OBJECTIVE: To observe the protective effect of Fisetin on sepsis-associated brain injury and explore its possible mechanism from the perspective of ferroptosis. METHODS: Sprague-Dawley (SD) rats (6-8-week-old male) were randomly divided into three groups: sham operation group (Sham group), colonic ligation and puncture (CLP) induced sepsis model group (CLP group) and Fisetin preprocessing group (CLP+Fisetin group), with 18 rats in each group (12 for observing survival rate and 6 for indicator testing). The CLP+Fisetin group was given Fisetin solution 50 mg×kg^-1×d^-1 by gavage continuously for 5 days before CLP, with dimethyl sulfoxide (DMSO) as the solute, while Sham group and CLP group were given the same dose of DMSO. The model was established at 2 hours after the last gavage. The general condition of each group of rats were observed, and the 10-day mortality were record. The behavioral testing (new object recognition experiment, elevated cross maze experiment) were performed after 7 days of modeling. After 24 hours of modeling, nerve reflex scoring was performed, and then the rats were euthanized and brain tissue was collected. The pathological changes of brain tissue were observed under a microscope by hematoxylin-eosin (HE) staining, the deposition of iron ion in brain tissue was observed by Prussian blue staining. The content of iron in brain tissue was determined by tissue iron kit, and the content of malondialdehyde (MDA) in brain tissue was determined by colorimetry. The expressions of tumor necrosis factor-α (TNF-α), neuron damage marker S100β, nuclear factor E2-related factor 2 (Nrf2), heme oxygenases-1 (HO-1) and glutathione peroxidase 4 (GPX4) were detected by Western blotting. RESULTS: On day 10 post-operation, 12, 3, and 7 animals survived in the Sham group, CLP group, and CLP+Fisetin group, respectively. Compared with the Sham group, rats in the CLP group showed significantly decreased nerve reflex score, new object discrimination index and open arm dwell time. HE staining showed arranged disorderly of neuronal cells, cytoplasm deep staining, nuclear condensation, unclear structures, neuron loss, and significant inflammation in the hippocampus in the hippocampus. Prussian blue staining showed iron ion deposition in the brain tissue. The contents of iron and MDA in brain tissue were elevated, and the expressions of TNF-α and S100β were up-regulated, while the expressions of Nrf2, HO-1, and GPX4 were down-regulated. Compared with the CLP group, the CLP+Fisetin group showed significantly increased neurological reflex score (7.33±1.15 vs. 4.67±1.53), improved new object discrimination index (0.44±0.02 vs. 0.32±0.04), and longer open arm dwell time (minutes: 78.33±9.29 vs. 41.15±9.64). Neuronal cells in the hippocampus were more organized, with less cytoplasmic staining, nuclear condensation, reduced neuronal loss, and fewer inflammatory cells. Iron ion deposition was reduced, and the contents of iron ions and MDA in brain tissue were decreased [iron ion (μg/g): 151.27±14.90 vs. 224.69±17.64, MDA (μmol/g): 470.0±44.3 vs. 709.3±65.4]. The expressions of TNF-α and S100β were significantly decreased (TNF-α/GAPDH: 0.651±0.060 vs. 0.896±0.022, S100β/GAPDH: 0.685±0.032 vs. 0.902±0.014), while the expressions of Nrf2, HO-1, and GPX4 were significantly increased (Nrf2/GAPDH: 0.708±0.108 vs. 0.316±0.112, HO-1/GAPDH: 0.694±0.022 vs. 0.538±0.024, GPX4/GAPDH: 0.620±0.170 vs. 0.317±0.039). All differences were statistically significant (all P < 0.05). CONCLUSION Fisetin pretreatment can inhibit ferroptosis and reduce sepsis-associated brain injury by Nrf2/HO-1/GPX4 pathway.
Animals ; Ferroptosis/drug effects* ; Rats, Sprague-Dawley ; NF-E2-Related Factor 2/metabolism* ; Sepsis/complications* ; Male ; Rats ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Neurons/drug effects* ; Signal Transduction ; Brain Injuries/metabolism* ; Flavonols ; Flavonoids/pharmacology* ; Heme Oxygenase-1/metabolism* ; Heme Oxygenase (Decyclizing)

Objective:To evaluate the performance of key performance indicator (KPI) lean teaching management system in clinical medical laboratory.Methods:Combining lean teaching management in universities with KPI system of enterprises, an innovative KPI lean teaching management system was developed and applied in Clinical Medical Laboratory of Guangdong Provincial People′s Hospital (GDPH). A total of 106 teachers, who had worked from January 2021 to December 2022 in GDPH, joined this study. Teachers were divided into 8 professional groups. Firstly, we quantified the teaching workload by class hours, evaluated the teaching outcomes base on national, provincial, school, and college levels to assign different teaching points, and linked the teaching KPI scores to the evaluation, salary, and professional title of teachers. Then, we analyzed the overall teaching points and teaching points for each professional group (2021-2022). Finally, we asked teaching managers, teachers, and colleagues to evaluate the KPI lean teaching management system and compared the effects before and after the implementation of this system.Results:Compared with 2021, the teaching scores of 106 teachers increased significantly from 1.0 (0.2, 2.7) to 3.8 (2.3, 6.0) in 2022 ( Z=8.1, P<0.01). The teaching scores of clinical molecules, clinical coagulation, clinical immunology, clinical microbiology, Huifu laboratory, and clinical biochemistry group were significantly higher in 2022 than the scores they got in 2021 (all P<0.05). Compared with 2021, there were 3 new set up of educational reform projects, 2 submitted teaching articles, 3 new competition awards, 7 outstanding teachers, and 5 outstanding students in 2022. After application of KPI lean teaching management, the evaluation scores of teaching work by teaching managers, teachers, and colleagues are all significantly improved ( P<0.05). Conclusion:KPI lean teaching management system could effectively enhance teachers′ work initiative, improve teaching efficiency and outcome, and promote the teaching quality. Therefore, based on the performance of KPI lean teaching management system in our study, it is possible to realize its potential in terms of lean management in clinical medical laboratory.

The effective implementation of curricular ideology should be vigorously promoted in the training process of postgraduate students in critical care medicine.The clinical practice of critical care medicine contains a large number of ideological elements.In the process of teaching,teachers need to explore the ideological and political elements closely related to critical care medicine,mainly including:correct value of life,self-supervision spirit,communication and collaboration ability,healer's benevolence,craftsmanship,honesty and integrity in medical practice,as well as the supremacy of the country and the people,and so on.In the process of implementing curriculum ideological and political teaching,teachers are required to continuously improve their professionalism and ethics,improve their teaching methods,and set a good example in their clinical work.In order to better implement the curriculum ideological and political education,it is necessary to establish a perfect teaching system and a unified curriculum ideological and political education material library.