颗粒软骨加α-氰基丙烯酸正丁酯胶结合3D打印技术辅助制作个性化耳支架

文题释义：α-氰基丙烯酸正丁酯：为组织胶水，临床上常用来作为组织粘连剂，这种黏合剂无毒、组织相容性好、粘连强度好，凝固后会形成一层带有网孔的生物膜，该网孔能通过组织液为软骨细胞提供营养物质，并不影响软骨细胞的存活。 颗粒软骨：常见于鼻整形中，取鼻中隔、鼻翼、耳郭或肋软骨，将其切成大小为0.5-1.5 mm颗粒状，用筋膜、脱细胞真皮或其他生物材料包裹后移植于填充区或不包裹直接进行移植填充。软骨材料是最接近真耳的支架材料。背景：传统耳再造手术中耳支架的制作容易导致再造耳失真，3D打印技术使个性化、高仿真的小耳再造成为可能。目的：探讨颗粒软骨加α-氰基丙烯酸正丁酯结合3D打印技术制作个性化耳支架的可行性。方法：根据耳畸形患者健侧耳制作患侧耳的3D耳支架阳模和阴模，将颗粒软骨用α-氰基丙烯酸正丁酯粘连放入阴模中，同时对比阳模微调，制成耳软骨支架后，将其植入新西兰大白兔背部，动态观察再造耳郭的形态，术后4，8，12周分批取出耳支架，组织学观察颗粒软骨间连接情况、软骨的存活状况等，免疫组化观察Ⅱ型胶原表达。动物实验获得湖南师范大学实验动物福利伦理审查委员会批准(批准号：201517)。结果与结论：①大体观察：与术前比较，术后4，8，12周的再造耳郭长度、宽度、高度无明显变化，质量明显增加(P < 0.05)；②组织学观察：颗粒软骨周围可见炎性细胞浸润，随着标本植入时间延长，炎性细胞逐渐减少，附着支架的筋膜中有较多血管生成；随着植入时间的延长，软骨膜内新生软骨细胞逐渐增多，体积逐渐增大，成熟软骨细胞逐渐增多；软骨碎片之间的α-氰基丙烯酸正丁酯未见明显分解，绝大部分软骨片之间仍被α-氰基丙烯酸正丁酯间隔，少部分软骨片之间有纤维连接形成，随着植入时间延长，软骨片之间的连接有增多的趋势；③免疫组化学观察：随着标本植入时间延长，Ⅱ型胶原表达逐渐增强；④结果表明：颗粒软骨加α-氰基丙烯酸正丁酯结合3D打印模具可以制作个性化耳支架。ORCID: 0000-0002-7481-0722(张帆) 中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程     

The capability of detecting small vessels beyond the conventional MRI sensitivity using iron‐based contrast agent enhanced susceptibility weighted imaging

Imaging brain microvasculature is important in cerebrovascular diseases. However, there is still a lack of non‐invasive, non‐radiation, and whole‐body imaging techniques to investigate them. The aim of this study is to develop an ultra‐small superparamagnetic iron oxide (USPIO) enhanced susceptibility weighted imaging (SWI) method for imaging micro‐vasculature in both animal (~10 μm in rat) and human brain. We hypothesized that the USPIO‐SWI technique could improve the detection sensitivity of the diameter of small subpixel vessels 10‐fold compared with conventional MRI methods. Computer simulations were first performed with a double‐cylinder digital model to investigate the theoretical basis for this hypothesis. The theoretical results were verified using in vitro phantom studies and in vivo rat MRI studies (n = 6) with corresponding ex vivo histological examinations. Additionally, in vivo human studies (n = 3) were carried out to demonstrate the translational power of the USPIO‐SWI method. By directly comparing the small vessel diameters of an in vivo rat using USPIO‐SWI with the small vessel diameters of the corresponding histological slide using laser scanning confocal microscopy, 13.3‐fold and 19.9‐fold increases in SWI apparent diameter were obtained with 5.6 mg Fe/kg and 16.8 mg Fe/kg ferumoxytol, respectively. The USPIO‐SWI method exhibited its excellent ability to detect small vessels down to about 10 μm diameter in rat brain. The in vivo human study unveiled hidden arterioles and venules and demonstrated its potential in clinical practice. Theoretical modeling simulations and in vitro phantom studies also confirmed a more than 10‐fold increase in the USPIO‐SWI apparent diameter compared with the actual small vessel diameter size. It is feasible to use SWI blooming effects induced by USPIO to detect small vessels (down to 10 μm in diameter for rat brain), well beyond the spatial resolution limit of conventional MRI methods. The USPIO‐SWI method demonstrates higher potential in cerebrovascular disease investigations.     

