<p>A recent study published in Nature Medicine introduces a unified medical image-text generative model (MINIM) that addresses the longstanding challenge of limited high-quality medical imaging datasets [<span>1</span>]. Generative artificial intelligence (AI) models like MINIM represent a promising advance that may help researchers and clinicians address data limitations and accelerate the development of AI-driven medical tools.</p><p>In clinical and research settings, acquiring large, diverse, and well-annotated medical imaging datasets remains a critical challenge. This scarcity is especially pronounced for rare diseases, emerging imaging technologies, and underrepresented patient populations, where data collection is limited by small sample sizes, privacy concerns, and legal restrictions on data sharing [<span>2</span>]. As a result, the development and generalizability of AI applications in healthcare are often constrained, limiting their potential for improving diagnosis and treatment. By synthesizing medical images across various imaging modalities and anatomical sites from textual instructions, MINIM offers a potential approach for augmenting existing datasets.</p><p>MINIM is a versatile, self-improving generative AI model notable for its multimodal capabilities. Unlike conventional image-text generative models, which are typically restricted to a single imaging modality [<span>3</span>], MINIM can generate high-quality synthetic images across a variety of modalities. During its development, the authors trained MINIM using a diverse set of medical images, including optical coherence tomography (OCT), fundus photography, chest X-ray, and chest computed tomography (CT), with each image paired with a corresponding textual description. This training strategy allowed the model to embed rich medical image-text knowledge into a stable diffusion framework (Figure 1A). During inference, MINIM generates synthetic images directly from text prompts (Figure 1B). By effectively combining images with their paired textual information, the model produces outputs that resemble real clinical data, potentially mitigating data scarcity in medical AI applications.</p><p>One notable finding is MINIM's strong performance in image synthesis across various medical imaging modalities. Wang et al. [<span>1</span>] benchmarked MINIM against state-of-the-art text-to-image generation models, including Imagen, DALLE, GigaGAN, and StyleGAN-T. Image quality and clinical relevance were assessed using both expert evaluations and six objective metrics: Fréchet inception distance (FID), inception score (IS), multi-scale structural similarity index measure (MS-SSIM), classification accuracy score (CAS), image-image retrieval (IIR), and image-text retrieval (ITR) (Figure 1C). Expert evaluations capture qualitative aspects of image realism and clinical relevance that are difficult to quantify, while objective metrics provide quantitative, reproducible measures of image quality,
最近发表在《自然医学》上的一项研究介绍了一种统一的医学图像-文本生成模型（MINIM），该模型解决了长期以来有限的高质量医学成像数据集[1]的挑战。像MINIM这样的生成式人工智能（AI）模型代表了一个有希望的进步，可以帮助研究人员和临床医生解决数据限制并加速人工智能驱动的医疗工具的开发。在临床和研究环境中，获取大型、多样化和注释良好的医学成像数据集仍然是一个关键的挑战。这种稀缺性在罕见疾病、新兴成像技术和代表性不足的患者群体中尤为明显，这些人群的数据收集受到样本量小、隐私问题和数据共享法律限制的限制。因此，人工智能在医疗保健领域的应用的发展和推广往往受到限制，限制了它们改善诊断和治疗的潜力。通过从文本说明中综合各种成像方式和解剖部位的医学图像，MINIM为增加现有数据集提供了一种潜在的方法。MINIM是一个通用的、自我改进的生成式人工智能模型，以其多模式功能而闻名。传统的图像-文本生成模型通常局限于单一成像模式[3]，而MINIM可以跨多种模式生成高质量的合成图像。在开发过程中，作者使用不同的医学图像集训练MINIM，包括光学相干断层扫描（OCT）、眼底摄影、胸部x射线和胸部计算机断层扫描（CT），每个图像都配有相应的文本描述。这种训练策略允许模型将丰富的医学图像-文本知识嵌入到稳定的扩散框架中（图1A）。在推理过程中，MINIM直接从文本提示生成合成图像（图1B）。通过有效地将图像与其配对的文本信息相结合，该模型产生的输出类似于真实的临床数据，有可能缓解医疗人工智能应用中的数据稀缺问题。一个值得注意的发现是MINIM在各种医学成像模式的图像合成方面的强大性能。Wang等人将MINIM与最先进的文本到图像生成模型（包括Imagen、DALLE、GigaGAN和StyleGAN-T）进行了基准测试。图像质量和临床相关性采用专家评价和六个客观指标进行评估：fr<s:1>起始距离（FID）、起始分数（IS）、多尺度结构相似指数测量（MS-SSIM）、分类准确性评分（CAS）、图像-图像检索（IIR）和图像-文本检索（ITR）（图1C）。专家评估捕捉到难以量化的图像真实感和临床相关性的定性方面，而客观指标提供了图像质量、多样性和保真度的定量、可重复度量。例如，在眼科OCT数据集中，MINIM的FID为65.3，IS为5.7±0.42，MS-SSIM为0.16±0.03，表明在保真度、多样性和临床真实性之间取得了更好的平衡。值得注意的是，91%的mini生成的OCT图像在强化学习微调后获得了临床医生的最高质量评分。将新型人工智能技术整合到临床实践中具有相当大的前景。然而，生成式人工智能领域的一个长期存在的问题是，有多少合成数据可以提高预测模型的性能。这项研究表明，MINIM不仅可以生成高质量的图像，而且还具有通过数据增强来增强临床决策支持系统的潜力。对于诊断分类，使用真实和合成数据的平衡混合训练的模型显示出显着的改进。例如，胸部CT诊断准确率从0.58提高到0.79。在表现不佳的类别中，如视网膜血管炎，临床医生选择的合成OCT图像增强了诊断性能。合成数据的使用还改善了医疗报告的生成，ROUGE-L分数的提高反映了与专家注释的更好一致性。在自监督学习中，合成图像的预训练在微调后提高了下游任务的性能，进一步证明了合成数据在医疗人工智能开发中的价值。Wang et al.[1]进一步证明了合成图像在提高肺癌和乳腺癌分类准确率方面的效用（图1D）。例如，在使用胸部CT扫描对肺癌中EGFR突变类型进行分类时，仅根据真实数据训练的模型达到了81.5%的最高准确率。当以1:1的比例添加最小化生成的合成图像时，这一比例提高到91.2%，当合成与真实的比例为5:1时，这一比例达到95.4%。同样，在乳房MRI的HER2状态预测中，当合成图像的数量超过真实图像的十倍时，准确率从单独使用真实数据的79.2%增加到94.0%。 这些发现表明，MINIM生成的合成数据可以提高模型在临床相关任务中的表现，最终支持更精确和个性化的干预措施。基础模型的最新进展强调了合成数据在提高模型性能方面的价值，特别是在现实世界数据集有限的情况下。例如，Hollmann等人引入了TabPFN，这是一种对大量合成数据进行预训练的表格基础模型。他们的研究表明，在精心设计的合成数据集上进行预训练可以提高预测的准确性和可解释性，即使只有小的真实数据集可用。这一发现与MINIM的目标高度相关，因为MINIM同样利用合成数据来缓解医学成像中的数据短缺。通过从文本提示生成跨多种模式的高质量图像，MINIM有可能增加有限的数据集，提高下游人工智能模型的性能，并增强临床可解释性。尽管其结果令人鼓舞，但作者承认需要在不同的前瞻性临床环境中进一步验证，以充分评估MINIM的广泛性和稳健性。虽然该模型显着提高了诊断性能，但仍存在一些挑战，例如潜在的过拟合，文本图像对齐有限，提示时间较长，以及与实际临床工作流程的集成。通过模型细化、扩展和多样化的训练数据集以及对抗性训练或自适应学习等技术来解决这些限制将是必不可少的。总之，这项研究代表了生成式人工智能在医疗保健领域应用的重大进展。MINIM从文本描述合成高质量医学图像的能力是解决医学成像关键挑战的重要一步。通过提高数据的可用性和多样性，MINIM可以支持人工智能驱动的诊断、个性化治疗计划和创新医疗技术的开发。展望未来，这些模型的临床翻译将取决于严格的验证、监管评估、临床医生的信任、有效的系统集成以及对患者安全和数据隐私的强有力保障。研究人员、临床医生和监管机构之间的持续合作将是安全、负责任地实施这些药物的关键。L.N.构思、起草并修改了手稿。所有作者都阅读并批准了最终稿件。作者声明无利益冲突。不适用。作者没有什么可报告的。
