To advance the bioactivity of artificial bone grafts, human induced pluripotent stem cell (hiPSC)-derived mesenchymal stem cells (iMSCs) are ideal seed cells. However, the instability in iMSC generation and their limited osteogenic capacity challenge their clinical application. In this study, we applied a novel strategy that combines a stable iMSC induction method that mimics the developmental process with an osteocytic Wnt-based osteogenic microenvironment, with the aim of creating a scalable, mechanistically defined platform to enhance bone regenerative efficiency. The small-molecule Wnt activator SKL2001-treated osteocyte osteogenic microenvironment (SOOME) substantially enhanced the osteogenic differentiation of iMSCs and promoted iMSCs-mediated bone defect repair in a rat femoral condyle defect model. Moreover, the SOOME-iMSC composite demonstrated its ability to promote angiogenesis and neurogenesis both in vitro and in vivo, and also enhanced osteoclast activity at the regeneration site. These findings suggest that the SOOME-treated iMSCs create a native-like osteomimetic microenvironment, which improves implant integration and bone tissue regeneration. This approach introduces a novel strategy for the standardized fabrication of seed cells with enhanced osteogenic potential, offering a promising solution for the fabrication and clinical application of bioactive bone graft materials.

To evaluate the diagnostic value of ultrasound for joint space width in knee osteoarthritis under standing weight-bearing conditions and identify reliable sonographic parameters for osteoarthritis severity grading, especially end-stage knee osteoarthritis. This cross-sectional study enrolled 256 patients with knee pain and suspected knee osteoarthritis from June to December 2025. All participants underwent standing weight-bearing radiography and ultrasound of the affected knee at 20° and 45° flexion. Radiographic assessments (Kellgren-Lawrence grading, joint space width, minimal joint space width) were performed by two senior orthopedists, while ultrasound evaluations (joint space width, total femoral and tibial osteophyte height, medial meniscal extrusion) were conducted by another two experienced orthopedists blinded to radiographic findings. Interrater reliability was analyzed using the weighted kappa coefficient and intraclass correlation coefficient. The Pearson product-moment correlation coefficient quantified the correlation between sonographic and radiographic measurements, and receiver operating characteristic curve analysis determined the diagnostic efficacy of ultrasound parameters for Kellgren-Lawrence grading. Participants had a mean age of 55.9 ± 11.7 years, mean body mass index of 25.22 ± 4.32 kg/m², and 81.6

Objective The development of osteoarthritis (OA) is closely associated with systemic metabolic disorders, yet there remains a lack of disease-modifying therapeutic strategies that simultaneously target metabolic abnormalities and inflammatory responses. This study aims to systematically evaluate the therapeutic potential of semaglutide, a long-acting glucagon-like peptide-1 receptor (GLP-1R) agonist used for diabetes management, in OA and to elucidate its underlying molecular mechanisms. Methods We utilized a zebrafish cartilage injury repair model to screen and assess the impact of several hypoglycemic drugs on cartilage regeneration. OA was induced in C57BL/6 mice by destabilization of the medial meniscus (DMM) surgery. Using systemic Glp-1r knockout mice, we systematically evaluated the effects of semaglutide on joint structure, function, and pain-related behaviors in vivo. RNA sequencing was performed to explore the regulator effects of semaglutide on extracellular matrix metabolism, associated signaling pathways, and autophagy in IL-1β-stimulated primary mouse chondrocytes. To verify the functional loss, the GLP-1R antagonist Exendin (9-39) and the autophagy inhibitor Bafilomycin A1 were employed. Results Drug screening using a zebrafish cartilage injury model demonstrated that semaglutide exerted the most significant pro-regenerative effects, markedly promoting cartilage repair. In wild-type (WT) mice with DMM-induced OA, semaglutide treatment significantly improved gait abnormalities and mechanical hyperalgesia without significantly affecting body weight, and alleviated cartilage destruction, synovitis, and subchondral bone sclerosis associated with abnormal chondrocyte metabolism. However, GLP-1R inhibition or Glp-1r knockout completely abolished the protective effects of semaglutide on chondrocyte metabolism and its therapeutic efficacy in OA. Moreover, Glp-1r gene deficiency exacerbated cartilage degeneration and bone structural damage, indicating that GLP-1R signaling is indispensable for maintaining cartilage homeostasis. Mechanistically, semaglutide inhibited the AKT/mTOR pathway through GLP-1R activation, thereby reversing IL-1β- and DMM-induced autophagy suppression and restoring the balance of extracellular matrix metabolism in chondrocytes. Conclusion Semaglutide exerts protective effects against OA by activating GLP-1R in chondrocytes, inhibiting the AKT/mTOR pathway, and enhancing chondrocyte autophagy. It alleviates abnormal cartilage metabolism in OA independently of body weight changes.Translational potential of this study: This study demonstrates, for the first time, that semaglutide exerts protective effects against OA independent of weight loss by directly activating chondrocyte GLP-1R, inhibiting the AKT/mTOR pathway, and enhancing autophagy. These findings provide robust preclinical evidence supporting the repositioning of semaglutide as a disease-modifying therapy, particularly for patients with OA and comorbid metabolic disorders such as diabetes. Furthermore, they indicate that GLP-1R and its downstream signaling pathways may represent potential therapeutic targets for OA, thereby opening new avenues for drug repurposing and precision interventions in metabolic OA.

