一种海洋来源ETP类化合物GQQ-ZML-2抑制H358细胞增殖作用与机制的研究

摘要：目的 探究化合物GQQ-ZML-2对H358细胞(KRASG12C)的增殖抑制作用并初步研究其作用机制。方法 采用磺酰罗丹明B法（SRB法）测定GQQ-ZML-2对不同KRAS突变的肿瘤细胞的细胞毒;采用流式细胞术检测细胞周期和细胞凋亡;利用荧光探针DCFH-DA检测细胞内总活性氧（ROS）水平;Western Blotting检测相关信号蛋白的表达水平;结果 GQQ-ZML-2选择性抑制H358细胞增殖,以浓度依赖的方式抑制克隆形成并将细胞周期阻滞于G2/M期而诱导细胞凋亡。机制研究表明GQQ-ZML-2引起KRAS G12C依赖的ROS产生,抑制AKT/mTOR和JAK2/STAT3信号通路。结论 GQQ-ZML-2是一种新型的具有选择性抑制H358细胞增殖作用的海洋来源化合物,其作用机制可能与诱导KRASG12C依赖的ROS增加相关。本文研究为开发新型的拮抗具有KRASG12C突变肿瘤的药物提供了实验依据。     

基于数据挖掘的含鸡血藤-黄芪药对方剂的组方规律分析

目的:通过数据挖掘分析含有鸡血藤-黄芪药对的中医方剂组方规律,以期为临床应用及相关新药研发提供理论依据。方法:以"鸡血藤""黄芪"为主题词,收集《中医方剂大辞典》《卫生部药品标准·中药成方制剂》及CNKI中含有鸡血藤-黄芪药对的方剂,录入中医传承辅助平台(V2.5)建立数据库,分析其用药、性味归经及主治病症频数,并对高频病症进行组方规律分析。结果:纳入含有鸡血藤-黄芪药对的方剂共89首,涉及主治疾病包括痹病、虚劳等8种(频数≥3);涉及中医证候包括气虚血瘀证、气血两虚证等8种(频数≥4);常用配伍药材24味(频数≥10);性味统计中以甘温药物的使用频数最高,归经统计中以肝脾经频数最高;与鸡血藤-黄芪配伍治疗痹病的核心药材有6种,治疗虚劳的核心药材有4种,治疗气虚血瘀证的核心药材有4种,治疗气血两虚证的核心药材有7种。结论:含鸡血藤-黄芪药对相关成药可着重对痹病、虚劳、中风及肿瘤等多种疾病进行调理,尤其是针对气虚血瘀证、气血两虚证患者,包括现代肿瘤晚期放化疗后等导致免疫力低下的虚劳患者。     

Effects of Forging and Heat Treatment on Martensite Lath,Recrystallization and Mechanical Properties Evolution of 18Ni(250) Maraging Steel

The manufacturing process of maraging steel parts include forging, heat treatment and other technological links, and the strengthening mechanism at different stages is different, which has an important impact on the process design of forgings. To investigate the strengthening behavior of maraging steel, forging experiments with different deformation amounts and heat treatment conditions were carried out, and the microstructural and mechanical properties evolution of 18Ni(250) steel was analyzed. The experimental results show that the size of the martensite lath is affected by multiple factors such as the influence of grain size, recrystallization and martensite substructure fraction. The strengthening mechanism of maraging steel during forging and heat treatment is different. Forging combined with heat treatment can refine grains, and the internal defects of the original material can be better eliminated. The thermal deformation can better play the role of grain refinement compared with cyclic phase transformation, which can improve the plasticity of 18Ni(250) maraging steel.     

