Isokinetic quadriceps symmetry helps in the decision to return to running after anterior cruciate ligament reconstruction

BackgroundAfter anterior cruciate ligament reconstruction (ACLR), the decision to allow a return to running is empirical, and the post-operative delay is the most-used criterion. The Quadriceps isokinetic-strength Limb Symmetry Index (Quadriceps LSI), with a cutoff of 60%, could be a useful criterion.ObjectiveTo determine the association between a Quadriceps LSI ≥ 60% and return to running after ACLR.MethodsOver a 10-year period, we retrospectively included 470 patients who underwent ACLR. Four months after ACLR, participants performed an isokinetic test; quadriceps concentric peak torque was used to calculate the Quadriceps LSI at 60?/s. With a Quadriceps LSI ≥ 60%, a return to running was suggested. At 6 months after ACLR, participants were clinically evaluated for a return to sport and post-operative middle-term complications. A multivariable predictive model was built to assess the efficiency diagnosis of this cutoff in order to consider cofounding factors. Quadriceps LSI cutoff ≥ 60% was assessed with sensitivity, specificity and the area under the receiver operating characteristic curve (AUC).ResultsAccording to our decision-making process with the 60% Quadriceps LSI cutoff at 60?/s, 285 patients were authorized to return to running at 4 months after ACLR and 185 were not, but 21% (n = 59) and 24% (n = 45), respectively, were not compliant with the recommendation. No iterative autograft rupture or meniscus pathology occurred at 6 months of follow-up. On multivariable logistic regression analysis, a return to running by using the 60% Quadriceps LSI cutoff was associated with undergoing the hamstring strand procedure (odds ratio 2.60, 95% confidence interval [CI] 1.75–3.84; P < 0.0001) and the absence of knee complications (1.18, 1.07–1.29; P = 0.001) at 4 months. The sensitivity and specificity of the 60% Quadriceps LSI cutoff were 83% and 70%, respectively. The AUC was 0.840 (95% CI 0.803–0.877).ConclusionsUsing the 60% cutoff of the isokinetic Quadriceps LSI at 4 months after ACLR could help in the decision to allow a return to running.     

miR-513a-5p慢病毒载体的构建及其对人骨肉瘤细胞放疗敏感性的影响

目的:构建miR-513a-5p慢病毒过表达载体，转染人骨肉瘤细胞株，观察miR-513a-5p对人骨肉瘤细胞放疗敏感性的影响。方法:PCR法扩增人miR-513a-5p基因，克隆入pLentis-CMV-GFP-MCS-PGK-PURO载体获得重组质粒pLentis-miR513a，双酶切鉴定并测序后将正确的重组质粒和对照质粒转染293FT细胞制备慢病毒，分别转染骨肉瘤HOS和U2OS细胞，qRT-PCR法及荧光显微镜鉴定转染结果。克隆形成实验、MTT法检测miR-513a-5p高表达HOS和U2OS细胞在X射线照射下细胞存活情况。结果:双酶切及测序结果确定成功构建miR-513a-5p慢病毒载体pLentis-miR513a。qRT-PCR结果提示，转染骨肉瘤细胞株后miR-513a-5p表达显著升高。克隆形成实验结果显示miR-513a-5p高表达后骨肉瘤细胞在X射线照射下细胞增殖减慢。MTT结果提示miR-513a-5p高表达骨肉瘤细胞经X射线照射后细胞存活减少。结论:成功构建了miR-513a-5p慢病毒载体，建立了高效稳定表达miR-513a-5p的骨肉瘤细胞株，高表达miR-513a-5p能显著增加X射线照射后骨肉瘤细胞的放疗敏感性。     

miR-548d抑制骨肉瘤细胞的增殖和迁移

目的:探讨miR-548d对骨肉瘤细胞增殖和迁移的影响。方法:通过Real time PCR及Western blot检测miR-548d和KRAS在30例骨肉瘤组织以及293、MG63和U2OS细胞中的表达情况。对30例骨肉瘤组织中miR-548d和KRAS含量的相关性进行分析，随后通过报告基因实验印证miR-548d对KRAS的靶向作用。MG63细胞中分别过表达或沉默miR-548d后，通过Western blot实验分析KRAS的变化情况，MTT实验观察miR-548d对细胞增殖的影响，Transwell实验观察miR-548d对其迁移能力的影响。结果:骨肉瘤组织及细胞中miR-548d表达较低，KRAS表达较高。在骨肉瘤组织中miR-548d与KRAS的表达呈负相关。报告基因实验证明miR-548d可以直接打靶KRAS。Western blot指出miR-548d可以抑制KRAS的表达。最后MTT和Transwell实验指出miR-548d可以抑制MG63细胞的增殖与迁移。结论:miR-548d可以通过打靶KRAS抑制骨肉瘤细胞的增殖和迁移。     

