Precision Clinical Medicine最新文献

{"title":"Checkpoint immunotherapy for NK/T cell lymphoma—Time for a showdown?","authors":"J. Chan, J. Lim, C. Ong","doi":"10.1093/pcmedi/pbab004","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab004","url":null,"abstract":"Editor's note A commentary on “Combination of anti-PD-1 antibody with P-GEMOX as a potentially effective immunochemotherapy for advanced natural killer/T cell lymphoma”.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"33 1","pages":"70 - 72"},"PeriodicalIF":5.3,"publicationDate":"2021-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88326614","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":"Neuroendocrine cells of the prostate: Histology, biological functions, and molecular mechanisms.","authors":"William Butler,&nbsp;Jiaoti Huang","doi":"10.1093/pcmedi/pbab003","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab003","url":null,"abstract":"<p><p>Prostate cancer (PCa) is a common cause of cancer-related mortality in men worldwide. Although most men are diagnosed with low grade, indolent tumors that are potentially curable, a significant subset develops advanced disease where hormone therapy is required to target the androgen receptor (AR). Despite its initial effect, hormone therapy eventually fails and the tumor progresses to lethal stages even through continued inhibition of AR. This review article focuses on the role of PCa cellular heterogeneity in therapy resistance and disease progression. Although AR-positive luminal-type cells represent the vast majority of PCa cells, there exists a minor component of AR-negative neuroendocrine (NE) cells that are resistant to hormonal therapy and are enriched by the treatment. In addition, it is now well accepted that a significant subset of hormonally treated tumors recur as small cell neuroendocrine carcinoma (SCNC), further highlighting the importance of targeting NE cells in addition to the more abundant luminal-type cancer cells. Although it has been long recognized that NE cells are present in PCa, their underlying function in benign prostate and molecular mechanisms contributing to PCa progression remains poorly understood. In this article, we review the morphology and function of NE cells in benign prostate and PCa as well as underlying molecular mechanisms. In addition, we review the major reported mechanisms for transformation from common adenocarcinoma histology to the highly lethal SCNC, a significant clinical challenge in the management of advanced PCa.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"4 1","pages":"25-34"},"PeriodicalIF":5.3,"publicationDate":"2021-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/pcmedi/pbab003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25580368","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":"Computational molecular docking and virtual screening revealed promising SARS-CoV-2 drugs.","authors":"Maryam Hosseini,&nbsp;Wanqiu Chen,&nbsp;Daliao Xiao,&nbsp;Charles Wang","doi":"10.1093/pcmedi/pbab001","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab001","url":null,"abstract":"<p><p>The pandemic of novel coronavirus disease 2019 (COVID-19) has rampaged the world, with more than 58.4 million confirmed cases and over 1.38 million deaths across the world by 23 November 2020. There is an urgent need to identify effective drugs and vaccines to fight against the virus. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the family of coronaviruses consisting of four structural and 16 non-structural proteins (NSP). Three non-structural proteins, main protease (Mpro), papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRp), are believed to have a crucial role in replication of the virus. We applied computational ligand-receptor binding modeling and performed comprehensive virtual screening on FDA-approved drugs against these three SARS-CoV-2 proteins using AutoDock Vina, Glide, and rDock. Our computational studies identified six novel ligands as potential inhibitors against SARS-CoV-2, including antiemetics rolapitant and ondansetron for Mpro; labetalol and levomefolic acid for PLpro; and leucal and antifungal natamycin for RdRp. Molecular dynamics simulation confirmed the stability of the ligand-protein complexes. The results of our analysis with some other suggested drugs indicated that chloroquine and hydroxychloroquine had high binding energy (low inhibitory effect) with all three proteins-Mpro, PLpro, and RdRp. In summary, our computational molecular docking approach and virtual screening identified some promising candidate SARS-CoV-2 inhibitors that may be considered for further clinical studies.