Nervous system disorders

  • 文章类型: Journal Article
    目的和背景:本研究试图确定人类表皮生长因子受体2(HER2)抑制剂之间的不良事件(AE)的相似性和差异性,尤其是与出血事件和神经系统疾病有关的事件。方法:本研究总结了不同类型,频率,和HER2抑制剂AE的系统器官类别(SOC)。收集并分析了2004年1月至2022年3月的美国食品和药物管理局不良事件报告系统(FAERS)数据。进行不相称性分析以检测每种HER2抑制剂的AE信号。卡方检验,Wilcoxon试验,和描述性分析用于比较特定SOCs或药物的AE差异。结果:共获得了关于8种HER2抑制剂的47,899例AE报告。曲妥珠单抗相关的AE在方案的数量和组合中报告最多。在单一疗法中,曲妥珠单抗的心脏疾病相关AE报告率最高(24.0%).然而,小分子药物在胃肠道疾病相关的不良事件发生率方面超过其他药物,新陈代谢和营养失调。呼吸系统疾病(47.3%)和血液系统疾病(22.4%)的最高报告率与曲妥珠单抗治疗相关(T-DXd)。接受曲妥珠单抗emtansine(TDM-1)治疗的患者报告的出血性事件发生率最高(7.28%)。尤其是颅内出血事件。此外,与其他HER2抑制剂相比,接受TDM-1合并血小板减少症的患者可能出现出血性事件(p<0.001).与曲妥珠单抗(0.5个月)和TDM-1(0.75个月)相关的颅内出血的中位发病时间较短。然而,不同年龄组或不同结局的患者颅内出血中位发病时间无显著差异.不成比例分析结果表明,脑出血是与T-DXd和TDM-1相关的阳性信号。此外,图卡替尼是神经系统疾病发生率最高的药物(31.38%).记忆障碍(83例)是图卡替尼的阳性信号。结论:与不同HER2抑制剂相关的AE的类型和报告率在多个系统中有所不同。此外,TDM-1治疗伴随的出血性事件和Tucatinib治疗伴随的神经系统疾病可能值得关注.
    Aim and background: This study attempted to identify similarities and differences in adverse events (AEs) between human epidermal growth factor receptor 2 (HER2) inhibitors, especially those related to hemorrhagic events and nervous system disorders. Methods: This study summarized the types, frequencies, and system organ classes (SOCs) of AEs of HER2 inhibitors. The US Food and Drug Administration Adverse Event Reporting System (FAERS) data from January 2004 through March 2022 was collected and analyzed. Disproportionality analyses were conducted to detect AEs signals for every HER2 inhibitor. The chi-square test, Wilcoxon test, and descriptive analysis were used to compare the differences of AEs for specific SOCs or drugs. Results: A total of 47,899 AE reports were obtained for eight HER2 inhibitors. Trastuzumab-related AEs were reported in the highest number and combination of regimens. In monotherapy, trastuzumab had the highest reported rate of cardiac disorders-related AEs (24.0%). However, small-molecule drugs exceeded other drugs in the reported rates of AEs related to gastrointestinal disorders, metabolism and nutrition disorders. The highest reported rates of respiratory disorders (47.3%) and hematologic disorders (22.4%) were associated with treatment with trastuzumab deruxtecan (T-DXd). Patients treated with trastuzumab emtansine (TDM-1) had the highest reported rate (7.28%) of hemorrhagic events, especially intracranial haemorrhage events. In addition, patients treated with TDM-1 with concomitant thrombocytopenia were likely to experience hemorrhagic events compared to other HER2 inhibitors (p < 0.001). The median time to onset of intracranial haemorrhage associated with trastuzumab (0.5 months) and TDM-1 (0.75 months) was short. However, there was no significant difference in median time to onset intracranial haemorrhage between patients in different age groups or with different outcomes. Disproportionality analysis results reveal that cerebral haemorrhage is a positive signal associated with T-DXd and TDM-1. In addition, tucatinib was the drug with the highest rate of reported nervous system disorders (31.38%). Memory impairment (83 cases) is a positive signal for tucatinib. Conclusion: The types and reporting rates of AEs associated with different HER2 inhibitors vary across multiple systems. In addition, hemorrhagic events concomitant with TDM-1 treatment and nervous system disorders concomitant with tucatinib treatment may be worthy of attention.
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  • 文章类型: Journal Article
    铁凋亡与程序性细胞死亡的其他凋亡形式不同,其特征在于铁和脂质过氧化的积累。铁通过与氧的Fenton反应在脂质的氧化中起关键作用。因此,铁的积累会导致磷脂过氧化,从而诱导铁凋亡。此外,谷胱甘肽的解毒作用在铁死亡过程中被破坏。越来越多的研究表明铁性凋亡与抑郁症等神经系统疾病有关,神经退行性疾病,中风,创伤性脑损伤,和脓毒症相关性脑病。本文就铁性凋亡的发病机制及其与各种神经系统疾病的关系作一综述。
    Ferroptosis is distinct from other apoptotic forms of programmed cell death and is characterized by the accumulation of iron and lipid peroxidation. Iron plays a crucial role in the oxidation of lipids via the Fenton reaction with oxygen. Hence, iron accumulation causes phospholipid peroxidation which induces ferroptosis. Moreover, detoxification by glutathione is disrupted during ferroptosis. A growing number of studies have implicated ferroptosis in nervous system disorders such as depression, neurodegenerative disease, stroke, traumatic brain injury, and sepsis-associated encephalopathy. This review summarizes the pathogenesis of ferroptosis and its relationship with various nervous system disorders.
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  • 文章类型: Journal Article
    Panax notoginseng saponins (PNS), also called \"sanqi\" in Chinese, are the main active ingredients which are extracted from the root of Panax notoginseng (Burk.) F. H. Chen., and they have been traditionally used as a medicine in China for hundreds of years with magical medicinal value. PNS have varied biological functions, such as anti-inflammatory effects, anti-cancer effects, anti-neurotoxicity, and the prevention of diabetes. Nervous system disorders, a spectrum of diseases originating from the nervous system, have a significant impact on all aspects of patients\' lives. Due to the dramatic gains in global life expectancy, the prevalence of nervous system disorders is growing gradually. Even if the mechanism of these diseases is still not clear, they are mainly characterized by neuronal dysfunction and neuronal death. Consequently, it is essential to find measures to slow down or prevent the onset of these diseases. At present, traditional Chinese medicines, as well as their active components, have gained widespread popularity in preventing and treating these diseases because of their merits, especially PNS. In this review, we predominantly address the recent advances in PNS researches and their biological functions, and highlight their applications in nervous system disorders, such as Alzheimer\'s disease (AD), Parkinson\'s disease (PD), and stroke.
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  • 文章类型: Journal Article
    Optic nerve trauma is a common occurrence that results in irreversible blindness. Currently, no effective strategies are known to prevent optic nerve degeneration. We assessed the therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) after optic nerve crush in the adult rat. Our results showed that BMSCs significantly promoted the regeneration of injured axons compared with phosphate buffered saline alone. Therefore, BMSC transplantation may be effective for the treatment of central nervous system disorders.
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