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.

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.

P2X4 Inhibition reduces microglia inflammation and apoptosis by NLRP3 and improves nervous system defects in rat brain trauma model.

The purinergic receptor P2X4 is an adenosine triphosphate (ATP)-gated cation channel, which plays an essential role in regulating various biological activities in the organism. This study was designed to investigate the potential role and mechanism of P2X4 in the traumatic brain injury (TBI) rat model. Real-time PCR, Western blot, immunofluorescence, apoptosis, brain water content and neurological score analysis were evaluated. We found that the expression level of P2X4 surrounding the injured area of the brain in the TBI rat model increased significantly after 48 h. Following the P2X4 selective antagonist 5-BDBD treatment, the neurological damage after TBI was significantly improved and brain edema was reduced. The inhibition of P2X4 effectively reduced the inflammation and apoptosis of microglia, and NLRP3 may be involved in this process. Our results indicate that inhibition of P2X4 may be a potential therapeutic approach for TBI by reducing the occurrence of inflammation and apoptosis of microglia, alleviating brain edema, and improving neurological deficits.

PI and T9-SPI: New Predictive Factors for Increased Kyphosis of the Thoracolumbar Junction in Thoracolumbar/Lumbar Adolescent Idiopathic Scoliosis.

Objectives: Studies have demonstrated that there is an increased thoracolumbar junction sagittal Cobb angle (TLJS) in thoracolumbar/lumbar adolescent idiopathic scoliosis (AIS) patients. The objectives were to ascertain the correlations between the spinopelvic alignments and TLJS and to explore potential predictive factors for hyperkyphotic TLJS in the sagittal plane in thoracolumbar/lumbar AIS. Methods: A total of 114 AIS patients with thoracolumbar/lumbar curve were included. Cobb angle, apical vertebrae rotation (AVR), thoracic kyphosis (TK), TLJS, lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), T1-spinopelvic inclination (T1-SPI), and T9-spinopelvic inclination (T9-SPI) were measured. After patients were organized into two subgroups based on TLJS, all parameters were compared between the two groups. Correlation analysis and multiple linear regression analysis were performed between the radiologic measurements and TLJS in all patients. Results: There was a significant difference between the non-kyphotic group and kyphotic group in mean Nash-Moe grade, TK, T9-SPI, PI, and SS. Correlation analysis showed that LL, PI, and SS were inversely associated with TLJS. TK, T9-SPI, and Nash-Moe grade were positively related to TLJS. The multiple linear regression analysis showed that TLJS could be predicted by the equation TLJS = -2.322 + 5.585 × Nash-Moe grade + 0.687 × T9-SPI - 0.208 × PI, with an adjusted R2 of 0.410. Conclusion: TLJS was positively correlated with greater AVR in the coronal plane, greater T9-SPI in the sagittal plane and inversely associated with PI among patients with thoracolumbar/lumbar scoliosis. Spine surgeons should pay more attention to the degree of AVR, T9-SPI, and PI when dealing with thoracolumbar/lumbar scoliosis with thoracolumbar junction kyphosis.

Low-dose X-ray irradiation induces morphological changes and cytoskeleton reorganization in osteoblasts.

Recently, research into the biological effects of low dose X-ray irradiation (LDI) has been a focus of interest. Numerous studies have suggested that cells exhibit different responses and biological effects to LDI compared with high doses. Preliminary studies have demonstrated that LDI may promote osteoblast proliferation and differentiation in vitro, thereby accelerating fracture healing in mice. However, the exact mechanism of action by which LDI exerts its effects remains unclear. Previous studies using microarrays revealed that LDI promoted the expression of genes associated with the cytoskeleton. In the current study, the effect of X-ray irradiation (0.5 and 5 Gy) on the morphology of MC3T3-E1 cells and fiber actin organization was investigated. Osteoblasts were treated with 0, 0.5 and 5 Gy X- ray irradiation, following which changes in the actin cytoskeleton were observed. The levels of RhoA, ROCK, cofilin and phosphorylated-cofilin were measured by reverse transcription-quantitative PCR and western blotting. Subsequently, osteoblasts were pretreated with ROCK specific inhibitor Y27632 to observe the changes of actin skeleton after X-ray irradiation. The results demonstrated that the cellular morphological changes were closely associated with radiation dose and exposure time. Furthermore, the gene expression levels of small GTPase RhoA and its effectors were increased following LDI. These results indicated that the RhoA/Rho-associated kinase pathway may serve a significant role in regulating LDI-induced osteoblast cytoskeleton reorganization.

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.

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.

