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 discuss the education of exercise rehabilitation specialty in China using World Health Organization rehabil-itation competency framework(RCF). Methods With reference to World Health Organization Rehabilitation in Health Systems and RCF,this paper discussed the objectives,course contents and human resource management of exercise rehabilitation in China. Results Rehabilitation service was an important part of health service to achieve the goals of United Nations 2030 health coverage,well-being of all people and sustainable development.Sports rehabilitation would cultivate profession-als with knowledge of rehabilitation medicine and exercise rehabilitation.We should establish the concept of"people-oriented",improve the multi-disciplinary human resource management system,and improve the provi-sion of multi-dimensional rehabilitation services in communities and hospitals,to cultivate professionals with both theoretical and practical abilities.RCF played an important role in developing teaching objectives,which helped for competency oriented education,curriculum settings,and an education system centered on competency. Conclusion Under the context in Rehabilitation in Health Systems and RCF,we have clarified the competency character-istics required for the training of sports rehabilitation professionals,optimized the training mode of sports rehabil-itation professionals,and explored the path to achieve the goals of sports rehabilitation talent training.

Male ; Humans ; Liquid Chromatography-Mass Spectrometry ; Chromatography, Liquid ; Tandem Mass Spectrometry ; Varicocele/diagnosis* ; Biomarkers

Objective To explore the genome-wide distribution of histone H3K27ac in intestinal type gastric cancer,analyze remodeling features of enhancers and regulome and construct a prediction model for prognosis.Methods H3K27ac CUT&Tag sequencing and RNA sequencing were performed in intestinal type gastric cancer tissues from 15 patients and normal gastric mucosa tissues from 18 healthy volunteers.Bioinformatics analysis was performed to identify the differences in genome distribution of H3K27ac modifications.Based on the distribution characteristics of H3K27ac,the enhancer elements were identified and the remodeling characteristics of enhancer and related regulome were explored.The prediction model for prognosis based on enhancer related target genes was constructed by univariate Cox and multivariate Cox regression analyses.Results The histone H3K27ac modification was mainly distributed in the enhancer region and displayed no significant differences in the genomic distribution patterns between normal and cancer tissues.Compared with normal gastric mucosa,the level of enhancer H3K27ac modification was higher in intestinal type gastric cancer.A total of 8847 enhancers with increased activity in intestinal type gastric cancer were identified,accounting for 8.3%of all enhancers,which might promote malignant behaviors such as proliferation and adhesion of gastric cancer cells.A prognosis-predicting model established based on a panel of 6 genes that upregulated by the acquired enhancer in cancers,which was able to predict the overall survival of patients.Conclusion Enhancer remodeling is one of the significant epigenetic features of intestinal type gastric cancer.These enhancers may drive malignant growth and adhesion of cancer cells by upregulating the expression of MYC,E2F3 and other genes.A prognosis model based on enhancer target genes is constructed.

Objective:To investigate the evidence-based practice of prevention and care of nasal and facial pressure injuries in patients with non-invasive positive pressure ventilation (NPPV) using the knowledge to action framework (KTA), and to explore its effectiveness.Methods:Using an evidence-based nursing approach, an evidence-based practice group was established to formulate a clinical problem, the literature from domestic and international databases were researched for relevant evidence, the evidence was introduced into clinical scenarios, an evidence-based practice plan was developed, and a strategy for applying the best evidence was constructed by conducting a baseline review of healthcare professionals and patients with NPPV, analyzing barriers and promoting factors, and making changes in clinical practice at the organizational level, the practitioner level, and the patient level. Purposive sampling method was used to select the healthcare staff of the cardiac surgical intensive care unit (CSICU) of the Shandong Provincial Hospital Affiliated to Shandong First Medical University, as well as the patients with NPPV admitted from October 1 to November 15, 2023 (pre-evidence-based practice) and November 16 to December 31 (post-evidence-based practice), as the subjects of the study. Through questionnaire analysis, the incidence of nasal and facial pressure injury of NPPV patients, the implementation rate of review indicators of medical staff, the score of the knowledge, belief and conduct of medical staff, and the compliance and comfort of patients before and after evidence-based practice were compared.Results:A total of 52 medical staff were included, aged (28.54±6.50) years old, with 3.00 (1.00, 12.75) years of working experience; 2 doctoral degree holders (3.85%), 4 master degree holders (7.69%), 46 bachelor degree holders (88.46%); 2 with senior title (3.85%), 17 with intermediate title (32.69%), and 33 junior titles (63.46%). Fifty patient questionnaires were collected before and after evidence-based nursing practice; the differences between before and after evidence-based practice in terms of gender, age, body weight, duration of ventilator usage, 24-hour bleeding and total bleeding were not statistically significant and were comparable. Compared with the pre-evidence-based practice, after carrying out the corresponding evidence-based nursing practice, the incidence of nasal and facial pressure injuries of NPPV patients decreased from 16.00% (8/50) to 4.00% (2/50, P < 0.05), the total implementation rate of review indicators of medical staff increased from 79.73% to 94.08% ( P < 0.01), and the total scores of knowledge, belief and conduct were significantly improved (141.96±13.88 vs. 114.65±19.72, P < 0.05), and compliance and comfort of patients were significantly improved (compliance score: 4.60±0.99 vs. 5.82±1.42, comfort score: 4.10±1.63 vs. 6.92±2.33, both P < 0.05]. Conclusion:The application of an evidence-based nursing approach to obtain evidence related to the prevention of nasal and facial pressure injuries in patients with NPPV can be used to guide clinical practice, significantly reducing the incidence of nasal and facial pressure injuries in such patients, improving the implementation rate of review indicators and the knowledge, belief, and conduct scores of medical staff, and enhancing compliance and comfort of NPPV patients.

