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Immunotherapy in non-small cell lung cancer: rationale, recent advances and future perspectives. 非小细胞肺癌的免疫治疗:基本原理、最新进展和未来展望。
IF 5.3 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2021-12-01 DOI: 10.1093/pcmedi/pbab027
Wenxin Luo, Zhoufeng Wang, Ting Zhang, Lan Yang, Jinghong Xian, Yalun Li, Weimin Li

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.

肺癌,以非小细胞肺癌(NSCLC)为主要类型,是全球第二大最常见的恶性肿瘤,也是癌症相关死亡的主要原因。以免疫检查点抑制剂(ICIs)为代表的免疫疗法是近年来治疗包括非小细胞肺癌在内的实体肿瘤的最大进展之一。然而,并不是所有的NSCLC患者对程序性死亡配体1 (PD-L1)和肿瘤突变负荷(TMB)的既定选择标准的免疫治疗都有有效的反应。此外,相当比例的患者在免疫治疗过程中经历了非常规的反应,包括假进展或超进展性疾病(HPD)、免疫相关毒性和原发性或获得性耐药。为了更好地了解非小细胞肺癌的免疫应答,为临床决策提供参考,我们在此综述免疫疗法治疗非小细胞肺癌的原理和最新进展。此外,我们还讨论了该方法目前面临的挑战和未来的策略,以提高其治疗非小细胞肺癌的有效性和安全性。
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引用次数: 14
AI in spotting high-risk characteristics of medical imaging and molecular pathology 人工智能在发现医学影像学和分子病理学高危特征中的应用
IF 5.3 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2021-12-01 DOI: 10.1093/pcmedi/pbab026
Chong Zhang, Jionghui Gu, Yangyang Zhu, Zheling Meng, Tong Tong, Dongyang Li, Zhenyu Liu, Yang Du, Kun Wang, Jie Tian
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.
医学影像为疾病诊断提供了全面的视角和丰富的信息。结合人工智能技术,医学影像可以进一步挖掘详细的病理信息。许多研究表明,肿瘤的宏观影像学特征与微观的基因、蛋白质和分子变化密切相关。为了探讨人工智能算法在医学影像信息深度分析中的作用,本文从医学影像分析方法、临床应用和医学影像在病理分子预测方向的发展三个方面对近年来发表的文章进行综述。我们相信,人工智能辅助医学影像分析将广泛地为精确和高效的临床决策做出贡献。
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引用次数: 1
Dichotomous roles of neutrophils in modulating pathogenic and repair processes of inflammatory bowel diseases 中性粒细胞在调节炎症性肠病的致病和修复过程中的双重作用
IF 5.3 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2021-11-15 DOI: 10.1093/pcmedi/pbab025
Huimin Chen, Xiaohan Wu, Chunjin Xu, Jian Lin, Zhanju Liu
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.
中性粒细胞被认为是一种复杂的先天免疫细胞,在维持肠道黏膜稳态中起着至关重要的作用。它们在病原体感染和肠道炎症的急性期发挥强大的促炎作用并招募其他免疫细胞,但矛盾的是,它们也限制外源微生物的入侵并促进粘膜恢复。中性粒细胞的过度激活或功能障碍导致异常的免疫反应,导致多种自身免疫性和炎症性疾病,包括系统性红斑狼疮、类风湿关节炎和炎症性肠病(IBD)。IBD作为一种难治性肠道炎症性疾病,其发病和进展与复杂的免疫反应过程有关,其中中性粒细胞参与其中。然而,关于中性粒细胞在IBD的致病和修复过程中的潜在作用的共识仍未完全了解。积累的浸润性中性粒细胞穿过上皮屏障,导致肠道微生物生态失调,加重肠道结构损伤,降低肠道炎症的消退,增加IBD期间血栓形成的风险。矛盾的是,在IBD中,活化的中性粒细胞还与有效消除入侵的微生物群、促进血管生成和肠黏膜组织修复有关。在这里,我们讨论了中性粒细胞在肠黏膜炎症的发生和消退中的有益和有害作用,希望对中性粒细胞在IBD发病机制中的功能提供一个精确的概述。
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引用次数: 17
Inhibitory activity of medicinal mushroom Ganoderma lucidum on colorectal cancer by attenuating inflammation
IF 5.3 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2021-08-28 DOI: 10.1093/pcmedi/pbab023
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
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.
