Precision Clinical Medicine最新文献

{"title":"Recent advances in single-cell sequencing technologies.","authors":"Lu Wen,&nbsp;Fuchou Tang","doi":"10.1093/pcmedi/pbac002","DOIUrl":"https://doi.org/10.1093/pcmedi/pbac002","url":null,"abstract":"<p><p>Single-cell omics sequencing was first achieved for the transcriptome in 2009, which was followed by fast development of technologies for profiling the genome, DNA methylome, 3D genome architecture, chromatin accessibility, histone modifications, etc., in an individual cell. In this review we mainly focus on the recent progress in four topics in the single-cell omics field: single-cell epigenome sequencing, single-cell genome sequencing for lineage tracing, spatially resolved single-cell transcriptomics and third-generation sequencing platform-based single-cell omics sequencing. We also discuss the potential applications and future directions of these single-cell omics sequencing technologies for different biomedical systems, especially for the human stem cell field.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":" ","pages":"pbac002"},"PeriodicalIF":5.3,"publicationDate":"2022-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/46/9e/pbac002.PMC9267251.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40584404","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}

{"title":"Multivariate competing endogenous RNA network characterization for cancer microRNA biomarker discovery: a novel bioinformatics model with application to prostate cancer metastasis.","authors":"Yuxin Lin,&nbsp;Xin Qi,&nbsp;Jing Chen,&nbsp;Bairong Shen","doi":"10.1093/pcmedi/pbac001","DOIUrl":"https://doi.org/10.1093/pcmedi/pbac001","url":null,"abstract":"<p><strong>Background: </strong>MicroRNAs (miRNAs) are post-transcriptional regulators with potential as biomarkers for cancer management. Data-driven competing endogenous RNA (ceRNA) network modeling is an effective way to decipher the complex interplay between miRNAs and spongers. However, there are currently no general rules for ceRNA network-based biomarker prioritization.</p><p><strong>Methods and results: </strong>In this study, a novel bioinformatics model was developed by integrating gene expression with multivariate miRNA-target data for ceRNA network-based biomarker discovery. Compared with traditional methods, the structural vulnerability in the human long non-coding RNA (lncRNA)-miRNA-messenger RNAs (mRNA) network was comprehensively analyzed, and the single-line regulatory or competing mode among miRNAs, lncRNAs, and mRNAs was characterized and quantified as statistical evidence for miRNA biomarker identification. The application of this model to prostate cancer (PCa) metastasis identified a total of 12 miRNAs as putative biomarkers from the metastatic PCa-specific lncRNA-miRNA-mRNA network and nine of them have been previously reported as biomarkers for PCa metastasis. The receiver operating characteristic curve and cell line qRT-PCR experiments demonstrated the power of <i>miR-26b-5p, miR-130a-3p</i>, and <i>miR-363-3p</i> as novel candidates for predicting PCa metastasis. Moreover, PCa-associated pathways such as prostate cancer signaling, <i>ERK/MAPK</i> signaling, and <i>TGF-β</i> signaling were significantly enriched by targets of identified miRNAs, indicating the underlying mechanisms of miRNAs in PCa carcinogenesis.</p><p><strong>Conclusions: </strong>A novel ceRNA-based bioinformatics model was proposed and applied to screen candidate miRNA biomarkers for PCa metastasis. Functional validations using human samples and clinical data will be performed for future translational studies on the identified miRNAs.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":" ","pages":"pbac001"},"PeriodicalIF":5.3,"publicationDate":"2022-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9267254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40587482","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}

{"title":"Management of severe asthma: from stepwise approach to therapy to treatable traits?","authors":"Gang Wang, V. McDonald, P. Gibson","doi":"10.1093/pcmedi/pbab028","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab028","url":null,"abstract":"","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"30 1","pages":"293-296"},"PeriodicalIF":5.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89285774","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}

{"title":"Immunotherapy in non-small cell lung cancer: rationale, recent advances and future perspectives.","authors":"Wenxin Luo,&nbsp;Zhoufeng Wang,&nbsp;Ting Zhang,&nbsp;Lan Yang,&nbsp;Jinghong Xian,&nbsp;Yalun Li,&nbsp;Weimin Li","doi":"10.1093/pcmedi/pbab027","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab027","url":null,"abstract":"<p><p>Lung cancer, with non-small cell lung cancer (NSCLC) being the major type, is the second most common malignancy and the leading cause of cancer-related death globally. Immunotherapy, represented by immune checkpoint inhibitors (ICIs), has been one of the greatest advances in recent years for the treatment of solid tumors including NSCLC. However, not all NSCLC patients experience an effective response to immunotherapy with the established selection criteria of programmed death ligand 1 (PD-L1) and tumor mutational burden (TMB). Furthermore, a considerable proportion of patients experience unconventional responses, including pseudoprogression or hyperprogressive disease (HPD), immune-related toxicities, and primary or acquired resistance during the immunotherapy process. To better understand the immune response in NSCLC and provide reference for clinical decision-making, we herein review the rationale and recent advances in using immunotherapy to treat NSCLC. Moreover, we discuss the current challenges and future strategies of this approach to improve its efficacy and safety in treating NSCLC.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"4 4","pages":"258-270"},"PeriodicalIF":5.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8982543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10268801","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}

