Abstract:With the prevalence of obesity and metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) has replaced chronic hepatitis B as the leading chronic liver disease in China. In recent years, continuous exploration of the epidemiology and natural history of this disease, proposals for renaming, rapid advancements in diagnostic techniques, and continuous updates in treatment methods have propelled significant progress in the related diagnostic and therapeutic fields.Recently, experts in the Chinese Society of Hepatology revised the “Guidelines for the Prevention and Treatment of Non-Alcoholic Fatty Liver Disease (2018 Updated Version)” and published the “Guidelines for the Prevention and Treatment of Metabolic Dysfunction-associated (Non-alcoholic) Fatty Liver Disease (Version 2024)”. The updated guideline provides guiding recommendations on important clinical issues such as renaming and sorting, screening and monitoring, diagnosis and assessment, treatment, and follow-up for this disease. This article aims to interpret the key updates in this guideline to help clinical practitioners gain a more comprehensive understanding and apply them to guide clinical practice.

Abstract:Aim To explore the mechanism of oxidized lipoprotein(a) (oxLp(a) inducing pyroptosis of vascular endothelial cells. Methods After incubating human umbilical vein endothelial cells (HUVEC) with 100 mg/L oxLp(a) for 24 hours, Western blot and RT-qPCR was used to detect pyroptosis related proteins, pro-inflammatory cytokines, mitochondrial related proteins NRF1, NRF2, PGC-1α and mitochondrial gene cytochrome b (CYTB), ELISA was used to detect the levels of inflammatory factors, scanning electron microscopy was used to detect cell membrane rupture, transmission electron microscopy was used to detect mitochondrial morphology, Hoechst33342/PI staining was used to detect cell apoptosis, MitoSOX probe was used to detect mitochondrial reactive oxygen species (mtROS), Flu-4AM probe was used to detect calcium ions, JC-1 probe was used to detect mitochondrial membrane potential (MMP), and Calcein AM staining was used to detect mitochondrial permeability transition pore (mPTP). Transfecting HUVEC with CYTB overexpressing lentivirus and analyzing its effects on oxLp(a) induced pyroptosis and mitochondrial function. ResultsAfter treatment with oxLp(a), the expression of NLRP3, pro-Caspase-1, Caspase-1, GSDMD and GSDMD-N proteins related to pyroptosis were significantly increased (P＜0.05); the protein and mRNA levels of CYTB and pro-inflammatory cytokine IL-1β, IL-18 were significantly increased (P＜0.05). Small pores appeared on the cell membrane, the percentage of PI stained positive cells significantly increased (P＜0.05). OxLp(a) significantly inhibited the expression of mitochondrial related proteins NRF1, NRF2 and PGC-1α, and the expression of mitochondrial gene CYTB, promoted an increase in mtROS generation, Ca²＋ overload, a decrease in ATP levels, a decrease in MMP, an increase in mPTP values, and abnormal mitochondrial morphology. After transfection with pHelper 2.0 lentivirus vector overexpressing CYTB, it was found that oxLp(a) induced HUVEC pyroptosis and mitochondrial morphological and functional abnormalities were partially reversed by overexpression of CYTB. Conclusion oxLp(a) promotes mitochondrial morphological and functional abnormalities and induces HUVEC pyroptosis by downregulating CYTB.

Abstract:Aim To investigate the effects of naringenin on atherosclerotic plaque extracellular matrix remodeling and plaque stability. Methods Murine vascular smooth muscle cells were isolated and treated with various doges of naringenin. ApoE－/－ mice were fed with high-fat diet and received naringenin by lavage for 16 weeks. Intraplaque necrotic core, contents of collagen and fibrous cap thickness were measured by Sirius red-Haematoxylin staining. Elastin was detected by Van Gieson staining. Matrix metalloproteinase (MMP) activity was determined by gelatin zymography and fluorescence-gelatin staining.Results Naringenin (50 μmol/L) increased signal tansducer and activator of transciption 6 (STAT6) phosphorylation and promoted tissue inhibitor of metalloproteinase-3 (TIMP-3) expression by 3.1-fold (P＜0.001). After naringenin (80 mg/kg) treatment, compared with the control group, the area of plaque necrotic core in aortic root decreased by 53% (P＜0.01), the thickness of fibrous caps increased by nearly 50% (P＜0.05), and the degree of elastic fiber degradation decreased. At the same time, naringenin promoted the expression of TIMP-3 in plaques, and correspondingly reduced the activity of MMP in plaques. Lentivirus mediated inhibition of TIMP-3 expression in vivo could reduce the protective effect of naringenin on plaque stability. Conclusion Naringin can increase the expression of TIMP-3 in smooth muscle cells, improve the composition of extracellular matrix, and promote the stability of atherosclerotic plaque.

