Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control.

Adult skeletal muscle stem cells, also known satellite cells (SCs), are quiescent and activate in response to injury. However, the activation mechanisms of quiescent SCs (QSCs) remain largely unknown. Here, we investigated the metabolic regulation of SC activation by identifying regulatory metabolites that promote SC activation. Using targeted metabolomics, we found that spermidine acts as a regulatory metabolite to promote SC activation and muscle regeneration in mice. Mechanistically, spermidine activates SCs via generating hypusinated eIF5A. Using SC-specific eIF5A-knockout (KO) and Myod-KO mice, we further found that eIF5A is required for spermidine-mediated SC activation by controlling MyoD translation. More significantly, depletion of eIF5A in SCs results in impaired muscle regeneration in mice. Together, the findings of our study define a novel mechanism that is essential for SC activation and acts via spermidine-eIF5A-mediated MyoD translation. Our findings suggest that the spermidine-eIF5A axis represents a promising pharmacological target in efforts to activate endogenous SCs for the treatment of muscular disease.

Histone deacetylase inhibition enhances extracellular vesicles from muscle to promote osteogenesis via miR-873-3p.

Regular physical activity is widely recognized for reducing the risk of various disorders, with skeletal muscles playing a key role by releasing biomolecules that benefit multiple organs and tissues. However, many individuals, particularly the elderly and those with clinical conditions, are unable to engage in physical exercise, necessitating alternative strategies to stimulate muscle cells to secrete beneficial biomolecules. Histone acetylation and deacetylation significantly influence exercise-induced gene expression, suggesting that targeting histone deacetylases (HDACs) could mimic some exercise responses. In this study, we explored the effects of the HDAC inhibitor Trichostatin A (TSA) on human skeletal muscle myoblasts (HSMMs). Our findings showed that TSA-induced hyperacetylation enhanced myotube fusion and increased the secretion of extracellular vesicles (EVs) enriched with miR-873-3p. These TSA-EVs promoted osteogenic differentiation in human bone marrow mesenchymal stem cells (hBMSCs) by targeting H2 calponin (CNN2). In vivo, systemic administration of TSA-EVs to osteoporosis mice resulted in significant improvements in bone mass. Moreover, TSA-EVs mimicked the osteogenic benefits of exercise-induced EVs, suggesting that HDAC inhibition can replicate exercise-induced bone health benefits. These results demonstrate the potential of TSA-induced muscle-derived EVs as a therapeutic strategy to enhance bone formation and prevent osteoporosis, particularly for individuals unable to exercise. Given the FDA-approved status of various HDAC inhibitors, this approach holds significant promise for rapid clinical translation in osteoporosis treatment.

Finite element analysis of three internal fixations for the posteromedial split fracture fragment in tibial plateau fractures.

Posteromedial tibial plateau fracture is one of the most challenging traumatic fractures. We aimed to compare and explain the biomechanical advantages and disadvantages of different internal fixation methods for the treatment of the posteromedial split fracture fragment in tibial plateau fractures. Finite element models of the tibial plateau fracture were constructed. Three different internal fixations were developed to treat the posteromedial split fracture fragment in tibial plateau fractures finite element models: (a) the novel anatomic locking plate fixation model, (b) the common anatomic locking plate fixation model, and (c) the reconstruction plate fixation model. We applied the same loading conditions to each model: 320 N axial compression. Under the same condition, the von Mises stress (VMS) and displacement distribution of the three internal fixations and tibia plateau were studied. The stress values of the novel anatomic locking plate are lower than the common anatomic locking plate and the reconstruction plate. Additionally, the novel anatomic locking plate fixation system exhibits smaller maximum displacement. In conclusion, our study indicated that the novel anatomic locking plate resulted in a lower stress distribution in the plate and screws, and better stability than the common anatomic locking plate and the reconstruction plate for the posteromedial split fracture fragment in tibial plateau fractures fixation under the same loading conditions. Thus, for the posteromedial split fracture fragment in tibial plateau fractures, the use of the novel anatomic locking plate internal fixation is recommended.

