Unicompartmental knee arthroplasty (UKA) has become an effective treatment for medial compartment osteoarthritis of the knee. However, its use in patients who also have patellofemoral joint osteoarthritis (PFOA) before surgery remains controversial. Restoring postoperative lower limb alignment and achieving accurate implant positioning are also important factors for the success of UKA, but there is still a lack of studies that combine both patient-related factors and surgical technique-related factors in the Chinese population. This study retrospectively analyzed 69 Chinese patients (79 knees) with medial compartment osteoarthritis who underwent Oxford UKA between May 2017 and December 2020. The severity and location of PFOA were assessed by MRI. Postoperative coronal alignment was categorized by the femorotibial angle (FTA) into neutral, mild varus, moderate varus, and extreme/out-of-range groups. Implant positioning was classified as ideal or non-ideal according to established radiographic target ranges for aLDFA, aMPTA, PTS, and component alignment angles. Functional outcomes were evaluated using VAS, KSS, WOMAC, and Kujala scores, with multifactorial interactions analyzed via multivariate analysis of covariance (MANCOVA). At a mean follow-up of 66.5 ± 9.6 months, Oxford UKA markedly improved overall patient function. While no cases of prosthesis loosening or revision were observed, three patients reported persistent postoperative pain and two presented with valgus deformity. Postoperative functional scores did not differ by PFOA severity or lesion location. Regarding lower-limb alignment, neutral and mild varus (< 6°) knees had higher KSS function scores than moderate varus and extreme/out-of-range knees and lower WOMAC scores. KSS knee scores were higher in neutral and mild varus than in the extreme group. Implant positioning (ideal vs non-ideal) was not associated with postoperative scores. Mid-term follow-up showed that Oxford UKA achieved satisfactory clinical outcomes. The severity and location of PFOA before surgery did not significantly affect postoperative knee function. Maintaining postoperative alignment within the target range (neutral to slight varus; within 6° of varus) may be associated with better functional recovery.

Early pain after total knee arthroplasty (TKA) can limit walking and knee training. Movement-related pain may be particularly relevant because it occurs during passive knee training, walking, and weight-bearing activity. Navigation and robotic systems can help the surgeon plan bone cuts, place implants, and balance soft tissue. However, surgeons still do not know whether these tools lower the overall pain burden during early recovery. This point is especially important for pain that appears during movement. This study compared early pain after conventional, navigation-assisted, and robotic-assisted TKA. We used the area under the curve (AUC) to describe cumulative pain from 24 to 72 h after surgery. We retrospectively reviewed 169 patients undergoing primary unilateral TKA from April 2025 to April 2026. Patients were grouped as conventional (n = 78), navigation-assisted (n = 39), or robotic-assisted TKA (n = 52). The primary outcome was the 24–72 h area under the curve (AUC) of visual analogue scale (VAS) pain during passive knee flexion-extension. Secondary outcomes included resting pain AUC, time-point VAS scores, walking pain at discharge, rescue analgesic frequency, morphine-equivalent consumption, early range of motion, swelling, quality of recovery, 3-month Knee Society Score, hospital stay, and complications. Multivariable regression adjusted for measured confounders. The study included 169 patients. Seventy-eight patients received conventional TKA, 39 patients received navigation-assisted TKA, and 52 patients received robotic-assisted TKA. The three groups had similar measured baseline features. Resting-pain AUC from 24 to 72 h did not differ among the groups. Passive-motion pain AUC differed significantly among the groups. The robotic-assisted group had a lower cumulative movement-related pain burden than the conventional group. The navigation-assisted group showed a lower AUC estimate, but this difference was not significant after adjustment. The difference between the robotic-assisted and navigation-assisted groups was not significant. Passive-motion VAS at 36 and 48 h was lower after robotic-assisted TKA than after conventional TKA. Walking pain at discharge was also lower in the robotic-assisted group. The groups did not differ in rescue analgesic frequency, morphine-equivalent rescue analgesic consumption, knee swelling, ROM recovery, QoR-15, length of stay, complications, or 3-month KSS. Robotic-assisted TKA was associated with lower early movement-related pain burden than conventional TKA, but the absolute time-weighted VAS difference was modest. These findings should be interpreted as associations rather than causal evidence of superiority. Movement-related pain AUC may be useful for evaluating early rehabilitation pain after TKA.

