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Treatment of advanced non-small cell lung cancer with driver mutations: current applications and future

《医学前沿（英文）》 2023年 第17卷 第1期   页码 18-42 doi: 10.1007/s11684-022-0976-4

摘要： With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations (“target-dependent resistance”) and in the parallel and downstream pathways (“target-independent resistance”). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.

关键词： non-small cell lung cancer     driver mutations     treatment strategy     resistant mechanism     immune-checkpoint inhibitors    

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Identification of novel mutations in and in a family with craniofacial microsomia: evidence of digenic

《医学前沿（英文）》   页码 1006-1009 doi: 10.1007/s11684-023-1000-3

摘要： Identification of novel mutations in and in a family with craniofacial microsomia: evidence of digenic inheritance

关键词： family craniofacial microsomia     Identification novel mutations    

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Detection of critical road roughness sections by trend analysis and investigation of driver speed interaction

Meltem SAPLIOGLU; Ayse UNAL; Melek BOCEK

《结构与土木工程前沿（英文）》 2022年 第16卷 第4期   页码 515-532 doi: 10.1007/s11709-022-0814-4

摘要： Pavement roughness (IRI—International Roughness Index values) influence the stability of traffic movements both on intercity roads and urban roads. This study is to determine the exact locations of critical pavement roughness values that affect traffic motion stability and comfort in city centre highway arteries. Roughness data with 10 m intervals were collected on a 3140 m divided road containing three consecutive signalized intersections in the city centre arterial. These data were analysed using the distance-dependent Mann-Kendall trend analysis method and checkerboard model. The sections where roughness is important were determined at a 95% confidence interval. The results will show where future pavement improvements should be prioritized for municipalities and road maintenance engineers and will form a basis for the urban road management system.

关键词： trend analysis     checkerboard model     IRI     driver speed    

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Distributed governance of Solar Radiation Management geoengineering: A possible solution to SRM’s “free-driver

Andrew LOCKLEY

《工程管理前沿（英文）》 2019年 第6卷 第4期   页码 551-556 doi: 10.1007/s42524-019-0055-y

摘要： Geoengineering (deliberate climate modification) is a possible way to limit Anthropogenic Global Warming (AGW) (Shepherd, 2009; National Research Council, 2015). Solar Radiation Management geoengineering (SRM) offers relatively inexpensive, rapid temperature control. However, this low cost leads to a risk of controversial unilateral intervention—the “free-driver” problem (Weitzman, 2015). Consequently, this creates a risk of counter-geoengineering (deliberate warming) (Parker et al., 2018), resulting in governance challenges (Svoboda, 2017) akin to an arms race. Free-driver deployment scenarios previously considered include the rogue state, Greenfinger (Bodansky, 2013), or power blocs (Ricke et al., 2013), implying disagreement and conflict. We propose a novel distributed governance model of consensually-constrained unilateralism: Countries’ authority is limited to each state’s fraction of the maximum realistic intervention (e.g., pre-industrial temperature). We suggest a division of authority based on historical emissions (Rocha et al., 2015)—noting alternatives (e.g., population). To aid understanding, we offer an analogue: An over-heated train carriage, with passenger-controlled windows. We subsequently discuss the likely complexities, notably Coasian side-payments. Finally, we suggest further research: Algebraic, bot and human modeling; and observational studies.

关键词： geoengineering     Solar Radiation Management     governance     decentralised    

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Characteristics of compensatory mutations in the

Shengfen Wang, Yang Zhou, Bing Zhao, Xichao Ou, Hui Xia, Yang Zheng, Yuanyuan Song, Qian Cheng, Xinyang Wang, Yanlin Zhao

