包埋NGF的壳聚糖-PLGA双壁微球制备及其相关性能研究

目的评估壳聚糖-聚乳酸-聚乙醇酸共聚物[poly(lactide-co-glycolide),PLGA]双壁微球在体外持续缓释具有生物活性的NGF的可行性。方法应用乳化-离子交联方法制备包埋NGF的、具有不同三聚磷酸钠(sodium tripolyphosphate,TPP)交联浓度[1%、3%、10%(W/V)]的壳聚糖-PLGA双壁微球,同时制备包埋NGF的PLGA微球。通过光镜、扫描电镜、激光共聚焦显微镜观察双壁微球的表面及内部形态,并行双壁微球的粒径分析和红外光谱分析。取包埋NGF的PLGA微球或1%、3%、10%TPP浓度交联的包埋NGF的壳聚糖-PLGA双壁微球(分别设为A、B、C、D组),于不同时间点行体外微球降解率测定、微球中NGF缓释率检测;以未包埋NGF的壳聚糖-PLGA双壁微球缓释液(设为A1组)作为对照,比较A1、B、C、D组体外微球缓释液中NGF的生物活性[以缓释液中具有阳性轴突延长反应的大鼠肾上腺嗜铬细胞瘤(PC12)细胞百分比表示]。结果包埋NGF的壳聚糖-PLGA双壁微球呈球形结构,具有相对粗糙的外表面;激光共聚焦显微镜观察示PLGA微球均匀分布于壳聚糖-PLGA双壁微球内;双壁微球的粒径范围为18.5~42.7μm;红外光谱分析结果说明双壁微球中壳聚糖的氨基与TPP中的磷酸基发生了静电反应。体外降解率测定显示,B、C、D组双壁微球降解速度明显快于A组,并随着TPP浓度的增加而逐渐减慢,培养各时间点各组间微球降解率比较差异均有统计学意义(P<0.05)。体外NGF缓释率测定显示,与A组PLGA微球相比,B、C、D组双壁微球以相对较慢的速度缓释NGF,且缓释速度随TPP浓度增加而减慢。除84 d外,各时间点B、C、D组间比较NGF总缓释率差异均有统计学意义(P<0.05)。体外NGF的生物活性评估显示,培养各时间点B、C、D组缓释液中具有阳性轴突延长反应的PC12细胞百分比均显著高于A1组(P<0.05)。培养7、28 d,B、C、D组间比较差异无统计学意义(P>0.05);56、84 d时,C、D组缓释液中具有阳性轴突延长反应的PC12细胞百分比显著高于B组(P<0.05),C、D组间差异无统计学意义(P>0.05)。结论包埋NGF的壳聚糖-PLGA双壁微球在周围神经损伤后的再生方面具有临床应用潜力。     

双平面截骨术治疗合并跖骨远端关节面角增大的重度■外翻

目的总结双平面截骨术治疗合并跖骨远端关节面角(distal metatarsal articular angle,DMAA)增大的重度[足母]外翻疗效。方法回顾性分析2014年6月-2017年12月收治并获完整随访的64例(94足)合并DMAA增大的重度[足母]外翻患者临床资料。患者均接受双平面截骨术(跖骨远端Reverdin截骨术+跖骨近端开放楔形截骨术)联合Akin截骨术及软组织手术。男10例(15足),女54例(79足);年龄26~66岁,平均44.5岁。单侧34例,双侧30例。参照美国矫形足踝协会(AOFAS)Maryland跖趾关节评分系统评分为(54.3±7.4)分,疼痛视觉模拟评分(VAS)为(6.0±2.0)分。比较手术前后AOFAS Maryland跖趾关节评分系统评分及VAS评分,以及[足母]外翻角(hallux valgus angle,HVA)、第1-2跖骨间角(first-second intermetatarsal angle,1-2IMA)、DMAA、第1跖骨长度(first metatarsal length,FML)。结果术后切口均Ⅰ期愈合。患者均获随访,随访时间12~15个月,平均13.2个月。4足发生并发症,其中[足母]僵硬、内侧切口边缘皮肤感觉麻木、转移性跖痛、第1跖骨头坏死各1足。术后1年AOFAS Maryland跖趾关节评分为(89.2±7.4)分,与术前比较差异有统计学意义(t=18.427,P=0.000);其中优78足、良12足、中3足、差1足,优良率为95.7%。VAS评分为(1.5±2.0)分,较术前明显改善(t=10.238,P=0.000)。X线片复查显示术后3个月截骨均达骨性愈合。术后6个月及1年HVA、1-2IMA、DMAA与术前比较,差异均有统计学意义(P<0.05);术后1年FML与术前比较,差异无统计学意义(t=0.136,P=0.863)。结论双平面截骨术可以显著改善合并DMAA增大的重度[足母]外翻患者临床症状以及影像学参数,术后并发症少。     

