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Pharmacogenomics 药物基因组学
IF 5.3 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2020-01-01 DOI: 10.1016/b978-0-12-819834-6.00006-9
J. Crabtree
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引用次数: 0
Index 指数
IF 5.3 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2020-01-01 DOI: 10.1016/b978-0-12-819834-6.20001-3
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引用次数: 0
Translating current biomedical therapies for long duration, deep space missions. 将目前的生物医学疗法转化为长时间的深空任务。
IF 5.3 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2019-12-01 Epub Date: 2019-11-15 DOI: 10.1093/pcmedi/pbz022
Sonia Iosim, Matthew MacKay, Craig Westover, Christopher E Mason

It is been shown that spaceflight-induced molecular, cellular, and physiologic changes cause alterations across many modalities of the human body, including cardiovascular, musculoskeletal, hematological, immunological, ocular, and neurological systems. The Twin Study, a multi-year, multi-omic study of human response to spaceflight, provided detailed and comprehensive molecular and cellular maps of the human response to radiation, microgravity, isolation, and stress. These rich data identified epigenetic, gene expression, inflammatory, and metabolic responses to spaceflight, facilitating a better biomedical roadmap of features that should be monitored and safe-guarded in upcoming missions. Further, by exploring new developments in pre-clinical models and clinical trials, we can begin to design potential cellular interventions for exploration-class missions to Mars and potentially farther. This paper will discuss the overall risks astronauts face during spaceflight, what is currently known about human response to these risks, what pharmaceutical interventions exist for use in space, and which tools of precision medicine and cellular engineering could be applied to aerospace and astronaut medicine.

研究表明,太空飞行引起的分子、细胞和生理变化会引起人体许多形态的改变,包括心血管、肌肉骨骼、血液、免疫、眼和神经系统。孪生研究是一项关于人类对航天反应的多年多组学研究,提供了人类对辐射、微重力、隔离和压力反应的详细和全面的分子和细胞图。这些丰富的数据确定了对太空飞行的表观遗传、基因表达、炎症和代谢反应,促进了更好的生物医学路线图,这些特征应该在即将到来的任务中进行监测和保护。此外,通过探索临床前模型和临床试验的新进展,我们可以开始设计潜在的细胞干预措施,用于火星和更远的探索级任务。本文将讨论宇航员在航天飞行期间面临的总体风险,目前已知的人类对这些风险的反应,在太空中存在哪些药物干预措施,以及哪些精确医学和细胞工程工具可以应用于航空航天和宇航员医学。
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引用次数: 22
DNA methylome study of human cerebellar tissues identified genes and pathways possibly involved in essential tremor. 人类小脑组织的DNA甲基组研究鉴定了可能与特发性震颤有关的基因和途径。
IF 5.3 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2019-12-01 Epub Date: 2019-12-08 DOI: 10.1093/pcmedi/pbz028
Jennifer L Paul, Khashayar Dashtipour, Zhong Chen, Charles Wang

Background: Essential tremor (ET) is a neurological syndrome of unknown origin with poorly understood etiology and pathogenesis. It is suggested that the cerebellum and its tracts may be involved in the pathophysiology of ET. DNA methylome interrogation of cerebellar tissue may help shine some light on the understanding of the mechanism of the development of ET. Our study used postmortem human cerebellum tissue samples collected from 12 ET patients and 11 matched non-ET controls for DNA methylome study to identify differentially methylated genes in ET.

Results: Using Nugen's Ovation reduced representation bisulfite sequencing (RRBS), we identified 753 genes encompassing 938 CpG sites with significant differences in DNA methylation between the ET and the control group. Identified genes were further analyzed with Ingenuity Pathway Analysis (IPA) by which we identified certain significant pathways, upstream regulators, diseases and functions, and networks associated with ET.

Conclusions: Our study provides evidence that there are significant differences in DNA methylation patterns between the ET and control samples, suggesting that the methylation alteration of certain genes in the cerebellum may be associated with ET pathogenesis. The identified genes allude to the GABAergic hypothesis which supports the notation that ET is a neurodegenerative disease, particularly involving the cerebellum.

