PURPOSE:To investigate the association between patient characteristics (age, sex, and body mass index), the timing of posterior cruciate ligament reconstruction (PCLR), and the prevalence of concomitant cartilage and meniscal injuries. METHODS:Patients who underwent primary isolated PCLR between August 2016 and July 2024 were included. The presence of cartilage and meniscal injuries was confirmed via arthroscopic evaluation. The status of cartilage was, meanwhile, graded intraoperatively according to the International Cartilage Repair Society classification. Multivariable logistic regression analyses were performed to identify independent risk factors associated with both any-grade cartilage injuries and specifically high-grade (grades III-IV) cartilage injuries. RESULTS:A total of 1003 patients (787 males and 216 females) with a mean age of 33.18 years who underwent primary PCLR were retrospectively reviewed. Longer time from injury to surgery, particularly exceeding 24 months, was significantly associated with a higher risk of patellofemoral cartilage injury (odds ratio [OR], 1.794; P = .016), lateral compartment cartilage injury (OR, 2.141; P = .016), medial compartment cartilage injury (OR, 3.105; P < .001), and medial meniscal injury (OR, 1.990; P = .041) compared with PCLR performed within 3 months of injury. Additionally, older age significantly increased the prevalence of all cartilage and meniscal injuries (P < .001). Increased body mass index was independently associated with a higher incidence of patellofemoral cartilage injury (P = .006). Subgroup analysis revealed that patients with time from injury to surgery exceeding 24 months reported higher preoperative visual analog scale scores (P = .016). CONCLUSIONS:The incidence of concomitant injuries were 43.87% for patellofemoral cartilage, 10.87% for lateral compartment cartilage, 15.15% for medial compartment cartilage, 8.28% for lateral meniscus, and 10.47% for medial meniscus. Furthermore, delayed PCLR, especially beyond 24 months postinjury, coupled with older age and higher body mass index, were all crucial factors related to a higher prevalence of cartilage and meniscal injuries following grade III PCL injuries. LEVEL OF EVIDENCE:Level III, retrospective cohort study.

Geometric curvature is a fundamental regulator of cellular functions and bone tissue regeneration, yet its interplay with degradation in biodegradable metals remains elusive due to the insufficient curvature range of existing scaffold design. Here, we introduce additively manufactured Zn-Mg scaffolds inspired by Calabi-Yau manifolds and triply periodic minimal surface, enabling a broad curvature distribution while maintaining consistent pore size and porosity. In vitro, convex regions facilitated Zn ion diffusion and Ca/P mineral deposition, whereas concave regions accumulated Zn ion and suppressed mineral formation. This spatially heterogeneous ion microenvironment reshapes cellular behaviors compared to inert Ti controls. On Ti scaffolds, osteoblasts preferentially migrate toward negatively curved regions due to curvature-driven ECM deformation and focal adhesion signaling. In contrast, on Zn scaffolds, moderate Zn2+ release at convex regions promotes proliferation and mineralization, mediating the intrinsic negative-curvature preference. In vivo, Zn-Mg scaffolds promoted bone regeneration and demonstrated uniform osteointegration compared to Ti controls. These findings reveal curvature-degradation coupling effects and establish architectural design principles for biodegradable metal implants.

