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Can propensity score matching replace randomized controlled trials?

World Journal of Methodology 2024年第1期14卷 58-70页

作者： Matthias Yi Quan Liau en qi toh Shamir Muhamed Surya Varma Selvakumar Vishalkumar Girishchandra Shelat Lee Kong Chian School of Medicine Nanyang Technological UniversitySingapore 308232Singapore Department of General Surgery Tan Tock Seng HospitalSingapore 308433Singapore Surgical Science Training Centre Tan Tock Seng HospitalSingapore 308433Singapore

Randomized controlled trials(RCTs)have long been recognized as the gold standard for establishing causal relationships in clinical *** that,various limitations of RCTs prevent its widespread implementation,ranging from the ethicality of withholding potentially-lifesaving treatment from a group to relatively poor external validity due to stringent inclusion criteria,amongst ***,with the introduction of propensity score matching(PSM)as a retrospective statistical tool,new frontiers in establishing causation in clinical research were opened *** predicts treatment effects using observational data from existing sources such as registries or electronic health records,to create a matched sample of participants who received or did not receive the intervention based on their propensity scores,which takes into account characteristics such as age,gender and *** its retrospective nature and its use of observational data from existing sources,PSM circumvents the aforementioned ethical issues faced by *** of RCTs exclude elderly,pregnant women and young children;thus,evidence of therapy efficacy is rarely proven by robust clinical research for this *** the other hand,by matching study patient characteristics to that of the population of interest,including the elderly,pregnant women and young children,PSM allows for generalization of results to the wider population and hence greatly increases the external *** of replacing RCTs with PSM,the synergistic integration of PSM into RCTs stands to provide better research outcomes with both methods complementing each *** example,in an RCT investigating the impact of mannitol on outcomes among participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial,the baseline characteristics of comorbidities and current medications between treatment and control arms were significantly different despite the randomization ***,PS

关键词： Propensity score matching Randomized controlled trials Randomization Clinical practice Validity Ethics

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Extracellular histones stimulate collagen expression in vitro and promote liver fibrogenesis in a mouse model via the TLR4-MyD88 signaling pathway

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World Journal of Gastroenterology 2020年第47期26卷 7513-7527页

作者： Zhi Wang Zhen-Xing Cheng Simon T Abrams Zi-qi Lin ED Yates qian Yu Wei-Ping Yu Ping-Sheng Chen Cheng-Hock toh Guo-Zheng Wang Department of Pathology and Pathophysiology Medical SchoolSoutheast UniversityNanjing 210009Jiangsu ProvinceChina Department of Gastroenterology Zhongda HospitalNanjing 210009Jiangsu ProvinceChina Department of Clinical Infection Microbiology and ImmunologyUniversity of LiverpoolLiverpool L697BEUnited Kingdom Department of Integrated Traditional Chinese and Western Medicine Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research CentreWest China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Integrative Biology University of LiverpoolLiverpool L697ZBUnited Kingdom Roald Dahl Haemostasis&Thrombosis Ctr Royal Liverpool University HospitalLiverpool L697BEUnited Kingdom

BACKGROUND Liver fibrosis progressing to liver cirrhosis and hepatic carcinoma is very common and causes more than one million deaths *** develops from recurrent liver injury but the molecular mechanisms are not fully ***,the TLR4-MyD88 signaling pathway has been reported to contribute to *** histones are ligands of TLR4 but their roles in liver fibrosis have not been *** To investigate the roles and potential mechanisms of extracellular histones in liver *** In vitro,LX2 human hepatic stellate cells(HSCs)were treated with histones in the presence or absence of non-anticoagulant heparin(NAHP)for neutralizing histones or TLR4-blocking *** resultant cellular expression of collagen I was detected using western blotting and immunofluorescent *** vivo,the CCl4-induced liver fibrosis model was generated in male 6-week-old ICR mice and in TLR4 or MyD88 knockout and parental *** histones were detected and the effect of NAHP was *** Extracellular histones strongly stimulated LX2 cells to produce collagen ***-enhanced collagen expression was significantly reduced by NAHP and TLR4-blocking *** CCl4-treated wild type mice,circulating histones were dramatically increased and maintained high levels during the duration of *** of NAHP not only reduced alanine aminotransferase and liver injury scores,but also significantly reduced *** the TLR4-blocking antibody reduced histone-enhanced collagen I production in HSC,the CCl4 model with TLR4 and MyD88 knockout mice was used to demonstrate the roles of the TLR4-MyD88 signaling pathway in CCl4-induced liver *** levels of liver fibrosis were indeed significantly reduced in knockout mice compared to wild type parental *** Extracellular histones potentially enhance fibrogenesis via the TLR4–MyD88 signaling pathway and NAHP has therapeutic potential by

