OBJECTIVE To formulate Guidelines for the standardized implementation of pharmacist-managed clinics （ 2026 edition ） in response to the challenges faced by such clinics in China， including uneven development， large discrepancies in service specifications， insufficient patient awareness， and limited medical insurance coverage. METHODS Led by the Pharmaceutical Affairs Professional Committee of the Chinese Hospital Association， the Evidence-based Pharmacy Professional Committee of the Chinese Pharmaceutical Association， and the Hospital Pharmacy Professional Committee of the Cross-strait Medical and Health Exchange Association， a total of 19 domestic hospital pharmacy experts were organized. Through a systematic review of national policies and literature research， current practical experience was summarized. Consensus on the contents of the guidelines was reached after in-depth discussions. RESULTS &CONCLUSIONS The guidelines covered five sections： definition and connotation of pharmacist-managed clinics， establishment requirements， implementation and management， post competency， and practical research. Firstly， the definition and connotation included three operational forms of pharmacist-managed clinics （independent mode， physician-pharmacist joint mode， and online pharmacist-managed clinic mode） and classified service modes （specialty-specific， drug-specific， and disease-specific pharmacist-managed clinics）. The establishment requirements were further refined， covering system construction （pharmaceutical service management system， quality control and assessment mechanism）， personnel qualifications （professional credentials， continuing education and professional training， etc）， service recipients， as well as service venues and facilities. Subsequently， the implementation and management of pharmacist-managed clinics were proposed， involving service procedures， intervention measures， documentation and records， patient education and follow-up， humanistic care， as well as risk management and quality control. Finally， post competency encompassed the competency requirements for pharmacists providing services in pharmacist-managed clinics， as well as the suggestions on teaching methods； practical research encouraged the conduct of high-quality pharmaceutical practice in the setting of pharmacist-managed clinics. The guidelines provide valuable guidance for the standardized implementation of pharmacist-managed clinics in China in terms of establishment， management， teaching， and research， fill the guideline gap in this field， and can promote the high-quality development of pharmacist-managed clinics.

Objective: To assess the clinical application value of a prediction model for red blood cell (RBC) demand in surgical procedures. Methods: Demographic data, laboratory parameters, anesthesia and transfusion records, and model prediction data were retrospectively collected from surgical patients at the First Medical Center of Chinese PLA General Hospital between 2018 and 2024. Statistical analysis was performed using the Chi-square test, t-test, and Mann-Kendall trend test. Results: From 2018 to 2024, the predictive model for RBC demand in surgical procedures was used to evaluate a total of 112 293 surgeries. During this period, the model call rate (77.49%-98.91%, P<0.05), compliance rate (56.81%-84.92%, P<0.05), and prediction accuracy rate (66.82%-94.17%, P<0.05) all showed significant upward trends. The total blood usage across the hospital (13645.4-7723.5 units, P<0.05) and the average blood usage per surgery (0.21-0.1 units, P<0.05) exhibited overall downward trends. Postoperative average hemoglobin levels in the non-compliance group (112.1-105.3 g/L in the non-compliance group vs 106.9-92.7 g/L in the compliance group, P<0.05) and the intraoperative excessive transfusion rate (5.06%-6.05% in the non-compliance group vs 0.09%-0.04% in the compliance group, P<0.05) were significantly higher in the non-compliance group compared to the compliance group. Conclusion: The predictive model for RBC demand in surgical procedures has played a positive role in conserving blood resources, optimizing blood resource allocation, and reducing intraoperative risks.

