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Giant Multilocular-Cystic Metaplastic Thymoma: A Case Report. 巨大多房囊性化生胸腺瘤1例报告。
IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-01-01 DOI: 10.2147/PGPM.S413757
Lihua Han, Bo Gao, En-Hua Wang, Liang Wang

The metaplastic thymoma with giant multilocular-cyst formation had not been documented. The metaplastic thymoma is an extremely rare primary thymic epithelial tumor with an indolent clinical course. It is characterized by a histologic biphasic appearance, which is consisted of solid epithelial areas and spindle cells as the background. This specific pattern can be easily mistaken as the type A thymoma or the type A components of type AB thymoma. When cystic change occurs in metaplastic thymoma, it will bring more challenges for both imaging and pathological diagnosis. Herein, we reported an extremely rare case of a 14.9-cm giant tumor located in the anterior mediastinum of an elderly female. The tumor is consisted of both multilocular cysts and solid components, with the largest cyst measuring 6 cm in diameter. The multilocular cyst contained hemorrhage, calcification, and cholesterol crystal cracks without cell lining. In the solid area, the epithelial cell nests were surrounded by spindle cells with scattered lymphocytes. With immunostains, neither type of cells was CD20 positive. The epithelial cells were positive for CK and P63, while the spindle cells expressed vimentin and EMA. Fluorescence in situ hybridization analysis revealed that the tumor harbored YAP1-MAML2 gene fusions. Accordingly, although the multilocular cystic pattern set a diagnostic challenge, the diagnosis of metaplastic thymoma was rendered due to the immunohistochemistry staining and YAP1-MAML2 gene rearrangement detection.

化脓性胸腺瘤合并巨大的多房囊肿尚未见文献记载。化生性胸腺瘤是一种极为罕见的原发性胸腺上皮性肿瘤,临床病程缓慢。它的特点是组织学上的双相外观,由实体上皮区和梭形细胞组成。这种特殊的模式很容易被误认为是A型胸腺瘤或AB型胸腺瘤的A型成分。当化脓性胸腺瘤发生囊性改变时,将给影像学和病理诊断带来更多的挑战。在此,我们报告一个极为罕见的病例,14.9厘米的巨大肿瘤位于前纵隔的老年女性。肿瘤由多房囊肿和实性组成,最大的囊肿直径为6cm。多房囊肿出血、钙化、无细胞壁的胆固醇结晶裂隙。实区上皮细胞巢被梭形细胞包围,淋巴细胞散在。免疫染色显示两种细胞均为CD20阳性。上皮细胞表达CK和P63阳性,梭形细胞表达vimentin和EMA。荧光原位杂交分析显示肿瘤中存在YAP1-MAML2基因融合。因此,尽管多房囊性模式给诊断带来了挑战,但由于免疫组织化学染色和YAP1-MAML2基因重排检测,诊断为化脓性胸腺瘤。
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引用次数: 0
One Rare Warfarin Resistance Case and Possible Mechanism Exploration. 一例罕见的华法林耐药病例及其可能的机制探讨。
IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-01-01 DOI: 10.2147/PGPM.S404474
Li Zhao, Zhenguo Zhai, Pengmei Li

One 59-year-old female patient with deep venous thrombosis (DVT) and pulmonary embolism (PE) was treated with 6 mg warfarin once daily as an anticoagulant. Before taking warfarin, her international normalized ratio (INR) was 0.98. Two days after warfarin treatment, her INR did not change from baseline. Due to the high severity of the PE, the patient needed to reach her target range (INR goal = 2.5, range = 2~3) rapidly, so the dose of warfarin was increased from 6 mg daily to 27 mg daily. However, the patient's INR did not improve with the dose escalation, still maintaining an INR of 0.97-0.98. We drew a blood sample half an hour before administering 27 mg warfarin and detected single nucleotide polymorphism for the following genes, which were identified to be relevant with warfarin resistance: CYP2C9 rs1799853, rs1057910, VKORC1 rs9923231, rs61742245, rs7200749, rs55894764, CYP4F2 rs2108622, and GGCX rs2592551. The trough plasma concentration of warfarin was 196.2 ng/mL after 2 days of warfarin administration with 27 mg QD, which was much lower than the therapeutic drug concentration ranges of warfarin (500-3,000 ng/mL). The genotype results demonstrate that the CYP4F2gene has rs2108622 mutation which can explain some aspect of warfarin resistance. Further investigations are necessary to fully characterize other pharmacogenomics or pharmacodynamics determinants of warfarin dose-response in Chinese.

