cancers

癌症
  • 文章类型: Journal Article
    评估ChatGPT的癌症治疗建议(REC)与国家综合癌症网络(NCCN)指南和专家意见的质量和一致性。
    三位泌尿科医师于2023年10月进行了定量和定性评估,分析了ChatGPT-4和ChatGPT-3.5对108前列腺的反应,肾,和膀胱癌提示使用两个零射提示模板。绩效评估涉及计算五个比率:专家批准/专家不同意和NCCN对齐的RECs与总ChatGPTRECs以及NCCN的覆盖率和依从率。考虑到正确性,专家在1-5个量表上对响应的质量进行了评级,全面性,特异性,和适当性。
    ChatGPT-4在前列腺癌查询中的表现优于ChatGPT-3.5,平均字数为317.3对124.4(p<0.001)和6.1对3.9REC(p<0.001)。其评估者批准的REC比率(96.1%与89.4%)并与NCCN指南保持一致(76.8%与49.1%,p=0.001)在所有质量维度上都是优异的,得分明显更好。在涵盖三种癌症的108个提示中,ChatGPT-4每例平均产生6.0个REC,评价者的支持率为88.5%,86.7%NCCN一致性,只有9.5%的分歧率。它在正确性方面取得了很高的分数(4.5),全面性(4.4),特异性(4.0),和适当性(4.4)。跨癌症类型的亚组分析,疾病状态,并报告了不同的提示模板。
    ChatGPT-4在提供符合临床指南和专家意见的准确和详细的泌尿系癌症治疗建议方面表现出显著的改善。然而,认识到人工智能工具并非没有缺陷,应该谨慎使用,这一点至关重要。ChatGPT可以补充,但不能取代,来自医疗保健专业人员的个性化建议。
    UNASSIGNED: To assess the quality and alignment of ChatGPT\'s cancer treatment recommendations (RECs) with National Comprehensive Cancer Network (NCCN) guidelines and expert opinions.
    UNASSIGNED: Three urologists performed quantitative and qualitative assessments in October 2023 analyzing responses from ChatGPT-4 and ChatGPT-3.5 to 108 prostate, kidney, and bladder cancer prompts using two zero-shot prompt templates. Performance evaluation involved calculating five ratios: expert-approved/expert-disagreed and NCCN-aligned RECs against total ChatGPT RECs plus coverage and adherence rates to NCCN. Experts rated the response\'s quality on a 1-5 scale considering correctness, comprehensiveness, specificity, and appropriateness.
    UNASSIGNED: ChatGPT-4 outperformed ChatGPT-3.5 in prostate cancer inquiries, with an average word count of 317.3 versus 124.4 (p < 0.001) and 6.1 versus 3.9 RECs (p < 0.001). Its rater-approved REC ratio (96.1% vs. 89.4%) and alignment with NCCN guidelines (76.8% vs. 49.1%, p = 0.001) were superior and scored significantly better on all quality dimensions. Across 108 prompts covering three cancers, ChatGPT-4 produced an average of 6.0 RECs per case, with an 88.5% approval rate from raters, 86.7% NCCN concordance, and only a 9.5% disagreement rate. It achieved high marks in correctness (4.5), comprehensiveness (4.4), specificity (4.0), and appropriateness (4.4). Subgroup analyses across cancer types, disease statuses, and different prompt templates were reported.
    UNASSIGNED: ChatGPT-4 demonstrated significant improvement in providing accurate and detailed treatment recommendations for urological cancers in line with clinical guidelines and expert opinion. However, it is vital to recognize that AI tools are not without flaws and should be utilized with caution. ChatGPT could supplement, but not replace, personalized advice from healthcare professionals.