{"title":"AI in spotting high-risk characteristics of medical imaging and molecular pathology","authors":"Chong Zhang, Jionghui Gu, Yangyang Zhu, Zheling Meng, Tong Tong, Dongyang Li, Zhenyu Liu, Yang Du, Kun Wang, Jie Tian","doi":"10.1093/pcmedi/pbab026","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab026","url":null,"abstract":"Abstract Medical imaging provides a comprehensive perspective and rich information for disease diagnosis. Combined with artificial intelligence technology, medical imaging can be further mined for detailed pathological information. Many studies have shown that the macroscopic imaging characteristics of tumors are closely related to microscopic gene, protein and molecular changes. In order to explore the function of artificial intelligence algorithms in in-depth analysis of medical imaging information, this paper reviews the articles published in recent years from three perspectives: medical imaging analysis method, clinical applications and the development of medical imaging in the direction of pathological molecular prediction. We believe that AI-aided medical imaging analysis will be extensively contributing to precise and efficient clinical decision.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"28 1","pages":"271 - 286"},"PeriodicalIF":5.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83416902","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}

{"title":"Dichotomous roles of neutrophils in modulating pathogenic and repair processes of inflammatory bowel diseases","authors":"Huimin Chen, Xiaohan Wu, Chunjin Xu, Jian Lin, Zhanju Liu","doi":"10.1093/pcmedi/pbab025","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab025","url":null,"abstract":"Abstract Neutrophils are considered as complex innate immune cells and play a critical role in maintaining intestinal mucosal homeostasis. They exert robust pro-inflammatory effects and recruit other immune cells in the acute phase of pathogen infection and intestinal inflammation, but paradoxically, they also limit exogenous microbial invasion and facilitate mucosal restoration. Hyperactivation or dysfunction of neutrophils results in abnormal immune responses, leading to multiple autoimmune and inflammatory diseases including systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel diseases (IBD). As a refractory intestinal inflammatory disease, the pathogenesis and progression of IBD are associated with complicated immune response processes in which neutrophils are profoundly involved. However, the consensus on potential roles of neutrophils in modulating pathogenic and repair processes of IBD remains not fully understood. Accumulated infiltrating neutrophils cross the epithelial barrier and contribute to microbial dysbiosis, aggravated intestinal architectural damage, compromised resolution of intestinal inflammation and increased risk of thrombosis during IBD. Paradoxically, activated neutrophils are also associated with effective elimination of invaded microbiota, promoted angiogenesis and tissue restoration of gut mucosa in IBD. Here, we discuss the beneficial and detrimental roles of neutrophils in the onset and resolution of intestinal mucosal inflammation, hoping to provide a precise overview of neutrophil functions in the pathogenesis of IBD.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"29 1","pages":"246 - 257"},"PeriodicalIF":5.3,"publicationDate":"2021-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81886816","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}