Dependable Automated Approach for Measuring the Retrograde Superior Ramus Screw Corridor in Pelvic Fracture Fixation.

BACKGROUND: Precise measurement of the intraosseous corridor within the superior pubic ramus is essential for the accurate percutaneous placement of a retrograde superior ramus screw (SRS). However, conventional manual measurement methods are often subjective, leading to variations in results among observers. Our goal was to develop an automated and dependable method for determining the retrograde SRS corridor. METHODS: We developed an automated technique that utilized a computed tomography (CT) image-based search algorithm to identify the retrograde SRS corridor with the maximum diameter. We evaluated the reliability of this automated approach in comparison to a manual method using 17 pelves. Subsequently, we used both methods to measure the diameter, length, and orientation of the retrograde SRS corridor in 204 pelves in a Chinese population and assessed the intra- and interobserver agreement of each method by calculating the root-mean-square error (RMSE) and constructing Bland-Altman plots. We determined the screw applicability (percentages of hemipelves that could be treated with specific sizes of screws) for each method. Additionally, we investigated potential factors influencing the corridor, such as sex, age, height, and weight, through regression analysis. RESULTS: The intra- and interobserver intraclass correlation coefficients (ICCs) for the automated method (0.998 and 0.995) were higher than those for the manual approach (0.925 and 0.918) in the assessment of the corridor diameter. Furthermore, the diameter identified by the automated method was notably larger than the diameter measured with the manual method, with a mean difference and RMSE of 0.9 mm and 1.1 mm, respectively. The automated method revealed a significantly smaller corridor diameter in females than in males (an average of 7.5 and 10.4 mm, respectively). Moreover, use of the automated method allowed 80.6% of the females to be managed with a 4.5-mm screw while a 6.5-mm screw could be utilized in 19.4%, surpassing the capabilities of the manual method. Female sex had the most substantial impact on corridor diameter (ß = -0.583). CONCLUSIONS: The automated method exhibited better reliability than the manual method in measuring the retrograde SRS corridor, and showed a larger corridor diameter for screw placement. Females had a significantly smaller corridor diameter than males. Given the intricate nature of the automated approach, which entails utilizing different software and interactive procedures, our current method is not readily applicable for traumatologists. We are working on developing integrated software with the goal of providing a more user-friendly solution for traumatologists in the near future. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Cartilage lacuna-biomimetic hydrogel microspheres endowed with integrated biological signal boost endogenous articular cartilage regeneration.

Despite numerous studies on chondrogenesis, the repair of cartilage-particularly the reconstruction of cartilage lacunae through an all-in-one advanced drug delivery system remains limited. In this study, we developed a cartilage lacuna-like hydrogel microsphere system endowed with integrated biological signals, enabling sequential immunomodulation and endogenous articular cartilage regeneration. We first integrated the chondrogenic growth factor transforming growth factor-ß3 (TGF-ß3) into mesoporous silica nanoparticles (MSNs). Then, TGF-ß3@MSNs and insulin-like growth factor 1 (IGF-1) were encapsulated within microspheres made of polydopamine (pDA). In the final step, growth factor-loaded MSN@pDA and a chitosan (CS) hydrogel containing platelet-derived growth factor-BB (PDGF-BB) were blended to produce growth factors loaded composite microspheres (GFs@µS) using microfluidic technology. The presence of pDA reduced the initial acute inflammatory response, and the early, robust release of PDGF-BB aided in attracting endogenous stem cells. Over the subsequent weeks, the continuous release of IGF-1 and TGF-ß3 amplified chondrogenesis and matrix formation. µS were incorporated into an acellular cartilage extracellular matrix (ACECM) and combined with a polydopamine-modified polycaprolactone (PCL) structure to produce a tissue-engineered scaffold that mimicked the structure of the cartilage lacunae evenly distributed in the cartilage matrix, resulting in enhanced cartilage repair and patellar cartilage protection. This research provides a strategic pathway for optimizing growth factor delivery and ensuring prolonged microenvironmental remodeling, leading to efficient articular cartilage regeneration.

