revascularization

血运重建
  • 文章类型: Journal Article
    缺血性心脏病(IHD)是全球主要的健康问题,也是导致死亡的主要原因。这项研究比较了经皮冠状动脉介入治疗(PCI)和冠状动脉旁路移植术(CABG)在治疗IHD中的有效性。关注它们对血运重建的影响,心肌梗死(MI),和术后中风。这项研究旨在评估和比较PCI和CABG治疗IHD的有效性基于过去5年的详尽文献回顾。强调IHD管理的最新进展和成果。
    综合文献综述分析了从PubMed等数据库中检索到的32项随机对照试验(RCT),科克伦图书馆,谷歌学者。这项研究特别评估了血运重建的发生率,中风,接受PCI或CABG治疗的患者的MI。CABG和PCI之间的比较仅集中在SYNTAX评分超过32的病变上。
    我们的研究结果强调了CABG在减少血运重建和MI方面优于PCI的显著疗效。血运重建的Mantel-Haenszel(M-H)值是1.85(95%置信区间(CI):1.65-2.07),标志着CABG的优势。此外,CABG在减少MI发生率方面表现优异(M-H=2.71,95%CI:1.13-6.53)。相比之下,PCI在减少卒中方面更有效(M-H=0.80,95%CI:0.60-1.10)。
    该研究证实了CABG在减少IHD患者血运重建和MI方面的优越性,强调PCI在降低卒中风险方面的有效性。这些发现强调了个性化治疗策略在IHD管理中的重要性,并强调需要持续的研究和循证指南来帮助IHD患者的治疗选择。
    UNASSIGNED: Ischemic heart disease (IHD) is a major global health issue and a leading cause of death. This study compares the effectiveness of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in the management of IHD, focusing on their impact on revascularization, myocardial infarction (MI), and post-procedural stroke. This study aimed to evaluate and compare the effectiveness of PCI and CABG in treating IHD based on an exhaustive literature review of the past 5 years, emphasizing recent advancements and outcomes in IHD management.
    UNASSIGNED: A comprehensive literature review analyzed 32 randomized controlled trials (RCTs) retrieved from databases such as PubMed, Cochrane Library, and Google Scholar. The study specifically assessed the incidences of revascularization, stroke, and MI in patients treated with either PCI or CABG. The comparison between CABG and PCI exclusively focused on lesions with a SYNTAX score exceeding 32.
    UNASSIGNED: Our findings highlight CABG\'s significant efficacy over PCI in reducing revascularization and MI. The aggregated Mantel-Haenszel (M-H) value for revascularization was 1.85 (95% confidence interval (CI): 1.65 - 2.07), signifying CABG\'s advantage. Additionally, CABG demonstrated superior performance in diminishing MI occurrences (M-H = 2.71, 95% CI: 1.13 - 6.53). In contrast, PCI was more effective in reducing stroke (M-H = 0.80, 95% CI: 0.60 - 1.10).
    UNASSIGNED: The study confirms CABG\'s superiority in reducing revascularization and MI in IHD patients, highlighting PCI\'s effectiveness in reducing stroke risk. These findings underscore the importance of personalized treatment strategies in IHD management and emphasize the need for ongoing research and evidence-based guidelines to aid in treatment selection for IHD patients.
