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

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

As the brain's resident immune cells, microglia perform crucial functions such as phagocytosis, neuronal network maintenance, and injury restoration by adopting various phenotypes. Dynamic imaging of these phenotypes is essential for accessing brain diseases and therapeutic responses. Although numerous probes are available for imaging pro-inflammatory microglia, no PET tracers have been developed specifically to visualize anti-inflammatory microglia. In this study, we present an ¹⁸F-labeled PET tracer (QTFT) that targets the P2Y₁₂, a receptor highly expressed on anti-inflammatory microglia. [¹⁸F]QTFT exhibited high binding affinity to the P2Y₁₂ (14.43 nmol/L) and superior blood-brain barrier permeability compared to other candidates. Micro-PET imaging in IL-4-induced neuroinflammation models showed higher [¹⁸F]QTFT uptake in lesions compared to the contralateral normal brain tissues. Importantly, this specific uptake could be blocked by QTFT or a P2Y₁₂ antagonist. Furthermore, [¹⁸F]QTFT visualized brain lesions in mouse models of epilepsy, glioma, and aging by targeting the aberrantly expressed P2Y₁₂ in anti-inflammatory microglia. In a pilot clinical study, [¹⁸F]QTFT successfully located epileptic foci, showing enhanced radioactive signals in a patient with epilepsy. Collectively, these studies suggest that [¹⁸F]QTFT could serve as a valuable diagnostic tool for imaging various brain disorders by targeting P2Y₁₂ overexpressed in anti-inflammatory microglia.

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 compare the therapeutic effects between the anesthetic and non-anesthetic closed reduction protocols for distal radius fractures based on the concept of Enhanced Recovery After Surgery (ERAS). Methods: A prospective study was conducted in a cohort of 186 patients with distal radius fracture who had been admitted to the Department of Orthopaedic Trauma, Beijing Jishuitan Hospital from September 2018 to January 2019. The patients were divided into 2 groups depending on the choice by themselves. Of them, 72 (intervention group) underwent the standardized closed reduction under brachial block anesthesia based on the concept of ERAS while the other 114 (control group) conventional closed reduction under no anesthesia. The 2 groups were compared in terms of emergency reduction times, swelling scores, reoperation rate, splint removal time, functional outcomes by the Patient-Rated Wrist Evaluation (PRWE) and radiographic outcomes by the Lidström criteria. Results: The patients in both groups were followed up for 6 months. The reduction times were fewer in the intervention group than in the control group (1.1±0.1 versus 1.6±0.1, P<0.05). The reoperation rate was significautly lower in the intervention group than in the control group [2.8%(2/72) versus 12.3%(14/114), P< 0.05]. Reduction deteriorated the swelling condition. Compared with the control group, the swelling was significantly less in the intervention group (2.0±0.1 versus 2.6±0.1, P<0.05). The splint removal time for the intervention group (5.3±0.2 weeks) was significantly shorter than that for the control group (6.9±0.2 weeks) (P<0.05). The intervention group had significantly better PWRE scores than the control group (23.4±1.0 versus 30.3±1.1, P<0.05), but there was no significant difference between groups in the Lidström evaluation (P>0.05). Conclusion Compared with conventional closed reduction, the closed reduction under anesthesia based on the ERAS concept is an effective method for the emergency treatment of distal radius fracture, because it may minimize the patients’ pain experience, increase the rate of successful reduction, decrease the rate of reoperation, shorten the splint fixation time and gain better functional outcomes.

To investigate the effects of adenosine triphosphate (ATP) on expression of inflammatory factors induced by lipopolysaccharide (LPS) in endothelial progenitor cells (EPCs), and to elucidate the possible mechanisms.
 Methods: Mononuclear cells were isolated from human umbilical cord blood by density gradient centrifugation, RT-PCR was performed to detect the expression of inflammatory factors induced by LPS (1 mg/mL) in EPCs, the effect of low concentration (5 μmol/L) of ATP on expression of IL-1β, MCP-1 and ICAM-1, and the effect of different concentrations (5, 50 μmol/L) of ATP on the expression of Toll-like receptor (TLR) 4, myeloid differentiation primary response protein 88 (MyD88) and CD14. Western blot was performed to detect expression of TLR4 regulated proteins MyD88 and CD14 or to detect the low concentration (1, 5 μmol/L) of ATP on the expression of TLR4, MyD88 and CD14 and the NF-κB signaling pathway.
 Results: EPCs highly expressed TLR4, and its ligand LPS (1 mg/mL) significantly upregulated mRNA expression of IL-1β, MCP-1 and ICAM-1 and protein expression of MyD88 and CD14 in a time-dependent manner (P<0.01), accompanied by activation of ERK and NF-κB signal pathway. ATP at low concentration (5 μmol/L) significantly inhibited LPS-induced mRNA expression of IL-1β, MCP-1 and ICAM-1(P<0.05), downregulated the LPS-induced protein expression of TLR4, MyD88 and CD14 in EPCs (P<0.05), and suppressed LPS-induced activation of NF-κB signaling pathway (P<0.05).
 Conclusion: ATP at low concentration may suppress LPS-induced expression of inflammatory factors in EPCs through negative regulation of the TLR4 signaling pathway.
Adenosine Triphosphate ; pharmacology ; Endothelial Progenitor Cells ; drug effects ; Gene Expression Regulation ; drug effects ; Humans ; Leukocytes, Mononuclear ; cytology ; Lipopolysaccharide Receptors ; genetics ; Lipopolysaccharides ; pharmacology ; Myeloid Differentiation Factor 88 ; genetics ; NF-kappa B ; metabolism ; Signal Transduction ; drug effects ; Toll-Like Receptor 4 ; genetics

Objective: To evaluate the safety and effectiveness of ultrasound-guided percutaneous nephrolithotomy (PCNL) accessed by SVOF-principle and two-step puncture techniques. Methods: A total of 838 cases with upper urinary stones underwent percutaneous nephrolithotomy successfully accessed by ultrasound-guided between June 2007 and December 2015 at Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. Of all cases were divided in two groups: hydronephrosis calyces puncture group include 425 cases and SVOF-principle puncture group include 413 cases. The access establishment time, operation time, stone free rate (SFR), postoperative complications, and postoperative hospitalization time between the two groups we compared by t test or χ² test. Results: Statistically significant differences were observed between hydronephrosis calyces puncture group and SVOF-principle puncturegroup in the first access establishment time ((16.5±8.4) minutes vs. (11.2±5.9) minutes, t=3.931, P=0.013), one-stage SFR (74.3% vs. 85.7%, χ²=16.868, P=0.000), postoperative hospitalization time ((6.4±2.1) days vs. (4.8±1.8)days, t=4.574, P=0.000), transfusion rate (7.1% vs. 2.9%, χ²=8.027, P=0.006), and embolization rate (3.3% vs. 1.0%, χ²=5.390, P=0.020). There were no statistically significant differences in operation time, total SFR, postoperative fever and sever infection between these two groups (all P>0.05). In both two groups, no serious complications such as peripheral organ injury and death occurred. Conclusions PCNL accessed guided by ultrasound with SVOF-principle and two-step puncture techniques has advantages of quick puncture location, high stone free rate, fewer complications and fast recovery. This technique is an effective and safe treatment option for upper urinary stones and deserved promotion and application in clinic.