Development and Validation of Physical Disability Index and Mental Disability Index and Their Associations With Falls Among Older Adults.

BACKGROUND: To enhance the precision of measuring, analyzing, and forecasting care needs for older adults with physical and/or mental disabilities, we developed the Physical Disability Index (PDI) and Mental Disability Index (MDI). Furthermore, we evaluated the reliability and validity of the PDI and MDI. Additionally, we investigate their associations with falls to further indicate the predictive validity. METHODS: A total of 11 621 older adults (53.1% women; mean age = 83.2; SD = 10.8) from 23 provinces in China were investigated in 2017-2018 to assess the reliability and validity of the PDI and MDI among older adults aged 65 to 105. Among which, 6 071 older adults with both baseline (2017-2018) and follow-up (2021) data were included in analyses to evaluate associations between the baseline health status determined by PDI and MDI and the number and severity of falls at baseline and follow-up. Cronbach's alpha was used to determine internal consistency. The convergent and divergent validity, known-group validity and concurrent validity were assessed. Multinomial logistic regression models were utilized to assess associations. RESULTS: We found satisfactory internal consistency (Cronbach's alpha ≥ 0.70) of the PDI and MDI in the total sample and sex-specific subgroups. Our results support the convergent and divergent validity, known-group validity, and concurrent validity of the PDI and MDI. We also found baseline physical disability and comorbid physical and mental disability are associated with a higher risk of baseline and follow-up falls. CONCLUSIONS: The PDI and MDI are reliable and valid instruments to assess physical and mental disability status among older adults, respectively.

Quantitative Analysis of Primary Compressive Trabeculae Distribution in the Proximal Femur of the Elderly.

OBJECTIVE: As osteoporosis progresses, the primary compressive trabeculae (PCT) in the proximal femur remains preserved and is deemed the principal load-bearing structure that links the femoral head with the femoral neck. This study aims to elucidate the distribution patterns of PCT within the proximal femur in the elderly population, and to assess its implications for the development and optimization of internal fixation devices used in hip fracture surgeries. METHODS: This is a retrospective cohort study conducted from March 2022 to April 2023. A total of 125 patients who underwent bilateral hip joint CT scans in our hospital were enrolled. CT data of the unaffected side of the hip were analyzed. Key parameters regarding the PCT distribution in the proximal femur were measured, including the femoral head's radius (R), the neck-shaft angle (NSA), the angle between the PCT-axis and the head-neck axis (α), the distance from the femoral head center to the PCT-axis (δ), and the lengths of the PCT's bottom and top boundaries (L-bottom and L-top respectively). The impact of gender differences on PCT distribution patterns was also investigated. Student's t-test or Mann-Whitney U test were used to compare continuous variables between genders. The relationship between various variables was investigated through Pearson's correlation analysis. RESULTS: PCT was the most prominent bone structure within the femoral head. The average NSA, α, and δ were 126.85 ± 5.85°, 37.33 ± 4.23°, and 0.39 ± 1.22 mm, respectively, showing no significant gender differences (p > 0.05). Pearson's correlation analysis revealed strong correlations between α and NSA (r = -0.689, p < 0.001), and R and L-top (r = 0.623, p < 0.001), with mild correlations observed between δ and NSA (r = -0.487, p < 0.001), and R and L-bottom (r = 0.427, p < 0.001). Importantly, our study establishes a method to accurately localize PCT distribution in true anteroposterior (AP) radiographs of the hip joint, facilitating precise screw placement in proximal femur fixation procedures. CONCLUSION: Our study provided unprecedented insights into the distribution patterns of PCT in the proximal femur of the elderly population. The distribution of PCT in the proximal femur is predominantly influenced by anatomical and geometric factors, such as NSA and femoral head size, rather than demographic factors like gender. These insights have crucial implications for the design of internal fixation devices and surgical planning, offering objective guidance for the placement of screws in hip fracture treatments.

