Preliminary identification of somatic mutations profile in ACL injury.

Anterior cruciate ligament (ACL) injury is a common orthopedic disease with a high incidence, long recovery time, and often requiring surgical treatment. However, the susceptibility factors for ACL injury are currently unclear, and there is a lack of analysis on the differences in the ligament itself. Previous studies have focused on germline mutations, with less research on somatic mutations. To determine the role of somatic mutations in ACL injuries, we recruited seven patients between the ages of 20 and 39 years diagnosed with ACL injuries, collected their peripheral blood, injured ligament ends, and healthy ligament ends tissues, and performed exome sequencing with gene function enrichment analysis. We detected multiple gene mutations and gene deletions, which were only present in some of the samples. Unfortunately, it was not possible to determine whether these somatic mutations are related to ligament structure or function, or are involved in ACL injury. However, this study provides valuable clues for future in-depth research.

Can the preoperative CT-based deep learning radiomics model predict histologic grade and prognosis of chondrosarcoma?

BACKGROUND AND PURPOSE: Computed tomography (CT) and biopsy may be insufficient for preoperative evaluation of the grade and outcome of patients with chondrosarcoma. The aim of this study was to develop and validate a CT-based deep learning radiomics model (DLRM) for predicting histologic grade and prognosis in chondrosarcoma (CS). METHODS: A multicenter 211 (training cohort/ test cohort, 127/84) CS patients were enrolled. Radiomics signature (RS), deep learning signature (DLS), and DLRM incorporating radiomics and deep learning features were developed for predicting the grade. Kaplan-Meier survival analysis was used to assess the association of the model-predicted grade with recurrence-free survival (RFS). Model performance was evaluated with the area under the receiver operating characteristic curve (AUC) and the Harrell's concordance index (C-index). RESULTS: The DLRM (AUC, 0.879; 95 % confidence interval [CI], 0.802-0.956) outperformed (z = 2.773, P=0.006) the RS (AUC, 0.715;95 % CI, 0.606-0.825) in predicting grade in the test cohort. RFS showed significant differences (log-rank test, P<0.05) between low-grade and high-grade patients stratified by DLRM. The DLRM achieved a higher C-index (0.805; 95 % CI, 0.694-0.916) than the RS (0.692, 95 % CI, 0.540-0.844) did in predicting RFS for CS patients in the test cohort. CONCLUSION: The DLRM can accurately predict the histologic grade and prognosis in CS.

Inflammatory Marker Changes Following Total Knee Arthroplasty for Rheumatoid Arthritis with Vancomycin-loaded Calcium Sulfate Bone Filling.

Rheumatoid arthritis (RA) patients undergoing total knee arthroplasty (TKA) face infection risk. The study evaluates vancomycin-loaded calcium sulfate bone as infection prevention. Patients with RA treated with TKA who had their femoral canal filled using either vancomycin-loaded calcium sulfate bone (experimental group [n = 35]) or the patient's own excised autologous bone (control group [n = 30]) at the Qingdao University Affiliated Hospital, Qingdao, China from January 1, 2017, to March 1, 2023, were retrospectively enrolled in this study. An experienced surgeon used midvastus approach. Surgeries included disinfection, antibiotics, and femoral filling. The age, gender, body mass index (BMI), comorbidities, and intraoperative details were extracted from the patient's medical records. Preoperation and postoperation markers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR]), pain scale (Visual Analog Scale [VAS]), infection rate, and Knee Society Score (KSS) were collected. Groups matched in age, gender, and BMI. No preoperative inflammatory marker differences were observed. However, compared to the control group, the postoperative inflammatory markers were significantly lower in the experimental group at 1-week postsurgery (CRP: 40.80 ± 23.17 vs. 60.80 ± 43.12 mg/L, p = 0.021; ESR: 72.06 ± 17.52 vs. 83.87 ± 21.52 mm/h, p = 0.012) and at 1-month postsurgery (CRP: 15.63 ± 6.56 vs. 21.17 ± 13.16 mg/L, p = 0.032; ESR: 25.25 ± 20.44 vs. 38.40 ± 25.26 mm/h, p = 0.024). There were no significant differences in the VAS (2.79 ± 0.90 vs. 2.70 ± 0.84 score, p = 0.689) and KSS (64.31 ± 17.88 vs. 66.57 ± 12.36) at 1-month postsurgery. Experimental group: zero infections; control group: only one infection. Administering vancomycin and calcium sulfate during TKA in RA patients reduces postoperative inflammation, but does not significantly affect infection risk; further research may be necessary for validation.

Research progress on macrophage polarization during osteoarthritis disease progression: a review.