BackgroundThe aging population with lumbar spinal stenosis (LSS) is leading to a higher prevalence of coexisting conditions, particularly degenerative lumbar scoliosis (DLS). However, large-scale studies on the prevalence of DLS in LSS patients are limited. The surgical management of LSS with DLS is controversial. Berjano’s DSD classification provides a framework based on the relationship between the responsible segment and scoliosis apex. Understanding the distribution of these patterns is an essential step toward elucidating the clinical characteristics of LSS patients with coexisting DLS.MethodsDLS was diagnosed according to the definition of a coronal curvature (main lumbar curve) of ≥10°. Patients were classified according to Berjano’s DSD classification. Spearmann correlation tests were conducted to examine the relationships between radiographic parameters and symptom scores in patients with coexisting conditions.ResultsA total of 443 patients (157 males and 286 females, mean age 65.5 ± 7.5 years, mean Cobb angle 18.0 ± 7.9°) met the criteria for DLS (Cobb angle ≥ 10°), leading to a coexisting prevalence of 26.2%, ranging from 12.0 to 35.6% increasing with age. Patients with Berjano type I, type II, type III, type IVa, and type IVb account for 35.0, 38.8, 13.3, 12.0, and 9.0%, respectively. In patients with LSS and comorbid DLS, VAS LBP and ODI scores were both correlated with sagittal parameters. VAS LBP was significantly correlated with the Cobb angle (p = 0.001), while ODI scores showed significant correlations with the C7 plumb line to central sacral vertical line (C7PL-CSVL) (p = 0.038). Meanwhile, significant correlations were observed between sagittal parameters, and the Cobb angle and C7PL-CSVL, respectively. The incidence of sagittal imbalance (SVA > 50 mm) in LSS patients with DLS was 41.1%, which increased with the severity of coronal imbalance.ConclusionThe prevalence of DLS in LSS patients is 26.2%, increasing with age. Berjano type II represents the highest proportion (38.8%). Spinal deformity significantly correlates with clinical symptoms, with coronal and sagittal deformities being interrelated.

The spatial distribution and dynamics of double-strand break (DSBs) repair controlled by microtubules are essential for preserving genomic stability. However, the processes through which extranuclear microtubules govern intranuclear DSB repair across the nuclear envelope (NE) remain poorly understood. This study uncovers a mechanism by which the microtubule-depolymerizing kinesin KIF2A regulates nonhomologous end joining (NHEJ) repair by mediating NE invagination. Our investigation reveals that damage-induced α-tubulin tyrosination triggers KIF2A binding to microtubules, subsequently inducing NE invagination through the microtubule-the linker of nucleoskeleton and cytoskeleton (LINC) complex and lamin B1. This invagination, in turn, provides a larger region of a stable NHEJ repair environment close to the NE, facilitating efficient NHEJ repair. Loss of KIF2A disrupts the formation of invaginations after DNA damage, impacting the formation of 53BP1 foci. Our study establishes KIF2A-mediated NE invagination as a critical regulator of the intricate relationships among microtubules, NE dynamics, and NHEJ repair, shedding light on a previously obscure pathway crucial for genome stability.

Background:Knee joint pain is very common in clinical practice, with a complex etiology in which osteoarthritis is the most frequent cause. Among the various types of osteoarthritis, tibiofemoral osteoarthritis (TFOA) is the most prevalent. Patients with lateral patellar compression syndrome (LPCS) also present with knee joint pain. This study aims to compare meniscal and articular cartilage injuries in patients with LPCS and those with TFOA. This study could provide insights into the clinical characteristics and radiological features that distinguish these two conditions. Methods:This study recruited 206 eligible patients from the Department of Sports Medicine at a hospital from March 2018 to February 2023. Patients were divided into two groups of 103: LPCS and TFOA. Magnetic resonance imaging was conducted using standardized protocols. Image analyses were undertaken by experienced radiologists to assess meniscal and cartilage injuries. Results:The mean age was 58.0±10.9 years in the LPCS group and 54.3±10.3 years in the TFOA group, with a significant difference between groups (P=0.01). Patients with LPCS exhibited a higher proportion of meniscal injuries (55.34% vs. 39.81%, P=0.03) and a significantly higher prevalence of posterior root tears of the medial meniscus (34.95% vs. 3.88%, P<0.001) compared with patients with TFOA. Significant differences in the grading of cartilage injuries were observed, particularly in the medial tibiofemoral compartment, where patients in LPCS group had higher grades of injury compared with TFOA patients (P<0.001). Specifically, in the medial compartment, grade 4 cartilage injuries were more frequent in the LPCS group (34.95% vs. 24.27%), while grade 1 injuries were more frequent in the TFOA group (53.40% vs. 29.13%). Among LPCS patients aged ≤50 years, 55% (11/20) had higher-grade cartilage injuries in the lateral compartment than in the medial compartment, suggesting more rapid cartilage damage progression in younger patients with LPCS. Conclusions:This study underscores the significant differences in meniscal and articular cartilage injuries between patients suffering from LPCS and patients with TFOA. The results highlight the importance of radiological features for accurate clinical differentiation and the need for 'tailored' treatment strategies.

