Prescription optimization is a crucial aspect in the study of traditional Chinese medicine （TCM） compounds. In recent years， the introduction of mathematical methods， data mining techniques， and artificial neural networks has provided new tools for elucidating the compatibility rules of TCM compounds. The study of TCM compounds involves numerous variables， including the proportions of different herbs， the specific extraction parts of each ingredient， and the interactions among multiple components. These factors together create a complex nonlinear dose-effect relationship. In this context， it is essential to identify methods that suit the characteristics of TCM compounds and can leverage their advantages for effective application in new drug development. This paper provided a comprehensive review of the cutting-edge optimization experimental design methods applied in recent studies of TCM compound compatibilities. The key technical issues， such as the optimization of source material selection， dosage optimization of compatible herbs， and multi-objective optimization indicators， were discussed. Furthermore， the evaluation methods for component effects were summarized during the optimization process， so as to provide scientific and practical foundations for innovative research in TCM and the development of new drugs based on TCM compounds.

OBJECTIVE To know about the perception and current status of drug risk management among pharmacists in Chinese medical institutions， providing insights and recommendations for enhancing the drug risk management system in medical institutions. METHODS A questionnaire survey was conducted across 28 provinces， cities， and autonomous regions； stratified radom sampling was employed to study the population of medical workers and pharmaceutical professionals in medical institutions nationwide. The survey included information on the survey population， the current status of drug risk management implementation in medical institutions， the cognition， definition and process of drug risk management related concepts， and the content and mode of drug risk management work in medical institutions. Finally， suggestions were collected from various medical institutions on the system construction of drug risk management. Descriptive statistical analysis was adopted to summarize the obtained data. RESULTS A total of 446 questionnaires were collected in this survey， including 420 valid questionnaires and 26 invalid questionnaires. The questionnaire collection rate was 100%，and the effective rate was 94.17%. 51.19% of the respondents No.2020YFC2009001）。 based their understanding of drug risk management on Management Measures for Adverse Drug Reaction Reports and Monitoring， while 87.38% recognized the need for drug risk management throughout the drug use process. 63.33% of the participants stated that their medical institutions had dedicated positions related to drug risk management， with the highest proportion （72.17%） was in third-grade class A medical institutions. 66.43% reported implementing risk management across all drug use stages. Suggestions for the development of drug risk management systems in medical institutions by the research participants focused on enhancing guiding documents， clarifying concepts， establishing information-sharing mechanisms. CONCLUSIONS The overall awareness of drug risk management in China’s medical institutions is high， with practices in place across various stages in multiple forms. However， there remains a need to strengthen institutional documents， management regulations， system development， and information-sharing mechanisms to improve collaborative governance， improve drug management levels， and ensure patient safety.

OBJECTIVES: Sepsis-associated acute lung injury (S-ALI) is one of the major causes of death in intensive care unit (ICU) patients, yet its mechanisms remain incompletely understood and effective therapies are lacking. Lytic cell death of macrophages is a key driver of the inflammatory cascade in S-ALI. PANoptosis, a newly recognized form of lytic cell death characterized by PANoptosome assembly and activation, involves plasma membrane rupture (PMR) mediated by ninjurin-1 (NINJ1), a recently identified pore-forming protein. Itaconic acid is known for its anti-inflammatory effects, but its role in macrophage PANoptosis during S-ALI is unclear. This study aims to investigate the protective effect of itaconic acid on macrophage PANoptosis in S-ALI to provide new therapeutic insights. METHODS: Male specific-pathogen-free C57BL/6J mice (6-8 weeks, 18-20 g) received intraperitoneal lipopolysaccharide (LPS) to establish a classical S-ALI model. Western blotting was used to assess PANoptosome-related proteins and enzymes involved in the itaconic acid metabolic pathway, while real-time reverse transcription polymerase chain reaction and metabolomics quantified itaconic acid levels. Primary peritoneal macrophages (PMs) were pretreated with the itaconate derivative 4-octyl itaconate (4-OI) and then exposed to tumor necrosis factor alpha (TNF-α) plus interferon gamma (IFN-γ) to induce PANoptosis. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. Western blotting was employed to quantify enzymes of the itaconate-metabolic pathway in PANoptotic macrophages, to evaluate the impact of 4-OI on PANoptosome-associated proteins, and to determine NINJ1 abundance in lung tissues from S-ALI mice and in PANoptotic macrophages. Fluorescent dye FM_4-64 was used to visualize 4-OI-mediated changes in PMR, whereas immunofluorescence staining mapped the effect of 4-OI on both the expression level and membrane localization of NINJ1 in PANoptotic macrophages. The effect of 4-OI on lactate dehydrogenase (LDH) release in culture supernatants and peripheal blood serum was assessed using a LDH assay kit, and non-denataring polyacylamide gel electrophoresis was used to assess the expression of NINJ1 in S-ALI mouse lung tissues and the impact of 4-OI on the expression of PANoptosis-associated NINJ1 multimeric reflected protein in macropahges. RESULTS: In S-ALI mouse lungs, PANoptosome components [NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Gasdermin D (GSDMD), Caspase-1, Z-DNA binding protein (ZBP1), and Caspase-3] and phosphorylated mixed lineage kinase domain-like protein (MLKL) S345 were significantly upregulated (all P<0.05), while metabolomics showed compensatory increases in itaconic acid and its key enzymes [aconitate decarboxylase 1 (ACOD1)/immunoresponsive gene 1 (IRG1)]. In macrophages, 4-OI obviously suppressed PANoptosome protein expression, reduced LDH release, restored plasma membrane integrity, and inhibited NINJ1 expression and oligomerization at the membrane (P<0.05). CONCLUSIONS Itaconic acid may alleviate macrophage PANoptosis in S-ALI by inhibiting NINJ1-mediated plasma membrane rupture. Targeting NINJ1 or enhancing itaconate pathways may offer a novel therapeutic strategy for S-ALI.
Animals ; Acute Lung Injury/pathology* ; Succinates/pharmacology* ; Sepsis/complications* ; Mice, Inbred C57BL ; Male ; Mice ; Macrophages/pathology* ; Cell Membrane/metabolism* ; Lipopolysaccharides ; Hydro-Lyases

