Aim To explore the compatibility and po-tential mechanism of effective components of Biejia-Ezhu against triple negative breast cancer(TNBC)and verify it by experiments.Methods Effective compo-nents and targets of Biejia-Ezhu were obtained by TC-MSP and Swiss Target Prediction.Disease targets of TNBC were obtained from OMMI and GeneCards data-bases.The PPI network was constructed using STRING database.GO and KEGG path enrichment analysis was performed using DAVID database.Cytoscape3.9.1 software was used to construct the"drug-component-target-disease"network,screen key targets and compo-nents for molecular docking,and further verify the com-patibility of key components and targets in vitro.Re-sults ① A total of 71 effective components were iden-tified in the Biejia-Ezhu drug pair.There were 146 drug targets associated with the disease.A total of 113 signaling pathways were identified by KEGG analysis.The 71 potential active components of Biejia-Ezhu mainly acted on key targets such as mTORC1,ULK1,TNF,EGFR,ESR1,STAT3,HIF1A,and PTGS2.Mo-lecular docking results showed that glycine and curcu-min were the key active components of Biejia-Ezhu,and both had strong docking activity against key target proteins mTORC1 and ULK1.②The results of in vitro experiment showed that glycine combined with curcu-min significantly inhibited the proliferation and clonal formation ability of TNBC cells(P＜0.05),up-regula-ted the expression of autophagy marker LC3 Ⅱ/Ⅰ,down-regulated the expression of EGFR,down-regula-ted the expression of pathway protein mTORC1,p-mTOR,p-ULK1,and promoted the expression of path-way protein ULK1(P＜0.05).Conclusion The key component of Biejia-Ezhu against triple-negative breast cancer is glycine-curcumin,the mechanism of which may be related to the regulation of the mTORC1/ULK1 signaling pathway to promote autophagy.

Objective:To investigate the predictive value of serum 25 hydroxyvitamin D3[25 (OH) D3], insulin-like growth factor 1 (IGF-1) and bone mineral density (BMD) in the occurrence of osteoporosis (OP) in postmenopausal women.Methods:A total of 87 postmenopausal women admitted to Shanxi Children’s Hospital from Jan. 2020 to Dec. 2023 were chosen and separated into OP group ( n=40) and non-OP group ( n=47) . The differences of clinical features, serum 25 (OH) D3, IGF-1 and BMD were compared, and the correlation analysis between serum 25 (OH) D3, IGF-1 and BMD (including L 1-4 BMD, femoral neck BMD and total hip BMD) was analyzed. Multivariate Logistic regression model and receiver operating characteristic (ROC) curve were used to analyze the influencing factors of OP occurrence in postmenopausal women and the predictive value of serum 25 (OH) D3 and IGF-1 combined with BMD for OP occurrence. Results:Compared with non-OP group, there were no significant differences in age, body mass index (BMI) , menopause time, serum calcium, serum phosphorus, alanine aminotransferase (ALT) , or aspartate aminotransferase (AST) levels in OP group ( t=1.42, 1.03, 1.71, 0.93, 0.76, 0.43, 0.04; P=0.161, 0.306, 0.092, 0.354, 0.452, 0.670, 0.966) , but the proportion of diabetes mellitus significantly increased ( χ2=4.37, P=0.037) . Compared with non-OP group, the levels of serum 25 (OH) D3 and IGF-1 and the values of L1-4 BMD, femoral neck BMD and total hip BMD in OP group significantly decreased ( t=5.37, 4.83, 8.31, 2.01, 3.11; P<0.001, P<0.001, P<0.001, P=0.048, P=0.003) . Correlation analysis showed that serum 25 (OH) D3 and IGF-1 were significantly positively correlated with L 1-4 BMD, femoral neck BMD and total hip BMD ( r=0.37, 0.42, 0.29, 0.33, 0.28, 0.29; P<0.001, P<0.001, P=0.024, P=0.015, P=0.032, P=0.021) . Multivariate Logistic analysis showed that serum 25 (OH) D3, IGF-1 and L 1-4 BMD were independent influencing factors for OP occurrence in postmenopausal women ( P=0.007, 0.019, 0.001) ROC curve showed that the area under the curve (AUC) values of serum 25 (OH) D3, IGF-1, L 1-4 BMD and their combination in the prediction of the occurrence of OP in postmenopausal women were 0.764, 0.752, 0.957 and 0.985, respectively. Conclusion:Serum 25 (OH) D3, IGF-1 and L 1-4 BMD can be used as predictors of OP occurrence in postmenopausal women, and the combined value of the three is higher.

