Enhanced Osteolysis Targeted Therapy through Fusion of Exosomes Derived from M2 Macrophages and Bone Marrow Mesenchymal Stem Cells: Modulating Macrophage Polarization.

Aseptic loosening of prostheses is a highly researched topic, and wear particle-induced macrophage polarization is a significant cause of peri-prosthetic osteolysis. Exosomes derived from bone marrow mesenchymal stem cells (BMSCs-Exos) promote M2 polarization and inhibit M1 polarization of macrophages. However, clinical application problems such as easy clearance and lack of targeting exist. Exosomes derived from M2 macrophages (M2-Exos) have good biocompatibility, immune escape ability, and natural inflammatory targeting ability. M2-Exos and BMSCs-Exos fused exosomes (M2-BMSCs-Exos) are constructed, which targeted the osteolysis site and exerted the therapeutic effect of both exosomes. M2-BMSCs-Exos achieved targeted osteolysis after intravenous administration inhibiting M1 polarization and promoting M2 polarization to a greater extent at the targeted site, ultimately playing a key role in the prevention and treatment of aseptic loosening of prostheses. In conclusion, M2-BMSCs-Exos can be used as a precise and reliable molecular drug for peri-prosthetic osteolysis. Fused exosomes M2-BMSCs-Exos  were originally proposed and successfully prepared, and exosome fusion technology provides a new theoretical basis and solution for the clinical application of therapeutic exosomes.

Healthy Tendon Stem Cell-Derived Exosomes Promote Tendon-To-Bone Healing of Aged Chronic Rotator Cuff Tears by Breaking the Positive-Feedback Cross-Talk between Senescent Tendon Stem Cells and Macrophages through the Modulation of Macrophage Polarization.

The re-tear rate of rotator cuff tears (RCT) after surgical repair is high, especially in aged patients with chronic tears. Senescent tendon stem cells (s-TSCs) generally exist in aged and chronically torn rotator cuff tendons and are closely associated with impaired tendon-to-bone healing results. The present study found a positive feedback cross-talk between s-TSCs and macrophages. The conditioned medium (CM) from s-STCs can promote macrophage polarization mainly toward the M1 phenotype, whose CM reciprocally accelerated further s-TSC senescence. Additional healthy tendon stem-cells derived exosomes (h-TSC-Exos) can break this positive feedback cross-talk by skewing macrophage polarization from the M1 phenotype to the M2 phenotype, attenuating s-TSCs senescence. S-TSC senescence acceleration or attenuation effects induced by M1 or M2 macrophages are associated with the inhibition or activation of the bone morphogenetic protein 4 signaling pathway following RNA sequencing analysis. Using an aged-chronic rotator cuff tear rat model, it is found that h-TSC-Exos can shift the microenvironment in the tendon-to-bone interface from a pro-inflammatory to an anti-inflammatory type at the acute postoperative stage and improve the tendon-to-bone healing results, which are associated with the rejuvenated s-TSCs. Therefore, this study proposed a potential strategy to improve the healing of aged chronic RCT.

Regulon active landscape reveals cell development and functional state changes of human primary osteoblasts in vivo.

BACKGROUND: While transcription factor (TF) regulation is known to play an important role in osteoblast development, differentiation, and bone metabolism, the molecular features of TFs in human osteoblasts at the single-cell resolution level have not yet been characterized. Here, we identified modules (regulons) of co-regulated genes by applying single-cell regulatory network inference and clustering to the single-cell RNA sequencing profiles of human osteoblasts. We also performed cell-specific network (CSN) analysis, reconstructed regulon activity-based osteoblast development trajectories, and validated the functions of important regulons both in vivo and in vitro. RESULTS: We identified four cell clusters: preosteoblast-S1, preosteoblast-S2, intermediate osteoblasts, and mature osteoblasts. CSN analysis results and regulon activity-based osteoblast development trajectories revealed cell development and functional state changes of osteoblasts. CREM and FOSL2 regulons were mainly active in preosteoblast-S1, FOXC2 regulons were mainly active in intermediate osteoblast, and RUNX2 and CREB3L1 regulons were most active in mature osteoblasts. CONCLUSIONS: This is the first study to describe the unique features of human osteoblasts in vivo based on cellular regulon active landscapes. Functional state changes of CREM, FOSL2, FOXC2, RUNX2, and CREB3L1 regulons regarding immunity, cell proliferation, and differentiation identified the important cell stages or subtypes that may be predominantly affected by bone metabolism disorders. These findings may lead to a deeper understanding of the mechanisms underlying bone metabolism and associated diseases.