药用蘑菇灵芝(Ganoderma lucidum, GL, Reishi或Lingzhi)具有抑制癌症的作用。然而,GL抗肿瘤活性的潜在机制尚不完全清楚。在这项研究中,我们描述了一种含有孢子和子实体混合物的GL的商业产品,即“GLSF”,在结直肠癌中调控的基因网络。我们发现,体外无毒浓度的GLSF提取物可显著增强紫杉醇诱导的CT26和HCT-15细胞的生长抑制和凋亡。GLSF抑制HEK-293细胞中NF-κB启动子活性,但不影响K562/DOX细胞中p -糖蛋白的功能。此外,我们发现,在CT26肿瘤细胞接种前1个月,给小鼠喂食含有GLSF的改良饲料,GLSF单独或与nab -紫杉醇联合可显著抑制肿瘤生长并诱导细胞凋亡。对glsf处理小鼠肿瘤组织的RNA-seq分析发现,与正常组织相比,有53个差异表达基因。许多glsf下调的基因参与NF-κ b调控的炎症通路,如IL-1β、IL-11和Cox-2。途径富集分析表明,几种涉及白细胞迁移和粘附的炎症途径受治疗影响最大。上游分析预测多种肿瘤抑制因子如α-catenin和TP53的激活和关键炎症介质的抑制。“癌变”是GLSF治疗的主要显著抑制生物学效应。这些结果表明,GLSF可以通过抑制NF-κ b调节的炎症和致癌机制改善结直肠癌的治疗效果。
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引用次数: 5
CRISPR/Cas9 mediated somatic gene therapy for insertional mutations: the vibrator mouse model CRISPR/Cas9介导的插入突变体细胞基因治疗:振动器小鼠模型
IF 5.3 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2021-08-19 DOI: 10.1093/pcmedi/pbab021
Xin Fu, Jie Zhu, Yaou Duan, P. Lu, Kang Zhang
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.
体细胞基因治疗在技术上仍然具有挑战性,特别是在中枢神经系统(CNS)中。在任何治疗方法中,基因传递的效率、受体细胞的有效性和总体获益所需细胞的比例是需要考虑的关键点。最近的研究已经证明了rna引导的核酸酶(如CRISPR/Cas9)在纠正点突变或去除显性突变方面的功效。在这里,我们使用病毒传递的Cas9质粒和两个引导rna来去除小鼠大脑中的隐性插入突变,振动器(vb)。由于插入内含子4的内源性逆转录病毒,vb小鼠表达了正常水平约20%的磷脂酰肌醇转移蛋白、α (PITPα) RNA和蛋白,导致早发性震颤、脑干和脊髓神经元变性和幼年死亡。CRISPR/Cas9原位病毒治疗有效地延缓了神经退行性变,减轻了震颤,并避免了青少年死亡。我们的研究证明了CRISPR/ cas9介导的基因治疗对出生后大脑插入突变的潜力。
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引用次数: 2
Improving T cell therapy: in vivo CRISPR-Cas9 screens tell us how to do 改进T细胞疗法:体内CRISPR-Cas9筛选告诉我们该怎么做
IF 5.3 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2021-07-22 DOI: 10.1093/pcmedi/pbab015
Tao Yin
Editor’s note A commentary on “In vivo CD8+ T cell CRISPR screening reveals control by Fli1 in infection and cancer”.
编者注:关于“体内CD8+ T细胞CRISPR筛选揭示Fli1在感染和癌症中的控制作用”的评论。
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引用次数: 1
Applications and challenges of CRISPR-Cas gene-editing to disease treatment in clinics. CRISPR-Cas 基因编辑技术在临床疾病治疗中的应用和挑战。
IF 5.1 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2021-07-10 eCollection Date: 2021-09-01 DOI: 10.1093/pcmedi/pbab014
Wenyi Liu, Luoxi Li, Jianxin Jiang, Min Wu, Ping Lin

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.

