OBJECTIVE To analyze and identify the metabolites of pirtobrutinib （PTN） in rats， and clarify the possible metabolic pathways of PTN in rats. METHODS Six rats were intragastrically administered with 10 mg/kg PTN suspension. Blood samples were collected from the rats 30 minutes before administration and at 0.25， 0.5， 1， 2， 4， 6， 8， 12， 24 hours after administration. Urine and feces samples were collected 12 hours before administration and 24 hours after administration. UHPLC- Orbitrap Exploris 240 system combined with Compound Discoverer 3.0 and Xcalibur 2.0 software were adopted for structural identification and metabolic pathway analysis of PTN metabolites in rat plasma， urine， and feces. RESULTS A total of 29 PTN metabolites were identified， including 17， 19 and 22 metabolites in plasma， urine and feces， respectively. The metabolic pathways of PTN mainly included oxidation， sulfation， glucuronidation， etc.， and its metabolites were mostly combination products of two or more different metabolic forms. In detail， a total of 26 metabolites were associated with phase Ⅰ metabolic reactions （14 oxidation metabolites， 9 reduction/dehydrogenation metabolites， 8 demethylation metabolites， and 5 hydrolysis metabolites）. Meanwhile， a total of 20 products were involved in phase Ⅱ metabolites （14 sulfation metabolites and 8 glucuronic acid binding metabolites）. CONCLUSIONS PTN exhibits a diverse range of metabolites in rat fecal samples， with the primary metabolic pathways being oxidation， sulfation， glucuronidation， and others.

ObjectiveTraditional Chinese medicine (TCM) constitutes a valuable cultural heritage and an important source of antitumor compounds. Poria (Poria cocos (Schw.) Wolf), the dried sclerotium of a polyporaceae fungus, was first documented in Shennong’s Classic of Materia Medica and has been used therapeutically and dietarily in China for millennia. Traditionally recognized for its diuretic, spleen-tonifying, and sedative properties, modern pharmacological studies confirm that Poria exhibits antioxidant, anti-inflammatory, antibacterial, and antitumor activities. Pachymic acid (PA; a triterpenoid with the chemical structure 3β-acetyloxy-16α-hydroxy-lanosta-8,24(31)-dien-21-oic acid), isolated from Poria, is a principal bioactive constituent. Emerging evidence indicates PA exerts antitumor effects through multiple mechanisms, though these remain incompletely characterized. Neuroblastoma (NB), a highly malignant pediatric extracranial solid tumor accounting for 15% of childhood cancer deaths, urgently requires safer therapeutics due to the limitations of current treatments. Although PA shows multi-mechanistic antitumor potential, its efficacy against NB remains uncharacterized. This study systematically investigated the potential molecular targets and mechanisms underlying the anti-NB effects of PA by integrating network pharmacology-based target prediction with experimental validation of multi-target interactions through molecular docking, dynamic simulations, and in vitro assays, aimed to establish a novel perspective on PA’s antitumor activity and explore its potential clinical implications for NB treatment by integrating computational predictions with biological assays. MethodsThis study employed network pharmacology to identify potential targets of PA in NB, followed by validation using molecular docking, molecular dynamics (MD) simulations, MM/PBSA free energy analysis, RT-qPCR and Western blot experiments. Network pharmacology analysis included target screening via TCMSP, GeneCards, DisGeNET, SwissTargetPrediction, SuperPred, and PharmMapper. Subsequently, potential targets were predicted by intersecting the results from these databases via Venn analysis. Following target prediction, topological analysis was performed to identify key targets using Cytoscape software. Molecular docking was conducted using AutoDock Vina, with the binding pocket defined based on crystal structures. MD simulations were performed for 100 ns using GROMACS, and RMSD, RMSF, SASA, and hydrogen bonding dynamics were analyzed. MM/PBSA calculations were carried out to estimate the binding free energy of each protein-ligand complex. In vitro validation included RT-qPCR and Western blot, with GAPDH used as an internal control. ResultsThe CCK-8 assay demonstrated a concentration-dependent inhibitory effect of PA on NB cell viability. GO analysis suggested that the anti-NB activity of PA might involve cellular response to chemical stress, vesicle lumen, and protein tyrosine kinase activity. KEGG pathway enrichment analysis suggested that the anti-NB activity of PA might involve the PI3K/AKT, MAPK, and Ras signaling pathways. Molecular docking and MD simulations revealed stable binding interactions between PA and the core target proteins AKT1, EGFR, SRC, and HSP90AA1. RT-qPCR and Western blot analyses further confirmed that PA treatment significantly decreased the mRNA and protein expression of AKT1, EGFR, and SRC while increasing the HSP90AA1 mRNA and protein levels. ConclusionIt was suggested that PA may exert its anti-NB effects by inhibiting AKT1, EGFR, and SRC expression, potentially modulating the PI3K/AKT signaling pathway. These findings provide crucial evidence supporting PA’s development as a therapeutic candidate for NB.