{"title":"Advancing Multimodal Medical Image Generation: A Self-Improving Generative Foundation Model","authors":"Yongjian Chen, Lui Ng","doi":"10.1002/mco2.70490","DOIUrl":"10.1002/mco2.70490","url":null,"abstract":"<p>A recent study published in Nature Medicine introduces a unified medical image-text generative model (MINIM) that addresses the longstanding challenge of limited high-quality medical imaging datasets [<span>1</span>]. Generative artificial intelligence (AI) models like MINIM represent a promising advance that may help researchers and clinicians address data limitations and accelerate the development of AI-driven medical tools.</p><p>In clinical and research settings, acquiring large, diverse, and well-annotated medical imaging datasets remains a critical challenge. This scarcity is especially pronounced for rare diseases, emerging imaging technologies, and underrepresented patient populations, where data collection is limited by small sample sizes, privacy concerns, and legal restrictions on data sharing [<span>2</span>]. As a result, the development and generalizability of AI applications in healthcare are often constrained, limiting their potential for improving diagnosis and treatment. By synthesizing medical images across various imaging modalities and anatomical sites from textual instructions, MINIM offers a potential approach for augmenting existing datasets.</p><p>MINIM is a versatile, self-improving generative AI model notable for its multimodal capabilities. Unlike conventional image-text generative models, which are typically restricted to a single imaging modality [<span>3</span>], MINIM can generate high-quality synthetic images across a variety of modalities. During its development, the authors trained MINIM using a diverse set of medical images, including optical coherence tomography (OCT), fundus photography, chest X-ray, and chest computed tomography (CT), with each image paired with a corresponding textual description. This training strategy allowed the model to embed rich medical image-text knowledge into a stable diffusion framework (Figure 1A). During inference, MINIM generates synthetic images directly from text prompts (Figure 1B). By effectively combining images with their paired textual information, the model produces outputs that resemble real clinical data, potentially mitigating data scarcity in medical AI applications.</p><p>One notable finding is MINIM's strong performance in image synthesis across various medical imaging modalities. Wang et al. [<span>1</span>] benchmarked MINIM against state-of-the-art text-to-image generation models, including Imagen, DALLE, GigaGAN, and StyleGAN-T. Image quality and clinical relevance were assessed using both expert evaluations and six objective metrics: Fréchet inception distance (FID), inception score (IS), multi-scale structural similarity index measure (MS-SSIM), classification accuracy score (CAS), image-image retrieval (IIR), and image-text retrieval (ITR) (Figure 1C). Expert evaluations capture qualitative aspects of image realism and clinical relevance that are difficult to quantify, while objective metrics provide quantitative, reproducible measures of image quality, ","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 12","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12701961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145764656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alternative splicing (AS) is an important posttranscriptional process that increases proteomic complexity of eukaryotes. Through the selective inclusion or exclusion of exons, AS fine-tunes gene expression and underpins diverse biological processes. Recent research revealed that AS is controlled not only by spliceosomal components but also by dynamic RNA structures and the spatial compartmentalization of splicing factors within biomolecular condensates formed via liquid–liquid phase separation (LLPS). Nevertheless, a unified framework connecting these mechanistic insights with emerging therapeutic strategies remains lacking. This review systematically integrates current knowledge of AS regulation, encompassing the architecture and dynamics of the core spliceosome, structural RNA elements such as G-quadruplexes, and LLPS-driven condensates exemplified by oncogenic SRSF9 droplets. It further delineates how AS influences cell development, immune modulation, and stress adaptation, while its dysregulation contributes to human pathologies, including SF3B1 mutant cancers, TDP-43-associated neurodegeneration, and cardiovascular disease. We critically appraise therapeutic innovations targeting aberrant splicing, including small molecule spliceosome modulators, antisense oligonucleotides like nusinersen, and CRISPR/dCas13-based RNA editing. By integrating molecular mechanisms with translational advances, this review provides a conceptual framework to accelerate RNA-targeted precision medicine in the era of spatial multiomics and artificial intelligence.