Objective:To explore the mechanism by which atractylodin regulates the ROS (reactive oxygen species) /AKT signaling pathway to induce apoptosis and cell cycle arrest in endometrial cancer cells, and to provide theoretical support for its potential application in the treatment of endometrial cancer.Methods:Endometrial cancer cell lines (Ishikawa and HEC-1A) were selected as experimental models. Cells were treated with different concentrations (1, 5, 10, 20 μM) of atractylodin. Cell proliferation was assessed by CCK-8 assay, apoptosis was analyzed by flow cytometry (FCM), and protein expression levels of AKT, p-AKT, Bcl-2, Caspase-3, and other AKT signaling pathway-related proteins were detected by Western blot. ROS levels were measured by flow cytometry.Results:Atractylodin treatment significantly inhibited the proliferation of endometrial cancer cells. Flow cytometry analysis revealed a marked increase in the apoptotic cell population. Western blot results showed that atractylodin treatment significantly decreased p-AKT expression, reduced Bcl-2 protein levels, and increased Caspase-3 expression. ROS level analysis showed that atractylodin treatment significantly elevated intracellular ROS generation, suggesting that atractylodin might induce AKT pathway inhibition through ROS, leading to cell cycle arrest and apoptosis.Conclusions:Atractylodin regulates the ROS/AKT signaling pathway to induce apoptosis and cell cycle arrest in endometrial cancer cells, exhibiting potential anti-endometrial cancer effects. This study provides new theoretical evidence for the application of atractylodin in the treatment of endometrial cancer and reveals its underlying mechanisms.

Objective To study the application of autologous natural killer(NK)cells in the treatment of advanced renal cell carcinoma and the changes of immune function and tumor markers in patients.Methods 61 patients with advanced renal cell carcinoma admitted to Gansu Wuwei Tumour Hospital from March 2023 to April 2024 were divided into targeting group(31 cases,given supportive treatment combined with sunitinib malate capsules)and cell group(30 cases,autologous NK cells combined with targeting group)according to the patient's willingness to treat combined with propensity score matching.6 weeks was a treatment cycle,and all patients were treated for 4 cycles.The clinical efficacy of the two groups after 4 cycles of treatment and the occurrence of adverse reactions during treatment were statistically analyzed.The levels of serum cytokines,tumor markers,lymphocyte function and immune function were compared between the two groups before and after 4 cycles of treatment.Results After 4 cycles of treatment,the objective remission rate and disease control rate in the cell group were higher than those in the targeting group(P<0.05).After 4 cycles of treatment,the levels of serum hypoxia-inducible factor-1α(HIF-1α),vascular endothelial growth factor(VEGF),platelet-derived growth factor(PDGF),carcinoembryonic antigen,carbohydrate antigen 125,carbohydrate antigen 199 and alpha-fetoprotein in the two groups were lower than those before treatment,and those in the cell group were lower than those in the targeting group(P<0.012 5).After 4 cycles of treatment,the levels of serum interleukin-2,interleukin-6,tumor necrosis factor-β,interferon-γ,peripheral blood CD3+,CD4+,NK cells and CD4+/CD8+in the two groups were higher than those before treatment.The levels of serum interleukin-2,tumor necrosis factor-β,interferon-γ,peripheral blood CD3+and NK cells in the cell group were higher than those in the targeting group(P<0.012 5).The level of CD8+in peripheral blood was lower than that before treatment(P<0.012 5),but there was no significant difference between the two groups(P>0.012 5).During the treatment,there was no significant difference in the incidence of diarrhea,nausea and vomiting,alopecia,liver function damage,decreased platelet level and decreased neutrophil level between the cell group and the targeting group(P>0.05).Conclusion The treatment of advanced renal cell carcinoma with autologous NK cells could improve the level of serum cytokines,reduce the level of tumor markers,regulate the function of lymphocytes and immune function,and had a good therapeutic effect.At the same time,it would not increase the incidence of adverse reactions,and the safety was good.

