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 understand the clinical manifestations, laboratory characteristics, and treatment of Staphylococcus aureus ( Sa) infection in children, and explore the predictive value of lymphocyte count, neutrophil to lymphocyte ratio(NLR), and high-sensitivity C-reactive protein to albumin ratio(CAR) in patient with secondary bloodstream infection(BSI). Methods:A retrospective analysis was conducted on 72 children with Sa infection admitted to the Nanchong Hospital of Beijing Anzhen Hospital Affiliated to Capital Medical University from January 2020 to April 2024. Clinical data including basic information, drug resistance, antibiotic treatment were collected. Differences in laboratory test results and inflammatory indicators were analyzed. The influencing factors of Staphylococcus aureus bacteraemia(SAB) in pediatric patients were analyzed using univariate/multivariate Logistic regression and correlation analysis. The predictive value was analyzed by receiver operating characteristic curve (ROC) and area under curve (AUC). Results:Seventy-two patients were selected, of whom 60 (83.33%) had skin and soft tissue infections (SSTIs), mainly community-associated Staphylococcus aureus(CA-SA)(50 cases), including 16 community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) cases (32.00%, 16/50). The detection rate of MRSA was 37.50% (27/72). The resistance rates of Sa to penicillin, clindamycin, and erythromycin were 97.22%(70/72), 69.44%(50/72), and 69.44%(50/72), respectively. Compared with the SSTIs group, the levels of lymphocyte count in children with bone and joint infections were significantly lower, while NLR and CAR levels were higher ( P<0.05). Fourteen patients had secondary SAB. In the secondary SAB group, lymphocyte counts were lower, while inflammatory indicators (NLR, CAR), and D-dimer were higher. CAR and NLR are positively correlated with the occurrence of bloodstream infections ( P<0.05). CAR ( OR=4.866, 95% CI: 1.37-17.25) and NLR ( OR=1.293, 95% CI: 1.032-1.620) were independent risk factors for secondary bloodstream infection, and ROC curve results showed that the combination of the two indicators had a higher sensitivity (0.929) and AUC (0.909) than individual testing. After undergoing effective treatment, the levels of CAR and NLR in the children in the secondary SAB group were significantly reduced. Wound infection patients underwent debridement treatment in 38 cases (52.78%, 38/72), while antibiotic treatment still primarily used first- and second-generation cephalosporins. For patients with secondary bloodstream infection, vancomycin was the first choice. Conclusions:Children′s wound infections with Sa primarily involve skin and soft tissue infections, commonly seen in CA-SA. NLR and CAR are independent risk factors for children with secondary bloodstream infection, and their combined detection has certain value for early diagnosis.

Objective:To describe the body mass index (BMI) level and long-term trends of Chinese older adults aged 65 and above.Methods:Older adults aged 65 and above from six waves (2002-2018) of the China Longitudinal Healthy Longevity Survey were selected as the study population. Multiple cross-sectional design with six survey waves conducted in 2002, 2005, 2008, 2011, 2014, and 2018 was adopted, enrolling 15 647, 15 358, 15 622, 9 166, 6 302, and 12 417 participants, respectively. Additionally, a total of 13, 755 participants were included in the cohort study design. Relevant information was collected through questionnaires and physical examinations. The χ2 trend test was used to compare the changes in the rates of underweight and overweight/obesity over the years, and the linear mixed-e?ects model (LMM) was used to fit trajectory curves of BMI changes with advancing age in older adults. Results:The baseline ages of the participants included in 2002, 2005, 2008, 2011, 2014, and 2018 were (85.16±11.26), (84.23±11.83), (84.99±12.16), (81.10±11.86), (78.89±11.30), and (83.08±12.42) years, respectively, with a relatively high proportion of females and rural residents. In the cohort study, the 13 755 participants had a median ( Q1, Q3) follow-up time of 6.5 (5.2, 10.0) years, with a cumulative follow-up duration of 109 041 person-years. In each wave, males had higher BMI than females, urban residents had higher BMI than rural residents, and BMI gradually decreased with increasing age (all P<0.001). The mean BMI of older adults in China increased from (19.37±3.80) kg/m2 in 2002 to (22.04±4.01) kg/m2 in 2018 ( P<0.001). Across all survey years, the prevalence of underweight was consistently higher in women than in men and in rural areas than in urban areas, with an upward trend as age increased (all P<0.001). In 2018, the underweight rates in the 65-79, 80-89, 90-99, and ≥100-year-old age groups were 8.0%, 16.7%, 26.2%, and 35.5%, respectively. Meanwhile, the prevalence of overweight/obesity was higher in men than in women and in urban areas than in rural areas, showing a declining trend with advancing age (all P<0.001). The prevalence of underweight among the older adults decreased significantly from 45.2% in 2002 to 18.9% in 2018 ( P<0.001), while the prevalence of overweight/obesity increased from 11.0% in 1998 to 29.6% in 2018 ( P<0.001). The trajectory curves fitted by the LMM model showed that individuals born in later decades had higher BMI levels at the same age compared to earlier cohorts. Conclusion:From 2002 to 2018, the BMI level among Chinese older adults showed an increasing trend. The prevalence of underweight showed a declining trend, while the rates of obesity and overweight increased. However, the underweight rate remained notably high among the oldest old.

