In hypoxic-ischemic brain damage (HIBD), the programmed cell death known as ferroptosis is significantly activated. Microglial cells demonstrate a high level of sensitivity to iron accumulation. Understanding how to regulate the dual role of microglia and transforming the microglial ferroptosis to a moderate and controllable process has considerable implications for the targeted treatment in HIBD. This paper serves as an overview of microglia-mediated ferroptosis in HIBD as a disease model. We discuss various aspects centered around microglia, including pathophysiological mechanisms, polarization and functions of microglia, molecular mechanisms of ferroptosis, signaling pathways, and therapeutic strategies. The review aims to provide a reference for studies of ferroptosis in microglia.
Microglia/physiology* ; Ferroptosis/physiology* ; Humans ; Animals ; Hypoxia-Ischemia, Brain/pathology* ; Signal Transduction

OBJECTIVES: To evaluate the therapeutic effect of gastrodin against hypoxic-ischemic brain damage (HIBD) in neonatal mice and explore the role of GPX4/SLC7A11/FTH1 signaling in mediating its effect. METHODS: Twenty-four 9- to 11-day-old C57BL/6J mice were randomized equally into 4 groups for sham operation, HIBD modeling by right common carotid artery ligation and subsequent exposure to hypoxia for 1 h, or gastrodin treatment at 100 or 200 mg/kg before and at 1 and 2 days after modeling. The mice then underwent neurological assessment (Zea-Longa scores), and the cerebral cortical penumbra tissue were collected for HE and Nissl staining, detection of ferroptosis biomarkers and protein expressions of GPX4, SLC7A11, and FTH1 with Western blotting and immunofluorescence co-localization, and observation of mitochondrial ultrastructure with electron microscopy. In cultured HT22 neuronal cells with oxygen-glucose deprivation (OGD) for 2 h, the effects of pretreatments with 0.5 mmol/L gastrodin, 10 μmol/L RSL3 (a GPX4 inhibitor), alone or in combination, were analyzed on expressions of ferroptosis-related proteins, cellular Fe²⁺, ROS, lipid peroxidation, MDA, and GSH levels, mitochondrial membrane potential (JC-1), and cell viability. RESULTS: Gastrodin treatment at the two doses both significantly ameliorated HIBD and neurological deficits of the mice, reduced mitochondrial damage and Fe²⁺, MDA and ROS levels, increased GSH level, and upregulated GPX4, SLC7A11, and FTH1 protein expressions. In HT22 cells, gastrodin pretreatment obviously attenuated OGD-induced ferroptosis and improved cell viability and mitochondrial function. Co-treatment with RSL3 potently abrogated the inhibitory effects of gastrodin on Fe²⁺, ROS, BODIPY-C11, and MDA levels and attenuated its protective effects on GSH level, cell viability, and mitochondrial membrane potential. CONCLUSIONS Gastrodin provides neuroprotective effects in neonatal mice with HIBD by suppressing neuronal ferroptosis via upregulating the GPX4/SLC7A11/FTH1 signaling pathway.
Animals ; Ferroptosis/drug effects* ; Hypoxia-Ischemia, Brain/drug therapy* ; Mice ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Glucosides/pharmacology* ; Animals, Newborn ; Benzyl Alcohols/pharmacology* ; Amino Acid Transport System y+/metabolism*

Objective:To explore the value of clinical and biparametric magnetic resonance imaging(bpMRI)in diagnosing extraprostatic ex-tension(EPE)of prostate cancer(PCa).Methods:This retrospective study assigned 107 patients into EPE(n=42)and organ-limited(n=65)groups based on their postoperative pathology after radical prostatectomy from August 2018 to May 2024 at Wuhu Second People's Hospit-al.The differences in the following clinical risk indicators were compared between the groups:age,total prostate specific antigen(tPSA),pro-state volume,prostate specific antigen density(PSAD)and International Society of Urological Pathology(ISUP)score for prostate puncture.The differences in MRI indicators,prostate imaging reporting and data system(PI-RADS)score and bpMRI were also identified.Binary Logist-ic regression analysis was used to construct clinical and joint models for diagnosing EPE,and screening independent influencing factors.The ROC curve analyze the independent influencing factors and diagnostic performance of the models.The DeLong test was used to compare the differences between the AUC models.A nomogram was draw,and performance evaluated.Results:The differences in tPSA,PSAD,ISUP score for prostate puncture,PI-RADS score,and bpMRI were statistically significant between the two groups(P<0.05).The clinical model AUC was 0.821;while the AUCs of the combined model and independent influencing factors PSAD(OR=25.992),ISUP score for prostate puncture(OR=1.676),and bpMRI(OR=10.729)were 0.899,0.813,0.770,and 0.793 respectively(P<0.001).The combined model was superior to the clinical model(Z=2.502 and P=0.012).The average AUC for 5-fold cross-validation was 0.887,with high model calibration and a threshold range of 5%-85%,indicating clinical benefits.Conclusions:The combined model nomogram derived from clinical and bpMRI indicators is highiy valuable for diagnosing PCa EPE.

