Abstract:The vagus nerve plays an important role in maintaining physiological homeostasis, including reflex pathways that regulate cardiac function. The anti-inflammatory potential of vagus nerve stimulation receives increasing attention. This article reviews the application and possible mechanisms of vagus nerve stimulation in the treatment of cardiovascular disease, with the expectation that it will provide new therapeutic approaches for the treatment of cardiovascular disease.

Abstract:Aim Krüppel-like factor (KLF) 2 and 4 are two core transcription factors closely related to vascular homeostasis, with multiple protective effects such as anti-inflammatory, anti-calcification and anti-thrombotic. The aim of this study is to elucidate and validate the vascular homeostasis related gene profile co-regulated by KLF2 and KLF4 in endothelial cells. Methods Human umbilical vein endothelial cells (HUVEC) were treated with adenovirus (Ad-KLF2 or Ad-KLF4) and control virus (Ad-NC) for 24 h, RNA was extracted from the cells and analyzed by transcriptomic sequencing. The sequencing results of overexpressed KLF2 and KLF4 were superimposed with the sequencing results of reported KLF2/KLF4 double-gene knockout mice. The selected differential expression genes were verified by real-time fluorescence quantitative PCR in HUVEC treated with Ad-KLF2 or Ad-KLF4, and in HUVEC treated with atorvastatin or resveratrol. Results Transcriptomic superposition revealed 256 differential expression genes were up-regulated by KLF2 and KLF4, and KEGG analysis showed that differential expression genes were enriched in hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, ECM-receptor interaction and focal adhesion; there were 145 differential expression genes down-regulated by KLF2 and KLF4, and KEGG analysis showed that differential expression genes were enriched in microRNA of cancer, mineral absorption, glycosaminoglycan biosynthesis-chondroitin sulfate/dermatan sulfate, p53 signaling pathway and biosynthesis of amino acids. Finally, six novel genes regulated by KLF2 and KLF4 were obtained. Conclusion FGFR3, SEMA4B, SEMA6A, PTX3, FABP4 and FABP5 may be novel genes that regulate vascular homeostasis in endothelial cells by the transcription factors KLF2 and KLF4.

Abstract:Aim To explore the role and mechanism of the effective ingredients of Scutellariae Radix in improving the fibrosis of diabetes cardiomyopathy (DCM). Methods The technology platform of Chinese medicine system pharmacology (TCMSP) and the small molecule drug target prediction (Swiss Target Prediction) platform were used to excavate the active components of Scutellariae Radix and the target of its response. DCM related disease gene targets were screened using GeneCards, Disgene, UniPort and OMIM databases, and intersecting genes were imported into the String 11.5 database to construct a drug-disease-protein interaction network diagram. Cytoscape 3.9.1 software was adopted to visualize the key target network. Metascape platform was used to explore the molecular targets of Scutellariae Radix effective ingredients against DCM, and draw pathway maps through the KEGG database. H9c2 and AC16 cardiomyocytes were stimulated with 5.5 mmol/L D-glucose as the normal glucose control group, 35 mmol/L D-glucose as the high glucose group, and 10 μmol/L Baicalin was used for intervention. The levels of TGF-β1, collagen Ⅰ (COLⅠ) and collagenⅢ (COLⅢ) mRNA were detected by RT-qPCR, and the expression of Smad2/3, p-Smad2/3, COLⅠ and COLⅢ protein were detected by Western blot, TGF-β1 level in supernatant was assessed by ELISA. Results Through the above platform, a total of 33 effective ingredients including Baicalin, 441 core targets, and 1 884 DCM disease genes were retrieved, 150 core genes for treating DCM with Scutellariae Radix were obtained. The drug-disease interacted genes such as TGF-β1, TP53, MMP-9 and IL-6 were obtained through String PPI, KEGG signaling pathways such as MAPK and PI3K/Akt were enriched. In vitro experiments showed high glucose stimulation of H9c2 and AC16 cardiomyocytes led to upregulation of TGF-β1, COLⅠ and COLⅢ mRNA levels, p-Smad2/3, COLⅠ and COLⅢ protein levels, and significantly increased the content of TGF-β1 in the supernatant, while Baicalin weakened its expression. Conclusion The active ingredients of Scutellariae Radix exert anti DCM effects through multiple targets, among which Baicalin inhibits TGF-β1/Smad signaling to improve high glucose induced cardiomyocyte fibrosis and plays a protective role in DCM.

