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Emerging molecular subtypes and therapeutic targets in B-cell precursor acute lymphoblastic leukemia

Jianfeng Li, Yuting Dai, Liang Wu, Ming Zhang, Wen Ouyang, Jinyan Huang, Saijuan Chen

《医学前沿（英文）》 2021年 第15卷 第3期   页码 347-371 doi: 10.1007/s11684-020-0821-6

摘要： B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is characterized by genetic alterations with high heterogeneity. Precise subtypes with distinct genomic and/or gene expression patterns have been recently revealed using high-throughput sequencing technology. Most of these profiles are associated with recurrent non-overlapping rearrangements or hotspot point mutations that are analogous to the established subtypes, such as rearrangements, rearrangements, rearrangements, rearrangements, / and/or rearrangements, like gene expression, PAX5alt (diverse alterations, including rearrangements, intragenic amplifications, or mutations), and hotspot mutations PAX5 (p.Pro80Arg) with biallelic alterations, IKZF1 (p.Asn159Tyr), and ZEB2 (p.His1038Arg). These molecular subtypes could be classified by gene expression patterns with RNA-seq technology. Refined molecular classification greatly improved the treatment strategy. Multiagent therapy regimens, including target inhibitors (e.g., imatinib), immunomodulators, monoclonal antibodies, and chimeric antigen receptor T-cell (CAR-T) therapy, are transforming the clinical practice from chemotherapy drugs to personalized medicine in the field of risk-directed disease management. We provide an update on our knowledge of emerging molecular subtypes and therapeutic targets in BCP-ALL.

关键词： BCP-ALL     subtypes     translocation     aneuploidy     sequence mutations    

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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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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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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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Ant colony optimization for assembly sequence planning based on parameters optimization

Zunpu HAN, Yong WANG, De TIAN

《机械工程前沿（英文）》 2021年 第16卷 第2期   页码 393-409 doi: 10.1007/s11465-020-0613-3

摘要： As an important part of product design and manufacturing, assembly sequence planning (ASP) has a considerable impact on product quality and manufacturing costs. ASP is a typical NP-complete problem that requires effective methods to find the optimal or near-optimal assembly sequence. First, multiple assembly constraints and rules are incorporated into an assembly model. The assembly constraints and rules guarantee to obtain a reasonable assembly sequence. Second, an algorithm called SOS-ACO that combines symbiotic organisms search (SOS) and ant colony optimization (ACO) is proposed to calculate the optimal or near-optimal assembly sequence. Several of the ACO parameter values are given, and the remaining ones are adaptively optimized by SOS. Thus, the complexity of ACO parameter assignment is greatly reduced. Compared with the ACO algorithm, the hybrid SOS-ACO algorithm finds optimal or near-optimal assembly sequences in fewer iterations. SOS-ACO is also robust in identifying the best assembly sequence in nearly every experiment. Lastly, the performance of SOS-ACO when the given ACO parameters are changed is analyzed through experiments. Experimental results reveal that SOS-ACO has good adaptive capability to various values of given parameters and can achieve competitive solutions.

关键词： assembly sequence planning     ant colony optimization     symbiotic organisms search     parameter optimization    

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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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基于petri网装配序列灰色聚类决策研究

莫茜,罗毅

《中国工程科学》 2008年 第10卷 第11期   页码 65-68

摘要：

利用petri网直观图形化特点建立装配模型，并根据petri网原理得出可行装配序列。影响可行装配序列的大部分因素是定性的、模糊的、非数值的，将装配序列看作灰色系统，采用灰色聚类决策方法对可行序列进行评估。分析了影响因素的灰色分类并且研究了灰色聚类决策步骤。实例分析表明，该方法为petri网原理所得可行序列进行正确的评估并且得出决策向量。

关键词： 装配序列     petri网     灰色聚类决策    

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Analysis of dispatching rules in a stochastic dynamic job shop manufacturing system with sequence-dependent