Objective To investigate the value of a nomogram model constructed from intratumoral and peritumoral magnetic resonance imaging radiomics combined with clinical characteristics in predicting the status of lymphovascular space invasion(LVSI)in cervical cancer.Methods A retrospective analysis was conducted on 178 cervical cancer patients confirmed by postoperative pathology,with 70 cases of LVSI(+)and 108 cases of LVSI(-).The patients were divided into a training set[142 cases,including 54 cases of LVSI(+)and 88 cases of LVSI(-)]and a test set[36 cases,including 16 cases of LVSI(+)and 20 cases of LVSI(-)]at a ratio of 8:2.All underwent magnetic resonance imaging before surgery,and regions of interest were manually delineated layer by layer on the T2WI sequence,with the peritumoral region being uniformly expanded outward.Univariate logistic analysis was performed on clinical factors to select independent factors for cervical cancer LVSI(+).Radiomic features were extracted separately from the intratumoral region,the peritumoral region,and the intratumoral-peritumoral region to construct radiomics models,and the differences between the peritumoral and the intratumoral-peritumoral models were compared.A combined model was established based on the radiomics scores of the optimal intratumoral-peritumoral model and clinical independent predictive factors,and a nomogram was plotted.Receiver operating characteristic curves were used to evaluate the diagnostic performance of each model,and decision curve analysis was used to assess the clinical value of the models.Results The combined model demonstrated the best performance among the various models,with AUC of 0.970 in the training set and 0.803 in the test set.Conclusion Intratumoral and peritumoral magnetic resonance imaging radiomics combined with clinical characteristics can effectively predict LVSI in cervical cancer.

Objective To investigate the role of theophylline drugs in acute exacerbation stage of chron-ic obstructive pulmonary disease (AECOPD).Methods The clinical data of 401 patients with AECOPD ad-mitted and treated in this hospital from January 2016 to September 2022 were retrospectively analyzed.The patients were divided into the drug group (n=308) and control group (n=93) according to whether or not u-sing theophylline drugs.The control group was given the conventional treatment,and the drug group was giv-en theophylline drugs on the basis of conventional treatment.The hospitalization duration,C-reactive protein (CRP),procalcitonin (PCT),blood routine[WBC,neutrophil,hemoglobin,hematocrit (HCT),platelet-lym-phocyte ratio (PLR),neutrophil to lymphocyte ratio (NLR),eosinophils,basophil]changes were compared between the two groups,and the parameters with differences conducted the subgroup analysis to observe the effect of different types of theophylline.Results Before treatment,there was no statistically significant differ-ence in the baseline data between the drug group and the control group,and the number of basophils between the aminophylline group and doxophylline group (P>0.05).After treatment,there was no statistically signif-icant difference in PCT,CRP,WBC,neutrophil,hemoglobin,HCT,PLR,NLR and eosinophil between the drug group and control group (P>0.05).The length of hospital stay in the drug group was shorter than that of the control group,and the basophils count was less than that of the control group,and the difference was statisti-cally significant (P<0.05).After treatment,there was no statistically significant difference in the hospitaliza-tion duration in the aminophylline group and doxophylline group in the drug group subgroups (P>0.05),but the basophils count was higher than that of the doxofylline group (P<0.05).Conclusion Theophylline drugs could significantly shorten the hospitalization duration and reduce the basophils in the patients with AECO-PD.There is no significant difference in shortening the hospitalization duration between aminophylline and doxophylline,but aminophylline's effect on basophils is significantly stronger than that of doxophylline.

Objective:To analyze the clinical and genetic characteristics of a family of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) caused by a new locus of HTRA1 mutation. Methods:The medical history and clinical data of a patient with CARASIL were collected, and genetic test was performed on some family members to observe the HTRA1 mutation. Results:The proband presented with cognitive impairment, suspicious lumbar lesions, and alopecia. Cranial imaging revealed extensive blank brain lesions and multiple microbleeding foci. The mother of the proband had psychiatric symptoms and stroke once, and the sixth younger sister had history of dementia and hypertension. Genetic test revealed that the proband and his two sons carried HTRA1 heterogenic mutation c.888C>G (p.I296M), and the two sons had alopecia. Conclusion:The c.888C>G(p.I296M) may be a new pathogenic mutation site of CARASIL.

Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) and adjuvant chemotherapy serves as a traditional standard treatment for locally advanced rectal cancer (LARC). However, such treatment suffers low pathological complete response (pCR) rates, which are merely less than 15%, and low anal-preservation rates, failing to meet the demand of patients for high quality of life. Recently, total neoadjuvant therapy (TNT) whereby postoperative adjuvant chemotherapy is performed preoperatively has further increased the pCR rate, gradually becoming a novel therapeutic approach. Nevertheless, the pCR rate of TNT remains below 30%. Presently, immune checkpoint inhibitors (ICIs) have been proved to be highly successful in treating various solid tumors, yet they are scarcely employed to treat LARC. In recent years, many clinical trials have been conducted to explore the application of nCRT combined with ICIs in the treatment of LARC. This paper reviews the advances in research on this therapy.