Objective To construct clinical imaging model,radiomics model,and a combined model based on the above two for predicting lymph node metastasis(LNM)of colon cancer(CC),and to compare the diagnostic performance of each model.Methods The data from 328 CC patients confirmed by surgical pathology were analyzed retrospectively,including 156 with LNM.All patients were randomly divided into training group(229 cases)and validation group(99 cases)at a ratio of 7∶3.The difference of clinical imaging indicators were compared between groups and a clinical imaging model for diagnosing LNM was constructed.The tumor three-dimensional volume of interest(VOI)was used for radiomics feature extraction,and after dimensionality reduction and selection,8 features were obtained to construct the Radiomics score(Radscore).A combined model of clinical imaging indicators and Radscore was built.The diagnostic performance of each model for LNM was compared,and the calibration and clinical benefit of the optimal model were evaluated.Results There were statistical differences in clinical imaging indicators between the two groups:carcinoembryonic antigen(CEA),CA199,tumor long diameter,and lymph node short diameter(P＜0.05).The area under the curve(AUC)of the clinical imaging model,radiomics model,and combined model were 0.721,0.814,0.854(training group),and 0.744,0.732,0.808(validation group),respectively.The AUC of the combined model was the highest,and both the training and validation groups were higher than that of the clinical imaging model(P＜0.05).The combined model demonstrated higher calibration,with a clinical benefit from decision curve analysis(DCA)threshold range of 0.09 to 0.91.Conclusion The nomogram constructed based on clinical imaging indicators and CT radiomics holds high value in diagnosing LNM of CC.

Heart failure(HF)is a highly morbid syndrome that seriously affects the physical and mental health of patients and generates an enormous socio-economic burden.In addition to cardiac myocyte oxidative stress and apoptosis,which are considered mechanisms for the development of HF,alterations in cardiac energy metabolism and pathological autophagy also contribute to cardiac abnormalities and ultimately HF.Silent information regulator 1(Sirt1)and adenosine monophosphate-activated protein kinase(AMPK)are nicotinamide adenine dinucleotide(NAD+)-dependent deacetylases and phosphorylated kinases,respectively.They play similar roles in regulating some pathological processes of the heart through regulating targets such as peroxisome proliferator-activated receptor γ coactivator 1α(PGC-1α),protein 38 mitogen-activated protein kinase(p38 MAPK),peroxisome proliferator-activated receptors(PPARs),and mammalian target of rapamycin(mTOR).We summarized the synergistic effects of Sirt1 and AMPK in the heart,and listed the traditional Chinese medicine(TCM)that exhibit cardioprotective properties by modulating the Sirt1/AMPK pathway,to provide a basis for the development of Sirt1/AMPK activators or inhibitors for the treatment of HF and other cardiovascular diseases(CVDs).

Objective:To construct a physical restraint reduction scheme based on eCASH concept (that is early Comfort using Analgesia, minimal Sedatives and maximal Human care for adult patients after cardiac surgery, and intervene, and to evaluate its effectiveness.Methods:A non-synchronous case-control study was conducted. A total of 486 patients after cardiac surgery admitted to the cardiac surgery intensive care Unit (ICU) of Shandong Provincial Hospital Affiliated to Shandong First Medical University from July to October 2022 were enrolled as subjects. According to the implementation time node of the physical restraint reduction scheme, 250 patients admitted from July to August were served as the control group, and 236 patients admitted from September to October were served as the observation group. The control group adopted the routine physical restraint nursing process, including selecting the appropriate restraint device according to the patient's condition and consciousness and following the doctor's advice, and checking on time to prevent adverse reactions. The observation group implemented the physical restraint reduction scheme based on eCASH concept, including preoperative visit, postoperative assessment of whether patients needed physical restraint according to the restraint decision wheel and the physical restraint flow, and adopted personalized nursing programs. The restraint rate, restraint duration, incidence of restraint-related complication (edema of the limbs, redness and swelling of the skin in the restricted area, skin rupture, etc.), restraint device application standard rate, delirium rate and incidence of unplanned extubation event were compared between the two groups.Results:There was no significant difference in age, gender, cardiopulmonary bypass, endotracheal catheter retention duration and operation type between the two groups with comparability. The restraint rate in the observation group was significantly lower than that in the control group [16.95% (40/236) vs. 84.40% (211/250), P < 0.01], and the restraint duration was significantly shorter than that in the control group [hours: 0 (0, 1.0) vs. 7.0 (5.5, 10.0), P < 0.01], the incidence of restraint-related complication and delirium were significantly lower than those in the control group [restraint-related complication: 0.85% (2/236) vs. 1.60% (4/250), delirium: 0% (0/236) vs. 2.80% (7/250), both P < 0.05], and the restraint device application standard rate was significantly higher than that in the control group [100.00% (40/40) vs. 90.52% (191/211), P < 0.05]. No unplanned extubation event occurred in both groups. Conclusion:The physical restraint reduction scheme based on eCASH concept in adult patients after cardiac surgery can effectively reduce the restraint rate and the incidence of restraint-related complication, shorten the restraint duration, reduce the incidence of delirium, improve the standardization of restraint device application, without increasing the incidence of unplanned extubation events.