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  • 文章类型: Editorial
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  • 文章类型: Journal Article
    肥胖和肥胖相关蛋白(FTO),最早鉴定的mRNAN6-甲基腺苷(M6A)脱甲基酶,已知在几个生物过程中发挥关键作用。因此,FTO是抗癌治疗的有希望的靶标。了解FTO靶标的生物学功能和调节机制可以作为药物开发的指南。尽管在开发FTO抑制剂方面做出了巨大努力,到目前为止,还没有特异性的小分子抑制剂进入临床试验。在这份手稿中,我们回顾了FTO与各种癌症之间的关系,从药物化学和其他领域的角度开发了针对FTO靶标的小分子抑制剂,并描述了它们的结构优化过程和结构-活性关系,为他们未来的发展方向提供线索。
    [方框:见正文]。
    Adiposity and obesity-related proteins (FTO), the earliest identified mRNA N6-methyladenosine (m6A) demethylases, are known to play crucial roles in several biological processes. Therefore, FTO is a promising target for anticancer treatment. Understanding the biological functions and regulatory mechanisms of FTO targets can serve as guidelines for drug development. Despite significant efforts to develop FTO inhibitors, no specific small-molecule inhibitors have entered clinical trials so far. In this manuscript, we review the relationship between FTO and various cancers, the small-molecule inhibitors developed against FTO targets from the perspective of medicinal chemistry and other fields, and describe their structural optimization process and structure-activity relationship, providing clues for their future development direction.
    [Box: see text].
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  • 文章类型: Journal Article
    甲状腺结节(TNs)已成为中国最常见的内分泌疾病。细针抽吸(FNA)仍然是评估TN恶性肿瘤的标准诊断方法,尽管大多数FNA结果表明是良性疾病。平衡诊断准确性,同时减轻良性结节患者的过度诊断带来了重大的临床挑战。精确,非侵入性,和高通量筛查方法用于高风险TN诊断是非常需要的,但仍未被探索。开发此类方法可以提高超声成像等非侵入性方法的准确性,并减少由侵入性程序引起的良性结节患者的过度诊断。在这里,我们研究了掺杂金的锆基金属有机骨架(ZrMOF/Au)纳米结构在甲状腺疾病代谢谱中的应用。这种方法能够以高通量高效提取尿液代谢物指纹,低背景噪声,和再现性。利用偏最小二乘判别分析和四种机器学习模型,包括神经网络(NN),随机森林(RF),逻辑回归(LR),和支持向量机(SVM),我们使用诊断小组对甲状腺癌(TC)和低危TNs进行鉴别诊断的准确率提高(98.6%).通过对代谢差异的分析,确定良性结节和恶性肿瘤之间的潜在通路变化。这项工作探索了使用ZrMOF/Au辅助LDI-MS平台快速筛查甲状腺疾病的潜力,为甲状腺恶性肿瘤的无创筛查提供了一种潜在的方法。将这种方法与超声等成像技术相结合,可以增强非侵入性诊断方法用于恶性肿瘤筛查的可靠性。有助于防止不必要的侵入性手术,并降低良性结节患者过度诊断和过度治疗的风险。
    Thyroid nodules (TNs) have emerged as the most prevalent endocrine disorder in China. Fine-needle aspiration (FNA) remains the standard diagnostic method for assessing TN malignancy, although a majority of FNA results indicate benign conditions. Balancing diagnostic accuracy while mitigating overdiagnosis in patients with benign nodules poses a significant clinical challenge. Precise, noninvasive, and high-throughput screening methods for high-risk TN diagnosis are highly desired but remain less explored. Developing such approaches can improve the accuracy of noninvasive methods like ultrasound imaging and reduce overdiagnosis of benign nodule patients caused by invasive procedures. Herein, we investigate the application of gold-doped zirconium-based metal-organic framework (ZrMOF/Au) nanostructures for metabolic profiling of thyroid diseases. This approach enables the efficient extraction of urine metabolite fingerprints with high throughput, low background noise, and reproducibility. Utilizing partial least-squares discriminant analysis and four machine learning models, including neural network (NN), random forest (RF), logistic regression (LR), and support vector machine (SVM), we achieved an enhanced diagnostic accuracy (98.6%) for discriminating thyroid cancer (TC) from low-risk TNs by using a diagnostic panel. Through the analysis of metabolic differences, potential pathway changes between benign nodule and malignancy are identified. This work explores the potential of rapid thyroid disease screening using the ZrMOF/Au-assisted LDI-MS platform, providing a potential method for noninvasive screening of thyroid malignant tumors. Integrating this approach with imaging technologies such as ultrasound can enhance the reliability of noninvasive diagnostic methods for malignant tumor screening, helping to prevent unnecessary invasive procedures and reducing the risk of overdiagnosis and overtreatment in patients with benign nodules.