1例59岁女性深静脉血栓(DVT)合并肺栓塞(PE)患者给予华法林6 mg抗凝治疗,每日1次。服用华法林前,其国际标准化比值(INR)为0.98。华法林治疗2天后,患者的INR与基线相比没有变化。由于PE的严重程度高,患者需要迅速达到目标范围(INR目标= 2.5,范围= 2~3),因此华法林的剂量从每天6mg增加到27mg。然而,患者的INR并没有随着剂量的增加而改善,仍然维持在0.97-0.98之间。在给药27 mg华法林前半小时采血,检测与华法林耐药相关基因CYP2C9 rs1799853、rs1057910、VKORC1 rs9923231、rs61742245、rs7200749、rs55894764、CYP4F2 rs2108622、GGCX rs2592551的单核苷酸多态性。以27 mg QD给药2 d后华法林血药谷浓度为196.2 ng/mL,远低于华法林治疗药物浓度范围(500 ~ 3000 ng/mL)。基因分型结果表明cyp4f2基因存在rs2108622突变,可以解释华法林耐药的某些方面。中国华法林剂量反应的其他药物基因组学或药效学决定因素需要进一步研究。
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引用次数: 0
The Relationship Between MMP17 Variants and Ischemic Stroke Risk in the Population from Shaanxi Province in China. 陕西省人群MMP17变异与缺血性脑卒中风险的关系
IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-01-01 DOI: 10.2147/PGPM.S396076
Weiping Li, Yanqing Liu, Xiaoling Xu, Qi Zhang, Xiao Zhang, Jie Zhang, Xiaochen Niu, Shiyao Yang, Xiaobo Zhang, Wenzhen Shi, Gejuan Zhang, Mingze Chang, Ye Tian

Background: Ischemic stroke (IS) was a multifactorial disease, which was the main cause of death and adult disability. Genetic factors cannot be ignored.

Objective: The present study discussed the relationship between MMP17 variants and the susceptibility of IS.

Methods: Based on the Agena MassARRAY platform, we genotyped single nucleotide polymorphisms (SNPs) on the MMP17 gene in 1345 participants (670 controls and 675 cases). We used logistic regression analysis to analyze the association of MMP17 SNPs with the risk of IS in the Chinese population, with odds ratio (OR) and 95% confidence intervals (CIs). False-positive report probability (FPRP) detected false positives on the significant results. Besides, we detected the SNP-SNP interaction to predict IS risk by multi-factor dimensionality reduction (MDR) analysis.

Results: In the total analysis, MMP17 rs7975920 conferred an increased susceptibility to IS. After a stratified analysis by age and gender, the significant association between rs7975920 and IS risk was displayed in the subjects aged >55 years old and females. After stratified analysis by smoking and drinking, MMP17 rs6598163 was related to the risk of IS in smokers and rs7975920 was associated with the risk of IS in smokers and was in correlation with IS risk in drinkers.

Conclusion: In short, we first observed that MMP17 rs7975920 and rs6598163 were related to the risk of IS. The above results provided a theoretical basis for the elaboration of the role of MMP17 in IS in the Chinese population.

背景:缺血性脑卒中是一种多因素疾病,是导致成人死亡和残疾的主要原因。遗传因素不容忽视。目的:探讨MMP17变异与IS易感性的关系。方法:基于Agena MassARRAY平台,对1345名参与者(对照组670人,病例675人)的MMP17基因单核苷酸多态性(snp)进行基因分型。我们采用logistic回归分析分析中国人群中MMP17 snp与IS风险的关系,采用比值比(OR)和95%置信区间(ci)。假阳性报告概率(FPRP)对显著结果检测假阳性。此外,我们通过多因素降维(MDR)分析检测SNP-SNP相互作用来预测IS风险。结果:在总分析中,MMP17 rs7975920增加了IS的易感性。根据年龄和性别进行分层分析后发现,rs7975920与IS风险在>55岁和女性受试者中存在显著相关性。通过吸烟和饮酒的分层分析,MMP17 rs6598163与吸烟者IS风险相关,rs7975920与吸烟者IS风险相关,与饮酒者IS风险相关。结论:总之,我们首先观察到MMP17 rs7975920和rs6598163与IS风险相关。以上结果为阐述MMP17在中国人群IS中的作用提供了理论基础。
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引用次数: 0
A Preliminary Study on the Correlation Between Age and Endometrial Receptivity. 年龄与子宫内膜容受性相关性的初步研究。
IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-01-01 DOI: 10.2147/PGPM.S406257
Song Guo, Di Zhang, Shan Zhao, Huan Zhang, Yijuan Sun, Li Yan

Background: It is well established that female fertility declines with age, primarily because of loss of ovarian function. However, few studies have clarified the relationship between increasing age and endometrial receptivity. Here, we aimed to study the impact of age on endometrial receptivity, meanwhile, we examined the expression of endometrial mesenchymal stem cell (eMSC) surface markers (CD146 and PDGF-Rβ), essential for endometrial development and re-growth, in different age groups.

