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Background: The association between brain and sarcopenia has not been clarified. We aim to investigate the causal association between brain structure, function, gene expression and sarcopenia-related traits., Methods: All participants were Europeans. GWAS data of Brain Imaging Data Structure (BIDs) was from the UK Biobank. Gene expression in 13 brain regions was acquired from the GTEx Consortium. The sarcopenia-related traits, including appendicular lean mass (ALM), whole body lean mass (WBLM), grip strength and sarcopenia diagnosed by the European Working Group on Sarcopenia in Older People (EWGSOP) or Foundation for the National Institutes of Health (FNIH), were from the IEU website. The inverse variance weighted (IVW), MR Egger, weighted median, weighted mode and Wald ratio methods were used for a two-sample Mendelian randomization (MR) analysis between brain structures and sarcopenia-related traits. The summary-data-based MR (SMR) was used to investigate brain genes causally influencing sarcopenia. We calculated the F-value, odds ratio with 95% CI and p-value. For the sensitivity analysis, the heterogeneity I 2 statistic, Cochrane's Q test, Egger's intercept test, MR-PRESSO and the leave-one-out sensitivity test were used. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein-protein interaction (PPI), transcription factor interaction prediction and miRNA interaction prediction analysis were used to reveal potential signalling pathways and mechanisms., Results: We included 3144 imaging phenotypes from 8428 participants in BIDs data. One hundred forty-one BIDs were identified to causally influence ALM, 160 BIDs showed significant causal effect on the WBLM, and 86 BIDs showed significant causal effect on grip strength. There were 48 or 32 BIDs causally associated with sarcopenia diagnosed by the EWGSOP or FNIH criteria respectively. After FDR correction, there were 35 BIDs showing causal effect on the ALM, 28 BIDs showing causal effect on the WBLM and 7 BIDs showing causal effect on grip strength (p < 0.05). Twelve to forty-eight genes in different brain regions showed causal effect on all the five sarcopenia-related traits. MMP24-AS1, HLA-DRB6, HLA-DQA2, DDX42, BAG6, NUSAP1, LINC00940, NME1-NME2 and AS3MT in the amygdala region showed detrimental effect on all the five sarcopenia-related traits, whereas HLA-DRB1, HLA-DQB1-AS1 and C6ORF3 showed protective effect (p < 0.05). The gene enrichment analysis indicated these screened genes was mainly enriched in immune-related signalling., Conclusion: We discovered the causal effect of BIDs and brain gene expression on sarcopenia. The positive genes were mainly enriched in immune-related signalling, suggesting an immune-based cross-organ regulation mechanism of brain-muscle axis., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Suspension bath-based 3D bioprinting (SUB3BP) is effective in creating engineered vascular structures. The transfer of oxygen and nutrients via engineered vascular networks is necessary for tissue or organ survival and integration following transplantation. Existing SUB3BP techniques face challenges in fabricating hierarchical structures with multicellular organization, including issues related to suspension bath removal, restricted material choices, and low accuracy. A next-generation SUB3BP technique that is removal-free and multicellular is presented. A simple, storable, stable, and scalable starch hydrogel design leverages the diverse spectrum of hydrogels available for use in SUB3BP. Starch granules (8.1 µm) create vascular structures with minimal surface roughness (2.5 µm) that simulate more natural vessel walls compared to prior research. The development of cells and organoids, as well as the bioprinting of multicellular skin models with vasculature, demonstrates that starch suspension baths eliminate the removal process and have the potential for fabricating artificial tissue with a hierarchical structure and multicellular distribution., (© 2024 Wiley‐VCH GmbH.)

Diabetic infected bone defects (DIBD) with abnormal immune metabolism are prone to the hard-to-treat bacterial infections and delayed bone regeneration, which present significant challenges in clinic. Control of immune metabolism is believed to be important in regulating fundamental immunological processes. Here, we developed a macrophage metabolic reprogramming hydrogel composed of modified silk fibroin (Silk-6) and poly-l-lysine (ε-PL) and further integrated with M2 Macrophage-derived Exo (M2-Exo), named Silk-6/ε-PL@Exo. This degradable hydrogel showed a broad-spectrum antibacterial performance against both Gram-positive and -negative bacteria. More importantly, the release of M2-Exo from Silk-6/ε-PL@Exo could target M1 macrophages, modulating the activity of the key enzyme hexokinase II (HK2) to control the inflammation-related NF-κB pathway, alleviate lactate accumulation, and inhibit glycolysis to normalize the cycle, thereby promoting M1-to-M2 balance. Using a rat model of DIBD, Silk-6/ε-PL@Exo hydrogel promoted infection control, balanced immune responses and accelerated the bone defect healing. Overall, this study demonstrates that this Silk-6/ε-PL @Exo is a promising filler biomaterial with multi-function to treat DIBD and emphasizes the importance of metabolic reprogramming in bone regeneration., Competing Interests: Declaration of competing interest Pengfei Lei reports financial support was provided by Key Project of Research and Development Plan of Hunan Province. Pengfei Lei reports financial support was provided by Major Science and Technology Projects of changsha. Pengfei Lei reports financial support was provided by the Natural Science Foundation Exploration Project of Zhejiang Province. Pengfei Lei reports financial support was provided by the Medical and Health Research Project of Zhejiang Province. Pengfei Lei reports was provided by Natural Science Foundation of Hunan Province. Pengfei Lei reports financial support was provided by National Key Research and Development Program of China. Yihe Hu reports financial support was provided by the Zhejiang Province Leading Geese Plan. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The regeneration of peripheral nerves after injury is often slow and impaired, which may be associated with weakened and denervated muscles subsequently leading to atrophy. Adipose-derived stem cells (ADSCs) are often regarded as cell-based therapeutic candidate due to their regenerative potential. The study aims to assess the therapeutic efficacy of gene-modified ADSCs on sciatic nerve injury. We lentivirally transduced ADSCs with shRNA-TWIST1 and transplanted modified cells to rats undergoing sciatic nerve transection and repair. Results showed that TWIST1 knockdown accelerated functional recovery of rats with sciatic nerve injury as faster nerve conduction velocity and higher wire hang scores obtained by rats transplanted with TWIST1-silenced ADSCs than scramble ADSCs. Although the rats experienced degenerated axons and decreased myelin sheath thickness after sciatic nerve injury 8 weeks after operation, those transplanted with TWIST1-silenced ADSCs exhibited more signs of regenerated nerve fibers surrounded by newly formed myelin sheaths than those with scramble ADSCs. The rats transplanted with TWIST1-silenced ADSCs presented increased expressions of neurotrophic factors including neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glial cell line-derived neurotrophic factor (GDNF) in the sciatic nerves than those with scramble ADSCs. These results suggest that genetically modifying TWIST1 in ADSCs could facilitate peripheral nerve repair after injury in a more efficient way than that with ADSCs alone., (© 2024. The Author(s).)

