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Olanzapine Pharmacokinetics: A Clinical Review of Current Insights and Remaining Questions 奥氮平药代动力学:当前见解和遗留问题的临床回顾
Pub Date : 2023-12-21 DOI: 10.2147/pgpm.s391401
Priyanka Kolli, Grace Kelley, Marianela Rosales, Justin Faden, Ryan Serdenes
Abstract: Olanzapine is one of the most widely used antipsychotics since its initial approval by the US Food and Drug Administration in 1996 and has undergone extensive pharmacokinetic study. Despite being utilized in clinical psychiatry for decades, there remain questions regarding the variety of available formulations, the utility of therapeutic drug monitoring, altered kinetic properties in special populations/medical illnesses, the use of high-dose olanzapine, and drug interactions, among many others. We performed a narrative literature review of olanzapine pharmacokinetics in June 2023 using the US National Library of Medicine’s PubMed.gov resource (https://www.ncbi.nlm.nih.gov/pubmed) and Google Scholar. Herein, we review clinically relevant aspects of olanzapine pharmacokinetic data while highlighting knowledge gaps and potential areas of future study.

Keywords: olanzapine, pharmacokinetics, drug-drug interactions, pharmacodynamics, clinical psychopharmacology
摘要:奥氮平自 1996 年获得美国食品和药物管理局首次批准以来,一直是使用最广泛的抗精神病药物之一,并进行了广泛的药代动力学研究。尽管奥氮平已在临床精神病学领域应用了数十年,但仍存在许多问题,包括现有制剂的多样性、治疗药物监测的效用、特殊人群/医疗疾病中动力学特性的改变、大剂量奥氮平的使用以及药物相互作用等等。2023 年 6 月,我们利用美国国立医学图书馆的 PubMed.gov 资源 (https://www.ncbi.nlm.nih.gov/pubmed) 和 Google Scholar 对奥氮平药代动力学进行了叙述性文献综述。在此,我们回顾了奥氮平药代动力学数据的临床相关方面,同时强调了知识差距和未来研究的潜在领域。关键词:奥氮平;药代动力学;药物相互作用;药效学;临床精神药理学
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引用次数: 0
A Case of Floating-Harbor Syndrome with “Growth and Language Development Delay” as Its Clinical Manifestation 以 "生长和语言发育迟缓 "为临床表现的浮港综合征病例
Pub Date : 2023-12-15 DOI: 10.2147/pgpm.s433444
Yi-Can Yang, Qiong Tang, Li-Juan Yan, Shi-Bin Zhang, Xiao-Min Ye, Dai Gong, Li Zou, Xiang-Lan Wen
Background: Floating-Harbor syndrome (FHS) is a rare autosomal dominant inherited disease characterized primarily by short stature, delayed language development, and typical facial features. There are currently few case reports, diagnoses and treatments for these syndromes at home and abroad.
Case Description: This study reports a case of a boy with “growth and language development delay” as the predominant clinical manifestation. FHS was clinically diagnosed based on his growth hormone (GH) deficiency, significant bone age delay, left testicular hydrocele, and the whole exon gene in peripheral blood, which indicated heterozygous mutation of SRCAP gene. Following the treatment with recombinant human GH (rhGH), the child exhibited height increase benefits, and his articulation improved after language therapy.
Conclusion: Genetic testing facilitates early detection, diagnosis, and treatment of the FHS. Additionally, treatment with rhGH effectively increases the height of these children, and language rehabilitation is especially important for their language development.

背景:浮港综合征(FHS)是一种罕见的常染色体显性遗传病,主要特征是身材矮小、语言发育迟缓和典型的面部特征。目前,国内外对此类综合征的病例报道、诊断和治疗方法很少:本研究报告了一例以 "生长和语言发育迟缓 "为主要临床表现的男孩。根据其生长激素(GH)缺乏、明显的骨龄延迟、左侧睾丸鞘膜积液以及外周血全外显子基因显示 SRCAP 基因杂合突变,临床诊断为 FHS。在接受重组人生长激素(rhGH)治疗后,患儿身高增加,语言表达能力也得到改善:结论:基因检测有助于FHS的早期发现、诊断和治疗。结论:基因检测有助于FHS的早期发现、诊断和治疗。此外,使用rhGH治疗可有效增加这些儿童的身高,而语言康复对他们的语言发展尤为重要。
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引用次数: 0
Circ_0000140 Alters miR-527/SLC7A11-Mediated Ferroptosis to Influence Oral Squamous Cell Carcinoma Cell Resistance to DDP Circ_0000140 可改变 miR-527/SLC7A11 介导的铁突变,从而影响口腔鳞状细胞癌细胞对 DDP 的耐受性
Pub Date : 2023-12-13 DOI: 10.2147/pgpm.s426205
Yu Ma, Jinbo Gao, Hongning Guo
Background: While there is prior evidence for the ability of circular RNAs (circRNAs) to shape the cisplatin (DDP) resistance of cancers in human patients, there has been relatively little research to date focused on the interplay between circRNAs and DDP resistance in the context of OSCC progression to date. In the present analysis, the functional role that circ_0000140 plays as a mediator of chemoresistance to DDP was thus explored in greater detail.
