Meniscus injuries, prevalent among osteoarthritis patients, the aging population, and athletes, present ongoing challenges in terms of repair and regeneration. As a result, the tissue-engineered meniscus (TEM) has become a prominent focus in regenerative medicine. Mechanical loading is hypothesized to be a critical stimulus for effective cartilage regeneration by mesenchymal stem cells (MSCs). Although Kartogenin (KGN) has been shown to promote chondrogenic differentiation in MSCs, its regenerative efficacy may be contingent upon the presence of biomechanical cues that simulate the native joint environment. Therefore, in tissue engineering strategies for meniscal repair, the synergistic application of biochemical stimulation (via KGN) and mechanical loading may be essential for functional cartilage regeneration. In this study, an in vitro TEM platform was developed with the capability of applying controlled dynamic mechanical loading. Human synovium-derived stem cells (hSDSCs), a readily accessible MSC population, were selected as the cellular component of the TEM. Constructs were evaluated for cartilage-specific extracellular matrix (ECM) production. In vivo, a mouse model of meniscal defects was employed to compare repair outcomes between unloaded and exercise-stimulated groups. Mechanical loading in vitro significantly enhanced ECM secretion, including collagen type II and aggrecan, compared with static culture. Correspondingly in vivo, mice subjected to normal exercise exhibited markedly improved meniscal repair at the defect site, whereas the unloaded group showed delayed and incomplete healing. These findings support the hypothesis that mechanical loading is essential for effective cartilage regeneration in TEM with KGN and hSDSC. Incorporating physiologically relevant mechanical stimulation may be the key to optimizing tissue-engineered therapies for meniscal repair.

Background:Surgical management of lumbar degenerative diseases (LDD) in octogenarians requires balancing effective neural decompression against diminishing physiological reserves. While general anesthesia (GA)-based endoscopic techniques (ENDO-GA) are highly effective, they often impose excessive systemic stress on frail patients. Conversely, percutaneous endoscopic lumbar discectomy under local anesthesia (PELD-LA) provides targeted decompression while mitigating these GA-associated risks. Given the scarcity of direct comparisons in this fragile population, this study evaluates the safety and efficacy of PELD-LA versus ENDO-GA. Methods:We retrospectively analyzed 100 consecutive octogenarians treated for LDD between January 2021 and December 2024. Patients were stratified into two specific surgical strategy groups: targeted decompression via PELD-LA (n=54) and extensive decompression via ENDO-GA (utilizing UBE or Delta techniques, n=46). To minimize selection bias, a 1:1 Propensity Score Matching (PSM) was conducted using specific covariates (age, sex, comorbidities, and ASA classification), yielding 39 matched pairs (n=78). Primary outcomes assessed perioperative safety and recovery efficiency (complications, PONV, ambulation time, and length of hospital stay).Secondary outcomes evaluated postoperative clinical efficacy (VAS and ODI at 3 months, and modified MacNab criteria at 12 months postoperatively). Results:After propensity score matching, baseline characteristics were well-balanced between the two groups. Perioperatively, the PELD-LA group exhibited significantly shorter operative times (97 vs 150 min, P<0.001), earlier ambulation (48 vs 72 h, P<0.001), and reduced length of hospital stay (9 vs 14 days, P<0.001) compared to the ENDO-GA group. Clinically, despite a smaller "targeted" decompression range, PELD-LA achieved long-term efficacy (MacNab criteria: 94.9% vs 94.9%, P=1.000) comparable to extensive decompression, while demonstrating superior early pain relief and functional improvement (VAS and ODI) at 3 months postoperatively (P<0.01). Crucially, the overall complication rate was significantly lower in the PELD-LA group (30.8% vs 82.1%, P<0.001), primarily driven by a marked reduction in postoperative nausea and vomiting (PONV) (23.1% vs 66.7%, P<0.001). Conclusion:Within our short-to-medium-term observation period, PELD-LA delivered clinical efficacy comparable to GA-based endoscopic procedures for octogenarians, while significantly reducing perioperative complications and accelerating recovery. Crucially, we do not assert that PELD-LA is universally superior; rather, we emphasize the importance of tailored patient selection. For frail patients with limited physiological reserve, PELD-LA serves as a physiologically rational strategy, balancing targeted decompression with the preservation of systemic stability.

