Injectable self-assembled GDF5-containing dipeptide hydrogels for enhanced tendon repair.

Owing to the tissue characteristics of tendons with few blood vessels and cells, the regeneration and repair of injured tendons can present a considerable challenge, which considerably affects the motor function of limbs and leads to serious physical and mental pain, along with an economic burden on patients. Herein, we designed and fabricated a dipeptide hydrogel (DPH) using polypeptides P11-4 and P11-8. This hydrogel exhibited self-assembly characteristics and could be administered in vitro. To endow the hydrogel with differentiation and regeneration abilities, we added different concentrations of growth differentiation factor 5 (GDF5) to form GDF5@DPH. GDF5@DPH promoted the aggregation and differentiation of tendon stem/progenitor cells and promoted the regeneration and repair of tendon cells and collagen fibers in injured areas. In addition, GDF5@DPH inhibited inflammatory reactions in the injured area. Owing to its injectable properties, DPH can jointly inhibit adhesion and scar hyperplasia between tissues caused by endogenous inflammation and exogenous surgery and can provide a favorable internal environment for the regeneration and repair of the injured area. Overall, the GDF5@DPH system exhibits considerable promise as a novel approach to treating tendon injury.

HMGB1 Modulates High Glucose-Induced Erroneous Differentiation of Tendon Stem/Progenitor Cells through RAGE/ß-Catenin Pathway.

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/ß-catenin signaling was activated in TSPCs under high glucose, and HMGB1 knockdown inhibited the activity of RAGE/ß-catenin signaling. Inhibition of RAGE/ß-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/ß-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.

Functional characterization of a catalase gene PtCat associated with sclerotia formation in Pleurotus tuber-regium.

Pleurotus tuber-regium (Fr.) Sing. can evade oxygen by forming sclerotia under oxidative stress, consequently averting the development of hyperoxidative state, during which the expression level of catalase gene (PtCat) is significantly up-regulated. To investigate the relationship between the catalase gene and sclerotia formation, over-expression and interference strains of the PtCat gene were obtained by Agrobacterium tumefaciens-mediated transformation for phenotypic analysis. In the absence of hydrogen peroxide (H2O2) stress, a minor difference was observed in the mycelial growth rate and the activity of antioxidant enzymes between the over-expression and interference strains. However, when exposed to 1-2 mM H2O2, the colony diameter of the over-expression strain was approximately 2-3× that of the interference strain after 8 days of culturing. The catalase activity of the over-expression strain increased by 1000 U/g under 2 mM H2O2 stress, while the interference strain increased by only 250 U/g. After one month of cultivation, the interference strain formed an oval sclerotium measuring 3.5 cm on the long axis and 2 cm on the short axis, while the over-expression strain did not form sclerotia. Therefore, it is concluded that catalase activity regulates the formation of sclerotia in P. tuber-regium.

Heterotopic mineralization (ossification or calcification) in aged musculoskeletal soft tissues: A new candidate marker for aging.

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.

The supplementation of Rothia as a potential preventive approach for bone loss in mice with ovariectomy-induced osteoporosis.

There is an inseparable link between bone metabolism and gut microbiota, and the supplementation of probiotics exhibits a significant role in maintaining the homeostasis of gut microbiota and inhibiting bone loss. This study aims to explore the preventive and therapeutic potentials and the specific mechanisms of Rothia on osteoporosis. The mice models of osteoporosis induced by ovariectomy (OVX) were built, and the regular (once a day) and quantitative (200 µL/d) gavage of Rothia was performed for 8 weeks starting from 1 week after OVX. Microcomputed tomography was used to analyze the bone mass and bone microstructure of mice in each group after sacrifice. Histological staining and immunohistochemistry were then applied to identify the expression of pro-inflammatory cytokines, intestinal permeability, and osteogenic and osteoclastic activities of mice. The collected feces of mice in each group were used for 16S rRNA high-throughput sequencing to detect the alterations in composition, abundance, and diversity of gut microbiota. This study demonstrated that the gavage of Rothia alleviated bone loss in mice with OVX-induced osteoporosis, improved OVX-induced intestinal mucosal barrier injury, optimized intestinal permeability (zonula occludens protein 1 and occludin), reduced intestinal inflammation (tumor necrosis factor-α and interleukin-1ß), and regulated imbalance of gut microbiota. Based on "gut-bone" axis, this study revealed that regular and quantitative gavage of Rothia can relieve bone loss in mice with OVX-induced osteoporosis by repairing the intestinal mucosal barrier injury, optimizing the intestinal permeability, inhibiting the release of pro-inflammatory cytokines, and improving the disorder of gut microbiota.

