19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

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.

OBJECTIVES: To evaluate the regulatory effects of lncRNA LINC00261 on proliferation, invasion, and metastasis of esophageal squamous cell carcinoma (ESCC) cells. METHODS: The differentially expressed RNAs in ESCC were identified using the GSE149612 dataset from the GEO database. PCR was used to detect LINC00261 expression levels in clinical ESCC and normal esophageal tissue samples and in multiple ESCC cell lines and normal esophageal epithelial cells (HEEC). In ESCC cells, the effects of overexpression of LINC00261 on cell proliferation, invasion, metastasis and apoptosis were analyzed using CCK-8 assay, clone formation assay, Transwell assay and flow cytometry. The potential targets of LINC00261 were predicted using bioinformatics tools including ENCORI and verified using dual-luciferase reporter assay and Western blotting. The effects of LINC00261 overexpression on ESCC were confirmed in a nude mouse model bearing ESCC xenograft. RESULTS: Analysis of the GSE149612 dataset revealed significantly lower LINC00261 expression in ESCC tissues and cell lines. In cultured ESCC cells, LINC00261 overexpression markedly suppressed cell proliferation, invasion, and metastasis and promoted cell apoptosis. Dual-luciferase reporter assays confirmed that LINC00261 targets the miR-23a-3p/ZNF292 axis. In the tumor-bearing mouse model, LINC00261 overexpression significantly inhibited ESCC xenograft proliferation and metastasis. CONCLUSIONS LINC00261 suppresses ESCC progression by targeting the miR-23a-3p/ZNF292 axis, suggesting a potential therapeutic strategy for ESCC treatment.
Humans ; MicroRNAs/genetics* ; Cell Proliferation ; Esophageal Neoplasms/genetics* ; Animals ; Esophageal Squamous Cell Carcinoma ; Mice, Nude ; RNA, Long Noncoding/genetics* ; Cell Line, Tumor ; Neoplasm Invasiveness ; Mice ; Carcinoma, Squamous Cell/genetics* ; Apoptosis ; Gene Expression Regulation, Neoplastic ; Neoplasm Metastasis

To investigate the current status of sleep quality among nurses in tertiary hospitals in China, analyze the correlations of work stress and perceived organizational support with the risk of sleep problems, and further examine the mediating effect of perceived organizational support between work stress and sleep problems in nurses.

Objective To explore the effects of home-based exercise rehabilitation on cardiac structure, valvular function, and exercise capacity in patients with severe aortic stenosis (AS) after transcatheter aortic valve replacement (TAVR). Methods 49 patients with severe AS who underwent TAVR at Zhongshan Hospital, Fudan University, from January 2024 to February 2025 were enrolled. They were divided into an exercise group (n＝25) or a non-exercise group (n＝24) based on participating or not in home-based rehabilitation after TAVR. The exercise group received 12 weeks of home-based exercise training (aerobic exercise plus resistance training every week); the non-exercise group received routine care. Transthoracic echocardiography (TTE) was used to assess cardiac structural parameters before discharge (T0) and after 12 weeks of exercise (T1). Functional outcomes including the 6-minute walk test (6MWT), Duke Activity Status Index (DASI), and Short Physical Performance Battery (SPPB) were compared between the two groups. A linear mixed-effects model was used to analyze the effect of home-based rehabilitation on echocardiographic parameters. Patients were stratified by baseline 6MWT (＜240 m as low-function subgroup, ≥240 m as high-function subgroup) to compare exercise-related outcomes between subgroups. Results At T1, the exercise group had a longer 6MWT distance than the non-exercise group (P＝0.012). The linear mixed-effects model showed that after 12 weeks of exercise, the left ventricular end-diastolic diameter (LVEDD) decreased in the exercise group but slightly increased in the non-exercise group, with a significant difference in changes over time between the two groups (P_interaction＝0.030). The exercise group also showed greater improvement in effective orifice area index (P_interaction＝0.028) and effective orifice area (P_interaction＝0.042) than the non-exercise group. Subgroup analysis revealed that in the low-function subgroup, the exercise group showed greater improvement in the 6MWT (P_interaction＝0.035) and the effective orifice area index (P_interaction＝0.046) compared to the non-exercise group; in the high-function subgroup, the exercise group showed greater improvement only in LVEDD compared to the non-exercise group (P_interaction＝0.046). Conclusions Home-based exercise rehabilitation improves exercise capacity, optimizes left ventricular remodeling, and enhances valvular function in patients with severe AS after TAVR, with greater benefits observed in patients with lower baseline 6MWT.

