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PARP Inhibitors in Colorectal Malignancies: A 2023 Update. PARP抑制剂在结直肠恶性肿瘤中的应用:2023年的最新进展
IF 1.4 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 DOI: 10.2174/0115748871260815231116060817
Nikolaos Skouteris, Georgios Papageorgiou

Background: Colorectal carcinoma (CRC) is one of the most common malignancies in the Western world, and metastatic disease is associated with a dismal prognosis. Poly-ADpribose polymerase (PARP) inhibitors gain increasing attention in the field of medical oncology, as they lead to synthetic lethality in malignancies with preexisting alterations in the DNA damage repair (DDR) pathway. As those alterations are frequently seen in CRC, a targeted approach through PARP inhibitors is expected to benefit these patients, both alone and in combination with other agents like chemotherapy, immunotherapy, antiangiogenics, and radiation.

Objective: This review article aims to better clarify the role of PARP inhibitors as a treatment option in patients with metastatic CRC with alterations in the DDR pathway.

Methods: We used the PubMed database to retrieve journal articles and the inclusion criteria were all human studies that illustrated the effective role of PARP inhibitors in patients with metastatic CRC with homologous repair deficiency (HRD) and the correct line of therapy.

Results: Current evidence supports the utilization of PARP inhibitors in CRC subgroups, as monotherapy and in combination with other agents. Up to now, data are insufficient to support a formal indication, and further research is needed.

Conclusion: Efforts to precisely define the homologous repair deficiency (HRD) in CRC - and eventually the subgroup of patients that are expected to benefit the most - are also underway.

背景:结直肠癌(CRC)是西方世界最常见的恶性肿瘤之一,其转移性疾病预后较差。聚肾上腺素聚合酶(PARP)抑制剂在肿瘤医学领域受到越来越多的关注,因为它们在DNA损伤修复(DDR)途径中预先存在改变的恶性肿瘤中导致合成致死性。由于这些改变在结直肠癌中很常见,通过PARP抑制剂的靶向治疗有望使这些患者受益,无论是单独治疗还是与化疗、免疫治疗、抗血管生成和放疗等其他药物联合治疗。目的:这篇综述文章旨在更好地阐明PARP抑制剂作为转移性结直肠癌患者DDR通路改变的治疗选择的作用。方法:我们使用PubMed数据库检索期刊文章,纳入标准是所有人类研究,这些研究表明PARP抑制剂在转移性结直肠癌同源修复缺陷(HRD)患者中的有效作用和正确的治疗路线。结果:目前的证据支持在结直肠癌亚组中使用PARP抑制剂,作为单药治疗或与其他药物联合治疗。到目前为止,数据不足以支持正式的指示,需要进一步的研究。结论:精确定义CRC中同源修复缺陷(HRD)以及最终预期获益最大的患者亚组的努力也在进行中。注册号:DOI: dx.doi.org/10.17504/protocols.io.dm6gp3ey8vzp/v1。
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引用次数: 0
Regulatory Procedures and Integrated Requirements for Early Phase Development of a Pharmaceutical Drug Product. 药品早期开发的监管程序和综合要求。
IF 1.4 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 DOI: 10.2174/0115748871251739231018104151
Gaurav, Niraj Sandeep Patil, Animesh Ranjan, Dilpreet Singh
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引用次数: 0
Is There an Association between 5a Reductase Inhibitors and Metabolic Syndrome? A Narrative Review of the Literature. 5a 还原酶抑制剂与代谢综合征有关联吗?文献综述。
IF 1.4 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 DOI: 10.2174/0115748871303638240529160610
Afroditi Ziogou, Alexios Giannakodimos, Evangelia Mitakidi, Tzelepis Konstantinos, Ilias Giannakodimos

Finasteride and dutasteride are 5a Reductase Inhibitors (5a-RIs) and comprise the mainstay of treatment for the management of patients with benign prostatic hyperplasia. 5a-RIs are expressed in a variety of tissues, such as adipose tissues and liver, resulting in a reduction of glucocorticoid levels and affecting androgen regulation and metabolic function. As a result, the administration of these regimens may generate adverse metabolic events, such as liver disease, hyperglycemia, hyperlipidemia, and diabetes mellitus. Although several studies have tried to record these adverse metabolic events both in human subjects and animal models, the exact mechanisms of these actions have not been well described yet in the literature. Further well-designed clinical trials are needed to elucidate the exact role of 5a reductase inhibitors in the progression of the metabolic syndrome. The aim of this study was to systematically review the literature concerning the role of dutasteride or finasteride in the progression of metabolic adverse events and further investigate possible pathophysiologic mechanisms.