{"title":"Alternative Splicing: Molecular Mechanisms, Biological Functions, Diseases, and Potential Therapeutic Targets","authors":"Zhi-Min Zhu, Xiao-Mei Wu, Yan Hu, Xiao-Lan Bian, Ya-Qin Wang, Qiong-Ni Zhu","doi":"10.1002/mco2.70545","DOIUrl":"10.1002/mco2.70545","url":null,"abstract":"<p>Alternative splicing (AS) is an important posttranscriptional process that increases proteomic complexity of eukaryotes. Through the selective inclusion or exclusion of exons, AS fine-tunes gene expression and underpins diverse biological processes. Recent research revealed that AS is controlled not only by spliceosomal components but also by dynamic RNA structures and the spatial compartmentalization of splicing factors within biomolecular condensates formed via liquid–liquid phase separation (LLPS). Nevertheless, a unified framework connecting these mechanistic insights with emerging therapeutic strategies remains lacking. This review systematically integrates current knowledge of AS regulation, encompassing the architecture and dynamics of the core spliceosome, structural RNA elements such as G-quadruplexes, and LLPS-driven condensates exemplified by oncogenic SRSF9 droplets. It further delineates how AS influences cell development, immune modulation, and stress adaptation, while its dysregulation contributes to human pathologies, including SF3B1 mutant cancers, TDP-43-associated neurodegeneration, and cardiovascular disease. We critically appraise therapeutic innovations targeting aberrant splicing, including small molecule spliceosome modulators, antisense oligonucleotides like nusinersen, and CRISPR/dCas13-based RNA editing. By integrating molecular mechanisms with translational advances, this review provides a conceptual framework to accelerate RNA-targeted precision medicine in the era of spatial multiomics and artificial intelligence.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 12","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12701963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145764644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Linbo Yao, Xinmin Yang, Robert Sutton, Qing Xia, Wei Huang
<p>Pancreatitis is a complex and progressive inflammatory disease of the pancreas, associated with a high risk of morbidity and mortality. It is well known that pancreatitis is a disease progression from the initial episode of acute pancreatitis (AP) to chronic pancreatitis (CP) via recurrent AP (RAP). However, little is known about identifying at risk of recurrences and progression or about pharmacological interventions to prevent these outcomes. While hypertriglyceridemia is a common cause of AP, with pancreatitis secondary to it typically presenting as an episode of AP or RAP, and rarely as CP. While it has been clearly established that the risk of AP correlates positively with triglyceride (TG) levels [<span>1</span>], and that familial chylomicronemia syndrome is extensively documented as a cause of pancreatitis spanning AP, RAP, and CP [<span>2</span>], a comprehensive genetic investigation of these causal links is still warranted. Furthermore, there is no clear casual effect evidence for lipid-lowering drugs (i.e., statins or fibrates) in reducing the likelihood of pancreatitis.</p><p>Therefore, we performed Mendelian randomization (MR) analysis to assess the causal associations between lipid levels and AP, CP, alcohol-induced AP and CP (AAP and ACP) using data from the FinnGen Consortium. Drug-target MR and colocalization analyses were further conducted to investigate the potential impact of 15 lipid-modifying targets on these pancreatitis subtypes. To ensure the validity of instrumental variables, a positive control analysis was conducted in parallel to test causal effect of selected druggable targets on coronary artery disease, which has a well-established causal association (see Supplementary Material for detailed methodology).</p><p>In the primary univariable MR analyses, we found that genetically proxied increases in TG levels were associated with a higher risk of all pancreatitis subcategories. In contrast, genetically proxied increases in high-density lipoprotein cholesterol (HDL-C) levels were causally associated with a decreased risk of AP, AAP, and CP. To account for potential confounding factors, we performed multivariable MR analyses. Specifically, we adjusted for genetically predicted cholelithiasis in AP and for genetically predicted alcohol consumption and smoking in CP. We also conducted multivariable MR analyses for AAP and ACP after adjusting for genetic liability to alcohol consumption. Our results were highly consistent across both univariable and multivariable analyses, showing that genetically proxied levels of TG and HDL-C are causally associated with pancreatitis, whereas no significant association was found between either total cholesterol or low-density lipoprotein cholesterol and any pancreatitis subcategory.</p><p>In the drug-target MR analyses, we attempted to evaluate effects of 15 lipid-modifying targets on pancreatitis, namely, <i>HMGCR</i>, <i>NPC1L1</i>, <i>PCSK9</i>, <i>APOB</i>, <i>LDLR</i>, <i>ABCG5</i
胰腺炎是一种复杂的进行性胰腺炎症性疾病，具有较高的发病率和死亡率。众所周知，胰腺炎是一种从急性胰腺炎（AP）初始发作到慢性胰腺炎（CP）经复发性AP （RAP）的疾病进展。然而，对于识别复发和进展的风险或预防这些结果的药物干预知之甚少。虽然高甘油三酯血症是AP的常见原因，继发胰腺炎通常表现为AP或RAP发作，很少表现为CP。虽然已经明确确定AP的风险与甘油三酯（TG）水平[1]呈正相关，并且家族性乳糜小铁血症综合征被广泛记录为胰腺炎的原因，包括AP、RAP和CP[1]，但对这些因果关系的全面遗传调查仍然是有必要的。此外，降脂药物（即他汀类药物或贝特类药物）在降低胰腺炎可能性方面没有明确的偶然效应证据。因此，我们使用FinnGen联盟的数据进行孟德尔随机化（MR）分析，以评估脂质水平与AP、CP、酒精诱导的AP和CP （AAP和ACP）之间的因果关系。进一步进行药物靶向MR和共定位分析，以研究15种脂质修饰靶点对这些胰腺炎亚型的潜在影响。为了确保工具变量的有效性，我们同时进行了一项正对照分析，以检验选定的可药物靶点对冠状动脉疾病的因果关系，这一因果关系已经确立（详细的方法见补充材料）。在主要的单变量MR分析中，我们发现遗传相关的TG水平升高与所有胰腺炎亚类的高风险相关。相比之下，高密度脂蛋白胆固醇（HDL-C）水平的遗传升高与AP、AAP和CP风险降低有因果关系。为了考虑潜在的混杂因素，我们进行了多变量磁共振分析。具体来说，我们调整了AP中遗传预测的胆石症，以及CP中遗传预测的饮酒和吸烟。在调整了饮酒的遗传倾向后，我们还对AAP和ACP进行了多变量MR分析。我们的结果在单变量和多变量分析中都是高度一致的，表明遗传相关的TG和HDL-C水平与胰腺炎有因果关系，而在总胆固醇或低密度脂蛋白胆固醇与任何胰腺炎亚类别之间没有发现显著的关联。在药物靶点MR分析中，我们试图评估15个脂质修饰靶点对胰腺炎的影响，即HMGCR、NPC1L1、PCSK9、APOB、LDLR、ABCG5、ABCG8、ACLY、ANGPTL3、MTTP、PPARA、PPARD、PPARG、APOC3和LPL。对于TG（表1），APOB介导的较高的遗传相关脂质水平增加了CP（比值比[OR] = 2.057, 95%可信区间[CI] 1.290-3.280, p = 0.002）和ACP （OR = 2.236, 95% CI 1.163-4.297, p = 0.016）的风险。同样，apo3与CP （OR = 1.366, 95% CI 1.111-1.679, p = 0.003）和ACP （OR = 1.442, 95% CI 1.080-1.926, p = 0.013）存在潜在关联。对于HDL-C（表1），靶向PPARG似乎可以降低AP （OR = 0.325, 95% CI 0.143-0.740, p = 0.007）、AAP （OR = 0.045, 95% CI 0.006-0.363, p = 0.004）、CP （OR = 0.295, 95% CI 0.100-0.871, p = 0.027）和ACP （OR = 0.187, 95% CI 0.041-0.852, p = 0.030）的风险，而靶向APOB和APOC3似乎与降低CP风险相关(APOB: OR = 0.459, 95% CI 0.263 - 0.805, p = 0.007；APOC3: OR = 0.580, 95% CI 0.364-0.924, p = 0.022)和ACP （APOB: OR = 0.417, 95% CI 0.190-0.916, p = 0.029; APOC3: OR = 0.412, 95% CI 0.214-0.972, p = 0.008）。