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Genetic Variations and Nonalcoholic Fatty Liver Disease:Field Synopsis,Systematic Meta-Analysis,and Epidemiological Evidence

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Biomedical and Environmental Sciences 2024年第7期37卷 762-773页

作者： Yamei Li Xiang Xiao Jie Wang Yixu Liu Xiongfeng Pan Haibin Yu jiayou luo Miyang luo Department of Epidemiology and Health Statistics School of Public HealthUniversity of South ChinaHengyang 421001HunanChina Department of Maternal and Child Health Xiangya School of Public HealthCentral South UniversityChangsha 410008HunanChina Supervision and Inspection Department of Shanghai Healthcare Security Bureau Shanghai 200003China Department of Epidemiology and Health Statistics Xiangya School of Public HealthCentral South UniversityChangsha 410008HunanChina

Objective To systematically summarize the published literature on the genetic variants associated with nonalcoholic fatty liver disease(NAFLD).Methods Literature from Web of Science,PubMed,and Embase between January 1980 and September 2022 was systematically ***-analyses of the genetic variants were conducted using at least five data *** epidemiologic credibility of the significant associations was graded using the Venice *** Based on literature screening,399 eligible studies were included,comprising 381 candidate gene association,16 genome-wide association,and 2 whole-exome sequencing *** identified 465 genetic variants in 173 genes in candidate gene association studies,and 25 genetic variants in 17 genes were included in the *** meta-analysis identified 11 variants in 10 genes that were significantly associated with NAFLD,with cumulative epidemiological evidence of an association graded as strong for two variants in two genes(HFE,TNF),moderate for four variants in three genes(TM6SF2,GCKR,and ADIPOQ),and weak for five variants in five genes(MBOAT7,PEMT,PNPLA3,LEPR,and MTHFR).Conclusion This study identified six variants in five genes that had moderate to strong evidence of an association with NAFLD,which may help understand the genetic architecture of NAFLD risk.

关键词： Nonalcoholic fatty liver disease Genetic association study Genetic variant Systematic review Meta-analysis

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全血铜、锌、钙、镁、铁与超重肥胖儿童非酒精性脂肪肝病的关联

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中南大学学报（医学版） 2024年第3期49卷 426-434页

作者：黄智航罗米扬戴文姚珍珍欧阳思思徐宁安周海湘李雄伟钟燕罗家有中南大学湘雅公共卫生学院流行病与卫生统计学系长沙410013 中南大学湘雅公共卫生学院儿少卫生与妇幼保健学系长沙410013 湖南省儿童医院儿童保健所长沙410007 宁乡市疾病预防控制中心长沙410600

目的:非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)是超重肥胖儿童中常见的一种代谢性疾病,其病因和发病机制尚未阐明,缺乏有效的预防和治疗手段。本研究旨在分析6~17岁超重肥胖儿童全血铜、锌、钙、镁、铁与NAFLD的关联... 详细信息

目的:非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)是超重肥胖儿童中常见的一种代谢性疾病,其病因和发病机制尚未阐明,缺乏有效的预防和治疗手段。本研究旨在分析6~17岁超重肥胖儿童全血铜、锌、钙、镁、铁与NAFLD的关联,为超重肥胖儿童NAFLD的预防和早期干预提供依据。方法:采用横断面研究设计,通过问卷调查收集于2019年1月至2021年12月在湖南省儿童医院就诊的超重肥胖儿童的相关资料,采集受试者凌晨空腹血并检测血糖、血脂、微量元素等指标。将超重肥胖儿童分为单纯超重肥胖组(n=400)和NAFLD组(n=202);根据ALT水平,将NAFLD组划分为单纯性脂肪肝(non-alcoholic fatty liver,NAFL)组和非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)组2个亚组。采用Logistic回归分析全血铜、锌、钙、镁、铁与NAFLD、NAFL和NASH之间的关联。结果:共纳入602名研究对象,其中73.6%为男性,年龄为10(9,11)岁,体重指数(body mass index,BMI)为24.9(22.7,27.4)kg/m~2。组间比较结果显示:NAFLD组的年龄、BMI、舒张压(diastolic blood pressure,DBP)、收缩压(systolic blood pressure,SBP)、甘油三酯(triglyceride,TG)、低密度脂蛋白(low density lipoprotein,LDL)、谷丙转氨酶(alanine transaminase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)均高于单纯超重肥胖组,高密度脂蛋白(high density lipoprotein,HDL)低于单纯超重肥胖组;NAFL组的年龄、BMI、DBP、SBP、ALT、AST均高于单纯超重肥胖组,HDL低于单纯超重肥胖组;NASH组的年龄、BMI、DBP、SBP、TG、LDL、ALT、AST均高于单纯超重肥胖组,HDL低于单纯超重肥胖组(均P<0.017)。根据各微量元素水平划分为四分位组,在调整混杂因素年龄、性别、BMI、血压、TG、HDL、LDL后,与最低分位组相比,铁元素最高分位组NAFLD的OR值为1.79(95%CI 1.07~3.00),铜、锌、钙、镁元素与NAFLD均不存在关联。NAFLD亚组分析结果显示:在调整混杂因素后,铁元素最高分位组NAFL的OR值为2.21(95%CI 1.26~3.88),未发现铁与NASH以及铜、锌、钙、镁与NAFL或NASH之间的关联。结论:铁水平过高增加超重肥胖儿童NAFLD(更有可能是NAFL)的患病风险,而铜、锌、钙、镁等与超重肥胖儿童NAFLD的患病风险无关。