关键词： Liver fibrosis Extracellular histones Non-anticoagulant heparin TLR4 MyD88 CCl4

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川西低品位钛铁矿磁-浮联合选别工艺试验研究

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有色金属工程 2024年第8期14卷 121-129页

作者：周凌志谢贤漆静李蒋陈杰江夏虎潇孙代馨昆明理工大学国土资源工程学院昆明650093 省部共建复杂有色金属资源清洁利用国家重点实验室昆明650093 金属矿尾矿资源绿色综合利用国家地方联合工程研究中心昆明650093

以川西地区某低品位钛铁矿为研究对象,针对该钛铁矿品位低、矿物组成成分复杂、有价矿物之间共生关系密切、且嵌布粒度细等问题,采用磁-浮混合工艺对该难选钛铁矿进行选矿工艺试验研究。通过试验研究,优化选矿工艺流程和药剂制度,为低... 详细信息

以川西地区某低品位钛铁矿为研究对象,针对该钛铁矿品位低、矿物组成成分复杂、有价矿物之间共生关系密切、且嵌布粒度细等问题,采用磁-浮混合工艺对该难选钛铁矿进行选矿工艺试验研究。通过试验研究,优化选矿工艺流程和药剂制度,为低品位钛铁矿的开发利用提供理论依据和技术支撑。结果表明:对TiO_(2)品位为7.45%的钛铁矿原矿,通过强磁-浮选联合工艺,并采用新型高选择性羧酸捕收剂toh精选后,可获得TiO_(2)品位为43.50%、回收率为74.30%的钛精矿。

关键词：钛铁矿浮选磁选捕收剂

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Discovery of CECR2 Bromodomain Inhibitors with High Selectivities over BPTF Bromodomain

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Chinese Journal of Chemistry 2022年第17期40卷 2072-2080页

作者： Haibo Lu Shijia Zu Zhe Duan Yueyao Feng Jie Wang Jingyi Ma qi Li Dongying Chen Bo Li Kaixian Chen Cheng Luo Jin Lin Tian Lu Hua Lin Biomedical Research Center of South China College of Life SciencesFujian Normal UniversityFuzhouFujian350117 China School of Pharmacy Fudan University826 Zhangheng RoadShanghai201203 China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of Sciences555 Zuchongzhi RoadShanghai201203 China University of Chinese Academy of Sciences 19 Yuquan RoadBeijing100049 China School of Pharmacy Nanchang UniversityNanchangJiangxi330006 China Laboratory of Pharmaceutical Analysis Shanghai Institute of Materia MedicaChinese Academy of Sciences555 Zuchongzhi RoadZhangjiang Hi-Tech ParkShanghai201203 China School of Pharmacy Fujian Medical UniversityFuzhouFujian350122 China Guizhou University of Traditional Chinese Medicine GuiyangGuizhou550025 China

