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Osteoarthritis (OA) is a common degenerative joint disease which currently lacks of effective agents. It is therefore urgent and necessary to seek an effective approach that can inhibit inflammation and promote cartilage matrix homeostasis. Cartilage progenitor cells (CPCs) are identified as a cell population of superficial zone in articular cartilage which possess strong migration ability, proliferative capacity, and chondrogenic potential. Recently, the application of CPCs may represent a novel cell therapy strategy for OA treatment. There is growing evidence that extracellular vesicles (EVs) are primary mediators of the benefits of stem cell-based therapy. In this study, we explored the protective effects of CPCs-derived EVs (CPCs-EVs) on IL-1β-induced chondrocytes. We found CPCs-EVs exhibited chondro-protective effects in vitro. Furthermore, our study demonstrated that CPCs-EVs promoted matrix anabolism and inhibited inflammatory response at least partially via blocking STAT3 activation. In addition, liquid chromatography-tandem mass spectrometry analysis identified 991 proteins encapsulated in CPCs-EVs. By bioinformatics analysis, we showed that STAT3 regulatory proteins were enriched in CPCs-EVs and could be transported to chondrocytes. To promoting the protective function of CPCs-EVs in vivo, CPCs-EVs were modified with cationic peptide ε-polylysine-polyethylene-distearyl phosphatidylethanolamine (PPD) for surface charge reverse. In posttraumatic OA mice, our results showed PPD modified CPCs-EVs (PPD-EVs) effectively inhibited extracellular matrix catabolism and attenuated cartilage degeneration. Moreover, PPD-EVs down-regulated inflammatory factors expressions and reduced OA-related pain in OA mice. In ex-vivo cultured OA cartilage explants, PPD-EVs successfully promoted matrix anabolism and inhibited inflammation. Collectively, CPCs-EVs-based cell-free therapy is a promising strategy for OA treatment. [ABSTRACT FROM AUTHOR]

Background: Kashin–Beck disease (KBD) is an endemic, chronic osteoarthropathy that seriously affects joint function and can lead to severe knee deformity. Osteotomy is considered to be one of the effective methods for the treatment of this disease. Therefore, we designed a novel type of osteotomy named combined proximal tibial osteotomy (CPTO), which combines the characteristics of opening‐wedge high tibial osteotomy and tibial condylar valgus osteotomy. Case presentation: We report the case of a 48‐year‐old male with knee pain and varus deformity who was diagnosed with KBD and varus knee osteoarthritis (Kellgren–Lawrence stage IV). Considering the patient's relatively young age, a varus deformity of the right knee of 16.79°, and an intra‐articular instability, we performed a CPTO treatment. In this procedure, we performed an L‐shaped osteotomy from the medial edge of the proximal tibia to the intercondylar eminence and an osteotomy from the medial side of the proximal tibia to the lateral side through the same incision, to adjust the leg alignment and the congruity of the joint by valgus correction. At 29 months follow‐up, this patient achieved satisfactory results, with a varus right knee of 2.87°. There was significant improvement in his right knee function, pain, and joint stability. Conclusions: CPTO may be an acceptable treatment for KBD patients with severe knee varus deformity and intra‐articular instability. It can be considered as an alternative treatment, especially for patients with advanced osteoarthritis needing knee preservation. [ABSTRACT FROM AUTHOR]

Complex-valued neural network is a kind of learning model which can deal with problems in complex domain. Fully complex extreme learning machine (CELM) is a much faster training algorithm than the complex backpropagation (CBP) scheme. However, it is at the cost of using more hidden nodes to obtain the comparable performance. An upper-layer-solution-aware algorithm has been proposed for training single-hidden layer feedforward neural networks, which performs much better than its counterparts, pseudo-inverse learning (PIL)/extreme learning machine and gradient decent-based backpropagation neural networks. Consequently, there exist two challenges that need to be dealt with: 1) How to combine the advantages of CBP and CELM to develop a novel complex learning algorithm? and 2) What is the convergent behavior of the presented algorithm? In this article, an input weights dependent complex-valued (IWDCV) learning algorithm based on Wirtinger calculus has been proposed, which effectively solves the nonanalytic problem of the common activation functions during training neural networks. In addition, the monotonicity of the error function and the deterministic convergence of the proposed model have been strictly proved, which theoretically guarantee the efficiency and effectiveness of the given model, IWDCV. Finally, for real and complex-valued problems, a variety of simulations have been done to demonstrate the comparable performance of the proposed algorithm which support the theoretical observations as well. [ABSTRACT FROM AUTHOR]

