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

Objective To investigate the mechanism of gastrodin for inhibiting microglia-mediated inflammation after hypoxic-ischemic brain damage(HIBD)in neonatal rats.Methods Thirty-nine 3-day-old SD rats were randomly divided into sham group,HIBD group and gastrodin treatment group.Western blotting was used to detect the expressions of TNF-α,IL-1β,IL-10 and TGF-β1 in the corpus callosum of the rats.The potential targets of gastrodin for treatment of HIBD were screened by network pharmacology analysis.The expressions of PI3K/AKT signaling pathway proteins following HIBD-induced microglial activation in the rats and in cultured microglial BV-2 cells with oxygen-glucose deprivation(OGD)were detected with Western blotting.The effects of LY294002(a specific inhibitor of the PI3K/AKT pathway)and gastrodin on TNF-α and TGF-β1 mRNA levels in BV-2 cells with OGD was detected with RT-qPCR.Results In the neonatal rats with HIBD,gastrodin treatment significantly decreased TNF-α and IL-1β expressions and enhanced IL-10 and TGF-β1 expressions in the ischemic corpus callosum.Network pharmacology analysis showed significant enrichment of the PI3K/AKT signaling pathway and a strong binding between gastrodin and PI3K.Gastrodin significantly promoted PI3K and AKT phosphorylation in neonatal rats with HIBD and in BV-2 cells exposed to OGD.In BV-2 cells with OGD,gastrodin obviously suppressed OGD-induced increase of TNF-α and reduction of TGF-β1 mRNA expressions,and this effect was strongly attenuated by LY294002 treatment.Conclusion Gastrodin can inhibit microglia-mediated inflammation in neonatal rats with HIBD by regulating the PI3K/AKT signaling pathway.

Objective To investigate the mechanism behind the protective effects of gastrodin against microglia-mediated inflammatory responses following hypoxic-ischemic brain damage(HIBD)in neonatal mice.Methods Thirty-six 10-day-old C57BL/6J mice were randomized into sham-operated group,HIBD(induced by ligation of the left common carotid artery followed by hypoxia for 40 min)group,and HIBD with gastrodin treatment groups(n=12).In gastrodin treatment group,100 mg/kg gastrodin was injected intraperitoneally 1 h before and at 2 and 12 h after hypoxia.After the treatments,the expressions of CCR5,AKT,p-AKT,and TNF-α and the co-expression of IBA1 and CCR5 in the corpus callosum of the mice were detected with Western blotting and immunofluorescence double staining.In a BV2 microglial cell model of oxygen-glucose deprivation(OGD),the effects of pretreatment with gastrodin and Maraviroc(an CCR5 antagonist)on protein expressions of CCR5,AKT,p-AKT,TNF-α and IL-1β were evaluated using Western blotting and immunofluorescence double staining.Results The neonatal mice with HIBD showed significantly increased expressions of CCR5 and TNF-α with lowered p-AKT expression in the brain tissues,and GAS treatment obviously reversed these changes.HIBD also significantly increased the co-expression of IBA1 and CCR5 in the corpus callosum of the mice,which was obviously lowered by gastrodin treatment.In BV2 cells,OGD significantly increased the expressions of CCR5,TNF-α,and IL-1β and decreased the expression of p-AKT,and these changes were inhibited by treatment with gastrodin,Maraviroc or their combination;the inhibitory effect of the combined treatment did not differ significantly from that of gastrodin or Maraviroc alone.Conclusion Gastrodin can produce neuroprotective effects in neonatal mice with HIBD by inhibiting inflammatory cytokine production and activate AKT phosphorylation via inhibiting CCR5.