Deep vein thrombosis (DVT) is a common perioperative complication in elderly patients with hip fractures and may lead to life-threatening pulmonary embolism (PE). Isolated calf muscle vein thrombosis (ICMVT), a prevalent subtype of DVT, is often asymptomatic and easily overlooked. Despite its clinical significance, current research on ICMVT remains limited, and there is a lack of validated tools for early identification. This study aimed to determine the incidence and independent risk factors of preoperative ICMVT in elderly patients with hip fractures. In addition, we sought to develop a nomogram-based predictive model using readily available clinical parameters to facilitate early recognition and targeted intervention in high-risk patients. We conducted a retrospective analysis of 673 elderly patients with hip fractures who were treated at our institution between June 2020 and June 2023. Patients were categorized into groups based on the presence or absence of preoperative isolated calf muscle vein thrombosis (ICMVT), as confirmed by duplex ultrasonography. Clinical and laboratory data were collected and compared. Univariate analysis followed by multivariate logistic regression was performed to identify independent risk factors associated with preoperative ICMVT. A predictive nomogram model was subsequently developed. The model’s performance was assessed in terms of discrimination, calibration, and clinical utility using the area under the receiver operating characteristic (ROC) curve, calibration plots, and decision curve analysis (DCA), respectively. The incidence of preoperative isolated calf muscle vein thrombosis (ICMVT) was 16.5

BACKGROUND:The objective of our study was to compare five low-dose perioperative dexamethasone (DEX) regimens on early recovery after total knee arthroplasty and identify an optimal route combination. METHODS:In a prospective, double-blind, randomized controlled trial, patients were randomized to five groups. The COMB (combination) group received a combined regimen of pre and postoperative intravenous (IV) doses with intraoperative periarticular injection (PAI), the IV2 group received pre and postoperative IV doses, the IV1 group received a single preoperative IV dose, the PAI group received intraoperative PAI, and the CON (control) group received no DEX. Outcomes within 72 hours were visual analog scale pain (rest, passive flexion, and ambulation); postoperative nausea and vomiting (PONV); opioid consumption; range of motion (ROM); C-reactive protein; interleukin-6; white blood cell count and neutrophil percentage; Knee Society Score; knee swelling; Quality of Recovery-15; lengths of stay; and complications. RESULTS:Versus the CON group, the COMB group showed lower rest pain on postoperative days (PODs) 1 to 3, and the PAI group showed lower pain on POD one to two. Both groups had lower passive flexion pain on POD one to two and lower ambulation pain on POD three. Compared with IV2 and IV1 groups, the COMB group yielded lower rest, passive-flexion, and ambulation pain across the same windows. The PONV rates were lower in the COMB, IV2, and IV1 groups than in CON and PAI groups; the PAI group did not differ from the CON group. Across POD one to three, ROM was higher in all intervention groups than in the CON group. Both C-reactive protein and interleukin-6 were lower in the COMB, IV2, and IV1 groups versus the CON group. Peripheral white blood cell count and neutrophil percentage increased in the COMB and PAI groups. There was one mild gastrointestinal bleed that occurred in the COMB group; no other serious adverse events were observed. CONCLUSIONS:In primary total knee arthroplasty, low-dose DEX reduced pain and PONV within 72 hours and facilitated early ROM recovery. A combined multiroute regimen balanced efficacy and safety, supporting optimized and individualized DEX pathways.

Osteosarcoma (OS) is a highly aggressive primary bone malignancy characterized by limited treatment options and poor clinical outcomes. Emerging evidence underscores the critical role of mitochondrial metabolism in tumor progression, positioning mitochondrial proteins as potential therapeutic targets. SLC25A10, a mitochondrial dicarboxylate carrier involved in redox homeostasis and fatty acid synthesis, has been implicated in various cancers; however, its role in OS remains unclear.In this study, we investigated the function of SLC25A10 in OS progression and its potential as a therapeutic target. Our results revealed that SLC25A10 expression is significantly upregulated in OS tissues and cell lines compared to normal bone tissue, and its elevated expression is associated with poor patient prognosis. Functional assays demonstrated that silencing SLC25A10 via shRNA or CRISPR/Cas9 significantly suppressed OS cell proliferation, migration, and mitochondrial function, resulting in mitochondrial membrane depolarization, oxidative damage, and apoptosis. In contrast, SLC25A10 overexpression promoted OS cell proliferation and migration. In vivo, knockout of SLC25A10 markedly inhibited the growth of subcutaneous OS xenografts in nude mice.Furthermore, we identified STUB1, an E3 ubiquitin ligase, as a negative regulator of SLC25A10. STUB1 knockdown reduced the ubiquitination of SLC25A10, leading to increased protein stability and elevated expression. Notably, lysine 254 (K254) was identified as a key site mediating STUB1-dependent ubiquitination of SLC25A10. STUB1-mediated downregulation of SLC25A10 suppressed OS cell proliferation and migration, indicating a tumor-suppressive role for STUB1 in OS through modulation of SLC25A10.Collectively, our findings demonstrate that SLC25A10 is essential for maintaining mitochondrial function and contributes to OS malignancy. Targeting SLC25A10 may represent a novel and promising therapeutic strategy for the treatment of osteosarcoma.