非那雄胺和度他雄胺是5a还原酶抑制剂(5a-RIs),是治疗良性前列腺增生患者的主要药物。5a-RIs 可在脂肪组织和肝脏等多种组织中表达,从而降低糖皮质激素水平,影响雄激素调节和代谢功能。因此,服用这些药物可能会产生不良代谢事件,如肝病、高血糖、高脂血症和糖尿病。虽然已有多项研究试图记录这些不良代谢事件在人类受试者和动物模型中的表现,但这些作用的确切机制尚未在文献中得到很好的描述。要阐明 5a 还原酶抑制剂在代谢综合征发展过程中的确切作用,还需要进一步设计完善的临床试验。本研究旨在系统回顾有关度他雄胺或非那雄胺在代谢不良事件进展中作用的文献,并进一步研究可能的病理生理机制。
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引用次数: 0
Confidence Interval: Advantages, Disadvantages and the Dilemma of Interpretation. 置信区间:解释的优势、劣势和困境。
IF 1.4 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 DOI: 10.2174/0115748871266250231120043345
Pramod K Sharma, Mamta Yadav

Confidence interval (CI) is one of the important reporting tools for research data as it not only provides valuable information about the effect size along with its width but also possible clinical significance. Unfortunately, this approach is not being utilized to its fullest extent. Determining point estimate always includes an element of uncertainty due to associated sampling error. A confidence interval may be an appropriate tool to measure this uncertainty. Further, the P value does not convey information about the magnitude of an effect and the error associated with it. Thus, in an ideal situation effect size should preferably be associated with a confidence interval to assess precision. Not only does CI let us assess likely effects but also decides whether the intervention applied could have clinical utility. In contrast, the p-value limits our option to either reject any differences that are not significant or accept those that are. However, confidence intervals are commonly misinterpreted. It is imperative to understand that the CI is not the range of effects that 95% of patients in the population exhibit. Moreover, it would also be erroneous to say that there is a 95% probability that the CI includes the true population effect. Interpretation is usually based on the context in which the confidence interval is being looked at. From a utility point of view and like other statistical tools confidence interval approach does have several advantages as well as disadvantages and is far beyond being a perfect statistical tool.

置信区间(CI)是研究数据的重要报告工具之一,因为它不仅能提供有关效应大小及其宽度的宝贵信息,还能提供可能的临床意义。遗憾的是,这种方法并未得到充分利用。由于相关的抽样误差,点估计值的确定总是包含不确定性因素。置信区间可能是衡量这种不确定性的合适工具。此外,P 值并不能传达效应大小和相关误差的信息。因此,在理想情况下,效应大小最好与置信区间相关联,以评估精确度。置信区间不仅能让我们评估可能的效果,还能决定所应用的干预措施是否具有临床实用性。与此相反,P 值限制了我们的选择,我们要么拒绝接受不显著的差异,要么接受显著的差异。然而,置信区间通常会被误解。我们必须明白,置信区间并不是人群中 95% 的患者所表现出的效应范围。此外,说 CI 包含真实人群效应的概率为 95% 也是错误的。对置信区间的解释通常是基于研究置信区间的背景。从实用性角度来看,置信区间法与其他统计工具一样,既有优点也有缺点,远非完美的统计工具。
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引用次数: 0
Role of Complement-dependent Cytotoxicity Crossmatch and HLA Typing in Solid Organ Transplant. 补体依赖性细胞毒性交叉配型和 HLA 分型在实体器官移植中的作用。
IF 1.4 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 DOI: 10.2174/0115748871266738231218145616
Arpit Tiwari, Sayali Mukherjee

Background: Solid organ transplantation is a life-saving medical operation that has progressed greatly because of developments in diagnostic tools and histocompatibility tests. Crossmatching for complement-dependent cytotoxicity (CDC) and human leukocyte antigen (HLA) typing are two important methods for checking graft compatibility and reducing the risk of graft rejection. HLA typing and CDC crossmatching are critical in kidney, heart, lung, liver, pancreas, intestine, and multi-organ transplantation.