ObjectiveTo integrate network pharmacology prediction with multi-level experimental verification methods， and to explore in depth the therapeutic efficacy and potential mechanism of luteolin in treating gout. MethodsDatabases were used to obtain potential pharmacodynamic targets of luteolin. Protein-protein interaction （PPI） network construction and network pharmacology analysis techniques were used to screen key core targets of luteolin in gout treatment. Further biological function enrichment analysis and signaling pathway analysis were performed on these targets. Molecular docking simulation was used to calculate the binding energy between luteolin and potential core targets， clarifying the strength of their interactions. In the in vivo experiment for hyperuricemia， 48 mice were randomly divided into a blank group， a model group， an allopurinol group （5 mg·kg^-1）， and low-dose （10 mg·kg^-1）， medium-dose （30 mg·kg^-1）， and high-dose （90 mg·kg^-1） luteolin groups. For the first three days， the blank and model groups were gavaged with an equal volume of normal saline， while the allopurinol group and luteolin groups were gavaged with corresponding drugs. From day 4 onwards， modeling was performed by intraperitoneal injection at 12：00 daily （normal saline for the blank group， and oxonic acid potassium-hypoxanthine mixture for other groups， with 300 mg·kg^-1 for each group）. Gavage intervention was administered at 18：00 daily （normal saline for the blank/model groups， and corresponding drugs for the treatment groups） until day 7. After sampling， levels of serum uric acid （UA）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） were measured. Levels of xanthine oxidase （XO） in the liver and kidney， ATP-binding cassette transporter G2 （ABCG2） and malondialdehyde （MDA） in the kidney， and superoxide dismutase （SOD） in the liver were determined. Renal HE staining was also performed. In the pharmacodynamic study of gouty arthritis， 36 rats were randomly divided into a blank group， a model group， a colchicine group （0.315 mg·kg^-1）， and low-dose （7 mg·kg^-1）， medium-dose （21 mg·kg^-1）， and high-dose （63 mg·kg^-1） luteolin groups. The model was established by vertically injecting 100 µL of 25 g·L^-1 monosodium urate suspension into the posterior lateral aspect of the right ankle joint （the blank group was injected with an equal volume of normal saline）， with repeated injections every two days for reinforcement. From day 2 after modeling， daily gavage administration was performed （normal saline for the blank/model groups， and corresponding drugs for the treatment groups） for a total of 16 days. During the experiment， ankle swelling and pain threshold were measured regularly. After sampling， levels of serum tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） were determined. Ankle joints were subjected to HE， Masson， and safranin O-fast green staining， and HE staining was also performed on ankle synovial tissue and various organs. Western blot was used to determine the expression levels of key proteins in gout-related signaling pathways. ResultsNetwork pharmacology analysis predicted that luteolin may regulate over 20 core targets， such as XO， ABCG2， nuclear factor erythroid 2-related factor 2 （Nrf2）， and SOD， through acting on signaling pathways including NF-κB， phosphoinositide 3-kinase/protein kinase B （PI3K/Akt）， and ABC transporters， thereby affecting uric acid metabolism and inflammatory responses. In the hyperuricemia model， compared with the blank group， the model group showed significantly increased serum UA level， liver and kidney XO activity， renal ABCG2 expression， and liver SOD activity （P<0.01）. Compared with the model group， the high-dose luteolin group significantly reduced serum UA level （P<0.01）， inhibited liver and kidney XO activity （P<0.01）， and significantly increased renal ABCG2 expression and liver SOD activity （P<0.01）， effectively alleviating renal oxidative stress damage and improving renal histopathological status. In the gouty arthritis model， compared with the blank group， the model group showed significant ankle swelling， decreased pain threshold， and significantly increased levels of IL-6， IL-1β， and TNF-α in serum and synovial tissue （P<0.01）. The high-dose luteolin group significantly reduced ankle swelling， prolonged hot plate pain threshold， effectively decreased the levels of the above inflammatory factors in serum and synovial tissue （P<0.01）， and significantly improved ankle pathological damage， showing good analgesic and anti-inflammatory effects. Western blot results further confirmed that luteolin significantly upregulated Nrf2 protein expression and downregulated XO and nucleotide-binding oligomerization domain （NOD）-like receptor protein 3 （NLRP3） expression in animals. ConclusionLuteolin can improve symptoms of hyperuricemia and gouty arthritis， and its potential mechanism may be related to inhibiting XO activity， increasing ABCG2 and SOD levels， and regulating Nrf2-mediated oxidative stress-related pathways.

