ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease （AD） based on network pharmacology， molecular docking， and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and the Encyclopedia of Traditional Chinese Medicine（ETCM） databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards， Online Mendelian Inheritance in Man（OMIM）， TTD， PharmGKB， and DrugBank databases were used to obtain the relevant targets of AD. The intersection （common targets） of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken， and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction（PPI） network. The CytoNCA plugin within Cytoscape was used to screen out the core targets， and the Metascape platform was used to perform gene ontology（GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2， and AutoDock Vina was used for molecular docking. Scopolamine （SCOP） was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control （CON） group （0.9% NaCl， n=8）， model （SCOP） group （3 mg·kg^-1·d^-1， n=8）， positive control group （3 mg·kg^-1·d^-1 of SCOP+3 mg·kg^-1·d^-1 of Donepezil， n=8）， and Kaixinsan group （3 mg·kg^-1·d^-1 of SCOP+6.5 g·kg^-1·d^-1 of Kaixinsan， n=8）. Mice in each group were administered with 0.9% NaCl， Kaixinsan， or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin （HE） staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay（ELISA） was used to determine the serum acetylcholine （ACh） and acetylcholinesterase （AChE） contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3（STAT3） and nuclear transcription factor（NF）-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained， and 578 potential targets （common targets） of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol， gijugliflozin， etc.. Potential core targets were STAT3， NF-κB p65， et al. GO functional enrichment analysis obtained 3 124 biological functions， 254 cellular building blocks， and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways， mainly involving cancer-related pathways， TRP pathway， cyclic adenosine monophosphate（cAMP） pathway， and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65， STAT3， and other targets involved in the NF-κB signaling pathway.

Functional cure is currently recommended by guidelines as the ideal treatment goal for the prevention and treatment of chronic hepatitis B （CHB） in China and globally， and it is defined as sustained and undetectable serum HBsAg and HBV DNA， HBeAg clearance， and presence or absence of HBsAg seroconversion， accompanied by resolution of liver inflammation， histopathological improvements， and a significant reduction in the incidence rate of end-stage liver disease. HBV can integrate into the host genome and contribute to the continuous production of HBsAg， which can occur in the early stage of chronic HBV infection. In addition to the covalently closed circular DNA that is hard to be eliminated in liver tissue， HBsAg derived from HBV integration independent of viral replication may be the most important factor for the difficulty in achieving functional cure after antiviral therapy in patients with hepatitis B. This article reviews the research advances in HBV integration in recent years and discusses its impact on functional cure.

Aromatic inhalation therapy is a key traditional Chinese medicine （TCM） approach for preventing respiratory infectious diseases. Its foundational theory， "aromatics acting on the spleen"， is deeply rooted in TCM principles and supported by modern medical research. The theory posits that the aromatic properties of medicinals primarily act on the spleen， and the aromatic inhalation therapy achieved its protective effects by modulation of the spleen and spleen channel to enhance the regulation of wei qi， striae and interstices. In TCM， the spleen is considered the mother of the lungs， with the function of nurturing lung； it is also seen as the source of wei qi， responsible for external defense； and the root of healthy qi， forming the foundation of acquired （postnatal） constitution. Thus， preventive strategies for respiratory infectious diseases focus on strengthening the spleen. From a modern medical perspective， the spleen's role in regulating lung immune responses， the shared immune functions of the respiratory and gastrointestinal mucosa， and the spleen's overall immune modulation provide scientific evidence for using aromatic inhalation therapy to prevent respiratory infections. Additionally， aromatic inhalation therapy offers several advantages， including direct action， rapid onset， minimal side effects， controllable risks， convenience， and ease of dissemination， making it a practical and effective preventive measure for respiratory infectious diseases.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

Objective: To analyze the epidemiological characteristics and changing trends of non suicidal self injury (NSSI) behaviors among middle school students in Jiading District of Shanghai, from 2015 to 2023, so as to provide a basis for the development of NSSI prevention and control measures among students. Methods: Using a stratified cluster random sampling method, a total of five times for Shanghai Adolescent Health Risk Behavior Surveys were conducted for every two years in Jiading District of Shanghai from 2015 to 2023. A total of 5 231 middle school students from junior high schools and senior high schools were selected for questionnaire surveys. Intergroup comparisons were performed using the x 2 test or the χ 2 trend test, and the JointPoint 5.0 software was used to analyze the changing trends, with the annual percent change (APC) used for evaluation. A binary Logistic regression model was employed to analyze the related factors of NSSI behavior among middle school students. Results: In 2023, the reported NSSI rate among middle school students in Jiading District was 14.2%. The rate was significantly higher among junior high school students (17.1%) than that among senior high school students (11.1%), and higher among females (19.2%) than that among males (10.0%) ( χ 2=10.04, 23.21, both P <0.01). From 2015 to 2023, the overall reported NSSI rate showed an increasing trend, rising from 8.6% in 2015 to 14.2% in 2023 ( χ 2 trend =22.25), with an APC of 6.64% ( t =3.49), and the APC for girls was 9.79 % ( t =3.20) (all P <0.05). Among students reporting NSSI, the proportion experiencing ≥6 episodes increased from 10.8% in 2015 to 19.2% in 2023 ( χ 2 trend =6.57, P <0.05). Multivariate Logistic regression analysis indicated that girls, junior high school students, those with insomnia, depressive emotion and drinkers had higher risks of NSSI, compared to boys, senior high school students, those without insomnia, non depressive emotion students and non drinkers ( OR =1.71, 1.96, 3.44, 4.76, 1.77, all P < 0.05 ). Conclusions The reported rate of NSSI among middle school students in Jiading District of Shanghai, increased annually from 2015 to 2023, and the proportion of repeated NSSI also showed an upward trend. Early intervention measures targeting middle school students, especially junior high school students and females, should be implemented to prevent and control its occurrence and development.