This brief proposes an enhanced fractional derivative that can prevent the tap weight coefficients from destroying the gradient information, solve the problem caused by the fractional extreme point, and improve the convergence speed with the help of error estimation information and Sign function. Based on this fractional derivative, an enhanced fractional least mean square (EFLMS) filter algorithm is proposed. We analyze the influence of unknown system vector on the convergence performance of the EFLMS algorithm. The computational complexity of the proposed algorithm is also analyzed. Simulation experiments show that the EFLMS algorithm achieves better performance in system identification than the classic least mean square (LMS) algorithm and the existing algorithms based on fractional calculus. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cell‐derived small extracellular vesicles (MSC‐sEVs) possess a great therapeutical potential for osteoarthritis (OA) treatment. However, the steric and electrostatic hindrance of cartilage matrix leads to very limited distribution of MSC‐sEVs in cartilage and low bioavailability of MSC‐sEVs after intra‐articular injection. To overcome this, a strategy to reverse the surface charge of MSC‐sEVs by modifying the MSC‐sEVs with a novel cationic amphiphilic macromolecule namely ε‐polylysine‐polyethylene‐distearyl phosphatidylethanolamine (PPD) was developed in this study. Through incubation with 100 μg/ml PPD, positively charged MSC‐sEVs (PPD‐sEVs) were obtained, and the modification process showed nearly no disturbance to the integrity and contents of sEVs and exhibited good stability under the interference of anionic macromolecules. A more effective cellular uptake and homeostasis modulation ability of PPD‐sEVs than unmodified MSC‐sEVs to chondrocytes was demonstrated. More importantly, PPD‐sEVs demonstrated significantly enhanced cartilage uptake, cartilage penetration, and joint retention capacity as compared to MSC‐sEVs. Intra‐articular injection of PPD‐sEVs into a mouse OA model showed significantly improved bioavailability than MSC‐sEVs, which resulted in enhanced therapeutic efficacy with reduced injection frequency. In general, this study provides a facile and effective strategy to improve the intra‐articular bioavailability of MSC‐sEVs and has a great potential to accelerate the clinical practice of MSC‐sEVs based OA therapy. [ABSTRACT FROM AUTHOR]

Background: Anterior cruciate ligament (ACL) tears are commonly seen with concomitant injuries to the posterolateral tibial plateau, while the occurrence of ACL injuries in posterolateral tibial plateau fractures (PTPFs) remains unclear., Purpose: To (1) explore the incidence of knee ligament (anterior or posterior cruciate ligament, medial or lateral collateral ligament) and medial or lateral meniscus injuries in patients with PTPF and (2) find reliable PTPF-related parameters to predict the risk of knee ligament and meniscal injuries., Study Design: Cross-sectional study; Level of evidence, 3., Methods: Patients diagnosed with PTPF who had computed tomography and magnetic resonance imaging (MRI) data were identified. Morphological parameters of the PTPF were measured on sagittal computed tomography images. Knee ligament and meniscal injuries were assessed using MRI. The association of ACL injuries with meniscal injuries was analyzed. Receiver operating characteristic (ROC) analysis was used to determine the value and cutoff point of the PTPF morphological parameters for diagnosing complete in-substance ACL tears., Results: Overall, 113 patients with PTPF were included. ACL injuries were present in 94 (83.2%) patients, including 43 (38.1%) avulsion fractures and 28 (24.8%) complete in-substance tears. Patients with in-substance ACL tears had a higher incidence of lateral meniscus posterior horn tears compared with the other patients ( P Bonferroni < .001). ROC analysis revealed that both the fracture depression angle (cutoff point, 25.5°) and the posterior articular surface loss percentage (cutoff point, 37.5%) had a sensitivity >90% and a specificity >80% for the diagnosis of complete in-substance ACL tears., Conclusion: ACL injuries were seen in 83.2% of the study patients. Complete in-substance ACL tears were associated with an increased incidence of lateral meniscus posterior horn tears. Among PTPF parameters, fracture depression angle and posterior articular surface loss percentage showed a high predictive value for the presence of complete in-substance ACL tears, thereby reducing delays in diagnosis and treatment., Competing Interests: The authors declared that they have no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto. Ethical approval for this study was obtained from the Ethics Committee of Shanghai Sixth People's Hospital (reference No. 2023-033)., (© The Author(s) 2024.)