Treatment With 2-BFI Attenuated Spinal Cord Injury by Inhibiting Oxidative Stress and Neuronal Apoptosis via the Nrf2 Signaling Pathway.

Previous reports showed that 2-(-2-benzofuranyl)-2-imidazoline (2-BFI) has antioxidant, anti-inflammatory and anti-apoptotic effects on neuroprotection in numerous disorders. However, the precise mechanisms remain elusive. The nuclear factor c factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway plays an important and essential role in the antioxidant and anti-inflammatory responses of the cell. Therefore, the purpose of this study was to investigate the potential neuroprotective effects of 2-BFI in a rat model of spinal cord injury (SCI) and to determine whether its neuroprotective effects are associated with the activation of Nrf2. To test this hypothesis, we examined the potential roles of 2-BFI in SCI models which were established in rats using a clip-compression injury method. Our results showed that treatment with 2-BFI twice daily improved locomotion recovery from SCI, which increased Nrf2 expression in both neurons and astrocytes, meanwhile, the level of heme oxygenase-1 (HO-1) also significantly enhanced. In addition, after the treatment with 2-BFI increased levels of superoxidase dismutase (SOD) and glutathione peroxidase (GPx) indicated the antioxidant effect of the drug. Furthermore, the upregulation of Bcl-2 and downregulation of Bax and caspase-3 implied antiapoptotic effects on neuroprotection of 2-BFI, which were verified by the Fluoro-Jade B (FJB) staining and TUNEL staining. Collectively, these results add to a growing body of evidence supporting that 2-BFI may attenuate SCI mediated by activation of the Nrf2/HO-1 signaling pathway.

Coating the plate with antibiotic cement to treat early infection after fracture fixation with retention of the implants: a technical note.

BACKGROUND: Local antibiotic therapy has gained increasing attraction in the prevention and treatment of fracture infection. However, no reports have used local antibiotic therapy in the management of early infection after fracture fixation with retention of implants. METHODS: The present surgical technique report the use of antibiotic impregnated bone cement in the management of early infection after fracture fixation. Initially, the fractures were fixed with plates. The average time from initial procedure to debridement was15 days (range 9 to 25 days). The infections were treated with irrigation, debridement, and retention of the implant. The lateral surface of the plates was coated with antibiotic cement and the bone defect was filled with antibiotic cement spacer after thorough debridement. RESULTS: Ten patients underwent this technique. The mean follow-up was 2.0 years (range 6 months to 4 years). The bone union rate was 100%, and the average time to bone healing was5.5 months.There was recurrence of infection in one patient before bone healing, but the implants were left in place until bone healed, and the infection was eradicated after implant removal. CONCLUSION: Coating the plate with antibiotic cement is a simple technique which may play a role in the management of early infection after fracture fixation.

Dexmedetomidine restores septic renal function via promoting inflammation resolution in a rat sepsis model.

BACKGROUND: Acute kidney injury occurred after sepsis, resulting in high mortality. This research aims to elucidate the mechanistic effect of DEX on the renal inflammation resolution during sepsis in rats. METHODS: The rats were randomly divided into a sham group and the other three cecal ligation and puncture (CLP) model groups, based on different treatments: placebo, DEX and 2-adrenergic receptor (AR) inhibitor atipamezole (AT) treatment (DEX + AT) groups. The survival of septic rats within 24 h was recorded. Tissue pathology, plasma IL-1ß, IL-6, TNF-α, lipoxygenase-5 and lipoxin A4 were evaluated. Western blotting and immunostaining was used to determine expression of TLR4, IκB, IKK, NF-κB p65 and pp65 in kidney tissue. Then qPCR was used to analyze the mRNA expression of renal α2A-AR, α2B-AR and α2C-AR. RESULTS: Rat mortality and kidney inflammation were significantly increased in septic rats. Specifically, IL-1ß, IL-6 and TNF-α plasma levels, NF-κB activity, and TLR4 expression in rat kidney tissues were increased after CLP. In the DEX treatment group, mortality was reduced, histology changes were minor, and lipoxygenase-5, and lipoxin A4 expression were increased. The expression of IL-1ß, IL-6 and TNF-α, NF-κB activity and TLR4 expression in rat kidney tissues were also decreased. These results indicated that DEX treatment alleviates acute kidney injury induced by CLP. However, the effects of DEX were apparently suppressed by atipamezole in the DEX + AT group. CONCLUSION: The current study demonstrated the protective effect of DEX on CLP-induced kidney injury, which may be effective by attenuating NF-κB pathway activation with lipoxin A4.

