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.

ObjectiveThe study aims to investigate the intervention effect of modified Xiangsha Liujunzitang （M-XSLJZ） on intestinal-derived lipopolysaccharide （LPS）-activated Kupffer cell inflammation in rats with hyperlipidemia spleen deficiency syndrome. MethodsSeventy male SD rats were randomly divided into seven groups （n=10）： blank control （CON）， high-fat diet without spleen deficiency （HFD）， high-fat diet with spleen deficiency （SD-HFD）， M-XSLJZ low-， medium-， and high-dose groups （XS-L， XS-M， XS-H）， and western medicine control （R）. Spleen deficiency was induced in SD-HFD， XS-L， XS-M， XS-H， and R groups via irregular diet combined with exhaustive swimming for 15 days. The CON group received a standard diet， while other groups were fed a high-fat diet for 10 weeks to establish the hyperlipidemia model. After successful modeling， rats were treated for 8 weeks： M-XSLJZ was administered at 3.51， 7.02， 14.04 g·kg^-1 in XS-L， XS-M， and XS-H groups， respectively. The R group received 9×10^-4 g·kg^-1 of a reference drug. D-xylose excretion rate was measured by the phloroglucinol method. Blood lipids were assessed using an automated biochemical analyzer. Hematoxylin-eosin （HE） staining was used to evaluate the pathological conditions of the liver， and oil red O staining was used to observe the lipid deposition in the liver. The levels of LPS， portal vein serum LPS， LPS-binding protein （LBP）， serum interleukin-6 （IL-6）， IL-1β， and tumor necrosis factor-α （TNF-α） were detected by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence was used to evaluate CD86 expression and CD68/TLR4 co-localization in the liver. Protein levels of TLR4， MyD88， NF-κB p65， and p-NF-κB p65 in Kupffer cells were analyzed via Western blot automated protein analysis. Hepatic IL-6， TNF-α， and IL-1β mRNA and protein levels were measured using Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultsCompared with the CON group， the SD-HFD group showed a decrease in D-xylose excretion （P<0.01）. TC， TG， HDL-C， and LDL-C increased （P<0.05， P<0.01）. A large number of hepatic lipid vacuoles and orange-red lipid droplet deposition appeared in the liver. Ileal LPS， portal LPS， and LBP increased （P<0.05， P<0.01）. The levels of serum IL-6， TNF-α， and IL-1β increased （P<0.01）. The expression of CD86 was upregulated （P<0.01）， and the co-expression of CD68 and TLR4 was enhanced. The protein levels of TLR4， MyD88， and p-p65 in Kupffer cells increased （P<0.01）. The mRNA and protein levels of IL-6， TNF-α， and IL-1β increased （P<0.05， P<0.01）. Compared with the HFD group， the SD-HFD group exhibited decreased D-xylose excretion （P<0.01）， higher HDL-C， LDL-C （P<0.05）， increased portal LBP and LPS （P<0.05）， increased serum IL-6 and TNF-α （P<0.01）， upregulated CD86 （P<0.01）， enhanced CD68/TLR4 co-expression， and higher TNF-α mRNA/protein （P<0.05）. Compared with the SD-HFD group， all M-XSLJZ treatment groups showed reduced TC， TG， and LDL-C （P<0.05， P<0.01）. XS-H and R groups displayed improved hepatic lipid deposition. XS-H and R groups had lower ileal LPS， portal LPS， and LBP levels （P<0.05， P<0.01）. All M-XSLJZ treatment groups exhibited reduced serum IL-6， IL-1β， and TNF-α （P<0.01）. The XS-H group showed downregulated CD86 （P<0.01） and weakened CD68/TLR4 co-expression. The XS-H group had reduced TLR4， MyD88， and p-NF-κB p65 in Kupffer cells （P<0.01）. XS-H and R groups showed lower IL-6， TNF-α， and IL-1β mRNA/protein （P<0.05， P<0.01）. ConclusionM-XSLJZ may exert its lipid-lowering effects by inhibiting intestinal-derived LPS and alleviating Kupffer cell inflammation in the liver.

