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Considerations in testing treatment effects on transient event driven health status changes measured by patient reported outcomes

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STATISTICS IN MEDICINE 2019年第29期38卷 5497-5511页

作者： liu, Jingyuan Legg, Jason C. Mo, May Zhang, xuwen Xiamen Univ Sch Econ Wang Yanan Inst Studies Econ Dept StatMOE Key Lab Econometr 422 Siming South Rd Xiamen 361005 Fujian Peoples R China Xiamen Univ Fujian Key Lab Stat Sci 422 Siming South Rd Xiamen 361005 Fujian Peoples R China Amgen Inc Global Biostat Sci Newbury Pk CA USA

Many treatments and drugs are intended to reduce the occurrence of negative events of interest, control the severity of the events, accelerate recovery from the events, or a combination of these effects. While assessing the clinical effect is typically the primary objective of a trial, testing the treatment effect on the health status of patients based on patient reported outcome (PRO) can be a useful component in determining the value of a treatment. Analysis of PROs in this setting, however, face the following challenges: the PRO value immediately after the event occurrence is often not captured, and the effect of the event on health status measured by the PRO is transient as subjects recover over time. Therefore, traditional statistical methods used to assess treatment effects suffer from low power for PROs. In this manuscript, we apply a kernel smoothing technique to estimate before- and after-event PRO values. We also propose new test outcomes based on observed and estimated PRO values and evaluate tests that focus on the tail distributions. We demonstrate that the tail distribution tests using the new outcomes can achieve high power under certain conditions.

关键词： maximum sequential difference modified area under curve patient reported outcome tail distribution test

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Phenotypic plasticity and genetic variation of cotton yield and its related traits under water-limited conditions

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The Crop Journal 2020年第6期8卷 966-976页

作者： Baoqi Li Qin Tian xuwen Wang Bei Han Li liu Xianhui Kong Aijun Si Juan Wang Zhongxu Lin Xianlong Zhang Yu Yu Xiyan Yang National Key Laboratory of Crop Genetic Improvement Huazhong Agricultural UniversityWuhan 430070HubeiChina Cotton Institute Xinjiang Academy of Agriculture and Reclamation ScienceShihezi 832000XinjiangChina

Global warming is limiting availability of water resources in arid and semi-arid regions,and so understanding water use efficiency(WUE)is increasingly important for agricultural production in those *** China is the largest cotton producing area,the problem of balancing WUE and efficient cotton production is a major *** this study,we used a natural population of 517 Upland cotton accessions to conduct a water-controlled trial in south and north of Xinjiang over two years.A total of 18 traits including agronomic traits,fiber yield indices and fiber quality indices,were investigated for broad-sense heritability and coefficient of *** water limitation was found to promote the establishment of favorable agronomic traits in cotton,associated with an increased cotton yield of 8.46%in Xinjiang,at the expense of a certain degree of fiber quality,such as decreased fiber length and an over-higher micronaire *** detected 33 QTL related to response to water limitation using a drought resistance coefficient(DRC),and 6 QTL were found using a comprehensive indicator of CIDT(comprehensive index of drought tolerance)at the genetic level by integrating resequencing *** novel QTL-hotspots including six differentially expressed genes(DEGs)were further identified related to the drought response of *** findings not only suggested a new approach to irrigation of cotton fields in Xinjiang,but also provided abundant genetic evidence for genetic breeders to study drought improvement of crops.

关键词： Upland cotton Water-limited conditions Fiber yield Fiber quality QTL hotspot

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Click-Nucleic-Acid-Containing Codelivery System Inducing Collapse of Cellular Homeostasis for Tumor Therapy through Bidirectional Regulation of Autophagy and Glycolysis

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ACS APPLIED MATERIALS & INTERFACES 2020年第52期12卷 57757-57767页

作者： Guo, Qin Chen, Qinjun Zhang, Yujie Zhou, Wenxi Li, xuwen Li, Chao Zhang, Yiwen Chen, Hongyi liu, Peixin Chu, Yongchao Sun, Tao Jiang, Chen Fudan Univ State Key Lab Med Neurobiol Key Lab Smart Drug Delivery Minist Educ Shanghai 201203 Peoples R China Fudan Univ MOE Frontiers Ctr Brain Sci Sch Pharm Dept Pharmaceut Shanghai 201203 Peoples R China

