Precision Clinical Medicine最新文献_第9页

Can the personalized medicine approach contribute in controlling tuberculosis in general and India in particular? 个体化医疗方法能否有助于控制结核病，特别是在印度?

IF 5.3 4区医学

Precision Clinical Medicine Pub Date : 2020-06-04 DOI: 10.1093/pcmedi/pbaa021

Nikhat Khan, Aparup Das

引用次数: 4

Improved gastrointestinal health for irritable bowel syndrome with metagenome-guided interventions. 宏基因组引导干预改善肠易激综合征胃肠道健康

IF 5.3 4区医学

Precision Clinical Medicine Pub Date : 2020-06-01 Epub Date: 2020-04-29 DOI: 10.1093/pcmedi/pbaa013

Cem Meydan, Ebrahim Afshinnekoo, Nate Rickard, Guy Daniels, Laura Kunces, Theresa Hardy, Loukia Lili, Sarah Pesce, Paul Jacobson, Christopher E Mason, Joel Dudley, Bodi Zhang

{"title":"Improved gastrointestinal health for irritable bowel syndrome with metagenome-guided interventions.","authors":"Cem Meydan, Ebrahim Afshinnekoo, Nate Rickard, Guy Daniels, Laura Kunces, Theresa Hardy, Loukia Lili, Sarah Pesce, Paul Jacobson, Christopher E Mason, Joel Dudley, Bodi Zhang","doi":"10.1093/pcmedi/pbaa013","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa013","url":null,"abstract":"Irritable bowel syndrome (IBS) is the most prevalent functional gastrointestinal disorder worldwide, and the most common reason for referral to gastroenterology clinics. However, the pathophysiology is still not fully understood and consequently current management guidelines are very symptom-specific, leading to mixed results. Here we present a study of 88 individuals with IBS who had baseline sequencing of their gut microbiome (stool samples), received targeted interventions that included dietary, supplement, prebiotic/probiotic, and lifestyle recommendations for a 30-day period, and a follow-up sequencing of their gut microbiome. The study's objectives were to demonstrate unique metagenomic signatures across the IBS phenotypes and to validate whether metagenomic-guided interventions could lead to improvement of symptom scores in individuals with IBS. Enrolled subjects also completed a baseline and post-intervention questionnaire that assessed their symptom scores. The average symptom score of an individual with IBS at baseline was 160 and at the endpoint of the study the average symptom score of the cohort was 100.9. The mixed IBS subtype showed the most significant reduction in symptom scores across the different subtypes (average decrease by 102 points, P = 0.005). The metagenomics analysis reveals shifts in the microbiome post-intervention that have been cross-validated with the literature as being associated with improvement of IBS symptoms. Given the complex nature of IBS, further studies with larger sample sizes, more targeted analyses, and a broader population cohort are needed to explore these results further.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"3 2","pages":"136-146"},"PeriodicalIF":5.3,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/pcmedi/pbaa013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38170632","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: 9

Double contrast-enhanced ultrasonography of a small intestinal neuroendocrine tumor: a case report of a recommendable imaging modality 小肠神经内分泌肿瘤的双重超声造影:推荐的成像方式1例报告

IF 5.3 4区医学

Precision Clinical Medicine Pub Date : 2020-04-17 DOI: 10.1093/pcmedi/pbaa011

Jie-ying Zhao, H. Zhuang, Yuan Luo, M. Su, M. Xiong, Yu-ting Wu

引用次数: 0

RNA-based therapies in animal models of Leber congenital amaurosis causing blindness Leber先天性黑朦致盲动物模型的rna治疗