BackgroundThe inflammatory response following hip fracture significantly influences postoperative functional recovery in patients. However, to date, no inflammatory index has been identified as a reliable and accurate predictor of functional recovery, especially in elderly patients with hip fractures. This study introduces and evaluates a novel inflammatory marker, the lymphocyte ratio-calcium index (LRCa3), for predicting one-year postoperative functional recovery and compares its performance to that of established markers, including the platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), aggregate index of systemic inflammation (AISI), and systemic inflammation response index (SIRI).MethodsA retrospective analysis was conducted on 111 elderly patients (≥65 years) who underwent hip fracture surgery, and their demographic and laboratory data were analyzed. Patients were classified into good or poor recovery groups based on the Harris hip score (HHS) 1 year postoperatively. LRCa3 was calculated as the lymphocyte ratio multiplied by the cube of the serum calcium level. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the predictive performance of the LRCa3 and other inflammatory indices. A nomogram prediction model was constructed.ResultsROC curve analysis revealed that, compared with the SII (AUC: 0.601), the SIRI (AUC: 0.61), the AISI (AUC: 0.577), and the MLR (AUC: 0.626) had superior predictive performance. Multivariate logistic regression revealed that the LRCa3 was an independent predictor of one-year functional recovery. The incorporation of LRCa3 into a nomogram further enhanced its predictive capacity, providing a more accurate tool for postoperative outcome assessment.ConclusionLRCa3 is a novel and effective biomarker for predicting postoperative functional recovery in elderly hip fracture patients. Its integration into clinical practice could facilitate individualized patient management and improve long-term outcomes.

Aims: Periprosthetic osteolysis (PPO), a leading cause of aseptic loosening in joint replacement, arose from complex interactions among osteoblasts, osteoclasts, and osteocytes. Given the pivotal role of connexin 43 (Cx43) in osteocyte communication and bone remodeling, investigating its function was essential for understanding the mechanisms of osteolysis. Our previous studies showed that titanium (Ti) particles increased Cx43 expression in osteocytes. However, the role of Cx43 in osteolysis remained unclear. This study investigated the role of Cx43-mediated regulation of osteocytes on osteoclastogenesis in wear debris-induced osteolysis. Results: Using Dmp1-cre conditional Cx43 knockout mice and the MLO-Y4 osteocyte cell line, we demonstrated that Cx43 deficiency reduced bone resorption and osteoclastogenesis, thereby improving bone remodeling in a Ti particle-induced osteolysis model. Sequencing analysis revealed that Cx43 gene expression changes might be linked to oxidative stress and the Janus Kinase (JAK)-STAT pathway. Elevated Cx43 expression in osteocytes stimulated by Ti particles increased STAT1 protein phosphorylation, induced oxidative stress, elevated the Receptor Activator of Nuclear Factor Kappa-Β Ligand (RANKL)/Osteoprotegerin (OPG) ratio, and promoted osteoclast activation and bone resorption. Conversely, Cx43 gene knockout decreased STAT1 protein phosphorylation and enhanced Nuclear Factor Erythroid 2-Related Factor 2 (NrF2) protein expression. Blocking the JAK-STAT signaling pathway activated by Cx43 increased NrF2 expression, reduced reactive oxygen species levels, and subsequently decreased the RANKL/OPG ratio. Innovation and Conclusions: This study identified a novel mechanism where Cx43 in osteocytes promoted osteoclastogenesis through JAK-STAT pathway activation and oxidative stress in wear debris-induced osteolysis. These findings highlighted the critical role of Cx43 in bone resorption and suggested targeting Cx43 or the JAK-STAT pathway as potential therapeutic strategies to mitigate osteolysis and improve implant longevity. Antioxid. Redox Signal. 43, 215-238.

The optimal surgical approach for tibial avulsion fractures of the posterior cruciate ligament (PCL) remains controversial. This study aimed to compare the clinical outcomes of four techniques: arthroscopic suture fixation, arthroscopic loop plate fixation, open reduction with cannulated screw fixation, and open reduction with anchor suture bridge fixation. A retrospective review was conducted of 73 patients treated between January 2019 and December 2023 using one of four surgical techniques: arthroscopic suture fixation (Group A, n = 26), arthroscopic loop plate fixation (Group B, n = 14), open reduction with cannulated screw fixation (Group C, n = 16), and open reduction with anchor suture bridge fixation (Group D, n = 17). Demographic data, operative time, pre- and postoperative visual analog scale (VAS) pain scores, Lysholm scores, International Knee Documentation Committee (IKDC) scores, knee range of motion (ROM), and postoperative complications were analyzed. No significant differences were observed in baseline demographic data among the four groups (P >.05). Operative time was shortest in Group D (60.41 ± 12.39 min), significantly less than in the other groups (P =.0001). At 3 months postoperatively, all groups demonstrated significant improvements in VAS, Lysholm, and IKDC scores (P <.0001); however, intergroup differences were not statistically significant (P >.05). Group A demonstrated significantly less ROM recovery compared with the other groups (P =.0171). At final follow-up, further improvements in functional scores and ROM were observed in all groups, with no significant intergroup differences (P >.05). Complication rates differed significantly among the groups (P =.0361), with Group D reporting the lowest rate (0

