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 value of ultrasound imaging characteristics combined with clinical indicators in assessing the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC).Methods:A retrospective analysis was conducted for patients who underwent pancreatic contrast-enhanced ultrasound (CEUS) from September 2017 to October 2023 at Peking Union Medical College Hospital and were diagnosed with PDAC based on pathological findings. Various parameters were recorded, including CA19-9 levels, tumor size, location, morphologic features, echogenicity, presence of internal cystic components, dilatation of the main pancreatic duct, peripheral vascular invasion, CEUS characteristics, presence or absence of liver metastasis, and treatment methods. In April 2024, patient survival information was obtained through telephone follow-up or review of medical records. Based on the results of the cox regression model analysis, a nomogram model of the risk of death was developed. The receiver operating characteristic (ROC) curves were applied to evaluate the predictive efficacy of the model. The calibration curves were plotted to evaluate the accuracy of the model, and clinical decision curves were used to evaluate the clinical benefit of the model.Results:This study included a total of 207 patients with PDAC. As of April 2024, 71 patients were alive and 136 died, with a median survival time of 14 months (95% CI: 12 -17). Multivariate analysis confirmed that the elevated CA19-9 ( HR=1.689, 95% CI: 1.102-2.588), tumor size >4 cm ( HR=1.641, 95% CI: 1.159-2.322), taller-than-wide shapes ( HR=1.450, 95% CI: 1.019-2.065), incomplete hypo-enhancement ( HR=1.618, 95% CI: 1.100-2.380), and liver metastasis ( HR=1.687, 95% CI: 1.175-2.423) were independent risk factors for survival in patients with PDAC. A nomogram model was further constructed for 6-month, 12-month and 3-year survival of patients with PDAC. The areas under the ROC curve were 0.679, 0.705 and 0.815, respectively. The calibration curves suggested that the model was more accurate, and the clinical decision curves showed that the model had a better clinical benefit. Conclusion:The combined use of ultrasound imaging characteristics and clinical indicators could effectively predict the prognosis of PDAC patients. Specifically, tumor size >4 cm, taller-than-wide shapes, incomplete hypo-enhancement, elevated CA19-9, and the presence of liver metastasis are correlated with poorer survival outcomes. The nomogram model constructed on the basis of these factors can be used to assess the survival of patients with PDAC.

Objective:To explore the value of ultrasound imaging characteristics combined with clinical indicators in assessing the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC).Methods:A retrospective analysis was conducted for patients who underwent pancreatic contrast-enhanced ultrasound (CEUS) from September 2017 to October 2023 at Peking Union Medical College Hospital and were diagnosed with PDAC based on pathological findings. Various parameters were recorded, including CA19-9 levels, tumor size, location, morphologic features, echogenicity, presence of internal cystic components, dilatation of the main pancreatic duct, peripheral vascular invasion, CEUS characteristics, presence or absence of liver metastasis, and treatment methods. In April 2024, patient survival information was obtained through telephone follow-up or review of medical records. Based on the results of the cox regression model analysis, a nomogram model of the risk of death was developed. The receiver operating characteristic (ROC) curves were applied to evaluate the predictive efficacy of the model. The calibration curves were plotted to evaluate the accuracy of the model, and clinical decision curves were used to evaluate the clinical benefit of the model.Results:This study included a total of 207 patients with PDAC. As of April 2024, 71 patients were alive and 136 died, with a median survival time of 14 months (95% CI: 12 -17). Multivariate analysis confirmed that the elevated CA19-9 ( HR=1.689, 95% CI: 1.102-2.588), tumor size >4 cm ( HR=1.641, 95% CI: 1.159-2.322), taller-than-wide shapes ( HR=1.450, 95% CI: 1.019-2.065), incomplete hypo-enhancement ( HR=1.618, 95% CI: 1.100-2.380), and liver metastasis ( HR=1.687, 95% CI: 1.175-2.423) were independent risk factors for survival in patients with PDAC. A nomogram model was further constructed for 6-month, 12-month and 3-year survival of patients with PDAC. The areas under the ROC curve were 0.679, 0.705 and 0.815, respectively. The calibration curves suggested that the model was more accurate, and the clinical decision curves showed that the model had a better clinical benefit. Conclusion:The combined use of ultrasound imaging characteristics and clinical indicators could effectively predict the prognosis of PDAC patients. Specifically, tumor size >4 cm, taller-than-wide shapes, incomplete hypo-enhancement, elevated CA19-9, and the presence of liver metastasis are correlated with poorer survival outcomes. The nomogram model constructed on the basis of these factors can be used to assess the survival of patients with PDAC.

