Simultaneous tissue profiling of eicosanoid and endocannabinoid lipid families in a rat model of osteoarthritis

We describe a novel LC method for the simultaneous and quantitative profiling of 43 oxylipins including eicosanoids, endocannabinoids, and structurally related bioactive lipids with modified acyl groups. The LC-MS/MS method uses switching at a defined time between negative and positive electrospray ionization modes to achieve optimal detection sensitivity for all the lipids. The validated method is linear over a range of 0.01–5 nmol/g (0.1–50 nmol/g for 2-arachidonoyl glycerol) with intra- and interday precision and accuracy between 1.38 and 26.76% and 85.22 and 114.3%, respectively. The method successfully quantified bioactive lipids in different tissue types in the rat, including spinal cord, dorsal root ganglia (DRGs), knee joint, brain, and plasma. Distinct regional differences in the pattern of lipid measured between tissue types were observed using principle component analysis. The method was applied to analyze tissue samples from an established preclinical rat model of osteoarthritis (OA) pain and showed that levels of 12-hydroxyeicosatetraenoic acid were significantly increased in the OA rat knee joint compared with controls, and that 15-hydroxyeicosatetraenoic acid was significantly increased in the DRGs in the model of OA compared with controls. The developed LC-MS/MS method has the potential to provide detailed pathway profiling in tissues and biofluids where the disruption of bioactive oxylipins may be involved in disease states.     

通滞苏润江胶囊联合塞来昔布对早期膝骨关节炎患者血清炎症因子和疼痛介质的影响

摘要 目的：观察通滞苏润江胶囊联合塞来昔布对早期膝骨关节炎（KOA）患者血清炎症因子和疼痛介质的影响。方法：选择2021年6月-2022年12月期间石家庄市人民医院收治的早期KOA患者80例,采用随机数字表法将患者分为对照组（塞来昔布,40例）和观察组（通滞苏润江胶囊联合塞来昔布,40例）。对比两组疗效、疼痛视觉模拟评分（VAS）、西安大略和麦克马斯特大学骨关节炎指数（WOMAC）评分、炎症因子和疼痛介质。结果：观察组临床总有效率高于对照组（P<0.05）。两组治疗1个月后VAS、WOMAC评分下降,且观察组低于对照组同时间点（P<0.05）。两组治疗1个月后肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）下降,且观察组低于对照组同时间点（P<0.05）。两组治疗1个月后前列腺素E₂（PGE₂）、P物质（SP）下降,且观察组低于对照组同时间点（P<0.05）。两组不良反应发生率对比未见统计学差异（P>0.05）。结论：塞来昔布和通滞苏润江胶囊联合治疗早期KOA患者,可缓解疼痛,提高临床治疗效果,改善关节功能,同时还可改善血清炎症因子和疼痛介质水平。     

A Pilot Clinical Study of Hyperacute Serum Treatment in Osteoarthritic Knee Joint: Cytokine Changes and Clinical Effects

The serum fraction of platelet-rich fibrin (hyperacute serum) has been shown to improve cartilage cell proliferation in in vitro osteoarthritic knee joint models. We hypothesize that hyperacute serum may be a potential regenerative therapeutic for osteoarthritic knees. In this study, the cytokine milieu at the synovial fluid of osteoarthritic knee joints exposed to hyperacute serum intraarticular injections was investigated. Patients with knee osteoarthritis received three injections of autologous hyperacute serum; synovial fluid was harvested before each injection and clinical monitoring was followed-up for 6 months. Forty osteoarthritic-related cytokines, growth factors and structural proteins from synovial fluid were quantified and analysed by Multivariate Factor Analysis. Hyperacute serum provided symptomatic relief regarding pain and joint stability for OA patients. Both patients “with” and “without effusion knees” had improved VAS, KOOS and Lysholm-Tegner scores 6 months after of hyperacute serum treatment. Synovial fluid analysis revealed two main clusters of proteins reacting together as a group, showing strong and significant correlations with their fluctuation patterns after hyperacute serum treatment. In conclusion, hyperacute serum has a positive effect in alleviating symptoms of osteoarthritic knees. Moreover, identified protein clusters may allow the prediction of protein expression, reducing the number of investigated proteins in future studies.     