背景:特发性震颤(ET)是一种病因不明的神经系统综合征,病因和发病机制尚不清楚。小脑及其束可能参与ET的病理生理过程,对小脑组织的DNA甲基化分析可能有助于理解ET的发生机制。本研究利用12例ET患者和11例非ET对照者的死后人类小脑组织样本进行DNA甲基化研究,以鉴定ET中差异甲基化基因。使用Nugen's Ovation reduced representation亚硫酸盐测序(RRBS),我们鉴定了753个基因,其中包含938个CpG位点,ET和对照组之间的DNA甲基化存在显著差异。通过独创性途径分析(Ingenuity Pathway Analysis, IPA),我们进一步分析了与ET相关的一些重要途径、上游调节因子、疾病和功能以及网络。结论:我们的研究提供了证据,证明ET与对照样本之间的DNA甲基化模式存在显著差异,提示小脑中某些基因的甲基化改变可能与ET的发病机制有关。已鉴定的基因暗示gaba能假说,该假说支持ET是一种神经退行性疾病,特别是涉及小脑的说法。
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引用次数: 1
Gut viruses firm the “Great Wall” 肠道病毒筑起“长城”
IF 5.3 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2019-12-01 DOI: 10.1093/pcmedi/pbz027
Anmin Wang, Shu Zhu
© The Author(s) 2019. Published by Oxford University Press on behalf of West China School of Medicine & West China Hospital of Sichuan University. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
©作者2019。牛津大学出版社代表四川大学华西医学院、华西医院出版。这是一篇基于知识共享署名非商业许可协议(http://creativecommons.org/ licenses/by-nc/4.0/)的开放获取文章,该协议允许在任何媒介上进行非商业再利用、分发和复制,前提是正确引用原创作品。如需商业再利用,请联系journals.permissions@oup.com
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引用次数: 0
5G and intelligence medicine-how the next generation of wireless technology will reconstruct healthcare? 5G与智能医疗——下一代无线技术将如何重构医疗?
IF 5.3 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2019-12-01 Epub Date: 2019-10-18 DOI: 10.1093/pcmedi/pbz020
Dong Li

Despite intensive efforts, there are still enormous challenges in provision of healthcare services to the increasing aging population. Recent observations have raised concerns regarding the soaring costs of healthcare, the imbalance of medical resources, inefficient healthcare system administration, and inconvenient medical experiences. However, cutting-edge technologies are being developed to meet these challenges, including, but not limited to, Internet of Things (IoT), big data, artificial intelligence, and 5G wireless transmission technology to improve the patient experience and healthcare service quality, while cutting the total cost attributable to healthcare. This is not an unrealistic fantasy, as these emerging technologies are beginning to impact and reconstruct healthcare in subtle ways. Although the technologies mentioned above are integrated, in this review we take a brief look at cases focusing on the application of 5G wireless transmission technology in healthcare. We also highlight the potential pitfalls to availability of 5G technologies.