Abstract:Aim To investigate the shared transcriptional characteristics of non-alcoholic fatty liver disease (NAFLD) and atherosclerosis (As) using bioinformatics techniques. The goal is to identify potential mechanisms and key targets of As that are linked to NAFLD through gene crosstalk analysis of both diseases. Additionally, the study will validate the expression levels of these key targets in animal tissues and human serum samples. Methods The gene expression profiles of NAFLD (dataset GSE89632) and As (dataset GSE43292) were obtained from GEO database. Differential gene analysis and weighted gene co-expression network analysis were conducted to identify common genes between the two diseases. These shared genes were further analyzed using the String database for protein interaction analysis and R software. Core genes were identified through calculations in Cytoscape software, validation with external datasets (GSE100927), and machine learning techniques (LASSO regression). Finally, key core genes were determined by creating nonalcoholic fatty liver and As mouse models on a high-fat diet and collecting peripheral serum samples from patients with NAFLD and coronary heart disease (CHD). Results Seventy-five shared genes were identified between the two diseases, with major enrichment pathways including cytokine-cytokine receptor interaction, IL-17 signaling pathway, lipid and atherosclerosis, and NF-κB signaling pathway. Through integration of multiple bioinformatics methods, two core genes (MMP-9 and CCL3) were identified. Subsequent animal experiments demonstrated a significant increase in MMP-9 and CCL3 levels in the liver and aortic sinus of mice fed with high-fat diet, MMP-9 and CCL3 levels in the liver tissue of high-fat diet-fed mice were 2.43 times (P＜0.001) and 1.35 times (P＜0.01) higher than the control group, in the aortic sinus tissue, MMP-9 and CCL3 levels were 2.10 times (P＜0.001) and 1.58 times (P＜0.01) higher. Human serum sample verification further supported these findings, showing MMP-9 and CCL3 levels in patients with both NAFLD and CHD to be 1.21 times (P＜0.01) and 1.29 times (P＜0.01) higher than in patients with CHD alone. Conclusion This study identified MMP-9 and CCL3 may play key roles in NAFLD-related As, providing potential targets for the study of NAFLD-related As.

Abstract:Aim To investigate the relationship between triglyceride-glucose (TyG) index and the risk of hypertension in middle-aged and older adults in China, and to provide scientific basis for the prevention and treatment of hypertension. Methods Data were obtained from the China health and retirement longitudinal study (CHARLS) in 2011. A multi-stage stratified sampling method was used to select participants. Restricted cubic spline regression model was used to analyze the dose-response relationship between TyG index and the risk of hypertension. Multivariate unconditional Logistic regression model was used to evaluate the association between TyG index and the risk of hypertension.Results A total of 9 987 subjects were included in the analysis, with an average age of (59.16±9.43) years, including 4 707 males (47.13%). The restricted cubic spline regression model showed that the risk of hypertension increased with the elevation of TyG index, and there was a linear association (overall association test P＜0.000 1, non-linear association test P＝0.201 9). The results of multivariate Logistic regression model showed that compared with Q1 (TyG index＜8.23), the OR(95%CI) of hypertension with Q2 (8.23≤TyG index＜8.59), Q3 (8.59≤TyG index＜9.04) and Q4 (TyG index≥9.04), were 1.09 (0.95～1.26), 1.53 (1.33～1.76) and 1.77 (1.52～2.06), respectively. Conclusions With the increase of TyG index, the risk of hypertension gradually increased. TyG index may be an independent risk factor of hypertension.

Abstract:Aim To explore the correlation between atherogenic index of plasma (AIP), triglyceride-glucose (TyG) index and their severity in patients with chronic coronary syndrome (CCS). Methods A total of 298 patients diagnosed with CCS by coronary angiography were retrospectively selected from Cardiology Department of the First Hospital of Lanzhou University, from May 2017 to May 2023. Clinical indexes were collected and Gensini scores were calculated based on the results of the coronary angiography, clinical data of different Gensini integral groups was compared. Linear regression was used to analyze factors that influence the elevation of Gensini scores, and receiver operator characteristic (ROC) curve was used to determine the predictive value of AIP and TyG index for the severity of coronary artery lesions in CCS. Results The research sample consisted mostly of males (77.9%) with a mean age of (61.9±8.0) years. The adjusted AIP (aAIP) and TyG index of high Gensini score group were higher than those of low Gensini score group and medium Gensini score group, and the differences were significant. Linear regression analysis revealed that total cholesterol (TC), high density lipoprotein cholesterol (HDLC), aAIP and TyG index were the factors influencing the elevated Gensini scores (all P＜0.05). Correlation analysis revealed that aAIP and TyG index were negatively correlated with left ventricular ejection fraction (LVEF), positively correlated with Gensini scores, and positively correlated with stent implantation and the number of stent implantation (all P＜0.05). The ROC curve results indicated that when the aAIP threshold was 1.924, the area under the ROC curve (AUC) for predicting Gensini score ≥41 points was 0.583 (95%CI 0.525～0.640), with a sensitivity of 92.62%, a specificity of 25.50%, and Yoden index of 0.181. When the TyG index threshold was 8.748, the AUC for predicting Gensini score ≥41 points was 0.768 (95%CI 0.716～0.815), with a sensitivity of 77.18%, specificity of 67.11%, and Yoden index of 0.443. Conclusion The aAIP and TyG index were positively correlated with the severity of coronary artery disease in CCS patients. Both elevated levels can predict the severity of coronary lesions in CCS patients, but TyG index showed superior predictive ability compared with aAIP.

