OBJECTIVE To construct an intelligent pharmaceutical Q&A platform for precision medication with low “artificial intelligence （AI） hallucination”， aiming to enhance the accuracy， consistency， and traceability of medication consultations. METHODS Medication package inserts were batch-processed and converted into structured data through Python programming to build a local pharmaceutical knowledge base. The retrieval and question-answering processes were designed based on large language models， and system integration and localized deployment were completed on Dify platform. By designing typical clinical medication questions and comparing the output of the intelligent pharmaceutical Q&A platform with the online version of DeepSeek across dimensions such as peak time retrieval， half-life， and dosage adjustment reasoning for patients with renal impairment， the accuracy and reliability of its retrieval and reasoning results were evaluated. RESULTS The intelligent pharmaceutical Q&A platform， constructed based on local drug package inserts， achieved 100% accuracy in retrieval and reasoning for peak time， half-life， and dosage adjustment schemes. In comparison， the online version of DeepSeek demonstrated accuracies of 30%（6/20）， 50%（10/20）， and 38%（23/60） across these three dimensions， respectively. CONCLUSIONS The constructed intelligent pharmaceutical Q&A platform is capable of accurately retrieving and extracting information from the local knowledge base based on clinical inquiries， thereby avoiding the occurrence of AI hallucinations and providing reliable medication decision support for healthcare professionals.

Objective With the vigorous development of nuclear reactors and controlled thermonuclear fusion research, the release of tritium, the predominant radionuclide in nuclear wastewater, into the environment has attracted widespread attention. Its impact on human health has also become a hot topic of research. This article presents a visual analysis of the literature on the biological effects of tritium ingestion by organisms over the past 70 years, with the aim of elucidating the biological effects of tritiated water and identifying current research hotspots and emerging trends. Methods We retrieved articles on the biological effects of tritium radiation published in the China National Knowledge Infrastructure (CNKI) and Web of Science (WOS) over the past 70 years. CiteSpace software was used to generate visual maps, including annual number of publications, countries of publication, keyword clustering, keyword timeline, keyword burst, and literature co-citation. Results A total of 437 articles were included. The cumulative number of annual publications exhibited a linear growth trend. Research hotspots focused on low-radioactivity tritiated water, dose rate effect, DNA double-strand break damage, genetic effect, and cancer mortality. Emerging research frontiers included human lymphocyte immune injury, oxidase activity, comparison of marine organisms in different living environments, comparison of tritium and ionizing radiation effects, changes in mitochondrial ATP content, and the hormetic effect of low-dose radiation. Conclusion In cellular and animal models, high doses of tritium exposure induce negative biological effects. However, whether low doses of tritium esposure elicit beneficial biological effects remains to be further explored. It is suggested that domestic and foreign teams enhance academic collaboration and discussions, focusing on current hotspots and frontiers to deepen our understanding of the biological effects induced by tritium radiation. This will provide scientific solutions for disease treatment and establish a scientific basis for the safe utilization of nuclear energy and the formulation of safety standards for nuclear wastewater discharge.

OBJECTIVE To systematically review the status on pharmacist competency assessment tools both domestically and internationally， providing a theoretical basis for constructing scientific and applicable pharmacist competency assessment tools in China. METHODS Through literature review and comparative analysis， 15 representative domestic and international pharmacist competency assessment tools were systematically summarized， and their theoretical foundations， core dimensions， methodological characteristics and practical applications were compared and implications were given. RESULTS &CONCLUSIONS International research has established relatively mature evaluation systems. Represented by those developed from the United Kingdom， the United States， and the International Pharmaceutical Federation， these assessment tools demonstrate scientific structure， wide application， and dynamic and international applicability. While domestic research has progressed in sub-specialties such as clinical pharmacists， licensed pharmacists and pediatric pharmacists， it still faces challenges including insufficient standardization， inadequate validation， delayed updates， and limitations in practical application. The reasons for the disparities in assessment tools between China and other countries include differences in pharmaceutical care models， varying pharmacist training systems， cultural and social background factors， as well as differences in industry management and international influence. Based on this， the author suggests promoting the development and research of assessment tools for pharmacist job competency in China from four aspects： mechanism construction， system refinement， standardization development， and practical implementation.

