Objective:To investigate the effect of human epidermal growth factor receptor 2 (HER2) on bladder cancer by regulating phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway via tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon peptide (YWHAE) and to examine its mechanism.Methods:The gene expression profiling interactive analysis (GEPIA) database was used to analyze HER2 expression in 408 bladder cancer tissues and 19 adjacent normal tissues. HER2 expression was then compared between 215 tumor protein 53 ( TP53) mutant and 193 TP53 non-mutant bladder cancer tissues. Tissue samples were obtained from patients who underwent surgical resection for bladder cancer in Tianjin Medical University General Hospital between June 2010 and March 2015. Immunohistochemistry and Western blotting were performed to validate HER2 and p53 protein expression, as well as analyze their correlation. Bladder cancer T24 cells were transfected with short hairpin RNA targeting HER2 (shHER2) control (shCon) or shHER2, designated as shCon and shHER2 groups. Bladder cancer UMUC3 cells were transfected with overexpression control (oeCon), HER2 overexpression (oeHER2), oeYWHAE, or short hairpin RNA targeting murine double minute 2 (MDM2) (shMDM2), and were designated as the oeCon, oeHER2, oeYWHAE and shMDM2 groups, respectively. UMUC3 cells were then treated with either 0.1% dimethyl sulfoxide or 100 mmol/L dihydrotestosterone and designated as the solvent control and dihydrotestosterone groups, respectively. Additionally, oeCon and oeYWHAE UMUC3 cells were treated with the PI3K inhibitor LY294002 (25 μmol/L), designated as the LY294002 and LY294002+oeYWHAE groups. On this basis, shHER2 was transfected into the oeCon and oeYWHAE groups, which were then designated as the shHER2-2 and shHER2-2+oeYWHAE groups. The relative expression levels of HER2, YWHAE mRNA, and HER2, p53, YWHAE, MDM2, phosphorylated Akt (p-Akt), and Akt proteins were determined using quantitative reverse transcription PCR and Western blotting. Cell Counting Kit-8, Transwell, and wound-healing assays were performed to evaluate the impact of HER2 on the proliferation, invasion, and migration of bladder cancer cells. Mass spectrometry and co-immunoprecipitation assays were performed to confirm the interaction between YWHAE and HER2, and immunofluorescence was used to detect p53 expression. BALB/c nude mice were subcutaneously injected with 5×10 6 UMUC3 cells in the scapular region. According to the random number table method, they were divided into negative the control group and the transfection group, with 3 mice in each group, and transfected with oeCon and oeHER2, respectively. Tumor volume and weight were measured and calculated, and HER2 and p53 protein expression in bladder cancer tissues was validated by immunohistochemistry and Western blotting. Independent sample t test or Mann-Whitney U test was used to compare the two groups. One-way analysis of variance or Kruskal-Wallis test was used for comparison of multiple groups. Results:GEPIA database analysis demonstrated significantly higher levels of HER2 expression in bladder cancer tissues and in TP53 mutant bladder cancers compared with adjacent normal tissues (both P<0.01). HER2 expression was inversely correlated with p53 expression ( r=?0.6). Immunohistochemistry and Western blotting confirmed that p53 expression level in the bladder cancer tissues (5.32±0.11) was higher than that in the adjacent normal tissues (2.00±0.01), while HER2 expression level in the bladder cancer tissues (1.13±0.02) was lower than that in the adjacent normal tissues (6.20±0.06) (both P<0.01). HER2 mRNA and protein expression, absorbance at 450 nm wavelength ( A450) values, and cell invasion number and cell migration distance in the shHER2 group were all lower than those in the shCon group [0.25±0.01 vs 1.00±0.05, 1.00± 0.01 vs 3.26±0.09, 1.36±0.04 vs 1.65±0.06, (107.00±5.51) vs (202.70±11.61) cells, and (298.70±6.94) vs (454.30±7.84) μm] ( P<0.05, 0.01). HER2 mRNA and protein expression, absorbance ( A450) values, and cell invasion number and cell migration distance in the oeHER2 group were all higher than those in the oeCon group [0.78±0.02 vs 0.46±0.01, 2.05±0.02 vs 1.00±0.00, 1.23±0.06 vs 0.78±0.03, (136.30±5.24) vs (59.00±5.51) cells, and (153.70±7.27) vs (66.33±33.84) μm] ( P<0.05, 0.01). HER2 protein expression level in the dihydrotestosterone group was higher than that in the solvent control (1.83±0.19 vs 1.00±0.00), while p53 protein expression level in the dihydrotestosterone group was lower than that in the solvent control group (1.10±0.10 vs 1.53±0.15) (both P<0.01). The differentially expressed protein between the dihydrotestosterone group and solvent control group was YWHAE. The expression levels of YWHAE mRNA and protein in the dihydrotestosterone group (1.10±0.12 and 3.05±0.03) were higher than those in the solvent control group (0.30±0.12 and 1.00±0.00) (both P<0.01). YWHAE protein expression level in the oeHER2 group was higher than that in the oeCon group (1.37±0.08 vs 1.00±0.00) ( P<0.01) and YWHAE expression level in the bladder cancer tissues was higher than that in the adjacent normal tissues ( P<0.01). YWHAE expression positively correlated with HER2 expression ( r=0.4). Co-immunoprecipitation confirmed direct binding between HER2 and YWHAE. Overexpression of YWHAE significantly reduced p53 expression. The relative expression level of MDM2 protein in the oeYWHAE group (2.73±0.09) was lower than that in the oeCon group (3.43±0.12) ( P<0.01). The relative expression level of MDM2 protein in the shMDM2 group (1.00±0.00) was lower than that in the oeYWHAE group, and the relative expression level of p53 protein (2.00±0.00) was higher than that in the oeYWHAE group (1.07±0.07) (both P<0.01). The relative expression levels of YWHAE and p-Akt protein in the oeYWHAE group (1.23±0.09, 3.00±0.06) were higher than those in the oeCon group (1.00±0.00, 1.13±0.03) ( P<0.05, 0.01). The relative expression level of p-Akt protein in LY294002 group (2.20±0.06) was lower than that in the oeCon group (3.30±0.10), and the relative expression level of p53 protein (2.10±0.06) was higher than that in the oeCon group (1.00±0.00) (both P<0.01). The relative expression level of p-Akt protein in LY294002+oeYWHAE group (2.00±0.06) was lower than that in the oeYWHAE group (3.53±0.14), and the relative expression level of p53 protein (2.10±0.06) was higher than that in the oeYWHAE group (1.00±0.06) (both P<0.01). The relative expression levels levels of YWHAE, p-Akt and MDM2 protein in the shHER2-2 group (1.60±0.15, 1.70±0.06, 0.80±0.06) were lower than those in the oeCon group (2.30±0.06, 2.30±0.06, 1.13±0.09), and the relative expression level of p53 protein (1.83±0.12) was higher than that in the oeCon group (1.00±0.00) ( P<0.05, 0.01). The relative expression level of YWHAE protein in the shHER2-2+oeYWHAE group (2.00±0.06) was lower than that in the oeCon group ( P<0.01), and the relative expression levels of MDM2 and p53 protein (2.63±0.15, 1.13±0.03) were higher than those in the oeCon group ( P<0.05, 0.01). The tumor volume, tumor weight, and relative expression levels of HER2, YWHAE, p-Akt, and MDM2 proteins on day 28 in the transfection group [(5 133.0±185.6) mm 3, (0.65±0.12) g, 2.23±0.02, 4.00±0.12, 3.33±0.06 and 2.24±0.02] were higher than those in the negative control group [(2 633.0±88.2) mm 3, (0.33±0.07) g, 0.98±0.02, 1.27±0.03, 1.29±0.02 and 1.46±0.06] (all P<0.01). The relative expression level of p53 protein (1.21±0.04) was lower than that in the negative control group (3.29±0.04) ( P<0.01). Conclusions:HER2 may promote the malignant progression of bladder cancer by regulating the PI3K-Akt pathway via YWHAE, thereby facilitating MDM2 nuclear translocation and p53 degradation. This ultimately enhances the proliferative, migratory, and invasive capacities of bladder cancer cells.

