Abstract:Aim Ischemic stroke (IS) is caused by acute ischemia of cerebral blood vessels, leading to brain tissue damage and neuronal apoptosis. The pathogenesis is complex, involving multiple cell death modes such as pyroptosis, ferroptosis and disulfide death. Disulfide death is a newly discovered form of death that helps to explore the pathological mechanisms of various diseases from a new perspective. The aim of this study is to discover and validate the differential expression of disulfide death-related genes in blood samples of ischemic patients and their association with immune regulation. Methods The relevant datasets of clinical patients (GSE16561 and GSE37587) were obtained through online big data. Differentially expressed genes related to disulfide death were identified, and gene enrichment analysis was conducted to further explore the potential mechanisms. Subsequently, immune cell infiltration was analyzed to investigate the dysregulation of immune cells in the context of IS. Finally, the accuracy of key genes was verified through ROC curves, column charts, calibration curves, and decision curves, and a disease prediction model was constructed to predict the risk of stroke. Results Based on this dataset, significant differential expression of 9 genes related to disulfide death was identified. Independent external validation was conducted using the microarray dataset GSE58294. Single item comparisons were performed on these differentially expressed genes in blood samples from 69 IS patients and 23 normal individuals.The results showed that the trends of LRPPRC, MYH9, NDUFA11, PRDX1 and RPN1, the 5 differentially expressed genes, were consistent. Immune infiltration analysis found that differentially expressed genes such as TLN1, MYH9, PRDX1, LRPPRC, NDUFA11 were also strongly correlated with CD8＋T cells, activated NK cells, macrophages, and neutrophils in IS patients. Functional enrichment analysis emphasized the important role of pathways such as focal adhesion, platelet aggregation, and activation in the occurrence and development of diseases. By using a column chart model for risk prediction, it was shown that the accuracy of these differentially expressed genes was good, and the ROC curve AUC value of the optimized combination of disulfide death-related genes could reach 0.844. Further validation through an external dataset (GSE58294) revealed that the ROC curve AUC value optimized for disulfide death-related genes reached 0.989, which had good clinical guidance significance for the risk of IS. Conclusions This study confirmed the existence of 5 disulfide death-related genes in IS patients through a dataset, including upregulation of MYH9 and downregulation of LRPPRC, NDUFA11, PRDX1 and RPN1. These gene alterations are suggested to influence IS disease progression and prognosis through immune inflammation and bleeding risk.

Abstract:Aim To study the distribution of CYP2C19, ABCB1, and PON1 genotypes and their correlation with clopidogrel resistance in patients with coronary heart disease in Taian. Methods A total of 594 patients with coronary heart disease who were treated with clopidogrel during hospitalization in Taian Central Hospital from January 2019 to March 2020 were selected. Fluorescence in situ hybridization was used to detect CYP2C19*2 (rs4244285), CYP2C19*3 (rs4986893), CYP2C19*17 (rs12248560), ABCB1 (rs1045642) and PON1 (rs662) gene types. Results CYP2C19*2, CYP2C19*3, CYP2C19*17 genotypes in patients with coronary heart disease in Taian were mainly with homozygous (GG). The frequencies of CYP2C19*2 GG, CYP2C19*3 GG, CYP2C19*17 CC, ABCB1 CT and PON1 AG were 48.0%, 89.6%, 97.0%, 46.8% and 47.1% respectively. There was no significant difference in CYP2C19*2, CYP2C19*3, CYP2C19*17, ABCB1, PON1 genotype distribution and allele distribution between male and female patients (P＞0.05). Significant regional differences in the frequency of CYP2C19 alleles and the distribution of metabolic types were found in patients with coronary heart disease in Taian. Among 594 patients included in the study, there were 287 patients with a risk level of clopidogrel resistance ≥ 2 in the composite evaluation of patients, approximately 48.3% of the total number of patients. This indicated that clopidogrel resistance was present in 48.3% of patients on the regular dose of clopidogrel. Of the 287 people with a risk level ≥ 2,6 had a normal CYP2C19 metabolic type, representing approximately 7.7% of the total number of patients. Conclusion There were gene polymorphisms observed in CYP2C19*2, CYP2C19*3, CYP2C19*17, ABCB1 and PON1 distribution in patients with coronary heart disease in Taian, and ABCB1 and PON1 gene polymorphisms would had an impact on the outcome of medication guidance in approximately 7.7%.

Abstract:Myocardial infarction with non-obstructive coronary artery (MINOCA) is a common acute coronary syndrome in clinical practice. Its diagnosis is more difficult than general acute coronary syndrome, and may be difficult to distinguish from other non ischemic diseases that can cause similar symptoms and myocardial damage. Delayed treatment timing can have a significant detrimental effect on patients. This article provides a review of the clinical diagnosis and treatment progress of MINOCA, with the aim of providing guidance for clinical practice.

