Analysis of the clinical characteristics and risk factors associated with contralateral hip fracture after initial hip fracture in elderly patients: a retrospective cohort study.

Fractures of the contralateral hip may easily occur in elderly patients after an initial hip fracture. The aim of this study was to investigate the clinical characteristics and major predisposing risk factors of contralateral hip fracture after initial hip fracture in the elderly, to provide a clinical basis for preventing contralateral hip fracture. The data of 1586 patients who had sustained first or second hip fractures and had been surgically treated in our department were retrospectively analyzed. Potential predictive factors for contralateral hip fracture and descriptive statistics associated with surgery (such as blood loss, operation time, and length of hospital stay) were recorded. Of these patients, 133 (8.4%) suffered contralateral hip fracture. The rates of contralateral fracture after femoral neck and intertrochanteric fracture were 5.4% and 10.7% respectively (P < 0.01). Fifty-four cases of contralateral hip fracture occurred within one year, an incidence of 40.6%, while 95 cases (71.4%) and 105 cases (78.9%) occurred within two and three years, respectively, with a interval duration of 21.6 months. The risk factors for contralateral hip fracture were found to be age, type of first fracture, bone mineral density, the Singh index, and concomitant internal medical diseases, which were found to be significantly associated with an increased risk of contralateral hip fracture in multivariate logistic regression analysis (P < 0.05). In conclusion, the presence of concomitant internal diseases, type of first fracture, bone mineral density, the Singh index, and age were found to be significant predictors of the risk of contralateral hip fracture in elderly patients after a first hip fracture.

Preliminary exploration of the biomechanical properties of three novel cervical porous fusion cages using a finite element study.

BACKGROUND: Porous cages are considered a promising alternative to high-density cages because their interconnectivity favours bony ingrowth and appropriate stiffness tuning reduces stress shielding and the risk of cage subsidence. METHODS: This study proposes three approaches that combine macroscopic topology optimization and micropore design to establish three new types of porous cages by integrating lattices (gyroid, Schwarz, body-centred cubic) with the optimized cage frame. Using these three porous cages along with traditional high-density cages, four ACDF surgical models were developed to compare the mechanical properties of facet articular cartilage, discs, cortical bone, and cages under specific loads. RESULTS: The facet joints in the porous cage groups had lower contact forces than those in the high-density cage group. The intervertebral discs in all models experienced maximum stress at the C5/6 segment. The stress distribution on the cortical bone surface was more uniform in the porous cage groups, leading to increased average stress values. The gyroid, Schwarz, and BCC cage groups showed higher average stress on the C5 cortical bone. The average stress on the surface of porous cages was higher than that on the surface of high-density cages, with the greatest difference observed under the lateral bending condition. The BCC cage demonstrated favourable mechanical stability. CONCLUSION: The new porous cervical cages satifies requirements of low rigidity and serve as a favourable biological scaffold for bone ingrowth. This study provides valuable insights for the development of next-generation orthopaedic medical devices.

[Finite element analysis of artificial ankle elastic improved inserts].

