OBJECTIVE:The global aging population has led to a significant increase in hip fractures among elderly patients, posing substantial clinical challenges. While early surgical intervention is widely advocated, its impact on postoperative complications and mortality in super-aged (≥ 80 years) hip fracture patients remains controversial. This study aimed to evaluate the association between early surgery and clinical outcomes in this population. METHODS:We conducted a retrospective cohort study of patients aged ≥ 80 years who underwent hip fracture surgery at a single-center orthopedic trauma center between January 2018 and November 2021. Participants were stratified into early surgery (≤ 48 h post-admission) and non-early surgery groups. Propensity score matching (PSM) was employed to control for confounding variables. Primary outcomes included 30-day, 90-day, 1-year, and 2-year mortality rates. Secondary outcomes encompassed perioperative transfusion rates, postoperative complications, hospital length of stay (LOS), and hospitalization costs. RESULTS:After PSM, a total of 300 patients were included. Compared with the non-early surgery group, the early surgery group had lower 1-year (11.6% vs. 28.0%, p < 0.001) and 2-year (36.0% vs. 50.7%, p = 0.010) postoperative mortality rates, a lower perioperative blood transfusion rate (32.7% vs. 53.3%, p < 0.001), lower incidences of postoperative pneumonia (15.3% vs. 29.3%, p = 0.004) and delirium (14.0% vs. 36.0%, p < 0.001), a shorter length of stay [8.6 days (7.5, 11.2) vs. 11.6 days (9.7, 14.9), p < 0.001], and lower hospitalization expenses [54,336 ¥ (48,965, 64,532) vs. 61,616 ¥ (50,758, 74,484), p = 0.001]. The serum albumin level at discharge in the early surgery group was higher (33.4 (31.6, 35.4) vs. 32.6 (30.7, 34.9), p = 0.039). Kaplan-Meier survival curve analysis showed that the all-cause mortality rate in the non-early surgery group increased (Log Rank p = 0.0066). Multivariate Cox analysis showed that age, BMI, admission hemoglobin, and non-early surgery were risk factors for 2-year mortality. CONCLUSION:Early surgical intervention for hip fractures in super-aged patients is associated with improved survival, reduced complications, and better resource utilization. These findings support the implementation of protocols to minimize preoperative delays in this vulnerable population.

Diabetic patients exhibit higher tendon injury incidence, with elevated risks of healing failure and re-rupture than healthy individuals, posing major clinical challenges. Tendon stem/progenitor cells (TSPCs) are crucial for tendon homeostasis maintenance, and their senescence underlies regenerative impairment. In this study, diabetic rat Achilles tendon-derived TSPCs (dTSPCs) were identified to exhibit accelerated cellular senescence and dysfunction. Mechanistically, the excessive activation of the Ras/MAPK axis, which mediates mitochondrial dysregulation and elevated reactive oxygen species (ROS) production, was a key driver of dTSPCs senescence and impaired diabetic tendon regenerative capacity. Accordingly, we developed a nanocomposite hydrogel system loaded with Ganoderma lucidum polysaccharides (GLPs), consists of a ROS-responsive PVA-TSPBA hydrogel encapsulating GLPs@ZIF-8 nanoparticles (GZPT). In vitro, GZPT effectively suppressed Ca²⁺ influx, thereby inhibiting aberrant Ras/MAPK axis activation mediated mitochondrial dysfunction and ROS overproduction, ultimately attenuating dTSPCs senescence and dysfunction. In vivo, GZPT enables sustained and precisely controlled release of GLPs, promoting structural regeneration and functional restoration of diabetic tendon defects by mitigating the prosenescent oxidative stress niche. These findings demonstrate that GZPT effectively enhances the functionality of senescent dTSPCs and facilitates diabetic tendon regeneration, suggesting that GZPT represents a promising clinical strategy for improving tendon structural and functional regeneration in diabetic patients.