Abstract:Non-alcoholic fatty liver disease (NAFLD), a metabolic stress-induced liver injury, is characterized by excessive accumulation of fat in the liver, which is closely related to insulin resistance and genetic susceptibility. It is estimated that 25% of the worlds population are currently diagnosed with NAFLD, which has a huge impact on socioeconomic development and peoples health. The prevalence of NAFLD in different countries/regions is different based on the living customs and population genetic differences in different regions, and there are also certain differences in the diagnostic criteria and treatment plans of NAFLD in the recommendations given by the national/regional diagnosis and treatment guidelines. This article aims to compare the latest domestic and international guidelines on the diagnosis and treatment of NAFLD, as well as summarise the latest research advances in the treatment of NAFLD, in order to provide recommendations for the clinical management of NAFLD.

Abstract:Aim To investigate the levels of krüppel-like factor 2 (KLF2) and endothelial nitric oxide synthase 3 (NOS3) in the serum of patients with acute cerebral infarction (ACI) of large-artery atherosclerosis (LAA) type, and to analyze their value in the diagnosis and disease assessment of LAA type ACI. Methods A total of 150 patients with LAA type ACI were divided into mild group (n＝36), moderate group (n＝48), and severe group (n＝66) based on their condition. Additionally, a control group (n＝150) was selected from health exminers during the same period. The levels of serum KLF2 and NOS3 in each group were compared; receiver operator characteristic(ROC) curve was applied to analyze the diagnostic value of serum KLF2 and NOS3 levels for LAA type ACI and the predictive value for the occurrence of severe LAA type ACI, respectively. Results The serum KLF2 and NOS3 levels were significantly lower in LAA type ACI group than those in control group (P＜0.05). The serum KLF2 and NOS3 levels in the mild, moderate and severe groups were significantly decreased in turn(P＜0.05). The area under the curve (AUC) of the combined diagnosis of serum KLF2 and NOS3 for LAA type ACI was 0.858, with a sensitivity of 73.33% and a specificity of 86.00%, which was superior to the individual diagnosis of KLF2 and NOS3 (Zcombined detection-KLF2＝3.796, Zcombined detection-NOS3＝4.689, all P＜0.001). The AUC of combined prediction of serum KLF2 and NOS3 for the occurrence of severe LAA type ACI was 0.878, with a sensitivity of 77.27% and a specificity of 90.48%, which was superior to the independent prediction of KLF2 and NOS3 (Zcombined detection-KLF2＝2.401, P＝0.016; Zcombined detection-NOS3＝3.070, P＝0.002). Conclusions The serum levels of KLF2 and NOS3 in patients with LAA type ACI were significantly reduced and negatively correlated with the severity of the disease. The combination of the two has high evaluation efficacy in the diagnosis and disease prediction of LAA type ACI.

Abstract:Macrophages play an important role in the development of inflammation, the core mechanism of atherosclerosis. In recent years, nanotechnology has provided a new perspective for the diagnosis and treatment of atherosclerosis with its unique characteristics of biological compatibility and precise targeting. In this paper, the pathological mechanism of atherosclerosis, the realization of atherosclerosis imaging by targeting macrophages with nanomaterials and the application of macrophage cell membrane biomimetic nanoparticles in anti-atherosclerosis were reviewed.

Abstract:Acute coronary syndrome (ACS) is one of the most serious cardiovascular diseases endangering human health. For a long time, plaque rupture (PR), the release of plaque contents accompanying and the formation of mural thrombus are considered as the major mechanism for the formation of ACS. With the application of optical coherence tomography (OCT), it is realized that, in addition to PR, plaque erosion (PE) is another important and common pathological mechanism of ACS. In recent years, the research on PE has made good progress. This paper will summarize the research progress on the diagnosis and treatment of PE.

