间充质基质/干细胞（MSCs）在许多研究中都有出现，其应用是一个正在发展的研究领域。科学家们正在研究MSCs的能力以及将其用于抗癌治疗的可能性，以及将此类治疗与目前临床使用的治疗方法相结合。本文概述了基于MSCs的治疗策略，评估了它们在癌症治疗背景下的潜力。这些是工程或生物技术方法，以有针对性且治疗有效的方式利用MSCs的天然特性。该综述重点关注创新方法，如通过基因修饰来表达所需的治疗分子，强调它们在临床实践中的潜在应用。创新策略包括修饰以表达抗癌蛋白、miRNA（微小RNA）、siRNA（小干扰RNA）、lncRNA（长链非编码RNA）和circRNA（环状RNA）以诱导特定效应，以及治疗性基因和溶瘤病毒的递送。然而，需要进一步研究来解决现有的障碍，本文也对此进行了讨论。MSCs临床应用中的一个主要挑战是它们的双向作用，这一问题仍然是当前研究的核心焦点，本文对此进行了探讨。
Associations between prenatal exposure to phthalates, bisphenols and their mixtures and early childhood allergic conditions and asthma were examined. Five hundred and fifty-six mother-child pairs from the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort participated. Urine samples collected from mothers during the second trimester of pregnancy were analyzed for phthalates and bisphenols. A child health questionnaire, completed by mothers when children were 12, 24, and 36 months, asked whether children had experienced allergic conditions (i.e., food allergies, eczema, rash) or asthma. In single-chemical models, associations varied with child age. Higher prenatal concentrations of mono-benzyl phthalate (MBzP) were associated with lower odds of eczema at 12 months. At 36 months, higher mono-methyl phthalate (MMP) was associated with increased odds of eczema, whereas higher mono-carboxy-octyl phthalate (MCOP) was associated with reduced odds. Higher prenatal MCOP was also associated with higher odds of rash at 12 months, and higher MMP was associated with higher odds of rash at 36 months. Higher bisphenol S (BPS) was associated with increased odds of asthma at 12 months but decreased odds of eczema and rash at 36 months. Sex-specific effects were also noted. In multi-chemical exposure least absolute shrinkage and selection operator (LASSO) models, several phthalate metabolites and BPS were selected as the best predictors of eczema and rash at 36 months of age. Bayesian kernel machine regression (BKMR) mixture models suggested that BPS was the most important chemical in predicting eczema in children at 36 months, while MMP and BPS were the most important chemicals in predicting rash at 36 months. Prenatal exposure to certain phthalate metabolites and BPS predicted allergic conditions and asthma in young children, with patterns varying by age and sex. Prenatal exposure to these chemicals may differentially influence immune development and contribute to the development of early-life allergic conditions, with potentially sex-specific susceptibility.
BACKGROUND: Endovascular transvenous embolization (TVE) was developed as a curative technique for brain arteriovenous malformations (bAVMs) with small nidi and a single draining vein. We describe a partial transvenous embolization technique (pTVE) as an intermediate embolization session to decrease hemorrhagic complications of larger nidi with multiple venous outlets. METHOD: We reviewed our single-center database of bAVMs treated endovascularly between January 2023 and March 2024. Six consecutive patients underwent 10 sessions of pTVE for ruptured AVMs. RESULTS: The median age of patients was 24.5 years. The median nidus size was 5 cm (range 4-6 cm). Three patients had grade III lesions according to the Spetzler-Martin classification, two were grade IV, and one was grade V. Four patients had draining veins with multiple efferent veins with each collecting vein, one patient had multiple efferent veins with one collecting vein, and one patient had one efferent vein with a long bifurcation. pTVE achieved partial occlusion in all cases without any hemorrhagic complications. One patient had the AVM totally occluded with two sessions of pTVE. Decision-making was facilitated by creating subcategories of venous angioarchitecture and detailing the technical particularities in the corresponding category. CONCLUSION: We described a novel treatment technique of transvenous embolization as an adjunct strategy for large bAVMs.
背景：本研究利用高危人群的健康社会决定因素（SDOH）数据建立了肺癌筛查（LCS）依从性预测模型。通过识别影响不依从的关键因素，我们试图改善对那些在15个月内不太可能完成年度LCS后续扫描的个体的风险分层。 方法：我们招募了188名符合高危吸烟包年标准的少数族裔个体，他们于2017年至2021年期间在洛杉矶县的四个临床中心接受了首次低剂量计算机断层扫描（LDCT）。参与者完成了一项经机构审查委员会批准的调查，评估人口统计学、烟草使用、社会需求、歧视和肺癌风险认知。首次LDCT时的居住地址进行了地理编码，以与邻里层面的SDOH指标相匹配。根据个体是否在2021年6月30日前接受首次LDCT，将数据分为训练组（N = 145）和测试组（N = 43）。检查电子病历中首次LCS后15个月内的LDCT随访情况。那些在首次LCS后15个月内接受后续LDCT的人被视为依从者。我们使用超参数调整训练了一个XGBoost分类器，并进行了Shapley加法解释（SHAP）分析以解释模型预测。 结果：该队列包括69名（37%）亚裔/太平洋岛民、53名（28%）黑人/非裔美国人以及49名（26%）西班牙裔/拉丁裔参与者。LCS不依从率为66%。XGBoost分类器的曲线下面积（AUROC）为0.81，精确率-召回率曲线下面积（AUPRC）为0.90，预测性能为：准确率 = 0.79，召回率 = 0.78，特异性 = 0.81，阳性预测值 = 0.88，阴性预测值 = 0.68。SHAP分析表明，邻里层面的SDOH因素，如学校教育水平和贫困程度，比吸烟状况等个体层面因素更能预测不依从情况。 结论：这种机器学习方法利用个体和邻里层面的SDOH因素准确预测了LCS不依从情况。这些发现强调了社区层面特征在为LCS依从性干预提供信息方面的相关性，并可能支持制定区域针对性策略以提高高危人群的依从性。
背景：类淋巴系统和外周炎症与帕金森病（PD）有关，但潜在机制仍不清楚。我们研究了扩大的血管周围间隙（EPVS），以探讨PD患者类淋巴系统、外周炎症、疾病进展和运动症状之间的相互作用。 方法：本研究纳入85例PD患者和87名健康对照（HC）。根据MDS-UPDRS评分，将患者分为震颤为主型（TD）和姿势不稳和步态障碍型（PIGD）亚组。使用Hoehn-Yahr（H-Y）量表评估疾病阶段。我们评估了基底节（BG）和半卵圆中心（CSO）的EPVS数量，收集血清白细胞计数及其衍生比值，探讨它们对运动症状和H-Y分期的潜在影响。 结果：PD患者的BG-EPVS和CSO-EPVS数量显著多于HC。此外，BG-EPVS和CSO-EPVS的数量与白细胞、中性粒细胞、中性粒细胞与淋巴细胞比值（NLR）、全身免疫炎症指数（SII）、H-Y分期和运动症状呈正相关，与淋巴细胞和淋巴细胞与单核细胞比值（LMR）呈负相关。然而，运动症状仅与中性粒细胞、NLR、SII和H-Y分期呈正相关。多元回归分析证实，中性粒细胞、NLR、SII和H-Y分期显著影响BG-EPVS数量、CSO-EPVS数量和MDS-UPDRS III评分。中介分析表明，EPVS数量介导了外周炎症、疾病进展和运动症状之间的关系。 结论：EPVS数量与外周炎症相关，并可能介导外周炎症和疾病进展对PD患者运动症状的影响。EPVS可能是类淋巴系统功能障碍的有效指标。
目的：本研究旨在评估被诊断为视网膜中央动脉阻塞（CRAO）患者患眼及对侧健康眼的视网膜微血管特征，并确定对侧眼中是否存在亚临床微血管改变。 方法：纳入30名单侧CRAO患者，患眼指定为A组，对侧健康眼为B组。纳入30名年龄匹配的健康个体作为C组作为对照组。所有参与者均接受最佳矫正视力（BCVA）评估、眼压测量、光学相干断层扫描（OCT）、光学相干断层扫描血管造影（OCTA）和颈部超声检查。测量视网膜微血管参数，包括中央视网膜厚度（CRT）、黄斑无血管区（FAZ）和血管密度（VD），并进行统计分析以确定对侧眼的亚临床改变。 结果：A组中央视网膜厚度（CRT）（327.77±35.85μm）高于C组（251.17±7.02μm，p<0.05），B组（240.30±5.19μm）低于C组（p<0.05）。所有组之间黄斑无血管区（FAZ）面积差异显著（A组：0.40±0.017mm²，B组：0.34±0.014mm²，C组：0.31±0.005mm²，p<0.05）。A组浅表毛细血管丛血管密度（SCP-VD）（40.21%±2.97%）低于B组（45.78%±3.16%）和C组（46.97%±2.60%，p<0.05），B组和C组之间无显著差异。深层毛细血管丛（DCP-VD）和放射状视乳头周围毛细血管（RPC-VD）密度在所有组之间差异显著（p<0.05）。B组的CRT与SCP-VD呈相关性（p = 0.016）。 结论：CRAO患者对侧健康眼中可能存在亚临床微血管改变，表明CRAO与全身血管变化之间可能存在关联。这些发现强调了对双眼进行早期评估的重要性。OCTA是一种用于可视化视网膜血管结构的有价值工具，并支持与CRAO相关的视网膜血管异常的早期检测和管理。
Precisely identifying cancer drivers helps us to understand the molecular mechanisms of cancer, offering critical targets for early diagnosis. Despite the increasing application of graph neural networks in predicting cancer driver genes, existing approaches do not fully leverage the information from gene networks, and are unable to effectively extract node features from directed graphs. To this end, we propose MDIGNN, a novel deep learning model designed to identify cancer driver genes by integrating directed gene networks with multi-omics data. First, we construct a directed graph through the integration of existing gene networks from diverse databases and multi-omics data. Then, to encode the edge directionality, we develop a graph neural network based on the magnetic Laplacian, which relies on a complex Hermitian matrix for representing the directed graph structure. Next, we apply the channel attention and spatial attention mechanisms to improve the model's feature representation ability. Finally, MDIGNN uses a fully connected layer to compute the cancer driver probability for each gene. In a comparative evaluation, MDIGNN outperforms existing state-of-the-art methods in the field, and it is capable of detecting potential cancer driver genes.