BackgroundThoracic ossification of the ligamentum flavum (TOLF) is frequently underrecognized in its early stage because radiographic abnormalities on routine chest radiographs are often subtle. We aimed to develop and externally validate a deep learning model for opportunistic screening of TOLF using routine chest radiographs.MethodsThis retrospective multicenter diagnostic study included an internal development cohort from Changzheng Hospital and an independent external validation cohort from South China Hospital. The internal cohort comprised 250 patients with TOLF and 250 control subjects collected between January 2017 and January 2023. The external cohort comprised 150 patients with TOLF and 150 control subjects. TOLF status was established on CT using predefined radiological criteria, whereas frontal and lateral chest radiographs were used only as model inputs. We evaluated multiple backbone architectures, including ResNet101, DenseNet169, Vision Transformer, and Swin Transformer, and additionally explored three dual-view fusion strategies. Model development was performed using 10-fold cross-validation in the internal cohort, and performance was summarized using bootstrap-derived 95% confidence intervals. Human-reader comparison was conducted in the internal cohort.ResultsIn backbone screening within the internal cohort, ResNet101 emerged as the best-performing architecture. After subsequent input-resolution optimization, the final lateral-view ResNet101 model achieved an accuracy of 97.0%, sensitivity of 94.0%, specificity of 100.0%, and an AUC of 0.970. None of the evaluated dual-view fusion strategies outperformed the best single lateral-view model, and the poorer performance of posterior-fusion models was mainly attributable to reduced sensitivity. Compared with experienced spine surgeons and imaging physicians, the internal ResNet101 model showed significantly higher sensitivity and overall accuracy (both p < 0.001). In the external validation cohort, the locked model maintained robust discrimination, with an AUC of 0.954 for frontal radiographs and 0.995 for lateral radiographs. The corresponding accuracy/sensitivity/specificity values were 90.0%/84.7%/95.3% for frontal radiographs and 93.7%/89.3%/98.0% for lateral radiographs.ConclusionA deep learning model based on routine chest radiographs may provide accurate and generalizable screening for TOLF across institutions. The lateral-view model showed the most consistent diagnostic performance, supporting its potential role as an opportunistic screening tool to prompt confirmatory CT evaluation.

Repairing spinal cord injury (SCI) remains hindered by two major unmet challenges: the inability to precisely reconstruct irregular lesion cavities, where tissue contraction and collapse disrupt anatomical continuity, and the lack of effective platforms for stable and localized delivery of fragile therapeutics such as exosomes, whose rapid clearance severely limits efficacy. Addressing these bottlenecks requires biomaterials that can simultaneously rebuild three-dimensional structure and orchestrate a pro-regenerative microenvironment. Here, we present a morphology-adaptive injectable microporous annealed particle scaffold (MS) for localized and long-term release of human umbilical cord MSC-derived exosomes (hucMSC-Exo). GelMA/SFMA microspheres were fabricated via solvent-free microfluidic electrospraying combined with liquid nitrogen-assisted cryo-processing, preserving exosome bioactivity. This “disassemble-and-reassemble” approach enables minimally invasive injection of microspheres into irregular lesion cavities, followed by body temperature-induced annealing and in situ photocuring to form a mechanically stable, interconnected three-dimensional scaffold, which supports cell infiltration, nutrient diffusion, and sustained exosome release. In vivo, MS@Exo suppressed inflammation and scar formation, enhanced angiogenesis, and promoted neuronal survival, axonal regeneration, and myelination, ultimately achieving superior functional recovery over MS or Exo alone, demonstrating a clear synergistic effect. Transcriptomic profiling further revealed that MS@Exo reprogrammed gene expression by downregulating extracellular matrix- and collagen-related pathways while upregulating neuronal, synaptic, and ion channel signaling networks, thereby shifting the repair process from an inflammatory-proliferative phase toward a differentiation-remodeling phase. Collectively, MS@Exo acts as an intelligent multifunctional scaffold that couples advanced fabrication with exosome-based therapy to overcome fundamental limitations in SCI repair, offering a broadly applicable strategy for reconstructing irregular tissue defects in regenerative medicine.