As a rapid proliferating tissue, tumor cells have to optimize nutrient utilization to withstand harsh conditions. Several approaches have been explored to inhibit the growth and metastasis of tumor by disrupting the reprogrammed tumor metabolism. However, nutrient limitations within solid tumors may induce the metabolic flexibility of malignant cells to sustain growth and survival using one nutrient to fill metabolite pools normally supplied by the other. To overcome this predicament, a promising click-nucleic-acid-containing platform for codelivery of rapamycin, anti-PFKFB4 siRNA, and targeting ligand aptamer AS1411 was applied. PFKFB4 could act as a promising target for tumor therapy for being a molecular fulcrum that could couple glycolysis to autophagy by promoting aggressive metastatic tumors. The downregulation of PFKFB4 can help inhibit the SRC3/Akt/mTOR pathway, leading autophagy to the direction of promoting apoptosis of tumor cells, which is induced by the collapse of tumor cellular homeostasis, while low dosages of rapamycin could decrease surgery-induced immune dysfunction. Enhanced tumor autophagy, favorable in vivo antitumor efficacy, and effective systematic immune activation are observed after treatment, suggesting that autophagy and glycolysis can serve as an integrated target for tumor treatment.

关键词： tumor metabolism codelivery click nucleic acid immune activation tumor therapy

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T1ρ和T2 mapping成像观察青少年尺桡骨远端骺板

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中国医学影像技术 2022年第5期38卷 739-742页

作者：张慈慈梁治平刘琼冯友珍钟敏之曾旭文暨南大学附属广州红十字会医院放射科广东广州510220 暨南大学附属第一医院影像中心广东广州510632

目的以T1ρ和T2 mapping成像观察青少年尺、桡骨远端骺板表现,分析其可行性。方法前瞻性纳入20名健康青少年志愿者,采集双侧腕关节T1ρ和T2 mapping,观察尺、桡骨远端骺板形态,测量尺骨远端骺板内、外侧区和桡骨远端骺板内侧区、中间区... 详细信息

目的以T1ρ和T2 mapping成像观察青少年尺、桡骨远端骺板表现,分析其可行性。方法前瞻性纳入20名健康青少年志愿者,采集双侧腕关节T1ρ和T2 mapping,观察尺、桡骨远端骺板形态,测量尺骨远端骺板内、外侧区和桡骨远端骺板内侧区、中间区及外侧区T1ρ和T2值;比较不同侧别、性别间尺、桡骨远端骺板总体及不同区域的T1ρ和T2值差异,分析尺、桡骨和远端骺板T1ρ及T2值与年龄的相关性。结果尺、桡骨远端骺板于T1ρ和T2 mapping原始图中均呈板状高信号。不同侧别、性别之间,尺、桡骨远端骺板总体及不同区域T1ρ和T2值差异均无统计学意义(P均>0.05)。桡骨远端骺板T1ρ值与年龄呈正相关(r=0.596,P=0.006),其余参数均与年龄无明显相关性(P均>0.05)。结论T1ρ及T2 mapping成像可直观显示青少年尺、桡骨远端骺板形态,定量观察骺板生化改变,可行性好。

关键词：尺骨桡骨生长板磁共振成像 T1ρ T2 mapping 前瞻性研究

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Identification of genetic loci associated with rough dwarf disease resistance in maize by integrating GWAS and linkage mapping

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PLANT SCIENCE 2022年 315卷 111100-111100页

作者： Zhao, Meiai liu, Shuangshuang Pei, Yuhe Jiang, xuwen Jaqueth, Jennifer S. Li, Bailin Han, Jing Jeffers, Daniel Wang, Jiabo Song, Xiyun Qingdao Agr Univ Coll Life Sci Key Lab Plant Biotechnol Univ Shandong Prov Qingdao 266109 Peoples R China Qingdao Agr Univ Coll Agron Key Lab Qingdao Major Crop Germplasm Resource Inn Qingdao 266109 Peoples R China Corteva Agrisci 7300 NW 62nd Ave Johnston IA 50131 USA Shandong Denghai Pioneer Jinan 254000 Shandong Peoples R China Yunnan Acad Agr Sci Yunnan Off Kunming 650205 Yunnan Peoples R China Southwest Minzu Univ Minist Educ Key Lab Qinghai Tibetan Plateau Anim Genet Resour Chengdu 160041 Sichuan Peoples R China