IF 5.3 4区医学

Precision Clinical Medicine Pub Date : 2020-03-12 DOI: 10.1093/pcmedi/pbaa009

Xia Wang, Xianghong Shan, K. Gregory-Evans, C. Gregory-Evans

{"title":"RNA-based therapies in animal models of Leber congenital amaurosis causing blindness","authors":"Xia Wang, Xianghong Shan, K. Gregory-Evans, C. Gregory-Evans","doi":"10.1093/pcmedi/pbaa009","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa009","url":null,"abstract":"Abstract Leber congenital amaurosis (LCA) is a severe, genetically heterogeneous recessive eye disease in which ~ 35% of gene mutations are in-frame nonsense mutations coding for loss-of-function premature termination codons (PTCs) in mRNA. Nonsense suppression therapy allows read-through of PTCs leading to production of full-length protein. A limitation of nonsense suppression is that nonsense-mediated decay (NMD) degrades PTC-containing RNA transcripts. The purpose of this study was to determine whether inhibition of NMD could improve nonsense suppression efficacy in vivo. Using a high-throughput approach in the recessive cep290 zebrafish model of LCA (cep290;Q1223X), we first tested the NMD inhibitor Amlexanox in combination with the nonsense suppression drug Ataluren. We observed reduced retinal cell death and improved visual function. With these positive data, we next investigated whether this strategy was also applicable across species in two mammalian models: Rd12 (rpe65;R44X) and Rd3 (rd3;R107X) mouse models of LCA. In the Rd12 model, cell death was reduced, RPE65 protein was produced, and in vivo visual function testing was improved. We establish for the first time that the mechanism of action of Amlexanox in Rd12 retina was through reduced UPF1 phosphorylation. In the Rd3 model, however, no beneficial effect was observed with Ataluren alone or in combination with Amlexanox. This variation in response establishes that some forms of nonsense mutation LCA can be targeted by RNA therapies, but that this needs to be verified for each genotype. The implementation of precision medicine by identifying better responders to specific drugs is essential for development of validated retinal therapies.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"181 1","pages":"113 - 126"},"PeriodicalIF":5.3,"publicationDate":"2020-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74545740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Clinical applications of exosome membrane proteins. 外泌体膜蛋白的临床应用。

IF 5.3 4区医学

Precision Clinical Medicine Pub Date : 2020-03-01 Epub Date: 2020-02-24 DOI: 10.1093/pcmedi/pbaa007

Qian Hu, Hang Su, Juan Li, Christopher Lyon, Wenfu Tang, Meihua Wan, Tony Ye Hu

{"title":"Clinical applications of exosome membrane proteins.","authors":"Qian Hu, Hang Su, Juan Li, Christopher Lyon, Wenfu Tang, Meihua Wan, Tony Ye Hu","doi":"10.1093/pcmedi/pbaa007","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa007","url":null,"abstract":"Extracellular vesicles (EVs) are small membranous particles that can mediate cell-to-cell communication and which are divided into at least three categories according to their subcellular origin and size: exosomes, microvesicles, and apoptotic bodies. Exosomes are the smallest (30-150 nm) of these EVs, and play an important role in EV-mediated cell-to-cell interactions, by transferring proteins, nucleic acids and, lipids from their parental cells to adjacent or distant cells to alter their phenotypes. Most exosome studies in the past two decades have focused on their nucleic acid composition and their transfer of mRNAs and microRNAs to neighboring cells. However, exosomes also carry specific membrane proteins that can identify the physiological and pathological states of their parental cells or indicate their preferential target cells or tissues. Exosome membrane protein expression can also be directly employed or modified to allow exosomes to serve as drug delivery systems and therapeutic platforms, including in targeted therapy approaches. This review will briefly summarize information on exosome membrane proteins components and their role in exosome-cell interactions, including proteins associated with specific cell-interactions and diseases, and the potential for using exosome membrane proteins in therapeutic targeting approaches.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"3 1","pages":"54-66"},"PeriodicalIF":5.3,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/pcmedi/pbaa007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37808778","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: 88

Potassium channels as potential drug targets for limb wound repair and regeneration. 钾通道作为肢体创伤修复和再生的潜在药物靶点。

IF 5.3 4区医学

Precision Clinical Medicine Pub Date : 2020-03-01 Epub Date: 2019-12-30 DOI: 10.1093/pcmedi/pbz029