Objective:To investigate the efficacy and safety of emergency administration of tranexamic acid (TXA) in reducing perioperative blood loss and blood transfusion rate in elderly patients with intertrochanteric femoral fractures. Methods:A retrospective analysis was conducted on the clinical data of 102 elderly patients with intertrochanteric femoral fractures who were admitted between October 2023 and May 2025 and met the selection criteria. Patients were divided into two groups based on whether TXA was administered in the emergency department: the TXA group (patients received a single intravenous infusion of 1 g TXA immediately upon emergency admission, n=50) and the control group (no TXA was used in the emergency department, n=52). There was no significant difference in baseline data between the two groups ( P>0.05), including age, gender, body mass index, American Society of Anesthesiologists (ASA) classification, AO/Orthopaedic Trauma Association (AO/OTA) fracture classification, underlying comorbidities, prothrombin time, activated partial thromboplastin time, fibrin degradation products, D-dimer, bone mineral density T-score, time from injury to admission, time from admission to surgery, hemoglobin (HB), and hematocrit (HCT) levels at emergency admission. The following parameters were collected and analyzed statistically: changes in HB and HCT on the day before surgery (compared with values at emergency admission); hidden blood loss (HBL) on the day before surgery; total blood loss (TBL) on postoperative day 1, day 3, and during the entire perioperative period; in-hospital blood transfusion rate; and incidence of complications such as thrombosis. Results:There was no significant difference in operation time between the two groups ( P>0.05). All patients were followed up 3-12 months (mean, 6.6 months). On the day before surgery, the decreases in HB and HCT in the TXA group were significantly lower than those in the control group ( P<0.05). The HBL on the day before surgery and perioperative TBL in the TXA group were significantly lower than those in the control group ( P<0.05), whereas there was no significant difference in TBL on postoperative day 1 or day 3 between the two groups ( P>0.05). The in-hospital blood transfusion rate in the TXA group (34.0%) was significantly lower than that in the control group (55.8%, P<0.05). During hospitalization and follow-up, no complication such as deep vein thrombosis of the lower extremities, pulmonary embolism, surgical site infection, or allergic reactions occurred in either group. Intermuscular venous thrombosis occurred in 4 patients (8.0%) in the TXA group and 5 patients (9.6%) in the control group, with no significant difference in incidence between the two groups ( P>0.05). Conclusion:Elderly patients with intertrochanteric femoral fractures experience significant blood loss due to initial trauma. Emergency administration of TXA can reduce trauma-induced preoperative HBL, perioperative TBL, and in-hospital blood transfusion rate without increasing the incidence of thromboembolic events, thus proving safe and effective.

BACKGROUND:Emerging economies, represented by BRICS countries (Brazil, China, India, Russian Federation and South Africa), have a substantial impact on the global rehabilitation needs. However, the rehabilitation needs of BRICS countries remain unascertained. This study aimed to explore the rehabilitation needs of the BRICS countries from 1990 to 2021 and predict the trend of rehabilitation needs. METHODS:Relevant data pertaining to eight condition categories (encompassing 27 individual conditions) requiring rehabilitation were retrieved from the Global Burden of Disease Study 2021. The joinpoint regression models were employed to calculate average annual percentage changes to quantify trends in age-standardized rates. The autoregressive integrated moving average models were used to predict rehabilitation needs until 2036. RESULTS:The number of prevalent cases of total conditions requiring rehabilitation increased from 634 million (95% uncertainty interval [UI] 608-664) in 1990 to 1.093 billion (95% UI 1.056-1.135) in 2021, an increase of 72.2%. The years lived with disability counts of total conditions increased from 79 million (95% UI 60-101) in 1990 to 147 million (95% UI 112-189) in 2021, an increase of 85.6%. Since 1990, the age-standardized prevalence rates of total rehabilitation needs have been decreasing in all BRICS countries. The number of people needing rehabilitation will continue to grow, with 1.469 billion people in BRICS countries requiring rehabilitation services by 2036. The highest contribution to the need for rehabilitation in BRICS countries was musculoskeletal disorders with about 676 million people (95% UI 630-716) across eight condition categories, and hearing loss with 232 million people (95% UI 205-260) among 27 individual conditions. CONCLUSIONS:The need for rehabilitation in BRICS countries has increased substantially over the past 32 years and will continue to increase until 2036. Although the rehabilitation needs are based on modeled estimates from the Global Burden of Disease Study 2021, we strongly recommend that rehabilitation services targeting these needs, particularly for musculoskeletal disorders and hearing loss within sensory impairments, be integrated into primary care systems.

