Pharmacological therapy

药物治疗
  • 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
    本文介绍了一项初步研究的结果,该研究调查了患者对药理学结果与手术结果的满意度阈值。
    总共150名参与者被介绍了两种描述药物治疗或手术干预的假设方案。每个场景都描述了一个潜在的结果,从10%的临床改善(值10)到100%的临床改善(值100),并要求参与者指出他们认为可以接受的满意水平。
    结果揭示了两种治疗方式之间满意度阈值的不同模式。在150名参与者之间,52,7%为男性,47,3%为女性。我们还确定了总共28,8%的人是医护人员。总的来说,药物治疗结局的结果观察到,平均值为60,88,标准差为22,77,中位数为60,模式为70;而手术结局的平均值为67,81,标准差为23,03,中位数为85,模式为80.我们还观察到,对于药物治疗结果,与非医护人员相比,医护人员的满意截止值较低。另一个有趣的发现是,对于药物治疗结果,与50岁以上的个体相比,50岁以下的个体有更高的令人满意的截止值。而对于手术结果,我们得到了相反的结果。总的来说,这项试点研究的结果,即使有限,与药物治疗结果相比,对手术结果的最低满意度期望更高.具体来说,参与者往往需要更有利的结果和手术干预结果,以满足他们的最低满意度标准.
    UNASSIGNED: This article presents the results of a pilot study investigating patients\' satisfaction thresholds for pharmacological outcomes versus surgical outcomes.
    UNASSIGNED: A total of 150 participants were presented with two hypothetical scenarios depicting either pharmacological therapy or surgical interventions. Each scenario described a potential outcome, from a 10% clinical improvement (value 10) to a 100% clinical improvement (value 100) and asked participants to indicate the satisfactory level they would find acceptable.
    UNASSIGNED: The results revealed distinct patterns in satisfaction thresholds between the two treatment modalities. Between the 150 participants, 52,7% were male and 47,3% female. We also identified a total of 28,8% whom were healthcare workers. Overall, the results for the pharmacological therapy outcomes observed a mean of 60,88 with a standard deviation of 22,77, a median of 60 and a mode of 70; while for the surgical outcomes the mean was 67,81 with a standard deviation of 23,03, the median 85 and the mode 80. We also observed that for the pharmacological therapy outcomes healthcare workers had a lower satisfactory cut off compared to non-healthcare workers. Another interesting finding was that for pharmacological therapy outcomes individuals under 50 y/o had a higher satisfactory cut off compared to individuals over 50 y/o, while for the surgical outcomes we got opposite results. Overall, the findings of this pilot study, even if limited, demonstrated higher minimum satisfaction expectations for surgical outcomes compared to pharmacological therapy outcomes. Specifically, participants tended to require more favorable results and outcomes from surgical interventions to meet their minimum satisfaction criteria.
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  • 文章类型: Journal Article
    背景:本系统综述调查了家族因素对10-17岁有饮食失调临床体征或症状的个体的影响。同时,它仔细检查了家庭参与治疗的情况,以及其他形式的干预。方法:PsycINFO,PubMed,和Scopus数据库用于全面搜索研究材料。在应用特定标准后,46篇文章被认为是合适的,并包括在系统评价中。该研究包括一组4794名青少年,他们被诊断为神经性厌食症(AN),神经性贪食症(BN),或暴饮暴食障碍(床)。此外,对1187名青少年进行了对照,1563父母,1809兄弟姐妹,还有11个亲戚。结果:家庭因素与饮食失调之间的联系主要取决于家庭的功能水平,对家庭动态的满意度,父母对孩子的态度,以及食物在家庭系统中的作用。家庭治疗是治疗AN最常用的心理治疗方法。BN中报告的发生率与认知行为疗法(CBT)模型的发生率密切相关。有关(增强)CBT的文章仅与BED相关。结论:基于家庭的方法对于理解至关重要,预防,解决青少年饮食失调问题。结合家庭动力学的研究并积极参与治疗过程,可以显着提高康复率并减少复发的发生。