Aim To identify the underlying target of bullatine A(BA)against rheumatoid arthritis(RA)u-sing limited proteolysis-small molecule mapping(LiP-SMap)drug target proteomics and to provide a scientif-ic basis for clinical application of Aconiti brachypodi Radix in the treatment of RA.Methods LiP-SMap drug target proteomics was employed to perform bioin-formatics analysis for comparing and validating the dif-ferential protein expression after BA intervention.A collagen-induced arthritis(CIA)model was estab-lished in DBA/1 mice using bovine type Ⅱ collagen.The mice were then divided into the CIA model group,methotrexate-positive control group(MTX group),and BA groups(10 mg·kg-1 and 20 mg·kg-1)based on their clinical scores.After drug intervention,the thera-peutic efficacy against RA was assessed by joint index scores and foot thickness measurements.Histopatholog-ical changes in the arthritic joints of CIA mice were e-valuated using hematoxylin and eosin(HE)staining.Enzyme-linked immunosorbent assay(ELISA)was employed to detect inflammatory cytokines interleukin-17(IL-17)and total IgG and IgG3 anti-collagen-spe-cific antibodies levels from the serum of CIA mice.Flow cytometry was used to detect the expression levels of intracellular Th17 cells(IL-17+CD4+T cells)and Th1 cells(IFN-γ+CD4+T cells).Fluorescent quanti-tative PCR was performed to detect the expression of genes related to differential proteins.Results The proteomic analysis identified Serpinb1a as a protein with strong binding affinity to BA,and KEGG enrich-ment analysis indicated IL-17 signaling pathway was a crucial pathway of BA in against RA.BA treatment significantly reduced clinical scores and foot thickness,improved local arthritis symptoms in CIA mice,and al-leviated inflammatory cell infiltration into arthritic joints(P＜0.05).Differential protein validation re-sults showed that BA had strong affinity with Serpinb1a(-5.92 kJ·mol-1)and downregulated the expres-sion of Serpinb1a mRNA.Furthermore,the administra-tion of BA markedly reduced serum IL-17 A levels from CIA mice,inhibited the expression of intracellular IL-17 A and IFN-γ cytokines in splenic CD4+T cells(P＜0.05),and significantly downregulated the transcrip-tional expression of IL-17F(P＜0.05).Conclusion BA exhibits therapeutic effects on collagen-induced arthritis,and its mechanism of action may involve the regulation of Serpinb1a and the IL-17 signaling path-way.