Objective:To compare the short-term effectiveness between Gamma 3 intramedullary nails and Gamma 3 U-Blade system in the treatment of osteoporotic intertrochanteric fractures in the elderly. Methods:A retrospective analysis was conducted on the clinical data of 124 elderly patients with osteoporotic intertrochanteric fractures, who were admitted between February 2020 and February 2023 and met the selection criteria. The fractures were fixed with Gamma 3 intramedullary nails in 65 patients (control group) and Gamma 3 U-Blade systems in 59 patients (UB group). The differences between the two groups were not significant in age, gender, body mass index, American Society of Anesthesiologists (ASA) classification, bone mineral density, time from injury to operation, fracture classification, and affected side ( P>0.05). The operation time, intraoperative blood loss, hospital stay, and fracture healing time were recorded; the tip-apex distance, fracture reduction quality, and lag screw position were evaluated on X-ray films at immediate after operation; the lag screw sliding distance and change value of neck-shaft angle were measured on X-ray films at last follow-up. Harris hip score at 1 year after operation and the occurrence of internal fixation-related complications were compared between the two groups. Results:The operation time, intraoperative blood loss, and hospital stay in the UB group increased compared to the control group, but the differences were not significant ( P>0.05). All patients in both groups were followed up 12-24 months (mean, 17.1 months). At 12 months after operation, there was no significant difference in the Harris hip score between the two groups ( P<0.05). Radiological examination showed that there was no significant difference between the two groups ( P>0.05) in terms of tip-apex distance, fracture reduction quality, and lag screw position. Fractures healed in both groups, and there was no significant difference in healing time ( P>0.05). At last follow-up, the change value of neck-shaft angle and lag screw sliding distance in the UB group were significantly lower than those in the control group ( P<0.05). During follow-up, no related complications occurred in the UB group, while 6 cases (9.2%) in the control group experienced complications, and the difference in the incidence was significant ( P<0.05). Conclusion:For the osteoporotic intertrochanteric fractures in the elderly, the Gamma 3 U-Blade system fixation can achieve good short-term effectiveness, with better imaging results compared to Gamma 3 intramedullary nails fixation.

Tendon stem/progenitor cell (TSPC) senescence contributes to age-related tendon degeneration, yet the molecular mechanisms underlying this process remain poorly understood. In present study, we investigated the role of High-Mobility Group A2 (HMGA2) in TSPCs senescence. During the tendon aging, we showed that HMGA2 expression decreases with age. In senescent TSPCs, HMGA2 overexpression significantly delayed TSPCs senescence. Additionally, overexpression of HMGA2 restored the age-related dysfunction of migration, tenogenic differentiation, and mitophagy. HMGA2 also suppressed the senescence-associated secretory phenotype (SASP), downregulating inflammatory cytokines such as IL-1β, IL-6, and TGF-β. Furthermore, we suggested that the PI3K-AKT signaling pathway is activated in senescent TSPCs, and HMGA2 overexpression could inhibit the PI3K-AKT signaling pathway activation, which demonstrates that HMGA2 might attenuate senescence and age-related dysfunction of TSPCs through the repression of PI3K-AKT signaling pathway. Our findings collectively indicated the crucial involvement of HMGA2 in TSPCs senescence regulation and suggested a novel target for preventing tendon aging.

PURPOSE:We aimed to analyse the global, regional, and national burdens of hip fractures in older adults from 1990 to 2021, with projections to 2050, on the basis of data from the GBD 2021 study. METHODS:We employed a joinpoint model to analyse trends in the burden of hip fractures from 1990‒2021. The estimated annual percentage change (EAPC) was used to quantify temporal trends over this period. We evaluated the relationship between the social development index and the burden of hip fracture in elderly people and conducted a health inequality analysis. Additionally, we applied Long-short Term Memory (LSTM) networks to forecast burden trends of hip fractures up to 2050. RESULTS:The global age-standardized incidence rate (ASIR) for hip fractures in older adults rose from 781.56 per 100,000 in 1990 to 948.81 in 2021. The 2021 age-standardized prevalence rate (ASPR) was 1,894.07, and the age-standardized YLD rate (ASDR) was 173.52. From 1990 to 2021, the incidence and prevalence increased by 168.71 % and 173.07 %, respectively, while the burden of DALYs decreased. Future trends were projected via the LSTM. The burden and risk factors for hip fractures varied significantly by sex, country, and region. Population and aging are primary contributors to the rising incidence of elderly hip fractures, with falls being the leading direct cause. CONCLUSION:From 1990 to 2021, the global burden of hip fractures in the elderly population, especially among older women, steadily increased. Population ageing highlights the urgent need for targeted public health interventions and resource allocation, including early diagnosis, effective prevention strategies, and region-specific management approaches.

