SC-514, a selective inhibitor of IKKβ attenuates RANKL-induced osteoclastogenesis and NF-κB activation

The RANKL-induced NF-κB signaling pathway is essential for osteoclastogenesis. This study aims to identify specific inhibitors targeting NF-κB signaling pathway, which might serve as useful small molecule inhibitors for the treatment and alleviation of osteoclast-mediated bone lytic diseases. By screening for compounds that selectively inhibit RANKL-induced NF-κB activation in RAW264.7 cells as monitored by luciferase reporter gene assay, we identified SC-514, a specific inhibitor of IKKβ, as a candidate compound targeting osteoclastogenesis. SC-514 dose-dependently inhibits RANKL-induced osteoclastogenesis with an IC50 of <5 μM. At high concentrations, SC-514 (≥12.5 μM) induced apoptosis and caspase 3 activation in RAW264.7 cells. Moreover, SC-514 specifically suppressed NF-κB activity owing to delayed RANKL-induced degradation of IκBα and inhibition of p65 nuclear translocation. Taken together, our results indicate that SC-514 impairs RANKL-induced osteoclastogenesis and NF-κB activation. Thus, targeting IKKβ by SC-514 presents as a potential treatment for osteoclast-related disorders such as osteoporosis and cancer-induced bone loss.     

伸直位骨性强直膝的全膝关节置换术

 目的 探讨伸直位骨性强直膝全膝关节置换术的手术方法与临床疗效。方法 2000 年6月至2007 年6 月, 对10 例伸直位骨性强直膝患者施行全膝关节置换术。男4 例, 女6 例;年龄29~63岁, 平均49 岁。双膝关节置换2 例, 单膝关节置换8 例。强直性脊柱炎3 例, 类风湿关节炎2 例, 血友病性关节炎1 例, 创伤性关节炎3 例, 化脓性关节炎1 例。膝关节均处于伸直位骨性强直畸形, 活动度0°, 美国特种外科医院(the Hospital for Special Surgery, HSS)膝关节评分(32.5±10.26)分。结果 全部病例随访3~10 年, 平均5.3 年。末次随访时HSS 膝关节评分提高至(87.75±6.45)分, 与术前比较差异有统计学意义(t=18.668, P=0.000)。关节活动度提高至97.08°±11.57°, 与术前比较差异有统计学意义(t=29.063, P=0.000)。术后发生皮肤坏死2 例、下肢深静脉栓塞1 例、假体周围骨折1 例、假体深部感染翻修1 例。术后X线复查未见假体松动。结论 采用髌旁内侧入路、股四头肌切开、二次截骨加软组织松解的全膝关节置换术可矫正伸直位骨性强直膝关节畸形, 配合正确的康复锻炼, 患者的膝关节功能和生活质量能得到明显提高。     

Proximal humerus exposure with the inverted-L anterolateral deltoid flip approach,anterolateral deltoid splitting approach,and deltopectoral approach: A comparative cadaveric study

BackgroundReduction of the posterior aspect of proximal humerus fracture, such as far-retracted greater tuberosity or posterior articular head split fracture via a deltopectoral or deltoid splitting approach, is difficult and usually needs extensive dissection. The inverted-L anterolateral deltoid flip approach, which is developed from the deltoid splitting approach, accesses the proximal humerus via lateral deltoid flap lifting. This study compared the area and arc of surgical exposure to the proximal humerus of this proposed approach to existing approaches.MethodsEleven cadaveric specimens were used. Deltopectoral and deltoid splitting approaches were carried out on the right and left shoulder, respectively. Soft tissue was retracted after completion of a surgical approach to expose the proximal humerus, and dot-to-dot marking pins were placed along the border of exposed area. An additional area with a full shoulder rotation was also marked on the deltopectoral side. An inverted-L deltoid flip approach was further carried out on a deltoid splitting side with a posterior extending incision along the acromion process and the deltoid detachment from the acromion process. The additional area of exposure was subsequently marked. All soft tissue around the proximal humerus was taken down, and the glenohumeral joint was disarticulated. Area of exposure and axial images were taken for further processing and measurement.ResultAn average distance of the axillary nerve from the acromion process of the deltoid splitting and the deltopectoral approaches were 49.15 mm and 57.35 mm, respectively (P < 0.05). The average area of exposure of the inverted-L deltoid flip, deltoid-splitting, deltopectoral, and deltopectoral with full rotation approaches were 2729.81mm², 1404.39mm², 1325.41mm², and 2354.78mm², respectively (P < 0.05). Mean arc of exposure lateral to bicipital groove of the inverted-L deltoid flip, deltoid splitting, deltopectoral, and deltopectoral with full rotation approaches were 151.75degrees, 105.02degrees, 61.68°, and 110.64°, respectively (P < 0.05).ConclusionThe inverted-L anterolateral deltoid flip approach provides the most posterior access to the proximal humerus. However, it requires more soft tissue dissection and awareness of tension on the axillary nerve. This approach could be an alternative for displaced posterior head splits or far-retracted greater tuberosity proximal humerus fractures.     

