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.

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.

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.

Based on PI3K/Akt Signaling Pathway, the Effects of Gubi Decoction on Chondrocyte Proliferation, Apoptosis, and Expression of Inflammatory Factors in a Rat Model of Osteoarthritis.

Objective: Given the crucial role of the PI3K/Akt signaling pathway in chondrocyte survival and inflammation in osteoarthritis (OA), this study aimed to investigate the effects of Gu Bi Tang on chondrocyte proliferation, apoptosis, and inflammatory factor expression in a rat model of OA, with a focus on the PI3K/Akt signaling pathway. Methods: Forty-five specific pathogen-free (SPF) C57 mice were randomly divided into three groups: the model group (Group A), the Gu Bi Tang group (Group B), and the Amfenac group (Group C), with 15 rats in each group. All 45 rats underwent anterior cruciate ligament transection (ACLT) surgery to establish an OA model. The ACLT procedure is a well-established method for inducing OA in rodents, as it leads to the destabilization of the knee joint and the development of degenerative changes characteristic of human OA. After 8 weeks of modeling, Group A rats received an equivalent volume of normal saline by gastric lavage, Group B rats were administered 13 mL/kg of Gu Bi Tang, and Group C rats received 19.5 mg/kg of Amfenac solution by gastric lavage. The dosages of Gu Bi Tang and Amfenac were selected based on previous studies examining the therapeutic effects of these interventions in rodent OA models. The gastric lavage frequency for all three groups was maintained at twice daily. The researchers analyzed cartilage morphological changes using toluidine blue staining, chondrocyte proliferation and apoptosis using the TUNEL method, and the expression of PI3K/AKT/mTOR proteins in chondrocytes using Western blotting. Additionally, the expression of inflammatory factors (TNF-α and IL-1ß) in serum was measured using ELISA. Results: Staining: Compared to the model group (Group A), both the Gu Bi Tang group (Group B) and the Amfenac group (Group C) showed significant improvement in cartilage tissue, with deeper toluidine blue staining. Toluidine blue staining is a marker of cartilage integrity and glycosaminoglycan content, indicating improved cartilage structure and composition in the treatment groups. Chondrocyte proliferation and apoptosis: Compared to the model group (Group A), both the Gu Bi Tang group (Group B) and the Amfenac group (Group C) significantly reduced chondrocyte apoptosis (P < .05). This reduction in chondrocyte death contributes to a healthier cartilage environment and helps prevent further cartilage degradation. Protein expression: In comparison to the model group (Group A), the expression of PI3K, AKT, and mTOR proteins in the joint cartilage of the Gu Bi Tang group (Group B) and the Amfenac group (Group C) significantly decreased, with the Amfenac group showing a greater reduction than the Gu Bi Tang group (P < .05). The inhibition of this detrimental PI3K/AKT/mTOR signaling pathway promotes chondrocyte survival and a more favorable cartilage homeostasis. Inflammatory factor expression: Prior to treatment, there was no significant difference in the expression levels of the inflammatory factors TNF-α and IL-1ß in serum among the three groups (P > .05). However, after treatment, both the Gu Bi Tang group (Group B) and the Amfenac group (Group C) showed a significant reduction in the serum expression of TNF-α and IL-1ß compared to the model group (Group A), with the Amfenac group showing a greater reduction than the Gu Bi Tang group (P < .05). This is important, as TNF-α and IL-1ß are key pro-inflammatory cytokines that drive the destructive processes in osteoarthritis. Conclusion: In summary, this study demonstrates that Gu Bi Tang exerts protective effects on chondrocytes in a rat model of osteoarthritis. Specifically, Gu Bi Tang was shown to inhibit chondrocyte apoptosis, reduce the expression of key proteins in the PI3K/AKT/mTOR signaling pathway, and decrease the levels of the pro-inflammatory cytokines TNF-α and IL-1ß. These findings suggest that Gu Bi Tang could offer a novel therapeutic approach for osteoarthritis by modulating key signaling pathways and inflammatory responses. The ability of Gu Bi Tang to preserve chondrocyte viability and maintain a more favorable cartilage homeostasis makes it a promising candidate for further investigation as a potential treatment for osteoarthritis. Future studies should explore the precise mechanisms by which Gu Bi Tang exerts its beneficial effects and evaluate its efficacy in additional animal models and clinical settings.

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.

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.

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.

Sema3A ameliorates the pathological progression of osteoarthritis by modulating mitochondrial damage in chondrocytes.

Osteoarthritis (OA) is a major disease that causes disability in middle-aged and elderly people. A comprehensive understanding of its pathogenesis is of great significance in finding new clinical diagnosis and treatment schemes. The role of Semaphorin 3A (Sema3A) in OS has attracted attention recently, and the purpose of this study is to analyze the mechanisms underlying its impact on OS. First, a rat model of OS was established. Hematoxylin-eosin (HE) and TUNEL staining showed that the modeled rats presented typical pathological manifestations of OS, confirming the success of the modeling. Sema3A was significantly underexpressed in OS rats. Subsequently, Sema3A abnormal expression vectors were constructed to intervene in chondrocytes isolated from OS rats. It was found that the proliferation of chondrocytes was decreased, the apoptosis was increased, and the mitochondrial damage and autophagy were intensified after silencing Sema3A expression, while the above pathological processes were reversed when Sema3A expression was increased. In conclusion, Sema3A has an important influence on the pathological progression of OS, and molecular therapies targeting to increase Sema3A expression may become a new treatment for OS in the future.