Methods: Participants were enrolled in this study between October 2020 and July 2021. All 31 patients were divided into three age groups; early (30-39 years old, n=10), intermediate (40-49 years old, n=12) and advanced (≥50 years old, n=9). We assessed localization and expression of CD146 and PDGF-Rβ by immunofluorescence and further analyzed selected endometrial receptivity markers (Homeobox A10 HOXA10, leukemia inhibitory factor LIF and osteopontin) and steroid hormone receptors by immunohistochemistry.

Results: There were no significant differences in expression of HOXA10 and OPN (p>0.05) among the three groups. However, we found a significant difference in LIF expression between the early and advanced age groups, with higher expression noted in the latter group (p=0.02). Similarly, estrogen receptor (ER) and progesterone receptor (PR) expression were significantly increased (p=0.01 and p=0.01, respectively) in the advanced age group compared with the early age group. There were no significant difference in CD146 and PDGF-Rβ expression among the three groups (p>0.05).

Conclusion: These results suggest that the age of the patient does not influence their endometrial receptivity. So, this study serves to increase our understanding of the impact of age and eMSCs on endometrial receptivity and expands the etiology of age-related infertility.

背景:众所周知,女性生育能力随着年龄的增长而下降,主要是因为卵巢功能的丧失。然而,很少有研究阐明年龄增长与子宫内膜容受性之间的关系。在此,我们旨在研究年龄对子宫内膜容受性的影响,同时,我们检测了不同年龄组子宫内膜间充质干细胞(eMSC)表面标志物(CD146和PDGF-Rβ)的表达,这是子宫内膜发育和再生所必需的。方法:参与者在2020年10月至2021年7月期间入组。31例患者分为3个年龄组;早期(30-39岁,n=10)、中期(40-49岁,n=12)和晚期(≥50岁,n=9)。我们通过免疫荧光检测CD146和PDGF-Rβ的定位和表达,并进一步通过免疫组织化学分析选定的子宫内膜容受性标志物(Homeobox A10 HOXA10、白血病抑制因子LIF和骨桥蛋白)和类固醇激素受体。结果:三组患者HOXA10、OPN的表达差异无统计学意义(p>0.05)。然而,我们发现早期和晚期年龄组之间LIF表达有显著差异,后者表达较高(p=0.02)。老年组雌激素受体(ER)和孕激素受体(PR)的表达也明显高于早期组(p=0.01和p=0.01)。三组间CD146、PDGF-Rβ表达差异无统计学意义(p>0.05)。结论:这些结果提示患者的年龄不影响其子宫内膜容受性。因此,本研究有助于增加我们对年龄和eMSCs对子宫内膜容受性的影响的理解,并扩展年龄相关性不孕的病因学。
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引用次数: 0
Discovery of Drug-Responsive Phenomic Alteration-Related Driver Genes in the Treatment of Coronary Heart Disease. 冠心病治疗中药物反应性表型改变相关驱动基因的发现
IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-01-01 DOI: 10.2147/PGPM.S398522
Shuang Guan, Ya-Nan Yu, Bing Li, Hao Gu, Lin Chen, Nian Wang, Bo Wang, Xi Liu, Jun Liu, Zhong Wang
Background The Xueyu Zheng (XYZ) phenome is central to coronary heart disease (CHD), but efforts to detect genetic associations in the XYZ phenome have been disappointing. Methods The phenomic alteration-related genes (PARGs) for the XYZ phenome were screened using |ρ| > 0.4 and p < 0.05 after treatment with Danhong injection at day 14 and day 30. Then, the driver genes for the Protein-Protein Interaction (PPI) networks of the PARGs established using STRING 11.0 were detected using a personalized network control algorithm (PNC). Finally, the molecular correlations of the driver genes with the XYZ phenome were analyzed with the Gene Ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways from a holistic viewpoint. Results A total of 525 and 309 PARGs in the XYZ phenome at day 14 and day 30 were identified. These genes were separately enriched in 48 and 35 pathways. Furthermore, five driver genes were detected. These genes were mainly correlated with endoplasmic reticulum stress-mediated apoptosis and autophagy regulation, which could suppress atherosclerosis progression. Conclusion Our study detected the drug-responsive PARGs of the XYZ phenome in CHD and provides an exemplary strategy to investigate the genetic associations among this common phenome and its component symptoms in patients with CHD. Trial Registration ClinicalTrials.gov, NCT01681316; registered on September 7, 2012.
背景:血凝征(XYZ)表型是冠心病的核心,但检测XYZ表型的遗传关联的努力令人失望。方法:丹红注射液治疗后第14天、第30天,采用|ρ| > 0.4、p < 0.05筛选XYZ表型组的表型改变相关基因(PARGs)。然后,使用个性化网络控制算法(PNC)检测使用STRING 11.0建立的PARGs蛋白-蛋白相互作用(PPI)网络的驱动基因。最后,利用基因本体(GO)生物学过程和京都基因与基因组百科全书(KEGG)途径从整体角度分析了驱动基因与XYZ现象组的分子相关性。结果:在第14天和第30天,XYZ表型中共鉴定出525个和309个PARGs。这些基因分别在48条和35条途径中富集。此外,还检测到5个驱动基因。这些基因主要与内质网应激介导的细胞凋亡和自噬调控相关,可抑制动脉粥样硬化的进展。结论:我们的研究在冠心病患者中检测到XYZ表型的药物反应性PARGs,并提供了一种典型的策略来研究这种常见表型与其组成症状之间的遗传关联。试验注册:ClinicalTrials.gov, NCT01681316;于2012年9月7日注册。
{"title":"Discovery of Drug-Responsive Phenomic Alteration-Related Driver Genes in the Treatment of Coronary Heart Disease.","authors":"Shuang Guan,&nbsp;Ya-Nan Yu,&nbsp;Bing Li,&nbsp;Hao Gu,&nbsp;Lin Chen,&nbsp;Nian Wang,&nbsp;Bo Wang,&nbsp;Xi Liu,&nbsp;Jun Liu,&nbsp;Zhong Wang","doi":"10.2147/PGPM.S398522","DOIUrl":"https://doi.org/10.2147/PGPM.S398522","url":null,"abstract":"Background The Xueyu Zheng (XYZ) phenome is central to coronary heart disease (CHD), but efforts to detect genetic associations in the XYZ phenome have been disappointing. Methods The phenomic alteration-related genes (PARGs) for the XYZ phenome were screened using |ρ| > 0.4 and p < 0.05 after treatment with Danhong injection at day 14 and day 30. Then, the driver genes for the Protein-Protein Interaction (PPI) networks of the PARGs established using STRING 11.0 were detected using a personalized network control algorithm (PNC). Finally, the molecular correlations of the driver genes with the XYZ phenome were analyzed with the Gene Ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways from a holistic viewpoint. Results A total of 525 and 309 PARGs in the XYZ phenome at day 14 and day 30 were identified. These genes were separately enriched in 48 and 35 pathways. Furthermore, five driver genes were detected. These genes were mainly correlated with endoplasmic reticulum stress-mediated apoptosis and autophagy regulation, which could suppress atherosclerosis progression. Conclusion Our study detected the drug-responsive PARGs of the XYZ phenome in CHD and provides an exemplary strategy to investigate the genetic associations among this common phenome and its component symptoms in patients with CHD. Trial Registration ClinicalTrials.gov, NCT01681316; registered on September 7, 2012.","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"201-217"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/98/18/pgpm-16-201.PMC10024908.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9513447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Influence of Cytochrome P450 Polymorphisms on Pharmacokinetic Profiles and Treatment Outcomes Among Malaria Patients in Sub-Saharan Africa: A Systematic Review. 细胞色素P450多态性对撒哈拉以南非洲疟疾患者药代动力学特征和治疗结果的影响:一项系统综述
IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-01-01 DOI: 10.2147/PGPM.S379945
Karol J Marwa, Anthony Kapesa, Erasmus Kamugisha, Göte Swedberg