BACKGROUND:Osteoarthritis (OA) is a degenerative joint disease. Recent studies have shown that ferroptosis plays a critical role in OA. Arachidonate-5-lipoxygenase (ALOX5), a pivotal enzyme regulating arachidonic acid metabolism, is involved in the synthesis of the pro-inflammatory leukotrienes. However, its role in ferroptosis and OA has not been elucidated. METHODS:Measuring the expression of ALOX5 and ferroptosis-related markers in human cartilage and synovial fluid. Constructed small interfering RNA or plasmids were used to knockdown or overexpress Alox5 to explore its role in chondrocyte. Transcription factors regulating Alox5 were predicted through database analysis, while RNA sequencing revealed signaling pathways modulated by Alox5. Subsequently, the role of ALOX5 in destabilization of medial meniscus (DMM) OA model was investigated by intra-articular injection of knockdown (AAV-ShAlox5) or overexpression (AAV-OEAlox5) adeno-associated virus. Finally, the therapeutic efficacy of ALOX5 inhibitor Zileuton, was verified in vivo and in vitro. RESULTS:We observed upregulated ALOX5 expression in human cartilage and Alox5 knockdown mitigated IL-1β- and FAC-induced chondrocyte damage by suppressing ferroptosis. Through database predictive analysis and experimental verification, ALOX5 was modulated by the JNK-p53 signaling axis. Through RNA-seq analysis, it was found that knockdown of Alox5 inhibited the activation of the JAK2-STAT3 signaling pathway, thereby delaying the process of ferroptosis and slowing down the wear of articular cartilage. In the mouse DMM model, intra-articular injection AAV-ShAlox5 delayed DMM-induced cartilage degeneration, whereas AAV-OEAlox5 exacerbated cartilage damage. Similarly, treatment with Zileuton alleviated ferroptosis and chondrocyte injury,demonstrating a protective effect in vivo and in vitro. CONCLUSIONS:In summary, our study demonstrated knockdown of Alox5 inhibited the JAK2/STAT3 signaling, thereby suppressing ferroptosis and alleviating cartilage damage. Intra-articular injection of the ALOX5 inhibitor Zileuton or AAV-ShAlox5 in the knee joint alleviated cartilage damage in the mouse DMM model. Mechanistically, our study reveals that the JNK-p53-ALOX5 signaling axis alleviates OA by regulating ferroptosis in chondrocytes.