Objective To investigate the mechanism of gastrodin for inhibiting microglia-mediated inflammation after hypoxic-ischemic brain damage(HIBD)in neonatal rats.Methods Thirty-nine 3-day-old SD rats were randomly divided into sham group,HIBD group and gastrodin treatment group.Western blotting was used to detect the expressions of TNF-α,IL-1β,IL-10 and TGF-β1 in the corpus callosum of the rats.The potential targets of gastrodin for treatment of HIBD were screened by network pharmacology analysis.The expressions of PI3K/AKT signaling pathway proteins following HIBD-induced microglial activation in the rats and in cultured microglial BV-2 cells with oxygen-glucose deprivation(OGD)were detected with Western blotting.The effects of LY294002(a specific inhibitor of the PI3K/AKT pathway)and gastrodin on TNF-α and TGF-β1 mRNA levels in BV-2 cells with OGD was detected with RT-qPCR.Results In the neonatal rats with HIBD,gastrodin treatment significantly decreased TNF-α and IL-1β expressions and enhanced IL-10 and TGF-β1 expressions in the ischemic corpus callosum.Network pharmacology analysis showed significant enrichment of the PI3K/AKT signaling pathway and a strong binding between gastrodin and PI3K.Gastrodin significantly promoted PI3K and AKT phosphorylation in neonatal rats with HIBD and in BV-2 cells exposed to OGD.In BV-2 cells with OGD,gastrodin obviously suppressed OGD-induced increase of TNF-α and reduction of TGF-β1 mRNA expressions,and this effect was strongly attenuated by LY294002 treatment.Conclusion Gastrodin can inhibit microglia-mediated inflammation in neonatal rats with HIBD by regulating the PI3K/AKT signaling pathway.

Objective To investigate the mechanism behind the protective effects of gastrodin against microglia-mediated inflammatory responses following hypoxic-ischemic brain damage(HIBD)in neonatal mice.Methods Thirty-six 10-day-old C57BL/6J mice were randomized into sham-operated group,HIBD(induced by ligation of the left common carotid artery followed by hypoxia for 40 min)group,and HIBD with gastrodin treatment groups(n=12).In gastrodin treatment group,100 mg/kg gastrodin was injected intraperitoneally 1 h before and at 2 and 12 h after hypoxia.After the treatments,the expressions of CCR5,AKT,p-AKT,and TNF-α and the co-expression of IBA1 and CCR5 in the corpus callosum of the mice were detected with Western blotting and immunofluorescence double staining.In a BV2 microglial cell model of oxygen-glucose deprivation(OGD),the effects of pretreatment with gastrodin and Maraviroc(an CCR5 antagonist)on protein expressions of CCR5,AKT,p-AKT,TNF-α and IL-1β were evaluated using Western blotting and immunofluorescence double staining.Results The neonatal mice with HIBD showed significantly increased expressions of CCR5 and TNF-α with lowered p-AKT expression in the brain tissues,and GAS treatment obviously reversed these changes.HIBD also significantly increased the co-expression of IBA1 and CCR5 in the corpus callosum of the mice,which was obviously lowered by gastrodin treatment.In BV2 cells,OGD significantly increased the expressions of CCR5,TNF-α,and IL-1β and decreased the expression of p-AKT,and these changes were inhibited by treatment with gastrodin,Maraviroc or their combination;the inhibitory effect of the combined treatment did not differ significantly from that of gastrodin or Maraviroc alone.Conclusion Gastrodin can produce neuroprotective effects in neonatal mice with HIBD by inhibiting inflammatory cytokine production and activate AKT phosphorylation via inhibiting CCR5.

Objective:To investigate the relationship between systemic immune-inflammation index (SII) and the prognosis of esophageal cancer patients treated with radical radiotherapy and to predict the prognosis of the patients using the SII combined with clinical staging.Methods:A retrospective analysis was conducted for 248 patients with esophageal cancer who were admitted to the Department of Radiotherapy in the Fourth Hospital of Hebei Medical University between 2014 and 2016. These patients included 146 males and 102 females, with a median age of 67 years. Among them, 134 patients received concurrent chemotherapy and 114 patients received radiotherapy alone. The SII before radiotherapy was defined as platelet count × neutrophil count/lymphocyte count. The patients were divided into a low-SII group and a high-SII group according to the optimal cutoff value of pretreatment SII determined by the receiver operating characteristics (ROC) curve. Survival analysis was calculated using the Kaplan-Meier method, and the Cox proportional hazards model was used for multivariate analysis. For these patients, the prognosis effects and the predictive value for survival of different SII levels combined with TNM staging were compared.Results:According to the ROC curves, the optimal cutoff value of SII before radiotherapy was 740.80. Based on this number, the patients were divided into a low-SII group (< 740.80, 150 cases) and a high-SII group (≥ 740.80, 98 cases). The objective response rate of the low-SII group was significantly higher than that of the high-SII group (86.0% vs 75.5%, χ2=4.39, P=0.036). The 1-, 3-, and 5-year overall survival (OS) rates of the low-SII group were 78.6%, 45.6%, and 32.3%, respectively. These rates were significantly higher than the corresponding rates of the high-SII group, which were 71.0%, 28.3%, and 16.4% ( χ2=11.22, P=0.001), respectively. Moreover, the 1-, 3- and 5-year progression-free survival (PFS) rates of the low-SII group were 67.0%, 36.9%, and 32.0%, respectively. Again, these rates were significantly higher than those of the high-SII group, which were 45.5%, 17.5%, and 12.5% ( χ2=15.38, P < 0.001), respectively. Multivariate analysis showed that TNM staging, treatment method, and SII were independent prognostic factors for OS and PFS ( HR=1.39-1.60, P<0.05). Patients with low SII and early clinical staging had a better prognosis than other subgroups ( χ2=13.68, 13.43, P=0.001). The area under curve (AUC) of SII combined with TNM staging (0.70) was higher than that of SII (0.63) and TNM staging (0.62) ( Z=2.48, 2.57, P < 0.05). Conclusions:Pretreatment SII has a high predictive value for the prognosis of esophageal cancer after radiotherapy, and higher SII indicates a worse prognosis. Thus, combining SII with TNM staging can improve the prediction accuracy of the prognosis of esophageal cancer patients.

