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.

Social behavior is extremely important for the physical and mental health of individuals, their growth and development, and for social development. Social behavioral disorders have become a typical clinical representation of a variety of psychiatric disorders and have serious adverse effects on the development of individuals. The prefrontal cortex, as one of the key areas responsible for social behavior, involves in many advanced brain functions such as social behavior, emotion, and decision-making. The neural activity of prefrontal cortex has a major impact on the performance of social behavior. Numerous studies demonstrate that neurons and glial cells can regulate certain social behaviors by themselves or the interaction which we called neural microcircuits; and the collaboration with other brain regions also regulates different types of social behaviors. The prefrontal cortex (PFC)-thalamus projections mainly influence social dominance and social preference; the PFC-amygdala projections play a key role in fear behavior, emotional behavior, social exploration, and social identification; and the PFC-nucleus accumbens projections mainly involve social preference, social memory, social cognition, and spatial-social associative learning. Based on the above neural mechanism, many studies have focused on applying the non-invasive neurostimulation to social deficit-related symptoms, including transcranial magnetic stimulation (TMS), transcranial electrical stimulation (TES) and focused ultrasound stimulation (FUS). Our previous study also investigated that repetitive transcranial magnetic stimulation can improve the social behavior of mice and low-intensity focused ultrasound ameliorated the social avoidance behavior of mice by enhancing neuronal activity in the prefrontal cortex. In this review, we summarize the relationship between neurons, glial cells, brain projection and social behavior in the prefrontal cortex, and systematically show the role of the prefrontal cortex in the regulation of social behavior. We hope our summarization will provide a reference for the neural mechanism and effective treatment of social disorders.

Objective:To investigate the correlation between the expression of GLI1 and im-mune invasion and clinical prognosis in gastric cancer.To study the effect of GLI1 expression on drug resistance in gastric cancer.Methods:The expression difference of GLI1 in gastric cancer and normal tissues was analyzed by using TCGA database,and the effect of clinical features and GLI1 gene ex-pression level on prognosis of patients with gastric cancer was analyzed.The correlation between GLI1 gene expression and tumor immune cell infiltration in gastric cancer tissues was analyzed to explore its influence on drug resistance of chemotherapy drugs and targeted drugs.Clinical samples were collect-ed to analyze the difference of GLI1 expression in gastric cancer and paracancer tissues.Results:The expression of GLI1 in gastric cancer tissues was 1.7 times that in normal tissues,and the overall sur-vival and disease-free survival of patients with high expression are shorter than those with low ex-pression(P＜0.05).The interstitial score,immune score and abundance of immunoinfiltrating cells were higher in the high expression of GLI1 in gastric cancer tissues.High expression of GLI1 reduces drug sensitivity and is positively correlated with the expression of immune checkpoint markers PDCD1(P＜0.05).GLI1 expression was significantly increased in patients with subdifferentiated gastric cancer.Conclusions:GLI1 expression is associated with the prognosis and immune infiltration of patients with gastric cancer,and it may lead to poor prognosis of patients by regulating chemotherapy resis-tance,which may be a potential therapeutic target and molecular marker for gastric cancer.

The excipient processing is an essential part of traditional Chinese medicine processing, and understanding its scientific connotations is a critical scientific issue that urgently needs resolution. Building upon a foundation where the composition of traditional Chinese medicine substances is fundamentally clear, this paper applies the techniques and methods of chemoinformatics to the study of the excipient processing mechanism. Relevant information on traditional Chinese medicines processed with four kinds of excipients (wine, vinegar, salt and honey) was collected, including properties, taste, meridian tropism, chemical components, etc. Molecular descritors and skeletons corresponding to each chemical component were calculated using chemoinformatics to characterize the properties and structural features of the components. Characteristic components associated with the four excipients (wine, vinegar, salt and honey) were explored through multivariate statistical analysis and Murcko skeleton analysis. Further analysis, taking honey-processed Astragali Radix as an example, the focus was on the impact of the processing excipient honey on the solubility and permeability of its characteristic pharmacologically active components (isoflavones). It was discovered that the excipient honey can increase their solubility and permeability, emphasizing that the impact of processing excipients on the pharmacological classification properties is a key breakthrough in elucidating the mechanism of excipient processing. In summary, this study analyzed the characteristic components associated with the processing excipients "wine, vinegar, salt and honey" based on their composition characteristics, providing data support for the research on the mechanism of excipient processing from a biopharmaceutical perspective.

