biological basis

生物学基础
  • 文章类型: Journal Article
    大多数甲状腺癌患者可以通过基于手术治疗的综合治疗方案获得良好的预后。然而,目前晚期甲状腺癌的治疗选择仍然有限.近年来,嵌合抗原受体修饰T细胞(CAR-T)治疗在肿瘤治疗领域受到广泛关注。在血液肿瘤的治疗中取得了显著的效果。然而,由于多种因素的制约,CAR-T治疗实体肿瘤的疗效,包括甲状腺癌,尚未达到预期。本文概述了CAR-T细胞的基本结构和治疗策略。概述了临床前研究和临床试验的进展,重点是与CAR-T细胞疗法治疗甲状腺癌相关的靶标,并讨论了CAR-T细胞治疗甲状腺癌的挑战和解决方案。总之,CAR-T细胞疗法是甲状腺癌的一种有前途的治疗方法,我们希望我们的审查将提供及时和更新的CAR-T细胞治疗甲状腺癌的研究,以推进该领域。
    The majority of patients with thyroid cancer can attain a favorable prognosis with a comprehensive treatment program based on surgical treatment. However, the current treatment options for advanced thyroid cancer are still limited. In recent years, chimeric antigen receptor-modified T-cell (CAR-T) therapy has received widespread attention in the field of oncology treatment. It has achieved remarkable results in the treatment of hematologic tumors. However, due to the constraints of multiple factors, the therapeutic efficacy of CAR-T therapy for solid tumors, including thyroid cancer, has not yet met expectations. This review outlines the fundamental structure and treatment strategies of CAR-T cells, provides an overview of the advancements in both preclinical investigations and clinical trials focusing on targets associated with CAR-T cell therapy in treating thyroid cancer, and discusses the challenges and solutions to CAR-T cell therapy for thyroid cancer. In conclusion, CAR-T cell therapy is a promising therapeutic approach for thyroid cancer, and we hope that our review will provide a timely and updated study of CAR-T cell therapy for thyroid cancer to advance the field.
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  • 文章类型: Journal Article
    目的医学成像提供了一个非侵入性的窗口来可视化肿瘤,通过影像组学将这些图像转化为定量数据,用于肿瘤表型分析。然而,复杂的网络链接成像功能,临床终点,肿瘤生物学大部分是未知的。本研究旨在揭示CT影像特征与临床特征之间的联系,包括肿瘤组织病理学分级,临床分期,内分泌症状,与肿瘤细胞生长的免疫组织化学标记物一起,如Ki-67指数和核有丝分裂率。
方法我们对137例胰腺神经内分泌肿瘤患者的数据进行了回顾性分析,这些患者接受了两个机构的对比增强CT扫描。我们的研究集中在三个临床因素:病理分级,临床分期,和内分泌症状状态,除了两个免疫组织化学标记:Ki-67指数和核有丝分裂率。我们计算了预定义的(2D和3D)和基于学习的特征(通过稀疏自动编码器,或SAE)来自扫描。为了挖掘成像特征之间的关系,临床因素,和免疫组织化学标记,我们采用了Spearman等级相关性和Benjamini-Hochberg方法。此外,我们开发并验证了影像组学特征以预测这些临床因素.