Primary osteoarthritis (OA) is a prevalent degenerative joint disease that mostly affects the knee joint. It is a condition that occurs around the world. Because of the aging population and the increase in obesity prevalence, the incidence of primary OA is increasing each year. Joint replacement can completely subside the pain and minimize movement disorders caused by advanced OA, while nonsteroidal drugs and injection of sodium hyaluronate into the joint cavity can only partially relieve the pain; hence, it is critical to search for new methods to treat OA. Increasing lines of evidence show that primary OA is a chronic inflammatory disorder, with synovial inflammation as the main characteristic. Macrophages, as one of the immune cells, can be polarized to produce M1 (proinflammatory) and M2 (anti-inflammatory) types during synovial inflammation in OA. Following polarization, macrophages do not come in direct contact with chondrocytes; however, they affect chondrocyte metabolism through paracrine production of a significant quantity of inflammatory cytokines, matrix metalloproteinases, and growth factors and thus participate in inducing joint pain, cartilage injury, angiogenesis, and osteophyte formation. The main pathways that influence the polarization of macrophages are the Toll-like receptor and NF-κB pathways. The study of how macrophage polarization affects OA disease progression has gradually become one of the approaches to prevent and treat OA. Experimental studies have found that the treatment of macrophage polarization in primary OA can effectively relieve synovial inflammation and reduce cartilage damage. The present article summarizes the influence of inflammatory factors secreted by macrophages after polarization on OA disease progression, the main signaling pathways that induce macrophage differentiation, and the role of different polarized types of macrophages in OA; thus, providing a reference for preventing and treating primary OA.

Simultaneous bilateral open wedge high tibial osteotomy versus simultaneous bilateral unicompartmental knee arthroplasty in the treatment of bilateral medial knee osteoarthritis: a retrospective study of an average three-year follow-up.

OBJECTIVE: There is growing evidence that simultaneous bilateral open wedge high tibial osteotomy(SBOWHTO) and simultaneous bilateral unicompartmental knee arthroplasty(SBUKA) is an effective surgical treatment for bilateral medial knee osteoarthritis (MKOA). However, which intervention is more beneficial for bilateral MKOA patients remains unknown. Therefore, the aim of this study was to compare the effectiveness of these two strategies through early clinical outcomes, complication rates, and prosthetic survival. METHODS: The clinical data of 60 patients with bilateral MKOA admitted to the Affiliated Hospital of Qingdao University from January 2018 to December 2022 were retrospectively analyzed, and they were divided into SBOWHTO group (n = 28) and SBUKA group (n = 32) according to different treatment methods. Clinical relevant indexes, Hospital for Special Surgery (HSS) score, Knee Society Knee (KSS) score, range of motion(ROM), postoperative complications and prosthetic survival rate were compared between the two groups. RESULTS: Patients in the SBOWHTO group were followed up for 27 to 50 months, with an average of (37.18 ± 6.84) months. Patients in the SBUKA group were followed up for 24 to 59 months, with an average of (39.38 ± 9.74) months. There were no significant differences in postoperative KSS, HSS and ROM between SBOWHTO group and SBUKA group (p > 0.05). There was no significant difference in complication rate between the two groups (p = 0.721). There was no significant difference in prosthetic survival rate (p = 0.622) and prosthetic survival curve (χ2 = 0.546, p = 0.46) between the two groups. CONCLUSIONS: This study compared early clinical outcomes, complication rates, and prosthesis retention rates after SBOWHTO and SBUKA, and found that the early clinical benefits of SBOWHTO and SBUKA were comparable in patients with bilateral MKOA.

A chitosan-based light-curing hydrogel dressing for accelerated healing of infected wounds.

Bacterial infections, excessive reactive oxygen species (ROS) accumulation and a persistent inflammatory response severely impede the wound healing process. In this study, we developed a novel multifunctional hydrogel dressing (LCPN) based on lipoic acid modified chitosan (LAMC), polypyrrole nanoparticles (PPy NPs) and nicotinamide mononucleotide (NMN) for accelerated healing of infected wounds. The synthesized LCPN hydrogel has several properties. Modification of lipoic acid significantly enhances the water solubility of chitosan making it easier to dissolve and absorb wound secretions. Interestingly, owing to the breaking and restructuring of disulfide bonds, LCPN hydrogel can be quickly bonded under UV light without relying on photoinitiators. In addition, the incorporation of PPy NPs not only enhances the electrical conductivity of LCPN hydrogel, but also confers photothermal antimicrobial capability to LCPN hydrogel. More importantly, the sustained release of NMN in LCPN hydrogel can significantly enhance cell proliferation, migration and antioxidant capacity, which is conducive to accelerated wound healing. In vitro and in vivo experiments have shown that LCPN hydrogel has excellent biocompatibility and the ability to promote wound healing. Therefore, the prepared multifunctional hydrogel is expected to be used as a novel dressing to accelerate wound healing.

