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.

OBJECTIVE To investigate the effect and mechanism of Jingangteng capsules in the treatment of non-alcoholic fatty liver disease （NAFLD）. METHODS Thirty-two SD rats were randomly divided into normal group and modeling group. The modeling group was fed a high-fat diet to establish a NAFLD model. The successfully modeled rats were then randomly divided into model group， atorvastatin group[positive control， 2 mg/（kg·d）]， and Jingangteng capsules low- and high-dose groups [0.63 and 2.52 mg/（kg·d）]， with 6 rats in each group. The pathological changes of the liver were observed by hematoxylin-eosin staining and oil red O staining. Enzyme-linked immunosorbent assay was performed to determine the serum levels of triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， alanine transaminase （ALT）， aspartate transaminase （AST）， tumour necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， IL-6， IL-18. 16S rDNA amplicon sequencing and metabolomics techniques were applied to explore the effects of Jingangteng capsules on gut microbiota and metabolisms in NAFLD rats. Based on the E-mail：591146765@qq.com metabolomics results， Western blot analysis was performed to detect proteins related to the nuclear factor kappa-B （NF-κB）/NOD-like receptor family protein 3 （NLRP3） signaling pathway in the livers of NAFLD rats. RESULTS The experimental results showed that Jingangteng capsules could significantly reduce the serum levels of TG， TC， LDL-C， AST， ALT， TNF-α， IL-1β， IL-6， IL-18， while increased the level of HDL-C， and alleviated the hepatic cellular steatosis and inflammatory infiltration in NAFLD rats. They could regulate the gut microbiota disorders in NAFLD rats， significantly increased the relative abundance of Romboutsia and Oscillospira， and significantly decreased the relative abundance of Blautia （P＜0.05）. They also regulated metabolic disorders primarily by affecting secondary bile acid biosynthesis， fatty acid degradation， O-antigen nucleotide sugar biosynthesis， etc. Results of Western blot assay showed that they significantly reduced the phosphorylation levels of NF-κB p65 and NF-κB inhibitor α， and the protein expression levels of NLRP3， caspase-1 and ASC （P＜0.05 or P＜0.01）. CONCLUSIONS Jingangteng capsules could improve inflammation， lipid accumulation and liver injury in NAFLD rats， regulate the disorders of gut microbiota and metabolisms， and inhibit NF-κB/NLRP3 signaling pathway. Their therapeutic effects against NAFLD are mediated through the inhibition of the NF-κB/NLRP3 signaling pathway.

BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female

OBJECTIVE: To study effective methods for reducing lung V₅, V₁₀, and mean lung dose (MLD) in the design of volumetric modulated arc therapy for central lung cancer by using different arc configurations and dose-limiting blocks designs. METHODS: Five groups of plans were designed for the enrolled patients. Group A used a full-arc field. Group B used a partial-arc field. Groups C, D, and E used full-arc fields with vertical-length, semi-ring, and triangular dose-limiting blocks added respectively. The dosimetric similarities of target areas and the dosimetric differences in lung V₅, V₁₀, V₂₀, and MLD among the groups were compared. RESULTS: Compared with group A, groups B, C, D, and E had decreased homogeneity and conformity of the target area, but significantly lower V₅ and V₁₀ of the whole lung. The MLD of groups C, D, and E was lower than that of group A. CONCLUSION Using a full-arc field combined with dose-limiting blocks can effectively reduce lung V₅, V₁₀, MLD, and monitor units (MU).
Lung Neoplasms/radiotherapy* ; Humans ; Radiotherapy, Intensity-Modulated/methods* ; Radiotherapy Planning, Computer-Assisted/methods* ; Radiotherapy Dosage ; Lung/radiation effects*

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*

Vascular damage plays a significant role in the onset and progression of Alzheimer's disease (AD). However, the precise molecular mechanisms underlying the induction of neuronal injury by vascular damage remain unclear. The present study aimed to examine the impact of fibrinogen (Fg) on tau pathology. The results showed that Fg deposits in the brains of tau P301S transgenic mice interact with tau, enhancing the cytotoxicity of pathological tau aggregates and promoting tau phosphorylation and aggregation. Notably, Fg-modified tau fibrils caused enhanced neuronal apoptosis and synaptic damage compared to unmodified fibrils. Furthermore, intrahippocampal injection of Fg-modified tau fibrils worsened the tau pathology, neuroinflammation, synaptic damage, neuronal apoptosis, and cognitive dysfunction in tau P301S mice compared to controls. The present study provides compelling evidence linking Fg and tau, thereby connecting cerebrovascular damage to tau pathology in AD. Consequently, inhibiting Fg-mediated tau pathology could potentially impede the progression of AD.
Animals ; tau Proteins/metabolism* ; Alzheimer Disease/metabolism* ; Fibrinogen/metabolism* ; Mice, Transgenic ; Mice ; Disease Models, Animal ; Memory Disorders/metabolism* ; Male ; Mice, Inbred C57BL ; Brain/metabolism* ; Hippocampus/metabolism* ; Protein Aggregation, Pathological/metabolism* ; Apoptosis ; Phosphorylation