BACKGROUND:The impact of posterior lateral tibial plateau fractures (PLTPFs) on knee joint stability after anterior cruciate ligament (ACL) reconstruction has garnered widespread attention. However, limited literature exists on the co-occurrence of ACL tibial avulsion fractures (ACLAFs) and PLTPFs. The objective of this study is to investigate the prevalence of PLTPFs in adult ACLAF patients and assess the impact of concurrent PLTPFs on postoperative knee function. METHODS:This retrospective study analyzed adults, who underwent arthroscopic surgery for ACLAF at our institution between January 2016 and January 2022. Demographic and preoperative/postoperative imaging data were collected, focusing on meniscus and ligament injuries, Segond fractures, PLTPFs, and tibial plateau slope. Patients were grouped into isolated ACLAF (I-ACLAF) and ACLAF with concurrent PLTPFs (ACLAF-PLTPF). The ACLAF-PLTPF group was further divided into Group A (PLTPFs not exceeding the anterior edge of the lateral meniscus posterior horn) and Group B (PLTPFs exceeding this edge). Clinical outcomes were evaluated using International Knee Documentation Committee and Tegner scores. The study also examined the morphology of PLTPFs and their specific affected areas. Statistical analysis was performed using the Mann-Whitney U tests for continuous variables and Fisher's exact tests for categorical variables. RESULTS:The study included 62 patients with a mean follow-up of 41 ± 17 months. Among these, 71.0% (44/62) patients with ACLAF also had PLTPFs. The ACLAF-PLTPF group showed a significantly steeper lateral tibial plateau slope than the I-ACLAF group (10.86° ± 5.47° vs. 7.17° ± 3.68°, p = 0.011). Segond fractures were present in 22.7% of the ACLAF-PLTPF group, compared to none in the I-ACLAF group (p = 0.027). IKDC and Tegner scores were lower in the ACLAF-PLTPF group (80.7 ± 5.2 and 4, respectively) than in the I-ACLAF group (87.4 ± 6.4 and 4.5, respectively), with statistical significance (p < 0.001 and p = 0.008, respectively). Older age correlated with a greater extent of concurrent PLTPFs (p = 0.038). Additionally, Patients in Group B exhibited a significantly higher incidence of meniscal injury (22.2% vs. 53.8%, p = 0.036) and poorer postoperative knee joint function compared to those in Group A (IKDC 82.3 ± 2.8 vs. 78.5 ± 5.6, p = 0.013). More extensive PLTPFs were linked to increased fracture collapse and a higher rate of lateral meniscus injuries. CONCLUSION:PLTPFs demonstrated a high prevalence in adults with ACLAF. Additionally, the ACLAF-PLTPF cohort frequently showed reduced postoperative knee function. Simultaneous management of severe concomitant PLTPFs may improve long-term outcomes in patients with ACLAF.

BACKGROUND:Body mass index (BMI) was used to classify overweight or obesity. The obesity paradox was observed in elderly hip fracture patients. However, obesity has been implicated as one of the major risk factors for hypertension and diabetes. This study aims to determine whether a high body mass index (BMI) remains a protective factor in hip fracture patients with comorbid hypertension or diabetes, and to identify the optimal BMI threshold that best supports motor function recovery. METHODS:This study included patients aged 65 years and older who have underwent hip fracture surgery. Harris Hip Score (HHS) was utilized to evaluate the functional recovery, the relationship between BMI and HHS was examined using both linear and generalized additive model (GAM). A threshold model was established with BMI of 24 kg/m2 and the difference between the threshold model and the GAM was compared utilizing the likelihood ratio test (LRT). RESULTS:A total of 213 patients were enrolled in the study. A nonlinear relationship was identified between BMI and HHS in patients with either hypertension or diabetes and the HHS demonstrated a significant downward trend with increasing BMI. The LRT revealed no significant difference between the threshold effect model with a BMI value of 24 kg/m2 and the GAM. CONCLUSIONS:This study reveals that the protective effect of high BMI on postoperative motor function in hip fracture patients is significantly modulated by comorbidities. We recommend modulating the BMI to approximately 24 kg/m2 for elderly patients with hip fractures and comorbid conditions such as hypertension and diabetes.