Effect of body mass index on 30-day complication rate and implant survival rate after simultaneous bilateral unicompartmental knee arthroplasty: a multicentre retrospective study.

OBJECTIVE: The practice of simultaneous bilateral unicompartmental knee arthroplasty (SBUKA) remains a topic of debate, particularly in patients with obesity. Thus, the purpose of this study was to assess the impact of body mass index (BMI) on the 30-day complication rate and the survival rate of the implant following SBUKA. METHODS: We retrospectively examined the clinical records of 245 patients (490 knees) who underwent SBUKA at the Affiliated Hospital of Qingdao University and the Third Hospital of Hebei Medical University between January 2010 and December 2020. Patients were categorised based on their BMI at the time of surgery into four groups: normal weight (BMI 18.5 to 22.9 kg/m2), overweight (BMI 23.0 to 24.9 kg/m2), obese (BMI 25.0 to 29.9 kg/m2), and severely obese (BMI ≥30 kg/m2). Variables such as length of hospital stay, duration of surgery, and costs of hospitalisation were compared across all groups. Additionally, we recorded the 30-day postoperative complication rate and the time from surgery to any required revision. The Kaplan-Meier survival analysis was employed to evaluate and compare the implant survival rates. RESULTS: The follow-up period for the 245 patients ranged from 39 to 114 months, with an average of 77.05±18.71 months. The incidence of complications within 30 days post-surgery did not significantly differ across the groups (χ2 = 1.102, p = 0.777). The implant survival rates from the lowest to the highest BMI groups were 97.14%, 93.9%, 94.44%, and 96.43%, respectively. Both the rate of implant revision (χ2 =1.612, p = 0.657) and the survival curves of the implants (p = 0.639) showed no statistically significant differences among the groups. CONCLUSIONS: BMI did not influence the 30-day complication rate nor the survival rate of implants following SBUKA, suggesting that SBUKA should not be contraindicated based on BMI alone.

Single-cell RNA sequencing reveals different chondrocyte states in femoral cartilage between osteoarthritis and healthy individuals.

Background: Cartilage injury is the main pathological manifestation of osteoarthritis (OA). Healthy chondrocyte is a prerequisite for cartilage regeneration and repair. Differences between healthy and OA chondrocyte types and the role these types play in cartilage regeneration and OA progression are unclear. Method: This study conducted single-cell RNA sequencing (scRNA-seq) on the cartilage from normal distal femur of the knee (NC group) and OA femur (OA group) cartilage, the chondrocyte atlas was constructed, and the differences of cell subtypes between the two groups were compared. Pseudo-time and RNA velocity analysis were both performed to verify the possible differentiation sequence of cell subtypes. GO and KEGG pathway enrichment analysis were used to explore the potential functional characteristics of each cell subtype, and to predict the functional changes during cell differentiation. Differences in transcriptional regulation in subtypes were explored by single-cell regulatory network inference and clustering (SCENIC). The distribution of each cell subtype in cartilage tissue was identified by immunohistochemical staining (IHC). Result: A total of 75,104 cells were included, they were divided into 19 clusters and annotated as 11 chondrocyte subtypes, including two new chondrocyte subtypes: METRNL+ and PRG4+ subtype. METRNL+ is in an early stage during chondrocyte differentiation, and RegC-B is in an intermediate state before chondrocyte dedifferentiation. With cell differentiation, cell subtypes shift from genetic expression to extracellular matrix adhesion and collagen remodeling, and signal pathways shift from HIF-1 to Hippo. The 11 subtypes were finally classified as intrinsic chondrocytes, effector chondrocytes, abnormally differentiated chondrocytes and dedifferentiated chondrocytes. IHC was used to verify the presence and distribution of each chondrocyte subtype. Conclusion: This study screened two new chondrocyte subtypes, and a novel classification of each subtype was proposed. METRNL+ subtype is in an early stage during chondrocyte differentiation, and its transcriptomic characteristics and specific pathways provide a foundation for cartilage regeneration. EC-B, PRG4+ RegC-B, and FC are typical subtypes in the OA group, and the HippO-Taz pathway enriched by these cell subtypes may play a role in cartilage repair and OA progression. RegC-B is in the intermediate state before chondrocyte dedifferentiation, and its transcriptomic characteristics may provide a theoretical basis for intervening chondrocyte dedifferentiation.

