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.

The rapid screening of bioactive constituents within traditional Chinese medicine (TCM) presents a significant challenge to researchers. Prevailing strategies for the screening of active components in TCM often overlook trace components owing to their concealment by more abundant constituents. To address this limitation, a fishing strategy based on offline two-dimensional liquid chromatography (2D-LC) combined with surface plasmon resonance (SPR) was utilized to screen bioactive trace components targeting peroxiredoxin 3 (PRDX3), using Uncaria alkaloids (UAs) as a case study. Initially, an orthogonal preparative offline 2D-LC system combining a positively charged C₁₈ column and a conventional C₁₈ column under disparate mobile phase conditions was constructed. To fully reveal the trace alkaloids, 13 2D fractions of UAs were prepared, and their components were characterized using mass spectrometry (MS). Subsequently, employing PRDX3 as the targeting protein, a SPR-based screening approach was established and rigorously validated with geissoschizine methyl ether (GSM) serving as a positive control for binding. Employing this refined strategy, 29 candidate binding alkaloids were fished from the 13 2D fractions. Notably, combining offline 2D-LC with SPR increased the yield of candidate binding components from 10 to 29 when compared to SPR-based screening alone. Subsequent binding affinity assays confirmed that PRDX3 was a direct binding target for the 12 fished alkaloids, with isovallesiachotamine (IV), corynoxeine N-oxide (CO-N), and cadambine (CAD) demonstrating the highest affinity for PRDX3. Their interactions were further validated through molecular docking analysis. Subsequent intracellular H₂O₂ measurement assays and transfection experiments confirmed that these three trace alkaloids enhanced PRDX3-mediated H₂O₂ clearance. In conclusion, this study introduced an innovative strategy for the identification of active trace components in TCM. This approach holds promise for accelerating research on medicinal components within this field.

Objective To analyze the acupoint selection law of acupuncture and moxibustion for postherpetic neuralgia(PHN)with R language data mining technology.Methods The clinical research literature on acupuncture and moxibustion treatment of PHN included in CNKI,Wanfang Data,VIP and CBM from January 1,2010 to July 1,2023 was retrieved,and the database was established by Excel 2016.R language was used to statistically analyze the frequency of acupoint usage,meridians,locations,specific acupoints,etc.Through association rule analysis and clustering analysis,the characteristics and law of acupoint selection for acupuncture and moxibustion treatment of PHN were obtained.Results A total of 198 articles were included,including 83 acupoints,with a total frequency of 714 times.The high-frequency acupoints include Ashi acupoint,Jiaji acupoint and Yanglingquan.The commonly used meridians were gallbladder meridian,spleen meridian and large intestine meridiam.The acupoints were mostly in the upper and lower limbs,with the Wushu acupoints,Yuan acupoints and Xiahe acupoints being the most common.The core acupoint was Ashi acupoint,Jiaji acupoint,Hegu,Quchi,and 9 sets of association rules and 5 effective clusters were obtained.Conclusion The most commonly used acupoints for acupuncture and moxibustion treatment of PHN are Ashi acupoint,Jiaji acupoint,Hegu and Quchi,which mainly follow the principle of combining local acupoint selection with distal acupoint selection.

Objective To construct a postoperative resistance exercise program for patients with gastric cancer,and to explore its intervention effect on symptom clusters and quality of life.Methods Based on the interactive attainment theory,the resistance exercise program was constructed through literature analysis and expert meeting method,and the feasibility of the program was confirmed through pre-experiments.The patients undergoing radical gastrectomy in the Department of Gastric Surgery of a tertiary hospital in Zhejiang province were selected as the study subjects by convenience sampling method,with 36 patients from November to December 2023 as the control group and 36 patients from January to March 2024 as the experimental group,and the intervention continued for 7 days.The experimental group received a resistance exercise program on the basis of conventional rapid recovery surgical care,and the control group received routine rapid recovery surgical care.On the first day before surgery,the 3rd postoperative day,and the 7th postoperative day,the Anderson Symptom Assessment Scale-Gastrointestinal Tumor-Specific Module Scale and the Functional Assessment of Cancer Therapy-General were used for evaluation.Results During the application of the program,a case was excluded from the experimental group,and a case was excluded from the control group.Ultimately,70 patients were included.The results of generalized estimating equation showed that there was an interaction effect between the 2 groups in the surgery-related symptom cluster and the energy deficiency symptom cluster(P＜0.05).Simple effect analysis showed that on the 7th day after surgery,the scores of the surgery-related symptom cluster in the experimental group and the control group were 3(1,5)and 5(3,9)respectively,and the scores of the energy deficiency symptom cluster were 6(8,18)and 14(8,19)respectively,with statistically significant differences(P＜0.05).The quality of life scores of the experimental group and the control group were(82.06±9.89)and(73.86±13.08)respectively,with statistically significant differences(P=0.004).No adverse events occurred in either group.Conclusion The resistance exercise program is scientific,safe and feasible,which can improve the surgery-related symptoms and energy deficiency symptoms,and improve the quality of life of patients with gastric cancer after surgery.