Objective To compare four perioperative low-dose dexamethasone regimens for early recovery after unicompartmental knee arthroplasty (UKA) and to identify an optimal regimen. Methods In this retrospective cohort study, a total of 247 patients who underwent UKA were allocated to four groups according to perioperative low-dose dexamethasone use: (1) IVDPAD, preoperative and postoperative intravenous dexamethasone plus intraoperative periarticular dexamethasone; (2) IVD, preoperative and postoperative intravenous dexamethasone; (3) PAD, intraoperative periarticular dexamethasone alone; and (4) CON, without dexamethasone. Outcomes within 72 h included visual analog scale pain scores at rest, during passive flexion and ambulation; postoperative nausea and vomiting; opioid consumption; knee range of motion; C-reactive protein; white blood cell count; and neutrophil percentage. Knee Society function score, knee swelling, recovery-15 quality, length of stay and complications were also recorded. Results Compared with the CON group, the IVDPAD and PAD groups presented lower VAS pain at rest on postoperative days 1–2, lower passive flexion pain on days 1–3 and lower ambulation pain on day 3. Compared with IVDs, IVDPADs are associated with less pain at rest and passive flexion pain on days 1–2. PONV incidence in the IVDPAD and IVD groups was significantly lower than that in the CON and PAD groups, with no significant difference between the PAD and CON groups. Knee ROM on days 1–3 was greater in the IVDPAD group than in the CON group. CRP was significantly lower in the IVDPAD and IVD groups than in the CON and PAD groups, whereas the WBC and neutrophil percentages increased in the IVDPAD and PAD groups. The length of stay was shorter in the IVDPAD and PAD groups. No serious adverse events occurred. Changes in blood glucose levels, the KSS function score, knee swelling, the QoR-15 score and overall complications did not differ significantly among the groups. Conclusions Under a standardized enhanced recovery after surgery pathway, the combined intravenous–periarticular low-dose dexamethasone regimen provides early benefits, likely through complementary systemic antiemetic and local anti-inflammatory effects. Overall, IVDPAD achieved a favorable balance between efficacy and safety and may help optimize dexamethasone pathways and stratify perioperative management after UKA.

The interplay among host genetic architecture, gut microbiota, metabolites and bone metabolism remains poorly understood. This study aims to comprehensively investigate the shared genetic factors, causal relationships, and the involvement of blood metabolites between gut microbiota and bone mass, based on datasets from European populations. Here, we estimate the polygenic SNP heritability for 1104 gut microbiota taxa, only 96 (8.7%) showed significant polygenic heritability. We identify 14 distinct gut microbiota taxa with pleiotropic effects on estimated heel bone mineral density (eBMD), 11 of them are found to have a causal association with eBMD. Following sensitivity and validation analyses, we find that the gut microbiota taxa family Bifidobacteriaceae; genus Bifidobacterium and species Bifidobacterium adolescentis exert causal effects leading to decreased eBMD. Mediation analyses indicate that the impact of these taxa on eBMD may be driven by their influence on circulating stearidonate (18:4n-3) levels via n-3 pathway, with mediating proportion from 77.53% to 87.24%. In conclusion, the genetically informed negative association between bifidobacterial taxa and bone mass may reflect the host-microbe interactions at LCT/MCM6 locus and represent an adaptive microbial response to lactose intolerance, thus, it could potentially be mitigated through supplementation with bifidobacterial probiotics and n-3 polyunsaturated fatty acids.

ABSTRACT Objective The incidence of anterior cruciate ligament (ACL) ruptures has been increasing annually. However, clinical surgeons have overlooked the impaction fractures of the posterolateral tibial plateau and lateral femoral condyle in patients with ACL ruptures. The purpose of the present study was to report the detection rate of the posterolateral tibial plateau impaction fractures in patients with ACL ruptures, and to evaluate the functional outcomes of patients following ACL reconstruction (ACLR) without treatment of the tibial fractures at a 2‐year postoperative follow‐up. Methods Four hundred eighty‐eight patients treated for ACL ruptures between January 2016 and June 2020 were retrospectively reviewed, and the posterolateral tibial plateau impaction fractures were classified based on MRI assessment. The detection rate of the posterolateral tibial plateau impaction fractures was calculated, and the functional outcomes (SF‐12 Mental Component Summaries, SF‐12 Physical Component Summaries, Tegner, Lysholm, IKDC, and KOOS) were evaluated at a 2‐year postoperative follow‐up. Results The detection rate of posterolateral tibial plateau impaction fractures was 41.6% among ACL ruptures. Of these, 285 cases (58.4%) had no fractures, 98 cases (20.1%) had type I impaction fractures, 41 cases (8.4%) had type IIA impaction fractures, 15 cases (3.1%) had type IIB impaction fractures, 22 cases (4.5%) had type IIIA impaction fractures, and 27 cases (5.5%) had type IIIB impaction fractures. Patients with type IIIA or IIIB impaction fractures showed an increased detection rate of contact mechanism compared to the other subgroups. Significant differences in Tegner (postoperation) and KOOS (QOL) were found between no fracture and type IIIB impaction fractures in patients following ACLR. Conclusions The detection rate of posterolateral tibial plateau impaction fractures in patients with ACL ruptures was high. Patients with type IIIB impaction fractures following ACLR had poor functional outcomes.