Background/introduction:Alkaptonuria (AKU) is a rare disorder of tyrosine metabolism characterized by homogentisic acid accumulation and ochronotic pigment deposition in connective tissues. Spinal involvement is common, but cervical disc herniation with clinically significant myeloradiculopathy requiring multilevel anterior surgery is infrequently reported. A distinctive operative hallmark is the diffusely dark ("black") intervertebral disc/nucleus pulposus, which may be the first clue to the underlying diagnosis. Case presentation:An adult patient presented with 6 months of progressive neck pain and bilateral upper-limb numbness/pain, most prominent in the lateral aspect of the right upper arm and involving all fingers of both hands, accompanied by gait disturbance described as a "cotton-like sensation." Neurologic examination demonstrated long-tract signs consistent with cervical myelopathy and superimposed radiculopathy. Cervical MRI showed multilevel disc degeneration with posterior protrusions, ventral dural sac compression, and intramedullary signal change, with the most severe stenosis at C4/5, C5/6, and C6/7. Interventions:Given progressive myeloradiculopathy with multilevel anterior compression, the patient underwent three-level C4-7 anterior cervical discectomy and fusion (ACDF) to achieve ventral decompression and segmental stabilization. Intraoperatively, the intervertebral discs and nucleus pulposus were diffusely black-pigmented, a gross appearance that strongly raised suspicion for ochronotic disc involvement. Representative disc material was collected for microbiological testing, which showed no bacterial or fungal growth. Because quantitative urinary homogentisic acid measurement and HGD genetic testing were not completed before manuscript preparation, the diagnosis was regarded as clinically probable rather than biochemically confirmed. Results/conclusions:Postoperatively, the patient showed early improvement in limb numbness and gait stability, and radiographs confirmed satisfactory implant position and cervical alignment. This case emphasizes that a "black disc" encountered during routine cervical discectomy should prompt immediate consideration of AKU/ochronosis, careful documentation and tissue sampling, and definitive metabolic testing (quantitative urinary homogentisic acid measurement, with HGD genetic testing when available). However, in the absence of biochemical or genetic confirmation, the intraoperative black-disc finding should be interpreted as a highly suggestive diagnostic clue rather than definitive proof of AKU. Standard cervical decompression and fusion principles remain effective for neurologic compromise, but recognition of a possible underlying metabolic disorder is essential for systemic evaluation and long-term surveillance.

To determine whether the longitudinal extent of intramedullary T2-weighted hyperintensity modifies the adjusted comparative outcomes of anterior versus posterior decompression in cervical ossification of the posterior longitudinal ligament (OPLL) with gait disturbance. In this single-center observational cohort, consecutive patients with cervical OPLL, gait abnormality, and MRI-confirmed intramedullary T2 hyperintensity (signal change ratio [SCR] > 1.2) underwent anterior or posterior decompression between January 2020 and January 2022 and were followed for 3 years. Hyperintensity extent was prespecified as focal (≤ 2 segments) or long segment (> 2 segments). Serial MRI (SCR and T2 hyperintensity length), plantar-pressure gait assessment, and neurological evaluations were obtained at predefined intervals. The primary functional endpoint was medial foot pressure (MFP,

