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 map the genome-wide distribution profile of histone H3K27me3 modification in diffuse gastric cancer tissues,identify target genes regulated by H3K27me3,and primarily explore the potential mechanism of its modification reprogramming in the occurrence and development of the tumor.Methods Normal gastric mucosal tissues and diffuse gastric cancer tissues were harvested from the patients who underwent examinations or treatments in the departments of gastroenterology and gastrointestinal surgery of our medical center between 2021 and 2023.There were 14 patients in the normal group(6 males and 8 females,average age of 46 years)and 14 patients in the gastric cancer group(8 males and 6 females,average age of 63 years).Cleavage under target and tagmentation(CUT&Tag)technology was employed to capture genomic regions modified by H3K27me3,and analyze the reprogramming characteristics of these modifications.RNA sequencing data,data from high-throughput chromosome conformation capture(Hi-C)technology,and publicly available single-cell data were integrated to investigate the target genes regulated by the reprogramming of H3K27me3 modifications in diffuse gastric cancer cells.Results The quality of the CUT&Tag and RNA sequencing data met the standards required for subsequent analysis.Histone H3K27me3 modifications in normal gastric mucosa and diffuse gastric cancer tissues were primarily distributed in distal intergenic regions and intronic regions.In gastric cancer tissues,compared to normal tissues,there was significant reprogramming of H3K27me3 modifications,characterized by a marked reduction in overall H3K27me3 signal intensity.The loss of 2 912 H3K27me3 signal peaks might lead to the up-regulation of 822 tumor-associated genes.Among them,56 genes displayed the most significant up-regulation(fold change in signal intensity≥2,P<0.05),with notable enrichment in the mammalian target of rapamycin complex 1(mTORC1)signaling pathway.Specifically,the methionine transporter SLC7A5 and the cystine transporter SLC7A11 were found to have the highest expression levels in gastric cancer tissues.Single-cell data revealed that the abnormal overexpression of SLC7A11 in diffuse gastric cancer was primarily observed in tumor epithelial cells.Further validation using public data and immunohistochemical experiments confirmed the elevated expression of SLC7A11 in diffuse gastric cancer,which is associated with poor prognosis in gastric cancer patients.Conclusion The reprogramming of histone H3K27me3 modification is an important epigenetic characteristic in diffuse gastric cancer.Loss of H3K27me3 signal peaks may up-regulate the expression of SLC7A11 in diffuse gastric cancer cells,and thereby promote tumor progression.

Objective To analyze clinical characteristics of mesenchymal-subtype gastric cancer(Mes-GC)by integrating multi-omics data and explore the characteristics of tumor cells and microenvironment associated with the risk for recurrence.Methods Gastric tumor tissue samples were collected from the patients who visited Department of Gastroenterology of Army Medical Center of PLA from January 2022 to December 2023.Transcriptome and genome sequencing were applied for these tissue samples,including 19 cases of diffuse-type gastric cancer,22 cases of intestinal-type gastric cancer,and 23 cases of mixed-type gastric cancer patients.Bioinformatics analysis was employed to investigate the differences in clinical characteristics and tumor microenvironment between Mes-GC and non-mesenchymal-subtype gastric cancer(non-Mes-GC)by integrating data resources including The Cancer Genome Atlas(TCGA),Gene Expression Omnibus(GEO),and National Genomics Data Center(NGDC).Results Compared to non-Mes-GC patients,Mes-GC ones were characterized by later clinical stages,deeper tumor infiltration,and higher rates of lymph node metastasis.Kaplan-Meier survival analysis confirmed that Mes-GC patients were associated with shorter survival time,poor prognosis as well as increased risk of cancer recurrence(P<0.05).Single-cell RNA sequencing data revealed that tumor cells in Mes-GC showed higher expression levels of the genes related to stemness,metastasis(P<0.05),and epithelial-mesenchymal transition(EMT).And in the tumor microenvironment,there were significant more myeloid cells,smooth muscle cells,endothelial cells and fibroblasts,with the most pronounced elevation in the proportion of fibroblasts(P<0.05).Moreover,the patients with larger proportion of fibroblasts were associated with poorer prognosis.Conclusion Mes-GC tumor cells exhibit higher stemness and EMT characteristics,and stromal cells such as myeloid cells,endothelial cells,and fibroblasts are enriched in the tumor microenvironment.These features may be key factors contributing to poor prognosis and high recurrence rate of Mes-GC.