Muscle-bone crosstalk via endocrine signals and potential targets for osteosarcopenia-related fracture.

Background: Osteosarcopenia is a syndrome coexisting sarcopenia and osteopenia/osteoporosis, with a high fracture risk. Recently, skeletal muscle and bone have been recognized as endocrine organs capable of communication through secreting myokines and osteokines, respectively. With a deeper understanding of the muscle-bone crosstalk, these endocrine signals exhibit an important role in osteosarcopenia development and fracture healing. Methods: This review summarizes the role of myokines and osteokines in the development and treatment of osteosarcopenia and fracture, and discusses their potential for osteosarcopenia-related fracture treatment. Results: Several well-defined myokines (myostatin and irisin) and osteokines (RANKL and SOST) are found to not only regulate skeletal muscle and bone metabolism but also influence fracture healing processes. Systemic interventions targeting these biochemical signals has shown promising results in improving the mass and functions of skeletal muscle and bone, as well as accelerating fracture healing processes. Conclusion: The regulation of muscle-bone crosstalk via biochemical signals presents a novel and promising strategy for treating osteosarcopenia and fracture by simultaneously enhancing bone and muscle anabolism. We propose that myostatin, irisin, RANKL, and SOST may serve as potential targets to treat fracture patients with osteosarcopenia. The translational potential of this article: Osteosarcopenia is an emerging geriatric syndrome where sarcopenia and osteoporosis coexist, with high fracture risk, delayed fracture healing, and increased mortality. However, no pharmacological agent is available to treat fracture patients with osteosarcopenia. This review summarizes the role of several myokines and osteokines in the development and treatment of osteosacropenia and fracture, as well as discusses their potential as intervention targets for osteosarcopenia-related fracture, which provides a novel and promising strategy for future osteosarcopenia-related fracture treatment.

Postoperative awake prone position in geriatric patients with hip fractures: a protocol for a randomized controlled trial on the efficacy of postoperative prone position in reducing pulmonary complications and improving oxygenation.

INTRODUCTION: Postoperative pulmonary complications (PPCs) are prevalent in geriatric patients with hip fractures. Low oxygen level is one of the most important risk factors for PPCs. Prone position has been proven efficacy in improving oxygenation and delaying the progress of pulmonary diseases, especially in patients with acute respiratory distress syndrome induced by multiple etiologies. The application of awake prone position (APP) has also attracted widespread attention in recent years. A randomized controlled trial (RCT) will be carried out to measure the effect of postoperative APP in a population of geriatric patients undergoing hip fracture surgery. METHODS: This is an RCT. Patients older than 65 years old admitted through the emergency department and diagnosed with an intertrochanteric or femoral neck fracture will be eligible for enrollment and assigned randomly to the control group with routine postoperative management of orthopedics or APP group with an additional prone position for the first three consecutive postoperative days (PODs). Patients receiving conservative treatment will not be eligible for enrollment. We will record the difference in the patient's room-air-breathing arterial partial pressure of oxygen (PaO2) values between the 4th POD (POD 4) and emergency visits, the morbidity of PPCs and other postoperative complications, and length of stay. The incidence of PPCs, readmission rates, and mortality rates will be followed up for 90 PODs. DISCUSSION: We describe the protocol for a single-center RCT that will evaluate the efficacy of postoperative APP treatment in reducing pulmonary complications and improving oxygenation in geriatric patients with hip fractures. ETHICS AND DISSEMINATION: This protocol was approved by the independent ethics committee (IEC) for Clinical Research of Zhongda Hospital, Affiliated to Southeast University, and is registered on the Chinese Clinical Trial Registry. The findings of the trial will be disseminated through peer-reviewed journals. ETHICS APPROVAL NUMBER: 2021ZDSYLL203-P01 TRIAL REGISTRATION: ChiCTR ChiCTR2100049311 . Registered on 29 July 2021. TRIAL STATUS: Recruiting. Recruitment is expected to be completed in December 2024.