Pankaj SHARMA,Ajai JAIN

《机械工程前沿（英文）》 2014年 第9卷 第4期   页码 380-389 doi: 10.1007/s11465-014-0315-9

摘要：

Stochastic dynamic job shop scheduling problem with consideration of sequence-dependent setup times are among the most difficult classes of scheduling problems. This paper assesses the performance of nine dispatching rules in such shop from makespan, mean flow time, maximum flow time, mean tardiness, maximum tardiness, number of tardy jobs, total setups and mean setup time performance measures viewpoint. A discrete event simulation model of a stochastic dynamic job shop manufacturing system is developed for investigation purpose. Nine dispatching rules identified from literature are incorporated in the simulation model. The simulation experiments are conducted under due date tightness factor of 3, shop utilization percentage of 90 % and setup times less than processing times. Results indicate that shortest setup time (SIMSET) rule provides the best performance for mean flow time and number of tardy jobs measures. The job with similar setup and modified earliest due date (JMEDD) rule provides the best performance for makespan, maximum flow time, mean tardiness, maximum tardiness, total setups and mean setup time measures.

关键词： scheduling     stochastic dynamic job shop     sequence-dependent setup times     dispatching rule     simulation    

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Transforming bacterial disease surveillance and investigation using whole-genome sequence to probe the

null

《医学前沿（英文）》 2018年 第12卷 第1期   页码 23-33 doi: 10.1007/s11684-017-0607-7

摘要：

Two decades have passed since the first bacterial whole-genome sequencing, which provides new opportunity for microbial genome. Consequently, considerable genetic diversity encoded by bacterial genomes and among the strains in the same species has been revealed. In recent years, genome sequencing techniques and bioinformatics have developed rapidly, which has resulted in transformation and expedited the application of strategy and methodology for bacterial genome comparison used in dissection of infectious disease epidemics. Bacterial whole-genome sequencing and bioinformatic computing allow genotyping to satisfy the requirements of epidemiological study in disease control. In this review, we outline the significance and summarize the roles of bacterial genome sequencing in the context of bacterial disease control and prevention. We discuss the applications of bacterial genome sequencing in outbreak detection, source tracing, transmission mode discovery, and new epidemic clone identification. Wide applications of genome sequencing and data sharing in infectious disease surveillance networks will considerably promote outbreak detection and early warning to prevent the dissemination of bacterial diseases.

关键词： genome sequencing     genomic epidemiology     bacteria     surveillance     infectious diseases    

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A novel sequence batch membrane carbonation photobioreactor developed for microalgae cultivation

Caiyun Hou, Sen Qiao, Yue Yang, Jiti Zhou

《环境科学与工程前沿（英文）》 2019年 第13卷 第6期 doi: 10.1007/s11783-019-1176-6

摘要： • A novel SBM-C-PBR was constructed for microalgae cultivation. • Membrane fouling was greatly mitigated by membrane carbonation. • NH4+ and P removal rates were around 80% in SBM-C-PBR. • Biomass was completely retained by membrane. In this study, a novel sequence batch membrane carbonation photobioreactor was developed for microalgae cultivation. Herein, membrane module was endowed functions as microalgae retention and CO2 carbonation. The results in the batch experiments expressed that the relatively optimal pore size of membranes was 30 nm, photosynthetically active radiation was 36 W/m2 and the CO2 concentration was 10% (v/v). In long-term cultivation, the microalgal concentration separately accumulated up to 1179.0 mg/L and 1296.4 mg/L in two periods. The concentrations of chlorophyll a, chlorophyll b and carotenoids were increased about 23.2, 14.9 and 6.3 mg/L respectively in period I; meanwhile, the accumulation was about 25.0, 14.5, 6.6 mg/L respectively in the period II. Furthermore, the pH was kept about 5.5–7.5 due to intermittent carbonation mode, which was suitable for the growth of microalgae. Transmembrane pressure (TMP) was only increased by 0.19 and 0.16 bar in the end of periods I and II, respectively. The pure flux recovered to 75%–80% of the original value by only hydraulic cleaning. Scanning electron microscope images also illustrated that carbonation through membrane module could mitigate fouling levels greatly.