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  • 文章类型: Journal Article
    目的:冠状动脉疾病的最佳血运重建策略取决于各种因素,比如疾病的复杂性,患者特征,和偏好。在复杂的情况下包括心脏团队对于确保最佳结果至关重要。经皮冠状动脉介入治疗和冠状动脉旁路移植术之间的决策必须考虑每个患者的临床资料和冠状动脉解剖结构。虽然目前的实践指南为冠状动脉疾病的各种表型的最佳血运重建方法提供了一些见解,支持这两种策略的证据都在不断发展和增长。鉴于大量的当代血运重建数据,本文旨在全面总结冠状动脉旁路移植术和经皮冠状动脉介入治疗在不同冠状动脉疾病表型患者中的应用。
    结果:当代证据表明,对于患有三支血管疾病的患者,冠状动脉旁路移植术优于经皮冠状动脉介入治疗,因为它具有更好的长期预后,包括较低的死亡率,心肌梗塞,和目标血管血运重建。同样,对于左主干冠状动脉疾病的患者,可以考虑经皮冠状动脉介入治疗和冠状动脉旁路移植术,因为他们在主要不良心脏事件方面表现出相似的功效,但经皮冠状动脉介入治疗的死亡风险可能略高.对于左前降支近端疾病,经皮冠状动脉介入治疗和冠状动脉旁路移植术都是可行的选择,但是冠状动脉旁路移植术显示重复血运重建的发生率较低,心绞痛的缓解更好。PCI与Taxus和心脏外科手术评分之间的协同作用可以通过预测不良事件的风险并指导经皮冠状动脉介入治疗和冠状动脉旁路移植术之间的选择来帮助决策。欧洲和美国的指导方针都同意包括一个可以开发和设计个性化的心脏团队,根据患者偏好的最佳治疗选择。随着技术和技术的改进,冠状动脉旁路移植术与经皮冠状动脉介入治疗在多种不同情况下之间的争论将继续发展。危险因素,pre,peri,两种血运重建策略所涉及的术后并发症将继续得到缓解,以优化冠状动脉旁路移植术或经皮冠状动脉介入治疗最终获益的患者的结局.避免不必要的血运重建的方法以及经皮技术的不断发展,可以使患者在可能的情况下避免手术干预。有了这样的变化,针对特定患者人群的血运重建指南可能会在未来几年发生变化,这可以作为这个时间日期审查的限制。
    OBJECTIVE: The optimal revascularization strategy for coronary artery disease depends on various factors, such as disease complexity, patient characteristics, and preferences. Including a heart team in complex cases is crucial to ensure optimal outcomes. Decision-making between percutaneous coronary intervention and coronary artery bypass grafting must consider each patient\'s clinical profile and coronary anatomy. While current practice guidelines offer some insight into the optimal revascularization approach for the various phenotypes of coronary artery disease, the evidence to support either strategy continues to evolve and grow. Given the large amount of contemporary data on revascularization, this review aims to comprehensively summarize the literature on coronary artery bypass grafting and percutaneous coronary intervention in patients across the spectrum of coronary artery disease phenotypes.
    RESULTS: Contemporary evidence suggests that for patients with triple vessel disease, coronary artery bypass grafting is preferred over percutaneous coronary intervention due to better long-term outcomes, including lower rates of death, myocardial infarction, and target vessel revascularization. Similarly, for patients with left main coronary artery disease, both percutaneous coronary intervention and coronary artery bypass grafting can be considered, as they have shown similar efficacy in terms of major adverse cardiac events, but there may be a slightly higher risk of death with percutaneous coronary intervention. For proximal left anterior descending artery disease, both percutaneous coronary intervention and coronary artery bypass grafting are viable options, but coronary artery bypass grafting has shown lower rates of repeat revascularization and better relief from angina. The Synergy Between PCI with Taxus and Cardiac Surgery score can help in decision-making by predicting the risk of adverse events and guiding the choice between percutaneous coronary intervention and coronary artery bypass grafting. European and American guidelines both agree with including a heart team that can develop and lay out individualized, optimal treatment options with respect for patient preferences. The debate between coronary artery bypass grafting versus percutaneous coronary intervention in multiple different scenarios will continue to develop as technology and techniques improve for both procedures. Risk factors, pre, peri, and post-procedural complications involved in both revascularization strategies will continue to be mitigated to optimize outcomes for those patients for which coronary artery bypass grafting or percutaneous coronary intervention provide ultimate benefit. Methods to avoid unnecessary revascularization continue to develop as well as percutaneous technology that may allow patients to avoid surgical intervention when possible. With such changes, revascularization guidelines for specific patient populations may change in the coming years, which can serve as a limitation of this time-dated review.
