RESUMO
Long-term exposure to lead (Pb) can result in chronic damage to the body through accumulation in the central nervous system (CNS) leading to neurodegenerative diseases, such as Alzheimer's disease (AD). This study delves into the intricate role of miR-671/CDR1as regulation in the etiology of AD-like lesions triggered by chronic Pb exposure in adult mice. To emulate the chronic effects of Pb, we established a rodent model spanning 10 months of controlled Pb administration, dividing 52 C57BL/6J mice into groups receiving varying concentrations of Pb (1, 2, or 4 g/L) alongside an unexposed control. Blood Pb levels were monitored using serum samples to ensure accurate dosing and to correlate with observed toxicological outcomes. Utilizing the Morris water maze, a robust behavioral assay for assessing cognitive functions, we documented a dose-dependent decline in learning and memory capabilities among the Pb-exposed mice. Histopathological examination of the hippocampal tissue revealed tell-tale signs of AD-like neurodegeneration, characterized by the accumulation of amyloid plaques and neurofibrillary tangles. At the molecular level, a significant upregulation of AD-associated genes, namely amyloid precursor protein (APP), ß-secretase 1 (BACE1), and tau, was observed in the hippocampal tissue of Pb-exposed mice. This was accompanied by a corresponding surge in the protein levels of APP, BACE1, amyloid-ß (Aß), and phosphorylated tau (p-tau), further implicating Pb in the dysregulation of these key AD markers. The expression of CDR1as, a long non-coding RNA implicated in AD pathogenesis, was found to be suppressed in Pb-exposed mice. This observation suggests a potential mechanistic link between Pb-induced neurotoxicity and the dysregulation of the CDR1as/miR-671 axis, which warrants further investigation. Moreover, our study identified a dose-dependent alteration in the intracellular and extracellular levels of the transcription factor nuclear factor-kappa B (NF-κB). This finding implicates Pb in the modulation of NF-κB signaling, a pathway that plays a pivotal role in neuroinflammation and neurodegeneration. In conclusion, our findings underscored the deleterious effects of Pb exposure on the CNS, leading to the development of AD-like pathology. The observed modulation of NF-κB signaling and miR-671/CDR1as regulation provides a plausible mechanistic framework for understanding the neurotoxic effects of Pb and its potential contribution to AD pathogenesis.
RESUMO
Background: The treatment of unstable femoral neck fractures (FNFs) remains a challenge. In this study, a new cannulated screw for unstable FNFs was designed to provide a new approach for the clinical treatment of these injuries, and its biomechanical stability was analyzed using finite element analysis and mechanical tests. Methods: An unstable FNF model was established. An internal fixation model with parallel inverted triangular cannulated screws (CSs) and a configuration with two superior cannulated screws and one inferior new cannulated screw (NCS) were used. The biomechanical properties of the two fixation methods were compared and analyzed by using finite element analysis and mechanical tests. Results: The NCS model outperformed the CSs model in terms of strain and stress distribution in computer-simulated reconstruction of the inverted triangular cannulated screw fixation model for unstable FNFs. In the biomechanical test, the NCS group showed significantly smaller average femoral deformation (1.08 ± 0.15 mm vs. 1.50 ± 0.37 mm) and fracture line displacement (1.43 ± 0.30 mm vs. 2.01 ± 0.47 mm). In the NCS group, the mean stiffness was significantly higher than that in the CSs group (729.37 ± 82.20 N/mm vs. 544.83 ± 116.07 N/mm), and the mean compression distance was significantly lower than that in the CSs group (2.87 ± 0.30 mm vs. 4.04 ± 1.09 mm). Conclusion: The NCS combined with two ordinary cannulated screws in an inverted triangle structure to fix unstable FNFs can provide better biomechanical stability than CSs and exhibit a length- and angle-stable construct to prevent significant femoral neck shortening.
RESUMO
OBJECTIVE: To investigate the application of tranexamic acid in the treatment of intertrochanteric fracture. METHODS: From January 2017 to October 2019, 100 patients with intertrochanteric fracture were randomly divided into observation group (48 cases) and control group(52 cases). All patients received the same surgical treatment. The control group was given tranexamic acid 20 minutes before operation, and 15 mg/kg diluted in 250 ml sodium chloride injection, intravenous drip;the observation group was given tranexamic acid 0.5 g dissolved in 20 ml normal saline injected into femoral bone marrow cavity for local treatment on the basis of the control group. The blood loss, operation time and postoperative hospital stay were compared between two groups. Hematocrit, hemoglobin, D-dimer and fibrinogen levels were analyzed before and after operation, and the incidence of thrombotic complications was observed. RESULTS: The total blood loss, dominant blood loss, hidden blood loss and postoperative drainage volume of the observation group were significantly lower than those of the control group (P<0.05), and the postoperative hospital stay was significantly shorter than that of the control group (P<0.05). The postoperative hemoglobin and hematocrit of two groups were significantly lower than those before operation (P<0.05), while the postoperative hemoglobin and hematocrit of the observation group were significantly higher than those of the control group (P<0.05). The incidence of thrombotic complications in the observation group was 10.42%, which was not significantly different from that in the control group (11.54%)(P>0.05). CONCLUSION: Tranexamic acid combined with systemic and local application has important clinical significance in reducing perioperative blood lossand blood cell loss in patients with intertrochanteric fracture, and has good safety.