Objective:To analyze the application effect of health failure mode and effect analysis (HFMEA) model in patients with artificial airways in the cardiovascular surgery intensive care unit (CSICU) by establishing a HFMEA project team, and to develop targeted improvement measures and processes.Methods:The patients undergoing cardiovascular surgeries and with established artificial airways in the Shandong Provincial Hospital Affiliated to Shandong First Medical University were recruited from October 2021 to March 2022. The enrolled patients were divided into the conventional management group and the HFMEA model management group according to random number table method. The conventional management group applied the conventional procedures for monitoring the air bag pressure. The HFMEA model management group used the HFMEA model to implement and improve the airbag pressure monitoring process. The efficacy of HFMEA was assessed by comparing the incidence of ventilator-associated pneumonia (VAP), the pass rate of airbag pressure monitoring, the duration of endotracheal intubation and the length of CSICU stay between two groups. The practicability of HFMEA model was evaluated by analyzing the theoretical assessment scores and practical skill scores of nurses and their satisfaction scores with HFMEA.Results:Compared with the conventional management group, the patients in the HFMEA mode management group had a significantly higher rate of passing airbag pressure monitoring [94.99% (2 994/3 152) vs. 69.97% (1 626/2 324), P < 0.01], shorter duration of endotracheal intubation and length of CSICU stay [duration of endotracheal intubation (hours): 6 (7, 12) vs. 6 (8, 13), length of CSICU stay (hours): 40 (45, 65) vs. 41 (46, 85), both P < 0.05], but the incidences of VAP between the two groups were similar. The theoretical assessment scores and practical skill scores of nurses were significantly higher (theoretical assessment score: 44.47±2.72 vs. 37.59±6.56, practical skill score: 44.56±2.66 vs. 40.03±4.32, total score: 89.03±3.07 vs. 77.63±9.56, all P < 0.05) in the HFMEA mode management group. And the satisfaction scores with airbag pressure management were also significantly higher in the HFMEA mode management group (7.72±1.11 vs. 6.44±1.32, P < 0.05). Conclusions:The application of the HFMEA can improve the airbag pressure measures and standardize the monitoring procedures in patients with artificial airways, and reduce the risk of clinical nursing. It is safe and effective for patients with invasive mechanical ventilation in the CSICU.

ObjectiveTo evaluate the efficacy and safety of a perioperative rehabilitation clinical pathway of acetabular fracture in light of orthopedics rehabilitation team approach. MethodsA prospective randomized control trial was conducted in 82 patients with acetabular fractures who had been admitted from the Emergency Department of Orthopaedic Trauma, Beijing Jishuitan Hospital from June, 2019 to January, 2021. The patients were randomly divided into control group (n = 41) and intervention group (n = 41). The control group was managed routinely, while the intervention group received the rehabilitation clinical pathway, for 24 weeks. The Visual Analogue Score (VAS) of pain, the Barthel Index (BI) and Majeed Pelvic Score were compared. ResultsFinally, 76 patients completed the trial. There was no statistical difference in VAS score between two groups in all periods (|Z| < 1.926, P > 0.05). The BI score was higher in the intervention group than in the control group at discharge, two weeks, six weeks and twelve weeks after operation (|Z| > 2.121, P < 0.05); and no significant difference was found before operation and 24 weeks after operation (|Z| < 1.862, P > 0.05). Majeed Pelvic Score was higher in the intervention group than in the control group two weeks, six weeks, twelve weeks and 24 weeks after operation (|Z| > 2.428, P < 0.05). Six, twelve and 24 weeks after operation, the excellent rate of Majeed Pelvic Score was higher in the intervention group than in the control group (χ² > 6.136, P < 0.05). ConclusionIn comparison with traditional protocol in acetabular fracture, the perioperative rehabilitation clinical pathway was proved effective and of great safety in the light of the integration of orthopedics and rehabilitation mode for improving the function and activities of daily living of patients.