Abstract:Aim To study the diagnostic and prognostic value of head and neck computed tomography angiography (CTA) combined with ambulatory arterial stiffness index in acute cerebral watershed infarction (ACWI). Methods 292 patients who met the diagnostic criteria of ischemic cerebrovascular disease in the Department of Neurology of Baoding Second Central Hospital from July 2018 to September 2020 were prospectively collected. All patients were examined by diffusion weighted imaging (DWI). According to the results of DWI, patients were divided into ACWI group (n＝134) and non-ACWI group (n＝158). All patients underwent head and neck CTA examination and neck ultrasound, to detect the presence, nature and location of carotid plaque and the stenosis, location and stenosis of head and neck vessels in patients. The prognosis of the patients was evaluated with the NIHSS. The general clinical data, NIHSS score at admission and discharge, ambulatory arterial stiffness index (AASI), vascular stenosis in the head and neck, location and stenosis were compared between the two groups. Multivariate analysis was conducted using Logistic regression model. Pearson test was used to analyze the correlation between AASI and head and neck CTA in patients with ACWI. ROC curve was used to evaluate the detection index of CTA in the head and neck and the effect of AASI on ACWI, and the factors affecting the prognosis of patients with ACWI were analyzed by establishing Cox proportional hazard regression model. Results Mean arterial pressure was the protective factor of ACWI on admission (P＜0.05). The degree of internal carotid artery (ICA) stenosis on the lesion side, the stenosis degree of MCA on the lesion side, the stenosis of multiple vessels on the lesion side and AASI were independent risk factors for ACWI (P＜0.05). ASSI was positively correlated with the degree of ICA stenosis, the degree of MCA stenosis and the number of stenotic vessels (P＜0.001). The diagnostic value of head and neck CTA combined with AASI in ACWI was greater than that in ACWI alone (P＜0.05). NIHSS score at discharge, focal side severe ICA stenosis, focal side MCA severe stenosis, lesion side multivessel stenosis and AASI were the key risk factors affecting the prognosis of ACWI patients (P＜0.05). Conclusion The degree of ICA stenosis on the lesion side, the stenosis degree of MCA on the lesion side, the stenosis of multiple vessels on the lesion side and AASI are independent risk factors for ACWI. Clinically, head and neck CTA combined with AASI can be used for early diagnosis and treatment of ACWI patients and improve the prognosis of the patients.

Abstract:Aim To evaluate the safety and effectiveness of percutaneous coronary intervention via distal transradial artery access. Methods Pubmed, Embase, Web of Science, Cochrane Library, China Biomedical Service System (Sinomed), China Knowledge Network (CNKI), Wanfang Data Knowledge Service Platform (Wanfang Data), VIP and other databases were searched by computer. The search time limit was from Janurary 2017 to May 2020. Two researchers conducted a Meta-analysis after analyzing and evaluating according to the Cochrance bias risk assessment tool.Results A total of 1 617 articles were obtained in various databases and other channels according to a predetermined search strategy, excluding unreasonable research design, no control group or control group as other parts of blood vessels (such as femoral artery, etc.), animal experiments, reviews, systematic reviews, and case reports were excluded. 10 articles were finally selected, Meta analysis results showed that there was no significant difference in the success rate of coronary puncture, the radial artery spasticity, and local hematoma (P＞0.05). However, the the radial artery occlusion was lower (OR＝0.4,5%CI(0.8,0.69),Z＝3.56,P＜0.05) in the distal radial artery path than in the traditional radial artery pathology. Conclusion Distal transradial artery access is safer and more effective than traditional radial artery access for coronary artery intervention. It can reduce radial artery occlusion and can be used as an alternative branch of the traditional route.

Abstract:Aim To confirm the role of kinesin superfamily member 16B (KIF16B) in the process of low density lipoprotein cholesterol (LDLC) uptake of hepatocyte which is regulated by the inducible degradation of low density lipoprotein receptor (IDOL). Methods The intracellular fluorescence intensity was observed by the inverted fluorescence microscope. The intracellular lipid content was measured by oil red O staining, and the LDLC uptake was detected by DiI-LDL uptake experiment. The low density lipoprotein receptor (LDLR) abundances on the cell surface of hepatocytes were assayed by immune flow cytometry. The protein expression of IDOL, KIF16B and LDLR was detected by Western blot, and the interaction between LDLR and KIF16B protein was carried out by co-immunoprecipitation. Results Compared with white light view, the observed green fluorescence results showed that both HepG2 and LO2 cells were infected by the RNA-interference or overexpression IDOL(RNAi/OE-IDOL) lentivirus. Compared with the non-lentivirus infected control group, both the intracellular lipid and the ability of the LDLC uptake were significantly decreased in the OE-IDOL group(P＜0.05), and also decreased in the abundances of LDLR on the surface of hepatocytes (P＜0.01); and vice versa, the contrary results of these three experiments were observed in the RNAi-IDOL group (P＜0.01), which indicated that overexpression IDOL would reduce the LDLC uptake of hepatocytes. Compared with the RNAi/OE-IDOL control group, the expression of LDLR and KIF16B protein was increased in the RNAi-IDOL group (P＜0.01), and the interaction between KIF16B and LDLR was enhanced (P＜0.01). While in the overexpression IDOL of HepG2 and LO2 cells, the expression of LDLR and KIF16B protein was decreased (P＜0.05), meanwhile the interaction between LDLR and KIF16B was correspondingly weakened. Conclusion The interaction between KIF16B and LDLR possibly affects the process of that IDOL regulates LDLC uptake of hepatocytes.