Methods: A systematic literature search was conducted on the internet, using PubMed, Scopus, and Google Scholar databases, to identify peer-reviewed publications about solid organ transplants, HLA typing, and CDC crossmatching.

Conclusion: Recent advances in HLA typing have allowed for high-resolution evaluation, epitope matching, and personalized therapy methods. Genomic profiling, next-generation sequencing, and artificial intelligence have improved HLA typing precision, resulting in better patient outcomes. Artificial intelligence (AI) driven virtual crossmatching and predictive algorithms have eliminated the requirement for physical crossmatching in the context of CDC crossmatching, boosting organ allocation and transplant efficiency. This review elaborates on the importance of HLA typing and CDC crossmatching in solid organ transplantation.

背景:实体器官移植是一项挽救生命的医疗手术,由于诊断工具和组织相容性测试的发展,这项手术取得了长足的进步。补体依赖性细胞毒性(CDC)交叉配型和人类白细胞抗原(HLA)分型是检查移植物相容性和降低移植物排斥风险的两种重要方法。HLA 分型和 CDC 交叉配型在肾、心、肺、肝、胰、肠和多器官移植中至关重要:利用 PubMed、Scopus 和 Google Scholar 数据库在互联网上进行了系统的文献检索,以确定有关实体器官移植、HLA 分型和 CDC 交叉配型的同行评审出版物:HLA 分型的最新进展使得高分辨率评估、表位匹配和个性化治疗方法成为可能。基因组剖析、下一代测序和人工智能提高了 HLA 分型的精确度,从而改善了患者的治疗效果。人工智能(AI)驱动的虚拟交叉配型和预测算法消除了疾控中心交叉配型中对物理交叉配型的要求,提高了器官分配和移植效率。本综述阐述了 HLA 分型和 CDC 交叉配对在实体器官移植中的重要性。
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引用次数: 0
Characterization of Intrinsically Disordered Proteins in Healthy and Diseased States by Nuclear Magnetic Resonance. 利用核磁共振表征健康和患病状态下的内在紊乱蛋白质。
IF 1.4 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 DOI: 10.2174/0115748871271420240213064251
Mohamad Hesam Shahrajabian, Wenli Sun

Introduction: Intrinsically Disordered Proteins (IDPs) are active in different cellular procedures like ordered assembly of chromatin and ribosomes, interaction with membrane, protein, and ligand binding, molecular recognition, binding, and transportation via nuclear pores, microfilaments and microtubules process and disassembly, protein functions, RNA chaperone, and nucleic acid binding, modulation of the central dogma, cell cycle, and other cellular activities, post-translational qualification and substitute splicing, and flexible entropic linker and management of signaling pathways.

Methods: The intrinsic disorder is a precise structural characteristic that permits IDPs/IDPRs to be involved in both one-to-many and many-to-one signaling. IDPs/IDPRs also exert some dynamical and structural ordering, being much less constrained in their activities than folded proteins. Nuclear magnetic resonance (NMR) spectroscopy is a major technique for the characterization of IDPs, and it can be used for dynamic and structural studies of IDPs.

Results and conclusion: This review was carried out to discuss intrinsically disordered proteins and their different goals, as well as the importance and effectiveness of NMR in characterizing intrinsically disordered proteins in healthy and diseased states.