TG和CP在APOC3基因区域共定位的后验概率为79%，条件是结果存在因果变异（表1）。为了增强我们研究结果的稳健性，我们使用来自AP （UK Biobank）以及东亚和欧洲联盟的独立数据集对AP和CP进行了复制分析。apob介导的TG水平影响的复制显示与CP（欧洲）有显著关联（OR = 2.192, 95% CI 1.100-4.370, p = 0.026）（表1），巩固了我们的主要发现。虽然apo3的相关性在这些复制数据集中没有达到统计学意义，但在我们的初步分析中缺乏显著相关性的lpl相关TG水平在东亚（OR = 2.800, 95% CI 1.578-4.966, p = 0.000）和欧洲（OR = 1.233, 95% CI 1.001-1.519, p = 0.049）数据集中显示与AP有明显关联（表1）。这一新证实的与LPL的关联为支持其与AP建立的临床联系提供了重要证据。 药物靶标分析通过支持特定脂质代谢途径在胰腺炎中的因果作用，加强了我们的核心发现。这些分析共同建立了apo3、APOB和LPL与胰腺炎风险相关的不同因果机制。首先，APOC3通过抑制LPL（清除TG的主要酶）来提高富含TG的脂蛋白的全身浓度。其次，APOB水平是循环中富含tg的脂蛋白颗粒数量的直接指标；遗传性APOB升高表明颗粒计数增加，从而增强了传递到胰腺的总TG负荷。最近的荟萃分析和随机临床试验证实了APOC3 mrna靶向治疗药物（包括volanesorsen[3]、plozasiran[4]和olezarsen[5]）在降低血清TG水平和降低AP风险方面的有效性。这些发现为我们的遗传结果提供了强有力的转化支持。总之，我们的研究结果表明，较高的血清TG和较低的血清HDL-C会增加胰腺炎的风险。药物靶标分析表明，靶向APOB、APOC3和LPL是降低多种形式胰腺炎风险的有希望的策略，这一发现值得进一步研究。WH和QX是联合资深作者。LY， XY和WH设计了这项研究。XY、WH和QX获得资助并指导学生。XY和WH起草了手稿。LY和XY进行了分析。RS有重要的智力输入。WH和RS对手稿进行了严格的修改。所有作者都阅读并认可了文章的最终版本。本研究由四川省科技计划项目重点研发计划（授予WH）资助；国家自然科学基金项目（82304985 - YX; 82270672 - WH; 82274321 - QX）。作者没有什么可报告的。作者声明无利益冲突。在这项MR研究中分析的所有汇总统计数据都是公开的，并来自已建立的全基因组关联研究联盟。胰腺炎亚型的主要数据来自FinnGen联盟（可访问https://r10.finngen.fi/），而血脂、复制分析和冠状动脉疾病控制的数据来自全球脂质遗传学联盟（https://csg.sph.umich.edu/willer/public/glgc-lipids2021/）和IEU GWAS数据库（https://gwas.mrcieu.ac.uk/）。综合数据集，包括单变量/多变量MR结果，外部验证数据和脂质修饰靶标（MR和共定位）的汇总统计数据，存放在Zenodo的https://doi.org/10.5281/zenodo.17707905。本研究没有开发新的软件；所有的分析都是使用公开可用的R包进行的。用于生成结果的R脚本可根据合理要求从相应作
{"title":"New Insights into the Genetic Association of Lipids and Lipid-Modifying Target Genes with Pancreatitis","authors":"Linbo Yao, Xinmin Yang, Robert Sutton, Qing Xia, Wei Huang","doi":"10.1002/mco2.70554","DOIUrl":"10.1002/mco2.70554","url":null,"abstract":"<p>Pancreatitis is a complex and progressive inflammatory disease of the pancreas, associated with a high risk of morbidity and mortality. It is well known that pancreatitis is a disease progression from the initial episode of acute pancreatitis (AP) to chronic pancreatitis (CP) via recurrent AP (RAP). However, little is known about identifying at risk of recurrences and progression or about pharmacological interventions to prevent these outcomes. While hypertriglyceridemia is a common cause of AP, with pancreatitis secondary to it typically presenting as an episode of AP or RAP, and rarely as CP. While it has been clearly established that the risk of AP correlates positively with triglyceride (TG) levels [<span>1</span>], and that familial chylomicronemia syndrome is extensively documented as a cause of pancreatitis spanning AP, RAP, and CP [<span>2</span>], a comprehensive genetic investigation of these causal links is still warranted. Furthermore, there is no clear casual effect evidence for lipid-lowering drugs (i.e., statins or fibrates) in reducing the likelihood of pancreatitis.</p><p>Therefore, we performed Mendelian randomization (MR) analysis to assess the causal associations between lipid levels and AP, CP, alcohol-induced AP and CP (AAP and ACP) using data from the FinnGen Consortium. Drug-target MR and colocalization analyses were further conducted to investigate the potential impact of 15 lipid-modifying targets on these pancreatitis subtypes. To ensure the validity of instrumental variables, a positive control analysis was conducted in parallel to test causal effect of selected druggable targets on coronary artery disease, which has a well-established causal association (see Supplementary Material for detailed methodology).</p><p>In the primary univariable MR analyses, we found that genetically proxied increases in TG levels were associated with a higher risk of all pancreatitis subcategories. In contrast, genetically proxied increases in high-density lipoprotein cholesterol (HDL-C) levels were causally associated with a decreased risk of AP, AAP, and CP. To account for potential confounding factors, we performed multivariable MR analyses. Specifically, we adjusted for genetically predicted cholelithiasis in AP and for genetically predicted alcohol consumption and smoking in CP. We also conducted multivariable MR analyses for AAP and ACP after adjusting for genetic liability to alcohol consumption. Our results were highly consistent across both univariable and multivariable analyses, showing that genetically proxied levels of TG and HDL-C are causally associated with pancreatitis, whereas no significant association was found between either total cholesterol or low-density lipoprotein cholesterol and any pancreatitis subcategory.</p><p>In the drug-target MR analyses, we attempted to evaluate effects of 15 lipid-modifying targets on pancreatitis, namely, <i>HMGCR</i>, <i>NPC1L1</i>, <i>PCSK9</i>, <i>APOB</i>, <i>LDLR</i>, <i>ABCG5</i","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 12","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12703042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Complex and dynamic networks of molecules are involved in human diseases. Single-cell and spatial multiomics approaches have created new avenues for understanding the pathogenesis and diagnosis of diseases. Cell connections and characteristics in diseases may be examined more thoroughly by integration single-cell and spatial multiomics. In this paper, we first reviewed the single-cell and spatial multiomics approaches. Subsequently, the use of single-cell and spatial multiomics to comprehend the mechanisms of human diseases, such as cancer (head and neck squamous cell carcinoma), neurodegenerative diseases, and aging, was discussed. Furthermore, we outline how deep learning approaches are now being applied to single-cell and spatial multiomics data analysis in an effort to better define the pathogenic alterations upstream and the downstream molecular effects of diseases. Particularly, single-cell and spatial multiomics are being utilized to help guide treatment plans, evaluate risks, and determine how they can affect precision medicine. Despite the relative youth of the field, the development of single-cell coupled with spatial multiomics promises to provide a powerful tool for elucidating the pathogenesis of diseases.