{"title":"Inhibitory activity of medicinal mushroom Ganoderma lucidum on colorectal cancer by attenuating inflammation","authors":"Mandy M Liu, Tiantian Liu, S. Yeung, Zhijun Wang, B. Andresen, C. Parsa, R. Orlando, Bingsen Zhou, Wei Wu, Xia Li, Yilong Zhang, Charles Wang, Ying Huang","doi":"10.1093/pcmedi/pbab023","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab023","url":null,"abstract":"Abstract The medicinal mushroom Ganoderma lucidum (GL, Reishi or Lingzhi) exhibits an inhibitory effect on cancers. However, the underlying mechanism of the antitumor activity of GL is not fully understood. In this study, we characterized the gene networks regulated by a commercial product of GL containing a mixture of spores and fruiting bodies namely “GLSF”, in colorectal carcinoma. We found that in vitro co-administration of GLSF extract at non-toxic concentrations significantly potentiated growth inhibition and apoptosis induced by paclitaxel in CT26 and HCT-15 cells. GLSF inhibited NF-κB promoter activity in HEK-293 cells but did not affect the function of P-glycoprotein in K562/DOX cells. Furthermore, we found that when mice were fed a modified diet containing GLSF for 1 month prior to the CT26 tumor cell inoculation, GLSF alone or combined with Nab-paclitaxel markedly suppressed tumor growth and induced apoptosis. RNA-seq analysis of tumor tissues derived from GLSF-treated mice identified 53 differentially expressed genes compared to normal tissues. Many of the GLSF-down-regulated genes were involved in NF-κB-regulated inflammation pathways, such as IL-1β, IL-11 and Cox-2. Pathway enrichment analysis suggested that several inflammatory pathways involving leukocyte migration and adhesion were most affected by the treatment. Upstream analysis predicted activation of multiple tumor suppressors such as α-catenin and TP53 and inhibition of critical inflammatory mediators. “Cancer” was the major significantly inhibited biological effect of GLSF treatment. These results demonstrate that GLSF can improve the therapeutic outcome for colorectal cancer through a mechanism involving suppression of NF-κB-regulated inflammation and carcinogenesis.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"139 1","pages":"231 - 245"},"PeriodicalIF":5.3,"publicationDate":"2021-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73265350","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}

{"title":"CRISPR/Cas9 mediated somatic gene therapy for insertional mutations: the vibrator mouse model","authors":"Xin Fu, Jie Zhu, Yaou Duan, P. Lu, Kang Zhang","doi":"10.1093/pcmedi/pbab021","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab021","url":null,"abstract":"Abstract Somatic gene therapy remains technically challenging, especially in the central nervous system (CNS). Efficiency of gene delivery, efficacy in recipient cells, and proportion of cells required for overall benefit are the key points needed to be considered in any therapeutic approach. Recent efforts have demonstrated the efficacy of RNA-guided nucleases such as CRISPR/Cas9 in correcting point mutations or removing dominant mutations. Here we used viral delivered Cas9 plasmid and two guide RNAs to remove a recessive insertional mutation, vibrator (vb), in the mouse brain. The vb mice expressed ∼20% of normal levels of phosphatidylinositol transfer protein, α (PITPα) RNA and protein due to an endogenous retrovirus inserted in intron 4, resulting in early-onset tremor, degeneration of brainstem and spinal cord neurons, and juvenile death. The in situ CRISPR/Cas9 viral treatment effectively delayed neurodegeneration, attenuated tremor, and bypassed juvenile death. Our studies demonstrate the potential of CRISPR/Cas9-mediated gene therapy for insertional mutations in the postnatal brain.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"34 1","pages":"168 - 175"},"PeriodicalIF":5.3,"publicationDate":"2021-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89723565","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}

{"title":"Improving T cell therapy: in vivo CRISPR-Cas9 screens tell us how to do","authors":"Tao Yin","doi":"10.1093/pcmedi/pbab015","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab015","url":null,"abstract":"Editor’s note A commentary on “In vivo CD8+ T cell CRISPR screening reveals control by Fli1 in infection and cancer”.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"89 1","pages":"176 - 178"},"PeriodicalIF":5.3,"publicationDate":"2021-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75198038","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}

{"title":"Applications and challenges of CRISPR-Cas gene-editing to disease treatment in clinics.","authors":"Wenyi Liu, Luoxi Li, Jianxin Jiang, Min Wu, Ping Lin","doi":"10.1093/pcmedi/pbab014","DOIUrl":"10.1093/pcmedi/pbab014","url":null,"abstract":"<p><p>Clustered regularly interspaced short palindromic repeats (CRISPR)-associated systems (Cas) are efficient tools for targeting specific genes for laboratory research, agricultural engineering, biotechnology, and human disease treatment. Cas9, by far the most extensively used gene-editing nuclease, has shown great promise for the treatment of hereditary diseases, viral infection, cancers, and so on. Recent reports have revealed that some other types of CRISPR-Cas systems may also have surprising potential to join the fray as gene-editing tools for various applications. Despite the rapid progress in basic research and clinical tests, some underlying problems present continuous, significant challenges, such as editing efficiency, relative difficulty in delivery, off-target effects, immunogenicity, etc. This article summarizes the applications of CRISPR-Cas from bench to bedside and highlights the current obstacles that may limit the usage of CRISPR-Cas systems as gene-editing toolkits in precision medicine and offer some viewpoints that may help to tackle these challenges and facilitate technical development. CRISPR-Cas systems, as a powerful gene-editing approach, will offer great hopes in clinical treatments for many individuals with currently incurable diseases.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"4 3","pages":"179-191"},"PeriodicalIF":5.1,"publicationDate":"2021-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39431646","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}