长期饮酒人群发生急性胰腺炎的风险因素分析:一项基于UK Biobank的自然人群研究

目的探讨有长期饮酒习惯人群急性胰腺炎(acute pancreatitis,AP)发生的风险因素。方法将由UK Biobank数据库中筛选的初次参与调查(2006年—2010年)和第二次随访(2014+)均为“目前饮酒状态”的志愿者作为目标人群(观察至2022年11月30日,期间新诊断AP 176人,未患AP 59512人)。收集目标人群入组时的手术史、饮食习惯等,并通过多因素Cox比例风险模型探讨其是否为AP发生的风险因素。同时以目标人群中有“饮酒类型”记录的人群为亚组,通过多因素Cox比例风险模型探讨不同酒类摄入量及增长量是否为AP发生的风险因素。结果多因素分析结果显示,每天摄入熟菜1~4汤匙,患AP风险分别为不摄入熟菜的44%(HR=0.44,95%CI:0.20~0.95)、39%(HR=0.39,95%CI:0.19~0.82)、42%(HR=0.42,95%CI:0.20~0.89)和41%(HR=0.41,95%CI:0.19~0.88);每天摄入2和3杯咖啡患AP风险为不摄入咖啡人群的45%(HR=0.45,95%CI:0.27~0.75)和39%(HR=0.39,95%CI:0.21~0.72);有胆源性疾病(BD)但未行胆囊切除术(CHO)患AP风险为无BD且未行CHO的7.82倍(HR=7.82,95%CI:5.30~11.54),有BD且行CHO患AP的风险仅为无BD且未行CHO的2.15倍(HR=2.15,95%CI:1.15~4.01)。亚组分析结果显示,不同酒类的摄入量均不影响AP的发生,但在此基础上纳入不同酒类摄入增长量后的结果表明,烈酒摄入增长量每升高1瓶/周、患AP的风险增长1.05倍(HR=1.05,95%CI:1.02~1.09,P<0.05)。结论在有长期饮酒习惯的人群中,熟菜和适量的咖啡摄入是AP发生的保护因素;患BD且不切除胆囊为AP发生的危险因素,而患BD且进行CHO人群的AP发生显著降低;烈酒摄入增长量上升也是AP发生的危险因素。

Association of alcohol consumption with aortic aneurysm and dissection risk:results from the UK Biobank cohort study

BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD.METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95% confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results.RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4% male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women.CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.

Biobanks and biomarkers:Their current and future role in biomedical research

The importance and utility of biobanks has increased exponentially since their inception and creation.Initially used as part of translational research,they now contribute over 40%of data for all cancer research papers in the United States of America and play a crucial role in all aspects of healthcare.Multiple classification systems exist but a simplified approach is to either classify as population-based or disease-oriented entities.Whilst historically publicly funded institutions,there has been a significant increase in industry funded entities across the world which has changed the dynamic of biobanks offering new possibilities but also new challenges.Biobanks face legal questions over data sharing and intellectual property as well as ethical and sustainability questions particularly as the world attempts to move to a low-carbon economy.International collaboration is required to address some of these challenges but this in itself is fraught with complexity and difficulty.This review will examine the current utility of biobanks in the modern healthcare setting as well as the current and future challenges these vital institutions face.

Clinical Analysis of the Colorectal Cohort within the Wales Cancer Biobank: A Study of Outcomes and Genetic Screening

Over the last 12 years, the Wales Cancer Biobank (WCB) has consented to more than 2000 patients with colorectal cancer (CRC). From these patients, clinical data has been collected and patients have been followed through their cancer journey. Clinical data from these patients have been analyzed to identify any correlation between disease grade and outcome. In a small cohort, consisting of 407 patients, WCB has performed genetic analysis on patient primary tumor samples, identifying and characterizing mutations in the KRAS, NRAS, BRAF, PIK3CA and TP53 genes. The majority of patients with CRC who were consented to WCB were male with a mean age of 69 years and received surgery as the primary treatment for their disease. Pathology and disease-free survival data confirmed worse prognoses associated with more advanced disease. Heterogeneity within the primary tumor was explored in a subgroup of patients. Analysis of the KRAS and TP53 genes confirmed that more than 40% of CRC patients who were tested, harbored a genetic mutation within these genes in their primary tumor. Due to the limited sample size tested, most mutations did not show significant differences in disease-free survival, however, mutation of the BRAF gene did show a decrease in the disease specific survival, in keeping with the published data. Analysis of the patients diagnosed with CRC within the Biobank has provided us with valuable information on the status of CRC disease and treatment within the Welsh population. Over 12 years of consenting, we have witnessed significant changes in the information that researchers are interested in when sourcing samples for translational research. The development of new drugs that are tailored to the genetics of a cancer is emerging and at WCB we are focusing our collections on samples and data that meet the needs of this ever-evolving field.