Transcriptome sequencing and bioinformatics analysis of gastrocnemius muscle in type 2 diabetes mellitus rats.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is one of the high risk factors for sarcopenia. However, the pathogenesis of diabetic sarcopenia has not been fully elucidated. This study obtained transcriptome profiles of gastrocnemius muscle in normal and T2DM rats based on high-throughput sequencing technology, which may provide new ideas for exploring the pathogenesis of diabetic sarcopenia. METHODS: Twelve adult male Sprague-Dawley rats were randomly divided into Control group and T2DM group, and gastrocnemius muscle tissue was retained for transcriptome sequencing and real-time quantitative polymerase chain reaction (qRT-PCR) 6 months later. Screening differentially expressed genes (DEGs), Cluster analysis, gene ontology (GO) functional annotation analysis and Kyoto Encyclopedia of Genes and Gnomes (KEGG) functional annotation and enrichment analysis were performed for DEGs. Six DEGs related to apoptosis were selected for qTR-PCR verification. RESULTS: Transcriptomic analysis showed that there were 1016 DEGs between the gastrocnemius muscle of T2DM and normal rats, among which 665 DEGs were up-regulated and 351 DEGs were down-regulated. GO analysis showed that the extracellular matrix organization was the most enriched in biological processes, with 26 DEGs. The extracellular matrix with 35 DEGs was the most abundant cellular component. The extracellular matrix structural constituent, with 26 DEGs, was the most enriched in molecular functions. The highest number of DEGs enriched in biological processes, cellular components and molecular functions were positive regulation of transcription by RNA polymerase II, nucleus and metal ion binding, respectively. There were 78, 230 and 89 DEGs respectively. KEGG pathway enrichment analysis showed that ECM-receptor interaction, PI3K-Akt signaling pathway and TGF-ß signaling pathway(p < 0.001) had higher enrichment degree and number of DEGs. qRT-PCR results showed that the fold change of Map3k14, Atf4, Pik3r1, Il3ra, Gadd45b and Bid were 1.95, 3.25, 2.97, 2.38, 0.43 and 3.6, respectively. The fold change of transcriptome sequencing were 3.45, 2.21, 2.59, 5.39, 0.49 and 2.78, respectively. The transcriptional trends obtained by qRT-PCR were consistent with those obtained by transcriptome sequencing. CONCLUSIONS: Transcriptomic analysis was used to obtain the "gene profiles" of gastrocnemius muscle of T2DM and normal rats. qRT-PCR verification showed that the genes related to apoptosis were differentially expressed. These DEGs and enrichment pathways may provide new ideas for exploring the pathogenesis of diabetic sarcopenia.

Enhancing tendon-bone integration and healing with advanced multi-layer nanofiber-reinforced 3D scaffolds for acellular tendon complexes.

Advancements in tissue engineering are crucial for successfully healing tendon-bone connections, especially in situations like anterior cruciate ligament (ACL) restoration. This study presents a new and innovative three-dimensional scaffold, reinforced with nanofibers, that is specifically intended for acellular tendon complexes. The scaffold consists of a distinct layered arrangement comprising an acellular tendon core, a middle layer of polyurethane/type I collagen (PU/Col I) yarn, and an outside layer of poly (L-lactic acid)/bioactive glass (PLLA/BG) nanofiber membrane. Every layer is designed to fulfill specific yet harmonious purposes. The acellular tendon core is a solid structural base and a favorable environment for tendon cell functions, resulting in considerable tensile strength. The central PU/Col I yarn layer is vital in promoting the tendinogenic differentiation of stem cells derived from tendons and increasing the expression of critical tendinogenic factors. The external PLLA/BG nanofiber membrane fosters the process of bone marrow mesenchymal stem cells differentiating into bone cells and enhances the expression of markers associated with bone formation. Our scaffold's biocompatibility and multi-functional design were confirmed through extensive in vivo evaluations, such as histological staining and biomechanical analyses. These assessments combined showed notable enhancements in ACL repair and healing. This study emphasizes the promise of multi-layered nanofiber scaffolds in orthopedic tissue engineering and also introduces new possibilities for the creation of improved materials for regenerating the tendon-bone interface.

Transcriptomics reveals dynamic changes in the "gene profiles" of rat supraspinatus tendon at three different time points after diabetes induction.