BACKGROUND:Rotator cuff impingement syndrome is a prevalent cause of supraspinatus tendinopathy, resulting in considerable pain and functional impairment. Excessive apoptosis of tenocytes has been recognized as a critical pathological mechanism in both supraspinatus tendinopathy and rotator cuff tears. Furthermore, mitochondrial degeneration and endoplasmic reticulum (ER) stress-induced apoptosis are significant factors in chronic multisystem diseases. However, it remains unclear whether mitochondrial damage and ER stress can also cause excessive apoptosis of tendon cells and contribute to the development of rotator cuff tendinopathy. PURPOSE:This study used a mouse model of acromion impingement to examine how mitochondrial dysfunction and ER stress in tendon cells contribute to excessive apoptosis and rotator cuff tendinopathy. STUDY DESIGN:Controlled laboratory study. METHODS:A total of 70 twelve-week-old male mice were randomly divided into an experimental group (n = 56), which received bilateral subacromial microclip placement, and a control group (n = 14) with normal tendon conditions. Supraspinatus tendons from the experimental group were harvested at 2, 4, 6, and 8 weeks postsurgery. Outcomes assessed included biomechanical analysis, histological analysis, gene expression, a DNA fragmentation assay (terminal deoxynucleotidyl transferase dUTP nick-end labeling [TUNEL]), immunohistochemical analysis, and transmission electron microscopy (TEM). RESULTS:Biomechanical analysis indicated a significant reduction in supraspinatus tendon failure force and stiffness in the impingement group compared with the control group (P < .0001). Histological evaluation demonstrated characteristic tendinopathic changes, including cellular rounding and collagen disorganization. TUNEL assay quantification revealed elevated apoptotic indices in the experimental group relative to controls, peaking at 4 weeks (16.72%; P < .01). Gene expression analysis identified the upregulation of mitochondrial apoptotic pathway markers and ER stress mediators, with maximal expression observed at the 4-week time point. Ultrastructural analysis via TEM revealed progressive mitochondrial depletion and loss of cristae. Additionally, the ER system exhibited considerable expansion, with rough ER cisternae significantly increasing in width compared to control specimens. CONCLUSION:This study reveals that rotator cuff impingement injuries can trigger collaborative apoptotic pathways linked to mitochondria and the ER. The resulting excessive apoptosis, metabolic imbalance, and loss of tendon cells play crucial roles in the development and progression of tendinopathy. CLINICAL RELEVANCE:The results of this study contribute meaningfully to the understanding of the early organelle-level pathological characteristics of tendinopathy.

Circular RNAs (circRNAs) are covalently closed, stable non-coding RNAs that regulate diverse cellular processes. Here, we identify circTspan3 - derived from exons 2-6 of the Tspan3 gene - as a key regulator of cartilage development. The expression of circTspan3 is significantly downregulated in X-box binding protein 1 (Xbp1) conditional knockout (cKO) mice displaying chondrodysplasia and positively correlates with anabolic markers of cartilage. The XBP1 spliced (XBP1s) transcriptionally upregulates circTspan3, which in turn promotes anabolic activity in chondrocytes while suppressing both apoptosis and ferroptosis. Mechanistically, phosphorylation of ANNEXIN A2 (ANXA2) at Ser26 facilitates the cytoplasmic translocation of circTspan3, where ANXA2 mediates its packaging into exosomes for paracrine signalling. Exosomal circTspan3 enhances growth-plate expansion and effectively repairs cartilage defects in vivo. These findings highlight circTspan3 as a key modulator of growth-plate homeostasis and suggest its translational potential in treating cartilage injury and growth-associated skeletal disorders.

The sarcopenia index (SI), defined as the ratio of serum creatinine to cystatin C, is a proposed biomarker of muscle mass and sarcopenia, yet its genomic basis and genetic architecture remain largely unexplored. We performed combined-sex and sex-stratified genome-wide association studies of SI in the UK Biobank. We examined the overlap between SI-associated loci and loci previously reported for sarcopenia-related traits. We assessed sexually dimorphic effects and gene–sex interactions, performed fine-mapping, and conducted credible gene prioritization, motif and transcription factor binding enrichment, gene-set enrichment, linkage disequilibrium score regression, and cross-phenotype colocalization. We identified 774 unique independent SI-associated loci across all analyses, with 747 detected in the combined-sex GWAS, 283 in the male-stratified GWAS, and 311 in the female-stratified GWAS; 367 of these loci had not been previously reported for conventional sarcopenia-related traits. Sex-stratified analyses highlighted the rs1145093–chr15q21.1–GATM region, where CARMA identified sex-differentiated causal variants. We prioritized 17 male-biased and 11 female-biased credible genes. Enrichment analyses implicated androgen receptor and GATA4 in males, and ESR1 and MYOD1 in females. Enrichment revealed shared pathways involving inflammation, cellular stress, and aging-related processes. LDSC showed inverse genetic correlations between SI and heart failure (rg = −0.19, p = 2.30 × 10− 9) and metabolic syndrome (rg = −0.12, p = 8.49 × 10− 8), and a positive correlation with chronic kidney disease. Compared with female SI, male SI exhibited two additional loci showing colocalization with four metabolic traits. These findings clarify the genetic architecture of SI and reveal sex-dependent mechanisms underlying sarcopenia, supporting precision risk assessment and targeted interventions. Sex-stratified GWAS identified 247 loci reaching genome-wide significance in only one sex among 774 independent SI-associated loci, of which 59 showed stronger associations in the corresponding sex-stratified GWAS than in the combined-sex analysis. The rs1145093–chr15q21.1–GATM region showed a prominent sex-dependent association via sex-stratified analyses. Sex-stratified functional annotation pointed to male-enriched androgen receptor and GATA4, female-enriched ESR1 and MYOD1, and common biological processes related to inflammation, stress response, and aging. Cross-phenotype colocalization identified rs1229984 at chr4q23 and rs9817452 at chr3q25.31 as loci showing male-stratified colocalization with four metabolic traits.