OBJECTIVE To establish a closed-loop management system for the whole-process traceability of outpatient drugs based on internet of things （IoT） and blockchain technology， and evaluate its implementation effects. METHODS A closed-loop management system for the whole-process traceability of outpatient drugs covering the entire drug lifecycle was designed using drug traceability codes integrated with IoT and blockchain technology. System effectiveness was evaluated from three dimensions： work efficiency， medication management quality and data safety by comparing indicators such as the acceptance time of incoming drugs and the number of collected drug traceability codes before the system implementation （October to December 2024） and after the system implementation （January to March 2025）. RESULTS A closed-loop management system for the whole-process traceability of outpatient drugs， centered around the drug traceability code management system， was successfully established. The acceptance time for incoming drugs was shortened from （4.65±0.26） h before implementation to （0.34±0.08） h after implementation （P＜ 0.05）. The number of collected drug traceability codes increased from 419 018 to 1 236 522， and the coverage rate of traceability codes rose from 28.36% to 89.88% （P＜0.05）. The time pharmacists spent on drug expiry management per week decreased from （128.40±19.20） min to （0.56±0.13） min （P＜0.05）， and the dispensing time for a single prescription （excluding a part of injections and repackaged drugs） was reduced from （143.25±17.67） s to （15.24±10.08） s （P＜0.05）. The time for drug return was reduced from 129.90 （122.32， 137.00） s to 104.36 （89.91， 117.33） s（P＜0.05）； the number of drug dispensing errors decreased from 2 cases to 0 cases. After the system was launched， there were no data security incidents in our outpatient pharmacy. CONCLUSIONS The constructed closed-loop management system for the whole-process traceability of outpatient drugs can significantly enhance drug traceability accuracy and drug management quality， improve pharmacist work efficiency， and reduce drug management risks， thus providing a feasible solution for the digital transformation of hospital pharmaceutical services.

The precise localization of pulmonary nodules has become an important technical key point in the treatment of pulmonary nodules by thoracoscopic surgery, which is a guarantee for safe margin and avoiding removal of too much normal lung parenchyma. With the development of medical technology and equipment, the methods of locating pulmonary nodules are also becoming less trauma and convenience. There are currently a number of methods applied to the preoperative or intraoperative localization of pulmonary nodules, including preoperative percutaneous puncture localization, preoperative transbronchial localization, intraoperative palpation localization, intraoperative ultrasound localization, and localization according to anatomy. The most appropriate localization method should be selected according to the location of the nodule, available equipment, and surgeon鈥檚 experience. According to the published literatures, we have sorted out a variety of different theories and methods of localization of pulmonary nodules in this article, summarizing their advantages and disadvantages for references.

Projection micro stereolithography three-dimensional(3D)printing method was proposed in this study to fabricate complex microchannels of combined cross-sections.By using 3D printing and polydimethylsiloxane(PDMS)replication methods,two inertial microfluidic chips of three-step and five-step cross-sections were fabricated,and the dimension precisions of the microchannels were controlled within 20 μm.Using the microfluidic chips,the movements of two fluorescent polystyrene particles with diameters of 10 and 6 μm in the stepped channels were investigated.In addition,numerical simulations were applied to demonstrate the inertial focusing mechanisms of particles in the channels.It was found that 10-μm particles had three equilibrium positions in the three-step channel,which located at the inner walls of the three steps,respectively,and most particles focused at the inner step.The 6-μm particles also had three equilibrium positions in the three-step channel.However,the particles migrated to the middle and the outer steps under high flow rates.In the five-step channel,when the flow rate was increased gradually,10-μm particles had a single and two equilibrium positions,respectively,and the particles migrated towards the inner channel wall under high flow rates.In comparison to 10-μm particles,6-μm particles had two stable equilibrium positions in the five-step channel at all flow rate range.It could be concluded that the quantity,shape and strength of the secondary flow vortex could be altered by changing structure of the combined cross-section,thus the equilibrium positions and quantities of the focusing particles could be also regulated.The research outcome might provide new insights for precise cell inertial manipulation and promote the application and development of inertial microfluidic technology in biomedical and other fields.