Maize rough dwarf disease (MRDD) is a viral disease that causes substantial yield loss, especially in China's summer planted maize area. Discovery of resistance genes would help in developing high-yielding resistant maize hybrids. Genome-wide association studies (GWASs) have advanced quickly and are now a powerful tool for dissecting complex genetic architectures. In this study, the disease severity index (DSI) of 292 maize inbred lines and an F6 linkage population were investigated across multiple environments for two years. Using the genotypes obtained from the Maize SNP 50K chip, a GWAS was performed with four analytical models. The results showed that 22 SNPs distributed on chromosomes 1, 3, 4, 6, 7 and 8 were significantly associated with resistance to MRDD (P<0.0001). The SNPs on chromosomes 3, 6 and 8 were consistent with the quantitative trait locus (QTL) regions from linkage mapping in an RIL population. Candidate genes identified by GWAS included an LRR receptor-like serine/threonine-protein kinase (GRMZM2G141288), and a DRE-binding protein (GRMZM2G006745). In addition, we performed an allele variation analysis of the SNP loci selected by GWAS and linkage mapping and found that the main alleles of the two SNP loci PZE_101170408 and PZE_106082685 on chromosome 1 differed in terms of disease-resistant materials and disease-susceptible materials. The identified SNPs and genes provide useful information for MRDD-related gene cloning and insights on the underlying disease resistance mechanisms, and they can be used in marker-assisted breeding to develop MRDD-resistant maize.

关键词： Maize MRDD GWAS Linkage mapping Candidate genes

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Comparison and development of a metagenomic next-generation sequencing protocol for combined detection of DNA and RNA pathogens in cerebrospinal fluid

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BMC INFECTIOUS DISEASES 2022年第1期22卷 326-326页

作者： Jiang, Hanfang Xing, Zhihao liu, Xiaorong Chai, Qiang Xin, Zefeng Zhu, Chunqing Lin, Ruihong Deng, xuwen Cui, Dong Gao, HongDan Ma, Dongli Shenzhen Childrens Hosp Inst Pediat Clin Lab Shenzhen Guangdong Peoples R China Shenzhen Childrens Hosp Inst Pediat Shenzhen Guangdong Peoples R China Bengbu Med Coll Med Technol Bengbu Anhui Peoples R China

Background: The purpose of this study was to evaluate different pretreatment, extraction, amplification, and library generation methods for metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) and to develop an efficient procedure for the simultaneous detection of DNA and RNA pathogens. Methods: We generated thirteen mock CSF samples with four representative pathogens of encephalitis. Each sample was subjected to ten different methods by varying sample pretreatment/nucleic acid extraction (microbial DNA, total DNA, total NA, total RNA, Whole Transcriptome Amplification (WTA)) and library generation (Illumina or NEB). Negative extraction controls (NECs) were used for each method variation. Results: We found that the quality of mNGS sequencing reads was higher from the NEB kit for library generation. Microbial DNA and total RNA increased microbial deposition by depleting the host DNA. Methods total NA and total RNA can detect gram-positive, gram-negative, RNA and DNA pathogens. We applied mNGS, including total NA and NEB library generation, to CSF samples from five patients diagnosed with infectious encephalitis and correctly determined all pathogens identified in clinical etiological tests. Conclusions: Our findings suggested that total nucleic acid extraction combined with NEB library generation is the most effective mNGS procedure in CSF pathogen detection. The optimization of positive criteria and databases can improve the specificity and sensitivity of mNGS diagnosis.