BACKGROUND:Studies have shown that platelet-derived growth factor BB can stimulate the proliferation and osteogenic differentiation of mesenchymal stem cells and accelerate the calcification process of osteoblast-like cells.However,its clinical application has problems such as short half-life and easy decomposition.Loading the growth factor onto a suitable biomaterial scaffold can enable its slow and continuous release and maintain an effective concentration,which has become a hot topic in current research.OBJECTIVE:To observe the effect of chitosan/reduced graphene oxide scaffolds loaded with platelet-derived growth factor BB on the repair of alveolar bone defect in rats.METHODS:(1)Chitosan/reduced graphene oxide scaffolds(referred to as CS/rGO scaffolds)and chitosan/reduced graphene oxide scaffolds loaded with different mass concentrations(5,10,15,and 20 mg/L)of platelet-derived growth factor BB(referred to as CS/rGO/PDGF-BB-5,CS/rGO/PDGF-BB-10,CS/rGO/PDGF-BB-15,and CS/rGO/PDGF-BB-20 scaffolds)were prepared respectively.The five groups of scaffolds were co-cultured with rat periodontal ligament stem cells.The cell proliferation and migration were detected by CCK-8 assay and Transwell chamber assay,respectively,to screen the appropriate growth factor loading mass concentration for subsequent experiments.CS/rGO scaffolds(or extracts)and CS/rGO/PDGF-BB-15 scaffolds(or extracts)were co-cultured with rat periodontal ligament stem cells,and the osteogenic differentiation and angiogenic ability of the cells were detected.(2)The alveolar bone defect model was prepared in front of the bilateral maxillary first molars of 16 SD rats,and the rats were randomly divided into 4 intervention groups:the blank control group did not receive any intervention,the simple scaffold group was implanted with CS/rGO/PDGF-BB-15 scaffold,the control group was implanted with CS/rGO scaffold and rat periodontal ligament stem cell complex,and the experimental group was implanted with CS/rGO/PDGF-BB-15 scaffold and rat periodontal ligament stem cell complex,with 4 rats in each group.Twelve weeks after surgery,the bone repair of the alveolar bone defect was observed by Micro CT scanning and hematoxylin-eosin staining.RESULTS AND CONCLUSION:(1)CS/rGO/PDGF-BB-5,CS/rGO/PDGF-BB-10,CS/rGO/PDGF-BB-15,and CS/rGO/PDGF-BB-20 scaffolds could promote the proliferation and migration of rat periodontal ligament stem cells.Among them,the CS/rGO/PDGF-BB-15 scaffold had the most significant effect on promoting cell proliferation and migration,and this scaffold was used for subsequent experiments.Compared with the CS/rGO scaffold,the CS/rGO/PDGF-BB-15 scaffold could promote the osteogenic and angiogenic differentiation of rat periodontal ligament stem cells.(2)Micro CT scanning and hematoxylin-eosin staining results showed that the experimental group had the best alveolar bone defect repair effect,and a large amount of new bone tissue and blood vessel formation could be seen.(3)The chitosan/reduced graphene oxide scaffold loaded with platelet-derived growth factor BB can effectively promote the repair of rat alveolar bone defects by promoting the proliferation,migration,angiogenic and osteogenic differentiation of rat periodontal ligament stem cells.

BACKGROUND:Studies have shown that platelet-derived growth factor BB can stimulate the proliferation and osteogenic differentiation of mesenchymal stem cells and accelerate the calcification process of osteoblast-like cells.However,its clinical application has problems such as short half-life and easy decomposition.Loading the growth factor onto a suitable biomaterial scaffold can enable its slow and continuous release and maintain an effective concentration,which has become a hot topic in current research.OBJECTIVE:To observe the effect of chitosan/reduced graphene oxide scaffolds loaded with platelet-derived growth factor BB on the repair of alveolar bone defect in rats.METHODS:(1)Chitosan/reduced graphene oxide scaffolds(referred to as CS/rGO scaffolds)and chitosan/reduced graphene oxide scaffolds loaded with different mass concentrations(5,10,15,and 20 mg/L)of platelet-derived growth factor