MiR-21-5p-expressing bone marrow mesenchymal stem cells alleviate myocardial ischemia/reperfusion injury by regulating the circRNA_0031672/miR-21-5p/programmed cell death protein 4 pathway

BACKGROUND For patients with coronary heart disease,reperfusion treatment strategies are often complicated by ischemia/reperfusion(I/R)injury(IRI),leading to serious organ damage and malfunction.The miR-21/programmed cell death protein 4(PDCD4)pathway is involved in the IRI of cardiomyocytes;however,the aberrant miR-21 expression remains unexplained.Therefore,this study aimed to explore whether circRNA_0031672 downregulates miR-21-5p expression during I/R and to dete-rmine whether miR-21-5p-expressing bone marrow mesenchymal stem cells(BMSCs)reduce myocardial IRI.METHODS CircRNA_0031672,miR-21-5p,and PDCD4 expressions were evaluated in the I/R rat model and hypoxia/re-oxy-genation(H/R)-treated H9C2 cells.Their interactions were subsequently investigated using luciferase reporter and RNA pull-down assays.Methyltransferase-like 3,a methyltransferase catalyzing N6-methyladenosine(m6A),was overexpressed in H9C2 cells to determine whether m6A modification influences miR-21-5p targeting PDCD4.BMSCs stably expressing miR-21 were co-cultured with H9C2 cells to investigate the protective effect of BMSCs on H9C2 cells upon H/R.RESULTS I/R downregulated miR-21-5p expression and upregulated circRNA_0031672 and PDCD4 expressions.CircRNA_0031672 knockdown increased miR-21-5p expression,but repressed PDCD4 expression,indicating that circRNA_0031672 com-petitively bound to miR-21-5p and prevented it from targeting PDCD4 mRNA.The m6A modification regulated PDCD4 expres-sion,but had no effect on miR-21-5p targeting PDCD4.The circRNA_0031672/miR-21-5p/PDCD4 axis regulated myocardial cells viability and apoptosis after H/R treatment;co-culture with miR-21-5p-expressing BMSCs restored miR-21-5p abundance in H9C2 cells and further reduced H9C2 cells apoptosis induced by H/R.CONCLUSIONS We identified a novel circRNA_0031672/miR-21-5p/PDCD4 signaling pathway that mediates the apoptosis of cardiomyocytes and successfully alleviates IRI in myocardial cells by co-culture with miR-21-5p-expressing BMSCs,offering novel insights into the IRI pathogenesis in cardiovascular diseases.

Effect of nifedipine in combined with magnesium sulfate on the hemorheology and coagulation indicators in patients with gestational hypertension

Objective:To explore the effect of nifedipine in combined with magnesium sulfate on the hemorheology and coagulation indicators in patients with gestational hypertension.Methods:A total of 90 patients with gestational hypertension were included in the study and randomized into the observation group and the control group with 45 cases in each group. The patients in the observation group were given magnesium sulfate in combined with nifedipine, while the patients in the control group were only given magnesium sulfate. The patients in the two groups were continuously treated for 2 weeks. The blood pressure, hemorheology indicators, and coagulation indicators before and after treatment in the two groups were detected and compared.Results: SBP, DBP, whole blood high, moderate, and low shear viscosity, plasma viscosity, and HCT after treatment in the two groups were significantly reduced when compared with before treatment (P<0.05). The levels of the above indicators after treatment in the observation group were significantly lower than those in the control group (P<0.05). PT, APTT, and TT after treatment in the two groups were significantly elevated when compared with before treatment (P<0.05), while Fib was significantly reduced (P<0.05). PT, APTT, and TT after treatment in the observation group were significantly higher than those in the control group (P<0.05), while Fib was significantly lower than that in the control group (P<0.05). Conclusions:Nifedipine in combined with magnesium sulfate can significantly stabilize the blood pressure level in patients with gestational hypertension, and improve the hemodynamic and coagulation indicators, with a significant efficacy.

Application of CRISPR-Cas9 technology in the screening of tumor resistance genes:A review

Drug resistance is a major problem faced by tumor cell-targeted drugs.Currently,functional gene screening is the most common strategy for screening drug resistance genes.In recent years,Crispr-cas9 gene editing technology has been widely used in the functional studies of tumor-related genes due to their characteristics of accuracy,simplicity and efficiency.The principle of CRISPR-Cas9 Library Screening Technology and its application in functional Gene Screening are reviewed.At the same time,the application prospect of the Crispr-Cas9 technology is forecasted.

