Liraglutide, a glucagon-like peptide-1 receptor agonist, inhibits bone loss in an animal model of osteoporosis with or without diabetes.

Introduction: Liraglutide (Lrg), a novel anti-diabetic drug that mimics the endogenous glucagon-like peptide-1 to potentiate insulin secretion, is observed to be capable of partially reversing osteopenia. The aim of the present study is to further investigate the efficacy and potential anti-osteoporosis mechanisms of Lrg for improving bone pathology, bone- related parameters under imageology, and serum bone metabolism indexes in an animal model of osteoporosis with or without diabetes. Methods: Eight databases were searched from their inception dates to April 27, 2024. The risk of bias and data on outcome measures were analyzed by the CAMARADES 10-item checklist and Rev-Man 5.3 software separately. Results: Seventeen eligible studies were ultimately included in this review. The number of criteria met in each study varied from 4/10 to 8/10 with an average of 5.47. The aspects of blinded induction of the model, blinding assessment of outcome and sample size calculation need to be strengthened with emphasis. The pre-clinical evidence reveals that Lrg is capable of partially improving bone related parameters under imageology, bone pathology, and bone maximum load, increasing serum osteocalcin, N-terminal propeptide of type I procollagen, and reducing serum c-terminal cross-linked telopeptide of type I collagen (P<0.05). Lrg reverses osteopenia likely by activating osteoblast proliferation through promoting the Wnt signal pathway, p-AMPK/PGC1α signal pathway, and inhibiting the activation of osteoclasts by inhibiting the OPG/RANKL/RANK signal pathway through anti-inflammatory, antioxidant and anti-autophagic pathways. Furthermore, the present study recommends that more reasonable usage methods of streptozotocin, including dosage and injection methods, as well as other types of osteoporosis models, be attempted in future studies. Discussion: Based on the results, this finding may help to improve the priority of Lrg in the treatment of diabetes patients with osteoporosis.

Predictors and prognosis of early neurological outcomes on patients with Vertebrobasilar artery occlusion undergoing endovascular treatment.

BACKGROUND: This research explored the factors influencing early neurological outcomes (ENO) in patients who had vertebrobasilar artery occlusion (VBAO) and received endovascular treatment (EVT), as well as examining the causal influence of ENO on the prognosis of VBAO patients. METHODS: A retrospective review was carried out on patients from 65 Chinese stroke centers, all within 24 hours of the estimated occlusion time. ENO includes early neurological improvement (ENI) and early neurological deterioration (END), defined as a decrease or an increase of at least 4 points in NIHSS score between baseline and 24 hours after EVT. Death within 24 hours after EVT also consider as END. END was further divided into explainable END and unexplainable END (unEND). Independent predictors of ENO and the association between ENO and outcomes in patients with VBAO were determined using center-adjusted analyses. The study developed a multivariate logistic regression model to examine the comparative risk of unEND versus explainable END on the clinical outcomes in VBAO patients. RESULTS: A total of 2257 patients were included. Glasgow Coma Scale (GCS) (OR 1.16, 95% CI 1.03-1.30) and successful reperfusion (OR 1.15, 95% CI 1.02-1.30) were associated with ENI. Baseline NIHSS (OR 0.60, 95% CI 0.53-0.68), successful reperfusion (OR 0.79, 95% CI 0.71-0.89) and puncture to reperfusion time (OR 1.17, 95% CI 1.03-1.33) were associated with END. When examining three-month prognostic indexes, both END and ENI were found to be linked to the three-month outcomes, but in opposite directions. A subgroup analysis of END suggested that unexplained END typically demonstrated a more favorable prognosis compared to explained END, although the prognosis remained generally unfavorable. CONCLUSIONS: ENO, whether they manifested as early improvement or deterioration, were linked to the prognosis of VBAO patients undergoing EVT. The outcomes after unEND were more favorable than those following explained END.

Rescue stenting after failure of endovascular thrombectomy for acute vertebrobasilar artery occlusion: data from the PERSIST registry.