Purpose::To assess the relationship between dislocation and functional outcomes in supination-external rotation (SER) ankle fractures.Methods::A retrospective case series study was performed on patients with ankle fractures treated surgically at a large trauma center from January 2015 to December 2021. The inclusion criteria were young and middle-aged patients of 18 - 65 years with SER ankle fractures that can be classified by Lauge-Hansen classification and underwent surgery at our trauma center. Exclusion criteria were serious life-threatening diseases, open fractures, fractures delayed for more than 3 weeks, fracture sites ≥ 2, etc. Then patients were divided into dislocation and no-dislocation groups. Patient demographics, injury characteristics, surgery-related outcomes, and postoperative functional outcomes were collected and analyzed. The functional outcomes of SER ankle fractures were assessed postoperatively at 1-year face-to-face follow-up using the foot and ankle outcome score (FAOS) and American Orthopedic Foot and Ankle Society ankle hindfoot score and by 2 experienced orthopedic physicians. Relevant data were analyzed using SPSS version 22.0 by Chi-square or t-test. Results::During the study period, there were 371 ankle fractures. Among them, 190 (51.2%) were SER patterns with 69 (36.3%) combined with dislocations. Compared with the no-dislocation group, the dislocation group showed no statistically significant differences in gender, age composition, fracture type, diabetes, or smoking history, preoperative waiting time, operation time, and length of hospital stay (all p > 0.05), but a significantly higher Lauge-Hansen injury grade ( p < 0.001) and syndesmotic screw fixation rate ( p = 0.033). Moreover, the functional recovery was poorer, revealing a significantly lower FAOS in the sport/rec scale ( p < 0.001). Subgroup analysis showed that among SER IV ankle fracture patients, FAOS was much lower in pain ( p = 0.042) and sport/rec scales ( p < 0.001) for those with dislocations. American Orthopedic Foot and Ankle Society ankle hindfoot score revealed no significant difference between dislocation and no-dislocation patients. Conclusion::Dislocation in SER ankle fractures suggests more severe injury and negatively affects functional recovery, mainly manifested as more pain and poorer motor function, especially in SER IV ankle cases.

Background Malnutrition is a prevalent issue among older patients with hip fracture and is significantly associated with poor outcomes. The Geriatric Nutritional Risk Index (GNRI) and Prognostic Nutritional Index (PNI) are nutritional screening tools that may assist in predicting outcomes in older patients undergoing hip fracture surgery. This study aimed to evaluate the effects of GNRI and PNI on 1-year mortality after hip fracture surgery in older patients. Methods This retrospective study included 577 patients aged 60 years and older with hip fractures treated surgically at a single center from January 2018 to December 2021. Nutritional status was evaluated using GNRI and PNI. The primary outcomes were 180-day and 1-year mortality, while secondary outcomes included short-term postoperative complications and length of stay. Univariate and multivariate analyses were performed to identify independent risk factors for 1-year mortality. Subgroup analysis was employed to identify potential population heterogeneity. Results Patients with low GNRI and low PNI had significantly higher 1-year mortality rates and short-term postoperative complication rates compared to those with higher scores. Low GNRI was an independent risk factor for one-year mortality (95% CI 1.09 - 3.25, P = 0.022). Subgroup analyses revealed significant heterogeneity, with males patients and patients with ASA III-IV showing higher hazard ratios for 1-year mortality associated with low GNRI. Pulmonary infections and older age were also identified as independent risk factors for one-year mortality. Conclusion This study demonstrated that low GNRI was the risk factor for 1-year mortality after hip fracture surgery in older patients.

Objective:To analyze the disease burden of pelvic fractures at the global, regional, and national levels from 1990 to 2023 using data from the 2023 Global Burden of Disease Study (GBD), and to predict the disease burden through 2050. Methods:Leveraging data from the GBD 2023, this study investigated the disease burden of pelvic fractures across 204 countries and regions. Assessment indicators included incidence rate, prevalence rate, and years lived with disability (YLDs). The Joinpoint regression model was employed to analyze trends in pelvic fracture burden from 1990 to 2023, while the average annual percentage change (AAPC) was used to quantify this temporal trend. The relationship between the socio-demographic index and pelvic fracture burden was evaluated. Furthermore, the long short-term memory (LSTM) model was applied to predict trends in pelvic fracture burden through 2050. Results:In 2023, the estimated number of new pelvic fracture cases globally was 7 479 884 [95% uncertainty interval ( UI): 5 293 401-10 611 876], representing a 42.74% increase from 1990. In the same year, the number of prevalent pelvic fracture cases and YLDs were 23 007 508 (95% UI: 21 021 518-25 327 165) and 3 909 228 person-years (95% UI: 2 725 498-5 194 385), respectively. Additionally, age-standardized rates exhibited an opposing downward trend. Significant disparities in the disease burden of pelvic fractures were identified across different age groups, genders, and social contexts. According to predictions from the LSTM model, the global age-standardized incidence rate (ASIR) of pelvic fractures will be approximately 88.44 per 100 000 persons by 2050, while the total number of incident cases will rise to 8 547 095. Conclusion:Although the overall incidence rate, prevalence rate, and YLDs of pelvic fractures have exhibited an upward trend over the past three decades, the ASIR, age-standardized prevalence rate (ASPR), and age-standardized years of life lost rate (ASYR) have shown a downward trend. It is predicted that over the upcoming 26-year period, the age-standardized rate of disease burden due to pelvic fractures will further decrease, while the number of incident cases and prevalent cases will continue to exhibit an upward trend. Formulating more targeted disease prevention strategies is critical to addressing disparities across genders, regions, and other dimensions, and to mitigating the burden of pelvic fractures.