The aim of this study is to establish a rapid,efficient,and sensitive method for detecting the infectious laryngotracheitis virus(ILTV).The DNA of ILTV was extracted and used as a tem-plate to develop a recombinant enzyme-mediated isothermal amplification(RAA)fluorescence de-tection method for ILTV through optimization of conditions,sensitivity analysis,and repeatability assessment.Additionally,the nucleic acids of avian influenza virus(AIV),IBV,and Newcastle dis-ease virus(NDV)were detected to verify the specificity of this method.Finally,this method was applied to analyze 59 clinical samples collected from multiple large-scale chicken farms in Hebei Province,and the results were compared with those obtained from real-time fluorescence quantifi-cation(qPCR)and PCR methods according to national standards.The results showed that the RAA detection method established in this study had a reaction system of 25.0 μL buffer,2.1 μL primer,0.6 μL probe,5.0 μL magnesium acetate,and 5.0 μL template.The reaction temperature was 39 ℃ and the amplification time was within 20 minutes.The sensitivity of this method was 101 copies/μL,and the specificity detection was 100％.Testing of 59 clinical samples showed that 17 were detected positive by both RAA fluorescence and qPCR,and 12 were detected by PCR,and the detection rate of RAA(fluorescence)was consistent with real-time fluorescence quantification and qPCR,which was higher than that of the PCR assay.The research results indicate that the RAA fluorescence method has a short detection time,good specificity and sensitivity,and can be used for rapid detection of ILTV.

Objective To investigate the functional changes of dendritic cells(DCs)in patients at different stages of hepatitis B virus(HBV)infection and analyze the mechanisms underlying DC dysfunction.Methods Single-cell RNA sequencing dataset GSE182159 was downloaded from the GEO database and classified into healthy control(HC),immune active(IA),and immune tolerant(IT)groups based on infection stage.Peripheral blood samples were collected from 7 IA patients,7 IT patients,and 12 healthy controls.Flow cytometry was used to isolate classical dendritic cells(cDC)and plasmacytoid dendritic cells(pDC).The expression levels of transcription factors in cDC and pDC were measured by quantitative real-time PCR(qRT-PCR).Bioinformatics analyses were per-formed using R and Python package.Results The proportions of DCs in IA and IT groups were higher than that in HC group.Func-tional enrichment analysis revealed that the differentially expressed genes(DEGs)of cDCs in the IA group were primarily enriched for the processes,such as inflammatory response,MHC classⅡantigen processing and presentation,cell migration,signal transduction,metabolism,and immune response.In contrast the IT group exhibited lower enrichment intensity and a significant reduction in interfer-on responses.The DEGs of pDC in the IA group were enriched in the processes of MHC-Ⅱantigen presentation,Fc receptor signal transduction,and metabolism,whereas those in the IT group were showed enrichment only in Fc receptor signal transduction and me-tabolism with a lower intensity.Both groups exhibited reduced synthesis of typesⅠandⅡinterferons in pDC,with the IT group showing a more pronounced downregulation.Cell-cell communication analysis demonstrated enhanced interactions between myeloid cells(except pDC)and T cells in the IA group,whereas the interactions between cDC/pDC and T cells in the IT group were reduced.Transcription factor analysis revealed that STAT2,STAT3,IRF1,and IRF5 were highly expressed in the IA group but their expression exhibited low-er expression levels in the IT group.In contrast,BHLHE40 was broadly upregulated in both cDC and pDC subsets within the IT group.The qRT-PCR results were consistent with the findings from the single-cell transcription factor analysis.Conclusion The IT phase of hepatitis B infection represents a critical period for cDC dysfunction,characterized by significant suppression of MHCⅡantigen presen-tation,metabolism,and interferon responsiveness.The functional impairment of pDC precedes that of cDC,as evidenced by a marked downregulation of interferon synthesis capacity observed during the IA phase.

