Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

Objective To explore the relationship of changes in bone mineral density and bone me-tabolism indicators with osteoporosis in elderly patients with hemiplegia after cerebral infarction.Methods A total of 197 elderly patients suffering post-stroke hemiplegia admitted to our hospital were enrolled between February 2018 and February 2021.Their bone mineral density and bone metabolism indicators were analyzed based on gender,disease course and hemiplegia severity.According to disease severity,they were divided into mild group(112 cases),moderate group(62 cases)and severe group(32 cases).Results Among the 197 elderly patients,83(42.13％)had osteoporosis.The males had significantly higher bone mineral density of proximal femur and levels of bone alkaline phosphatase(BALP)and osteocalcin,and lower levels of serum type Ⅰ collagen(CICP)and C-terminal telopeptides of type Ⅰ collagen(CTXI)than the females(P＜0.01,P＜0.05).Compared with the patients with hemiplegia course for 3-6 months,bone mineral density values of greater trochanter and total hip,and levels of BALP and osteocalcin were obviously de-creased,while levels of CICP and CTXI were notably increased in those with the course of 7-12 months and 13-24 months(P＜0.05).Compared with the mild group,bone mineral density val-ues of greater trochanter and total hip,and levels of BALP and osteocalcin were significantly de-creased,while levels of CICP and CTXI were significantly increased in moderate group and severe group(P＜0.05).Compared with the moderate group,bone mineral density values of greater tro-chanter,intertrochanteric site and total hip were significantly decreased in the severe group(P＜0.05).The bone mineral density of above parts was negatively correlated with CICP levels(r=-0.458,r=-0.403,r=-0.355,r=-0.482,P＜0.01)and CTXI levels(r=-0.305,r=-0.291,r=-0.273,r=-0.384,P＜0.05,P＜0.01),while positively correlated with BGP level(r=0.476,r=0.428,r=0.386,r=0.518,P＜0.01).Conclusion The incidence of osteoporosis is quite higher in the elderly patients with post-stroke hemiplegia.There exist bone mineral density decline and abnormal bone metabolism,and their changes are related to gender,course and severi-ty of hemiplegia.

The concept of theranostics, where individual patient-level biological information is used to choose the optimal therapy for that individual, has become more popular in the modern era of ‘personalised’ medicine. With the growth of theranostics, nuclear medicine as a specialty is uniquely poised to grow along with the ever-increasing number of concepts combining imaging and therapy. This special report summarises the status and growth of Theranostic Nuclear Medicine in Singapore.We will cover our experience with the use of radioiodine, radioiodinated metaiodobenzylguanidine, peptide receptor radionuclide therapy, prostate specific membrane antigen radioligand therapy, radium-223 and yttrium-90 selective internal radiation therapy.We also include a section on our radiopharmacy laboratory, crucial to our implementation of theranostic principles. Radionuclide theranostics has seen tremendous growth and we hope to be able to grow alongside to continue to serve the patients in Singapore and in the region.
Hope ; Humans ; Lutetium ; Membranes ; Nuclear Medicine ; Prostate ; Radium ; Receptors, Peptide ; Singapore ; Theranostic Nanomedicine ; Yttrium

The concept of theranostics, where individual patient-level biological information is used to choose the optimal therapy for that individual, has become more popular in the modern era of ‘personalised’ medicine. With the growth of theranostics, nuclear medicine as a specialty is uniquely poised to grow along with the ever-increasing number of concepts combining imaging and therapy. This special report summarises the status and growth of Theranostic Nuclear Medicine in Singapore.We will cover our experience with the use of radioiodine, radioiodinated metaiodobenzylguanidine, peptide receptor radionuclide therapy, prostate specific membrane antigen radioligand therapy, radium-223 and yttrium-90 selective internal radiation therapy.We also include a section on our radiopharmacy laboratory, crucial to our implementation of theranostic principles. Radionuclide theranostics has seen tremendous growth and we hope to be able to grow alongside to continue to serve the patients in Singapore and in the region.

INTRODUCTIONThe 2005 American Association for Study of Liver Diseases (AASLD) diagnostic criteria allow non-invasive diagnosis of hepatocellular carcinoma (HCC) based on their enhancement pattern but we have observed a high incidence of atypical enhancement characteristics in HCC associated with portal vein thrombosis. This study seeks to examine the radiological features of this particular subgroup.

MATERIALS AND METHODSPatients with HCC and portal vein thrombosis who underwent pre-treatment multiphasic CT imaging were drawn from a surgical database. The arterial, portal venous and delayed phase images were assessed qualitatively and quantitatively (with region of interest [ROI] analysis) for lesion hypervascularity and washout. The background enhancement of the left and right lobes of the liver was also quantifi ed by ROI analysis.

RESULTSTwenty-fi ve lesions in 25 patients were selected for analysis. Qualitative analysis showed that 10/25 (40%) lesions demonstrated arterial hypervascularity while 16/25 (64%) lesions showed washout. Ten out of 25 (40%) lesions demonstrated both arterial hypervascularity and washout. Quantitative analysis showed that the average absolute lesion enhancement from precontrast to arterial phases was 49.1 (± 17.1) HU for hypervascular lesions compared to 23.8 (± 16.6) HU for non-hypervascular lesions (P <0.01). The mean absolute enhancement of the background liver parenchyma in the arterial phase was 13.79 (± 7.9) HU for hypervascular lesions compared to 36.6 (± 30.6) HU for non-hypervascular lesions (P = 0.03).

CONCLUSIONA large proportion of HCC with portal vein thrombosis lack characteristic arterial hypervascularity, which may be secondary to compensatory increased arterial supply to the background liver. This is a potential pitfall when applying imaging criteria for diagnosis of HCC.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular ; complications ; diagnostic imaging ; Female ; Humans ; Liver Neoplasms ; complications ; diagnostic imaging ; Male ; Middle Aged ; Pattern Recognition, Automated ; Portal Vein ; diagnostic imaging ; physiopathology ; Retrospective Studies ; Tomography, X-Ray Computed ; methods ; Venous Thrombosis ; diagnostic imaging ; etiology