The Evaluation Characteristics of Type B Aortic Intramural Hematoma and Ten Years Treatment Outcomes

Background: Type B aortic intramural hematoma (IMH-B) is recognized as a subset of aortic dissection. The evolution of uncomplicated IMH-B is very difficult to predict. How and when to deal with this disease is unclear. The present study constructed two models to explore this problem. One is the morphology evolution model, which explored the risk factors and predictors for the IMH-B patients. Another is the predictive model confirmed the predictors and the time for invasive treatment of uncomplicated IMH-B patients. Objective: To explore the evolution predictors and detect the time for invasive treatment of uncomplicated IMH-B patients. Methods: Themorphology evolution model demonstrated that all 81 patients were diagnosis with CTA images. The initial and follow-up data were retrospectively studied. The evolution data were collection and measurement from initial and follow-up CTA images data. The predictive model showed that predictors of progression were detected with cox regression analysis. Results: All 81IMH-B patients were followed-up ranged from 1.2 to 36 months (median, 22 months). 26 patients accepted invasive treatment (24 underwent TEVAR and 2 underwent Surgery). 55 patients received medical treatment. Invasive treatment (IT) group overall events are 1/26 (3.8%); medical treatment (MT) group overall events are 33/55 (60.0%); IT group vs. MT group: p < 0.001. Moreover, we found that most events related aorta occurred within 30 days. Multivariate Cox regression analysis MDAD (hazard ratio, 3.58;95% CI, 1.25- 5.78;p < 0.001), MDAHT (hazard ratio, 4.26;95% CI, 0.85 - 7.84;p < 0.001), and IMH with PAU (hazard ratio, 3.58;95% CI, 1.02 - 5.63;p < 0.001) were confirmed as the independent predictors. Conclusions: MDAD > 45 mm, MDAHT > 10 mm, and IMH with PAU may be the important predictors for uncomplicated IMH-B patients. Most adverse aorta related events occurred within 30 days. It would be careful follow-up, closely observe for these patients within 30 days, and take necessary treatment strategies in time.

The prognostic role of N-terminal prohormone brain natriuretic peptide and TIMI risk score in patients with ST segment elevation myocardial infarction

Background ST segment elevation myocardial infarction （STEMI） remains a major cause of death world-wide. The thrombolysis in myocardial infarction （TIMI） risk score is a risk assessment tool to detect high risk STEMI patients. NT-proBNP has been used to assess the severity of heart failure. However, the predictive power of TIMI risk score is not high enough to identify all high-risk patients, and whether NT-proBNP adds power to the TIMI risk score for predicting in-hospital mortality is unclear. Methods 664 STEMI patients were included and divided into 3 groups according to TIMI risk score ≤3 （n=211）, 4-6 （n=281）, and ≥7 （n=172）. The relation-ships between TIM! risk score and events were evaluated. The modified TIMI risk score was constructed through multivariate logistic regression analysis. Results The proportion of in-hospital death （0.5% vs. 3.2% vs. 10.5%, P〈0.001） and major adverse clinical events （MACEs） （14.2% vs. 22.8% vs. 40.1%, P〈0.001） increased as higher TIMI risk score was. ROC curve showed that the AUC of NT-proBNP for predicting in-hospital death was 0.792, with optimal cut-off being 3500pg/mL. Multivariate logistic regression analysis revealed that TIMI risk score （OR=1.26, 95% CI 1.05-1.50, P=0.012） and NT-proBNP〉3500pg/mL （OR=7.30, 95% CI 2.56-20.83, P〈0.001） were independently associated with in-hospital death. Adding NT-proBNP to TIMI risk score produced higher predictive value （AUC： 0.871 vs. 0.804, P=0.040）. Conclusion NT-proBNP is associated with in-hospital death in STEMI patients and has an additive prognostic value to TIMI risk score.

Prognostic value of magnesium in serum of patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention

Background Fewer studies were performed to evaluate the relationship between magnesium level in serum and mortality after percutaneous coronary intervention（PCI） for patients with ST-segment elevation myocardial infarction（STEMI）. In this study, we explored the association between magnesium level in serum and adverse outcomes in STEMI patients undergoing PCI. Methods All 1476 consecutive patients with STEMI undergoing PCI were divided into three groups, magnesium 〈 0.8（n = 331）, 0.8-1.0（n = 1100） and 〉1.0 mmol/L（n = 45）based on the levels of serum magnesium. The association between magnesium and in-hospital and one-year death was analyzed. With multivariate logistic regression analysis. Results The in-hospital mortality（6.3% vs. 2.5%vs. 4.4%, P = 0.004） and major adverse clinical events（7.9% vs. 3.6% vs. 6.7%, P = 0.005） were significantly higher in patients with hypomagnesemia. Kaplan-Meier analysis demonstrated that the cumulative rate of oneyear mortality after PCI was higher in patients with hypomagnesemia（Log-rank = 9.89, P = 0.007）. Conclusion Hypomagnesemia is a predictor of higher in-hospital and one-year mortality after PCI for STEMI patients.

A review of vasopeptidase inhibitors in heart failure

Background The incidence of acute myocardial infarction（AMI） has become an important social health problem throughout the world. Heart failure after AMI could significantly affect the life quality of patients. Drug therapy has great significance role in inhibiting the remodeling of the cardiac muscle. Vasopeptidase inhibitors（VPIs） could overcome some limitations of traditional drugs by improving the quality of life. This article is aimed to review the progress in the study of VPI drugs and several ways of preventing and controlling heart failure after AMI.