ObjectiveTo investigate the therapeutic effects of the Anemarrhenae Rhizoma water extract （AR） on Alzheimer's disease （AD） model rats and to explore its potential underlying mechanisms. MethodsMale rats were intraperitoneally injected with D-galactose （100 mg·kg^-1） for 42 days， and on day 14， 1 μL of β-amyloid （Aβ_25-35， 2 g·L^-1） solution was injected into the hippocampus. Rats were randomly divided into a model group， low-dose AR （0.6 g·kg^-1）， medium-dose AR （1.2 g·kg^-1）， high-dose AR （2.4 g·kg^-1）， and a positive control group （donepezil， 5 mg·kg^-1）. Healthy rats receiving only a hippocampal injection of 1 μL of sterile saline served as the sham-operated group. From day 21， rats in the treatment groups were administered the corresponding drugs by gavage once daily for 21 consecutive days， while the blank control and model groups received an equal volume of saline. Learning and memory abilities were assessed using the Morris water maze. Brain tissue damage was observed by hematoxylin and eosin （HE） staining， and neuronal apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEL） staining. Levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and interleukin-10 （IL-10） in brain tissues were measured by enzyme-linked immunosorbent assay （ELISA）. BV2 microglial cells were co-cultured with Aβ_25-35 （40 μmol·L^-1） for 2 h， and cell viability was determined by the CCK-8 assay to screen the optimal concentration of AR-containing serum （S-AR）. Cells were divided into blank control， Aβ_25-35， S-AR， EX527 ［silent information regulator 1 （SIRT1） inhibitor］， and S-AR+EX527 groups. Immunofluorescence staining was used to detect the expression of CD16， CD206， and high-mobility group box 1 （HMGB1）. Western blot analysis was performed to measure the protein expression of CD16， inducible nitric oxide synthase （iNOS）， CD206， arginase （Arg）， and proteins related to the SIRT1/HMGB1/nuclear factor-κB （NF-κB） signaling pathway. ResultsIn vivo experiments showed that， compared with the sham-operated group， the model group exhibited reduced platform crossings and time spent in the target quadrant （P<0.01）， prolonged escape latency， increased hippocampal neuronal apoptosis （P<0.01）， and obvious hippocampal damage. The expression levels of IL-6， TNF-α， IL-10， CD16， and iNOS in brain tissues were significantly elevated （P<0.01）， while CD206 and Arg protein expression showed an increasing trend without statistical significance. Compared with the model group， all AR-treated groups significantly increased platform crossings and target quadrant time （P<0.05， P<0.01）， alleviated hippocampal damage， reduced escape latency and neuronal apoptosis， downregulated the expression of TNF-α， IL-6， CD16， and iNOS （P<0.05， P<0.01）， and upregulated the expression of IL-10， CD206 and Arg （P<0.05， P<0.01）. In vitro experiments demonstrated that， compared with the blank control group， the Aβ_25-35 group showed increased fluorescence intensity of CD206， CD16， and HMGB1， as well as elevated protein expression of iNOS and CD16 （P<0.01）， while CD206 and Arg protein expression exhibited an increasing trend without statistical significance. After S-AR intervention， CD206 fluorescence intensity and the protein expression of Arg and CD206 were significantly increased （P<0.01）， whereas the fluorescence intensity of CD16 and HMGB1 and the protein expression of iNOS and CD16 were significantly decreased （P<0.01）. These effects were reversed by EX527 （P<0.05， P<0.01）. Furthermore， compared with the blank control group， the Aβ_25-35 group showed significantly increased cytoplasmic HMGB1 expression and p-p65/p65 ratio （P<0.01）， along with significantly decreased SIRT1 and nuclear HMGB1 expression （P<0.01）. In contrast， the S-AR group exhibited opposite trends compared with the Aβ_25-35 group， and the regulatory effects of S-AR on these proteins were reversed by EX527 （P<0.01）. ConclusionAR exerts neuroprotective effects in AD model rats by regulating microglial polarization and alleviating neuroinflammation， potentially through modulation of the SIRT1/HMGB1/NF-κB signaling pathway.