Titanium and its alloys are widely used for orthopedic implants, but their intrinsic bioinertness may hinder osseointegration. In this study, titanium dioxide nanotube (TNT) arrays were fabricated on Ti-6Al-4V scaffolds via anodization, and their effects on the adhesion behavior of human bone marrow mesenchymal stem cells (hBMSCs) were investigated. Surface characterization showed that anodization successfully generated ordered TNT layers, increased surface roughness, enhanced protein adsorption, and induced an apparent superhydrophilic wetting response. Compared to the untreated scaffold and TNT50, the small-diameter TNT10 surface significantly promoted hBMSC adhesion and proliferation. Microscope imaging further revealed enhanced cell spreading, F-actin organization, and vinculin expression on TNT surfaces, with the most prominent focal adhesion-related staining observed in TNT10. Quantitative proteomic analysis showed that TNT10 was associated with coordinated remodeling of adhesion- and cytoskeleton-related molecular programs, including focal adhesion, cell-substrate junction, and regulation of the actin cytoskeleton. In contrast, TNT50, despite supporting obvious cytoskeletal remodeling, was more compatible with a dynamic, higher-turnover adhesion state. Overall, these findings suggest that small-diameter TNTs provide a more favorable interfacial microenvironment for stable early hBMSC adhesion on porous titanium scaffolds.

Arthroscopic lateral retinacular release (LRR) is an effective treatment for lateral patellar compression syndrome (LPCS), but postoperative rehabilitation remains crucial. Low-load blood flow restriction training (LL-BFRT) has been shown to be beneficial in sports medicine; however, its effect on postoperative recovery in LPCS is unclear. In this randomized controlled trial, 60 patients after LRR were assigned to receive either routine rehabilitation with LL-BFRT or routine rehabilitation alone for 4 weeks. Outcomes included Lysholm score, knee extension peak torque, quadriceps thickness, thigh circumference, VAS, and ROM. Within- and between-group comparisons were conducted using paired and unpaired t-tests or their non-parametric equivalents, according to data distribution and homogeneity of variance (SPSS; P < 0.05 was considered statistically significant). A total of 51 patients (Control: n = 26, age 45.3 ± 11.6 years, BMI 24.0 ± 3.1; LL-BFRT: n = 25, age 42.4 ± 10.2 years, BMI 25.2 ± 3.4) completed the trial. While both groups showed post-intervention improvements, the LL-BFRT group demonstrated greater gains than the control group in knee extensor strength at 60°/s (mean increase 20.85 vs. 8.24 N·m), vastus medialis thickness (0.33 vs. 0.12 cm), and thigh circumference (2.34 vs. 1.15 cm). Although the between-group differences in VAS and Lysholm scores were not statistically significant, the mean changes in the LL-BFRT group exceeded the minimal clinically important difference (MCID) thresholds for both outcomes (VAS: 2 cm; Lysholm: 11.1 points), indicating clinically meaningful within-group improvement. LL-BFRT augments routine rehabilitation by specifically improving knee extensor strength, vastus medialis hypertrophy, and thigh circumference in patients with LPCS after LRR, and may represent an effective strategy to enhance postoperative recovery.

Objective To evaluate the efficacy and safety of Ruyi Zhenbao tablet (RYZBT), a traditional Tibetan medicinal formula, for the treatment of lumbar disc herniation (LDH), that is frequently associated with lower back pain (LBP), through rigorous randomized controlled trials (RCTs). Methods This multicenter, randomized, positive-controlled trial study will include 400 participants diagnosed with LDH, and include an enrollment period, a 4-week treatment period, and a 4-week follow-up period. Participants will be randomly assigned at a 1:1 ratio for treatment with either RYZBT or diclofenac sodium sustained-release tablet (DSSRT) for 4 weeks. The time points of visits are set at baseline, during treatment (weeks 1, 2, and 4), and during follow-up (weeks 2 and 4 post-treatment). The relevant outcome will be recorded at each timepoint. The primary outcomes include the Visual Analog Scale (VAS) scores for LBP and leg pain, as well as the Japanese Orthopaedic Association scores for functional assessment. Secondary outcomes comprise the VAS scores for numbness, Oswestry Disability Index, rescue treatments, patient health education, and safety assessments. Discussion This study has been designed to provide robust and reliable evidence of the efficacy and safety of RYZBT in alleviating LDH symptoms, with the goal of supporting evidence-based clinical applications. By using DSSRT as a positive control, the placebo effect will be effectively minimized, enabling a more accurate assessment of RYZBT efficacy.