OBJECTIVE: There is increasing evidence that type 2 diabetes mellitus (T2DM) is an independent risk factor for the occur of tendinopathy. Therefore, this study is the first to explore the dynamic changes of the "gene profile" of supraspinatus tendon in rats at different time points after T2DM induction through transcriptomics, providing potential molecular markers for exploring the pathogenesis of diabetic tendinopathy. METHODS: A total of 40 Sprague-Dawley rats were randomly divided into normal (NG, n = 10) and T2DM groups (T2DM, n = 30) and subdivided into three groups according to the duration of diabetes: T2DM-4w, T2DM-8w, and T2DM-12w groups; the duration was calculated from the time point of T2DM rat model establishment. The three comparison groups were set up in this study, T2DM-4w group vs. NG, T2DM-8w group vs. NG, and T2DM-12w group vs. NG. Differentially expressed genes (DEGs) in 3 comparison groups were screened. The intersection of the three comparison groups' DEGs was defined as key genes that changed consistently in the supraspinatus tendon after diabetes induction. Cluster analysis, gene ontology (GO) functional annotation analysis and Kyoto encyclopedia of genes and genomes (KEGG) functional annotation and enrichment analysis were performed for DEGs. RESULTS: T2DM-4w group vs. NG, T2DM-8w group vs. NG, and T2DM-12w group vs. NG detected 519 (251 up-regulated and 268 down-regulated), 459 (342 up-regulated and 117 down-regulated) and 328 (255 up-regulated and 73 down-regulated) DEGs, respectively. 103 key genes of sustained changes in the supraspinatus tendon following induction of diabetes, which are the first identified biomarkers of the supraspinatus tendon as it progresses through the course of diabetes.The GO analysis results showed that the most significant enrichment in biological processes was calcium ion transmembrane import into cytosol (3 DEGs). The most significant enrichment in cellular component was extracellular matrix (9 DEGs). The most significant enrichment in molecular function was glutamate-gated calcium ion channel activity (3 DEGs). The results of KEGG pathway enrichment analysis showed that there were 17 major pathways (p < 0.05) that diabetes affected supratinusculus tendinopathy, including cAMP signaling pathway and Calcium signaling pathway. CONCLUSIONS: Transcriptomics reveals dynamic changes in the"gene profiles"of rat supraspinatus tendon at three different time points after diabetes induction. The 103 DEGs identified in this study may provide potential molecular markers for exploring the pathogenesis of diabetic tendinopathy, and the 17 major pathways enriched in KEGG may provide new ideas for exploring the pathogenesis of diabetic tendinopathy.

Causal relationship between serum metabolites and juvenile idiopathic arthritis: a mendelian randomization study.

BACKGROUND: Juvenile Idiopathic Arthritis (JIA) is a condition that occurs when individuals under the age of 16 develop arthritis that lasts for more than six weeks, and the cause is unknown. The development of JIA may be linked to serum metabolites. Nevertheless, the association between JIA pathogenesis and serum metabolites is unclear, and there are discrepancies in the findings across studies. METHODS: In this research, the association between JIA in humans and 486 serum metabolites was assessed using genetic variation data and genome-wide association study. The identification of causal relationships was accomplished through the application of univariate Mendelian randomization (MR) analysis. Various statistical methods, including inverse variance weighted and MR-Egger, were applied to achieve this objective. To ensure that the findings from the MR analysis were trustworthy, a number of assessments were carried out. To ensure the accuracy of the obtained results, a range of techniques were utilised including the Cochran Q test, examination of the MR-Egger intercept, implementation of the leave-one-out strategy, and regression analysis of linkage disequilibrium scores. In order to identify the specific metabolic pathways associated with JIA, our primary objective was to perform pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes. RESULTS: Two-sample summary data MR analyses and sensitivity analyses showed that five metabolites were significantly causally associated with JIA, including two risk factors-kynurenine (odds ratio [OR]: 16.39, 95% confidence interval [CI]: 2.07-129.63, p = 5.11 × 10- 6) and linolenate (OR: 16.48, 95% CI: 1.32-206.22, p = 0.030)-and three protective factors-3-dehydrocarnitine (OR: 0.32, 95% CI: 0.14-0.72, p = 0.007), levulinate (4-oxovalerate) (OR: 0.40, 95% CI: 0.20-0.80, p = 0.010), and X-14,208 (phenylalanylserine) (OR: 0.68, 95% CI: 0.51-0.92, p = 0.010). Furthermore, seven metabolic pathways, including α-linolenic acid metabolism and pantothenate and CoA biosynthesis, are potentially associated with the onset and progression of JIA. CONCLUSION: Five serum metabolites, including kynurenine and 3-dehydrocarnitine, may be causally associated with JIA. These results provide a theoretical framework for developing effective JIA prevention and screening strategies.

Establishment of a prognostic risk model for osteosarcoma and mechanistic investigation.