2016—2022年基于UK Biobank数据库的心血管疾病研究热点的可视化分析

目的分析基于英国生物样本数据库(UK Biobank)开展的关于心血管疾病的研究热点和发展趋势,为研究者开展心血管疾病相关研究提供科学参考。方法在Web of Science核心集数据库中检索2016年至2022年期间基于UK Biobank数据库开展的关于心血管疾病研究的文献,运用Citespace 6.1.R 2和VOSviewer 1.6.18软件分别从国家、机构、关键词等方面对心血管疾病的研究热点和发展趋势进行可视化分析。结果研究共纳入284篇文献,整体发文量处于增长趋势;发文量排在第1位的作者是S.PETERSEN,发文量最多的国家是英国,发文量最多的机构是英国牛津大学;关键词突现分析提示,近5年研究趋势主要集中在危险因素分析(adiposity,body mass index)、全基因组关联研究(genome-wide association study)与疾病预后分析(therapy,all-cause mortality)等方面的研究。另外,以“smoking”为代表的危险因素探讨、基因表达(loci,expression)和以孟德尔随机化为代表的偏倚控制方法探讨(Mendelian randomization,bias)是现阶段基于UK Biobank数据库开展的有关脑血管疾病的研究热点。结论当前基于UK Biobank数据库的心血管疾病研究处于快速发展期,英国与美国在该领域开展的研究较多,近5年该领域研究趋势和热点主要集中在心血管疾病的危险因素分析、基因表达、疾病预后分析与偏倚控制方法等方面。

Living biobank-based cancer organoids: prospects and challenges in cancer research

Biobanks bridge the gap between basic and translational research.Traditional cancer biobanks typically contain normal and tumor tissues,and matched blood.However,biospecimens in traditional biobanks are usually nonrenewable.In recent years,increased interest has focused on establishing living biobanks,including organoid biobanks,for the collection and storage of viable and functional tissues for long periods of time.The organoid model is based on a 3D in vitro cell culture system,is highly similar to primary tissues and organs in vivo,and can recapitulate the phenotypic and genetic characteristics of target organs.Publications on cancer organoids have recently increased,and many types of cancer organoids have been used for modeling cancer processes,as well as for drug discovery and screening.On the basis of the current research status,more exploration of cancer organoids through technical advancements is required to improve reproducibility and scalability.Moreover,given the natural characteristics of organoids,greater attention must be paid to ethical considerations.Here,we summarize recent advances in cancer organoid biobanking research,encompassing rectal,gastric,pancreatic,breast,and glioblastoma cancers.Living cancer biobanks that contain cancerous tissues and matched organoids with different genetic backgrounds,subtypes,and individualized characteristics will eventually contribute to the understanding of cancer and ultimately facilitate the development of innovative treatments.

Assessment of Knowledge, Attitudes and Support of Health Professionals towards Biobanks in Eastern Morocco

Background: Health professionals play a key role in increasing the rate of biobanking participation. Here, we assessed the knowledge and attitude of health professionals in Eastern Morocco towards biobanks and their willingness to recruit patients into biobanks. Methods: A cross-sectional study carried out among health professionals working in various public and private health centers in Eastern Morocco. The data were obtained using a self-administered anonymous questionnaire. Results: 600 health professionals were included in the study. Only 37.5% of them had knowledge of biobanks. Associations analysis showed that among health professionals, physicians had more knowledge of biobanks (OR = 2.50, p = 0.000), and health professionals working at the University Hospital had more knowledge of biobanks compared to those working in the other participating health centers (p Conclusions: This study indicates that health professionals in Eastern Morocco showed a notable lack of knowledge about biobanks. However, the majority were willing to donate their own biospecimens and supported the recruitment of patients into biobanks. This study was a good opportunity to raise awareness among health professionals about the interest of biobanks in the development of biomedical research in Eastern Morocco.