Pharmaceutical cocrystals is an advanced technology to improve the physicochemical and biological properties of drugs. However, there are few studies on the in vivo metabolism of pharmaceutical cocrystals. In this study, the pharmacokinetics of wogonin cocrystal in normal rats was further studied on the basis of the previous preparation of wogonin-aloperine cocrystal. Firstly, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established for simultaneous determination of wogonin and its metabolite wogonoside in rat plasma, and to investigate the methodology. The method was applied to the pharmacokinetic study of wogonin-aloperine cocrystal (Wog-Alop) in rats. The results showed that wogonin and its metabolite wogonoside had a good linear relationship in the range of 1-800 ng·mL^-1, and the precision, accuracy, matrix effect and stability in this range met the requirements of biological analysis. Compared with direct administration of wogonin, the C_max of wogonin and its metabolite in rats increased to 7.44-fold and 9.15-fold, AUC_0-t increased to 1.67-fold and 3.72-fold, and oral bioavailability of wogonin increased to 187.66% after cocrystal administration. Wog-Alop cocrystal can significantly improve the C_max, AUC, and oral bioavailability of wogonin and its metabolite, which provides a new perspective for the clinical application of wogonin. This study was approved by the Experimental Animal Ethics Review Committee of Beijing University of Chinese Medicine (approval number: BUCM-2023032307-1148).

The incidence of intrahepatic cholangiocarcinoma (ICC) continues to rise, and there are no effective drugs to treat it. The immune microenvironment plays an important role in the development of ICC and is currently a research hotspot. Icaritin (ICA) is an innovative traditional Chinese medicine for the treatment of advanced hepatocellular carcinoma. It is considered to have potential immunoregulatory and anti-tumor effects, which is potentially consistent with the understanding of "Fuzheng" in the treatment of tumor in traditional Chinese medicine. However, whether ICA can be used to treat ICC has not been reported. Therefore, in this study, sgp19/kRas, an in situ ICC mouse model with intact immune system, was selected to evaluate the efficacy of ICA in the treatment of ICC in vivo for the first time, and the effects of ICA on the tumor immune microenvironment of ICC mice were analyzed by flow cytometry. This experiment was approved by the Experimental Animal Ethics Committee of Capital Medical University (approval number: AEEI-2023-138). In this study, sgp19/kRas ICC mouse model was treated with oral gavage of 100 mg·kg^-1 ICA. We found that ICA significantly inhibited tumor growth and tumor cell proliferation in the sgp19/kRas ICC mouse model after 3 weeks of treatment. Flow cytometry analysis indicated that ICA treatment markedly reduced the proportion of M2 macrophages and increased the number of CD3⁺CD4⁺ T cells. In vitro experiments demonstrated that ICA promoted macrophage polarization towards the M1 phenotype while inhibiting polarization towards the M2 phenotype. Furthermore, transcriptomic analysis suggested that ICA enhanced Toll-like receptor 9 (TLR9) expression, influencing macrophage nitric oxide metabolism synthesis pathways and receptor-related activities, thereby regulating macrophage polarization. In summary, this study demonstrates that ICA treatment significantly delays tumor progression in sgp19/kRas ICC mouse models. Mechanistically, ICA may achieve its anti-ICC effects by upregulating TLR9 receptor expression levels, promoting macrophage polarization towards the M1 phenotype, and altering the tumor immune microenvironment.

Objective To investigate the role of bufalin(BU)in inhibiting M2-type macrophage-mediated colorec-tal cancer metastasis.Methods Human acute leukemia mononuclear cells(THP-1)were differentiated into M0 macrophages using phorbol ester induction(PMA)for 48 hours.The M0 macrophages were then treated with IL-4 and IL-13 medium.Surface markers and morphological changes were observed through ELISA,morphology,and RT-qPCR experiments.RT-PCR and ELISA experiments were conducted to detect the surface markers TGF-β and IL-10 of M2 macrophages.The secretion level of IL-6 in the supernatant of M2 macrophages and colorectal cancer cells HCT116 was compared using ELISA.Additionally,the effect of conditioned medium on colorectal cancer cell HCT116 was assessed through Transwell,Wound healing,RT-qPCR,and Western blot experiments.Subsequent-ly,bufalin was added to the conditioned medium and the changes in AKT/PI3K protein,migration,and epithelial-mesenchymal transition ability in HCT116 were observed using Western blot,Transwell,Wound healing and RT-qPCR experiments.Results THP-1 were successfully differentiated into M2 macrophages.The activation of AKT/PI3K protein in HCT116 cells was induced by the secretion of IL-6 from M2 macrophages,which in turn promoted the migration and epithelial-mesenchymal transition ability of the HCT116 cells.The migration and epithelial-mes-enchymal transition mediated by M2 macrophages in HCT116 cells were effectively inhibited by Bufalin.Conclu-sion The release of IL-6 from M2 macrophages activates the AKT/PI3K signaling pathway in colorectal cancer cells,thereby promoting their migration and epithelial-mesenchymal transition capacity.Moreover,bufalin exhibits inhibitory effects on this effect.