Wengeng Zhang, Pragnya Das, Sarah Kelangi, Marianna Bei

{"title":"Potassium channels as potential drug targets for limb wound repair and regeneration.","authors":"Wengeng Zhang, Pragnya Das, Sarah Kelangi, Marianna Bei","doi":"10.1093/pcmedi/pbz029","DOIUrl":"https://doi.org/10.1093/pcmedi/pbz029","url":null,"abstract":"Background: Ion channels are a large family of transmembrane proteins, accessible by soluble membrane-impermeable molecules, and thus are targets for development of therapeutic drugs. Ion channels are the second most common target for existing drugs, after G protein-coupled receptors, and are expected to make a big impact on precision medicine in many different diseases including wound repair and regeneration. Research has shown that endogenous bioelectric signaling mediated by ion channels is critical in non-mammalian limb regeneration. However, the role of ion channels in regeneration of limbs in mammalian systems is not yet defined.Methods: To explore the role of potassium channels in limb wound repair and regeneration, the hindlimbs of mouse embryos were amputated at E12.5 when the wound is expected to regenerate and E15.5 when the wound is not expected to regenerate, and gene expression of potassium channels was studied.Results: Most of the potassium channels were downregulated, except for the potassium channel kcnj8 (Kir6.1) which was upregulated in E12.5 embryos after amputation.Conclusion: This study provides a new mouse limb regeneration model and demonstrates that potassium channels are potential drug targets for limb wound healing and regeneration.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"3 1","pages":"22-33"},"PeriodicalIF":5.3,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/pcmedi/pbz029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37809955","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: 6

Double negative T cells, a potential biomarker for systemic lupus erythematosus. 双阴性T细胞，系统性红斑狼疮的潜在生物标志物。

IF 5.3 4区医学

Precision Clinical Medicine Pub Date : 2020-03-01 Epub Date: 2020-01-20 DOI: 10.1093/pcmedi/pbaa001

Jessy J Alexander, Alexander Jacob, Anthony Chang, Richard J Quigg, James N Jarvis

{"title":"Double negative T cells, a potential biomarker for systemic lupus erythematosus.","authors":"Jessy J Alexander, Alexander Jacob, Anthony Chang, Richard J Quigg, James N Jarvis","doi":"10.1093/pcmedi/pbaa001","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa001","url":null,"abstract":"Systemic lupus erythematosus (SLE) is an autoimmune disease that is a challenge to diagnose and treat. There is an urgent need for biomarkers to help define organ involvement, and more effective therapies. A unique population of T cells, the CD3+CD4-CD8- (DNeg) cells, is significantly increased in lupus patients. Twenty-seven cases (53%) of pediatric SLE patients had elevated DNeg cells in their peripheral blood, which correlated with kidney function (R2 = 0.54). Significant infiltration of DNeg cells was observed in both adult and pediatric lupus kidneys by immunofluorescence. For the first time, this study provides direct evidence that DNeg cells facilitate kidney injury in preclinical 8-week-old MRL/lpr lupus mice. In lupus mice, the increase in DNeg cells tracked with worsening disease and correlated with kidney function (R2 = 0.85). Our results show that DNeg cells per se can cause kidney dysfunction, increase in number with increase in disease pathology, and could serve as a potential biomarker.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"3 1","pages":"34-43"},"PeriodicalIF":5.3,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/pcmedi/pbaa001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37808776","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: 19

Apatinib treatment for unresectable gastrointestinal stromal tumor with synchronous gastric cancer 阿帕替尼治疗不可切除的胃肠道间质瘤合并同步胃癌

IF 5.3 4区医学

Precision Clinical Medicine Pub Date : 2020-02-18 DOI: 10.1093/pcmedi/pbaa005

Huanji Xu, Sheng Zhou, Q. Hu, D. Cao

引用次数: 4

Benign lymph node microenvironment is associated with response to immunotherapy 良性淋巴结微环境与免疫治疗应答相关