关键词：超重肥胖儿童非酒精性脂肪肝病微量元素

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脂肪细胞因子通路基因多态性与肥胖儿童非酒精性脂肪性肝病的关联

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中南大学学报（医学版） 2024年第5期49卷 775-783页

作者：王洁潘雄峰韦佳李雄伟周海湘徐宁安康如彤钟燕罗家有中南大学湘雅公共卫生学院儿少卫生与妇幼保健学系长沙410013 宁乡市疾病预防控制中心长沙410699 湖南省儿童医院儿童保健所长沙410007

目的:非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)存在明显的遗传易感性,脂肪细胞因子通过参与胰岛素抵抗和肝脏脂肪变性等过程,在NAFLD的发生和发展中发挥重要作用,但参与脂肪细胞因子通路的基因与NAFLD之间的关联... 详细信息

目的:非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)存在明显的遗传易感性,脂肪细胞因子通过参与胰岛素抵抗和肝脏脂肪变性等过程,在NAFLD的发生和发展中发挥重要作用,但参与脂肪细胞因子通路的基因与NAFLD之间的关联仍不明确。本研究旨在探索脂肪细胞因子通路的基因多态性位点及其交互作用与肥胖儿童NAFLD的关联。方法:采用病例对照研究,将肥胖儿童分为NAFLD组和对照组。采集受试者外周静脉血2 mL,提取DNA后采用多重PCR和高通量测序对脂肪细胞因子通路的14个单核苷酸多态性(single nucleotide polymorphism,SNP)进行分型检测。采用单因素及多因素Logistic回归分析各SNP与肥胖儿童NAFLD的关联。基于显性模型,联合使用交叉分析和Logistic回归分析相加或相乘交互作用。采用广义多因子降维法(generalized multifactor dimensionality reduction,GMDR)检测14个SNP之间基因-基因交互作用与肥胖儿童NAFLD之间的关联。结果:共纳入1 022例儿童,NAFLD组与对照组各511例。在调整年龄、性别、BMI后,多因素Logistic回归结果显示:PPARG rs1801282在3个遗传模型中与肥胖儿童NAFLD存在关联,分别是杂合子模型(CG vs CC,OR=0.58,95%CI 0.36~0.95,P=0.029)、显性模型(CG+GG vs CC,OR=0.62,95%CI 0.38~1.00,P=0.049)、超显性模型(CC+GG vs CG,OR=1.72,95%CI 1.06~2.80,P=0.028);PRKAG2 rs12703159在4个遗传模型中与肥胖儿童NAFLD存在关联,分别是杂合子模型(CT vs CC,OR=1.51,95%CI 1.10~2.07,P=0.011)、显性模型(CT+TT vs CC,OR=1.50,95%CI 1.10~2.03,P=0.010)、超显性模型(CC+TT vs CT,OR=0.67,95%CI 0.49~0.92,P=0.012)、加性模型(CC vs CT vs TT,OR=1.40,95%CI 1.07~1.83,P=0.015)。但PPARG rs1801282与PRKAG2 rs12703159间的相乘及相加交互作用均与肥胖儿童NAFLD不存在关联。经GMDR分析,调整年龄、性别、BMI后,14个SNP之间的交互作用均无统计学意义(均P>0.05)。结论:PPARG rs1801282、PRKAG2 rs12703159突变型与肥胖儿童NAFLD存在关联,但未发现SNP交互作用与肥胖儿童NAFLD之间的关联。