Objective To summarize the best evidences of thirst management in the patients with tra-cheal intubation to provide the evidence-based evidence for clinical practice.Methods According to the"6S"evidence pyramid model,the literatures on thirst management of the patients with tracheal intubation were systematically retrieved from the relevant guide websites,evidence-based databases,association websites and original literature databases at home and abroad.The databases included BMJ Best Practice,Up To Date,JBI Evidence-Based Health Care Center Database,Guidelines International Network(GIN),National Institute for Health and Clinical Excellence,National Institute for Health and Clinical Excellence(NICE),Scottish Inter-collegiate Guidelines Network(SIGN),Registered Nurses'Association of Ontario,Canada(RNAO),National Guideline Clearing House(NGC),Cochrane Library,American Society of Critical Care Medicine(SCCM),A-merican Association of Critical Care(AACN),European Society of Intensive Medicine(ESIM),Chinese Socie-ty of Critical Care Medicine,PubMed,Embase,CNKI,Wanfang Medical Network,VIP Database and Chinese Biomedical Literature Database(SinoMed).The retrieval limit was from the database establishment to August 31,2023.Two researchers trained by evidence-based nursing independently completed the literature quality e-valuation,and the literatures meeting the quality standards conducted the evidence extracted and summary.Results A total of 23 literatures were included,including 1 clinical decision,1 evidence summary,12 random-ized controlled trials,3 quasi-experimental studies,and 6 cross-sectional studies.Eighteen pieces of best evi-dence were formed,including six aspects:definition of thirst,classification of thirst degree,risk factors,assess-ment methods,intervention strategies and quality management.Conclusion Nurses should conduct the clini-cal transform and application of the best evidences by combining the clinical situation and specific department policies to alleviate the thirst symptoms in the patients with tracheal intubation.

Objective To summarize the best evidence for diaphragm rehabilitation in mechanically ven-tilated ICU patients with ventilator-associated diaphragm dysfunction based on evidence-based methods.Meth-ods A systematic search was conducted across guideline websites,professional associations,and Chinese/English databases for evidence regarding diaphragm rehabilitation in mechanically ventilated ICU patients.The search timeframe spanned from database inception to December 31,2024.Two researchers independently per-formed quality assessment and synthesized the evidence.Results Twenty articles were included:2 clinical de-cisions,1 guideline,2 evidence summaries,3 systematic reviews,7 randomized controlled trials(RCT),and 5 expert consensuses/opinions.Twenty-seven pieces of evidence were formed across 6 themes:rehabilitation team,rehabilitation assessment,rehabilitation interventions,outcome evaluation,precautions,and education/training.Conclusion This study summarizes the best evidence for diaphragm rehabilitation in ICU mechani-cally ventilated patients.Healthcare professionals should implement diaphragm rehabilitation by integrating this evidence with specific clinical contexts to improve patient outcomes and enhance nursing quality.

Objective To explore the relationship between minimal residual disease(MRD)on the 19th day(D19)and prognosis of children with acute B-lymphoblastic leukemia(B-ALL),as well as the correlation with related biological changes.Methods A total of 88 children with B-ALL newly diagnosed in this hospital from April 2016 to April 2020 who met the enrollment conditions were analyzed for induction therapy D19 MRD,overall survival(OS)rate,event-free survival(EFS)rate,chromosome karyotype,fusion gene and mu-tation gene.MRD≥ 0.01％was considered positive,and they were divided into MRD positive group and MRD negative group.The characteristics of OS rate,EFS rate,immunophenotype and molecular biology/cytogenet-ics were compared between the two groups over a period of 3 years.Results The 3-year OS rate and EFS rate of 88 pediatric patients were 92.0％and 86.4％,respectively.The rates of OS rate and EFS rate in MRD posi-tive group were lower than those in MRD negative group,with statistical significance(P＜0.05).The detec-tion rate of CD10 in MRD positive group was lower than that in MRD negative group,and the difference was statistically significant(P＜0.05).Thirty-two patients(36.4％)detected 8 types of 35 fusion genes.The de-tection rates of BCR-ABL1 and E2A-PBX1 in MRD positive group were higher than those in MRD negative group,and the differences were statistically significant(P＜0.05).Among 48 cases(54.5％)of pediatric pa-tients,41 types of 91 mutated genes were detected,and the remaining mutated genes were less than 5 cases.Abnormal karyotype was detected in 18 cases(20.5％),and no mitotic phase was detected in 17 cases.There was no difference in MRD between normal and abnormal karyotype.Binary Logistic regression analysis showed that BCR-ABL1 and E2A-PBX1 were prognostic factors of children with B-ALL.Conclusion The positive D19 MRD is the influential factor of adverse OS and EFS in children with B-ALL.Both E2A-PBX1 and BCR-ABL1 have adverse effects on the prognosis of children with B-ALL.