BACKGROUND:Acute Achilles tendon rupture is a common and serious injury in sports medicine. Clinical studies demonstrate that both surgical and nonsurgical interventions can achieve satisfactory outcomes; however, considerable debate exists regarding the optimal treatment modality for this injury. Currently, most animal experimental studies on acute Achilles tendon rupture lack clinical relevance due to inadequate fixation of the ankle joint. METHODS:This study involved 162 male C57BL/6 mice and 30 Scx-CreER T2 ; Rosa26-tdTomato transgenic mice. The injury+repair groups underwent Achilles tenotomy followed by Kessler suture repair, while the injury+no repair groups underwent tenotomy alone. Ankle joints were immobilized at 160° (plantar flexion) or 90° (neutral alignment). Samples were collected at 2 and 4 weeks post-injury for biomechanical, histological, and quantitative real-time PCR (qPCR) analyses, including tracing of Scx + tendon progenitor stem cells. RESULTS:Biomechanical analysis was performed 2 and 4 weeks post-injury. At 2 weeks, the injury+repair group immobilized at a maximum plantar flexion angle of 160° showed significantly higher failure force and stiffness compared with the injury+no repair+160° group. However, there was no significant difference between the groups at 4 weeks (p > 0.05). The failure force in each 160° group was significantly higher than in the corresponding 90° group (p < 0.0001). Histological analysis indicated better collagen fiber alignment and higher expression of collagen type I alpha 1 (COL1A1) in the injury+repair groups. qPCR revealed generally higher expression of tendon repair-related genes ( Scx, Tnmd, Tgfb1 ) in the injury+repair groups, while inflammatory factors ( Il1b, Il6 ) were higher in the injury+no repair+90° group. Scx + tendon progenitor stem cell tracing showed the greatest percentage in the injury+repair+160° group. CONCLUSIONS:Both surgical and nonsurgical treatments for acute Achilles tendon rupture achieved satisfactory tendon healing results when the ankle joint was maintained in maximum plantar flexion. However, surgical treatment yielded superior histological tendon repair. CLINICAL RELEVANCE:The results suggest that clinical trials may show immobilization in maximum plantar flexion following surgery to be optimal for tendon healing.

Geriatric femoral neck fracture (FNF) represents a pressing global health challenge, imposing substantial burdens on medical resources while being associated with high complication rates and suboptimal clinical outcomes. In recent years, the direct anterior approach (DAA) has emerged as a mainstream surgical strategy for hip joint arthroplasty (HJA) in developed countries, owing to its minimally invasive nature, neuromuscular-sparing anatomical interval, preservation of soft tissue integrity, and alignment with enhanced recovery after surgery principles, collectively contributing to significant improvements in clinical outcomes of HJA for elderly patients with FNF. However, no unified consensus exists regarding standardized techniques and procedural protocols for DAA-HJA in this specific patient population. Consequently, there is an urgent need to develop an evidence-based expert consensus to address key clinical dilemmas inherent to DAA-HJA in geriatric FNF. Sponsored by the Joint Surgery Group of the Chinese Medical Association, this expert consensus builds upon the foundational Chinese Expert Consensus on Direct Anterior Approach Hip Arthroplasty for the Surgical Treatment of Geriatric Femoral Neck Fracture (2023 Edition). A multidisciplinary expert panel was convened to standardize core issues and procedural norms for DAA-HJA in geriatric FNF. Two rounds of modified Delphi questionnaires and one consensus conference were conducted for voting, with a predefined consensus threshold of ≥ 70