Currently, the treatment of bone defects in arthroplasty is a challenge in clinical practice. Nonetheless, commercially available orthopaedic scaffolds have shown limited therapeutic effects for large bone defects, especially for massiveand irregular defects. Additively manufactured porous tantalum, in particular, has emerged as a promising material for such scaffolds and is widely used in orthopaedics for its exceptional biocompatibility, osteoinduction, and mechanical properties. Porous tantalum has also exhibited unique advantages in personalised rapid manufacturing, which allows for the creation of customised scaffolds with complex geometric shapes for clinical applications at a low cost and high efficiency. However, studies on the effect of the pore structure of additively manufactured porous tantalum on bone regeneration have been rare. In this study, our group designed and fabricated a batch of precision porous tantalum scaffolds via laser powder bed fusion (LPBF) with pore sizes of 250 μm (Ta 250), 450 μm (Ta 450), 650 μm (Ta 650), and 850 μm (Ta 850). We then performed a series of in vitro experiments and observed that all four groups showed good biocompatibility. In particular, Ta 450 demonstrated the best osteogenic performance. Afterwards, our team used a rat bone defect model to determine the in vivo osteogenic effects. Based on micro-computed tomography and histology, we identified that Ta 450 exhibited the best bone ingrowth performance. Subsequently, sheep femur and hip defect models were used to further confirm the osteogenic effects of Ta 450 scaffolds. Finally, we verified the aforementioned in vitro and in vivo results via clinical application (seven patients waiting for revision total hip arthroplasty) of the Ta 450 scaffold. The clinical results confirmed that Ta 450 had satisfactory clinical outcomes up to the 12-month follow-up. In summary, our findings indicate that 450 μm is the suitable pore size for porous tantalum scaffolds. This study may provide a new therapeutic strategy for the treatment of massive, irreparable, and protracted bone defects in arthroplasty., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Pengfei Lei reports financial support was provided by Key Project of Research and Development Plan of Hunan Province. Pengfei Lei reports financial support was provided by Major Science and Technology Projects of changsha. Pengfei Lei reports financial support was provided by the Clinical Research Fund of the National Clinical Research Center for Geriatric Disorders. Pengfei Lei reports financial support was provided by the Natural Science Foundation Exploration Project of Zhejiang Province,. Pengfei Lei reports financial support was provided by the Medical and Health Research Project of Zhejiang Province. Pengfei Lei reports was provided by Natural Science Foundation of Hunan Province. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Implant-associated infection (IAI) is a prevalent and potentially fatal complication of orthopaedic surgery. Boosting antibacterial immunity, particularly the macrophage-mediated response, presents a promising therapeutic approach for managing persistent infections. In this study, we successfully isolated and purified a homogeneous and neutral water-soluble polysaccharide, designated as AM-1, from the edible fungus Agaricus blazei Murrill. Structure analysis revealed that AM-1 (Mw = 3.87 kDa) was a low-molecular-weight glucan characterized by a primary chain of →4)-α-D-Glcp-(1 → and side chains that were linked at the O-6 and O-3 positions. In vivo assays showed that AM-1 effectively attenuated the progression of infection and mitigated infectious bone destruction in IAI mouse models. Mechanistically, AM-1 promotes intracellular autophagy-lysosomal biogenesis by inducing the nuclear translocation of transcription factor EB, finally enhancing the bactericidal capabilities and immune-modulatory functions of macrophages. These findings demonstrate that AM-1 significantly alleviates the progression of challenging IAIs as a presurgical immunoenhancer. Our research introduces a novel therapeutic strategy that employs natural polysaccharides to combat refractory infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Macrophage metabolism dysregulation, which is exacerbated by persistent stimulation in infectious and inflammatory diseases, such as diabetic infectious bone defects (DIBD), eventually leads to the failure of bone repair. Here, we have developed an injectable, macrophage-modulated GAPDH-Silence drug delivery system. This microsphere comprises chondroitin sulfate methacrylate (CM) and methacrylated gelatin (GM), while the dimethyl fumarate (DMF)-loaded liposome (D-lip) is encapsulated within the microsphere (CM@GM), named D-lip/CM@GM. Triggered by the over-expressed collagenase in DIBD, the microspheres degrade and release the encapsulated D-lip. D-lip could modulate metabolism by inhibiting GAPDH, which suppresses the over-activation of glycolysis, thus preventing the inflammatory response of macrophages in vitro. While beneficial for macrophages, D-lip/CM@GM is harmful to bacteria. GAPDH, while crucial for glycolysis of staphylococcal species (S. aureus), can be effectively countered by D-lip/CM@GM. We are utilizing existing drugs in innovative ways to target central metabolism for effective eradication of bacteria. In the DIBD model, our results confirmed that the D-lip/CM@GM enhanced bacteria clearance and reprogrammed dysregulated metabolism, thereby significantly improving bone regeneration. In conclusion, this GAPDH-Silence microsphere system may provide a viable strategy to promote diabetic infection bone regeneration., (© 2024. The Author(s).)

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., (© 2024 The Authors. Small published by Wiley‐VCH GmbH.)

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)/β-tricalcium phosphate (β-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/β-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., (© 2024. The Author(s).)

Background: Unrepairable massive rotator cuff tears (UMRCTs) are challenging to surgeons owing to the severely retracted rotator cuff musculotendinous tissues and extreme defects in the rotator cuff tendinous tissues., Purpose: To fabricate a tendon stem cell-derived exosomes loaded scaffold (TSC-Exos-S) and investigate its effects on cellular bioactivity in vitro and repair in a rabbit UMRCT model in vivo., Study Design: Controlled laboratory study., Methods: TSC-Exos-S was fabricated by loading TSC-Exos and type 1 collagen (COL-I) into a 3-dimensional bioprinted and polycaprolactone (PCL)-based scaffold. The proliferation, migration, and tenogenic differentiation activities of rabbit bone marrow stem cells (BMSCs) were evaluated in vitro by culturing them in saline, PCL-based scaffold (S), COL-I loaded scaffold (COL-I-S), and TSC-Exos-S. In vivo studies were conducted on a rabbit UMRCT model, where bridging was repaired with S, COL-I-S, TSC-Exos-S, and autologous fascia lata (FL). Histological and biomechanical analyses were performed at 8 and 16 weeks postoperatively., Results: TSC-Exos-S exhibited reliable mechanical strength and subcutaneous degradation, which did not occur before tissue regeneration. TSC-Exos-S significantly promoted the proliferation, migration, and tenogenic differentiation of rabbit BMSCs in vitro. In vivo studies showed that UMRCT repaired with TSC-Exos-S exhibited significant signs of tendinous tissue regeneration at the bridging site with regard to specific collagen staining. Moreover, no significant differences were observed in the histological and biomechanical properties compared with those repaired with autologous FL., Conclusion: TSC-Exos-S achieved tendinous tissue regeneration in UMRCT by providing mechanical support and promoting the trend toward tenogenic differentiation., Clinical Relevance: The present study proposes a potential strategy for repairing UMRCT with severely retracted musculotendinous tissues and large tendinous tissue defects., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This work was supported by the National Natural Science Foundation of China (grant No. 82072426). 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.