Hmga1-overexpressing lentivirus protects against osteoporosis by activating the Wnt/ß-catenin pathway in the osteogenic differentiation of BMSCs.

Postmenopausal osteoporosis is associated with bone formation inhibition mediated by the impaired osteogenic differentiation potential of bone marrow mesenchymal stem cells (BMSCs). However, identifying and confirming the essential genes in the osteogenic differentiation of BMSCs and osteoporosis remain challenging. The study aimed at revealing the key gene that regulated osteogenic differentiation of BMSCs and led to osteoporosis, thus exploring its therapeutic effect in osteoporosis. In the present study, six essential genes related to the osteogenic differentiation of BMSCs and osteoporosis were identified, namely, fibrillin 2 (Fbn2), leucine-rich repeat-containing 17 (Lrrc17), heat shock protein b7 (Hspb7), high mobility group AT-hook 1 (Hmga1), nexilin F-actin-binding protein (Nexn), and endothelial cell-specific molecule 1 (Esm1). Furthermore, the in vivo and in vitro experiments showed that Hmga1 expression was increased during the osteogenic differentiation of rat BMSCs, while Hmga1 expression was decreased in the bone tissue of ovariectomized (OVX) rats. Moreover, the expression of osteogenic differentiation-related genes, the activity of alkaline phosphatase (ALP), and the number of mineralized nodules were increased after Hmga1 overexpression, which was partially reversed by a Wnt signaling inhibitor (DKK1). In addition, after injecting Hmga1-overexpressing lentivirus into the bone marrow cavity of OVX rats, the bone loss, and osteogenic differentiation inhibition of BMSCs in OVX rats were partially reversed, while osteoclast differentiation promotion of BMSCs in OVX rats was unaffected. Taken together, the present study confirms that Hmga1 prevents OVX-induced bone loss by the Wnt signaling pathway and reveals that Hmga1 is a potential gene therapeutic target for postmenopausal osteoporosis.

Text Mining and Drug Discovery Analysis: A Comprehensive Approach to Investigate Diabetes-Induced Osteoporosis.

Purpose: Osteoporosis (OP) and diabetes are prevalent diseases in orthopedic and endocrinology departments, with OP potentially arising as a complication of diabetes. However, the mechanism underlying diabetes-induced osteoporosis (DOP) remains enigmatic, and drug discovery in this domain is restricted, hindering research into the DOP's etiology and treatment. With the ultimate goal of preventing OP in diabetic patients, the objective of this study is to mine the genes and pathways linked to DOP using bioinformatics and databases. Method: The present study employed text mining as the initial approach to retrieve genes commonly associated with diabetes and OP. Subsequently, functional annotation was conducted to investigate the roles and functionalities. In order to explore the interactions between proteins relevant to DOP, we constructed protein-protein interaction (PPI) networks. Furthermore, to obtain key genes and candidate drugs for DOP treatment, we conducted drug-gene interaction (DGI) analysis, complemented by a thorough examination of transcriptional factors (TFs)-miRNA co-regulation. Results: The results through text mining revealed 110 genes that are commonly associated with both diabetes and OP. Subsequent enrichment analysis narrowed down the list to 95 symbols that were involved in PPI analysis. After DGI analysis, we identified 7 genes targeted by 11 drugs, which represent candidates for treating DOP. Conclusion: This study unveils ANDECALIXIMAB, SILTUXIMAB, OLOKIZUMAB, SECUKINUMAB, and IXEKIZUMAB as promising potential drugs for DOP treatment, demonstrating the significance of utilizing text mining and pathway analysis to investigate disease mechanisms and explore existing therapeutic options.