Methods: Both qPCR and Western immunoblotting were employed as appropriate to detect circ_0000140, miR-527, and SLC7A11 levels, while interactions among these factors were detected through RNA immunoprecipitation, RNA pull-down, and dual luciferase report assays. MTT assays were used to assess cellular viability as a means of gauging DDP sensitivity.
Results: Both tissue samples from DDP-resistant OSCC patient tumors and OSCC cell lines resistant to DDP exhibited pronounced circ_0000140 upregulation. Knocking down this circRNA significantly increased the DDP sensitivity of both tested DDP-resistant OSCC cell lines and promoted ferroptosis, whereas knocking down miR-527 was sufficient to reverse these effects, which were recapitulated by miR-527 overexpression. Conversely, the effects of overexpressing miR-527 were reversed by the restoration of SLC7A11 expression. Consistently, this circRNA was able to increase DDP IC50 values and to suppress ferroptosis in both tested cell lines through this miR-527/SLC7A11 signaling axis.
Conclusion: These results revealed that circ_0000140/miR-527/SLC7A11-mediated ferroptosis may provide novel insights into the development of this cancer type and the emergence of chemoresistance in the future.

背景:尽管已有证据表明环状RNA(circRNA)能够影响人类癌症患者的顺铂(DDP)耐药性,但迄今为止,关于环状RNA与OSCC进展背景下DDP耐药性之间相互作用的研究相对较少。在本分析中,我们更详细地探讨了circ_0000140作为DDP化疗耐药性介质的功能作用:方法:采用 qPCR 和 Western 免疫印迹法检测 circ_0000140、miR-527 和 SLC7A11 的水平,同时通过 RNA 免疫沉淀、RNA 拉取和双荧光素酶报告检测这些因子之间的相互作用。MTT测定用于评估细胞活力,作为衡量DDP敏感性的一种手段:结果:对DDP耐药的OSCC患者肿瘤组织样本和对DDP耐药的OSCC细胞系均表现出明显的circ_0000140上调。敲除该circRNA可显著提高两种耐DDP OSCC细胞系的DDP敏感性并促进铁变态反应,而敲除miR-527足以逆转这些效应,miR-527的过表达可再现这些效应。相反,恢复 SLC7A11 的表达可逆转过表达 miR-527 的影响。一致的是,该circRNA能够通过miR-527/SLC7A11信号轴增加DDP IC50值并抑制两种测试细胞系的铁突变:这些结果表明,circ_0000140/miR-527/SLC7A11介导的铁突变可能为该癌症类型的发展和未来化疗耐药性的出现提供了新的见解。
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引用次数: 0
A Review on Probable Causes of Cardiotoxicity Caused by Common Cancer Drugs and the Role of Traditional Chinese Medicine in Prevention and Treatment 常用抗癌药物引起心脏毒性的可能原因及中医药在防治中的作用综述
Pub Date : 2023-12-06 DOI: 10.2147/pgpm.s427585
Miao Zhou, Wenyan Wang, Jiahao Weng, Zhikun Lai
Abstract: Cancer is a widespread disease in our nation, characterized by a high occurrence rate. The use of tumor medications has been linked to an increased chance of cardiovascular complications, including a notable occurrence of heart toxicity. This has caused significant concern among healthcare professionals. This article provides a comprehensive compilation of drugs recognized for their potential to cause heart toxicity. Furthermore, extensive research has been conducted to investigate and categorize the effects of heart toxicity, with the purpose of promoting awareness, facilitating early intervention, and ultimately reducing the occurrence of heart toxicity. At the same time, there is an anticipation that Traditional Chinese Medicine (TCM) can capitalize on its unique attributes to address such ailments. To establish its effectiveness, it is crucial to carry out extensive clinical trials or retrospective analyses. The purpose of this article is to summarize the possible mechanisms of cardiac toxicity caused by commonly used chemotherapy drugs and summarize the possible mechanisms of adverse cardiac toxicity, laying the groundwork for subsequent research.