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  • 文章类型: Journal Article
    背景:保持牙髓的活力和功能对于牙齿的完整性至关重要,长寿,和稳态。旨在治疗不可逆性牙髓炎和坏死,从传统的根管治疗向再生牙髓治疗转变。
    目的:这篇广泛且多部分的综述提出了与牙髓-牙本质复合物再生相关的关键实验室和实践问题,旨在促进再生牙髓治疗的临床转化和提高人类生活质量。
    在这篇多部分评论论文中,我们首先从细胞移植和细胞归巢的角度介绍了用于牙髓牙本质复合物再生的新兴潜在组织工程策略的全景,强调干细胞的关键再生成分,生物材料,和有益的微环境。然后,这篇综述提供了有关当前临床实践的牙髓再生/修复方法的详细信息,包括直接盖髓和根血运重建,特别关注开发此类疗法的剩余障碍和光明前景。接下来,特别关注致力于讨论通过使用外来体和细胞聚集体来建立功能组织的创新仿生观点,这将有利于牙髓工程协议的临床翻译。最后,我们总结了对再生牙髓药的基础研究和临床应用应给予的认真考虑。特别是,这篇综述文章强调了与残余感染和炎症相关的重大挑战,并确定了未来在创建抗菌和免疫调节微环境方面的有见地的方向,以便临床医生和研究人员能够全面了解再生牙髓治疗的关键临床方面.
    BACKGROUND: Maintaining the vitality and functionality of dental pulp is paramount for tooth integrity, longevity, and homeostasis. Aiming to treat irreversible pulpitis and necrosis, there has been a paradigm shift from conventional root canal treatment towards regenerative endodontic therapy.
    OBJECTIVE: This extensive and multipart review presents crucial laboratory and practical issues related to pulp-dentin complex regeneration aimed towards advancing clinical translation of regenerative endodontic therapy and enhancing human life quality.
    UNASSIGNED: In this multipart review paper, we first present a panorama of emerging potential tissue engineering strategies for pulp-dentin complex regeneration from cell transplantation and cell homing perspectives, emphasizing the critical regenerative components of stem cells, biomaterials, and conducive microenvironments. Then, this review provides details about current clinically practiced pulp regenerative/reparative approaches, including direct pulp capping and root revascularization, with a specific focus on the remaining hurdles and bright prospects in developing such therapies. Next, special attention was devoted to discussing the innovative biomimetic perspectives opened in establishing functional tissues by employing exosomes and cell aggregates, which will benefit the clinical translation of dental pulp engineering protocols. Finally, we summarize careful consideration that should be given to basic research and clinical applications of regenerative endodontics. In particular, this review article highlights significant challenges associated with residual infection and inflammation and identifies future insightful directions in creating antibacterial and immunomodulatory microenvironments so that clinicians and researchers can comprehensively understand crucial clinical aspects of regenerative endodontic procedures.
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  • 文章类型: Journal Article
    使用计算机断层扫描(FFR-CT)的血流储备分数的诊断性能受到钙化斑块的存在的影响。减法可以消除冠状动脉计算机断层扫描血管造影(CCTA)中钙化的影响,以增加诊断冠状动脉狭窄的信心。我们的目的是研究减影后FFR-CT预测早期血运重建的准确性。
    根据79例冠心病患者237条血管的CCTA数据,相减CCTA图像是在本地后处理工作站获得的,分析了常规和减影FFR-CT测量值以及血管最窄段近端和远端FFR-CT值的差异(ΔFFR-CT)预测早期冠状动脉血流动力学重建的准确性。
    以FFR-CT≤0.8为标准,常规和减影FFR-CT测量预测早期血运重建的准确性分别为73.4%和77.2%,船舶水平为64.6%和72.2%,分别。在患者和血管水平上,减影后FFR-CT测量的特异性均显着高于常规FFR-CT(P分别为0.013和0.015)。在船只层面,常规和减法后ΔFFR-CT的接收器工作特性曲线下面积分别为0.712和0.797,分别,显示差异(P=0.047),最佳截止值分别为0.07和0.11。
    减影后FFR-CT测量可增强预测早期血运重建的特异性。狭窄段减影后ΔFFR-CT值>0.11可能是早期血运重建的重要指标。
    UNASSIGNED: The diagnostic performance of fractional flow reserve with computed tomography (FFR-CT) is affected by the presence of calcified plaque. Subtraction can remove the influence of calcification in coronary computed tomography angiography (CCTA) to increase confidence in the diagnosis of coronary artery stenosis. Our purpose is to investigate the accuracy of post-subtraction FFR-CT in predicting early revascularization.
