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Multimodal data integration using deep learning predicts overall survival of patients with glioma 利用深度学习进行多模态数据整合可预测胶质瘤患者的总体生存率
Pub Date : 2024-08-08 DOI: 10.1002/viw.20240001
Yifan Yuan, Xuan Zhang, Yining Wang, Hongyan Li, Zengxin Qi, Zunguo Du, Ying‐Hua Chu, Danyang Feng, Jie Hu, Qingguo Xie, Jianping Song, Yuqing Liu, Jiajun Cai
Gliomas are highly heterogenous diseases with poor prognosis. Precise survival prediction could benefit further clinical decision‐making, clinical trial incursion, and health economics. Recent research has emphasized the prognostic value of magnetic resonance imaging, pathological specimens, and circulating biomarkers. However, the integrative potential and efficacy of these modalities require to be further validated. After incorporating 218 patients of The Cancer Genome Atlas glioma datasets of and 54 patients of the Huashan cohort with complementary prognostic information, we established a squeeze‐and‐excitation deep learning feature extractor for T1‐contrast enhanced images and histological slides and explored to screen significant circulating 5‐hydroxymethylcytosines (5hmC) profiles for glioma survival by least absolute shrinkage and selection operator‐Cox regression. Therefore, a prognostication predictive model with high efficiency was obtained through survival support vector machine multimodal integration of radiologic imaging, histopathologic imaging features, genome‐wide 5hmC in circulating cell‐free DNA and clinical variables, suggesting a valid strategy (concordance‐index = 0.897; Brier score = 0.118) for improved survival risk stratification of glioma patients.
胶质瘤是一种预后不良的高度异质性疾病。精确的生存预测有利于进一步的临床决策、临床试验和卫生经济学。最近的研究强调了磁共振成像、病理标本和循环生物标志物的预后价值。然而,这些方法的综合潜力和疗效还有待进一步验证。在纳入了具有互补预后信息的218例癌症基因组图谱胶质瘤患者数据集和54例华山队列患者数据集后,我们建立了一个针对T1对比增强图像和组织学切片的挤压-激发深度学习特征提取器,并探索通过最小绝对缩减和选择算子-Cox回归筛选出胶质瘤生存的重要循环5-羟甲基胞嘧啶(5hmC)谱。因此,通过对放射学成像、组织病理学成像特征、循环无细胞DNA中的全基因组5hmC和临床变量进行生存支持向量机多模态整合,获得了一个高效的预后预测模型,为改善胶质瘤患者的生存风险分层提供了一种有效的策略(一致性指数=0.897;布赖尔评分=0.118)。
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引用次数: 0
Advancements of non‐invasive imaging technologies for the diagnosis and staging of liver fibrosis: Present and future 用于肝纤维化诊断和分期的无创成像技术的进展:现状与未来
Pub Date : 2024-07-15 DOI: 10.1002/viw.20240010
Wenpeng Huang, Yushuo Peng, L. Kang
Liver fibrosis is a reparative response triggered by liver injury. Non‐invasive assessment and staging of liver fibrosis in patients with chronic liver disease are of paramount importance, as treatment strategies and prognoses depend significantly on the degree of fibrosis. Although liver fibrosis has traditionally been staged through invasive liver biopsy, this method is prone to sampling errors, particularly when biopsy sizes are inadequate. Consequently, there is an urgent clinical need for an alternative to biopsy, one that ensures precise, sensitive, and non‐invasive diagnosis and staging of liver fibrosis. Non‐invasive imaging assessments have assumed a pivotal role in clinical practice, enjoying growing popularity and acceptance due to their potential for diagnosing, staging, and monitoring liver fibrosis. In this comprehensive review, we first delved into the current landscape of non‐invasive imaging technologies, assessing their accuracy and the transformative impact they have had on the diagnosis and management of liver fibrosis in both clinical practice and animal models. Additionally, we provided an in‐depth exploration of recent advancements in ultrasound imaging, computed tomography imaging, magnetic resonance imaging, nuclear medicine imaging, radiomics, and artificial intelligence within the field of liver fibrosis research. We summarized the key concepts, advantages, limitations, and diagnostic performance of each technique. Finally, we discussed the challenges associated with clinical implementation and offer our perspective on advancing the field, hoping to provide alternative directions for the future research.