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., (© 2024 European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

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., (© 2024. The Author(s).)

Objective: Insulin-like growth factor binding protein 7 (IGFBP7) has a strong affinity to insulin. This study aimed to evaluate the relationship between IGFBP7 and complications among type 2 diabetes mellitus (T2DM) patients., Design: A total of 1449 T2DM patients were selected from a cross-sectional study for disease management registered in the National Basic Public Health Service in Changshu, China, and further tested for their plasma IGFBP7 levels. Logistic regressions and Spearman's rank correlation analyses were used to explore the associations of IGFBP7 with diabetic complications and clinical characteristics, respectively., Results: Among the 1449 included T2DM patients, 403 (27.81%) had complications. In patients with shorter duration (less than five years), the base 10 logarithms of IGFBP7 concentration were associated with T2DM complications, with an adjusted odds ratio (OR) of 2.41 [95% confidence interval (95%CI) = 1.06-5.48]; while in patients with longer duration (more than five years), plasma IGFBP7 levels were not associated with T2DM complications. Furthermore, in T2DM patients with shorter duration, those with two or more types of complications were more likely to have higher levels of IGFBP7., Conclusion: IGFBP7 is positively associated with the risk of complication in T2DM patients with shorter duration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

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., (© 2023 Wiley-VCH GmbH.)

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., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

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., (Copyright © 2023 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the accuracy, safety, and short-term effectiveness of a domestic robot-assisted system in total knee arthroplasty (TKA) by a multicenter randomized controlled trial., Methods: Between December 2021 and February 2023, 138 patients with knee osteoarthritis who received TKA in 5 clinical centers were prospectively collected, and 134 patients met the inclusion criteria were randomly assigned to either a trial group ( n =68) or a control group ( n =66). Seven patients had lost follow-up and missing data, so they were excluded and the remaining 127 patients were included for analysis, including 66 patients in the trial group and 61 patients in the control group. There was no significant difference ( P >0.05) in gender, age, body mass index, side, duration of osteoarthritis, Kellgren-Lawrence grading, preoperative Knee Society Score (KSS) and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) score between the two groups. The trial group completed the TKA by domestic robot-assisted osteotomy according to the preoperative CT-based surgical planning. The control group was performed by traditional osteotomy plate combined with soft tissue release. Total operation time, osteotomy time of femoral/tibial side, intraoperative blood loss, and postoperative complications were recorded and compared between the two groups. The radiographs were taken at 5 and 90 days after operation, and hip-knee-ankle angle (HKA), lateral distal angle of femur (LDFA), and posterior tibial slope (PTS) were measured. The difference between the measured values of the above indexes at two time points after operation and the preoperative planning target values was calculated, and the absolute value (absolute error) was taken for comparison between the two groups. The postoperative recovery of lower limb alignment was judged and the accuracy was calculated. KSS score and WOMAC score were used to evaluate the knee joint function of patients before operation and at 90 days after operation. The improvement rates of KSS score and WOMAC score were calculated. The function, stability, and convenience of the robot-assisted system were evaluated by the surgeons., Results: The total operation time and femoral osteotomy time of the trial group were significantly longer than those of the control group ( P <0.05). There was no significant difference in the tibial osteotomy time and the amount of intraoperative blood loss between the two groups ( P> 0.05). The incisions of both groups healed by first intention after operation, and there was no infection around the prosthesis. Nine patients in the trial group and 8 in the control group developed lower extremity vascular thrombosis, all of which were calf intermuscular venous thrombosis, and there was no significant difference in the incidence of complications ( P >0.05). All patients were followed up 90 days. There was no significant difference in KSS score and WOMAC score between the two groups at 90 days after operation ( P >0.05). There was significant difference in the improvement rate of KSS score between the two groups ( P <0.05), while there was no significant difference in the improvement rate of WOMAC score between the two groups ( P >0.05). Radiological results showed that the absolute errors of HKA and LDFA in the trial group were significantly smaller than those in the control group at 5 and 90 days after operation ( P <0.05), and the recovery accuracy of lower limb alignment was significantly higher than that in control group ( P <0.05). The absolute error of PTS in the trial group was significantly smaller than that in the control group at 5 days after operation ( P <0.05), but there was no significant difference at 90 days between the two groups ( P >0.05). The functional satisfaction rate of the robot-assisted system was 98.5% (65/66), and the satisfaction rates of stability and convenience were 100% (66/66)., Conclusion: Domestic robot-assisted TKA is a safe and effective surgical treatment for knee osteoarthritis, which can achieve favorable lower limb alignment reconstruction, precise implant of prosthesis, and satisfactory functional recovery.

Background: Sleep is an important physiological behavior in humans that is associated with the occurrence and development of various diseases. However, the association of sleep duration with health-related outcomes, including obesity-related factors, musculoskeletal diseases, and mortality because of different causes, has not been systematically reported., Objective: This study aims to systematically investigate the effect of sleep duration on health-related outcomes., Methods: Overall, 54,664 participants with sleep information from 8 survey cycles of the National Health and Nutrition Examination Survey (2005-2020) were included in the analysis. Health-related outcomes comprised obesity-related outcomes (ie, BMI, obesity, waist circumference, and abdominal obesity), metabolism-related outcomes (ie, uric acid, hyperuricemia, and bone mineral density [BMD]), musculoskeletal diseases (ie, osteoarthritis [OA] and rheumatoid arthritis [RA]), and mortality because of different causes. The baseline information of participants including age, sex, race, educational level, marital status, total energy intake, physical activity, alcohol consumption, smoking, hypertension, and diabetes was also collected as covariates. Information about the metabolism index, disease status, and covariates was acquired from the laboratory, examination, and questionnaire data. Survival information, including survival status, duration, and cause of death, was obtained from the National Death Index records. Quantile regression models and Cox regression models were used for association analysis between sleep duration and health-related outcomes. In addition, the threshold effect analysis, along with smooth curve fitting method, was applied for the nonlinear association analysis., Results: Participants were divided into 4 groups with different sleep durations. The 4 groups showed significant differences in terms of baseline data (P<.001). The quantile regression analysis indicated that participants with increased sleep duration showed decreased BMI (β=-.176, 95% CI -.220 to -.133; P<.001), obesity (odds ratio [OR] 0.964, 95% CI 0.950-0.977; P<.001), waist circumference (β=-.219, 95% CI -.320 to -.117; P<.001), abdominal obesity (OR 0.975, 95% CI 0.960-0.990; P<.001), OA (OR 0.965, 95% CI 0.942-0.990; P=.005), and RA (OR 0.940, 95% CI 0.912-0.968; P<.001). Participants with increased sleep duration also showed increased BMD (β=.002, 95% CI .001-.003; P=.005), as compared with participants who slept <5.5 hours. A significant saturation effect of sleep duration on obesity, abdominal obesity, and hyperuricemia was detected through smooth curve fitting and threshold effect analysis (sleep duration>inflection point). In addition, a significant threshold effect of sleep duration on BMD (P<.001); OA (P<.001); RA (P<.001); and all-cause (P<.001), cardiovascular disease-cause (P<.001), cancer-cause (P=.005), and diabetes-cause mortality (P<.001) was found. The inflection point was between 6.5 hours and 9 hours., Conclusions: The double-edged sword effect of sleep duration on obesity-related outcomes, embolism-related diseases, musculoskeletal diseases, and mortality because of different causes was detected in this study. These findings provided epidemiological evidence that proper sleep duration may be an important factor in the prevention of multisystem diseases., (©Ting Lei, Mingqing Li, Hu Qian, Junxiao Yang, Yihe Hu, Long Hua. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 07.11.2023.)