Internalization ofStaphylococcus aureusby cultured osteoblasts

Staphylococcus aureusis the most common cause of both acute and chronic osteomyelitis; however, the pathogenesis of osteomyelitis is poorly understood. We investigated the ability ofS. aureusto associate with chick osteoblasts in culture and have demonstrated internalization of bacteria by the osteoblasts. Two strains ofS. aureuswere examined that were ingested by osteoblasts to different extents, suggesting strain differences in uptake. Initial association ofS. aureusstrains with osteoblasts was independent of the presence of matrix collagen produced by the osteoblasts. Internalization of bacteria required live osteoblasts, but not liveS. aureus, indicating osteoblasts are active in ingesting the organisms. The bacteria were not killed by the osteoblasts, since viable bacteria were cultured several hours after ingestion.     

具有梯度模量的3D打印糖尿病鞋垫设计

目的 以精准降低足底压力为目标,提出一种快捷、低成本的个性化糖尿病足部建模及鞋垫的设计方案.方法 通过对标准足骨模型进行缩放的方法,构建患者足部有限元模型,分析足部生物力学,并根据鞋垫模量和足底压力数学映射模型,建立具有梯度模量的个性化鞋垫三维模型.利用3D打印技术进行鞋垫制造,并开展实验验证.结果 采用缩放建模方法所...     

Imperatorin suppresses IL-1β-induced iNOS expression via inhibiting ERK-MAPK/AP1 signaling in primary human OA chondrocytes

Joint inflammation is a key player in the pathogenesis of osteoarthritis (OA). Imperatorin, a plant-derived small molecule has been reported to have anti-inflammatory properties; however, its effect on chondrocytes is not known. Here, we investigated the effects of Imperatorin on interleukin-1β (IL-1β) induced expression of inducible nitric oxide synthase (iNOS) and nitric oxide production in primary human OA chondrocytes and cartilage explants culture under pathological conditions and explored the associated signaling pathways. We pretreated chondrocytes or explants with Imperatorin (50 μM) followed by IL-1β (1 ng/ml), and the culture supernatant was used to determine the levels of nitrite production by Griess assay and chondrocytes were harvested to prepare cell lysate or RNA for gene expression analysis of iNOS by Western blot or qPCR and in explants by immunohistochemistry (IHC). Pretreatment of primary chondrocytes and cartilage explants with Imperatorin suppressed IL-1β induced expression of iNOS and NO production. Imperatorin blocked the IL-1β-induced phosphorylation of ERK-MAPK/AP1 signaling pathway to suppress iNOS expression. The role of ERK in the regulation of iNOS expression was verified by using ERK inhibitor. Interestingly, we also found that Imperatorin binds to iNOS protein and inhibits its activity in vitro. Our data demonstrated that Imperatorin possess strong anti-inflammatory activity and may be developed as a therapeutic agent for the management of OA.     

Beta amyloid-induced time-dependent learning and memory impairment: involvement of HPA axis dysfunction

Metabolic Brain Disease - Aβ aggregation is one of the pathological biomarkers of Alzheimer’s disease (AD). However, the possible mechanism related to Aβ-induced pathological...     