Spinal interbody fusion cages must be able to bear heavy loads while integrating seamlessly with the surrounding bone. However, the cages currently used in spinal surgery often fall short on both fronts. To meet the multi-faceted requirements, here, we introduce, for the first time, additively manufactured, biodegradable Zn-Mg interbody fusion cages with multi-scale structural control, combining eutectic microstructure, heterogeneous grain architecture, and gyroid lattices reinforced by interpenetrating ribs. The resulting cages showed a compressive strength comparable to that of cortical bone, together with good ductility and low elastic modulus. In vitro, balanced release of Zn2+ and Mg2+ enhanced osteogenic differentiation while mitigating Zn2+ toxicity. Zn-Mg extracts effectively alleviated the negative effects of estrogen deficiency on osteoblasts and osteoclasts. In an anterior cervical discectomy and fusion (ACDF) sheep model, the Zn-Mg cages exhibited excellent biocompatibility, rapid osseointegration, and robust mechanical interlocking, and maintained intervertebral stability during in vivo degradation for 24 weeks. The AM Zn-Mg cages through dual biomechanical-biological optimization are demonstrated to be a transformative alternative to current permanent metallic and polymeric implants in spinal fusion.

STUDY DESIGN:Prospective cohort study. OBJECTIVE:To establish a simple and clinically available paraspinal muscle and bone density (PMBD) score to predict mechanical complications after lumbar fusion. SUMMARY OF BACKGROUND DATA:Mechanical complications are common issues in posterior lumbar interbody fusion (PLIF). Current evaluations are often unidimensional and complex, with lack of clinical relevance for treatment. METHODS:The study analyzed a cohort of 255 patients (165 women and 90 men) followed for at least 1 year after posterior lumbar interbody fusion. The PMBD score comprised 3 parameters identified by binary logistic regression analysis: paraspinal muscle endurance and morphology (PMEM) score, L1 vertebral body computed tomography Hounsfield Units value (L1CT), and age. The statistical weights of each parameter were created by rounding odds ratios (OR) to the nearest integer. The predictive performance of the PMBD score was evaluated by the area under the receiver operating characteristic curve (AUC). RESULTS:Fifty-three patients (20.7%) experienced mechanical complications. The PMBD score ranged from 0 to 4. Patients with higher PMBD score exhibited higher rates of mechanical complications ( P <0.001). Binary logistic regression revealed that the PMBD score was an independent factor of mechanical complications ( P <0.001). The AUC of the score was 0.818, significantly higher than PMEM score (AUC=0.761, P <0.05), L1CT (AUC=0.690, P <0.05), and age (AUC=0.634, P <0.05). Sensitivity of PMBD was 0.714 (30/42), and specificity was 0.822 (175/213). In terms of the PMBD categories, patients were categorized as low (0-1 score), moderate (2 score), high risk (3-4 score) with a progressive complications rate (7.0%, 31.1%, and 62.5%, P <0.001). CONCLUSION:The PMBD score was a practical assessment tool integrating muscle and bone density to predict mechanical complications after PLIF, with a superior predictive performance compared with previous evaluation methods. Surgeons could utilize the PMBD score for preoperative risk stratification and might formulate individualized surgery procedure.