Yoda1 pretreated BMSC derived exosomes accelerate osteogenesis by activating phospho-ErK signaling via Yoda1-mediated signal transmission.

Segmental bone defects, arising from factors such as trauma, tumor resection, and congenital malformations, present significant clinical challenges that often necessitate complex reconstruction strategies. Hydrogels loaded with multiple osteogenesis-promoting components have emerged as promising tools for bone defect repair. While the osteogenic potential of the Piezo1 agonist Yoda1 has been demonstrated previously, its hydrophobic nature poses challenges for effective loading onto hydrogel matrices.In this study, we address this challenge by employing Yoda1-pretreated bone marrow-derived mesenchymal stem cell (BMSCs) exosomes (Exo-Yoda1) alongside exosomes derived from BMSCs (Exo-MSC). Comparatively, Exo-Yoda1-treated BMSCs exhibited enhanced osteogenic capabilities compared to both control groups and Exo-MSC-treated counterparts. Notably, Exo-Yoda1-treated cells demonstrated similar functionality to Yoda1 itself. Transcriptome analysis revealed activation of osteogenesis-associated signaling pathways, indicating the potential transduction of Yoda1-mediated signals such as ErK, a finding validated in this study. Furthermore, we successfully integrated Exo-Yoda1 into gelatin methacryloyl (GelMA)/methacrylated sodium alginate (SAMA)/ß-tricalcium phosphate (ß-TCP) hydrogels. These Exo-Yoda1-loaded hydrogels demonstrated augmented osteogenesis in subcutaneous ectopic osteogenesis nude mice models and in rat skull bone defect model. In conclusion, our study introduces Exo-Yoda1-loaded GELMA/SAMA/ß-TCP hydrogels as a promising approach to promoting osteogenesis. This innovative strategy holds significant promise for future widespread clinical applications in the realm of bone defect reconstruction.

Multifunctional fucoidan-loaded Zn-MOF-encapsulated microneedles for MRSA-infected wound healing.

Infected wound healing remains a challenging task in clinical practice due to several factors: (I) drug-resistant infections caused by various pathogens, (II) persistent inflammation that hinders tissue regeneration and (III) the ability of pathogens to persist intracellularly and evade antibiotic treatment. Microneedle patches (MNs), recognized for their effecacious and painless subcutaneous drug delivery, could greatly enhance wound healing if integrated with antibacterial functionality and tissue regenerative potential. A multifunctional agent with subcellular targeting capability and contained novel antibacterial components, upon loading onto MNs, could yield excellent therapeutic effects on wound infections. In this study, we sythesised a zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) loaded with low molecular weight fucoidan (Fu) and further coating by hyaluronic acid (HA), obtained a multifunctional HAZ@Fu NPs, which could hinders Methicillin-resistant Staphylococcus aureus (MRSA) growth and promotes M2 polarization in macrophages. We mixed HAZ@Fu NPs with photocrosslinked gelatin methacryloyl (GelMA) and loaded it into the tips of the MNs (HAZ@Fu MNs), administered to mice model with MRSA-infected full-thickness cutaneous wounds. MNs are able to penetrate the skin barrier, delivering HAZ@Fu NPs into the dermal layer. Since cells within infected tissues extensively express the HA receptor CD44, we also confirmed the HA endows the nanoparticles with the ability to target MRSA in subcellular level. In vitro and in vivo murine studies have demonstrated that MNs are capable of delivering HAZ@Fu NPs deep into the dermal layers. And facilitated by the HA coating, HAZ@Fu NPs could target MRSA surviving at the subcellular level. The effective components, such as zinc ions, Fu, and hyaluronic acid could sustainably released, which contributes to antibacterial activity, mitigates inflammation, promotes epithelial regeneration and fosters neovascularization. Through the RNA sequencing of macrophages post co-culture with HAZ@Fu, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis reveals that the biological functionalities associated with wound healing could potentially be facilitated through the PI3K-Akt pathway. The results indicate that the synergistic application of HAZ@Fu NPs with biodegradable MNs may serve as a significant adjunct in the treatment of infected wounds. The intricate mechanisms driving its biological effects merit further investigation.