BB(referred to as CS/rGO/PDGF-BB-5,CS/rGO/PDGF-BB-10,CS/rGO/PDGF-BB-15,and CS/rGO/PDGF-BB-20 scaffolds)were prepared respectively.The five groups of scaffolds were co-cultured with rat periodontal ligament stem cells.The cell proliferation and migration were detected by CCK-8 assay and Transwell chamber assay,respectively,to screen the appropriate growth factor loading mass concentration for subsequent experiments.CS/rGO scaffolds(or extracts)and CS/rGO/PDGF-BB-15 scaffolds(or extracts)were co-cultured with rat periodontal ligament stem cells,and the osteogenic differentiation and angiogenic ability of the cells were detected.(2)The alveolar bone defect model was prepared in front of the bilateral maxillary first molars of 16 SD rats,and the rats were randomly divided into 4 intervention groups:the blank control group did not receive any intervention,the simple scaffold group was implanted with CS/rGO/PDGF-BB-15 scaffold,the control group was implanted with CS/rGO scaffold and rat periodontal ligament stem cell complex,and the experimental group was implanted with CS/rGO/PDGF-BB-15 scaffold and rat periodontal ligament stem cell complex,with 4 rats in each group.Twelve weeks after surgery,the bone repair of the alveolar bone defect was observed by Micro CT scanning and hematoxylin-eosin staining.RESULTS AND CONCLUSION:(1)CS/rGO/PDGF-BB-5,CS/rGO/PDGF-BB-10,CS/rGO/PDGF-BB-15,and CS/rGO/PDGF-BB-20 scaffolds could promote the proliferation and migration of rat periodontal ligament stem cells.Among them,the CS/rGO/PDGF-BB-15 scaffold had the most significant effect on promoting cell proliferation and migration,and this scaffold was used for subsequent experiments.Compared with the CS/rGO scaffold,the CS/rGO/PDGF-BB-15 scaffold could promote the osteogenic and angiogenic differentiation of rat periodontal ligament stem cells.(2)Micro CT scanning and hematoxylin-eosin staining results showed that the experimental group had the best alveolar bone defect repair effect,and a large amount of new bone tissue and blood vessel formation could be seen.(3)The chitosan/reduced graphene oxide scaffold loaded with platelet-derived growth factor BB can effectively promote the repair of rat alveolar bone defects by promoting the proliferation,migration,angiogenic and osteogenic differentiation of rat periodontal ligament stem cells.

Objective: To systematically evaluate the influencing factors for repeated implantation failure (RIF) after in vitro fertilization-embryo transfer (IVF-ET) in China, so as to provide the evidence for prevention of RIF. Methods: Literature on influencing factors for RIF in China were retrieved from CNKI, Wanfang Data, VIP, China Medical Literature Service System, PubMed, Web of Science, Cochrane Library and Embase from inception to September, 2024. A meta-analysis was performed using RevMan 5.3 and Stata 14.0 softwares. Literature were excluded one by one for sensitivity analysis. Publication bias was evaluated using Egger's test. Results: Initially 4 836 relevant articles were retrieved, and 12 of them were finally included, with a total sample size of 11 554 individuals. There were 10 case-control studies, 1 cohort study, and 1 cross-sectional study; and 10 high-quality studies and 2 medium-quality studies. The meta-analysis showed that factors including advanced age (OR=1.121, 95%CI: 1.035-1.215), prolonged infertility duration (OR=1.237, 95%CI: 1.091-1.403), abnormal hysteroscopy findings (OR=2.205, 95%CI: 1.119-4.348), positive anti-nuclear antibody (ANA) (OR=2.393, 95%CI: 1.473-3.886), and positive anti-beta2 glycoprotein Ⅰ antibody (β2-GPⅠ-Ab) (OR=2.824, 95%CI: 1.987-4.013) were associated with an increased risk of RIF; while factors including the large number of embryos transferred (OR=0.309, 95%CI: 0.098-0.973), thicker endometrium (OR=0.601, 95%CI: 0.556-0.650), and higher granulocyte colony-stimulating factor (G-CSF) levels (OR=0.657, 95%CI: 0.511-0.845) were associated with a reduced risk of RIF. Conclusion IVF-ET RIF is associated with age, infertility duration, number of embryos transferred, endometrial thickness, hysteroscopy findings, G-CSF levels, ANA and β2-GPⅠ-Ab.