Cervical Spondylotic Myelopathy (CSM) is a degenerative spinal condition resulting from cervical cord compression, often manifesting as intramedullary hyperintensity on T2-weighted MRI (HCS), reflecting chronic ischemic injury. Although anterior cervical surgery achieves cord decompression, neurological recovery remains inconsistent, particularly in patients with diabetes mellitus (DM), which may impair microvascular integrity and neural repair. Glycated hemoglobin (HbA1c) is an established marker of chronic glycemic control, yet its relationship with postoperative HCS resolution in diabetic CSM patients is unclear. This single-center retrospective study enrolled diabetic CSM patients undergoing anterior cervical decompression and fusion (January 2016-January 2022) by a single surgeon. Inclusion required preoperative HCS (Spinal Cord Ratio, SCR >= 1.23), and available preoperative, 6-month, and 24-month MRI and clinical follow-up. Exclusions comprised prior cervical surgery, trauma, infection, or tumor. Primary outcomes were HCS resolution, quantified as Cord Resolution ratio at 6 (CR1) and 24 months (CR2), and clinical improvement via JOA score recovery rates (Recovery1, Recovery2). Preoperative HbA1c was the independent variable; covariates included demographics, comorbidities, and radiographic parameters. Reliability of imaging measures was assessed with ICC. Multivariate linear regression identified predictors of outcomes. Patients were stratified by 24-month HCS improvement into "Good" (CR2 >= 0.15) vs. "Poor" recovery groups. Binary logistic regression and ROC analyses determined risk factors and optimal HbA1c cutoff. Mean preoperative HbA1c was 8.3%-3.7%. Higher HbA1c independently predicted poorer 24-month HCS resolution (CR2: beta=-0.108, P=0.003) and inferior clinical recovery (Recovery2: P=0.046), but not 6-month outcomes. HbA1c was an independent risk factor for poor 24-month recovery (OR=0.401, P=0.026). ROC analysis indicated HbA1c optimally predicted HCS recovery (AUC=0.715), with <= 6.8% cutoff yielding 71.4% sensitivity and 76.0% specificity. Preoperative HbA1c significantly predicts long-term HCS resolution and neurological outcome in diabetic CSM patients after anterior cervical surgery. Targeting HbA1c <= 6.8% may optimize recovery, underscoring the importance of perioperative glycemic control.

This study aimed to investigate the impact of different body mass index (BMI) categories on postoperative gait parameters and neurological recovery in patients with Cervical Spondylotic Myelopathy (CSM) undergoing Anterior Cervical Discectomy and Fusion (ACDF), and to clarify the relationship between BMI and postoperative functional outcomes as well as its predictive value. A total of 192 CSM patients who underwent ACDF surgery between January 2020 and December 2022 were consecutively enrolled and divided into three groups according to the WHO Asian BMI standards: Normal Weight group (18.5 ≤ BMI < 25 kg/m2, n = 68), Overweight group (25 ≤ BMI < 30 kg/m2, n = 66), and Obesity group (BMI ≥ 30 kg/m2, n = 58). Gait parameters (spatiotemporal parameters, joint kinematics, and angular accelerations) were collected and the modified Japanese Orthopaedic Association (mJOA) score was assessed preoperatively, at 6 months, and 2 years postoperatively. Recovery differences among groups were compared. Statistical analyses included repeated measures ANOVA, analysis of covariance (ANCOVA), and Receiver Operating Characteristic (ROC) curve analysis. At 6 months postoperatively, only the Stance Phase percentage was significantly higher in the Obesity group compared to the Normal Weight group (P < 0.05), with no significant inter-group differences observed in other gait parameters or neurological function scores. At 2 years postoperatively, multiple gait parameters showed significant gradient differences: step speed, cadence, step length, ankle dorsiflexion angle, knee and hip joint angular accelerations all decreased progressively with increasing BMI (all P < 0.05). The neurological recovery rate (RR) showed a similar gradient (Normal group: 72.51

Ossification of posterior longitudinal ligament (OPLL) is a complex multifactorial spinal disorder characterized by ectopic bone formation within the ligament, leading to progressive spinal canal stenosis and neurological deficits. While its epidemiological and clinical profiles are well-established, the precise molecular pathogenesis remains incompletely understood. This review systematically synthesizes recent advances in understanding the mechanistic underpinnings of OPLL, highlighting the interplay of genetic predisposition, epigenetic regulation, metabolic disorders, and biomechanical stress. Pathological manifestations, anatomical features, and the dual-origin hypothesis of OPLL are elaborated, alongside its phenotypic overlaps with ankylosing spondylitis and the contribution of inflammatory signaling cascades. Susceptibility loci identified via genome-wide association studies and their functional relevance to key regulatory pathways are summarized. Epigenetic regulation, encompassing pre and posttranscriptional modifications, is highlighted with particular attention to the roles of long noncoding RNAs (lncRNAs) and microRNAs (miRNAs). Metabolic mechanisms implicated in OPLL, including diabetes, lipoprotein receptor-related protein 5 signaling, and lipid metabolism dysregulation, are discussed, as is the critical role of biomechanical stress in disease progression. By integrating insights across multiple disciplines, this review establishes a comprehensive pathophysiological framework for OPLL, with the goal of bridging basic science and clinical practice and identifying promising avenues for the development of targeted therapeutic strategies.