Fibrosis is characterized by excessive extracellular matrix (ECM) deposition driven by mechanical stress, yet the underlying molecular mechanisms remain incompletely understood. To investigate whether mechanical stress-induced ECM remodeling is mediated by YAP/TAZ-TEAD signaling and whether pharmacological modulation can mimic or reverse these effects. Nucleus pulposus (NP) cells were exposed to mechanical stress and treated with the MST1/2 inhibitor XMU-MP-1 or the YAP/TAZ-TEAD inhibitor Verteporfin (VP). Nuclear localization of YAP/TAZ-TEAD, expression of canonical TEAD target genes (CTGF, CYR61, ANKRD1), and ECM markers (Col1, Col2, α-SMA, FN, CTGF) were analyzed by Western blot, qPCR, and immunofluorescence. Mechanical stress induced nuclear accumulation of YAP/TAZ-TEAD, upregulated TEAD target genes, and promoted profibrotic ECM remodeling. XMU-MP-1 recapitulated these effects, while VP suppressed TEAD-dependent transcription and reversed ECM remodeling without affecting nuclear localization. YAP/TAZ-TEAD signaling mediates mechanically induced ECM remodeling. Activation of this pathway drives profibrotic gene expression, and disruption of YAP-TEAD interaction effectively reverses these changes, highlighting a potential therapeutic target for fibrosis.
BACKGROUND: Prurigo nodularis (PN) is a neuroimmune skin disease characterized by the presence of chronic itch (≥6 weeks) and multiple white-pink papules, nodules and/or plaques. OBJECTIVES: The OLYMPIA long-term extension (OLYMPIA-LTE) trial evaluates long-term, over 184 weeks, safety and efficacy of nemolizumab in adults with moderate-to-severe PN. METHODS: Adults with moderate-to-severe PN, who completed phase 2b (NCT03181503) and phase 3 (OLYMPIA 1&2) lead-in trials, were eligible for the ongoing OLYMPIA-LTE trial. Patients receiving nemolizumab monotherapy (continuous-nemolizumab) during lead-in trials continued their regimen, while those on placebo (nemolizumab-naïve) initiated nemolizumab monotherapy. The primary endpoint was long-term safety. Efficacy assessments included the proportion of patients achieving a ≥4-point improvement from baseline Peak Pruritus Numerical Rating Scale (PP-NRS4), Sleep Disturbance Numerical Rating Scale (SD-NRS4) and Dermatology Life Quality Index (DLQI4) scores, Investigator's Global Assessment (IGA) score 0/1 (clear/almost clear), and 75% healed pruriginous lesions (Prurigo Activity and Severity score item-5b). Observed cases up to week 100, regardless of rescue medication, are presented, without imputation of missing data. RESULTS: At interim analysis data cut-off (21 July 2024), 290/508 (57%) patients completed week 100 (median exposure: 839.5 days). Treatment-emergent adverse events (TEAEs) occurred in 89% of patients (452/508; exposure time-adjusted incidence rate: 197.5/100 patient-years) and were mostly mild/moderate (26%/52%) in severity. TEAEs occurring in ≥5% of patients at any given year were COVID-19 (28%), nasopharyngitis (20%), upper respiratory tract infection (13%), neurodermatitis (worsening of PN; 13%), back pain (9%), headache (9%), arthralgia (9%), cough (8%), hypertension (8%) and nummular eczema (8%). At week 100, among evaluable patients treated with nemolizumab, 92% achieved PP-NRS4, 86% SD-NRS4, 91% DLQI4, 74% IGA 0/1 and 84% observed healing of >75% of pruriginous lesions. CONCLUSIONS: Long-term treatment with nemolizumab was well tolerated and led to disease control with clinically meaningful improvements in itch intensity, pruriginous lesions and quality of life. CLINICAL TRIAL REGISTRATION NO: NCT04204616, RD.06.SPR.202699 and 2019-004294-13 (EudraCT Number).