To improve the evaluation indicators of medical quality in TCM hospitals; To realize objective, fair, and accurate evaluation of the quality of TCM. Based on relevant literature on medical quality in traditional Chinese medicine hospitals research and thematic group discussions, 21 evaluation indicators for TCM characteristics were formed. A questionnaire survey was conducted among 40 experts, and 37 were effectively collected, with a positive coefficient of 92.50%. After two rounds of expert consultation, the evaluation indicators were determined to be: the intensity of outpatient use of TCM decoction pieces (utilization rate of TCM decoction pieces, prescription number of TCM decoction pieces, dosage of TCM decoction pieces, and service price of TCM decoction pieces), the intensity of the use of TCM technology (proportion of TCM technology, number of TCM projects, cost of TCM technology, and course of treatment). Case studies were conducted on relevant data from 10 departments using the operational decision support system (BI) platform of Yueyang Integrated Traditional Chinese and Western Medicine Hospital affiliated with Shanghai University of Traditional Chinese Medicine to verify the rationality of indicators. The 10 departments were analyzed and evaluated, and the results obtained were basically consistent with the actual medical quality situation of the hospital. The indicators used in this study can reflect the actual medical quality situation, and have a certain degree of scientificity, feasibility, and applicability, providing reference for improving the medical quality evaluation indicators of TCM hospitals.

Nanozyme is novel nanoparticle with enzyme-like activity, which can be classified into peroxidase-like nanozyme, catalase-like nanozyme, superoxide dismutase-like nanozyme, oxidase-like nanozyme and hydrolase-like nanozyme according to the type of reaction they catalyze. Since researchers first discovered Fe₃O₄ nanoparticles with peroxidase-like activity in 2007, a variety of nanoparticles have been successively found to have catalytic activity and applied in bioassays, inflammation control, antioxidant damage and tumor therapy, playing a key role in disease diagnosis and treatment. We summarize the use of nanozymes with different classes of enzymatic activity in the diagnosis and treatment of diseases and describe the main factors influencing nanozyme activity. A Mn-based peroxidase-like nanozyme that induces the reduction of glutathione in tumors to produce glutathione disulfide and Mn²⁺, which induces the production of reative oxygen species (ROS) in tumor cells by breaking down H₂O₂ in physiological media through Fenton-like action, thereby inhibiting tumor cell growth. To address the limitation of tumor tissue hypoxia during photodynamic tumor therapy, the effect of photodynamic therapy is significantly enhanced by using hydrogen peroxide nanozymes to catalyze the production of oxygen from H₂O₂. In pathological states, where excess superoxide radicals are produced in the body, superoxide dismutase-like nanozymes are able to selectively regulate intracellular ROS levels, thereby protecting normal cells and slowing down the degradation of cellular function. Based on this principle, an engineered nanosponge has been designed to rapidly scavenge free radicals and deliver oxygen in time to save nerve cells before thrombolysis. Starvation therapy, in which glucose oxidase catalyzes the hydrolysis of glucose to gluconic acid and hydrogen peroxide in cancer cells with the involvement of oxygen, attenuates glycolysis and the production of intermediate metabolites such as nucleotides, lipids and amino acids, was used to synthesize an oxidase-like nanozyme that achieved effective inhibition of tumor growth. Furthermore, by fine-tuning the Lewis acidity of the metal cluster to improve the intrinsic activity of the hydrolase nanozyme and providing a shortened ligand length to increase the density of its active site, a hydrolase-like nanozyme was successfully synthesized that is capable of cleaving phosphate bonds, amide bonds, glycosidic bonds and even biofilms with high efficiency in hydrolyzing the substrate. All these effects depend on the size, morphology, composition, surface modification and environmental media of the nanozyme, which are important aspects to consider in order to improve the catalytic efficiency of the nanozyme and have important implications for the development of nanozyme. Although some progress has been made in the research of nanozymes in disease treatment and diagnosis, there are still some problems, for example, the catalytic rate of nanozymes is still difficult to reach the level of natural enzymes in vivo, and the toxic effects of some heavy metal nanozymes material itself. Therefore, the construction of nanozyme systems with multiple functions, good biocompatibility and high targeting efficiency, and their large-scale application in diagnosis and treatment is still an urgent problem to be solved. (1) To improve the selectivity and specificity of nanozymes. By using antibody coupling, the nanoparticles are able to specifically bind to antigens that are overexpressed in certain cancer cells. It also significantly improves cellular internalization through antigen-mediated endocytosis and enhances the enrichment of nanozymes in target tissues, thereby improving targeting during tumor therapy. Some exogenous stimuli such as laser and ultrasound are used as triggers to control the activation of nanozymes and achieve specific activation of nanozyme. (2) To explore more practical and safer nanozymes and their catalytic mechanisms: biocompatible, clinically proven material molecules can be used for the synthesis of nanoparticles. (3) To solve the problem of its standardization and promote the large-scale clinical application of nanozymes in biomonitoring. Thus, it can go out of the laboratory and face the market to serve human health in more fields, which is one of the future trends of nanozyme development.