Background: Sub-Saharan Africa (SSA) population is genetically diverse and heterogenous thus variability in drug response among individuals is predicted to be high. Cytochrome P450 (CYP450) polymorphisms is a major source of variability in drug response. This systematic review presents the influence of CYP450 single nucleotide polymorphisms (SNPs), particularly CYP3A4*1B, CYP2B6*6 and CYP3A5*3 on antimalarial drug plasma concentrations, efficacy and safety in SSA populations.

Methods: Searching for relevant studies was done through Google Scholar, Cochrane Central Register of controlled trials (CENTRAL), PubMed, Medline, LILACS, and EMBASE online data bases. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used. Two independent reviewers extracted data from the studies.

Results: Thirteen studies reporting the influence of CYP450 SNPs on plasma concentrations, efficacy and safety were included in the final data synthesis. CYP3A4*1B, CYP3A5*5, CYP2B6*6 and CYP2C8*2 did not affect antimalarial drug plasma concentration significantly. There was no difference in treatment outcomes between malaria patients with variant alleles and those with wild type alleles.

Conclusion: This review reports lack of influence of CYP3A4*1B, CYP3A5*3, CYP2C8*3 and CYP2B6*6 SNPs on PK profiles, efficacy and safety in SSA among P. falciparum malaria patients.