本文全面综述了混凝土的动态拉伸行为，重点关注其对大坝等抗震和易受冲击结构的影响。本研究的独特之处在于：首次明确针对大骨料大坝混凝土在地震应变率范围（10⁻⁴至10⁻²秒）内的行为进行全面综合，这一点在现有文献中至关重要但研究较少；整合了关于湿度效应、加载历史和循环加载等对大坝安全评估至关重要的最新实验和数值研究进展；严格对照最新研究评估现行混凝土大坝设计指南，以确定工程实践与科学依据之间的差距。通过广泛综合实验数据、数值模拟和现有指南，该研究考察了影响动态抗拉强度的关键因素，包括应变率效应、裂缝扩展、测试技术以及诸如含水量、加载历史和骨料尺寸等材料变量。分析了层裂试验、分离式霍普金森压杆装置和循环加载试验方案的实验结果，结果表明，根据应变率、饱和度水平和预加载条件，动态增强因子范围为1.1至超过12。严格评估了惯性效应、自由水（通过斯特凡效应）和微观结构不均匀性在增强或降低拉伸性能方面的作用。讨论了有限元、离散元及近场动力学等数值模型模拟裂缝扩展、惯性主导响应和湿度相互作用的能力。该综述确定并分析了现行设计指南。主要结论强调，有必要将含水量、加载历史和细观尺度不均匀性纳入动态本构模型，同时采用标准化测试方案，以弥合实验室数据与实际应用之间的差距。研究结果主张更新工程指南，以反映率相关断裂力学和多尺度建模的最新进展，确保混凝土基础设施在极端动态载荷下更安全、更具韧性。
上皮-间质转化（EMT）在肿瘤进展和转移中至关重要，长链非编码RNA（lncRNA）是关键调控元件。本研究在中国人群中探讨了EMT相关lncRNA的基因变异与结直肠癌（CRC）风险之间的关联。开展了一项病例对照研究，纳入1888例未经治疗的CRC病例和1888例无癌对照。采用多变量逻辑回归模型评估单核苷酸多态性（SNP）对CRC风险的影响，而表达数量性状位点（eQTL）分析使用来自基因型-组织表达（GTEx）项目的数据，并使用癌症基因组图谱（TCGA）数据库评估基因表达。四个功能相关的SNP（AC106786.1 rs76180806、rs2277930、LINC00578 rs28711160和RP1-193H18.2 rs17823238）与CRC风险显著相关（比值比[OR]=1.52，95%置信区间[CI]=1.26-1.83，P=1.57×10；OR=1.34，95%CI=1.15-1.57，P=3.30×10；OR=1.21，95%CI=1.09-1.33，P=3.30×10；OR=0.83，95%CI=0.75-0.92，P=3.30×10）。值得注意的是，rs28711160对LINC00578表达表现出显著的eQTL效应（P=2.09×10），且LINC00578表达水平与CRC风险密切相关。这些发现表明，EMT相关lncRNA（AC106786.1、LINC00578、RP1-193H18.2）中的基因变异可能导致CRC易感性，并可作为候选生物标志物，为CRC的遗传结构提供了新见解。
BACKGROUND: Alzheimer's disease (AD) is neuropathologically defined by the buildup of misfolded proteins such as extracellular amyloid-β (Aβ) and intracellular tau neurofibrillary tangles. AD also extends beyond these pathological processes, and additional mechanisms such as synaptic dysfunction, microglial activity, astrocytic neuroinflammation play an important role as biomarkers of AD progression. In vivo evaluation and quantification of these molecular processes are possible with positron emission tomography (PET) imaging. As disease-modifying therapies are entering clinical use, biomarkers' importance for early diagnosis and longitudinal monitoring of the disease increases. RESULTS: Aβ is the earliest signature of AD which can be measured with PET imaging, followed by tau-PET positivity, which is highly specific and central for staging and longitudinal monitoring. FDG-PET continues to serve as a gold standard for detecting neurodegeneration, challenged by emerging dual-phase PET protocols for amyloid and tau imaging, which integrate perfusion as a measure of neurodegeneration and pathology information in a single session, enhancing diagnostic efficiency. Synaptic density imaging reveals early synaptic loss linked to cognitive performance and decline. Neuroinflammation tracers can visualize microglial and astrocytic activation, contributing to disease onset and progression. Novel PET tracers targeting alpha-synuclein and TDP-43 show great promise for detecting co-pathologies which can contribute to AD clinical heterogeneity. CONCLUSION: PET imaging has advanced the field by enabling visualization of AD-related changes and providing measurable outcomes for clinical trials and disease-modifying therapies. Imaging of related pathologies can further improve diagnostic accuracy and provide important insights into disease heterogeneity. Moving forward, integrating multiple PET biomarkers into personalized diagnostic approaches will be crucial.
细胞衰老促进腹主动脉瘤（AAA）的病理过程；然而，AAA中衰老的调控机制仍不清楚。在此，我们试图确定gasdermin-E（GSDME）依赖性非经典细胞焦亡在AAA中的作用。GSDME依赖性非经典细胞焦亡在AAA小鼠模型和患者的病变血管壁中被激活。GSDME缺陷抑制血管衰老和AAA进展。单细胞RNA测序（scRNA-seq）、大量RNA测序和多重流式细胞术的联合分析表明，GSDME对于AAA中血管平滑肌细胞（VSMC）的重编程以及巨噬细胞、单核细胞和中性粒细胞免疫状态的转变至关重要。在具有GSDME缺失背景的小鼠中，将GSDME重新引入VSMC而非髓系细胞中，可重现诱导的血管衰老和AAA，而达沙替尼加槲皮素的衰老细胞清除疗法可消除这种现象。这些结果表明，VSMC中GSDME依赖性非经典细胞焦亡可能是AAA中的一个“主开关”，也是治疗AAA的一个潜在靶点。
Organoids are self-organizing three-dimensional (3D) cellular structures derived from stem cells. They can mimic the anatomical and functional properties of real organs. They have transformed in vitro disease modeling by closely replicating the structural and functional characteristics of human tissues. The complexity and variability of organoid-derived data pose significant challenges for analysis and clinical translation. Artificial Intelligence (AI) has emerged as a crucial enabler, offering scalable and high-throughput tools for interpreting imaging data, integrating multi-omics profiles, and guiding experimental workflows. This review aims to discuss how AI is reshaping organoid-based research by enhancing morphological image analysis, enabling dynamic modeling of organoid development, and facilitating the integration of genomics, transcriptomics, and proteomics for disease classification. Moreover, AI is increasingly used to support drug screening and personalize therapeutic strategies by analyzing patient-derived organoids. The integration of AI with organoid-on-chip systems further allows for real-time feedback and physiologically relevant modeling. Drawing on peer-reviewed literature from the past decade, Furthermore, CNNs have been used to analyze colonoscopy and histopathological images in colorectal cancer with over 95% diagnostic accuracy. We examine key tools, innovations, and case studies that illustrate this evolving interface. As this interdisciplinary field matures, the future of AI-integrated organoid platforms depends on establishing open data standards, advancing algorithms, and addressing ethical and regulatory considerations to unlock their clinical and translational potential.
主题：本系统评价和荟萃分析评估了与单焦点镜片或安慰剂相比，近视控制干预措施是否能使近视儿童和青少年的脉络膜厚度（ChT）产生可测量的变化。主要目的是描述ChT调节模式。 临床相关性：近视是全球最常见的眼部疾病，预计到2050年将影响全球50%的人口。高度近视会增加诸如近视性黄斑病变和视网膜脱离等并发症的风险。治疗效果的早期生物标志物至关重要，鉴于ChT对视觉和药物刺激具有快速且双向的反应，它已成为一个有前景的候选指标。 方法：该方案已在国际系统评价前瞻性注册库（PROSPERO；CRD420251144689）中注册。遵循系统评价和荟萃分析的首选报告项目（PRISMA）2020指南以及系统评价评估测量工具2（AMSTAR - 2）标准，纳入评估儿科人群近视控制干预后ChT变化的随机对照试验（RCT）。于2025年8月5日完成对PubMed、科学网和Scopus的检索。两名评审员使用Cochrane工具独立筛选、提取并评估偏倚风险。计算合并平均差及95%置信区间（CI），并采用推荐分级、评估、制定与评价对证据确定性进行评级。 结果：分析了11项RCT，共2190只眼。重复低强度红光疗法导致脉络膜增厚幅度最大（平均差 = 24.1μm，95%CI：19.8 - 28.5；I² = 77%）。阿托品产生了适度但显著的效果（平均差 = 10.6μm，95%CI：6.7 - 14.5），异质性较高（I² = 97%）。角膜塑形术使脉络膜厚度持续增加（平均差 = 13.3μm，95%CI：9.5 - 17.1；I² = 6%），而多焦点眼镜显示出中等效果（平均差 = 13.2μm，95%CI：5.7 - 20.7；I² = 0%）。大多数干预措施的证据确定性评级为高，阿托品的证据确定性评级为中等。 结论：近视控制干预措施可使ChT早期出现可测量的增加。这些发现描述了脉络膜调节模式，但其临床相关性仍不确定。需要进一步开展将ChT与疗效指标相结合的研究。 财务披露：专有或商业披露信息可在本文末尾的脚注和披露部分中找到。
Eutectogels, obtained from the combination of deep eutectic systems (DESs) or natural deep eutectic systems (NADESs) with polymers, represent a new class of sustainable soft materials. Combining the tunable properties of DESs, such as low volatility, ionic conductivity, and biocompatibility, with the structural integrity of gels, these materials can be designed to have improved mechanical flexibility, self-healing ability, and environmental stability. Recent research focused on understanding how the composition of DESs, polymer type, or crosslinking mechanisms influence the physicochemical behavior and performance of eutectogels. Advances in this field enabled their use in diverse biotechnological applications, particularly in drug delivery, transdermal systems, wound healing, and tissue engineering, where they demonstrate improved biofunctionality and adaptability compared to traditional hydrogels. Nevertheless, challenges related to scalability, reproducibility, long-term stability, and toxicity must be addressed to reach their full potential. Progress in this area relies on multidisciplinary efforts between green chemistry, materials science, and bioengineering. Overcoming these hurdles could allow eutectogels to evolve from academic concepts into a new generation of sustainable, high-performance soft materials with broad applicability in the biotechnology field.