ObjectiveTo systematically evaluate the safety of Tianzhi granules used in the treatment of mild-to-moderate vascular dementia. MethodA randomized， double-blind， double-simulated， positive drug/placebo parallel controlled multi-center phase Ⅳ clinical trial and an open multi-center phase Ⅳ clinical trial of Tianzhi granules in the treatment of mild-to-moderate vascular dementia were conducted. Safety data of 1 492 patients were included and analyzed according to inclusion and exclusion criteria. The main evaluation measures were the incidence rate of adverse events/adverse reactions， laboratory indicators， vital signs， and electrocardiogram （ECG） results. ResultA total of six adverse events possibly related to the test drug occurred in 520 patients of the double-blind trial， and the symptoms were all mild and recovered. The incidence of adverse events was not statistically different among Tianzhi granules， donepezil， and placebo groups. Nine adverse events possibly related to the test drug were observed in 972 patients of the open trial， and the symptoms were mild and recovered. Laboratory tests （blood routine， urine routine， liver function， kidney function， and coagulation） and vital signs were compared before treatment （baseline） and after treatment of 12 and 24 weeks， respectively. There was no statistical significance in the main indicators before and after treatment. In the double-blinded trial， there was no significant difference in safety indicators between different groups before and after treatment. The most frequent adverse reaction was gastrointestinal discomfort， with an incidence rate of 6.64‰. ConclusionAdverse reactions occasionally occur in patients using Tianzhi granules， and it is safe to use Tianzhi granules to treat mild-to-moderate vascular dementia clinically.

Objective:To explore the effect of early eschar dermabrasion combined with antimicrobial soft silicone foam dressing (hereinafter referred to as foam dressing) in treating the deep partial-thickness burn wounds in children.Methods:This study was a randomized controlled trial. From June 2021 to December 2022, 78 pediatric patients with deep partial-thickness burns who met the inclusion criteria were admitted to the Department of Burns in Guiyang Steel Plant Employees Hospital. According to the random number table, the pediatric patients were divided into two groups, with 38 cases left in combined treatment group (with 20 males and 18 females, aged 26.00 (16.75, 39.75) months) and 39 cases in foam dressing group (with 21 males and 18 females, aged 19.00 (14.00, 31.00) months) after the exclusion of one dropped-out child in follow-up. The pediatric patients in combined treatment group underwent eschar dermabrasion of the wound within 48 hours after injury, the wound was covered with foam dressing after operation, and the dressing was replaced once every 7 days; for the pediatric patients in foam dressing group, the wound was sterilized within 48 hours after injury and covered with foam dressing, and the dressing was replaced once every 2 to 3 days. After the wound healing, the children in both groups were routinely applied with silicone gel twice a day for 3 weeks before started wearing elastic sleeves for more than 18 hours a day, and continuously for over than 6 months. The degree of pain during dressing change was evaluated using the children's pain behavior inventory FLACC. The adverse reactions during the treatment period, number of dressing changes, and wound healing time were observed and recorded. Six months after wound healing, the Vancouver scar scale (VSS) was used to evaluate the condition of the wound scar.Results:When changing dressing, the FLACC score for pain of pediatric patients in combined treatment group was 3.5 (2.0, 5.0), which was significantly lower than 6.0 (5.0, 8.0) in foam dressing group ( Z=-5.40, P<0.05). During the treatment period, no adverse reactions such as wound edema, fluid accumulation, or peripheral skin rash allergies occurred in any pediatric patient in both groups. The number of dressing changes of pediatric patients in combined treatment group was 3 (3, 4) times, which was significantly less than 8 (7, 10) times in foam dressing group ( Z=-7.58, P<0.05). The wound healing time of pediatric patients in combined treatment group was (19±5) days, which was significantly shorter than (25±6) days in foam dressing group ( t=-4.48, P<0.05). Six months after wound healing, the VSS score for scar of pediatric patients in combined treatment group was 5 (2, 8), which was significantly lower than 7 (5, 10) in foam dressing group ( Z=-3.05, P<0.05). Conclusions:Compared with using foam dressings alone, early eschar dermabrasion combined with foam dressings can reduce the number of dressing changes, alleviate the pain during dressing changes, and shorten the wound healing time in treating children with deep partial-thickness burns, and effectively alleviate scar hyperplasia by combining with anti-scar treatment post burns.