Objective: To discuss the influence of artificial ankle elastic improved inserts (hereinafter referred to as "improved inserts") in reducing prosthesis micromotion and improving joint surface contact mechanics by finite element analysis. Methods: Based on the original insert of INBONE Ⅱ implant system (model A), four kinds of improved inserts were constructed by adding arc or platform type flexible layer with thickness of 1.3 or 2.6 mm, respectively. They were Flying goose type_1.3 elastic improved insert (model B), Flying goose type_2.6 elastic improved insert (model C), Platform type_1.3 elastic improved insert (model D), Platform type_2.6 elastic improved insert (model E). Then, the CT data of right ankle at neutral position of a healthy adult male volunteer was collected, and finite element models of total ankle replacement (TAR) was constructed based on model A-E prostheses by software of Mimics 19.0, Geomagic wrap 2017, Creo 6.0, Hypermesh 14.0, and Abaqus 6.14. Finally, the differences of bone-metal prosthesis interface micromotion and articular surface contact behavior between different models were investigated under ISO gait load. Results: The tibia/talus-metal prosthesis interfaces micromotion of the five TAR models gradually increased during the support phase, then gradually fell back after entering the swing phase. The improved models (models B-E) showed lower bone-metal prosthesis interface micromotion when compared with the original model (model A), but there was no significant difference among models A-E ( P>0.05). The maximum micromotion of tibia appeared at the dome of the tibial bone groove, and the ​​micromotion area was the largest in model A and the smallest in model E. The maximum micromotion of talus appeared at the posterior surface of the central bone groove, and there was no difference in the micromotion area among models A-E. The contact area of the articular surface of the insert/talus prosthesis in each group increased in the support phase and decreased in the swing phase during the gait cycle. Compared with model A, the articular surface contact area of models B-E increased, but there was no significant difference among models A-E ( P>0.05). The change trend of the maximum stress on the articular surface of the inserts/talus prosthesis was similar to that of the contact area. Only the maximum contact stress of the insert joint surface of models D and E was lower than that of model A, while the maximum contact stress of the talar prosthesis joint surface of models B-E was lower than that of model A, but there was no significant difference among models A-E ( P>0.05). The high stress area of the lateral articular surface of the improved inserts significantly reduced, and the articular surface stress distribution of the talus prosthesis was more uniform. Conclusion: Adding a flexible layer in the insert can improve the elasticity of the overall component, which is beneficial to absorb the impact force of the artificial ankle joint, thereby reducing interface micromotion and improving contact behavior. The mechanical properties of the inserts designed with the platform type and thicker flexible layer are better.

FGF21 prevents neuronal cell ferroptosis after spinal cord injury by activating the FGFR1/ß-Klotho pathway.

Spinal cord injury (SCI) is a kind of traumatic nervous system disease caused by neuronal death, causing symptoms like sensory, motor, and autonomic nerve dysfunction. The recovery of neurological function has always been a intractable problem that has greatly distressed individuals and society. Although the involvement of iron-dependent lipid peroxidation leading to nerve cell ferroptosis in SCI progression has been reported, the underlying mechanisms remain unaddressed. Thus, this study aimed to investigate the potential of recombinant human FGF21 (rhFGF21) in inhibiting ferroptosis of nerve cells and improving limb function after SCI, along with its underlying mechanisms. In vivo animal model showed that FGFR1, p-FGFR1, and ß-Klotho protein gradually increased over time after injury, reaching a peak on the third day. Moreover, rhFGF21 treatment significantly reduced ACSL4, increased GPX4 expression, reduced iron deposition, and inhibited ferroptosis. Meanwhile, rhFGF21 decreased cell apoptosis following acute spinal cord damage. In contrast, FGFR1 inhibitor PD173074 partially reversed the rhFGF21-induced therapeutic effects. Overall, this work revealed that rhFGF21 activates the FGFR1/ß-Klotho pathway to decrease ferroptosis of nerve cells, suggesting that FGF21 could be a new therapeutic target for SCI neurological rehabilitation.

Guanine-rich RNA sequence binding factor 1 regulates neuronal ferroptosis after spinal cord injury in rats via the GPX4 signaling pathway.