The Preventive Effects of Probiotic Prevotella histicola on the Bone Loss of Mice with Ovariectomy-Mediated Osteoporosis.

It has been demonstrated that the disturbance of gut microbiota (GM) is closely related to the reduction of bone mass and incidence of osteoporosis (OP). The aim of this study is to investigate whether the supplementation of Prevotella histicola (Ph) can prevent the bone loss in mice with ovariectomy (OVX)-mediated OP, and further explore relevant mechanisms. Regular (once a day for 8 consecutive weeks) and quantitative (200 µL/d) perfusion of Ph (the bacteria that orally gavaged) was conducted starting from 1 week after the construction of mice models. Bone mass and bone microstructure were detected by Micro-computed tomography (Micro-CT). Expressions of intestinal permeability, pro-inflammatory cytokines, and osteogenic and osteoclastic activities of mice were analyzed by histological staining and immunohistochemistry (IHC). 16S rRNA high throughput sequencing technique was applied to analyze the alterations of composition, abundance, and diversity of collected feces. Regular and quantitative perfusion of Ph mitigated the bone loss in mice with OVX-mediated OP. Compared with OVX + PBS group, perfusion of Ph repressed osteoclastogenesis and promoted osteogenesis, reduced release of pro-inflammatory cytokine cytokines (interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α)), and reversed expressions of tight junction proteins (zonula occludens protein 1 (ZO-1) and Occludin). Besides, the perfusion of Ph improved the composition, abundance, and diversity of GM. Collectively, this study revealed that regular and quantitative perfusion of Ph can improve the bone loss in mice with OVX-mediated OP by repairing intestinal mucosal barrier damage, optimizing intestinal permeability, inhibiting release of pro-osteoclastogenic cytokines, and improving disturbance of GM.

HMGB1: a potential new target for tendinopathy treatment.

Tendinopathy describes a complex pathology of the tendon characterized by abnormalities in the microstructure, composition, and cellularity of the tendon, leading to pain, limitation of activity and reduced function. Nevertheless, the mechanism of tendinopathy has not been fully elucidated, and the treatment of tendinopathy remains a challenge. High mobility group box 1 (HMGB1), a highly conserved and multifaceted nuclear protein, exerts multiple roles and high functional variability and is involved in many biological and pathological processes. In recent years, several studies have suggested that HMGB1 is associated with tendinopathy and may play a key role in the pathogenesis of tendinopathy. Therefore, this review summarizes the expression and distribution of HMGB1 in tendinopathy, focuses on the roles of HMGB1 and HMGB1-based potential mechanisms involved in tendinopathy, and finally summarizes the findings on HMGB1-based therapeutic approaches in tendinopathy, probably providing new insight into the mechanism and further potential therapeutic targets of tendinopathy.

Linking the relation between gut microbiota and glucocorticoid-induced osteoporosis.

Osteoporosis (OP) is the most prevalent metabolic bone disease, characterized by the low bone mass and microarchitectural deterioration of bone tissue. Glucocorticoid (GC) clinically acts as one of the anti-inflammatory, immune-modulating, and therapeutic drugs, whereas the long-term use of GC may cause rapid bone resorption, followed by prolonged and profound suppression of bone formation, resulting in the GC-induced OP (GIOP). GIOP ranks the first among secondary OP and is a pivotal risk for fracture, as well as high disability rate and mortality, at both societal and personal levels, vital costs. Gut microbiota (GM), known as the "second gene pool" of human body, is highly correlated with maintaining the bone mass and bone quality, and the relation between GM and bone metabolism has gradually become a research hotspot. Herein, combined with recent studies and based on the cross-linking relationship between GM and OP, this review is aimed to discuss the potential mechanisms of GM and its metabolites on the OP, as well as the moderating effects of GC on GM, thereby providing an emerging thought for prevention and treatment of GIOP.