Objective:To investigate the relationship of delayed cardiac tamponade (CT) after left atrial appendage closure (LAAC) in atrial fibrillation (AF) patients and implanted occluders and adjacent anatomical structures.Methods:This study was a retrospective study. Thirteen AF patients with LAAC complicated with delayed CT and with concurrent emergency pericardiocentesis drainage in Zhoupu Hospital, Shanghai University of Medicine & Health Sciences from August 2016 to June 2021 were selected. The follow-up time was (16±12) months. The clinical data of these patients were retrospectively analyzed, including the relationship between the left atrial appendage and pulmonary artery, vein anatomy by left atrium computed tomography angiography (CTA) before and after LAAC.Results:Thirteen patients with delayed CT were treated by pericardiocentesis and drainage after LAAC and aged (72.1±8.3) years, and 7 patients were male, Six patients received cryoablation simultaneously. The classification types of left atrial appendage included cauliflower and chicken wing types were 8 and 5 respectively. The seal plate diameter of the lobe-and-disc devices was (29.5±2.8)mm; 10 patients had cardiac CTA reviewed. The occluder was attached to pulmonary artery in 8 patients, attached to left superior pulmonary vein only in one patient, and attached to pulmonary artery and left superior pulmonary vein in one patient. The prognosis was good except one patient who died 2 days after LAAC.Conclusions:Delayed CT after LACC is closely related to the location of left atrial appendage adjacent to pulmonary artery and left superior pulmonary vein, and is related to larger occluder and anchor hook.

Objective:To investigate the relationship between Onodera′s prognostic nutritional index (PNI) and prognosis of patients with esophageal squamous cell carcinoma (ESCC) after definitive chemoradiotherapy or radiotherapy, aiming to provide a convenient, effective and accurate predictive indicator for evaluating the long-term survival of patients after treatment.Methods:Clinical data of 231 ESCC patients treated with definitive chemoradiotherapy or radiotherapy at the Fourth Hospital of Hebei Medical University from 2013 to 2015 were retrospectively analyzed. The PNI values of each patient at different radiotherapy periods were calculated and the ROC curve was used to determine the optimal cutoff value of PNI before radiotherapy, 231 patients were divided into the better-nourishment group ( n=86) and worse-nourishment group ( n=145). Kaplan- Meier method was used for survival analysis. Cox proportional hazards model was utilized to analyze the relationship between different nutritional status and prognosis. The short-term clinical efficacy and incidence of acute toxicities were statistically compared between two groups. Results:The mean values of PNI before, at week 3, week 6 and 1 month after radiotherapy were48.68±5.08, 39.68±4.87, 43.74±4.89 and48.31±4.92, respectively. The optimal cutoff value of pretreatment PNI was 49.25, the area under the curve (AUC) was 0.655, the sensitivity and specificity were 68.6% and 60.9%, respectively. The 5-year overall survival (OS) and progression-free survival (PFS) rates in the better-nourishment group (PNI≥49.25) were 36.0% and 31.3%, significantly better than 19.3% and 18.6% in the worse-nourishment group (PNI<49.25)( P=0.001, P=0.039). Multivariate analysis showed PNI before the therapy was an independent prognostic factor for OS ( P=0.021). Stratified analysis demonstrated that Stage Ⅰ/Ⅱ and concurrent chemotherapy patients in the better-nourishment group all obtained significantly better OS than their counterparts in the worse-nourishment group ( P=0.007, P=0.004). In addition, the objective response rate in the better-nourishment group was significantly higher than that in the worse-nourishment group ( P=0.047), whereas the incidence of ≥3 grade radiation esophagitis was lower than that in the worse-nourishment group ( P=0.060). Conclusions:Pretreatment PNI is a convenient and reliable indicator for predicting the long-term survival of ESCC patients after definitive chemoradiotherapy or radiotherapy. Patients with higher PNI have relatively better prognosis and radiotherapy tolerance, especially in those with early stage or concurrent chemotherapy.

