肌肉骨骼系统慢性疼痛管理专家共识

肌肉骨骼系统慢性疼痛是临床最常见的慢性疼痛。目前,国内外医师对慢性疼痛的认识、临床实践环境、镇痛药物种类/使用经验/了解程度、医保药品收录均有差异,故有效、规范化的慢性疼痛管理显得尤为必要。因此,亟待制定完善的、基于生物-心理-社会医学等因素的跨学科慢性疼痛管理共识,提高广大医务人员对慢性疼痛的认识与重视、规范指导慢性疼痛的管理,提高医疗质量、降低医疗成本,消除患者感觉、情感、认知和社会维度的痛苦体验,在治疗患者原发疾病的同时,改善患者的心理需求和社会功能需求。通过查阅文献,本共识专家组遵循循证医学原则,经过反复讨论和通信修改,对肌肉骨骼系统慢性疼痛管理达成共识,供广大骨科医师在临床工作中参考。     

高脂饮食大鼠肝脏脂肪性变及NPC1L1基因表达的变化

目的：探讨NPC1L1及其胆固醇代谢相关基因在高脂饮食诱导肝脏脂肪性变中的可能作用.方法：实验大鼠分为普通饮食组及高脂饮食组,饲喂8周后取肝脏组织,酶法测定肝脏组织中总胆固醇（TC）、磷脂、高密度脂蛋白（HDL）、甘油三酯（TG）含量,RT-PCR检测肝脏组织中NPC1L1,SREBP-1c,FAS及ABCA1基因的表达变化,并在光镜及电镜下观察肝脏病理变化.结果：高脂饮食大鼠肝脏组织TC（67.6±3.1mg/gvs31.8±2.6 mg/g,P〈0.01）,TG（29.1±2.3 mg/gvs12.5±1.6 mg/g,P〈0.01）及磷脂（23.8±2.6 mg/gvs19.8±2.2 mg/g,P〈0.05）均较正常饮食大鼠增加.高脂饮食喂养组大鼠肝脏组织中胆固醇代谢相关基因NPC1L1（3.91±0.26,P〈0.01）,SREBP21c（2.84±0.23,P〈0.01）、FASmRNA（6.45±0.25,P〈0.01）表达水平显著高于正常饮食组,而ABCA1mRNA（0.56±0.18,P〈0.05）表达较正常饮食组降低.结论：肝脏组织NPC1L1表达增加及脂肪代谢相关基因SREBP-1c,FAS,ABCA1的表达     

High levels of β‐catenin signaling reduce osteogenic differentiation of stem cells in inflammatory microenvironments through inhibition of the noncanonical Wnt pathway

Periodontal ligament stem cells (PDLSCs), a new population of mesenchymal stem cells (MSCs), have been isolated from the periodontal ligament (PDL). The capacity of multipotency and self‐renewal makes them an excellent cell source for bone regeneration and repair. However, their bone‐regeneration ability could be awakened in inflammatory microenvironments, which may be the result of changes in their differentiation potential. Recently, genetic evidences has shown that the Wnt pathway plays an important role in bone homeostasis. In this study we have determined the specific role of β‐catenin in osteogenic differentiation of PDLSCs obtained from inflammatory microenvironments (P‐PDLSCs). The inflammatory microenvironment, while inhibiting osteogenic differentiation potential, promotes proliferation of MSCs. A higher the level of β‐catenin in P‐PDLSCs than in H‐PDLSCs (PDLSCs obtained from a healthy microenvironment) resulted in the same disparity in canonical Wnt signaling pathway activation between each cell type. Here we show that activation of β‐catenin suppresses the noncanonical Wnt/Ca²⁺ pathway, leading to increased proliferation but reduced osteogenic differentiation of P‐PDLSCs. Downregulation of the levels of β‐catenin by treatment with dickkopf‐1 (DKK‐1) leads to activation of the noncanonical Wnt/Ca²⁺ pathway, which, in turn, results in the promotion of osteogenic differentiation in P‐PDLSCs. Interestingly, β‐catenin can affect both the canonical Wnt/β‐catenin pathway and the noncanonical Wnt/Ca²⁺ pathway. Our data indicate that β‐catenin plays a central role in regulating osteogenic differentiation of MSCs in inflammatory microenvironments. Given the important role of Wnt signaling in osteogenic differentiation, it is possible that agents that can modify this pathway may be of value in bone regeneration by MSCs in chronic inflammatory microenvironments. © 2011 American Society for Bone and Mineral Research     

小分子化合物S1抑制K562细胞增殖及其机理研究

目的:探讨小分子化合物S1对K562细胞的抑制作用及机理,为S1治疗慢性粒细胞白血病（chronic myeloid leukemia,CML）提供理论与实验基础。方法:MTT法检测不同浓度S1对K562细胞增殖的抑制作用;应用Chou-Talalay计算联合指数,观察单独应用S1与S1联合阿糖胞苷对K562细胞增殖抑制的协同作用;Western-blotting方法检测不同浓度S1作用后K562细胞系中Bcl-2蛋白表达水平的变化。结果:与对照组相比,S1可以抑制K562细胞的增殖（P<0.05）;S1与阿糖胞苷联合应用对K562细胞的生长抑制具有协同作用,联合指数CI<1;S1可下调K562细胞系中抗凋亡蛋白Bcl-2的表达。结论:小分子化合物可通过下调抗凋亡蛋白Bcl-2的表达抑制K652细胞的增殖,并与阿糖胞苷具有协同作用。