Abstract:Aim To explore the effect of Pueraria Lobata Flowers Extract (PFE) on lipid accumulation in macrophage-derived foam cells. Methods The concentration of PFE in THP-1-derived foam cells was screened by MTT, intracellular lipid accumulation was detected by oil red O staining and cholesterol detection kit, intracellular cholesterol efflux levels were detected by cholesterol efflux assay kit, RT-qPCR and Western blot were used to analyze mRNA and protein expression. Results PFE significantly reduced lipid accumulation in THP-1-derived foam cells. PFE did not affect the mRNA expression of CD36, scavenger receptor-AⅠ (SR-AⅠ), sterol regulatory element-binding protein 2 (SREBP2), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), but it could upregulate the mRNA and protein expression levels of ATP-binding cassette transporter A1 (ABCA1) (P＜0.05), and promote the intracellular cholesterol efflux of macrophage-derived foam cells (P＜0.01). PFE could activate the activity of peroxisome proliferator-activated receptor γ (PPARγ) (P＜0.01) and upregulate the mRNA and protein expression levels of PPARγ (P＜0.05). Compared with the PFE control group, the expression of PPARγ and ABCA1 proteins decreased and cholesterol efflux decreased after GW9662 treatment (all P＜0.01). Conclusion PFE could significantly prevent the lipid accumulation in THP-1-derived foam cells and inhibit the formation of foam cells by upregulating ABCA1 expression and cholesterol efflux mediated by PPARγ.

Abstract:Aim To investigate the effect of alfentanil on myocardial ischemia-reperfusion injury (MIRI) in rats and its regulatory mechanism on the sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P) signaling pathway during this process. Methods SPF grade SD male rats were randomly divided into sham surgery group, model group, positive drug group (compound salvia miltiorrhiza group), low dose alfentanil group, high dose alfentanil group, and high alfentanil+SphK1 agonist group (alfentanil+PMA group), with 20 rats in each group. Except the sham operation group, the MIRI model was reproduced by ligating the left anterior descending coronary artery and reperfusion. The activities of serum lactate dehydrogenase (LDH), creatine kinase (CK) and aspartate aminotransferase (AST) were detected by automatic biochemical analyzer; TTC was applied to detect the size of myocardial infarction in rats; HE staining was applied to observe the morphological characteristics of rat myocardial tissue; TUNEL staining was applied to detect myocardial cell apoptosis in rats; ELISA was applied to detect the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and S1P; kits were applied to detect content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) in myocardial tissue; Western blot was applied to detect the expression level of SphK1 protein in myocardial tissue. Results Compared with the sham surgery group, the pathological damage to the myocardial tissue of rats was severe in the model group, the activities of serum central muscle injury markers LDH, CK, and AST, myocardial infarction area, myocardial cell apoptosis rate, the levels of TNF-α, IL-6, IL-1β, MDA, S1P and the expression of SphK1 protein all increased, the activity of SOD decreased (P＜0.05). Compared with the model group, the myocardial tissue damage of rats was reduced in the positive drug group and the low and high dose alfentanil groups, the activities of serum central muscle injury markers LDH, CK, and AST, myocardial infarction area, myocardial cell apoptosis rate, the levels of TNF-α, IL-6, IL-1β, MDA, S1P and the expression of SphK1 protein all decreased, the activity of SOD increased (P＜0.05). The SphK1 agonist was able to reverse the impact of high-dose alfentanil on the above indicators (P＜0.05). Conclusion Alfentanil has protective effect on MIRI rats, and its mechanism may be related to the inhibition of SphK1/S1P signaling pathway.

Abstract:Aim To investigate the relationship between fibrinogen (FIB) and the progression of coronary plaque stenosis rate in patients with type 2 diabetes mellitus (T2DM). Methods Hospitalized T2DM patients who underwent two or more coronary CT angiography (CCTA) examinations in the First Affiliated Hospital of Xi'an Jiaotong University from January 2015 to December 2020 were included. The subjects were divided into high FIB and low FIB groups according to the median of FIB. The differences in the progression of coronary plaque stenosis rate and other clinical characteristics were compared between the two groups, and the relationship between FIB level and the progression of coronary plaque stenosis rate was analyzed by Spearman's correlation analysis and Logistic regression. Results A total of 145 patients were included, 73 in the high FIB group and 72 in the low FIB group at baseline, with a median follow-up time of 25 (8,0) months between CCTA. The age, proportion of women, and the progression of coronary plaque stenosis rate were higher in the high FIB group than those in the low FIB group, and the differences were statistically significant (P＜0.05). FIB level was positively correlated with the change in coronary plaque stenosis rate (r²＝0.308, P＜0.001). Multivariate Logistic regression analysis showed that FIB level was a risk factor for the progression of coronary plaque stenosis rate in patients with T2DM (OR＝5.5,5%CI:1.97～14.02, P＜0.001), after adjusting for age, sex and other clinical risk factors. Conclusion High baseline FIB level is an independent risk factor for the progression of coronary plaque stenosis rate in patients with T2DM, and monitoring FIB level is beneficial to cardiovascular risk stratification in patients with T2DM.