IF 5.3 4区医学

Precision Clinical Medicine Pub Date : 2020-02-12 DOI: 10.1093/pcmedi/pbaa003

Maria I Toki, Deepika Kumar, F. Ahmed, D. Rimm, Mina L. Xu

{"title":"Benign lymph node microenvironment is associated with response to immunotherapy","authors":"Maria I Toki, Deepika Kumar, F. Ahmed, D. Rimm, Mina L. Xu","doi":"10.1093/pcmedi/pbaa003","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa003","url":null,"abstract":"Abstract Introduction Benign lymph nodes have been considered the hubs of immune surveillance in cancer patients. The microenvironment of these lymphoid tissues can be immune suppressed, hence allowing for tumor progression. Understanding the spectrum of benign findings in bystander lymph nodes in immune checkpoint blockade therapy could prove to be key to understanding the mechanism and assessing treatment response. Methods Benign lymph nodes and spleen were evaluated from patients treated with immunotherapy who subsequently received postmortem examination. We used quantitative immunofluorescence (QIF) to assess tumor infiltrating lymphocytes (TIL) and macrophage marker expression and characterized activation status using a novel multiplexed QIF assay including CD3, GranzymeB, and Ki67. We performed immunohistochemistry to correlate results of QIF. Results Benign lymph nodes from non-responders to immunotherapy showed significantly higher expression of cytotoxic markers and proliferation index (Ki67) in T cells compared to responders. Higher expression of PD-L1 in macrophages was also observed. There was no significant difference in CD3+ expression, but higher levels of CD8+ T cells as well as CD20+ B cells were seen in lymph nodes of non-responders. No significant differences were seen between responder and non-responder splenic tissue. Findings were supported by traditional immunostaining methods. Conclusions While most studies in biomarkers for immunotherapy focus on tumor microenvironment, we show that benign lymph node microenvironment may predict response to immunotherapy. In responding patients, bystander lymph nodes appear to have been mobilized, resulting in reduced cytotoxic T cells. Conversely, patients whose disease progressed on immunotherapy demonstrate higher levels of macrophages that express increased PD-L1, and activated T cells not recruited to the tumor site.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"119 1","pages":"44 - 53"},"PeriodicalIF":5.3,"publicationDate":"2020-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86124052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

A precision medicine approach to managing 2019 novel coronavirus pneumonia. 2019年新型冠状病毒肺炎的精准医疗方法

IF 5.3 4区医学

Precision Clinical Medicine Pub Date : 2020-02-04 DOI: 10.1093/pcmedi/pbaa002

Minjin Wang, Yanbing Zhou, Zhiyong Zong, Zongan Liang, Yu Cao, Hong Tang, Bin Song, Zixing Huang, Yan Kang, Ping Feng, Binwu Ying, Weimin Li

{"title":"A precision medicine approach to managing 2019 novel coronavirus pneumonia.","authors":"Minjin Wang, Yanbing Zhou, Zhiyong Zong, Zongan Liang, Yu Cao, Hong Tang, Bin Song, Zixing Huang, Yan Kang, Ping Feng, Binwu Ying, Weimin Li","doi":"10.1093/pcmedi/pbaa002","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa002","url":null,"abstract":"In December 2019, several patients with pneumonia of an unknown cause were detected in Wuhan, China. On 7 January 2020, the causal organism was identified as a new coronavirus, later named as the 2019 novel coronavirus (2019-nCoV). Genome sequencing found the genetic sequence of 2019-nCoV homologous to that of severe acute respiratory syndrome-associated coronavirus. As of 29 January 2020, the virus had been diagnosed in more than 7000 patients in China and 77 patients in other countries. It is reported that both symptomatic and asymptomatic patients with 2019-nCoV can play a role in disease transmission via airborne and contact. This finding has caused a great concern about the prevention of illness spread. The clinical features of the infection are not specific and are often indistinguishable from those of other respiratory infections, making it difficult to diagnose. Given that the virus has a strong ability to spread between individuals, it is of top priority to identify potential or suspected patients as soon as possible-or the virus may cause a serious pandemic. Therefore, a precision medicine approach to managing this disease is urgently needed for detecting and controlling the spread of the virus. In this article, we present such an approach to managing 2019-nCoV-related pneumonia based on the unique traits of the virus recently revealed and on our experience with coronaviruses at West China Hospital in Chengdu, China.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"3 1","pages":"14-21"},"PeriodicalIF":5.3,"publicationDate":"2020-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/pcmedi/pbaa002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37868584","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: 50