The periosteum plays a critical role in bone development, shaping, remodeling, and fracture healing due to its abundance of osteoprogenitor cells, osteoblasts, and capillary network. However, the role of periosteum in bone injury healing has been underestimated, thus there is an urgent need to develop a multifunctional artificial periosteum that mimics the natural one. To tackle this issue, electrospinning technology was employed to fabricate an artificial periosteum composed of Poly-ε-caprolactone (PCL) doped with tantalum (Ta) and zinc oxide (ZnO) nanoparticles to enhance its antibacterial, osteogenic, and angiogenic properties. The in vitro cell experiments have demonstrated that the PCL/Ta/ZnO artificial periosteum exhibits excellent biocompatibility and can effectively facilitate osteogenic differentiation of BMSCs as well as angiogenic differentiation of EPCs. Antibacterial experiments have demonstrated the excellent bactericidal effects of PCL/Ta/ZnO artificial periosteum against both S. aureus and E. coli. The subcutaneous infection and critical-sized skull bone defect models have validated its in vivo properties of antibacterial activity, promotion of osteogenesis, and angiogenic potential. The PCL/Ta/ZnO artificial periosteum demonstrates remarkable efficacy in infection control and favorable immunomodulation, thereby achieving rapid vascularized bone repair. In conclusion, the utilization of PCL/Ta/ZnO tissue-engineered periosteum has been demonstrated to exhibit antibacterial properties, pro-vascularization effects, and promotion of osteogenesis at the site of bone defects. This promising approach could potentially offer effective treatment for bone defects., Competing Interests: Declaration of competing interest All authors have no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

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., (© 2023. The Author(s).)

Electrospinning technology, as a novel approach, has been extensively applied in the field of tissue engineering. Nanofiber membranes prepared by electrospinning can effectively mimic the structure and function of natural bone matrix, providing an ideal scaffold for attachment, proliferation, and differentiation of bone cells while inducing osteogenic differentiation and new bone formation. However, it lacks bioactivities such as osteoinduction, angiogenesis and the ability to promote nerve regeneration. In the presence of complex critical bone defects, a single component electrospun membrane often fails to suffice for bone repair needs. Based on this, we prepared a biofunctionalized membrane loaded with Tantalum(Ta)/Whitlockite(WH) nanoparticles (poly-ε-caprolactone (PCL)/Ta/WH) in order to promote high-quality bone defect repair through neurovascular coupling effect. According to the results of in vitro and in vivo experiments, the early Mg 2+ release of WH can effectively increase the local nerve and vascular density, and synergize with Tantalum nanoparticles (TaNPs) to create a rich nerve-vascular microenvironment. This allows the PCL/Ta/WH membrane to repair bone defects in multiple dimensions and achieve high-quality repair of bone tissue, providing new solutions for the treatment of critical bone defects in clinical., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Accumulating epidemiological studies have demonstrated that smoking caused damage to human health. However, these studies almost focused on the individual smoking pattern rather than the toxic ingredients of tobacco smoke. Despite the exact accuracy of cotinine as a smoking exposure biomarker, there were few studies investigating the association between serum cotinine and human health. This study aimed to provide novel evidence about the harmful effect of smoking on systemic health from the perspective of serum cotinine., Methods: All used data was acquired from 9 survey cycles (2003-2020) of the National Health and Nutrition Examination Survey (NHANES) program. The mortality information of participants was derived from the National Death Index (NDI) website. The disease status of participants, including respiratory, cardiovascular, and musculoskeletal diseases, was obtained from questionnaire surveys. The metabolism-related index, including obesity, bone mineral density (BMD), and serum uric acid (SUA), was obtained from examination data. Multiple regression methods, smooth curve fitting, and threshold effect models were used for association analyses., Results: With a total of 53,837 subjects included, we detected an L-shaped association between serum cotinine and obesity-related index, a negative association between serum cotinine and BMD, a positive association between serum cotinine and nephrolith and coronary heart disease (CHD), a threshold effect of serum cotinine on hyperuricemia (HUA), osteoarthritis (OA), chronic obstructive pulmonary disease (COPD), and stroke, as well as a positive saturate effect of serum cotinine on asthma, rheumatoid arthritis (RA), all-cause, cardiovascular disease (CVD)-cause, cancer-cause, and diabetes-cause mortality., Conclusions: In this study, we investigated the association between serum cotinine and multiple health outcomes, indicating the systematic toxicity of smoking exposure. These findings provided novel epidemiological evidence about how passive exposure to tobacco smoke affects the health condition of the general US population., Competing Interests: Declaration of competing interest The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., (© 2023 Federation of American Societies for Experimental Biology.)

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease and closely associated with both genetic and environmental factors. Volatile organic chemicals (VOC), a common environment pollutant, was associated with some autoimmune diseases, while whether VOC exposure or which VOC leads to RA is yet clarified., Methods: A cross-sectional study using data from the 6 survey cycles (2005-2006, 2011-2012, 2013-2014, 2015-2016, 2017-2018, 2017-2020) of NHANES program was performed. The RA or non-arthritis status of participant was identified through a questionnaire survey. The quantile logistic regression method was used for correlation analysis between VOC metabolites (VOCs) in urine and RA. The covariates included age, gender, race, educational level, marital status, total energy intake, physical activity, smoking, hypertension, diabetes, urine creatinine, albumin and marihuana use., Results: A total of 9536 participants (aged 20 to 85) with 15 VOCs, comprising 618 RA and 8918 non-arthritis participants, was finally included for analysis. Participants in the RA group showed higher VOCs in urine than that in the non-arthritis group. A positive association between 2 VOCs (AMCC: Q4: OR=2.173, 95%CI: 1.021, 4.627. 3HPMA: Q2: OR=2.286, 95%CI: 1.207 - 4.330; Q4: OR=2.663, 95%CI: 1.288 -5.508.) and RA was detected in the model 3, which was independent of all the covariates. The relative parent compounds of the two VOCs included N,N-Dimethylformamide and acrolein., Discussion: These findings suggested that the VOC exposure significantly associated with RA, providing newly epidemiological evidence for the establishment that environmental pollutants associated with RA. And also, more prospective studies and related experimental studies are needed to further validate the conclusions of this study., Competing Interests: The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lei, Qian, Yang and Hu.)