Differences between medical school and PGY1 learning outcomes: An explanation for new graduates not being “work ready”?

Abstract

Background: Widespread concerns about new medical graduates’ ‘work readiness’ may reflect, in part, differences in mandatory learning outcomes for medical students and new medical graduates.

Purpose: To examine differences between required medical student and PGY1 (first year resident) training program outcomes, and the nature and magnitude of these differences.

Method: Comparison, systematic identification and thematic analysis of differences between the graduate outcomes in the Australian Medical Council Standards for the Assessment and Accreditation of Primary Medical Programs and those in the New Zealand Curriculum Framework for Prevocational Training.

Results: The relationship between these outcome statements were categorized as: essentially similar; continuity; partial discontinuity; and complete discontinuity of learning trajectory. Areas requiring substantial new learning may reflect medical schools’ focus on individual student performance, and on learning and assessments based on single episodes of often uncomplicated illness. This contrasted with a post-graduate focus on integrated health care delivery by teams and management of complex illnesses over the whole patient care journey.

Conclusions: Characterizing these marked differences between pre-graduate and postgraduate standards, within a trajectory of learning, explains some of the difficulties in students’ preparation for work readiness. These could inform learning interventions to support new graduates’ professional development to ensure patient safety. Development and revision of accreditation standards should include formal review against the expectations of the preceding and succeeding phases of learning.     

红景天苷下调KRT17增加紫杉醇对卵巢癌细胞的化疗敏感性

[目的] 红景天苷是从景天科植物大株红景天的干燥根及根茎或干燥全草中提取的一种化合物，具有多种药理作用。研究旨在探讨红景天苷下调角蛋白家族成员17（KRT17）影响紫杉醇对卵巢癌细胞的化疗敏感性。[方法] 红景天苷、紫杉醇单独或联用处理SKOV-3细胞，将细胞随机分为4组：对照组、红景天苷单独处理组、紫杉醇单独处理组和联合处理组，Cell Counting Kit-8（CCK-8）法检测细胞毒性，5-乙炔基-2’-脱氧尿苷（EDU）检测细胞增殖，Hoechst 33258检测细胞凋亡。免疫荧光法检测自噬体形成情况，蛋白免疫印迹法检测KRT17和细胞自噬相关蛋白表达水平。[结果] 与对照组比较，红景天苷、紫杉醇单独处理组随浓度的升高，对SKOV-3细胞的毒性增强，细胞增殖数、P62蛋白表达降低，细胞凋亡率、LC3荧光斑点数、LC3-Ⅱ/LC3-I比值、Beclin1蛋白表达升高。且红景天苷与紫杉醇协同处理效果优于红景天苷、紫杉醇单独处理组，可能是红景天苷通过下调KRT17蛋白表达实现的。[结论] 红景天苷下调KRT17增加紫杉醇对卵巢癌细胞的化疗敏感性。     