Integrative analysis of genomic and epigenomic regulation reveals miRNA mediated tumor heterogeneity and immune evasion in lower grade glioma.

The expression dysregulation of microRNAs (miRNA) has been widely reported during cancer development, however, the underling mechanism remains largely unanswered. In the present work, we performed a systematic integrative study for genome-wide DNA methylation, copy number variation and miRNA expression data to identify mechanisms underlying miRNA dysregulation in lower grade glioma. We identify 719 miRNAs whose expression was associated with alterations of copy number variation or promoter methylation. Integrative multi-omics analysis revealed four subtypes with differing prognoses. These glioma subtypes exhibited distinct immune-related characteristics as well as clinical and genetic features. By construction of a miRNA regulatory network, we identified candidate miRNAs associated with immune evasion and response to immunotherapy. Finally, eight prognosis related miRNAs were validated to promote cell migration, invasion and proliferation through in vitro experiments. Our study reveals the crosstalk among DNA methylation, copy number variation and miRNA expression for immune regulation in glioma, and could have important implications for patient stratification and development of biomarkers for immunotherapy approaches.

The clinical efficacy of Medial Sustain Nail(MSN) and Proximal femoral nail anti-rotation(PFNA) for fixation of medial comminuted trochanteric fractures: a prospective randomized controlled trial.

PURPOS: To evaluate the clinical efficacy of the Medial Sustain Nail (MSN) for medial comminuted trochanteric fractures fixation in comparison to Proximal Femoral Nail Antirotation (PFNA) through a clinical study. METHODS: A non-inferiority randomized controlled trial was conducted at a single centre between July 2019 and July 2020. Fifty patients diagnosed comminuted trochanteric fractures were randomly assigned to either the MSN group (n = 25) or the PFNA group (n = 25). A total of forty-three patients were included in the final study analysis. The primary outcome measure was Short Form 36 health surgery physical component summary (SF-36 PCS) score. Secondary outcomes included the Oxford Hip Scores (OHS), weight bearing, complication relate to implant and so on. This study was not blined to surgeons, but to patients and data analysts. RESULTS: The MSN demonstrated significantly better functional outcomes as measured by SF-36 PCS and OHS at six months postoperative compared to PFNA (p < 0.05). Union of fractures in the MSN group reached 90.9% at three months after surgery, whereas the PFNA group achieved a union rate of 57.1% (p < 0.05). Furthermore, weight-bearing time of MSN group was earlier than PFNA group (p < 0.05). Additionally, complications related to implant usage were more prevalent in the PFNA group (33.3%) compared to the MSN group (4.5%) (p < 0.05). CONCLUSION: MSN exhibited superior quality of life outcomes compared to PFNA at six months postoperative. This indicates that MSN effectively reconstructs medial femoral support in patients with comminuted trochanteric fractures, which facilitates early weight-bearing and accelerates the recovery process. TRIAL REGISTRATION: Trial registration number: NCT01437176, Date of the trial registration:2011-9-1, Date of commencement of the study:2011-9, Date of enrolment/recruitment of the study subjects:2019-7.

Novel biomimetic macromolecules system for highly efficient lubrication, ROS scavenging and osteoarthritis treatment.

The early stages of osteoarthritis (OA) in the joints are typically characterized by two key factors: the dysfunction of articular cartilage lubrication and inflammation resulting from the excessive production of reactive oxygen species (ROS). Synthetic injectable macromolecular materials present great potential for preventing the progression of early OA. In this study, to mimic the excellent lubricity of brush-like aggregates found in natural synovial fluid, we develop a novel macromolecular biolubricant (CS-PS-DA) by integrating adhesion and hydration groups onto backbone of natural biomacromolecules. CS-PS-DA exhibits a strong affinity for cartilage surfaces, enabling the formation of a stable lubrication layer at the sliding interface of degraded cartilages to restore joint lubrication performance. In vitro results from ROS scavenging and anti-inflammatory experiments indicate the great advantage of CS-PS-DA to decrease the levels of proinflammatory cytokines by inhibiting ROS overproduction. Finally, in vivo rats OA model demonstrates that intra-cavitary injection of CS-PS-DA could effectively resist cartilage wear and mitigated inflammation in the joints. This novel biolubricant provides a new and timely strategy for the treatment of OA.

