Ferroptosis, M6A and immune checkpoint-related gene expression in the middle temporal gyrus of the Alzheimer's disease brain

Qinfeng Liu, Fan Yang, Sijia Wu, Kai Yuan, Liyu Huang, Suping Cai *.

Alzheimer's disease (AD) is a common genetically related cognitive disorder. Studies have shown that ferroptosis, N⁶-Methyladenosine (M6A) and immune checkpoint are related to the development of AD. However, the effects of these three gene pathways on AD progression are still unclear. Here, we used genes expressed in the middle temporal gyrus (MTG) to study the differences in ferroptosis, M6A and immune checkpoint-related gene in 97 Alzheimer's disease and 98 normal controls (NC). We then conducted correlation analysis between ferroptosis, M6A and immune checkpoint-related gene expression levels to investigate the relationship between these genes and AD. Compared to the NC, the gene expression from MTG in AD are as follows: (1) in ferroptosis related genes, the expression of CARS, CDKN1A, HSPB1, MT1G, EMC2, SAT1 and SLC1A5 was increased, while the expression of ACSL4, ATP5MC3, CSID1, CS, DPP4, GLS2 and GPX4 was decreased; (2) in M6A-related genes, the expression of HNRNPA2B1, IGF2BP2, RBM15B and YTHDC1 was increased, while the expression of FTO, YTHDC2 and YTHDF2 was decreased; (3) the expression of immune checkpoint-related genes (including CTLA4, HAVCR2 and LAG3) was increased. Further, we determined related gene pathways among these genes by conducting a literature review. By verifying the dataset, we can well verify our results and prove that our results have good robustness. We concluded of gene expression that a complete set of ferroptosis, M6A and immune checkpoint regulatory mechanisms is activated in the MTG during AD development.

阿尔茨海默病（Alzheimer's disease, AD）是一种常见的遗传相关认知障碍。研究表明铁死亡、N⁶-甲基腺苷（N⁶-Methyladenosine, M6A）和免疫检查点与AD的发生有关。然而，这三种基因涉及到的通路对AD进展的影响仍不清楚。在这里，我们利用颞中回（Middle temporal gyrus, MTG）表达的基因来研究97名阿尔茨海默病和98名正常对照（Normal controls, NC）中铁死亡、M6A和免疫检查点相关基因的差异。然后我们对铁死亡、M6A 和免疫检查点相关基因表达水平进行相关性分析，以探讨这些基因与 AD 之间的关系。与NC相比，AD中MTG的基因表达量如下：（1）铁死亡相关基因中，CARS、CDKN1A、HSPB1、MT1G、EMC2、SAT1和SLC1A5的表达量增加，而ACSL4、ATP5MC3、CSID1、CS、DPP4、GLS2 和 GPX4 降低；(2)M6A相关基因中, HNRNPA2B1、IGF2BP2、RBM15B、YTHDC1表达量升高,而FTO、YTHDC2、YTHDF2表达量降低; (3)免疫检查点相关基因(包括CTLA4、HAVCR2和LAG3)表达增加。此外，我们通过文献综述确定了这些基因所涉及到的通路。相关分析和文献研究表明，MTG中铁死亡、m6A和免疫检查点相关基因的异常表达与AD的发生密切相关，揭示了在分子水平上AD可能得发病机制。

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Defining a radiomics feature selection method for predicting response to transarterial chemoembolization in hepatocellular carcinoma patients

Helen Zhang, Li Yang, Amanda Laguna, Jing Wu, Beiji Zou, Alireza Mohseni, Rajat S. Chandra, Tej I. Mehta, Hossam A. Zaki, Paul Zhang, Zhicheng Jiao, Ihab R. Kamel, Harrison X. Bai *. 

Aim: To assess the utility of different radiomics feature selection methods in predicting transarterial chemoembolization (TACE) response in hepatocellular carcinoma (HCC) patients.