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective To explore the effect of Shugan Lipi decoction on inflammation and intestinal flora,Toll like receptor 4(TLR4),T cell immunoglobulin domain and mucin domain-3(Tim-3)in non-alcoholic steatohepatitis(NASH)rats.Methods The NASH model was established by feeding methionine and choline deficient diet for 4 weeks.SD rats were randomly divided into blank group(intragastric administration with 0.9％NaCl),model group(NASH model,intragastric administration with 0.9％NaCl),and experimental group(NASH model,intragastric administration with 6.18g·kg-1 Shugan Lipi decoction).Illumina sequencing by synthesis method was used to detect the 16S rRNA sequence of rat Intestinal microbiota.Western blot method was used to detect the expression levels of Tim-3 and TLR4 proteins.Enzyme-linked immunosorbent assay was used to detect tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and IL-10 levels in each group of rats.Results After 4 weeks of medication,the relative abundance of Bacteroidetes in the blank,model and experimental groups were(47.96±10.52)％,(42.90±15.01)％and(57.15±10.99)％;the relative abundance of Firmicutes were(49.27±9.99)％,(53.06±11.47)％and(39.99±11.88)％;the relative expression levels of Tim-3 protein were 1.03±0.07,0.24±0.06 and 1.57±0.11;the relative expression levels of TLR4 protein were 1.04±0.11,3.23±0.33 and 0.94±0.27;the levels of TNF-α were(403.03±25.25),(576.87±60.29)and(385.16±37.67)pg·mL-1;the levels of IL-6 were(125.35±14.07),(189.75±34.30)and(113.71±18.35)pg·mL-1;the levels of IL-10 were(123.20±15.96),(66.71±11.94)and(119.54±10.57)pg·mL-1,respectively.The above indexes in the experimental group showed statistically significant differences compared with the model group(P＜0.01,P＜0.05).Conclusion Shugan Lipi decoction may regulate inflammatory cytokines by affecting intestinal flora and TLR4,Tim-3 protein expression,affect liver inflammatory response,and improve NASH.

In recent years, clinicians have paid more attention to the biological and esthetic effects of the 2 mm keratinized mucosa width (KMW) around dental implant. How to increase the keratinized mucosa is the focus of clinicians. While the free gingival graft (FGG) is still the gold standard of keratinized mucosa augmentation, alveolar ridge preservation (ARP), connective tissue graft (CTG) and apically positioned flap (APF) can also be used to obtain more than 2 mm keratinized mucosa width when they are used before implantation, with implantation, within the implant-healing phase, with second stage of implantation or after rehabilitation according to different indications. This article comprehensively summarizes the influencing factors of timing and surgical procedures for keratinized mucosa augmentation, providing guidance for clinicians to treat peri-implant keratinized mucosa deficiencies.