Compared with total knee arthroplasty, unicondylar knee replacement has the advantage of preserving the knee tissue structure and motor function to the greatest extent. Pre-clinical in-vitro test is an important tool to evaluate the safety and effectiveness of unicondylar knee prostheses, and it is also a key focus of the product registration process. Through collection, comparison, and analysis of current regulations, technical standards, guidelines, and related research literature, this paper expounds on the relevant research methods for the pre-clinical in-vitrotesting of unicondylar knee prostheses. At the same time, in conjunction with current evaluation requirements and experience, the study discusses the focus of pre-clinical performance research for unicondylar knee prostheses during the registration process to clarify the performance evaluation requirements of this product category. This aims to provide a reference for the pre-clinical performance research of unicondylar knee prostheses and to standardize industry testing standards.
Knee Prosthesis ; Arthroplasty, Replacement, Knee ; Humans ; Prosthesis Design ; Materials Testing

Objective:To analyze the electrocardiogram (ECG) data of congenital long QT syndrome (LQTS) patients, and to identify the ECG parameters for prediction of life-threatening arrhythmic events (LAEs).Methods:This cohort study enrolled patients diagnosed with congenital LQTS at the Department of Cardiology, Beijing Tsinghua Changgung Hospital from September 2014 to May 2023. Baseline clinical and ECG data were collected. Patients were followed with LAEs as the primary endpoint. Based on the occurrence of LAEs, patients were divided into two groups: the event group and the event-free group. Cox regression analysis was used to identify independent predictors of LAEs in LQTS patients.Results:A total of 293 patients diagnosed with congenital LQTS were included, aged 32.5 (19.0, 41.8) years, including 201 females (68.6%). Sixty-six patients experienced LAEs and 227 patients did not. Compared to the event-free group, the event group had a younger onset age (13.0 (5.5, 20.5) years vs. 26.0 (13.0, 35.0) years), a slower heart rate (69.0 (59.5, 76.5) beats/min vs. 77.0 (67.0, 88.0) beats/min), a higher proportion with family history of sudden cardiac death (30.3% vs. 14.5%), as well as longer QT intervals (500.0 (467.0, 594.0) ms vs. 428.0 (402.0, 470.0) ms) and QTc intervals (544.0 (502.5, 589.0) ms vs. 489.0 (480.0, 504.0) ms). Additionally, the event group had higher peak T-wave alternans value (65.0 (42.5, 85.3) μV vs. 44.0 (36.0, 54.0) μV), a higher proportion of patients with documented torsades de pointes (TdP) or ventricular fibrillation (VF) on 24-hour Holter monitoring (39.3% vs. 4.9%), and higher rates of pharmacological treatment (100.0% vs. 9.7%) and device therapy or left cardiac sympathetic denervation (45.5% vs. 2.2%) (all P<0.05). Multivariate Cox regression analysis identified that the heart rate<60 beats/min ( HR=2.0, 95% CI: 1.0-3.7) and QTc interval ≥500 ms ( HR=2.9, 95% CI: 1.5-5.6) on 12-lead ECG, as well as peak T-wave alternans value ≥55.5 μV ( HR=3.2, 95% CI: 1.3-7.8) and documented TdP or VF ( HR=2.0, 95% CI: 1.1-3.7) on 24-hour Holter monitoring were independent predictors of LAEs in LQTS patients (all P<0.05). Conclusion:Heart rate <60 beats/min and QTc interval ≥500 ms on 12-lead ECG, along with peak T-wave alternans value ≥55.5 μV and documented TdP or VF on 24-hour Holter monitoring, have been identified as independent predictors of LAEs in patients with LQTS. These ECG parameters may serve as valuable early indicators of sudden cardiac death in LQTS patients.

