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期刊论文 6

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不良地质 1

异常阈值 1

断层 1

矿物异常 1

蚀变 1

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Progress and challenges in RET-targeted cancer therapy

《医学前沿（英文）》 2023年 第17卷 第2期   页码 207-219 doi: 10.1007/s11684-023-0985-y

摘要： The rearranged during transfection (RET) is a receptor protein tyrosine kinase. Oncogenic RET fusions or mutations are found most often in non-small cell lung cancer (NSCLC) and in thyroid cancer, but also increasingly in various types of cancers at low rates. In the last few years, two potent and selective RET protein tyrosine kinase inhibitors (TKIs), pralsetinib (BLU-667) and selpercatinib (LOXO-292, LY3527723) were developed and received regulatory approval. Although pralsetinib and selpercatinib gave high overall response rates (ORRs), < 10% of patients achieved a complete response (CR). The RET TKI-tolerated residual tumors inevitably develop resistance by secondary target mutations, acquired alternative oncogenes, or MET amplification. RET G810 mutations located at the kinase solvent front site were identified as the major on-target mechanism of acquired resistance to both selpercatinib and pralsetinib. Several next-generation of RET TKIs capable of inhibiting the selpercatinib/pralsetinib-resistant RET mutants have progressed to clinical trials. However, it is likely that new TKI-adapted RET mutations will emerge to cause resistance to these next-generation of RET TKIs. Solving the problem requires a better understanding of the multiple mechanisms that support the RET TKI-tolerated persisters to identify a converging point of vulnerability to devise an effective co-treatment to eliminate the residual tumors.

关键词： pralsetinib     selpercatinib     RET-alteration     lung cancer     thyroid cancer     tumor-agnostic therapy     drug resistance    

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Gut microbial balance and liver transplantation: alteration, management, and prediction

null

《医学前沿（英文）》 2018年 第12卷 第2期   页码 123-129 doi: 10.1007/s11684-017-0563-2

摘要：

Liver transplantation is a conventional treatment for terminal stage liver diseases. However, several complications still hinder the survival rate. Intestinal barrier destruction is widely observed among patients receiving liver transplant and suffering from ischemia–reperfusion or rejection injuries because of the relationship between the intestine and the liver, both in anatomy and function. Importantly, the resulting alteration of gut microbiota aggravates graft dysfunctions during the process. This article reviews the research progress for gut microbial alterations and liver transplantation. Especially, this work also evaluates research on the management of gut microbial alteration and the prediction of possible injuries utilizing microbial alteration during liver transplantation. In addition, we propose possible directions for research on gut microbial alteration during liver transplantation and offer a hypothesis on the utilization of microbial alteration in liver transplantation. The aim is not only to predict perioperative injuries but also to function as a method of treatment or even inhibit the rejection of liver transplantation.

关键词： gut microbial balance     liver transplantation     ischemia–reperfusion     acute rejection    

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Topological reorganization and functional alteration of distinct genomic components in gallbladder cancer

《医学前沿（英文）》 doi: 10.1007/s11684-023-1008-8

摘要： Altered three-dimensional architecture of chromatin influences various genomic regulators and subsequent gene expression in human cancer. However, knowledge of the topological rearrangement of genomic hierarchical layers in cancer is largely limited. Here, by taking advantage of in situ Hi-C, RNA-sequencing, and chromatin immunoprecipitation sequencing (ChIP-seq), we investigated structural reorganization and functional changes in chromosomal compartments, topologically associated domains (TADs), and CCCTC binding factor (CTCF)-mediated loops in gallbladder cancer (GBC) tissues and cell lines. We observed that the chromosomal compartment A/B switch was correlated with CTCF binding levels and gene expression changes. Increased inter-TAD interactions with weaker TAD boundaries were identified in cancer cell lines relative to normal controls. Furthermore, the chromatin short loops and cancer unique loops associated with chromatin remodeling and epithelial–mesenchymal transition activation were enriched in cancer compared with their control counterparts. Cancer-specific enhancer–promoter loops, which contain multiple transcription factor binding motifs, acted as a central element to regulate aberrant gene expression. Depletion of individual enhancers in each loop anchor that connects with promoters led to the inhibition of their corresponding gene expressions. Collectively, our data offer the landscape of hierarchical layers of cancer genome and functional alterations that contribute to the development of GBC.