HIF2A mediates lineage transition to aggressive phenotype of cancer-associated fibroblasts in lung cancer brain metastasis.

Brain metastasis is the most devasting form of lung cancer. Recent studies highlight significant differences in the tumor microenvironment (TME) between lung cancer brain metastasis (LCBM) and primary lung cancer, which contribute significantly to tumor progression and drug resistance. Cancer-associated fibroblasts (CAFs) are the major component of pro-tumor TME with high plasticity. However, the lineage composition and function of CAFs in LCBM remain elusive. By reanalyzing single-cell RNA sequencing (scRNA-seq) data (GSE131907) from lung cancer patients with different stages of metastasis comprising primary lesions and brain metastasis, we found that CAFs undergo distinctive lineage transition during LCBM under a hypoxic situation, which is directly driven by hypoxia-induced HIF-2α activation. Transited CAFs enhance angiogenesis through VEGF pathways, trigger metabolic reprogramming, and promote the growth of tumor cells. Bulk RNA sequencing data was utilized as validation cohorts. Multiplex immunohistochemistry (mIHC) assay was performed on four paired samples of brain metastasis and their primary lung cancer counterparts to validate the findings. Our study revealed a novel mechanism of lung cancer brain metastasis featuring HIF-2α-induced lineage transition and functional alteration of CAFs, which offers potential therapeutic targets.

Establishment and validation of an artificial intelligence web application for predicting postoperative in-hospital mortality in patients with hip fracture: a national cohort study of 52 707 cases.

BACKGROUND: In-hospital mortality following hip fractures is a significant concern, and accurate prediction of this outcome is crucial for appropriate clinical management. Nonetheless, there is a lack of effective prediction tools in clinical practice. By utilizing artificial intelligence (AI) and machine learning techniques, this study aims to develop a predictive model that can assist clinicians in identifying geriatric hip fracture patients at a higher risk of in-hospital mortality. METHODS: A total of 52 707 geriatric hip fracture patients treated with surgery from 90 hospitals were included in this study. The primary outcome was postoperative in-hospital mortality. The patients were randomly divided into two groups, with a ratio of 7:3. The majority of patients, assigned to the training cohort, were used to develop the AI models. The remaining patients, assigned to the validation cohort, were used to validate the models. Various machine learning algorithms, including logistic regression (LR), decision tree (DT), naïve bayesian (NB), neural network (NN), eXGBoosting machine (eXGBM), and random forest (RF), were employed for model development. A comprehensive scoring system, incorporating 10 evaluation metrics, was developed to assess the prediction performance, with higher scores indicating superior predictive capability. Based on the best machine learning-based model, an AI application was developed on the Internet. In addition, a comparative testing of prediction performance between doctors and the AI application. FINDINGS: The eXGBM model exhibited the best prediction performance, with an area under the curve (AUC) of 0.908 (95% CI: 0.881-0.932), as well as the highest accuracy (0.820), precision (0.817), specificity (0.814), and F1 score (0.822), and the lowest Brier score (0.120) and log loss (0.374). Additionally, the model showed favorable calibration, with a slope of 0.999 and an intercept of 0.028. According to the scoring system incorporating 10 evaluation metrics, the eXGBM model achieved the highest score (56), followed by the RF model (48) and NN model (41). The LR, DT, and NB models had total scores of 27, 30, and 13, respectively. The AI application has been deployed online at https://in-hospitaldeathinhipfracture-l9vhqo3l55fy8dkdvuskvu.streamlit.app/ , based on the eXGBM model. The comparative testing revealed that the AI application's predictive capabilities significantly outperformed those of the doctors in terms of AUC values (0.908 vs. 0.682, P <0.001). CONCLUSIONS: The eXGBM model demonstrates promising predictive performance in assessing the risk of postoperative in-hospital mortality among geriatric hip fracture patients. The developed AI model serves as a valuable tool to enhance clinical decision-making.