肝纤维化是肝损伤引发的一种修复反应。对慢性肝病患者的肝纤维化进行无创评估和分期至关重要,因为治疗策略和预后在很大程度上取决于肝纤维化的程度。虽然肝纤维化传统上是通过侵入性肝活检来分期的,但这种方法容易出现取样误差,尤其是活检样本量不足时。因此,临床上迫切需要一种可替代活检的方法,以确保对肝纤维化进行精确、灵敏和无创的诊断和分期。无创成像评估在临床实践中发挥着举足轻重的作用,因其在诊断、分期和监测肝纤维化方面的潜力而日益受到欢迎和认可。在这篇综合性综述中,我们首先深入探讨了无创成像技术的现状,评估了其准确性以及在临床实践和动物模型中对肝纤维化诊断和管理产生的变革性影响。此外,我们还深入探讨了肝纤维化研究领域中超声成像、计算机断层扫描成像、磁共振成像、核医学成像、放射组学和人工智能的最新进展。我们总结了每种技术的关键概念、优势、局限性和诊断性能。最后,我们讨论了与临床实施相关的挑战,并提出了我们对推进该领域发展的看法,希望能为未来的研究提供可供选择的方向。
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引用次数: 0
Complexes of bacteria‐recognizing engineered phage lysin and red‐colored bacteria microparticles as optical bioprobes for simple, rapid, naked‐eye detection of syphilis‐specific antibodies from clinical samples 细菌识别工程噬菌体溶酶和红色细菌微颗粒复合物作为光学生物探针,用于从临床样本中简单、快速、裸眼检测梅毒特异性抗体
Pub Date : 2024-06-10 DOI: 10.1002/viw.20230120
Wei Hu, Lin Zhang, Ye Tan, Jian Luo, Jingping Xin, Gen Zhang, Jinyin Xu, Yangyang Zhang, Ya Xu, Ke Li, Yan Zhang, Chuanbin Mao
Serological detection of syphilis‐specific antibodies is the most widely used clinical method for diagnosing syphilis. However, the current methods in clinical practice are too diverse, complicating result interpretation and wasting medical resources. To meet the resultant demand for a simple fast naked‐eye detection method, we employed the bacterial cell‐binding domain (CBD) of bacteriophage lysin to functionalize bio‐microparticles (engineered non‐culturable red‐colored Staphylococcus aureus bacteria), forming a bioprobe that can detect the syphilis‐specific antibodies from human serum in 5 min with naked eyes. Specifically, CBD is bioengineered by fusion with one of three antigens of the syphilis‐causing bacteria Treponema pallidum separately. The three resulting fusion proteins bind to the bacteria surface through the CBD motif, generating a bioprobe with the antigens exposed. When the bioprobe is added to the serum samples collected from the syphilis patients, the syphilis‐specific antibodies bind the antigens on the bioprobes and cross‐link them, forming eye‐visible red aggregates for the naked‐eye antibody detection. The bioprobe was validated on 209 clinical samples, revealing its high clinical sensitivity and specificity. Exploiting the natural biorecognition between the bacteria‐specific phage‐derived species and the phage host bacteria represents a promising strategy for producing facile probes for rapid point‐of‐care testing of infectious diseases.
梅毒特异性抗体的血清学检测是临床上最广泛使用的梅毒诊断方法。然而,目前临床上使用的方法种类繁多,结果判读复杂,浪费医疗资源。为了满足对一种简单快速的裸眼检测方法的需求,我们利用噬菌体溶酶的细菌细胞结合域(CBD)对生物微粒(经过工程化的不可培养的红色金黄色葡萄球菌)进行功能化,形成了一种生物探针,可以在5分钟内用裸眼从人体血清中检测出梅毒特异性抗体。具体来说,CBD 是通过分别与梅毒致病菌苍白螺旋体的三种抗原之一融合而形成的生物工程。由此产生的三种融合蛋白通过 CBD 基序与细菌表面结合,生成暴露有抗原的生物探针。将生物探针加入梅毒患者的血清样本中,梅毒特异性抗体会与生物探针上的抗原结合并交联,形成肉眼可见的红色聚集体,供肉眼抗体检测。该生物探针在 209 份临床样本上进行了验证,显示其具有很高的临床灵敏度和特异性。利用细菌特异性噬菌体衍生物种与噬菌体宿主细菌之间的天然生物识别性,是生产用于传染性疾病快速护理点检测的简便探针的一种有前途的策略。
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引用次数: 0
Novel strategies for enhanced fluorescence visualization of glioblastoma tumors based on HPMA copolymers conjugated with tumor targeting and/or cell‐penetrating peptides 基于与肿瘤靶向肽和/或细胞穿透肽共轭的 HPMA 共聚物的胶质母细胞瘤肿瘤荧光可视化增强新策略
Pub Date : 2024-04-24 DOI: 10.1002/viw.20230116
Eliška Grosmanová, R. Pola, M. Filipová, M. Henry, Jean-Luc Coll, T. Etrych
Nano‐sized polymer systems are often used as carriers for drugs and contrast agents to increase circulation time and solubility and to reduce possible side effects. These nanomedicines usually accumulate in tumor tissue due to the enhanced permeability and retention (EPR) effect. However, a targeting group may be attached to the polymer carrier in addition to the active substance to further increase tumor accumulation and specificity. In this study, the oligopeptide sequence RGD was chosen to target αvβ3 integrins overexpressed in the tumor vasculature and on some tumor cells. A set of polymer conjugates bearing a fluorescent dye and RGD peptide of different structures (linear, cyclic, branched) was prepared for use in tumor diagnosis, with a potential future application in navigated surgery. The accumulation of the most promising candidate, a targeted fluorescent nanoprobe, increased by 35% in glioblastoma tumors compared to the non‐targeted control, which accumulated only due to the EPR effect. However, the administration of a polymer‐bound modified cilengitide as an antiangiogenic treatment did not show a beneficial effect in the suppression of angiogenesis.