关键词：肥胖儿童非酒精性脂肪性肝病脂肪细胞因子单核苷酸多态性交互作用广义多因子降维法

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2021年湖南省长沙县新发现的高血压患者特征、血压控制情况及影响因素分析

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实用预防医学 2024年第2期31卷 214-219页

作者：杨娴郭雨欣刘丹陈智严俊霞罗家有中南大学湘雅公共卫生学院儿少卫生与妇幼保健系湖南长沙410078 长沙县黄花镇卫生院湖南长沙410100 中南大学湘雅公共卫生学院流行病与卫生统计学系湖南长沙410078 长沙县疾病预防控制中心湖南长沙410100 长沙县星沙医院湖南长沙410100

目的描述湖南省长沙县新发现的高血压患者基本情况,并分析其血压控制现状及相关影响因素。方法以湖南省长沙县各乡镇卫生院/社区卫生服务中心2021年新发现的高血压患者为研究对象,对其建档时的情况及随访时血压控制情况和相关影响因素... 详细信息

目的描述湖南省长沙县新发现的高血压患者基本情况,并分析其血压控制现状及相关影响因素。方法以湖南省长沙县各乡镇卫生院/社区卫生服务中心2021年新发现的高血压患者为研究对象,对其建档时的情况及随访时血压控制情况和相关影响因素进行分析。不同特征组间控制满意率比较采用χ2检验,血压控制情况影响因素分析采用多因素logistic回归分析。结果长沙县2021年共新发现高血压患者17477人,其中男性8757人(50.11%),女性8720人(49.89%);主要以45~64岁人群为主(9216人,52.73%);病例来源以主动就诊者居多,占52.34%;轻、中、重度高血压患者分别占53.86%、31.69%及14.45%;13.98%的高血压患者诊断有糖尿病。年度随访人数为17391人,随访率为99.51%,血压控制满意率为79.10%。多因素logistic回归分析结果显示,与主动就诊的患者相比,通过首诊测压发现的病人(OR=1.20,95%CI:1.03~1.41)血压控制情况较差,而调查或体检发现的病人血压控制情况较好(OR=0.87,95%CI:0.78~0.97);此外,超重(OR=1.10,95%CI:1.01~1.21)、肥胖(OR=1.28,95%CI:1.12~1.45)、饮酒(OR=1.25,95%CI:1.10~1.42)、每周运动6次以上(OR=1.18,95%CI:1.05~1.33)、中度高血压(OR=1.34,95%CI:1.21~1.48)、重度高血压(OR=1.58,95%CI:1.29~1.95)、有靶器官损害(OR=1.46,95%CI:1.17~1.81)、重度摄盐(OR=1.20,95%CI:1.04~1.37)、遵医行为一般(OR=1.28,95%CI:1.11~1.47)、遵医行为差(OR=2.66,95%CI:1.93~3.68)、间断服药(OR=1.19,95%CI:1.00~1.40)、不服药(OR=1.24,95%CI:1.02~1.51)的患者血压控制情况差,而每周运动1~5次(1~2次/周OR=0.80,95%CI:0.68~-0.94)(3~5次/周OR=0.70,95%CI:0.64~0.78)、有糖尿病(OR=0.82,95%CI:0.73~0.93)或者其心脑血管相关临床疾病(OR=0.60,95%CI:0.45~0.80)、有家庭医生签约(OR=0.69,95%CI:0.63~0.75)的病人血压控制情况较好。结论湖南省长沙县高血压防控工作有待提升,今后应针对血压控制相关影响因素优化措施,加强防控,以减轻心脑血管疾病负担。

关键词：高血压主动就诊血压控制影响因素

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宫颈癌复发的影响因素及风险预测模型

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中南大学学报（医学版） 2022年第12期47卷 1711-1720页

作者：李吉娜罗家有刘高明颜仕鹏中南大学湘雅公共卫生学院儿少卫生与妇幼保健学系长沙410008 湖南省肿瘤医院中南大学湘雅医学院附属肿瘤医院护理部长沙410013 湖南省肿瘤防治研究办公室长沙410006