Objective:To explore the value of diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) of MRI in evaluating the response of osteosarcoma to neoadjuvant chemotherapy (NAC) in different cycles, and to analyze the diagnostic efficacy of each ADC and its difference.Methods:A total of 31 patients with pathologically confirmed osteosarcoma in the Nanjing Drum Tower Hospital, Nanjing University Medical School from January 2019 to December 2022 were retrospectively analyzed. All patients received NAC before surgery, and routine MRI and DWI were performed before and during chemotherapy. The ADC values were measured before, during and after chemotherapy (ADCpre, ADCmid, ADCpost), and the difference were calculated. According to whether the tumor necrosis rate was more than 90%, the patients were divided into good response group and poor response group. The differences of ADC values in each stage within the two groups were compared, and the differences of related parameters between the two groups were compared, and the diagnostic efficacy of each parameter in predicting tumor necrosis rate was analyzed by receiver operating characteristic(ROC) curve.Results:The ADC values of the two groups at different stages of NAC were compared. Except for the intermediate ADCmid and ADCpost in the poor response group ( P = 0.226), all the ADC values were statistical differences ( P<0.05). There were significant differences in ADCmid and ADCpost between the good response group and the poor response group (1.52 ± 0.39 vs. 1.39 ± 0.25, 1.65 ± 0.16 vs. 1.46 ± 0.44, P<0.05), but there was no significant difference in ADCpre between the two groups ( P>0.05). ROC curve showed that the area under the curve of ADCmid, ADCpost and △ADC3 (ADCpost -ADCpre) were 0.897, 0.810 and 0.714, respectively, and ADCmid had the best diagnostic efficiency. Conclusions:ADCmid, ADCpost and △ADC3 can be used to evaluate the efficacy of NAC in osteosarcoma. The ADCmid can provide some reference for the adjustment and improvement of clinical treatment.

Objective To explore the feasibility and diagnostic value of ultra-fast scanning scheme based on deep learning-based reconstruction(DLR)for cervical MR examination.Methods Thirty-six subjects were prospectively enrolled and underwent both conventional scheme(scan time:6 min 14 s)and ultra-fast scheme(2 min)cervical spine MR scanning to acquire encompassing sagittal T1WI,sagittal adipose suppression T2WI and axial T2WI.The ultra-fast MRI were reconstructed using DLR method.The subjective and objective evaluations on imaging qualities of different MRIs were compared,along with the inter-observer agreement for diagnosing intervertebral disc degeneration and herniation.Results Compared with conventional MRI,artifacts in ultra-fast DLR images significantly reduced(P＜0.05).The subjective evaluation results of MRI had good agreement(all Kappa≥0.60).Compared with conventional MRI,the sagittal T1WI,T2WI and axial T2WI obtained with ultra-fast DLR showed significantly improved signal-to-noise ratio(SNR)of the spinal cord,cerebrospinal fluid(CSF)and vertebral body,as well as the spinal cord/CSF contrast(all P＜0.001).The Kappa value of 2 physicians for diagnosing intervertebral disc degeneration based on ultra-fast DLR and conventional scheme images was 0.94 and 1.00,respectively,of intervertebral disc herniation was 0.96 and 0.98,respectively.Conclusion Compared with conventional scanning scheme,using ultra-fast DLR scheme in cervical MR examination could shorten scanning time while achieve similar image quality and diagnostic accuracy.

A virus was successfully isolated from a sick cat exhibiting clinical signs such as oral mu-cosal ulceration,nasal mucosal redness,and increased nasal secretions utilizing F81 cells.Through a comprehensive analysis as such PCR amplication,sequencing,morphology,serology,and animal re-gression tests,the virus was identified as a feline calicivirus and named FCV-BJ,an inactivated vac-cine was developed from this isolated strain its safety and efficacy were assessed.The results re-vealed that the isolated FCV-BJ strain exhibited characteristic serological and morphological fea-tures consistent with caliciviruses.Furthermore,inoculation of cats with the FCV-BJ demonstrated the strain is highly virulent and the cats manifested the clinical signs of feline calicivirus infection.For the vaccination trial,domestic cats were immunized with inactivated fifth-generation virus cell culture at varying dilutions,followed by a booster immunization after 21 days.Fourteen days after the challenge with the virus,cats immunized with 107.0 TCID50/mL or higher remained largely healthy,while all cats in the control group developed clinical signs of FCV.These findings suggest that the inactivated vaccine derived from the FCV-BJ isolate exhibits strong immunogenicity and protective efficacy at a minimum immunization dose of 107.0 TCID50/mL.This strain holds promise as a candidate for vaccine production,providing a valuable reference and foundation for future re-search and development of feline calicivirus vaccines.

