Management of vertebral fragility fractures: a clinical care pathway developed by a multispecialty panel using the RAND/UCLA Appropriateness Method

BACKGROUND CONTEXT

Vertebral fragility fractures (VFFs), mostly due to osteoporosis, are very common and are associated with significant morbidity and mortality. There is a lack of consensus on the appropriate management of patients with or suspected of having a VFF.

氧化低密度脂蛋白对巨噬细胞的作用及机制

目的 观察氧化低密度脂蛋白(oxLDL)对巨噬细胞增殖和分泌巨噬细胞迁移抑制因子(MMIF/MIF)的作用.方法 (1)制备人单核细胞来源巨噬细胞(MDMs),25、50和75 mg/L浓度oxLDL培养12、24、48 h后,细胞计数试剂盒(CCK-8)法检测细胞增殖,酶联免疫吸附法测定上清MIF浓度;不含oxLDL培养为正常对照(NC)组.(2)制备含稳转核因子-κB (NF-κB)-LUC质粒的MDMs,同法培养,荧光素酶底物(Luciferase)检测细胞NF-κB通路活性.(3)含NF-κB-LUC质粒的MDMs中加入终质量浓度为0、10 μmol/L的NF-κB通路抑制剂BAY 11-7082,同法培养并检测上清MIF浓度.结果 (1)与NC组比较,25、50、75 mg/L oxLDL组12 h时MDMs增殖显著升高,48 h时分别达到17.7％、27.8％和41.2％ (P ＜0.01);其上清液MIF也在12h起升高,48 h时分别是NC组的1.49、1.67和2.09倍(P＜0.01).(2)与NC组比较,oxLDL各组在12h即可检测到NF-κB通路明显激活,24h时MDMs内NF-κB通路活性分别增加38.1％、60.3％和61.1％ (P＜0.01).(3)加入BAY11-7082后,各组上清液MIF浓度在12 h即出现明显下降,48 h时分别下降58.6％、69.3％、69.7％和73.5％ (P＜0.01).结论 25 ～ 75 mg/L浓度的oxLDL可促进MDMs增殖和MIF的分泌,其作用随oxLDL作用时间的延长和浓度的增高而增强.oxLDL可能通过诱导激活NF-κB信号通路促进MDMs合成分泌MIF.     

针刺抗炎研究进展

背景 创伤、烧伤、手术等容易导致机体发生全身炎性反应综合征、脓毒症、多器官功能不全综合征(multiple organ disfunction syndrome,MODS),甚至死亡.调控过度的炎症反应是防治脓毒症和MODS的重要手段之一. 目的 阐释针刺抗炎的作用及机制. 内容 针刺对多种炎性疾病有良好的治疗作用,对脓毒症和MODS亦有一定的防治作用.针刺可通过对免疫细胞、免疫球蛋白、神经递质和细胞因子等的调节,发挥抗炎作用.此外,下丘脑-垂体-肾上腺轴、胆碱能抗炎通路和内源性大麻素系统参与了针刺的抗炎机制. 趋向 针刺抗炎的确切机制尚不清楚,是否还有其他机制参与针刺的抗炎作用还有待阐明.     

骨巨细胞瘤基因组学研究进展

骨巨细胞瘤( giant cell tumor of bone,GCTB)通常被认为是一种交界性骨肿瘤,具体发病机制不详且易复发,目前除了手术暂无其他有效的治疗方案。但随着快速减法杂交( rapid subtractive hybridization,RaSH)和实时定量聚合酶链式反应( quantitative real-time polymerase chain reaction, qRT-PCR)等技术在GCTB研究领域的运用,基因突变、基因表达谱、基因转染及信号通路等基因组学事件在GCTB中得到了进一步的探索。这些研究正逐渐揭示了GCTB的发病机制,同时也改进了这种骨肿瘤的早期诊断及治疗方案。本文旨在总结GCTB基因组学研究现状,以期能发现早期特异性诊断指标,并在此基础上改进治疗方案及减少该病的术后复发率。     

Glaucoma severity affects diffusion tensor imaging (DTI) parameters of the optic nerve and optic radiation

Objectives

To evaluate whether MR diffusion tensor imaging (DTI) of the optic nerve and optic radiation in glaucoma patients provides parameters to discriminate between mild and severe glaucoma and to determine whether DTI derived indices correlate with retinal nerve fibre layer (RNFL) thickness.