Objective To explore the therapeutic effect and mechanism of pachymic acid(PA)on Helicobacter py-lori(Hp)-associated gastritis in rats.Methods A rat model of Hp-associated gastritis was established;all rats were separated into control group(CT group),model group(group M),PA low-dose group(PA L group),PA high-dose group(PA H group),and PA H+phosphatidylinositol 3-kinase(PI3K)activator(740 Y-P)group;the gastric mucosal injury index(UI)of rats in each group was evaluated,transmission electron microscopy was applied to observe the morphology of gastric mucosal cells.HE staining was applied to evaluate the pathological characteristics of gastric mucosa.ELISA was applied to detect the levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),IL-10,induc-ible nitric oxide synthase(iNOS),and superoxide dismutase(SOD)in gastric tissue.Western blot method was applied to detect the expression of PI3K,phosphorylated PI3K(p-PI3K),protein kinase B(AKT),p-AKT,nuclear factor(NF)-κB p65,and p-NF-κB p65 proteins.Results Compared with the CT group,the gastric mucosa erosion,epithelial ede-ma,congestion,and severe ulcers were observed in the group M,with epithelial cell pyknosis and inflammatory cell in-filtration,the UI,IL-6,TNF-α,iNOS,and the expression levels of p-PI3K/PI3K,p-AKT/AKT,p-NF-κB p65/NF-κB p65 proteins increased,the levels of IL-10 and SOD decreased(P<0.05);compared with group M,the gastric mucosal damage and inflammatory cell infiltration in the PA L and PA H groups were improved,the UI,IL-6,TNF-α,iNOS by the host animal and the expression of p-PI3K/PI3K,p-AKT/AKT,p-NF-κB p65/NF-κB p65 proteins all decreased,the level of IL-10 and SOD was increased(P<0.05);compared with the PA H group,the pathological damage of the gastric mucosa in the PA H+740 Y-P group was aggravated,with epithelial cell pyknosis.The UI,IL-6,TNF-α,iNOS,and the expression of p-PI3K/PI3K,p-AKT/AKT,p-NF-κB p65/NF-κB p65 proteins increased,the levels of IL-10 and SOD decreased(P<0.05).Conclusions PA might facilitate the treatment of Hp-associated gastritis in rats by inhibiting the PI3K/AKT/NF-κB signaling pathway.

Objective:To investigate the value of serum miR-145 and matrixmetallo proteinase-2 (MMP-2) levels in predicting pathologic complete response (pCR) after neoadjuvant chemotherapy in triple-negative breast cancer.Methods:125 patients with triple-negative breast cancer who received neoadjuvant chemotherapy in the Hospital from Jan. 2022 to Dec. 2023 were prospectively included as the study objects, and 130 healthy people matching the age of the case group who underwent physical examination in our hospital during the same period were included as the healthy control group. Real-time fluorescence quantitative polymerase chain reaction was used to detect the serum miR-145 level of all subjects. Serum MMP-2 levels were determined by enzyme-linked immunosorbent assay (ELISA). After neoadjuvant chemotherapy, patients were evaluated according to Miller-Payne (MP) grading criteria and divided into pCR group and non-PCR group.Results:The serum miR-145 level in patients with tertiary breast cancer was 1.49±0.27, which was significantly lower than that in healthy control group (2.79±0.49), with statistical significance ( t=20.33, P<0.001). The serum MMP-2 level in triple negative breast cancer patients was (153.07±38.36) ng/mL, which was significantly higher than that in healthy control group (84.38±12.63) ng/mL, and the difference was statistically significant ( t=26.13, P<0.001). After neoadjuvant chemotherapy, the serum miR-145 level in non-PCR patients before treatment was 1.36±0.21, which was significantly lower than that in pCR group (1.74±0.20), with statistical significance ( t=9.93, P<0.001). After neoadjuvant chemotherapy, the serum MMP-2 level in non-PCR patients before treatment was (169.57±30.45) ng/mL, which was significantly higher than that in pCR group (121.61±31.79) ng/mL, and the difference was statistically significant ( t=8.24, P<0.001). Pearson correlation analysis showed that there was a significant negative correlation between serum miR-145 and MMP-2 levels in patients with triple-negative breast cancer before treatment ( r=-0.47, P<0.001). ROC curve analysis results showed that serum miR-145 and MMP-2 levels before treatment predicted the sensitivity and specificity of pCR after neoadjuvant chemotherapy for triple-negative breast cancer were 82.9% and 74.4%, 45.1% and 99.8%, respectively. The sensitivity and specificity of pCR after neoadjuvant chemotherapy for triple-negative breast cancer were 84.1% and 88.4%, respectively. Conclusion:Serum miR-145 and MMP-2 levels are related to the efficacy of neoadjuvant chemotherapy in patients with triple-negative breast cancer, and the combined application of the two has certain predictive value.