背景:撒哈拉以南非洲(SSA)人口具有遗传多样性和异质性,因此预测个体之间药物反应的变异性很高。细胞色素P450 (CYP450)多态性是药物反应变异性的主要来源。本系统综述了CYP450单核苷酸多态性(snp),特别是CYP3A4*1B、CYP2B6*6和CYP3A5*3对SSA人群抗疟药物血药浓度、疗效和安全性的影响。方法:通过Google Scholar、Cochrane Central Register of controlled trials (Central)、PubMed、Medline、LILACS和EMBASE在线数据库检索相关研究。采用了系统评价和荟萃分析的首选报告项目(PRISMA)指南。两名独立的审稿人从研究中提取了数据。结果:13项报告CYP450 snp对血药浓度、疗效和安全性影响的研究纳入最终数据合成。CYP3A4*1B、CYP3A5*5、CYP2B6*6、CYP2C8*2对抗疟药血药浓度无显著影响。携带变异等位基因的疟疾患者和携带野生型等位基因的疟疾患者的治疗结果没有差异。结论:CYP3A4*1B、CYP3A5*3、CYP2C8*3和CYP2B6*6 snp对恶性疟原虫SSA患者PK谱、疗效和安全性的影响尚不明确。
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引用次数: 1
Mental Health Prescribers' Perceptions on the Use of Pharmacogenetic Testing in the Management of Depression in the Middle East and North Africa Region. 中东和北非地区心理健康处方医师对使用药物遗传学检测治疗抑郁症的看法
IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-01-01 DOI: 10.2147/PGPM.S410240
Shimaa Aboelbaha, Monica Zolezzi, Oraib Abdallah, Yassin Eltorki

Objective: A wide variety of commercial pharmacogenetic (PGx) tools are available worldwide to guide treatment selection for depression based on individuals' genetic profiles. However, the use of genetic testing to inform psychiatric care has faced challenges due to the limited training and education for mental health clinicians. The aim of this study was to explore the knowledge, level of engagement, and perspectives on the use of PGx testing when making depression management decisions among practicing psychiatrists within the Middle East and North Africa (MENA) region.

Methods: This is a qualitative study using semi-structured interviews. Consenting psychiatrists were interviewed through an online platform (SkypeTM or Microsoft TeamsTM). Interviews were audio recorded, transcribed, and thematically analyzed with the assistance of NVivo® software.

Results: Eighteen interviews from 12 countries have been conducted. Analysis of the current interviews produced five major themes including: (1) Overall perceptions and attitudes; (2) Knowledge and awareness; (3) Education, training, and professional experience; (4) Facilitators and barriers; and (5) Ethical dilemmas. These themes support the notion that there is limited, mostly basic, education, knowledge, and training regarding genetic testing in the management of depression, although there is significant interest and willingness in the part of prescribers to adopt this strategy in their practice.

Conclusion: The findings of the study suggest that psychiatrists practicing in the MENA region appear to be interested in implementing PGx testing when managing people with depression. However, it is also important to recognize that this cannot be achieved unless more supporting strategies are implemented within their current health system environment.

目的:在世界范围内,有各种各样的商业药物遗传学(PGx)工具可以根据个体的遗传特征来指导抑郁症的治疗选择。然而,由于对心理健康临床医生的培训和教育有限,使用基因检测来告知精神病学护理面临挑战。本研究的目的是探讨中东和北非(MENA)地区执业精神科医生在制定抑郁症管理决策时使用PGx测试的知识,参与水平和观点。方法:采用半结构化访谈法进行定性研究。通过在线平台(SkypeTM或Microsoft TeamsTM)对同意的精神科医生进行访谈。访谈录音,转录,并在NVivo®软件的帮助下进行主题分析。结果:共进行了来自12个国家的18次访谈。对当前访谈的分析产生了五个主要主题,包括:(1)总体看法和态度;(2)知识和意识;(三)学历、培训和从业经历;(4)促进因素和障碍;(5)伦理困境。这些主题支持这样一种观点,即在抑郁症的管理中,关于基因检测的教育、知识和培训是有限的,主要是基础的,尽管处方者在实践中有很大的兴趣和意愿采用这种策略。结论:研究结果表明,在中东和北非地区执业的精神科医生似乎对在治疗抑郁症患者时实施PGx测试感兴趣。然而,同样重要的是要认识到,除非在目前的卫生系统环境中实施更多的支持性战略,否则无法实现这一目标。
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引用次数: 1
The Allelic Expression of RNA Editing Gene ADARB1 in Hepatocellular Carcinoma Treated with Transarterial Chemoembolization. RNA编辑基因ADARB1在肝细胞癌经动脉化疗栓塞治疗中的等位基因表达
IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-01-01 DOI: 10.2147/PGPM.S402115
Jiajia Zeng, Linyu Han, Teng Wang, Linying Huang, Yanxiu Zheng, Nasha Zhang, Ziqiang Li, Ming Yang

