Polymeric micro/nanoparticles: Particle design and potential vaccine delivery applications

Particle based adjuvant showed promising signs on delivering antigen to immune cells and acting as stimulators to elicit preventive or therapeutic response. Nevertheless, the wide size distribution of available polymeric particles has so far obscured the immunostimulative effects of particle adjuvant, and compromised the progress in pharmacological researches. To conquer this hurdle, our research group has carried out a series of researches regarding the particulate vaccine, by taking advantage of the successful fabrication of polymeric particles with uniform size. In this review, we highlight the insight and practical progress focused on the effects of physiochemical property (e.g. particle size, charge, hydrophobicity, surface chemical group, and particle shape) and antigen loading mode on the resultant biological/immunological outcome. The underlying mechanisms of how the particles-based vaccine functioned in the immune system are also discussed. Based on the knowledge, particles with high antigen payload and optimized attributes could be designed for expected adjuvant purpose, leading to the development of high efficient vaccine candidates.     

原发性高血压患者血压变异性与尿微量白蛋白/尿肌酐比值研究

目的：探讨原发性高血压患者血压变异性（BPV）与尿微量白蛋白/尿肌酐的关系。方法：103例符合入选标准的原发性高血压患者作为高血压组,并选96例健康体检者作为对照组,予24h监测动态血压、血压变异性及尿微量白蛋白,比较两组血压变异性与尿微量白蛋白/尿肌酐的关系。结果：各组患者在年龄、性别、吸烟史、总胆固醇、甘油三酯、空腹血糖以及体重指数等指标方面比较无差异性(P>0.05),高血压组患者昼间SBPV、夜间SBPV和24h SBPV均显著高于对照组(P<0.01);高血压组尿微量白蛋白、尿微量白蛋白/尿肌酐比值显著高于对照组(P<0.05)。结论：血压变异程度与尿微量白蛋白/尿肌酐具有相关性,可预测高血压早期的肾功能损害。     

紫草萘醌色素微乳液抑制肝癌细胞增殖的实验研究

目的观察紫草萘醌醇提物对肝癌细胞体内外增殖的影响。方法紫草萘醌醇提取物制备成微乳液(LE);加入人肝癌细胞系、人胚肾细胞系和小鼠成纤维细胞系的体外培养,MTT法检测细胞增殖;小鼠皮下接种肝癌细胞制作荷瘤模型,分别应用LE或5-FU,观察其生活状态、生存时间以及瘤重等指标。结果体外共育48~72h,LE抑制人肝癌细胞系的增殖;这种作用具有浓度依赖特点,而且相同浓度下不影响正常传代细胞的生长。体内应用可明显抑制移植小鼠肝癌的生长,延长荷瘤小鼠生存期;有效剂量2.5~10mg·kg-1·d-1。应用LE还可提高受者小鼠的生活质量。结论无论在体外或体内,LE对肿瘤细胞的增殖都表现量-效依赖的抑制作用。     

硝酸甘油泵入治疗视网膜中央动脉阻塞的临床观察

目的研究硝酸甘油泵入治疗视网膜中央动脉阻塞(CRAO)的有效性。方法32例(32眼)确诊为视网膜中央动脉阻塞患者,随机分为微泵组及对照组,每组16例(16眼)。对照组患者给予舌下含服硝酸甘油片联合常规治疗,微泵组患者给予静脉泵入硝酸甘油联合常规治疗。比较两组患者治疗后最佳矫正视力、视网膜水肿发生情况及治疗前后臂-视网膜循环时间。结果治疗后,微泵组患者最佳矫正视力为(0.35±0.11),对照组患者最佳矫正视力为(0.16±0.07),微泵组患者治疗后最佳矫正视力优于对照组,差异具有统计学意义(P<0.05)。治疗后,微泵组患者的视网膜水肿发生率为31.25%(5/16),明显低于对照组的68.75%(11/16),差异具有统计学意义(P<0.05)。微泵组患者治疗前臂-视网膜循环时间为(38.7±2.4)s,治疗1周后臂-视网膜循环时间为(20.4±2.3)s;对照组患者治疗前臂-视网膜循环时间为(36.9±3.5)s,治疗1周后臂-视网膜循环时间为(29.3±3.1)s;两组患者治疗前臂-视网膜循环时间比较,差异无统计学意义(P>0.05);治疗1周后,两组患者的臂-视网膜循环时间均短于治疗前,且微泵组短于对照组,差异具有统计学意义(P<0.05)。结论硝酸甘油泵入治疗视网膜中央动脉阻塞效果显著,可有提高患者的视力,促进视网膜血液循环的恢复。     

Liver steatosis assessment: Correlations among pathology,radiology, clinical data and automated image analysis software