关键词： 3D genome     cancer     TADs     loop     gene regulation    

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Paternal environmental exposure-induced spermatozoal small noncoding RNA alteration meditates the intergenerational

《医学前沿（英文）》 2022年 第16卷 第2期   页码 176-184 doi: 10.1007/s11684-021-0885-y

摘要： Studies of human and mammalian have revealed that environmental exposure can affect paternal health conditions as well as those of the offspring. However, studies that explore the mechanisms that meditate this transmission are rare. Recently, small noncoding RNAs (sncRNAs) in sperm have seemed crucial to this transmission due to their alteration in sperm in response to environmental exposure, and the methodology of microinjection of isolated total RNA or sncRNAs or synthetically identified sncRNAs gradually lifted the veil of sncRNA regulation during intergenerational inheritance along the male line. Hence, by reviewing relevant literature, this study intends to answer the following research concepts: (1) paternal environmental factors that can be passed on to offspring and are attributed to spermatozoal sncRNAs, (2) potential role of paternal spermatozoal sncRNAs during the intergenerational inheritance process, and (3) the potential mechanism by which spermatozoal sncRNAs meditate intergenerational inheritance. In summary, increased attention highlights the hidden wonder of spermatozoal sncRNAs during intergenerational inheritance. Therefore, in the future, more studies should focus on the origin of RNA alteration, the target of RNA regulation, and how sncRNA regulation during embryonic development can be sustained even in adult offspring.

关键词： small noncoding RNAs     epigenetic inheritance     paternal intergenerational inherence     extracellular vesicles    

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基于矿物异常分析的隧道内不良地质识别方法及案例分析 Article

许振浩, 余腾飞, 林鹏, 李术才

《工程（英文）》 2023年 第27卷 第8期   页码 150-160 doi: 10.1016/j.eng.2022.09.013

摘要：

准确有效地识别不良地质对隧道安全高效的施工至关重要。目前的不良地质识别方法主要依赖于地质学家的经验，容易出现误判和漏判。本研究提出了一种基于矿物异常分析的隧道不良地质识别方法（adverse geology identification through mineral anomaly analysis, AGIMAA），该方法基于地质异常理论，将矿物异常作为不良地质的识别标志。该方法首先基于探索性数据分析（exploration data analysis, EDA）计算矿物异常阈值，然后根据阈值评估矿物异常，最后根据矿物异常特征分析识别不良地质。建立了背景样本动态扩充流程，通过调整异常阈值实现对矿物异常的动态评估。该方法已在花岗岩隧道中得到验证和应用。在隧道里程142+800-142+860范围内，根据原岩矿物斜长石和角闪石含量的异常减少，以及蚀变矿物绿泥石、浊沸石和绿帘石含量的异常增加，成功识别出F37断层。当隧道进入不良地质影响区时，本研究所提出的方法可提供及时预警，并可识别隧道是在逐渐接近断层还是在远离断层。此外，本文还讨论了该方法的适用性、准确性及改进方向。该方法将传统隧道内不良地质识别分析从定性分析层面提高到了定量识别层面，可为采矿和地下工程中的不良地质识别提供参考和指导。

关键词： 矿物异常     不良地质     断层     蚀变     异常阈值    

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Alteration of heat shock protein 20 expression in preeclamptic patients and its effect in vascular and

Fanfan Li, Mengzhou He, Meitao Yang, Yao Fan, Yun Chen, Xi Xia, Yin Xie, Dongrui Deng

《医学前沿（英文）》 2018年 第12卷 第5期   页码 542-549 doi: 10.1007/s11684-017-0576-x

摘要：

Preeclampsia (PE) is a pregnancy-specific, multi-system disorder and the leading cause of maternal and perinatal morbidity and mortality in obstetrics worldwide. Excessive vasoconstriction and dysregulated coagulation function are closely associated with PE. Heat shock protein 20 (HSP20) is ubiquitously expressed under normal physiological conditions and has important roles in vascular dilatation and suppression of platelet aggregation. However, the role of HSP20 in the pathogenesis of PE remains unclear. In this study, we collected chorionic plate resistance arteries (CPAs) and serum from 118 healthy pregnant women and 80 women with PE and detected the levels of HSP20 and its phosphorylated form. Both HSP20 and phosphorylated HSP20 were downregulated in CPAs from women with PE. Comparison of the vasodilative ability of CPAs from the two groups showed impaired relaxation responses to acetyl choline in preeclamptic vessels. In addition to the reduced HSP20 in serum from women with PE, the platelet distribution width and mean platelet volume were also decreased, and the activated partial thromboplastin time and thromboplastin time were elevated. With regard to the vital roles of HSP20 in mediating vasorelaxation and coagulation function, the decreased HSP20 might contribute to the pathogenesis of PE.

关键词： preeclampsia     heat shock protein 20     vascular relaxation     coagulation-fibrinolytic system    

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标题 作者 时间 类型 操作

Progress and challenges in RET-targeted cancer therapy

期刊论文

Gut microbial balance and liver transplantation: alteration, management, and prediction

null

期刊论文

Topological reorganization and functional alteration of distinct genomic components in gallbladder cancer

期刊论文

Paternal environmental exposure-induced spermatozoal small noncoding RNA alteration meditates the intergenerational

期刊论文

基于矿物异常分析的隧道内不良地质识别方法及案例分析

许振浩, 余腾飞, 林鹏, 李术才

期刊论文

Alteration of heat shock protein 20 expression in preeclamptic patients and its effect in vascular and

Fanfan Li, Mengzhou He, Meitao Yang, Yao Fan, Yun Chen, Xi Xia, Yin Xie, Dongrui Deng

期刊论文