Quercetin-3-O-glc-1-3-rham-1-6-glucoside decreases Aß production, inhibits Aß aggregation and neurotoxicity, and prohibits the production of inflammatory cytokines.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with the hallmark of aggregation of beta-amyloid (Aß) into extracellular fibrillar deposition. Accumulating evidence suggests that soluble toxic Aß oligomers exert diverse roles in neuronal cell death, oxidative stress, neuroinflammation, and the eventual pathogenesis of AD. Aß is derived from the sequential cleavage of amyloid-ß precursor protein (APP) by ß-secretase (BACE1) and γ-secretase. The current effect of single targeting is not ideal for the treatment of AD. Therefore, developing multipotent agents with multiple properties, including anti-Aß generation and anti-Aß aggregation, is attracting more attention for AD treatment. Previous studies indicated that Quercetin was able to attenuate the effects of several pathogenetic factors in AD. Here, we showed that naturally synthesized Quercetin-3-O-glc-1-3-rham-1-6-glucoside (YCC31) could inhibit Aß production by reducing ß-secretase activity. Further investigations indicated that YCC31 could suppress toxic Aß oligomer formation by directly binding to Aß. Moreover, YCC31 could attenuate Aß-mediated neuronal death, ROS and NO production, and pro-inflammatory cytokines release. Taken together, YCC31 targeting multiple pathogenetic factors deserves further investigation for drug development of AD.

Design of a novel lateral mass screw-plate system for the treatment of unstable atlas fractures: a finite element analysis.

BACKGROUND: Osteosynthesis of unstable atlas fractures preserves joint motion and therefore has a distinct advantage over a range of treatment procedures. To prevent the potential disadvantages associated with osteosynthesis, a new atlas lateral mass screw-plate (LMSP) system has been designed. However, the biomechanical role of using the LMSP system in atlas internal fixation is not known. The aim of this study was to compare the biomechanical stability of a new LMSP with traditional posterior screw and rod (PSR) fixation techniques on the occipitocervical junction (C0-C2) through finite element analysis. METHODS: A nonlinear C0-C2 finite element model of the intact upper cervical spine was developed and validated. The unstable model using the PSR system was then compared with the model using the LMSP system for fixation. A vertical load of 40 N was applied to the C0 to simulate head weight, while a torque of 1.5 Nm was applied to the C0 to simulate flexion, extension, lateral bending, and axial rotation. RESULTS: The range of motion of both systems was close to the intact model. Compared with the LMSP system model, the PSR system model increased flexion, extension, lateral bending, and axial rotation by 4.9%, 3.0%, 5.0%, and 29.5% in the C0-C1 segments, and 4.9%, 2.7%, 2.4%, and 22.6% in the C1-C2, respectively. In flexion, extension, and lateral bending motion, the LMSP system model exhibited similar stress to the PSR system model, while in axial rotation, the PSR system model exhibited higher stress. CONCLUSIONS: The findings of our study indicate that the two tested system models provide comparable stability. However, better stability was achieved during axial rotation with the LMSP system, and in this system, the maximum von Mises stress was less than that of the PSR one. As the atlantoaxial joint functions primarily as a rotational joint, the use of the LMSP system may provide a more stable environment for the joint that has become unstable due to fracture.

Direct osteosynthesis in the treatment of atlas burst fractures: a systematic review.