《医学前沿（英文）》 2020年 第14卷 第1期   页码 51-59 doi: 10.1007/s11684-019-0720-x

摘要： The aim of this study was to characterize gene mutations in (MTB) and investigate the factors associated with mutations and the relation between mutations and tuberculosis (TB) transmission. A total of 245 MTB clinical isolates from patients with TB in six provinces and two municipalities in China were characterized based on gene mutations through DNA sequencing of and genes, phenotyping via standard drug susceptibility testing, and genotypic profiling by mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing. Approximately 36.4% of the rifampin-resistant isolates harbored nonsynonymous mutations in the gene. Twenty-nine nonsynonymous single mutations and three double mutations were identified. The mutations at locus 483 (11.3%) were predominant, and the mutations at V483G, W484G, I491V, L516P, L566R, N698K, and A788E accounted for 54.5% of the total detected mutations. Fifteen new mutations in the gene were identified. Rifampin resistance and mutations at locus 531 were significantly associated with mutations. MIRU-VNTR genotype results indicated that 18.4% of the studied isolates were clustered, and the mutations were not significantly associated with MIRU-VNTR clusters. A large proportion of mutation was observed in the rifampicin-resistant MTB isolates. However, the findings of this study do not support the association of mutation with compensated transmissibility.

关键词： tuberculosis     drug resistance     compensatory mutations     transmission    

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122-binding site polymorphism at the interleukin-1 α gene and its interaction with hepatitis B virus mutations

null

《医学前沿（英文）》 2014年 第8卷 第2期   页码 217-226 doi: 10.1007/s11684-014-0326-2

摘要：

This study was designed to investigate the contribution of miRNA-122-binding site polymorphism at the IL-1A gene and its multiplicative interactions with hepatitis B virus (HBV) mutations in the risk of hepatocellular carcinoma (HCC). A total of 1021 healthy controls, 302 HBV surface antigen (HBsAg) seroclearance subjects, and 2011 HBsAg-positive subjects (including 1021 HCC patients) were enrolled in this study. Quantitative PCR was used to genotype rs3783553. HBV mutations were determined by direct sequencing. Multivariate logistic regression analyses were performed to test the associations of rs3783553, mutations, and their interactions with the risk of HCC. No significant association was found between rs3783553 and the risk of HCC among healthy controls, HBsAg seroclearance subjects, HBsAg-positive subjects without HCC, and all controls. Additionally, rs3783553 was not significantly associated with chronic HBV infection, liver cirrhosis, HBV e antigen seroconversion, abnormal alanine aminotransferase, and high viral load (>104 copies/ml). However, the TTCA insertion allele of rs3783553 was significantly associated with an increased frequency of HBV C7A mutation compared with homozygous TTCA deletion carriers [(del/ins+ ins/ins) vs. del/del, adjusted odds ratio (OR)=1.48, 95% confidence interval (CI)=1.09-2.02, P=0.013]. Multiplicative interaction of rs3783553 with HBV preS deletion significantly reduced the risk of HCC in males, with an adjusted OR of 0.64 (95% CI=0.42-0.98; P=0.041) after age and HBV genotype were adjusted. Although rs3783553 did not significantly affect genetic susceptibility to HBV-related HCC, its variant allele may predispose the host to selecting HBV C7A mutation during evolution and significantly reduce the risk of HCC caused by HBV preS deletion. This study provides an insight into the complex host-virus interaction in HBV-induced hepatocarcinogenesis and is helpful in determining HBsAg-positive subjects who are likely to develop HCC.

关键词： hepatocellular carcinoma (HCC)     interaction     miRNA-122-binding site     IL-1A     rs3783553     hepatitis B virus (HBV) mutations    

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Approaching the upper boundary of driver-response relationships: identifying factors using a novel framework

《环境科学与工程前沿（英文）》 2023年 第17卷 第6期 doi: 10.1007/s11783-023-1676-2

摘要：

● A novel framework integrating quantile regression with machine learning is proposed.