BACKGROUND: Among acute vertebrobasilar artery occlusion (VBAO) patients, successful reperfusion is a strong predictor of favorable outcomes. However, failed reperfusion (FR) with endovascular thrombectomy (EVT) in VBAO was observed to occur in 18-50% of cases. We aim to evaluate the safety and efficacy of rescue stenting (RS) for VBAO after failed EVT. METHODS: Patients with VBAO who received EVT were enrolled retrospectively. Propensity score matching was performed as the primary analysis to compare the outcomes between patients with RS and FR. Furthermore, a comparison between using the self-expanding stent (SES) and balloon-mounted stent (BMS) in the RS group was also conducted. The primary and secondary outcomes were defined as a 90-day modified Rankin Scale (mRS) score 0-3, and a 90-day mRS score 0-2, respectively. Safety outcomes included all-cause mortality at 90 days and symptomatic intracranial hemorrhage (sICH). RESULTS: The RS group showed a significantly higher rate of 90-day mRS score 0-3 (46.6% vs 20.7%; adjusted OR (aOR) 5.06, 95% CI 1.88 to 13.59, P=0.001) and a lower rate of 90-day mortality (34.5% vs 55.2%; aOR 0.42, 95% CI 0.23 to 0.90, P=0.026) than the FR group. The rates of 90-day mRS score 0-2 and sICH were not significantly different between the RS group and FR group. There were no differences in all outcomes between SES and BMS groups. CONCLUSIONS: RS appeared to be a safe and effective rescue approach in patients with VBAO who failed EVT, and there was no difference between using SES and BMS.

Cinnamaldehyde Alleviates Bone Loss by Targeting Oxidative Stress and Mitochondrial Damage via the Nrf2/HO-1 Pathway in BMSCs and Ovariectomized Mice.

Osteoporosis (OP) is typically brought on by disruption of bone homeostasis. Excessive oxidative stress and mitochondrial dysfunction are believed to be the primary mechanisms underlying this disorder. Therefore, in order to restore bone homeostasis effectively, targeted treatment of oxidative stress and mitochondrial dysfunction is necessary. Cinnamaldehyde (CIN), a small molecule that acts as an agonist for the nuclear factor erythroid 2-related factor (Nrf2), has been found to possess antiapoptotic, anti-inflammatory, and antioxidant properties. We found that CIN, while rescuing apoptosis, can also reduce the accumulation of reactive oxygen species (ROS) to improve mitochondrial dysfunction and thus restore the osteogenic differentiation potential of BMSCs disrupted by hydrogen peroxide (H2O2) exposure. The role of CIN was preliminarily considered to be a consequence of Nrf2/HO-1 axis activation. The ovariectomized mice model further demonstrated that CIN treatment ameliorated oxidative stress in vivo, partially reversing OVX-induced bone loss. This improvement was seen in the trabecular microarchitecture and bone biochemical indices. However, when ML385 was concurrently injected with CIN, the positive effects of CIN were largely blocked. In conclusion, this study sheds light on the intrinsic mechanisms by which CIN regulates BMSCs and highlights the potential therapeutic applications of these findings in the treatment of osteoporosis.

Effect of INR on Outcomes of Endovascular Treatment for Acute Vertebrobasilar Artery Occlusion.