Assessing the Association between Important Dietary Habits and Osteoporosis: A Genetic Correlation and Two-Sample Mendelian Randomization Study

Objective: Osteoporosis (OP) is the most common bone disease. The genetic and metabolic factors play important roles in OP development. However, the genetic basis of OP is still elusive. The study aimed to explore the relationships between OP and dietary habits. Methods: This study used large-scale genome-wide association study (GWAS) summary statistics from the UK Biobank to explore potential associations between OP and 143 dietary habits. The GWAS summary data of OP included 9434 self-reported OP cases and 444,941 controls, and the GWAS summary data of the dietary habits included 455,146 participants of European ancestry. Linkage disequilibrium score regression (LDSC) was used to detect the genetic correlations between OP and each of the 143 dietary habits, followed by Mendelian randomization (MR) analysis to further assess the causal relationship between OP and candidate dietary habits identified by LDSC. Results: The LDSC analysis identified seven candidate dietary habits that showed genetic associations with OP including cereal type such as biscuit cereal (coefficient = −0.1693, p value = 0.0183), servings of raw vegetables per day (coefficient = 0.0837, p value = 0.0379), and spirits measured per month (coefficient = 0.115, p value = 0.0353). MR analysis found that OP and PC17 (butter) (odds ratio [OR] = 0.974, 95% confidence interval [CI] = (0.973, 0.976), p value = 0.000970), PC35 (decaffeinated coffee) (OR = 0.985, 95% CI = (0.983, 0.987), p value = 0.00126), PC36 (overall processed meat intake) (OR = 1.035, 95% CI = (1.033, 1.037), p value = 0.000976), PC39 (spirits measured per month) (OR = 1.014, 95% CI = (1.011, 1.015), p value = 0.00153), and servings of raw vegetables per day (OR = 0.978, 95% CI = (0.977, 0.979), p value = 0.000563) were clearly causal. Conclusions: Our findings provide new clues for understanding the genetic mechanisms of OP, which focus on the possible role of dietary habits in OP pathogenesis.     

多层螺旋CT胃成像及2D MPR对胃病的显示

CT技术的进步包括多层螺旋CT的引进以及3D成像软件的开发,2DMPR和CT胃造影在同一组数据内可以获得胃部疾病的完整信息,而传统的方法则需要行胃镜、上消化道造影（UGIS）、内镜超声和CT共同完成。多层螺旋CT可以无创评价胃壁以及胃周病变范围,检测和评价胃的恶性肿瘤以及胃的各种炎性病变。     

联合检测对地中海贫血实验诊断的应用价值

目的 评价红细胞平均体积（MCV）、红细胞脆性试验和血红蛋白（Hb）电泳在地中海贫血诊断及其产前筛查中的价值。方法 选择2004年至2005年间在我院进行系统产前检查的已被基因诊断证实的210例地中海贫血夫妇的筛查实验结果进行回顾性分析。结果 MCV、红细胞脆性试验及Hb电泳单项检测在地中海贫血产前筛查的灵敏度和特异度分别为97．6％、89．5％、90．0％及76．0％、89．3％、97．3％;MCV与Hb电泳、红细胞脆性试验与Hb电泳2项平行联合检测的灵敏度及特异度分别为100．0％、86．7％及99．0％、89．3％,系列联合检测的灵敏度及特异度分别为89．0％、99．7％及87．1％、100．0％。MCV、红细胞脆性试验及Hb电泳3项平行联合检测的灵敏度及特异度分别为100．0％、79．7％;3项系列联合检测灵敏度及特异度为86．7％、100．0％。经u检验,平行联合检测的灵敏度与各单项检测灵敏度之间、系列联合检测的特异度与各单项检测特异度之间差异有统计学意义（P〈0．05）。结论 MCV、红细胞脆性试验及Hb电泳3项联合检测是地中海贫血诊断及其产前筛查中最理想的试验方法。     

补中益气汤加味辅助电刺激生物反馈治疗气虚型盆底功能障碍性疾病的疗效分析

目的 探讨补中益气汤加味辅助电刺激生物反馈治疗气虚型盆底功能障碍(PFD)性疾病的疗效和对其生活质量的影响.方法 选取2017年2月至2018年8月达州市中西医结合医院治疗的256例气虚型PFD患者的临床资料作为研究对象,进行回顾性分析.根据治疗方案将患者分为研究组(n=131)和对照组(n=125).对照组入院后均给...     