聚类规则间隔短回文重复序列(CRISPR)相关系统(Cas)是针对特定基因的高效工具,可用于实验室研究、农业工程、生物技术和人类疾病治疗。Cas9 是迄今为止应用最广泛的基因编辑核酸酶,在治疗遗传性疾病、病毒感染、癌症等方面显示出巨大前景。最近的报道显示,其他一些类型的 CRISPR-Cas 系统也可能具有惊人的潜力,加入基因编辑工具的行列,用于各种应用。尽管基础研究和临床试验取得了快速进展,但一些潜在的问题仍带来了持续、重大的挑战,如编辑效率、传递相对困难、脱靶效应、免疫原性等。本文总结了CRISPR-Cas从台前到床边的应用,强调了目前可能限制CRISPR-Cas系统作为基因编辑工具包在精准医疗中应用的障碍,并提出了一些有助于应对这些挑战和促进技术发展的观点。CRISPR-Cas 系统作为一种强大的基因编辑方法,将为许多目前无法治愈的疾病患者的临床治疗带来巨大希望。
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引用次数: 0
COVID-19 has triggered a new century of vaccination and infection control for the benefit of all mankind COVID-19开启了疫苗接种和感染控制的新世纪,造福全人类
IF 5.3 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2021-06-01 DOI: 10.1093/pcmedi/pbab010
B. Marshall
Modern safe vaccinations were pioneered in 1796 by Edward Jenner in England, when he noticed that milkmaids had beautiful complexions, clear of the blemishes from smallpox scars. This was attributed to their exposure to ‘cowpox’ in localised blisters, which seemed to protect them from the more severe and often fatal ‘smallpox’. In the twentieth century, the importance of immunity was emphasised by the very first Nobel Prize in Medicine, awarded to Emil Adolf von Bering who recognised the therapeutic role of antibodies in blood,1 using plasma from a recovered human (or horse) to protect and treat diphtheria, and eventually inventing the diphtheria vaccine in 1907. The first vaccines were simply made, being denatured protein extracts of live cultured bacteria, so there was no danger of causing the disease from the vaccination. Diphtheria-Pertussis-Tetanus (DPT) vaccine has long been available and is given to infants, making these three dreaded diseases of children uncommon in Western countries. My first personal experience with vaccination was as a 6-year-old (school grade 1) with my mother and 3-yearold brother attending the town hall in Kalgoorlie, Western Australia, for a mass polio vaccination administering the Salk vaccine. I remember that the vaccine was in a 50 ml multiple use bottle containing an estimated 25 dosages of 2 ml. The hall was pandemonium, with lines of people and numerous crying children. Hygiene in the stuffy, packed hall was less than ideal, the multiuse needles simply being soaked in alcohol for sterilisation between patients, becoming blunt and unsafe for use. But there had been at least a 12-month delay before the Salk vaccine could be used in Australia, as one of the early batches from Cutter Labs USA was withdrawn. The virus antigen made from cultured polio virus had not been sterilised adequately in 1955, resulting in more than 250 cases of actual polio in the USA. This caused the FDA to go on high alert, insisting on more stringent manufacturing and quality control procedures, followed by large-scale phase 1, 2 and 3 testing for all new vaccines. The concept is that, because vaccines are given to healthy people, a one-in-a-million incidence of severe side effects (or death) may be too much, even when preventing a dangerous disease such as polio or more recently COVID-19. Attenuated live polio vaccine replaced the Salk injected vaccine after 1960. Under the umbrella of the school vaccination programme, I received the new format whereby a drop of the pink vaccine was placed on a sugar cube and then eaten. The success of the new Sabin vaccine was its simplicity and oral format. After all, polio is an enterovirus, and I suppose family members could be infected with the live vaccine strain if schoolchildren experienced a very mild gastrointestinal illness at home. The live vaccination trivalent Sabin strain could cause overt polio in very few cases so that, as the actual wild-strain polio became extremely rare, vaccinations