Objective:To investigate the effects of wheat-grain moxibustion at the Guanyuan point on testosterone(T)synthe-sis and the hypothalamic-pituitary-gonadal(HPG)axis in naturally aged mice.Methods:We fed 40 twelve-month-old SPF male C57BL/6J mice with a normal diet for 3 months,randomized them into a moxibustion and an aged group of an equal number,and se-lected 7 four-month-old ones as young controls.We treated the animals of the moxibustion group by wheat-grain moxibustion at the Guanyuan point,once 5 moxibustion sticks,qd,5 times a week,and fed those of the aged group normally,all for 12 weeks.After treatment,we obtained the testicular index of the mice,observed the histomorphology of the testis tissue by HE staining,measured the contents of T in the testis,gonadotropin-releasing hormone(GnRH)in the hypothalamus and total T(tT),free T(fT),luteinizing hormone(LH)and follicle-stimulating hormone(FSH)in the serum by ELISA,and determined the expressions of silence information regulator-1(SIRT1),P53,glutathione peroxidase(GPX4)and cholesterol side-chain?cleavage enzym e(CYP11A1)in the testis by Western blot.Results:Compared with the young controls,the mice in the aged group showed obviously losing and dull hair,energy declination,loose structure of the spermatogenic tubule with different degrees of cell loss and rupture,reduced testicular index,and ev-ident aging phenotype.In comparison with the aged mice,the animals of the moxibustion group were fairly energetic and exhibited dis-tinct structure of the spermatogenic tubules,orderly arranged and highly differentiated cells at all levels,significantly increased T lev-el,up-regulated expressions of SIRT1,GPX4 and CYP11 A1,and down-regulated expression of P53 in testis tissue,and elevated levels of GnRH,FSH,LH,tT and fT in the HPG axis.Conclusion:Wheat-grain moxibustion at the Guanyuan point protects testosterone synthesis in the testis tissue of naturally aged mice,promotes negative feedback regulation of the HPG axis,and improves low testoster-one.

Objective:To explore the correlation between the oxygenation index and the monitored parameters of lung injury view in ventilator,so as to provide a basis for monitoring the change of oxygenation index by the parameters of lung injury view.Methods:A total of 28 patients who received mechanical ventilation treatment and admitted to respiratory department of the First Affiliated Hospital with Nanjing Medical University from May 14 to September 30,2024 were selected.The monitored parameters of lung injury views of them during mechanical ventilation treatment with invasive ventilators were collected,including platform pressure(Pplat),driving pressure(ΔP),mechanical energy(Emech),ratio of tidal volume to ideal body weight(TVe/IBW),etc..Then,the data of oxygenation index were obtained.Finally,135 valid data were screened out.The 84 pieces of data with oxygenation index≤300mmHg were included in low oxygen group,and 51 data with oxygenation index>300mmHg were included in normal group.The correlations between oxygenation index and Pplat,ΔP,Emech,TVe/IBW were conducted by pairwise analysis.Results:In the low oxygen group,the oxygenation index was[(196.302±74.522)mmHg]significantly negative correlation with Emech[(12.686±5.401)J/min](ρ=-0.425,P<0.05),but not was significant correlation with Pplat,ΔP,and TVe/IBW(P>0.05).In the normal group,there were not significant correlations between the oxygenation index and Pplat,ΔP,Emech and TVe/IBW(P>0.05).There was a significant negative correlation between Emech and rank of oxygenation index(β=-0.389,P<0.05)in the low oxygen group.Conclusion:The visualization function of the Emech of the monitored parameters in lung injury view of ventilator can provide help for monitoring the changes of oxygenation index of patients in the low oxygen group,and can improve the oxygenation of patients by optimizing mechanical energy.However,it is necessary to balance the contradiction between ventilation intensity and protection for lung.

