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Post-cardiac arrest brain injury (PCABI) is the leading cause of death and disability in survivors of cardiac arrest (CA), where autophagy and ferroptosis are believed to play a pivotal role. Liraglutide, a synthetic, long-acting glucagon-like peptide-1 (GLP-1) analog, can exert organ-protective effects through regulating autophagy and ferroptosis. This study aimed to investigate whether liraglutide had a neuroprotective after cardiac arrest and cardiopulmonary resuscitation and explore its potential mechanisms. We used the 8-min asphyxial cardiac arrest and cardiopulmonary resuscitation model in Sprague–Dawley rats to determine the possible mechanism. The histological changes, proinflammatory factors, apoptosis, autophagy and ferroptosis in hippocampal tissues were detected. Furthermore, the neurologic deficits scores (NDS) and 7-day survival rate was observed respectively. Our results showed that autophagyand apoptosis were activated and the expressions of proteins reached significance at 24h after CA/ROSC. Moreover, rapamycin enhanced apoptosis, ferroptosis and aggravated neuro-pathological damage while 3-methyladenine reduced that. Furthermore, liraglutide treatment improved the 7-day survival rate and NDS, reduced histology injury and inhibited apoptosis, ferroptosisand inflammatory cytokines released after cardiac arrest, and these effects were offset by autophagy agonist. These results suggested that liraglutide could exert a protective role against post-cardiac arrest brain injury, which could be partially mediated by partially inhibiting autophagy and ferroptosis.

Sepsis refers to host response disorders caused by infection, which can lead to life-threatening organ dysfunction. And the lungs bear the brunt of the disease. RNA-binding motif protein 3 (RBM3) is an important cold-shock protein that is upregulated in response to mild hypothermia or hypoxia. In this study, we aimed to investigate whether RBM3 is involved in sepsis-associated acute lung injury (ALI). Intraperitoneal injection of LPS (10 mg/kg) was performed in wild-type (WT) and RBM3 knockout (KO, RBM3-/-) mice to establish an in vivo sepsis model. An NLRP3 inflammasome inhibitor, MCC950 (50 mg/kg), was injected intraperitoneally 30 min before LPS treatment, and serum, lung tissues, and BALF were collected 24 h later for further analysis. In addition, we also collected serum from sepsis patients and healthy volunteers to detect RBM3 expression. The results showed that the expression of RBM3 in the lung tissues of LPS-induced sepsis mice and the serum of patients with sepsis was significantly increased and positively correlated with disease severity. In addition, RBM3 knockout (KO) mice had a low survival rate, and RBM3 KO mice had more severe lung damage, inflammation, lung cell apoptosis, and oxidative stress than WT mice. After the LPS treatment, the levels of nucleotide binding and oligomerization domain-like receptor family 3 (NLRP3) inflammasomes and mononuclear cell nuclear factor-κB (NF-κB) in the lung tissues of RBM3 KO mice were significantly higher. However, they were only slightly elevated in WT mice. Interestingly, MCC950 improved LPS-induced acute lung injury in WT mice and RBM3 KO mice, and inhibited the expression of NLRP3, caspase-1, and IL-1β. In conclusion, RBM3 was overexpressed in sepsis patients and LPS-induced mice. The RBM3 gene deficiency aggravated sepsis-associated ALI through the NF-κB/NLRP3 pathway.

Purpose In the flipped classroom teaching of the key and difficult chapters, the purpose of this study is investigate whether the use of rain classroom software can achieve the maximum teaching benefits for more students. Methods A total of one hundred and twenty-two third-year anesthesiology students from clinical medical college of Southwest Medical University were randomly divided into two groups, with 61 students in each group. One group was taught with flipped classroom teaching mode as the control group (FC group: flipped classroom group) and the other group was taught with flipped classroom software as the experimental group (FR group: flipped classroom + rain). The teaching content is the chapter of "acid base electrolyte balance and blood gas analysis". The teaching effect was evaluated by relevant theoretical tests, and the subjective feelings of students on the improvement of learning ability were evaluated by questionnaire survey. Results Compared with FC group, the theoretical test scores of FR group were higher, and the subjective evaluation of multiple learning ability improvement in FR group was also higher. (P < 0.05). Conclusions In the flipped classroom teaching of key and difficult sections, using rain classroom software can make more students obtain greater teaching income than using flipped classroom teaching only.