Abstract:Aim To investigate the clinical efficacy and preliminary mechanism of Yiqi Huoxue Jiangzhuo decoction combined with butylphthalide in the treatment of transient ischemic attack (TIA). Methods A total of 120 patients with TIA admitted to the First People's Hospital of Nanyang from January 2022 to March 2023 were selected as the research subjects and randomly divided into three groups with 40 cases in each group. The control group 1 was given butylphthalide, the control group 2 was given Yiqi Huoxue Jiangzhuo decoction, and the observation group was given Yiqi Huoxue Jiangzhuo decoctionn combined with butylphthalide for 2 months of treatment. After 2 months of treatment, the clinical efficacy and adverse reaction rate were compared among the three groups. The ABCD2 scores, national institute of health stroke scale (NIHSS) scores, and serum biochemical indicators (soluble CD40 ligand (sCD40L), lipoprotein-associated phospholipase A2 (Lp-PLA2), high-sensitive C-reactive protein (hs-CRP), peripheral blood Kelch-like epichlorohydrin-related protein-1 (Keap1)-nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway-related protein levels (Keap1, Nrf2, ARE) , and hemodynamic indicators (mean blood flow velocity (Vm), mean blood flow volume (Qm), cerebral vascular resistance (R) were compared before treatment and at 1 and 2 months after treatment in the three groups. Results The total clinical efficacy rate in observation group was significantly higher than that in control group 1 and control group 2 (P＜0.05), but there was no significant difference between the two control groups (P＞0.05). Compared with before treatment, the ABCD2 scores and NIHSS scores in the three groups showed a significant downward trend after 1 month and 2 months of treatment, and the decrease in observation group was larger than that in control group 1 and control group 2 (P＜0.05), but there was no significant difference between the two control groups (P＞0.05). Compared with before treatment, sCD40L, Lp-PLA2, and hs-CRP in the three groups showed a significant downward trend after 1 month and 2 months of treatment, and the decrease in observation group was larger than that in control group 1 and control group 2 (P＜0.05). Compared with before treatment, Keap1 protein in the three groups showed a significant downward trend after 1 month and 2 months of treatment, and the decrease in observation group was larger than that in control group 1 and control group 2 (P＜0.05), but there was no significant difference between the two control groups (P＞0.05). Compared with before treatment, the Nrf2 protein and ARE protein in the three groups showed a significant increase trend after 1 month and 2 months of treatment, and the increase amplitude in observation group was larger than that in control group 1 and control group 2 (P＜0.05), but there was no significant difference between the two control groups (P＞0.05). Compared with before treatment, Qm, Vm of the three groups increased and R decreased significantly at 1 month and 2 months after treatment, and the Qm, Vm in observation group were significantly higher than that in control group 1 and control group 2, while R was significantly lower than that in control group 1 and control group 2 (P＜0.05). Conclusion Yiqi Huoxue Jiangzhuo decoction combined with butylphthalide is more effective than butylphthalide and Yiqi Huoxue Jiangzhuo decoction alone in treating TIA, can improve neurological function, cerebral hemodynamics, inhibit inflammatory response, and has a certain degree of safety, and its mechanism of action is related to the regulation of Keap1-Nrf2/ARE signaling pathway.