Quantitating hepatic steatosis is important in many liver diseases and liver transplantation. Since steatosis estimation by pathologists has inherent intra- and inter-observer variability, we compared and contrasted computerized techniques with magnetic resonance imaging measurements, pathologist visual scoring, and clinical parameters. Computerized methods applied to whole slide images included a commercial positive pixel count algorithm and a custom algorithm programmed at our institution. For all liver samples (n = 59), including pediatric, adult, frozen section, and permanent specimens, statistically significant correlations were observed between pathology, radiology, and each image analysis modality (r = 0.75–0.97, p < 0.0001), with the strongest correlations in the pediatric cohort. Statistically significant relationships were observed between each method and with body mass index (r = 0.37–0.56, p from <0.0001 to <0.05) and with albumin (r = 0.55–0.64, p < 0.05) but not with alanine aminotransferase or aspartate aminotransferase. Although pathologist assessments correlated (r = 0.64–0.86, 0.92–0.97, and 0.78–0.91 for microvesicular, macrovesicular, and overall steatosis, respectively), the absolute values of hepatic steatosis visual assessment were susceptible to intra- and inter-observer variability, particularly for microvesicular steatosis. Image analysis, pathologist assessments, radiology measurements, and several clinical parameters all showed correlations in this study, providing evidence for the utility of each method in different clinical and research settings.     

不同相主牙胶尖对根尖区三维封闭的Micro CT观察

目的 观察α相与β相主牙胶尖在热垂直加压充填法中对根尖区的三维封闭作用.方法 实验筛选出根尖区4mm具有侧支根管或根尖分歧的下颌第一前磨牙20颗,以镍钛根管锉ProtaPer冠向下法预备至F3,将20例样本随机分为2组,分别采用α相牙胶与β相牙胶,以热垂直加压根管充填技术进行根管充填.充填完成前、后采用微计算机断层扫描技术对根尖区4mm容积进行扫描及三维重建,计算根尖区4mm充填程度即充填后容积与充填前容积之比,观察2种不同相的主牙胶尖对根尖区的封闭效果.结果 2种牙胶的根尖区充填程度均在81％以上,α相牙胶组在根尖区的充填程度与β相牙胶组差异无统计学意义.结论 α相牙胶组与β相牙胶组均对根尖区有良好的三维封闭效果,二者无显著性差异.     

微型金属螺钉治疗骨性锤状指的临床体会

目的 探讨微型金属螺钉治疗骨性锤状指畸形的疗效。方法 12例骨性锤状指畸形患者,采用手指背侧“S”形切口显露骨折断端,应用微型金属螺钉固定末节指骨骨折块。术后以低温塑料夹板行单指固定,4周后去除外固定并开始循序渐进的功能锻炼,早期练习程度以患指轻度肿胀为止,晚期根据X线片显示的骨折愈合情况予以加强,术后随访时采用Dargan功能评定标准评定治疗效果。结果 12例全部获得随访,切口均一期愈合,未出现伤口感染,关节无明显疼痛,通过4～20个月的随访,治疗效果优良率为91.7%。结论 微型金属螺钉治疗骨性锤状指的操作方法简便易行,术后患指可以早期活动,避免了关节僵直及皮肤感染等并发症,功能恢复效果肯定,值得推广。     

Topographical variations in articular cartilage and subchondral bone of the normal rat knee are age-related

In osteoarthritis animal models the rat knee is one of the most frequently investigated joint. However, it is unknown whether topographical variations in articular cartilage and subchondral bone of the normal rat knee exist and how they are linked or influenced by growth and maturation. Detailed knowledge is needed in order to allow interpretation and facilitate comparability of published osteoarthritis studies. For the first time, the present study maps topographical variations in cartilage thickness, cartilage compressive properties and subchondral bone microarchitecture between the medial and lateral tibial compartment of normal growing rat knees (7 vs. 13 weeks). Thickness and compressive properties (aggregate modulus) of cartilage were determined and the subchondral bone was analyzed by micro-computed tomography. We found that articular cartilage thickness is initially homogenous in both compartments, but then differentiates during growth and maturation resulting in greater cartilage thickness in the medial compartment in the 13-week-old animals. Cartilage compressive properties did not vary between the two sites independently of age. In both age-groups, subchondral plate thickness as well as trabecular bone volume ratio and trabecular thickness were greater in the medial compartment. While a high porosity of subchondral bone plate with a high topographical variation (medial/lateral) could be observed in the 7-week-old animals, the porosity was reduced and was accompanied by a reversion in topographical variation when reaching maturity. Our findings highlight that there is a considerable topographical variation in articular cartilage and subchondral bone within the normal rat knee in relation to the developmental status.