    Background: This systematic review investigated the impact of familial factors on individuals aged 10-17 who have clinical signs or symptoms of eating disorders. Simultaneously, it scrutinized the involvement of the family in therapy, as well as other forms of intervention. Methods: The PsycINFO, PubMed, and Scopus databases were used to search for research material comprehensively. After applying specific criteria, 46 articles were deemed suitable and included in the systematic review. The study comprised a cohort of 4794 adolescents who received a diagnosis of either Anorexia Nervosa (AN), Bulimia Nervosa (BN), or Binge-Eating Disorder (BED). In addition, controls were utilized for 1187 adolescents, 1563 parents, 1809 siblings, and 11 other relatives. Results: The connection between family factors and eating disorders is primarily determined by the families\' level of functioning, satisfaction with the family dynamic, parents\' attitudes toward their children, and the role of food within the family system. Family Therapy was the most used psychotherapeutic approach in the treatment of AN. The incidence of reports in BN closely paralleled that of Cognitive-Behavioral Therapy (CBT) models. Articles about (Enhanced) CBT were exclusively associated with BED. Conclusions: Family-based approaches are crucial in comprehending, preventing, and addressing eating disorders in adolescents. Incorporating the study of family dynamics and actively engaging families in the treatment process can significantly enhance recovery rates and decrease the occurrence of relapses.
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  • 文章类型: Journal Article
    迄今为止,已鉴定出400多种人乳头瘤病毒(HPV)。尽管针对最常见的生殖器HPV创建了有效的预防性疫苗,这些病毒仍然是人类中最常见的病原体之一。根据世卫组织的数据,它们是所有癌症的5%的原因。更常见的是持续性和复发性良性病变,如生殖器和普通疣。HPV对许多消毒剂具有抗性并且相对不易受到外部条件的影响。目前还没有抑制病毒复制的药物,治疗是基于去除病变或刺激宿主免疫系统。本文介绍了HPV的系统性以及不同遗传类型之间HPV结构的差异,血统,和亚血统,基于文献和GenBank数据。我们还提出了由HPV引起的疾病的发病机制,特别关注E6,E7和其他病毒蛋白在良性和癌性病变发展中所起的作用。我们讨论了HPV感染治疗的进一步前景,包括,其中,阻止HPV进入细胞的物质,病毒早期蛋白质的抑制剂,和一些植物来源的抑制病毒复制的物质,以及治疗性疫苗的新可能性。
    To date, more than 400 types of human papillomavirus (HPV) have been identified. Despite the creation of effective prophylactic vaccines against the most common genital HPVs, the viruses remain among the most prevalent pathogens found in humans. According to WHO data, they are the cause of 5% of all cancers. Even more frequent are persistent and recurrent benign lesions such as genital and common warts. HPVs are resistant to many disinfectants and relatively unsusceptible to external conditions. There is still no drug available to inhibit viral replication, and treatment is based on removing lesions or stimulating the host immune system. This paper presents the systematics of HPV and the differences in HPV structure between different genetic types, lineages, and sublineages, based on the literature and GenBank data. We also present the pathogenesis of diseases caused by HPV, with a special focus on the role played by E6, E7, and other viral proteins in the development of benign and cancerous lesions. We discuss further prospects for the treatment of HPV infections, including, among others, substances that block the entry of HPV into cells, inhibitors of viral early proteins, and some substances of plant origin that inhibit viral replication, as well as new possibilities for therapeutic vaccines.