内在无序蛋白(IDPs)活跃于不同的细胞程序中,如染色质和核糖体的有序组装、与膜的相互作用、蛋白质和配体的结合、分子的识别、结合和通过核孔的运输、微丝和微管的过程和解体、蛋白质功能、RNA伴侣和核酸结合、中心教条的调节、细胞周期和其他细胞活动、翻译后修饰和替代剪接,以及灵活的熵链接和信号通路的管理。内在无序是一种精确的结构特征,它允许 IDPs/IDPRs 参与一对多和多对一的信号传递。IDPs/IDPRs还具有一定的动态和结构有序性,其活动受到的限制比折叠蛋白要少得多。核磁共振(NMR)光谱是表征 IDPs 的主要技术,可用于 IDPs 的动态和结构研究。本综述旨在讨论固有无序蛋白及其不同目标,以及核磁共振在表征健康和疾病状态下的固有无序蛋白方面的重要性和有效性。
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引用次数: 0
Carob (Ceratonia siliqua L.), Pharmacological and Phytochemical Activities of Neglected Legume of the Mediterranean Basin, as Functional Food. 角豆树(Ceratonia siliqua L.),作为功能性食品的地中海盆地被忽视的豆科植物的药理学和植物化学活性。
IF 1.4 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 DOI: 10.2174/0115748871278128240109074506
Mohamad Hesam Shahrajabian, Wenli Sun

Carob (Ceratonia siliqua L.) has been widely cultivated in different parts of the world, particularly in the Mediterranean region, and the tree belongs to the family Leguminosae. Several studies have indicated that carobs and their products can improve human health and help prevent different specific chronic diseases. Carob can considered as functional food due to its high content in dietary fibers, low-fat content, and high content of minerals. Its fruit is a pod containing 10%-20% seeds, and the pods consist of sugars, proteins, crude fibers, minerals, vitamins, polyphenols, vitamins, and lipids. In many countries in the Middle east, carob is mainly used to prepare as a traditional drink and some kinds of confectioneries. The powders can be utilized to prepare carob juice concentrate. The systematic review of documents from clinical trials and scientific societies dedicated to traditional medicine in China has been carried out. The goal of this review article is a survey of chemical compounds, and pharmaceutical benefits of carob, especially by considering traditional medicinal sciences. Moreover, clinical trials research promotes studies to highlight and focus on the scope of application of traditional medicinal science in the growing system of medicine.

角豆树(Ceratonia siliqua L.)属于豆科植物,在世界各地都有广泛种植,尤其是在地中海地区。多项研究表明,角豆树及其产品可以改善人体健康,有助于预防各种慢性疾病。角豆树膳食纤维含量高、脂肪含量低、矿物质含量高,因此可被视为功能性食品。角豆树的果实是一个豆荚,含有 10%-20% 的种子,豆荚中含有糖、蛋白质、粗纤维、矿物质、维生素、多酚、维生素和脂类。在中东的许多国家,角豆树主要用于制作传统饮料和一些糖果。角豆树粉末可用于制作角豆树浓缩汁。我们对中国传统医学的临床试验和科学协会的文献进行了系统回顾。这篇综述文章的目的是调查角豆树的化学成分和药物功效,特别是考虑到传统医学。此外,临床试验研究还促进了对传统医药科学在不断发展的医药体系中的应用范围的强调和关注。
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引用次数: 0
Cancer Patients' Attitudes Towards the Anti-Covid-19 Vaccine: A Collective Case Study. 癌症患者对抗Covid-19疫苗的态度:一项集体案例研究。
IF 1.4 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 DOI: 10.2174/0115748871258981231024103349
Mara Mirandola, Federica Andreis, Chiara Deori, Sonia Abdel Kader, Anna Chiara Wedenissow, Clelia Malighetti, Fausto Meriggi, Alberto Zaniboni

Aim: The purpose of the present study was to determine cancer patients' attitudes toward the anti-COVID-19 vaccine.

Background: Historically, the scientific community's responsibility was to investigate attitudes about vaccination. The course of COVID-19 in cancer patients makes them a high priority for vaccination. Cancer patients are at greater risk of serious complications and death because of COVID-19 infection.

Objective: The purpose of the present study was to determine cancer patients' attitudes toward the anti-COVID-19 vaccine. We examined several constructs that potentially influenced cancer patients' perceptions of the vaccine: health status, knowledge of COVID-19 and vaccination, cancer patients' perceptions of vulnerability, and attitudes toward general vaccines.

Methods: We conducted a collective case study with 200 cancer patients undergoing treatment, and divided the sample into two groups: patients who "expected to heal" (Group A) and patients who "expected to chronicize" (Group B). Data were collected through a purpose-built questionnaire consisting of 22 questions and a study of medical records.