Specific Decrease in B-Cell-Derived Extracellular Vesicles Enhances Post-Chemotherapeutic CD8+ T Cell Responses

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TC股骨转子间骨折半髋假体系统的研制及力学测试

目的针对老年不稳定型股骨转子间骨折,研制一套新型半髋假体系统———TC(Trochanteric Prosthesis Sys-tem)半髋假体系统,以保存粗隆部骨量,达到早期功能锻炼的要求。方法选择1名正常成年男性志愿者,对其双侧股骨进行CT薄层扫描,所得图像信息以DICOM格式储存,导入有限元建模软件建立股骨中上段三维模型。利用计算机Pro/E软件进行半髋假体的辅助设计,计算机数控快速成型技术制造半髋假体的金属模型,在尸体骨上反复验证和修改完善后,开模铸造正式假体。将所研制假体模拟植入人体股骨后进行三维有限元分析。选择1名老年男性的新鲜尸体股骨标本,制作A2.2型(AO分型)股骨转子间骨折模型,模拟手术植入装配所研制的半髋假体系统。按照国家行业标准YY0117和YY0118的要求进行材料的性能测试、假体头颈部疲劳测试、假体柄部疲劳测试以及模拟植入新鲜尸体股骨后的抗压、抗扭转等生物力学性能测试。结果新型股骨转子间骨折半髋假体试样的头颈部、柄体部的疲劳性能测试结果 500万次(8 Hz),假体未断裂或失效;植入新鲜尸体股骨后抗压达到2 kN,试样未失效,抗扭转最大扭矩达到15.5 N.m。有限元分析应力云图显示假体柄与股骨接触应力主要由股骨转子部以下的骨干部所承担,最大平均Von Mises应力值为17.6～26.4 MPa,而大、小转子处的应力水平较低,最大平均Von Mises应力值分别为2.7、4.9 MPa。结论本研究所研制的老年不稳定型股骨转子间骨折半髋假体系统具有操作简便、固定牢靠、充分保存转子部骨量的特点,并且能够达到早期功能锻炼的生物力学要求。     

股骨转子间骨折内固定失败的风险评估

 目的 总结分析股骨转子间骨折内固定治疗失败的原因, 初步提出股骨转子间骨折的内固定手术失败风险评估表。方法 回顾性分析2008 年4 月至2011年4 月, 四家医院收治的267 例接受内固定治疗的股骨转子间骨折患者, 分析患者的年龄、性别、高血压、糖尿病、烟酒史、激素史、骨质疏松程度及骨折分型等因素与内固定失败的相关性。通过手术风险评估表评分, 将患者分为手术失败低危风险组、中危风险组和高危风险组, 比较各组内固定术后失败率差异是否有统计学意义。结果 接受内固定手术治疗的267例患者中42 例患者治疗失败。患者高龄、糖尿病、严重骨质疏松、骨折不稳定等危险因素与内固定失败相关, 而患者的性别、高血压、烟酒史、激素应用史等因素与内固定失败无关。糖尿病史、骨质疏松程度、骨折稳定性是患者内固定失败的危险因素(OR 分别为3.76, 2.37 和2.74, P<0.05)。股骨转子间骨折内固定失败患者主要集中在中、高危风险组。结论 严重骨质疏松、不稳定性骨折以及糖尿病均为致股骨转子间骨折手术失败的重要因素。对低危风险组的股骨转子间骨折患者可以首选内固定治疗, 而对中危风险组和高危风险组患者建议谨慎选择内固定治疗, 对高龄、高危风险组患者必要时可行人工关节置换术。     

全膝关节置换术中下肢机械轴的研究进展

下肢机械轴(femorotibial mechanical axis,FTMA)是影响全膝关节置换术(total knee arthroplasty,TK A)后临床疗效的重要因素之一.通常认为TKA 后下肢力线对准范围控制在中性FTMA±3°之内,在改善关节功能、延长假体生存率及降低翻修率等更具优势,可获得到更好的临...     

“Out-in” position in the surgical treatment of three-column tibial plateau fractures: A technical note

Three-column classification of tibial plateau fractures is based on computerized tomography (CT) images, and the patients with three-column fractures can be treated with posteromedial combined with anterolateral approach in the floating position. However, there are certain disadvantages to operating in a "floating position". Therefore, we proposed an "out-in" position for those fractures. The patient is placed in supine position on the operating table, and the healthy hip is elevated. For the posteromedial approach, the affected limb should be placed on a rectangular fluoroscopy table and kept in abduction and external rotation (out); for the anterolateral approach, the affected limb is retracted into the operating bed and kept in neutral position (in).This position has been shown to be highly effective for easy operation as well as intraoperative image monitoring. Furthermore, it highlights the advantage of anterior-posterior joint fracture reduction.     

Peripheral Blood Stem Cell Therapy Does Not Improve Outcomes of Femoral Head Osteonecrosis With Cap-Shaped Separated Cartilage Defect

A combination treatment with porous tantalum rod implantation and intra-arterial infusion of peripheral blood stem cells (PBSCs) provides a promise for treating early and intermediate stages of osteonecrosis of the femoral head (ONFH). However, its clinical indications and application restrictions remain unclear. This study aims to determine the clinical, histological, and radiological outcomes of a combination treatment using mechanical support and a targeted intra-arterial infusion of PBSCs for painful ONFH with a cap-shaped separation (CSS) cartilage defect. Compared with the standard pain management (control group), this combination treatment did not improve the Harris Hip Score (HHS) at 36 months. Micro-CT and histologic analyses showed severe focal destruction in all CSS-ONFH femoral heads in both the combination and control groups. Femoral heads showed a higher percentage of bone lesions in the combination treatment group than in the control group. There was no significant difference in osteoclast number in the subchondral bone areas between the two groups. A high level of expression of inflammatory cytokines, including tumor necrosis factor-α and interleukin-1β, was detected in blood vessels around the subchondral bone in both groups. The RANKL/OPG (receptor activator of the nuclear factor-kB ligand/osteoprotegerin) ratio was also similar between the control and combination treatment groups. Our results indicate that this combination treatment is not an effective method for the treatment of patients with painful CSS-ONFH. Moreover, this combination treatment did not inhibit inflammatory osteoclastogenesis in patients with more advanced disease. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:269-276, 2020