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The work is focused on the design of drugs that prevent and treat Alzheimer’s disease (AD) and its complications. A series of 3–(4-aminophenyl)-coumarin derivatives designed, synthesised, fully characterised and evaluated in vitro/vivo. The biological assay experiments showed that some compounds displayed a clearly selective inhibition for acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Among all compounds, compound 4m exhibited the highest AChE inhibition with an IC50 value of 0.091 ± 0.011 µM and compound 4k exhibited the highest BuChE inhibition with an IC50 value of 0.559 ± 0.017 µM. A zebrafish behaviour analyser (Zebrobox) was used to determine the behavioural effects of the active compound on the movement distance of the aluminium chloride-induced zebrafish. Compound 4m offered a potential drug design concept for the development of therapeutic or preventive agents for AD and its complications.

Abstract Background Circulating thyroid-stimulating hormone (TSH) levels within the normal reference range can affect the cardiovascular system. The present study investigated the prognostic value of normal TSH levels in patients presenting with acute myocardial infarction (AMI) following percutaneous coronary intervention (PCI). Methods Between January 2013 and July 2019, 1240 patients with AMI and normal thyroid function were enrolled and classified according to TSH tertile. The trial endpoint was all-cause mortality. The integrated discrimination index (IDI) and the net reclassification index (NRI) were used to assess the combined predictive values of the TSH levels and the Global Registry of Acute Coronary Events (GRACE) scores. Results After a median 44.25-month follow-up, 195 individuals died. Even after covariate adjustment by multivariate Cox regression (HR: 1.56; 95% CI 1.08–2.25; P = 0.017), the patients in the third TSH tertile were at the highest risk of all-cause mortality. A subgroup analysis revealed significant interactions between the TSH levels and the GRACE scores (high risk vs. low/medium risk) (P = 0.019). The addition of the TSH levels to the GRACE scores substantially improved the prediction of all-cause mortality, especially for high-risk patients (NRI = 0.239; IDI = 0.044; C-statistic value range 0.649–0.691; all significant). Conclusions The third TSH tertile is associated with a higher incidence of all-cause mortality than the first TSH tertile in high-risk patients presenting with AMI after PCI.

The management strategies of thoracolumbar (TL) burst fractures include posterior, anterior, and combined approaches. However, the rigid constructs pose a risk of proximal junctional failure. In this study, we aim to systemically evaluate the biomechanical performance of different TL reconstruction constructs using finite element analysis. Furthermore, we investigate the motion and the stress on the proximal junctional level adjacent to the constructs. We used a T10-L3 finite element model and simulated L1 burst fracture. Reconstruction with posterior instrumentation (PI) alone (U2L2 and U1L1+(intermediate screw) and three-column spinal reconstruction (TCSR) constructs (U1L1+PMMA and U1L1+Cage) were compared. Long-segment PI resulted in greater global motion reduction compared to constructs with short-segment PI. TCSR constructs provided better stabilization in L1 compared to PI alone. Decreased intradiscal and intravertebral pressure in the proximal level were observed in U1L1+IS, U1L1+PMMA, and U1L1+Cage compared to U2L2. The stress and strain energy of the pedicle screws decreased when anterior reconstruction was performed in addition to PI. We showed that TCSR with anterior reconstruction and SSPI provided sufficient immobilization while offering additional advantages in the preservation of physiological motion, the decreased burden on the proximal junctional level, and lower risk of implant failure.

Objectives: To evaluate the effect of thrombus aspiration (TA) strategy on the outcomes and its interaction with D-dimer levels in patients with ST-segment elevation myocardial infarction (STEMI) during primary percutaneous coronary intervention (PCI) in “real-world” settings.Materials and Methods: This study included 1,295 patients with STEMI who had undergone primary PCI with or without TA between January 2013 and June 2017. Patients were first divided into a TA+PCI group and a PCI-only group, and the baseline characteristics and long-term mortality between the two groups were analyzed. Furthermore, we studied the effect of TA on the clinical outcomes of patients grouped according to quartiles of respective D-dimer levels. The primary outcome was all-cause mortality, and the secondary outcomes were new-onset heart failure (HF), rehospitalization, re-PCI, and stroke.Results: In the original cohort, there were no significant differences in all-cause mortality between the TA+PCI and PCI-only groups (hazard ratio, 0.789; 95% confidence interval, 0.556–1.120; p = 0.185). After a mean follow-up of 2.5 years, the all-cause mortality rates of patients in the TA + PCI and PCI-only groups were 8.5 and 16.2%, respectively. Additionally, differences between the two groups in terms of the risk of HF, re-PCI, rehospitalization, and stroke were non-significant. However, after dividing into quartiles, as the D-dimer levels increased, the all-cause mortality rate in the PCI group gradually increased (4.3 vs. 6.0 vs. 7.0 vs. 14.7%, p < 0.001), while the death rate in the TA+PCI group did not significantly differ (4.6 vs. 5.0 vs. 4.0 vs. 3.75%, p = 0.85). Besides, in the quartile 3 (Q3) and quartile 4 (Q4) groups, the PCI-only group was associated with a higher risk of all-cause mortality than that of the TA+PCI group (Q3: 4.0 vs. 7.0%, p = 0.029; Q4: 3.75 vs. 14.7%, p < 0.001). Moreover, the multivariate logistic regression analysis demonstrated that TA is inversely associated with the primary outcome in the Q4 group [odds ratio (OR), 0.395; 95% CI, 0.164–0.949; p = 0.038].Conclusions: The findings of our real-world study express that routine manual TA during PCI in STEMI did not improve clinical outcomes overall. However, patients with STEMI with a higher concentration of D-dimer might benefit from the use of TA during primary PCI. Large-scale studies are recommended to confirm the efficacy of TA.