Evolution of Musculoskeletal Electronics.

The musculoskeletal system, constituting the largest human physiological system, plays a critical role in providing structural support to the body, facilitating intricate movements, and safeguarding internal organs. By virtue of advancements in revolutionized materials and devices, particularly in the realms of motion capture, health monitoring, and postoperative rehabilitation, "musculoskeletal electronics" has actually emerged as an infancy area, but has not yet been explicitly proposed. In this review, the concept of musculoskeletal electronics is elucidated, and the evolution history, representative progress, and key strategies of the involved materials and state-of-the-art devices are summarized. Therefore, the fundamentals of musculoskeletal electronics and key functionality categories are introduced. Subsequently, recent advances in musculoskeletal electronics are presented from the perspectives of "in vitro" to "in vivo" signal detection, interactive modulation, and therapeutic interventions for healing and recovery. Additionally, nine strategy avenues for the development of advanced musculoskeletal electronic materials and devices are proposed. Finally, concise summaries and perspectives are proposed to highlight the directions that deserve focused attention in this booming field.

Inhibiting the "isolated island" effect in simulated bone defect repair using a hollow structural scaffold design.

The treatment of bone tissue defects remains a complicated clinical challenge. Recently, the bone tissue engineering (BTE) technology has become an important therapeutic approach for bone defect repair. Researchers have improved the scaffolds, cells, and bioactive factors used in BTE through various existing bone repair material preparation strategies. However, due to insufficient vascularization, inadequate degradation, and fibrous wrapping, most BTE scaffolds impede new bone ingrowth and the reconstruction of grid-like connections in the middle and late stages of bone repair. These non-degradable scaffolds become isolated and disordered like independent "isolated islands", which leads to the failure of osteogenesis. Consequently, we hypothesized that the "island effect" prevents successful bone repair. Accordingly, we proposed a new concept of scaffold modification-osteogenesis requires a bone temporary shelter (also referred to as the empty shell osteogenesis concept). Based on this concept, we consider that designing hollow structural scaffolds is the key to mitigating the "isolated island" effect and enabling optimal bone regeneration and reconstruction.

CHRONIC CRITICAL ILLNESS-INDUCED MUSCLE ATROPHY: INSIGHTS FROM A TRAUMA MOUSE MODEL AND POTENTIAL MECHANISM MEDIATED VIA SERUM AMYLOID A.

ABSTRACT: Background: Chronic critical illness (CCI), which was characterized by persistent inflammation, immunosuppression, and catabolism syndrome (PICS), often leads to muscle atrophy. Serum amyloid A (SAA), a protein upregulated in critical illness myopathy, may play a crucial role in these processes. However, the effects of SAA on muscle atrophy in PICS require further investigation. This study aims to develop a mouse model of PICS combined with bone trauma to investigate the mechanisms underlying muscle weakness, with a focus on SAA. Methods: Mice were used to examine the effects of PICS after bone trauma on immune response, muscle atrophy, and bone healing. The mice were divided into two groups: a bone trauma group and a bone trauma with cecal ligation and puncture group. Tibia fracture surgery was performed on all mice, and PICS was induced through cecal ligation and puncture surgery in the PICS group. Various assessments were conducted, including weight change analysis, cytokine analysis, hematological analysis, grip strength analysis, histochemical staining, and immunofluorescence staining for SAA. In vitro experiments using C2C12 cells (myoblasts) were also conducted to investigate the role of SAA in muscle atrophy. The effects of inhibiting receptor for advanced glycation endproducts (RAGE) or JAK2 on SAA-induced muscle atrophy were examined. Bioinformatic analysis was conducted using a dataset from the GEO database to identify differentially expressed genes and construct a coexpression network. Results: Bioinformatic analysis confirmed that SAA was significantly upregulated in muscle tissue of patients with intensive care unit-induced muscle atrophy. The PICS animal models exhibited significant weight loss, spleen enlargement, elevated levels of proinflammatory cytokines, and altered hematological profiles. Evaluation of muscle atrophy in the animal models demonstrated decreased muscle mass, grip strength loss, decreased diameter of muscle fibers, and significantly increased expression of SAA. In vitro experiment demonstrated that SAA decreased myotube formation, reduced myotube diameter, and increased the expression of muscle atrophy-related genes. Furthermore, SAA expression was associated with activation of the FOXO signaling pathway, and inhibition of RAGE or JAK2/STAT3-FOXO signaling partially reversed SAA-induced muscle atrophy. Conclusions: This study successfully develops a mouse model that mimics PICS in CCI patients with bone trauma. Serum amyloid A plays a crucial role in muscle atrophy through the JAK2/STAT3-FOXO signaling pathway, and targeting RAGE or JAK2 may hold therapeutic potential in mitigating SAA-induced muscle atrophy.