Results: Data analysis showed that both groups, Group A (M= 3.89 SD= 0.64) and Group B (M= 3.98 SD= 0.64), had a favorable attitude toward the anti-COVID-19 vaccine. This favorable attitude toward the anti-COVID-19 vaccine depended on several factors: perception of vulnerability to COVID-19, perception of the severity of their oncological situation, and communication with oncologists.

Conclusion: Our study highlighted the plurality of factors that influence attitudes toward the anti-COVID-19 vaccine. It is therefore of fundamental importance to increase the use of the shared decision-making approach (SDM) to guide the patient to an informed choice.

目的:本研究旨在确定癌症患者对抗COVID-19疫苗的态度。背景:从历史上看,科学界的责任是调查人们对疫苗接种的态度。癌症患者的新冠肺炎病程使他们成为接种疫苗的高度优先对象。由于新冠肺炎感染,癌症患者出现严重并发症和死亡的风险更大。目的:本研究旨在确定癌症患者对抗新冠肺炎疫苗的态度。我们研究了几种可能影响癌症患者对疫苗认知的结构:健康状况、对新冠肺炎和疫苗接种的了解、癌症患者对脆弱性的认知以及对普通疫苗的态度。方法:我们对200名正在接受治疗的癌症患者进行了集体病例研究,并将样本分为两组:“有望治愈”的患者(a组)和“有望慢性化”的患者。数据是通过一份由22个问题组成的专门问卷和一项医疗记录研究收集的。结果:数据分析显示,A组(M=3.89 SD=0.64)和B组(M/3.98 SD=0.64。这种对抗新冠肺炎疫苗的积极态度取决于几个因素:对新冠肺炎脆弱性的认知、对肿瘤病情严重性的认知以及与肿瘤医生的沟通。结论:我们的研究强调了影响人们对抗COVID-19疫苗态度的多种因素。因此,更多地使用共享决策方法(SDM)来引导患者做出明智的选择至关重要。
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引用次数: 0
Iranian Traditional Medicine (ITM) and Natural Remedies for Treatment of the Common Cold and Flu. 伊朗传统医学和治疗普通感冒和流感的自然疗法。
IF 1.4 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 DOI: 10.2174/0115748871275500231127065053
Mohamad Hesam Shahrajabian, Wenli Sun

Traditional Iranian medicine is usually used for both prevention and relief of cold and flu symptoms in China, Iran, and many other Asian countries all over the world. There are 4 kinds of influenza viruses. Unlike type B, which may cause seasonal epidemics, type A viruses can cause pandemics, and influenza C may lead to mild human infection with little public health effects. A literature review was done by using multiple databases such as ISI Web of knowledge, PubMed, Science Direct and Google Scholar. The most notable antiviral medicinal plants for flu and cold are honeysuckle flowers, thyme leaf, green chiretta, andrographis, peppermint oil and leaf and calendula. The most important expectorant medicinal plants for cold and flu are snake root, tulsi, licorice root, slippery elm, clove, and sage leaf. Recommended immunostimulant medicinal plants for cold and flu are eucalyptus, Echinacea root, ginseng, garlic, slippery elm, marshmallow, Usnea lichen, Isatis root, ginger root, and myrrh resin. Iranian traditional medicine, which is one of the oldest schools of traditional medicine, is one of the main concepts of disease and health, and it can be considered as an important complementary and alternative medicine, as in some cases, modern medicine has many side effects, low efficiency, and high costs. Medicinal plants and herbs, which are included in many traditional systems, have significant and promising bioactive components in organic life.