Endovascular treatment (EVT) has been proven to be the standard treatment for acute vertebrobasilar artery occlusion (VBAO). This study aimed to analyze the effects of international normalized ratio (INR) indicators on outcomes in patients with acute VBAO treated with EVT. Dynamic data on INR in patients with VBAO who received endovascular treatment (EVT) at 65 stroke centers in China were retrospectively enrolled. Outcome measures included the modified Rankin Scale (mRS) score at 90 days and 1 year and symptomatic intracranial hemorrhage (sICH). The associations between elevated INR (INR > 1.1), INR variability (time-weighted variance of INR changes), and various clinical outcomes were analyzed in all patients and subgroups stratified by oral anticoagulation (OAC) by mixed logistic regression analysis. A total of 1825 patients met the study criteria, of which 1384 had normal INR and 441 had elevated INR. Multivariate analysis showed that elevated INR was significantly associated with poor functional outcomes (mRS 4-6) at 90 days (odds ratio [OR] 1.36, 95% confidence interval [CI] 1.08-1.72) and 1 year (OR 1.32, 95% CI 1.05-1.66), but was not associated with an increased risk of sICH (OR 1.00, 95% CI 0.83-1.20). Similar associations exist between INR variability and poor functional outcomes at 90 days (OR 2.17, 95% CI 1.09-4.30), 1 year (OR 2.28, 95% CI 1.16-4.46), and sICH (OR 1.11, 95% CI 0.93-1.33). Subgroup analyses further revealed that elevated INR and INR variability remained associated with poor functional outcomes in patients not receiving oral anticoagulation (OAC) therapy, while no significant associations were observed in OAC-treated patients, regardless of whether they were on warfarin or direct oral anticoagulants. Elevated INR and INR variability in VBAO patients treated with EVT were associated with poor functional outcomes. The mechanism underlying the association between elevated INR and poor functional outcomes might be attributed to the fact that elevated INR indirectly reflects the burden of comorbidities, which could independently worsen outcomes. These findings underscore the importance of a comprehensive and dynamic evaluation of INR levels in the management of VBAO patients receiving EVT, providing valuable insights for optimizing patient outcomes.

A Novel Anti-Osteoporosis Mechanism of VK2: Interfering with Ferroptosis via AMPK/SIRT1 Pathway in Type 2 Diabetic Osteoporosis.

Type 2 diabetic osteoporosis (T2DOP) is a chronic bone metabolic disease. Compared with traditional menopausal osteoporosis, the long-term high glucose (HG) microenvironment increases patients' risk of fracture and osteonecrosis. We were accumulating evidence that implicated ferroptosis as a pivotal mechanism of glucolipotoxicity-mediated death of osteocytes and osteoblast, a novel form of programmed cell death resulting from uncontrolled lipid peroxidation depending on iron. Vitamin K2 (VK2), a fat-soluble vitamin, is clinically applied to prevent osteoporosis and improve coagulation. This study aimed to clarify the role and mechanism of VK2 in HG-mediated ferroptosis. We established the mouse T2DOP model by intraperitoneal injection of streptozotocin solution and a high-fat and high-sugar diet. We also cultured bone marrow mesenchymal stem cells (BMSCs) in HG to simulate the diabetic environment in vitro. Based on our data, VK2 inhibited HG-mediated bone loss and ferroptosis, the latter manifested by decreased levels of mitochondrial reactive oxygen species, lipid peroxidation, and malondialdehyde and increased glutathione in vitro. In addition, VK2 treatment was capable of restoring bone mass and strengthening the expression of SIRT1, GPX4, and osteogenic markers in the distal femurs. As for further mechanism exploration, we found that VK2 could activate AMPK/SIRT1 signaling, and knockdown of SIRT1 by siRNA prevented the VK2-mediated positive effect in HG-cultured BMSCs. Summarily, VK2 could ameliorate T2DOP through the activation of the AMPK/SIRT1 signaling pathway to inhibit ferroptosis.

Application of interpretable machine learning algorithms to predict distant metastasis in osteosarcoma.

BACKGROUND: Osteosarcoma is well-established as the most common bone cancer in children and adolescents. Patients with localized disease have different prognoses and management than those with metastasis at the time of diagnosis. The purpose of this study was to explore potential risk factors for metastatic disease. METHODS: The Surveillance, Epidemiology, and End Results (SEER) Program database was used to identify patients diagnosed with osteosarcoma between 2004 and 2015. We developed prediction models for distant metastasis using six machine learning (ML) techniques, including logistic regression (LR), support vector machine (SVM), Gaussian Naive Bayes (GaussianNB), Extreme Gradient Boosting (XGBoost), random forest (RF), and k-nearest neighbor algorithm (kNN). The adaptive synthetic (ADASYN) technique was used to deal with imbalanced data. The Shapley Additive Explanation (SHAP) analysis generated visualized explanations for each patient. Finally, the average precision (AP), sensitivity, specificity, accuracy, F1 score, precision-recall curves, calibration plots, and decision curve analysis (DCA) were conducted to evaluate the models' effectiveness. RESULTS: The six machine learning algorithms achieved AP of 0.661-0.781 for predicting distant metastasis. The RF model yielded the best performance with an accuracy of 71.8 percent and an AP of 0.781 and was highly dependent on tumor size, primary surgery, and age. SHAP analysis provided model-independent interpretation, highlighting significant clinical factors associated with the risk of metastasis in osteosarcoma patients. CONCLUSIONS: An accurate machine learning-based prediction model was established for metastasis in osteosarcoma patients to help clinicians during clinical decision-making.