如何利用UK Biobank申请研究数据和生物样本

UK Biobank是一项庞大和详细的前瞻性研究工程,由维康信托基金、英国医学研究委员会、英国卫生部、苏格兰政府和西北地区发展局发起成立。其储存着海量疾病与健康相关的研究数据和生物样本,全球的科研人员均可通过在线申请获得这些研究数据和生物样本并将其用于已批准的研究项目中。本文详细介绍了如何通过UK Biobank检索及申请研究数据和生物样本。

Clinical Biobanks, from the World to China

The 2009 annual special issue of Time Magazine on March 23rd summarized the ＇10 Ideas Changing the World Right Now＇, in which ＇Biobank＇ had been listed as the eighth. Biobank or biorepository has been developed since last century. Tissue banks represented the early type of clinical biobanks and mainly concentrated on clinical usage such as transplantation at the beginning. The first tissue bank in the United States started in 1949 is the United States Navy Tissue Bank. In 1976, the foundation of American Association of Tissue Banks （AATB） claimed the official show of biobanks on social stage （www.aatb.org）. From the end of 20th Century to the beginning of 21st Century, diverse biobanks of clinical samples, seed banks, gene banks, germplasm banks of non-human species and other various types have sprung up.

Biobanking in the digital pathology era

Digital Pathology is becoming more and more important to achieve the goal of precision medicine.Advances in whole-slide imaging,software integration,and the accessibility of storage solutions have changed the pathologists’clinical practice,not only in terms of laboratory workflow but also for diagnosis and biomarkers analysis.In parallel with the pathology setting advancement,translational medicine is approaching the unprecedented opportunities unrevealed by artificial intelligence(AI).Indeed,the increased usage of biobanks’datasets in research provided new challenges for AI applications,such as advanced algorithms,and computer-aided techniques.In this scenario,machine learning-based approaches are being propose in order to improve biobanks from biospecimens collection repositories to computational datasets.To date,evidence on how to implement digital biobanks in translational medicine is still lacking.This viewpoint article summarizes the currently available literature that supports the biobanks’role in the digital pathology era,and to provide possible practical applications of digital biobanks.

Use of Residual Material in Biobanking： Solidarity, Common Good, and Informed Consent

Biological residual materials can be obtained from surgical activities or from pathological waste material collected for analysis and stored in formalin. This material can be stored in biobanks with the purpose of future research. Formalin-fixed tissue and also formalin-fixed paraffin embedded tissues are not suitable for all kinds of genetic studies on DNA or RNA, as formalin solution is well known for damaging nucleic acids. Therefore, for the purpose of conducting genetic studies, samples should be frozen in order to maintain a good quality of DNA/RNA over time Biobanks, in which waste samples are frozen, are undoubtedly expensive to maintain; however, it could be useful and important to consider their possible implication in particular research, regarding for example the tumor cells growth process, or when the procurement of samples is difficult. Regarding the relationship between informed consent and tissue collection, storage and research, two choices are possible： irreversible or reversible sample anonymization. These procedures involve different approaches and possible solutions that we will seek to define. Also, an important ethical aspect in regard to the role of biobanks is encouraging sample donation. For donors, seeing human sample being kept rather than discarded and seeing them become useful for research highlight the importance of the human body and improve the attitude towards donation. This process might also facilitate the giving of informed consent more trustfully and willingly.