The aim of this meta-analysis was to investigate the efficacy and safety of intra-articular injection of mesenchymal stem cells (MSCs) alone for the treatment of unoperated knee osteoarthritis (OA). Four databases were systematically searched (before August 1, 2024) to include randomized controlled trials (RCTs) of MSCs for OA. The population of this study was OA patients who had not received any surgical treatment. The intervention was intra-articular injection of MSCs without other adjuvant therapy. Outcomes included Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), 100-mm Visual Analog Score (VAS), Knee Injury and Osteoarthritis Prognostic Score (KOOS), and adverse events. After screening the literature according to the eligibility criteria, extracting the data, and evaluating the quality, Meta-analysis was performed using Revman 5.3 software. The review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. 8 RCTs and 502 patients with OA were included in the study. Compared with the control group, MSCs significantly improved 6-month WOMAC [MD = 7.44, 95

OBJECTIVE:To analyze musculoskeletal disorders (MSDs) prevalence trends, sex, age, and regional inequalities to improve prevention and treatment strategies. DESIGN:This study analyzed epidemiologic trends and health inequities of 7 MSDs (rheumatoid arthritis [RA], osteoarthritis [OA], low back pain, neck pain, amputations, fractures, and other injuries) from 1990 to 2021 using Global Burden of Diseases (GBD) data. Joinpoint regression and Autoregressive Integrated Moving Average models assessed historical trends and projected burdens to 2050. Sex, age, and Sociodemographic Index (SDI) differences in MSD burden were also analyzed. SETTING:The MSDs are a major cause of global disability, affecting life quality and socioeconomic systems. PARTICIPANTS:Data from the GBD 2021 on the prevalence and years lived with disability of 7 major MSDs across different ages and genders in 204 countries and territories from 1990 to 2021. INTERVENTIONS:Not applicable. MAIN OUTCOME MEASURES:Building upon the data from GBD 2021, our primary outcomes focused on quantifying the epidemiologic burden of 7 MSDs through age-standardized prevalence rates and years lived with disability rates, while examining their temporal trends using Joinpoint regression for historical patterns (1990-2021) and Autoregressive Integrated Moving Average modeling for future projections (2022-2050). We further evaluated health inequities by analyzing disparities related to sex and age, along with socioeconomic inequalities measured through the Slope Index of Inequality and concentration index across 5 SDI quintiles. These comprehensive assessments were applied to 7 MSDs to provide a complete picture of global rehabilitation needs and their evolving patterns. RESULTS:From 1990 to 2021, global MSD burden increased markedly, with OA exhibiting the most pronounced rise in prevalence (6069.89/100,000, 95% UI 5378.74-6705.20). By 2050, OA will dominate the disease burden, particularly among women, and fractures will exhibit diverging trends; specifically, declining in high-SDI regions and rising in low-SDI areas. Most MSDs (OA/low back pain/neck pain/RA) exhibited similar sex differences. At the same time, the increase in age leads to a significant increase in the burden of RA. The burden of MSDs among women and the elderly highlights the urgent needs for equitable rehabilitation resources. CONCLUSIONS:This study highlights the escalating burden of MSDs, driven by aging populations, lifestyle changes, and unequal access to health care. Enhancing the quality and coverage of rehabilitation services particularly in low-SDI regions, and addressing sex and age disparities are crucial for mitigating global impact of MSDs.