肝转移是结直肠癌患者死亡的主要原因，然而，名为中性粒细胞的免疫细胞在此过程中的作用仍很复杂。在本研究中，我们识别出三种不同的中性粒细胞亚型：抗肿瘤高密度中性粒细胞、促肿瘤成熟低密度中性粒细胞和未成熟低密度中性粒细胞。我们在此表明，肿瘤衍生的粒细胞-巨噬细胞集落刺激因子（GM-CSF）通过AKT-核因子κB-活化T细胞核因子5（NFAT5）信号轴将抗肿瘤中性粒细胞转变为促肿瘤状态。这些活化的中性粒细胞在受到CXC趋化因子受体2（CXCR2）配体进一步刺激时，会释放出称为中性粒细胞胞外陷阱的网状结构，这些结构通过促进癌细胞生长、抑制免疫反应以及为肝转移做好准备来促进癌症扩散。重要的是，我们证明使用消耗中性粒细胞的抗体或抑制其促肿瘤活性的药物可有效减少小鼠的肝转移。我们的研究确定了特定的中性粒细胞亚群是癌症进展的关键驱动因素，并突出了它们在预防转移扩散方面的治疗潜力。
综述目的：本综述综合了最近发表的关于骨质疏松症相关椎体骨折的流行病学和管理方面社会人口学（基于年龄、性别、种族/民族或收入/保险）差异的科学证据。 最新发现：我们确定了23项研究，这些研究调查并报告了在骨质疏松症相关椎体骨折的流行病学和管理方面存在的基于年龄、性别、种族/民族、保险和收入的差异。与白人成年人相比，这些骨折在老年人中通常更常见，而在黑人成年人中则较少见。椎体强化术有时用于治疗骨质疏松症相关椎体骨折，并且在少数族裔中使用较少。在骨质疏松症相关椎体骨折的流行病学和管理方面报告的社会人口学差异在各项研究中并不一致。然而，相对较少的研究调查了这些差异的原因，而这些原因对于确定这些差异是否代表真正的医疗差距很重要，从而为可以减少这些差距的干预措施提供依据。在骨质疏松症相关椎体骨折的流行病学和管理方面存在基于年龄、性别、种族/民族、保险和收入的差异。需要进一步开展工作以了解这些差异的根本原因，以便制定干预措施来解决这些问题。
固态电池因其安全性和能量密度而备受关注。基于聚偏氟乙烯（PVDF）的固体聚合物电解质（SPE）由于其优异的柔韧性、机械性能和加工性能而显示出巨大的应用潜力。然而，有限的离子电导率限制了其应用。此外，抑制锂枝晶的生长是固态电池中另一个需要解决的关键问题。添加离子导电填料（如LiLaZrO）以提高离子电导率是主要方法。在先前的工作中，我们发现用镓基液态金属对LiLaZrO进行表面改性可以改善界面相容性并抑制锂枝晶的生长，从而提高电池性能。在本研究中，我们将镓基液态金属改性的LiLaZrO与PVPF-HFP相结合，并采用相分离法制备了具有多孔网络的复合膜。吸收电解质后，得到凝胶电解质（GPEs）。通过填料改性以及孔径和连通性的优化，该凝胶电解质在室温下实现了3.8×10 S·cm的离子电导率。配备改性凝胶电解质的半电池在1C下可循环400次，保留率为96.24%，显示出良好的循环稳定性。本研究为凝胶电解质的设计和应用提供了思路。
背景：尽管登革热病例数和免疫功能低下情况均呈上升趋势，但关于免疫功能低下个体中严重登革热的常见程度，相关研究有限。这些数据对于为数量不断增加的免疫功能低下旅行者提供建议的人来说至关重要。 方法：我们对报告免疫功能低下人群中登革热频率或结局的研究进行了系统评价和荟萃分析。排除非人研究和综述文章。使用ROBINS-E工具评估偏倚风险。 结果：纳入85项研究；63项存在非常高的偏倚风险。不同免疫功能低下患者队列中登革热的发生率在0.3%至6.3%之间。在1182例登革热病例中，664例患有自身免疫性疾病，388例为实体器官移植后（SOT），20例为干细胞移植后（HSCT），28例患有血液系统恶性肿瘤，24例患有非血液系统恶性肿瘤，58例为HIV阳性。严重登革热和死亡率估计分别为0.27[0.22 - 0.33]和0.14[0.10 - 0.18]，排除非常高风险或小样本研究后分别降至0.16[0.09 - 0.27]和0.04[0.03 - 0.05]。23例（5.6%）移植后登革热患者被认为与供体相关。HSCT患者的死亡率达66.7%，SOT患者为10%。血液中登革热RNA在4个月内可检测到，尿液中在2年内可检测到；9个月时从尿液中分离出活病毒。 结论：免疫功能低下人群尤其是HSCT患者中的登革热与高严重程度和死亡率相关。它还具有病毒持续存在时间延长的可能性。
受损中枢神经系统的 spared 区域会经历动态重塑，并展现出显著的治疗开发潜力。与存活的神经元和神经胶质细胞相互作用的损伤远端星形胶质细胞（LRA）会发生反应性转变，但其分子和功能特性尚不清楚。在这里，我们使用多种转录谱分析方法，研究了创伤性脊髓损伤后小鼠脊髓 spared 区域的 LRA。我们发现，LRA 获得了一系列分子上不同、神经解剖学上受限的反应状态，这些状态在脊髓损伤后会发生演变。我们在退化的白质中鉴定出转录上独特的反应性 LRA，它们指导清除富含脂质的髓磷脂碎片以促进组织修复的局部小胶质细胞的特化和功能。星形胶质细胞衍生的基质细胞蛋白 CCN1 推动了这种 LRA 功能适应。星形胶质细胞来源的 CCN1 的缺失导致局部小胶质细胞过度、异常激活，其特征是分子特化异常、髓磷脂和轴突碎片的细胞内积累反映出碎片处理受损，以及脂质代谢失调，脂滴积累明显减少。从机制上讲，我们发现 CCN1 与小胶质细胞的 SDC4 结合以增加脂质储存，将这个信号轴与清除碎片的小胶质细胞中至关重要的与修复相关的脂质缓冲反应联系起来。因此，星形胶质细胞 CCN1 缺失导致的小胶质细胞缺陷最终导致白质碎片清除减弱和脊髓损伤后神经功能恢复受损。表达 Ccn1 的白质星形胶质细胞由局部髓磷脂损伤诱导产生，并在小鼠和人类的多种脱髓鞘疾病中出现，这表明它们在白质修复中具有基本的、进化上保守的作用。我们的研究结果表明，特定背景线索塑造了区域上不同的 LRA 反应状态，其功能适应协调了神经修复的多细胞过程并影响疾病结局。
Cellular senescence is defined as a state of permanent cell cycle arrest, providing a natural barrier against cancer. However, senescent cells are very metabolically active and secrete a complex mixture of bioactive molecules collectively known as the senescence-associated secretory phenotype (SASP), which play a dual role in cancer biology. While the SASP can suppress tumors by facilitating immunosurveillance, it can also promote tumor progression by fostering a pro-inflammatory milieu, stimulating angiogenesis, enhancing invasiveness, and enabling immune evasion. In Head and Neck Cancers (HNCs), a highly heterogeneous group of malignancies, SASP has emerged as a critical player in disease progression and treatment resistance. Persistent DNA damage response (DDR) signaling drives SASP and thereby contributes to the progression of head and neck cancer by modulating the tumour microenvironment. It influences the tumor microenvironment (TME) by facilitating epithelial-to-mesenchymal transition (EMT), promoting cancer stem cell-like properties, and impairing the efficacy of radiotherapy, chemotherapy, and immune checkpoint inhibitors. These effects underscore the need for targeted interventions to regulate SASP activity. This review presents a comprehensive overview of the molecular mechanisms underlying SASP generation and its effects on HNCs. We discuss the dual roles of SASP in tumor suppression and progression, its contribution to therapy resistance, and emerging therapeutic strategies, including novel senolytic and senomorphic drugs. Finally, we highlight key challenges and future directions for translating SASP-targeted therapies into clinical practice, emphasizing the need for biomarker discovery, and a deeper understanding of SASP heterogeneity. By targeting the SASP, there is potential to enhance therapeutic outcomes and improve the management of HNCs.