Associations of diet with infectious diseases in UK Biobank

The current study used multivariable logistic regression analysis to investigate associations between the intake frequencies of 13 food groups(or four diet groups)and infectious diseases.The analysis included 487849 participants from the UK Biobank,with 75209 participants diagnosed with infectious diseases.Participants reporting the highest intake frequency of processed meat(odds ratio[OR]=1.0964,95%confidence interval[CI]:1.0622–1.1318)and red meat(OR=1.0895,95%CI:1.0563–1.1239)had a higher risk of infectious diseases,compared with those with the lowest intake frequency.Consuming fish 2.0–2.9 times(OR=0.8221,95%CI:0.7955–0.8496),cheese≥5.0 times(OR=0.8822,95%CI:0.8559–0.9092),fruit 3.0–3.9 servings(OR=0.8867,95%CI:0.8661–0.9078),and vegetables 2.0–2.9 servings(OR=0.9372,95%CI:0.9189–0.9559)per week were associated with a lower risk of infection.Low meat-eaters(OR=0.9404,95%CI:0.9243–0.9567),fish-eaters(OR=0.8391,95%CI:0.7887–0.8919),and vegetarians(OR=0.9154,95%CI:0.8561–0.9778)had a lower risk of infectious diseases,compared with regular meat-eaters.The mediation analysis revealed that glycosylated hemoglobin,white blood cell count,and body mass index served as the mediators in the associations between diet and infectious diseases.The current study indicates that the intake frequency of food groups is a risk factor for infectious diseases,and fish-eaters have a lower risk of infection.

Harmonizing the COVID-19 sample biobanks: Barriers and opportunities for standards, best practices and networks

The coronavirus disease 2019(COVID-19)pandemic has highlighted the practice of infectious diseases biobanking,as well as existing challenges and opportunities.Thus,the future of infectious diseases biobanking in the post-pandemic era,shall not be an“entry-level version”of its counterpart in non-communicable diseases and large population cohorts,but incorporate the lessons learned.Biobanks constitute a critical research infrastructure supported by harmonized practices through the implementation of international standards,and perceived within the broader scope of healthcare's intersection with research.This perspective paper considers the barriers in biobanking and standardization of practices,as well as the emerging opportunities in the field.

Association of accelerometer-measured sleep duration and different intensities of physical activity with incident type 2 diabetes in a population-based cohort study

Purpose:The aim of the current study was to investigate the association of accelerometer-measured sleep duration and different intensities of physical activity(PA)with the risk of incident type 2 diabetes in a population-based prospective cohort study.Methods:Altogether,88,000 participants(mean age=62.2±7.9 years,mean±SD)were included from the UK Biobank.Sleep duration(short:<6 h/day;normal:6-8 h/day;long:>8 h/day)and PA of different intensities were measured using a wrist-won accelerometer over a 7-day period between 2013 and 2015.PA was classified according to the median or World Health Organization-recommendation:total volume of PA(high,low),moderate-to-vigorous PA(MVPA)(recommended,not recommended),and light-intensity PA(high,low).Incidence of type 2diabetes was ascertained using hospital records or death registries.Results:During a median follow-up of 7.0 years,1615 incident type 2 diabetes cases were documented.Compared with normal sleep duration,short(hazard ratio(HR)=1.21,95%confidence interval(95%CI):1.03-1.41)but not long sleep duration(HR=1.01,95%CI:0.89-1.15)was associated with excessive type 2 diabetes risk.This increased risk among short sleepers seems to be protected against by PA.Compared with normal sleepers with high or recommended PA,short sleepers with low volume of PA(HR=1.81,95%CI:1.46-2.25),not recommended(below the World Health Organization-recommended level of)MVPA(HR=1.92,95%CI:1.55-2.36),or low light-intensity PA(HR=1.49,95%CI:1.13-1.90)had a higher risk of type 2 diabetes,while short sleepers with a high volume of PA(HR=1.14,95%CI:0.88-1.49),recommended MVPA(HR=1.02,95%CI:0.71-1.48),or high light-intensity PA(HR=1.14,95%CI:0.92-1.41)did not.Conclusion:Accelerometer-measured short but not long sleep duration was associated with a higher risk of incident type 2 diabetes.A higher level of PA,regardless of intensity,potentially ameliorates this excessive risk.