主要结果3D成像特征显示与临床因素和免疫组织化学标志物的关系最强。对于与病理等级的关联,2D的相关系数(CC)的平均绝对值,SAE,和3D特征分别为0.3318±0.1196、0.2149±0.0361和0.4189±0.0882。而对于与Ki-67指数和核有丝分裂率的关联,3D特征也显示出更高的相关性,CC为0.4053±0.0786和0.4061±0.0806。此外,基于3D特征的特征在临床因素预测中表现最佳. 重要性我们发现了成像特征之间的关系,临床因素,和免疫组织化学标记。3D特征显示与临床因素和免疫组织化学标记物有较高的相关性。
    Objective.Medical imaging offered a non-invasive window to visualize tumors, with radiomics transforming these images into quantitative data for tumor phenotyping. However, the intricate web linking imaging features, clinical endpoints, and tumor biology was mostly uncharted. This study aimed to unravel the connections between CT imaging features and clinical characteristics, including tumor histopathological grading, clinical stage, and endocrine symptoms, alongside immunohistochemical markers of tumor cell growth, such as the Ki-67 index and nuclear mitosis rate.Approach.We conducted a retrospective analysis of data from 137 patients with pancreatic neuroendocrine tumors who had undergone contrast-enhanced CT scans across two institutions. Our study focused on three clinical factors: pathological grade, clinical stage, and endocrine symptom status, in addition to two immunohistochemical markers: the Ki-67 index and the rate of nuclear mitosis. We computed both predefined (2D and 3D) and learning-based features (via sparse autoencoder, or SAE) from the scans. To unearth the relationships between imaging features, clinical factors, and immunohistochemical markers, we employed the Spearman rank correlation along with the Benjamini-Hochberg method. Furthermore, we developed and validated radiomics signatures to foresee these clinical factors.Main results.The 3D imaging features showed the strongest relationships with clinical factors and immunohistochemical markers. For the association with pathological grade, the mean absolute value of the correlation coefficient (CC) of 2D, SAE, and 3D features was 0.3318 ± 0.1196, 0.2149 ± 0.0361, and 0.4189 ± 0.0882, respectively. While for the association with Ki-67 index and rate of nuclear mitosis, the 3D features also showed higher correlations, with CC as 0.4053 ± 0.0786 and 0.4061 ± 0.0806. In addition, the 3D feature-based signatures showed optimal performance in clinical factor prediction.Significance.We found relationships between imaging features, clinical factors, and immunohistochemical markers. The 3D features showed higher relationships with clinical factors and immunohistochemical markers.
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  • 文章类型: Journal Article
    甘蔗,热带和亚热带地区的重要经济作物,贡献了世界上80%的糖产量和40%的生物乙醇产量。它是一种关键的糖料作物,占中国食糖产量的85%。开发高产新品种,高糖,良好的抗逆性对制糖行业的可持续增长至关重要。杂交育种是目前应用最广泛、最有效的方法,超过98%的中国甘蔗品种是由这种方法产生的。在过去的二十年里,我国育种家发展了高异质复合高糖育种理论,导致第五代甘蔗品种的成功选育。其中,YZ08-1609,糖果属的复杂杂种。,由云南省农业科学院甘蔗研究所(YSRI)开发。YZ08-1609的平均甘蔗产量比ROC22高14.4%。它对花叶病有很强的抵抗力,对干旱胁迫具有高度的耐受性,但中度易患黑穗病。值得注意的是,YZ08-1609的蔗糖含量为20.3%,创下国际纪录,赢得“糖之王”的美誉。总结经验,启发育种,我们在这里提供了父母选择的详细见解,育种过程,和YZ08-1609的特点。此外,在转录和代谢水平上都挖掘了其高产和高糖的生物学机制。还讨论了甘蔗品种选育的挑战和前景,尤其是高糖甘蔗品种的选育。为高糖品种的未来发展奠定了基础。
    Sugarcane, a significant cash crop in tropical and subtropical regions, contributes to 80% of sugar production and 40% of bioethanol production in the world. It is a key sugar crop, accounting for 85% of sugar production in China. Developing new varieties with high yield, high sugar, and better stress resistance is crucial for the sustainable growth of sugar industry. Hybrid breeding is the most widely used and effective method, with over 98% of Chinese sugarcane varieties resulting from this approach. Over the past two decades, Chinese breeders have developed the theory of high-heterogeneous composite high-sugar breeding, leading to the successful breeding of the fifth-generation sugarcane varieties. Among them, YZ08-1609, a complex hybrid of Saccharum spp., was developed by Sugarcane Research Institute (YSRI) of Yunnan Academy of Agricultural Sciences. The average cane yield of YZ08-1609 was 14.4% higher than ROC22. It is highly resistant to mosaic disease, and highly tolerant to drought stress, but moderately susceptible to smut disease. Notably, YZ08-1609 stands out with a sucrose content of 20.3%, setting an international record, earning the reputation as \"King of Sugar\". To summarize experience and inspire breeding, we provided here the detailed insights into the selection of parents, breeding process, and characteristics of YZ08-1609. Besides, the biological mechanisms underlying its high yield and high sugar was excavated at both transcriptional and metabolic levels. The challenges and prospects in breeding sugarcane varieties especially with high sugar were also discussed, offering a foundation for the future development of high-sugar varieties.
