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multitarget stool DNA tests increases colorectal cancer screening among previously noncompliant Medicare patients

World Journal of Gastroenterology 2017年第3期23卷 464-471页

作者： Mark Prince Lynn Lester Rupal Chiniwala Barry Berger USMD Health System ArlingtonTX 76017United States USMD Health System Fort WorthTX 76104United States USMD Health System Irving TexasTX 75039United States Exact Sciences Corporation MadisonWI 53729United States

AIM To determine the uptake of noninvasive multitarget stool DNA (mt-s DNA) in a cohort of colorectal cancer(CRC) screening non-compliant average-risk Medicare patients.METHODS This cross sectional primary care office-based study examined mt-s DNA uptake in routine clinical practice among 393 colorectal cancer screening non-compliant Medicare patients ages 50-85 ordered by 77 physicians in a multispecialty group practice (USMD Physician Services, Dallas, TX) from October, 2014-September, 2015. Investigators performed a Health Insurance Portability and Accountability Act compliant retrospective review of electronic health records to identify mt-s DNA use in patients who were either > 10 years since last colonoscopy and/or > 1 year since last fecal occult blood test. Test positive patients were advised to get diagnostic colonoscopy and thereafter patients were characterized by the most clinically significant lesion documented on histopathology of biopsies or excisional tissue. Descriptive statistics were employed. Key outcome measures included mt-s DNA compliance and diagnostic colonoscopy compliance on positive cases.RESULTS Over 12 mo, 77 providers ordered 393 mt-sD NA studies with 347 completed (88.3% compliance). Patient mean age was 69.8 (50-85) and patients were 64% female. Mt-sD NA was negative in 85.3%(296/347) and positive in 14.7%(51/347). Follow-up colonoscopy was performed in 49 positive patients (96.1% colonoscopy compliance) with two patients lost to follow up. Index findings included: colon cancer(4/49, 8.2%), advanced adenomas (21/49, 42.9%), non-advanced adenomas(15/49, 30.6%), and negative results (9/49, 18.4%). The positive predictive value for advanced colorectal lesions was 51.0% and for any colorectal neoplasia was 81.6%. The mean age of patients with colorectal cancer was 70.3 and all CRC's were localized Stage Ⅰ(2) and Stage Ⅱ (2), three were located in the proximal colon and one was located in the distal colon.CONCLUSION Mt-s DNA provided medical benefit to screening noncompliant Medicare p

关键词： multitarget stool DNA Advanced adenoma Screening compliance Colonoscopy Colorectal cancer screening Preventive

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Short-Range multitarget Motion Parameter Estimation Method Based on Hough Transform

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Chinese Journal of Electronics 2019年第2期28卷 344-348页

作者： LYU Peng WEI Guohua CUI Wei School of Information and Electronics Beijing Institute of Technology Institute of Electronics Chinese Academy of Sciences

This study proposes a novel short-range multitarget motion parameter estimation method based on Hough transform. The proposed method can be used for multitarget detection, motion parameter estimation, and data association. In our proposed method, the measured radial distance and Doppler frequency versus time data is mapped to the motion parameter space by Hough transform. The motion parameter space data is binarized to determine the number of targets. The unsupervised nearest neighbor clustering technique is used to determine the search space of targets. The maximum value in each search space is estimated as the motion parameter of the corresponding target. Simulation results show that the proposed method has higher parameter estimation accuracy than that of conventional methods.

关键词： Clustering Hough transform multitarget Parameter estimation Short-range

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multitarget stool DNA for colorectal cancer screening:A review and commentary on the United States Preventive Services Draft Guidelines

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World Journal of Gastrointestinal Oncology 2016年第5期8卷 450-458页

作者： Barry M Berger Bernard Levin Robert J Hilsden Medical Affairs Exact Sciences Corporation Scientific Advisory Board Exact Sciences Departments of Medicine and Community Health Sciences University of Calgary

multitarget stool DNA(mt-sDNA) testing was approved for average risk colorectal cancer(CRC) screening by the United States Food and Drug Administration and thereafter reimbursed for use by the Medicare program(2014).The United States Preventive Services Task Force(USPSTF) October 2015 draft recommendation for CRC screening included mt-s DNA as an "alternative" screening test that "may be useful in select clinical circumstances",despite its very high sensitivity for early stage CRC.The evidence supporting mt-s DNA for routine screening use is robust.The clinical efficacy of mt-s DNA as measured by sensitivity,specificity,life-years gained(LYG),and CRC deaths averted is similar to or exceeds that of the other more specifically recommended screening options included in the draft document,especially those requiring annual testing adherence.In a population with primarily irregular screening participation,tests with the highest point sensitivity and reasonable specificity are more likely to favorably impact CRC related morbidity and mortality than those depending on annual adherence.This paper reviews the evidence supporting mt-s DNA for routine screening and demonstrates,using USPSTF's modeling data,that mt-s DNA at three-year intervals provides significant clinical net benefits and fewer complications per LYG than annual fecal immunochemical testing,high sensitivity guaiac based fecal occult blood testing and 10-year colonoscopy screening.