ObjectiveTo explore the mechanisms of Yangjing Tongluo prescription （YJTL） in the treatment of intrauterine adhesion （IUA） from the perspective of oxidative stress mediated by the Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2/heme oxygenase-1 （Keap1/Nrf2/HO-1） signaling pathway. MethodsA total of 48 rats with normal estrous cycles were selected and randomly divided into a normal group （n=8） and a modeling group （n=40）. An IUA rat model was established using a dual-injury method combining surgical curettage and infection. Eight rats were randomly selected from the modeling group for a pilot experiment to confirm successful model establishment. After successful modeling， the remaining 32 rats were randomly divided into a model group， a low-dose YJTL group （YJTL-L）， a high-dose YJTL group （YJTL-H）， and a Progynova group. Rats in the normal and model groups were administered purified water （15 mL·kg^-1） by gavage daily， while rats in the YJTL-L， YJTL-H， and Progynova groups received YJTL at doses of 6.43 and 12.86 g·kg^-1 and Progynova at 2.06 × 10^-4 g·kg^-1， respectively， for 14 consecutive days. The general condition， uterine morphology， and uterine index of the rats were monitored. Histopathological changes in uterine tissue were observed using hematoxylin-eosin （HE） staining. Serum levels of reactive oxygen species （ROS） and glutathione peroxidase （GSH-Px） were measured by enzyme-linked immunosorbent assay （ELISA）. Protein expression levels of Keap1， Nrf2， and HO-1 in endometrial tissue were detected by Western blot. Immunofluorescence （IF） was used to assess the distribution of Nrf2 and HO-1， as well as the expression of Nrf2 in the cytoplasm and nucleus. ResultsCompared with the normal group， rats in the model group exhibited poor mental status and reduced mobility， markedly edematous and tortuous uterine morphology， decreased gland number， and inflammatory reactions in the endometrium， along with an increased uterine organ index （P<0.05）. Serum ROS levels were significantly increased （P<0.05）， while serum GSH-Px levels were significantly decreased （P<0.05）. In endometrial tissue， Keap1 protein expression was increased （P<0.05）， whereas Nrf2 and HO-1 protein expression was decreased. Mild nuclear translocation of Nrf2 was observed， accompanied by increased relative fluorescence intensity of nuclear Nrf2 and decreased relative fluorescence intensity of cytoplasmic HO-1. Compared with the model group， all treatment groups showed varying degrees of improvement in the above symptoms and pathological changes. Serum ROS levels were reduced （P<0.05）， serum GSH-Px levels were increased （P<0.05）， Keap1 protein expression in endometrial tissue was decreased， and Nrf2 and HO-1 protein expression was increased in a dose-dependent manner （P<0.05）. Notably， significant nuclear translocation of Nrf2 was observed， with correspondingly increased relative fluorescence intensity of nuclear Nrf2 and enhanced relative fluorescence intensity of cytoplasmic HO-1. ConclusionYJTL may enhance antioxidant capacity and repair oxidative damage to the endometrial basal layer by regulating the Keap1/Nrf2/HO-1 signaling pathway.

Alzheimer's disease (AD) is a neurodegenerative disease with clinical hallmarks of progressive cognitive impairment. Synergistic effects of the Aβ-Tau cascade reaction are tightly implicated in AD pathology, and microglial NLRP3 inflammasome activation drives neuronal tauopathy. However, the underlying mechanism of how Aβ mediates NLRP3 inflammasome remains unclear. Herein, we determined that oligomeric Aβ (o-Aβ) bound to microglial Kv2.1 and promoted Kv2.1-dependent potassium efflux to activate NLRP3 inflammasome resulting in neuronal tauopathy by using Kv2.1 inhibitor drofenine (Dfe) as a probe. The underlying mechanism has been intensively investigated by assays with Kv2.1 knockdown in vitro (si-Kv2.1) and in vivo (AAV-ePHP-si-Kv2.1). Dfe deprived o-Aβ of its capability to promote microglial NLRP3 inflammasome activation and neuronal Tau hyperphosphorylation by inhibiting the Kv2.1/JNK/NF-κB pathway while improving the cognitive impairment of 5×FAD-AD model mice. Our results have highly addressed that the Kv2.1 channel is required for o-Aβ-driven microglial NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Dfe as a Kv2.1 inhibitor shows potential in the treatment of AD.

Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

OBJECTIVES: To explore the mechanism by which Pulsatilla saponin D (PSD) inhibits invasion and metastasis of triple-negative breast cancer (TNBC). METHODS: The public databases were used to identify the potential targets of PSD and the invasion and metastasis targets of TNBC to obtain the intersection targets between PSD and TNBC. The "PSD-target-disease" interaction network was constructed and protein-protein interaction (PPI) analysis was performed to obtain the core targets, which were analyzed for KEGG pathway and GO functional enrichment. Molecular docking study of the core targets and PSD was performed, and the therapeutic effect and mechanism of PSD were verified using Transwell assay and Western blotting in cultured TNBC cells. RESULTS: Network pharmacology analysis identified a total of 285 potential PSD targets and 26 drug-disease intersection core targets. GO analysis yielded 175 entries related to the binding of biomolecules (protein, DNA and RNA), enzyme activities, and regulation of gene transcription. KEGG analysis yielded 46 entries involving pathways in cancer, chemical carcinogenesis-receptor activation, microRNAs in cancer, chemical carcinogenesis-reactive oxygen species, PD-L1 expression and PD-1 checkpoint pathway in cancer. Molecular docking showed high binding affinities of PSD to MTOR, HDAC2, ABL1, CDK1, TLR4, TERT, PIK3R1, NFE2L2 and PTPN1. In cultured TNBC cells, treatment with PSD significantly inhibited cell invasion and migration and lowered the expressions of MMP2, MMP9, N-cadherin and the core proteins p-mTOR, ABL1, TERT, PTPN1, HDAC2, PIK3R1, CDK1, TLR4 as well as NFE2L2 expressionin the cell nuclei. CONCLUSIONS The inhibitory effects of PSD on TNBC invasion and metastasis are mediated by multiple targets and pathways.
Humans ; Triple Negative Breast Neoplasms/metabolism* ; Saponins/pharmacology* ; Pulsatilla/chemistry* ; Female ; Molecular Docking Simulation ; Cell Line, Tumor ; Neoplasm Invasiveness ; Protein Interaction Maps ; Neoplasm Metastasis ; Signal Transduction/drug effects* ; Cell Movement/drug effects*