3D bioprinting enables rapid fabrication of complex biological structures for tissue engineering applications. However, optimizing bioink formulation remains challenging due to complex relationships among material properties, printability, and cell viability. While the perimeter ratio (Pr) is commonly used to evaluate printability, it cannot adequately capture the full geometric fidelity required for comprehensive printability assessments, thereby limiting robust bioink design. To address this limitation, a novel Hausdorff distance (HD) metric is employed to quantify printability, directly measuring the maximum deviation between the designed and printed structures. Furthermore, multiple machine-learning approaches were applied to alginate-hyaluronic acid composite inks and rat pheochromocytoma-derived PC12 cells to assess printability and cell viability. Rheological parameters were characterized using support vector regression (SVR) with⩾ 0.974. Multi-layer perceptron (MLP) regressors achievedvalues of 0.932 and 0.945 when predicting HD values of printed grid structures and cell viability, respectively. A regression-based convolutional neural network (CNN) was developed to predict HD values directly from grid structure images, achieving anof 0.986. Through optimization, optimal as-extruded cell viability (⩾95%) was achieved while maintaining high printability (HD ⩽ 0.20). The optimal ink composition was further demonstrated with good long-term cell viability and proliferation potential. This proposed AI-integrated approach can dramatically reduce ink optimization time by rapidly predicting rheological properties, printability, and cell viability from minimal experimental data.
阿尔茨海默病神经病理改变（ADNCs）是认知障碍的主要原因，其患病率仍不确定。最近基于血液的生物标志物能够对ADNCs进行可扩展评估。在此，我们在来自挪威一个基于人群的57岁以上个体队列的11486份血浆样本中测量了苏氨酸217位点的磷酸化tau，作为ADNCs的替代标志物。ADNCs的估计患病率随年龄增长而增加，从58 - 69.9岁人群中的不到8%增至90岁以上人群中的65.2%。在70岁及以上的参与者中，10%患有临床前阿尔茨海默病，10.4%患有前驱性阿尔茨海默病，9.8%患有阿尔茨海默病痴呆症。此外，在70岁及以上人群中，60%的痴呆症患者、32.6%的轻度认知障碍患者以及23.5%的认知未受损人群存在ADNCs。我们的研究结果表明，与之前估计的相比，老年个体中阿尔茨海默病痴呆症的患病率更高，而年轻群体中临床前阿尔茨海默病的患病率更低。
背景：虽然盆底肌肉锻炼（PFME）在预防和治疗盆底功能障碍方面已得到认可，但最佳的临床实施模式仍不明确，影响产后依从性的因素也尚未完全了解。 目的：本系统评价从产后女性的角度评估了盆底肌肉锻炼依从性的障碍和促进因素，以为行为改变策略提供参考。 方法：检索了九个数据库（CINAHL、PubMed、Web of Science、Embase、Cochrane Library、中国生物医学文献数据库、中国知网、万方数据、维普资讯），检索时间从建库至2025年7月1日。符合条件的研究包括定性研究和混合方法研究，报告了关于产后盆底肌肉锻炼障碍/促进因素的可定性提取数据。使用乔安娜·布里格斯研究所定性评估标准评估研究质量。主题分析将研究结果映射到能力、机会、动机-行为（COM-B）模型。 结果：在筛选了968篇摘要和134篇全文后，纳入了9项研究（8项定性研究和1项混合方法研究）。研究确定了与以下领域相关的障碍和促进因素：身体能力（例如孕前运动基础、分娩创伤和疼痛）、心理能力（例如对盆底健康知识的缺乏、代际误解以及阻碍交流的性方面的污名）、身体机会（例如时间限制、数字工具赋能）、社会机会（例如医疗服务质量和家庭支持网络）、反思性动机（例如风险感知驱动、即时反馈强化、对锻炼效果的不确定性）和自动性动机（例如锻炼行为的便利性、过程中的无聊感、身体形象需求以及外部关怀和鼓励）。 结论：研究结果确定了影响产后女性参与盆底肌肉锻炼的关键因素，并提出了几种干预策略。鉴于目前关于该主题的定性研究较少，有必要进行更多研究以进一步阐明影响产后女性坚持盆底肌肉训练方案的复杂、相互作用的因素。
背景：结直肠癌（CRC）的进展受肿瘤微环境影响，尤其是肿瘤相关巨噬细胞（TAM），其常具有免疫抑制功能。CD300e是一种参与免疫调节的髓系受体，在CRC中的作用尚不明确。 方法：使用全身性和髓系特异性CD300e基因敲除小鼠，在氧化偶氮甲烷/葡聚糖硫酸钠和MC38小鼠CRC模型中进行功能研究，并通过过继转移实验评估巨噬细胞内在效应。人体研究包括分析CRC患者配对的肿瘤组织和正常组织中CD300e的表达，以及将患者来源的结肠肿瘤类器官与单核细胞进行体外共培养，以研究CD300e的诱导和TAM极化。 结果：在体内，CD300e缺陷导致肿瘤负荷降低、TAM上主要组织相容性复合体表达增强以及T细胞反应改善。CD300e缺陷的巨噬细胞表现出吞噬活性增加、抗原呈递增强以及对T细胞增殖和细胞毒性的支持。过继转移证实巨噬细胞内在的CD300e表达足以抑制T细胞功能并促进肿瘤生长。在CRC患者中，CD300e在肿瘤浸润的单核细胞和巨噬细胞中选择性上调，导致以抗原呈递受损为特征的抑制表型。体外肿瘤来源的信号诱导CD300e表达并促进促肿瘤巨噬细胞表型。 结论：我们的研究结果确定CD300e是CRC中巨噬细胞介导的免疫抑制的关键调节因子，也是重编程TAM以增强免疫治疗的潜在靶点。
顺铂诱导的听力损失（CIHL）是顺铂的主要剂量限制性毒性，主要由耳蜗毛细胞中的氧化应激和细胞凋亡引起。本研究旨在探讨异甘草素（ISL，一种天然的Nrf2激动剂）对CIHL的耳保护作用，并阐明ISL潜在的抗CIHL机制。最初，使用荧光素酶报告基因系统从植物化学文库中鉴定出ISL为天然Nrf2激动剂。然后在HEI-OC1细胞、耳蜗外植体和顺铂诱导的耳毒性小鼠模型中研究了ISL的耳保护作用。在顺铂诱导的耳毒性小鼠中，ISL显著恢复了全频听性脑干反应（ABR）阈值，并减轻了顺铂诱导的耳蜗毛细胞损失。在HEI-OC1细胞和耳蜗外植体中，ISL显著减轻了顺铂引发的活性氧（ROS）过量产生、线粒体功能障碍和毛细胞凋亡。机制上，ISL共价修饰KEAP1的两个关键半胱氨酸残基（Cys226和Cys288），随后稳定Nrf2并上调下游抗氧化蛋白的表达，包括NAD（P）H醌氧化还原酶1（NQO1）、血红素加氧酶-1（HO-1）和超氧化物歧化酶（SOD）。总的来说，我们的研究结果清楚地表明，ISL通过共价修饰KEAP1上的两个关键半胱氨酸残基激活Keap1-Nrf2-ARE信号通路，显著减轻顺铂诱导的听力损失（CIHL）。