Cholestyramine alleviates bone and muscle loss in irritable bowel syndrome via regulating bile acid metabolism.

Irritable bowel syndrome (IBS) is a widespread gastrointestinal disorder known for its multifaceted pathogenesis and varied extraintestinal manifestations, yet its implications for bone and muscle health are underexplored. Recent studies suggest a link between IBS and musculoskeletal disorders, but a comprehensive understanding remains elusive, especially concerning the role of bile acids (BAs) in this context. This study aimed to elucidate the potential contribution of IBS to bone and muscle deterioration via alterations in gut microbiota and BA profiles, hypothesizing that cholestyramine could counteract these adverse effects. We employed a mouse model to characterize IBS and analysed its impact on bone and muscle health. Our results revealed that IBS promotes bone and muscle loss, accompanied by microbial dysbiosis and elevated BAs. Administering cholestyramine significantly mitigated these effects, highlighting its therapeutic potential. This research not only confirms the critical role of BAs and gut microbiota in IBS-associated bone and muscle loss but also demonstrates the efficacy of cholestyramine in ameliorating these conditions, thereby contributing significantly to the field's understanding and offering a promising avenue for treatment.

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.

Deciphering Immune Landscape Remodeling Unravels the Underlying Mechanism for Synchronized Muscle and Bone Aging.

Evidence from numerous studies has revealed the synchronous progression of aging in bone and muscle; however, little is known about the underlying mechanisms. To this end, human muscles and bones are harvested and the aging-associated transcriptional dynamics of two tissues in parallel using single-cell RNA sequencing are surveyed. A subset of lipid-associated macrophages (triggering receptor expressed on myeloid cells 2, TREM2+ Macs) is identified in both aged muscle and bone. Genes responsible for muscle dystrophy and bone loss, such as secreted phosphoprotein 1 (SPP1), are also highly expressed in TREM2+ Macs, suggesting its conserved role in aging-related features. A common transition toward pro-inflammatory phenotypes in aged CD4+ T cells across tissues is also observed, activated by the nuclear factor kappa B subunit 1 (NFKB1). CD4+ T cells in aged muscle experience Th1-like differentiation, whereas, in bone, a skewing toward Th17 cells is observed. Furthermore, these results highlight that degenerated myocytes produce BAG6-containing exosomes that can communicate with Th17 cells in the bone through its receptor natural cytotoxicity triggering receptor 3 (NCR3). This communication upregulates CD6 expression in Th17 cells, which then interact with TREM2+ Macs through CD6-ALCAM signaling, ultimately stimulating the transcription of SPP1 in TREM2+ Macs. The negative correlation between serum exosomal BCL2-associated athanogene 6 (BAG6) levels and bone mineral density further supports its role in mediating muscle and bone synchronization with aging.

[Research progress of pubic symphysis diastasis].

Objective: To review the research progress of pubic symphysis diastasis and provide effective reference for orthopedic surgeons in the diagnosis and treatment of pubic symphysis diastasis. Methods: The anatomy, injury mechanism, treatment, and other aspects of pubic symphysis diastasis were summarized and analyzed by reviewing the relevant research literature at domestically and internationally in recent years. Results: The incidence of pubic symphysis diastasis is high in pelvic fractures, which is caused by the injury of the ligaments and fibrocartilage disc around the pubic symphysis by external force. The treatment plan should be individualized according to the pelvic stability and the needs of patients, aiming to restore the stability and integrity of the pelvis and improve the quality of life of patients after surgery. Conclusion: At present, the research on pubic symphysis diastasis still needs to be improved. In the future, high-quality, multi-center, and large-sample studies are of great significance for the selection of treatment methods and the evaluation of effectiveness for patients with pubic symphysis diastasis.

Effect of denosumab on glucose metabolism in postmenopausal osteoporotic women with prediabetes: a study protocol for a 12-month multicenter, open-label, randomized controlled trial.