Osteochondral defect (OCD) regeneration remains challenging because of the hierarchy of the native tissue including both the articular cartilage and the subchondral bone. Constructing an osteochondral scaffold with biomimetic composition, structure, and biological functionality is the key to achieve its high-quality repair. In the present study, an injectable and 3D printable bilayered osteochondral hydrogel based on compositional gradient of methacrylated sodium alginate, gelatin methacryloyl, and β-tricalcium phosphate (β-TCP), as well as the biochemical gradient of kartogenin (KGN) in the two well-integrated zones of chondral layer hydrogel (CLH) and osseous layer hydrogel (OLH) is developed. In vitro and subcutaneous in vivo evaluations reveal that apart from the chondrogenesis of the embedded bone mesenchymal stem cells induced by CLH with a high concentration of KGN, a low concentration of KGN with β-TCP in the OLH synergistically achieves superior osteogenic differentiation by endochondral ossification, instead of the intramembranous ossification using OLH with only β-TCP. The biomimetic construct leveraging KGN as the only biochemical inducer can facilitate cartilage and subchondral bone restoration in the in vivo osteochondral defect. This one-stone-two-birds strategy opens up a new facile approach for OCD regeneration by exploiting the biological functions of the bioactive drug molecule KGN., (© 2023 Wiley-VCH GmbH.)

Aseptic loosening of the prosthesis is a severe complication after joint replacement. It is of great practical significance and social value to discover the prevention and treatment strategies for this condition. Exosomes from urine-derived stem cells (Exos) have great potential in promoting bone repair, reconstruction, and regulating bone metabolism. However, they are easily eliminated by macrophages and incapable of targeting the osteolysis zone. In this study, based on macrophage "homing" into periprosthetic osteolysis region and cell membrane encapsulating nanotechnology, exosomes from urine-derived stem cells were encapsulated with macrophage membrane (MM) to prevent periprosthetic osteolysis. We found that macrophage membrane encapsulated urine-derived stem cell-derived exosomes (MM-Exos) can be targeted delivery to the osteolysis zone and enhance the therapeutic effectiveness of Exos, which alleviated wear particles-induced calvarial osteolysis. Furthermore, MM-Exos could provide immunological camouflage and allow the Exos to avoid phagocytosis by macrophages and stimulate cellular uptake by bone marrow-derived stem cells (BMSCs). Therefore, we demonstrated the unique ability of the macrophage membrane as a targeted transport of exosomes from urine-derived stem cells for the prevention and treatment of periprosthetic osteolysis. These biomimetic nanoparticles provided a new therapeutic exosome delivery system for preventing wear particles-induced osteolysis. STATEMENT OF SIGNIFICANCE: Macrophage membrane encapsulated urine-derived stem cell-derived exosomes (MM-Exos) can be targeted delivery to the osteolysis zone and enhance the therapeutic effect of Exos on peri‑prosthetic osteolysis prevention. MM-Exos could allow the Exos to avoid phagocytosis by macrophages and promote the uptake of Exos by BMSCs., Competing Interests: Declaration of Competing Interest All other authors declare no competing interests., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: Our aim in this study was to identify the associations between growth differentiation factor 15 (GDF15) and type 2 diabetes mellitus (T2DM) complications in a community-based population in China., Methods: Based on a cross-sectional study registered in the National Basic Public Health Service for disease management of Changshu in China, a total of 1,689 T2DM patients were enrolled and tested further for plasma GDF15 levels. Macrovascular (cardiovascular disease and diabetic foot) and microvascular (diabetic kidney disease [DKD], diabetic retinopathy, and neuropathy) complications were evaluated. Logistic regression models were conducted to identify the associations of GDF15 with the risk of diabetes complications, and linear regression models were used to assess relationships between GDF15 and other clinical features., Results: Overall, 459 of the 1,689 T2DM patients (27.18%) had complications. GDF15 levels were significantly higher in patients with any type of complication compared with their counterparts. With each standard deviation increase of base 10 logarithms of GDF15 (lg-GDF15), the risk of overall complications increased by 1.17-fold (95% confidence interval [CI], 1.03 to 1.32). In contrast to macrovascular complications, associations of GDF15 with microvascular complications appeared to be stronger (adjusted odds ratio [OR], 1.24; 95% CI, 1.08 to 1.43), especially for DKD (adjusted OR, 1.51; 95% CI, 1.19 to 1.93). Subgroup analyses showed that the strength of association between GDF15 and complications varied by distinct age and T2DM duration subgroups. Patients with 2 or more types of complications had higher levels of GDF15 than those with fewer types of complications. Also, linear relationships were identified between GDF15 and several liver and kidney function indices., Conclusion: Higher GDF15 levels were associated with T2DM complications, especially DKD. GDF15 may serve as a biomarker for monitoring the deterioration of T2DM., (Copyright © 2022. Published by Elsevier Inc.)

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., (© 2023. The Author(s).)