Prexasertib (LY2606368) reduces clonogenic survival by inducing apoptosis in primary patient-derived osteosarcoma cells and synergizes with cisplatin and talazoparib

Progress in the systemic control of osteosarcoma has been limited over the past decades thus indicating the urgent clinical need for the development of novel treatment strategies. Therefore, we have recently developed new preclinical models to study promising novel agents for the treatment of pediatric osteosarcoma. The checkpoint kinase (chk) inhibitor prexasertib (LY2606368) and its salt form (LSN2940930) have recently been shown to be active in adult and pediatric malignancies, including sarcoma. We have now tested the potency of prexasertib in clonogenic survival assays in two new lines of primary patient-derived osteosarcoma cells and in two established osteosarcoma cell lines as a single agent and in combination with cisplatin and the poly ADP-ribose polymerase (PARP) inhibitor talazoparib. Prexasertib alone results in strongly reduced clonogenic survival at low nanomolar concentrations and acts by affecting cell cycle progression, induction of apoptosis and induction of double-stranded DNA breakage at concentrations that are well below clinically tolerable and safe plasma concentrations. In combination with cisplatin and talazoparib, prexasertib acts in a synergistic fashion. Chk1 inhibition by prexasertib and its combination with the DNA damaging agent cisplatin and the PARP-inhibitor talazoparib thus emerges as a potential new treatment option for pediatric osteosarcoma which will now have to be tested in preclinical primary patient derived in vivo models and clinical studies.     

Forearm wearable resistance effects on sprint kinematics and kinetics

Objectives

Arm swing is a distinctive characteristic of sprint-running with the arms working in a contralateral manner with the legs to propel the body in a horizontal direction. The purpose of this study was to determine the acute changes in kinematics and kinetics when wearable resistance (WR) of 1 kg (equivalent to ～1% body mass) was attached to each forearm during over ground short distance (20 m) maximal sprint-running.

Giant-cell-rich tumors of bone

Neoplasms of bone with numerous non-neoplastic osteoclast type giant cells are relatively common and exhibit diverse phenotypes of the neoplastic cells. These tumors have a broad spectrum of biological potential which necessitates accurate recognition and diagnosis. Their clinicopathological features are overlapping, therefore, immunohistochemistry and molecular studies may be required for evaluation. Correlation with imaging studies provides additional information that should be incorporated into the pathological interpretation.     

8字钢板临时阻滞在儿童下肢不等长中的应用效果分析

目的探讨8字钢板临时骨骺阻滞在儿童下肢不等长(lower limb discrepancy,LDD)治疗中的有效性及可行性。方法回顾性分析自2011年11月至2017年1月复旦大学附属儿科医院小儿骨科收治的14例LLD患儿临床资料,通过双下肢全长站立位X线片测量术前、术后股骨、胫骨长度变化,通过生长曲线分析使用8字钢板临时阻滞术后肢体不等长的改善情况,计算其在骨骺阻滞中的作用和效率。结果对14例患儿共17个部位(股骨远端及胫骨近端)行内外侧联合8字钢板阻滞,平均随访时间(29.4±8.53)个月,阻滞长度中位数为18.8 mm(5~40 mm),平均阻滞率为(59.5±18.0)%。本组病例均未出现骨骺早闭及骺板损伤的情况。此外通过分析发现,阻滞部位(胫骨近端或股骨远端)、年龄、性别、侧别对阻滞率没有影响(P>0.05),而骨骺阻滞时间与阻滞率呈正相关(r=0.438,P<0.05)。结论8字钢板在LLD中的临时性骨骺阻滞为非完全性阻滞,可以作为LLD病人治疗的一种选择,但是其矫形能力有限,术前应充分评估患儿的生长潜力。此外,术后密切随访也是取得理想治疗效果的关键。