BACKGROUND: Participants with prediabetes are at a high risk of developing type 2 diabetes (T2D). Recent studies have suggested that blocking the receptor activator of nuclear factor-κB ligand (RANKL) may improve glucose metabolism and delay the development of T2D. However, the effect of denosumab, a fully human monoclonal antibody that inhibits RANKL, on glycemic parameters in the prediabetes population is uncertain. We aim to examine the effect of denosumab on glucose metabolism in postmenopausal women with osteoporosis and prediabetes. METHODS: This is a 12-month multicenter, open-label, randomized controlled trial involving postmenopausal women who have been diagnosed with both osteoporosis and prediabetes. Osteoporosis is defined by the World Health Organization (WHO) as a bone mineral density T score of ≤ - 2.5, as measured by dual-energy X-ray absorptiometry (DXA). Prediabetes is defined as (i) a fasting plasma glucose level of 100-125 mg/dL, (ii) a 2-hour plasma glucose level of 140-199 mg/dL, or (iii) a glycosylated hemoglobin A1c (HbA1c) level of 5.7-6.4%. A total of 346 eligible subjects will be randomly assigned in a 1:1 ratio to receive either subcutaneous denosumab 60 mg every 6 months or oral alendronate 70 mg every week for 12 months. The primary outcome is the change in HbA1c levels from baseline to 12 months. Secondary outcomes include changes in fasting and 2-hour blood glucose levels, serum insulin levels, C-peptide levels, and insulin sensitivity from baseline to 12 months, and the incidence of T2D at the end of the study. Follow-up visits will be scheduled at 3, 6, 9, and 12 months. DISCUSSION: This study aims to provide evidence on the efficacy of denosumab on glucose metabolism in postmenopausal women with osteoporosis and prediabetes. The results derived from this clinical trial may provide insight into the potential of denosumab in preventing T2D in high-risk populations. TRIAL REGISTRATION: This study had been registered in the Chinese Clinical Trials Registry. REGISTRATION NUMBER: ChiCTR2300070789 on April 23, 2023. https://www.chictr.org.cn .

Biomechanical evaluation of novel intra- and extramedullary assembly fixation for proximal humerus fractures in the elderly.

Purpose: A novel intra- and extramedullary assembly fixation method was introduced, which achieved good clinical results in complex proximal humeral fractures; however, evidence of its comparability with traditional fixation is lacking. This biomechanical study aimed to compare it with traditional fixation devices in osteoporotic proximal humeral fractures. Methods: Three-part proximal humeral fractures with osteopenia were created on 12 pairs of fresh frozen humerus specimens and allocated to three groups: 1) lateral locking plate, 2) intramedullary nail, and 3) intra- and extramedullary assembly fixation. The specimens were loaded to simulate the force at 25° abduction. Thereafter, an axial stiffness test and a compound cyclic load to failure test were applied. Structural stiffness, number of cycles loaded to failure, and relative displacement values at predetermined measurement points were recorded using a testing machine and a synchronized 3D video tracking system. Results: In terms of initial stiffness and the number of cycles loaded to failure, the intra- and extramedullary assembly fixation group showed notable improvements compared to the other groups (p <0.017). The mean relative displacement value of measurement points in the intra- and extramedullary assembly fixation group was smaller than that in the other two groups. However, there was no significant difference until 10,000 cycles. The mean relative displacement of the intramedullary nail group (3.136 mm) exceeded 3 mm at 7,500 cycles of loading. Conclusion: In this test model, axial fixation can provide better mechanical stability than non-axial fixation. The intra- and extramedullary assembly fixation is better able to prevent the varus collapse for elderly proximal humeral fractures with posteromedial comminution.

Skeletal muscle-secreted DLPC orchestrates systemic energy homeostasis by enhancing adipose browning.

MyoD is a skeletal muscle-specifically expressed transcription factor and plays a critical role in regulating myogenesis during muscle development and regeneration. However, whether myofibers-expressed MyoD exerts its metabolic function in regulating whole body energy homeostasis in vivo remains largely unknown. Here, we report that genetic deletion of Myod in male mice enhances the oxidative metabolism of muscle and, intriguingly, renders the male mice resistant to high fat diet-induced obesity. By performing lipidomic analysis in muscle-conditioned medium and serum, we identify 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC) as a muscle-released lipid that is responsible for MyoD-orchestrated body energy homeostasis in male Myod KO mice. Functionally, the administration of DLPC significantly ameliorates HFD-induced obesity in male mice. Mechanistically, DLPC is found to induce white adipose browning via lipid peroxidation-mediated p38 signaling in male mice. Collectively, our findings not only uncover a novel function of MyoD in controlling systemic energy homeostasis through the muscle-derived lipokine DLPC but also suggest that the DLPC might have clinical potential for treating obesity in humans.

The dual role of microglia in neuropathic pain after spinal cord injury: Detrimental and protective effects.

Spinal cord injury (SCI) is a debilitating condition that is frequently accompanied by neuropathic pain, resulting in significant physical and psychological harm to a vast number of individuals globally. Despite the high prevalence of neuropathic pain following SCI, the precise underlying mechanism remains incompletely understood. Microglia are a type of innate immune cell that are present in the central nervous system (CNS). They have been observed to have a significant impact on neuropathic pain following SCI. This article presents a comprehensive overview of recent advances in understanding the role of microglia in the development of neuropathic pain following SCI. Specifically, the article delves into the detrimental and protective effects of microglia on neuropathic pain following SCI, as well as the mechanisms underlying their interconversion. Furthermore, the article provides a thorough overview of potential avenues for future research in this area.