Objective By using intravoxel incoherent motion(IVIM)double exponential model liver multi-b value diffusion-weighted imaging(DWI)scanning technique to analyze the lesion's IVIM parameters before and after interventional treatment of hepatocellular carcinoma(HCC)with conventional transcatheter arterial chemoembolization(TACE)combined with CalliSpheres drug-loaded microspheres(DEB-TACE),based on which to quantitatively evaluate the efficacy of interventional therapy for HCC.Methods A total of 40 HCC patients,who were admitted to the Department of Interventional Therapy of Anqing Municipal Hospital of China from June 2022 to November 2023 to receive DEB-T ACE,were enrolled in this study.Routine MR examination,DWI and IVIM-DWI scan were performed before and at 1,3 and 6 months after treatment,and a total of 40 interest lesions were selected.The ADC value,perfusion fraction(f),pure diffusion coefficient(D),and perfusion-related diffusion coefficient(D*)of each lesion were analyzed.The receiver operating characteristic(ROC)curve was drawn to analyze the prognosis assessment value of IVIM-DWI parameters.Results After DEB-TACE treatment,the ADC value and D value were increased,and the f value was decreased when compared with their preoperative values,the differences were statistically significant(all P＜0.01).The ADC value and D value in the patients of effective group were remarkably higher than those in the patients of ineffective group,the differences were statistically significant(both P＜0.01);the f value in the patients of effective group was slightly lower than that in the patients of ineffective group,and the difference was statistically significant(P＜0.05).The areas under ROC curve of ADC value,D value and f value for evaluating efficacy were 0.762,0.877,and 0.708 respectively.The area under the curve for the joint assessment of the three parameters was 0.928,with the highest efficacy.Conclusion IVIM-DWI can quantitatively determine the microperfusion and activity of HCC lesions before and after interventional DEB-TACE treatment,and it can also evaluate the curative efficacy of interventional therapy for HCC as well as the outcome of HCC lesions.

Objective To explore the trajectory and influencing factors of changes in physical ac-tivity(PA)in patients with non-small cell lung cancer(NSCLC)during chemotherapy.Methods A random sampling method was used to select NSCLC patients receiving chemotherapy in Suzhou Ninth People's Hospital as the research objects.Patients' materials were collected using a general informa-tion questionnaire,the M.D.Anderson Symptom Inventory(MDASI),the Family Adaptation,Part-nership,Growth,Affection,and Resolve index(APGAR),and the Self-Rated Approaches for Health Promotion Scale(SRAHP).The International Physical Activity Questionnaire-long-form(IPAQ-L)was used to assess patients' PA levels before the first chemotherapy course(T0),before the second course(T1),before the fourth course(T2),and before the sixth course(T3).The latent growth mixture model(LGMM)was used to identify the trajectory types of patients' physical activity metabolic equivalents(MET).Unordered multinomial Logistic regression analysis was used to explore the influencing factors of PA change trajectories in NSCLC patients during chemotherapy.Results A total of 213 NSCLC patients completed this study.The PA values of NSCLC patients at T0,T1,T2 and T3 were(1 091.29±285.76),(456.43±92.78),(467.61±94.72),and(934.35±199.18)MET-min/week,respectively,with significant between-group differences(F=645.601,P＜0.001).After fitting with the LGMM,three latent categories were selected:the low PA maintenance group(ac-counting for 28.64％),the medium PA decline followed by late-stage recovery group(accounting for 51.64％),and the medium PA decline followed by mid-stage recovery group(accounting for 19.72％).Analysis showed that age,tumor stage,health behavior capacity,symptom severity and symptom distress,and family care were influencing factors for the PA trajectorycategories of NSCLC patients during chemotherapy(all P＜0.05).Analysis of variable interaction effects found that health behavior capacity(OR=0.376,95％CI,0.192 to 0.853)had a strong protective effect on the medium PA decline followed by mid-stage recovery group(there was an interaction effect,P＜0.05).Conclusion There is population heterogeneity in PA among NSCLC patients during chemo-therapy.Medical staffs should develop targeted measures based on the population characteristics and influencing factors of patients' PA trajectories to improve their PA levels.