Objective: To investigate the immune mechanism of osteosarcoma (OS)-specific markers to mitigate bone destruction in the aggressive OS, prone to recurrence and metastasis. Methods: Gene expression patterns from the Gene Expression Omnibus (GEO) database (GSE126209) were analyzed using weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) analysis, least absolute shrinkage and selection operator (LASSO) modeling, and survival analysis to identify charged multivesicular body protein 4C (CHMP4C). Subsequently, its role in regulating the immune system and immune cell infiltration was explored. CHMP4C expression and signaling molecules in OS were assessed in osteosarcoma cell lines (MG63, U2OS, HOS) and hFOB1.19 cells using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence staining. The impact of CHMP4C upregulation and interference on OS-related signaling molecules in MG63 cells was studied. Functional validation of CHMP4C in MG63 OS cells was confirmed through cell counting Kit-8 (CCK-8), transwell, and colony formation assays. In vivo experiments were conducted using Specific Pathogen Free (SPF)-grade male BALB/C nude mice for OS xenograft studies. Results: Based on the gene expression profiles analysis of six osteosarcoma samples and six normal tissue samples, we identified 1,511 upregulated DEGs and 5,678 downregulated DEGs in normal tissue samples. A significant positive correlation between the "yellow-green" module and OS was found through WGCNA analysis. Expression levels of CHMP4C, phosphorylated Glycogen Synthase Kinase 3ß (p-GSK3ß), and ß-catenin were notably higher in U2OS, HOS, and MG63 OS cells than in hFOB1.19 human osteoblasts. Overexpressing CHMP4C in MG63 OS cells upregulated CHMP4C, p-GSK3ß, and ß-catenin while downregulating GSK3ß, leading to increased proliferation and migration of MG63 cells. Conversely, interrupting CHMP4C had the opposite effect. High expression of CHMP4C significantly accelerated the growth of OS in nude mice, resulting in substantial upregulation of CHMP4C, p-GSK3ß, and ß-catenin expression and suppression of Glycogen Synthase Kinase 3ß (GSK3ß) expression in OS tissues. Conclusion: CHMP4C may serve as a specific immunomodulatory gene for OS. Its activation of the Wnt/ß-catenin signaling pathway, mainly by increasing the phosphorylation echelon of GSK3ß, promotes the invasion and spread of OS.

Identification of key autophagy-related genes and pathways in spinal cord injury.

Spinal cord injury (SCI) can cause a range of functional impairments, and patients with SCI have limited potential for functional recovery. Previous studies have demonstrated that autophagy plays a role in the pathological process of SCI, but the specific mechanism of autophagy in this context remains unclear. Therefore, we explored the role of autophagy in SCI by identifying key autophagy-related genes and pathways. This study utilized the GSE132242 expression profile dataset, which consists of four control samples and four SCI samples; autophagy-related genes were sourced from GeneCards. R software was used to screen differentially expressed genes (DEGs) in the GSE132242 dataset, which were then intersected with autophagy-related genes to identify autophagy-related DEGs in SCI. Subsequently, the expression levels of these genes were confirmed and analyzed with gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). A protein-protein interaction (PPI) analysis was conducted to identify interaction genes, and the resulting network was visualized with Cytoscape. The MCODE plug-in was used to build gene cluster modules, and the cytoHubba plug-in was applied to screen for hub genes. Finally, the GSE5296 dataset was used to verify the reliability of the hub genes. We screened 129 autophagy-related DEGs, including 126 up-regulated and 3 down-regulated genes. GO and KEGG pathway enrichment analysis showed that these 129 genes were mainly involved in the process of cell apoptosis, angiogenesis, IL-1 production, and inflammatory reactions, the TNF signaling pathway and the p53 signaling pathway. PPI identified 10 hub genes, including CCL2, TGFB1, PTGS2, FN1, HGF, MYC, IGF1, CD44, CXCR4, and SERPINEL1. The GSE5296 dataset revealed that the control group exhibited lower expression levels than the SCI group, although only CD44 and TGFB1 showed significant differences. This study identified 129 autophagy-related genes that might play a role in SCI. CD44 and TGFB1 were identified as potentially important genes in the autophagy process after SCI. These findings provide new targets for future research and offer new perspectives on the pathogenesis of SCI.

A formula for instability-related bone loss: estimating glenoid width and redefining bare spot.

PURPOSE: The aim of the study reveals a new intuitive method for preoperatively assessing defect ratio in glenoid deficiency based on the native glenoid width and the bare spot. METHODS: A linear relationship, i.e. the rh formula, between the native glenoid width (2r) and height (h) was revealed by a cadaver cohort (n = 204). To validate the reliability of the rh formula, 280 3D-CT images of intact glenoids were recruited. To evaluate the accuracy of rh formula in estimating glenoid defect, the 65 anterior-inferior defect models were artificially established based on the 3D-CT images of intact glenoids. Moreover, a clinically common anterior-posterior (AP) method was compared with the rh formula, to verify the technical superiority of rh formula. RESULTS: The regression analysis indicated a linear relationship between the width and height of intact glenoid: 2r = 0.768 × h - 1.222 mm (R2 = 0.820, p < 0.001). An excellent reliability was found between the formula prediction and model width (ICC = 0.911, p = 0.266). An excellent agreement was found between the predicted values and model parameters (glenoid width, ICCrh = 0.967, prh = 0.778; defect ratio, prh = 0.572, ICCrh = 0.997). And, it is of higher accuracy compared to the AP method (glenoid width, ICCAP = 0.933, pAP = 0.001; defect ratio, ICCAP = 0.911, pAP = 0.033). CONCLUSION: Applying the cadaver-based formula on 3D-CT scans accurately predicts native glenoid width and redefines bare spot for preoperatively determining glenoid bone loss.