BACKGROUND:Nucleus pulposus (NP) deterioration plays a significant role in the development of intervertebral disc degeneration (IVDD) and low back pain (LBP). This paper aims to identify potential genes within degenerated NP tissue and elucidate the pathogenesis of IVDD through bioinformatics analysis. METHODS:We conducted a transcriptomic analysis of patient's degenerative NP tissue employing advanced bioinformatics techniques and machine learning algorithms. Utilizing hdWGCNA, we successfully acquired WGCNA single-cell sequencing data and pinpointed crucial genes implicated in IVDD. Subsequently, we employed the Monocle3 package to perform pseudotime sequence analysis, enabling the identification of genes associated with the differentiation and developmental processes of NP tissue. Following this, normalized and logarithmically transformed the bulk sequencing data. Subsequently, we conducted preliminary screening using single-factor logistic regression on the genes derived from single-cell sequencing. Next, we applied two machine learning techniques, namely, SVM-RFE and random forest, to discern pivotal pathogenic genes. Finally, we used validation sets to verify trends and qualitativeness and performed in vitro and in vivo validation analyses of normal and degenerative NP tissues. RESULTS:909 genes associated with IVDD were identified through hdWGCNA, while pseudotime sequence analysis uncovered 1964 genes related to differentiation and developmental processes. The two had 208 genes in common. Subsequently, we conducted an initial screening of single-cell genes by integrating the bulk database with single logistic regression. Next, we utilized machine learning techniques to identify the IVDD genes CDH, DPH5, and SELENOF. PCR analysis confirmed that the expression of CDH and DPH5 in degraded nucleus pulposus cells (NPCs) was decreased by 31% and 28% in vivo, and 36% and 29% in vitro, respectively, while SELENOF showed the opposite trend. Furthermore, IVDD was validated through imaging and histological staining. CONCLUSION:As pathogenic genes in IVDD, our findings indicate that CTH, DPH5, and SELENOF are important players and might be promising therapeutic targets for IVDD treatment.

Background: With the recent rise in anterior cruciate ligament (ACL) reconstruction surgeries in China, a corresponding increase in surgical failures has been observed. Variability in primary surgical techniques and the intricacies of failure mechanisms have introduced significant challenges in diagnosing failures, planning procedures, and conducting revision surgeries. Methods: In response to these challenges, the Chinese Association of Orthopaedic Surgeons (CAOS) and the Chinese Society of Sports Medicine (CSSM) initiated the development of an expert consensus on ACL reconstruction failure and revision. Utilizing a modified Delphi method, 67 domestic experts from relevant fields were invited for consensus formulation and review. Results: The expert panel achieved a high degree of consensus on twelve key aspects. The consensus clearly defines ACL reconstruction failure and outlines multiple contributing factors, with surgical errors, especially incorrect bone tunnel placement, identified as primary causes. It also emphasizes the significant impact of patient-specific variables on the likelihood of failure. Recommendations for revision surgeries include careful determination of revision indications, preserving meniscal integrity to reduce the risk of joint degeneration, and a preference for single-stage or two-stage surgeries based on individual patient evaluations. A unified approach for managing bone defects remains absent, necessitating comprehensive assessments. Graft selection should be tailored to each patient, with autografts, allografts, or synthetic ligaments as viable options. For patients with a highly positive pivot shift test or those engaged in high-demand athletic activities, anterolateral structure augmentation or reconstruction is recommended. Conclusion: The consensus emphasizes the critical need for individualized approaches in ACL revision surgery. By clearly defining failure criteria and outlining strategies for surgical revisions, these statements are expected to serve as a guide for refining clinical practice, reducing complications, and improving surgical outcomes. The translational potential of this article: 1) Establishment of Evidence-Based Clinical Guidelines: This article presents a rigorously developed expert consensus on ACL reconstruction failure and revision, providing evidence-based clinical guidelines that are directly applicable in surgical practice. The standardization of these protocols across medical institutions has the potential to reduce variability in patient care and improve surgical outcomes on a national scale. 2) Advancement of Precision Medicine in ACL Surgery: By emphasizing the need for patient-specific approaches in the management of ACL reconstruction failure, this consensus supports the advancement of precision medicine in orthopaedic surgery. The tailored recommendations for graft selection, surgical techniques, and rehabilitation protocols can lead to more personalized and effective treatments, reducing the risk of complications and enhancing recovery. 3) Catalyst for Innovation in Surgical Techniques: The article identifies critical gaps and challenges in current ACL revision practices, providing a foundation for future research and innovation. By outlining the complexities and controversies in surgical decision-making, this work serves as a catalyst for the development of new surgical techniques and technologies aimed at improving patient outcomes. 4) Framework for Future Research and Development: The consensus not only addresses immediate clinical needs but also sets a clear agenda for future research in ACL revision. By offering a structured approach to the diagnosis and management of ACL failures, this article guides both basic and translational research efforts, ensuring that future innovations are aligned with clinical realities and patient needs.