Background: Increasing evidence have been provided that the exposure to environment pollutants was associated obesity, while whether the exposure to volatile organic chemicals (VOC) was associated with obesity or abdominal obesity is yet to be clarified., Method: A cross-sectional study using data from the 6 survey cycles (2005-2006, 2011-2018, 2017-2020) of NHANES program was performed. Obesity and abdominal obesity were identified as a BMI >30 and a waist circumference >102 cm for men or >88 cm for women respectively. The quantile logistic regression method was used to analyze the association between VOC metabolites (VOCs) in urine and obesity, and the quantile regression method was used for the association analysis between VOCs in urine and BMI, as well as waist circumference., Results: A total of 17 524 participants (4965 obesity, 7317 abdominal obesity) were included, and participants in the obesity or abdominal obesity groups showed higher VOCs in urine than that in the control group. The CEMA was identified as the risk factor for obesity and abdominal obesity in all the 4 models, and its detected OR for obesity in the Q2 to Q4 of model 3 was 1.169 (Q2, p < 0.05), 1.306 (Q3, p < 0.001) and 1.217 (Q4, p < 0.01) respectively. And its OR for abdominal obesity in the Q2 to Q4 of model 3 was 1.222 (Q2, p < 0.01), 1.448 (Q3, p < 0.001) and 1.208 (Q4, p < 0.05) respectively. A significantly positive association between CEMA and BMI, as well as waist circumference, was also detected., Conclusion: In this study, we found that the exposure to VOC (Acrolein, Acrylamide, Acrylonitrile, 1,3-Butadiene, Crotonaldehyde, Cyanide, N,N-Dimethylformamide, Ethylbenzene, styrene, Propylene oxide, Toluene and Xylene) was significantly associated with obesity or abdominal obesity. And also, more prospective studies and related experimental researches should be carried out to further demonstrate the conclusion of this study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The key to critical bone regeneration in tissue engineering relies on an ideal bio-scaffold coated with a controlled release of growth factors. Gelatin methacrylate (GelMA) and Hyaluronic acid methacrylate (HAMA) have been a novel topic of interest in bone regeneration while introducing appropriate nano-hydroxyapatite (nHAP) to improve its mechanical properties. And the exosomes derived from human urine-derived stem cells (human USC EXOs) have also been reported to promote osteogenesis in tissue engineering. The present study aimed to design a new GelMA-HAMA/nHAP composite hydrogel as a drug delivery system. The USC EXOs were encapsulated and slow-released in the hydrogel for better osteogenesis. The characterization of the GelMA-based hydrogel showed excellent controlled release performance and appropriate mechanical properties. The in vitro studies showed that the USC EXOs/GelMA-HAMA/nHAP composite hydrogel could promote the osteogenesis of bone marrow mesenchymal stem cells (BMSCs) and the angiogenesis of endothelial progenitor cells (EPCs), respectively. Meanwhile, the in vivo results confirmed that this composite hydrogel could significantly promote the defect repair of cranial bone in the rat model. In addition, we also found that USC EXOs/GelMA-HAMA/nHAP composite hydrogel can promote the formation of H-type vessels in the bone regeneration area, enhancing the therapeutic effect. In conclusion, our findings suggested that this controllable and biocompatible USC EXOs/GelMA-HAMA/nHAP composite hydrogel may effectively promote bone regeneration by coupling osteogenesis and angiogenesis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Periprosthetic osteolysis is the leading cause of prosthesis failure and subsequent total joint revision. Wear particles produced by prosthetic materials are the main biological factors that cause periprosthetic osteolysis. Reducing the inflammatory response induced by the phagocytosis of wear particles by macrophages, blocking the activation of osteoclastogenesis, and promoting bone regeneration are essential for preventing the aseptic loosening of prostheses. In this study, we demonstrated that cellular senescence played a vital role during the process of ultra-high molecular weight polyethylene (UHMWPE) particle-induced osteolysis. Administration of the senolytic drug navitoclax (ABT263) could eliminate senescent cells and inhibit the secretion and inflammatory state of the senescence-associated secretory phenotype (SASP). We also discovered that ABT263 inhibited the formation of osteoclasts and had a significant therapeutic effect on UHMWPE particle-induced osteolysis based on the results of UHMWPE-induced mouse cranial osteolysis. Therefore, our research provided innovative strategies and ideas for the prevention and treatment of periprosthetic osteolysis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Infected bone defects (IBDs) cause significant economic and psychological burdens, posing a huge challenge to clinical orthopedic surgeons. Traditional approaches for managing IBDs possess inevitable shortcomings; therefore, it is necessary to develop new functionalized scaffolds. Tantalum (Ta) has been widely used in load-bearing orthopedic implants due to its good biocompatibility and corrosion resistance. However, undecorated Ta could only structurally repair common bone defects, which failed to meet the clinical needs of bacteriostasis for IBDs. Researchers have made great efforts to functionalize Ta scaffolds to enhance their antibacterial activity through various methods, including surface coating, alloying, and micro- and nanostructure modifications. Additionally, several studies have successfully utilized Ta to modify orthopedic scaffolds for enhanced antibacterial function. These studies remarkably extended the application range of Ta. Therefore, this review systematically outlines the advances in the fundamental and clinical application of Ta in the treatment of IBDs, focusing on the antibacterial properties of Ta, its functionalization for bacteriostasis, and its applications in the modification of orthopedic scaffolds. This study provides researchers with an overview of the application of Ta in the treatment of IBDs.

Infected bone defects (IBDs) remains a challenging problem for orthopedists. Clinically, routine management for IBDs has two stages: debridement and systematic antibiotics administration to control infection, and secondary grafting to repair bone defects. Whereas the efficacy is not satisfactory, because the overuse of antibiotics may lead to systemic toxicity, and the emergence of drug-resistant bacteria, as well as the secondary surgery would cause additional trauma and economic burden to the patients. Therefore, it is imperative to develop a novel scaffold for one-stage repair of IBDs. In this study, vancomycin (Van) was encapsulated into poly(lactic co-glycolic acid) (PLGA) microspheres through the double emulsion method, which were then loaded into the additively-manufactured porous tantalum (AM-Ta) through gelatin methacryloyl (GelMA) hydrogel to produce the composite Ta/GelMA hydrogel (Gel)/PLGA/vancomycin(Van) scaffolds for repairing IBDs. Physiochemical characterization of the newly-developed scaffold indicated that the releasing duration of Van was over 2 weeks. Biological experiments indicated good biocompatibility of the composite scaffold, as well as bacteriostasis and osteointegration properties, which showed great potential for clinical application. The construction of this novel scaffold would provide new sight into the development of orthopaedic implants, shedding a novel light on the treatment of IBDs., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

The abundant neurovascular network in the periosteal fibrous layer is essential for regulating bone homeostasis and repairing bone defects. However, the majority of the current studies only focus on the structure or function, and most of them merely involve osteogenesis and angiogenesis, lacking an in-depth study of periosteal neurogenesis. In this study, a photothermal double-layer biomimetic periosteum with neurovascular coupling was proposed. The outer layer of biomimetic periosteum is a conventional electrospinning membrane to prevent soft tissue invasion, and the inner layer is an oriented nanofiber membrane to promote cell recruitment and angiogenesis. From the perspective of functional bionics, based on the whitlockite (WH) similar to bone composition, we doped Nd (the trivalent form of neodymium element) in it as the inducing element of photothermal response to prepare photothermal whitlockite (Nd@WH). The sustained release of Mg 2+ in Nd@WH can effectively promote the up-regulation of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF). The release of Ca 2+ and PO 4 3- ions and photothermal osteogenesis jointly promote bone regeneration. Under the combined effect of structure and function, the formation of nerves, blood vessels, and related collagens greatly simulates the microenvironment of extracellular matrix and periosteum regeneration and ultimately promotes bone regeneration. In this study, physical and chemical characterization proved that the bionic periosteum has good flexibility and operability. The in vitro cell experiment and in vivo calvarial defect model verified that PPCL/Nd@WH biomimetic periosteum had excellent bone tissue regeneration function compared with other groups. Finally, PPCL/Nd@WH provides a new idea for the design of bionic periosteum., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

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 ( P Interaction < 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.