目的:宫颈癌是全球女性生殖系统中最常见的恶性肿瘤,治疗后的宫颈癌患者复发率高,严重威胁妇女的生命健康。目前尚未见有关宫颈癌复发风险预测的研究报道。本研究基于宫颈癌复发的影响因素,建立宫颈癌复发风险预测模型,为宫颈癌复发防... 详细信息

目的:宫颈癌是全球女性生殖系统中最常见的恶性肿瘤,治疗后的宫颈癌患者复发率高,严重威胁妇女的生命健康。目前尚未见有关宫颈癌复发风险预测的研究报道。本研究基于宫颈癌复发的影响因素,建立宫颈癌复发风险预测模型,为宫颈癌复发防治提供科学依据。方法:选择1992年1月至2005年12月湖南省肿瘤医院收治的4358例宫颈癌患者为研究对象,随访宫颈癌患者治疗后的复发情况。对其可能的影响因素进行单因素分析,将单因素分析有统计学意义或单因素分析无统计学意义但专业上认为可能有意义的变量纳入多元Cox回归分析,建立宫颈癌复发风险预测模型,预测模型通过列线图展示。采用受试者工作特征(receiver operating characteristic,ROC)曲线、一致性曲线和临床决策曲线对模型进行评价。结果:单因素分析显示:不同年龄、初潮年龄、生产次数、流产次数、临床分期和治疗方式的宫颈癌患者复发率比较,差异均有统计学意义(均P15岁)+0.459×(流产次数≥3)+0.416×(临床Ⅱ期)+0.613×(临床Ⅲ/Ⅳ期)+0.366×(治疗方式为手术+化学治疗)+0.015×(治疗方式为单纯化学治疗)。本研究构建的宫颈癌复发Cox风险预测模型曲线下面积为0.736(95%CI:0.684~0.789),最佳预测阈值为0.857,灵敏度为0.576,特异度为0.810。从临床决策曲线看净获益值较高,有效性良好。结论:患者年龄、初潮年龄、流产次数、临床分期和治疗方式是影响宫颈癌复发的独立因素,本研究构建的宫颈癌复发Cox比例风险模型可较好地预测宫颈癌复发的风险。

关键词：宫颈癌复发影响因素风险预测模型 Cox回归

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Large language model and domain-specific model collaboration for smart education

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Frontiers of Information Technology & Electronic Engineering 2024年第3期25卷 333-341页

作者： Yawei luo Yi YANG School of Software Technology Zhejiang UniversityNingbo 315048China College of Computer Science and Technology Zhejiang UniversityHangzhou 310027China

In this paper,we introduce the large language model and domain-specific model collaboration(LDMC)framework designed to enhance smart *** LDMC framework leverages the comprehensive and versatile knowledge of large domain-general models,combines it with the specialized and disciplinary knowledge from small domainspecific models(DSMs),and incorporates pedagogy knowledge from learning theory *** integration yields multiple knowledge representations,fostering personalized and adaptive educational *** explore various applications of the LDMC framework in the context of smart education.

关键词： smart language knowledge

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Switching Behavior of Cascode GaN Under Influence of Gate Driver

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CSEE Journal of Power and Energy Systems 2024年第4期10卷 1816-1833页

作者： Bin luo Guangzhao luo Sihai Li School of Automation Northwestern Polytechnical UniversityXi’an 710072China

With high-frequency,low power dissipation and high-efficiency characteristics,Gallium nitride(GaN)power devices are of significant benefit in designing high-speed motor drives,as they improve performance and reduce ***,due to the cascode structure,coupling with the parasitics in gate driver and power circuits,power converters based on cascode GaN are prone to overshoot and oscillate on switching waveforms,which may lead to serious EMC problems,or even device *** complicated structure of cascode GaN device makes the gate driver design comparatively *** analytical model of the switching process considering gate driver parameters is proposed in this *** influence of gate driver parameters on switching behavior is investigated from the perspective of switching speed,waveform overshoot,and power ***-offs among overshoot,switching speed,and power loss are discussed;guidelines to design gate driver parameters are given.