Noninterportal capsulotomy of hip arthroscopy showed improved outcomes in borderline hip dysplasia: A retrospective study with minimum 2-year follow-up.

PURPOSE: The present study aimed to evaluate the functional outcomes of hip arthroscopy using a noninterportal capsulotomy technique to address labral tears in patients with borderline hip dysplasia (BHD). Additionally, we also compared these outcomes with those of patients with BHD who underwent the standard repaired interportal capsulotomy (RIPC) arthroscopy. METHODS: Data from patients with BHD were retrieved from a database of patients who underwent arthroscopic hip surgery with noninterportal capsulotomy or RIPC to treat labral tears between January 2014 and December 2020. Data collected included both pre- and postoperative patient-reported outcomes (PROs). RESULTS: A total of 58 patients (noninterportal capsulotomy, n = 37; RIPC, n = 21) with a mean age of 30.9 ± 5.6 and 28.6 ± 5.5 years, respectively, met the inclusion criteria. All of the patients underwent a minimal 2-year follow-up. The mean lateral centre-edge angle was 23.3 ± 1.2° in the noninterportal capsulotomy group and 23.7 ± 1.0° in the RIPC group, with no significant difference. The PROs improved from the preoperative to the latest follow-up, with a p < 0.001. There were no differences between the groups. CONCLUSION: Using strict patient selection criteria, hip arthroscopy with noninterportal capsulotomy demonstrated significant pre- to postoperative improvements in patients with BHD and achieved results comparable to those from hip arthroscopy with RIPC. LEVEL OF EVIDENCE: Level III.

PLGA nanoparticles engineering extracellular vesicles from human umbilical cord mesenchymal stem cells ameliorates polyethylene particles induced periprosthetic osteolysis.

The wear particle-induced dissolution of bone around implants is a significant pathological factor in aseptic loosening, and controlling prosthetic aseptic loosening holds crucial social significance. While human umbilical cord mesenchymal stem cell-derived exosomes (HucMSCs-Exos, Exos) have been found to effectively promote osteogenesis and angiogenesis, their role in periprosthetic osteolysis remains unexplored. To enhance their in vivo application, we engineered HucMSCs-Exos-encapsulated poly lactic-co-glycolic acid (PLGA) nanoparticles (PLGA-Exos). In our study, we demonstrate that PLGA-Exos stimulate osteogenic differentiation while inhibiting the generation of reactive oxygen species (ROS) and subsequent osteoclast differentiation in vitro. In vivo imaging revealed that PLGA-Exos released exosomes slowly and maintained a therapeutic concentration. Our in vivo experiments demonstrated that PLGA-Exos effectively suppressed osteolysis induced by polyethylene particles. These findings suggest that PLGA-Exos hold potential as a therapeutic approach for the prevention and treatment of periprosthetic osteolysis. Furthermore, they provide novel insights for the clinical management of osteolysis.

Tranexamic Acid Causes Chondral Injury Through Chondrocytes Apoptosis Induced by Activating Endoplasmic Reticulum Stress.

