目的 探讨抗增殖蛋白2（PHB2）脓毒症心肌损伤线粒体功能的调控机制。方法 体外培养大鼠心肌细胞株（H9C2）,分为对照组、脂多糖（LPS）组、LPS+PHB2 siRNA（si-PHB2）组。检测氧化应激指标细胞内丙二醛（MDA）水平、荧光探针检测细胞内活性氧（ROS）水平;线粒体指标：三磷酸腺苷（ATP）水平、线粒体膜电位、线粒体电镜、线粒体半定量评分;免疫印迹法检测PHB2、PTEN诱导激酶1（PTNKI）、帕金蛋白（Parkin）、线粒体转录因子（TFAM）的表达。结果 LPS刺激后MDA水平和ROS水平升高、ATP水平低,LPS+si-PHB2组MDA（6.21±0.39 vs 3.59±0.33, P<0.05）、细胞内的ROS（15 131.37±88.72 vs 8 628.67±71.95, P<0.05）的水平较LPS组升高,ATP（3.46±0.34 vs 4.52±0.25, P<0.05）和线粒体膜电位水平（0.33±0.04 vs 0.55±0.09, P<0.05）进一步降低;电镜观察显示与正常组相比,LPS组、LPS+si-PHB2组出现不同程度线粒体损伤,线粒体损伤半定量评分显示LPS+si-PHB2组的损伤较LPS组更为明显（1.42±0.10 vs 0.81±0.04, P<0.05）; 免疫印迹法结果显示LPS处理后PHB2、PINK1、Parkin 表达上调,TFAM表达下调,LPS+si-PHB2组的线粒体自噬相关蛋白PINK1（1.33±0.06 vs 1.79±0.21, P<0.05）、Parkin（1.43±0.08 vs 1.86±0.09, P<0.05）和线粒体生物发生关键蛋白TFAM（0.29±0.01 vs 0.74±0.06, P<0.05）表达均较LPS组降低。结论 LPS可促进大鼠心肌细胞PHB2表达,si-PHB2干扰后线粒体自噬蛋白和生物发生蛋白表达抑制,心肌细胞氧化应激损害和线粒体功能障碍加重,提示PHB2表达上调可能恢复线粒体稳态改善脓毒症心肌损伤的线粒体功能。
Objective To explore the regulatory mechanism of septic myocardial injury by prohibitin 2（PHB2）. Methods Rat myocardial cell lines（H9C2）were cultured in vitro and divided into control group,LPS group,LPS + PHB2 siRNA（si-PHB2） group. The indicators for detecting oxidative stress include the levels of intracellular malondialdehyde（MDA）and reactive oxygen species（ROS）. The indicators for mitochondrial detection include adenosine triphosphate（ATP）levels,mitochondrial membrane potential,mitochondrial electron microscopy,and semi-quantitative mitochondrial scoring. Western blotting was used to detect the expression of PHB2,PTEN induced putative kinase（PINK1）,Parkin,mitochondrial transcription factor A（TFAM）. Results After LPS stimulation,MDA level and intracellular ROS level increased,ATP level decreased. Compared with LPS group,MDA（6. 21±0. 39 vs 3. 59±0. 33, P<0. 05）level and intracellular ROS level（15 131. 37±88. 72 vs 8 628. 67±71. 95, P<0. 05）in LPS + si-PHB2 group increased significantly,while ATP（3. 46±0. 34 vs 4. 52±0. 25, P<0. 05）and MMP（0. 33±0. 04 vs 0. 55±0. 09, P<0. 05）level further decreased. Compared with the normal group,the structure of mitochondria in LPS group and LPS + si-PHB2 group was damaged in different degree. The semi-quantitative score of mitochondrial damage showed that the damage in LPS + si-PHB2 group was more obvious than that in LPS group（1. 42±0. 10 vs 0. 81±0. 04, P<0. 05）. Western blotting showed that the expression of PHB2,PINK1 and Parkin were up-regulated and the expression of TFAM was down-regulated after LPS treatment,mitohagy-related proteins PINK1（1. 33±0. 06 vs 1. 79±0. 21, P<0. 05）,Parkin（1. 43±0. 08 vs 1. 86±0. 09, P<0. 05）and mitochondrial biogenetic protein TFAM（0. 29±0. 01 vs 0. 74±0. 06, P<0. 05）in LPS+si-PHB2 group were lower than those in LPS group. Conclusions LPS can promote the expression of PHB2 in rat cardiomyocytes. After interfering with PHB2 expression,we found that mitochondrial autophagy and biogenesis are inhibited,and mitochondrial dysfunction,oxidative stress exacerbated,suggesting that the up-regulation of PHB2 expression may restore mitochondrial homeostasis and improve mitochondrial function in septic myocardial injury.