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  • 文章类型: Journal Article
    胃肠道癌症占所有癌症的11.6%,并且是全球第二常见的癌症类型。中药(TCM),连同西药或单独使用,在预防和治疗癌症方面具有独特的优势,包括胃肠道癌症。辨证论治是中医理论体系的基本特征。中医证候是辨证施治的结果,是治疗的基础。基因组学,转录组学,蛋白质组学,代谢组学,肠道微生物群,和血清学,围绕中央法律产生的,用于研究胃肠道肿瘤中医证候的生物学基础。本文就目前消化道肿瘤中医证候的生物学基础研究作一综述,为今后消化道肿瘤中医证候的研究提供参考。
    Gastrointestinal cancers account for 11.6 % of all cancers, and are the second most frequently diagnosed type of cancer worldwide. Traditional Chinese medicine (TCM), together with Western medicine or alone, has unique advantages for the prevention and treatment of cancers, including gastrointestinal cancers. Syndrome differentiation and treatment are basic characteristics of the theoretical system of TCM. TCM syndromes are the result of the differentiation of the syndrome and the basis of treatment. Genomics, transcriptomics, proteomics, metabolomics, intestinal microbiota, and serology, generated around the central law, are used to study the biological basis of TCM syndromes in gastrointestinal cancers. This review summarizes current research on the biological basis of TCM syndrome in gastrointestinal cancers and provides useful references for future research on TCM syndrome in gastrointestinal cancers.
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  • 文章类型: Multicenter Study
    背景:乳腺病变的准确诊断和腋窝淋巴结(ALN)转移的辨别很大程度上取决于放射科医师的经验。
    目的:开发一种基于深度学习的全过程系统(DLWPS),用于乳腺病变的分割和诊断以及ALN转移的区分。
    方法:回顾性。
    方法:1760例乳腺癌患者,他们被分为训练集和验证集(1110名患者),内部(476名患者),和外部(174名患者)测试集。
    3.0T/动态对比增强(DCE)-MRI序列。
    结果:DLWPS是使用分割和分类模型开发的。基于DLWPS的分割模型是由U-Net框架开发的,注意模块和边缘特征提取模块相结合。使用三个网络的输出得分的平均得分作为基于DLWPS的分类模型的结果。此外,探讨了无DLWPS辅助和有DLWPS辅助的放射科医师诊断。为了揭示DLWPS的潜在生物学基础,基于RNA测序数据进行遗传分析.
    方法:骰子相似系数(DI),接收器工作特性曲线下面积(AUC),准确度,灵敏度,特异性,和Kappa值。
    结果:分割模型在内部和外部测试集中达到了0.828和0.813的DI,分别。在乳腺病变诊断中,DLWPS在内部测试组中的AUC为0.973,在外部测试组中的AUC为0.936.对于ALN转移区分,DLWPS在内部测试组中的AUC为0.927,在外部测试组中的AUC为0.917.在乳腺病变诊断和ALN转移辨别方面,放射科医生在DLWPS辅助下的一致性从0.547提高到0.794,从0.848提高到0.892,分别。此外,10例具有ALN转移的乳腺癌与有氧电子传递链和细胞质翻译的途径有关。
    结论:DLWPS的表现表明,它可以促进放射科医生对乳腺病变以及ALN转移和非转移的判断。
    方法:4技术效率阶段:3.
    Accurate diagnosis of breast lesions and discrimination of axillary lymph node (ALN) metastases largely depend on radiologist experience.
    To develop a deep learning-based whole-process system (DLWPS) for segmentation and diagnosis of breast lesions and discrimination of ALN metastasis.
    Retrospective.
    1760 breast patients, who were divided into training and validation sets (1110 patients), internal (476 patients), and external (174 patients) test sets.
    3.0T/dynamic contrast-enhanced (DCE)-MRI sequence.
    DLWPS was developed using segmentation and classification models. The DLWPS-based segmentation model was developed by the U-Net framework, which combined the attention module and the edge feature extraction module. The average score of the output scores of three networks was used as the result of the DLWPS-based classification model. Moreover, the radiologists\' diagnosis without and with the DLWPS-assistance was explored. To reveal the underlying biological basis of DLWPS, genetic analysis was performed based on RNA-sequencing data.
    Dice similarity coefficient (DI), area under receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and kappa value.
    The segmentation model reached a DI of 0.828 and 0.813 in the internal and external test sets, respectively. Within the breast lesions diagnosis, the DLWPS achieved AUCs of 0.973 in internal test set and 0.936 in external test set. For ALN metastasis discrimination, the DLWPS achieved AUCs of 0.927 in internal test set and 0.917 in external test set. The agreement of radiologists improved with the DLWPS-assistance from 0.547 to 0.794, and from 0.848 to 0.892 in breast lesions diagnosis and ALN metastasis discrimination, respectively. Additionally, 10 breast cancers with ALN metastasis were associated with pathways of aerobic electron transport chain and cytoplasmic translation.