Materials and methods: This study employed a dataset of 136 paired MR T1-weighted contrast-enhanced abdominal images with liver tumor masks before and after TACE. TACE response for each image pair was classified by European Association for the Study of the Liver (EASL) and modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines. 100D feature vectors were generated for the paired tumor areas. Eighteen existing feature selection methods were employed to select the top-k features to train and test a non-linear support vector machine (SVM) with a Gaussian kernel. Five-cross validation was performed to identify the highest performing feature selection methods.

Results: For all benchmarks, a L0-based method selecting the top-5 or top-10 features achieved the highest performance. For images classified with EASL criteria that were analyzed with the L0-based method, the accuracy (ACC), area under curve (AUC), and balanced F score (F1-score) were 0.75 ± 0.06, 0.75 ± 0.09, and 0.80 ± 0.05, respectively. For images classified with mRECIST criteria that were analyzed with the L0-based method, the ACC, AUC, and F1-score were 0.75 ± 0.07, 0.71 ± 0.16, and 0.82 ± 0.04, respectively.

Conclusion: A L0-based method that selected the top-5/10 most important features predicted TACE response in HCC patients with the highest accuracy under both EASL and mRECIST criteria. This proof-of-concept investigation represents a step forward in the development of a reliable clinical decision-making tool for management of intermediate HCC patients undergoing TACE.

肝细胞癌 (Hepatocellular carcinoma, HCC) 是全球癌症相关死亡的第四大原因, 许多HCC患者在诊断时为中期或晚期阶段，错失手术治疗手段。目前，治疗该患者群体的金标准是经动脉化疗栓塞 (Transarterial chemoembolization, TACE)。由于肿瘤负荷和肝功能等患者个体特征不同，导致患者对TACE治疗反应也存在很大差异。影像组学在机器学习中的应用可以辅助TACE候选对象的选择和预后预测。目前，有许多不同的特征选择方法可以产生高度可变的模型性能。对不同特征选择方法的评估可能有助于提高基于影像组学的模型的整体性能，并突出某些特征在分类中的作用。本研究纳入了TACE前后136个配对MR T1加权对比增强腹部图像以及肝肿瘤掩模的数据集。每个病例对TACE治疗反应均由欧洲肝脏研究协会(EASL)和修改后的实体瘤反应评估标准 (mRECIST) 指南进行分类。配对的肿瘤区域生成100D特征向量。采用十八种现有的特征选择方法来选择top-k个特征来训练和测试具有高斯核的非线性支持向量机（SVM）。进行五交叉验证以确定性能最高的特征选择方法。对于所有基准测试，基于L0的方法选择前5或前10特征实现了最高性能。对于使用基于L0的方法分析的EASL标准分类的图像，准确度 (ACC)、曲线下面积 (AUC) 和平衡 F 分数 (F1分数) 分别为0.75±0.06、0.75±0.09和0.80±0.05。对于使用基于L0的方法分析的mRECIST 标准分类的图像，ACC、AUC 和 F1 分数分别为0.75±0.07、0.71±0.16和0.82±0.04。基于L0的方法选择前5/10个最重要的特征，在EASL和mRECIST标准下预测 HCC患者的TACE反应，准确性最高。这项研究代表了在开发用于管理接受 TACE的HCC中期患者的可靠临床决策工具方面向前迈出了一步。

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Metabolite changes and impact factors in mild traumatic brain injury patients: A review on magnetic resonance spectroscopy

Sihong Huang *, Yanjun Lyu, Tianming Liu, Dajiang Zhu.

The high incidence of mild traumatic brain injury (mTBI) and the associated postconcussion symptoms, such as headache and cognitive deficits, have captured the significant attention from researchers globally. Magnetic resonance spectroscopy (MRS), a non-invasively technique derived from Magnetic Resonance Imaging (MRI),provides a complement approach to investigating brain metabolites as biomarkers for in vivo pathophysiological changes following mTBI, which are not evident in traditional MRI or CT scans. However, the separate review of MRS in mTBI patients has been limited, given the myriad factors involved and wide spectrum of TBI severity. In this review, we first delve into metabolite changes after mTBI, highlighting a reduction in N-acetyl-aspartate (NAA) as a relatively stable marker associated with neuronal loss or disfunction following mTBI. We then discuss the varying results observed for different metabolites and enumerate possible factors contributing to theseinconsistent findings. These factors include variations in experimental methods, such as scanner types, acquisition methods, and region of interest. Additionally, we address subjects-specific factors, such as occupation, cause of injury, control group selection, injury stage, severity, the number of traumatic events, and the assessment of clinical features. Finally, we discuss the trend for future research in this field.