PURPOSE: To investigate whether tranexamic acid (TXA) is cytotoxic in chondrocyte and cartilage tissues, as well as explore the mechanisms behind the possible toxicity in detail. METHODS: We detected the cell viability of chondrocytes in vitro and the change of morphology and specific in vivo contents of cartilage after TXA treatment. Furthermore, we detected apoptosis in cartilage. We used apoptosis-specific staining, reactive oxygen species detection, mitochondrial membrane potential detection, flow cytometry, and western blot for apoptosis detection. Finally, we detected the activation of endoplasmic reticulum stress (ERS) in TXA-treated chondrocytes to clarify the mechanism behind chondrocyte apoptosis. RESULTS: TXA presented an increasing toxic effect with increasing concentrations, especially in the 100 mg/mL group. In addition, we found that 50 mg/mL and 100 mg/mL TXA significantly increased apoptosis in cartilage and subchondral bone. TXA could induce chondrocyte apoptosis in cell and protein levels with reactive oxygen species generation and mitochondrial membrane depolarization. An apoptosis inhibitor could inhibit the induced apoptosis. Next, TXA induced calcium overload in chondrocytes and increased ERS-specific protein expression, whereas ERS inhibitor blocked ERS activation and further inhibited chondrocyte apoptosis. CONCLUSIONS: We concluded that TXA had a toxic effect on chondrocytes by inducing apoptosis through ERS activation, especially in 50 mg/mL and 100 mg/mL groups. We recommend TXA concentrations of less than 50 mg/mL in joint surgeries. CLINICAL RELEVANCE: It is still unclear whether TXA has a toxic effect on cartilage when topically used in joint surgeries. The concentration also varies. This study provides additional evidence that TXA at high concentrations will cause cartilage damage, which will help to provide a new understanding of the clinical administration of TXA.

Dietary inflammation index and osteoarthritis in the elderly: is there a mediating role of physical activity?

We examined whether physical activity (PA) explains the association between dietary inflammatory potential and osteoarthritis (OA) in the elderly. A total of 1249 elderly people (≥65 years) were eligible for this study from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016. The semi-quantitative Food Frequency Questionnaire (FFQ) and Global PA Questionnaire (GPAQ) were used to evaluate the diet and PA of the elderly, respectively. The multivariable logistic regression model estimated the odds ratio (OR) and 95% confidence interval (CI) between Energy-adjusted Dietary Inflammatory Index (E-DII) and OA. The interaction of E-DII and PA on depressive events was tested, and the mediation analysis of PA was performed. The average E-DII in this study was +0.68 (SE 0.08), and the score ranges from -5.32 (most anti-inflammatory) to +4.26 (most pro-inflammatory). In comparison with the first quartile, the elderly from the second quartile (OR: 1.16 [95% CI: 1.06, 1.68]) to the fourth quartile (OR: 1.64 [95% CI: 1.13, 2.37]) had a higher risk of OA before adjustment for PA. An interaction was observed between E-DII and PA in terms of the risk of OA (PInteraction < 0.001). The whole related part was mediated by PA (20.08%). Our findings indicated that the higher pro-inflammatory potential of diet was associated with a higher risk of OA, and low PA was an important part of the mediating factor in the relationship between systemic low-grade dietary inflammation and the risk of OA.

Chemogenetic stimulation of proprioceptors remodels lumbar interneuron excitability and promotes motor recovery after SCI.

Motor recovery after severe spinal cord injury (SCI) is limited due to the disruption of direct descending commands. Despite the absence of brain-derived descending inputs, sensory afferents below injury sites remain intact. Among them, proprioception acts as an important sensory source to modulate local spinal circuits and determine motor outputs. Yet, it remains unclear whether enhancing proprioceptive inputs promotes motor recovery after severe SCI. Here, we first established a viral system to selectively target lumbar proprioceptive neurons and then introduced the excitatory Gq-coupled Designer Receptors Exclusively Activated by Designer Drugs (DREADD) virus into proprioceptors to achieve specific activation of lumbar proprioceptive neurons upon CNO administration. We demonstrated that chronic activation of lumbar proprioceptive neurons promoted the recovery of hindlimb stepping ability in a bilateral hemisection SCI mouse model. We further revealed that chemogenetic proprioceptive stimulation led to coordinated activation of proprioception-receptive spinal interneurons and facilitated transmission of supraspinal commands to lumbar motor neurons, without affecting the regrowth of proprioceptive afferents or brain-derived descending axons. Moreover, application of 4-aminopyridine-3-methanol (4-AP-MeOH) that enhances nerve conductance further improved the transmission of supraspinal inputs and motor recovery in proprioception-stimulated mice. Our study demonstrates that proprioception-based combinatorial modality may be a promising strategy to restore the motor function after severe SCI.