PURPOSE: The treatment of unstable atlas fractures remains a controversial topic. The study aims at assessing the prognosis and efficacy of osteosynthesis for unstable atlas fractures through a review of the current literature and additionally aims to compare outcomes between the transoral and posterior approaches. METHODS: A systematic review of databases including PubMed, EMBASE, Cochrane, Web of Science, CNKI, and Wanfang was conducted. Titles and abstracts were screened by two reviewers to identify studies meeting pre-defined inclusion criteria for comprehensive analysis. RESULTS: The systematic review included 28 articles, 19 employing the posterior approach and 9 utilizing the transoral approach. It covered osteosynthesis in 297 patients with unstable atlas fractures, comprising 169 treated via the posterior approach and 128 via the transoral approach. Analysis revealed high healing rates and clinical improvement in both approaches, evidenced by improvements in the visual analog scale, range of motion, atlantodens interval, and lateral displacement distance post-surgery. CONCLUSION: Osteosynthesis offers effective treatment for unstable atlas fractures. Both transoral and posterior approaches can achieve good clinical outcomes for fracture, and biomechanical studies have confirmed that osteosynthesis can maintain the stability of the occipitocervical region, preserve the motor function of the atlantoaxial and occipito-atlantoaxial joints, and greatly improve the quality of life of patients. However, variations exist in the indications and surgical risks associated with each method, necessitating their selection based on a thorough clinical evaluation of the patient's condition.

C1 anatomy and dimensions relative to pedicle screw placement.

The recent C1 pedicle screw technique for upper cervical vertebral stabilization allows longer screws to be implanted by setting the screw entry point through the posterior arch of C1, which could provide better biomechanics. However, there is controversy regarding the placement of C1 pedicle screws at different angles. We retrospectively reviewed the computed tomography (CT) scans of 300 patients. The trajectories of medial inclination of 0°, 5°, 10°, and 15° and trajectory of the maximum medial inclination angle were designed for each C1 pedicle on CT images. Screw track length at each angle, the angle of maximum medial inclination, pedicle height, distance from the screw entry point to the midpoint of the C1 posterior tubercle, and screw perforation rate at each angle were measured. The average maximum inclination angle was 17.01°, the maximum inclination angle screw track length was 31.05 mm, and the distance from the screw entry point to the midpoint of the C1 posterior nodule was 21.65 mm. The screw perforation rate was 46.73% at 15° of medial inclination, but only 5.61% at 10°, and no screw perforation at 5°. 26.47% C1 pedicle height < 4 mm. There was no significant difference between the measured data on the left and right sides(P > 0.05), and the measurement of female patients was usually smaller and significantly different from that of male patients(p < 0.05). Our data indicate that a reasonable screw inclination angle of 10° and the safety zone of screw angle can provide safety and avoid screw perforation. However, personalized measurement before surgery is essential.

Associations between the morphological parameters of proximal tibiofibular joint (PTFJ) and changes in tibiofemoral joint structures in patients with knee osteoarthritis.

BACKGROUND: To describe the longitudinal associations between the morphological parameters of proximal tibiofibular joint (PTFJ) and joint structural changes in tibiofemoral compartments in patients with knee osteoarthritis (OA). METHODS: The participants were selected from the Vitamin D Effects on Osteoarthritis (VIDEO) study. PTFJ morphological parameters were measured on coronal and sagittal MRI. The contacting area (S) of PTFJ and its projection areas onto the horizontal (load-bearing area, Sτ), sagittal (lateral stress-bolstering area, Sφ), and coronal plane (posterior stress-bolstering area, Sυ) were assessed. Knee structural abnormalities, including cartilage defects, bone marrow lesions (BMLs), and cartilage volume, were evaluated at baseline and after 2 years. Log binominal regression models and linear regression models were used to assess the associations between PTFJ morphological parameters and osteoarthritic structural changes. RESULTS: In the longitudinal analyses, the S (RR: 1.45) and Sτ (RR: 1.55) of PTFJ were significantly and positively associated with an increase in medial tibial (MT) cartilage defects. The Sτ (ß: - 0.07), Sυ (ß: - 0.07), and S (ß: - 0.06) of PTFJ were significantly and negatively associated with changes in MT cartilage volume. The Sτ (RR: 1.55) of PTFJ was positively associated with an increase in MT BMLs, and Sφ (RR: 0.35) was negatively associated with an increase in medial femoral BMLs. CONCLUSIONS: This longitudinal study suggests that higher load-bearing area of PTFJ could be a risk factor for structural changes in medial tibiofemoral (MTF) compartment in knee OA. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01176344 Anzctr.org.au Identifier: ACTRN12610000495022 Date of registration: 7 May 2010.