Plant-derived extracellular vesicles (PDEVs), describe a group of nanoparticles released by plants. These particles are characterized by a lipid bilayer structure containing various proteins, lipids, nucleic acids, and unique metabolites. Although the study on PDEVs is relatively new, having only been around for ten years, they have shown promising development prospects in both basic research and clinical transformation areas. Evidence suggests that PDEVs have excellent application prospects in regulating inflammation and treating tumors. Their distinctive, vesicle-mimicking architecture and stellar biocompatibility render them prime candidates for ferrying various anti-cancer agents, including RNA, proteins, and conventional chemotherapy drugs. Increasingly, studies have shown that PDEVs can be engineered as an innovative platform for combination cancer immunotherapy. Consequently, this paper provides an extensive summary of current developments in engineering methods and strategies for PDEVs in cancer treatment and combined cancer immune therapeutics. The essential characteristics of PDEVs, including the biogenesis process and components, as well as their anti-tumor activity and mechanism, are summarized. Finally, the in vivo safety of PDEVs as delivery vectors and the challenges of scale-up production and clinical transformation are discussed.

Objective:To analyze the vaccination recommendations and follow-up for children with special health status.Methods:In this retrospective cohort study, 509 children who attended the Consultation Clinic of Vaccination for Special Health Children in Beijing Children′s Hospital from August 2020 to February 2023 were selected, the children were given vaccination planning advice after the assessment. The clinical data were collected, including the general situation, special health conditions, vaccination recommendations and implementation status, occurrence and outcomes of suspected adverse events following immunization (AEFI) after vaccination. The vaccination situation and safety in these children were evaluated.Results:Among the 509 children, the most common special health conditions were cardiovascular system diseases (103 cases), followed by neurological diseases (88 cases) and neonatal problems (82 cases). After comprehensive evaluation and multidisciplinary collaboration, 399 children (78.4%) were recommended to receive vaccination/catch-up vaccination according to the immunization program, 63 children (12.4%) were recommended to receive some vaccines but temporarily suspend others, and 47 children (9.2%) were recommended to temporarily suspend vaccination. A total of 449 children (88.2%) were actually vaccinated, AEFI occurred in 49 children and 45 cases were considered as general reactions.Conclusions:The majority of children with special health status can be vaccinated, and the overall compliance and safety are high. The individualized immunization evaluation model of multidisciplinary collaboration is conducive to the completion of the immunization program of children with special health status.