Objective:To evaluate the predictive performance of machine learning methods for predicting the risk of death in traumatic hemorrhage, and address the low prediction accuracy of traditional trauma scores, provide a reference for developing a more robust prediction method for severe trauma patients.Methods:Clinical data of severe trauma patients from the National Trauma Medical Center between April 1, 2023, and March 31, 2024 were collected. ElasticNet, Recursive Feature Elimination, and Mutual Information-based feature selection methods were used to screen variables and compared with traditional hypothesis testing methods. Built the prediction models for mortality risk in traumatic hemorrhage using Logistic Regression, ElasticNet, and Support Vector Machine (SVM) and compared the predictive performance.Results:The study included 5,601 trauma patients, the results of the variable screening and importance ranking were consistent with three feature selection methods. The classification accuracy and AUC values for the three models were as follows: Overall accuracy was 83.2%, survival accuracy was 84.0%, death accuracy was 76.3%, and an AUC was 0.86 in logistic regression; Overall accuracy was 78.9%, survival accuracy was 78.5%, death accuracy was 81.7%, and an AUC was 0.88 in ElasticNet; Overall accuracy was 84.7%, survival accuracy was 86.1%, death accuracy was 72.4%, and an AUC was 0.86 in SVM. The prediction performance of three models is quite little.Conclusion:Machine learning methods can effectively improve the prediction of death risk for traumatic hemorrhage,and has wide applications.

Objective:To describe the body mass index (BMI) level and long-term trends of Chinese older adults aged 65 and above.Methods:Older adults aged 65 and above from six waves (2002-2018) of the China Longitudinal Healthy Longevity Survey were selected as the study population. Multiple cross-sectional design with six survey waves conducted in 2002, 2005, 2008, 2011, 2014, and 2018 was adopted, enrolling 15 647, 15 358, 15 622, 9 166, 6 302, and 12 417 participants, respectively. Additionally, a total of 13, 755 participants were included in the cohort study design. Relevant information was collected through questionnaires and physical examinations. The χ2 trend test was used to compare the changes in the rates of underweight and overweight/obesity over the years, and the linear mixed-e?ects model (LMM) was used to fit trajectory curves of BMI changes with advancing age in older adults. Results:The baseline ages of the participants included in 2002, 2005, 2008, 2011, 2014, and 2018 were (85.16±11.26), (84.23±11.83), (84.99±12.16), (81.10±11.86), (78.89±11.30), and (83.08±12.42) years, respectively, with a relatively high proportion of females and rural residents. In the cohort study, the 13 755 participants had a median ( Q1, Q3) follow-up time of 6.5 (5.2, 10.0) years, with a cumulative follow-up duration of 109 041 person-years. In each wave, males had higher BMI than females, urban residents had higher BMI than rural residents, and BMI gradually decreased with increasing age (all P<0.001). The mean BMI of older adults in China increased from (19.37±3.80) kg/m2 in 2002 to (22.04±4.01) kg/m2 in 2018 ( P<0.001). Across all survey years, the prevalence of underweight was consistently higher in women than in men and in rural areas than in urban areas, with an upward trend as age increased (all P<0.001). In 2018, the underweight rates in the 65-79, 80-89, 90-99, and ≥100-year-old age groups were 8.0%, 16.7%, 26.2%, and 35.5%, respectively. Meanwhile, the prevalence of overweight/obesity was higher in men than in women and in urban areas than in rural areas, showing a declining trend with advancing age (all P<0.001). The prevalence of underweight among the older adults decreased significantly from 45.2% in 2002 to 18.9% in 2018 ( P<0.001), while the prevalence of overweight/obesity increased from 11.0% in 1998 to 29.6% in 2018 ( P<0.001). The trajectory curves fitted by the LMM model showed that individuals born in later decades had higher BMI levels at the same age compared to earlier cohorts. Conclusion:From 2002 to 2018, the BMI level among Chinese older adults showed an increasing trend. The prevalence of underweight showed a declining trend, while the rates of obesity and overweight increased. However, the underweight rate remained notably high among the oldest old.