Introduction: Transarterial chemoembolization (TACE) is the commonly used therapy of unresectable hepatocellular carcinoma (HCC), though the prognosis of different TACE-treated HCC patients varies, which may be due to the heterogeneity of HCC tumors caused by genetic variants and epigenetic changes such as RNA editing. There is dysregulated RNA adenosine-to-inosine (A-to-I) editing in HCC and RNA-edited genes are involved in the epigenetic process. It remains unclear how genetic variants of RNA editing genes affect the prognosis of HCC cases treated by TACE.

Methods: In this study, we examined 28 potentially functional single-nucleotide polymorphisms (SNPs) of four RNA editing genes (ADARB1, ADAR, ADARB2 and AIMP2) in two independent TACE patient cohorts.

Results: We found that ADARB1 rs1051367 and rs2253763 polymorphisms were markedly associated with the prognosis of HCC cases who received TACE in both cohorts. In HCC cells, the rs2253763 C-to-T change in ADARB1 3'-untranslated region attenuated its binding with miR-542-3p and allele-specifically elevated ADARB1 levels. Consistent with this, patients carrying the rs2253763 C allele showed reduced ADARB1 expression in cancer tissues and notably shorter survival after TACE therapy in comparison with individuals with the T allele. Ectopic ADARB1 profoundly enhanced the efficacy of oxaliplatin, one of the common TACE chemotherapeutic drugs.

Discussion: Our findings highlighted the value of ADARB1 polymorphisms as prognostic markers in TACE therapy for HCC patients. Notably, our findings revealed that targeting the ADARB1 enzyme may be a promising therapeutic strategy in combination with TACE for HCC cases.

简介:经动脉化疗栓塞(transcarterial chemoembolization, TACE)是不可切除肝细胞癌(HCC)的常用治疗方法,但不同TACE治疗的HCC患者预后存在差异,这可能是由于基因变异和RNA编辑等表观遗传改变导致HCC肿瘤的异质性所致。HCC中存在RNA腺苷-肌苷(A-to-I)编辑失调,RNA编辑基因参与表观遗传过程。目前尚不清楚RNA编辑基因的遗传变异如何影响TACE治疗的HCC患者的预后。方法:在这项研究中,我们在两个独立的TACE患者队列中检测了4个RNA编辑基因(ADARB1、ADAR、ADARB2和AIMP2)的28个潜在功能单核苷酸多态性(snp)。结果:我们发现在两个队列中,ADARB1 rs1051367和rs2253763多态性与接受TACE的HCC患者的预后显著相关。在HCC细胞中,ADARB1 3'-非翻译区rs2253763 C-to-T的变化减弱了其与miR-542-3p的结合,并且等位基因特异性地升高了ADARB1水平。与此一致的是,携带rs2253763 C等位基因的患者在癌症组织中ADARB1表达降低,与携带T等位基因的个体相比,TACE治疗后的生存期明显缩短。异位ADARB1显著提高了TACE常用化疗药物之一奥沙利铂的疗效。讨论:我们的研究结果强调了ADARB1多态性作为HCC患者TACE治疗预后标志物的价值。值得注意的是,我们的研究结果表明,靶向ADARB1酶与TACE联合治疗HCC病例可能是一种很有前景的治疗策略。
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引用次数: 0
Plasma Homocysteine (Hcy) Concentration Functions as a Predictive Biomarker of SPECT-Evaluated Post-Ischemic Hyperperfusion in Acute Ischemic Stroke. 血浆同型半胱氨酸(Hcy)浓度可作为急性缺血性卒中spect评估后缺血高灌注的预测性生物标志物。
IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-01-01 DOI: 10.2147/PGPM.S400767
Yingqiu Wang, Renhua Hou, Yan Liu

Introduction: Homocysteine (Hcy) concentration has been reported to be associated with ischemic stroke. In this study, we aimed to investigate the potential of plasma Hcy in the prediction of post-ischemic hyperperfusion in AIS patients, which was diagnosed with the single-photon emission computed tomography (SPECT) method.

Methods: A total of 112 ischemic stroke patients were recruited in this study. According to whether the patients were subjected to post-ischemic hyperperfusion, all recruited subjects were divided into a post-ischemic hyperperfusion (+) group (N=48) and post-ischemic hyperperfusion (-) group (N=64). The basic demographical data, clinicopathological data and laboratory biochemical data were collected and compared. Level of homocysteine (Hcy) and cystatin-C (Cys-C) and their potential as predictive biomarker are also investigated.