Application of machine learning model to predict lacunar cerebral infarction in elderly patients with femoral neck fracture before surgery.

BACKGROUND: Femoral neck fracture and lacunar cerebral infarction (LCI) are the most common diseases in the elderly. When LCI patients undergo a series of traumas such as surgery, their postoperative recovery results are often poor. Moreover, few studies have explored the relationship between LCI and femoral neck fracture in the elderly. Therefore, this study will develop a ML (machine learning)-based model to predict LCI before surgery in elderly patients with a femoral neck fracture. METHODS: Professional medical staff retrospectively collected the data of 161 patients with unilateral femoral neck fracture who underwent surgery in the Second Affiliated Hospital of Wenzhou Medical University database from January 1, 2015, to January 1, 2020. Patients were divided into two groups based on LCI (diagnosis based on cranial CT image): the LCI group and the non-LCI group. Preoperative clinical characteristics and preoperative laboratory data were collected for all patients. Features were selected by univariate and multivariate logistic regression analysis, with age, white blood cell (WBC), prealbumin, aspartate aminotransferase (AST), total protein, globulin, serum creatinine (Scr), blood urea nitrogen (Bun)/Scr, lactate dehydrogenase (LDH), serum sodium and fibrinogen as the features of the ML model. Five machine learning algorithms, Logistic regression (LR), Gradient Boosting Machine (GBM), Extreme Gradient Boosting (XGBoost), Random Forest (RF), and Decision tree (DT), were used in combination with preoperative clinical characteristics and laboratory data to establish a predictive model of LCI in patients with a femoral neck fracture. Furthermore, indices like the area under the receiver operating characteristic (AUROC), sensitivity, specificity, and accuracy were calculated to test the models' performance. RESULTS: The AUROC of 5 ML models ranged from 0.76 to 0.95. It turned out that the RF model demonstrated the highest performance in predicting LCI for femoral neck fracture patients before surgery, whose AUROC was 0.95, sensitivity 1.00, specificity 0.81, and accuracy 0.90 in validation sets. Furthermore, the top 4 high-ranking variables in the RF model were prealbumin, fibrinogen, globulin and Scr, in descending order of importance. CONCLUSION: In this study, 5 ML models were developed and validated for patients with femoral neck fracture to predict preoperative LCI. RF model provides an excellent predictive value with an AUROC of 0.95. Clinicians can better conduct multidisciplinary perioperative management for patients with femoral neck fractures through this model and accelerate the postoperative recovery of patients.

Development of a nomogram to predict surgical site infection after closed comminuted calcaneal fracture.