背景：丙戊酸（VPA）是一种组蛋白脱乙酰酶抑制剂，对骨稳态具有剂量依赖性作用。本研究调查低剂量VPA是否通过靶向氧化应激和铁死亡来预防去卵巢（OVX）诱导的骨质疏松症。 方法：OVX大鼠接受低剂量（100mg/kg/d）或高剂量（300mg/kg/d）VPA治疗12周。通过显微CT分析骨微结构。通过测量丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽（GSH）和铁来评估全身氧化还原状态。检测铁死亡标志物（谷胱甘肽过氧化物酶4（GPX4）、长链脂酰辅酶A合成酶4（ACSL4）、铁蛋白重链1（FTH1）、核受体辅激活因子4（NCOA4））。在用VPA（0.5 - 3mM）预处理的MC3T3 - E1细胞中，用erastin诱导铁死亡。进一步评估EZH2/H3K27me3信号通路和破骨细胞生成。 结果：OVX诱导骨丢失、氧化应激（MDA/铁升高，SOD/GSH降低）和铁死亡激活（ACSL4/NCOA4增加，GPX4/FTH1降低）。低剂量VPA逆转了这些变化，改善了骨密度和微结构，并减少了骨吸收。高剂量VPA没有显示出保护作用。在体外，1mM VPA减轻了erastin诱导的脂质过氧化、线粒体损伤和铁死亡。机制上，VPA激活EZH2/H3K27me3信号通路，增强NCOA4启动子处的H3K27me3富集以抑制铁蛋白自噬和铁死亡。VPA还抑制了核因子κB受体活化因子配体（RANKL）诱导的破骨细胞分化。 结论：低剂量VPA通过恢复氧化还原稳态、通过EZH2/H3K27me3激活在表观遗传上抑制NCOA4介导的铁蛋白自噬以及抑制破骨细胞生成来改善骨质疏松症。这些发现确定低剂量VPA为一种多方面的抗骨质疏松剂，并突出了EZH2/H3K27me3/NCOA4轴作为骨氧化还原生物学中的关键调节途径。
乳腺癌（BRCA）的异质性促进了恶性肿瘤的进展和治疗抵抗，但蛋白酶在此过程中的作用仍有待阐明。在本研究中，我们鉴定出丝氨酸蛋白酶3（PRSS3），它是丝氨酸蛋白酶家族中不可或缺的成员，通过其抑制铁死亡的能力，被确定为BRCA中的致癌驱动因子。对90对BRCA组织样本进行免疫组化分析显示，PRSS3在76.47%的HER2阳性亚型、87.30%的腔面A/B型病例以及90%的三阴性乳腺癌（TNBC）肿瘤中高表达。PRSS3水平升高与晚期临床分期、淋巴结转移以及Ki-67表达增加显著相关。通过功能获得和功能缺失的BRCA细胞模型进行的转录组分析与功能研究表明，PRSS3促进肿瘤进展主要归因于其剪接异构体1（PRSS3-V1），它与蛋白酶激活受体2（PAR2）相互作用，并在体外和体内增强ERK1/2磷酸化。沉默PRSS3通过多种机制显著诱导细胞周期停滞和铁死亡细胞死亡，包括丙二醛和乳酸脱氢酶水平升高、通过调节转铁蛋白受体1（TfR1）和铁蛋白重链1以及活性氧积累不稳定铁、线粒体膜功能障碍以及NLRP3炎性小体激活。这些效应是由铁死亡的两个关键调节因子SLC7A11和GPX4的下调介导的，导致脂质过氧化增加。用PAR2激动剂SLIGKV-NH2或TfR1抑制剂铁抑素II处理可减弱这些效应。此外，PRSS3敲低提高了BRCA细胞对紫杉醇和阿霉素的化疗敏感性，并减轻了对曲妥珠单抗的耐药性。我们的研究结果揭示了BRCA中一种新的PRSS3介导的铁死亡逃逸机制。靶向PRSS3-PAR2-ERK1/2轴可能具有治疗潜力，PRSS3-V1可作为BRCA亚型分层的有价值生物标志物。
球形聚电解质刷（SPBs）在生物医学领域备受关注，尤其是在基因递送方面，但其刷状结构通常是固定的，可调性和响应性有限。在此，我们报道了一种光控超分子SPB（AuNP@CDs@Azo-PD），它是通过可逆的主客体相互作用将偶氮苯封端的聚（甲基丙烯酸2-（二甲氨基）乙酯）（Azo-PD）组装到β-环糊精功能化的金纳米颗粒（AuNP@CDs）上构建而成。所得的纳米结构呈现出具有刷状聚合物冠层的核壳结构。通过动态光散射（DLS）和紫外可见光谱对该系统进行表征，证实了纳米载体的成功形成及其在紫外照射下进行可控结构转变的能力。对SPB系统的基因递送能力进行了进一步评估，结果表明其具有优异的生物相容性和有效的质粒DNA包封能力，并能抵御血清核酸酶。体外转染研究表明，AuNP@CDs@Azo-PD实现了与Lipofectamine 3000相当的转染效率，具有高效的基因表达并抑制了PI3K/AKT信号通路。此外，紫外触发的PTEN基因释放导致增强的肿瘤抑制效果，包括减少细胞增殖、迁移和增加细胞凋亡。这些发现证明了AuNP@CDs@Azo-PD作为一种用于可控基因递送和癌症治疗的多功能且响应性纳米平台的潜力。
全基因组关联研究、连锁图谱分析和转录组分析表明，TraesCS1B02G308200是与小麦氮素利用效率相关的候选基因。提高小麦生产中的氮素利用效率（NUE）可以在减少氮肥施用量的同时大幅提高作物产量。在本研究中，在两个群体中检测了与NUE相关农艺性状的QTL：（1）来自中国黄淮流域的243份小麦种质资源的自然群体（CH群体）和（2）由Avocet和Chilero杂交衍生的重组自交系（RIL）群体（AC群体）。在两个生长季的两个试验地点，在正常和低氮胁迫两种氮素处理条件下对9个农艺性状进行了评估。基于所有环境下9个性状的低氮耐受指数，分别通过关联分析和连锁分析鉴定出836个和154个QTL。通过对Chilero在拔节期、开花期和灌浆期的进一步转录组分析，在两个群体的共定位区间内共鉴定出48个差异表达基因。一个稳定的QTL，QYSI1B.2（chr1B: 501.04 - 508.02 Mb），在两个群体中均得到成功验证。通过检查局部连锁不平衡，QYSI1B.2被精细定位到一个更小的物理区域，跨度为506.02 - 507.19 Mb。通过评估其表达水平，鉴定出一个可能的候选基因TraesCS1B02G308200，它编码一个WRKY转录因子。这些发现为探索小麦NUE潜在的分子靶点奠定了基础。
血红蛋白病，包括β地中海贫血（Bthal）和镰状细胞病（SCD），是最常见的遗传性血液疾病之一。影响血红蛋白合成的基因突变会导致严重贫血和多器官并发症。旨在纠正或改造造血系统的基因治疗（GT）的发展，尽管最初受到若干限制，但已经实现了两种造血干细胞（HSC）药物产品的上市许可，这两种产品分别通过慢病毒载体基因添加和CRISPR-Cas9基因编辑技术构建。尽管如此，这些方法的成功促使我们对这些疾病中的造血干细胞生物学和骨髓（BM）微环境的认识进行批判性反思。在这里，我们回顾了通过基因添加和基因编辑进行基因治疗的临床应用，以及关于造血干细胞和骨髓生态位特征及功能在血红蛋白病中的新发现。从开发联合策略以改善骨髓微环境以更好地支持基因校正细胞的角度，审视了造血干细胞-生态位中缺陷网络的识别。
本研究基于保护动机理论和人-环境匹配理论，探讨员工对人工智能信任和人工智能威胁的认知如何塑造他们与人工智能的协作以及随后的职业可持续性。通过在线调查收集了532名员工的数据，使用偏最小二乘法结构方程模型（PLS-SEM）分析了各构念之间的关系。结果表明，对人工智能的信任对员工与人工智能的协作产生积极且显著的影响，而威胁感知则通过动机途径间接影响协作。此外，多变型职业取向正向调节人工智能信任与协作之间的联系，表明自我导向的职业态度增强了与人工智能系统的适应性互动。这些发现强调，趋近动机和回避动机在塑造协作结果中发挥着不同的作用，而协作结果反过来又提升了职业可持续性的各个方面。该研究通过整合认知评估和动机视角来解释人机互动动态，为理论做出了贡献，并为在数字工作场所促进有效的人工智能整合和可持续职业发展提供了管理启示。
炎症性肠病（IBD）因其异质性而带来了重大的诊断和治疗挑战。在此，我们分析了244名个体呼出的挥发性有机化合物（VOC），发现了与IBD相关的独特代谢特征。使用先进的热脱附气相色谱-串联质谱法，我们鉴定出64种内源性代谢物，包括碳氢化合物升高、有机酸及其衍生物减少，以及脂质和类脂质分子。整合来自1660名个体的肠道微生物群数据，我们将这些代谢变化与微生物失调联系起来，其特征是有益细菌减少和氧化应激增加。机器学习确定了一个由10种VOC组成的生物标志物组，在IBD各亚型和活动状态中均实现了卓越的诊断准确性（AUC = 0.88）。一种新型风险评分系统进一步提高了诊断精度。在结肠炎模型中的益生菌干预证实，恢复微生物平衡，特别是通过丁酸盐的产生，可减轻炎症并修复肠道屏障。这些发现使呼吸组学成为IBD诊断、分层和针对微生物群的治疗的开创性工具。