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"4 1","pages":"1-16"},"PeriodicalIF":5.3,"publicationDate":"2021-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/pcmedi/pbab001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25580367","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":"Strategies for advanced personalized tuberculosis diagnosis: Current technologies and clinical approaches.","authors":"Xuerong Chen,&nbsp;Tony Y Hu","doi":"10.1093/pcmedi/pbaa041","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa041","url":null,"abstract":"<p><p>Diagnosis of tuberculosis can be difficult as advances in molecular diagnosis approaches (especially nanoparticles combined with high-throughput mass spectrometry for detecting mycobacteria peptide) and personalized medicine result in many changes to the diagnostic framework. This review will address issues concerning novel technologies from bench to bed and new strategies for personalized tuberculosis diagnosis.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"4 1","pages":"35-44"},"PeriodicalIF":5.3,"publicationDate":"2021-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/pcmedi/pbaa041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25580369","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":"RhoA and Cdc42 in T cells: Are they targetable for T cell-mediated inflammatory diseases?","authors":"Fukun Guo","doi":"10.1093/pcmedi/pbaa039","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa039","url":null,"abstract":"<p><p>Many inflammatory diseases are not curable, necessitating a better understanding of their pathobiology that may help identify novel biological targets. RhoA and Cdc42 of Rho family small GTPases regulate a variety of cellular functions such as actin cytoskeletal organization, cell adhesion, migration, proliferation, and survival. Recent characterization of mouse models of conditional gene knockout of RhoA and Cdc42 has revealed their physiological and cell type-specific roles in a number of cell types. In T lymphocytes, which play an important role in the pathogenesis of most, if not all, of the inflammatory diseases, we and others have investigated the effects of T cell-specific knockout of RhoA and Cdc42 on T cell development in the thymus, peripheral T cell homeostasis, activation, and differentiation to effector and regulatory T cells, and on T cell-mediated allergic airway inflammation and colitis. Here we highlight the phenotypes resulting from RhoA and Cdc42 deletion in T cells and discuss whether pharmacological targeting of RhoA and Cdc42 is feasible in treating asthma that is driven by allergic airway inflammation and colitis.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"4 1","pages":"56-61"},"PeriodicalIF":5.3,"publicationDate":"2021-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/pcmedi/pbaa039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25580336","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":"Clinical longitudinal evaluation of COVID-19 patients and prediction of organ-specific recovery using artificial intelligence","authors":"Winston Wang, Charlotte L Zhang, K. Wei, Ye Sang, Jun Shen, Guangyu Wang, Alexander X. Lozano","doi":"10.1093/pcmedi/pbaa040","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa040","url":null,"abstract":"Abstract Within COVID-19 there is an urgent unmet need to predict at the time of hospital admission which COVID-19 patients will recover from the disease, and how fast they recover to deliver personalized treatments and to properly allocate hospital resources so that healthcare systems do not become overwhelmed. To this end, we have combined clinically salient CT imaging data synergistically with laboratory testing data in an integrative machine learning model to predict organ-specific recovery of patients from COVID-19. We trained and validated our model in 285 patients on each separate major organ system impacted by COVID-19 including the renal, pulmonary, immune, cardiac, and hepatic systems. To greatly enhance the speed and utility of our model, we applied an artificial intelligence method to segment and classify regions on CT imaging, from which interpretable data could be directly fed into the predictive machine learning model for overall recovery. Across all organ systems we achieved validation set area under the receiver operator characteristic curve (AUC) values for organ-specific recovery ranging from 0.80 to 0.89, and significant overall recovery prediction in Kaplan-Meier analyses. This demonstrates that the synergistic use of an artificial intelligence (AI) framework applied to CT lung imaging and a machine learning model that integrates laboratory test data with imaging data can accurately predict the overall recovery of COVID-19 patients from baseline characteristics.