Study DesignRetrospective Cohort Study.ObjectiveTo propose a new technique named "lateral mass gutter" and investigate its role in augmenting spinal canal cross-sectional area (SCA) during laminoplasty.MethodsThis study included 105 patients who received cervical laminoplasty from February 2021 to February 2024. Patients were allocated to the conventional (CON) group or the lateral mass (LM) group according to the guttering technique used intraoperatively. Propensity score matching with a caliper of 0.2 was utilized to reduce selection bias. Intergroup comparisons encompassed clinical outcomes (Visual Analog Scale (VAS) of neck pain, Japanese Orthopaedic Association (JOA) score), radiographic measurements (SCA, laminoplasty opening angle (LOA), hinge fractures, hinge fusion, C2-7 Cobb angle) and postoperative complications (cerebrospinal fluid leakage, incisional fat liquefaction, C5 nerve root palsy, axial neck pain, cervical spine instability).ResultsFollowing propensity score matching, baseline parameters were comparable between the CON and LM groups (37 patients per group, P > 0.05). Compared to the CON group, the LM group exhibited a significantly smaller LOA, a lower incidence of hinge fractures, a higher rate of hinge fusion, greater improvement in JOA and a larger expansion in the SCA (P < 0.05). No statistically significant differences were observed between the two groups regarding VAS of neck pain or postoperative complications (P > 0.05).ConclusionCompared to conventional guttering technique, lateral mass gutter significantly reduces hinge fracture, promotes hinge fusion, enhances spinal canal expansion and optimizes postoperative neurological recovery in posterior cervical laminoplasty.

Background:Magnesium-based implants facilitate bone regeneration via degradation. However, the epigenetic mechanisms, particularly N6-methyladenosine (m6A) modification regulated by Mg2+, remain incompletely understood. This study investigated the role of Mg2+ in osteogenic differentiation through the METTL3-RhoA axis and evaluated its potential in intervertebral fusion. Methods:The optimal Mg2+ concentration was identified using MC3T3-E1 cells. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and MeRIP-PCR were employed to identify m6A target genes. Functional assays (knockdown, overexpression, and rescue) validated the METTL3-YTHDF1-RhoA pathway. A rat tail intervertebral fusion model with magnesium implants was used to assess in vivo effects. Results:Treatment with 4 mM Mg2+ significantly enhanced osteogenic activity and increased METTL3 levels. Mechanistically, METTL3 promoted m6A methylation of RhoA mRNA, which was subsequently bound by YTHDF1, enhancing translation and activating the RhoA/ROCK pathway. In vivo, magnesium implants accelerated fusion and improved trabecular bone quality; however, these effects were inhibited by METTL3 or RhoA inhibitors. Conclusion:Mg2+ enhances osteogenic differentiation through the METTL3-YTHDF1-RhoA/ROCK pathway. The translational potential of this article:This study provides an epigenetic framework for optimizing magnesium-based orthopedic implants and suggests that targeting the m6A-RhoA axis could improve spinal fusion outcomes.