The elevated expression of Th17-related cytokines and receptors is associated with skin lesion severity in early systemic sclerosis

ObjectiveThe objective was to survey the expression and localization of Th17-related cytokines and their correlation with skin lesion severity in early systemic sclerosis (SSc).MethodsThe mRNA expression was detected by real-time quantitative polymerase chain reaction (RT-qPCR) from 21 SSc patients and 12 healthy controls (HC). The protein expression was examined by immunohistochemistry (IHC) and Western blotting.ResultsThe RT-qPCR analysis showed a significantly higher expression of IL-17A, IL-21, IL-22, IL-26, IL-17RA, IL-21R, and IL-22R1 mRNA; consistently, the IHC analysis showed an over-expression of IL-17RA, IL-21R and IL-22R1 and the Western blotting analysis showed an over-expression of IL-17A, IL-21, IL-21R and IL-22R1 in early SSc skin lesions. The mRNA levels of IL-21 were higher in diffuse cutaneous than limited cutaneous SSc lesions. The mRNA expression of IL-26, IL-22, IL-22R1, mRNA and protein expression of IL-17A, IL-21, IL-21R were positively correlated with the modified Rodnan skin score of SSc. In addition, the mRNA levels of ICAM-1 were positively correlated with IL-17A/IL-17RA, and VEGFA and IL-4 were both positively correlated with IL-21/IL-21R, while TGF-β were moderately negatively correlated with IL-22/IL-22R1.ConclusionsTh17 cytokines contribute to progression in early SSc skin lesions. IL-21/IL-21R could act as potential biomarkers presenting early SSc skin lesions severity.     

3D打印导航模板辅助髓芯减压植骨治疗ARCOⅡ期非创伤性股骨头坏死

文题释义：3D打印导航模板：即3D打印技术与计算机虚拟导航相结合的技术,依据CT或者MRI成像的三维模型,结合快速成型的3D打印技术将虚拟三维导航模板打印成实体用于设计手术方案或引导术中操作。髓芯减压植骨：股骨头坏死非塌陷期常用的保髋术式之一,通过钻孔降低股骨头内的高压,改善静脉回流,促进毛细血管再生,同时通过减压通道对股骨头内坏死区域植入人工骨或自体骨,分散股骨头局部应力集中,避免股骨头进一步塌陷。 背景：髓芯减压植骨是治疗ARCOⅡ期非创伤性股骨头坏死的主要术式,但是存在定位不准确,坏死骨清除不彻底或过多的风险。 目的：观察3D打印导航模板辅助髓芯减压植骨治疗ARCOⅡ期非创伤性股骨头坏死的精确性和安全性。方法：收集2017年1至11月西安交通大学附属红会医院收治的80例(96髋)ARCOⅡ期非创伤性股骨头坏死患者,将其随机分为2组,3D组40例(48髋)行3D打印导航模板辅助髓芯减压植骨;对照组40例(48髋)行传统髓芯减压植骨,即未使用导航模板。2组患者对治疗方案均知情同意,且得到医院伦理委员会批准。分别记录2组手术时间、术中透视次数、术中失血量,观察术后第3,6,12,24个月X射线片复查结果,评估股骨头存活率、髋关节Harris评分、疼痛目测类比评分等指标,进行疗效对比。结果与结论：①3D组与对照组比较,手术时间由(132.57±14.86) min缩短至(82.63±10.31) min,术中透视次数由(16.80±2.15)次降低至(4.93±1.36)次,失血量由(143.23±17.98)mL降低至(75.64±16.23)mL,3D组在手术时间、透视次数、失血量方面均优于对照组(P < 0.05);②术后24个月影像学随访结果显示,3D组仅2例股骨头发生塌陷,但髋关节功能尚可,未行人工髋关节置换,股骨头存活率为96%;对照组中有9例股骨头发生塌陷,其中4例因髋关节活动受限行人工全髋置换,股骨头存活率为81%;3D组股骨头存活率高于对照组(P=0.024);③与对照组比较,3D组在Harris评分、目测类比评分方面均有所改善(P < 0.05);④提示将3D 打印导航模板应用于髓芯减压植骨治疗ARCOⅡ期非创伤性股骨头坏死,可减少手术时间、术中透视次数及出血量,提高术中定位的精确性和安全性。 ORCID: 0000-0001-8758-1626(陈冬冬) 中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程