Objective To explore the potential categories and influencing factors of the fear of progression in patients with inflammatory bowel diseases(IBD).Methods IBD patients who received inpatient treatment in a tertiary hospital in Nanjing from July 2022 to July 2023 were selected as the study subjects by convenience sampling method.The General Demographic Information Questionnaire,the Chinese version of the Fear of Progression Questionnaire-Short Form(FoP-Q-SF),the Chinese version of Inflammatory Bowel Disease Self-efficacy Scale(IBD-SES),and Social Support Rating Scale(SSRS)were administered to the participants.We applied one-way ANOVA and Logistic regression analysis to identify the factors associated with the potential categories of the fear of progression.Results A total of 303 retumed questionnaires(out of the 310)were valid,resulting an effective response rate of 97.74％.According to the results of latent profile analysis,we classified the respondents into 3 categories by the fear of progression,namely"low risk fear of disease adaptation group"(n=127,41.91％),"medium risk fear of illness distress group"(n=139,45.88％),"high risk fear of dysfunction group"(n=37,12.21％).3 groups showed statistically significant differences in permanent address,self-rated financial pressure,current disease status and self-efficacy(P＜0.05).Conclusion Patients with IBD had obvious differences in characteristics on the fear of progression.Nursing personnel should formulate personalized intervention strategies based on the classification characteristics of the fear of progression of IBD patients.Moreover,nurses should focus on improving patients'self-efficacy and promoting patients to treat medical care,stress and emotion management correctly.

Objective To compare the effect of palliative mitral valve surgeries and medication therapies for secondary non-ischemic mitral regurgitation. Methods The clinical data of patients with non-ischemic functional mitral regurgitation treated in our hospital between 2009 and 2019 were retrospectively analyzed. Patients with a left ventricular ejection fraction (LVEF)＜40% underwent a dobutamine stress test, and a positive result was determined when the LVEF improved by more than 15% compared to the baseline value. Positive patients were divided into a surgery group and a medication group. The surgery group underwent surgical mitral valve repair or replacement, while the medication group received simple medication treatment. Follow-up on survival and cardiac function status through outpatient or telephone visits every six months after surgery, and patients underwent cardiac ultrasound examination one year after surgery. The main research endpoint was a composite endpoint of all-cause death, heart failure readmission, and heart transplantation, and the differences in cardiac function and cardiac ultrasound parameters between the two groups were compared. Results Ultimately 41 patients were collected, including 28 males and 13 females with an average age of 55.5±11.1 years. Twenty-five patients were in the surgery group and sixteen patients in the medication group. The median follow-up time was 16 months, ranging 1-96 months. The occurrence of all-cause death in the surgery group was lower than that in the medication group (HR=0.124, 95%CI 0.024-0.641, P=0.034). The difference between the two groups was not statistically significant in the composite endpoint (HR=0.499, 95%CI 0.523-1.631, P=0.229). The New York Heart Association (NYHA) grade of the surgery group was better (NYHA Ⅰ-Ⅱ accounted for 68.0% in the surgury group and 18.8% in the medication group, P<0.01) as well as the grade of mitral valve regurgitation (87.5% of the patients in the medication group had moderate or above regurgitation at follow-up, while all the patients in the surgery group had moderate below regurgitation, P<0.01). There was no statistical difference in preoperative and follow-up changes in echocardiograph parameters between the two groups (P＞0.05). Conclusion For non-ischemic functional mitral regurgitation, if the cardiac systolic function is well reserved, mitral valve surgery can improve survival and quality of life compare to simple medication therapy.