Non-canonical STING-PERK pathway dependent epigenetic regulation of vascular endothelial dysfunction via integrating IRF3 and NF-κB in inflammatory response

Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis, while the underlying mechanism remains elusive. Here, we report that the non-canonical stimulator of interferon genes (STING)-PKR-like ER kinase (PERK) pathway was significantly activated in both human and mice atherosclerotic arteries. Typically, STING activation leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor-kappa B (NF-κB)/p65, thereby facilitating IFN signals and inflammation. In contrast, our study reveals the activated non-canonical STING-PERK pathway increases scaffold protein bromodomain protein 4 (BRD4) expression, which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines, thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation process. Endothelium-specific STING and BRD4 deficiency significantly decreased the plaque area and inflammation. Mechanistically, this pathway is triggered by leaked mitochondrial DNA (mtDNA) via mitochondrial permeability transition pore (mPTP), formed by voltage-dependent anion channel 1 (VDAC1) oligomer interaction with oxidized mtDNA upon cholesterol oxidation stimulation. Especially, compared to macrophages, endothelial STING activation plays a more pronounced role in atherosclerosis. We propose a non-canonical STING-PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3, NF-κB and BRD4 in inflammatory responses, which provides emerging therapeutic modalities for vascular endothelial dysfunction.

Gene co-expression network analysis reveals a novel lncRNA-associated competing endogenous RNA network for ruptured intracranial aneurysms / 中华老年医学杂志

Objective:To provide clues for exploring the molecule mechanisms underlying ruptured intracranial aneurysms(IAs)by constructing a competitive endogenous RNA(ceRNA)network.Methods:Gene expression data sets of 21 ruptured IAs(RIAs)and 21 unruptured IAs samples were downloaded from the Gene Expression Omnibus(GEO)database.First, mRNAs and long non-coding RNAs(lncRNAs)related to ruptured IAs were identified by integrated analysis of weighted gene co-expression network analysis(WGCNA)and differential gene expression analysis with DESeq2, respectively.Then, mRNA-miRNA associations were obtained based on miRWalk 2.0; miRNA-lncRNA associations were predicted based on miRcode and data from the literature.Lastly, a ceRNA network including mRNAs, miRNAs, and lncRNAs was constructed via combining lncRNA-miRNA associations and lncRNA-miRNA associations.Results:A total of 470 mRNAs and 78 lncRNAs related to ruptured IAs were obtained through WGCNA and differential gene expression analysis.Based on the databases, 49 miRNAs were predicted to be able to bind to the above mRNAs and lncRNAs, and in combination with data from the literature, 13 miRNAs, 7 lncRNAs and 73 mRNAs were screened to construct a ceRNA network.Conclusions:A new ruptured IA-related ceRNA network including 13 miRNAs, 7 lncRNAs and 73 mRNAs has been constructed and may provide some clues for exploring the mechanisms underlying ruptured IAs.

Investigation of structural and psychological empowerment of midwives in 15 hospitals in Suzhou / 中华护理杂志

Objective To investigate the status and analyze the influencing factors of structural empowerment and psychological empowerment of midwives in Suzhou.Methods Using convenience sampling,totally 309 midwives from fifteen hospitals in Suzhou were investigated with the Conditions of Work Effectiveness Questionnaire-Ⅱ (CWEQ-Ⅱ) and Psychological Empowerment Scale (PES).Results The scores of structural and psychological empowerment of midwives were (18.07±3.12) and (14.82±2.01).There was a significantly positive correlation between midwives' structural and psychological empowerment (r=0.396,P＜0.01).Hospital level and whether participate in midwifery standardization training had an impact on structural empowerment score(P＜0.05).Age,parental status,job title,salary,delivery room working hours,number of night shifts per month,and whether or not participate in teaching had an impact on psychological empowerment score(P＜0.05).Conclusion Midwives' structural and psychological empowerments are at a moderate level.Administrators should take targeted intervention to create an empowerment-allowing working environment for midwives,stabilize midwives work force,strengthen midwifery discipline construction and make full specialized features of midwives.

Expression of BAG3 protein in colon cancer tissue detected by tissue microarray method and its clinical significance / 吉林大学学报(医学版)

Objective:To explore the expression of Bcl related anti-apoptotic protein 3 (BAG3 protein)in colon cancer and its clinical significance,and to clarify the relationship between its expression and the occurrence and development of colon cancer.Methods:A total of 90 cases of colon cancer tissue and paracancerous tissue were selected, the expressions of BAG3 protein in different tissues were detected by tissue microarray and immunohistochemical SP method;Kaplan-Meier method,univariate analysis and multivariate analysis were used to investigate the relationship between the clinicopathological parameters and the prognosis of the patients with colon cancer.Results:The expression of BAG3 protein in the colon cancer tissue was high,and the positive expression rates of BAG3 protein in the colon cancer tissue and paracancerous tissue were 37.8% and 0.01%,respectively, and the difference was significant (P < 0.05).The expression of BAG3 protein was associated with gender and tumor size (P <0.05),but there was no correlation between the expression of BAG3 protein in the colon cancer tissue and age,pathologic grade,TNM stage,and lymph node metastasis (P >0.05).The Kaplan-Meier results showed that the expression of BAG3 protein in the colon cancer tissue was not related with the prognosis of the patients and the survival rates of the younger patients and the higher TNM staging patients were high. Conclusion:The expression of BAG3 protein in the colon cancer tissue is high,and its expression is associated with the tumor size;BAG3 protein may act as a tumor marker and therapeutic target for colon cancer.

A applicational analysis about the effect of Marine Injection on combined therapy of benign tracheobronchial stenosis / 中国基层医药

Objective To preliminaryly explore the effect and adverse reaction of Marine Injection combined therapy through local spray in benign tracheobronchial stenosis.Methods 19 cases of bronchial tuberculosis were collected in our department.By assessing cough,shortness of breath and other symptoms,chest high -resolution CT (HRCT)of three -dimensional reconstruction,and length were observed by ultrafine bronchial stenosis.According to the pathogeny and types of stenosis,combined multiple intervention were sequentially adopted,and then Marine Injec-tion was sprayed through one -off endoscopic spray tube.All the subjects were divided into the two groups,the higher concentration Marine injection (1 200 mg/mL)group was chosen with the condition of serious inflammation,edema, ulcer and necrosis,obvious local granulation tissue hyperplasia,severe scar stenosis,and the length of stenosis greater than 2 cm or the sectional area of stenosis less than 50% of the normal sectional area,otherwise the low concentration (600 mg/mL)group was chosen.The subjects were reexamined by clinical symptoms,high -resolution CT (HRCT) of three -dimensional reconstruction,and ultrafine bronchoscopy a week after the surgery to dynamically observe the local changes.Depending on the situation,the injection was sprayed once a week,adding up to 2 -4 times.Follow -up visit lasted for 3 months,cough,expectoration or hemoptysis,and dyspnea were observed.Results 11 cases were effective fully,17 cases were effective substantially,7 cases were ineffective,the total effective rate was 80% (28 /35).The overall complication rate was 42.8% (15 /35),no deaths occurred.No complications related to local spra-ying of Marine were seen.Conclusion Local spray of Marine Injection may have preferable effect that inhibits scar formationand prevention airway restenosis.It is worth further study with a high security,precise clinic effect,easy oper-ation and etc.