Robotic simulation of identical athletic-task kinematics on cadaveric limbs exhibits a lack of differences in knee mechanics between contralateral pairs

Limb asymmetry is a known factor for increased ACL injury risk. These asymmetries are normally observed during in vivo testing. Prior studies have developed in vitro testing methodologies driven by in vivo kinematics to investigate knee mechanics relative to ACL injury. The objective of this study was to determine if mechanical side-to-side asymmetries persist in contralateral pairs during in vitro simulation testing. In vivo kinematics were recorded for male and female drop vertical jump and sidestep cutting tasks. The recorded kinematics were used to robotically simulate the motions on 7 contralateral pairs of cadaveric lower extremities specimens. ACL and MCL force, torque, and strains were recorded and analyzed for differences between contralateral pairs. There was a general lack of mechanical differences between limb sides. Adduction peak torque for the male sidestep cut movement was significantly different between limb sides (p=0.04). However, this is consistent with ACL injury mechanics in that movement in the frontal plane (abduction/adduction) increases injury risk and it is possible loading differences in this plane may have resulted from tolerances within the setup process. The findings of this study indicate that contralateral knee joints were representative of each other during biomechanical in vitro tests. In future cadaveric robotic simulations, contralateral limbs can be used interchangeably. In addition, direct comparisons of the structural behaviors of isolated conditions for contralateral knee joints can be performed.     

Real-time biofeedback can increase and decrease vertical ground reaction force,knee flexion excursion,and knee extension moment during walking in individuals with anterior cruciate ligament reconstruction

Individuals with anterior cruciate ligament reconstruction (ACLR) often exhibit a “stiffened knee strategy” or an excessively extended knee during gait, characterized by lesser knee flexion excursion and peak internal knee extension moment (KEM). The purpose of this study was to determine the effect of real-time biofeedback (RTBF) cuing an acute change in peak vertical ground reaction force (vGRF) during the first 50% of the stance phase of walking gait on: (1) root mean square error (RMSE) between actual vGRF and RTBF target vGRF; (2) perceived difficulty; and (3) knee biomechanics. Acquisition and short-term recall of these outcomes were evaluated. Thirty individuals with unilateral ACLR completed 4 separate walking sessions on a force-measuring treadmill that consisted of a control (no RTBF) and 3 experimental loading conditions using RTBF including: (1) 5% vGRF increase (high-loading), (2) 5% vGRF decrease (low-loading) and (3) symmetric vGRF between limbs. Bilateral biomechanical outcomes were analyzed during the first 50% of the stance phase, and included KEM, knee flexion excursion, peak vGRF, and instantaneous vGRF loading rate (vGRF-LR) for each loading condition. Peak vGRF significantly increased and decreased during high-loading and low-loading, respectively compared to control loading. Instantaneous vGRF-LR, peak KEM and knee flexion excursion significantly increased during the high-loading condition compared to low-loading. Perceived difficultly and RMSE were lower during the symmetrical loading condition compared to the low-loading condition. Cuing an increase in peak vGRF may be beneficial for increasing KEM, knee flexion excursion, peak vGRF, and vGRF-LR in individuals with ACLR. Clinical Trials Number: NCT03035994.     

Evaluation of an intact,an ACL-deficient,and a reconstructed human knee joint finite element model

The human knee joint has a three-dimensional geometry with multiple body articulations that produce complex mechanical responses under loads that occur in everyday life and sports activities. Understanding the complex mechanical interactions of these load-bearing structures is of use when the treatment of relevant diseases is evaluated and assisting devices are designed. The anterior cruciate ligament (ACL) in the knee is one of four main ligaments that connects the femur to the tibia and is often torn during sudden twisting motions, resulting in knee instability. The objective of this work is to study the mechanical behavior of the human knee joint and evaluate the differences in its response for three different states, i.e., intact, ACL-deficient, and surgically treated (reconstructed) knee. The finite element models corresponding to these states were developed. For the reconstructed model, a novel repair device was developed and patented by the author in previous work. Static load cases were applied, as have already been presented in a previous work, in order to compare the calculated results produced by the two models the ACL-deficient and the surgically reconstructed knee joint, under the exact same loading conditions. Displacements were calculated in different directions for the load cases studied and were found to be very close to those from previous modeling work and were in good agreement with experimental data presented in literature. The developed finite element model for both the intact and the ACL-deficient human knee joint is a reliable tool to study the kinematics of the human knee, as results of this study show. In addition, the reconstructed human knee joint model had kinematic behavior similar to the intact knee joint, showing that such reconstruction devices can restore human knee stability to an adequate extent.     