Objective:To analyze and summarize the imaging characteristics and clinical follow-up results of Ewing sarcoma of bone.Methods:The imaging data of 23 patients with Ewing sarcoma confirmed by pathology who treatment in Drum Tower Hospital Affiliated to Nanjing University School of Medicine from May 2010 to October 2021 were retrospectively analyzed, and clinical follow-up was performed.Results:Of the 23 patients with Ewing sarcoma of the bone in this group, a total of 18 patients had follow-up results and 5 cases were lost to follow-up. Of the 18 cases, 6 cases died and 12 cases survived. The main cause of death was lung metastasis. There were 27 lesions in total, femoral diaphysis was the most common site of the disease; bone structure destruction and soft tissue mass shadows could be seen in the images of each lesion. Periosteal reaction could be seen in most of the lesions (92.59%, 25/27). There were certain differences in signs of bone destruction and periosteal reaction between different bone types.Conclusions:The imaging of Ewing sarcoma of bone mainly manifests various types of bone destruction, soft tissue masses and periosteal reactions. Ewing sarcoma of bone is mainly bone marrow metastasis and lung metastasis, and lung metastasis is the main cause of death.

Objective:To analyze the characteristics of aneurysmal bone cysts (ABC) and related factors of postoperative recurrence, so as to improve the clinical diagnosis and treatment level of ABC in children.Methods:The clinical data of children pathologically diagnosed as ABC after surgery in the Affiliated Hospital of Zunyi Medical University from January 2010 to December 2018 were retrospectively analyzed.Clinical characteristics of the patients, including age, gender, lesion sites, and main clinical manifestations (pain, swelling, local tenderness, joint dysfunction and pathological fracture) were analyzed and summarized.Before operation, imaging Enneking staging was carried out, cyst volume was estimated, and the distance from cysts to the epiphyseal plate was measured.During surgery, patients received lesion curettage, local cautery and bone grafting, and the pathological fractures were treated with auxiliary internal fixation.Results were determined by Neer imaging grading after surgery, and grades Ⅰ and Ⅱ were postoperative recurrence.Possible recurrence factors were analyzed statistically by Fisher′ s exact test. Results:A total of 29 cases meeting the criteria were included, including 19 males and 10 females.The age ranged from 3.6 to 14.0 years old, averaging 9.2 years old; 12 patients were smaller than 10 years old and 17 patients were older than 10 years old.The cysts of 9 cases were located in proximal femur (31.0%), 5 cases in proximal humerus (17.2%), and 4 cases in proximal fibula (13.8%); The other 11 cases (37.9%) occurred in the middle and distal end; 26 cases (89.7%) had local tenderness, 25 cases (86.2%) showed varying degrees of pain, 18 cases (62.1%) presented local swelling, 15 cases (51.7%) were accompanied by joint dysfunction, and 12 cases (41.4%) were combined with pathological fractures.According to Enneking staging results, 18 cases (62.1%) were at rest stage, 7 cases (24.1%) at active stage, and 4 cases (13.8%) at invasive stage.Cyst volume was estimated to be 3.3-172.0 cm 3, with a median of about 50.8 cm 3.The distance from cysts to the epiphyseal plate was 0-85.0 mm, with a median of 20.8 mm.All children were followed up for 2.2-10.1 years (averaging 3.8 years). There were 6 cases (20.7%) of grades Ⅰ and Ⅱ according to Neer grading standard, and they suffered from recurrence about 2.5-20.3 months after surgery (averaging 12.5 months). The recurrence rate was higher in patients with cyst volume >50.8 cm 3 (42.9%, 6/14 cases) as well as in patients at active stage and invasive stage (45.5%, 5/11 cases) ( P<0.05). There was no statistical difference between the recurrence rate of ABC in different gender, age, the distance from cysts to the epiphyseal plate and pathological fractures. Conclusions:ABC is prone to occur in the proximal metaphysis of the long bones of children′s extremities.Main manifestations are pain, swelling, local tenderness and joint dysfunction, and ABC is frequently accompanied by pathological fractures.A higher postoperative recurrence rate is related to a larger cyst size and the active and invasion phases of the cyst, but gender, age, the distance from the cyst to the epiphyseal plate and pathological fractures are not significantly related to the postoperative recurrence rate.