Methods

3-Tesla DTI was performed on 90 subjects (30 normal, 30 mild glaucoma and 30 severe glaucoma subjects) and the FA and MD of the optic nerve and optic radiation were measured. The categorisation into mild and severe glaucoma was done using the Hodapp–Parrish–Anderson (HPA) classification. RNFL thickness was also assessed on all subjects using OCT. Receiver operating characteristic (ROC) analysis and Spearman's correlation coefficient was carried out.

Results

FA and MD values in the optic nerve and optic radiation decreased and increased respectively as the disease progressed. FA at the optic nerve had the highest sensitivity (87%) and specificity (80%). FA values displayed the strongest correlation with RNFL thickness in the optic nerve (r = 0.684, p ≤ 0.001) while MD at the optic radiation showed the weakest correlation with RNFL thickness (r = −0.360, p ≤ 0.001).

Conclusions

The high sensitivity and specificity of DTI-derived FA values in the optic nerve and the strong correlation between DTI-FA and RNFL thickness suggest that these parameters could serve as indicators of disease severity.     

Manipulation of the ubiquitin-proteasome pathway by small DNA tumor viruses

Viruses have evolved to use cellular pathways to their advantage, including the ubiquitin-proteasome pathway of protein degradation. In several cases, viruses produce proteins that highjack cellular E3 ligases to modify their substrate specificity in order to eliminate unwanted cellular proteins, in particular inhibitors of the cell cycle. They can also inhibit E3 ligase to prevent specific protein degradation or even use the system to control the level of expression of their own proteins. In this review we explore the specific ways that small DNA tumor viruses exploit the ubiquitin-proteasome pathway for their own benefit.     

Adeno-associated virus-2 and its primary cellular receptor—Cryo-EM structure of a heparin complex

Adeno-associated virus serotype 2 (AAV-2) is a leading candidate vector for gene therapy. Cell entry starts with attachment to a primary receptor, Heparan Sulfate Proteoglycan (HSPG) before binding to a co-receptor. Here, cryo-electron microscopy provides direct visualization of the virus-HSPG interactions. Single particle analysis was performed on AAV-2 complexed with a 17 kDa heparin fragment at 8.3 Å resolution. Heparin density covers the shoulder of spikes surrounding viral 3-fold symmetry axes. Previously implicated, positively charged residues R_448/585, R_451/588 and R_350/487 from another subunit cluster at the center of the heparin footprint. The footprint is much more extensive than apparent through mutagenesis, including R_347/484, K_395/532 and K_390/527 that are more conserved, but whose roles have been controversial. It also includes much of a region proposed as a co-receptor site, because prior studies had not revealed heparin interactions. Heparin density bridges over the viral 3-fold axes, indicating multi-valent attachment to symmetry-related binding sites.     

Effects of muscarinic receptor stimulation and nitric oxide synthase inhibition on gastric tone and gastric myoelectrical activity in canines

Aims:  This study was designed to assess whether the muscarinic receptor stimulation and nitric oxide synthase inhibition were equally effective on gastric fundic tone or gastric myoelectrical activity (GMA) in canines, and the correlation between gastric fundic tone and GMA.
Methods:  Gastric fundic tone and GMA were recorded on seven dogs implanted with serosal electrodes and a gastric cannula.
Results:  Bethanechol and L-nitro-N-arginine (L-NNA) significantly increased gastric fundic tone; gastric volume was decreased with bethanechol or L-NNA ( P  < 0.05). Increased spike activities were observed after both bethanechol and L-NNA. The percentage of slow waves superimposed with spikes was increased with bethanechol ( P  < 0.001) and L-NNA ( P  < 0.05). There was a significant reduction in dominant frequency (DF) ( P  < 0.05), dominant power (DP) ( P  < 0.05) and percentage of normal slow waves (%N) ( P  < 0.05) with bethanechol, while no significant change was observed with L-NNA. The variation of gastric tone was not correlated with parameters of GMA.
Conclusions:  Muscarinic receptor stimulation and nitric oxide synthase inhibition have similar effects on gastric tone and gastric spike activities, but different effects on gastric slow waves. Gastric fundic tone does not correlate with gastric slow waves.