的释放。PlGF 是参与血管生成和血管生成的重要分子。在不同的炎症性疾病中,AngII 会通过多种信号通路刺激 PlGF。在 SARS-CoV-2 感染中,PlGF 和 AngII 相互作用,导致促炎细胞因子的产生和 Covid-19 并发症的发生。AngII 和 PlGF 相互作用并参与炎症性疾病的进展;因此,我们在本综述中旨在强调 PlGF/AngII 轴在 Covid-19 中的潜在作用。
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引用次数: 0
Multiple delivery strategies of nanocarriers for myocardial ischemia-reperfusion injury: current strategies and future prospective. 纳米载体治疗心肌缺血再灌注损伤的多种给药策略:当前策略与未来展望。
IF 6 2区 材料科学 Q2 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2024-12-01 Epub Date: 2023-12-26 DOI: 10.1080/10717544.2023.2298514
Shengnan Li, Fengmei Li, Yan Wang, Wenqun Li, Junyong Wu, Xiongbin Hu, Tiantian Tang, Xinyi Liu

Acute myocardial infarction, characterized by high morbidity and mortality, has now become a serious health hazard for human beings. Conventional surgical interventions to restore blood flow can rapidly relieve acute myocardial ischemia, but the ensuing myocardial ischemia-reperfusion injury (MI/RI) and subsequent heart failure have become medical challenges that researchers have been trying to overcome. The pathogenesis of MI/RI involves several mechanisms, including overproduction of reactive oxygen species, abnormal mitochondrial function, calcium overload, and other factors that induce cell death and inflammatory responses. These mechanisms have led to the exploration of antioxidant and inflammation-modulating therapies, as well as the development of myocardial protective factors and stem cell therapies. However, the short half-life, low bioavailability, and lack of targeting of these drugs that modulate these pathological mechanisms, combined with liver and spleen sequestration and continuous washout of blood flow from myocardial sites, severely compromise the expected efficacy of clinical drugs. To address these issues, employing conventional nanocarriers and integrating them with contemporary biomimetic nanocarriers, which rely on passive targeting and active targeting through precise modifications, can effectively prolong the duration of therapeutic agents within the body, enhance their bioavailability, and augment their retention at the injured myocardium. Consequently, these approaches significantly enhance therapeutic effectiveness while minimizing toxic side effects. This article reviews current drug delivery systems used for MI/RI, aiming to offer a fresh perspective on treating this disease.

急性心肌梗死具有发病率和死亡率高的特点,现已成为严重危害人类健康的疾病。恢复血流的常规手术治疗可迅速缓解急性心肌缺血,但随之而来的心肌缺血再灌注损伤(MI/RI)和心力衰竭已成为研究人员一直在努力攻克的医学难题。心肌缺血/再灌注损伤的发病机制涉及多种机制,包括活性氧过度产生、线粒体功能异常、钙超载以及诱发细胞死亡和炎症反应的其他因素。这些机制促使人们探索抗氧化和炎症调节疗法,以及开发心肌保护因子和干细胞疗法。然而,这些调节病理机制的药物半衰期短、生物利用度低、缺乏靶向性,再加上肝脏和脾脏的螯合作用以及心肌部位血流的持续冲刷,严重影响了临床药物的预期疗效。为解决这些问题,采用传统纳米载体并与当代仿生纳米载体相结合,通过精确修饰实现被动靶向和主动靶向,可有效延长治疗药物在体内的存留时间,提高生物利用度,并增强其在损伤心肌的存留。因此,这些方法能显著提高治疗效果,同时最大限度地减少毒副作用。本文回顾了目前用于治疗心肌梗塞/心肌梗死的给药系统,旨在为治疗这种疾病提供一个全新的视角。
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引用次数: 0
Surface functionalized nanomaterial systems for targeted therapy of endocrine related tumors: a review of recent advancements. 用于内分泌相关肿瘤靶向治疗的表面功能化纳米材料系统:最新进展综述。
IF 6.5 2区 材料科学 Q2 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2024-12-01 Epub Date: 2024-08-13 DOI: 10.1080/10717544.2024.2390022
Limei Liu, Miao Yang, Ziyang Chen

The application of multidisciplinary techniques in the management of endocrine-related cancers is crucial for harnessing the advantages of multiple disciplines and their coordinated efforts in eliminating tumors. Due to the malignant characteristics of cancer cells, they possess the capacity to develop resistance to traditional treatments such as chemotherapy and radiotherapy. Nevertheless, despite diligent endeavors to enhance the prediction of outcomes, the overall survival rate for individuals afflicted with endocrine-related malignancy remains quite miserable. Hence, it is imperative to investigate innovative therapy strategies. The latest advancements in therapeutic tactics have offered novel approaches for the therapy of various endocrine tumors. This paper examines the advancements in nano-drug delivery techniques and the utilization of nanomaterials for precise cancer cures through targeted therapy. This review provides a thorough analysis of the potential of combined drug delivery strategies in the treatment of thyroid cancer, adrenal gland tumors, and pancreatic cancer. The objective of this study is to gain a deeper understanding of current therapeutic approaches, stimulate the development of new drug DDS, and improve the effectiveness of treatment for patients with these diseases. The intracellular uptake of pharmaceuticals into cancer cells can be significantly improved through the implantation of synthetic or natural substances into nanoparticles, resulting in a substantial reduction in the development of endocrine malignancies.