Steroid-induced osteonecrosis of the femoral head (SONFH) is a rapidly progressing and disabling complication of long-term glucocorticoid therapy, lacking effective early-stage intervention mechanisms. Its early manifestation involves a fate shift in bone marrow mesenchymal stem cells (BMSCs) characterized by decreased osteogenic differentiation (OGD) and increased adipogenic differentiation (AGD), yet the upstream regulatory mechanisms remain unclear. Herein, we integrated AGD-related microRNA (miRNA) microarray data with exosomal miRNA sequencing data and identified miR-199a-3p as a crucial candidate driver of this lineage imbalance. Our results revealed the up-regulation of miR-199a-3p in SONFH tissues and in glucocorticoid-treated cellular models, and indicated that its overexpression suppresses the OGD of BMSCs while markedly promoting the AGD. Further integrating mRNA-sequencing profiling during AGD with target prediction, protein-protein interaction network analysis, and dual-luciferase reporter assays, we confirmed integrin β8 (ITGB8) as a direct target of miR-199a-3p, which is consistently decreased in SONFH tissues and during adipogenic induction. We further revealed that miR-199a-3p suppressed the OGD of BMSCs by repressing ITGB8 expression, thereby inactivating the focal adhesion kinase (FAK)-extracellular signal-regulated kinase (ERK)-runt-related transcription factor 2 (RUNX2) signaling cascade. Conversely, silencing miR-199a-3p restores ITGB8 levels, reactivates this pathway, and corrects the OGD/AGD bias. In vivo, local administration of antagomiR-199a-3p in a SONFH rat model markedly improved trabecular bone architecture, increased bone mass, and up-regulated RUNX2 expression. These findings reveal for the first time that the miR-199a-3p/ITGB8-FAK-ERK-RUNX2 axis represents an unrecognized pathogenic pathway in SONFH, and support the local suppression of miR-199a-3p as a translatable early intervention strategy.

Osteoarthritis (OA) is characterized by the progressive degeneration of the synovial joint, leading to irreversible damage to articular cartilage and subchondral bone. While animal models have advanced our understanding of OA, numerous unresolved issues still remain. The zebrafish, known for its transparent body, rapid developmental, and impressive regenerative capabilities, offers substantial potential for osteoarthritis research. This study seeks to establish a new OA model utilizing the zebrafish jaw joint, acting as a supplement to traditional animal models. In the future, this model could serve as a valuable platform for delving deeper into the mechanisms of this disease, as well as for advancing drug discovery and therapeutic interventions. Leveraging the skeletal structure of zebrafish, we targeted the largest jaw joint for our research. A custom fixation device was crafted, and a microinjection system was utilized to inject mono-iodoacetate (MIA) or collagenase type II (CTII) into the joint cavity of zebrafish. Subsequent analyses included histological staining, immunohistochemistry, OA research society international (OARSI) scoring, and real-time in vivo imaging were performed at 7, 14, and 28 days post injection. Our results effectively demonstrated the presence of synovial inflammation and cartilage damage within the zebrafish mandible, affirming the feasibility of inducing OA in zebrafish. In conclusion, the local injection of chemical agents into the joint cavity of zebrafish effectively induced the occurrence of OA. Establishing the zebrafish OA model enhances the array of animal models available for OA research. Moreover, zebrafish present distinct advantages, including robust regenerative abilities, genetic editing simplicity, and efficient drug screening. Consequently, this offers a fresh avenue for investigating the pathogenesis, prevention, and potential therapeutic approaches for human OA.