1796年,英国的爱德华·詹纳(Edward Jenner)发现挤牛奶的女工肤色美丽,没有天花疤痕留下的污点,于是开创了现代安全疫苗接种的先河。这是由于他们在局部水泡中暴露于“牛痘”,这似乎可以保护他们免受更严重且往往致命的“天花”的侵害。20世纪,第一个诺贝尔医学奖强调了免疫的重要性,该奖项授予了埃米尔·阿道夫·冯·白令,他认识到血液中抗体的治疗作用,1使用康复的人(或马)的血浆来保护和治疗白喉,并最终在1907年发明了白喉疫苗。第一批疫苗是简单制作的,是由活培养细菌的变性蛋白质提取物制成的,因此接种疫苗没有引起疾病的危险。白喉-百日咳-破伤风(DPT)疫苗很早就有了,而且是给婴儿接种的,这使得这三种可怕的儿童疾病在西方国家并不常见。我第一次接触疫苗是在6岁的时候(小学一年级),当时我的母亲和3岁的弟弟在西澳大利亚州卡尔古利的市政厅参加大规模脊髓灰质炎疫苗接种活动,接种索尔克疫苗。我记得疫苗装在一个50毫升的多次使用的瓶子里,估计每2毫升装25剂。大厅里一片混乱,人们排着队,还有许多哭泣的孩子。在闷热拥挤的大厅里,卫生状况并不理想,多用途针头只是在酒精中浸泡,以便在病人之间消毒,使用起来变得钝钝且不安全。但是,至少在12个月之后,Salk疫苗才能在澳大利亚使用,因为美国卡特实验室的早期批次之一被撤回。1955年,由培养的脊髓灰质炎病毒制成的病毒抗原没有充分消毒,导致美国实际发生250多例脊髓灰质炎病例。这使得FDA保持高度警惕,坚持更严格的生产和质量控制程序,随后对所有新疫苗进行大规模的1、2和3期测试。其理念是,由于疫苗是给健康人接种的,即使在预防脊髓灰质炎或最近的COVID-19等危险疾病时,百万分之一的严重副作用(或死亡)发生率也可能过高。1960年后,脊髓灰质炎减毒活疫苗取代了索尔克注射疫苗。在学校疫苗接种计划的保护下,我接受了一种新的形式,将一滴粉红色的疫苗放在方糖上,然后食用。新Sabin疫苗的成功之处在于它的简单性和口服形式。毕竟,小儿麻痹症是一种肠道病毒,我认为,如果学童在家中出现非常轻微的胃肠道疾病,家庭成员可能会感染这种活疫苗菌株。三价Sabin活疫苗株在极少数情况下会引起明显的脊髓灰质炎,因此,当实际的野生脊髓灰质炎株变得极其罕见时,疫苗株脊髓灰质炎变得相对更常见。因此,大多数脊髓灰质炎疫苗接种再次使用更新的Sabin二价疫苗模型,将疫苗引起的脊髓灰质炎病例减少到接近零1995年,我应莫里斯·希勒曼(Maurice Hilleman)博士的邀请前往费城,他开发了许多目前使用的常见疫苗,最著名的是麻疹、腮腺炎、风疹(MMR)疫苗。为了研制疫苗,他利用他受感染的女儿的非传统来源分离出腮腺炎病毒。那次访问使我看到了生产疫苗的许多可能性,从嵌合减毒病毒到鼻吸入,甚至是转基因香蕉等食品中的疫苗的“圣杯”。早在2005年获得诺贝尔奖(因幽门螺杆菌和消化性溃疡)之前,我就在泰国获得了玛希隆亲王医学奖。这是亚洲
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引用次数: 0
AI based colorectal disease detection using real-time screening colonoscopy 基于人工智能的结直肠疾病实时筛查结肠镜检查
IF 5.3 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2021-05-20 DOI: 10.1093/pcmedi/pbab013
Jia-Ling Jiang, Qianrong Xie, Zhuo Cheng, Jianqiang Cai, Tian Xia, Hang Yang, Bo Yang, Hui-min Peng, Xue-song Bai, Mingque Yan, Xue Li, Jun Zhou, Xuan Huang, Liang Wang, Haiyan Long, Pingxi Wang, Yanpeng Chu, Fanwei Zeng, Xiu-wei Zhang, Guangyu Wang, Fanxin Zeng
Abstract Colonoscopy is an effective tool for early screening of colorectal diseases. However, the application of colonoscopy in distinguishing different intestinal diseases still faces great challenges of efficiency and accuracy. Here we constructed and evaluated a deep convolution neural network (CNN) model based on 117 055 images from 16 004 individuals, which achieved a high accuracy of 0.933 in the validation dataset in identifying patients with polyp, colitis, colorectal cancer (CRC) from normal. The proposed approach was further validated on multi-center real-time colonoscopy videos and images, which achieved accurate diagnostic performance on detecting colorectal diseases with high accuracy and precision to generalize across external validation datasets. The diagnostic performance of the model was further compared to the skilled endoscopists and the novices. In addition, our model has potential in diagnosis of adenomatous polyp and hyperplastic polyp with an area under the receiver operating characteristic curve of 0.975. Our proposed CNN models have potential in assisting clinicians in making clinical decisions with efficiency during application.