{"title":"Single-Cell and Spatial Multiomics: Applications for Diseases","authors":"Wentao Li, Chao Chen, Xin Zhu, Chenping Zhang","doi":"10.1002/mco2.70553","DOIUrl":"10.1002/mco2.70553","url":null,"abstract":"<p>Complex and dynamic networks of molecules are involved in human diseases. Single-cell and spatial multiomics approaches have created new avenues for understanding the pathogenesis and diagnosis of diseases. Cell connections and characteristics in diseases may be examined more thoroughly by integration single-cell and spatial multiomics. In this paper, we first reviewed the single-cell and spatial multiomics approaches. Subsequently, the use of single-cell and spatial multiomics to comprehend the mechanisms of human diseases, such as cancer (head and neck squamous cell carcinoma), neurodegenerative diseases, and aging, was discussed. Furthermore, we outline how deep learning approaches are now being applied to single-cell and spatial multiomics data analysis in an effort to better define the pathogenic alterations upstream and the downstream molecular effects of diseases. Particularly, single-cell and spatial multiomics are being utilized to help guide treatment plans, evaluate risks, and determine how they can affect precision medicine. Despite the relative youth of the field, the development of single-cell coupled with spatial multiomics promises to provide a powerful tool for elucidating the pathogenesis of diseases.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 12","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12703058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Parkinson's disease (PD) is a progressive neurodegenerative disorder with a growing global burden. Current pharmacological therapies remain limited to symptomatic management, owning to an incomplete understanding of the mechanisms driving α‑synuclein aggregation and disease progression. This review provides an integrated overview of PD across epidemiological, etiological, pathophysiological, and clinical dimensions. It emphasizes established and emerging risk factors, including environmental toxins, lifestyle variables, and gut microbiota dysbiosis and delineates how peripheral–central pathways such as the gut–brain, erythrocyte–brain, and kidney–brain axes contribute to PD pathogenesis. At the molecular level, we explore key disruptions including proteostatic failure, aberrant phase separation, oxidative stress, neuroinflammation, synaptic dysfunction, iron dyshomeostasis, and impaired cholesterol metabolism. These encompass microbiome‑targeted interventions and blood-based approaches. We further evaluate a spectrum of management strategies ranging from primary prevention and biomarker‑guided early detection to innovative experimental treatments such as cellular therapies, transfusion‑based modalities, and microbial modulation. By integrating recent advances in systemic pathophysiology with translational perspectives, this review highlights how molecular and cellular dysregulations underlie clinical phenotypes. Finally, we discuss promising biomarkers derived from microbial, inflammatory, and erythrocyte pathways that may facilitate early diagnosis and the development of disease‑modifying therapies.
{"title":"Parkinson's Disease: The Epidemiology, Risk Factors, Molecular Pathogenesis, Prevention, and Therapy","authors":"Xue-Yao Guo, Dong-Yan Song, Ming-Yang Wu, Jing-Qi Zhang, Jia-Yi Li, Lin Yuan","doi":"10.1002/mco2.70540","DOIUrl":"https://doi.org/10.1002/mco2.70540","url":null,"abstract":"<p>Parkinson's disease (PD) is a progressive neurodegenerative disorder with a growing global burden. Current pharmacological therapies remain limited to symptomatic management, owning to an incomplete understanding of the mechanisms driving α‑synuclein aggregation and disease progression. This review provides an integrated overview of PD across epidemiological, etiological, pathophysiological, and clinical dimensions. It emphasizes established and emerging risk factors, including environmental toxins, lifestyle variables, and gut microbiota dysbiosis and delineates how peripheral–central pathways such as the gut–brain, erythrocyte–brain, and kidney–brain axes contribute to PD pathogenesis. At the molecular level, we explore key disruptions including proteostatic failure, aberrant phase separation, oxidative stress, neuroinflammation, synaptic dysfunction, iron dyshomeostasis, and impaired cholesterol metabolism. These encompass microbiome‑targeted interventions and blood-based approaches. We further evaluate a spectrum of management strategies ranging from primary prevention and biomarker‑guided early detection to innovative experimental treatments such as cellular therapies, transfusion‑based modalities, and microbial modulation. By integrating recent advances in systemic pathophysiology with translational perspectives, this review highlights how molecular and cellular dysregulations underlie clinical phenotypes. Finally, we discuss promising biomarkers derived from microbial, inflammatory, and erythrocyte pathways that may facilitate early diagnosis and the development of disease‑modifying therapies.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 12","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70540","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145750970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is an aggressive subtype of T-ALL. Once refractory or relapsed, it is associated with a poor prognosis, with a complete remission (CR) rate of 36%–46% following re-induction therapy. Previously, we reported a synergistic effect of venetoclax (VEN) and homoharringtonine (HHT) in ETP-ALL, which potentially elicits notable clinical responses. Herein, we investigated the efficacy and safety of the V-HAG regimen (VEN, HHT, cytarabine, and granulocyte colony-stimulating factor [G-CSF]) in patients with refractory/relapsed ETP-ALL through a prospective, multicenter, single-arm, open-label, phase 2 clinical trial. A total of 18 patients were enrolled, and 100% of these patients achieved CR or CR with incomplete hematological recovery (CRi) after 1 cycle of the V-HAG regimen as re-induction therapy. As a follow-up, both the relapse rate and mortality rate were 33.3%. The 1-year overall survival and relapse-free survival were 76.7% (95% confidence interval [CI]: 53.2%-100.0%) and 55.7% (95% CI: 28.8%–82.6%), respectively. The most common grade 3–4 adverse events were neutropenia (100%), anemia (88.9%), and thrombocytopenia (100%). Notably, the VEN- and HHT-based therapy, V-HAG regimen, exhibits an extremely high efficacy in the treatment of patients with refractory/relapsed ETP-ALL with good tolerance, and it provides a promising therapeutic strategy for improving their outcomes.