Negative pressure wound therapy versus gauze dressings in managing open fracture wound of lower limbs: A meta-analysis of randomized controlled trials.

BACKGROUND: The superiority of negative pressure wound therapy (NPWT) to standard gauze dressings for managing open fractures of the lower limbs remains controversial. This study aimed to comprehensively compare their clinical efficacy through a meta-analysis using randomized controlled trials (RCTs) alone. We hypothesized that NPWT would be more superior against infections. METHODS: A literature search was implemented in various databases, including PubMed, Web of Science, Medline, Clinicaltrial.gov, and Cochrane Library, etc, to screen eligible RCTs. All included RCTs were evaluated for risk of bias using the Cochrane Collaboration tool. In accordance with the heterogeneity assessment, a fixed-effect or random-effect model was chosen for the data analysis. RESULTS: Ten RCTs, including 2780 patients, were eligible for the meta-analysis. We found that patients in the NPWT group showed a lower overall infection rate (MD=0.70, 95% CI: 0.54-0.90, P = 0.005), acute wound infection rate (MD = 0.35, 95% CI: 0.16-0.77, P = 0.009), and shorter hospital stay (MD = 24.00, 95% CI: 6.82-84.46, P < 0.00001) compared with the control group. The NPWT group showed a higher proportion of patients with wound coverage than the control group. No significant difference was found between the two groups in terms of function score and other complications, including deep infection rate, amputation, and bone nonunion. CONCLUSIONS: From the pooled results, we suggest that NPWT may be superior than traditional gauze dressings for managing open fractures of the lower limbs.

Ferroptosis-related gene signature associates with immunity and predicts prognosis accurately in patients with osteosarcoma.

Osteosarcoma has been the most common malignant bone tumor in children and adolescents, while the 5-y survival of osteosarcoma patients gained no significant improvement over the past decades. This study aimed to explore the role of ferroptosis-related genes (FRGs) in the development and prognosis of osteosarcoma. The datasets of osteosarcoma patients including RNA sequencing data and clinical information were acquired from the TRGET and Gene Expression Omnibus (GEO) databases. The identification of molecular subgroups with different FRG expression patterns was achieved through nonnegative matrix factorization (NMF) clustering. The prognostic model was constructed using the least absolute shrinkage and selection operator (LASSO) algorithm and multivariate Cox regression analysis. The ESTIMATE algorithm was applied for determining the stromal score, immune score, ESTIMA score, and tumor purity of osteosarcoma patients. Functional analyses including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, Gene Set Enrichment Analysis (GSEA), and Gene Set Variation Analysis (GSVA) were conducted to explore the underlying mechanisms in the development and prognosis of osteosarcoma. Two molecular subgroups with different FRGs expression patterns were identified. The molecular subgroups with higher immune score and more active immune status showed better prognostic survival. On the basis of FRGs, a prognostic model and a nomogram integrating clinical characteristics were constructed and their prediction efficiency for osteosarcoma prognosis were well validated. Gene functional enrichment analysis showed that these differentially expressed FRGs were mainly enriched in immunity-related signaling pathways, indicating that FRGs may affect the development and prognosis of osteosarcoma by regulating the immune microenvironment. The expression profiles of FRGs were closely related to the immunity status and prognostic survival of osteosarcoma patients. The interaction between ferroptosis and immunity in the development of osteosarcoma could provide a new insight into the exploration of molecular mechanisms and targeted therapies of osteosarcoma patients.

Fabrication and characterization of microstructure-controllable COL-HA-PVA hydrogels for cartilage repair.