Spinal cord injury (SCI) can trigger multiple forms of neuronal cell death. Among these, ferroptosis stands out as a particularly important style of cell death due to its iron overload-dependent lipid peroxidative regulatory mechanism. The guanine-rich RNA sequence binding factor 1 (GRSF1) is an RNA-binding protein that has been implicated in cellular senescence, mitochondrial function, oxidative stress, erythropoiesis, and embryonic brain development. However, the function of GRSF1 in neuronal ferroptosis after SCI remains unclear. Here, we established a SCI rat model in vivo and evaluated the function of GRSF1 on neuronal ferroptosis by inhibiting and overexpressing GRSF1. We firstly verified the protein expression of GRSF1 and GPX4 at different time points after SCI. According of changes in expression, we chose 3 d post SCI to assess the effect of GRSF1 on ferroptosis. We found that GRSF1 expression decreased after SCI. In addition, GRSF1 was mainly localized in the cytoplasm of neurons. The results also showed that overexpression of GRSF1 promoted recovery of neurological functional after SCI. Further investigation revealed that GRSF1 might attenuate neuronal ferroptosis by regulating the GPX4 protein expression levels. In summary, our findings indicate that GRSF1 attenuates injury in SCI and reduces neuron ferroptosis and promotes functional recovery via GPX4.

Inhibition of Connexin43 Improves the Recovery of Spinal Cord Injury Against Ferroptosis via the SLC7A11/GPX4 Pathway.

Ferroptosis plays a key role in the process of spinal cord injury (SCI). As a signal amplifier, connexin 43 (CX43) participates in cell death signal transduction and aggravates the propagation of injury. However, it remains unclear whether CX43 plays a regulatory role in ferroptosis after SCI. The SCI rat model was established by an Infinite Vertical Impactor to investigate the role of CX43 in SCI-induced ferroptosis. Ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, and a CX43-specific inhibitor (Gap27) were administered by intraperitoneal injection. Behavioral analysis was assessed according to the Basso-Beattie-Bresnahan (BBB) Motor Rating Scale and the inclined plate test. The levels of ferroptosis-related proteins were estimated by qRT-PCR and western blotting, while the histopathology of neuronal injury induced by SCI was evaluated by immunofluorescence, Nissl, FJB and Perl's Blue staining. Meanwhile, transmission electron microscopy was used to observe the ultrastructural changes characteristic of ferroptosis. Gap27 strongly inhibited ferroptosis and therefore improved the functional recovery of SCI, which was similar to the treatment of Fer-1. Notably, the inhibition of CX43 decreased P-mTOR/mTOR expression and reversed the decrease in SLC7A11 induced by SCI. As a result, the levels of GPX4 and glutathione (GSH) increased, while the levels of the lipid peroxidation products 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) decreased. Together, inhibition of CX43 could alleviate ferroptosis after SCI. These findings reveal a potential mechanism of the neuroprotective role of CX43 after SCI and provide a new theoretical basis for clinical transformation and application.

Biomechanical assessment of disease outcome in surgical interventions for medial meniscal posterior root tears: a finite element analysis.

BACKGROUND: The adverse consequences of medial meniscus posterior root tears have become increasingly familiar to surgeons, and treatment strategies have become increasingly abundant. In this paper, the finite element gait analysis method was used to explore the differences in the biomechanical characteristics of the knee joint under different conditions. METHODS: Based on CT computed tomography and MR images, (I) an intact knee (IK) model with bone, cartilage, meniscus and main ligaments was established. Based on this model, the posterior root of the medial meniscus was resected, and (ii) the partial tear (PT) model, (iii) the entire radial tear (ERT) model, and (iv) the entire oblique tear (EOT) model were established according to the scope and degree of resection. Then, the (v) meniscus repair (MR) model and (vi) partial meniscectomy (PM) model were developed according to the operation method. The differences in stress, displacement and contact area among different models were evaluated under ISO gait loading conditions. RESULTS: Under gait loading, there was no significant difference in the maximum stress of the medial and lateral tibiofemoral joints among the six models. Compared with the medial tibiofemoral joint stress of the IK model, the stress of the PM model increased by 8.3%, while that of the MR model decreased by 18.9%; at the same time, the contact stress of the medial tibiofemoral joint of the ERT and EOT models increased by 17.9 and 25.3%, respectively. The displacement of the medial meniscus in the ERT and EOT models was significantly larger than that in the IK model (P < 0.05), and the tibial and femoral contact areas of these two models were lower than those of the IK model (P < 0.05). CONCLUSIONS: The integrity of the posterior root of the medial meniscus plays an important role in maintaining normal tibial-femoral joint contact mechanics. Partial meniscectomy is not beneficial for improving the tibial-thigh contact situation. Meniscal repair has a positive effect on restoring the normal biomechanical properties of the medial meniscus.