    UNASSIGNED: Based on CCTA data of 237 vessels from 79 patients with coronary artery disease, subtraction CCTA images were obtained at a local post-processing workstation, and the conventional and post-subtraction FFR-CT measurements and the difference in proximal and distal FFR-CT values of the narrowest segment of the vessel (ΔFFR-CT) were analyzed for their accuracy in predicting early coronary artery hemodynamic reconstruction.
    UNASSIGNED: With FFR-CT ≤ 0.8 as the criterion, the accuracy of conventional and post-subtraction FFR-CT measurements in predicting early revascularization was 73.4% and 77.2% at the patient level, and 64.6% and 72.2% at the vessel level, respectively. The specificity of post-subtraction FFR-CT measurements was significantly higher than that of conventional FFR-CT at both the patient and vessel levels (P of 0.013 and 0.015, respectively). At the vessel level, the area under the curve of receiver operating characteristic was 0.712 and 0.797 for conventional and post-subtraction ΔFFR-CT, respectively, showing a difference (P = 0.047), with optimal cutoff values of 0.07 and 0.11, respectively.
    UNASSIGNED: The post-subtraction FFR-CT measurements enhance the specificity in predicting early revascularization. The post-subtraction ΔFFR-CT value of the stenosis segment > 0.11 may be an important indicator for early revascularization.
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  • 文章类型: Editorial
    暂无摘要。
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  • 文章类型: Journal Article
    背景:急性心肌梗死(AMI)并发心源性休克(CS)患者经皮冠状动脉介入治疗(PCI)的最佳血管通路部位仍不确定。虽然由于并发症发生率和死亡率较低,观察数据有利于经桡动脉通路(TRA),经股动脉(TFA)PCI具有较短的进入和手术时间等优点,随着更快的升级到机械循环支持(MCS)。在这项研究中,我们旨在调查经股动脉入路的相关因素,并比较TRA和TFA在接受PCI的AMI-CS患者中的死亡率.
    方法:分析了全国范围内接受PCI的AMI-CS患者(2017-2021)的数据。我们比较了病人的人口统计,程序细节,以及TRA和TFA组之间的结果。Logistic回归确定了入路部位因素和桡骨股交叉预测因素。倾向评分匹配(PSM)分析检查了进入地点对死亡率的影响。
    结果:在1562名患者中,45%的患者接受了TRAPCI,随着时间的推移有增加的趋势。TFA患者通常是女性,有冠状动脉旁路移植术(CABG)的病史,降低血压,更高的复苏率和插管率,和乳酸水平升高。PSM之后,TRA的30天死亡率较低(33%vs.46%,p<0.001)。交叉的预测因素包括左冠状动脉介入治疗,多血管PCI和MCS启动。
    结论:TRA和TFAPCI在AMI-CS中存在显著差异。与TRA相比,TFA在血流动力学较差的患者中更为常见,并且与30天死亡率更高相关。这种死亡率差异在倾向评分匹配分析中仍然存在。
    BACKGROUND: The optimal vascular access site for percutaneous coronary interventions (PCI) in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) remains uncertain. While observational data favor transradial access (TRA) due to lower complication rates and mortality, transfemoral (TFA) PCI offers advantages such as shorter access and procedure times, along with quicker escalation to mechanical circulatory support (MCS). In this study, we aimed to investigate factors associated with a transfemoral approach and compare mortality rates between TRA and TFA in AMI-CS patients undergoing PCI.
    METHODS: Data from a nationwide registry of AMI-CS patients undergoing PCI (2017-2021) were analyzed. We compared patient demographics, procedural details, and outcomes between TRA and TFA groups. Logistic regression identified access site factors and radial-to-femoral cross-over predictors. Propensity score matched (PSM) analysis examined the impact of access site on mortality.
    RESULTS: Of 1562 patients, 45% underwent TRA PCI, with an increasing trend over time. TFA patients were more often female, had a history of coronary artery bypass grafting (CABG), lower blood pressure, higher resuscitation and intubation rates, and elevated lactate levels. After PSM, 30-day mortality was lower in TRA (33% vs. 46%, p <0.001). Predictors for cross-over included left coronary artery interventions, multivessel PCI, and MCS initiation.