The evolution of cancer genomic medicine in Japan and the role of the National Cancer Center Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer research.At the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and beyond.Although CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of cancer.Looking back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be developed.The quantity and quality of these samples will be compatible with omics analyses.All biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

基于PEST-SWOT分析的生物样本库可持续发展新模式探索

生物样本库在精准医学、转化医学和生物医药等方面的作用日益凸显,构建可持续发展的生物样本库成为行业发展的必然需求。但样本库持续投入不足、缺乏自身造血机制和样本利用率低等问题已成为困扰样本库可持续发展的关键问题。文章以共建共享为出发点,模拟了态势分析法(PEST-SWOT)模型在生物样本库可持续发展应用中的构建,并基于此模式下探讨政府与社会资本合作(public-private partnership,PPP)模式在生物样本库可持续发展策略中的可行性,分析PEST-SWOT模型下PPP模式在生物样本库建设与发展中的新策略,即引导政府和社会资本有效整合,促进生物样本库发展的新模式,为生物样本库可持续发展提供理论支撑,为生物样本库学科建设提供新思路。

美欧Biobank建设及管理现状研究

鉴于Biobank在未来医学研究中的作用,为了促进我国Biobank的健康发展,全文通过对国内外的Biobank的建设情况及其基本管理措施和经验进行了总结、归纳与分析,为我国Biobank的发展提供借鉴。

UK Biobank数据的应用介绍

UK Biobank(英国生物银行)是一个大型生物医学数据库和研究资源,包含来自50万英国参与者的生物遗传和健康信息,涵盖了丰富的基本结构化数据、高通量的基因组学遗传数据和多模态影像数据,但是由于其数据体量大,使用方式复杂,因此国内研究者使用的并不广泛。本文首先介绍UK Biobank的健康相关结构数据、基因数据和影像数据等内容,随后分别对不同数据的下载使用方法进行详细描述,最后探索近几年使用UK Biobank数据库进行的最新研究,并围绕将人工智能技术应用于UK Biobank数据的典型研究和发展方向进行探讨,以期在人体解剖生理和遗传变异、表型特征等方面有更多的科学研究成果出现。

肿瘤类器官临床前转化研究及应用

越来越深入的肿瘤机制研究和临床精准治疗对肿瘤模型的建立提出了更高的要求,肿瘤类器官应用越来越广泛。该模型被认为可以再现亲代肿瘤的基因组、转录组、蛋白质组等多组学特征,具有细胞系模型所缺乏的异质性。基于这些特征,肿瘤类器官逐渐成为一个具有代表性的临床前模型,助力于新的研究成果转化以及患者的精准治疗。本文将从肿瘤类器官的研究及应用的角度总结其最新进展,重点关注当前建立肿瘤类器官方法以及应用中所面临的机遇和挑战。

卵巢恶性肿瘤类器官库的初建

背景卵巢恶性肿瘤异质性导致患者个体治疗效果差异大,经典治疗方案无法实现患者个体化治疗。可靠的卵巢恶性肿瘤体外模型可作为患者“替身”进行研究和药物敏感性测定,其结果为卵巢恶性肿瘤患者的精准治疗提供新思路。目的建立卵巢恶性肿瘤类器官生物库,在基因组学层面验证类器官与对应卵巢癌组织的一致性,探索类器官模型药敏结果预测临床疗效的可行性。方法分离患者组织来源的卵巢恶性肿瘤细胞,在基质胶三维环境中培养形成类器官。利用全外显子测序技术检测并对比类器官与对应卵巢恶性肿瘤组织的基因组学特征。类器官培养2~3 d后加入化疗单药或联合方案药物,进行药物敏感性测定。结果本研究建立了卵巢恶性肿瘤类器官生物库,包含来自113例患者的122个类器官系,培养成功率达90.4%。全外显子测序分析显示卵巢恶性肿瘤类器官在基因组学层面与亲本肿瘤组织具有一致性。卵巢恶性肿瘤类器官药敏结果对临床疗效的预测准确性达70.7%,敏感度为75%,特异度为55.6%。结论本研究在体外成功建立了卵巢恶性肿瘤类器官生物库,类器官模型可反映亲本肿瘤的基因组学特征,其药敏结果可反映临床疗效。卵巢恶性肿瘤类器官库为卵巢恶性肿瘤研究、药物开发、临床治疗方案制定提供了可靠的临床前模型。