纳米聚合物系统通常被用作药物和造影剂的载体,以增加循环时间和溶解度,并减少可能出现的副作用。由于增强的渗透性和滞留(EPR)效应,这些纳米药物通常会在肿瘤组织中积聚。不过,除了活性物质外,聚合物载体上还可以附着一个靶向基团,以进一步增加肿瘤积累和特异性。本研究选择了寡肽序列 RGD 来靶向肿瘤血管和某些肿瘤细胞上过度表达的 αvβ3 整合素。研究人员制备了一组含有荧光染料和不同结构(线性、环状、支链)RGD 肽的聚合物共轭物,用于肿瘤诊断,未来可能应用于导航手术。与仅因 EPR 效应而积累的非靶向对照组相比,最有希望的候选靶向荧光纳米探针在胶质母细胞瘤肿瘤中的积累增加了 35%。然而,作为一种抗血管生成治疗方法,使用聚合物结合的改良西仑吉肽并未显示出抑制血管生成的有益效果。
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引用次数: 0
Nanomedicine‐encouraged cellular autophagy promoters favor liver fibrosis progression reversal 纳米药物鼓励的细胞自噬促进因子有利于逆转肝纤维化进程
Pub Date : 2024-04-23 DOI: 10.1002/viw.20240003
Cheng Qian, Yan Zhang, Xiaoyang Chen, Chunyan Zhu, Xiulin Dong, Weiwei Chen, Xuejun Ni, Kun Zhang, Yifei Yin
Liver fibrosis is a major risk factor for hepatocellular carcinoma origin, and its progression not only correlates with oxidative stress and inflammation, but also is encouraged by autophagy hold‐up. Therefore, new solutions to effectively attenuate oxidative stress and inflammation and coincidently favor autophagy are highly demanded to reverse liver fibrosis, and even hamper its escalation into hepatocellular carcinoma. Herein, the porous manganese‐substituted Prussian blue (PMPB) analogs are harnessed to activate autophagy, scavenge reactive oxygen species (ROS), and suppress inflammation for liver fibrosis therapy. PMPB can effectively inhibit macrophage activation, facilitate macrophage autophagy, eradicate ROS, and blockade cellular cross‐talk, thus impeding further inflammation progression. Moreover, the favorable spontaneous capture of PMPB by Kupffer cells allows more PMPB accumulation in liver to significantly attenuate liver injury and collagen deposition, thereby inhibiting the progression of liver fibrosis. PMPB‐based nanomedicine shows great potentials in promoting autophagy activation, eliminating ROS, inhibiting inflammation, and protecting hepatocytes from oxidative stress‐arised damages, which eventually attenuate the extent of liver fibrosis, holding great promise in clinical translation for treating liver fibrosis.