Keywords: chemotherapeutic drugs, cardiotoxicity, mechanisms, TCM intervention
摘要:癌症是我国普遍存在的疾病,具有发病率高的特点。肿瘤药物的使用与心血管并发症的机会增加有关,包括心脏毒性的显著发生。这引起了医疗保健专业人员的极大关注。这篇文章提供了一个全面的汇编,公认的药物,以其潜在的心脏毒性。此外,人们还开展了广泛的研究,对心脏毒性的影响进行调查和分类,目的是提高认识,促进早期干预,最终减少心脏毒性的发生。与此同时,人们期望中医能够利用其独特的属性来治疗这些疾病。为了确定其有效性,进行广泛的临床试验或回顾性分析至关重要。本文旨在总结常用化疗药物引起心脏毒性的可能机制,总结不良心脏毒性的可能机制,为后续研究奠定基础。关键词:化疗药物;心脏毒性;机制
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引用次数: 0
Novel Autophagy-Related Blood Biomarkers Associated with Immune Cell Infiltration in Ankylosing Spondylitis 与强直性脊柱炎免疫细胞浸润相关的新型自噬相关血液生物标志物
Pub Date : 2023-12-05 DOI: 10.2147/pgpm.s428035
Hanbing Song, Hongpeng Liu, XiaoDong Li, Bing Lv, Zonghan Tang, Qipeng Chen, Danqi Zhang, Fei Wang
Background: This study aims to identify new therapeutic targets and explore the molecular mechanism of ankylosing spondylitis (AS), a rheumatic immune disease that mainly affects the sacroiliac and spinal joints. Despite extensive research, the exact cause of AS is still unknown. The research team utilized a bioinformatics approach to achieve their objectives.
Methods: The GSE73754 dataset was downloaded from GEO database. Autophagy-related genes (ARGs) were collected from the Human Autophagy-dedicated Database. The limma package was used to screen for differentially expressed genes (DEGs), which were then intersected with the autophagy-related genes (ARGs) to identify differentially expressed autophagy-related genes (DEARGs). Subsequently, the DEARGs associated with AS were subjected to GO-BP and KEGG enrichment analyses using the clusterProfiler package. Core genes were identified using the cytoHubba plug-in of Cytoscape and were validated by clinical blood samples. Additionally, the Cell algorithm was utilized to evaluate the proportion of immune cell infiltration.
Results: A total of 29 DEARGs were identified, which were found to be mainly enriched in autophagy, apoptosis, and necroptosis through functional enrichment analysis. Two core genes, HSPA5 and SQSTM1, were confirmed to have diagnostic value in AS. Immune cell infiltration analysis revealed CD8+ T cells, CD8+ T effector memory (Tem), natural killer (NK) cells, T gamma delta (Tgd) cells, and T-helper 1 (Th1) cells as major participants in AS development. Furthermore, HSPA5 expression was significantly correlated with Th1 cells, CD8+ T cells, CD4+ memory cells, and macrophages.
Conclusion: This study suggested that HSPA5 and SQSTM1 can serve as useful diagnostic biomarkers for AS. These findings lay the foundation for identifying crucial mRNAs in the whole blood of AS patients, which may aid in the development of novel markers for AS.

背景:强直性脊柱炎(AS)是一种主要影响骶髂关节和脊柱关节的风湿性免疫疾病,本研究旨在寻找新的治疗靶点并探索其分子机制。尽管进行了广泛的研究,但AS的确切病因仍不清楚。研究小组利用生物信息学方法来实现他们的目标。方法:从GEO数据库下载GSE73754数据集。自噬相关基因(ARGs)从人类自噬专用数据库中收集。利用limma包筛选差异表达基因(differential expression genes, DEGs),然后与自噬相关基因(autophagy-related genes, ARGs)交叉鉴定差异表达自噬相关基因(differentialexpressed autophagy-related genes, DEARGs)。随后,使用clusterProfiler包对与AS相关的dearg进行GO-BP和KEGG富集分析。利用Cytoscape软件cytoHubba插件对核心基因进行鉴定,并通过临床血液样本进行验证。此外,利用Cell算法评估免疫细胞浸润比例。结果:共鉴定出29个DEARGs,通过功能富集分析发现它们主要富集于自噬、凋亡和坏死下垂。两个核心基因HSPA5和SQSTM1被证实在AS中具有诊断价值。免疫细胞浸润分析显示,CD8+ T细胞、CD8+ T效应记忆(Tem)、自然杀伤(NK)细胞、T γ δ (Tgd)细胞和T辅助1 (Th1)细胞是as发展的主要参与者。此外,HSPA5的表达与Th1细胞、CD8+ T细胞、CD4+记忆细胞和巨噬细胞显著相关。结论:本研究提示HSPA5和SQSTM1可作为as的诊断标志物。这些发现为识别AS患者全血中的关键mrna奠定了基础,这可能有助于开发新的AS标志物。
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引用次数: 0
BICDL1 Predicts Poor Prognosis and is Correlated with Methylation and Immune Infiltration in Colorectal Cancer BICDL1 预测结直肠癌的不良预后,并与甲基化和免疫渗透相关
Pub Date : 2023-12-01 DOI: 10.2147/pgpm.s424209
Hongbiao Luo, Ji Luo, Ning Ding, Tao Zhang, Yongheng He
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引用次数: 0
Identification of P3H1 as a Predictive Prognostic Biomarker for Bladder Urothelial Carcinoma Based on the Cancer Genome Atlas Database 基于癌症基因组图谱数据库的P3H1作为膀胱尿路上皮癌预测预后的生物标志物的鉴定
Pub Date : 2023-12-01 DOI: 10.2147/pgpm.s437974
Yuanfeng Zhang, Yang Chen, Zhiming Chen, Xinye Zhou, Shaochuan Chen, Kaijian Lan, Zhiping Wang, Yonghai Zhang
Purpose: The extracellular matrix in the tumor microenvironment are closely related to the development of tumors. This study’s primary aim is to study the association between prolyl 3-hydroxylase 1 (P3H1) which mainly expresses collagen in extracellular matrix and the progression and prognosis of bladder cancer (BC).