Objective: To compare the long-term outcomes in ST-elevation myocardial infarction (STEMI) patients who underwent early or late delayed percutaneous coronary intervention (PCI) using drug-eluting stents (DES). Methods: This study was a retrospective, observational and single-center study. Consecutive STEMI patients (n=977), who admitted to Fuwai Hospital in 2013 and underwent successful selective PCI using drug-eluting stents (DES) within 3 to 35 days after symptom onset were enrolled and divided into the early delayed PCI (3-14 d) group (n=495) and the late delayed PCI (15-35 d) group (n=482). General clinical data of the patients and related data of coronary angiography and interventional therapy were collected, and the endpoint events were followed up. The primary endpoint was 2-year major adverse cardiac and cerebrovascular events (MACCE) including cardiac death, recurrent myocardial infarction, definite or probable stent thrombosis and ischemic stroke. The secondary endpoint was 2-year ischemia-driven target vessel revascularization. The incidence of endpoint events of the two groups was compared, and it was compared again after the primary baseline characteristics such as age and gender were matched by the propensity scoring method at a 1∶1 ratio. Results: A total of 910 (93.1%) patients who underwent delayed PCI were transferred from other hospitals, and 292 (29.9%) patients received thrombolysis before PCI. The time interval before PCI was 14 (10, 20) days. The incidence of 2-year MACCE (3.0%(15/495) vs. 2.3%(11/482), P=0.468) and ischemia-driven target vessel revascularization (3.8%(19/495) vs. 5.0%(24/482), P=0.385) were similar between the two groups. The incidence of 2-year MACCE (3.3%(15/453 vs. 2.4%(11/453), P=0.426) and ischemia-driven target vessel revascularization (4.2% (19/453) vs. 4.9%(22/453), P=0.632) were also similar between the two groups after matching propensity score. Conclusion The long-term clinical outcomes after early delayed PCI using DES is statistically equivalent to those of late delayed PCI using DES for STEMI patients who missed the time window for emergency PCI.

Objective:To characterize limb traumatic osteomyelitis in a regional trauma center in South China.Methods:The case system at Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital was searched for the data of confirmed limb traumatic osteomyelitis from January 1, 2010 through September 1, 2019. The clinical items collected were gender, age of onset, cause of injury, injury nature (open or closed), infected site (single site or multiple sites), intraoperative culture of pathogenic microorganisms, number and type of pathogenic microorganisms, and amputation. The above data were sorted out and analyzed statistically.Results:A total of 674 patients suffered limb traumatic osteomyelitis in South China with a male to female ratio of 4.81∶ 1. The limb traumatic osteomyelitis resulted mainly from open injury (64.09%, 432/674). It was mainly caused by a traffic accident (39.51%, 211/534). It was featured by single-site infection (83.68%, 564/674). It affected mainly the lower limbs: the tibia (53.19%, 300/564), the femur (18.97%, 107/564), the calcaneus (11.70%, 66/564) and other foot bones (4.61%, 26/564). The positive rate of intraoperative microorganisms culture was 65.26% (355/544). In the majority of patients (74.65%, 265/355), the traumatic osteomyelitis was caused by infection of a single pathogenic microorganism. The most common single pathogenic microorganism was Staphylococcus aureus (38.11%, 101/265), followed by Pseudomonas aeruginosa (20.00%, 53/265). The rate of amputation related to traumatic osteomyelitis was 3.71% (25/674), and the overall disability rate was 4.45% (30/674).Conclusions:In South China, more males were prone to limb traumatic osteomyelitis. Most cases were secondary to an open fracture and caused by a traffic accident. Traumatic osteomyelitis usually occurred at a lower limb. The most common pathogenic microorganism was Staphylococcus aureus.