关键词： Driver-response     Upper boundary of relationship     Interpretable machine learning     Quantile regression     Total phosphorus     Chlorophyll a    

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Distinct gene expression pattern of mutations coordinated by target repression and promoter hypermethylation

《医学前沿（英文）》 2022年 第16卷 第4期   页码 627-636 doi: 10.1007/s11684-020-0815-4

摘要： Runt-related transcription factor 1 (RUNX1) is an essential regulator of normal hematopoiesis. Its dysfunction, caused by either fusions or mutations, is frequently reported in acute myeloid leukemia (AML). However, RUNX1 mutations have been largely under-explored compared with RUNX1 fusions mainly due to their elusive genetic characteristics. Here, based on 1741 patients with AML, we report a unique expression pattern associated with RUNX1 mutations in AML. This expression pattern was coordinated by target repression and promoter hypermethylation. We first reanalyzed a joint AML cohort that consisted of three public cohorts and found that RUNX1 mutations were mainly distributed in the Runt domain and almost mutually exclusive with NPM1 mutations. Then, based on RNA-seq data from The Cancer Genome Atlas AML cohort, we developed a 300-gene signature that significantly distinguished the patients with RUNX1 mutations from those with other AML subtypes. Furthermore, we explored the mechanisms underlying this signature from the transcriptional and epigenetic levels. Using chromatin immunoprecipitation sequencing data, we found that RUNX1 target genes tended to be repressed in patients with RUNX1 mutations. Through the integration of DNA methylation array data, we illustrated that hypermethylation on the promoter regions of RUNX1-regulated genes also contributed to dysregulation in RUNX1-mutated AML. This study revealed the distinct gene expression pattern of RUNX1 mutations and the underlying mechanisms in AML development.

关键词： RUNX1     gene mutation     acute myeloid leukemia     transcriptional repression     DNA methylation    

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Fuel type preference of taxi driver and its implications for air emissions

Feng WANG,Beibei LIU,Bing ZHANG,Jun BI

《环境科学与工程前沿（英文）》 2015年 第9卷 第4期   页码 702-711 doi: 10.1007/s11783-014-0665-x

摘要： Natural gas became an available fuel for taxis in 2005 and had occupied a market share of 43.6% in taxi industry till 2010 in Nanjing, China. To investigate the energy replacement pattern as well as the pollutants reduction potential of the taxi industry, first, the fuel preference determinants of taxi drivers for their next taxis are analyzed. Results show that as an important alternative for the traditional gasoline, natural gas is widely accepted (75%) by taxi drivers. Different from the previous studies which focused on the early stage of cleaner fuel replacement, taxi drivers with various characteristics (such as age, working experience, and education level) are consistent with their fuel preference when they choose their next taxis. Result suggests that policies that concern consumers with specific characteristics may have little effects on the change of the market share, when the alternative fuel market has been developed well. In addition, the increased share of gas in the fuel market achieves a 7.2% reduction of energy consumption. Considering life cycle emissions, the following air pollutants, namely Greenhouse Gases (GHGs), carbonic oxide (CO), nitrogen oxide (NO ), particulate matters (PM) and hydrocarbons (C H ), gain 10.0%, 3.5%, 20.5%, 36.1%, and 26.4% of reduction respectively. Assuming all taxi fleets powered by natural gas with local policy intervention, the energy conservation and the five major air pollutant emissions could achieve the maximum reductions with 12.2%, 16.0%, 8.8%, 22.5%, 44.2%, and 49.4% correspondingly.

关键词： fuel preference     energy replacement     environmental impacts     taxi    

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Experimental Study on the Piezoelectric Prestage Driver of Electrohydraulic Servo Valves

CHENG Guang-ming, SHEN Chuan-liang, YANG Zhi-gang

《机械工程前沿（英文）》 2006年 第1卷 第1期   页码 56-59 doi: 10.1007/s11465-005-0017-4

摘要：

A piezoelectric actuated prestage driver of hydraulic servo valves for the low-frequency response of electrohydraulic servo valve electromagnetic prestage driver was presented. The new driver was driven by piezoelectric multilayer actuators. The displacement of a piezoelectric multilayer actuator was amplified by a flexure-hinged amplifier based on the principles of triangle amplification. Static and dynamic characteristics were tested on the model machine. The characteristics of good linearity, high resolution, and high-frequency response were approved. The natural frequency reached 1.201 kHz using finite element analysis, and the practice measurement result was 1 kHz.

