Experiment on the feasibility of using modified gelatin nanoparticles as insulin pulmonary administration system for diabetes therapy

Polymeric nanoparticles are widely used as targeted carriers for biomacromolecules. In this paper, modified gelatin nanoparticles were prepared and their feasibility as insulin pulmonary administration system was investigated. D: ,L: -glyceraldehyde and poloxamer 188 were used for gelatin nanoparticle preparation. Novel water-in-water emulsion technique was used to prepare insulin-loaded nanoparticles. Morphological examination of insulin-loaded nanoparticles was carried out using scanning electron microscopy (SEM). Intratracheal instillation of insulin-loaded nanoparticles was performed to evaluate animal hypoglycemic effect. With fluorescence labeling of insulin, alveolar deposition and absorption of insulin-loaded nanoparticles were investigated. Histological changes in the lung were also observed to evaluate the safety. From the micromorphology observation, insulin-loaded nanoparticles under gelatin-poloxamer 188 ratio at 1:1 showed smooth and uniform surface, with average particle size 250 nm and Zeta potential -21.1 mV. From animal experiment, insulin-loaded nanoparticles under gelatin-poloxamer 188 ratio at 1:1 promoted insulin pulmonary absorption effectively and showed good relative pharmacological bioavailability. Proved by alveolar deposition result, FITC-insulin-loaded nanoparticle group was characterized by an acute and rapid hypoglycemic effect. In addition, nanoparticles could guarantee the safety of lung by reducing insulin deposition in lung. A transient weak inflammatory response was observed at 1 day after administration. With good physical characterization, high bioavailability, fast and stable hypoglycemic effect, insulin-loaded nanoparticles might be developed as a novel insulin pulmonary system for diabetes therapy.     

复发性椎动脉夹层1例并文献回顾

正1病例介绍1.1首次发病患者男性,29岁,因"突发头痛2天"于2018年12月27日到南方医科大学深圳医院就诊。患者于入院2 d前休息时无明显诱因突发头痛,右侧枕部为主,呈持续性胀痛,阵发性加重,严重时自觉难以忍受。本院门诊头颅CT提示:右侧小脑半球大片状低密度影,拟"头痛原因待查"收入院。既往史:否认"高血压、糖尿病、冠心病"等慢性病史。     

白血病患儿外周血T细胞亚群检测的临床意义

本研究观察急性白血病患儿外周血T细胞在不同病程阶段的变化,了解白血病患儿的免疫状况。应用流式细胞术检测42例急性白血病患儿,另选取50例正常儿童（对照组）外周血CD4^＋、CD8^＋、CD4^＋/CD8^＋比值、CD3^＋以及NK细胞在不同病程阶段的动态变化。结果表明：急性淋巴细胞白血病（ALL）与急性髓系白血病（AML）初诊患儿的CD3^＋,CD4^＋、CD8^＋细胞比例和CD4^＋/CD8^＋比值均值显著低于对照组（P〈0.05）,初诊时急性白血病患儿的NK细胞值显著低于对照组（P〈0.05）;ALL与AML患儿完全缓解期（CR）3、6和12个月时的NK细胞水平虽然缓慢上升,但与对照组比较仍具有统计学差异（P〈0.05）。结论：急性白血病患儿在病情发生以及治疗过程中细胞免疫功能存在紊乱,经治疗获CR后患儿病情好转,细胞免疫渐渐恢复,但恢复速率慢,该结果为患儿后续使用免疫调节剂治疗提供依据。     

10μg重组乙型肝炎疫苗的安全性研究

目的评价10μg/剂重组乙型肝炎疫苗(酿酒酵母HepB-SC)用于2~15岁健康人群接种的安全性。方法将1 716例2~15岁的健康人群按照1∶1随机分为试验组及对照组,试验组(857例)和对照组(859例)分别接种10μg/剂、5μg/剂HepB-SC。接种后对受试者进行安全性观察和随访。结果接种HepB-SC后28d内,试验组和对照组不良反应发生率分别为27.30%、25.15%,差异无统计学意义(P0.05),且8种全身不良反应症状发生率差异也无统计学意义(P0.05)。出现的7种局部不良反应症状中,仅疼痛和硬结的发生率试验组高于对照组(疼痛,8.98%∶6.05%;硬结,8.98%∶5.70%,P0.05),但出现的硬结和疼痛症状主要为无需处理的1级反应。两组受试者均未发生严重/危及生命的不良反应或出现过敏反应。结论 2~15岁人群接种10μg/剂HepB-SC具有良好的安全性。     

真性红细胞增多症和原发性血小板增多症患者中JAK2V617F突变负荷与临床特征相关性

为分析真性红细胞增多症（polycythemiavera,PV）和原发性血小板增多症（essentialthrombocythemia,ET）患者JAK2V617F突变负荷和患者临床特征的相关性,利用荧光实时定量PCR方法检测90例初诊骨髓增殖性疾病（myeloproliferativedisorder,MPD）患者（包括47例PV和43例ET）外周血标本中JAK2V617F突变基因负荷,统计分析JAK2V617F负荷和患者外周血中血红蛋白、红细胞压积、白细胞计数和血小板计数的相关性。结果表明：突变阳性的ET患者中JAK2V617F负荷（0．209±0．192）较PV患者中（0．441±0．270）低（P=0．028）。在PV和ET患者中JAK2V617F负荷和患者外周血中血红蛋白（PV：R=0．518,P〈0．001;ET：R：0．528,P=0．005）、红细胞压积（PV：R：0．510,P〈0．001;ET：R=0．524,P=0．005）和白细胞计数（PV：R=0．584,P=〈0．001;ET：R：0．471,P=0．013）都呈正相关。在PV患者中,JAK2V617F突变负荷和血小板计数呈负相关（R=-0．354,P=0．020）;但在ET患者中,JAK2V617F负荷和血小板计数无明显相关性（R=0．233,P=0．242）。结论：在PV患者和ET患者中,JAK2V617F突变负荷和患者外周血中血红蛋白、红细胞压积和白细胞计数都呈正相关。在PV患者中,JAK2V617F负荷和血小板计数呈负相关,而在ET患者中JAK2V617F负荷和血小板计数无明显相关性。     