Objective To observe the value of contrast-enhanced ultrasound(CEUS)for evaluating blood supply pattern of pancreatic ductal adenocarcinoma(PDAC).Methods A total of 210 single PDAC patients proved by pathology who underwent CEUS and contrast enhanced CT(CECT)examination were retrospectively enrolled.Blood supply patterns of PDAC,i.e.deficient or rich blood supply were evaluated based on findings of CEUS 25 s(CEUS-25 s)and 35 s(CEUS-35 s)after contrast agents injection and CECT,respectively.The evaluation results were compared among different methods.Disease free survival(DFS)and overall survival(OS)of patients with deficient and rich blood supply PDAC shown on CEUS-25 s were followed up and compared.Results CEUS-25 s found 60.00％(126/210)PDAC with deficient blood supply(poor blood supply group),while 40.00％(84/210)with rich blood supply(rich blood supply group).CEUS-35 s showed that the proportion deficient blood supply PDAC increased to 70.48％(148/210,P＜0.05),22 lesions changed from rich blood supply pattern on CEUS-25 s to deficient blood supply pattern.CECT displayed deficient blood supply in 91.90％(193/210)PDAC but rich blood supply in 8.10％(17/210)PDAC,both being significant different compared with results of CEUS-25 s and CEUS-35 s(both P＜0.05).Fifteen-five cases in deficient blood supply group and 39 in rich blood supply group completed 12(8,25)months'follow-up,and the median DFS of patients in deficient blood supply group and rich blood supply group was 8(6,10)and 12(7,17)months,respectively,with the median OS of 14(9,17)and 19(16,24)months,respectively.The median DFS and OS in poor blood supply group were both shorter than those in rich blood supply group(x2=17.227,27.166,both P＜0.001).Conclusion CEUS had important clinical value for evaluating blood supply pattern of PDAC.

Objective To observe the value of contrast-enhanced ultrasound(CEUS)for evaluating blood supply pattern of pancreatic ductal adenocarcinoma(PDAC).Methods A total of 210 single PDAC patients proved by pathology who underwent CEUS and contrast enhanced CT(CECT)examination were retrospectively enrolled.Blood supply patterns of PDAC,i.e.deficient or rich blood supply were evaluated based on findings of CEUS 25 s(CEUS-25 s)and 35 s(CEUS-35 s)after contrast agents injection and CECT,respectively.The evaluation results were compared among different methods.Disease free survival(DFS)and overall survival(OS)of patients with deficient and rich blood supply PDAC shown on CEUS-25 s were followed up and compared.Results CEUS-25 s found 60.00％(126/210)PDAC with deficient blood supply(poor blood supply group),while 40.00％(84/210)with rich blood supply(rich blood supply group).CEUS-35 s showed that the proportion deficient blood supply PDAC increased to 70.48％(148/210,P＜0.05),22 lesions changed from rich blood supply pattern on CEUS-25 s to deficient blood supply pattern.CECT displayed deficient blood supply in 91.90％(193/210)PDAC but rich blood supply in 8.10％(17/210)PDAC,both being significant different compared with results of CEUS-25 s and CEUS-35 s(both P＜0.05).Fifteen-five cases in deficient blood supply group and 39 in rich blood supply group completed 12(8,25)months'follow-up,and the median DFS of patients in deficient blood supply group and rich blood supply group was 8(6,10)and 12(7,17)months,respectively,with the median OS of 14(9,17)and 19(16,24)months,respectively.The median DFS and OS in poor blood supply group were both shorter than those in rich blood supply group(x2=17.227,27.166,both P＜0.001).Conclusion CEUS had important clinical value for evaluating blood supply pattern of PDAC.

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