Inguinal hernia (IH) is a common complication in prostate cancer patients undergoing radical prostatectomy (RP), which seriously affects their quality of life.The repair of IH is often challenging due to the adhesion in the inguinal area caused by previous surgery.This article focuses on the risk factors for IH after RP, including surgical approach, postoperative anatomical changes, low body mass index (BMI), muscle loss, advanced age, international prostate symptom score (IPSS), and patent sheath process, and prevention strategies for IH after RP, including robot assisted laparoscopic radical prostatectomy (RARP) with IH repair, preservation of the posterior pubic space in RARP, treatment of the spermatic cord, extraperitoneal RARP, and intraoperative management of the sheath like process, aiming to provide reference for urologists and to improve patients' quality of life.

Objective:To elucidate the primary elements pertaining to the perception of relapse risk and to in-vestigate the characteristics and alterations of perception of the risk of recurrence in patients with schizophrenia.Methods:By using the method of phenomenological study,semi-structured in-depth interviews were conducted among schizophrenic patients with first onset,first recurrence and multiple recurrences.Twenty-three 23 outpatient and inpatient cases that met the criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)were included,and all patients had PANSS scores below 60.The interview data were collated and analyzed according to Colaizzi analysis.Results:The perception of recurrence risk in patients with schizophrenia en-compassed 4 major themes and 11 sub-themes,namely susceptibility(limited overall understanding,transition from optimism to objectivity),detection of early warning symptoms(dynamic escalation,assistance from family mem-bers in identification),understanding risk factors(lack of understanding,the relationship between psychosocial fac-tors and relapse,dynamic understanding of medication-relapse relationship),and apprehension of the consequences of recurrence(care burden and financial constraints,impaired social functioning and maladjustment,impact on pub-lic safety,personal health risks).Conclusion:The content of risk perception of recurrence in patients with schizo-phrenia is relatively substantial.The overall level of risk perception of recurrence in patients with schizophrenia is low.

Objective:To analyze the current prevalence of pre-diabetes (PDM) and its relationship with overweight and obesity in an adult health check-up population.Methods:This study was a cross-sectional and retrospective cohort study and was applied using whole-cluster random sampling method. A total of 491 379 adults who underwent health check-ups at the Health Management Centre of Sichuan Provincial People′s Hospital from January 2017 to July 2023 were selected to analyze the epidemiological characteristics of PDM and overweight-obesity, as well as the trend of change over time. A retrospective cohort study was conducted on 19 001 of the subjects who underwent≥3 health check-ups and did not have diabetes and PDM at baseline, and the relationships between body mass index, waist circumference and the risk for developing PDM were analyzed using Cox proportional risk regression models. And the dose-response relationship between body mass index, waist circumference and the risk for developing PDM was analyzed using restricted cubic spline regression (RCS).Results:Of the 491 379 cases included in the cross-sectional study, 275 084 were male and 216 295 were female, 163 158 cases were under 40 years old, and 328 221 cases were 40 years old and above; the total prevalence of PDM was 19.41% in 2017-2023, with an overall increasing trend. Of the 19 001 people included in the cohort study, a total of 2 487 (13.09%) new cases of PDM were identified at the end of follow-up. After adjusting for confounding factors, overweight ( HR=1.150, 95% CI: 1.047-1.263), obesity ( HR=1.335, 95% CI: 1.149-1.552) and abdominal obesity ( HR=1.218, 95% CI: 1.105-1.342) were risk factors for PDM. The risk of PDM rised with the increase of body mass index (>22.9 kg/m 2, Pnon-linear=0.973) and waist circumference (>80 cm, Pnon-linear=0.830), with a linear dose-response mode. In different gender and age groups, it was found the greater the body mass index (>24.1 kg/m 2 for men,>21.5 kg/m 2 for women;>23.3 kg/m 2 for age≥40 years,>24.1 kg/m 2 for age<40 years) and waist circumference (>85 cm for men, >73 cm for women; >82 cm for age ≥40 years, >85 cm for age <40 years), the higher the risk of PDM. Conclusions:The prevalence of PDM is on the rise in the adult health check-up population. To prevent PDM, it is necessary to control the body mass index and waist circumference to a lower level than the overweight and obesity standards.