Clinical significance of microRNA-1180-3p for colorectal cancer and effect of its alteration on cell function.

An early diagnosis and effective prognostic factors would greatly reduce the mortality rate of colorectal cancer (CRC). This research is intended to complete the evaluation of the prognostic value and potential role of miR-1180-3p in CRC. The miR-1180-3p levels were reduced in CRC patients' tissues, blood, and human CRC cell lines. The ability of miR-1180-3p was explored in discrimination of CRC patients and healths and the value in overall survival estimate. The effect of miR-1180-3p dysregulation on the CRC cellular function was investigated. miR-1180-3p is downregulated in CRC tissues, blood and cells than normal ones. This lower expression was correlated with vascular invasion, lymph node metastasis, and TNM stage. With the use of ROC curve, miR-1180-3p showed discriminating ability in CRC patients and healthy subjects. With the result of Kaplan-Meier analysis and multi-multivariate Cox analysis, miR-1180-3p was an independent predictor for CRC patients' overall survival. Utilizing CCK-8, Transwell and matrigel assays, overexpression of miR-1180-3p reduced cancer cell proliferation and mobility, but induced apoptosis, by targeting COL12A1. miR-1180-3p might function as a suppressor in CRC progression and allowed the discovery of a new biomarker for diagnosis, prognosis and therapy target for CRC.

A novel CX3CR1 inhibitor AZD8797 facilitates early recovery of rat acute spinal cord injury by inhibiting inflammation and apoptosis.

The present study aimed to evaluate the effect of the CX3CR1 inhibitor AZD8797 in early recovery after acute SCI and elucidate its potential mechanism in blocking inflammation and apoptosis. Adult rats were sacrificed after 3, 7, 10, or 14 days of SCI. The injured spinal tissues were collected for assessing C­X3­C motif chemokine ligand 1(CX3CL1)/C­X3­C motif chemokine receptor 1 (CX3CR1) expression at each time point via western blotting (WB) and quantitative PCR. The cellular localization of the proteins was detected by immunofluorescence. Another batch of rats (subdivided into sham, injury model, AZD8797 and methylprednisolone groups) were used to evaluate locomotive recovery with a Basso Beattie Bresnahan score. Based on the expression level of CX3CR1, these rats were sacrificed at the most prominent stage of CX3CR1 expression (10 days after SCI), for assessing the serum levels of tumor necrosis factor­α/interleukin (IL)­6/IL­1ß and the expression of CX3CL1/CX3CR1/caspase 3/Bcl­2/Bax in the spinal cord tissues through WB and ELISA. Additionally, apoptosis and necrosis in the injured spinal cord were evaluated by terminal deoxynucleotidyl transferase­-mediated dUTP nick­end labeling staining/fluoro­jade B staining. Expression levels of both CX3CR1 and CX3CL1 reached their peak 10 days after the injury, followed by a dramatic downward trend at 14 days. The enhanced expression of CX3CR1 was detected in astrocytes and microglia of the injured spinal cord. AZD8797 improved locomotive recovery after 10 days of SCI and was as effective as methylprednisolone. The effect of AZD8797 was mediated by suppressing apoptosis, necrosis and inflammatory responses, as assessed by WB/ELISA and morphological examinations. The current study has demonstrated that AZD8797 can effectively block overwhelming inflammation, apoptosis and necrosis after SCI and facilitate early recovery of locomotive function.

Integrative identification of unexpected kinase-inhibitor interactions in the MAPK-mediated proliferation and differentiation of Mc3T3-E1 osteoblasts.