Introduction Aged tendon exhibits impaired regenerative capacity due to the accumulation of senescent tendon stem/progenitor cells (TSPCs), which secrete senescence-associated secretory phenotype (SASP) factors and display compromised differentiation. Despite its clinical significance in recurrent tendon injury, no targeted therapies exist to counteract TSPCs senescence. Objectives This study aimed to investigate the anti-senescent effects of quercetin on TSPCs through a mechanistic exploration of the AKT/mitochondrial/SASP axis and to develop a dipeptide-hydrogel delivery system (DPH@QUE) for the localized treatment of age-related tendon injury. Methods Senescent TSPCs were treated with quercetin in vitro to assess SASP reduction and tenogenic differentiation via molecular profiling. Mechanistically, AKT phosphorylation and mitochondrial function were analyzed. In vivo, DPH@QUE was administered to aged rat Achilles tendon injury models, with histopathological and functional evaluations conducted at 8 weeks post-intervention. Results Quercetin significantly alleviated senescence in TSPCs, as evidenced by decreased secretion of SASP and enhanced tenogenic differentiation. Mechanistically, the inhibition of AKT phosphorylation ameliorated mitochondrial dysfunction and suppressed SASP secretion by modulating the NF-κB/NLRP3 signaling axis, thereby attenuating TSPCs senescence. Furthermore, the sustained release of quercetin using a dipeptide hydrogel into the site of Achilles tendon injury in elderly rats produced exceptional anti-inflammatory and reparative effects, effectively restoring endogenous tendon regeneration. Conclusion Our findings suggest quercetin could alleviate senescent phenotypes in TSPCs through AKT-mediated mitochondrial stabilization and SASP suppression. The DPH@QUE delivery system enables effective translation of these anti-aging effects into functional tendon regeneration, providing a novel therapeutic strategy for aging tendon injury.

Tendinopathy is a common musculoskeletal disorder in individuals with diabetes. Tendon stem/progenitor cells (TSPCs) play an essential role in tendon repair, regeneration and homeostasis maintenance. Although studies have demonstrated that diabetic tendinopathy is closely associated with the altered differentiation of TSPCs, the underlying mechanisms remain largely unknown. This study was designed to investigate the role of the HMGB1/RAGE/β-catenin axis in the differentiation imbalance of TSPCs and diabetic tendinopathy. Rat diabetes models were induced with streptozotocin (65 mg/kg). TSPCs were isolated at week 2 and the patellar tendons were isolated at weeks 2 and 4 for histological analysis. The activation of the HMGB1/RAGE/β-catenin axis in TSPCs and diabetic tendons was determined by western blot, ELISA, qRT-PCR and immunohistochemical staining. TSPCs and the diabetic tendons were then treated with lentivirus targeting HMGB1 or glycyrrhizin or FPS-ZM1 or PNU-74654 to demonstrate the role of this axis in TSPCs differentiation and diabetic tendinopathy. Alizarin red staining was performed to evaluate the calcium nodule formation. The mRNA expression of the osteogenic and tenogenic genes in TSPCs and diabetic tendons was examined by qRT-PCR and immunohistochemical staining. Recombinant HMGB1 was injected around the patellar tendons to further study the role of HMGB1 in tendinopathy, the histological changes were evaluated by HE stating and the expression of RAGE, β-catenin and the osteogenic genes in tendons was detected by immunohistochemical staining at weeks 2 and 4. We established a rat diabetes model. In diabetic TSPCs, the activity of the HMGB1/RAGE/β-catenin axis was increased. Diabetic TSPCs exhibited increased osteogenic differentiation potential and reduced tenogenic differentiation ability. Blockade of this axis attenuated the differentiation imbalance of diabetic TSPCs. In addition, we also demonstrated the activation of the HMGB1/RAGE/β-catenin axis in diabetic tendons. The expression of tendon-related markers was decreased and the expression of osteogenic markers was increased in diabetic tendons. Inhibition of this axis could ameliorate these non-tenogenic alterations. Furthermore, injection of recombinant HMGB1 promoted the development of tendinopathy, increased the expression of RAGE and β-catenin and upregulated the expression of osteogenic markers in tendon tissue. Our findings revealed the critical role of the HMGB1/RAGE/β-catenin axis in the differentiation imbalance of TSPCs and diabetic tendinopathy, highlighting a novel essential mechanism involved in the pathogenesis of diabetic tendinopathy and providing a promising therapeutic target and approach for diabetic tendinopathy.