Objective:To evaluate the safety and efficacy of transtobturator urethral sling operation in the treatment of male stress urinary incontinence.Methods:A retrospective analysis was conducted on the clinical data of 13 male patients with stress urinary incontinence who underwent transvaginal sling procedure at Peking University People's Hospital from June 2011 to July 2024. The patients' average age was (71.6±5.4) years. Among them, 9 patients had undergone radical prostatectomy, and 4 had undergone transurethral resection of the prostate (TURP). Of the 13 patients, 7 had moderate urinary incontinence, and 6 had severe urinary incontinence. The median daily number of urine pads used by the 13 patients before surgery was 5 (3, 8), and the median score of the Incontinence Quality of Life Questionnaire (I-QOL) was 16 (12, 28). The median score of the Male Stress Urinary Incontinence Grading Scale (MSIGS) was 2 (2, 3). All the 13 patients underwent transvaginal sling procedure. The patients were placed in the lithotomy position, and the urethral bulb was dissected anatomically beneath the scrotum. The sling was guided by a needle and pulled out through the obturator foramen, and placed over the urethral bulb. The sling was tightened and the tension adjusted to fully suspend the urethra. A urinary catheter was left in place for 1-7 days after surgery. The patients' postoperative daily use of urine pads, scores of the I-QOL and MSIGS, and postoperative complications were followed up.Results:Postoperative follow-up ranged from 2 to 139 months, with a median follow-up time of 12 months. Of the 13 patients, 2 were cured, 9 had improved and 2 had no significant improvement. The number of diapers used per day by patients postoperatively was 1 (1, 4) pieces, the I-QOL score was 75 (46, 82), and the MSIGS score was 1 (0, 2), which were all significantly improved compared to preoperative values ( P<0.01). Among the 6 severe stress urinary incontinence patients who were followed up, the number of diapers used per day was significantly reduced compared to preoperative values[ 2(1, 5) vs. 8(7, 8) pieces], and the I-QOL score was significantly improved [ 60(35, 70) vs. 12(10, 16) ], while the MSIGS score was significantly lower [ 2(1, 3) vs. 3(2, 4) ]. Among the 7 moderate stress urinary incontinence patients, the number of diapers used per day was significantly reduced compared to preoperative values [1 (0, 1) vs. 4 (4, 5) pieces], and the I-QOL score was significantly improved [ 80(75, 82) vs. 21(18, 30) ], while the MSIGS score was significantly lower [ 0 (0, 1) vs. 2 (2, 3) ]. The symptoms of 1 patient were not significantly improved after the surgery, and were improved after Virtue sling suspension 3 years later. Conclusions:The use of transtobturator urethral sling operation for the treatment of moderate to severe male stress urinary incontinence has shown clear efficacy, with a low incidence of postoperative complications.

ObjectiveTo investigate the efficacy and safety of Shengxiantang in the treatment of early Parkinson's disease with autonomic dysfunction of Qi deficiency pattern. MethodA total of 82 eligible patients were randomized into control group （41 cases） and traditional Chinese medicine （TCM） group （41 cases）. On the basis of standardized treatment of western medicine， TCM group was prescribed Shengxiantang while control group were treated with placebo for 12 consecutive weeks additionally. Scale for Outcomes in Parkinson's Disease-Autonomic （SCOPA-AUT） questionnaire， Unified Parkinson's Disease Rating Scale （UPDRS）， Traditional Chinese Medicine Qi Deficiency Symptom Score of Parkinson's Disease （TCMQDSSPD）， serum levels of glutathione peroxidase （GPx） and superoxide dismutase （SOD）， daily dosage of pramipexole and levodopa and benserazide hydrochloride， and safety index were evaluated both before and after treatment. ResultAfter treatment， the total score of SCOPA-AUT， gastrointestinal score， urinary score， and thermoregulatory score in the control group were higher than those before treatment （P<0.01）， while the above sores in the TCM group were lower than those before treatment （P<0.05， P<0.01）. In addition， the cardiovascular score， pupillomotor score， and sexual score in two groups showed no significant difference from those before treatment. After treatment， the total score of SCOPA-AUT， gastrointestinal score， urinary score， and thermoregulatory score in the TCM group were lower than those in the control group （P<0.05， P<0.01）， and cardiovascular score， pupillomotor score， and sexual score showed no significant difference between two groups. After treatment， the total score of TCMQDSSPD， main symptom scores， and minor symptom scores in the control group had no significant difference from those before treatment. The total score of TCMQDSSPD and minor symptom scores of TCM group were lower than those before treatment （P<0.01）， while the main symptom scores of the TCM group showed no significant difference from those before treatment. After treatment， the UPDRS score， serum GPx and SOD levels， and daily dosage of pramipexole and levodopa and benserazide hydrochloride demonstrated no significant difference from those before treatment in the two groups and between the two groups. No abnormality was found in the safety indexes. ConclusionBased on the standardized treatment of western medicine， Shengxiantang can effectively and safely improve the autonomic symptoms of gastrointestinal system， urinary system， and thermoregulation， as well as the symptoms of Qi deficiency syndrome in early Parkinson's disease with autonomic dysfunction.

Humans ; Myelin Sheath ; Astrocytes ; Phagocytosis ; Macrophages ; Ischemia