Objective To study the hearing intervention effects of the Shokz condyle-stimulated headband bone-conduction hearing aid on patients with conductive,mixed,and sensorineural hearing loss and to explore its clinical application prospects.Methods A total of 55 patients with hearing loss(age 18～82)participated in the study.Among them,9 had conductive hearing loss,15 had sensorineural hearing loss,and 31 had mixed hearing loss.Their bilat-eral bone conduction pure tone thresholds at 0.5,1,2,and 4 kHz were all ≤60 dB HL.The patients were fitted with the condyle-stimulated headband bone-conduction hearing aid.Hearing thresholds in sound field,single-syllable speech recogni-tion scores in quiet,and sentence recognition thresholds in quiet were assessed before fitting and on the day of 14±2 after fitting to compare differences in results.The effectiveness of the hearing aids on the day of 14±2 after fitting was also eval-uated using the IOI-HA questionnaire.Results After wearing the bone-conduction hearing aid,the average hearing thresh-old and sentence recognition threshold of the patients decreased significantly compared with before fitting(the average hear-ing threshold:56.5±8.2 dB HL before fitting,39.3±4.9 dB HL on the day of 14±2 after fitting;sentence recognition threshold:48.6±9.7 dB HL before fitting,34.3±5.6 dB HL on the day of 14±2 after fitting),and the difference was statistically significant(P＜0.001).The single-syllable speech recognition score before fitting was 29.8％±11.4％,and on the day of 14±2 after fitting,it was 72.4％±14.4％,the difference was statistically significant(P＜0.001).The av-erage total score of the IOI-HA questionnaire was 29.0±3.8 points.Conclusion Condyle-stimulated headband bone-con-duction hearing aids can significantly improve the hearing and speech recognition ability of patients with conductive,mixed and sensorineural hearing loss whose bone conduction pure tone thresholds at 0.5～4 kHz were ≤60 dB HL.It may poten-tially improve the quality of life for patients with hearing loss and holds substantial clinical application value.

Objective:To explore the effect of exercise on the memory of rats modeling vascular cognitive impairment (VCI) and also its effects on the hippocampal Sema3G/neuropilin-2 (Nrp2)/PlexinA4 signaling pathway.Methods:Eighteen male Sprague-Dawley rats were randomly divided into a sham-operated group, a model group, and an exercise group, each of 6. The model and exercise groups underwent VCI modeling via bilateral common carotid artery occlusion, while the sham-operated group received the same surgical procedure without vessel ligation or transection. Beginning forty-eight hours after the surgery, the exercise group carried out daily 30-minute treadmill training sessions, 5 days a week, for a total of 4 weeks, while the other two groups were placed on the same treadmill with it not in operation. After the intervention, cognitive functioning was assessed using the novel object recognition (NOR) test and a Y-maze test. Western blotting was employed to evaluate the expression of Sema3G, Nrp2, PlexinA4, and Rac1 in the hippocampus. Immunofluorescence staining was used to observe the distribution of Nrp2 and PlexinA4 in the hippocampus.Results:Compared with the model group, the exercise group exhibited significantly higher NOR indices during both the short-term and long-term memory testing phases after the intervention. Those rats also tended to have significantly longer total exploration times in the novel arm of the Y-maze test. The western blotting revealed that the expression levels of Sema3G, PlexinA4, and Rac1 in the hippocampus were significantly higher in the exercise group compared to the model group, on average. Immunofluorescence showed significantly increased PlexinA4 fluorescence intensity in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus, and significantly elevated Nrp2 fluorescence intensity in the CA3 region in the exercise group compared to the model group. The Pearson correlation coefficients for Nrp2/PlexinA4 co-localization in the CA1, CA3 and DG regions were significantly higher in the exercise group than in the model group.Conclusions:Exercise training significantly improves memory function in rats with VCI, and this effect may be associated with activation of the hippocampal Sema3G/Nrp2/PlexinA4 signaling pathway.