Osteomyelitis is a disease with a complex etiology and a high recurrence rate, which causes significant distress to both patients and physicians. There is currently no clear understanding of the factors that influence the progression of osteomyelitis. Previously, only small-sample observational studies have demonstrated an association between osteomyelitis, plasma lipidomics and immune cell characteristics. The objective of this study is to analyze the causal relationship between lipidomics and osteomyelitis by Mendelian randomization and to determine the mediating role of immune cells in this process. This study validated the causal relationship between osteomyelitis and 179 lipid species by two-sample Mendelian randomization analysis using publicly available genetic data. To ensure the reliability of the findings, this study employed both sensitivity analysis and inverse Mendelian randomization analysis. Furthermore, this study used two-step Mendelian to quantify the proportion of immune cell characteristics mediated lipidomics in osteomyelitis. After rigorous screening of instrumental variables, and multiple Mendelian randomization methods, this study identified a causal relationship between 5 lipid species and 20 immune cell traits and osteomyelitis. Through a comprehensive analysis of causality, this study identified an increased risk of osteomyelitis with increased Diacylglycerol (d40:2) levels (inverse variance-weighted method, [OR] per SD increase in osteomyelitis = 1.147 [95

Early recognition of malnutrition is essential to improve the prognosis of older patients with hip fracture. The Nutritional Risk Screening 2002 (NRS-2002), the Short-Form Mini Nutritional Assessment (MNA-SF) and the Global Leadership Initiative on Malnutrition (GLIM) are widely used in malnutrition diagnosis. However, criteria for predicting postoperative hip joint motor function in older patients with hip fractures are still necessary. The objective of this study was to select the most appropriate criteria from the NRS-2002, the MNA-SF and the GLIM in predicting the postoperative hip joint motor function recovery 1 year after surgery. This retrospective observational study included 161 patients aged ≥ 65 years with hip fractures. The nutritional status of patients was determined by the NRS-2002, MNA-SF and GLIM. The Harris hip joint score (HHS), the primary outcome of this study, was used to evaluate hip joint motor function. HHS was classified as excellent (HHS > 75) or non-excellent outcomes (HHS ≤ 75). Logistic regression models for hip joint motor function recovery were constructed. Both the receiver operating characteristic curve and the decision curve analysis were used to select the most predictive criteria. The overall mean age of the 161 patients was 77.90 ± 8.17. As a result, NRS-2002 (OR:0.06, 95%CI [0.01, 0.17]), MNA-SF (OR:0.05, 95%CI [0.00, 0.23]) and GLIM (OR of moderate: 0.03, 95%CI [0.01, 0.11]; OR of severe: 0.02 [0.00, 0.07]) were predictive for recovery of hip joint motor function. Additionally, both the area under curve of the receiver operating characteristic curve (NRS-2002: 81.2 [73.8, 88.6], MNA-SF: 76.3 [68.5, 84.2], GLIM: 86.2 [79.6,92.8]) and the decision curve analysis showed the GLIM was better than others. Compared with NRS-2002 and MNA-SF, GLIM was a more suitable nutritional assessment criteria to predict the postoperative recovery of hip joint motor function for older patients with hip fracture 1 year after surgery.