89例成人融合基因Aml1／Eto阳性急性髓系白血病长期生存分析

本研究探讨影响成人aml1／eto阳性急性髓系白血病患者长期生存的顸后因素。回顾性分析2004年1月至2008年7月本院89例成人aml1／eto阳性急性髓系白血病患者的临床资料,应用Log—Rank检验和Cox回归模型对患者的性别、年龄、初诊时白细胞计数、髓外白血病、中枢神经系统白血病、免疫表型、染色体、诱导缓解方案、诱导缓解疗程数、获得缓解时间、aml1／eto融合基因表达和异基因造血干细胞移植进行了单因素和多因素综合分析。结果表明：89例患者1—42个月随访（中位24个月）的5年预计总体生存率（OS）为（50．0±2．3）％,5年预计无复发生存率（RFS）为（47．0±1．9）％。单因素分析显示,初诊时白细胞计数、髓外白血病、中枢神经系统白血病、表达CD56、诱导缓解疗程数、获得缓解时间、aml1／eto融合基因表达、接受异基因造血干细胞移植均为影响中国成人aml1／eto阳性急性髓系白血病患者长期生存的主要因素。多因素分析显示,初诊时白细胞计数、中枢神经系统白血病、CD56表达、获得缓解所需时间、amll／eto融合基因变化以及接受造血干细胞移植均是影响aml1／eto阳性急性髓系白血病患者长期生存的重要的独立因素。结论：成人aml1／eto阳性急性髓系白血病具有不同于其他人群的特性,其预后相对较差,对于具有不良预后因素的aml1／eto阳性AML成年患者应该建议接受造血干细胞移植。     

卒中后抑郁的评估进展

卒中后抑郁发病率较高,准确的评估有利于临床诊疗。目前,对卒中后抑郁的评估多依赖 量表。对于不影响语言表达的卒中患者,汉密尔顿抑郁量表、卒中后抑郁分级量表和蒙哥马利抑郁 量表应用最为广泛,且其信度和效度均较高。对于失语患者的卒中后抑郁评价量表虽然开发的比较 多,但临床应用相对较局限,其中卒中失语抑郁问卷和失语抑郁评估量表应用相对较多。目前针对卒 中后抑郁评估量表的应用人群、评估指标有所差异,在应用这些量表时,相比原发疾病,评估者更重 视抑郁情绪的问题,这可能会造成患者的不配合和排斥,从而影响量表评价的准确性,这些局限性 有待进一步研究解决。     

造血细胞因子家族因子的空间结构比较

通过对造血细胞因子家族的立体结构的比较,尤其是对核心结构即对由4个α-螺旋形成的左手超螺旋结构的长度、走向、RMS值及疏水性等的比较,以及对loop区的结构和二硫键的分析,说明在核心结构中,4个α-螺旋构成了up-up-down-down的结构特征在家族内具有高度保守性,指出4螺旋结构中心由疏水氨基酸构成的疏水核心及分子内二硫键对稳定结构及稳定结合位点的重要性。另外,分析了分子中与不同受体结合的两个位点,指出了位点上的残基,并说明了位点Ⅰ是与特异性受体结合,位点Ⅱ是与共同受体结合并转导信号。     

Expression of NOD2 and NLRP3 in the articular cartilage of a rabbit model of osteoarthritis established by arthrorisis using plaster cast北大核心

BACKGROUND: Nucleotide-binding oligomerization domain (NOD)-like receptor plays an important role against inflammatory responses caused by pathogens and non-pathogens, as well as in the initial stage of autoimmune response. Meanwhile, NOD2 and NOD-like receptor protein 3 (NLRP3) are the representative proteins of NOD-like receptor family. OBJECTIVE: To detect the expression of NOD2 and NLRP3 in a rabbit model of osteoarthritis. METHODS: Thirty New Zealand rabbits were randomly divided into six groups (n=5 per group), including five experimental groups (2, 4, 6, 8 and 10 weeks) and one control group. The model of osteoarthritis was established by fixing the left knee joints using plaster cast, and were sacrificed at postoperative 2, 4, 6, 8 and 10 weeks. The controls received no intervention, and were killed at 10 weeks postoperatively. The left distal femur articular cartilage was taken for safranin-fast green staining. The pathological changes were evaluated by Mankin’s scores, and the expression levels of NOD2 and NLRP3 were detected by immunohistochemistry. RESULTS AND CONCLUSION: The Mankin’s scores in the experimental groups were significantly higher than those in the control group (P < 0.01). Moreover, the scores in the experimental groups were significantly increased with time (P < 0.01). The expression levels of NOD2 and NLRP3 in the chondrocytes were also increased with time (P < 0.01). These results indicate that the expresison of NOD2 and NLRP3 in the cartilage cells is positively correlated with the pathological changes of osteoarthritis, which may be through promoting apoptosis in cartilage cells, thus accelerating the development of osteoarthritis. © 2018, Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.