Cat's eye syndrome chromosome candidate 2 bromodomain(CECR2 BRD)and Bromodomain PHD transcription factor bromodomain(BPTF BRD)are the same subfamily proteins,both of which are highly conserved in sequence and binding *** remain in the development of small molecules to inhibit one of the two bromodomains(BRDs),in view of each subtype may possess unique physiological and pathological *** is still a lack of effective selective inhibitors of CECR2 BRD,which makes it difficult to fully understand the pathogenesis of CECR2-BRD in diseases,especially ***,we report our efforts to discover a series of highly selective CECR2 BRD inhibitors over BPTF BRD based on ***-based molecular optimization led to the discovery of DC-CEi-26,whose IC_(50) for CECR2 BRD was 96.7±14.9 nmol/L and selectivity was up to 590×over BPTF ***-CEi-26 showed weak potencies for other classic BRDs in different subfamily,which may serve as a chemical probe for CECR2 BRD biological research.

关键词： CECR2 bromodomain BPTF bromodomain Inhibitors Structure-activity relationships chemical probe

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Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in hepatocellular carcinoma:the PLANET study

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National Science Review 2022年第3期9卷 96-109页

作者： Weiwei Zhai Hannah Lai Neslihan Arife Kaya Jianbin Chen Hechuan Yang Bingxin Lu Jia qi Lim Siming Ma Sin Chi Chew Khi Pin Chua Jacob Josiah Santiago Alvarez Pauline Jieqi Chen Mei Mei Chang Lingyan Wu Brian K.P.Goh Alexander Yaw-Fui Chung Chung Yip Chan Peng Chung Cheow Ser Yee Lee Juinn Huar Kam Alfred Wei-Chieh Kow Iyer Shridhar Ganpathi Rawisak Chanwat Jidapa Thammasiri Boon Koon Yoong Diana Bee-Lan Ong Vanessa H.de Villa Rouchelle D.Dela Cruz Tracy Jiezhen Loh Wei Keat Wan Zeng Zeng Anders Jacobsen Skanderup Yin Huei Pang Krishnakumar Madhavan Tony Kiat-Hon Lim Glenn Bonney Wei qiang Leow Valerie Chew Yock Young Dan Wai Leong Tam Han Chong toh Roger Sik-Yin Foo Pierce Kah-Hoe Chow Genome Institute of Singapore Agency for Science Technology and Research Key Laboratory of Zoological Systematics and Evolution Institute of Zoology Chinese Academy of Sciences Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences School of Biological Sciences Nanyang Technological University Division of Biosciences Faculty of Life Sciences Division of Surgery and Surgical Oncology National Cancer Centre Department of Hepato-Pancreato-Biliary and Transplant Surgery Singapore General Hospital Division of Hepatobiliary and Pancreatic Surgery Department of Surgery University Surgical Cluster National University Health System Hepato-Pancreato-Biliary Surgery Unit Department of Surgery National Cancer Institute Division of Pathology National Cancer Institute Department of Surgery Faculty of Medicine University of Malaya Department of Surgery and Center for Liver Disease Management and Transplantation The Medical City 13. Department of Laboratories The Medical City Department of Pathology Singapore General Hospital Institute for Infocomm Research ASTAR Department of Pathology National University Health System Translational Immunology Institute (TII) Sing Health Duke-NUS Academic Medical Centre Division of Gastroenterology and Hepatology University Medicine Cluster National University Hospital Department of Biochemistry Yong Loo Lin School of Medicine National University of Singapore Cancer Science Institute of Singapore National University of Singapore Division of Medical Oncology National Cancer Center Singapore Cardiovascular Research Institute National University of Singapore National University Healthcare System Singhealth-Duke-NUS Academic Surgery Program Duke-NUS Graduate Medical School Institute of Molecular and Cell Biology Agency for Science Technology and Research

Intra-tumor heterogeneity(ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic(transcriptomic and immune)heterogeneity. Using one of the largest prospective surgical cohorts for hepatocellular carcinoma(HCC)with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients(331 samples). We found that while genomic ITH was rather constant across stages, phenotypic ITH had a very different trajectory and quickly diversified in stage Ⅱ patients. Most strikingly, 30% of patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types.

关键词： hepatocellular carcinoma intra-tumor heterogeneity phenotypic evolution tumor evolution

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