人工单髁置换治疗膝关节骨关节炎的应用进展

人工单髁关节置换在治疗单间室骨关节炎已经有超过30年的历史,尽管早期的报告不尽如人意,但目前是可靠并安全的治疗关节炎的方法。单髁置换术的成功关键在于合适的患者的选择、细致的手术技术和避免对畸形的过度矫正。本文对人工单髁置换手术的发展历史作了简单回顾,然后分别对膝关节内、外侧单髁置换术患者的选择、手术要点、临床疗效、失败原因作一综述,并对其未来研究进行展望。     

全膝关节置换术对膝关节骨关节炎患者关节功能的影响

目的:探讨全膝关节置换术(TKA)对膝关节骨关节炎患者术后关节功能的影响。方法:回顾性分析2013年8月-2015年8月我院收治的76例膝关节骨关节炎患者的临床资料,所有患者均采用全膝关节置换术治疗。观察并比较患者手术前后膝关节HSS评分、膝关节疼痛目测类比评分(VAS)、膝关节屈曲活动度(ROM)的变化情况。结果:患者术后膝关节HSS评分、膝关节疼痛评分VAS及ROM均明显高于术前,差异具有统计学意义(P0.05);术前HSS评分、膝关节疼痛VAS评分、膝关节ROM、胫骨平台后倾角(PSA)以及股骨前髁偏距(ACO)与术后膝关节HSS评分呈正相关关系,而内翻畸形角度与术后膝关节HSS评分呈负相关关系,差异具有统计学意义(P0.05)。结论:全髋关节置换术能够改善骨关节炎患者的膝关节功能,并且术前膝关节HSS评分、膝关节疼痛VAS评分及PSA与术后患者髋关节功能恢复程度有关。     

Evolutionary morphology of the Tenrecoidea (Mammalia) hindlimb skeleton

The tenrecs of Central Africa and Madagascar provide an excellent model for exploring adaptive radiation and functional aspects of mammalian hindlimb form. The pelvic girdle, femur, and crus of 13 tenrecoid species, and four species from the families Solenodontidae, Macroscelididae, and Erinaceidae, were examined and measured. Results from qualitative and quantitative analyses demonstrate remarkable diversity in several aspects of knee and hip joint skeletal form that are supportive of function‐based hypotheses, and consistent with studies on nontenrecoid eutherian postcranial adaptation. Locomotor specialists within Tenrecoidea exhibit suites of characteristics that are widespread among eutherians with similar locomotor behaviors. Furthermore, several characters that are constrained at the subfamily level were identified. Such characters are more indicative of postural behavior than locomotor behavior. J. Morphol., 2009. © 2008 Wiley‐Liss, Inc.     

Expression of hindlimb abnormalities under rearing temperature effects during the larval development of the salamander Pleurodeles waltl (urodele amphibian)

Anomalie m.p. is a spontaneous and heritable hindlimb abnormality described earlier. Twenty years later, Pleurodeles waltl larvae from the strain bearing anomalie m.p. and reared at room temperature or at 30°C, expressed abnormalities (ectrodactylia, hemimelia, ectromelia). A morphological study of all the hindlimbs and an analysis of the hindlimb skeleton of samples from the experimental animals confirmed that most of the skeletal malformations were identical to those previously reported and affected the disto-proximal and prepostaxial pattern of the hindlimb. Analysis of the effects of rearing temperature on the expression of anomalie m.p. showed that the effects varied according to the developmental period at which the heat treatment was applied; the sooner the heat treatment began, the more numerous and more various were the degrees of severity of the malformations. Moreover, heat treatment induced the expression of two additional malformations not yet described: the first one, named 'reversed knee joint', was characterized by a reversal of the knee joint, and the second one, named 'twisted foot', by a downward twisting of the foot. The epigenetic effects of rearing at 30°C on hindlimb development are discussed with regard to the differentiation or patterning.