轻度脑外伤（mild traumatic brain injury, mTBI）的高发病率和相关的脑震荡后症状（如：头痛和认知功能减退）引起了全球研究人员的极大关注。磁共振波谱 (Magnetic resonance spectroscopy, MRS) 是一种源自磁共振成像 (Magnetic resonance imaging, MRI) 的非侵入性技术，为研究大脑代谢物作为 mTBI 体内病理生理变化的生物标志物提供了一种补充方法，而这些变化在传统 MRI 或 CT 扫描中并不明显。然而，考虑到涉及的因素众多以及 TBI 严重程度的广泛性，对 mTBI 患者的 MRS 单独审查受到限制。在这篇综述中，我们首先深入研究 mTBI 患者大脑代谢物的变化，发现NAA在mTBI后一致性的减低，揭示了mTBI后的神经元损伤或功能异常，可以用作相对稳定的生物标志物，但其他代谢物结果存在明显差异，增高或是减低均有汇报。许多因素导致了这些结果的异质性，所以我们进一步对先前关于mTBI患者的MRS研究中造成结果不一致的原因进行了综述。主要列出了不同的实验方法，如扫描仪、采集方法和感兴趣区选择的异同；以及与受试者相关的因素，如职业，受伤原因，对照组的选择，疾病分期，疾病严重程度，创伤次数，以及临床特征的评估等对于结果的影响。最后，我们讨论了该领域未来研究的趋势。

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A review of dose prediction methods for tumor radiation therapy

Xiaoyan Kui, Fang Liu, Min Yang, Hao Wang, Canwei Liu, Dan Huang, Qinsong Li *, Liming Chen, Beiji Zou.

Radiation therapy (RT) is currently the main clinical treatment of tumors. Before treatment initiation, precise delineation of the planned target volume (PTV) and organs at risk (OAR) is essential. This segmentation, together with the dose prediction algorithm, aids in the calculation and evaluation of the dose distribution, and ultimatelyin the refinement of the treatment plan. To provide a comprehensive view of the current landscape of research on dose prediction methods, we meticulously collected and summarized papers published between 2017 and 2023. First, we present our rigorous literature search approach, providing a statistical analysis of the pooled papers and an elaborate overview of the evaluation metrics that are commonly and consistently employed in this domain. Then, we focus on a detailed survey of the evolutionary trajectories of dose prediction methods. This comprehensive investigation covers a spectrum ranging from traditional Knowledge-Based Planning (KBP) methods to emerging deep learning-based methods, which include input improvement methods, U-Net-based methods, GAN-based methods, and other deep learning-based methods. Throughout this exposition, we have carefully outlined the strengths and limitations inherent in these various approaches. Finally, we conclude with a summary of the primary challenges facing the field and propose several prospective research directions to effectively address them.

放射治疗（Radiation therapy, RT）作为肿瘤治疗的主要手段之一。在实施前，临床放疗医师和物理治疗师根据计算机断层扫描影像进行模拟放疗定位，对放疗靶区（Planned target volume, PTV）和危及器官（Organs at risk, OAR）进行细致分割至关重要。这种分割与剂量预测算法一起有助于剂量分布的计算和评估，并最终有助于治疗计划的细化。为了全面了解剂量预测方法的研究现状，我们收集和总结了2017年至2023年发表的论文。首先，我们提出了严格的文献检索方法，对合并的论文进行了统计分析和详细的概述。本研究涵盖了从传统的基于知识的规划（Knowledge-Based Planning, KBP）方法到新兴的基于深度学习（Deep learning, DL）的方法，其中包括改进模型输入的方法、基于 U-Net 的方法、基于 GAN 的方法和其他基于深度学习的方法。通过对现有剂量预测方法的广泛调查，本研究梳理了该领域的最新技术进展，并指出了一些亟待在未来研究中解决的关键挑战，包括罕见肿瘤类型数据不足、模型适用性和泛化性不足以及缺乏统一的评估指标。并据此提出了几个未来研究的关键方向：构建多中心大样本数据集，结合大模型提高模型的通用性，以及建立统一的评估指标标准。