Intervertebral disc degeneration (IVDD) is frequently implicated in low back pain (LBP), yet the severity of degeneration on imaging often fails to parallel pain intensity or functional limitation. Modic changes capture abnormal marrow signal at the disc-vertebral interface, but they primarily describe subendplate marrow signal rather than lesion continuity across the disc, cartilaginous endplate, and adjacent marrow. The disc-endplate-bone marrow complex (DEBC) classification provides a complementary lesion-level imaging framework that integrates disc signal, endplate integrity, and adjacent marrow response. By incorporating short tau inversion recovery (STIR) sequences, DEBC may help identify imaging features suggestive of edema-like lesion activity; however, STIR hyperintensity should not be interpreted as direct proof of inflammation, pain generation, or a specific molecular program. This narrative and critical review synthesizes imaging, mechanistic, omics, and translational evidence to evaluate the biological plausibility and current limitations of the DEBC framework. We argue that DEBC should not replace Modic classification, assign pain causality, or guide treatment as a stand-alone criterion. Rather, its current value lies in generating testable hypotheses, improving lesion-level stratification, and supporting future imaging-to-molecular validation. Longitudinal imaging, histopathology, spatial omics, and clinical outcome studies are needed to determine whether DEBC types correspond to reproducible lesion ecologies, pain-associated phenotypes, or treatment-response patterns.

Diabetes mellitus (DM) may adversely affect neurological recovery after cervical decompression, but its relationship with postoperative plantar pressure restoration in cervical spondylotic myelopathy (CSM) remains insufficiently defined. To evaluate whether preoperative glycated hemoglobin (HbA1c) is associated with postoperative improvement in plantar pressure distribution after posterior single-door laminoplasty in patients with CSM and DM. This retrospective single-center study evaluated diabetic patients with CSM treated with posterior single-door laminoplasty and followed for at least 24 months. Dynamic plantar pressure assessment was performed preoperatively and at final follow-up, with medial foot pressure (MFP) and lateral foot pressure (LFP) used as the primary biomechanical outcomes. Linear and logistic regression analyses were used to examine the association between preoperative HbA1c and plantar pressure recovery after adjustment for selected clinical and radiological variables. Receiver operating characteristic (ROC) analysis was performed as an exploratory assessment of discrimination. Postoperatively, plantar loading shifted toward a more physiological distribution, with reduced MFP and increased LFP. Higher preoperative HbA1c was independently associated with smaller improvements in both ΔMFP2 and ΔLFP2 at 2 years. Radiological parameters, including canal narrowing ratio and modified K-line interval, showed associations with outcome in univariable analyses, but their effects were attenuated after adjustment. HbA1c demonstrated fair discriminatory ability for unfavorable plantar pressure recovery, with AUC values of 0.72 for ΔMFP2 and 0.68 for ΔLFP2. In diabetic patients with CSM undergoing posterior laminoplasty, poorer preoperative glycemic control was associated with less favorable improvement in plantar pressure distribution at long-term follow-up. HbA1c may be useful as one component of preoperative risk stratification within a laminoplasty cohort, but its discriminatory performance was only fair and should not be interpreted as a stand-alone treatment threshold.

BACKGROUND:Intervertebral disc degeneration (IDD) is the main reason for lower back pain, it has a vicious circle that ECM degradation, inflammation, and cell death. Ferroptosis is a kind of iron-reliant regulated cell death brought about by lipid peroxidation, it has come to be a major player in the loss of nucleus pulposus (NP) cells. Importantly, ferroptosis releases DAMPs that promote local sterile inflammation, creating a positive feedback loop of pathogenesis. Epigallocatechin gallate (EGCG) which is a major component of green tea has anti-inflammatory and antioxidant effects, however, whether it has a potential to target ferroptosis and inflammatory signaling in IDD is unknown. METHODS:An in vitro model of LPS-stimulated rat NP cells, we studied the impact of EGCG on the viability, inflammation (IL-1β, IL-6), ECM metabolism (COL2A1, ACAN), and ferroptosis markers (GPX4, SLC7A11, ACSL4, LPCAT3). ROS, GSH, MDA, mitochondrial ultrastructure. In vivo therapeutic effect was assessed by histological examination (H & E, Safranin O - Fast Green) and immunofluorescence in rat needle - puncture IDD model. Mechanisms were worked out via RNA-seq and Western blot. RESULTS:EGCG protected NP cells from LPS - induced injury. Then, it lessened inflammatory cytokine creation; then, it did result in anabolic ECM gene expression, and also it sternly put a stop to ferroptosis. This was reflected in reduced iron loading, reduced lipid peroxidation (reduced MDA, increased GSH), and reversed expression of ferroptosis related proteins (upregulated GPX4, SLC7A11; downregulated ACSL4, LPCAT3). EGCG preserved normal mt morphology. In vivo,EGCG improved the degeneration of the disc and kept NP tissue architecture, ECM component expression was also upregulated. Mechanistically, RNA-seq and biochemical analysis found out that EGCG's protection was caused by blocking the MAPK signaling pathway, a central control center for inflammation and ferroptosis. CONCLUSION:From our conclusion, in IDD, it was observed that the protection offered by EGCG was mainly inflammation and Ferrip-tosis of NP cells to avoid the process of MAPK pathway. Collectively, these results indicate that EGCG ameliorates IDD by attenuating inflammation and ferroptosis in NP cells, primarily through inhibition of the MAPK signaling pathway.