    CONCLUSIONS: Significant differences exist between TRA and TFA PCI in AMI-CS. TFA was more common in patients with worse hemodynamics and was associated with higher 30-day mortality compared to TRA. This mortality difference persisted in the propensity score matched analysis.
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  • 文章类型: Case Reports
    识别非ST段抬高型急性心肌梗死(NSTEMI)的梗死相关动脉(IRA)可能非常具有挑战性,特别是在由于某些限制而无法进行冠状动脉成像的医院中。这是因为,通过血管造影,大多数患者出现多支冠状动脉疾病(CAD),弥漫性疾病,或非显著的CAD。我们介绍了一例60岁的女性患者,其胸骨下胸痛和心悸持续6小时。第一医院联系12导联心电图(ECG)显示室性心动过速(VT),血流动力学不稳定,稳定后,患者被送往导管插入实验室进行立即经皮冠状动脉介入治疗(PCI).有了室性心动过速形态学的线索,转换后的心电图,和冠状动脉造影,患者成功在左回旋支动脉行PCI.
    Identifying the infarct-related artery (IRA) in a non-ST-segment-elevation acute myocardial infarction (NSTEMI) can be very challenging, particularly in a hospital that cannot perform intracoronary imaging due to certain limitations. This is because, by angiography, most patients present with multivessel coronary artery disease (CAD), diffuse disease, or non-significant CAD. We present a case of a 60-year-old female patient presented with substernal chest pain and palpitations of 6 h duration. The first hospital contact 12-lead electrocardiogram (ECG) showed ventricular tachycardia (VT) with unstable hemodynamics, after stabilization patient was transported to the catheterization laboratory for immediate percutaneous coronary intervention (PCI). With a clue of VT morphology, post-converted ECG, and coronary angiography, the patient successfully underwent PCI in the left circumflex artery.
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  • 文章类型: English Abstract
    Peripheral arterial occlusive disease (PAOD) is a frequent manifestation of atherosclerosis with a high risk of cardiovascular events (myocardial infarction, stroke, amputation, cardiovascular death). A distinction is made between the stable form of intermittent claudication and chronic limb-threatening ischemia (CLTI, pain at rest, wounds). The most frequent risk factors are diabetes mellitus and smoking. As the disease is often asymptomatic early diagnostic necessary. Measurement of the ankle-brachial index (ABI) is suitable for screening. Consistent treatment of cardiovascular risk factors and antithrombotic medication are important. At the stage of intermittent claudication, exercise training should be performed. In CLTI early endovascular or surgical revascularization must be performed to avoid amputation of the extremity.
    UNASSIGNED: Die periphere arterielle Verschlusskrankheit (pAVK) ist eine häufige Manifestation der Atherosklerose mit hohem Risiko für kardiovaskuläre Ereignisse (Myokardinfarkt, Schlaganfall, Amputation, kardiovaskulärer Tod). Man unterscheidet die stabile Form der Claudicatio intermittens von der chronisch kritischen Extremitätenischämie („chronic limb-threatening ischemia“ [CLTI]; Ruheschmerz, Wunden). Die häufigsten Risikofaktoren sind Diabetes mellitus und Rauchen. Da die Erkrankung oft asymptomatisch verläuft, ist eine frühzeitige Diagnostik notwendig. Zum Screening eignet sich die Messung des Knöchel-Arm-Index („ankle-brachial index“, ABI). In der Therapie sind die konsequente Behandlung der Risikofaktoren und eine antithrombotische Medikation wichtig. Im Stadium der Claudicatio intermittens sollte Gefäßsport durchgeführt werden. Bei CLTI muss eine rasche endovaskuläre oder chirurgische Revaskularisation erfolgen, um die Amputation der Extremität zu verhindern.