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Lung cancer screening, diagnosis, and treatment: The radiologist's perspective

Bingqing Long, Zeng Xiong *, Manzo Habou.

Lung cancer is a significant contributor to cancer-related deaths worldwide. However, there are variations in lung cancer incidence and mortality rates across different regions. Lung cancer ranks as the top malignancy for both new cases and deaths in China, accounting for 18.06% of new cancer cases and 23.9% of cancer-related deaths. Overthe past decade, large-scale cohort clinical studies have confirmed that low-dose CT (LDCT) screening can reduce lung cancer mortality, primarily due to early diagnosis and early treatment. In recent years, an increasing number of medical institutions in China have initiated or planned LDCT lung cancer screening programs. However, there are significant differences in the understanding and diagnostic and treatment capabilities of LDCT lung cancer screening within the country. Demographic factors and cancer prevention policies influence disease incidence and treatment approaches. In light of these changes, imaging reports must adapt accordingly. This paper aimsto review the problems involved in lung nodule screening, diagnosis, and treatment stages from the radiologist'sperspective and suggest feasible solutions.

肺癌是全球癌症相关死亡的重要因素。然而，不同地区的肺癌发病率和死亡率存在差异。肺癌是我国新发病例和死亡人数最多的恶性肿瘤，占癌症新发病例的18.06%和癌症相关死亡的23.9%。过去十年，大规模队列临床研究证实，低剂量CT（Low-dose CT, LDCT）筛查通过早期诊断和早期治疗可以降低肺癌死亡率。但国内对LDCT肺癌筛查的认识、诊断和治疗能力存在显着差异。人口因素和癌症预防政策影响疾病的发病率和治疗方法。本文旨在从放射科医生的角度回顾肺结节筛查、诊断和治疗阶段涉及的问题，并提出可行的解决方案。在筛查阶段，作者关注了国内外肺癌筛查高危人群的界定、对女性非吸烟人群的关注、提出应针对性别差异按不同年龄标准来界定高危人群，以及使用人+人工智能的筛查模式、同质化培训及质量控制、肺癌筛查数据拓展挖掘应用三项有效措施来应对和分析海量的CT肺癌筛查数据；在诊断阶段，作者介绍了肺癌与非肺癌病变的鉴别诊断、早期肺癌的分类管理、中晚期肺癌影像学分期、多发肺结节的综合判断；在诊疗阶段，作者在过度诊疗、早期肺癌手术时机的选择、肺癌外科手术方式的选择、放射科门诊和多学科会诊等方面关注了影像学对临床诊疗的指导作用，强调肺结节的个性化管理和科普宣教，使患者能理性、科学地去看待疾病。在肺结节筛查和个性化管理过程中，作为放射科医生，在筛、诊、疗等多个环节均可以起到重要的作用。我们应关注到肺癌手术患者临床流行病学特点的变化，在临床工作多个环节中予以调整，使患者真正从临床实践的改善中获益。

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Magnetic resonance-guided focused ultrasound in intracranial diseases: Clinical applications and future directions

Haoxuan Lu, Yujue Zhong, Yongqin Xiong, Xiaoyu Wang, Jiayu Huang, Yan Li, Xin Lou*.