多学科技术在内分泌相关癌症治疗中的应用,对于发挥多学科优势、协同消灭肿瘤至关重要。由于癌细胞的恶性特征,它们有能力对化疗和放疗等传统疗法产生抗药性。然而,尽管人们一直在努力提高预后预测能力,但内分泌相关恶性肿瘤患者的总体生存率仍然相当凄惨。因此,研究创新的治疗策略势在必行。治疗策略的最新进展为各种内分泌肿瘤的治疗提供了新方法。本文探讨了纳米给药技术的进步,以及利用纳米材料通过靶向治疗精确治愈癌症的方法。本综述全面分析了联合给药策略在治疗甲状腺癌、肾上腺肿瘤和胰腺癌方面的潜力。本研究的目的是深入了解当前的治疗方法,促进新药物 DDS 的开发,提高这些疾病患者的治疗效果。通过将合成或天然物质植入纳米颗粒,可显著改善癌细胞对药物的胞内吸收,从而大大降低内分泌恶性肿瘤的发病率。
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引用次数: 0
Effects of SGLT2 inhibitors on the onset of esophageal varices and extrahepatic cancer in type 2 diabetic patients with suspected MASLD: a nationwide database study in Japan. SGLT2 抑制剂对疑似 MASLD 的 2 型糖尿病患者食管静脉曲张和肝外癌症发病的影响:日本全国数据库研究。
IF 6.9 2区 材料科学 Q2 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2024-12-01 Epub Date: 2024-10-11 DOI: 10.1007/s00535-024-02158-z
Takumi Kawaguchi, Yoshiyuki Fujishima, Daisuke Wakasugi, Fusayo Io, Yuri Sato, Saeko Uchida, Yukiko Kitajima

Background & aim: SGLT2 inhibitors (SGLT2i) improve hepatic steatosis in patients with type 2 diabetes mellitus (T2DM) and MASLD. We aimed to investigate the impact of SGLT2i on the incidence of liver-related events and extrahepatic cancer compared to DPP4 inhibitors (DPP4i) in patients with T2DM and suspected MASLD using a medical claims database in Japan.

Methods: We conducted a retrospective study using a Japanese medical claims database. Among patients with T2DM who were prescribed SGLT2i or DPP4i (n = 1,628,656), patients with suspected MASLD were classified into SGLT2i (n = 4204) and DPP4i (n = 4204) groups. Effects of SGLT2i on the following outcomes were compared to DPP4i: (1) changes in HbA1c and ALT levels after 6 months, (2) changes in hepatic fibrosis index, and (3) the incidence of liver-related events/extrahepatic cancer over 12 months.

Results: After 6 months, DPP4i significantly decreased HbA1c levels compared to SGLT2i. In contrast, SGLT2i significantly decreased ALT levels compared to DPP4i. SGLT2i significantly decreased FIB-4 index compared to DPP4i over 12 months. Although no significant difference was observed in the incidence of overall liver-related events between the two groups, SGLT2i significantly reduced the incidence of esophageal varices (HR 0.12, 95%CI 0.01-0.95, P = 0.044). Moreover, SGLT2i significantly suppressed the incidence of extrahepatic cancer (HR 0.50, 95%CI 0.30-0.84, P = 0.009) compared to DPP4i.

Conclusion: SGLT2i was more beneficial than DPP4i in improving the hepatic inflammation and fibrosis indices. Moreover, SGLT2i suppressed the incidence of esophageal varices and extrahepatic cancer compared to DPP4i. SGLT2i may suppress life-threatening events in patients with T2DM and suspected MASLD.

背景和目的:SGLT2 抑制剂(SGLT2i)可改善 2 型糖尿病(T2DM)和 MASLD 患者的肝脂肪变性。我们旨在利用日本的医疗索赔数据库,调查与 DPP4 抑制剂(DPP4i)相比,SGLT2i 对 T2DM 和疑似 MASLD 患者肝脏相关事件和肝外癌症发病率的影响:我们利用日本医疗索赔数据库进行了一项回顾性研究。在处方 SGLT2i 或 DPP4i 的 T2DM 患者(n = 1628656 人)中,疑似 MASLD 患者被分为 SGLT2i 组(n = 4204 人)和 DPP4i 组(n = 4204 人)。比较了 SGLT2i 和 DPP4i 对以下结果的影响:(1) 6 个月后 HbA1c 和 ALT 水平的变化;(2) 肝纤维化指数的变化;(3) 12 个月内肝脏相关事件/肝外癌的发生率:6个月后,与SGLT2i相比,DPP4i能显著降低HbA1c水平。相反,与 DPP4i 相比,SGLT2i 能显著降低 ALT 水平。与 DPP4i 相比,SGLT2i 能在 12 个月内明显降低 FIB-4 指数。虽然两组患者的总体肝脏相关事件发生率无明显差异,但 SGLT2i 能显著降低食管静脉曲张的发生率(HR 0.12,95%CI 0.01-0.95,P = 0.044)。此外,与 DPP4i 相比,SGLT2i 能明显抑制肝外癌的发病率(HR 0.50,95%CI 0.30-0.84,P = 0.009):结论:在改善肝脏炎症和纤维化指数方面,SGLT2i 比 DPP4i 更为有益。此外,与 DPP4i 相比,SGLT2i 可抑制食管静脉曲张和肝外癌症的发病率。SGLT2i可抑制T2DM和疑似MASLD患者发生危及生命的事件。
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ACS Applied Nano Materials
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