关键词： flexure-hinged amplifier     kHz     amplification     high-frequency     electromagnetic    

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嵌入式无线接入点网络驱动的设计与实现

王质礼,胡爱群,宋宇波

《中国工程科学》 2005年 第7卷 第10期   页码 91-94

摘要：

分析了嵌入式Linux系统下网络驱动的体系机构和工作原理，结合PCMCIA驱动接口，着重论述了嵌入式Linux无线接入点网络驱动的基本软件模型和实现流程, 给出了网络驱动的性能测试结果。

关键词： 嵌入式Linux     网络设备驱动     PCMCIA    

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宿主微生物组内的基因组突变——适应性进化或净化选择 Review

张家超, Rob Knight

《工程（英文）》 2023年 第20卷 第1期   页码 96-102 doi: 10.1016/j.eng.2021.11.018

摘要：

二代测序技术转变了人们评估宿主相关微生物区系和微生物组的分类组成功能的能力。未来10 年将会开展更多的人类微生物组研究，特别是那些探索微生物组内基因组突变的研究。本文聚焦于微生物组内菌株之间的共同进化，塑造了宿主肠道微生物种内和种间的菌株水平多样性。还探讨了微生物基因组突变与常见代谢疾病之间的关联，以及病原体和益生菌在入侵和定植过程中的适应性进化。最后，讨论了注释和分析微生物基因组突变方法和算法的研究进展。

关键词： 肠道菌群     基因组突变     适应性进化     净化选择     单核苷酸变异    

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Association of novel mutations and heplotypes in the preS region of hepatitis B virus with hepatocellular

Jia-Xin XIE, Jian-Hua YIN, Qi ZHANG, Rui PU, Wen-Ying LU, Hong-Wei ZHANG, Guang-Wen CAO, Jun ZHAO, Hong-Yang WANG,

《医学前沿（英文）》 2010年 第4卷 第4期   页码 419-429 doi: 10.1007/s11684-010-0160-0

摘要： The association of viral mutations and haplotypic carriages with mutations in the preS region of hepatitis B virus (HBV) genotypes B and C with hepatocellular carcinoma (HCC) is of great significance for the prediction of this malignancy, but it remains obscure. We analyzed the preS sequences of HBV genotypes B and C from 1172 HBV-infected subjects including 231 patients with HCC. As compared with the HBV-infected subjects without HCC, C2875T, G2946C, A3054C, C3060A, T3066C, C3116T, A3120C, G3191A, A1C, C7A, C10A, A31C, C76T, G105C, and G147C in both genotypes were significantly associated with increased risks of HCC. C2875A, G2950A, G2951A, A3054T, C3060T, T3066A, T3069G, A3120T, and G3191C were significantly associated with increased risks of HCC in genotype C, whereas these mutations were inversely associated with HCC in genotype B. Multivariate regression analyses showed that C76A/T was a novel factor independently associated with an increased risk of HCC, as compared with those without HCC. The frequencies of haplotypes 2964A-3116T-preS2 start codon wild-type-7C, 2964C-3116T-7A-76C, and 2964A-3116T-7C-76A/T were significantly higher in the patients with HCC (<0.001), whereas a haplotypic carriage with a single mutation and another three wild-types were inversely associated with HCC. Conclusively, the association of HBV mutations in the preS region with HCC depends on HBV genotype and haplotypic carriage with two or more mutations that are each associated with an increased risk of HCC independently.

关键词： hepatitis B virus     hepatocellular carcinoma     mutation     genotype     haplotype    

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Molecular pathogenesis of acute myeloid leukemia: A diverse disease with new perspectives