Objective To explore the feasibility and safety of fastest recovery after surgery(FRAS)in laparoscopic surgery of gastrointestinal tumors.Methods The clinical data of patients undergoing laparoscopic surgery for gastrointestinal tumors under FRAS and enhanced recovery after surgery(ERAS)from Jan.2023 to May 2024 were collected,and perioperative safety and medical cost were analyzed.Results A total of 87 patients were enrolled,including 43 in the FRAS group and 44 in the ERAS group.Compared with the ERAS group,the FRAS group had significantly shorter surgical time(3.0[2.5,3.5]h vs 3.0[2.5,4.0]h),first postoperative movement time([2.85±4.29]h vs[20.18±6.13]h),first postoperative oral feeding time(2.0[2.0,3.0]h vs 24.0[15.0,48.0]h),postoperative hospital stay(24.0[20.0,40.0]h vs 192.0[150.0,216.0]h),lower hospitalization costs(50 515.61[46 650.44,56 827.12]yuan vs 65 555.09[58 683.21,86 239.02]yuan),and lower medication costs(2 671.09[2 063.31,3 127.09]yuan vs 7 326.90[5 104.66,10 674.26]yuan)(all P＜0.05).Conclusion It is safe and feasible to use FRAS during the perioperative period of laparoscopic radical gastrectomy for gastrointestinal tumors,and FRAS can also reduce the costs of hospitalization and medications.

ObjectiveTo study on the different therapeutic effects and potential mechanisms of Rhei Radix et Rhizoma（RH） before and after steaming with wine on constipation model mice. MethodsFifty-four male ICR mice were randomly divided into control group， model group， lactulose group（1.5 mg·kg^-1）， high， medium and low dose groups of RH and RH steaming with wine（PRH）（8， 4， 1 g·kg^-1）. Except for the control group， the constipation model was replicated by gavage of loperamide hydrochloride（6 mg·kg^-1） in the other groups. After 2 weeks of modeling， each administration group was gavaged with the corresponding dose of drug solution， and the control and model groups were given an equal volume of normal saline， 1 time/d for 2 consecutive weeks. After administration， the feces were collected for 16S rRNA sequencing， the levels of gastrin（GAS）， motilin（MTL）， interleukin-6（IL-6）， γ-interferon（IFN-γ） in the colonic tissue were detected by enzyme-linked immunosorbent assay（ELISA）， the histopathological changes of colon were observed by hematoxylin-eosin（HE） staining， flow cytometry was used to detect the proportion changes of CD4⁺， CD8⁺ and regulatory T cell（Treg） in peripheral blood. ResultsCompared with the control group， the model group showed significantly decrease in fecal number in 24 h， fecal quality and fecal water rate（P<0.01）， the colon was seen to have necrotic shedding of mucosal epithelium， localized intestinal glands in the lamina propria were degenerated， necrotic and atrophied， a few lymphocytes were seen to infiltrate in the necrotic area in a scattered manner， the contents of GAS and MTL， the proportions of CD4⁺， CD8⁺ and Treg were significantly reduced（P<0.01）， the contents of IL-6 and IFN-γ were significantly elevated（P<0.05， P<0.01）. Compared with the model group， the fecal number in 24 h， fecal quality and fecal water rate of high-dose groups of RH and PRH were significantly increased（P<0.05， P<0.01）， the pathological damage of the colon was alleviated to varying degrees， the contents of GAS， MTL， IL-6 and IFN-γ were significantly regressed（P<0.05， P<0.01）， and the proportions of CD4⁺ and CD8⁺ were significantly increased（P<0.01）， although the proportion of Treg showed an upward trend， there was no significant difference. In addition， the results of intestinal flora showed that the number of amplicon sequence variant（ASV） and Alpha diversity were decreased in the model group compared with the control group， and there was a significant difference in Beta diversity， with a decrease in the relative abundance of Lactobacillus and an increase in the relative abundances of Bacillus and Helicobacter. Compared with the model group， the ASV number and Alpha diversity were increased in the high-dose groups of RH and PRH， and there was a trend of regression of Beta diversity to the control group， the relative abundance of Lactobacillus increased， and the relative abundances of Bacillus and Helicobacter decreased. ConclusionRH and PRH can improve dysbacteriosis， promote immune system activation， inhibit the release of inflammatory factors for enhancing the gastrointestinal function， which may be one of the potential mechanisms of their therapeutic effect on constipation.