Tendon repair remains challenging owing to the limited capacity for endogenous repair. Vasoactive intestinal peptide (VIP) promotes bone tissue regeneration; however, its role in tendon repair remains unclear. In the present study, we demonstrated that VIP stimulated M2 polarization of macrophages and facilitated tendon regeneration by regulating immune homeostasis and maintaining the function of tendon stem/progenitor cells (TSPCs). Additionally, we established GelMa-loaded VIP@PLGA@ZIF-8 (VPZ) nanoparticles (VPZG) to enable the sustained and localized release of VIP at the site of patellar tendon injury in SD rats. The results of the in vitro experiments demonstrated that VPZG regulated the homeostasis of macrophage polarization by downregulating the NF-κB axis. VPZG also promoted efferocytosis and suppressed the release of proinflammatory factors. Additionally, VPZG enhanced the tenogenic differentiation of TSPCs when cocultured with macrophages. In vivo, we implanted VPZG at the site of patellar tendon injury, where it released VIP sustainably and slowly to promote tendon regeneration. This effect was achieved through the downregulation of the expression levels of various inflammatory factors, as well as the regulation of local immune homeostasis. In conclusion, our results demonstrated that VPZG facilitated tendon injury repair by regulating immune homeostasis and enhancing TSPC function. These findings suggest that VPZG is a promising avenue for the clinical improvement of tendon injury treatment.

Exercise is crucial for postmenopausal osteoporosis (PMOP) management, yet the comparative efficacy of different exercise modalities and the underlying mechanisms remain unclear. This study investigated the differential effects of distance-matched high-intensity interval training (HIIT) and moderate-intensity continuous exercise (MICE) on ovariectomy (OVX)-induced osteoporosis (OP) in mice. After 12 weeks of training, micro-CT analysis revealed that MICE, but not HIIT, significantly attenuated OVX-induced bone loss and microstructural deterioration. Crucially, only MICE suppressed osteoclastogenesis and reduced proinflammatory factors (interleukin [IL]-6, IL-1β, and tumor necrosis factor-alpha [TNF-α]) expression in the femur, serum, and colon. Mechanistically, MICE uniquely restored gut microbiota (GM) diversity, mitigated dysbiosis, and enhanced intestinal barrier integrity by upregulating the expression of tight junction proteins (TJPs; ZO-1, occludin, and claudin-1), thereby reducing systemic inflammation. In contrast, HIIT failed to ameliorate GM imbalance and intestinal permeability. Our findings demonstrate that the protective effect of MICE on OVX-induced OP is mediated through the gut-bone axis by modulating GM, repairing the intestinal barrier, and suppressing inflammatory osteoclast activation. This study provides novel evidence that the benefits of exercise on PMOP are modality-dependent, highlighting MICE as a superior strategy and offering mechanistic insights for optimizing exercise prescriptions.

Background:Elderly patients have an impaired functional state and multiple comorbidities, resulting in poor postoperative rehabilitation ability and high rates of disability and mortality. However, little evidence exists on mortality predictors for geriatric hip fractures within the context of the multidisciplinary team co-management model. This study aimed to investigate the incidence and explore preoperative indicators of 1-year mortality following hip fractures in the elderly under this model. Methods:A total of 439 elderly patients (130 men and 309 women) surgically treated for hip fractures under the multidisciplinary team co-management model between January 2018 and June 2021were included. Data regarding demographics, health state-related variables, injury- and admission-related variables, and preoperative laboratory test results were collected from medical records. Univariate and multivariate logistic regression analyses were used to identify preoperative indicators for 1-year mortality. Results:A total of 49 patients died within 1 year of hip fracture surgery between January 2018 and June 2021, with an accumulated mortality rate of 11.16%. In univariate analysis, 14 items were found to be significant. In the multivariable logistic regression model, age >85 years, body mass index <21.0 kg/m2, time from injury to admission >9.5 h, preoperative haemoglobin <117 g/L, serum albumin <33.9 g/L, lactate dehydrogenase >292 U/L, and blood urea nitrogen >8.5 mmol/L were the independent preoperative indicators for 1-year mortality after surgery in elderly patients with hip fracture under the multidisciplinary team co-management model. Conclusions:This study establishes a novel set of preoperative predictors for 1-year mortality in geriatric hip fracture patients managed under an MDT model, distinct from previous investigations focusing on postoperative interventions. The identified indicators enable early risk stratification, facilitating timely preoperative optimization. These findings underscore the prognostic value of integrating clinical and biochemical markers before surgery, warranting validation in multicenter prospective studies. Further prospective studies should be conducted to elucidate these associations and assess the effectiveness of targeted measures.