Felicitas THOL, Arnold GANSER

《医学前沿（英文）》 2010年 第4卷 第4期   页码 356-362 doi: 10.1007/s11684-010-0220-5

摘要： Acute myeloid leukemia (AML) is a very heterogeneous neoplasm of the hematopoietic stem cell. Despite important achievements in the treatment of AML, the long term survival of patients with the disease remains poor. Understanding the pathogenesis of AML better is crucial for finding new treatment approaches. During AML development hematopoietic precursor cells undergo clonal transformation in a multistep process through acquisition of chromosomal rearrangements and/or different gene mutations. Over recent years, novel gene mutations have been found in patients with AML. These mutations can be divided into two important categories, class I mutations that confer a proliferation advantage and class II mutations that inhibit myeloid differentiation. Screening for some of these mutations is now part of the initial diagnostic work-up in newly diagnosed AML patients. Information about the mutation status of specific genes is useful for risk-stratification, minimal residual disease (MRD) monitoring and increasingly also for targeted therapy, especially for patients with cytogenetically normal AML (CN-AML). Besides chromosomal rearrangements and gene mutations, epigenetic regulation of genes – meaning changes in gene expression by mechanisms other than changes in the underlying DNA sequence – also represents an important mechanism of leukemogenesis. This article reviews some of the most common mutations in CN-AML and gives a perspective of the translation of these discoveries from bench to bedside.

关键词： acute myeloid leukemia     mutations     risk stratification    

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Genetic evidence in planar cell polarity signaling pathway in human neural tube defects

null

《医学前沿（英文）》 2014年 第8卷 第1期   页码 68-78 doi: 10.1007/s11684-014-0308-4

摘要：

Neural tube defects (NTDs) are a group of birth anomalies having a profound physical, emotional, and financial effects on families and communities. Their etiology is complex, involving environmental and genetic factors that interact to modulate the incidence and severity of the developing phenotype. The planar cell polarity (PCP) pathway controls the process of convergent extension (CE) during gastrulation and neural tube closure and has been implicated in the pathogenesis of NTDs in animal models and human cohorts. This review summarizes the cumulative results of recent studies on PCP signaling pathway and human NTDs. These results demonstrate that PCP gene alterations contribute to the etiology of human NTDs.

关键词： planar cell polarity     neural tube defects     rare mutations    

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标题 作者 时间 类型 操作

Treatment of advanced non-small cell lung cancer with driver mutations: current applications and future

期刊论文

Identification of novel mutations in and in a family with craniofacial microsomia: evidence of digenic

期刊论文

Detection of critical road roughness sections by trend analysis and investigation of driver speed interaction

Meltem SAPLIOGLU; Ayse UNAL; Melek BOCEK

期刊论文

Distributed governance of Solar Radiation Management geoengineering: A possible solution to SRM’s “free-driver

Andrew LOCKLEY

期刊论文

Characteristics of compensatory mutations in the

Shengfen Wang, Yang Zhou, Bing Zhao, Xichao Ou, Hui Xia, Yang Zheng, Yuanyuan Song, Qian Cheng, Xinyang Wang, Yanlin Zhao

期刊论文

122-binding site polymorphism at the interleukin-1 α gene and its interaction with hepatitis B virus mutations

null

期刊论文

Approaching the upper boundary of driver-response relationships: identifying factors using a novel framework

期刊论文

Distinct gene expression pattern of mutations coordinated by target repression and promoter hypermethylation

期刊论文

Fuel type preference of taxi driver and its implications for air emissions

Feng WANG,Beibei LIU,Bing ZHANG,Jun BI

期刊论文

Experimental Study on the Piezoelectric Prestage Driver of Electrohydraulic Servo Valves

CHENG Guang-ming, SHEN Chuan-liang, YANG Zhi-gang

期刊论文

嵌入式无线接入点网络驱动的设计与实现

王质礼,胡爱群,宋宇波

期刊论文

宿主微生物组内的基因组突变——适应性进化或净化选择

张家超, Rob Knight

期刊论文

Association of novel mutations and heplotypes in the preS region of hepatitis B virus with hepatocellular

Jia-Xin XIE, Jian-Hua YIN, Qi ZHANG, Rui PU, Wen-Ying LU, Hong-Wei ZHANG, Guang-Wen CAO, Jun ZHAO, Hong-Yang WANG,

期刊论文

Molecular pathogenesis of acute myeloid leukemia: A diverse disease with new perspectives

Felicitas THOL, Arnold GANSER

期刊论文

Genetic evidence in planar cell polarity signaling pathway in human neural tube defects

null

期刊论文