INTRODUCTION:Osteoarthritis (OA), the most common degenerative joint disease, can eventually lead to disability. However, no safe or effective intervention is currently available. Therefore, there is an urgent need to develop effective drugs that reduce cartilage damage and treat OA. OBJECTIVES:This study aimed to ascertain the potential of panaxatriol, a natural small molecule, as a therapeutic drug for alleviating the progression of OA. METHODS:An in vitro culture of human cartilage explants and C28/I2 human chondrocytes and an in vivo surgically induced OA mouse model were used to evaluate the chondroprotective effect of panaxatriol. The Drug Affinity Responsive Target Stability assay, CRISPR-Cas9 assay, Whole-transcriptome RNA sequencing analysis and agonist or antagonist assays were used to identify the target and potential signaling pathways of panaxatriol. Poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) was used to construct the sustained-release system of panaxatriol. RESULTS:Panaxatriol protected against OA by regulating chondrocyte metabolism. Ubiquitin-fold modifier 1-specific E3 ligase 1 (UFL1) was identified as a novel target of panaxatriol. Whole transcriptome RNA sequencing showed that UFL1 was closely related to cell senescence. Panaxatriol inhibited chondrocyte senescence through UFL1/forkhead box O1 (FOXO1)/P21 and UFL1/NF-κB/SASPs signaling pathways. It also could inhibit fibrocartilage formation during cartilage repair via the UFL1/FOXO1/Collagen 1 signaling pathway. Finally, we constructed a sustained-release system for panaxatriol based on PLGA-PEG, which reduced the number of intra-articular injections, thereby alleviating joint swelling and injury. CONCLUSIONS:Panaxatriol exerts anti-senescence effects and has the potential to delay OA progression and reduce cartilage repair fibrosis by targeting UFL1.

Femoral neck fracture (FNF) in the elderly poses significant challenge for global health, consuming substantial medical resources, and resulting in high complication rates and suboptimal outcomes. Hip joint arthroplasty (HJA) is currently the primary treatment for elderly FNF, but traditional surgical approaches still face issues such as dislocation, limping, and leg length discrepancy. In the recent years, direct anterior approach (DAA) has become the mainstream for HJA in developed countries, due to its minimal invasive philosophy, neuromuscular interval, soft tissue retention and accelerated recovery, and it significantly improves the clinical outcomes of HJA for elderly FNF. However, there is currently a lack of unified understanding regarding the techniques and processes for DAA-HJA in treating elderly FNF. Therefore, the expert panel of this consensus previously published the "Chinese Expert Consensus on the Surgical Treatment of Femoral Neck Fracture by Direct Anterior Approach Hip Arthroplasty for Elderly Patient (2023 Edition)", which normalized the indications, surgical techniques, and standard procedures for DAA-HJA in elderly FNF. With the rapid progress of robotic technology in joint surgery and the extensive investigation probing its clinical value, we have supplemented and revised the application of robotic surgery in elderly FNF with 9 modified recommendations. These recommendations aim to further promote standardized, systematic, and individualized diagnostic and treatment concepts, ultimately improving patients' functional prognosis.

Although periprosthetic joint infection (PJI) can affect multiple joints simultaneously, most individuals with multiple joint involvement exhibit PJI in only one joint. Data regarding the metachronous PJI management for these patients are limited. This study aimed to explore the risk factors for metachronous PJI in patients with multiple prosthetic joints, thereby guiding and optimizing clinical practice. The MEDLINE, Web of Science, Cochrane Library, and EMBASE were searched for all clinical studies of metachronous PJI from inception until May 2024. The clinical studies on risk factors for metachronous PJI in patients with multiple prosthetic joints after experiencing a periprosthetic infection were collected, with two authors independently screening the literatures. Newcastle Ottawa scale was used as a quality assessment tool for the included studies, and the meta-analysis was conducted to evaluate the potential risk factors of metachronous PJI. A total of 1,544 patients with PJI after multiple joint arthroplasties were reported in 9 studies, including 189 with metachronous PJI. The meta-analysis showed that methicillin-resistant staphylococcus aureus (MRSA; OR, 3.43; 95