With the intensification of population aging in China, the incidence of osteoarthritis (OA) is increasing year by year among the middle-aged and elderly population, seriously affecting their health and quality of life. Currently, there is no specific treatment for OA, which makes it particularly important to seek new treatment strategies. Through literature review, we found a promising traditional Chinese medicine, the bark of Dictamnus dasycarpus Turcz, and extracted its active component dictamnine (DIC). For a long time, the biological activities of DIC, such as anti-inflammatory, anti-fungal, and anti-angiogenic, have been widely studied and recognized. Although we have some understanding of the anti-inflammatory effect of DIC, the specific effect on OA and its potential mechanism are still at the preliminary stage of research. To fill this research gap, we aim to explore the effectiveness of DIC in treating OA and reveal its potential anti-inflammatory mechanism. The research results show that DIC can exert pharmacological effects through multiple signaling pathways such as HIF-1α, NQO1, NRF2, and MAPK. Further mechanism studies reveal that DIC mainly inhibits the hypoxia-inducible factor-1α (HIF-1α)/heme oxygenase-1 (HO-1) signaling pathway and acts on chondrocytes to alleviate their ferroptosis phenomenon. This discovery provides a new idea for the treatment of OA and makes DIC a potential therapeutic candidate. Our research not only expands our understanding of the pharmacological effects of DIC, but also opens up a new direction for the drug development of OA, and is worthy of further in-depth exploration and development.

Mechanical memory, or when cells retain traits from their physical environment, influences stem cell fate. During cartilage repair, the extra-cellular mechanical microenvironment could direct stem cell behavior through mechanical memory. In this study, we developed a micropattern-based method to impart mechanical memory in human synovial-derived stem cells (hSSCs), through the process of mechanical dosing. Photolithography was employed to create gelatin hydrogels with grooved patterns at the micron scale (20-200 μm). Mechanical dosing was applied by culturing hSSCs on groove-patterned hydrogel substrates for 3 days to establish mechanical memory. Based on protein and gene expression analyses, 50 μm was identified as the optimal groove size for promoting chondrogenesis. Extending the mechanical dosing period to 6 days further enhanced the effect. RNA sequencing revealed that 6 days of mechanical dosing increased expression of TGF-β3, Sox9, and ACAN genes. In a mouse model of full-thickness cartilage defect, 6 day mechanically dosed hSSCs demonstrated enhanced cartilage repair. Super-resolution imaging and microindentation assays showed that mechanical dosing reconfigures load-bearing cytoskeletal structures, establishing mechanical memory that promotes chondrogenesis via TGF-β pathway activation. Together, this study demonstrates that microgroove-patterned hydrogels could induce chondrogenic mechanical memory in hSSCs, improving their cartilage repair potential. This approach offers a promising strategy for advancing tissue engineering and regenerative medicine.

This letter comments on Nagumo et al.'s study evaluating 1024-matrix reconstruction for intracranial perforating artery visualisation in 64-slice cerebral CTA, affirming its cost-effective value for standard CT scanners (https://doi.org/10.1002/jmrs.70055). We endorse the key finding that 1024-matrix improves small artery detection via higher sampling density, while highlighting the need for cross-vendor validation, workflow impact quantification, and clinical outcome assessment. This simple post-processing strategy is highly scalable, and further multicentre studies are warranted to confirm its universal utility.