关键词： Encephalitis Next-generation sequencing Metagenomic diagnosis

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夹脊温针与中药熏蒸结合西医常规疗法治疗腰椎间盘突出急性炎症期的临床研究

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国际中医中药杂志 2023年第9期45卷 1095-1099页

作者：袁绪文董海彦吴月刘一畅亳州市中医院针灸科亳州236800

目的评价夹脊温针与中药熏蒸结合西医常规疗法对腰椎间盘突出症(LDH)急性炎症期患者的临床疗效。方法随机对照试验研究。选取2019年12月-2021年12月本院140例LDH急性炎症期患者作为观察对象,采用随机数字表法将患者分为2组,每组70例。... 详细信息

目的评价夹脊温针与中药熏蒸结合西医常规疗法对腰椎间盘突出症(LDH)急性炎症期患者的临床疗效。方法随机对照试验研究。选取2019年12月-2021年12月本院140例LDH急性炎症期患者作为观察对象,采用随机数字表法将患者分为2组,每组70例。对照组给予西医常规疗法治疗,观察组在对照组基础上联合夹脊温针与中药熏蒸治疗。2组均连续治疗1个月。分别于治疗前后进行中医证候评分,采用VAS量表评估腰椎疼痛程度,日本骨科协会评估治疗(JOA评分)评估腰椎功能障碍程度,采用ELISA法检测血清CRP、IL-6、TNF-α水平,评价临床疗效。结果观察组总有效率为95.71%(67/70)、对照组为82.86%(58/70),2组比较差异有统计学意义(χ^(2)=6.05,P=0.014)。观察组治疗后中医证候积分[(4.45±1.09)分比(10.67±2.82)分,t=16.85]、VAS评分[(1.54±0.43)分比(3.28±1.04)分,t=12.94]低于对照组(P<0.01),JOA评分中主观感觉[(7.54±2.87)分比(6.24±1.76)分,t=5.72]、体征[(6.76±2.00)分比(4.34±1.67)分,t=7.77]、日常活动受限[(9.56±3.27)分比(7.89±2.97)分,t=3.16]、膀胱功能[(2.88±0.84)分比(2.63±0.64)分,t=2.89]评分及总分[(25.04±7.44)分比(20.35±6.87)分,t=4.63]高于对照组(P<0.01)。观察组治疗后血清IL-6[(18.12±4.23)μg/L比(26.46±4.58)μg/L,t=11.19]、CRP[(18.87±6.07)mg/L比(25.89±5.72)mg/L,t=7.04]、TNF-α[(24.42±5.37)ng/L比(29.45±5.44)ng/L,t=5.51]水平低于对照组(P<0.01)。结论夹脊温针与中药熏蒸结合西医常规疗法可有效缓解LDH急性炎症期患者的腰部疼痛感,降低炎症因子水平,提高临床疗效。

关键词：椎间盘移位腰椎针刺疗法温针疗法熏洗疗法

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茯砖茶改善2型糖尿病小鼠代谢紊乱的效果研究

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茶叶科学 2022年第1期42卷 63-75页

作者：代昕玥葛炳钢张旭雯刘文武段继春傅冬和湖南农业大学茶学教育部重点实验室湖南长沙410128 国家植物功能成分利用工程技术研究中心湖南长沙410128 湖南省植物功能成分利用协同创新中心湖南长沙410128 湖南省农业科学院茶叶研究所湖南长沙410125 湖南德康茶业科技有限公司湖南长沙410001

为探究茯砖茶能否通过调节肠道微生物群改善2型糖尿病(T2DM)的代谢紊乱,建立T2DM小鼠模型,给予400 mg·kg^(-1)茯砖茶水提取物灌胃干预,观测T2DM小鼠的饮食量、饮水量、空腹体重、空腹血糖、糖耐量等日常指标,血清中胰岛素(INS)、... 详细信息