Background: The surgical treatment of posterolateral tibial plateau fractures involves a challenging and diverse set of considerations, one of which is the lack of proper and satisfactory internal fixations to purchase posterolateral fragments. Evaluating the configuration of internal fixations is often overlooked, despite it being important to outcomes of fracture fixation. This study aimed to (I) propose a new digital methodology of internal fixation evaluation that based on actual fracture cases and (II) evaluate the fixation effectiveness of four commercially available proximal tibial lateral plate-screw constructs for posterolateral fragments., Methods: Tibial plateau fractures involving the posterolateral column were retrospectively reviewed. The reconstructed three-dimensional (3D) fracture models were virtually reduced, and targeted internal fixations were modeled digitally in specialized software. Four implants from three manufacturers (DePuy Synthes, Westchester, NY, USA; Zimmer, Warsaw, IN, USA; and Biomet, Warsaw, IN, USA) were placed on each fracture in an optimal position to simulate surgical fixation and quantitatively evaluate fixation effectiveness. The fragment was considered to be "captured" if it was purchased by at least two screws. The 3D fracture maps and heat maps were created by graphically superimposing all uncaptured fracture fragments onto a tibia template., Results: This study included 144 posterolateral tibial plateau fractures. When not using screws in a variable angle (VA) manner, the fixation effectiveness for posterolateral fragments was 58.3% for the DePuy Synthes locking compression plates (LCP), 47.9% for the DePuy Synthes VA-LCP, 50.7% for the Zimmer plate, and 43.8% for the Biomet plate. In contrast, the capturing rates boosted to 76.4% and 71.5% when utilizing VA screws in the DePuy Synthes VA-LCP and the Biomet plate. The high-frequency uncaptured areas tended to concentrate on the rim of the posterolateral wall and were mainly distributed in the posterior 1/2 to 3/4 of the parallel position of the fibula head., Conclusions: The proposed new digital methodology was demonstrated feasible and may improve the quantitative evaluation of the implants and optimize the design of implants. The commercially available proximal tibial lateral plate-screw constructs were insufficient in capturing posterolateral fragments, and design-improved or additional implants may be necessitated., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-750/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: Distal femur fractures are complex injuries with a high rate of fracture healing problems. Since the widespread of computed tomographic imaging in the diagnosis of distal femur fractures, many fracture characteristics have been discovered. This study aimed to depict the location and frequency of distal femur fracture lines and further analyze the morphological characteristics using the 3-dimensional computed tomography (CT) mapping technique, thus providing more information to solve this challenging clinical problem., Methods: In total, 217 distal femur fractures in 216 patients were retrospectively reviewed. Fracture fragments on CT were digitally reconstructed and virtually reduced to match a template model. The contour of every fracture fragment was then marked with smooth curves, and the overlap of all fracture lines allowed for the creation of 3-dimensional fracture maps and heat maps. Fracture characteristics were summarized based on these maps., Results: This study included 114 left knee injuries, 101 right knee injuries, and 1 case with bilateral injury. Distal femur fractures were most likely to occur among patients aged 61 to 70 years. On the heat map of all 217 fractures, fracture line hot zones were mainly concentrated around the metaphysis, the lateral part of the intercondylar notch, and the patellofemoral joint. Distal femur fractures with three Arbeitsgemeinschaft für Osteosynthesefragen Foundation/Orthopaedic Trauma Association (AO/OTA) types demonstrated distinct fracture characteristics. In total, there were 58 coronal plane fractures (41.1%) in 141 intercondylar fractures., Conclusions: The intercondylar fracture patterns in AO/OTA type B and type C fractures were similar, while the supracondylar characteristics in AO/OTA type A and type C were different. The findings in this study can help orthopaedic surgeons better understand the fracture morphology on the basis of AO/OTA classification. Further studies are needed to establish a standard biomechanical fracture model and new fixation strategy for better clinical outcomes., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-21-4591/coif). The authors report that this study was granted by AO Innovation Translation Center of the AO Foundation to reveal the morphologic details of the distal femur fractures (AO/OTA types 33A, 33B, and 33C). The authors have no other conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: Multi-fragmentary patella fractures (MFPFs) are common patella fracture type. Low-profile plate fixation seems to be promising advancement in the treatment of such difficult fractures. There is no systematic morphologic study specifically for MFPFs to provide objective reference for the improvement of future implants and biomechanical models. This study aimed to delineate and quantify the location and spatial frequency of fracture lines, comminution zones, and coronal plane fragments in MFPFs using three-dimensional (3D) CT mapping technique., Methods: A total of 187 MFPFs were retrospectively reviewed and analyzed. Fractures were digitally reconstructed from CT data, and fracture lines, comminution zones, and coronal fragments were graphically overlaid onto a 3D patella template. Fracture characteristics were summarized qualitatively based on the fracture maps and quantitatively on the counts and volume of each fragment. Furthermore, according to the classic fracture patterns concerning MFPFs, subgroup analysis was conducted., Results: On average, we observed 7 fragments in each fracture, 3 of which were <1 cm 3 . Most fractures (81.2%) had coronal fragments on the anterior and/or posterior patella surfaces. We identified three classic patella fracture patterns: transverse with comminution, stellate, and "displaced comminuted" in 104, 54, and 29 knees, respectively. 3D maps demonstrated distinct distribution fracture patterns of fracture lines, comminution zones, and coronal fragments., Conclusions: Supero-medial corner of the patella was seldomly involved, and might be used as the cornerstone for fixation. Coronal fragments were common on both anterior and posterior patella surfaces, justifying the application of anterior plate osteosynthesis characterized by multi-planar fixation. Comminution areas mainly concentrated in the lower half of the patella, potentially suitable for an implant in combination with sutures or circumferential cerclage wiring. The described 3D features of MFPFs could provide reference for the design of future implants and biomechanical models., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-1814). The authors report that this study was granted by AOTrauma Asia Pacific of the AO Foundation to reveal the morphologic details of the multi-fragmentary patella fracture (AO/OTA-34C3)., (2021 Annals of Translational Medicine. All rights reserved.)