关键词： Membrane carbonation     SBM-C-PBR     Cultivate microalgae     Membrane fouling    

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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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Assembly design system based on engineering connection

Wensheng YIN

《机械工程前沿（英文）》 2016年 第11卷 第4期   页码 423-432 doi: 10.1007/s11465-016-0382-1

摘要：

An assembly design system is an important part of computer-aided design systems, which are important tools for realizing product concept design. The traditional assembly design system does not record the connection information of production on the engineering layer; consequently, the upstream design idea cannot be fully used in the downstream design. An assembly design model based on the relationship of engineering connection is presented. In this model, all nodes are divided into two categories: The component and the connection. Moreover, the product is constructed on the basis of the connection relationship of the components. The model is an And/Or graph and has the ability to record all assembly schemes. This model records only the connection information that has engineering application value in the product design. In addition, this model can significantly reduce the number of combinations, and is very favorable for the assembly sequence planning in the downstream. The system contains a connection knowledge system that can be mapped to the connection node, and the connection knowledge obtained in practice can be returned to the knowledge system. Finally, VC++6.0 is used to develop a prototype system called Connect-based Assembly Planning (CAP). The relationship between the CAP system and the commercial assembly design system is also established.

关键词： product design     assembly design     engineering connection     assembly sequence planning    

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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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Characterization of the dissolved organic matter in sewage effluent of sequence batch reactor: the impact

Jin GUO, Feng SHENG, Jianhua GUO, Xiong YANG, Mintao MA, Yongzhen PENG

《环境科学与工程前沿（英文）》 2012年 第6卷 第2期   页码 280-287 doi: 10.1007/s11783-011-0336-0

摘要： Dissolved organic matter (DOM) transformation in sequence batch reactor (SBR) fed with carbon sources of different biodegradability was investigated. During the biologic degradation process, the low molecular weight (MW) fraction (<1 kDa) gradually decreased, while the refractory compounds with higher aromaticity were aggregated. Size exclusion chromatography (SEC) and fluorescence of excitation emission matrices (EEM) demonstrated that more biopolymers (polysaccharides or proteins) and humic-like substances were presented in the extracellular polymeric substance (EPS) extracted from the SBR fed with sodium acetate or glucose, while the EPS from SBR fed with slowly biodegradable dissolved organic carbon (DOC) substrate-starch had relatively less biopolymers. Comparing the EfOM in sewage effluent of three SBRs, the effluent from SBR fed with starch is more aromatic. Organic carbon with MW>1 kDa as well as the hydrophobic fraction in DOM gradually increased with the carbon sources changing from sodium acetate to glucose and starch. The DOC fractionation and the EEM all demonstrated that EfOM from the effluent of the SBR fed with starch contained more fulvic acid-like substances comparing with the SBR fed with sodium acetate and glucose.

关键词： effluent organic matter (EfOM)     extracellular polymeric substance (EPS)     molecular weight distribution (MWD)     hydrophobic     hydrophilic     excitation emission matrices (EEM)    

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标题 作者 时间 类型 操作

Emerging molecular subtypes and therapeutic targets in B-cell precursor acute lymphoblastic leukemia

Jianfeng Li, Yuting Dai, Liang Wu, Ming Zhang, Wen Ouyang, Jinyan Huang, Saijuan Chen

期刊论文

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

期刊论文

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

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

Ant colony optimization for assembly sequence planning based on parameters optimization

Zunpu HAN, Yong WANG, De TIAN

期刊论文

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

期刊论文

基于petri网装配序列灰色聚类决策研究

莫茜,罗毅

期刊论文

Analysis of dispatching rules in a stochastic dynamic job shop manufacturing system with sequence-dependent

Pankaj SHARMA,Ajai JAIN

期刊论文

Transforming bacterial disease surveillance and investigation using whole-genome sequence to probe the

null

期刊论文

A novel sequence batch membrane carbonation photobioreactor developed for microalgae cultivation

Caiyun Hou, Sen Qiao, Yue Yang, Jiti Zhou

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

Assembly design system based on engineering connection

Wensheng YIN

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

Characterization of the dissolved organic matter in sewage effluent of sequence batch reactor: the impact

Jin GUO, Feng SHENG, Jianhua GUO, Xiong YANG, Mintao MA, Yongzhen PENG

期刊论文