Infectious disease animal models serve as indispensable tools for understanding the transmission patterns,pathogenesis,and anti-infective medicine.During the preparation and application of infectious animal disease models,situations inevitably arise that violate animal welfare and ethics,such as animal pain,suffering,and distress.Considering the biosafety factors,animal mortality is still used as the experimental endpoint in most experiments on infectious animals,which poses extremely high requirements for animal welfare and ethics.It is imperative to establish guiding principles or norms for the welfare and ethics of infectious animal experiments.Based on the fundamental principles of the welfare and ethics of experimental animals,this paper explores the special welfare and ethical requirements in infectious animal experiments.It emphasizes that infectious animal experiments should fully consider the balance among the scientific objectives of the research plan,animal welfare and ethics,and occupational health and safety of personnel.Based on literature research and comparative analysis of the welfare and ethical requirements of conventional animal experiments,special welfare and ethics requirements for infectious animal experiments are proposed,including personnel requirements,experimental animal selection standards,living environment management and equipment,special care and veterinary care,and humane endpoints.Personnel are required to undergo effective biosafety training,and sufficient authority should be granted to the Institutional Animal Care and Use Committee(IACUC),veterinarians,and veterinary technicians to ensure the implementation of animal welfare and ethics practices.The selection of laboratory animals should fully consider the requirements of research objectives,welfare,ethics,and biosafety,with the susceptibility and body size of laboratory animals being the key concerns in high-level biosafety laboratories.It is also clarified that the humane endpoint is an indispensable element of welfare and ethics in infectious animal experiments.Environmental enrichment and special care are necessary guarantees for achieving animal welfare and ethics.Therefore,this study can serve as a reference for relevant work.

Infectious disease animal models serve as indispensable tools for understanding the transmission patterns,pathogenesis,and anti-infective medicine.During the preparation and application of infectious animal disease models,situations inevitably arise that violate animal welfare and ethics,such as animal pain,suffering,and distress.Considering the biosafety factors,animal mortality is still used as the experimental endpoint in most experiments on infectious animals,which poses extremely high requirements for animal welfare and ethics.It is imperative to establish guiding principles or norms for the welfare and ethics of infectious animal experiments.Based on the fundamental principles of the welfare and ethics of experimental animals,this paper explores the special welfare and ethical requirements in infectious animal experiments.It emphasizes that infectious animal experiments should fully consider the balance among the scientific objectives of the research plan,animal welfare and ethics,and occupational health and safety of personnel.Based on literature research and comparative analysis of the welfare and ethical requirements of conventional animal experiments,special welfare and ethics requirements for infectious animal experiments are proposed,including personnel requirements,experimental animal selection standards,living environment management and equipment,special care and veterinary care,and humane endpoints.Personnel are required to undergo effective biosafety training,and sufficient authority should be granted to the Institutional Animal Care and Use Committee(IACUC),veterinarians,and veterinary technicians to ensure the implementation of animal welfare and ethics practices.The selection of laboratory animals should fully consider the requirements of research objectives,welfare,ethics,and biosafety,with the susceptibility and body size of laboratory animals being the key concerns in high-level biosafety laboratories.It is also clarified that the humane endpoint is an indispensable element of welfare and ethics in infectious animal experiments.Environmental enrichment and special care are necessary guarantees for achieving animal welfare and ethics.Therefore,this study can serve as a reference for relevant work.