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  • 文章类型: Case Reports
    外周动脉疾病(PAD)是动脉壁中钙和脂肪沉积的累积(动脉粥样硬化)。这是一个重要的临床问题,特别是在有多级病变的情况下。一名患者接受了严重PAD的序贯血管成形术治疗,其特征是影响两个膝下动脉的多级病变。近端血管和膝下血管主要被观察到受到PAD的影响。因此,患者可能患有位于小腿的PAD。在股pop段,下肢动脉或主动脉粥样硬化闭塞性疾病可导致显著的预后。在有高血压和糖尿病病史的患者中,观察到双腿休息时严重跛行和疼痛。做了血管造影,股骨浅层,腿部,和胫骨动脉已被证明有主要的狭窄和闭塞。由于以股浅动脉血管内血运重建为起点的病变的复杂性,因此使用了渐进式治疗。然后通过血管成形术和支架置入术修复the动脉和胫骨动脉。治疗后,患者的症状明显改善,包括消除他们的休息不适和跛行。踝臂指数(ABI)的测量表明,受影响的肢体灌注得到了改善。六个月后,随访血管造影显示血管完整,无再狭窄.该病例报告显示了复发性血管成形术治疗复杂的多水平PAD的成功结果。给予症状缓解和维持肢体灌注。这项研究需要评估这种治疗在与其他人相当的患者人群中的长期结果和寿命。
    Peripheral artery disease (PAD) is the buildup of calcium and fatty deposits in the arterial walls (atherosclerosis). This is an important clinical issue, specifically in cases with multilevel lesions. A patient underwent sequential angioplasty treatment for major PAD, which was characterized by multilevel lesions affecting both the infrapopliteal arteries. The proximal vessels and infrapopliteal vessels are mostly observed to be affected by PAD, thus the patient likely has PAD localized to the lower leg. In the femoropopliteal segment, lower extremity artery or aortic atherosclerotic occlusive disease can lead to significant outcomes. Severe claudication and pain during rest in both legs were observed in a patient with a history of hypertension and diabetes mellitus. With an angiography, the superficial femoral, popliteal, and tibial arteries have been shown to have major stenoses and occlusions. A progressive treatment was used because of the complexity of the lesions initiating with endovascular revascularization of the superficial femoral artery. The popliteal and tibial arteries were then repaired with angioplasty and stent placement. After the treatment, the patient\'s symptoms significantly improved, including elimination of their rest discomfort and claudication. Measurements of the ankle-brachial index (ABI) indicated that the affected limbs\' perfusion was refined. Six months later, a follow-up angiography revealed intact vessels with no restenosis. This case report shows the successful outcome of recurrent angioplasty in curing complicated multilevel PAD, giving symptomatic relief and maintaining limb perfusion. This research is required to assess the long-term outcomes and longevity of this kind of treatment in patient populations that are comparable to others.
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  • 文章类型: Journal Article
    背景:早产儿视网膜病变(ROP)是一种发生在早产儿视网膜上的增生性视网膜血管疾病,是导致儿童失明的主要原因。抗VEGF和视网膜光凝是目前ROP的主流治疗方法,但是它们会出现各种并发症。氢气(H2)被广泛认为是缺氧缺血性疾病的有用的神经保护和抗氧化治疗方法,而没有毒性作用。然而,H2是否提供生理血管生成促进,ROP进展中的新生血管抑制和神经胶质保护作用在很大程度上是未知的。本研究旨在探讨H2对视网膜血管生成的影响,氧诱导的视网膜病变(OIR)小鼠视网膜的新生血管形成和神经胶质功能障碍。
    方法:在本研究中,将7日龄和野生型(WT)或Nrf2缺陷(Nrf2-/-)的小鼠暴露于75%的氧气中5天,然后恢复到正常的空气条件。给予不同阶段的氢气(H2)吸入。血管闭塞,新生血管形成,并对血管渗漏进行分析比较。计算新生血管内皮细胞核的数量,行视网膜切片常规HE染色。使用DyLight594标记的GSLI-isolectinB4(IB4)进行免疫组织化学,以及针对增殖细胞核抗原(PCNA)的一级抗体,胶质纤维酸性蛋白(GFAP),Iba-1蛋白质印迹法检测NF-E2相关因子2(Nrf2)的表达,血管内皮生长因子(VEGF),Notch1、Dll4和HIF-1α。此外,测定靶基因如NQO1、HO-1、Notch1、Hey1、Hey2和Dll4的表达。在低氧条件下用H2处理的人脐静脉内皮细胞(HUVECs)用作体外模型。RT-PCR检测Nrf2、Notch/Dll4和靶基因的mRNA表达。使用免疫荧光染色观察活性氧(ROS)的表达。
    结果:我们的结果表明,3-4%H2不会干扰视网膜生理性血管生成,但改善OIR小鼠的血管闭塞和新生血管形成。此外,H2可防止密度降低,并逆转氧诱导损伤引起的视网膜星形胶质细胞的形态和功能变化。此外,H2吸入减少小胶质细胞活化,特别是在OIR小鼠的新生血管形成领域。H2通过在体内促进Nrf2活化和抑制Dll4诱导的Notch信号通路在血管再生中起保护作用。此外,H2通过负调节Dll4/Notch途径并通过Nrf2途径降低ROS水平来促进低氧下HUVECs的增殖,这与我们在体内的发现一致。此外,视网膜氧敏感机制(HIF-1α/VEGF)也参与氢介导的视网膜血管再生和新生血管抑制.