Osteotomy Correction Angle Cut-off Points Can Guide the Operation to Prevent a Significant Decrease in Patella Height.

OBJECTIVE: Patients who undergo a biplanar ascending medial open-wedge high tibial osteotomy with an excessive correction angle might experience patella infera and even knee pain after surgery. The purpose of this study was to identify the cut-off points for the degree of knee varus correction of open-wedge high tibial osteotomy, which is related to the symptomatic patellar position change. METHODS: This retrospective study included 124 patients (mean age 61.69 ± 6.28 years; 78 women, 46 men) with varying degrees of varus knee osteoarthritis. All patients had undergone standard biplanar medial open-wedge high tibial osteotomy. They were divided into nine groups according to the change in hip-knee-ankle angle. Plain radiographs and three-dimensional CT images were obtained preoperatively and 18 months postoperatively. Patellar height was assessed using the Caton-Deschamps index, the Insall-Salvati index, and the Blackburne-Peel index. The patellofemoral index and patellar tilt were used to evaluate the degree of horizontal displacement of the patella. The varus correction, medial-proximal tibial angles, joint line convergence angles, and hip-knee-ankle angles were also measured. The subjective score was evaluated using the Western Ontario and McMaster Universities osteoarthritis index (WOMAC). RESULTS: There were significant changes in patella indexes in each group after surgery, among which there was no significant difference in patellar height changes for Groups A to F (p > 0.05), which were significantly lower than those in Group G, H, and I (p < 0.001). The patellar tilt and patellofemoral index also followed the same trend. The improvement in WOMAC scores for Groups G, H, and I was also significantly less for Groups A to F (p < 0.001). CONCLUSION: The patellar height, patellar tilt, and patellofemoral index all changed significantly in parallel with increasing degrees of osteotomy correction. The cut-off points for correction angle are 12.5° to 13.4°. When the correction angle is larger than this range, the patellar position can be significantly affected. Postoperative patellofemoral joint pain may be related to the changes in patella position.

Effect of Knee Valgus Deformity on Symptomatic Venous Thromboembolism and Prosthesis Revision Risk after Total Knee Arthroplasty: A Multicenter Retrospective Study.

OBJECTIVE: Symptomatic venous thromboembolism (VTE) and prosthesis failure are the most serious complications after total knee arthroplasty (TKA). However, whether knee valgus deformity aggravates these complications has not been fully clarified. To study the difference between perioperative symptomatic VTE and prosthesis revision rate in patients with valgus knee osteoarthritis by comparing with patients undergoing TKA for varus deformity and analyze the reasons for revision. At the same time, the distribution and radiographic features of lower extremity deep venous thrombosis were recorded. METHODS: The data of patients who underwent TKA in two tertiary hospitals from January 2016 to December 2020 were retrospectively reviewed, and a total of 8917 patients were included. According to preoperative manifestations of knee malformations, all patients were divided into two groups: valgus group (n = 412) and varus group (n = 8505). Main indicators included the incidence of symptomatic VTE and prosthesis revision. Secondary outcomes included general information on operative time, Kellgren and Lawrence score, total hospital stay, and total costs. The patient data of the two groups were analyzed by Pearson chi-square test, Student t test, or Mann-Whitney U test. The revision was evaluated using Kaplan-Meier survival analysis. RESULTS: The proportion of valgus knees in TKA patients was 4.62% (412/8917). The incidence of VTE was 6.23‰ (53/8505) and 16.99‰ (7/412) in the varus and valgus groups, and the results were statistically different (p = 0.009). There was no significant difference in echogenicity, number of occluded vessels, and thrombus length between the valgus group (p = 0.102; p = 0.645; p = 0.684). Patients with valgus deformity had 12.14‰ (5/412) prosthesis revision, the incidence of varus deformity was 4.82‰ (41/8505), and the revision risk of valgus group was 2.5 times higher than varus group, and the results were statistically different (p = 0.043). The operation time and hospital stay in the valgus group were longer than those in the varus group, and the results were statistically different (p = 0.018; p < 0.001). CONCLUSIONS: Valgus deformity increases risk of symptomatic VTE and prosthesis revision after TKA. These results have guiding significance for the prevention of complications after TKA in patients with valgus deformity.