结肠镜检查是早期筛查结直肠疾病的有效工具。然而,结肠镜检查在区分不同肠道疾病中的应用在效率和准确性方面仍面临很大的挑战。本文基于来自16 004个人的117 055张图像构建并评估了一个深度卷积神经网络(CNN)模型,该模型在验证数据集中对息肉、结肠炎、结直肠癌(CRC)患者与正常人的识别准确率达到0.933。在多中心实时结肠镜检查视频和图像上进一步验证了该方法,在检测结直肠疾病方面取得了准确的诊断性能,具有较高的准确性和精密度,可以跨外部验证数据集进行推广。将该模型的诊断性能与熟练内窥镜医师和新手进行比较。此外,我们的模型在腺瘤性息肉和增生性息肉的诊断中具有潜力,受者工作特征曲线下面积为0.975。我们提出的CNN模型在帮助临床医生在应用过程中有效地做出临床决策方面具有潜力。
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引用次数: 1
Spaceflight decelerates the epigenetic clock orchestrated with a global alteration in DNA methylome and transcriptome in the mouse retina. 太空飞行减缓了小鼠视网膜中与DNA甲基组和转录组整体改变相协调的表观遗传时钟。
IF 5.3 4区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2021-05-17 eCollection Date: 2021-06-01 DOI: 10.1093/pcmedi/pbab012
Zhong Chen, Seta Stanbouly, Nina C Nishiyama, Xin Chen, Michael D Delp, Hongyu Qiu, Xiao W Mao, Charles Wang

Astronauts exhibit an assortment of clinical abnormalities in their eyes during long-duration spaceflight. The purpose of this study was to determine whether spaceflight induces epigenomic and transcriptomic reprogramming in the retina or alters the epigenetic clock. The mice were flown for 37 days in animal enclosure modules on the International Space Station; ground-based control animals were maintained under similar housing conditions. Mouse retinas were isolated and both DNA methylome and transcriptome were determined by deep sequencing. We found that a large number of genes were differentially methylated with spaceflight, whereas there were fewer differentially expressed genes at the transcriptome level. Several biological pathways involved in retinal diseases such as macular degeneration were significantly altered. Our results indicated that spaceflight decelerated the retinal epigenetic clock. This study demonstrates that spaceflight impacts the retina at the epigenomic and transcriptomic levels, and such changes could be involved in the etiology of eye-related disorders among astronauts.

在长时间的太空飞行中,宇航员的眼睛会出现各种临床异常。这项研究的目的是确定太空飞行是否会诱导视网膜的表观基因组和转录组重编程或改变表观遗传时钟。这些老鼠在国际空间站的动物封闭舱中飞行了37天;地面上的对照动物也在类似的饲养条件下饲养。分离小鼠视网膜,采用深度测序法测定DNA甲基组和转录组。我们发现大量基因在太空飞行中被差异甲基化,而在转录组水平上差异表达的基因较少。与黄斑变性等视网膜疾病相关的几种生物学途径发生了显著改变。我们的研究结果表明,太空飞行使视网膜表观遗传时钟减速。这项研究表明,太空飞行在表观基因组和转录组水平上影响视网膜,这种变化可能涉及宇航员眼睛相关疾病的病因学。
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引用次数: 6
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Precision Clinical Medicine
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