Objectives: Pneumonia is a common perioperative complication in geriatric patients with hip fractures. This study aimed to analyze demographic characteristics, mortality rates, postoperative outcomes, and perioperative comorbidities, identify risk factors for mortality, and develop a nomogram for predicting the prognosis of these patients. Methods: Data on patients hospitalized for arthroplasty for hip fractures from 2020 to 2023 at three hospitals were retrospectively analyzed. Patients were divided into the P group (patients with hip fractures complicated with pneumonia) and the C group (patients with hip fractures without pneumonia) and demographic characteristics, mortality, postoperative outcomes, and perioperative comorbidities of the patients were analyzed. Multiple logistic regression was then used to identify independent risk factors for inpatient mortality in the P group and a nomogram was constructed to predict inpatient mortality. The predictive performance of the nomogram was assessed using receiver operating characteristic curves, decision curve analysis, and calibration curves. Results: A total of 311 patients participated in the study. Patients in the P group had longer hospitalization ( p = 0.001), higher inpatient mortality ( p < 0.001), higher mortality (30 days) ( p < 0.001), and a poorer recovery of hip function ( p < 0.001). Multiple logistic regression showed that age, BMI, total hip arthroplasty, diabetes, and chronic obstructive pulmonary disease were independent risk factors for inpatient mortality in the P group; these factors were incorporated in the nomogram. The C-index of the nomogram was 0.868 (95% CI: 0.802–0.933), and the C-index of internal bootstrapping validation was 0.851 (95% CI: 0.793–0.908), indicating the effectiveness of the nomogram in predicting patient prognosis. Conclusions: Coinfection with pneumonia adversely affected both recovery of hip function and survival in geriatric patients with hip fractures. Age, BMI, total hip arthroplasty, diabetes, and chronic obstructive pulmonary disease were found to be independent risk factors for mortality in this patient population.

OBJECTIVE:Osteoarthritis (OA) often coexists with metabolic traits (MTs), causing significant disability. Our study aims to uncover the shared genetic mechanisms between OA and MTs, revealing novel OA-MT related genes, proteins and pathways. DESIGN:We first explored the clinical associations between OA and MTs based on UK Biobank data. Using GWAS statistics for 9 OA subtypes and 51 MTs, we identified both global and regional genetic correlations. Multi-trait GWAS helped revealed credible genes and relevant pathways through various methods. Protein-level analyses were also conducted to identify key proteins. We developed polygenic scores (PGS), machine learning models and drug repurposing strategies were explored to translate these findings into clinical applications. RESULTS:We identified 152 trait pairs with significant associations and 709 local regions linked to OA-MT. Key SNVs like rs13135092 (SLC39A8) and rs34811474 (ANAPC4) were associated with multiple OA-MT pairs. Lipid and glucose metabolism emerged as central pathways, with tissue-specific enrichment analyses revealing key gene clusters in hepatocytes, arteries, and brain regions. Protein-level analyses identified 205 protein subgroups. PGS integrating MTs outperformed model based solely on OA, improving AUC by 17.5%. Causal gene-based models showed strong diagnostic accuracy (average AUC = 0.875 in external cohorts). Drug prediction highlighted fenofibrate as a promising treatment among 71 candidates. CONCLUSIONS:This study provides new insights into the genetic links between OA and MTs. We identified genes, proteins, and pathways related to comorbidities, revealing shared mechanisms, highlighting the potential of integrating metabolic factors to improve OA prediction, diagnosis, and treatment.

Background Osteoarthritis (OA) is characterized by the progressive degeneration of the synovial joint, leading to irreversible damage to articular cartilage and subchondral bone. While animal models have advanced our understanding of OA, numerous unresolved issues still remain. The zebrafish, known for its transparent body, rapid developmental, and impressive regenerative capabilities, offers substantial potential for osteoarthritis research. This study seeks to establish a new OA model utilizing the zebrafish jaw joint, acting as a supplement to traditional animal models. In the future, this model could serve as a valuable platform for delving deeper into the mechanisms of this disease, as well as for advancing drug discovery and therapeutic interventions. Materials and Results: Leveraging the skeletal structure of zebrafish, we targeted the largest jaw joint for our research. A custom fixation device was crafted, and a microinjection system was utilized to inject mono-iodoacetate (MIA) or collagenase type II (CTII) into the joint cavity of zebrafish. Subsequent analyses included histological staining, immunohistochemistry, OA research society international (OARSI) scoring, and real-time in vivo imaging were performed at 7, 14, and 28 days post injection. Our results effectively demonstrated the presence of synovial inflammation and cartilage damage within the zebrafish mandible, affirming the feasibility of inducing OA in zebrafish. Conclusion In conclusion, the local injection of chemical agents into the joint cavity of zebrafish effectively induced the occurrence of OA. Establishing the zebrafish OA model enhances the array of animal models available for OA research. Moreover, zebrafish present distinct advantages, including robust regenerative abilities, genetic editing simplicity, and efficient drug screening. Consequently, this offers a fresh avenue for investigating the pathogenesis, prevention, and potential therapeutic approaches for human OA.