Bioabsorbable zinc (Zn)-based materials for bone defect repair have received increasing attention. Based on 3D printing technology, this study innovatively designed and manufactured pure Zn and Ti6Al4V porous scaffolds. The pore size of the scaffold was 700 μm and the porosity was 70%. Compared with the traditional Ti6Al4V scaffolds, it was found that the Zn scaffolds had a larger deformation, the ultimate compressive stress was 18 MPa, but the ultimate strain could exceed 20%, while Ti6Al4V was only 6%. The elastic modulus of the Zn scaffolds was also lower than that of Ti6Al4V, which was 0.25 GPa, which can meet bone repair requirements in the non-weight-bearing area. However, Zn scaffolds had better strain capacity and lower elastic modulus, so they had less stress-shielding effect on bone. Degradation experiments also proved that the Zn scaffold had good degradation performance. Further in vivo and in vitro experiments showed that the Zn scaffolds had better osteogenic ability than the Ti6Al4V scaffolds. The findings of our study underscore the potential of integrating pure Zn into 3D printed scaffolds for their application in orthopedic scenarios.

Intervertebral disc degeneration (IVDD) is the primary factor contributing to low back pain (LBP). Unlike elderly patients, many young IVDD patients usually have a history of trauma or long-term abnormal stress, which may lead to local inflammatory reaction causing by immune cells, and ultimately accelerates degeneration. Research has shown the significance of M1-type macrophages in IVDD; nevertheless, the precise mechanism and the route by which it influences the function of nucleus pulposus cell (NPC) remain unknown. Utilizing a rat acupuncture IVDD model and an NPC degeneration model induced by lipopolysaccharide (LPS), we investigated the function of M1 macrophage-derived exosomes (M1-Exos) in IVDD both in vivo and in vitro in this study. We found that M1-Exos enhanced LPS-induced NPC senescence, increased the number of SA-β-gal-positive cells, blocked the cell cycle, and promoted the activation of P21 and P53. M1-Exos derived from supernatant pretreated with the exosome inhibitor GW4869 reversed this result in vivo and in vitro. RNA-seq showed that Lipocalin2 (LCN2) was enriched in M1-Exos and targeted the NF-κB pathway. The quantity of SA-β-gal-positive cells was significantly reduced with the inhibition of LCN2, and the expression of P21 and P53 in NPCs was decreased. The same results were obtained in the acupuncture-induced IVDD model. In addition, inhibition of LCN2 promotes the expression of type II collagen (Col-2) and inhibits the expression of matrix metalloproteinase 13 (MMP13), thereby restoring the equilibrium of metabolism inside the extracellular matrix (ECM) in vitro and in vivo. In addition, the NF-κB pathway is crucial for regulating M1-Exo-mediated NPC senescence. After the addition of M1-Exos to LPS-treated NPCs, p-p65 activity was significantly activated, while si-LCN2 treatment significantly inhibited p-p65 activity. Therefore, this paper demonstrates that M1 macrophage-derived exosomes have the ability to deliver LCN2, which activates the NF-κB signaling pathway, and exacerbates IVDD by accelerating NPC senescence. This may shed new light on the mechanism of IVDD and bring a fresh approach to IVDD therapy.

BackgroundOsteoporosis is a multifactorial bone disease in which lipid metabolism plays an important role. Bone Mineral Density (BMD) measured by Dual-energy X-ray Absorptiometry (DXA) is a critical indicator for diagnosing osteoporosis. The cardiometabolic index (CMI) is a novel metric that combines two quantitative indicators of blood lipids—triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C). This study explores the association between CMI and BMD and seeks to elucidate the role of lipid metabolism in the context of bone health.MethodsBased on the data of the National Health and Nutrition Examination Survey (NHANES) 2017–March 2020-pre-pandemic, weighted multiple linear regression and smooth curve fitting were used to study the relationship between CMI and femoral BMD. Stratified analyses were also conducted for age, gender, BMI, ethnicity, diabetes and hypertension status. And, the saturation threshold effect of CMI was further analyzed using a two-stage linear regression model.ResultThis study enrolled a total of 1,650 participants (48.7% males), with an average age of 63.0 ± 8.6 years. After adjusting for multiple confounding factors, CMI was positively correlated with total femur BMD, trochanter BMD, and intertrochanter BMD, while the correlation with femur neck BMD was not statistically significant. In the fully adjusted model, each unit increase in CMI was associated with a 0.026 (g/cm2) increase in total femur BMD, a 0.022 (g/cm2) increase in trochanter BMD, and a 0.034 (g/cm2) increase in intertrochanter BMD. Subjects in the highest quartile of CMI had a 0.034 (g/cm2) increase in total femur BMD, a 0.035 (g/cm2) increase in trochanter BMD, and a 0.039 (g/cm2) increase in intertrochanter BMD in the fully-adjusted model compared to those in the lowest quartile. In addition, saturation was observed between CMI and total femur BMD, trochanter BMD and intertrochanter BMD, with saturation thresholds of 1.073, 1.431 and 1.073, respectively.ConclusionCMI is strongly associated with BMD, indicating its potential relevance in bone metabolism. However, the role of CMI in the context of bone health, especially regarding osteoporosis risk, requires further investigation in large-scale prospective studies.