Objective:To evaluate the safety and efficacy of donor-purified CD34 + stem cell boosts in patients with poor hematopoietic reconstruction (PHR) after haploid hematopoietic stem cell transplantation (haplo-HSCT) for aplastic anemia (AA) . Method:A retrospective analysis was conducted on 11 patients with AA and PHR who underwent haplo-HSCT and received donor-purified CD34 + stem cell boosts at Peking University People’s Hospital. Recovery of blood cell counts, incidence of graft-versus-host disease (GVHD), and overall survival (OS) were assessed. Results:Of the 11 patients with PHR, two were diagnosed with prolonged isolated thrombocytopenia (PT), one was primary poor graft function (PGF), and eight were diagnosed with secondary PGF. The median time to PHR diagnosis was 110 days (range: 60-330 days), and the median interval from transplantation to purified CD34 + hematopoietic stem cell infusion was 194 days (range: 125-456 days). The two patients with PT achieved complete platelet recovery at 22 and 13 days after CD34 + stem cell infusion, respectively. Among the remaining nine patients with PGF, six achieved complete hematopoietic recovery, with a median absolute neutrophil count recovery time of 19 days (8-158 days), HGB recovery time of 32.5 days (range: 13-158 days), and platelet recovery time of 31.5 days (range: 7-171 days). The incidence of chronic GVHD after infusion was 18.2%, with no cases of acute GVHD observed. The OS rate was 90.9% (10/11) in the 11 patients, with a median follow-up of 614 days (range: 153-1 765 days) . Conclusion:Donor-purified CD34 + stem cell boost may be an effective therapeutic strategy for PHR in patients with AA after haplo-HSCT.

Objective To construct a predictive model for high-grade pathological components of early invasive lung adenocarcinoma(ILAC)based on radiomics.Methods Collecting information on total 495 patients who underwent radical operation and were pathologically diagnosed as stage Ⅰ in the cardiothoracic surgery of Zhoushan Hospital from January 2015 to December 2019,including gender,age,pathological findings,tumor markers and preoperative chest CT images.The micropapillary and solid components in postoperative pathology were defined as"high-grade pathological components",while those without high-grade pathological components were classified into the low-grade group and those with high-grade pathological components were classified into the high-grade group.And patients were randomly divided into the training set(343 cases)and the validation set(152 cases)with a ratio of 7∶3 using the simple randomization grouping method.The region of interest of nodules on CT images were delineated layer by layer by scientific research platform and 1950 radiomics features were extracted.And then those features were filtrated by F-test,Pearson correlation coefficient,and L1 based feature selection.A model was built by using Logistic regression machine learning classifier,named mod 2,and radscore was also obtained.Differences between general information and CT features were analyzed.Binary Logistic regression analysis was used to construct a model for statistically significant variables,named mod 1.At the same time,Radscore was added to build the mod and named comb mod.The area under the curve(AUC),sensitivity and specificity of the three models were calculated.A nomogram was also drawn.Results A total of 495 patients were divided into the training set(n=343)and the validation set(n=152).Gender,carcinoma embryonic antigen(CEA),nodule,and maximum diameter were screened out in clinical features and involved in constructing the mod 1.Twelve features were selected from the radiomics features to build mod 2.Comb mod performed best,training set AUC:0.887,validation set AUC:0.875,and had good clinical practicability.Conclusion The model composed of general feature,CT feature and radiomics features could accurately predict high-grade pathological components in early ILAC,and provide references for clinicians to choose surgical method for patients.

Objective To investigate the expression of T cell immunoglobulin and mucin domain-containing protein 3(TIM-3)in peripheral blood mononuclear cells and its relationship with non-small cell lung cancer(NSCLC).Methods TIM-3 expression in monocytes from the peripheral blood of 116 NSCLC patients and 37 healthy volunteers was analyzed via flow cytometry.The expression of TIM-3 in macrophages from tissues was detected via multiplex immunohistochemical staining.Transwell migration experiments were used to detect the migration ability of monocytes.Real-time PCR and ELISA were used to detect the mRNA and protein expression of TIM-3 in monocytes.Results Compared with that in healthy volunteers,TIM-3 expression was upregulated in the peripheral blood monocytes of NSCLC patients(P＜0.05).TIM-3 was expressed mainly in macrophages in adjacent tissues and positively correlated with its expression in monocytes in NSCLC patients(P＜0.05).Furthermore,high TIM-3 expression promoted monocyte migration in NSCLC patients(P＜0.05),and high TIM-3 expression in peripheral blood monocytes indicated poor prognosis(P＜0.05).Conclusion TIM-3 expression in peripheral blood monocytes may be a useful indicator of the disease prognosis of NSCLC patients and TIM-3 could be a new target for immunotherapeutic strategies.