Primary spontaneous osteonecrosis of the knee (SONK) is a debilitating condition that primarily affects elderly patients with an unknown etiology. Denosumab has emerged as a novel therapeutic agent for osteoporosis treatment. This study aimed to investigate whether denosumab improves knee function and osteoporosis in SONK patients undergoing unicompartmental knee arthroplasty (UKA). Between January 1, 2018, and December 31, 2022, patients with knee osteonecrosis undergoing UKA were enrolled. Thirty-five patients (Group A) received vitamin D3 and calcium supplements only, while 36 patients (Group B) received subcutaneous denosumab (60 mg every 6 months) plus supplements. Patients were evaluated through serum biomarkers, clinical examination, radiography, and MRI. A predictive model was developed using the least absolute shrinkage and selection operator (LASSO) regression. The mean follow-up was 2.11 ± 0.99 years. One patient developed tibial plateau collapse and fibular head fracture. At 24 months, Group B showed significantly better HSS scores (T = 15.07, P = 0.04), VAS scores (T = 1.11, P = 0.04), and ROM (T = 15.07, P = 0.02) compared to Group A. Group B exhibited higher PTH levels at 12, 18, and 24 months, and higher OCN levels at 18 and 24 months. At 24 months, Group B had lower CTX but higher T-scores and BMD. Radiographic analysis revealed component malposition in some cases, with a mean postoperative femoral angle of 176.1° ± 2.3°. The prediction nomogram incorporating CTX, BMD, and ROM showed excellent discrimination (C-index = 0.925, 95% CI: 0.881-0.969), confirmed by internal validation (C-index = 0.97). Clinically, the 7-point improvement in HSS scores observed in Group B corresponds to a transition from 'poor' to 'good' knee function, while the 0.8-unit increase in femoral neck T-score translates into a 30% reduction in major-fracture risk over 10 years (FRAX-adjusted), indicating meaningful gains in patient mobility, pain relief, and long-term skeletal protection.

ABSTRACTObjectiveConversion to hip arthroplasty (cHA) is a widely utilized and effective surgical intervention for addressing the failure of internal fixation in intertrochanteric femoral fractures (FIF‐INF). Although previous studies have confirmed that the failure rate of internal fixation is higher in unstable intertrochanteric femoral fractures, but whether the efficacy and complications of cHA after failure differ from those in stable fractures remains unclear. This study aimed to evaluate and compare the clinical and radiological outcomes, as well as the incidence of complications associated with hip arthroplasty over a minimum follow‐up period of 3 years after the failure of internal fixation in both stable and unstable intertrochanteric femoral fractures.MethodsThis multicenter study retrospectively analyzed patients who underwent hip arthroplasty subsequent to the failure of FIF‐INF from December 2012 to December 2020 at various participating research centers. Cases demonstrating excellent and acceptable quality fracture reduction, as defined by the criteria established by Chang et al., were included. According to AO/OTA classification criteria of intertrochanteric fractures, the fractures were classified into stable fractures (31‐A1) and unstable fractures (31‐A2, A3). There were 47 patients with stable fractures and 56 patients with unstable fractures. Clinical and radiological evaluations were conducted for all patients. This study employed independent samples t‐tests, χ2 tests or Fisher's exact test, and both univariate and multivariate logistic regression analyses.ResultsA total of 103 patients were analyzed. The HHS in the stable group improved from a preoperative mean of 47.08 ± 5.50 to 89.13 ± 4.75 at the final follow‐up, whereas that in the unstable group increased from 45.43 ± 6.36 to 83.87 ± 4.67. The improvement scores for the stable and unstable groups were 42.05 ± 4.69 and 38.81 ± 3.06, respectively, with a statistically significant difference (p < 0.0001). VAS scores decreased from the preoperative levels of 7.13 ± 0.92 and 7.61 ± 0.82 to 2.36 ± 0.87 and 2.91 ± 0.79, respectively, indicating a significant reduction in pain in both groups; however, the unstable group reported more severe postoperative pain (p = 0.001). The incidence of postoperative complications following cHA was significantly greater in the unstable group (28.57%) than in the stable group (10.64%) (p = 0.047).ConclusioncHA is an effective treatment modality for the failure of internal fixation in intertrochanteric femoral fractures. Compared with stable fractures, patients with initial unstable fractures that have failed experience a greater incidence of postoperative complications, relatively poorer joint function, and more pronounced pain following cHA.

ObjectiveIntracranial infection is a serious complication after neurosurgery. However, the early diagnosis of post-neurosurgical intracranial infection (PNICI) remains challenging. The purpose of this study was to compare clinical characteristics and common laboratory indicators in patients with and without intracranial infections after neurosurgery and construct a diagnostic model of PNICI and assess its diagnostic efficacy.MethodsA total of 623 patients who underwent neurosurgery from January 2018 to October 2021 were enrolled and divided into a training set and a validation set. SPSS 22.0 software was used to compare the differences in basic information and laboratory examination results between the two groups to screen out valuable indicators. Subsequently, a nomogram for the diagnosis of PNICI was established. Then, the receiver operating characteristic (ROC) curve, calibration diagram, and decision curve analysis (DCA) were performed to evaluate the discriminative ability, consistency, and clinical usefulness of the nomogram.ResultsThe diagnostic model of PNICI consisted of seven variables: meningeal irritation, fever, postoperative drainage, cerebrospinal fluid (CSF) white blood cells, CSF chlorine, the CSF/blood glucose ratio, and blood neutrophil percentage. The model achieved an area under the ROC curve of 0.958 in the training set and 0.966 in the validation set. At the optimal cutoff of 0.397, the training set demonstrated 90.4% sensitivity and 90.8% specificity. The calibration curves and DCA curves of the nomogram demonstrated that the model exhibited good goodness of fit and showed a net benefit from its use.ConclusionsWe developed an easily applicable nomogram using routinely available indicators. This tool enables early risk stratification for PNICI, facilitating timely interventions that may reduce infection-related complications. However, multicenter prospective validation data are required to further confirm the clinical utility.

