Structure and Function of the Oxidoreductase DsbA1 from Neisseria meningitidis

Neisseria meningitidis encodes three DsbA oxidoreductases (NmDsbA1-NmDsbA3) that are vital for the oxidative folding of many membrane and secreted proteins, and these three enzymes are considered to exhibit different substrate specificities. This has led to the suggestion that each N. meningitidis DsbA (NmDsbA) may play a specialized role in different stages of pathogenesis; however, the molecular and structural bases of the different roles of NmDsbAs are unclear. With the aim of determining the molecular basis for substrate specificity and how this correlates to pathogenesis, we undertook a biochemical and structural characterization of the three NmDsbAs. We report the 2.0-Å-resolution crystal structure of the oxidized form of NmDsbA1, which adopted a canonical DsbA fold similar to that observed in the structures of NmDsbA3 and Escherichia coli DsbA (EcDsbA). Structural comparisons revealed variations around the active site and candidate peptide-binding region. Additionally, we demonstrate that all three NmDsbAs are strong oxidases with similar redox potentials; however, they differ from EcDsbA in their ability to be reoxidized by E. coli DsbB. Collectively, our studies suggest that the small structural differences between the NmDsbA enzymes and EcDsbA are functionally significant and are the likely determinants of substrate specificity.     

Effect of screw position on load transfer in lumbar pedicle screws: a non-idealized finite element analysis

Angled screw insertion has been advocated to enhance fixation strength during posterior spine fixation. Stresses on a pedicle screw and surrounding vertebral bone with different screw angles were studied by finite element analysis during simulated multidirectional loading. Correlations between screw-specific vertebral geometric parameters and stresses were studied. Angulations in both the sagittal and axial planes affected stresses on the cortical and cancellous bones and the screw. Pedicle screws pointing laterally (vs. straight or medially) in the axial plane during superior screw angulation may be advantageous in terms of reducing the risk of both screw loosening and screw breakage.     

Selection of Nest Trees by Cavity‐nesting Birds in the Neotropical Atlantic Forest

One of the five most important global biodiversity hotspots, the Neotropical Atlantic forest supports a diverse community of birds that nest in tree cavities. Cavity‐nesting birds may be particularly sensitive to forestry and agricultural practices that remove potential nest trees; however, there have been few efforts to determine what constitutes a potential nest tree in Neotropical forests. We aimed to determine the characteristics of trees and cavities used in nesting by excavators (species that excavate their own nest cavity) and secondary cavity‐nesters (species that rely on existing cavities), and to identify the characteristics of trees most likely to contain suitable cavities in the Atlantic forest of Argentina. We used univariate analyses and conditional logistic regression models to compare characteristics of nest trees paired with unused trees found over three breeding seasons (2006–2008). Excavators selected dead or unhealthy trees. Secondary cavity‐nesters primarily selected cavities that were deep and high on the tree, using live and dead cavity‐bearing trees in proportion to their availability. Nonexcavated cavities suitable for birds occurred primarily in live trees. They were most likely to develop in large‐diameter trees, especially grapia Apuleia leiocarpa and trees in co‐dominant or suppressed crown classes. To conserve cavity‐nesting birds of the Atlantic forest, we recommend a combination of policies, economic assistance, environmental education, and technical support for forest managers and small‐scale farmers, to maintain large healthy and unhealthy trees in commercial logging operations and on farms.     

Countercurrent tangential chromatography for large-scale protein purification

Recent advances in cell culture technology have created significant pressure on the downstream purification process, leading to a "downstream bottleneck" in the production of recombinant therapeutic proteins for the treatment of cancer, genetic disorders, and cardiovascular disease. Countercurrent tangential chromatography overcomes many of the limitations of conventional column chromatography by having the resin (in the form of a slurry) flow through a series of static mixers and hollow fiber membrane modules. The buffers used in the binding, washing, and elution steps flow countercurrent to the resin, enabling high-resolution separations while reducing the amount of buffer needed for protein purification. The results obtained in this study provide the first experimental demonstration of the feasibility of using countercurrent tangential chromatography for the separation of a model protein mixture containing bovine serum albumin and myoglobin using a commercially available anion exchange resin. Batch uptake/desorption experiments were used in combination with critical flux data for the hollow fiber filters to design the countercurrent tangential chromatography system. A two-stage batch separation yielded the purified target protein at >99% purity with 94% recovery. The results clearly demonstrate the potential of using countercurrent tangential chromatography for the large-scale purification of therapeutic proteins.     

骨折切开复位内固定手术与经皮钢板内固定手术治疗pilon III型骨折的临床研究

目的：分析比较切开复位内固定术与经皮钢板内固定术治疗pilon III型骨折的临床疗效,为治疗pilonIII型骨折选择更好的方法提供依据。方法：选取pilonIII型骨折患者7l例,随机分为对照组35例和观察组36例,比较两组的临床优良率、手术时间、血肿吸收和恢复时间以及后遗症症的发生情况。结果：对照组和观察组的优良率分别为74．29％、94．44％,差异有统计学意义,P〈O．05。观察组的手术时间、血肿吸收和恢复时间均较对照组有缩短,其中以手术时间和恢复时间差异显著,且不良反应相对较少,P〈0．05。结论：切开复位内固定术治疗pilonIII型骨折疗效优于经皮钢板内固定术,能缩短手术及恢复所需时间,对改善患者的预后有重大意义。     