INTRODUCTION:Osteoarthritis (OA) is a prevalent degenerative joint disease, with postmenopausal women being disproportionately affected. Early pathological alterations in subchondral bone remodeling are increasingly recognized as pivotal precursors to articular cartilage degeneration. However, the precise mechanisms by which estrogen deficiency drives this deleterious bone-to-cartilage crosstalk remain poorly understood. OBJECTIVE:This study aimed to elucidate the role of osteoblast-derived Connective Tissue Growth Factor (CTGF) in mediating bone-to-cartilage crosstalk under estrogen-deficient conditions and to delineate the underlying molecular signaling pathways. METHODS:To simulate postmenopausal conditions, we established an estrogen-deficient OA model via bilateral ovariectomy (OVX-OA). Integrated bioinformatic strategies were utilized to screen for potential protein contributors of the osteoblast-chondrocyte interaction and identify candidate upstream transcription factors. Cartilage degeneration was assessed via Safranin O staining and qRT-PCR. The expression of CTGF, EGFR, NF-κB, and cartilage matrix markers was quantified by immunohistochemistry (IHC), qRT-PCR, and western blotting. Immunoprecipitation-mass spectrometry (IP-MS) was employed to characterize the molecular interactome of the identified mediators. RESULTS:We identified CTGF as the key contributor of OVX-osteoblast-induced chondrocyte dysfunction. CTGF knockdown in OVX-osteoblasts reversed the detrimental effects of osteoblasts on chondrocytes. CTGF was found to form a complex with EGFR, activating the EGFR/NF-κB pathway and promoting OA development. Treatment with the CTGF-neutralizing antibody neutralized excessive CTGF activity, significantly attenuating subchondral bone remodeling and alleviating cartilage degeneration. CONCLUSION:Abnormally increased CTGF contributes to detrimental bone-to-cartilage crosstalk following estrogen loss by activating the EGFR/NF-κB axis in chondrocytes. These results delineate CTGF as a critical pathological nexus, the pharmacological sequestration of which may yield potent therapeutic avenues for attenuating estrogen deficiency-induced OA.

BACKGROUND:Autologous osteoperiosteal transplantation (AOPT) is a promising treatment for large cystic osteochondral lesions of the talus (OLTs), but the influence of lesion laterality remains unclear. The purpose of this study was to compare the clinical and radiologic outcomes of lateral vs medial large cystic OLTs treated with AOPT. METHODS:Patients with lateral or medial large cystic OLTs who underwent AOPT between 2010 and 2023 were retrospectively reviewed. Patients were propensity matched in 1:1 ratio on sex, age, body mass index, affected side, and lesion profiles (area, depth, volume). Clinical outcomes were assessed using the visual analog scale for pain (VAS), the Foot Ankle Outcome Score (FAOS), and the ankle activity score (AAS). The final FAOS score was designated as the primary outcome measure. Radiologic outcomes were evaluated using the MOCART (magnetic resonance observation of cartilage repair tissue) 2.0 ankle score. RESULTS:A total of 22 matched patients per group were included, with a mean follow-up of 84.6 ± 45.9 months. The lateral group comprised 20 males and 2 females (mean age, 40.4 ± 11.2 years), whereas the medial group included 18 males and 4 females (mean age, 38.0 ± 8.4 years). Both groups demonstrated significant improvements in total FAOS scores (lateral: 53.4 ± 13.8 to 87.2 ± 10.1, P < .001; medial: 51.1 ± 12.6 to 89.7 ± 8.4, P < .001) and in all secondary clinical outcomes at final follow-up (all P < .001), with no intergroup differences (all P > .05). Similarly, there were no significant differences in the total MOCART 2.0 ankle score (73.8 ± 10.7 vs 73.0 ± 9.9; nonsignificant) or in any of its individual subcomponents. CONCLUSION:This cohort study demonstrated that AOPT yields comparable mid‑ to long‑term clinical and radiologic outcomes for medial and lateral large cystic OLTs, and that radiologic results were not significantly associated with clinical outcomes.