Objective:To understand the clinical manifestations, laboratory characteristics, and treatment of Staphylococcus aureus ( Sa) infection in children, and explore the predictive value of lymphocyte count, neutrophil to lymphocyte ratio(NLR), and high-sensitivity C-reactive protein to albumin ratio(CAR) in patient with secondary bloodstream infection(BSI). Methods:A retrospective analysis was conducted on 72 children with Sa infection admitted to the Nanchong Hospital of Beijing Anzhen Hospital Affiliated to Capital Medical University from January 2020 to April 2024. Clinical data including basic information, drug resistance, antibiotic treatment were collected. Differences in laboratory test results and inflammatory indicators were analyzed. The influencing factors of Staphylococcus aureus bacteraemia(SAB) in pediatric patients were analyzed using univariate/multivariate Logistic regression and correlation analysis. The predictive value was analyzed by receiver operating characteristic curve (ROC) and area under curve (AUC). Results:Seventy-two patients were selected, of whom 60 (83.33%) had skin and soft tissue infections (SSTIs), mainly community-associated Staphylococcus aureus(CA-SA)(50 cases), including 16 community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) cases (32.00%, 16/50). The detection rate of MRSA was 37.50% (27/72). The resistance rates of Sa to penicillin, clindamycin, and erythromycin were 97.22%(70/72), 69.44%(50/72), and 69.44%(50/72), respectively. Compared with the SSTIs group, the levels of lymphocyte count in children with bone and joint infections were significantly lower, while NLR and CAR levels were higher ( P<0.05). Fourteen patients had secondary SAB. In the secondary SAB group, lymphocyte counts were lower, while inflammatory indicators (NLR, CAR), and D-dimer were higher. CAR and NLR are positively correlated with the occurrence of bloodstream infections ( P<0.05). CAR ( OR=4.866, 95% CI: 1.37-17.25) and NLR ( OR=1.293, 95% CI: 1.032-1.620) were independent risk factors for secondary bloodstream infection, and ROC curve results showed that the combination of the two indicators had a higher sensitivity (0.929) and AUC (0.909) than individual testing. After undergoing effective treatment, the levels of CAR and NLR in the children in the secondary SAB group were significantly reduced. Wound infection patients underwent debridement treatment in 38 cases (52.78%, 38/72), while antibiotic treatment still primarily used first- and second-generation cephalosporins. For patients with secondary bloodstream infection, vancomycin was the first choice. Conclusions:Children′s wound infections with Sa primarily involve skin and soft tissue infections, commonly seen in CA-SA. NLR and CAR are independent risk factors for children with secondary bloodstream infection, and their combined detection has certain value for early diagnosis.

Objective:To analyze the application value of color Doppler ultrasound,microribonucleic acid-19a(miR-19a)and miR-210 in carotid artery stenosis.Methods:A total of 102 patients with carotid artery stenosis who were diagnosed and treated in Cangzhou People's Hospital from October 2020 to October 2022 were selected as the research group,and 102 health persons who underwent color Doppler ultrasound of physical examination in hospital at the same period were selected as the health control group.Both two groups underwent color Doppler ultrasound examination and digital subtraction angiography(DSA)within one week after admitted to hospital.The miR-19a and miR-210 between the two groups were compared,and the miR-19a and miR-210 of patients with different stenosis degrees of research group also were compared.And then,the diagnostic values of color Doppler,miR-19a,miR-210 and the combination of them were analyzed in diagnosing carotid artery stenosis.Results:The results of color Doppler ultrasound in detecting common carotid artery 102 patients of research group indicated that 15 cases were normal,and 15 cases occurred mild stenosis,and 21 cases occurred moderate stenosis,and 21 cases occurred severe stenosis and 33 cases occurred complete occlusion.The miR-19a of the research group was significantly higher than that of the health control group,and the miR-210 of the research group was significantly lower than that of the health control group(t=10.755,-5.903,P<0.05).The miR-19a results of the research group indicated that the miR-19a of mild stenosisthat of moderate stenosis>severe stenosis>complete occlusion,and the differences were statistical significant(F=160.399,147.462,P<0.05),respectively.The receiver operating characteristic(ROC)curve analysis showed that the area under curve(AUC)values of color Doppler ultrasound,miR-19a,miR-210 and combined diagnosis of them for carotid artery stenosis were respectively 0.892,0.842,0.729 and 0.978,and the sensitivity and specificity of the combined diagnosis were respectively 97.1%and 95.1%.Conclusion:The combined diagnosis of color Doppler ultrasound,miR-19a and miR-210 has higher diagnostic value for carotid artery stenosis.