Background: Massive irreparable rotator cuff tears (MIRCTs) are among the most challenging shoulder conditions to treat surgically. Supraspinatus tendon reconstruction (STR) is a recently introduced technique for MIRCTs based on fascia lata-muscle interface healing, which completely differs from the classic bridging technique with fascia lata-tendon interface healing. However, histological and biomechanical comparisons of the fascia-muscle and fascia-tendon interfaces have not been performed.Purpose: To investigate the histological and biomechanical healing of the fascia-bone interface and fascia-muscle interface after chronic MIRCTs in a rat model using different surgical methods.Study Design: Controlled laboratory study.Methods: The authors established a chronic MIRCT model in the right shoulder of rats and then repaired it using the STR or bridging repair technique. Evaluations were performed at 2, 4, 8, and 12 weeks, including histological, imaging, biomechanical, and functional analyses.Results: Both techniques resulted in good fascia-bone interface healing based on the histological results. The STR group had significantly more cartilage formation at 8 and 12 weeks and higher Modified Tendon Maturity Score after 12 weeks at the fascia-bone interface compared with the bridging repair group and formed the typical 4-layered structure. Collagen fibers in the fascia-muscle and fascia-tendon interfaces exhibited normal muscle-tendon interface characteristics at 12 weeks. However, the STR group had more improvement in fatty infiltration compared with the bridging repair group. The ultimate failure load and stiffness did not differ between the STR and bridging repair groups 4 weeks postoperatively in both the fascia-bone interface and supraspinatus muscle-fascia-bone integrity. Movement distance and grasp time were significantly longer in the STR group than in the bridging repair group at 12 weeks and attached the level in the normal control groups.Conclusion: These results suggest that the fascia-muscle interface from the STR technique is histologically and functionally better than the fascia-tendon interface. Moreover, this study provides a theoretical basis for the clinical use of the STR technique.Clinical Relevance: The fascia-muscle interface and fascia-tendon interface were the key points of the STR and bridging techniques, respectively. The fascia-muscle interface is histologically and functionally superior to the bridging technique, and the STR technique might be a better choice for the treatment of MIRCTs.

PurposeThis study aimed to determine whether the Achilles tendon tissue can undergo the pathological process of Achilles tendon regeneration after the Panda Rope Bridge Technique (PRBT).MethodsRats (n = 120) that operated with Achilles tendon rupture were divided into three treatment groups: Defect group (D group), PRBT group and Defect + Fix group (DF group). The D group represented natural healing with no treatment, the PRBT group represented healing receiving PRBT treatment and the DF group represented healing through conservative treatment by ankle fixation. The morphological, histological and biomechanical properties of the defective Achilles tendon were assessed at 7, 10, 12, 14, 28 and 56 days postoperatively.ResultsCompared to that observed in the other two groups, defected rat Achilles tendons that underwent PRBT recruited more cells earlier, eventually forming mature tendons, as revealed by histological analysis. PRBT also enabled defected tendons to regain stronger mechanical properties, thereby improving the prognosis. This improvement may be related to the earlier polarization of macrophages.ConclusionBy establishing and using a novel surgical model of Achilles tendon rupture in rats, most injured Achilles tendons can regenerate and regain normal histological properties, whereas tendons with other interventions formed fibrotic scar tissue. The strong regenerative capacity of tendon tissue enabled us to describe the pathological process of tendon regeneration after PRBT surgery in detail, which would aid in the treatment of tendon injuries. PRBT promotes Achilles tendon regeneration and has the potential to become a standard treatment.Level of EvidenceNot applicable.