Objective:To investigate the effect of sleep on physical performance and the correlation between sleep quality and physical performance in the elderly.Methods:In this prospective multicenter case-control study, 472 elderly people aged 60-80 years were recruited from three regions in China, Beijing, Tianjin, and Hainan Province.Basic information of study participants was collected through face-to-face interviews, and physical performance of study participants was assessed by the time up and go(TUG)test on site, with 106 cases(22.5%)in the normal physical performance group and 366 cases(77.5%)in the abnormal group.The Pittsburgh Sleep Quality Index(PSQI)and the Epworth Sleepiness Scale(ESS)were applied to assess sleep quality of study subjects.Correlation analysis was performed to examine factors affecting subjects' physical performance.Results:Age, history of alcohol consumption, BMI, past medical history, the ESS score, daytime sleepiness, and some components of PSQI, such as sleep quality, sleep efficiency, sleep disturbances, use of sleeping drugs and daytime dysfunction, were influencing factors of the TUG score.Two components of PSQI, sleep duration and habitual sleep efficiency, and the ESS score were positively correlated with physical performance.Logistic regression analysis showed that risk factors for decreased physical performance in the elderly included increased age( OR=1.125, 95% CI: 1.083-1.168, P<0.01), history of alcohol consumption( OR=0.482, 95% CI: 0.384-0.605, P<0.001), abnormally high body mass index( OR=1.663, 95% CI: 1.340-2.063, P<0.01), hyperlipemia( OR=0.156, 95% CI: 0.077-0.318, P<0.01), digestive system diseases( OR=0.154, 95% CI: 0.044-0.532, P<0.01), use of sleeping drugs( OR=0.415, 95% CI: 0.202-0.854, P<0.05), daytime sleepiness( OR=4.234, 95% CI: 2.800-6.403, P<0.01), a high habitual sleep efficiency score of PSQI( OR=1.425, 95% CI: 1.214-1.672, P<0.01)and a high sleep disturbances score in PSQI( OR=3.356, 95% CI: 2.337-4.819, P<0.01). Conclusions:The incidence of physical performance decline is high in the elderly.There is a correlation between physical performance and sleep quality.

Objective:To explore the function of MDM2 and its relationship with p53 at the cellular level during H 2O 2 induced oxidative damage. Methods:MLE-12 HALI cell models were established using 0.5 mmol/L H 2O 2, and were divided into three groups: normal control group, H 2O 2 injury group, H 2O 2+MDM2 overexpressed group, and H 2O 2+MDM2 shRNA group. Infection of MLE-12 cells with adenovirus vector overexpressing and silencing MDM2; Using immunoprecipitation (Co-IP) to analyze the interaction between MDM2 and p53; Western blotting was used to detect the protein expression levels of MDM2, p53, Bcl-2, Bax, and cleared caspase-3 after HALI modeling; Measure the apoptosis rate of cells in each group. Results:After transcriptome sequencing,the p53 signaling pathway closely related to HALI. Compared with the normal group, the expression of MDM2 in the H 2O 2 injury group was lower ( P<0.05); Compared with the H 2O 2 injury group, overexpression of MDM2 resulted in a decrease in the apoptosis rate of MLE-12 cells ( P<0.05), a decrease in the expression levels of p53, Bax, and cleared caspase-3 proteins, and an upregulation of MDM2 and Bcl-2 protein expression ( P<0.05). Compared with the H 2O 2 injury group, when MDM2 was silenced, the cell apoptosis rate increased ( P<0.05), and the expression levels of p53, Bax, and cleared caspase-3 proteins were upregulated, while the expression levels of MDM2 and Bcl-2 proteins decreased ( P<0.05). Co-IP experiments showed that MDM2 binds to p53 protein. Conclusions:MDM2 can exert a protective effect on HALI by inhibiting MLE-12 cell apoptosis through the p53/Bcl-2/Bax axis.

Objective:To investigate the interaction of platelet factor 4(PF4)with tumor necrosis factor-α(TNF-α)in the pathoge-nesis of chronic periodontitis(Ⅲ-C).Methods:22 patients with chronic periodontitis(Ⅲ-C)and 22 subjects with periodontal health were recruited.Before and after periodontal treatment,the concentration of PF4 and TNF-α in gingival crevicular fluid(GCF)and ser-um,the amount of PF4 released by platelets after lipopolysaccharide(LPS)stimulated peripheral blood platelets were measured by ELISA.Flow cytometry was used to calculate the number of platelets in GCF before and after treatment.Results:The concentrations of PF4 and TNF-α in the GCF and serum of the patients were higher than those in the periodontal healthy group(P＜0.05).After treat-ment,the concentrations of PF4 and TNF-α in the GCF were significantly lower than those before treatment(P＜0.05),and the con-centrations of PF4 and TNF-α in the serum were unchanged(P＞0.05).After LPS stimulation of the platelets in blood before and after treatment,the concentration of PF4 released by the platelets was much higher in the patients than that in the healthy controls(P＜0.01),and the concentration was significantly lower after periodontal treatment than before treatment(P＜0.01).The number of CD41/CD61 double positive platelets and CD45 negative cells in GCF before periodontal treatment were 85 times and 87 times higher than those in periodontal healthy subjects,respectively(P＜0.01).Conclusion:PF4 and TNF-α have synergistic effect in the patho-genesis of chronic periodontitis.