Objective:To explore the effectiveness of the comprehensive healthcare management model for children with bacterial meningitis after discharge.Methods:This study was a retrospective cohort study that included 268 children with bacterial meningitis who were discharged from the infectious medicine ward of Beijing Children′s Hospital from September 2018 to September 2023. The children were managed with a multidisciplinary collaborative comprehensive healthcare management model after discharge. Outpatient data at 1 month and 6, 12 and 24 months after discharge were collected, including (height, weight, body mass index, nutritional feeding status, hearing and vision screening results, Gesell developmental assessment results and intervention guidance services. The follow-up interval or frequency was dynamically adjusted or increased according to the child′s situation. The paired sample t-test and chi square test were applied to compare the differences in Gesell developmental quotient (DQ) and developmental delay rate between the first and last assessments to preliminarily explore the effectiveness of the comprehensive healthcare management model for children with bacterial meningitis after discharge. Results:All the 268 children completed their first assessment one month after discharge, and 37 children were found to have abnormal physical growth, mainly obesity (28 children), and another 9 children were malnutrition. Nutritional intervention and feeding guidance services were provided to all the 37 children, and as of the last follow-up, 20 children′s physical growth evaluations had turned normal. A total of 188 children completed at least 2 developmental assessments, with an interval of (14.2±9.4) months between the first and last assessments (range: 3.1-49.5 months). The DQ values of in the energy region of adaptability, gross motor skills, fine motor skills, language, and personal social skills at the last assessment were significantly higher than those at the first assessment [(91.93±13.28) vs (80.73±15.96) points, (91.69±12.96) vs (78.31±16.58) points, (89.32±16.11) vs (80.68±15.63) points, (90.10±16.65) vs (82.04±18.43) points, (92.01±14.05) vs (77.82±17.42) points]; moreover, the rates of developmental delay in each energy region were significantly lower than those at the initial assessment (9.6% vs 35.1%, 9.6% vs 42.0%, 18.1% vs 33.0%, 13.3% vs 31.9%, 9.6% vs 42.0%) (all P<0.05). Among the 200 children who completed the hearing screening, 18 were found with hearing abnormalities, and 2 were diagnosed with hearing loss in the Otolaryngology Department. Among 217 children who completed vision screening, 23 had abnormalities, and 5 were diagnosed with ophthalmic abnormalities in Ophthalmology Department (2 with strabismus, 2 with refractive errors, and 1 with optic nerve injury). Two children were found to have autism-like behavior during monitoring, and were referred to a developmental behavior clinic to be diagnosed with autism spectrum disorder and were given early diagnosis and intervention guidance. Conclusion:The comprehensive healthcare management model for children with bacterial meningitis after discharge can integrate clinical and healthcare resources, which is beneficial for improving the prognosis and enhancing the quality of life for children with special health status.

Objective To investigate the inhibitory effects of pyruvate-ferredoxin oxidoreductase(PFOR)by luteolin and its anti-Clostridium difficile effect.Methods The PFOR encoding sequence of Clostridium difficile was cloned into the expression vector pET-2a and transformed into competent Escherichia coli.The crude enzyme was prepared after induction with IPTG(Isopropyl β-D-Thiogalactoside).The inhibitory rate of the test compounds on PFOR was determined after an 8-hour anaerobic reaction between PFOR and 40 μmol·L-1 of test compounds at 25℃.The minimum inhibitory concentration(MIC)of PFOR inhibitors against C.difficile strains(ATCC BAA 1382 and ATCC BAA 1870)was determined by monitoring the OD600 of the bacterial culture.Molecular docking was performed to investigate the possible interaction mechanisms between PFOR and inhibitors.Results Among the tested compounds,the luteolin showed the strongest inhibitory activity against PFOR,with a single-point inhibition rate of approximately 33%,which is comparable to that observed with the positive inhibitor nitazoxanide(40%).Molecular docking revealed that luteolin could form hydrogen bonds with Asp428,Val431,Gly429,Asp456,Lys458,Lys459,and other residues in the PFOR domain.The MIC of luteolin against C.difficile was approximately 32 μg·mL-1.Conclusion Luteolin exhibits good activity against C.difficile,and PFOR may be a target for its antibacterial action.

OBJECTIVE To investigate the activation of xanthine oxidase(XO)from the human liver by vitamin K3 and the mechanism.METHODS Using human liver S9(0.1 g·L-1)as the source,XO was incubated with substrate xanthine of 0,2,4,8,and 16 μmol·L-1 at 37℃ for 90 min.The Michaelis constant(Km)of the reaction of xanthine oxidation was determined using the liquid chromatography diode array method.At the concentration of Km,the three-point method(1,10 and 100 μmol·L-1)was used to detect the activity of vitamin K3 activators.The multi-point method(vitamin K3 1,2,5,10,20,50,100,200 and 400 μmol·L-1)was adopted to determine the half effective concentration(EC50)of activated XO.Kinetic parameters(Km and Vmax)and the fit of double reciprocal curves were determined via vitamin K3 of 1/2EC50,EC50 and 2EC50.The changes in kinetic behavior at different concentrations of vitamin K3 were observed and their types of activation were analyzed.The interactions between XO and activator vitamin K3 were explored via molecular docking.RESULTS The Km of XO-mediated xanthine oxidation reac-tion was 4.71 μmol·L-1.As an activator of this reaction,vitamin K3 activated XO in a concentration-dependent manner(according to the logistic fitting formula y=A2+(A1-A2)/(1+(x/x0)^p),with an EC50 of 32.0 μmol·L-1.The kinetic parameters also changed after the addition of vitamin K3.The Km value decreased(4.71-1.34 μmol·L-1)with the increase of vitamin K3 concentrations,while the Vmax value increased(0.08-1.31 μmol·min-1·g-1),leading to an increase in Vmax/Km(17.0-977.6 mL·min·g-1).In addition,the double reciprocal curve fitting found that the activation type of vitamin K3 on XO was mixed.The molecular docking results showed that vitamin K3 bound to the molybdopterin domain of XO and maintained hydrogen bonding interactions with Arg599 and Ser605.CONCLUSION Vitamin K3 is an activator of XO,which can form hydrogen bonds with Arg599 and Ser605 in the XO domain,regu-late its affinity with the substrate xanthine,activate XO and increase the uric acid level.