ObjectiveTo construct an animal model of respiratory syncytial virus（RSV）-infected pneumonia suitable for preclinical studies. MethodsThe virulence of RSV to the four cell lines was observed by cytopathic effect （CPE）， and 50% tissue culture infective dose（TCID₅₀） was calculated. Twenty BALB/c mice were randomly divided into a normal group and a model group. Six BALB/c-hIGF1R mice served as the humanized IGF1R model group. Except for the normal group， the other groups received intranasal RSV infection on days 1 and 3 to establish a viral pneumonia model. The efficacy of establishing an RSV-induced pneumonia animal model based on humanized insulin-like growth factor 1 receptor （IGF1R） mice was evaluated by measuring organ indices， peripheral blood lymphocyte percentages， pulmonary pathology and imaging， and pulmonary viral load. Additionally， ten BALB/c mice served as normal group， and thirty-two BALB/c-hIGF1R mice were randomly assigned to humanized IGF1R model group， ribavirin group （82.5 mg·kg^-¹·d^-¹）， and high and low dose groups of Lianhua Qingwen （3.3 mg·kg^-¹·d^-¹ ， 1.65 mg·kg^-¹·d^-¹）， with 8 mice per group. The viral load in lung tissue was measured after ribavirin and Lianhua Qingwen intervention， and the model was applied to the evaluation of anti-RSV drugs. ResultsIn the lungs of the humanized IGF1R model group， large solid and diffuse ground-glass shadows were seen， and the lung volume was significantly increased （P<0.01）. The lung index was significantly increased （P<0.01）， and both the spleen index and thymus index were significantly decreased （P<0.01）. The percentages of CD3⁺ and CD4⁺T cells were significantly decreased （P<0.05）， and there was a large amount of inflammation and stasis in the perivascular area of the lung tissue， which was predominantly characterized by lymphocytes. The endothelium of blood vessels was partially detached， with a small number of eosinophils. After infecting BALB/c-hIGF1R mice with RSV， the expression of viral nucleic acids in the lung tissue of the mice was significantly increased， with significant differences compared with the normal group （P<0.01）. The expression of viral nucleic acids in the ribavirin group and the high and low dose groups of Lianhua Qingwen was significantly reduced， with significant differences compared with the normal group （P<0.01）. ConclusionHumanized IGF1R mice are more susceptible to respiratory SVC， and the animal model of RSV-infected pneumonia based on humanized IGF1R mice was successfully constructed， which is suitable for the evaluation of anti-RSV drugs.

ObjectiveTo explore the effects of the Tibetan medicine Sanwei Doukoutang （SWDK） on cognitive dysfunction in mice suffering from Alzheimer's disease （AD） and its related mechanism. MethodsFifty SPF 5 × FAD mice were randomly divided into model group， total ginsenoside group（0.04 g·kg^-1）， high-， medium-， and low-dose groups of SWDK （32.60， 16.30， 8.15 g·kg^-1）， with 10 mice in each group， and ten wild-type mice of the same age were used as the normal group， male and female in 1∶1. Gavage administration was performed once daily for 8 weeks. The Morris water maze test and contextual fear memory experiment were used to observe learning and memory function. Hematoxylin-eosin （HE） staining was utilized to observe the changes in the pathomorphology of brain tissue in mice. The levels of synaptophysin （SYP） and postsynaptic dense substance 95 （PSD95） in mice serum were detected by enzyme-linked immunosorbent assay （ELISA）. The positive expression of brain-derived neurotrophic factor（BDNF） in the dentate gyrus （DG） region of mouse brain tissue was observed by immunohistochemistry （IHC）. The protein levels of BDNF， Wnt family member 3A（Wnt3a）， and β-catenin were detected in the hippocampus of mice by Western blot. ResultsCompared with the normal group of mice， the model group of mice had significantly more complex swimming routes and lower swimming speed （P<0.01）， significantly lower percentage of time spent in the target quadrant （P<0.01）， and a significantly lower percentage of freezing time （P<0.05）. The number of neurons in the hippocampal region of mice was obviously reduced and unevenly arranged. The levels of SYP and PSD95（P<0.01） in the serum of mice were reduced， and the positive expression of BDNF in the DG region of the brain tissue of mice was reduced. The levels of hippocampal BDNF， Wnt3a， and β-catenin proteins in the hippocampus of mice were obviously reduced （P<0.05， P<0.01）. Compared with the model group， the mice in the SWDK group and the total ginsenoside group had significantly shorter swimming routes， the high- and medium- dose SWDK groups significantly higher swimming speeds （P<0.01）， significantly higher percentage of time spent in the target quadrant （P<0.01）， obviously higher percentage of Freezing time （P<0.05）， and obviously more neurons in the hippocampal region of the mice with tighter arrangement. The mice had elevated levels of serum SYP （P<0.05， P<0.01）， PSD95 （P<0.01）， increased BDNF-positive cells in the DG region of brain tissue， and obviously elevated levels of BDNF， Wnt3a， and β-catenin proteins in the hippocampus of mice （P<0.05， P<0.01）. ConclusionSWDK can significantly improve the cognitive dysfunction of AD mice， and its mechanism may be related to regulating the Wnt/β-catenin signaling pathway， which promotes BDNF expression and thereby enhances synaptic plasticity， allowing neuronal signaling to be restored.

