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Objective:To investigate the effects of ginkgolide B on neurological function recovery and the Wnt/β-catenin pathway after ischemic stroke in mice.Methods:Fifty-five C57/BL6 mice were selected, of which 10 mice were kept as the sham group and the remaining 45 mice were constructed as the ischemic stroke model. There were 40 mice who finally completed the modeling, and then they were randomly divided into the blank control group (GB0w), short-course administration group (GB1w), long-term administration group (GB2w), and long-term administration+antagonist group (GB2w+PRI-724), with 10 mice in each group. There was no drug intervention after MCAO in GB0w. The mice in GB1w were given ginkgolide B (10 mg/kg) 0.1 ml within 1 week after MCAO; in GB2w were given ginkgolide B (10 mg/kg) 0.1 ml within 2 weeks after MCAO; and in GB2w+PRI-724 were nasally fed ginkgolide B (10 mg/kg) 0.1 ml within 2 weeks after MCAO; and selective antagonist PRI-724 was given 3 h before administration of ginkgolide B on days 8 to 14. Neurological function scores, walking on rotor bar test scores, expression of transforming growth factor-β1 (TGF-β1), fibroblast growth factor 4 (FGF4), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), Wnt, β-catenin, and glycogen synthase kinase-3β (GSK-3β) were compared among the groups.Results:Compared with the sham group, the expressions of MDA, TNF-α, IL-6, FGF4, and GSK-3β in GB0w, GB1w, GB2w, and GB2w+ PRI-724 were increased, and the expressions of GSH-Px, SOD, TGF-β1, β-catenin, and Wnt were decreased (all P < 0.001). Compared with GB0w, the expressions of SOD, GSH-Px, TGF-β1, Wnt, and β-catenin were increased in GB1w, GB2w, and GB2w+PRI-724, and the expressions of MDA, TNF-α, IL-6, FGF4, and GSK-3β were decreased (all P < 0.001). Compared with GB1w, the expressions of GSH-Px, SOD, TGF-β 1, Wnt, and β-catenin were increased in GB2w and GB2w+PRI-724, and the expressions of IL-6, TNF-α, MDA, FGF4, and GSK-3β were decreased (all P < 0.001). Compared with GB2w, the neural function score, walking on the stick test score, and expressions of IL-6, TNF-α, FGF4, MDA, and GSK-3β were increased in GB2w+PRI-724, while the expressions of GSH-Px, TGF-β1, SOD, Wnt, and β-catenin were decreased (all P < 0.001). Conclusions:Ginkgolide B can effectively improve the neurological function of ischemic stroke mice and may be related to the Wnt/β-catenin pathway.
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ObjectiveTo investigate the regulatory effects of Ginkgolide B on the biological characteristics of brain T cells and their interactions with glial cells during the recovery phase of ischemic stroke in mice. Methods36 adult C57BL/6 mice were randomly assigned to three groups: sham-operated group (Sham group), control group (PBS group), and Ginkgolide B treatment group (GB group). The Sham group underwent only sham surgeries, whereas the PBS and GB groups were subjected to a middle cerebral artery occlusion (MCAO) model using the filament method, followed by intranasal administration of an equivalent volume of either PBS or Ginkgolide B solution for 14 days post-injury. Neurological function changes were evaluated in all three groups using the rotarod test and a neurological scoring system. On day 15, single-cell sequencing was performed on fresh tissues from the brain injury areas, surrounding cortex, corpus callosum, and striatum of mice in the PBS and GB group to assess the biological characteristics of T cells and their subpopulations, and further explore the interactions and mechanisms among T cells, microglia, and oligodendrocytes. ResultsCompared with the Sham group, both PBS and GB group exhibited significant improvements in neurological scores and reduced pre-fall motor durations (P < 0.001). Compared with the PBS group, the GB group showed a downward trend in neurological scores and an upward trend in pre-fall motor durations on days 5, 10, and 15 post-ischemic brain injury, with a significant increase in pre-fall motor duration on day 15 (P < 0.05). Compared with the PBS group, the GB group exhibited a significant increase in T cell proliferative activity in the brain 15 days post brain injury (P < 0.05). The number of proliferative T cells and the levels of lipid metabolism were significantly elevated (P < 0.05), and there was a significant increase in extracellular matrix remodeling in all T cells (P < 0.05). Additionally, the interactions between T cells and both microglia and oligodendrocytes, as well as among the microglia themselves and between microglia and oligodendrocytes, were significantly enhanced in the GB group. This was primarily evident in the strengthened interactions between CD74 and macrophage migration inhibitory factor (MIF), as well as colony stimulating factor 1 receptor (CSF1R) and colony stimulating factor 1 (CSF1) (P < 0.05). However, the inflammatory levels of T cells showed no significant differences compared with the PBS group. ConclusionA mouse model of ischemic stroke can be successfully established by MCAO operation. Ginkgolide B may promote neurological recovery post-brain injury in mice by modulating the biological characteristics of T cells within the brain and their interactions with glial cells.
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Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.
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Objective To analyze the chemical components in the ethanol extract of Sanse tablets with anti-complement activity, and to provide scientific basis for its therapeutic effects. Methods The classical anti-complement pathway was used to compare the activity of different portions of Sanse tablet alcohol extract, and to identify the fraction with anti-complement activity. The chemical composition in active fraction was analyzed by UPLC-Q-TOF-MS/MS. The chemical components were identified by comparing the retention time, exact molecular weight and mass spectrum information with the standard chemicals. Results The ethyl acetate fraction of the Sanse tablet ethanol extract had the best anti-complement activity. 42 chemicals were identified, including 16 alkaloids, 15 terpenoids, 6 flavonoids and 5 phenolic acids. Conclusion The characterization of the chemical components in the anti-complement active fraction of Sanse tablets provides a scientific basis for the therapeutic effects of Sanse tablets, which will help the future development of the compound preparations of Chinese medicine in our hospital.
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OBJECTIVE:To upgrade the management of the out-patient pharmacy and provide all the patients, doctors and nurses with good service. METHODS: HIS was applied to the real stock management of the out-patient pharmacy in our hospital. RESULTS: Due to the HIS, the amount of drugs was identical with the account; the overstock and stocktaking error rate were greatly decreased, and the account was clear & the supervision was easy. CONCLUSION: The work efficiency and quality of the out-patient pharmacy was greatly improved by the scientific normalized management.