与正常组织细胞微环境相比,肿瘤微环境具有一定的异质性,包括偏酸性、氧化还原状态失衡、存在高浓度活性氧以及酶过量表达等。根据以上肿瘤微环境特点,可设计出一系列通过各种特殊微环境响应型连接臂相连的小分子或聚合物前药纳米粒。其中,多柔比星阿霉素作为一类最常见的广谱抗肿瘤药物在治疗肿瘤的过程中发挥重要作用。文章探讨了在肿瘤微环境特异性的生理状态下针对不同微环境所设计的多柔比星前药及其释放特性等,归纳总结了肿瘤微环境响应型多柔比星前药的研究进展。
Compared with normal tissue cell microenvironment, there is some differences in tumor microenvironment, such as partial acidity, imbalance of redox state, high concentration of reactive oxygen species and cathepsin. According to the above characteristics of tumor microenvironment, a series of small molecule or polymer prodrug nanoparticles connected by various special microenvironment responsive structures can be designed. Doxorubicin, as one of the most common broad-spectrum antitumor drugs, plays an important role in the treatment of tumors. This review discusses the doxorubicin prodrug designed for different tumor microenvironments under the physiological state of tumor microenvironment specificity and their release characteristics, and summarizes the research progress of tumor microenvironment-responsive doxorubicin prodrug.
随着糖尿病患者的增加,因肺炎住院的糖尿病患者数也呈现出明显上升趋势。由于糖代谢紊乱及机体免疫功能下降等因素,细菌在高血糖的机体环境中快速繁殖并分泌大量毒素,增加了抗菌药物使用的时间跨度和细菌清除难度,对患者预后造成了极大的威胁。文章主要对糖尿病合并细菌性肺炎患者的病原学特征、耐药情况及药物治疗等进行阐述,旨在进一步为临床预防和治疗提供参考依据。
With the increasing incidence in diabetes, the number of hospitalized diabetes patients with pneumonia is also increasing. Due to factors such as glucose metabolism disorders and decreased immune function in the body, bacteria rapidly multiply and secrete a large amount of toxins in the hyperglycemic environment,increasing the duration of antibiotic use and the difficulty of bacterial clearance, posing a great threat to patient prognosis. This article mainly elaborates on the pathogenic characteristics, drug resistance, and drug treatment of diabetes patients with bacterial pneumonia, aiming to provide reference for the clinical prevention and treatment.
儿童孤立性直肠溃疡综合征（SRUS）是一种较为罕见的慢性直肠疾病,儿童发病率低且缺乏明确统计学数据。该病主要表现为便血、排黏液便和排便不尽感,临床诊断较为困难,常易误诊为其他疾病。其发病机制尚不明确,可能与排便习惯异常、直肠黏膜异常、血管异常以及遗传易感性等多种因素有关,其中 CHEK2 基因的 p.H371Y 突变可能在发病机制中起关键作用。诊断需综合病史、体格检查以及排粪造影、超声内镜、肠镜检查与组织病理活检等多种辅助检查手段。治疗上目前尚无统一指南,主要包括改善饮食和排便习惯、生物反馈治疗、药物治疗、内镜下治疗和外科手术治疗等,但总体治疗难度较大且复发率较高。本文对儿童 SRUS 的流行病学、发病机制、临床表现、诊断和治疗等方面的研究进展进行综述,旨在提高临床医师对该病的诊疗水平,为未来进一步的研究提供参考依据。
Solitary rectal ulcer syndrome（SRUS）in children is a chronic and benign disease of the rectum characterized by ulcers. The clinical incidence of SRUS in children is not high, but it is prone to misdiagnose and miss diagnosis,which can delay the optimal treatment opportunity. This article reviews the research progress on the epidemiology,pathogenesis, clinical manifestations, diagnosis and treatment of SRUS in children, aiming to improve the diagnostic and therapeutic level of clinicians.