中药治疗卒中后认知障碍疗效和安全性的系统评价

目的:评价中药治疗卒中后认知障碍(PSCI)的疗效与安全性。方法:计算机检索中国知网数据库,万方数据库,维普数据库,中国生物医学文献数据库,PubMed,The Cochrane library和ClinicalTrials.gov共7个数据库,纳入中药治疗PSCI的随机对照试验(RCT)。使用Cochrane偏倚风险评估工具对纳入研究的方法学质量进行评价,并对纳入研究进行描述性分析,应用RevMan 5.3软件进行Meta定量分析。结果:共纳入16项RCT,1296例受试者,干预组649例,对照组647例。研究结果显示中药联合西药组和中药组干预在改善PSCI患者蒙特利尔认知评估量表,简易精神状态检查量表,Barthel指数评定量表,日常生活能力量表,中国脑卒中临床神经功能缺损程度评分量表和美国国立卫生研究院卒中量表的评分上均优于西药组,且未见严重的不良反应。结论:中药在改善PSCI患者的认知功能水平方面具有潜在优势,对改善日常生活能力及神经功能缺损症状也有一定疗效,并未观察到严重不良事件。本文纳入研究的方法学质量不高,建议后续开展高质量的RCT来研究中药治疗PSCI的疗效和安全性,为该疾病的临床诊疗提供决策依据。     

GOLPH3蛋白在新疆哈萨克族食管鳞癌中的表达及其临床意义

目的:研究GOLPH3蛋白在新疆哈萨克族（哈族）食管鳞癌中的表达及其临床意义。方法:本次研究选取50例术前未经放化疗干预且手术切除的新疆哈族食管鳞癌组织及50例哈族癌旁相对正常食管组织作为研究对象，截止日期为2018年6月，应用免疫组织化学技术，检测GOLPH3蛋白在哈族食管鳞癌组织及癌旁组织的表达特点及情况。结果:GOLPH3蛋白在哈族食管鳞癌组织的表达率为70.0%，高于癌旁正常组织28.0%，差异具有统计学意义(P=0.001)；低分化组阳性表达率82.9%高于高分化组40.0%，差异具有统计学意义(P=0.02)；淋巴结转移组阳性表达率85.3%高无淋巴结转移组37.5%，差异具有统计学意义(P=0.01)；临床分期在Ⅲ-Ⅳ组阳性表达率83.3%，高于Ⅰ-Ⅱ组的50.0%，差异具有统计学意义(P=0.012)；男性组中GOLPH3蛋白的表达阳性率为64.7%，女性组为81.3%，差异无统计学意义(P=0.234)；高龄组（≥60岁）GOLPH3蛋白的表达阳性率79.2%，低龄组（＜60岁）为61.5%，差异无统计学意义(P=0.174)。结论:GOLPH3蛋白的表达可能与哈族食管鳞癌的分化、增殖和转移等过程有关。     

MicroRNA‐375‐3p enhances chemosensitivity to 5‐fluorouracil by targeting thymidylate synthase in colorectal cancer

Resistance to chemotherapy is a major challenge for the treatment of patients with colorectal cancer (CRC). Previous studies have found that microRNAs (miRNAs) play key roles in drug resistance; however, the role of miRNA‐373‐3p (miR‐375‐3p) in CRC remains unclear. The current study aimed to explore the potential function of miR‐375‐3p in 5‐fluorouracil (5‐FU) resistance. MicroRNA‐375‐3p was found to be widely downregulated in human CRC cell lines and tissues and to promote the sensitivity of CRC cells to 5‐FU by inducing colon cancer cell apoptosis and cycle arrest and by inhibiting cell growth, migration, and invasion in vitro. Thymidylate synthase (TYMS) was found to be a direct target of miR‐375‐3p, and TYMS knockdown exerted similar effects as miR‐375‐3p overexpression on the CRC cellular response to 5‐FU. Lipid‐coated calcium carbonate nanoparticles (NPs) were designed to cotransport 5‐FU and miR‐375‐3p into cells efficiently and rapidly and to release the drugs in a weakly acidic tumor microenvironment. The therapeutic effect of combined miR‐375 + 5‐FU/NPs was significantly higher than that of the individual treatments in mouse s.c. xenografts derived from HCT116 cells. Our results suggest that restoring miR‐375‐3p levels could be a future novel therapeutic strategy to enhance chemosensitivity to 5‐FU.