{"title":"Venetoclax and Homoharringtonine-Based Therapy Exhibited a Striking Response in Refractory/Relapsed Early T-Cell Precursor Acute Lymphoblastic Leukemia","authors":"Xiang Zhang, Hongsheng Zhou, Liping Mao, Yinjun Lou, Lijing Shen, Ying Lu, Zhenfang Liu, Xiuzhen Tong, Aiping Zhang, Tingbo Liu, Na Zhang, Xingnong Ye, Juying Wei, Meihong Luo, Shaoyuan Wang, Qingxian Bai, Jian Hou, Qifa Liu, Hongyan Tong, Jie Jin, Wenjuan Yu","doi":"10.1002/mco2.70549","DOIUrl":"https://doi.org/10.1002/mco2.70549","url":null,"abstract":"<p>Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is an aggressive subtype of T-ALL. Once refractory or relapsed, it is associated with a poor prognosis, with a complete remission (CR) rate of 36%–46% following re-induction therapy. Previously, we reported a synergistic effect of venetoclax (VEN) and homoharringtonine (HHT) in ETP-ALL, which potentially elicits notable clinical responses. Herein, we investigated the efficacy and safety of the V-HAG regimen (VEN, HHT, cytarabine, and granulocyte colony-stimulating factor [G-CSF]) in patients with refractory/relapsed ETP-ALL through a prospective, multicenter, single-arm, open-label, phase 2 clinical trial. A total of 18 patients were enrolled, and 100% of these patients achieved CR or CR with incomplete hematological recovery (CRi) after 1 cycle of the V-HAG regimen as re-induction therapy. As a follow-up, both the relapse rate and mortality rate were 33.3%. The 1-year overall survival and relapse-free survival were 76.7% (95% confidence interval [CI]: 53.2%-100.0%) and 55.7% (95% CI: 28.8%–82.6%), respectively. The most common grade 3–4 adverse events were neutropenia (100%), anemia (88.9%), and thrombocytopenia (100%). Notably, the VEN- and HHT-based therapy, V-HAG regimen, exhibits an extremely high efficacy in the treatment of patients with refractory/relapsed ETP-ALL with good tolerance, and it provides a promising therapeutic strategy for improving their outcomes.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 12","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70549","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145750811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zona pellucida (ZP) proteins, essential for oocyte development, undergo posttranslational regulation through furin-mediated cleavage. Nevertheless, our understanding of the functional significance of furin-mediated cleavage of ZP proteins in female reproduction remains limited. Here, using mouse models with disrupted furin cleavage sites in ZP1, ZP2, and ZP3, we found that loss of the furin site in ZP2 caused female infertility associated with empty follicle syndrome (EFS), manifested by the failure to retrieve oocytes after ovarian hyperstimulation. In contrast, female mice carrying cleavage-resistant variants at the furin sites of ZP1 and ZP3 exhibited defective ZP in a subset of oocytes, leading to reduced fecundity. Mechanistically, disruption of the furin cleavage site in ZP2 impaired the transmembrane transport of the non-cleaved ZP2 protein and subsequently reduced the levels of SNARE proteins, ultimately triggering oocyte apoptosis through activation of the p53 and PI3K signaling pathways. Collectively, we uncovered the essential role of furin-mediated cleavage of ZP proteins in female fertility and provided new mechanistic insights into the pathogenesis of EFS. These findings open new avenues for investigating the contribution of posttranslational modifications to female reproduction and for developing potential therapeutic strategies to treat female infertility.