Objective:To explore the effect of Shenxianling granules on the pharmacokinetics of ondansetron. Methods:A method for detecting the plasma concentration of ondansetron using highperformance liquid chromatography (HPLC) was established. The reliability of the method was validated through specificity, linear relationship, precision, stability, repeated experiments, and sample recovery rate testing. Thirty six healthy male New Zealand rabbits were randomly divided into 2 groups, with 18 rabbits in each group. Rabbits in the single ondansetron group (single drug group) received intravenous injection of ondansetron 0.92 mg/kg through the ear vein. Rabbits in the Shenxianling granules combined with ondansetron group (combination drug group) were firstly given 575 mg/kg of Shenxianling granules by gavage continuously for 10 days, and on the morning of the 11th day, ondansetron 0.92 mg/kg was intravenously injected. Blood samples were collected before administration and at 5 minutes, 10 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours and 24 hours after administration of ondansetron. The blood concentration of ondansetron was detected using HPLC method and pharmacokinetic parameters were calculate. Results:Two New Zealand rabbits in the combination drug group developed agitation and cough, and then died on the second and fifth day of gavage, respectively. Therefore a total of 18 and 16 rabbits in the single drug group and the combination drug group completed the experiment, respectively. After ondansetron administration, the plasma concentration of ondansetron increased rapidly in the single drug group and remained at low levels in the combination drug group. From 5 minutes to 10 hours after administration, the plasma concentration of ondansetron at the 13 blood sampling time points in the combination drug group was significantly lower than that in the single drug group, and the differences were statistically significant (all P<0.001). Compared with the single drug group, the plasma clearance half-life of ondansetron in the combination drug group was significantly prolonged, the peak time, peak concentration, concentration at the last time and area under the curve (AUC) were all significantly reduced, and the percen- tage of residual or extrapolated area to the overall AUC, apparent volume of distribution, and clearance/bioavailability ratio were significantly increased; the differences were statistically significant (all P<0.001). Conclusions:There is a significant interaction between Shenxianling granules and ondansetron, leading to a decreased plasma concentration of ondansetron. The mechanism may be related to Shenxianling granules altering the tissue distribution of ondansetron within the body.

Purpose To explore the characteristics of gray matter(GM)volume changes in migraine patients using 7T MRI and voxel-based morphometry(VBM).Materials and Methods This prospective study enrolled 30 migraine patients and 41 age-and gender-matched healthy controls from Beijing Tiantan Hospital,Capital Medical University between November 2023 and November 2024.All participants underwent 7T MRI with 3D T1-weighted magnetization-prepared two rapid gradient-echo(MP2RAGE)sequences for structural brain imaging.VBM analysis was performed to quantify GM,white matter,cerebrospinal fluid and total brain volumes,followed by calculations of their relative percentages.The difference in GM volume between the two groups was compared to identify brain regions with characteristic GM volume changes in migraine patients.And the correlation between these characteristic GM volume alterations and clinical scales was analyzed.Results Migraine patients exhibited significantly lower total GM volume compared to healthy controls(t=2.096,P=0.040),while no group differences were observed in white matter or cerebrospinal fluid volumes(t=0.980,0.151;P=0.330,0.880).VBM analysis revealed reduced GM volume in the left orbitofrontal cortex(t=4.301,P=0.022),left hippocampus(t=5.226,P=0.006)and left parahippocampal gyrus(t=3.960,P=0.040)in the migraine group.Negative correlations were identified between:left orbitofrontal cortex GM volume and headache duration(r=-0.506,P=0.008),left hippocampal GM volume and patient health questionnaire-9 scores(r=-0.620,P=0.003),and left parahippocampal GM volume and visual analogue scale scores(r=-0.449,P=0.019).Conclusion VBM analysis based on 7T MP2RAGE data demonstrates characteristic GM volume reductions in the left orbitofrontal cortex,left hippocampus and left parahippocampal gyrus in migraine patients,with these structural alterations significantly correlate with depressive symptoms and headache burden.The observed microstructural abnormalities may reflect underlying pathophysiological mechanisms related to pain processing,emotional regulation and long-term disease burden in migraine.

Pain is a distressing experience in sensory,emotional,cognitive,and social dimensions associated with existed or potential tissue damage.Studies have demonstrated the efficacy of acupuncture analgesia,but the underlying mechanisms are not fully understood.Bioelectrical signals,as one of the basic characteristics of life activities,play a key role in the process of acu-puncture analgesia.Through advanced neurophysiological techniques and multimodal imaging,it has been found that acupuncture can trigger specific changes in bioelectric signals,thus producing analgesic effects.With the rapid development of modern medi-cal technology,the study of bioelectrical signals has gradually delved into the cellular and molecular levels,providing more possi-bilities to reveal the analgesic mechanism of acupuncture.This review focuses on the close connection between bioelectrical sig-naling phenomena and acupuncture analgesia mechanism,summarizes the current research status of bioelectrical signaling phe-nomena in acupuncture analgesia mechanism by collating related literature.The future research directions were prospected,ai-ming to provide theoretical basis and new ideas for further understanding and applying acupuncture analgesia.