中国女性与日本女性股骨颈几何参数的比较

目的：股骨颈脆性骨折是后果最严重、医疗花费最高和病死率最高的骨质疏松性骨折类型。股骨颈几何参数(femoral neck geometric parameters,FNGPs)是反映股骨颈几何学特征的重要参数,与股骨颈强度和脆性骨折风险密切相关。股骨颈脆性骨折的发病率存在明显的种族差异,但FNGPs是否有种族差异尚未明确。本研究旨在比较中国女性与日本女性FNGPs的差异。方法：本研究为横断面研究,从湖南省长沙市及周边地区招募女性健康志愿者3 859名,年龄为10.0～86.0(45.7±17.1)岁。测量并记录研究对象的体重、身高,并计算其体重指数(body mass index,BMI),采用双能X线骨密度测量仪测量研究对象的股骨颈投射骨面积(bone area, BA)和股骨颈骨密度(bone mineral density,BMD)。采用BA和/或BMD计算各种FNGPs,包括股骨颈轴长中点的外周直径(outer diameter,OD)、横截面积(cross-sectional area,CSA)、平均皮质厚度(cortical thickness,CT)、内皮质直径(endo...     

基于扫描式葡萄糖监测系统的儿童1型糖尿病患者血糖波动的影响因素

目的：经典1型糖尿病(type 1 diabetes mellitus,T1DM)患者由于胰岛β细胞破坏、胰岛素绝对缺乏,需终身依赖外源性胰岛素治疗。中国糖尿病患儿中T1DM约占90%,发病率快速增加且低龄化严重。流行病学研究显示中国患儿平均糖化血红蛋白(glycated haemoglobin,HbA1c)整体偏高、达标率低。良好的血糖管理是糖尿病治疗的重点,维持血糖在目标范围内可阻止或延缓T1DM患者慢性血管并发症。本研究旨在利用扫描式葡萄糖监测系统(flash glucose monitoring system,FGMS)了解湖南省和河南省T1DM患儿的血糖控制情况,分析该群体血糖波动的影响因素。方法：选择2017年8月至2020年8月于两省16所医院内分泌科就诊的T1DM患儿215例,年龄≤14岁,均佩戴FGMS采集血糖数据,分析HbA1c、病程和葡萄糖扫描频率与血糖波动的相关性;根据患儿病程、HbA1c、葡萄糖扫描频率及胰岛素注射方式等因素进行分组比较。结果：HbA1c、病程与平均血糖、血糖标准差、平均血糖波动幅度(mean amplitude of glucose excu...     

误诊为低度恶性纤维组织细胞瘤的假肌源性血管内皮瘤1例并文献复习

假肌源性血管内皮瘤(pseudomyogenic hemangioendothelioma,PHE)是一种十分罕见的血管源性肿瘤,组织学上肿瘤性血管和内皮分化的形态特征皆不明显,易与上皮样肉瘤、上皮样血管内皮细胞瘤或肌源性肿瘤相混淆。PHE好发于青年男性,多见于四肢,典型表现为单个肢体多个中心侵犯,可累及皮肤及皮下组织各层,常伴有显著的疼痛。PHE组织病理特点为肿瘤呈浸润性生长,肿瘤细胞主要由疏松的呈束状或片状分布的梭形细胞组成,形态上可出现横纹肌母细胞样或上皮样细胞,可伴有炎症细胞浸润,以中性粒细胞多见,核异型及核分裂像少见。肿瘤细胞常阳性表达细胞角蛋白(cytokeratin,CK)、ETS相关基因(ETS-related gene,ERG)、Friend白血病病毒整合基因(Friend leukemia virus integration 1,FLI1)和整合酶相互作用分子1(integrase interactor 1,INI1),部分患者阳性表达CD31。1例青年女性因发现皮下肿块伴剧烈疼痛就诊,先后被误诊为带状疱疹、低度恶性纤维组织细胞瘤和上皮样血管内皮细胞瘤。本文结合相关...