Kinase-targeted therapy is a new and promising approach to disease treatment. However, some kinase inhibitors have been observed to cause an off-target adverse risk for skeletal system by influencing the growth of osteoblasts. It is known that the proliferation and differentiation of osteoblasts are essentially regulated by MAPK signaling pathway, and many off-target events are considered to influence this pathway. Here, the unexpected MAPK-inhibitor interactions in mouse MC3T3-E1 osteoblastic cells were investigated in detail using an integrative protocol. With bioinformatics analysis we successfully profiled a systematic noncognate interaction spectrum for off-target kinase inhibitors against mouse MAPK kinases, from which 13 potential MAPK-inhibitor interactions were identified. The inhibitors Nilotinib, Dasatinib and Bosutinib were suggested as promising candidates; their cytotoxicity on MC3T3-E1 and inhibitory activity against MAPK kinase were tested at cellular and molecular levels, respectively. We also tested two known MAPK inhibitors SP600125 and SB203580 as positive controls. Consequently, the Dasatinib was found to have high off-target risk for unexpectedly targeting osteoblast MAPK signaling pathway.

Influence of N-acetyl cysteine (NAC) and 2-methylene-1,3-dioxepane (MDO) on the properties of polymethyl methacrylate (PMMA) bone cement.

The properties of polymethyl methacrylate (PMMA) bone cement make it a popular bone filling material. However, its disadvantages, such as lack of biodegradability and osteogenesis, restrict its clinical application. Studies have indicated the osteogenic properties of N-acetyl cysteine (NAC) and the biodegradability of 2-methylene-1,3-dioxepane/methyl methacrylate-based (MDO/MMA) copolymers. In this study, we developed bioactive PMMA cements through modification with fixed concentrations of NAC and different proportions of MDO. The purpose of this study was to compare the mechanical properties, morphology, NAC release, biocompatibility, degradability and mineralization capability of modified bone cements with those of conventional cement. The specific-modified specimens (NAC-p (5% MDO-co-MMA)) exhibited a lower bending modulus but had little effect on compressive strength. This material was morphologically compact and nonporous, similar to conventional PMMA bone cement. NAC could be released from NAC-p (5% MDO-co-MMA) continuously and appropriately. NAC-p (5% MDO-co-MMA) was biologically safe and showed satisfactory tissue compatibility. Ester was introduced into the polymer, which reinforced the degradation properties of NAC-p (5% MDO-co-MMA). NAC-p (5% MDO-co-MMA) enhanced the mineralization capability of osteoblastic cells.

Minimally invasive versus conventional dynamic hip screw for the treatment of intertrochanteric fractures in older patients.

The purpose of this study was to compare minimally invasive and conventional dynamic hip screw techniques for the treatment of intertrochanteric fractures in older patients. Relevant randomized, controlled studies were included. The methodological quality was assessed, and data were extracted independently. Five studies (353 fractures) that compared minimally invasive and conventional dynamic hip screw techniques were included. The rates of serious postoperative complications, operative time (minutes), hemoglobin decrease (g/dL), postoperative Harris Hip Scores, and length of stay (days) were the outcomes of interest. A lower rate of serious postoperative complications was correlated with the minimally invasive dynamic hip screw group compared with the conventional dynamic hip screw group (relative risk, 0.35; 95% confidence interval [CI], 0.16, 0.78), average operative time (weighted mean difference, -16.32; 95% CI, -28.78 to -3.86), hemoglobin decrease (weighted mean difference, -1.44; 95% CI, -1.98 to -0.89), and length of stay (weighted mean difference, -3.72; 95% CI, -5.44 to -2.01) were lower in the minimally invasive dynamic hip screw group, and the postoperative Harris Hip Score (weighted mean difference, 1.42; 95% CI, 0.23 to 2.60) was higher in the minimally invasive dynamic hip screw group.