Effect of intratracheal dexmedetomidine administration on recovery from general anaesthesia after gynaecological laparoscopic surgery: a randomised double-blinded study.

OBJECTIVES: To examine the efficacy of intratracheal dexmedetomidine (Dex) injection for the prevention of the laryngeal response on emergence from general anaesthesia following gynaecological laparoscopic surgery. DESIGN: Prospective, randomised, double-blinded, controlled trial. SETTING: A general hospital, Guangdong Province, China. PARTICIPANTS: All patients who underwent elective laparoscopic gynaecological surgery, aged 18-60 years old, 40-80 kg in weight, American Society of Anesthesiologists class I-II were eligible. Patients were excluded if they had respiratory disease, heart disorders which might represent risk factors of potential complications of Dex such as bradycardia, heart block, coronary heart disease, uncontrolled hypertension or the long-term use of sedative drugs. INTERVENTION: Patients were randomly allocated to either receive intratracheal Dex (DT), intravenous Dex (DV) or intravenous saline (CON, n=30, respectively). In the DT and DV groups, Dex (0.5 µg/kg) was diluted and mixed in 1 or 20 mL of saline, respectively, and injected via the intratracheal or intravenous route 30 min before the completion of the surgery. OUTCOME MEASURES: The primary outcome was the coughing extent among the three groups. Secondary outcomes included awareness time, extubation time, postoperative visual analogue scale and Steward recovery score. RESULTS: Compared with the CON group, the extent of coughing was significantly reduced in both the DV group and the DT group. Furthermore, the mean time to awareness (13.4 (4.3) vs 8.8 (2.9), p<0.001) and the extubation time (14.3 (4.3) vs 8.4 (3.6), p<0.001) were reduced in the DT group. Patients in the DT group also experienced better early recovery quality and less pain than those in the CON group. Furthermore, intratracheal Dex administration contributed to improved stability in haemodynamics with no significant side effects. CONCLUSIONS: Intratracheal Dex administration may avoid untoward laryngeal responses for patients emerging from general anaesthesia after gynaecological laparoscopy. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-15007611.

The inhibition of microRNA-31 weakens acute spinal cord injury through nuclear factor-κB and TGF-ß/Smad 2 in rat.

Therefore, the aim of the present study is to evaluate that the therapeutic potential of microRNA-31 after spinal cord injury (SCI) in rats and to expound the potential neuroprotective mechanisms. In SCI model, microRNA-31 expression was up-regulated, compared with negative group. In vitro model, over-expression of microRNA-31 increases cell apoptosis and inflammation, compared with negative control group. Over-expression of microRNA-31 induced nuclear factor-κB (NF-κB), TGF-ß and p-Smad 2 protein expression in vitro model of SCI, compared with negative control group. NF-κB inhibitor suppressed the effects of microRNA-31 on inflammation of vitro model of SCI. Meanwhile, TGF-ß inhibitor suppressed the effects of microRNA-31 on apoptosis of in vitro model of SCI. The results clearly show that anti-microRNA-31 weakens inflammation and apoptosis by NF-κB and TGF-ß/Smad 2 pathway in SCI.

Unipolar Versus Bipolar Hemiarthroplasty for Displaced Femoral Neck Fractures in Elderly Patients.

Hip replacement using hemiarthroplasty (HA) is a common surgical procedure in elderly patients with femoral neck fractures. However, questions remain regarding the choice of unipolar or bipolar HA. A meta-analysis of randomized, controlled trials (RCTs) was performed to determine whether bipolar HA was associated with lower rates of dislocation, reoperation, acetabular erosion, mortality, and general complications, as well as lower Harris Hip Scores, compared with unipolar HA. The authors searched PubMed and the Cochrane Register of Controlled Trials database, and 8 RCTs (including a total of 1100 patients) were selected for meta-analysis. Risk ratios (RRs) and weighted mean differences (WMDs) from each trial were pooled using random-effects or fixed-effects models depending on the heterogeneity of the included studies. There were no differences in dislocation (RR=1.20; 95% confidence interval [CI], 0.47 to 3.07), reoperation (RR=0.64; 95% CI, 0.33 to 1.26), acetabular erosion (RR=2.29; 95% CI, 0.85 to 6.12), mortality (RR=0.85; 95% CI, 0.63 to 1.13), and general complications (RR=1.05; 95% CI, 0.70 to 1.56). The authors found no difference in postoperative Harris Hip Scores between patients undergoing unipolar vs bipolar HA (WMD=-1.32; 95% CI, -3.29 to 0.65; P=.19). Unipolar and bipolar HA achieved similar clinical outcomes in patients with displaced femoral neck fractures.