Polyvinyl alcohol (PVA) hydrogel has gained interest in cartilage repair because of its highly swollen, porosity, and viscoelastic properties. However, PVA has some deficiencies, such as its poor biocompatibility and microstructure. This research aimed to design novel hydroxyapatite (HA)-collagen (COL)-PVA hydrogels. COL was added to improve cell biocompatibility, and the microstructure of the hydrogels was controlled by fused deposition modeling (FDM). The feasibility of the COL-HA-PVA hydrogels in cartilage repair was evaluated by in vitro and in vivo experiments. The scanning electron microscopy results showed that the hybrid hydrogels had interconnected macropore structures that contained a COL reticular scaffold. The diameter of the macropore was 1.08-1.85 mm, which corresponds to the diameter of the denatured PVA column. The chondrocytes were then seeded in hydrogels to assess the cell viability and formation of the cartilage matrix. The in vitro results revealed excellent cellular biocompatibility. Osteochondral defects (8 mm in diameter and 8 mm in depth) were created in the femoral trochlear of goats, and the defects were implanted with cell-seeded hydrogels, cell-free hydrogels, or a blank control. The in vivo results showed that the COL-HA-PVA hydrogels effectively repaired cartilage defects, especially the conditions inoculated with chondrocyte in advance. This research suggests that the COL-HA-PVA hydrogels have promising application in cartilage repair.

Is high flexion total knee arthroplasty a rewarding procedure? An updated meta-analysis of prospective randomized controlled trials.

INTRODUCTION: The aim of this study is to provide an updated meta-analysis comparing the benefits and clinical outcomes between high flexion (HF)-TKA and standard (S)-TKA. MATERIALS AND METHODS: A detailed database analysis was carried out using Web of Science, PubMed, EMBASE, Cochrane Library, MEDLINE and Clinicaltrial.gov, to identify eligible studies. The meta-analysis and sensitivity analysis were performed using Review Manager 5.3 software and STATA 12.0. RESULTS: Twenty-two randomized control trials (RCTs), including 2841 patients and 4268 knees, were eligible for the meta-analysis. The pooled results of subgroup analysis reveal that there was significant difference between HF-TKA and S-TKA in each subgroup in terms of postoperative ROM, with a higher degree of knee flexion for HF-TKA than S-TKA. However, no statistical difference was identified between HF-TKA and S-TKA in other clinical outcomes including various functional scores and complications. CONCLUSIONS: On the basis of this meta-analysis, we can recommended HF-TKA as an alternative choice to S-TKA for patients requiring higher knee flexion in their daily activities.

Lateral augmentation reconstruction system versus modified Brostrom-Gould procedure: A meta-analysis of RCTs.

BACKGROUND: The aim of this study is to compare the clinical efficacy between the ligament augmentation reconstruction system (LARS) and the modified Brostrom-Gould (MBG) operations in the treatment of chronic ankle instability. METHODS: We searched the MEDLINE, EMBASE, PubMed, Web of Science, the Cochrane library, and the Clinicaltrial.gov databases for eligible studies. The Review Manager 5.3 software was applied to compare various postoperative functional scoring, ankle stability and complications between the two groups. RESULTS: Four randomized controlled trials including a total of 209 patients were conducted. No significant difference was found in terms of postoperative FAOS, FAAM, ankle stability and complications between the LARS and MBG group. CONCLUSIONS: The present meta-analysis suggested that there was no clinical superiority for the LARS operation over the MBG operation for patients with chronic ankle instability.

Pseudogene PTENP1 sponges miR-214 to regulate the expression of PTEN to modulate osteoclast differentiation and attenuate osteoporosis.