Segmental bone defects, accompanied by periosteum stripping or injury, usually lead to delayed bone union or nonunion, which have challenged orthopedic surgeons. The periosteum, which provides essential blood supply and initial stem cells for bone tissue, plays an important role in the repair of bone defects. The reconstruction of the destroyed periosteum has attracted the attention of researchers exploring more satisfactory therapies to repair bone defects. However, periosteum-like biomaterials have yet to meet the clinical requirements and resolve this challenging problem. In this study, we manufactured a nanofiber periosteum replacement based on poly-ε-caprolactone (PCL), in which tantalum nanoparticles (TaNPs) and nanoscale magnesium oxide (MgO) were introduced to enhance its osteogenic and angiogenic ability. The results of in vitro experiments indicated that the PCL/Ta/MgO periosteum replacement, with excellent cytocompatibility, promoted the proliferation of both bone marrow mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs). Furthermore, the incorporation of TaNPs and nano-MgO synergistically enhanced the osteogenic differentiation of BMSCs and the angiogenic properties of EPCs. Similarly, the results of in vivo experiments from subcutaneous implantation and critical-sized calvarial defect models showed that the PCL/Ta/MgO periosteum replacement combined the osteogenesis and angiogenesis abilities, promoting vascularized bone formation to repair critical-sized calvarial defects. The results of our study suggest that the strategy of stimulating repairing bone defects can be achieved with the periosteum repaired in situ and that the proposed periosteum replacement can act as a bioactive medium to accelerate bone healing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nan, Liu, Zhang, Sun, Hu and Lei.)

Chronic wounds are characterized by long-term inflammation and persistent infection, which make them difficult to heal. Therefore, an urgent desire is to develop a multifunctional wound dressing that can prevent wound infection and promote wound healing by creating a favorable microenvironment. In this study, a curcumin-based metal-organic framework (QCSMOF-Van), loaded with vancomycin and coated with quaternary ammonium salt chitosan (QCS), was prepared. Multifunctional composite hydrogels were conveniently synthesized by combining methacrylic anhydride modified gelatin and methacrylic anhydride modified oxidized sodium alginate with QCSMOF-Van through radical polymerization and Schiff base reaction. It is important to note that the QCSMOF-Van could capture bacteria through the positive charges on the surface of QCS. In this process, due to the synergistic effect of broad-spectrum antibacterial Zn 2+ and vancomycin, the metabolism of bacteria was well inhibited, and the efficient capturing and rapid killing of bacteria were achieved. The QCSMOF-Van hydrogels could precisely regulate the balance of M1/M2 phenotypes of macrophages, thereby promoting the regeneration of nerves and blood vessels, which promotes the rapid healing of chronic wounds. This advanced cascade management strategy for tissue regeneration highlights the potential of multifunctional composite hydrogels in chronic wound dressings.

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.)

Osteosarcoma is the most common malignant tumor in children and adolescents and its diagnosis and treatment still need to be improved. Necroptosis has been associated with many malignancies, but its significance in diagnosing and treating osteosarcoma remains unclear. The objective is to establish a predictive model of necroptosis-related genes (NRGs) in osteosarcoma for evaluating the tumor microenvironment and new targets for immunotherapy. In this study, we download the osteosarcoma data from the TARGET and GEO websites and the average muscle tissue data from GTEx. NRGs were screened by Cox regression analysis. We constructed a prediction model through nonnegative matrix factorization (NMF) clustering and the least absolute shrinkage and selection operator (LASSO) algorithm and verified it with a validation cohort. Kaplan-Meier survival time, ROC curve, tumor invasion microenvironment and CIBERSORT were assessed. In addition, we establish nomograms for clinical indicators and verify them by calibration evaluation. The underlying mechanism was explored through the functional enrichment analysis. Eight NRGs were screened for predictive model modeling. NRGs prediction model through NMF clustering and LASSO algorithm was established. The survival, ROC and tumor microenvironment scores showed significant statistical differences among subgroups (P < 0.05). The validation model further verifies it. By nomogram and calibration, we found that metastasis and risk score were independent risk factors for the poor prognosis of osteosarcoma. GO and KEGG analyses demonstrate that the genes of osteosarcoma cluster in inflammatory, apoptotic and necroptosis signaling pathways. The significant role of the correlation between necroptosis and immunity in promoting osteosarcoma may provide a novel insight into detecting molecular mechanisms and targeted therapy., (© 2022. The Author(s).)

3D-printed porous tantalum scaffold has been increasingly used in arthroplasty due to its bone-matching elastic modulus and good osteoinductive ability. However, the lack of antibacterial ability makes it difficult for tantalum to prevent the occurrence and development of periprosthetic joint infection. The difficulty and high cost of curing periprosthetic joint infection (PJI) and revision surgery limit the further clinical application of tantalum. Therefore, we fabricated vancomycin-loaded porous tantalum scaffolds by combining the chemical grafting of (3-aminopropyl)triethoxysilane (APTES) and the electrostatic assembly of carboxymethyl chitosan and vancomycin for the first time. Our in vitro experiments show that the scaffold achieves rapid killing of initially adherent bacteria and effectively prevents biofilm formation. In addition, our modification preserves the original excellent structure and biocompatibility of porous tantalum and promotes the generation of mineralized matrix and osteogenesis-related gene expression by mesenchymal stem cells on the surface of scaffolds. Through a rat subcutaneous infection model, the composite bioscaffold shows efficient bacterial clearance and inflammation control in soft tissue and creates an immune microenvironment suitable for tissue repair at an early stage. Combined with the economic friendliness and practicality of its preparation, this scaffold has great clinical application potential in the treatment of periprosthetic joint infection.