    The performance of DLWPS indicates that it can promote radiologists in the judgment of breast lesions and ALN metastasis and nonmetastasis.
    4 TECHNICAL EFFICACY STAGE: 3.
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  • 文章类型: Journal Article
    海马形态改变是阿尔茨海默病(AD)的主要标志之一。然而,目前尚不清楚海马影像组学特征是否能作为轻度认知障碍(MCI)进展为AD痴呆的预测因子,以及这些特征是否能提供神经生物学基础.这项研究的主要目的是验证海马放射学特征是否可以作为AD的强大磁共振成像(MRI)标记。基于多变量分类器的支持向量机(SVM)分析提供了个体水平的预测,用于区分AD患者(n=261)与正常对照(NC;n=231),准确率为88.21%,并进行了站点间交叉验证。进一步分析,独立的阿尔茨海默病神经成像倡议(ADNI)数据集(n=1228)加强了这些发现。在MCI组中,系统分析表明,已识别的特征与临床特征显着相关(例如,载脂蛋白E(APOE)基因型,多基因风险评分,脑脊液(CSF)Aβ,CSFTau),和认知能力的纵向变化;更重要的是,在5年的随访中,随着MMSE评分的变化,影像组学特征模式持续改变.这些综合结果表明,海马影像组学特征可以作为AD/MCI临床应用的强大生物标志物,并进一步提供了基于海马影像组学预测MCI受试者是否会转化为AD的证据。这项研究的结果有望对AD/MCI的早期诊断产生实质性影响。
    Hippocampal morphological change is one of the main hallmarks of Alzheimer\'s disease (AD). However, whether hippocampal radiomic features are robust as predictors of progression from mild cognitive impairment (MCI) to AD dementia and whether these features provide any neurobiological foundation remains unclear. The primary aim of this study was to verify whether hippocampal radiomic features can serve as robust magnetic resonance imaging (MRI) markers for AD. Multivariate classifier-based support vector machine (SVM) analysis provided individual-level predictions for distinguishing AD patients (n = 261) from normal controls (NCs; n = 231) with an accuracy of 88.21% and intersite cross-validation. Further analyses of a large, independent the Alzheimer\'s Disease Neuroimaging Initiative (ADNI) dataset (n = 1228) reinforced these findings. In MCI groups, a systemic analysis demonstrated that the identified features were significantly associated with clinical features (e.g., apolipoprotein E (APOE) genotype, polygenic risk scores, cerebrospinal fluid (CSF) Aβ, CSF Tau), and longitudinal changes in cognition ability; more importantly, the radiomic features had a consistently altered pattern with changes in the MMSE scores over 5 years of follow-up. These comprehensive results suggest that hippocampal radiomic features can serve as robust biomarkers for clinical application in AD/MCI, and further provide evidence for predicting whether an MCI subject would convert to AD based on the radiomics of the hippocampus. The results of this study are expected to have a substantial impact on the early diagnosis of AD/MCI.
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  • 文章类型: Journal Article
    这项研究的目的是:(1)确定和排名表型不同的动物的剩余饲料摄入量(RFI)的效率(高:HE或低:LE);(2)评估它们与摄食行为的关系,瘤胃和血液参数,性能,和红外热成像;(3)确定此类测量是否可用作饲养奶牛的饲料效率标记。三十八只小母牛,使用143d±4(平均值±SD)的年龄和108.7kg±17.9的体重。在试验的91天期间,用总混合日粮喂养动物。HE和LE在-0.358和0.337kg/d之间观察到RFI的DMI表型差异,分别。HE的干物质摄入量(dryi)较低(2.5kgdmi/dvs.3.1kgdmi/d),随着消费量的增加,访问饲料箱的次数也是如此(59vs.71).采食量是所述差异的最佳预测因子。水的摄取量和对饲料箱的访问次数与RFI呈中等相关性。瘤胃发酵变量,血液代谢产物,血液激素(如其他摄入行为变量),红外热成像无法准确预测HE或LE动物。
    The objectives of this study were: (1) to identify and rank phenotypically divergent animals for residual feed intake (RFI) regarding their efficiency (high: HE or low: LE); (2) to evaluate their relationships with ingestive behavior, ruminal and blood parameters, performance, and infrared thermography; and (3) to determine if such measurements can be used as feed efficiency markers in rearing dairy heifers. Thirty-eight heifers, 143 d ± 4 (Mean ± SD) of age and 108.7 kg ± 17.9 of body weight were used. The animals were fed with a total mixed ration during the 91 d of the trial. A phenotypic divergence of DMI for RFI was observed between -0.358 and 0.337 kg/d for HE and LE, respectively. Dry matter intake (DMI) was lower in the HE (2.5 kg DMI/d vs. 3.1 kg DMI/d), as was the number of visits to the feed bin with consumption (59 vs. 71). Feed intake was the best predictor of said divergence. Water intake and number of visits to the feed bin were presented moderate correlations with RFI. The ruminal fermentation variables, blood metabolites, blood hormones (such as the other ingestive behavior variables), and infrared thermography were not able to accurately predict HE or LE animals.