Abstract:Aim To analyze the risk factor of the cardiac rupture (CR) in patients with acute ST-segment elevation myocardial infarction (STEMI). Based on this, the nomogram model of acute STEMI patients with CR was established. Methods Through Ningxia Medical University General Hospital's big data research platform and hospital information system retrieval, 5 412 patients with acute STEMI from January 2015 to December 2019 were continuously included in the study, of which 91 patients with CR were included as CR group; 5 321 patients non-combined with CR were included as non-CR group. LASSO regression, univariate and multivariate Logistic regression were used to analyze the risk factors of CR in patients with acute STEMI, and the CR nomogram predictive model was established. The nomogram model was validated and evaluated by using receiver operating characteristic(ROC) curve, Hosmer-Lemeshow test and clinical decision curve analysis (DCA). Results LASSO regression results showed that age, female, hypertension history, first medical contact time, shock index, Killip grade, white blood cell count, d-dimer, lactic acid, anterior myocardial infarction, β-blocker administration within 24 hours, angiotensin converting enzyme inhibitor/angiotensin receptor antagonist (ACEI/ARB) administration within 24 hours, emergency percutaneous coronary intervention (PCI) were 13 risk factors of CR (P＜0.05). The screened 13 risk factors were analyzed by univariate and multivariate Logistic regression, the results suggested that age, Killip grade, first medical contact time, white blood cell count, not undergoing emergency PCI and not taking ACEI/ARB drugs within 24 hours were the risk factors of CR in patients with acute STEMI. The acute STEMI with CR nomogram model was established according to the above 6 risk variables. The area under the ROC curve before and after the internal verification of the nomogram model was 0.946 (95%CI:0.927～0.961), 0.947 (95%CI:0.927～0.959), and the sensitivity was 0.957 and 0.904, respectively,the specificity was 0.858 and 0.876, respectively, which indicated that the model had good discrimination degree. The Hosmer-Lemeshow test showed that the deviation between the predicted value and the observed value was not statistically significant (χ²=12.70, P=0.122), indicating that the nomogram model had a good calibration. The DCA curve indicated that the predictive probability threshold of the model was from 0.00 to 0.40, and the clinical net benefit was the highest, indicating that the model had good clinical efficacy. Conclusion The nomogram model established in this study has better distinction, calibration and clinical effectiveness. It can effectively predict the probability of acute STEMI with CR, and provide some help for clinical diagnosis and treatment, so as to reduce the incidence of CR.

Abstract:Aim To explore the correlation of serum angiopoietin-1 (Ang-1) and human cartilage glycoprotein-39 (YKL-40) levels with coagulation function and inflammatory response in patients with Kawasaki's disease (KD) complicated with coronary artery lesion (CAL). Methods From January 2018 to December 2,0 children with KD were selected as the study subjects, and 90 healthy children who were examined in this hospital during the same period were selected as the control group. According to whether CAL was combined, they were divided into non-CAL group (69 cases) and CAL group (21 cases), the levels of serum Ang-1, YKL-40, coagulation function, and inflammatory factors were compared between the two groups. Pearson analysis was used to investigate the relationship between serum Ang-1, YKL-40 levels and coagulation function, inflammatory reaction indicators in children with KD combined with CAL. Multivariate Logistic regression analysis was used to identify the factors affecting CAL in children with KD. Results There were significant differences in serum Ang-1 and YKL-40 levels among the control group, the non-CAL group and the CAL group (all P＜0.05). With the increase of the severity of the disease, the serum Ang-1 level in the control group, the non-CAL group and the CAL group decreased gradually, and the YKL-40 level increased gradually (all P＜0.05). Serum Ang-1 was negatively correlated with fibrinogen (FIB), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and white blood cell count (WBC) (all P＜0.05), YKL-40 was positively correlated with FIB, CRP, TNF-α, IL-6 and WBC (all P＜0.05). Multivariate Logistic regression analysis showed that YKL-40 was a risk factor for CAL in children with KD, and Ang-1 was a protective factor (P＜0.05). Conclusion The level of serum Ang-1 decreased and the level of YKL-40 increased in children with KD complicated with CAL, which was correlated with coagulation function and inflammatory response.