肝纤维化是肝细胞癌起源的一个主要风险因素,其进展不仅与氧化应激和炎症相关,自噬抑制也会助长肝纤维化。因此,要逆转肝纤维化,甚至阻止其升级为肝细胞癌,亟需有效减轻氧化应激和炎症反应并同时促进自噬的新方案。本文利用多孔锰取代普鲁士蓝(PMPB)类似物来激活自噬、清除活性氧(ROS)和抑制炎症,从而治疗肝纤维化。PMPB 能有效抑制巨噬细胞活化,促进巨噬细胞自噬,清除 ROS,阻断细胞间的交叉对话,从而阻止炎症进一步发展。此外,PMPB 还能被 Kupffer 细胞自发捕获,使更多的 PMPB 聚集在肝脏中,显著减轻肝损伤和胶原沉积,从而抑制肝纤维化的进展。基于 PMPB 的纳米药物在促进自噬激活、消除 ROS、抑制炎症、保护肝细胞免受氧化应激引起的损伤等方面显示出巨大的潜力,最终可减轻肝纤维化的程度,在治疗肝纤维化的临床转化方面大有可为。
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引用次数: 0
Surface‐enhanced Raman scattering spatial fingerprinting decodes the digestion behavior of lysosomes in live single cells 表面增强拉曼散射空间指纹解码活体单细胞中溶酶体的消化行为
Pub Date : 2024-04-19 DOI: 10.1002/viw.20240004
Fugang Liu, Zhirui Sun, Bingyi Li, Jiaqing Liu, Zhou Chen, Jian Ye
Lysosome, the digestive organelle in eukaryotic cells, plays an important role in the degradation and recirculation of cellular products as well as in maintaining the stability of cellular metabolic microenvironment. Surface‐enhanced Raman scattering (SERS) is a molecular fingerprint technology with high detection sensitivity and photostability, suited for revealing various intracellular molecular information by inducing endocytosis of SERS‐active nanoparticles. However, it remains challenging to selectively extract the molecular information of specific organelles (e.g., lysosomes) from a high‐dimensional spectral set. Herein, we proposed a novel paradigm by combining label‐free SERS spectroscopy with confocal fluorescence imaging to investigate the digestion behavior of lysosomes in cells. The structural similarity algorithm was innovatively introduced and exhibited its effectiveness in screening out the wavenumbers in the SERS spectral set with high correlation with the metabolic behaviors of lysosomes. With comprehensive experiments on HeLa single cells, we captured the intracellular macromolecular digestion phenomenon and discovered the changing pattern of cellular SERS spectra after starvation‐induced autophagy, and analyzed the molecular information within the lysosomes in three‐dimensional space.
溶酶体是真核细胞的消化器,在细胞产物的降解和再循环以及维持细胞代谢微环境的稳定方面发挥着重要作用。表面增强拉曼散射(SERS)是一种分子指纹技术,具有高检测灵敏度和光稳定性,适合通过诱导SERS活性纳米颗粒的内吞来揭示细胞内的各种分子信息。然而,从高维光谱集中选择性地提取特定细胞器(如溶酶体)的分子信息仍是一项挑战。在此,我们提出了一种新的范例,将无标记 SERS 光谱与共焦荧光成像相结合,研究细胞中溶酶体的消化行为。我们创新性地引入了结构相似性算法,该算法能有效筛选出 SERS 光谱集中与溶酶体代谢行为高度相关的波数。通过对 HeLa 单细胞的综合实验,我们捕捉到了细胞内大分子消化现象,发现了饥饿诱导自噬后细胞 SERS 光谱的变化规律,并在三维空间中分析了溶酶体内的分子信息。
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引用次数: 0
Masthead: (View 2/2024) 刊头:(查看 2/2024)
Pub Date : 2024-04-01 DOI: 10.1002/viw2.291
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引用次数: 0
The study of anti‐rabies virus effect of Shougong powder 首乌粉的抗狂犬病毒作用研究
Pub Date : 2024-02-05 DOI: 10.1002/viw.20230033
Minmin Zhang, Yun Fan, Xueliang Wang, Jinghua Wang, Rong Chen, Husheng Pan, Yanqun Xiao, Heyao Wang, Weigang Huang, Hualiang Wang
Rabies is a lethal infectious disease caused by rabies virus (RABV). The mortality rate is very high after the appearance of clinical symptoms, with a survival rate of almost 0%. There is presently no cure for rabies. In the present study, we investigated whether the extract of Shougong powder—a calcium powder prepared from gecko that has demonstrated immunomodulatory properties in mice—is an effective treatment for rabies. The antiviral effects of the extract were evaluated both in vitro and in vivo with the cytotoxicity and antiviral assays and by immunofluorescence analysis, quantitative real‐time (qRT)‐PCR, and western blotting. The results showed that Shougong powder and its extract increased survival rate in RABV‐infected mice is up to 60% and 50%, respectively, even in 20 times of LD50, whereas the control groups treated with isoprinosine (IPS) or saline are only 20% and 0% survival (p = .011). qRT‐PCR and western blotting analyses showed that the extract strongly inhibited viral mRNA expression and protein synthesis in vitro: expression of the N, P, M, G, and L genes of RABV was decreased by 28.8%–45.0% in the IPS group (p < .05) and by 50.1%–59.0% in the extract group (p < .05) relative to the control group. These results demonstrate that Shougong powder has certain antiviral effects against RABV and can potentially be used for the treatment for rabies.