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  • 文章类型: Journal Article
    在皮肤中实现G蛋白偶联受体(GPCR)靶向药物的功效和特异性仍然具有挑战性。了解GPCR功能障碍的分子机制对于开发靶向治疗至关重要。遗传学的最新进展,信号转导,和结构研究显著提高了我们对正常和病理状态下皮肤GPCR功能的理解。在这次审查中,我们总结了皮肤损伤中致病性GPCRs的最新发现,慢性炎症性皮肤病,皮肤恶性肿瘤,以及潜在有效药物的开发。我们还讨论了通过瞬时受体电位(TRP)通道和结构阐明靶向皮肤GPCR复合物,这为涉及皮肤病的GPCRs的治疗靶向提供了新的机会。这些见解有望为各种皮肤状况带来更有效和更具体的治疗。
    Achieving the efficacy and specificity of G-protein-coupled receptor (GPCR) targeting-drugs in the skin remains challenging. Understanding the molecular mechanism underlying GPCR dysfunction is crucial for developing targeted therapies. Recent advances in genetic, signal transduction, and structural studies have significantly improved our understanding of cutaneous GPCR functions in both normal and pathological states. In this review, we summarize recent discoveries of pathogenic GPCRs in dermal injuries, chronic inflammatory dermatoses, cutaneous malignancies, as well as the development of potent potential drugs. We also discuss targeting of cutaneous GPCR complexes via the transient receptor potential (TRP) channel and structure elucidation, which provide new opportunities for therapeutic targeting of GPCRs involved in skin disorders. These insights are expected to lead to more effective and specific treatments for various skin conditions.
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  • 文章类型: Editorial
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  • 文章类型: Journal Article
    糖尿病伤口是医疗保健领域最具挑战性的问题之一,需要创新的方法来促进有效的愈合。近年来,基于脂质纳米颗粒的药物递送系统已成为通过刺激血管生成来增强糖尿病伤口修复的有希望的策略.这些纳米粒子提供了独特的优势,包括改善药物稳定性,有针对性的交付,和受控释放,使它们有希望增强新血管的形成。在这次审查中,我们总结了利用脂质纳米粒递送血管生成剂和促进糖尿病伤口血管生成的最新进展。此外,我们对关键方面进行了深入的探索,包括复杂的脂质纳米颗粒的设计和制造,他们潜在的行动机制,以及临床前研究的全面概述。此外,我们讨论了与安全性相关的关键考虑因素,以及将这些创新系统转化为临床实践。通过综合和分析现有的知识,我们的综述提供了对未来前景和挑战的有价值的见解,这些前景和挑战与利用基于脂质纳米颗粒的药物递送系统在糖尿病伤口愈合的复杂过程中促进强大的血管生成的潜力有关。
    Diabetic wound is one of the most challenge in healthcare, requiring innovative approaches to promote efficient healing. In recent years, lipid nanoparticle-based drug delivery systems have emerged as a promising strategy for enhancing diabetic wound repair by stimulating angiogenesis. These nanoparticles offer unique advantages, including improved drug stability, targeted delivery, and controlled release, making them promising in enhancing the formation of new blood vessels. In this review, we summarize the emerging advances in the utilization of lipid nanoparticles to deliver angiogenic agents and promote angiogenesis in diabetic wounds. Furthermore, we provide an in-depth exploration of key aspects, including the intricate design and fabrication of lipid nanoparticles, their underlying mechanisms of action, and a comprehensive overview of preclinical studies. Moreover, we address crucial considerations pertaining to safety and the translation of these innovative systems into clinical practice. By synthesizing and analyzing the available knowledge, our review offers valuable insights into the future prospects and challenges associated with utilizing the potential of lipid nanoparticle-based drug delivery systems for promoting robust angiogenesis in the intricate process of diabetic wound healing.