This study compared anterior and posterior surgeries regarding sagittal spinocranial angle (SCA) and other sagittal balance metrics, analyzed correlations between radiographic changes and clinical outcomes, and identified the superior surgical strategy for multilevel cervical spondylotic myelopathy (MCSM). This retrospective cohort enrolled 51 patients receiving anterior cervical discectomy and fusion (ACDF) and 69 undergoing posterior laminoplasty (LP) between 2014 and 2021, with a minimum 24-month follow-up. Serial radiography, CT, and MRI measured SCA, surrogate C7 slope (for unavailable T1 slope), C2-C7 Cobb angle (CA), cSVA, and T1sCA at preoperation, early postoperation (5-7 days), and final follow-up. Clinical endpoints included JOA score, neurological recovery rate (RR), NDI, and SF-36. Multivariate regression and linear mixed-effects models adjusted for age, gender, BMI, baseline scores, and operative segments to clarify the independent impacts of surgery and sagittal parameter shifts on clinical results. Both procedures significantly improved all quality-of-life metrics (P < .05). ACDF yielded superior final RR (50.50 ± 24.71% vs 44.98 ± 17.77%, P = .026) and lower NDI (12.90 ± 4.15 vs 14.97 ± 3.52, P = .009). At final follow-up, ACDF presented larger C7 slope and CA (all P ≤ .047), alongside reduced SCA, T1sCA and cSVA (all P < .001). Multivariate analyses confirmed ACDF independently predicted lower follow-up NDI (β = -2.31, P = .009), while elevated ΔSCA independently aggravated NDI (β = 0.38, P = .002); neither ACDF nor ΔSCA independently correlated with JOA RR (all P > .05). ACDF independently drove postoperative SCA reduction (β = -11.52, P < .001). Relative to LP, ACDF reduces postoperative SCA and improves NDI and neurological recovery. Constrained by its retrospective nonrandomized design, these findings await prospective randomized verification; surgical selection should be individualized per patient pathology and sagittal balance.

Acute neuroinflammation drives secondary degeneration after spinal cord injury (SCI), yet the precise immune cell states and upstream regulatory circuits that initiate this response remain unresolved. Defining these early-state determinants at multi-omics resolution is essential for identifying mechanistically grounded therapeutic targets. We implemented an integrated multi-omics framework combining high-temporal-resolution single-cell RNA sequencing, bulk transcriptomics, histological validation, and systems-level network modeling across uninjured and early post-injury time points. Cell-cell communication analysis delineated intercellular signaling architecture within the acute lesion niche. Transcriptional regulatory network inference with in silico perturbation identified candidate master regulators. Network-based compound prioritization and target engagement validation were followed by functional testing in activated macrophages and a mouse SCI model. We resolved a temporally restricted S100a4+ macrophage state that rapidly emerged after injury, peaked at 1 day, and subsequently contracted. This state was defined by a coordinated transcriptional program integrating enhanced migratory capacity, amplified pro-inflammatory and pyroptotic signaling, and repression of homeostatic and reparative modules, constituting the dominant acute inflammatory signature at the tissue level. Systems-level analysis established a Cebpb-centered regulatory circuitry governing this state, thereby defining a C/EBPβ-S100a4+ macrophage axis as a principal driver of early neuroinflammation. Network topology positioned this axis as a densely connected and self-reinforcing hub within the injury microenvironment. Computational drug prioritization identified baicalein as a candidate regulator of C/EBPβ-dependent signaling. ChIP-qPCR and nuclear-cytoplasmic fractionation validated that baicalein effectively reduced the nuclear translocation of C/EBPβ and its binding to the S100a4 promoter. Experimental validation demonstrated that baicalein suppressed C/EBPβ expression, attenuated downstream inflammatory and pyroptotic pathways, and significantly improved functional recovery following SCI. This study delineates a C/EBPβ-S100a4+ macrophage axis that mechanistically structures the acute inflammatory landscape of SCI and represents a tractable therapeutic vulnerability. These findings advance a state-specific, network-informed framework for early immunomodulation in spinal cord injury.