目的 初步探究胆管结扎诱导的梗阻性胆汁淤积对大鼠肝细胞的影响。方法 10只Lewis大鼠随机分为对照组和胆汁淤积组,每组各5只,胆汁淤积组采用胆管结扎2周诱导梗阻性胆汁淤积大鼠模型。苏木精-伊红染色和苯胺蓝染色比较组织病理变化,使用生化分析比较两组小鼠肝功能情况。采用改良的两步胶原酶灌注分离原代肝细胞,通过RT-qPCR检测两组小鼠肝细胞标志基因、细胞增殖标志基因以及胆管细胞标志基因的表达情况。结果 与对照组相比,胆汁淤积组肝脏表现为明显的肝组织紊乱和纤维胶原蛋白沉积以及肝功能的损害。胆汁淤积组较对照组的原代肝细胞更高表达细胞增殖标志基因：细胞增殖标志物（Ki67）基因,叉头盒M1蛋白（Foxm1）基因,增殖细胞核抗原（Pcna）基因和肝细胞生长因子（HGF）基因（P<0.05）;胆汁淤积组的原代肝细胞表达更低水平的肝细胞标志基因：白蛋白（Alb）基因,多药耐药相关蛋白2（Mrp2）基因,胆盐输出泵（Bsep）基因和肝细胞连环蛋白1（Catenin1）基因（P<0.05）,同时表达更高水平的胆管细胞标志基因：细胞角蛋白7（Ck7）基因,细胞角蛋白 19（Ck19）基因,胆管细胞多药耐药性蛋白1（Mdr1）基因和胆管细胞囊性纤维化跨膜传导调节因子（Cftr）基因（P<0.05）以及肝祖细胞标志基因：上皮细胞黏附分子（Epcam）基因和Y染色体性别决定区-盒转录因子9（Sox9）基因（P<0.05）。结论 胆汁淤积可诱导肝细胞向胆管细胞特性转化的可塑性。
Objective To explore the effect of bile duct ligation induced obstructive cholestasis on rat hepatocytes. Methods Ten Lewis rats were randomly divided into control group and cholestasis group, and the cholestasis was induced by bile duct ligation for 2 weeks. The histopathological changes were compared by H&E and aniline blue staining and the liver function was compared by biochemical analysis. Primary hepatocytes were isolated by modified two-step collagenase perfusion, and the expressions of hepatocyte marker genes, cell proliferation marker genes and cholangiocyte marker genes were detected by RT-qPCR. Results Compared with the control group,the liver of the cholestatic group showed obvious disordered histopathology, deposition of fibrous collagen and impaired liver function. Compared with the control group, the primary hepatocytes in the cholestasis group expressed higher cell proliferation-related genes（Ki67,Foxm1,Pcna and HGF）（P<0. 05）. Primary hepatocytes in the cholestasis group expressed lower levels of hepatocyte marker genes（Alb,Mrp2,Bsep and Catenin1）（P<0. 05）,and higher levels of cholangiocyte marker genes（Ck7,Ck19,Mdr1 and Cftr）（P<0. 05）and higher levels of the hepatic progenitor cell marker genes（Epcam and Sox9）（P<0. 05）. Conclusions Cholestasis induces rat hepatocyte plasticity in the transformation into bile duct properties.