冠心病强化标准化药物治疗最新进展

冠状动脉粥样硬化性心脏病的患病人数呈逐年上升趋势,目前治疗冠心病的方法主要包括改善生活方式,药物治疗,经皮冠状动脉介入治疗（PCI）和外科冠状动脉旁路移植手术治疗（CABG）。虽然介入治疗在治疗阻塞性冠心病取得了显著的进展,但因支架再狭窄,晚期血栓形成,及未知的机制,其死亡率未见明显下降。冠状动脉旁路移植手术虽可降低死亡率,但因其为侵入性操作及手术费用的较高成本,不能为大部分患者接受。近几年来进行了一些全球多中心的临床试验研究,以评估不同诊疗方案对冠心病的预后及远期疗效。目前一些研究表明强化标准化药物治疗（optimal medical therapy,OMT）可与再血管化治疗同效。本文将针对冠心病强化标准化药物治疗方面的实验研究进展进行简要综述。     

人工关节置换与加压螺钉内固定治疗高龄骨质疏松性股骨颈骨折的疗效观察

目的:探讨人工关节置换与加压螺钉内固定治疗高龄骨质疏松性股骨颈骨折的疗效。方法:选取2010年8月至2013年3月我院收治的120例高龄骨质疏松性股骨颈骨折患者,将所有患者随机分为人工置换组和内固定组两组,每组各60例,内固定组采用加压螺钉内固定术治疗,人工置换组采取人工关节置换术治疗,评定两组患者的手术时间、术中出血量、下地时间、术后并发症发生率及末次随访时Harris评分优良率。结果:人工置换组手术时间及术中出血量分别为(124.8±16.7)min、(369.2±99.7)ml,明显高于内固定组的(73.5±15.1)min、(78.4±25.6)ml;但人工置换组术后下地时间为(15.3±4.8)d,明显低于内固定组的(40.2±7.5)d;人工置换组与内固定组患者术后并发症的发生率分别为20%、66.7%,人工置换组明显低于内固定组,其中,泌尿系褥疮的组间差异最为显著;末次随访时Harris评分优良率,相比于内固定组的61.67%,人工置换组为78.33%,明显偏高。差异有统计学意义(P0.05)。结论:加压螺钉内固定术和人工关节置换术在治疗高龄骨质疏松性股骨颈骨折方面各有优劣,对于能够耐受人工关节置手术且经济条件好的的老年患者而言,采用人工关节置换术治疗,疗效更佳。     

急性心肌梗死患者冠脉介入治疗后血浆apelin的变化及作用

目的:观察急性心肌梗死(AMI)患者围手术期血浆apelin的表达变化,分析AMI合并2型糖尿病(T2DM)患者血浆apelin的表达与预后的相关性,探讨apelin在冠脉介入治疗(PCI)中的心脏保护作用。方法:72例于2012年2月~8月在我院心内科接受冠状动脉造影确诊为AMI并成功完成PCI的冠心病患者,分别在术前、术后0小时、术后4小时、术后24小时收集血清,酶联免疫吸附法测定血浆apelin-13水平;进一步对糖尿病及非糖尿病AMI患者(每组各20例)进行亚组分析,随访两组患者在术后6个月时主要不良心脑血管事件(MACCE)。结果:AMI患者术后0 h组apelin水平与术前基线水平明显降低(31.54±5.48 vs35.15±6.48 ng/L,P0.05);术后4小时及24小时组apelin水平较术前明显升高(39.65±5.48 vs 35.15±6.48 ng/L,43.93±5.37 vs35.15±6.48 ng/L,P0.05)。糖尿病与非糖尿病组apelin水平术前无明显差异;糖尿病组在术后各时间点的apelin水平均明显高于非糖尿病组(31.12±5.50 vs 29.21±6.53 ng/L,40.57±5.37 vs 33.49±3.89 ng/L,43.50±7.41 vs 34.54±3.52 ng/L,P0.05)。两组术后6个月随访T2DM组LVEF值改善明显高于NT2DM组,但MACCE事件无明显差异。结论:AMI患者PCI术后存在血浆apelin表达的升高,其中糖尿病患者在术后血浆apelin表达较非糖尿病患者明显增高,提示PCI冠脉血运重建可促进糖尿病患者apelin分泌,调节胰岛素抵抗改善预后。     

下肢动脉硬化闭塞症血管成形术的疗效观察

目的:探讨血管成形术治疗下肢动脉硬化闭塞症的临床应用价值。方法:对我院78例下肢动脉硬化闭塞患者的临床资料进行回顾性分析。78例患者(98条血管)术前经CTA诊断后,行腔内血管成形术(PTA)和血管支架植入术治疗,治疗后随访1~18个月,分析踝/肱指数(ABI)、血管内径、皮温及足背动脉搏动的变化。结果:成功完成77例(98.7%)患者、97条(99.0%)患肢的PTA和支架植入术,除1例下肢动脉完全闭塞患者导丝未能成功通过病变导致介入失败外,其余病例经介入治疗后均开通,术中所有病例均未发生血肿、血管壁破裂、穿孔或内支架移位,远端血管血栓栓塞等并发症。术后,患者下肢缺血症状消失或明显减轻,踝/肱指数(ABI)由术前(0.39±0.23)恢复至(0.86±0.26),下肢血管内径及足背动脉搏动均明显改善。结论:PTA和血管支架植入术是一种治疗下肢动脉硬化闭塞症安全有效的方法,成功率高,并发症少,再狭窄率低。