BACKGROUND: Compared with open comminuted calcaneal fractures, less emphasis is placed on postoperative surgical site infection (SSI) of closed comminuted calcaneal fractures. This study aimed to identify the risk factors associated with SSI and build a nomogram model to visualize the risk factors for postoperative SSI. METHODS: We retrospectively collected patients with closed comminuted calcaneal fractures from the Second Affiliated Hospital of Wenzhou Medical University database from 2017 to 2020. Risk factors were identified by logistics regression analysis, and the predictive value of risk factors was evaluated by ROC (receiver operating characteristic curve). Besides, the final risk factors were incorporated into R4.1.2 software to establish a visual nomogram prediction model. RESULTS: The high-fall injury, operative time, prealbumin, aspartate aminotransferase (AST), and cystatin-C were independent predictors of SSI in calcaneal fracture patients, with OR values of 5.565 (95%CI 2.220-13.951), 1.044 (95%CI 1.023-1.064), 0.988 (95%CI 0.980-0.995), 1.035 (95%CI 1.004-1.067) and 0.010 (95%CI 0.001-0.185) (Ps < 0.05). Furthermore, ROC curve analysis showed that the AUC values of high-fall injury, operation time, prealbumin, AST, cystatin-C, and their composite indicator for predicting SSI were 0.680 (95%CI 0.593-0.766), 0.756 (95%CI 0.672-939), 0.331 (95%CI 0.243-0.419), 0.605 (95%CI 0.512-0.698), 0.319 (95%CI 0.226-0.413) and 0.860 (95%CI 0.794-0.926), respectively (Ps < 0.05). Moreover, the accuracy of the nomogram to predict SSI risk was 0.860. CONCLUSIONS: Our study findings suggest that clinicians should pay more attention to the preoperative prealbumin, AST, cystatin C, high-fall injury, and operative time for patients with closed comminuting calcaneal fractures to avoid the occurrence of postoperative SSI. Furthermore, our established nomogram to assess the risk of SSI in calcaneal fracture patients yielded good accuracy and can assist clinicians in taking appropriate measures to prevent SSI.

CORM-3 Attenuates Oxidative Stress-Induced Bone Loss via the Nrf2/HO-1 Pathway.

Bone metabolism occurs in the entire life of an individual and is required for maintaining skeletal homeostasis. The imbalance between osteogenesis and osteoclastogenesis eventually leads to osteoporosis. Oxidative stress is considered a major cause of bone homeostasis disorder, and relieving excessive oxidative stress in bone mesenchymal stem cells (BMSCs) is a potential treatment strategy for osteoporosis. Carbon monoxide releasing molecule-3 (CORM-3), the classical donor of carbon monoxide (CO), possesses antioxidation, antiapoptosis, and anti-inflammatory properties. In our study, we found that CORM-3 could reduce reactive oxygen species (ROS) accumulation and prevent mitochondrial dysfunction thereby restoring the osteogenic potential of the BMSCs disrupted by hydrogen peroxide (H2O2) exposure. The action of CORM-3 was preliminarily considered the consequence of Nrf2/HO-1 axis activation. In addition, CORM-3 inhibited osteoclast formation in mouse primary bone marrow monocytes (BMMs) by inhibiting H2O2-induced polarization of M1 macrophages and endowing macrophages with M2 polarizating ability. Rat models further demonstrated that CORM-3 treatment could restore bone mass and enhance the expression of Nrf2 and osteogenic markers in the distal femurs. In summary, CORM-3 is a potential therapeutic agent for the treatment of osteoporosis.

Risk Factors for Pulmonary Embolism in ICU Patients: A Retrospective Cohort Study from the MIMIC-III Database.

Pulmonary embolism (PE) is a common and potentially lethal form of venous thromboembolic disease in ICU patients. A limited number of risk factors have been associated with PE in ICU patients. In this study, we aimed to screen the independent risk factors of PE in ICU patients that can be used to evaluate the patient's condition and provide targeted treatment. We performed a retrospective cohort study using a freely accessible critical care database Medical Information Mart for Intensive Care (MIMIC)-III. The ICU patients were divided into two groups based on the incidence of PE. Finally, 9871 ICU patients were included, among which 204 patients (2.1%) had pulmonary embolism. During the multivariate logistic regression analysis, sepsis, hospital_LOS (the length of stay in hospital), type of admission, tumor, APTT (activated partial thromboplastin time) and platelet were independent risk factors for patients for PE in ICU, with OR values of 1.471 (95%CI 1.001-2.162), 1.001 (95%CI 1.001-1.001), 3.745 (95%CI 2.187-6.414), 1.709 (95%CI 1.247-2.341), 1.014 (95%CI 1.010-1.017) and 1.002 (95%CI 1.001-1.003) (Ps < 0.05). ROC curve analysis showed that the composite indicator had a higher predictive value for ICU patients with PE, with a ROC area under the curve (AUC) of 0.743 (95%CI 0.710 -0.776, p < 0.001). Finally, sepsis, tumor, platelet count, length of stay in the hospital, emergency admission and APTT were independent predictors of PE in ICU patients.