The Regulation of the AMPK/mTOR Axis Mitigates Tendon Stem/Progenitor Cell Senescence and Delays Tendon Aging.

Age-related tendon disorders are closely linked with tendon stem/progenitor cell (TSPC) senescence. However, the underlying mechanisms of TSPC senescence and promising therapeutic strategies for rejuvenation of TSPC senescence remain unclear. In this study, the senescent state of TSPCs increased with age. It was also verified that the AMPK inhibition/mTOR activation is correlated with the senescent state of TSPCs. Furthermore, a low dose of metformin mitigated TSPC senescence and restored senescence-related functions, including proliferation, colony-forming ability, migration ability and tenogenic differentiation ability at the early stage of aging. The protective effects of metformin on TSPCs were regulated through the AMPK/mTOR axis. An in vivo study showed that metformin treatment postpones tendon aging and enhances AMPK phosphorylation but reduces mTOR phosphorylation in a natural aging rat model. Our study revealed new insight and mechanistic exploration of TSPC senescence and proposed a novel therapeutic treatment for age-related tendon disorders by targeting the AMPK/mTOR axis at the early stage of aging.

What are Risk Factors of Postoperative Pneumonia in Geriatric Individuals after Hip Fracture Surgery: A Systematic Review and Meta-Analysis.

Postoperative pneumonia (POP) is a common postoperative complication. Negative consequences associated with POP included prolonged hospital length of stay, more frequent intensive care unit (ICU) stays, and a higher rate of sepsis, readmission, and mortality. This meta-analysis aimed to assess the incidence and risk factors associated with POP after hip fracture surgery in elderly patients. PubMed, Web of Science, and Cochrane Library were searched (up to March 31, 2022). All studies on the risk factors for POP after hip fracture surgery in elderly patients, published in English, were reviewed. The qualities of the included studies were assessed using the Newcastle-Ottawa Scale. Data were pooled, and a meta-analysis was performed. Ten studies, including 12,084 geriatric patients undergoing hip fracture surgery, were included. Of these 12,084 patients, POP occurred in 809 patients. The results indicated that age (mean difference [MD] = 4.95, 95% confidence interval [CI]: 3.22-6.69), male (odds ratio [OR] = 1.41, 95% CI: 1.02-1.93), the American Society of Anaesthesiologists classification ≥3 (OR = 3.48, 95% CI: 1.87-6.47), dependent functional status (OR = 5.23, 95% CI: 2.18-12.54, P = 0.0002), smoking (OR = 1.33, 95% CI: 1.07-1.65), chronic obstructive pulmonary disease (OR = 3.76, 95% CI: 2.07-6.81), diabetes mellitus (OR = 1.19, 95% CI: 1.01-1.40), coronary heart disease (OR = 1.74, 95% CI: 1.23-2.46), arrhythmia (OR = 1.47, 95% CI: 1.01-2.14), cerebrovascular disease (OR = 1.88, 95% CI: 1.56-2.27), dementia (OR = 2.36, 95% CI: 1.04-5.36), chronic renal failure (OR = 1.85, 95% CI: 1.29-2.67), hip arthroplasty (OR = 1.30, 95% CI: 1.08-1.56), delayed surgery (OR = 6.40, 95% CI: 3.00-13.68), preoperative creatinine (MD = 5.32, 95% CI: 0.55-10.08), and preoperative serum albumin (MD = -3.01, 95% CI: -4.21 - -1.80) were risk factors for POP. Related prophylactic measures should be provided in geriatric patients with the above-mentioned risk factors to prevent POP after hip fracture surgery.

Targeting Senescent Tendon Stem/Progenitor Cells to Prevent or Treat Age-Related Tendon Disorders.