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  • 文章类型: Journal Article
    背景:膝关节骨性关节炎是一种退行性和炎症性疾病,引起疼痛并恶化患者的生活质量。存在各种保守治疗选择,但是科学证据和临床实践之间的差距仍然存在。这项前瞻性多中心观察性研究的目的是描述膝骨关节炎患者的真实门诊地域管理,并分析在全国调查中筛查的症状性膝骨关节炎患者人群的人体测量和临床特征之间的相关性。方法:教育国家项目分为三个模块:第一个和最后一个通过网络研讨会;第二个在日常实践中举行。参与者必须登记结构化的观察,然后将其存储在国家数据库中并进行分析以确定相关性。亚组按身体成分分层,膝骨关节炎的放射学严重程度,疼痛,和功能能力。结果:该项目已由155名医生加入,收集了2.656个关于在意大利接受膝关节骨关节炎治疗的真实世界门诊患者的观察结果。与身体成分相关的真实世界药理学和康复治疗数据,膝骨关节炎的放射学严重程度,疼痛,和功能能力报告。结论:目前,没有使用有效组合治疗练习的标准化方案,物理代理,以及控制膝骨关节炎进展的药物.这项真实的国家调查被证明有助于描述膝关节骨关节炎的治疗管理的现状,并强调需要填补科学证据与临床实践之间的空白。
    Background: Knee osteoarthritis is a degenerative and inflammatory disease causing pain and worsening patients\' quality of life. Various conservative treatment options exist, but a gap between scientific evidence and clinical practice is still present. The aim of this prospective multicenter observational study is to describe the real outpatient territorial management of patients with knee osteoarthritis and to analyze the correlation between the anthropometric and clinical characteristics of the population of patients suffering from symptomatic knee osteoarthritis who were screened in the national survey. Methods: The educational national project was divided into three modules: the first and the last through webinars; and the second held in daily practice. The participants had to register structured observations, which were then stored in a national database and analyzed in order to identify correlations. The subgroups were stratified by body composition, radiological severity of knee osteoarthritis, pain, and functional ability. Results: The project has been joined by 155 physicians, and 2.656 observations about real-world outpatients being treated for knee osteoarthritis in Italy were collected. Data relating to real-world pharmacological and rehabilitation therapies in correlation with body composition, the radiological severity of knee osteoarthritis, pain, and functional ability were reported. Conclusions: Currently, there are no standardized protocols using effective combinations of therapeutic exercises, physical agents, and medications to control the progression of knee osteoarthritis. This real-word national survey proved to be useful for describing the current state of the art of therapeutic management of knee osteoarthritis and for emphasizing the need to fill the gap between scientific evidence and clinical practice.
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  • 文章类型: Journal Article
    目的:尽管肺静脉隔离(PVI),但持续性房颤(AF)患者的复发率为50%,对于第二次治疗没有共识。我们i-STRATIFICATION研究的目的是为PVI后房颤复发患者的最佳药物和消融治疗分层提供证据。通过计算机内试验。
    方法:800名虚拟患者的队列,随着心房解剖结构的变化,电生理学,和组织结构(低电压区域,LVA),针对从离子电流到心电图的临床数据进行了开发和验证。PVI后出现AF的虚拟患者接受了12次二次治疗。
    结果:522名虚拟患者在PVI后出现持续房颤。仅包括左心房消融术的第二次消融术显示55%的疗效,仅在小右心房(<60mL)成功。当考虑额外的腔静脉-三尖瓣峡部消融时,Marshall-Plan对小左心房(<90mL)足够(66%疗效)。对于更大的左心房,需要更积极的消融方法,例如二尖瓣前线(75%的疗效)或后壁隔离加二尖瓣峡部消融(77%的疗效)。具有LVA的虚拟患者极大地受益于左心房和右心房的LVA消融(100%疗效)。相反,在没有LVA的情况下,协同消融和药物治疗可终止房颤。在没有消融的情况下,患者的离子电流底物调节了抗心律失常药物的反应,是对胺碘酮或vernakalant的最佳分层至关重要的内向流。
    结论:计算机模拟试验根据虚拟患者特征确定房颤治疗的最佳策略,证明人体建模和仿真作为临床辅助工具的力量。
    OBJECTIVE: Patients with persistent atrial fibrillation (AF) experience 50% recurrence despite pulmonary vein isolation (PVI), and no consensus is established for secondary treatments. The aim of our i-STRATIFICATION study is to provide evidence for stratifying patients with AF recurrence after PVI to optimal pharmacological and ablation therapies, through in silico trials.