Results: No significant differences were spotted between the post-ischemic hyperperfusion group (+) and post-ischemic hyperperfusion (-) group in respect to the basic demographical and clinicopathological data. And the serum Hcy levels were lower in the post-ischemic hyperperfusion (+) group. Moreover, ROC analysis indicated significant relationships between Hcy levels and the onset of post-ischemic hyperperfusion.

Conclusion: In conclusion, we validated that the plasma Hcy concentration can be used as a predictive biomarker of SPECT-evaluated post-ischemic hyperperfusion in patients suffering from acute ischemic stroke.

简介:同型半胱氨酸(Hcy)浓度已被报道与缺血性卒中相关。在这项研究中,我们旨在探讨血浆Hcy在预测AIS患者缺血后高灌注中的潜力,AIS患者是用单光子发射计算机断层扫描(SPECT)方法诊断的。方法:本研究共招募112例缺血性脑卒中患者。根据患者是否存在缺血后高灌注,将所有招募的受试者分为缺血后高灌注(+)组(N=48)和缺血后高灌注(-)组(N=64)。收集基本人口学资料、临床病理资料和实验室生化资料进行比较。同型半胱氨酸(Hcy)和胱抑素- c (Cys-C)水平及其作为预测性生物标志物的潜力也进行了研究。结果:缺血后高灌注组(+)与缺血后高灌注组(-)在基本人口学和临床病理数据上均无显著差异。缺血高灌注后(+)组血清Hcy水平较低。此外,ROC分析显示Hcy水平与缺血后高灌注的发生有显著关系。结论:总之,我们验证了血浆Hcy浓度可以作为急性缺血性脑卒中患者spect评估后缺血高灌注的预测性生物标志物。
{"title":"Plasma Homocysteine (Hcy) Concentration Functions as a Predictive Biomarker of SPECT-Evaluated Post-Ischemic Hyperperfusion in Acute Ischemic Stroke.","authors":"Yingqiu Wang,&nbsp;Renhua Hou,&nbsp;Yan Liu","doi":"10.2147/PGPM.S400767","DOIUrl":"https://doi.org/10.2147/PGPM.S400767","url":null,"abstract":"<p><strong>Introduction: </strong>Homocysteine (Hcy) concentration has been reported to be associated with ischemic stroke. In this study, we aimed to investigate the potential of plasma Hcy in the prediction of post-ischemic hyperperfusion in AIS patients, which was diagnosed with the single-photon emission computed tomography (SPECT) method.</p><p><strong>Methods: </strong>A total of 112 ischemic stroke patients were recruited in this study. According to whether the patients were subjected to post-ischemic hyperperfusion, all recruited subjects were divided into a post-ischemic hyperperfusion (+) group (N=48) and post-ischemic hyperperfusion (-) group (N=64). The basic demographical data, clinicopathological data and laboratory biochemical data were collected and compared. Level of homocysteine (Hcy) and cystatin-C (Cys-C) and their potential as predictive biomarker are also investigated.</p><p><strong>Results: </strong>No significant differences were spotted between the post-ischemic hyperperfusion group (+) and post-ischemic hyperperfusion (-) group in respect to the basic demographical and clinicopathological data. And the serum Hcy levels were lower in the post-ischemic hyperperfusion (+) group. Moreover, ROC analysis indicated significant relationships between Hcy levels and the onset of post-ischemic hyperperfusion.</p><p><strong>Conclusion: </strong>In conclusion, we validated that the plasma Hcy concentration can be used as a predictive biomarker of SPECT-evaluated post-ischemic hyperperfusion in patients suffering from acute ischemic stroke.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"481-489"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2a/e1/pgpm-16-481.PMC10226540.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9924329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Integrated Bioinformatics Analysis and Experimental Verification of Immune Cell Infiltration and the Related Core Genes in Ulcerative Colitis. 溃疡性结肠炎免疫细胞浸润及相关核心基因的综合生物信息学分析与实验验证。
IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2023-01-01 DOI: 10.2147/PGPM.S406644
Danya Zhao, Danping Qin, Liming Yin, Qiang Yang

Background: Ulcerative colitis is a recurrent autoimmune disease. At present, the pathogenesis of UC is not completely clear. Hence, the etiology and underlying molecular mechanism need to be further investigated.

Methods: Three sets of microarray datasets were included from the Gene Expression Omnibus database. The differentially expressed genes in two sets of datasets were analyzed using the R software, and the core genes of UC were screened using machine learning. The sensitivity and specificity of the core genes were evaluated with the receiver operating characteristic curve in another microarray dataset. Subsequently, the CIBERSORT tool was used to analyze the relationship between UC and its core genes and immune cell infiltration. To verify the relationship between UC and core genes and the relationship between core genes and immune cell infiltration in vivo.