BACKGROUND CONTEXT Patients with degenerative lumbar spinal stenosis (LSS) often experience limited long-term relief from conservative therapies, with many progressing to surgery. Limaprost, a prostaglandin E1 analog, may improve symptoms by enhancing microcirculation in compressed neural tissues. This multicenter prospective study evaluates its real-world effectiveness and safety. PURPOSE To evaluate the effectiveness and safety of limaprost in degenerative LSS and to identify predictors of subsequent surgical intervention. STUDY DESIGN/SETTING Multicenter prospective observational cohort study. PATIENT SAMPLE A total of 1,139 patients with degenerative lumbar spinal stenosis. OUTCOME MEASURES Primary outcomes included changes in Oswestry Disability Index (ODI) and Japanese Orthopaedic Association (JOA) subjective symptom scores. Secondary outcomes included visual analog scale (VAS) scores for pain and numbness, EuroQol-5 Dimension (EQ-5D), and walking capacity. METHODS Patients were categorized into four groups: limaprost monotherapy (n=308), standard combination (n=234), other combination (n=531), and non-limaprost control (n=66). Outcomes were assessed at 2 weeks and at 1, 3, and 6 months. Changes from baseline were compared across groups. Odds ratios (OR) with 95% confidence intervals (CI) were used to assess risk of subsequent surgical intervention. RESULTS Compared with controls, the limaprost monotherapy group demonstrated significantly greater improvement in ODI at 3 months (p=0.0123). Improvements in JOA subjective scores were greater in the monotherapy group beginning at 1 month (all p<0.05). At 6 months, all limaprost groups showed significantly greater improvements than controls in ODI and JOA scores (all p<0.05), as well as superior outcomes in pain and numbness VAS, EQ-5D, and walking capacity. Among patients without prior LSS surgery, limaprost monotherapy was associated with a significantly reduced risk of subsequent surgery (OR 0.07, 95% CI 0.01–0.39; p=0.003). Adverse event rates were low across all groups (0.9%–2.2%). CONCLUSIONS Limaprost-containing regimens are associated with improved symptoms, functional outcomes, and quality of life in patients with degenerative LSS compared with non-limaprost therapy. Limaprost monotherapy may also reduce the likelihood of subsequent surgical intervention in patients without prior surgery. FDA Device/Drug Status Limaprost (limaprost alfadex) (Investigational/Not Approved).

PURPOSE:To determine the maximal outcome improvement (MOI) thresholds for International Knee Documentation Committee (IKDC) score and Lysholm score anchored by patients' willingness to undergo posterior cruciate ligament (PCL) reconstruction again and identify predictors of failure to achieve these thresholds. METHODS:A retrospective review was conducted on patients who underwent primary PCL reconstruction. MOI was defined as the percentage of postoperative improvement relative to maximum possible improvement. Receiver-operating characteristic analyses were performed to determine the MOI thresholds based on patients' willingness to undergo PCL reconstruction as assessed through an anchor question at final follow-up. Multivariable logistic regression analyses were performed to identify predictors of failure to achieve these thresholds. RESULTS:A total of 217 patients were included, with a median follow-up of 63 months (range: 36-84 months). MOI thresholds were 34.5% for IKDC score (area under curve = 0.837) and 37.2% for Lysholm score (area under curve = 0.825), where the latter was calculated after excluding 11 patients with perfect preoperative scores. The proportions of patients achieving the MOI thresholds were 68.7% for IKDC score and 56.3% for Lysholm score. Independent predictors of failure to achieve these MOI thresholds included older age (odds ratio [OR] = 0.952), female sex (OR = 0.166), chronic injury (>12 months; OR = 0.377), and higher preoperative IKDC score (OR = 0.947). For Lysholm score, significant predictors included female sex (OR = 0.403), chronic injury (OR = 0.452), and higher preoperative Lysholm score (OR = 0.968). CONCLUSIONS:MOI thresholds for patients' willingness to undergo PCL reconstruction were 34.5% (IKDC score) and 37.2% (Lysholm score), achieved by 68.7% and 56.3% of patients, respectively. Older age, female sex, chronic injury (>12 months), and higher preoperative patient-reported outcome scores were negative predictors of achieving these MOI thresholds. LEVEL OF EVIDENCE:Level IV, retrospective case series.