Currently， viral pneumonia （VP） presents a major challenge to global public health. Traditional Chinese medicine （TCM） prevention and treatment of VP is guided by the core concept of strengthening vital energy and eliminating pathogenic factors rather than targeting specific pathogens， alongside a holistic approach of syndrome differentiation and treatment. By summarizing the clinical syndromes of patients， the core pathogenesis was clarified to achieve individualized therapy. Animal models for disease-syndrome combination integrate the etiology and pathogenesis of VP and simulate the individualized manifestations of patients at different disease stages， providing an experimental platform for elucidating the theoretical basis of TCM in treating VP and promoting the development of effective TCM formulations. However， there are limitations in the application and promotion of disease-syndrome combination animal models due to the lack of standardization and normalization of model construction systems， which arise from diverse species selection， compound modeling methods， and multidimensional evaluation indicators. This paper systematically reviewed the recent research on animal models for disease-syndrome combination in VP from the perspective of species selection， modeling methods， evaluation indicators， and application status. Furthermore， it summarized the advantages and limitations of existing models， identifies future directions for improvement， and proposes optimization strategies. This review provides a reference for establishing standardized and normalized animal models for disease-syndrome combinations in VP， supporting the theoretical modernization of TCM in preventing and controlling emerging respiratory infectious diseases， and contributing to the development of new TCM drugs.

ObjectiveTo construct an animal model of respiratory syncytial virus（RSV）-infected pneumonia suitable for preclinical studies. MethodsThe virulence of RSV to the four cell lines was observed by cytopathic effect （CPE）， and 50% tissue culture infective dose（TCID₅₀） was calculated. Twenty BALB/c mice were randomly divided into a normal group and a model group. Six BALB/c-hIGF1R mice served as the humanized IGF1R model group. Except for the normal group， the other groups received intranasal RSV infection on days 1 and 3 to establish a viral pneumonia model. The efficacy of establishing an RSV-induced pneumonia animal model based on humanized insulin-like growth factor 1 receptor （IGF1R） mice was evaluated by measuring organ indices， peripheral blood lymphocyte percentages， pulmonary pathology and imaging， and pulmonary viral load. Additionally， ten BALB/c mice served as normal group， and thirty-two BALB/c-hIGF1R mice were randomly assigned to humanized IGF1R model group， ribavirin group （82.5 mg·kg^-¹·d^-¹）， and high and low dose groups of Lianhua Qingwen （3.3 mg·kg^-¹·d^-¹ ， 1.65 mg·kg^-¹·d^-¹）， with 8 mice per group. The viral load in lung tissue was measured after ribavirin and Lianhua Qingwen intervention， and the model was applied to the evaluation of anti-RSV drugs. ResultsIn the lungs of the humanized IGF1R model group， large solid and diffuse ground-glass shadows were seen， and the lung volume was significantly increased （P<0.01）. The lung index was significantly increased （P<0.01）， and both the spleen index and thymus index were significantly decreased （P<0.01）. The percentages of CD3⁺ and CD4⁺T cells were significantly decreased （P<0.05）， and there was a large amount of inflammation and stasis in the perivascular area of the lung tissue， which was predominantly characterized by lymphocytes. The endothelium of blood vessels was partially detached， with a small number of eosinophils. After infecting BALB/c-hIGF1R mice with RSV， the expression of viral nucleic acids in the lung tissue of the mice was significantly increased， with significant differences compared with the normal group （P<0.01）. The expression of viral nucleic acids in the ribavirin group and the high and low dose groups of Lianhua Qingwen was significantly reduced， with significant differences compared with the normal group （P<0.01）. ConclusionHumanized IGF1R mice are more susceptible to respiratory SVC， and the animal model of RSV-infected pneumonia based on humanized IGF1R mice was successfully constructed， which is suitable for the evaluation of anti-RSV drugs.