Objective To investigate the implementation of surveillance,prevention and control measures for healthcare-associated infection(HAI)in maternal and child healthcare(MCH)institutions,and provide policy evi-dence for optimizing HAI prevention and control in MCH institutions.Methods Stratified sampling was conducted among the MCH institutions at provincial,municipal and county levels in 8 provinces/autonomous regions.A uni-fied questionnaire was designed and the online survey was conducted through"Questionnaire Star".Results The data from 123 MCH institutions were included in the analysis.90.24％of the MCH institutions carried out compre-hensive surveillance on HAI.The ratios of MCH institutions which implemented targeted surveillance on HAI in neonatal intensive care unit(NICU),surgical site infection,multidrug-resistant organisms(MDROs)and HAI in intensive care units(non-NICU excluded)were 89.66％,85.96％,80.77％,and 74.19％,respectively.51.22％MCH institutions adopted information surveillance system on HAI cases.94.31％MCH institutions carried out surveillance on hand hygiene compliance.Over 90％MCH institutions carried out surveillance on environment hy-giene in high-risk departments.71.54％MCH institutions conducted centralized cleaning,disinfection,sterilization and supply for reusable medical instruments in the central sterile supply department(CSSD).Over 90％MCH insti-tutions established three-level pre-examination triage systems.86.18％set up transitional wards.MCH institutions generally adopted a management model with established effective communication,full appointment visits,and sepa-rate visits for special medical groups,such as registered pregnant women,high-risk newborns,healthcare groups,and long-term rehabilitation patients.However,the ratio of institutions conducting on-line follow-up visits was less than 50％.Conclusion MCH institutions have generally carried out comprehensive and targeted surveillance on HAI.Information surveillance need to be facilitated.Hand hygiene and environmental hygiene surveillance has been popularized to a certain extent at all levels of MCH institutions.The cleaning,disinfection,sterilization,and supply processes of reusable medical devices in a few MCH institutions are not standardized.Special medical populations get effective management.On-line healthcare is to be further promoted.

To explore the mechanism of spleen- were obtained for the treatment of acute-on-chronic livstrengthening and moisture-nourishing liver prescription er failure, and 244 intersecting target genes and 7 core (JPLSYGF) in the treatment of acute-on-chronic liver target genes were screened. Molecular docking showed failure using network pharmacology and the molecular that the core target genes AKT1, SRC, VEGFA, docking. Methods Relying on TCMSP and Gene- STAT3 , EGFR, MAPK3 , HRAS had good affinity with Cards and other databases, the relevant targets of JPL- quercetin, the main active component in the JPLSYGF in the treatment of acute-on-chronic liver failure SYGF, and had strong binding activity. In addition, in were obtained. String and Cytoscape were used to con- vivo tests verified that the JPLSYGF could reduce the struct PPI networks of targets, core targets were expression of HRAS, EGFR, STAT3 , SRC, and VEGscreened out, and DAVID was used for GO function FA, to delay the progression of acute-on-chronic liver annotation and KEGG pathway enrichment analysis. failure. Conclusions JPLSYGF may act on core tar- The main active ingredients of the traditional Chinese gets such as HRAS, EGFR, STAT3, SRC, VEGFA medicine compound formula for JPLSYGF were select- and so on, to achieve the effect of treating acute-oned with a bioavailability OB value of =Э 30% and a chronic liver failure. drug-like DL^O. 18 as the screening conditions, and.

Objective This study was to develop a"Spleen Deficiency Certificate Scale for County Residents"and test its reliability.It was then developed as an objective tool for Chinese medicine evidence and symptoms for the prevention and control of chronic diseases among county residents.Methods The scale was compiled based on the team's previous foundation.The reliability of the scale was evaluated using internal consistency reliability and split-half reliability,while its validity was evaluated using structural validity,content validity,calibration validity,and discriminant validity.Results The study included 213 adults from Lanxi,of whom 155 were tested for intestinal flora.Seven scale entries were identified:Fatigue,fear of cold,bland mouth,loss of appetite,diarrhea,weak bowel movements,and tooth-marked tongue.In the reliability test,Cronbach's alpha coefficient was 0.828 and McDonald's ω coefficient was 0.825.The"stomach pain"and"bloating"entries did not meet the inclusion requirements and were recommended to be deleted.The Spearman-Brown coefficient was 0.839.The exploratory factor analysis of the two common factors explained 61.6%of the cumulative variance.The calibration validity indicated that the ratio of salivary amylase activity before and after acid stimulation was 0.826±0.253 in the group with spleen deficiency.Significant differences(P<0.05)in the genera Dialister,Shigella,Leuconostoc,Photobacterium,Trabulsiella,and Parvimonas between the spleen deficiency group and the non-spleen deficiency group.Conclusion The Spleen Deficiency Scale for County Residents demonstrates good reliability and validity.