Age-related tendon disorder, a primary motor system disease, is characterized by biological changes in the tendon tissue due to senescence and seriously affects the quality of life of the elderly. The pathogenesis of this disease is not well-understood. Tendon stem/progenitor cells (TSPCs) exhibit multi-differentiation capacity. These cells are important cellular components of the tendon because of their roles in tendon tissue homeostasis, remodeling, and repair. Previous studies revealed alterations in the biological characteristics and tenogenic differentiation potential of TSPCs in senescent tendon tissue, in turn contributing to insufficient differentiation of TSPCs into tenocytes. Poor tendon repair can result in age-related tendinopathies. Therefore, targeting of senescent TSPCs may restore the tenogenic differentiation potential of these cells and achieve homeostasis of the tendon tissue to prevent or treat age-related tendinopathy. In this review, we summarize the biological characteristics of TSPCs and histopathological changes in age-related tendinopathy, as well as the potential mechanisms through which TSPCs contribute to senescence. This information may promote further exploration of innovative treatment strategies to rescue TSPCs from senescence.

Short report: relationship between self-reported sleep characteristics and falls-associated fractures in elderly individuals: a population-based study.

Currently, the data for effect of sleep on falls-associated fractures in elderly individuals are still limited. This current study was aimed to assess the link between self-reported sleep characteristics and falls-associated fractures in elderly individuals. This study included a total of 20,497 participants from National Health and Nutritional Examination Survey (NHANES) 2005-2008, and 6,174 participants aged 45 years and older were identified. Self-reported sleep characteristics and conditions of falls-associated fractures of individuals were obtained via the method of personal questionnaires. In a total of 610 participants with exact history of fractures, 168 individuals with falls-associated fractures were identified, and the prevalence was 27.5%. The mean age of falls-associated fractures group was (72.1 ± 8.8) years, and the female (P < 0.001) occupied a higher proportion. Factors of living alone (P = 0.003), combined with hypertension (P = 0.003) and osteoporosis (P < 0.001), sleeping less or more (P = 0.009), and frequent snoring (P = 0.007) were linked to falls-associated fractures. Compared with sleep duration of 6 to 8 h/night, sleep duration of ≤4 h/night (odds ratio [OR] 1.858, 95% confidence interval [CI] 1.115-3.094) and of ≥9 h/night (OR 1.932, 95% CI 1.195-3.123) were related to an increased risk of falls-associated fractures. Collectively, our nationwide data noted that sleep characteristics were closely related to falls-associated fractures in elderly individuals, and a longer sleep duration may exhibit a protective effect against the falls-associated fractures, but it should be limited within 9 h/night.

The regulative effect and repercussion of probiotics and prebiotics on osteoporosis: involvement of brain-gut-bone axis.

Osteoporosis (OP) is a systemic disease characterized by decreased bone mass and degeneration of bone microstructure. In recent years, more and more researches have focused on the close relationship between gut microbiota (GM) and the occurrence and progression of OP, and the regulation of probiotics and prebiotics on bone metabolism has gradually become a research hotspot. Based on the influence of brain-gut-bone axis on bone metabolism, this review expounds the potential mechanisms of probiotics and prebiotics on OP from next perspectives: regulation of intestinal metabolites, regulation of intestinal epithelial barrier function, involvement of neuromodulation, involvement of immune regulation and involvement of endocrine regulation, so as to provide a novel and promising idea for the prevention and treatment of OP in the future.

Fecal microbiota transplantation as a promising treatment option for osteoporosis.

Osteoporosis is a systemic metabolic bone disease characterized by the descending bone mass and destruction of bone microstructure, which tends to result in the increased bone fragility and associated fractures, as well as high disability rate and mortality. The relation between gut microbiota and bone metabolism has gradually become a research hotspot, and it has been verified that gut microbiota is closely associated with reduction of bone mass and incidence of osteoporosis recently. As a novel "organ transplantation" technique, fecal microbiota transplantation (FMT) mainly refers to the transplantation of gut microbiota from healthy donors to recipients with gut microbiota imbalance, so that the gut microbiota in recipients can be reshaped and play a normal function, and further prevent or treat the diseases related to gut microbiota disorder. Herein, based on the gut-bone axis and proven regulatory effects of gut microbiota on osteoporosis, this review expounds relevant basic researches and clinical practice of FMT on osteoporosis, thus demonstrating the potentials of FMT as a therapeutic option for osteoporosis and further providing certain reference for the future researches.