M2 Microglia-derived Exosomes Promote Spinal Cord Injury Recovery in Mice by Alleviating A1 Astrocyte Activation.

M2 microglia transplantation has previously demonstrated beneficial effects on spinal cord injury (SCI) by regulating neuroinflammation and enhancing neuronal survival. Exosomes (EXOs), secreted by almost all cell types, embody partial functions and properties of their parent cells. However, the effect of M2 microglia-derived EXOs (M2-EXOs) on SCI recovery and the underlying molecular mechanisms remain unclear. In this study, we isolated M2-EXOs and intravenously introduced them into mice with SCI. Considering the reciprocal communication between microglia and astroglia in both healthy and injured central nervous systems (CNSs), we subsequently focused on the influence of M2-EXOs on astrocyte phenotype regulation. Our findings indicated that M2-EXOs promoted neuron survival and axon preservation, reduced the lesion area, inhibited A1 astrocyte activation, and improved motor function recovery in SCI mice. Moreover, they inhibited the nuclear translocation of p65 and the activation of the NF-κB signalling pathway in A1 astrocytes. Therefore, our research suggests that M2-EXOs mitigate the activation of neurotoxic A1 astrocytes by inhibiting the NF-κB signalling pathway, thereby improving spinal tissue preservation and motor function recovery following SCI. This positions M2-EXOs as a promising therapeutic strategy for SCI.

Comparison of different degrees of varus deformity correction with open-wedge high tibial osteotomy: a retrospective study over 5 years.

OBJECTIVE: This study aims to investigate the clinical efficacy and complications associated with open-wedge high tibial osteotomy (OWHTO) in the treatment of medial compartment knee osteoarthritis. Additionally, the compensatory changes in the hip, patellofemoral, and ankle regions will be assessed through imaging. METHODS: A retrospective analysis of clinical data pertaining to 86 patients who underwent OWHTO at the Affiliated Hospital of Qingdao University from January 2015 to September 2018 was conducted. The weight-bearing line ratio (WBLR) was measured postoperatively, and patients were categorized into a normal group (50% < WBLR ≤ 62.5%, n = 67) and an overcorrection group (WBLR > 62.5%, n = 19). Various parameters, including hip-knee-ankle angle (HKA), medial proximal tibial angle (MPTA), lateral distal femoral angle (LDFA), joint line convergence angle (JLCA), and posterior tibial slope (PTS), were measured before surgery and at the last follow-up to assess lower limb line correction. The compensatory changes in adjacent joints were evaluated by measuring hip abductor angle (HAA), tibial plafond inclination (TPI), talus inclination angle (TIA), Carton-Deschamps index, lateral patellar tilt (LPT), lateral patellar shift (LPS), medial patellofemoral space, and lateral patellofemoral space in both groups. The American Hospital for Special Surgery (HSS) score and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) of the affected knee were assessed before surgery and at the last follow-up, and the incidence of complications in both groups was analyzed. RESULTS: Postoperative complications occurred in 26.32% (five cases) of the overcorrection group and 5.97% (four cases) of the normal group, with a statistically significant difference (χ2 = 4.548, p = 0.033). No significant differences were observed in HSS and WOMAC between the two groups at the last follow-up. HAA was - 2.44 ± 1.98° in the overcorrection group and - 1.16 ± 2.1° in the normal group, with a statistically significant difference (t = 2.32, p = 0.023). There were no significant differences in other imaging indexes. CONCLUSION: Overcorrection of varus deformity may not significantly impact clinical outcomes within 5 years post-OWHTO but may elevate the incidence of postoperative complications and lead to increased compensatory adduction of the hip.

Single-cell RNA sequencing reveals the impact of mechanical loading on knee tibial cartilage in osteoarthritis.

Articular cartilage degeneration is one of the major pathogenic alterations observed in knee osteoarthritis (KOA). Mechanical stress has been verified to contribute to KOA development. To gain insight into the pathogenic mechanism of KOA development, we investigated chondrocyte subsets under different mechanical loading conditions via single-cell RNA sequencing (scRNA-seq). Articular cartilage tissues from both high mechanical loading (named the OATL group) and low mechanical loading (named the OATN group) surfaces were obtained from the proximal tibia of KOA patients, and scRNA-seq was conducted. Chondrocyte subtypes, including a new subset, HTC-C (hypertrophic chondrocytes-C), and their functions, development and interactions among cell subsets were identified. Immunohistochemical staining was also conducted to verify the existence and location of each chondrocyte subset. Furthermore, differentially expressed genes (DEGs) and their functions between regions with high and low mechanical loading were identified. Based on Gene Ontology terms for the DEGs in each cell type, the characteristic of cartilage degeneration in the OATL region was clarified. Mitochondrial dysfunction may be involved in the KOA process in the OATN region.