Objective:To investigate clinical value of real time three-dimensional transesophageal echocardiography(RT-3D-TEE)in assessing patients with mitral valve prolapse(MVP)combined with mitral regurgitation(MR).Methods:The clinical data of 99 patients with MVP that combined with MR,who admitted to CANGZHOU People's Hospital from February 2020 to October 2023 and were confirmed by RT-3D-TEE,were retrospectively analyzed.According to two dimensional(2D)comprehensive method,they were divided into mild MR group(43 cases)and moderate-severe MR group(56 cases)as the degree of disease condition.The RT-3D-TEE parameters of the two groups were compared.The combined predictive indexes of RT-3D-TEE parameters were obtained by logistic regression analysis.Receiver operating characteristic(ROC)curve was drawn to analyze the values of single and combined RT-3D-TEE parameter in assessing the degree of disease condition of MVP patients with MR.Result:The anterolateral to posteromedial diameter(DAIPm),anterior-to-posterior diameter(DAP),nonplanarity angle(θNPA),annulus area in 3D(A3D),annulus perimeter(AP),total valve leaflet area of mild MR group were respectively(3.20±0.39)cm,(2.82±0.26)cm and(115.77±12.60)°,(6.90±1.28)cm2,(9.36±0.83)cm and(7.71±1.46)cm2,which were significantly less than those[(3.66±0.36)cm,(3.24±0.40)cm,(125.41±13.23)°,(7.99±1.59)cm2,(10.47±1.15)cm and(9.38±1.81)cm2]of moderate-severe MR group,respectively,and the differences of these indicators between two groups were significant(t=6.092,5.965,3.670,3.680,5.333,4.929,P＜0.05).The involution-index of mild group was(26.39±4.39),which was significantly larger than that(22.94±3.65)of moderate-severe MR group(t=4.264,P＜0.05).There were no significant differences in valve annulus height(H),angle of anterior leaflet(θAnt)and angle of posterior leaflet(θPost)between the two groups(P＞0.05).The area under curve(AUC)values of ROC curve of DAIPm,DAP,θNPA,involution-index,A3D,AP and Total valve leaflet area were respectively 0.818,0.831,0.712,0.737,0.704,0.806 and 0.765 in assessing the disease degree of MVP patients with MR.The AUC value of combined detection of them was 0.990.Conclusion:DAIPm,DAP,θNPA,involution-index,A3D,AP and Total valve leaflet area of RT-3D-TEE parameters had a certain value in assessing the disease degree of MVP patients with MR,and the assessment value of combined detection is higher.

Alzheimer′s disease(AD)is a chronic progressive neurodegenerative disease in the elderly,which causes heavy burden for the society and family.The current drugs could only improve the cognitive symptoms in the short term,but could not reverse or stop the disease progression.In view of the complexity of AD,multi-targe-ted drugs could be a potential strategy for the treatment of AD.Flavonoids,widely exising in the natural world, have multiple pharmacological activities.This paper summarizes flavonoids as promising multi-targeted anti-AD candidates according to the reported references previonsly published,which could provide important evidences in the development of anti-AD durgs.

Objective To investigate whether decursin(Dec) could inhibit EC109 cells proliferation by suppression of janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in human esophageal squamous cell carcinoma.Methods The EC109 cells were treated with Dec(20,40,and 80 pmmol/L) for48 h.The cell viability was evaluated by MTT;the apoptotic cells was labelled by TUNEL;the mitochondrial oxidative stress level was detected by fluorescent staining;and western blotting was used to analyze the proteins of JAK2/STAT3 signaling and apoptosis in EC109 cells,respectively.After co-application of JAK2 / STAT3 antagonist(AG490),the inhibitory ability of Dec to EC109 was observed from the in vivo and in vitro levels.Results Compared to the control group,different concentrations of Dec dose-dependently down-regulated expressions of p-JAK2 [(55.89 ± 6.04) ％] and p-STAT3 [(45.27 ± 8.65) ％],repressed EC109 cell activity(0.43 ± 0.078),increased apoptotic rate[(35.31 ± 8.41)％],reduced MMP levels[(37.23 ± 6.89)％],promoted reactive oxygen species(ROS) [(231.81 ± 19.63)％],decreased glutathione (GSH) activity [(46.78 ± 6.91)％,P＜0.05].However,Dec did not significantly affect the activity of the normal esophageal epithelium HET-1A cells(P ＞0.05).Meanwhile,Dec obviously leaded to reduction of Bcl2,increment of Bax,and augment of Caspase-3 cleavage (P ＜0.05).Additionally,the inhibitory effect of Dec on EC109 was specifically intensified after co-application of AG490 in vivo and in vitro levels(P ＜0.05).Conclusion Dec can fight against human esophageal squamous cell carcinoma in vitro and in vivo via activation of mitochondrial oxidative stress-induced apoptosis which was mediated by JAK2/STAT3 pathway.