Fecal microbiota transplantation ameliorates bone loss in mice with ovariectomy-induced osteoporosis via modulating gut microbiota and metabolic function.

Background: Osteoporosis (OP) is a systemic metabolic bone disease characterized by decreased bone mass and destruction of bone microstructure, which tends to result in enhanced bone fragility and related fractures. The postmenopausal osteoporosis (PMOP) has a relatively high proportion, and numerous studies reveal that estrogen-deficiency is related to the imbalance of gut microbiota (GM), impaired intestinal mucosal barrier function and enhanced inflammatory reactivity. However, the underlying mechanisms remain unclear and the existing interventions are also scarce. Methods: In this study, we established a mouse model induced by ovariectomy (OVX) and conducted fecal microbiota transplantation (FMT) by gavage every day for 8 weeks. Subsequently, the bone mass and microarchitecture of mice were evaluated by the micro computed tomography (Micro-CT). The intestinal permeability, pro-osteoclastogenic cytokines expression, osteogenic and osteoclastic activities were detected by the immunohistological analysis, histological examination, enzyme-linked immunosorbent assay (ELISA) and western blot analysis accordingly. Additionally, the composition and abundance of GM were assessed by 16S rRNA sequencing and the fecal short chain fatty acids (SCFAs) level was measured by metabolomics. Results: Our results demonstrated that FMT inhibited the excessive osteoclastogenesis and prevented the OVX-induced bone loss. Specifically, compared with the OVX group, FMT enhanced the expressions of tight junction proteins (zonula occludens protein 1 (ZO-1) and Occludin) and suppressed the release of pro-osteoclastogenic cytokines (tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß)). Furthermore, FMT also optimized the composition and abundance of GM, and increased the fecal SCFAs level (mainly acetic acid and propionic acid). Conclusions: Collectively, based on GM-bone axis, FMT prevented the OVX-induced bone loss by correcting the imbalance of GM, improving the SCFAs level, optimizing the intestinal permeability and suppressing the release of pro-osteoclastogenic cytokines, which may be an alternative option to serve as a promising candidate for the prevention and treatment of PMOP in the future. The translational potential of this article: This study indicates the ingenious involvement of GM-bone axis in PMOP and the role of FMT in reshaping the status of GM and ameliorating the bone loss in OVX-induced mice. FMT might serve as a promising candidate for the prevention and treatment of PMOP in the future.

A narrative review of the moderating effects and repercussion of exercise intervention on osteoporosis: ingenious involvement of gut microbiota and its metabolites.

Osteoporosis (OP) is a systemic bone disease characterized by the decreased bone mass and destruction of bone microstructure, which tends to result in the enhanced bone fragility and related fractures, as well as high disability rate and mortality. Exercise is one of the most common, reliable and cost-effective interventions for the prevention and treatment of OP currently, and numerous studies have revealed the close association between gut microbiota (GM) and bone metabolism recently. Moreover, exercise can alter the structure, composition and abundance of GM, and further influence the body health via GM and its metabolites, and the changes of GM also depend on the choice of exercise modes. Herein, combined with relevant studies and based on the inseparable relationship between exercise intervention-GM-OP, this review is aimed to discuss the moderating effects and potential mechanisms of exercise intervention on GM and bone metabolism, as well as the interaction between them.

Risk factors for postoperative delirium in geriatric patients with hip fracture: A systematic review and meta-analysis.