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"3 1","pages":"62 - 69"},"PeriodicalIF":5.3,"publicationDate":"2020-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81067654","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":"Making radiation therapy more effective in the era of precision medicine","authors":"Xingchen Peng, Zhi-Gong Wei, L. Gerweck","doi":"10.1093/pcmedi/pbaa038","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa038","url":null,"abstract":"Abstract Cancer has become a leading cause of death and constitutes an enormous burden worldwide. Radiation is a principle treatment modality used alone or in combination with other forms of therapy, with 50%–70% of cancer patients receiving radiotherapy at some point during their illness. It has been suggested that traditional radiotherapy (daily fractions of approximately 1.8–2 Gy over several weeks) might select for radioresistant tumor cell sub-populations, which, if not sterilized, give rise to local treatment failure and distant metastases. Thus, the challenge is to develop treatment strategies and schedules to eradicate the resistant subpopulation of tumorigenic cells rather than the predominant sensitive tumor cell population. With continued technological advances including enhanced conformal treatment technology, radiation oncologists can increasingly maximize the dose to tumors while sparing adjacent normal tissues, to limit toxicity and damage to the latter. Increased dose conformality also facilitates changes in treatment schedules, such as changes in dose per treatment fraction and number of treatment fractions, to enhance the therapeutic ratio. For example, the recently developed large dose per fraction treatment schedules (hypofractionation) have shown clinical advantage over conventional treatment schedules in some tumor types. Experimental studies suggest that following large acute doses of radiation, recurrent tumors, presumably sustained by the most resistant tumor cell populations, may in fact be equally or more radiation sensitive than the primary tumor. In this review, we summarize the related advances in radiotherapy, including the increasing understanding of the molecular mechanisms of radioresistance, and the targeting of these mechanisms with potent small molecule inhibitors, which may selectively sensitize tumor cells to radiation.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"1 1","pages":"272 - 283"},"PeriodicalIF":5.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77303209","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":"Long-term spaceflight and the cardiovascular system.","authors":"Nicholas A Vernice,&nbsp;Cem Meydan,&nbsp;Ebrahim Afshinnekoo,&nbsp;Christopher E Mason","doi":"10.1093/pcmedi/pbaa022","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa022","url":null,"abstract":"<p><p>While early investigations into the physiological effects of spaceflight suggest the body's ability to reversibly adapt, the corresponding effects of long-term spaceflight (>6 months) are much less conclusive. Prolonged exposure to microgravity and radiation yields profound effects on the cardiovascular system, including a massive cephalad fluid translocation and altered arterial pressure, which attenuate blood pressure regulatory mechanisms and increase cardiac output. Also, central venous pressure decreases as a result of the loss of venous compression. The stimulation of baroreceptors by the cephalad shift results in an approximately 10%-15% reduction in plasma volume, with fluid translocating from the vascular lumen to the interstitium. Despite possible increases in cardiac workload, myocyte atrophy and notable, yet unexplained, alterations in hematocrit have been observed. Atrophy is postulated to result from shunting of protein synthesis from the endoplasmic reticulum to the mitochondria via mortalin-mediated action. While data are scarce regarding their causative agents, arrhythmias have been frequently reported, albeit sublethal, during both Russian and American expeditions, with QT interval prolongation observed in long, but not short duration, spaceflight. Exposure of the heart to the proton and heavy ion radiation of deep space has also been shown to result in coronary artery degeneration, aortic stiffness, carotid intima thickening via collagen-mediated action, accelerated atherosclerosis, and induction of a pro-inflammatory state. Upon return, long-term spaceflight frequently results in orthostatic intolerance and altered sympathetic responses, which can prove hazardous should any rapid mobilization or evacuation be required, and indicates that these cardiac risks should be especially monitored for future missions.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"3 4","pages":"284-291"},"PeriodicalIF":5.