背景：自身免疫性疾病（AIDs）涉及具有复杂遗传基础的免疫功能障碍。本研究检测了15种自身免疫性疾病之间的遗传相关性和定向遗传关联，以确定共同的免疫途径。 方法：我们检索了15种自身免疫性疾病的全基因组关联研究（GWAS）汇总统计数据，并使用连锁不平衡评分回归（LDSC）和Z分数相关性分析遗传重叠。通过多基因分析（MAGMA）将单核苷酸多态性（SNPs）分配给基因，并使用多效性基因检测方法（PLACO）评估多效性。进行了功能注释（FUMA）和通路富集分析（MAGMA、MSigDB）。两样本孟德尔随机化（MR）研究了疾病与免疫细胞特征之间的因果关系。 结果：原发性胆汁性胆管炎（PBC）的单核苷酸多态性遗传力最高（43.3%），其次是系统性红斑狼疮（SLE）（32.84%）。大多数疾病对显示出正遗传相关性。我们确定了76个多效性基因，其中HCP5、NOTCH4和SKIV2L在所有15种疾病中都有共享，且集中在扩展的主要组织相容性复合体（MHC）区域。富集分析突出了细胞因子信号传导、抗原呈递和T细胞介导的途径。孟德尔随机化显示类风湿性关节炎（RA）、系统性红斑狼疮（SLE）和系统性硬化症（SS）之间存在定向遗传关联，原发性胆汁性胆管炎增加系统性红斑狼疮的风险（比值比[OR]=1.253），炎症性肠病（IBD）对1型糖尿病（T1D）有轻微保护作用（OR=0.959）。细胞类型孟德尔随机化显示SKIV2L在多个T细胞和髓系亚群中起作用，而NOTCH4的作用仅限于M2巨噬细胞，突出了具有广泛影响与髓系聚焦影响的不同MHC区域枢纽。 结论：这些发现描绘了共享的遗传成分，突出了多效性基因，尤其是SKIV2L、HCP5和NOTCH4，将扩展的MHC结构与T细胞和髓系程序联系起来。它们为确定生物标志物开发和靶向治疗的共同途径和细胞类型提供了遗传框架。
将机器学习的优势与快速积累的高通量测序数据相结合，有助于我们进行生物学发现和推动分子医学发展。近年来，批量RNA测序技术已成为一种经济高效且广泛应用的方法，用于获取测试样本的完整转录组图谱，从而能够识别关键的癌症相关表达模式。反过来，各种机器学习算法能够开发出信息丰富的诊断和预后模型，确保对高维RNA测序数据进行高效处理。这些方法的融合在肿瘤学领域显示出巨大的前景。在这篇叙述性综述中，我们将肿瘤学中基于批量RNA测序的机器学习模型描述为一个从数据预处理到模型验证的完整工作流程。我们提供了算法选择和研究设计的实用建议，并讨论了批量RNA测序反卷积作为一种经济高效的替代单细胞RNA测序的方法，用于分析肿瘤细胞组成。这些见解为开发具有转化潜力的可重复诊断和预后模型提供了实用指南。
通过电刺激对明确脑区进行术中图谱定位的清醒手术（AwS）已成为胶质瘤手术的一个重要组成部分。然而，AwS对低级别胶质瘤（LGG）切除范围（EOR）的影响存在争议。本系统评价旨在研究AwS对LGG患者切除情况和神经学结局的影响。我们在PubMed、Embase和Scopus数据库中进行了文献检索。纳入所有比较成人LGG患者AwS与全身麻醉（GA）下手术的研究。采用ROBINS-I（“干预非随机研究中的偏倚风险”）评估研究质量。分别使用风险比（RR）和95%置信区间（CI）的标准化均数差（SMD）来计算二分类结局和连续变量的效应量。本系统评价和荟萃分析纳入了10项研究。共735例患者，其中AwS组401例，GA组334例。我们发现术前MRI上肿瘤体积无显著差异（SMD：-0.14；95%CI：-0.31至0.03；p=0.11）。两组间平均体积EOR无差异（SMD：0.79；95%CI：-0.24至1.81；p=0.13）。AwS组和GA组的早期运动（RR：0.50；95%CI：0.16 - 1.51；p=0.23）和总体神经学结局（RR：0.67；95%CI：0.23 - 1.93；p=0.46）相当。包括运动和语言功能缺损在内的晚期神经学结局，AwS组明显更好（RR：0.27；95%CI：0.13 - 0.54；p=0.0002）。我们的荟萃分析表明，LGG患者AwS与非清醒手术的总体EOR相当。虽然早期神经学结局无显著差异，但接受AwS的LGG患者长期总体神经学结局更好。
引言：本研究旨在开发并验证人工智能与学术写作问卷（AI - AWQ），以评估参与者对人工智能的看法。主要重点是探索在教育环境中影响对人工智能态度的因素。 方法：本研究采用混合方法来开发和验证AI - AWQ的心理测量特性。该问卷由30个项目组成，采用5点李克特量表评分（1 = 从不，5 = 总是），对伊朗设拉子医科大学252名医学和牙科学生进行了调查，这些学生在2023 - 2024学年修读了学术写作课程。使用探索性因子分析（EFA）对数据进行分析，并采用方差最大化旋转来阐明潜在因素。 结果：共分析了252份完整问卷，其中59.5%来自伊朗学生，其余受访者为国际学生。探索性因子分析结果显示抽样充足性令人满意（KMO = 0.930），Bartlett球形检验显著（P < 0.001），证实数据适合进行因子分析。结构效度检验提取了五个不同的因子——人工智能的感知有效性、伦理和真实性担忧、人工智能支持的写作过程、人工智能反馈与写作提升以及情感和动机影响——这些因子共同解释了总方差的77.99%。该问卷显示出很强的效度和信度，内容效度指数（CVI）为0.903，内容效度比率（CVR）为0.882，Cronbach's alpha系数为0.883，证实了总体内部一致性。 结论：研究结果表明，AI - AWQ为测量对人工智能的看法提供了可靠性和有效性的初步证据，深入了解了人工智能与学术写作的多面性。本研究有助于理解在教育背景下塑造个人对人工智能看法的因素，并为进一步研究奠定了基础。
Mesothelin (MSLN) is a glycosylphosphatidylinositol (GPI)-anchored membrane protein that promotes malignant behaviors including tumor cell proliferation, migration and immune evasion through activation of multiple signaling pathways, such as MAPK/ERK and PI3K/AKT. MSLN is widely overexpressed in malignant tumors but shows low expression levels in normal tissues. This differential expression pattern renders MSLN an important clinical therapeutic target. Currently, MSLN-based tumor-targeting approaches predominantly involve antibody-drug conjugates (ADC), cancer vaccines, oncolytic viruses and chimeric antigen receptor T-cell (CAR-T) therapies. These therapeutic modalities have demonstrated encouraging efficacy in preclinical studies and phase I/II clinical trials. However, challenges such as unclear molecular mechanisms of MSLN signaling pathways and extracellular domain shedding impose limitations on targeted therapeutic strategies. Therefore, this review comprehensively discusses the gene and protein structures of MSLN, its biological functions, and related targeted therapeutic strategies, providing new insights into MSLN-targeted cancer therapy.