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  • 文章类型: Journal Article
    背景:核孔复合物(NPC)是复杂且动态的蛋白质结构,其跨越核膜并充当在细胞核和细胞质之间运输分子的看门人。NPC包含多达30种称为核孔蛋白(NUP)的不同蛋白质。然而,越来越多的研究表明,NPC在基因调控中起着重要作用,病毒感染,癌症,有丝分裂,遗传性疾病,肾脏疾病,免疫系统疾病,以及退化性神经和肌肉病变。
    目的:在这篇综述中,介绍了NPCs的结构和功能。然后我们描述了NPCs各组分的生理和病理作用,为将来的临床应用提供了方向。
    方法:本文综述了PubMed的相关文献。
    结论:这篇综述总结了目前关于NPCs在人体生理和病理学中的意义的研究。强调NPC相关疾病的机制基础。
    BACKGROUND: Nuclear pore complexes (NPCs) are sophisticated and dynamic protein structures that straddle the nuclear envelope and act as gatekeepers for transporting molecules between the nucleus and the cytoplasm. NPCs comprise up to 30 different proteins known as nucleoporins (NUPs). However, a growing body of research has suggested that NPCs play important roles in gene regulation, viral infections, cancer, mitosis, genetic diseases, kidney diseases, immune system diseases, and degenerative neurological and muscular pathologies.
    OBJECTIVE: In this review, we introduce the structure and function of NPCs. Then We described the physiological and pathological effects of each component of NPCs which provide a direction for future clinical applications.
    METHODS: The literatures from PubMed have been reviewed for this article.
    CONCLUSIONS: This review summarizes current studies on the implications of NPCs in human physiology and pathology, highlighting the mechanistic underpinnings of NPC-associated diseases.
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  • 文章类型: Journal Article
    紧急直接获得全科医生(GP)的诊断服务是一种新的途径,可以捕获由于模糊的症状表现而可能错过的任何癌症诊断。因此,全科医生应注意NHSEngland提到的关键症状,这些症状应促使紧急直接转诊胸部X光检查(CXR),胸部计算机断层扫描(CT),MRI大脑,超声(美国)腹部和骨盆,腹部和骨盆CT.通过实施这种方法,我们可以大大减少诊断时间,同时尽量减少在开始调查之前访问全科医生和专家预约的次数。然而,只有当诊断扫描的使用得到改善时,这种途径的使用才能得到改善.这需要通过确保该国所有全科医生都可以直接请求MRI大脑来实现,胸部CT,腹部,还有骨盆.需要进一步研究紧急直接访问途径的影响,以及调查没有获得这些重要诊断服务的全科医生的数量,以充分改善和衡量这种转诊途径的进展。
    Urgent direct access to diagnostic services for general practitioners (GPs) is a new pathway to capture any cancer diagnoses that may have been missed due to vague symptom presentations. Hence, GPs should look out for the key symptoms mentioned by NHS England that should prompt urgent direct access referrals for chest X-ray (CXR), computed tomography (CT) chest, MRI brain, ultrasound (US) abdomen and pelvis, and CT abdomen and pelvis. By implementing this approach, we can significantly reduce the time to diagnosis, while minimizing the number of visits to GP and specialist appointments prior to initiating investigations. However, the use of this pathway can only improve if access to diagnostic scans is improved. This needs to be done by ensuring all GPs in the country have access to directly request MRI brains, CT chest, abdomen, and pelvis. Further research into the impact of the urgent direct access pathway as well as investigating the number of GPs without access to these vital diagnostic services is required to fully improve and measure the progress of this referral pathway.