Background: The effect of breast cancer heterogeneity on prognosis of patients is still unclear, especially the role of immune cells in prognosis of breast cancer. Therefore, the discovery of new markers to assess the effect of breast cancer heterogeneity on patient prognosis is crucial to improve prognosis and survival of patients.Methods: Single cell transcriptome sequencing data of breast cancer were downloaded from GEO database. PCA and UMAP were used for dimensionality reduction analysis and cell clustering. Find All Markers function was used to calculate differential genes in each cluster, and Do Heatmap function was used to plot the distribution of differential genes in each clusters. CellPhoneDB was used to analyze ligand-receptor interactions. TRRUST database combined with Cytoscape were used to construct a receptor-ligand-transcription factor interaction network. WGCNA is used to analyze pivotal modules associated with breast cancer prognosis. Univariate regression analysis and KM survival analysis were used to identify prognostic genes in prognostic modules. Multivariate regression analysis combined with risk scoring were used to construct a breast prognosis model, which was verified by TCGA and ICGC sample data.Result: In this study, 14 cell clusters were identified in two single-cell datasets (GSE75688 and G118389). The results of ligand receptor interaction network revealed that macrophages and DC cells were the most frequently interacting cells with other cells in breast cancer. The results of WGCNA analysis suggested that the MEblue module is most relevant to the overall survival time of triple-negative breast cancer. Twenty-four prognostic genes in the blue module were identified by univariate Cox regression analysis and KM survival analysis. Multivariate regression analysis combined with risk analysis was used to analyze 24 prognostic genes to construct a prognostic model. The verification result of our prognostic model showed that there were significant differences in the expression of PCDH12, SLIT3, ACVRL1, and DLL4 genes between the high-risk group and the low-risk group.Conclusion: PCDH12, SLIT3, ACVRL1 and DLL4 are prognostic biomarkers and relate to the type and proportion of immune cells in breast cancer.

Background: RNA m6A methylation regulator has been shown to play an important regulatory role in tumorigenesis and progression. However, the role and characteristics of RNA m6A methylation in breast cancer are not yet clear. Objective: To analyze the effect of the expression pattern of M6A methylation factor on the progression of breast cancer by bioinformatics.Results: This study uses bioinformatics to analyze three data sets of TCGA-BRCA, GSE96058 and GSE25066. According to the expression level of m6A-related genes, breast cancer samples are divided into 4 subtypes: quiescent, m6A-methylation, protein-binding, and mixed. The results of R-survival analysis showed that the survival of breast cancer samples of the four subtypes was significantly different. The analysis of breast cancer gene expression features showed that there are significant differences in the number of exon skip among the four subtypes. For tumor driver genes, the degree of TP53 mutation and copy number loss are the most in the protein-binding subtype. Among DNA damage repair genes, the copy number of RAD54B in the protein binding subtype is significantly increased, while other DNA damage repair-related genes have fewer mutations and copy number deletions are common. The effect of m6A methylation on the proportion of infiltrated immune cells indicates that Macrophages M0 and Mast cells resting are significantly different in the four m6A subgroups, and are related to patient prognosis. The number of sensitive samples of chemotherapeutics (taxane anthracyclines) is the lowest in the quiescent subtype. In addition, the highest tumor stemness index in breast cancer samples is the protein-bound type, and the lowest is the m6A methylated type. Conclusion: The results of our analysis suggest that the reduced expression level of m6A methylation writer gene and the high expression of m6A reader protein in the four methylation subtypes of breast cancer are key to the progression of breast cancer.

Background To retrospectively evaluate Doppler ultrasound findings for patients with popliteal vascular entrapment syndrome (PVES). Methods Twenty-four patients (30 legs) who underwent surgical intervention for PVES were included in this study. The popliteal artery, popliteal vein, and surrounding musculotendinous structures were explored in all symptomatic lower extremities using ultrasound. Intraoperative findings served as the gold standard. In the absence of popliteal artery occlusion, popliteal arteries were examined using Doppler ultrasound at rest and during a provocative maneuver. Results Ultrasonography in 25 cases (25/30, 83%) showed that gastrocnemius medial head or popliteal vascular anomalies were consistent with surgical photography results. According to Whelan and Rich classification, the classic type I was found in five limbs, type II in twelve limbs, type III in seven limbs, and type V in one limb. In the remaining five cases (5/30, 17%), no anatomical abnormalities of the popliteal fossa were discovered by the ultrasound examination. Among these, two cases (2/30, 7%) were misdiagnosed as lower extremity atherosclerosis and popliteal vascular depression was not found. In addition, increasing blood flow velocity was found in three cases (3/30, 10%) of compressed popliteal arteries using Duplex scanning during active plantar flexion, with decreasing flow at the distal end. Color Doppler ultrasound of the affected popliteal vessels showed varied degrees of vascular structure pathology, including arterial stenosis in ten limbs, occlusion in fifteen limbs, and aneurysm in two limbs. Conclusion Doppler ultrasound may have a high diagnostic rate in PVES. Due to its simplicity, repeatability, functional evaluation of blood flow, and non-invasiveness, it can be used as a primary screening examination modality in PVES. Provocative maneuvers could help clinicians diagnose PVES.