狂犬病是由狂犬病毒(RABV)引起的一种致命传染病。出现临床症状后死亡率非常高,存活率几乎为 0%。目前还没有治愈狂犬病的方法。在本研究中,我们研究了守宫粉(一种从壁虎中提取的钙粉,在小鼠体内具有免疫调节作用)的提取物是否能有效治疗狂犬病。通过细胞毒性和抗病毒试验以及免疫荧光分析、实时定量 (qRT) PCR 和 Western 印迹分析,对首乌粉提取物的体外和体内抗病毒效果进行了评估。结果表明,首乌粉及其提取物能提高 RABV 感染小鼠的存活率,即使在 20 倍半数致死剂量的情况下,存活率也分别高达 60% 和 50%,而用异丙肌苷(IPS)或生理盐水治疗的对照组存活率仅为 20% 和 0%(p = .011)。qRT-PCR 和 Western 印迹分析表明,首乌藤提取物在体外强烈抑制病毒 mRNA 的表达和蛋白质的合成:与对照组相比,IPS 组 RABV 的 N、P、M、G 和 L 基因的表达量减少了 28.8%-45.0%(p < .05),提取物组则减少了 50.1%-59.0%(p < .05)。这些结果表明,首乌粉对 RABV 有一定的抗病毒作用,可用于狂犬病的治疗。
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引用次数: 0
The study of anti‐rabies virus effect of Shougong powder 首乌粉的抗狂犬病毒作用研究
Pub Date : 2024-02-05 DOI: 10.1002/viw.20230033
Minmin Zhang, Yun Fan, Xueliang Wang, Jinghua Wang, Rong Chen, Husheng Pan, Yanqun Xiao, Heyao Wang, Weigang Huang, Hualiang Wang
Rabies is a lethal infectious disease caused by rabies virus (RABV). The mortality rate is very high after the appearance of clinical symptoms, with a survival rate of almost 0%. There is presently no cure for rabies. In the present study, we investigated whether the extract of Shougong powder—a calcium powder prepared from gecko that has demonstrated immunomodulatory properties in mice—is an effective treatment for rabies. The antiviral effects of the extract were evaluated both in vitro and in vivo with the cytotoxicity and antiviral assays and by immunofluorescence analysis, quantitative real‐time (qRT)‐PCR, and western blotting. The results showed that Shougong powder and its extract increased survival rate in RABV‐infected mice is up to 60% and 50%, respectively, even in 20 times of LD50, whereas the control groups treated with isoprinosine (IPS) or saline are only 20% and 0% survival (p = .011). qRT‐PCR and western blotting analyses showed that the extract strongly inhibited viral mRNA expression and protein synthesis in vitro: expression of the N, P, M, G, and L genes of RABV was decreased by 28.8%–45.0% in the IPS group (p < .05) and by 50.1%–59.0% in the extract group (p < .05) relative to the control group. These results demonstrate that Shougong powder has certain antiviral effects against RABV and can potentially be used for the treatment for rabies.
狂犬病是由狂犬病毒(RABV)引起的一种致命传染病。出现临床症状后死亡率非常高,存活率几乎为 0%。目前还没有治愈狂犬病的方法。在本研究中,我们研究了守宫粉(一种从壁虎中提取的钙粉,在小鼠体内具有免疫调节作用)的提取物是否能有效治疗狂犬病。通过细胞毒性和抗病毒试验以及免疫荧光分析、实时定量 (qRT) PCR 和 Western 印迹分析,对首乌粉提取物的体外和体内抗病毒效果进行了评估。结果表明,首乌粉及其提取物能提高 RABV 感染小鼠的存活率,即使在 20 倍半数致死剂量的情况下,存活率也分别高达 60% 和 50%,而用异丙肌苷(IPS)或生理盐水治疗的对照组存活率仅为 20% 和 0%(p = .011)。qRT-PCR 和 Western 印迹分析表明,首乌藤提取物在体外强烈抑制病毒 mRNA 的表达和蛋白质的合成:与对照组相比,IPS 组 RABV 的 N、P、M、G 和 L 基因的表达量减少了 28.8%-45.0%(p < .05),提取物组则减少了 50.1%-59.0%(p < .05)。这些结果表明,首乌粉对 RABV 有一定的抗病毒作用,可用于狂犬病的治疗。
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引用次数: 0
Masthead: (View 1/2024) 刊头:(查看 1/2024)
Pub Date : 2024-02-01 DOI: 10.1002/viw2.290
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引用次数: 0
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