Background: Whether there was clinical superiority for the single-radius prosthesis over the multi-radius prothesis in total knee arthroplasty (TKA) still remains to be clarified. We updated a meta-analysis including prospective randomized controlled trials (RCTs) to compare the clinical prognosis of patients receiving single-radius TKA (SR-TKA) or multi-radius TKA (MR-TKA)., Methods: We searched the databases of PubMed, Web of Science, EMBASE, Cochrane Library, MEDLINE for eligible RCTs. Two reviewers evaluated the study quality according to the Risk of Bias tool of the Cochrane Library and extracted the data in studies individually. The extracted data included the baseline data and clinical outcome. The baseline data include the author's name, country, and year of included studies, the name of knee prosthesis used in studies, sample size, follow-up time, and BMI of patients. The clinical data comprised primary indicators including postoperative knee range of motion (ROM), sit-to-stand rest, severe postoperative scorings, such as visual analog scale (VAS), American Knee Society knee score (AKS), Oxford knee scoring (OKS), and SF-36 Quality of Life Scale, as well as various secondary indicators of complications including anterior knee pain, postoperative infection, aseptic prosthesis loosening, and prosthesis revision. The data analysis was performed using Review Manager 5.3 software and STATA 12.0. The sensitivity analysis was performed using STATA 12.0., Results: A total of 13 RCTs, along with 1720 patients and 1726 knees, were finally included in our present meta-analysis. We found that patients in SR-TKA group performed better in the sit-to-stand test (OR = 1.89, 95% CI: 1.05-3.41, p = 0.03) and satisfaction evaluation (OR = 3.27, 95% CI: 1.42-7.53, p = 0.005), which were only evaluated in two included RCTs. While no significant difference was found between SR-TKA and MR-TKA groups in terms of postoperative ROM, VAS scoring, AKS scoring, SF-36 scoring, OKS scoring, and various complications including anterior knee pain, postoperative infection, aseptic prosthesis loosening, and prosthesis revision., Conclusion: In conclusion, our present meta-analysis indicated that SR implants were noninferior to MR implants in TKA, and SR implants could be an alternative choice over MR implants, since patients after SR-TKA felt more satisfied and performed better in the sit-to-stand test, with no significant difference in complications between SR-TKA and MR-TKA groups. While more relevant clinical trials with long-term follow-up time and specific tests evaluating the function of knee extension mechanism should be carried out to further investigate the clinical performance of SR implants., (© 2022 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Backgrounds: Postoperative wound complication is a major risk factor for the development of Periprosthetic joint infection. We innovatively invented a new dressing system to reduce the occurrence of postoperative wound complications and improve the quality of life of patients after total hip arthroplasty., Methods: A total of 120 patients who underwent primary unilateral total hip arthroplasty were enrolled in this study. The data collected included the number of dressing changes, costs of the dressings, postoperative hospital stay, The Visual Analogue Scale (VAS) score, The Harris Hip Score (HHS), ASEPSIS score, The Stony Brook Scar Evaluation Scale (SBSES), wound complications, the frequency of showers and satisfaction. Data were statistically analyzed., Results: The average number of dressing changes was 0.74 ± 0.46, while the average postoperative hospital stay was 3.67 ± 0.97 days. The average cost of the new dressings throughout a treatment cycle was 57.42 ± 15.18 dollars. The VAS score decreased from 5.63 ± 1.09 before the operation to 0.88 ± 0.54 one month after the operation. The HHS score increased from 70.18 ± 7.84 before the operation to 80.36 ± 4.08 one month after the operation. The results of the four indexes of the ASEPSIS score were all 0. The SBSES score was 3.55 ± 0.61 at two weeks after the operation, and 4.38 ± 0.71 at one month after the operation. No wound complications were recorded until one month after the operation when the satisfaction rate was 92.53 ± 3.62%., Conclusion: In this study, we have invented a new dressing system for surgical wounds after total hip arthroplasty and confirmed its efficacy., Chinese Clinical Trial Registry: ChiCTR2000033822, Registered 13/ June/2020., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Su, Wang, Gao, Hu, Zhong and Lei.)

Bacteria have brought great harm to the public, especially after the emergence of multidrug-resistant bacteria. This has rendered traditional antibiotic therapy ineffective. In recent years, hyperthermia has offered new treatments to remove bacteria. Microwaves (MW) are a component of the electromagnetic spectrum and can rapidly heat materials. Taking advantage of this characteristic of MW, related studies have shown that both thermal and non-thermal effects of MW can inactivate various bacteria. Even though the understanding of MW in the field of bacteria is not sufficient for widespread use at present, MW has performed well in dealing with microorganisms and controlling infection. This review will focus on the application of MW in bacteria and discuss the advantages, prospects and challenges of using MW in the bacterial field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Wang, Hu and Wang.)

Medicine treatments for bone-related diseases such as osteoporosis, bone metastasis, osteomyelitis, and osteolysis are often limited by insufficient drug concentration at the lesion sites owing to the low perfusion of bone tissue. A carrier that can deliver multiple bone destruction site-targeting drugs is required to address this limitation. Here, we reported a novel bone-targeting nano-drug delivery platform formed by the integration of zoledronate (ZOL) and zeolitic imidazolate framework-8 (ZIF-8) nanoparticles. The ZOL mixed zeolitic imidazolate framework (ZZF) nanoparticles were synthesized in water at room temperature (25 °C), where many biomacromolecules could maintain their activity. This allowed the ZZF nanoparticles to adapt the encapsulation ability and pH response release property from ZIF-8 and the excellent bone targeting performance of ZOL simultaneously. Considering the ease of preparation and biomacromolecule-friendly drug delivery of this nano platform, it may be useful in treating bone-related diseases., (© 2022. The Author(s).)

Bone nonunion or delayed union, caused by stripping or injuring of periosteum, is the most common sequelae of segmental bone defects. The preservation of periosteum, or the use of periosteal grafts, can significantly improve the integration of bone graft, speeding up the process of bone reconstruction. However, in most cases, periosteum cannot be preserved with bioactivity. Thus, it is pivotal to develop artificial periosteum. In this study, artificial periosteum of PLGA/MgO/Quercetin was prepared by electrospinning. PLGA/MgO/Quercetin membranes were shown to have a highly porous surface and microstructure, as observed by scanning electron microscopy. Along with excellent biocompatibility, PLGA/MgO/Quercetin membranes promoted cell proliferation and migration, as well as osteogenic differentiation of BMSCs (Bone marrow mesenchymal stem cells) in a dose-dependent manner through the activation of Wnt/β-Catenin pathway. The PLGA/MgO/Quercetin membranes, with an appropriate concentration of quercetin (<1 ​wt%), promoted EPCs (Endothelial progenitor cells) angiogenesis. In a subcutaneous implantation model and rat skull defect model, optimal osteogenesis and angiogenesis function were observed for the PLGA/20 ​wt% MgO/0.1 ​wt% Quercetin membrane. In conclusion, PLGA/MgO membranes, with an appropriate concentration of quercetin, show a variety of biological activities and are promising materials for the generation of artificial periosteum., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Purpose: The purpose of this study was to determine the relationship between psychological health and postoperative recovery and satisfaction in patients undergoing total joint arthroplasty (TJA)., Methods: We prospectively enrolled patients undergoing TJA from July 2019 to December 2020. A psychological evaluation was conducted according to the Hospital Anxiety and Depression Scale (HADS). Based on the preoperative HADS scores, we grouped the patients into two groups: the symptomatic group and the asymptomatic group. Data on the Harris Hip Score (HHS), Knee Society Knee Scoring System (KSS), Forgotten Joint Score-12 (FJS-12), Short Form-12 (SF-12), and Numeric Rating Scale (NRS) for pain in these two groups were collected preoperatively and postoperatively. Then, these data were analyzed by Statistical Package for Social Sciences (SPSS) version 19., Results: The final cohort consisted of 80 patients. Patients undergoing TJA had significantly decreased HADS and NRS scores and improved HHS, KSS, SF-12, and FJS-12 scores (all p < 0.001). Compared with the symptomatic group, the asymptomatic group showed better postoperative recovery ( p < 0.05), especially after total knee arthroplasty (TKA) ( p < 0.05). Good postoperative recovery positively impacted the patients' postoperative psychological state., Conclusion: Finally, the psychological state can affect recovery after TJA, and successful TJA can help improve patients' psychological states, especially after TKA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Xing, Zhong, Pan, He, Hu and Wang.)