Objective This study aimed to construct a risk scoring model based on DNA methylation featuresof ferroptosis-related gene,and systematically evaluate its predictive value for the prognosis and immunotherapy response of patients with colon canc-er.Methods Transcriptomic,DNA methylation,and clinical data of colon cancer patients were obtained from the Cancer Genome At-las(TCGA)and Gene Expression Omnibus(GEO)databases.Ferroptosis-related genes were identified from the FerrDb database.Fer-roptosis scores(FS)for each patient were calculated using the single-sample gene set enrichment analysis(ssGSEA)method,and con-struct a risk scoring model by combining differential methylation CpG sites with Cox regression analysis.The prognostic performance of the model was evaluated using receiver operating characteristic(ROC)curves,a nomogram,and decision curve analysis.The multiple algorithms were used to analyze the relationship between colon cancer models and immune cell infiltration,immunotherapy response,and chemotherapy sensitivity.Results A total of 49 ferroptosis-related genes significantly associated with overall survival(OS)were identified for calculating FS.The OS of colon cancer patients in the high-FS group was significantly shorter than that in the low-FS group(P=0.0075).The constructed DNA methylation risk score models included key CpG sites,and the ROC curves and multivariate Cox regression analysis at 1-,3-,and 5-years overall survival rate in the TCGA cohort and the GSE17536 validation cohort showed that the model was an independent prognostic factor for colon cancer patients.The low-risk group had higher immune scores and infil-tration levels of B cells and dendritic cells,while the high-risk group had a higher abundance of fibroblasts.Patients in the high-risk group showed upregulation of PD-L1 expression and higher immune phenotype scores.In addition,the model could also predict the sensitivity differences of commonly used chemotherapeutic drugs such as doxorubicin,gemcitabine,and paclitaxel.Conclusion The risk scoring model established using DNA methylation features of ferroptosis-related gene can be used to predict the prognosis of colon cancer patients and provide a new biomarker for achieving precision treatment.

This study aims to investigate the biological function of the Clumping factor B(clfB)gene in Staphylococcus aureus.The recombinant plasmid pBT2-△clfB was constructed and elec-troporated into Staphylococcus aureus J57 to delete clfB by homologous recombination.The ex-pression plasmid pLI50-clfB was constructed,modified,and electroporated into clfB gene deletion strain △clfB and constructed a complementation strain(C△clfB).J57,△clfB,and C△clfB were cultured at 37℃ for 12 h,and the growth curves of each strain were plotted.The hemolytic properties of each strain were analyzed by contact method,the motility of each strain on TSA plates was determined,and the autolysis rate of each strain under the action of TritonX-100 was determined.Crystal violet staining was used to detect each strain's biofilm formation ability,and biofilm components formed by each strain were quantitatively analyzed.The K-B method was used to determine the sensitivity of each strain to commonly used antibiotics.ClfB gene deletion strain△clfB and the complemented strain C△clfB were successfully constructed.The growth curves of the deletion strain were almost consistent with those of the wild and complemented strains,and there was no significant difference.Compared with J57 and C△clfB,the hemoly ability and the athletic of △clfB decreased.In the condition of TritonX-100,the autolysis rate of △clfB was significantly lower than that of J57 and C△clfB(P＜0.01).Compared with J57 and C△clfB,the ability of △clfB to form biofilm was significantly lower than that of J57 and C△clfB(P＜0.05),and the content of extracellular DNA and protein in the biofilm was significantly decreased.In con-trast,the content of soluble polysaccharides was significantly increased(P＜0.05).Compared with J57 and C△clfB,△clfB was more sensitive to chloramphenicol,gentamicin,and kanamycin while more resistant to linezolid.ClfB gene is closely related to the autolysis,hemolytic activity,athlet-ic,and biofilm formation ability of Staphylococcus aureus,affecting the sensitivity of bacteria to certain antibiotics.