Osteoarthritis (OA) is the most prevalent degenerative joint disease and is closely related to obesity. The molecular mechanisms underlying obesity-induced metabolic alterations that lead to cartilage degeneration have not been fully elucidated. Succinate, a key intermediate in the Krebs cycle, exhibits signaling functions that extend beyond its traditional metabolic role. This study demonstrates that succinate is significantly accumulated in the knee joint of obesity-associated OA. Succinate exacerbates obesity-associated cartilage degeneration through a combination of extracellular and intracellular pathways, which converge on mitochondrial dysfunction. Mechanistically, extracellular succinate activates G protein-coupled receptor succinate receptor-1 (SUCNR1), triggering mitochondrial fission and activation of the cGAS-STING pathway. Intracellular succinate reduces NADPH levels and promotes mitochondrial reactive oxygen species (mtROS) accumulation, in association with increased IDH2 succinylation. Additionally, sirtuin 5 (SIRT5) acts as an IDH2 desuccinylase and exerts a protective effect against intracellular succinate-induced cartilage degeneration. To target both intracellular and extracellular succinate, the phenylboronic acid-modified gelatin hydrogel is designed to load the SUCNR1 inhibitor 5 g and the SIRT5 agonist puerarin. This injectable ROS-responsive system targeting succinate exhibits remarkable therapeutic efficacy in vivo. These findings suggest that targeting succinate provides a novel therapeutic strategy for obesity-associated OA.

4D scaffolds offer transformative potential for bone implants. Yet their application to metallic materials is constrained by the scarcity of suitable alloys and the requirement for harsh external stimuli to trigger shape change. Here, we introduce 4D metallic metamaterials driven by controlled biodegradation that combine biodegradable constraints with biometals of higher corrosion potential. We show that upon electrochemical degradation of the constraint, the metamaterials recover their original geometry-via stretching, bending, or expansion-generating programmable recovery forces tuned through structural design parameters. We demonstrate that when turned into scaffolds for bone implants, the 4D metallic metamaterials are cytocompatible and promote bone regeneration through the synergistic effects of bioactivity and mechanical stimulation in vivo. This strategy establishes a paradigm in 4D shape transformation of metal via metamaterial design, enabling bioactive, self-recovering implants with broad applicability across biomedical engineering.

This study aims to develop an automatic lumbar muscles segmentation and processing tool based on the Segment Anything Model (SAM), and to explore the association between lumbar muscles degeneration and coronal parameters in patients with adult degenerative scoliosis (ADS). Fifty-six ADS patients were included. Lumbar muscles (PM: psoas major, MF: multifidus, ES: erector spinae) cross-sectional area (CSA) and fatty infiltration (FI) at L3-L4 were measured via direct, ImageJ-based, and SAM-based (Spyder) methods. We assessed measurement consistency and time efficiency across methods. Correlations between muscle degeneration and ADS coronal parameters were analyzed using Spyder-derived data. CSA measurement showed acceptable consistency (ICC 0.627–0.881, P < 0.001), FI poor (ICC 0.252–0.442, P < 0.001). Spyder was > 10-fold faster than direct measurement and 2-fold faster than ImageJ (P < 0.001). ADS patients had larger concave-side CSA (PM, ES) and higher concave MF FI (P < 0.05). Lumbar curve angle correlated positively with concave PM FI (r = 0.273, P = 0.042) and negatively with convex MF CSA (r=-0.406, P = 0.002). The SAM-based automated lumbar muscles tool “Spyder” enables accurate, efficient automated lumbar muscles segmentation in ADS, offering an efficient ADS research and diagnosis tool. Asymmetric lumbar muscles changes may correlate with coronal deformity.