Objective:To quantitatively analyze the protein expression changes of the optic nerve in an SD rat model of non-arteritic anterior ischemic optic neuropathy (NAION), and to make bioinformatics analysis of the differential proteins.Methods:Ten 8-week-old SPF male SD rats with a body mass of 200-250 g were selected.The NAION model was established using the method of rose bengal and laser photodynamics.Four from the 8 rats with successful model were selected as the NAION model group.Another 4 body weight- and age-matched healthy SD rats without eye diseases were taken as the normal control group.The optic nerve was dissected on the 7th day after modeling.The samples were prepared by the enzyme digestion method, and the proteins were identified and quantitatively detected by isobaric tag for relative and absolute quantification labeling combined with liquid chromatography-tandem mass spectrometry.The proteins with expression fold greater than 1.5 times and significant differences between the two groups ( P<0.05) were defined as differentially expressed proteins and analyzed by bioinformatics.The use and care of animals complied with Regulations for the Administration of Affair Concerning Experimental Animals by the State Science and Technology Commission of China.The study protocol was approved by an Animal Ethical and Welfare Committee of Tianjin Medical University Eye Hospital (No.TJYY2021041029). Results:Three days after modeling, the optic disc of rats was swollen and fluorescein leakage in the optic disc was detected in fluorescein fundus angiography images in the NAION model group, which indicated the model was established successfully.A total of 1 291 quantifiable proteins including 80 differentially expressed proteins were identified.Compared with the normal control group, there were 5 up-regulated proteins and 75 down-regulated proteins.The expression levels of collagen alpha-1(V) chain (Col5A1), cAMP-dependent protein kinase catalytic subunit beta (Prkacb) and disks large homolog 1(Dlg1) were increased, and the expression levels of neurofilament medium polypeptide (Nefm), microtubule-associated protein 1B (Map1b), Ras-related protein Ral-A (Rala), serine/threonine-protein kinase N2 (Pkn2) and platelet-activating factor acetylhydrolase IB subunit beta (Pafah1b1) were decreased.Differentially expressed proteins were mainly involved in the biological processes, including regulation of the cytoskeleton, cellular response to hypoxia, axon production and extension, regulation of synapse, regulation of neuron apoptosis and axo-dendritic transport, etc.KEGG pathway enrichment analysis showed that differentially expressed proteins were mainly involved in metabolic pathways, synaptic vesicle circulation and platelet activation.Conclusions:The expression of proteins related to signal pathways such as nerve growth, energy metabolism, axo-dendritic transport and apoptosis is involved in the apoptosis of neurons in NAION.

Objective:To analyze the protein expression changes in the retina of non-arteritic anterior ischemic optic neuropathy (NAION) in rats.Methods:The rat NAION (rNAION) model was established by Rose Bengal and laser. Twenty Sprague-Dawley rats were randomly divided into 4 groups, the normal control group, the laser control group, the RB injection control group, and the rNAION model group, with 5 rats in each group. The right eye was used as the experimental eye. The retina was dissected at the third day after modeling. Enzyme digestion method was used for sample preparation and data collection was performed in a non-dependent collection mode. The data were quantitatively analyzed by SWATH quantitative mass spectrometry, searching for differential proteins and performing function and pathway analysis.Results:Compared with the other three control groups, a total of 184 differential proteins were detected in the rNAION group (expression fold greater than 1.5 times and P<0.05), including 99 up-regulated proteins and 85 down-regulated proteins. The expressions of glial fibrillary acidic protein, guanine nucleotide binding protein 4, laminin 1, 14-3-3γ protein YWHAG were increased. Whereas the expressions of Leucine-rich glioma-inactivated protein 1, secretory carrier-associated membrane protein 5, and Clathrin coat assembly protein AP180 were decreased. The differential proteins are mainly involved in biological processes such as nerve growth, energy metabolism, vesicle-mediated transport, the regulation of synaptic plasticity, apoptosis and inflammation. Pathway enrichment analysis showed that PI3K-Akt signaling pathway and complement and thrombin reaction pathway was related to the disease. Conclusion:The protein expressions of energy metabolism, nerve growth, synaptic vesicle transport and PI3K-Akt signaling pathway can regulate the neuronal regeneration and apoptosis in NAION.