为探究茯砖茶能否通过调节肠道微生物群改善2型糖尿病(T2DM)的代谢紊乱,建立T2DM小鼠模型,给予400 mg·kg^(-1)茯砖茶水提取物灌胃干预,观测T2DM小鼠的饮食量、饮水量、空腹体重、空腹血糖、糖耐量等日常指标,血清中胰岛素(INS)、总胆汁酸(TBA)、总胆固醇(TC)、总甘油三酯(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)、白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)水平,以及胰腺、回肠的病理学变化,并对小鼠粪便进行了肠道菌群16 SrRNA测序。结果显示,茯砖茶显著改善了小鼠的糖脂代谢紊乱和炎症,明显修复了T2DM导致的胰腺和回肠损伤。茯砖茶能显著降低T2DM引起的疣微菌门相对丰度异常增加,恢复肠道微生物群多样性。茯砖茶能增加肠道厚壁菌门、Eubacterium_oprostanoligenes_roup、肠杆菌属、Acetatifactor、双歧杆菌属、Prevotella_9、Faecalibacterium、A2、Coriobacteriaceae及Eggerthellaceae等有益菌,说明茯砖茶可通过增加肠道有益菌群,调节肠道菌群失调,进而改善T2DM的代谢紊乱。

关键词：茯砖茶 2型糖尿病肠道菌群

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竖向分布筋不连接装配式剪力墙抗震性能试验研究

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建筑结构 2021年第17期51卷 5-9,24页

作者：肖绪文曹志伟刘星廖显东同济大学土木工程学院建筑工程系上海200092 中国建筑股份有限公司北京100029 中国建筑第八工程局工程研究院上海200135 清华大学土木水利学院北京100084

为解决如今装配式剪力墙安装过程中竖向钢筋接头数量多导致的安装难等问题,提出了一种新型竖向分布筋不连接装配式剪力墙(简称SGBL装配式剪力墙),其主要特点为墙体竖向分布钢筋断开连接,边缘构件主筋根据本文提出的等承载力设计方法进... 详细信息

为解决如今装配式剪力墙安装过程中竖向钢筋接头数量多导致的安装难等问题,提出了一种新型竖向分布筋不连接装配式剪力墙(简称SGBL装配式剪力墙),其主要特点为墙体竖向分布钢筋断开连接,边缘构件主筋根据本文提出的等承载力设计方法进行加大以弥补抗弯承载力的损失。为研究SGBL装配式剪力墙墙体抗震性能,开展了4片足尺剪力墙试件的低周往复试验,包括两片现浇对比剪力墙试件以及两片SGBL装配式剪力墙试件。试验结果表明:SGBL装配式剪力墙试件破坏形态与现浇对比剪力墙试件基本相同,采用本文提出的等承载力设计方法后,SGBL装配式剪力墙承载力与现浇剪力墙基本一致。同时SGBL装配式剪力墙耗能能力好于现浇剪力墙,表明这种SGBL装配式剪力墙不仅可以解决连接接头数量过多所导致的安装难问题,且在不削弱抗震性能的同时具备较高的经济价值。

关键词：装配式剪力墙竖向分布钢筋等承载力设计方法抗震性能

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矿井水深度除氟的实验研究及经济技术分析

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绿色科技 2023年第16期25卷 154-160,165页

作者：项绪文赵伟贾新强沈军刘娟山东省环科院环境工程有限公司山东济南250100

为将矿井水的氟化物从6.2 mg/L降低到1 mg/L以下,对化学沉淀、羟基磷灰石吸附、离子交换等工艺进行了实验研究及工程经济技术分析。实验结果表明:复配除氟剂沉淀、羟基磷灰石吸附、树脂离子交换工艺能够将氟离子从6.2 mg/L降低到1 mg/L... 详细信息

为将矿井水的氟化物从6.2 mg/L降低到1 mg/L以下,对化学沉淀、羟基磷灰石吸附、离子交换等工艺进行了实验研究及工程经济技术分析。实验结果表明:复配除氟剂沉淀、羟基磷灰石吸附、树脂离子交换工艺能够将氟离子从6.2 mg/L降低到1 mg/L以下。但钙铝药剂难以稳定将氟离子降低到1 mg/L以下。复配除氟剂沉淀、羟基磷灰石吸附及树脂离子交换除氟工艺的处理成本分别为1.14、0.91、1.59元/t。3种工艺中,投资费用最高的是树脂离子交换工艺,最低的是化学沉淀工艺。

关键词：含氟废水化学沉淀吸附离子交换除氟剂

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