Osteoarthritis (OA) is a common degenerative joint disease characterized by progressive cartilage degeneration. Cartilage fibrosis is one of the key pathological events and is also the direct cause of repair failure due to fibrocartilage formation after microfracture surgery. Mitogen-activated protein kinase kinase 4 (MKK4) is a MAP2 kinase that activates c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase. It is a key kinase in the stress-activated protein kinase (SAPK)/mitogen-activated protein kinase (MAPK) signaling network. The OA-related data set from the GEO database showed that MKK4 expression was upregulated in the cartilage of OA patients. This phenomenon was also confirmed in the clinical samples we collected. Therefore, inhibiting MKK4 is a potential strategy for the treatment of cartilage fibrosis. HRX-215 is a recently discovered inhibitor of MKK4 that has been shown to have anti-fibrotic activity, but its therapeutic potential in osteoarthritis is not yet clear. This study found that HRX-215 promoted chondrocyte proliferation, increased the proportion of S-phase cells, and slowed down oxidative stress-driven extracellular matrix degradation by inhibiting MKK4. In in vivo experiments, HRX-215 significantly delayed cartilage degeneration and fibrosis in both the rat ACLT osteoarthritis model and the rat microfracture model. HRX-215 also has an inhibitory effect on the expression of MKK4 in human chondrocytes. Taken together, the results of this study indicate that HRX-215 inhibits cartilage fibrosis by targeting MKK4, providing a promising therapeutic candidate for osteoarthritis and microfracture repair

STUDY DESIGN:A mixed-methods study. OBJECTIVE:To develop and perform the initial validation of the Lumbar Surgery Quality of Life (LSQoL), a multidimensional patient-reported outcome measure for patients with lumbar degenerative diseases. SUMMARY OF BACKGROUND DATA:Patient-reported outcome measures (PROMs) are widely used to evaluate outcomes in lumbar degenerative diseases but are often applied in combination, with each instrument capturing only specific aspects of patient status. Consequently, improvement in traditional measures such as the Oswestry Disability Index (ODI) does not always correspond to patient-perceived recovery or satisfaction, highlighting the need for multidimensional tools that better reflect patient experience. METHODS:The LSQoL was developed using a multistage mixed-method approach, including literature review, patient interviews, expert consensus through the Delphi method, and weighting via the Analytic Hierarchy Process (AHP). The instrument was validated in 1,996 patients with lumbar degenerative diseases. Internal consistency, test-retest reliability, construct validity, and correlations with established PROMs and patient-reported recovery and satisfaction were evaluated. RESULTS:The LSQoL consists of 21 items across five dimensions: pain, neurological function, activities of daily living, emotional status, and working ability. Internal consistency was acceptable to good (Cronbach's α: 0.744-0.805), and test-retest reliability was strong (ICC: 0.759-0.906). Factor analyses supported a stable multidimensional structure. The LSQoL demonstrated moderate correlations with established PROMs and stronger correlations with patient-reported recovery and satisfaction. CONCLUSION:The LSQoL is a reliable and valid PROM that provides a comprehensive assessment of quality of life in patients with lumbar degenerative diseases. It is suitable for evaluating patient-reported outcomes both before and after lumbar surgery.

Low back pain often involves paraspinal muscle degeneration. Rehabilitation robots can provide high-consistency exercise therapy, but current technologies face the challenge of delivering personalized training to patients with various muscular conditions. To solve the issue, this work proposes an automated framework that translates sparse clinical magnetic resonance imaging (MRI) scans into personalized robotic lumbar rehabilitation strategies. First, a Bayesian fusion method with adaptive observation confidence is proposed to enable automatic posterior inference of the 3D paraspinal muscle geometry from sparse MRI. Key biomechanical parameters, including physiological cross-sectional area and fat infiltration, are extracted from the reconstructed muscle shapes to create a patientspecific musculoskeletal model. Based on the personalized model, a hierarchical optimization framework is developed to generate rehabilitation strategies of the combined multi-degree-of-freedom (multi-DOF) motions and dynamic interaction forces to maximize the target muscle activation. Validation on multi-center datasets demonstrates 90% dice similarity for the muscle reconstruction. Personalized validation experiments on volunteers with varying muscle fat infiltration levels revealed that conventional empirical force strategies failed to adapt to individual differences, leading to risks of activation overload or insufficient stimulation. In contrast, the proposed personalized strategy reduced the activation level variance by 60.49% compared to the empirical strategy and maintained the target activation error within 4%. The results demonstrate that the proposed framework significantly mitigates individual uncertainties, ensuring both safety and effectiveness in robotic rehabilitation.