关键词： Gallium nitride(GaN) gate driver oscillation and overshoot switching characteristics

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Catalyst design and structure control for photocatalytic refineries of cellulosic biomass to fuels and chemicals

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Journal of Energy Chemistry 2024年第7期94卷 102-127页

作者： Lulu Sun Nengchao luo State Key Laboratory of Catalysis Dalian National Laboratory for Clean EnergyDalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023LiaoningChina

Lignocellulosic biomass is the largest renewable hydrocarbon resource on *** cellulose,one of the major components of lignocellulose,powered by solar energy is a promising way of providing lowcarbon-footprint energy chemicals such as H_(2),HCOOH,CO,and transportation ***-of-the-art biorefineries target the full use of biomass feedstocks as they have a maximum collection radius of 75-100 km,requesting efficient and selective photocatalysts that significantly influence the outcome of photocatalytic ***-performed photocatalysts can harvest a broad solar spectrum and are active in breaking the chemical bonds of cellulose,decreasing the capital investments of ***,photocatalysts should control the selectivity of cellulose conversion,originating target products to level down separation *** separation in photocatalysts and interfacial charge transfer between photocatalysts and cellulose affect the activity and selectivity of cellulose refineries to H2 and carbonaceous *** account for the challenges above,this review summarizes photocatalysts for the refineries of cellulose and downstream platform molecules based on the types of products,with the structure features of different types of photocatalysts discussed in relation to the targets of either improving the activity or product *** addition,this review also sheds light on the methods for designing and regulating photocatalyst structures to facilitate photocatalytic refineries of cellulose and platform molecules,meanwhile summarizing proposed future research challenges and opportunities for designing efficient photocatalysts.

关键词： Photocatalysts Biorefineries Cellulose Fuels Hydrogen

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Precision regulation of plant aromatic amino acid homeostasis

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Science China(Life Sciences) 2024年第6期67卷 1316-1317页

作者： Jie luo Yazhouwan National Laboratory(YNL) Sanya 572025China School of Breeding and Multiplication(Sanya Institute of Breeding and Multiplication) Hainan UniversitySanya 572025China

The aromatic amino acids(AAAs)phenylalanine(Phe),tyrosine(Tyr),and tryptophan(Trp)are not only building blocks of proteins,but also precursors of numerous primary and specialized metabolites(Schenck and Maeda,2018).For instance,Trp is a precursor of the phytohormone auxin and the plant defense compounds indole glucosinolates,while Phe serves as a precursor of lignin,coumarin and *** plant natural products such as morphine and vitamin E are derived from Tyr,and have been employed in human medicine and nutrition(Schenck and Maeda,2018;Wu et al.,2022;Yokoyama et al.,2021).

关键词： aromatic instance coumarin

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Detecting APT-Exploited Processes through Semantic Fusion and Interaction Prediction

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Computers, Materials & Continua 2024年第2期78卷 1731-1754页

作者： Bin luo Liangguo Chen Shuhua Ruan Yonggang luo School of Cyber Science and Engineering Sichuan UniversityChengdu610065China Key Laboratory of Data Protection and Intelligent Management(Sichuan University) Ministry of EducationChengdu610065China Cyber Science Research Institute Sichuan UniversityChengdu610065China

Considering the stealthiness and persistence of Advanced Persistent Threats(APTs),system audit logs are leveraged in recent studies to construct system entity interaction provenance graphs to unveil threats in a ***-based provenance graph APT detection approaches require elaborate rules and cannot detect unknown attacks,and existing learning-based approaches are limited by the lack of available APT attack samples or generally only perform graph-level anomaly detection,which requires lots of manual efforts to locate attack *** paper proposes an APT-exploited process detection approach called ThreatSniffer,which constructs the benign provenance graph from attack-free audit logs,fits normal system entity interactions and then detects APT-exploited processes by predicting the rationality of entity ***,ThreatSniffer understands system entities in terms of their file paths,interaction sequences,and the number distribution of interaction types and uses the multi-head self-attention mechanism to fuse these ***,based on the insight that APT-exploited processes interact with system entities they should not invoke,ThreatSniffer performs negative sampling on the benign provenance graph to generate non-existent edges,thus characterizing irrational entity interactions without requiring APT attack *** last,it employs a heterogeneous graph neural network as the interaction prediction model to aggregate the contextual information of entity interactions,and locate processes exploited by attackers,thereby achieving fine-grained APT *** results demonstrate that anomaly-based detection enables ThreatSniffer to identify all attack *** to the node-level APT detection method APT-KGL,ThreatSniffer achieves a 6.1%precision improvement because of its comprehensive understanding of entity semantics.

关键词： Advanced persistent threat provenance graph multi-head self-attention graph neural network

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