关键词： Colorectal cancer screening multitarget stool DNA Stool DNA The United States Preventive Services Task Force Cancer Intervention Surveillance Modeling Network Fecal immunological technique Modeling Interval

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A Decorrelation Constant Modulus Algorithm for multitarget Separation Using Adaptive Arrays

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Wuhan University Journal of Natural Sciences 2007年第6期12卷 1063-1065页

作者： XU Jin ZHU Guoqiang YUAN Fei School of Electronic Information Wuhan University Wuhan 430072 Hubei China

In this paper, an adaptive digital filter algorithm is presented to optimize the signal-to-noise ratio of an antenna array with multiuser signal inputs. These synchronous communication signals have constant envelope property and are transmitted through a Multiple-Input/Multiple-Output （MIMO） linear channel. This Multiuser Constant Modulus Algorithm （MU-CMA） using an antenna array can compensate for both Interuser Interference （IUI） and Intersymbol Interference （ISI）. The method is derived by minimizing the cost function of the constant modulus signals as well as cross-correlations between them. The simulation result in this paper shows the performance of this algorithm.

关键词： constant modulus multitarget adaptive array

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Recent Advances of Traditional Chinese Medicine in the Regulation of Myocardial Mitochondrial Function

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World Journal of Traditional Chinese Medicine 2022年第1期8卷 50-58页

作者： Shi-Yao Wan Jin-Gui Hu Yu Zhang Bo-Yang Yu Jun-Ping Kou Fang Li Research Center for Traceability and Standardization of TCMs Jiangsu Key Laboratory of TCM Evaluation and Translation ResearchSchool of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjingChina

Cardiovascular disease is a crucial disease threatening human health, and its mortality rate ranks first among Chinese residents. Myocardial mitochondrial dysfunction is the main cause of various heart diseases such as myocardial infarction, myocarditis, hypertrophic cardiomyopathy, and heart failure. In recent years, many studies have confirmed that traditional Chinese medicine(TCM) can be used to improve myocardial mitochondrial function and treat heart disease. The purpose of this review was to analyze the regulatory mechanism of myocardial mitochondrial function by summarizing the effect of TCM on cardiovascular disease.

关键词： Cardiovascular disease mitochondrial function multipathway multitarget traditional Chinese medicine

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No synergism between bis(propyl)-cognitin and rasagiline on protecting dopaminergic neurons in Parkinson's disease mice

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Neural Regeneration Research 2016年第8期11卷 1339-1346页

作者： Cheng-you Zheng Bao-jian Guo Wei Cai Wei Cui Shing-hung Mak Yu-qiang Wang Simon Ming-yuen Lee Yi-fan Han Zai-jun Zhang Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardiocerebrovascular Diseases Jinan University College of Pharmacy School of Medicine Ningbo University Department of Applied Biology and Chemical Technology Institute of Modern Chinese MedicineThe Hong Kong Polytechnic University State Key Laboratory of Quality Research of Chinese Medicine and Institute of Chinese Medical Sciences University of Macao

Rasagiline,a monoamine oxidase-B inhibitor,and bis（propyl）-cognitin（B3C）,a novel dimer are reported to be neuroprotective.Herein,the synergistical neuroprotection produced by rasagiline and B3 C was investigated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP）-induced mice of Parkinsonism.By using neurobehavioural tests,high-performance liquid chromatography and western blot assay,we showed that B3 C at 0.3 mg/kg,rasagiline at 0.02 mg/kg,as well as co-treatment with B3 C and rasagiline prevented MPTP-induced behavioural abnormities,increased the concentrations of dopamine and its metabolites in the striatum,and up-regulated the expression of tyrosine hydroxylase in the substantia nigra.However,the neuroprotective effects of co-treatment were not significantly improved when compared with those of B3 C or rasagiline alone.Collectively,we have demonstrated that B3 C at 0.3 mg/kg and rasagline at 0.02 mg/kg could not produce synergistic neuroprotective effects.

关键词： nerve regeneration Parkinson＇s disease bis（propyl）-cognitin rasagiline monoamine oxidase B dopamine multitarget synergism neuroprotection neural regeneration

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Progress of Research in Antitumor Mechanisms with Chinese Medicine

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Chinese Journal of Integrative Medicine 2009年第4期15卷 316-320页

作者：韩淑燕李萍萍 Peking University School of Oncology Beijing Cancer Hospital & Institute

The anti-tumor effects of Chinese herbal medicines and their prescription preparations attracted more and more attention at home and abroad.Thus,it is becoming a hot research topic to exploit the anti-tumor mechanisms of Chinese medicine,and some of them have been partly clarified with the improved research ability to date.In brief,the Chinese herbal medicines possess unique advantages on the treatment of tumors through their multiple actions on multiple targets.