{"title":"Furin-Mediated Cleavage of Zona Pellucida Proteins Is Essential for Oocyte Development","authors":"Tiechao Ruan, Xiang Wang, Xueguang Zhang, Yan Wang, Chuan Jiang, Sixian Wu, Yunchuan Tian, Xinyao Tang, Jun Ma, Shikun Zhao, Liangchai Zhuo, Mohan Liu, Siyu Dai, Zhenbo Wang, Wenming Xu, Ying Shen","doi":"10.1002/mco2.70542","DOIUrl":"https://doi.org/10.1002/mco2.70542","url":null,"abstract":"<p>Zona pellucida (ZP) proteins, essential for oocyte development, undergo posttranslational regulation through furin-mediated cleavage. Nevertheless, our understanding of the functional significance of furin-mediated cleavage of ZP proteins in female reproduction remains limited. Here, using mouse models with disrupted furin cleavage sites in ZP1, ZP2, and ZP3, we found that loss of the furin site in ZP2 caused female infertility associated with empty follicle syndrome (EFS), manifested by the failure to retrieve oocytes after ovarian hyperstimulation. In contrast, female mice carrying cleavage-resistant variants at the furin sites of ZP1 and ZP3 exhibited defective ZP in a subset of oocytes, leading to reduced fecundity. Mechanistically, disruption of the furin cleavage site in ZP2 impaired the transmembrane transport of the non-cleaved ZP2 protein and subsequently reduced the levels of SNARE proteins, ultimately triggering oocyte apoptosis through activation of the p53 and PI3K signaling pathways. Collectively, we uncovered the essential role of furin-mediated cleavage of ZP proteins in female fertility and provided new mechanistic insights into the pathogenesis of EFS. These findings open new avenues for investigating the contribution of posttranslational modifications to female reproduction and for developing potential therapeutic strategies to treat female infertility.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 12","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70542","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145750968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yalun Li, Jin Zhou, Li Jiang, Hua Xie, Zonglian Gong, Ke Wang, Yan Zhang, Yan Li, Weimin Li, Panwen Tian
In this Phase II study, 13 patients with stage IIIB/IV non-small cell lung cancer with acquired resistance to immune checkpoint inhibitors were treated with tislelizumab, sitravatinib, and docetaxel. The efficacy and safety were evaluated. The combination treatment achieved median progression-free survival of 7.6 months, median overall survival of 17.2 months, an objective response rate of 58.3% (1 not evaluable), and a disease control rate of 100%. Grade ≥ 3 treatment-related adverse events were primarily neutropenia and leukopenia. Exploratory analyses showed a trend toward increased T cell receptor (TCR) diversity following treatment. High pre-treatment CD8+ T cell polyfunctional strength index (PSI) showed a trend toward association with early treatment response and deeper tumor shrinkage, while CD8+ PSI decreased post-therapy in responders, although not significantly. Larger changes in CD4+ T cell PSI were associated with longer PFS. Although these data indicate clinical benefit and immunologic correlates, the limited sample size precludes definitive conclusions. Furthermore, the observed changes in TCR and PSI dynamics are preliminary, hypothesis-generating, and may provide insights for optimizing therapeutic strategies. However, validation via large-scale, randomized controlled clinical trials remains warranted.
Trial registration: Chictr.org.cn, ChiCTR2200065547. Registered in 2022-11-08, https://www.chictr.org.cn/showproj.html?proj=183439.
{"title":"A Phase II Study of Sitravatinib Combined With Tislelizumab Plus Docetaxel for Acquired Resistance to PD-(L)1 in Patients With Advanced/Metastatic Non-Small Cell Lung Cancer","authors":"Yalun Li, Jin Zhou, Li Jiang, Hua Xie, Zonglian Gong, Ke Wang, Yan Zhang, Yan Li, Weimin Li, Panwen Tian","doi":"10.1002/mco2.70538","DOIUrl":"https://doi.org/10.1002/mco2.70538","url":null,"abstract":"<p>In this Phase II study, 13 patients with stage IIIB/IV non-small cell lung cancer with acquired resistance to immune checkpoint inhibitors were treated with tislelizumab, sitravatinib, and docetaxel. The efficacy and safety were evaluated. The combination treatment achieved median progression-free survival of 7.6 months, median overall survival of 17.2 months, an objective response rate of 58.3% (1 not evaluable), and a disease control rate of 100%. Grade ≥ 3 treatment-related adverse events were primarily neutropenia and leukopenia. Exploratory analyses showed a trend toward increased T cell receptor (TCR) diversity following treatment. High pre-treatment CD8<sup>+</sup> T cell polyfunctional strength index (PSI) showed a trend toward association with early treatment response and deeper tumor shrinkage, while CD8<sup>+</sup> PSI decreased post-therapy in responders, although not significantly. Larger changes in CD4<sup>+</sup> T cell PSI were associated with longer PFS. Although these data indicate clinical benefit and immunologic correlates, the limited sample size precludes definitive conclusions. Furthermore, the observed changes in TCR and PSI dynamics are preliminary, hypothesis-generating, and may provide insights for optimizing therapeutic strategies. However, validation via large-scale, randomized controlled clinical trials remains warranted.</p><p><b>Trial registration</b>: Chictr.org.cn, ChiCTR2200065547. Registered in 2022-11-08, https://www.chictr.org.cn/showproj.html?proj=183439.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 12","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70538","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145750771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
O-GlcNAcylation is a reversible posttranslational modification of proteins that has garnered significant attention in recent years. By regulating the structure and function of proteins, it plays a critical role in various biological processes. Normal O-GlcNAcylation is essential for maintaining internal homeostasis and is involved in controlling fundamental biological events such as gene expression, the cell cycle regulation, metabolism, and signal transduction. Conversely, aberrant O-GlcNAcylation is closely linked to the onset and progression of various diseases—including neurodegenerative diseases, cancers, cardiovascular diseases, and immune-related diseases—where it drives pathological development. Currently, there is a lack of comprehensive reviews systematically addressing the specific mechanisms of O-GlcNAcylation under both physiological and pathological conditions. Therefore, this article aims to summarize its dual role in maintaining organismal homeostasis and promoting disease pathogenesis, providing an integrated evaluation of the biological significance of this modification in health and diseases. Furthermore, it discusses the potential of O-GlcNAcylation as a therapeutic target, explores its clinical applications, and analyzes the current challenges and future directions in drug development, thereby offering theoretical insights and research perspectives for related fields.