The efficacy of Schroth exercises combined with the Chêneau brace for the treatment of adolescent idiopathic scoliosis: a retrospective controlled study.

PURPOSE: We aimed to determine the global effects of the Chêneau brace combined with Schroth exercises on adolescent idiopathic scoliosis (AIS). METHODS: We analyzed 192 patients with AIS who underwent the Chêneau brace treatment alone or combined with Schroth best practice (SBP) from June 2013 to October 2019. There were 138 patients in the Brace group and 54 patients in the Brace + SBP group. Radiographs were obtained at various treatment durations. Answers to the health-related quality of life (HRQoL) questionnaire were recorded before the intervention and at the time of treatment wean. RESULTS: The Cobb angle (-3.55°; p < 0.001) and C7-CSVL (-3.03 mm; p < 0.001) significantly decreased in the Brace + SBP group. Thoracic kyphosis (TK) decreased in both the Brace + SBP group (-1.85°; p = 0.0152) and the Brace group (-5.06; p < 0.001). Changes before and after treatment of TK were significantly different between groups (p < 0.001). The 22-item Scoliosis Research Society function score, self-image, mental health, and EuroQol 5-Dimension scores were significantly higher in the Brace + SBP group. The satisfaction score was higher in the Brace + SBP group (3.77 ± 0.63 vs. 3.13 ± 0.79; p < 0.001). CONCLUSIONS: Compared to bracing alone, the Schroth exercises plus bracing had a better effect on coronal balance. Schroth exercises improve flatback deformity caused by bracing and positively influence the HRQoL in AIS patients who received the Chêneau brace treatment.Implications for RehabilitationBracing and physiotherapy are common treatments for adolescent idiopathic scoliosis (AIS).The Chêneau brace treatment causes flatback deformity and muscle stiffness in AIS patients.The Schroth method helps patients increase muscle strength, halt curve progression, increase vital capacity, and maintain improved posture.The Schroth exercises could improve flatback deformity caused by bracing and positively influence the health-related quality of life in AIS patients who received the Chêneau brace treatment.

Intra-operative application of ultrasonography combined with limited radiography for the treatment of supracondylar humerus fractures in children: a randomized controlled trial.

AIMS: To introduce a new method of intra-operative application of ultrasonography (US) combined with limited radiography to treat supracondylar humerus fractures in children and evaluate its effect on radiation protection. MATERIAL AND METHODS:  Fifty patients were randomly divided into the radiography-only group (RO group, n = 22) and the US combined with the limited radiography group (UR group, n = 28). US was performed to evaluate fracture displacement and to guide reduction in the UR group. The primary outcome measures were the average number of radiography instances and the quantitative value of radiation emission. Secondary outcome measures were length of hospital stays, loss of range of motion, loss of carrying angle, loss of Baumann angle, fracture healing time, pin site infection, compartment syndrome, cubitus varus, cubitus valgus, and iatrogenic ulnar nerve injury. RESULTS: Average number of radiography instances and quantitative value of radiation emission in the UR group decreased compared with the RO group (p<0.05). There were no significant differences between the groups regarding mean time to surgery, the average length of hospital stays, average surgery time, radiological union time, Flynn grade, or loss of Baumann angle. Pin site infection was seen in one patient in the RO group and two patients in the UR group. No other complications occurred. CONCLUSION: Intra-operative application of US combined with limited radiography decreases radiation exposure during treatment of supracondylar humerus fractures in children without compromising the therapeutic effect.

Is vitamin K2 a treatment choice for atypical femoral fractures in patients with secondary osteoporosis?