ObjectiveTo explore the effects of the Tibetan medicine Sanwei Doukoutang （SWDK） on cognitive dysfunction in mice suffering from Alzheimer's disease （AD） and its related mechanism. MethodsFifty SPF 5 × FAD mice were randomly divided into model group， total ginsenoside group（0.04 g·kg^-1）， high-， medium-， and low-dose groups of SWDK （32.60， 16.30， 8.15 g·kg^-1）， with 10 mice in each group， and ten wild-type mice of the same age were used as the normal group， male and female in 1∶1. Gavage administration was performed once daily for 8 weeks. The Morris water maze test and contextual fear memory experiment were used to observe learning and memory function. Hematoxylin-eosin （HE） staining was utilized to observe the changes in the pathomorphology of brain tissue in mice. The levels of synaptophysin （SYP） and postsynaptic dense substance 95 （PSD95） in mice serum were detected by enzyme-linked immunosorbent assay （ELISA）. The positive expression of brain-derived neurotrophic factor（BDNF） in the dentate gyrus （DG） region of mouse brain tissue was observed by immunohistochemistry （IHC）. The protein levels of BDNF， Wnt family member 3A（Wnt3a）， and β-catenin were detected in the hippocampus of mice by Western blot. ResultsCompared with the normal group of mice， the model group of mice had significantly more complex swimming routes and lower swimming speed （P<0.01）， significantly lower percentage of time spent in the target quadrant （P<0.01）， and a significantly lower percentage of freezing time （P<0.05）. The number of neurons in the hippocampal region of mice was obviously reduced and unevenly arranged. The levels of SYP and PSD95（P<0.01） in the serum of mice were reduced， and the positive expression of BDNF in the DG region of the brain tissue of mice was reduced. The levels of hippocampal BDNF， Wnt3a， and β-catenin proteins in the hippocampus of mice were obviously reduced （P<0.05， P<0.01）. Compared with the model group， the mice in the SWDK group and the total ginsenoside group had significantly shorter swimming routes， the high- and medium- dose SWDK groups significantly higher swimming speeds （P<0.01）， significantly higher percentage of time spent in the target quadrant （P<0.01）， obviously higher percentage of Freezing time （P<0.05）， and obviously more neurons in the hippocampal region of the mice with tighter arrangement. The mice had elevated levels of serum SYP （P<0.05， P<0.01）， PSD95 （P<0.01）， increased BDNF-positive cells in the DG region of brain tissue， and obviously elevated levels of BDNF， Wnt3a， and β-catenin proteins in the hippocampus of mice （P<0.05， P<0.01）. ConclusionSWDK can significantly improve the cognitive dysfunction of AD mice， and its mechanism may be related to regulating the Wnt/β-catenin signaling pathway， which promotes BDNF expression and thereby enhances synaptic plasticity， allowing neuronal signaling to be restored.