Magnetic resonance-guided focused ultrasound (MRgFUS) is a non-invasive technique for neuroregulation thatoffers several advantages, including non-invasiveness, no need for general anesthesia requirement, real-timetarget localization, and real-time temperature monitoring. Currently, the U.S. Food and Drug Administrationhas approved this technology for the treatment of essential tremor and Parkinson's disease, and its indications arecontinually expanding to encompass various intracranial diseases. In this article, we summarize clinical trials ofhigh-intensity FUS in the treatment of intracranial diseases. Next, we introduce the preclinical and clinical studieson low-intensity FUS-induced blood-brain barrier opening and neuromodulation. Finally, we discuss the challenges and future directions of this technology. This review aims to guide future clinical trials and provide newperspectives for investigating the neural mechanisms of MRgFUS.

MRgFUS是一种非侵入性神经调节技术，具有无创、无需全身麻醉、实时靶点定位和实时温度监测等显著优势。目前美国食品药品监督管理局已批准该技术用于治疗特发性震颤和帕金森病，其适应症正在不断扩大，涵盖各种中枢神经系统疾病。本文从高强度聚焦超声介导的热消融、低强度聚焦超声介导的血脑屏障开放和低强度聚焦超声介导的神经调节三个方面，总结了MRgFUS相关临床研究领域最新的临床应用进展，并指出了一些亟待在未来研究中解决的关键挑战，包括未能将颅骨密度比值低的患者纳入适应治疗范围内；术中通过间接靶点进行定位而不是实现靶点可视化，以及如何选择合适的靶点进行治疗。并据此提出了几个未来研究的关键方向：通过创新性的研究来扩大MRgFUS适应症的范围；开展更多神经影像学研究，以实现个性化靶点定位及可视化；在临床实践方面，需要开展更多的临床试验，探索不同靶点及多靶点治疗的可能性。同时，未来还需要更多无创神经影像学研究来探索MRgFUS治疗后脑功能及结构的神经重塑机制。本研究向我们展示了MRgFUS技术目前的临床研究进展，为未来临床试验的开展提供了指导，并为探索神经调节技术的神经机制提供了新的视角。

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Research and application progress of radiomics in neurodegenerative diseases

Junbang Feng, Ying Huang, Xiaocai Zhang, Qingning Yang, Yi Guo, Yuwei Xia, Chao Peng *, Chuanming Li *.

Neurodegenerative diseases refer to degenerative diseases of the nervous system caused by neuronal degeneration and apoptosis. Usually, the onset of the disease is insidious, and the progression is slow, which can last for several years to decades. Clinical symptoms only appear in the later stages of pathological changes when the degree of nerve cell loss reaches or exceeds a certain threshold. Traditional electrophysiological and medical imaging techniques lack valuable indicators and markers. Therefore, early diagnosis and differentiation are very difficult. Radiomics is a new medical imaging technology merged in recent years, which can extract a large number of invisible features from raw image data with high throughput, and quantitatively analyze the pathological and physiological changes. It demonstrates important potential value in the diagnosis, grading, and prognosis evaluation of NDs. This review provides an overview of the research progress of radiomics in neurodegenerative diseases, emphasizing the process principles of radiomics and its application in the diagnosis, classification, and prediction of these diseases. This helps to deepen the understanding of neurodegenerative diseases and promote early diagnosis and treatment in clinical practice.

神经退行性疾病（Neurodegenerative diseases, ND）是指由神经元变性和凋亡引起的神经系统退行性疾病。通常，该病起病隐袭，进展缓慢，可持续数年至数十年。只有在病理变化的后期，当神经细胞丢失的程度达到或超过一定阈值时，才会出现临床症状。传统的电生理学和医学成像技术缺乏有价值的指标和标记。因此，早期诊断和鉴别诊断非常困难。影像组学是近年来新兴的医学影像技术，可以高通量地从原始图像数据中提取大量不可见的特征，并定量分析病理和生理变化。它在 ND 的诊断、分级和预后评估中具有重要的潜在价值。本文介绍了影像组学在神经退行性疾病中的研究进展，重点介绍了影像组学的流程原理及其在神经退行性疾病诊断、分类和预测中的应用。这有助于加深对神经退行性疾病的认识，促进临床实践的早期诊断和治疗。

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编辑：欧漫

审核：赵伟