An atypical femoral fracture (AFF) is a rare complication associated with excessive inhibition of osteoclast expression during treatment of osteoporosis. We herein describe a patient who had been treated with alendronate for more than 10 years and subsequently developed an AFF that healed after treatment with vitamin K2 (VK2). We also discuss the potential beneficial effects of VK2 on the healing of AFFs. A 48-year-old Asian man with secondary osteoporosis was treated with alendronate for more than 10 years. The patient underwent surgical treatment for a complete AFF of the right femur. Six months postoperatively, he complained of pain in his left thigh. X-ray examination revealed an incomplete AFF of the left femoral shaft. He was then treated with VK2. After 4 months of VK2 treatment, the patient reported that the pain in his left thigh had decreased, and follow-up X-ray examination demonstrated healing of the left AFF line. This case report indicates that VK2 may be a potential direction for pharmacological treatment of AFFs in future research.

Apelin-13 induces mitophagy in bone marrow mesenchymal stem cells to suppress intracellular oxidative stress and ameliorate osteoporosis by activation of AMPK signaling pathway.

Osteoporosis is characterized by impaired bone metabolism. Current estimates show that it affects millions of people worldwide and causes a serious socioeconomic burden. Mitophagy plays key roles in bone marrow mesenchymal stem cells (BMSCs) osteoblastic differentiation, mineralization, and survival. Apelin is an endogenous adipokine that participates in bone homeostasis. This study was performed to determine the role of Apelin in the osteoporosis process and whether it affects mitophagy, survival, and osteogenic capacity of BMSCs in in vitro and in vivo models of osteoporosis. Our results demonstrated that Apelin was down-regulated in ovariectomized-induced osteoporosis rats and Apelin-13 treatment activated mitophagy in BMSCs, ameliorating oxidative stress and thereby reviving osteogenic function via AMPK-α phosphorylation. Besides, Apelin-13 administration restored bone mass and microstructure as well as reinstated mitophagy, enhanced osteogenic function in OVX rats. Collectively, our findings reveal the intrinsic mechanisms underlying Apelin-13 regulation in BMSCs and its potential therapeutic values in the treatment of osteoporosis.

The Isolation and Molecular Characterization of an Astrovirus From "Yellow" Chickens, China.

Chicken astrovirus (CAstV) infection is strongly associated with kidney disease, gout, "white chicks" hatchery disease, and runting and stunting syndrome (RSS). In the present study, 82.5% of 154 clinical samples from different provinces in China were positive for CAstV by RT-PCR. One CAstV isolate, designated as AAstV/Chicken/CHN/2017/NJ01, was successfully isolated from the small intestine of "Yellow" chickens using LMH cells. The genome sequence and structure analyses revealed that NJ1701 had the typical characteristics of avian astroviruses which was genetically distinct from other Avastrovirus. This isolate was classified as Group B subgroup i based on phylogenetic analysis of complete ORF2 (capsid) amino acid sequences. Meanwhile, growth depression and hatchability reduction were observed in the chicken embryo infection experiment. The results in the current study will contribute to our understanding of chicken astrovirus in China.

Degradation of subchondral bone collagen in the weight-bearing area of femoral head is associated with osteoarthritis and osteonecrosis.

BACKGROUND: The aim of the study was to evaluate the change of subchondral bone collagen and trabecular bone in the weight-bearing area of femoral head from patients with osteoarthritis (OA) or osteonecrosis of femoral head (ONFH), and discuss the effect of collagen degradation on OA and ONFH. METHODS: Femoral heads from patients with femoral neck fracture (FNF) were collected as control group. All collected samples were divided into OA group (N = 10), ONFH group (N = 10), and FNF group (N = 10). Differences of subchondral bone collagen were compared through scanning electron microscope (SEM) observation, immunohistochemistry staining, and Masson's trichrome staining. Alteration of subchondral bone was displayed through hematoxylin and eosin (H&E) staining and gross morphology. RESULTS: SEM results showed that collagen fibers in OA and ONFH group appeared to be thinner, rougher, sparser, and more wizened. Immunohistochemistry and Masson's trichrome staining results demonstrated that the content of collagen fibers in the OA and ONFH group was obviously less than the FNF group. H&E staining results showed that trabecular bone in OA and ONFH group appeared to be thinner and ruptured. Gross morphology results showed that the degeneration and destruction of cartilage and subchondral bone in OA and ONFH group were severer than FNF group. The characteristics mentioned above in ONFH group were more apparent than OA group. CONCLUSIONS: This study revealed that degradation of collagen fibers from subchondral bone in the weight-bearing area of femoral head was associated with OA and ONFH, which may help to find new therapeutic strategies of the diseases.