Abstract:Aim To investigate the effect of artificial intelligence (AI) assisting doctors with different seniority in predicting the enlargement of hematoma in the early stage of cerebral hemorrhage. Methods A total of 108 patients diagnosed with cerebral hemorrhage in Central Hospital Affiliated to Dalian University of Technology were retrospectively collected. CT images at admission and 24 hours after admission were collected. DICOM images obtained from plain CT scan were input into AI-CAD model developed by Biomind in collaboration with Temple of Heaven. A total of 9 doctors of different senior-level were selected in neurosurgery department of our hospital. Firstly, independent prediction was applied in the patients and then the study predicted whether patients would delelop hematoma enlargement within 24 hours combined with the results of auxiliary AI. The accuracy of independent prediction of doctors with different seniority and assisted AI prediction of aneurysm stability was calculated respectively. McNemar of paired samples was used to test the significance of difference between independent prediction coincidence rate and assisted AI prediction accuracy among different doctors. Results The accuracy of high, middle and low seniority doctors independently predicting the early expansion of cerebral hemorrhage was 58.95%, 50.62% and 38.89%, respectively, and the accuracy of prediction was significantly improved after assisted AI (P＜0.001), the highest increase rate was low seniority doctors (25.92%), followed by middle seniority doctors (19.75%) and high seniority doctors (11.73%). The ability of senior physicians to independently predict the expansion of intracerebral hemorrhage was strongest in patients and non-patients, with sensitivity of 18.75% (95%CI:9.44%～33.10%) and specificity of 65.94% (95%CI:59.98%～71.45%). The sensitivity of middle seniority doctors was 16.67% (95%CI:7.97%～30.76%), the specificity was 56.52% (95%CI:50.44%～62.42%), and the sensitivity of low seniority doctors was 8.33% (95%CI:2.70%～20.87%), the specificity was 44.20% (95%CI:38.29%～50.28%). However, after AI assisted the prediction of senior doctors, the sensitivity and specificity of each seniority group of doctors increased. The sensitivity of high seniority doctors was 60.42% (95%CI:45.29%～73.88%), the specificity was 72.46% (95%CI:66.72%～77.57%), the sensitivity of middle seniority doctors was 64.58% (95%CI:49.40%～77.45%), the specificity was 71.38% (95%CI:65.59%～76.56%), and the sensitivity of low seniority doctors was 68.75% (95%CI:53.60%～80.91%), the specificity was 64.13% (95%CI:58.13%～69.73%). Conclusion AI-CAD assisted doctors with high, middle and low seniority can improve the accuracy of predicting the enlargement of hematoma in early stage of cerebral hemorrhage, especially the ability of doctors with low seniority to find patients can be significantly improved, which can make up for the lack of work experience of doctors with low seniority to a certain extent.

Abstract:Abdominal aortic aneurysm (AAA) is a common disease in the elderly, with an increasing incidence rate, easy rupture, high mortality, and no effective drugs to slow down the development of AAA. The pathogenesis of AAA is closely related to extracellular matrix degradation, apoptosis of vascular smooth muscle cells and inflammation. It has been found that arachidonic acid derivatives, especially prostaglandins such as prostaglandin E2 (PGE2), prostaglandin D2 (PGD2) and thromboxane A2(TXA2), play important roles in the development of AAA. Therefore, this review discusses the mechanism of arachidonic acid derivatives in the development of AAA, as well as the latest research progress of the drugs, to provide ideas for the treatment of AAA and the discovery of new drug targets.

Abstract:Brain abundant membrane attached signal protein 1 (BASP1) was first discovered in the rat brain and is primarily enriched in brain, heart, mouth, skin, stomach, kidneys and many other human organs. The BASP1 protein is evolutionarily conserved. It participates in cellular biological processes such as cell signaling, cell migration, apoptosis, and gene transcription as an inherently disordered protein (IDP), and is involved in a series of pathophysiological processes such as neural development, kidney development, and germ cell formation. BASP1 plays a very important function in glucose, lipid metabolism diseases and tumor diseases, and is considered to be a potential disease treatment target and molecular diagnostic marker.

Abstract:Wall shear stress is an important parameter in hemodynamics. Normal wall shear stress maintains the physiological state of blood vessels, while abnormal wall shear stress is closely related to the pathological progression of atherosclerosis and aneurysm, which is one of the risk factors for the occurrence of malignant cardiovascular and cerebrovascular events. Abnormal wall shear stress destroys the normal function of endothelial cells through different pathogenesis, mediates the initiation and evolution of these two diseases. This article reviews the impact of wall shear stress on atherosclerosis and aneurysm based on literature research in recent years.

Abstract:Cardiovascular diseases are still one of the diseases that lead to high mortality. Currently, drugs for preventing and treating cardiovascular diseases can significantly improve symptoms, but there are still shortcomings in reducing mortality rates. Therefore, new drugs that can improve symptoms and reduce mortality are needed. As a kind of hydroxylase inhibitor, roxadustat can effectively improve the symptoms of hypoxia by regulating the expression of hypoxia inducible factor (HIF). HIF is involved in almost all developmental, pathological or physiological processes in the body, including erythropoietin production, iron uptake, and metablism, cellular differentiation, energy metablism, inflammation and immune regulation. At present, the drug has a good prospect in the treatment of renal anemia, but it is rarely used in cardiovascular diseases. In this paper, the effects of roxadustat on cardiovascular diseases were systematically and comprehensively discussed, and some help was provided for the treatment of cardiovascular diseases.