在中国、伊朗和世界上许多其他亚洲国家,伊朗传统医学通常用于预防和缓解感冒和流感症状。流感病毒有四种。与可能引起季节性流行病的B型病毒不同,A型病毒可引起大流行,而C型流感可能导致轻微的人类感染,对公共卫生几乎没有影响。利用ISI Web of knowledge、PubMed、Science Direct和Google Scholar等多个数据库进行文献综述。治疗流感和感冒最显著的抗病毒药用植物是金银花、百里香叶、绿灯芯草、穿心莲、薄荷油和金盏花。对感冒和流感最重要的祛痰药用植物是蛇根、杜尔茜、甘草根、榆树、丁香和鼠尾草叶。推荐用于感冒和流感的免疫刺激药用植物有桉树、紫锥菊根、人参、大蒜、榆树、棉花糖、Usnea地衣、板蓝根、姜根和没药树脂。伊朗传统医学是最古老的传统医学流派之一,是疾病和健康的主要概念之一,可被视为一种重要的补充和替代医学,因为在某些情况下,现代医学有许多副作用,效率低,费用高。药用植物和草药,包括在许多传统系统中,是有机生命中重要的和有前途的生物活性成分。
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引用次数: 0
Gender Differences in Patients with Prolactinoma: Single-center Ukrainian Experience. 泌乳素瘤患者的性别差异:乌克兰单中心经验。
IF 1.4 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-01-01 DOI: 10.2174/0115748871288948240325080936
Oleksandr Voznyak, Iaroslav Zinkevych, Andrii Lytvynenko, Nazarii Hryniv, Roman Ilyuk, Nazarii Kobyliak

Introduction: Prolactinomas are the most common type of pituitary gland tumors that secrete overly prolactin. They account for approximately 60% of all hormone-secreting hypophysis tumors.

Aim: This study aims to analyze gender differences in patients with prolactinomas who were operated on transsphenoidal surgery and conduct a single-center retrospective analysis of patient data.

Material and methods: This study evaluated the medical records of 109 patients (61 females and 48 males) from 2009 to 2019 at Feofaniya Clinical Hospital of the State Administration of Affairs in Kyiv, Ukraine. The primary criterion for including patients was a Serum Prolactin (PRL) level of over 100 ng/ml and the presence of a pituitary adenoma (PA) as observed on MRI. Additionally, the histological examination needed to confirm the presence of Prolactin-Secreting Pituitary Adenomas (PSPAs) without plurihormonal activity through both microscopy and immunohistochemical (IHC) staining.

Results: Significant differences in preoperative PRL levels were not observed. However, males had significantly larger tumor sizes and prevalence of macroadenomas. In male patients, the preoperative PLR levels showed a weak negative correlation with age (r=-0.304, p < 0.036) and a positive correlation with tumor size (r=0.555, p < 0.001) and cavernous sinus invasion (r=0.339, p < 0.018). In females, preoperative PRL was significantly associated only with tumor size and Knosp grade.

Conclusion: Prolactin-Secreting Pituitary Adenomas (PSPAs) are more common in women than men and are characterized by larger and more invasive tumors with high PRL levels at diagnosis. The PRL level and tumor size before surgery can predict early biochemical remission in both males and females with an accuracy of 58.3% and 68.8%, respectively.

简介泌乳素瘤是垂体肿瘤中最常见的一种,会过度分泌泌乳素。目的:本研究旨在分析经蝶窦手术的泌乳素瘤患者的性别差异,并对患者数据进行单中心回顾性分析:本研究评估了乌克兰基辅国家事务管理局费奥法尼亚临床医院2009年至2019年109名患者(61名女性和48名男性)的病历。纳入患者的主要标准是血清泌乳素(PRL)水平超过 100 ng/ml,以及核磁共振成像观察到存在垂体腺瘤(PA)。此外,组织学检查需要通过显微镜和免疫组化(IHC)染色确认存在无多激素活性的泌乳素分泌型垂体腺瘤(PSPA):术前PRL水平无明显差异。然而,男性患者的肿瘤体积明显更大,大腺瘤的发病率也更高。在男性患者中,术前PLR水平与年龄呈弱负相关(r=-0.304,p<0.036),与肿瘤大小(r=0.555,p<0.001)和海绵窦侵犯(r=0.339,p<0.018)呈正相关。在女性患者中,术前PRL仅与肿瘤大小和Knosp分级显著相关:结论:泌乳素分泌型垂体腺瘤(PSPA)在女性中的发病率高于男性,其特点是肿瘤更大、侵袭性更强、诊断时PRL水平较高。手术前的 PRL 水平和肿瘤大小可预测男性和女性的早期生化缓解,准确率分别为 58.3% 和 68.8%。
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引用次数: 0
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