Objective.Pharmacokinetic (PK) parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provide quantitative characterization of tissue perfusion and permeability. However, existing deep learning methods for PK parameter estimation rely on either temporal or spatial features alone, overlooking the integrated spatial-temporal characteristics of DCE-MRI data. This study aims to remove this barrier by fully leveraging the spatial and temporal information to improve parameter estimation.Approach.A spatial-temporal information-driven unsupervised deep learning method (STUDE) was proposed. STUDE combines convolutional neural networks (CNNs) and a customized Vision Transformer to separately capture spatial and temporal features, enabling comprehensive modeling of contrast agent dynamics and tissue heterogeneity. Besides, a spatial-temporal attention feature fusion module was proposed to enable adaptive focus on both dimensions for more effective feature fusion. Moreover, the extended Tofts model imposed physical constraints on PK parameter estimation, enabling unsupervised training of STUDE. The accuracy and diagnostic value of STUDE was compared with the orthodox non-linear least squares (NLLS) and representative deep learning-based methods (i.e. gated recurrent unit, convolutional neural network, U-Net, and VTDCE-Net) on a numerical brain phantom and 87 glioma patients, respectively.Main results.On the numerical brain phantom, STUDE produced PK parameter maps with the lowest systematic and random errors even under low signal-to-noise ratio (SNR) conditions (SNR = 10 dB). On glioma data, STUDE generated parameter maps with reduced noise compared to NLLS and demonstrated superior structural clarity compared to other methods. Furthermore, STUDE outshined all other methods in the identification of glioma isocitrate dehydrogenase mutation status, achieving the area under the curve (AUC) values at 0.840 and 0.908 for the receiver operating characteristic curves ofKtransand Ve, respectively. A combination of all PK parameters improved AUC to 0.926.Significance.STUDE advances spatial-temporal information-driven and physics-informed learning for precise PK parameter estimation, demonstrating its potential clinical significance.

Autophagy maintains the homeostasis of the internal environment by clearing misfolded proteins and damaged organelles, which can reduce neuronal apoptosis in the early stage of spinal cord injury (SCI) and promote neural function recovery. Previous studies have shown that decreased acetylation modification of histone H4 lysine16 acetylation (H4K16ac) induces the expression of downstream autophagy genes. However, the role of H4K16ac modification and its impact on autophagy and apoptosis in the early stage of SCI remains unclear. This study aimed to determine the relationship between H4K16ac and autophagy, apoptosis in the early stage of SCI, and the effects of regulating H4K16ac on autophagy and apoptosis. In this study, the state of nerve cells after spinal cord injury was simulated by the rat pheochromocytoma cell line (PC12 cells) injured by oxygen–glucose deprivation (OGD) Model. Using OGD model in NGF-differentiated PC12 cells, we assessed H4K16ac dynamics via Western blot, immunofluorescence, and qPCR. Autophagy and apoptosis were evaluated through transmission electron microscopy, LC3B/p62 analysis, TUNEL staining, and flow cytometry. Results showed that OGD reduced H4K16ac in a time-dependent manner, correlating with enhanced autophagy (increased LC3B-II/I, Beclin1, ATG5; decreased p62) and apoptosis (elevated Bax/Bcl-2, cleaved caspase-3). Pharmacological inhibition of deacetylases by Trichostatin A (TSA) restored H4K16ac, suppressed autophagy, and exacerbated apoptosis. Similarly, Sirtuin 1 (SIRT1) knockdown upregulated H4K16ac, inhibited autophagic flux, and promoted apoptosis via the Bax/Bcl-2/caspase-3 pathway. These findings reveal that H4K16ac downregulation post-SCI enhances autophagy as a protective response, while its restoration via SIRT1 inhibition disrupts this balance, aggravating neuronal apoptosis.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-10352-z.

Abstract Bone marrow-derived mesenchymal stem cells (BMSCs) have been proven to be recruited into the tumor microenvironment and contribute to gastric cancer (GC) progression, However, the exact mechanisms remain poorly understood. This study explored the potential mechanism of RYK-silenced BMSCs on gastric cancer cell apoptosis. Firstly, BMSCs were transfected with the RYK siRNA and their corresponding negative controls, and cell co-culture were used to explore the interaction between different BMSCs and NCI-N87 cells. Then, Cancer cell cycle apoptosis was evaluated by flow cytometry. Western blot analysis was performed to determine the protein levels of Caspase3, Bax, and Bcl-2 in NCI-N87 cells. Then metabolomics was used to analyze the differential metabolites in different BMSCs. Furthermore, the NCI-N87 cells were treated with dihydrocapsaicin (DHC), and the proliferation activity, apoptosis level, and expression of apoptosis-related proteins in the NCI-N87 cells were detected after different DHC treatments. Compared to NCI-N87 cells cultured alone, co-culture with si-NC-modified BMSCs reduced apoptosis in NCI-N87 cells. However, co-culture with si-RYK-BMSCs significantly increased apoptosis. Additionally, DHC, a metabolic product secreted by BMSCs after RYK interference, suppresses NCI-N87 cell growth, promotes cell death, and increases the expression of apoptosis-related proteins. These findings suggest that RYK silencing-modified BMSCs can induce the apoptosis of NCI-N87 cells, potentially through increased secretion of DHC.