Objective To evaluate the clinical efficacy and safety of Jiangzhi Hugan Soft Extract(composed of stir-fried Dioscoreae Rhizoma,Poria,Ginseng Radix et Rhizoma,Bupleuri Radix,Citri Sarcodactylis Fructus,Persicae Semen,Polygoni Cuspidati Rhizoma,etc.)in treating non-alcoholic fatty liver disease(NAFLD)with internal dampness-turbidity accumulation syndrome.Methods Sixty patients with NAFLD of dampness-turbidity accumulation syndrome treated at the Gastroenterology Department of Maoming Hospital of Guangzhou University of Chinese Medicine(Maoming Hospital of Traditional Chinese Medicine)from November 2023 to December 2024 were enrolled.The patients were divided into trial group and control group using stratified randomization,with 30 patients in each group.Both groups received lifestyle interventions(diet control and exercise),with the trial group additionally receiving Jiangzhi Hugan Soft Extract for 4 weeks.Outcomes included body mass index(BMI),liver function indicators[alanine aminotransferase(ALT),aspartate aminotransferase(AST),gamma-glutamyl transferase(GGT)],lipid profiles[total cholesterol(TC),triglycerides(TG)],traditional Chinese medicine(TCM)syndrome scores,efficacy evaluation,and safety assessment.Results(1)After 4 weeks of treatment,the overall response rate in the trial group was 93.33％(28/30),while that in the control group was 60.00％(18/30).The intergroup comparison(by rank sum test)showed that the efficacy of TCM syndrome in the trial group was significantly superior to that in the control group,with a statistically significant difference(P＜0.01).(2)After treatment,the BMI of patients in both groups was improved significantly compared to before treatment(P＜0.01).The improvement in BMI was significantly greater in the trial group than in the control group.The difference in the change of BMI between the two groups was statistically significant before and after treatment(P＜0.05).(3)After treatment,the levels of ALT,AST,and GGT in both groups decreased compared to before treatment(P＜0.01).The trial group showed a significantly greater reduction in ALT,AST,and GGT levels than the control group.The difference between the two groups was statistically significant before and after treatment(P＜0.05).(4)After treatment,both groups showed a significant decrease in TC and TG levels compared to pre-treatment levels(P＜0.05).The trial group demonstrated a more pronounced reduction in TC levels than the control group.The difference between the two groups was statistically significant before and after treatment(P＜0.05).(5)There were no significant adverse reactions occurring in either group during treatment,indicating a high level of safety.Conclusion Jiangzhi Hugan Soft Extract effectively improves BMI,liver function,and lipid profile in NAFLD patients with dampness-turbidity accumulation syndrome,demonstrating good clinical efficacy and high safety,warranting further clinical application.

The"2024 Guideline for the Primary Prevention of Stroke:A Guideline from the American Heart Association/American Stroke Association"published in October,2024 is the updated version of the"2014 Guideline for the Primary Prevention of Stroke"published 10 years ago.The new guideline updated several recommendations and included several new topics.This article introduced briefly the recommended content of the new version of the guideline to provide reference for clinical practice in the primary prevention of stroke in China.

Objective:To investigate the status of leisure crafting and post competence and their correlation among anesthesia specialist nurses.Methods:A convenience sampling method was used to conducted a questionnaire survey on 280 anesthesia specialist nurses at grade A tertiary hospitals in 19 provinces of China. Data were collected using a general information questionnaire, the Chinese version of Leisure Crafting Scale, and the Post Competency Scale for Anesthesia Specialist Nurses. SPSS 24.0 was used for t test and one-way analysis of variance. A Pearson correlation analysis was used to assess relationships between variables. Results:The total score of leisure crafting was (30.41±6.69) and the average score was (3.38±0.74). The total score of post competency was (141.76±21.76) and the average score was (3.73±0.57). A positive correlation was observed between leisure crafting and post competency ( r=0.215, P<0.01). Conclusions:Managers should encourage anesthesia specialist nurses to actively engage in leisure crafting and provide diverse opportunities for leisure crafting to improve their post competence and ultimately the quality of anesthesia nursing.

Objective:To investigate the status of leisure crafting and post competence and their correlation among anesthesia specialist nurses.Methods:A convenience sampling method was used to conducted a questionnaire survey on 280 anesthesia specialist nurses at grade A tertiary hospitals in 19 provinces of China. Data were collected using a general information questionnaire, the Chinese version of Leisure Crafting Scale, and the Post Competency Scale for Anesthesia Specialist Nurses. SPSS 24.0 was used for t test and one-way analysis of variance. A Pearson correlation analysis was used to assess relationships between variables. Results:The total score of leisure crafting was (30.41±6.69) and the average score was (3.38±0.74). The total score of post competency was (141.76±21.76) and the average score was (3.73±0.57). A positive correlation was observed between leisure crafting and post competency ( r=0.215, P<0.01). Conclusions:Managers should encourage anesthesia specialist nurses to actively engage in leisure crafting and provide diverse opportunities for leisure crafting to improve their post competence and ultimately the quality of anesthesia nursing.