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  • 文章类型: Journal Article
    结构协方差网络(SCN)已成功用于结构磁共振成像(sMRI)研究。然而,大多数SCN是由单一标记构建的,该标记对区分不同疾病阶段不敏感。这项研究的目的是设计一种新颖的区域放射组学相似性网络(R2SN),可以在形态网络分析中提供更全面的信息。通过计算从每个受试者的任何一对区域提取的影像组学特征之间的Pearson相关性来构建R2SN(AAL图谱)。我们进一步评估了R2SN的小世界属性,我们通过测试-重测分析评估了不同数据集的可重复性。还探索了R2SNs与一般智力/基因的区域间共表达之间的关系。R2SN可以在不同的数据集中复制,无论使用不同的特征子集。R2SN在测试-重测分析中显示出高再现性(组内相关系数>0.7)。此外,确定了R2SN的小词属性(σ>2)以及基因表达(R=0.29,p<0.001)与一般智力之间的高度相关性。此外,结果也在Brainnetome图谱中重复。R2SN提供了一种新颖的,可靠,和基于sMRI理解人体形态协方差的生物学似然方法。
    A structural covariance network (SCN) has been used successfully in structural magnetic resonance imaging (sMRI) studies. However, most SCNs have been constructed by a unitary marker that is insensitive for discriminating different disease phases. The aim of this study was to devise a novel regional radiomics similarity network (R2SN) that could provide more comprehensive information in morphological network analysis. R2SNs were constructed by computing the Pearson correlations between the radiomics features extracted from any pair of regions for each subject (AAL atlas). We further assessed the small-world property of R2SNs, and we evaluated the reproducibility in different datasets and through test-retest analysis. The relationships between the R2SNs and general intelligence/interregional coexpression of genes were also explored. R2SNs could be replicated in different datasets, regardless of the use of different feature subsets. R2SNs showed high reproducibility in the test-retest analysis (intraclass correlation coefficient > 0.7). In addition, the small-word property (σ > 2) and the high correlation between gene expression (R = 0.29, p < 0.001) and general intelligence were determined for R2SNs. Furthermore, the results have also been repeated in the Brainnetome atlas. R2SNs provide a novel, reliable, and biologically plausible method to understand human morphological covariance based on sMRI.
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  • 文章类型: Journal Article
    The neuropeptide oxytocin is released both into the blood and within the brain in response to reproductive stimuli, such as birth, suckling and sex, but also in response to social interaction and stressors. Substance use disorders, or addictions, are chronic, relapsing brain disorders and are one of the major causes of global burden of disease. Unfortunately, current treatment options for substance use disorders are extremely limited and a treatment breakthrough is sorely needed. There is mounting preclinical evidence that targeting the brain oxytocin system may provide that breakthrough. Substance use disorders are characterised by a viscous cycle of bingeing and intoxication, followed by withdrawal and negative affect, and finally preoccupation and anticipation that triggers relapse and further consumption. Administration of oxytocin has been shown to have a potential therapeutic benefit at each stage of this addiction cycle for numerous drugs of abuse. This multidimensional therapeutic utility is likely due to oxytocin\'s interactions with key biological systems that underlie the development and maintenance of addiction. Only a few human trials of oxytocin in addicted populations have been completed with the results thus far being mixed. There are numerous other trials underway, and the results are eagerly awaited. However, the ability to fully harness the potential therapeutic benefit of targeting the brain oxytocin system may depend on the development of molecules that selectively stimulate the oxytocin system, but that have superior pharmacokinetic properties to oxytocin itself.
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