PURPOSE: Oral frailty screening and care for elderly cancer patients undergoing chemotherapy have yet to be integrated into cancer care protocols, and there persists a notable deficiency in knowledge concerning the experiences of elderly cancer patients suffering from oral frailty. This study aims to explore the experiences and responses of elderly Chinese cancer patients undergoing chemotherapy for oral frailty. METHODS: Beginning in February 2024, a purposive sampling approach was used to select elderly cancer patients undergoing chemotherapy who scored four or higher on the Oral Frailty Index-8 scale for semi-structured interviews. Two researchers analyzed the data using interpretive phenomenological research methods. RESULTS: Twenty-five elderly cancer patients undergoing chemotherapy with oral frailty were recruited. Four themes were identified: (1) The eroded mouth, impairment and decline; (2) confronting a failing body, at a loss and exhausted; (3) navigating uncertainty, helplessness and struggles; and (4) finding a new balance, transcendence and personal growth. Among these four themes, the researchers developed 13 subthemes. CONCLUSION: The experiences and coping processes of oral frailty in elderly cancer patients undergoing chemotherapy are complex, encompassing both positive and negative physical and psychological experiences. Oncology nurses must emphasize the oral health of elderly cancer patients undergoing chemotherapy and integrate oral frailty screening and care throughout the entire cancer treatment process.
Colorectal cancer (CRC) remains the third leading cause of mortality among cancer patients in developed countries. Each new study in this field can contribute to better detection, diagnosis, and treatment of this disease. Our study aimed to assess transcriptional activity of genes associated with the biotransformation of xenobiotics and endobiotics in all three phases in the CRC , including correlations between them, as well as the aromatic hydrocarbon receptor (AhR) pathways. Based on transcriptome analysis (1252 mRNAs) of the CRC tissue and healthy colon, the upregulation or downregulation of 46 significant mRNAs was presented. The study also revealed the downregulation of and upregulation of and , previously undistinguished and potentially therapeutically valuable in CRC. The diagnostic potential of , , , and was demonstrated. It was stated that the , , , and did not correlate in healthy intestinal tissue whereas , , , , , and did not correlate in CRC. The disturbed transcriptional activity of genes related to the biotransformation process at all stages of CRC suggests that this may be the cause of its occurrence; the genes ought to be taken into account in preventive strategies and the treatment of patients.
BACKGROUND: Although large language models (LLMs) show great promise in processing medical text, they are prone to generating incorrect information, commonly referred to as hallucinations. These inaccuracies present a significant risk for clinical applications where precision is critical. Additionally, relying on human experts to review LLM-generated content to ensure accuracy is costly and time-consuming, which sets a barrier against large-scale deployment of LLMs in health care settings. OBJECTIVE: The primary objective of this study was to develop an automatic artificial intelligence (AI) system capable of extracting structured information from unstructured medical data and using advanced reasoning techniques to support reliable clinical decision making. A key aspect of this objective is ensuring that the system incorporates self-verification mechanisms, enabling it to assess the accuracy and reliability of its own outputs. By integrating such mechanisms, we aim to enhance the system's robustness, reduce reliance on human intervention, and improve the overall trustworthiness of AI-driven medical summarization and evaluation. METHODS: The proposed framework comprises 2 layers: a summarization layer and an evaluation layer. The summarization layer uses Llama2-70B (Meta AI) and Mistral-7B (Mistral AI) models to generate concise summaries from unstructured medical data, focusing on tasks such as consumer health question summarization, biomedical answer summarization, and dialog summarization. The evaluation layer uses GPT-4-turbo (OpenAI) as a judge, leveraging pairwise comparison strategies and different prompt strategies to evaluate summaries across 4 dimensions: coherence, consistency, fluency, and relevance. To validate the framework, we compare the judgments generated by the LLM assistants in the evaluation layer with those provided by medical experts, offering valuable insights into the alignment and reliability of AI-driven evaluations within the medical domain. We also explore a way to handle disagreement among human experts and discuss our methodology in addressing diversity in human perspectives. RESULTS: The study found variability in expert consensus, with average agreement rates of 19.2% among all experts and 54% among groups of 3 experts. GPT-4 (OpenAI) demonstrated alignment with expert judgments, achieving an average agreement rate of 83.06% with at least 1 expert and comparable performance in cross-validation tests. The enhanced guidance in prompt design (prompt-enhanced guidance) improved GPT-4's alignment with expert evaluations compared with a baseline prompt, highlighting the importance of effective prompt engineering in auto-evaluation of summarization tasks. We also evaluated open-source LLMs, including Llama-3.3 (Meta AI) and Mixtral-Large (Mistral AI), and a domain-specific LLM, OpenBioLLM (Aaditya Ura), for comparison as LLM judges. CONCLUSIONS: This study highlights the potential of LLMs as reliable tools for unstructured medical data summarization and evaluation to reduce the dependency on human experts and also states the limitations. The proposed framework, multiagent summarization and auto-evaluation, demonstrates scalability and adaptability for clinical applications while addressing key challenges like hallucination and position bias.
背景：术后恶心呕吐（PONV）是外科手术常见的并发症，尤其是在根治性胸腔镜肺癌手术中，会导致患者不适、延迟康复并增加医疗成本。盐酸戊乙奎醚（PHC）是一种新型抗胆碱能药物，可能因其对M和M毒蕈碱受体的选择性拮抗作用，从而降低与手术和麻醉相关的不良反应，如PONV。本研究旨在探讨PHC在降低根治性胸腔镜肺癌手术后PONV发生率和严重程度方面的疗效和安全性。 方法：本单中心、前瞻性、双盲、随机对照临床试验将纳入446例计划行根治性胸腔镜肺癌手术的患者。入选参与者将按1:1的比例随机分配至试验组或对照组，每组223例患者。试验组将在麻醉前静脉注射0.25mg PHC，并在术后48小时内静脉输注0.25mg PHC，而对照组将接受生理盐水而非PHC。主要结局将是术后24小时内PONV的发生率。次要结局将包括不同时间间隔（术后0 - 6、6 - 12和12 - 24小时）内PONV的发生率和严重程度；术后48小时使用视觉模拟量表评估的外科医生和患者满意度；以及术后48小时内口干、头晕、脸红、皮肤干燥、尿潴留、谵妄和体温升高等不良反应的发生情况。将进行意向性分析。 讨论：我们假设静脉注射PHC可降低PONV的发生率和严重程度，并提高外科医生和患者的满意度。本试验的结果可能对改善根治性胸腔镜肺癌手术患者的预后和优化术后护理具有重要意义。 试验注册：本试验方案于2024年4月19日在中国临床试验注册中心注册（注册号：ChiCTR2400083
BACKGROUND/OBJECTIVES: Itch is the most burdensome symptom in atopic dermatitis (AD) and prurigo nodularis (PN) and is associated with significant psychological distress, sleep deprivation and impaired quality of life. Achieving rapid control of itch is expected to minimize symptomatology and disease burden. Nemolizumab, which targets the interleukin 31 (IL-31) pathway, rapidly relieved itch in Phase 2 trials; thus, a post hoc analysis of four pivotal randomized controlled clinical trials of nemolizumab in AD and PN was performed to further evaluate the improvement of itch over the first 14 days of therapy. METHODS: Data from ARCADIA 1 and 2 in AD (N = 1728) and OLYMPIA 1 and 2 in PN (N = 560) were analysed. Patients reported itch intensity and sleep disturbance daily. Differences in the proportion of itch and sleep responders (patients with ≥4-point improvement from baseline in peak pruritus numerical rating scale [PP-NRS] or sleep disturbance [SD-NRS] score) between nemolizumab and placebo groups were calculated. RESULTS: Nemolizumab rapidly reduced itch in AD (ARCADIA 1 and 2), with a difference versus placebo in PP-NRS responders apparent by Day 2 (pooled data: 10.7% vs. 2.9%; 95% CI: 5.6-10.1; p < 0.0001) that steadily increased through Day 14. Nemolizumab also reduced itch rapidly in PN (OLYMPIA 1 and 2); a difference versus placebo occurred by Day 2 (pooled data: 17.2% vs. 3.7%; 95% CI: 6.8-16.7; p < 0.0001). Early improvement (Day 2) was also observed in sleep in nemolizumab-treated patients. In pooled analyses in AD, 9.9% (nemolizumab) versus 4.6% (placebo; 95% CI: 2.8-7.7; p = 0.0001) were SD-NRS responders and in PN, 13.4% versus 4.3% (95% CI: 4.0-13.0; p = 0.0013). Itch and sleep response data in individual studies were consistent with the pooled data. CONCLUSIONS: This analysis confirms previously reported data that nemolizumab relieves itch and sleep disturbance by Day 2 in patients with moderate-to-severe AD and PN, indicating that targeting the IL-31 pathway presents an important way to achieve rapid itch response.
Zotero 插件