Objectives: This systematic review and meta-analysis was conducted to identify the potential risk factors for postoperative delirium in geriatric patients with hip fracture. Methods: PubMed, EMBASE, and Cochrane Library were searched from inception until December 31st, 2021. A combined searching strategy of subject words and free words was adopted. Studies involving risk factors for postoperative delirium in elderly patients undergoing hip fracture surgeries were reviewed. Qualities of included studies were assessed using the Newcastle-Ottawa Scale. Data were pooled and a meta-analysis was performed using Review Manager 5.3. Results: A total of 37 studies were included. The following risk factors were significant: advanced age (per year increase) (OR: 1.05, 95% CI 1.04-1.07), age>80 years (OR: 2.26, 95% CI 1.47-3.47), male (OR: 1.53, 95% CI 1.37-1.70), preoperative cognitive impairment (OR:3.20, 95% CI 2.12-4.83), preoperative dementia (OR: 2.74, 95% CI 2.18-3.45), preoperative delirium (OR: 9.23, 95% CI 8.26-10.32), diabetes (OR: 1.18, 95% CI 1.05-1.33), preoperative functional dependence (OR: 1.31, 95% CI 1.11-1.56), ASA level (per level increase) (OR: 1.63, 95% CI 1.04-2.57), ASA level≥3(OR: 1.76, 95% CI 1.39-2.24), low albumin (OR: 3.30, 95% CI 1.44-7.55), medical comorbidities (OR: 1.15, 95% CI 1.06-1.25), Parkinson's disease (OR: 4.17, 95% CI 1.68-10.31) and surgery delay>48 h (OR: 1.90, 95% CI 1.36-2.65). Conclusions: Clinicians should be alert to patients with those risk factors. To identify the risk factors more precisely, more research studies with larger sample size and better design should be conducted.

Oral versus intravenous tranexamic acid in elderly patients with intertrochanteric fracture undergoing proximal femur intramedullary nailing: A prospective cohort study.

Objective: To investigate and compare the efficacy and safety of intravenous and oral application of tranexamic acid (TXA) in geriatric patients undergoing intertrochanteric fracture surgeries. Methods: All patients with intertrochanteric fracture admitted to the trauma center of the Zhongda hospital were selected after January 1st, 2020. The final patients were divided into three groups. Oral group: 2 â€‹g oral TXA 2 â€‹h preoperatively; intravenous group: 15 â€‹mg/kg intravenous TXA before incision; control group: no intervention. The main outcome measures were blood transfusion rate and total blood loss. Secondary outcomes include intraoperative blood loss, postoperative blood loss, perioperative blood transfusion volumes, length of hospital stay, thromboembolism events and other adverse events. Results: From January 1, 2020 to December 31, 2020, 124 patients with intertrochanteric fracture were enrolled. According to the inclusion and exclusion criteria, 105 patients were included, including 32 patients in the oral group, 36 patients in the intravenous group and 37 patients in the control group. The demographic characteristics of each group were similar. The blood transfusion rate in the control group was significantly more than that in the experimental group (64.9% vs 40.6% vs 36.1%, P â€‹= â€‹0.041). There was no significant difference between the oral group and the intravenous group (P â€‹= â€‹0.704). The total blood loss of the oral group and the intravenous group were less than the control group (990.29 â€‹± â€‹250.19 â€‹ml vs 997.47 â€‹± â€‹452.34 â€‹ml vs 1408.54 â€‹± â€‹461.74 â€‹ml), the difference was statistically significant (P â€‹= â€‹0.001), and there was no significant difference between the intravenous group and the oral group (P â€‹= â€‹0.459). The perioperative blood transfusion volumes of the oral group and the intravenous group were less than the control group (250.00 â€‹± â€‹198.62 â€‹ml vs 227.78 â€‹± â€‹179.27 â€‹ml vs 367.57 â€‹± â€‹323.90 â€‹ml), the difference was statistically significant (P â€‹= â€‹0.001), and there was no significant difference between the intravenous group and the oral group (P â€‹= â€‹0.832). During hospitalization and follow-up, there were no thromboembolism events such as deep vein thrombosis and pulmonary embolism. Conclusion: It is safe and effective to use TXA intravenously and orally in elderly patients with intertrochanteric fracture. The results of the two methods are similar in safety and effectiveness. Oral TXA is recommended because of its cost-benefit superiority and its ease of administration. The translational potential of this article: The result of this prospective cohort study shows that the utilization of oral TXA in elderly patients with intertrochanteric fracture undergoing proximal femur intramedullary nailing possesses great potential in reducing blood loss and cost-benefit superiority.