尽管作出了巨大努力,但在向日益老龄化的人口提供保健服务方面仍面临巨大挑战。最近的观察引起了人们对医疗保健费用飙升、医疗资源不平衡、医疗保健系统管理效率低下以及不方便的医疗体验的关注。然而,人们正在开发尖端技术来应对这些挑战,包括但不限于物联网(IoT)、大数据、人工智能和5G无线传输技术,以改善患者体验和医疗服务质量,同时降低医疗保健的总成本。这并非不切实际的幻想,因为这些新兴技术正开始以微妙的方式影响和重建医疗保健。虽然上述技术是集成的,但在本文中,我们将简要介绍5G无线传输技术在医疗保健中的应用案例。我们还强调了5G技术可用性的潜在缺陷。
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引用次数: 122
Uveitis-glaucoma-hyphema syndrome associated with an in-the-bag square-edge intraocular lens 葡萄膜炎-青光眼-前房积血综合征与袋内方边人工晶状体相关
IF 5.3 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2019-11-29 DOI: 10.1093/pcmedi/pbz026
Jin Yang, Xiaodi Qiu, Lei Cai, Qi Fan, Anjian Wang, Kang Zhang, Yi Lu
Abstract A 54-year-old woman presented with recurrent redness and blurred vision of the left eye with elevated intraocular pressure (IOP) for one year. She was treated as “iridocyclitis” and ``Posner-Schlossman syndrome'' at the local hospitals. However, the patient developed intermittent ocular inflammation and hyphema. Patient had a cataract surgery and intraocular lens (IOL) implantation in the left eye one year before at the local hospital. A diagnostic procedure was performed and the possible pathogenesis was discussed.
摘要一名54岁女性患者以左眼反复发红、视力模糊伴眼压升高1年为临床表现。她在当地医院接受了“虹膜睫状体炎”和“Posner-Schlossman综合征”的治疗。然而,患者出现间歇性眼部炎症和前房积血。患者一年前在当地医院接受了白内障手术和左眼人工晶状体植入术。进行了诊断程序,并讨论了可能的发病机制。
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引用次数: 2
Effect of autologous NK cell immunotherapy on advanced lung adenocarcinoma with EGFR mutations 自体NK细胞免疫治疗晚期EGFR突变肺腺癌的疗效观察
IF 5.3 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2019-11-22 DOI: 10.1093/pcmedi/pbz023
Guodai Hong, Xuemei Chen, Xizhuo Sun, Meiling Zhou, Bing Liu, Zhu Li, Zhen-dong Yu, Wenbin Gao, Tao Liu
Abstract This study investigated the efficiency of natural killer (NK) cell immunotherapy on non-small cell lung cancer with and without EGFR mutations in order to evaluate the response rate (RR) and progression-free survival (PFS). Among the 48 patients recruited, 24 were clinically confirmed to be EGFR mutation positive. The study group was treated with autologous NK cell immunotherapy. Comparisons of the lymphocyte number, serum tumour-related biomarkers, circulating tumour cells (CTC), Karnofsky Performance Status (KPS) and survival curves were carried out before and after NK cell immunotherapy. The safety and short-term effects were evaluated, followed by median PFS and RR assessments. The serum CEA and CA125 values were found lower in the NK cell therapy group than that of the non-NK treatment group (p < 0.05). The χ2 test showed a 75% RR of the study group A, significantly higher than that of the control group B (16.7%; p < 0.01). The RR of groups C (58.3%) and D (41.7%) were not statistically significant. The p values of the 4 groups were 0.012, 0.012, 0.166 and 1 from group A to group D, respectively. The median PFS was 9 months in EGFR mutation positive group undergoing NK cell infusion interference. By evaluating the changes in immune function, tumour biomarkers, CTC, KPS and PFS, we demonstrated that NK cell therapy had better clinical therapeutic effects on EGFR mutation-positive lung adenocarcinoma.
摘要本研究旨在探讨自然杀伤细胞(NK)免疫治疗对EGFR突变和非EGFR突变的非小细胞肺癌的疗效,以评估其缓解率(RR)和无进展生存期(PFS)。在纳入的48例患者中,24例临床证实为EGFR突变阳性。实验组采用自体NK细胞免疫治疗。比较NK细胞免疫治疗前后淋巴细胞数量、血清肿瘤相关生物标志物、循环肿瘤细胞(CTC)、Karnofsky Performance Status (KPS)和生存曲线。评估安全性和短期效果,然后评估中位PFS和RR。NK细胞治疗组血清CEA、CA125值明显低于非NK细胞治疗组(p < 0.05)。χ2检验显示,a研究组的RR为75%,显著高于对照组B组(16.7%;P < 0.01)。C组(58.3%)、D组(41.7%)的RR差异无统计学意义。A组与D组的p值分别为0.012、0.012、0.166和1。EGFR突变阳性组接受NK细胞输注干扰,中位PFS为9个月。通过免疫功能、肿瘤生物标志物、CTC、KPS和PFS的变化,我们证明NK细胞治疗对EGFR突变阳性肺腺癌有更好的临床治疗效果。
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引用次数: 6
Genome-wide characterization of copy number variations in diffuse large B-cell lymphoma with implications in targeted therapy 弥漫性大b细胞淋巴瘤拷贝数变异的全基因组特征及其靶向治疗的意义