股骨转子间骨折是最常见的髋部骨折,内固定手术为其目前治疗的首选方式。头颈钉位置是评估手术效果和判断治疗预后的重要因素,合适的置钉位置有利于稳定骨折、加速康复以及改善预后。目前头颈钉位置最经典的评估方式为尖顶距（TAD）,但TAD至今仍存在较多争议。近年来提出的轴刀角、尖颈距离比、偏心距（ED）以及标准化TAD（STAD）为临床实践拓展了新视野。文章通过对上述头颈钉位置的评估方法及局限性进行文献综述,旨在为临床手术置钉时提供相应的参考。ED和STAD的提出,为未来人工智能评估头颈钉位置提供了可能。
Femoral intertrochanteric fracture is one of the most common hip fractures, and the internal fixation is the preferred treatment. The position of cephalic fixator is an important factor to evaluate the effect of operation and the prognosis of treatment. Tip-apex-distance（TAD）is the most classical method to evaluate the position of cephalic fixator, but it is still controversial. In recent years, the axis-blade angle,tip-neck distance ratio, eccentric distance（ED）and standardized TAD（STAD）have been proposed,though with limitations, they also provide a new perspective for clinical practice. In this study, we reviewed the literature on the evaluation of the position of cephalic fixator in order to provide the corresponding references and guidance for the clinical operation of internal fixation. Both STAD and ED may be the theoretical possibility of artificial intelligence evaluation of the position of cephalic fixator in the future.
目的 探讨基于迷你临床演练评估（Mini-CEX）的可视化思维导图联合案例教学在全科住院医师规范化培训中的应用效果。方法 选取参加全科住院医师规范化培训的52例学员并分为试验组（n=26）和对照组（n=26）。对照组采取以案例讲授为主的传统教学模式，试验组采取基于Mini-CEX的可视化思维导图联合案例教学模式。对比两组Mini-CEX评分、考核成绩及教学满意度。结果 试验组Mini-CEX测评的问诊技巧、体格检查、临床判断、诊治能力、技能操作及整体表现得分均高于对照组（P＜0.05）。试验组理论知识［（86.89±4.75）分 vs （82.96±4.87分）］、专业技能［（84.20±3.46）分 vs （70.18±4.93）分］及病历书写成绩［（80.64±5.26）分 vs （75.58±5.94）分］均高于对照组（t分别为2.678、13.685、2.764，P分别为0.009、＜0.001、0.007）。试验组住院医师教学满意度高于对照组（P＜0.05）。结论 基于Mini-CEX的可视化思维导图联合案例教学模式用于全科住院医师规范化培训，有助于提高教学效果及教学满意度。
Objective To evaluate the effect of visual mind mapping combined with case teaching based on mini-clinical evaluation exercise（Mini-CEX）for standardized training of general practitioners．Methods A total of 52 students who participated the standardized training of general practitioners were selected and divided into an experimental group（n=26）and a control group（n=26）．The control group adopted the traditional teaching mode based on case teaching and the experimental group adopted the visual mind mapping combined with case teaching based on Mini-CEX．The Mini-CEX score，assessment results and teaching satisfaction of two groups were compared．Results The interrogation skills，physical examination，clinical judgment，diagnosis and treatment ability，skill operation and overall performance of Mini-CEX in experimental group were higher than control group（P＜0.05）．Theoretical knowledge score（［86.89±4.75］ vs ［82.96±4.87］），professional skills score（［84.20±3.46］ vs［70.18±4.93］）and medical record writing score（［80.64±5.26］ vs ［75.58±5.94］）of experimental groups were higher than control group（t=2.678，13.685，2.764，P=0.009，＜0.001，0.007）．The teaching satisfaction of residents in experimental group was higher than control group（P＜0.05）．Conclusions The visual mind mapping combined with case teaching based on Mini-CEX for standardized training of general practitioners is helpful to improve teaching effect and teaching satisfaction．