Results: A total of 36 DEGs were identified. AQP8, HMGCS2, and VNN1 were determined to be the core genes of UC. These genes had high sensitivity and specificity in receiver operating characteristic curve analysis. According to the analysis of immune cell infiltration, neutrophils, monocytes, and macrophages were positively correlated with UC. AQP8, HMGCS2, and VNN1 were also correlated with immune cell infiltration to varying degrees. In vivo experiments verified that the expressions of neutrophils, monocytes, and macrophages increased in the UC colon. Furthermore, the expressions of AQP8 and HMGCS2 decreased, whereas that of VNN1 increased. Azathioprine treatment improved all the indicators to different degrees.

Conclusion: AQP8, HMGCS2, and VNN1 are the core genes of UC and exhibit different degrees of correlation with immune cells. These genes are expected to become new therapeutic targets for UC. Moreover, the occurrence and development of UC are influenced by immune cell infiltration.

背景:溃疡性结肠炎是一种复发性自身免疫性疾病。目前,UC的发病机制尚不完全清楚。因此,病因和潜在的分子机制需要进一步研究。方法:从Gene Expression Omnibus数据库中获取三组微阵列数据集。使用R软件分析两组数据集中的差异表达基因,并使用机器学习筛选UC的核心基因。核心基因的敏感性和特异性用另一个微阵列数据集的接收器工作特征曲线进行评估。随后,利用CIBERSORT工具分析UC及其核心基因与免疫细胞浸润的关系。验证UC与核心基因的关系以及核心基因与体内免疫细胞浸润的关系。结果:共鉴定出36个deg。AQP8、HMGCS2和VNN1是UC的核心基因。这些基因在受试者工作特性曲线分析中具有较高的敏感性和特异性。免疫细胞浸润分析发现,中性粒细胞、单核细胞和巨噬细胞与UC呈正相关。AQP8、HMGCS2、VNN1也与免疫细胞浸润有不同程度的相关性。体内实验证实,UC结肠中中性粒细胞、单核细胞和巨噬细胞的表达增加。AQP8和HMGCS2表达降低,VNN1表达升高。硫唑嘌呤处理对各指标均有不同程度的改善。结论:AQP8、HMGCS2、VNN1是UC的核心基因,与免疫细胞有不同程度的相关性。这些基因有望成为UC的新的治疗靶点。此外,UC的发生发展受免疫细胞浸润的影响。
{"title":"Integrated Bioinformatics Analysis and Experimental Verification of Immune Cell Infiltration and the Related Core Genes in Ulcerative Colitis.","authors":"Danya Zhao,&nbsp;Danping Qin,&nbsp;Liming Yin,&nbsp;Qiang Yang","doi":"10.2147/PGPM.S406644","DOIUrl":"https://doi.org/10.2147/PGPM.S406644","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis is a recurrent autoimmune disease. At present, the pathogenesis of UC is not completely clear. Hence, the etiology and underlying molecular mechanism need to be further investigated.</p><p><strong>Methods: </strong>Three sets of microarray datasets were included from the Gene Expression Omnibus database. The differentially expressed genes in two sets of datasets were analyzed using the R software, and the core genes of UC were screened using machine learning. The sensitivity and specificity of the core genes were evaluated with the receiver operating characteristic curve in another microarray dataset. Subsequently, the CIBERSORT tool was used to analyze the relationship between UC and its core genes and immune cell infiltration. To verify the relationship between UC and core genes and the relationship between core genes and immune cell infiltration in vivo.</p><p><strong>Results: </strong>A total of 36 DEGs were identified. <i>AQP8, HMGCS2</i>, and <i>VNN1</i> were determined to be the core genes of UC. These genes had high sensitivity and specificity in receiver operating characteristic curve analysis. According to the analysis of immune cell infiltration, neutrophils, monocytes, and macrophages were positively correlated with UC. <i>AQP8, HMGCS2</i>, and <i>VNN1</i> were also correlated with immune cell infiltration to varying degrees. In vivo experiments verified that the expressions of neutrophils, monocytes, and macrophages increased in the UC colon. Furthermore, the expressions of <i>AQP8</i> and <i>HMGCS2</i> decreased, whereas that of <i>VNN1</i> increased. Azathioprine treatment improved all the indicators to different degrees.</p><p><strong>Conclusion: </strong><i>AQP8, HMGCS2</i>, and <i>VNN1</i> are the core genes of UC and exhibit different degrees of correlation with immune cells. These genes are expected to become new therapeutic targets for UC. Moreover, the occurrence and development of UC are influenced by immune cell infiltration.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"629-643"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b1/f7/pgpm-16-629.PMC10296601.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10113420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Pharmacogenomics & Personalized Medicine
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