The association of tendinopathy with diabetes has been well recognized. Tendon stem/progenitor cells (TSPCs) play critical roles in tendon repair, regeneration, and homeostasis maintenance. Diabetic TSPCs exhibit enhanced erroneous differentiation and are involved in the pathogenesis of diabetic tendinopathy, whereas the underlying mechanism of the erroneous differentiation of TSPCs remains unclear. Here, we showed that high glucose treatment promoted the erroneous differentiation of TSPCs with increased osteogenic differentiation capacity and decreased tenogenic differentiation ability, and stimulated the expression and further secretion of HMGB1 in TSPCs and. Functionally, exogenous HMGB1 significantly enhanced the erroneous differentiation of TSPCs, while HMGB1 knockdown mitigated high glucose-promoted erroneous differentiation of TSPCs. Mechanistically, the RAGE/β-catenin signaling was activated in TSPCs under high glucose, and HMGB1 knockdown inhibited the activity of RAGE/β-catenin signaling. Inhibition of RAGE/β-catenin signaling could ameliorate high glucose-induced erroneous differentiation of TSPCs. These results indicated that HMGB1 regulated high glucose-induced erroneous differentiation of TSPCs through the RAGE/β-catenin signaling pathway. Collectively, our findings suggest a novel essential mechanism of the erroneous differentiation of TSPCs, which might contribute to the pathogenesis of diabetic tendinopathy and provide a promising therapeutic target and approach for diabetic tendinopathy.

Objective:To investigate the perioperative changes in serum interleukin 6 (IL-6) levels in elderly male patients with intertrochanteric fractures, and provide evidence for inflammatory control in this patient population. Methods:The clinical data of 40 male patients aged more than 60 years with intertrochanteric fractures who met the selection criteria between January 2021 and December 2022 were retrospectively analyzed, including 25 non-osteoporosis patients (T value>-2.5, group A) and 15 osteoporosis patients (T value≤-2.5, group B). In addition, 40 healthy men aged more than 60 years old were included as controls (group C) according to the age matching rule. There was no significant difference in age, smoking history, drinking history, body mass index, complications (hypertension and diabetes), alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatinine, and total protein among the 3 groups ( P>0.05). Serum samples were collected from group C subjects and from groups A and B patients preoperatively and on postoperative days 1, 3, 5, and 7. IL-6 levels were measured using ELISA assay. Pearson correlation analysis was used to assess the relationship between IL-6 levels and T values at various time points in groups A and B. Postoperative complications during hospitalization and 1-year mortality rates were recorded for groups A and B. Results:Preoperative IL-6 levels were significantly higher in groups A and B than in group C ( P<0.05), with group B being significantly higher than group A ( P<0.05). In groups A and B, IL-6 levels increased significantly on postoperative day 1 compared to preoperative levels and then gradually decreased, approaching preoperative levels by postoperative day 7. IL-6 levels in group B were significantly higher than those in group A at all postoperative time points ( P<0.05). Correlation analysis showed that IL-6 levels were negatively correlated with T values at all perioperative time points in all patients from groups A and B ( P<0.05). Complications occurred in 4 patients (16.0%) in group A, including 2 cases of pulmonary infection, 1 case of urinary tract infection, and 1 case of heart failure, and in 3 patients (20.0%) in group B, including 2 cases of pulmonary infection and 1 case of gastrointestinal bleeding. There was no significant difference in the incidence of complications between the two groups ( χ 2=0.104, P=0.747). There were 2 cases (8.0%) and 4 cases (26.7%) died within 1 year after operation in groups A and B, respectively, and there was no significant difference in 1-year mortality rates between the two groups ( χ 2=2.562, P=0.109). Conclusion:Serum IL-6 levels significantly increase in the early postoperative period in elderly male patients with intertrochanteric fractures, especially in those with osteoporosis. Monitoring the inflammatory state and promptly controlling the inflammatory response during the perioperative period, may reduce complications and improve postoperative survival in this patient population.

Aging can lead to various disorders in organisms and with the escalating impact of population aging, the incidence of age-related diseases is steadily increasing. As a major risk factor for chronic illnesses in humans, the prevention and postponement of aging have become focal points of research among numerous scientists. Aging biomarkers, which mirror molecular alterations at diverse levels in organs, tissues, and cells, can be used to monitor and evaluate biological changes associated with aging. Currently, aging biomarkers are primarily categorized into physiological traits, imaging characteristics, histological features, cellular-level alterations, and molecular-level changes that encompass the secretion of aging-related factors. However, in the context of the musculoskeletal soft tissue system, aging-related biological indicators primarily involve microscopic parameters at the cellular and molecular levels, resulting in inconvenience and uncertainty in the assessment of musculoskeletal soft tissue aging. To identify convenient and effective indicators, we conducted a comprehensive literature review to investigate the correlation between ectopic mineralization and age-related changes in the musculoskeletal soft tissue system. Here, we introduce the concept of ectopic mineralization as a macroscopic, reliable, and convenient biomarker for musculoskeletal soft tissue aging and present novel targets and strategies for the future management of age-related musculoskeletal soft tissue disorders.