关键词： tumor Chinese medicine mechanism of action multitarget

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Design, synthesis and antitumor evaluations of nucleoside base hydroxamic acid derivatives as DNMT and HDAC dual inhibitors

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Chinese Chemical Letters 2021年第8期32卷 2479-2483页

作者： Qinsheng Sun Qiuzi Dai Cunlong Zhang Yan Chen Lei Zhao Zigao Yuan Yuyang Jiang School of Life Science Tsinghua UniversityBeijing 100084China National&Local United Engineering Lab for Personalized Anti-tumor Drugs The State Key Laboratory of Chemical OncogenomicsKey Laboratory of Chemical BiologyTsinghua Shenzhen International Graduate SchoolTsinghua UniversityShenzhen 518055China Institute of Biomedical Health Technology and Engineering Shenzhen Bay LaboratoryShenzhen 518055China National&Local United Engineering Lab for Personalized Anti-tumor Drugs Shenzhen Kivita Innovative Drug Discovery InstituteShenzhen 518110China School of Pharmaceutical Sciences Tsinghua UniversityBeijing 100084China

DNA methyl transferase(DNMT) and histone deacetylase(HDAC) are well recognized epigenetic targets for discovery of antitumor agents.In this study,we designed and synthesized a series of nucleoside base hydroxamic acid derivatives as DNMT and HDAC dual inhibitors.MTT assays and enzymatic inhibitory activity tests indicated that compound 204 exhibited potent DNMT1 and HDAC1/6 inhibitory potency simultaneously in enzymatic levels and at cellular levels,inducing hypomethylation of p16 and hyperacetylation of histones H_(3) K9 and H4 K8.Besides,204 remarkably inhibited proliferation against cancer cells U937 by prompting G0/G1 cell cycle arrest.Molecular docking models explained the functional mechanism of 204 inhibiting DNMT1 and HDAC.Preliminary studies on metabolic profiles revealed that 204 showed desirable stability in liver microsomes.Our study suggested that 204 inhibiting DNMT and HDAC concurrently can be a potential lead compound for epigenetic cancer therapy.

关键词： Epigenetic DNMT HDAC multitarget Antitumor bioactivity

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Design,synthesis and biological evaluation of novel phthalazinone acridine derivatives as dual PARP and Topo inhibitors for potential anticancer agents

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Chinese Chemical Letters 2020年第2期31卷 404-408页

作者： Qiuzi Dai Jiwei Chen Chunmei Gao Qinsheng Sun Zigao Yuan Yuyang Jiang Department of Chemistry Tsinghua UniversityBeijing 100084China The State Key Laboratory of Chemical Oncogenomics Key Laboratory of Chemical BiologyThe Graduate School at ShenzhenTsinghua UniversityShenzhen 518055China College of Chemistry and Chemical Engineering Shenzhen UniversityShenzhen 518060China Department of Pharmacology and Pharmaceutical Sciences School of MedicineTsinghua UniversityBeijing 100084China

In this study,we designed and synthesized a series of phthalazinone acridine derivatives as dual PARP and Topo inhibitors.MTT assays indicated that most of the compounds significantly inhibited multiple cancer cells proliferation.In addition,all the compounds displayed Topo Ⅱ inhibition activity at 10 mol/L,and also possessed good PARP-1 inhibitory activities.Subsequent mechanistic studies showed that compound 9 a induced remarkable apoptosis and caused prominent S cell cycle arrest in HCT116 cells.Our study suggested that 9 a inhibiting Topo and PARP concurrently can be a potential lead compound for cancer therapy.

关键词： Topo PARP multitarget Acridines Antitumor bioactivity

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新型多靶点抗叶酸制剂——multitarget Antifolate(MTA)

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临床肿瘤学杂志 2004年第4期9卷 435-437,F003页

作者：王国华张湘茹沧州中西医结合医院肿瘤内科河北沧州061001 中国医学科学院肿瘤医院内科 010000

抗代谢药是最早被发现的抗肿瘤药物之一.氨甲喋呤(MTX),作为一个叶酸类似物,在二十世纪四十年代末期被发现[1],如今仍然被临床广泛应用.5-氟尿嘧啶(5-FU)为胸腺嘧啶脱氧核苷酸合成酶(TS)抑制剂,于20世纪60年代被引入临床[2].这两种药物... 详细信息

抗代谢药是最早被发现的抗肿瘤药物之一.氨甲喋呤(MTX),作为一个叶酸类似物,在二十世纪四十年代末期被发现[1],如今仍然被临床广泛应用.5-氟尿嘧啶(5-FU)为胸腺嘧啶脱氧核苷酸合成酶(TS)抑制剂,于20世纪60年代被引入临床[2].这两种药物在应用过程中所出现的一些问题使研究者们想设计一种作用于叶酸合成多位点的药物[3].拓优得(Raltitrexed)即是在研究中的产物之一.它是一个特效的以叶酸为基础的TS抑制剂,已经在一些国家认可用于治疗结肠癌.然而,在治疗其他各种实体瘤上拓优得并未得到广泛应用[4].

关键词：多靶点抗叶酸制剂 multitarget Antifolate MTA 氨甲喋呤抗肿瘤药

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