Three-Dimensional-Printed Spherical Hollow Structural Scaffolds for Guiding Critical-Sized Bone Regeneration.

The treatment of bone tissue defects continues to be a complex medical issue. Recently, three-dimensional (3D)-printed scaffold technology for bone tissue engineering (BTE) has emerged as an important therapeutic approach for bone defect repair. Despite the potential of BTE scaffolds to contribute to long-term bone reconstruction, there are certain challenges associated with it including the impediment of bone growth within the scaffolds and vascular infiltration. These difficulties can be resolved by using scaffold structural modification strategies that can effectively guide bone regeneration. This study involved the preparation of biphasic calcium phosphate spherical hollow structural scaffolds (SHSS) with varying pore sizes using 3D printing (photopolymerized via digital light processing). The chemical compositions, microscopic morphologies, mechanical properties, biocompatibilities, osteogenic properties, and impact on repairing critical-sized bone defects of SHSS were assessed through characterization analyses, in vitro cytological assays, and in vivo biological experiments. The results revealed the biomimetic properties of SHSS and their favorable biocompatibility. The scaffolds stimulated cell adhesion, proliferation, differentiation, and migration and facilitated the expression of osteogenic genes and proteins, including Col-1, OCN, and OPN. Furthermore, they could effectively repair a critical-sized bone defect in a rabbit femoral condyle by establishing an osteogenic platform and guiding bone regeneration in the defect region. This innovative strategy presents a novel therapeutic approach for assessing critical-sized bone defects.

Biomechanical Research of Three Parallel Cannulated Compression Screws in Oblique Triangle Configuration for Fixation of Femoral Neck Unstable Fractures.

OBJECTIVE: Surgical treatment with internal fixation, specifically percutaneous fixation with three cannulated compression screws (CCSs), is the preferred choice for young and middle-aged patients. The mechanical advantage of the optimal spatial configuration with three screws provides maximum dispersion and cortical support. We suspect that the spatial proportion of the oblique triangle configuration (OTC) in the cross-section of the femoral neck isthmus (FNI) may significantly improve shear and fatigue resistance of the fixed structure, thereby stabilizing the internal fixation system in femoral neck fracture (FNF). This study aims to explore the mechanical features of OTC and provide a mechanical basis for its clinical application. METHODS: Twenty Sawbone femurs were prepared as Pauwels type III FNF models and divided equally into two fixation groups: OTC and inverted equilateral triangle configuration (IETC). Three 7.3 mm diameter cannulated compression screws (CCSs) were used for fixation. The specimens of FNF after screw internal fixation were subjected to static loading and cyclic loading tests, respectively, with five specimens for each test. Axial stiffness, 5 mm failure load, ultimate load, shear displacement, and frontal rotational angle of two fragments were evaluated. In the cyclic loading test, the load sizes were 700 N, 1400 N, and 2100 N, respectively, and the fracture end displacement was recorded. Results were presented as means ± SD. Data with normal distributions were compared by the Student's t test. RESULTS: In the static loading test, the axial stiffness, ultimate load, shear displacement, and frontal rotational angle of two fragments were (738.64 vs. 620.74) N/mm, (2957.61 vs. 2643.06) N, (4.67 vs. 5.39) mm, and (4.01 vs. 5.52)° (p < 0.05), respectively. Comparison between the femoral head displacement after 10,000 cycles of 700N cyclic loading and total displacement after 20,000 cycles of 700-1400N cyclic loading showed the OTC group was less than the IETC group (p < 0.05). A comparison of femoral head displacement after 10,000 cycles of 1400N and 2100N cycles and total displacement after 30,000 cycles of 700-2100N cycles showed the OTC group was less than another group, but the difference was not significant (p > 0.05). CONCLUSION: When three CCSs are inserted in parallel to fix FNF, the OTC of three screws has obvious biomechanical advantages, especially in shear resistance and early postoperative weight-bearing, which provides a mechanical basis for clinical selection of ideal spatial configuration for unstable FNF.