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  • 文章类型: Journal Article
    不幸的是,尽管在预防和治疗疾病方面取得了相当大的进展,但心血管疾病和癌症仍然是发达国家和发展中国家死亡的主要原因。胰岛素抵抗(IR)与相关的高胰岛素血症(Hypein)是一种无声的大流行,其患病率在发达国家和发展中国家都在不断增长,现在超过了总人口的51%。IR/Hypein,尽管大量的科学文献支持其对2型糖尿病的发展的不利作用,心血管改变,肿瘤,神经系统疾病,和细胞衰老,尚未被认为是独立的风险因素,因此,没有在普通人群中进行筛查,也没有得到充分的治疗。现在有很多物质,毒品,和天然物质,与错误生活方式的纠正有关,可以帮助减少IR/Hypein。我们相信,现在是针对这一关键风险因素实施预防计划的时候了。因此,本手稿旨在强调IR/Hypein是2型糖尿病的独立危险因素,心血管疾病,癌症,细胞衰老,和神经精神疾病,通过有关该主题的现有科学文献来支持我们的信念。
    Unfortunately, cardiovascular diseases and cancers are still the leading causes of death in developed and developing countries despite the considerable progress made in the prevention and treatment of diseases. Maybe we missed something? Insulin resistance (IR) with associated hyperinsulinemia (Hypein) is a silent pandemic whose prevalence is continually growing in developed and developing countries, now exceeding 51% of the general population. IR/Hypein, despite the vast scientific literature supporting its adverse action on the development of type 2 diabetes, cardiovascular alterations, tumors, neurological disorders, and cellular senescence, is not yet considered an independent risk factor and, therefore, is not screened in the general population and adequately treated. There are now numerous substances, drugs, and natural substances that, in association with the correction of a wrong lifestyle, can help to reduce IR/Hypein. We are convinced that the time has come to implement a prevention plan against this critical risk factor. Therefore, this manuscript aims to highlight IR/Hypein as an independent risk factor for type 2 diabetes, cardiovascular diseases, cancers, cellular senescence, and neuropsychiatric disorders, supporting our conviction with the available scientific literature on the topic.
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  • 文章类型: Journal Article
    与病原体感染相关的癌症逐渐成为全球人类健康的重要威胁,研究病原体致癌机理具有重要意义。当前的机理研究依赖于动物和二维(2D)细胞培养模型,但是传统方法已被证明不足以快速模拟由新病原体引起的疾病。因此,研究重点已经转移到类器官模型上,可以在体外复制靶组织或器官的结构和遗传特征,为研究病原体诱导的致癌机制提供了新的平台。本文综述了类器官技术在四种病原体相关癌症研究中的应用:与幽门螺杆菌相关的胃癌,与乙型肝炎病毒或丙型肝炎病毒相关的肝癌,由大肠杆菌引起的结直肠癌,以及与人乳头瘤病毒有关的宫颈癌。这篇综述还提出了类器官技术在未来优化类器官模型和推进与病原体感染相关的癌症治疗方面的一些局限性。
    Cancers associated with pathogen infections are gradually becoming important threats to human health globally, and it is of great significance to study the mechanisms of pathogen carcinogenesis. Current mechanistic studies rely on animal and two-dimensional (2D) cell culture models, but traditional methods have been proven insufficient for the rapid modeling of diseases caused by new pathogens. Therefore, research focus has shifted to organoid models, which can replicate the structural and genetic characteristics of the target tissues or organs in vitro, providing new platforms for the study of pathogen-induced oncogenic mechanisms. This review summarizes the application of organoid technology in the studies of four pathogen-associated cancers: gastric cancer linked to Helicobacter pylori, liver cancer associated with hepatitis B virus or hepatitis C virus, colorectal cancer caused by Escherichia coli, and cervical cancer related to human papillomavirus. This review also proposes several limitations of organoid technology to optimize organoid models and advance the treatment of cancer associated with pathogen infections in the future.