IF 5.3 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2019-11-21 DOI: 10.1093/pcmedi/pbz024
Prashanthi Dharanipragada, N. Parekh
Abstract Diffuse large B-cell lymphoma (DLBCL) is the aggressive form of haematological malignancies with relapse/refractory in ~ 40% of cases. It mostly develops due to accumulation of various genetic and epigenetic variations that contribute to its aggressiveness. Though large-scale structural alterations have been reported in DLBCL, their functional role in pathogenesis and as potential targets for therapy is not yet well understood. In this study we performed detection and analysis of copy number variations (CNVs) in 11 human DLBCL cell lines (4 activated B-cell–like [ABC] and 7 germinal-centre B-cell–like [GCB]), that serve as model systems for DLBCL cancer cell biology. Significant heterogeneity observed in CNV profiles of these cell lines and poor prognosis associated with ABC subtype indicates the importance of individualized screening for diagnostic and prognostic targets. Functional analysis of key cancer genes exhibiting copy alterations across the cell lines revealed activation/disruption of ten potentially targetable immuno-oncogenic pathways. Genome guided in silico therapy that putatively target these pathways is elucidated. Based on our analysis, five CNV-genes associated with worst survival prognosis are proposed as potential prognostic markers of DLBCL.
弥漫性大b细胞淋巴瘤(DLBCL)是一种侵袭性血液系统恶性肿瘤,约40%的病例复发或难治性。它主要是由于各种遗传和表观遗传变异的积累而发展起来的,这些变异有助于其攻击性。虽然大范围的结构改变在DLBCL中有报道,但它们在发病机制中的功能作用以及作为潜在治疗靶点的作用尚未得到很好的理解。在这项研究中,我们检测和分析了11种人DLBCL细胞系(4种活化b细胞样[ABC]和7种生发中心b细胞样[GCB])的拷贝数变异(CNVs),这些细胞系可作为DLBCL癌细胞生物学的模型系统。在这些细胞系的CNV谱中观察到的显著异质性和与ABC亚型相关的不良预后表明,个体化筛查对于诊断和预后目标的重要性。在细胞系中表现出复制改变的关键癌症基因的功能分析揭示了十种潜在靶向免疫致癌途径的激活/破坏。基因组引导的硅治疗,假定目标是这些途径被阐明。根据我们的分析,五个与最差生存预后相关的cnv基因被提出作为DLBCL的潜在预后标志物。
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引用次数: 3
Mutation spectrum in GNAQ and GNA11 in Chinese uveal melanoma 中国葡萄膜黑色素瘤GNAQ和GNA11突变谱
IF 5.3 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2019-11-13 DOI: 10.1093/pcmedi/pbz021
Edward D. Zhang, Meixia Zhang, Gen Li, Charlotte L. Zhang, Zhihuan Li, Guangxi Zang, Z. Su, Ming Zhang, Daoman Xiang, Ling Zhao, Jie Zhu
Abstract Uveal melanoma is the most common intraocular cancer in the adult eye. R183 and Q209 were found to be mutational hotspots in exon 4 and exon 5 of GNAQ and GNA11 in Caucasians. However, only a few studies have reported somatic mutations in GNAQ or GNA11 in uveal melanoma in Chinese. We extracted somatic DNA from paraffin-embedded biopsies of 63 Chinese uveal melanoma samples and sequenced the entire coding regions of exons 4 and 5 in GNAQ and GNA11. The results showed that 33% of Chinese uveal melanoma samples carried Q209 mutations while none had R183 mutation in GNAQ or GNA11. In addition, seven novel missense somatic mutations in GNAQ (Y192C, F194L, P170S, D236N, L232F, V230A, and M227I) and four novel missense somatic mutations in GNA11 (R166C, I200T, S225F, and V206M) were found in our study. The high mutation frequency of Q209 and the novel missense mutations detected in this study suggest that GNAQ and GNA11 are common targets for somatic mutations in Chinese uveal melanoma.
葡萄膜黑色素瘤是成人眼内最常见的恶性肿瘤。在白种人GNAQ和GNA11的外显子4和外显子5上发现R183和Q209是突变热点。然而,仅有少数研究报道了中国人葡萄膜黑色素瘤中GNAQ或GNA11的体细胞突变。我们从63个中国葡萄膜黑色素瘤样本的石蜡包埋活检中提取体细胞DNA,并对GNAQ和GNA11外显子4和5的整个编码区进行了测序。结果显示,33%的中国葡萄膜黑色素瘤样本携带Q209突变,而GNAQ和GNA11中没有R183突变。此外,在GNAQ中发现了7个新的错义体细胞突变(Y192C、F194L、P170S、D236N、L232F、V230A和M227I),在GNA11中发现了4个新的错义体细胞突变(R166C、I200T、S225F和V206M)。Q209的高突变频率和本研究检测到的新型错义突变表明,GNAQ和GNA11是中国葡萄膜黑色素瘤体细胞突变的共同靶点。
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引用次数: 3
期刊
Precision Clinical Medicine
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