    RESULTS: A cohort of 800 virtual patients, with variability in atrial anatomy, electrophysiology, and tissue structure (low-voltage areas, LVAs), was developed and validated against clinical data from ionic currents to electrocardiogram. Virtual patients presenting AF post-PVI underwent 12 secondary treatments. Sustained AF developed in 522 virtual patients after PVI. Second ablation procedures involving left atrial ablation alone showed 55% efficacy, only succeeding in the small right atria (<60 mL). When additional cavo-tricuspid isthmus ablation was considered, Marshall-PLAN sufficed (66% efficacy) for the small left atria (<90 mL). For the bigger left atria, a more aggressive ablation approach was required, such as anterior mitral line (75% efficacy) or posterior wall isolation plus mitral isthmus ablation (77% efficacy). Virtual patients with LVAs greatly benefited from LVA ablation in the left and right atria (100% efficacy). Conversely, in the absence of LVAs, synergistic ablation and pharmacotherapy could terminate AF. In the absence of ablation, the patient\'s ionic current substrate modulated the response to antiarrhythmic drugs, being the inward currents critical for optimal stratification to amiodarone or vernakalant.
    CONCLUSIONS: In silico trials identify optimal strategies for AF treatment based on virtual patient characteristics, evidencing the power of human modelling and simulation as a clinical assisting tool.
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  • 文章类型: Journal Article
    肥胖代表着重大的健康挑战,与II型糖尿病等疾病有着错综复杂的联系,代谢综合征,和肝脏脂肪变性.几种现有的肥胖治疗方法表现出有限的疗效,不良副作用或长期维持治疗效果的能力有限。最近,调节辅酶Q(CoQ)代谢已成为治疗代谢综合征的有希望的靶标。这种潜在的干预可能涉及通过使用其生物合成前体的类似物来调节内源性CoQ生物合成,例如β-间苯二酸(β-RA)。这里,我们显示口服补充β-RA,纳入饮食诱导的肥胖(DIO)小鼠的饮食中,导致体重大幅下降。通过使白色脂肪组织(WAT)中线粒体CoQ代谢正常化,部分阐明了β-RA的抗肥胖作用。此外,我们确定了肝脏脂质代谢的HFN4α/LXR依赖性转录组激活,这有助于β-RA的抗肥胖作用。因此,β-RA减轻WAT肥大,预防肝脏脂肪变性,抵消WAT和肝脏的代谢异常,并通过降低胰岛素/胰高血糖素比率和胃抑制肽(GIP)的血浆水平来增强葡萄糖稳态。此外,β-RA的药代动力学评估支持其翻译潜力。因此,β-RA作为一种有效的,安全,以及用于治疗和/或预防肥胖症的可翻译的治疗选择,代谢功能障碍相关脂肪变性肝病(MASLD)。
    Obesity represents a significant health challenge, intricately linked to conditions such as type II diabetes, metabolic syndrome, and hepatic steatosis. Several existing obesity treatments exhibit limited efficacy, undesirable side effects or a limited capability to maintain therapeutics effects in the long-term. Recently, modulation Coenzyme Q (CoQ) metabolism has emerged as a promising target for treatment of metabolic syndrome. This potential intervention could involve the modulation of endogenous CoQ biosynthesis by the use of analogs of the precursor of its biosynthesis, such as β-resorcylic acid (β-RA). Here, we show that oral supplementation with β-RA, incorporated into the diet of diet-induced obese (DIO) mice, leads to substantial weight loss. The anti-obesity effects of β-RA are partially elucidated through the normalization of mitochondrial CoQ metabolism in white adipose tissue (WAT). Additionally, we identify an HFN4α/LXR-dependent transcriptomic activation of the hepatic lipid metabolism that contributes to the anti-obesity effects of β-RA. Consequently, β-RA mitigates WAT hypertrophy, prevents hepatic steatosis, counteracts metabolic abnormalities in WAT and liver, and enhances glucose homeostasis by reducing the insulin/glucagon ratio and plasma levels of gastric inhibitory peptide (GIP). Moreover, pharmacokinetic evaluation of β-RA supports its translational potential. Thus, β-RA emerges as an efficient, safe, and translatable therapeutic option for the treatment and/or prevention of obesity, metabolic dysfunction-associated steatotic liver disease (MASLD).
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