Extracellular vesicles produced by 3D cultured MSCs promote wound healing by regulating macrophage activation through ANXA1.

The conundrum of wound healing has transformed into an imminent medical challenge. Presently, cell-free therapy centered around extracellular vesicles (EVs) has become a pivotal and promising research avenue. EVs generated from three-dimensional (3D) cell cultures have been previously established to possess enhanced tissue regeneration potential, although the underlying mechanisms remain elusive. In this study, we observed higher expression of annexin ANXA1 in 3D-cultured EVs. Remarkably, 3D-EVs with elevated ANXA1 expression demonstrated a more potent capacity to promote macrophage polarization from the M1 phenotype to the M2 phenotype. Concurrently, they exhibited superior abilities to enhance cell migration and tube formation, facilitating expedited wound healing in animal experiments. Conversely, the application of an ANXA1 inhibitor counteracted the positive effects of 3D-EVs. Taken together, our data validate that extracellular vesicles derived from 3D-cultured MSCs regulate macrophage polarization via ANXA1, thereby fostering wound healing.

Head-to-head comparison of [68Ga]Ga-FAPI PET and [18F]FDG PET in the detection of bone and lymph node metastasis in various cancers: A systematic review and meta-analysis.

PURPOSE: The aim of our meta-analysis and systematic review was to contrast the positivity rates of [68Ga]Ga-FAPI PET and [18F]FDG PET in detecting bone and lymph node metastases across diverse cancer types. METHODS: We conducted a comprehensive search for eligible articles up until August 2023, utilizing databases including PubMed, Embase, and Web of Science. Studies focusing on the positivity rate of [68Ga]Ga-FAPI PET vs. [18F]FDG PET for bone and lymph metastasis were included. Using random-effect model, the positivity rate for [68Ga]Ga-FAPI PET and [18F]FDG PET were generated. In order to gauge the heterogeneity among aggregated studies, we utilized the I2 statistic. Additionally, we applied the Quality Assessment of Diagnostic Performance Studies (QUADAS-2) methodology to evaluate the caliber of the studies encompassed in our analysis. RESULTS: A total of 430 publications were initially identified in the search. Eventually, 25 studies, involving 779 patients, met the inclusion criteria. In terms of bone metastasis, the findings indicate no statistically significant difference between the use of [68Ga]Ga-FAPI PET and [18F]FDG PET (P = 0.34). However, concerning lymph node metastasis, the results demonstrate significant difference between the two imaging agents (P = 0.04). CONCLUSIONS: This systematic review suggests that [68Ga]Ga-FAPI PET appears to outperform [18F]FDG PET in detecting lymph node metastases. However, when it comes to bone metastasis, no statistically significant difference was observed. It is crucial to acknowledge that the insights concerning bone metastasis stem from studies with comparatively modest sample sizes. Consequently, there is a pressing demand for further, expansive prospective studies in this field.