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  • 文章类型: Journal Article
    Ataxin-2(ATXN2)最初是在脊髓小脑共济失调2型(SCA2)的背景下发现的,但它已经成为各种神经退行性疾病的关键角色。这篇综述探讨了ATXN2在人类疾病中的多方面作用。揭示其不同的分子和细胞途径。ATXN2对疾病的影响超出了功能结果;它主要与各种RNA结合蛋白(RBP)相互作用,以调节疾病中转录后基因表达的不同阶段。随着研究的进展,还发现ATXN2在各种癌症的发展中起重要作用,包括乳腺癌,胃癌,胰腺癌,结肠癌,还有食道癌.这种全面的探索强调了ATXN2在疾病发病机理中的关键作用,值得科学界进一步研究。通过回顾ATXN2在疾病中的调节功能的最新发现,这篇文章帮助我们了解与这种有趣的蛋白质有关的一系列人类疾病的复杂分子机制。
    Ataxin-2 (ATXN2) was originally discovered in the context of spinocerebellar ataxia type 2 (SCA2), but it has become a key player in various neurodegenerative diseases. This review delves into the multifaceted roles of ATXN2 in human diseases, revealing its diverse molecular and cellular pathways. The impact of ATXN2 on diseases extends beyond functional outcomes; it mainly interacts with various RNA-binding proteins (RBPs) to regulate different stages of post-transcriptional gene expression in diseases. With the progress of research, ATXN2 has also been found to play an important role in the development of various cancers, including breast cancer, gastric cancer, pancreatic cancer, colon cancer, and esophageal cancer. This comprehensive exploration underscores the crucial role of ATXN2 in the pathogenesis of diseases and warrants further investigation by the scientific community. By reviewing the latest discoveries on the regulatory functions of ATXN2 in diseases, this article helps us understand the complex molecular mechanisms of a series of human diseases related to this intriguing protein.
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  • 文章类型: Journal Article
    髓源性生长因子(MYDGF)是一种新型分泌蛋白,具有有效的抗凋亡和组织修复特性,存在于近140个人类组织和细胞系中。在口腔上皮和皮肤中丰度最高。最初,在骨髓来源的单核细胞和巨噬细胞中发现MYDGF用于心肌梗死后的心脏保护和修复。随后的研究表明,MYDGF在其他心血管疾病中起着重要作用(例如,动脉粥样硬化和心力衰竭),代谢紊乱,肾脏疾病,自身免疫性/炎症性疾病,和癌症。尽管基本机制尚未得到充分探索,MYDGF在健康和疾病中的作用可能涉及细胞凋亡和增殖,组织修复和再生,抗炎,和糖脂代谢调节。在这次审查中,我们总结了目前在了解MYDGF在健康和疾病中的作用方面的进展,专注于它的结构,功能和机制。图形摘要显示了MYDGF在不同器官和疾病中的当前作用(图。1).
    Myeloid-derived growth factor (MYDGF) is a novel secreted protein with potent antiapoptotic and tissue-repairing properties that is present in nearly 140 human tissues and cell lines, with the highest abundance in the oral epithelium and skin. Initially, MYDGF was found in bone marrow-derived monocytes and macrophages for cardioprotection and repair after myocardial infarction. Subsequent studies have shown that MYDGF plays an important role in other cardiovascular diseases (e.g., atherosclerosis and heart failure), metabolic disorders, renal disease, autoimmune/inflammatory disorders, and cancers. Although the underlying mechanisms have not been fully explored, the role of MYDGF in health and disease may involve cell apoptosis and proliferation, tissue repair and regeneration, anti-inflammation, and glycolipid metabolism regulation. In this review, we summarize the current progress in understanding the role of MYDGF in health and disease, focusing on its structure, function and mechanisms. The graphical abstract shows the current role of MYDGF in different organs and diseases (Fig. 1).
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