    结论:总的来说,我们的结果表明,H2可能是一种有前景的POR治疗药物,其在人ROP中的有益作用可能涉及Nrf2-Notch轴以及HIF-1α/VEGF通路的激活.
    BACKGROUND: Retinopathy of Prematurity (ROP) is a proliferative retinal vascular disease occurring in the retina of premature infants and is the main cause of childhood blindness. Nowadays anti-VEGF and retinal photocoagulation are mainstream treatments for ROP, but they develop a variety of complications. Hydrogen (H2) is widely considered as a useful neuroprotective and antioxidative therapeutic method for hypoxic-ischemic disease without toxic effects. However, whether H2 provides physiological angiogenesis promotion, neovascularization suppression and glial protection in the progression of ROP is largely unknown.This study aims to investigate the effects of H2 on retinal angiogenesis, neovascularization and neuroglial dysfunction in the retinas of oxygen-induced retinopathy (OIR) mice.
    METHODS: In this study, mice that were seven days old and either wild-type (WT) or Nrf2-deficient (Nrf2-/-) were exposed to 75% oxygen for 5 days and then returned to normal air conditions. Different stages of hydrogen gas (H2) inhalation were administered. Vascular obliteration, neovascularization, and blood vessel leakage were analyzed and compared. To count the number of neovascularization endothelial nuclei, routine HE staining of retinal sections was conducted. Immunohistochemistry was performed using DyLight 594 labeled GSL I-isolectin B4 (IB4), as well as primary antibodies against proliferating cell nuclear antigen (PCNA), glial fibrillary acidic protein (GFAP), and Iba-1. Western blots were used to measure the expression of NF-E2-related factor 2 (Nrf2), vascular endothelial growth factor (VEGF), Notch1, Dll4, and HIF-1α. Additionally, the expression of target genes such as NQO1, HO-1, Notch1, Hey1, Hey2, and Dll4 was measured. Human umbilical vein endothelial cells (HUVECs) treated with H2 under hypoxia were used as an in vitro model. RT-PCR was used to evaluate the mRNA expression of Nrf2, Notch/Dll4, and the target genes. The expression of reactive oxygen species (ROS) was observed using immunofluorescence staining.
    RESULTS: Our results indicate that 3-4% H2 does not disturb retinal physiological angiogenesis, but ameliorates vaso-obliteration and neovascularization in OIR mice. Moreover, H2 prevents the decreased density and reverses the morphologic and functional changes in retinal astrocytes caused by oxygen-induced injury. In addition, H2 inhalation reduces microglial activation, especially in the area of neovascularization in OIR mice. H2 plays a protective role in vascular regeneration by promoting Nrf2 activation and suppressing the Dll4-induced Notch signaling pathway in vivo. Also, H2 promotes the proliferation of HUVECs under hypoxia by negatively regulating the Dll4/Notch pathway and reducing ROS levels through Nrf2 pathway aligning with our findings in vivo.Moreover, the retinal oxygen-sensing mechanisms (HIF-1α/VEGF) are also involved in hydrogen-mediated retinal revascularization and neovascularization suppression.
    CONCLUSIONS: Collectively, our results indicate that H2 could be a promising therapeutic agent for POR treatment and that its beneficial effect in human ROP might involve the activation of the Nrf2-Notch axis as well as HIF-1α/VEGF pathways.
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