Methods: The clinical and transcriptome data were acquired from the cancer genome atlas database. BLCAsubtyping is used to evaluate tissue subtypes of BC. The COX proportional hazards can be used to evaluate the survival process’s influencing factors. Immunohistochemistry was used to identify differences in the expression of P3H1 in cancer and paired adjacent tissues. GSEA was used to investigate the underlying biological processes. Finally, ssGSEA, TIMER and pRRophetic were used to study the relationship between P3H1 and immune cell infiltration and drug sensitivity.
Results: The expression of P3H1 was substantially higher in highly invasive BC samples than in low invasive BC. P3H1 was an independent predictor of overall survival (HR = 1.12, p = 0.03). P3H1 expression was significantly higher in tumor tissues than adjacent normal tissues in clinical tissue samples, and was significantly higher in highly stage cancer than low stage cancer samples. Samples with high P3H1 expression had a higher level of immune cell infiltration and immune function, as well as a significant correlation with macrophage and dendritic cell infiltration and TGF-beta, Th1 cells, and macrophage regulation (cor > 0.3, p < 0.05). P3H1 high expression samples were substantially more sensitive to docetaxel, cisplatin, vinblastine, camptothecin, paclitaxel, and other medicines than P3H1 low expression samples.
Discussion: P3H1 is a possible oncogene and an independent predictor of poor prognosis in BC; it also has enhanced sensitivity to docetaxel, cisplatin, vinblastine, camptothecin, paclitaxel, and other medications.

Keywords: prolyl 3-hydroxylase 1, bladder cancer, immune infiltration, drug sensitivity
目的:肿瘤微环境中的细胞外基质与肿瘤的发生发展密切相关。本研究的主要目的是研究细胞外基质中主要表达胶原蛋白的脯氨酸3-羟化酶1 (P3H1)与膀胱癌(BC)进展及预后的关系。方法:从癌症基因组图谱数据库中获取临床和转录组数据。blc分型用于评估BC的组织亚型。COX比例危险度可用于评价生存过程的影响因素。免疫组织化学用于鉴定P3H1在癌症和配对邻近组织中的表达差异。GSEA用于研究潜在的生物学过程。最后利用ssGSEA、TIMER和prophytic研究P3H1与免疫细胞浸润和药物敏感性的关系。结果:P3H1在高浸润性BC样本中的表达明显高于低浸润性BC样本。P3H1是总生存的独立预测因子(HR = 1.12, p = 0.03)。临床组织样本中P3H1在肿瘤组织中的表达明显高于癌旁正常组织,在高分期癌样本中P3H1的表达明显高于低分期癌样本。P3H1高表达的样品具有较高的免疫细胞浸润和免疫功能,并且与巨噬细胞和树突状细胞浸润以及tgf - β、Th1细胞和巨噬细胞调节(cor >0.3, p <0.05)。P3H1高表达样本对多西他赛、顺铂、长春碱、喜树碱、紫杉醇等药物的敏感性明显高于P3H1低表达样本。讨论:P3H1是一种可能的癌基因,是BC预后不良的独立预测因子;它对多西紫杉醇、顺铂、长春碱、喜树碱、紫杉醇和其他药物也有增强的敏感性。关键词:脯氨酸3-羟化酶1;膀胱癌;免疫浸润
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Pharmacogenomics and Personalized Medicine
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