{"title":"Protein O-GlcNAcylation in Health and Diseases","authors":"Zhihong Ran, Chuanbao Chen, Jingfeng Ou, Guanyi Wu, Chao Yang, Xiaoyou Liu","doi":"10.1002/mco2.70536","DOIUrl":"https://doi.org/10.1002/mco2.70536","url":null,"abstract":"<p>O-GlcNAcylation is a reversible posttranslational modification of proteins that has garnered significant attention in recent years. By regulating the structure and function of proteins, it plays a critical role in various biological processes. Normal O-GlcNAcylation is essential for maintaining internal homeostasis and is involved in controlling fundamental biological events such as gene expression, the cell cycle regulation, metabolism, and signal transduction. Conversely, aberrant O-GlcNAcylation is closely linked to the onset and progression of various diseases—including neurodegenerative diseases, cancers, cardiovascular diseases, and immune-related diseases—where it drives pathological development. Currently, there is a lack of comprehensive reviews systematically addressing the specific mechanisms of O-GlcNAcylation under both physiological and pathological conditions. Therefore, this article aims to summarize its dual role in maintaining organismal homeostasis and promoting disease pathogenesis, providing an integrated evaluation of the biological significance of this modification in health and diseases. Furthermore, it discusses the potential of O-GlcNAcylation as a therapeutic target, explores its clinical applications, and analyzes the current challenges and future directions in drug development, thereby offering theoretical insights and research perspectives for related fields.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 12","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70536","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145750826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jian Ji, Juan D. Roa G, Shu-Ling Chong, Quan Wang, Chin Seng Gan, Jane P. W. Ng, Thelma Elvira Teran Miranda, Freddy Israel Pantoja Chamorro, Lawrence Chi Ngong Chan, Qalab Abbas, Jacqueline S. M. Ong, Ivan J. Ardila, Yasser M. Kazzaz, Jesús A. Domínguez-Rojas, Hiroshi Kurosawa, Susana Beatriz Reyes Domínguez, Natalia Elizabeth Gómez Arriola, Natalia Zita Watzlawik, Adriana Yock-Corrales, Rubén Eduardo Lasso Palomino, Gabriela Aparicio, Paula Caporal, Rosa Elena de la Torre Gómez, Chunfeng Liu, Rujipat Samransamruajkit, Nattachai Anantasit, Deborah M. Turina, Marisol Fonseca Flores, Pei-Chuen Lee, Francisco J. Pilar-Orive, Hongxing Dang, Yek Kee Chor, Meixiu Ming, Juan C. Jaramillo-Bustamante, Sebastián González-Dambrauskas, Jan Hau Lee, Suyun Qian
Evidence for the use of prophylactic anti-seizure medication (ASM) in traumatic brain injury (TBI) in reducing the occurrence of early post-traumatic seizure (EPTS) remains equivocal. This study aimed to analyze the prevalence of EPTS in children with TBI, compare clinical characteristics of those with and without EPTS, and explore the association between prophylactic ASM and EPTS. We performed an observational study among 28 pediatric intensive care units in 15 countries from January 2014 to October 2022. The rate of EPTS was compared between individuals prescribed prophylactic ASM and those who were not. Logistic regression was used to examine the association between ASM and EPTS. Among 697 children with TBI, 161 (23.1%) developed EPTS and 280 (40.2%) received prophylactic ASM treatment. Use of prophylactic ASM was associated with a lower likelihood of developing EPTS (27/280 (9.6%) vs. 134/417 (32.1%), p < 0.001). The most frequently used prophylactic ASMs were phenytoin, levetiracetam, and phenobarbital. Age ≤ 4 years and GCS ≤ 8 were associated with increased odds of developing EPTS (aOR 2.29, 95% CI 1.54–3.40, p < 0.001 and aOR 1.80, 95% CI 1.18–2.74, p = 0.01). Our data provide evidence supporting the potential protective role of prophylactic ASM against EPTS.
在创伤性脑损伤（TBI）中使用预防性抗癫痫药物（ASM）以减少早期创伤后癫痫发作（EPTS）的发生的证据仍不明确。本研究旨在分析TBI患儿EPTS的患病率，比较有EPTS和没有EPTS的患儿的临床特征，探讨预防性ASM与EPTS的关系。2014年1月至2022年10月，我们在15个国家的28个儿科重症监护室进行了一项观察性研究。比较处方预防性ASM和未处方预防性ASM的个体之间EPTS的发生率。采用Logistic回归分析ASM与EPTS之间的关系。697例TBI患儿中，161例（23.1%）发展为EPTS， 280例（40.2%）接受预防性ASM治疗。使用预防性ASM与发生EPTS的可能性较低相关(27/280 （9.6%)vs. 134/417 (32.1%), p < 0.001）。最常用的预防性asm是苯妥英、左乙拉西坦和苯巴比妥。年龄≤4岁和GCS≤8与发生EPTS的几率增加相关（aOR 2.29, 95% CI 1.54-3.40, p < 0.001; aOR 1.80, 95% CI 1.18-2.74, p = 0.01）。我们的数据为预防性ASM对EPTS的潜在保护作用提供了证据。
{"title":"Association Between Prophylactic Anti-Seizure Medication and Early Post-Traumatic Seizures: An International Observational Multicenter Study","authors":"Jian Ji, Juan D. Roa G, Shu-Ling Chong, Quan Wang, Chin Seng Gan, Jane P. W. Ng, Thelma Elvira Teran Miranda, Freddy Israel Pantoja Chamorro, Lawrence Chi Ngong Chan, Qalab Abbas, Jacqueline S. M. Ong, Ivan J. Ardila, Yasser M. Kazzaz, Jesús A. Domínguez-Rojas, Hiroshi Kurosawa, Susana Beatriz Reyes Domínguez, Natalia Elizabeth Gómez Arriola, Natalia Zita Watzlawik, Adriana Yock-Corrales, Rubén Eduardo Lasso Palomino, Gabriela Aparicio, Paula Caporal, Rosa Elena de la Torre Gómez, Chunfeng Liu, Rujipat Samransamruajkit, Nattachai Anantasit, Deborah M. Turina, Marisol Fonseca Flores, Pei-Chuen Lee, Francisco J. Pilar-Orive, Hongxing Dang, Yek Kee Chor, Meixiu Ming, Juan C. Jaramillo-Bustamante, Sebastián González-Dambrauskas, Jan Hau Lee, Suyun Qian","doi":"10.1002/mco2.70524","DOIUrl":"https://doi.org/10.1002/mco2.70524","url":null,"abstract":"<p>Evidence for the use of prophylactic anti-seizure medication (ASM) in traumatic brain injury (TBI) in reducing the occurrence of early post-traumatic seizure (EPTS) remains equivocal. This study aimed to analyze the prevalence of EPTS in children with TBI, compare clinical characteristics of those with and without EPTS, and explore the association between prophylactic ASM and EPTS. We performed an observational study among 28 pediatric intensive care units in 15 countries from January 2014 to October 2022. The rate of EPTS was compared between individuals prescribed prophylactic ASM and those who were not. Logistic regression was used to examine the association between ASM and EPTS. Among 697 children with TBI, 161 (23.1%) developed EPTS and 280 (40.2%) received prophylactic ASM treatment. Use of prophylactic ASM was associated with a lower likelihood of developing EPTS (27/280 (9.6%) vs. 134/417 (32.1%), <i>p</i> < 0.001). The most frequently used prophylactic ASMs were phenytoin, levetiracetam, and phenobarbital. Age ≤ 4 years and GCS ≤ 8 were associated with increased odds of developing EPTS (aOR 2.29, 95% CI 1.54–3.40, <i>p</i> < 0.001 and aOR 1.80, 95% CI 1.18–2.74, <i>p =</i> 0.01). Our data provide evidence supporting the potential protective role of prophylactic ASM against EPTS.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 12","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70524","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145750843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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