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/pcmedi/pbaa022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38775507","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":"Vegetarian diets, circulating miRNA expression and healthspan in subjects living in the Blue Zone.","authors":"Tiantian Liu,&nbsp;Nicole M Gatto,&nbsp;Zhong Chen,&nbsp;Hongyu Qiu,&nbsp;Grace Lee,&nbsp;Penelope Duerksen-Hughes,&nbsp;Gary Fraser,&nbsp;Charles Wang","doi":"10.1093/pcmedi/pbaa037","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa037","url":null,"abstract":"<p><p>A long-term vegetarian diet plays a role in the longevity and maintenance of the healthspan, but the underlying mechanisms for these observations are largely unknown. Particularly, it is not known whether a long-term vegetarian dietary pattern may affect the circulating miRNA expression in such a way as to modulate the healthspan. The Adventist Health Study-2 (AHS-2) cohort includes a large number of older adults who primarily follow vegetarian dietary patterns and reside in Loma Linda, California, one of five \"Blue Zones\" in the world in which a higher proportion of the population enjoys a longer than average lifespan. We performed miRNA-seq in 96 subjects selected from the AHS-2 cohort with different dietary patterns. We identified several differentially expressed miRNAs between vegetarians and non-vegetarians, which are involved in immune response and cytokine signaling, cell growth and proliferation as well as age-related diseases such as cardiovascular diseases and neurodegenerative diseases. Overall, our study showed that a vegetarian diet modulates aging-associated circulating miRNAs in a sex-dependent manner of differential expression for certain miRNAs, which may be related in a beneficial manner to the healthspan. Further investigation is needed to validate these miRNAs as potential biomarkers for diet-modulated longevity in humans.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"3 4","pages":"245-259"},"PeriodicalIF":5.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/pcmedi/pbaa037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38775506","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":"Bilateral simultaneous primary acute angle-closure glaucoma","authors":"Charlotte L. Zhang, Wico Lai, Ian Ziyar, L. Lau, Jie Xu","doi":"10.1093/pcmedi/pbaa035","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa035","url":null,"abstract":"Dear Editor, Acute primary angle-closure glaucoma (PACG) is an important cause of blindness in East Asia.1 It is estimated that the overall prevalence of PACG will increase from 1.44% to 2.01% from 2020 to 2050.2 Acute PACG is typically related to increased high intraocular pressure (IOP), with symptoms including red eye, blurred vision, nausea, vomiting, and headache. Delay in timely IOPlowering treatment can result in permanent optic nerve damage and vision loss.3 Axial hyperopia is the main ocular risk factor for development of primary closure of the anterior chamber angle, while its systemic risk factors include older age, east Asian ethnic origin, and female sex.4 Although generally deemed to be a bilateral condition, PACG often occurs unilaterally, and bilateral simultaneous onset is very rare. For patients with unilateral onset, even if the effect of treatment is not satisfactory, relatively good outcomes can be achieved by carrying out early intervention on the fellow eye. However, for bilateral cases, the condition is usually severe and often comes with a poor prognosis. Therefore, appropriate preventive measures are critical. Here, we present a case of bilateral simultaneous acute PACG related to hyperopia. A 58-year-old Chinese woman presented with intermittent headaches, nausea, vomiting, and acute pain in both eyes for 1 month, which had worsened recently. The patient reported no history of taking anticholinergic and sympathomimetic drugs, nor was any other cause identified. The vital signs included a body temperature of 37.4◦C, blood pressure 150/96 mmHg, and a pulse 90 beats/min. Visual acuities were CF in 50 cm in both eyes and IOP was 51 and 53 mmHg in the right and left eye, respectively. Slit lamp examination revealed conjunctiva hyperemia, corneal edema, mid-dilated pupils, and shallow anterior chambers peripherally and centrally (Fig. 1). Fundus examination had a hazy view. B-scan ultrasonography demonstrated that retinas were attached in both eyes. Initial treatments included systemic acetazolamide 250 mg twice a day, pilocarpine 2% four times a day, brinzolamide 1.0% twice-a-day, and fixed-combination eye drops containing timolol maleate 0.5% and brimonidine tartrate 0.2% twice-a-day. A few hours later, the IOPs reduced to 28 OD and 32 OS mmHg respectively. The patient underwent a laser peripheral iridotomy and was sent home with prednisolone acetate eye drops to be applied four times a day, acetazolamide 500 mg every","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"2 1","pages":"297 - 300"},"PeriodicalIF":5.3,"publicationDate":"2020-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78610984","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}