Objective To explore the repair effect and mechanism of human amniotic mesenchymal stem cells(hAMSCs)on endometrial injury.Methods hAMSCs were isolated using a two-enzyme digestion and then cultured.The third-passage(P3)cells were harvested to detect the surface markers by flow cytometry and to identify their trilineage differentiation potentials.Eighteen nulliparous female SD rats(8～9 weeks old,weighing 250～280 g)were randomly divided into 3 groups(n=6):normal control group,model group,and hAMSCs group.A rat model of intrauterine adhesions(IUA)was established in SD rats by using curettage combined with lipopolysaccharide(LPS)infection.In 2 weeks after modeling,the hAMSCs group received a bilateral uterine horn transplantation of 0.2 mL hAMSCs(1.0×10? cells/mL),while the model group received a same volume of PBS into both uterine horns.All rats were sacrificed in 2 weeks after transplantation.HE and Masson staining was used to observe endometrial thickness and gland number as well as endometrial fibrosis area.RT-qPCR and Western blotting were performed to detect the mRNA and protein levels of TGF-β1,Smad3,Smad7,epithelial-mesenchymal transition(EMT)markers(E-cadherin,Vimentin),fibrosis factor α-SMA,and endometrial estrogen receptor(ER)and progesterone receptor(PR)in endometrial tissues.Results The obtained cells were identified as hAMSCs due to the characteristics of surface markers and differentiation potentials.Compared with the normal control group,the model group showed decreased endometrial thickness,reduced gland number,increased fibrosis area,and enhanced mRNA and protein levels of fibrosis-related factors TGF-β1,Smad3,Vimentin,and α-SMA(P<0.01),while down-regulation of fibrosis-inhibiting molecule Smad7,the EMT marker E-cadherin,and endometrial receptors ER and PR at both mRNA and protein levels(P<0.01).hAMSCs transplantation increased endometrial thickness and gland number,decreased fibrosis area,and down-regulated mRNA expression of the aforementioned fibrosis-related factors(P<0.01),and up-regulated the mRNA expression levels of Smad7,E-cadherin,ER,and PR(P<0.01).The hAMSCs group also exhibited obviously down-regulated protein levels of TGF-β1,Smad3,and α-SMA(P<0.05),while enhanced protein levels of Smad7 and PR(P<0.05).Conclusion Intrauterine transplantation of hAMSCs can promote the repair of endometrial injury,and inhibits endometrial EMT and fibrosis through the TGF-β1/Smad7 signaling pathway.

Objective To construct CD19-targeted chimeric antigen receptor natural killer(CAR-NK)cells armored with interleukin15(IL15)or IL15 receptor-linker(RLI)and preliminarily validate their proliferative capacity and anti-tumor activity in vitro.Methods Natural killer cells(NK92 and NK92MI)from patients with human malignant non-Hodgkin lymphoma were cultured,and CD19-targeted CAR-NK cells armored with IL15 or RLI were prepared using retroviral vector particles.IL15 secretion was measured by ELISA,and proliferative capacity was assessed via CFSE dilution assays.Human B-lymphocytic leukemia cells(Nalm6-GFP-Luc)and human colon cancer cells overexpressing CD19(hCD19-SW620-GFP-Luc)were cultured,with surface CD19 expression confirmed(>99%positivity for both).Anti-tumor activity was evaluated by measuring cytotoxicity at effector-to-target(E:T)ratios using luciferase-based assays(4/12 h),detecting surface CD107a expression via flow cytometry,and quantifying cytokine release using CBA assays.Results NK92/NK92MI-CD19 CAR cells armored with IL15 or RLI were successfully generated.IL15 secretion was significantly higher in armored groups versus non-armored controls(P<0.01).Without IL-2 stimulation,IL15/RLI enhanced CAR-NK proliferation(P<0.05).Both armored designs significantly increased tumor-killing efficiency(P<0.05)and CD107a degranulation.IL15/RLI-armored NK92-CD19 CAR cells exhibited elevated release of IL2,IL10,IL6,TNF-α,sFas,IFN-γ,and Granulysin(P<0.05),while armored NK92MI-CD19 CAR cells showed additional increases in Granzyme A,Granzyme B,and Perforin(P<0.05).Conclusion IL15/RLI-armored NK92/NK92MI-CD19 CAR cells demonstrate potent anti-tumor activity,supporting their combined clinical therapeutic potential for tumors.