Proanthocyanidins-Mediated Nrf2 Activation Ameliorates Glucocorticoid-Induced Oxidative Stress and Mitochondrial Dysfunction in Osteoblasts.

The widespread use of therapeutic glucocorticoids has increased the frequency of glucocorticoid-induced osteoporosis (GIOP). One of the potential pathological processes of GIOP is an increased level of oxidative stress and mitochondrial dysfunction, which eventually leads to osteoblast apoptosis. Proanthocyanidins (PAC) are plant-derived antioxidants that have therapeutic potential against GIOP. In our study, a low dose of PAC was nontoxic to healthy osteoblasts and restored osteogenic function in dexamethasone- (Dex-) treated osteoblasts by suppressing oxidative stress, mitochondrial dysfunction, and apoptosis. Mechanistically, PAC neutralized Dex-induced damage in the osteoblasts by activating the Nrf2 pathway, since silencing Nrf2 partly eliminated the protective effects of PAC. Furthermore, PAC injection restored bone mass and promoted the expression of Nrf2 in the distal femur of Dex-treated osteoporotic rats. In summary, PAC protect osteoblasts against Dex-induced oxidative stress and mitochondrial dysfunction via the Nrf2 pathway activation and may be a promising drug for treating GIOP.

Decreased Radiation Exposure Using Ultrasound-Assisted Reduction and Fixation of Femoral Shaft Fractures in Children: A Pilot Study.

Elastic stable intra-medullary nail procedures have been used to treat femoral fractures in children for some time. Radiation exposure generated by intra-operative radioscopy may induce side effects in children and staff. This study introduces a method of ultrasound-assisted reduction and fixation of femoral fractures in children to decrease radiation exposure. We included 21 children and evaluated displacement of fractures using multi-section scanning. All fracture reductions were performed with ultrasonography. A hyperechoic point with a posterior acoustic shadow can be seen under the proximal and distal segments after the nail passes through the fracture site. Comparison with radioscopy suggests that this is a viable method of reduction and fixation of femoral shaft fractures in children, and can effectively decrease radiation exposure.

Vitamin K2 Can Rescue the Dexamethasone-Induced Downregulation of Osteoblast Autophagy and Mitophagy Thereby Restoring Osteoblast Function In Vitro and In Vivo.

Chronic long-term glucocorticoids (GC) use is associated with glucocorticoid-induced osteoporosis (GIOP) by inhibiting the survival and impairing the functions of osteoblasts. Autophagy and mitophagy play key roles in osteoblast differentiation, mineralization and survival, and mounting evidence have implicated osteoblast autophagy and mitophagy as a novel mechanism in the pathogenesis of GIOP. Vitamin K2 (VK2) is an essential nutrient supplement that have been shown to exert protective effects against osteoporotic bone loss including GIOP. In this study, we showed that the glucocorticoid dexamethasone (Dex) deregulated osteoblast autophagy and mitophagy by downregulating the expression of autophagic and mitophagic markers LC3-II, PINK1, Parkin. This consequently led to inhibition of osteoblast differentiation and mineralization function in vitro. Interestingly, co-treatment with VK2 significantly attenuated the Dex-induced downregulation of LC3-II, PINK1, Parkin, thereby restoring autophagic and mitophagic processes and normal osteoblastic activity. In addition, using an established rat model of GIOP, we showed that VK2 administration can protect rats against the deleterious effects of Dex on bone by reinstating autophagic and mitophagic activities in bone tissues. Collectively, our results provide new insights into the role of osteoblast autophagy and mitophagy in GIOP. Additionally, the use of VK2 supplementation to augment osteoblast autophagy/mitophagy may significantly improve clinical outcomes of GIOP patients.