The p21-activated kinase 4 (PAK4), a key regulator of malignancy, is negatively correlated with immune infiltration and has become an emergent drug target of cancer therapy. Given the lack of high efficacy PAK4 inhibitors, we herein reported the identification of a novel inhibitor 13 bearing a tetrahydrobenzofuro[2,3-c]pyridine tricyclic core and possessing high potency against MIA PaCa-2 and Pan02 cell lines with IC₅₀ values of 0.38 and 0.50 μmol/L, respectively. This compound directly binds to PAK4 in a non-ATP competitive manner. In the mouse Pan02 model, compound 13 exhibited significant tumor growth inhibition at a dose of 100 mg/kg, accompanied by reduced levels of PAK4 and its phosphorylation together with immune infiltration in mice tumor tissue. Overall, compound 13 is a novel allosteric PAK4 inhibitor with a unique tricyclic structural feature and high potency both in vitro and in vivo, thus making it worthy of further exploration.

BACKGROUND: Macrophage polarization anomalies and dysfunction play a crucial role in the pathogenesis of immune thrombocytopenia (ITP). Itaconate is a Krebs cycle-derived immunometabolite synthesized by myeloid cells to modulate cellular metabolism and inflammatory responses. This study aimed to evaluate the immunoregulatory effects of an itaconate derivative on macrophages in patients with ITP. METHODS: Peripheral blood-derived macrophages from patients with ITP and healthy controls were treated with 4-octyl itaconate (4-OI), a derivative of itaconate that can penetrate the cell membrane. Macrophage polarization, antigen-presenting functions, and phagocytic capability were measured via flow cytometry and enzyme-linked immunosorbent assay (ELISA). Macrophage glycolysis in patients with ITP and the metabolic regulatory effect of 4-OI were detected using a Seahorse XFe96 Analyzer. An active murine model of ITP was used to evaluate the therapeutic effects of 4-OI in vivo . RESULTS: 4-OI reduced the levels of CD80 and CD86 in M1 macrophages and suppressed the release of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 pro-inflammatory cytokines, suggesting that 4-OI could hinder the polarization of macrophages toward an M1 phenotype. We found that 4-OI pretreated M1 macrophages reduced the proliferation of CD4 + T cells and promoted the differentiation of regulatory T cells. In addition, after 4-OI treatment, the phagocytic capacity of M1 macrophages toward antibody-coated platelets decreased significantly in patients with ITP. In addition, the glycolytic function of M1 macrophages was elevated in individuals with ITP compared to those in healthy controls. 4-OI treatment downregulated glycolysis in M1 macrophages. The glycolysis inhibitor 2-deoxy-d-glucose (2-DG) also inhibited the polarization of M1 macrophages and restored their functions. In vivo , 4-OI treatment significantly increased platelet counts in the active ITP murine model. CONCLUSIONS Itaconate derivative 4-OI inhibited M1 macrophage polarization and restored impaired functions through metabolic reprogramming. This study provides a novel therapeutic option for ITP.
Macrophages/metabolism* ; Humans ; Animals ; Succinates/pharmacology* ; Mice ; Male ; Female ; Adult ; Middle Aged ; Flow Cytometry ; Tumor Necrosis Factor-alpha/metabolism* ; Enzyme-Linked Immunosorbent Assay ; Purpura, Thrombocytopenic, Idiopathic/metabolism* ; Glycolysis/drug effects* ; Metabolic Reprogramming

Drug-drug interaction (DDI) refers to the interaction between two or more drugs in the body, altering their efficacy or pharmacokinetics. Fully considering and accurately predicting DDI has become an indispensable part of ensuring safe medication for patients. In recent years, many deep learning-based methods have been proposed to predict DDI. However, most existing computational models tend to oversimplify the fusion of drug structural and topological information, often relying on methods such as splicing or weighted summation, which fail to adequately capture the potential complementarity between structural and topological features. This loss of information may lead to models that do not fully leverage these features, thus limiting their performance in DDI prediction. To address these challenges, we propose a relation-aware cross adversarial network for predicting DDI, named RCAN-DDI, which combines a relationship-aware structure feature learning module and a topological feature learning module based on DDI networks to capture multimodal features of drugs. To explore the correlations and complementarities among different information sources, the cross-adversarial network is introduced to fully integrate features from various modalities, enhancing the predictive performance of the model. The experimental results demonstrate that the RCAN-DDI method outperforms other methods. Even in cases of labelled DDI scarcity, the method exhibits good robustness in the DDI prediction task. Furthermore, the effectiveness of the cross-adversarial module is validated through ablation experiments, demonstrating its superiority in learning multimodal complementary information.