BACKGROUND AIMS: Osteoporosis (OP) is a common bone metabolic disease with a high incidence. Our study aimed to explore the pseudogene PTENP1/miR-214/PTEN axis to modulate the osteoclast differentiation in osteoporosis. METHODS: Patients with osteoporosis were recruited in our study, and RANKL-induced osteoclast differentiation and ovariectomy-induced osteoporosis mouse model were established in vitro and in vivo, respectively. RESULTS: Pseudogene PTENP1 and PTEN were significantly down-regulated and miR-214 was up-regulated in osteoporosis patients. In addition, overexpression of PTENP1 or silence of miR-214 inhibited the expression levels of osteoclast specific markers and osteoclast differentiation induced by RANKL. Overexpression of PTENP1 or silence of miR-214 also inhibited the levels of phosphorylation of PI3K and AKT, p65 nuclear translocation, IκBα degradation and the expression level of NFATc1. AlsoSilence of PTENP1 or overexpression of miR-214 induced the osteoclast differentiation under normal physiological condition. Pseudogene PTENP1 sponged miR-214 to regulate the expression of PTEN. CONCLUSIONS: In an ovariectomy-induced osteoporosis mouse model, obvious pathological changes in bone tissues were found, and bone marrow mononuclear cells in this group were more likely to differentiate into osteoclasts. Therefore, pseudogene PTENP1 sponged miR-214 to regulate the expression of PTEN to inhibit osteoclast differentiation and attenuate osteoporosis by suppressing the PI3K/AKT/NF-κB signaling pathway.

Surgery simulation teaching based on real reconstruction aid versus traditional surgical live teaching in the acquisition of an adult total hip arthroplasty surgical technique for developmental dysplasia of the hip: a randomized comparative study.

BACKGROUND: A simulation and model (SM) teaching aid using 3D printing was developed to improve a training course for total hip arthroplasty of adult developmental dysplasia of the hip (adult DDH-THA). We named this new method Surgery Simulation Teaching based on a Real Reconstruction Aid (RRA-SST). A prospective randomized comparison was performed with the traditional surgical live teaching method to evaluate the training effectiveness of RRA-SST for adult DDH-THA. METHODS: Twenty-six trainees, who were already practicing but were not experienced, participated in the study. We randomly divided the trainees into two groups: Group A (n = 13) received RRA-SST and group B (n = 13) received traditional surgical live teaching. A surgery simulation test and a questionnaire were used for evaluation. Next, each group received training with the other teaching method, and then the test and questionnaire were used again for evaluation. RESULTS: After the first test, the RRA-SST method was shown to produce better results than the traditional surgical live teaching method. After the second test, the results showed the training effect in both groups reached the same level, which was level as Group A RRA-SST results. Analysis of the questionnaire results showed that the training effect of RRA-SST was higher than that of traditional surgical live teaching, from multiple perspectives. CONCLUSIONS: The use of RRA-SST improved participant performance according to simulation assessment. RRA-SST can be helpful for trainees who are already practicing but not experienced when developing proficiency in adult DDH-THA surgical techniques.

Effect of patient-specific instrument on lowering threshold for junior physicians to perform total hip arthroplasty on developmental dysplasia of the hip patients.

PURPOSE: To create a patient-specific instrument (PSI) in lowering the surgical experience requirement for junior physicians to perform total hip arthroplasty (THA) on developmental dysplasia of the hip (DDH) patients. METHODS: Combined with rapid prototyping technology, we created a PSI and established DDH hip model in vitro. We enrolled 48 junior physicians and randomly assigned them into two groups. After creation of the PSI, they performed simulated THA surgery on a full-scale hip model with or without PSI on DDH models. The planned prothesis orientation, post-operative prothesis orientation, and surgery time were recorded. RESULTS: The final cup inclination was 42.0 ± 0.8° in PSI group and 37.8 ± 2.0° in control group, while final cup anteversion was 16.0 ± 0.7° in PSI group and 24.7 ± 3.5° in control group. The △inclination in PSI group was smaller than that in control group (4.2 ± 0.5° vs 9.5 ± 1.4°, P < 0.01), so does △inclination (2.9 ± 0.4° in PSI group vs 15.2 ± 2.5° in control group, P < 0.01). The outlier percent was 8.3% in PSI group and 70.8% in control group (P < 0.01). At the same time, the PSI group did not prolong the operation time (P = 0.551). CONCLUSION: The PSI can greatly increase the accuracy of placing the cup orientation and lower the threshold for junior physicians to perform THA on DDH patients. It could be a training tool for them to increase their THA surgical skills.