Abstract:Aim To investigate the relationship between systemic inflammatory immune index (SII) and systemic inflammatory response index (SIRI) and the risk of in-hospital major adverse cardiovascular events (MACE) in patients with acute myocardial infarction (AMI). Methods Retrospective analysis was conducted on AMI patients admitted to the Second Cardiovascular Disease Area of Suining Central Hospital from February 2021 to May 2022. Based on inclusion and exclusion criteria, 246 patients were finally enrolled. According to whether MACE occurred during hospitalization, they were divided into event group and non-event group, and baseline data of the two groups were compared.All variables except SII and SIRI were included in a univariate-multivariate Logistic regression analysis to screen factors affecting the risk of MACE, and were used as significant covariates for adjustment to evaluate the relationship between SII and SIRI and the risk of MACE respectively. Results The results of multivariate Logistic regression analysis showed that emergency PCI, left ventricular ejection fraction, albumin level and age were significant factors affecting the risk of in-hospital MACE in AMI patients (OR＝0.2,5%CI:0.194～0.960, P＝0.038; OR＝0.0,5%CI:0.890～0.969, P＝0.001; OR＝0.0,5%CI:0.621～0.845, P＜0.001; OR＝1.3,5%CI:1.070～1.228, P＜0.001), and a basic model was established based on this. After adjusting for the significant covariates, SII and SIRI were both independent risk factors for in-hospital MACE (OR＝1.4,5%CI:1.001～1.008, P＝0.002; OR＝4.7,5%CI:2.597～8.142, P＜0.001). The areas under the curves of SII and SIRI were 0.658 and 0.785, respectively, and the optimal cutoff values were 434.83 and 1.03. Restricted cubic spline analysis showed that SII (Nonlinear P＝0.639) and SIRI (Nonlinear P＝0.683) were linearly related to the risk of MACE after adjusting significant covariates. Threshold effect analysis showed that when SIRI＞0.93, the risk of MACE began to increase. Conclusion Elevated levels of SII and SIRI are independent risk predictors for the occurrence of in-hospital MACE in AMI patients.

Abstract:Myocardial infarction is the most common cause of heart failure, and myocardial remodeling can occur after infarction, thus contributing to the progression of heart failure. The occurrence of post-infarction ventricular remodeling is closely related to m⁶A methylation. m⁶A methylation is a reversible and highly dynamic process. This process is mainly mediated by m⁶A methylation positive and negative regulatory enzymes and is involved in the occurrence of post-infarction myocardial remodeling through mechanisms such as cellular autophagy. This article mainly reviews relevant literature in recent years. Firstly, a brief introduction is given to m⁶A methylation, followed by an introduction to the role of m⁶A methylase in regulating myocardial remodeling. Finally, a summary analysis is conducted on the mechanism of m⁶A methylation in regulating myocardial remodeling from the perspectives of autophagy, inflammation, cell apoptosis, calcium ion homeostasis, extracellular matrix remodeling, and ferroptosis. The feasibility of using m⁶A methylation serological detection as a diagnostic tool for myocardial remodeling after myocardial infarction is discussed, in order to provide reference for related research.

Abstract:Histone deacetylase 3 (HDAC3) is an epigenetic modification enzyme, which participates in the occurrence and development of atherosclerosis (As). It is significant to search for effective HDAC3 inhibitors for the treatment of atherosclerosis. This article reviews the relationship between HDAC3 and atherosclerosis, the latest research progress of HDAC3 inhibitors, and the therapeutic effects of some traditional Chinese medicine on cardiovascular diseases by inhibiting HDAC3. It aims to provide new ideas for developing anti-atherosclerotic drugs targeting HDAC3.

Abstract:Vascular calcification refers to the process of calcium salt deposition in the blood vessel wall, leading to vascular stiffening and loss of elasticity. It commonly occurs in middle-aged and elderly individuals, especially those with chronic conditions such as atherosclerosis, hypertension, diabetes, and chronic kidney disease. Vascular calcification is an active process, and one of the key events is the transdifferentiation of smooth muscle cells into osteoblast-like cells. These cells release calcium ions during the calcification process, leading to calcium salt deposition and the formation of calcified plaques. Vascular calcification is regulated by various factors, including high levels of phosphate and calcium, oxidative stress, and mechanical stress. Traditional Chinese medicine research has shown potential in attenuating vascular calcification, with substances such as Ganoderma lucidum spore powder and its derivatives, Panax notoginseng, baicalin, geniposide, and triptolide. These studies provide important evidence for further understanding and intervention in vascular calcification and reveal potential inhibitory factors that could be explored for future treatments.

Abstract:Atherosclerosis (As) is the pathological basis of various vascular diseases, which affects the function of important organs. Recent studies have found that N⁶-methyladenosine (m⁶A) modification plays a vital role in As. This paper summarizes the regulatory effects of m⁶A modification on vascular endothelial cell (VEC) injury, vascular smooth muscle cell (VSMC) transformation, macrophage (M) differentiation, foam cell (FC) formation, pyroptosis, and lipid regulation, and summarizes the regulation function of some m⁶A regulatory proteins in As.

Abstract:Atherosclerotic calcified nodule is rare but important cause of coronary artery thrombosis and acute coronary syndrome. Eruptive calcified nodule is characterized by clusters of burst like calcified fragments protruding into the lumen accompanied by ruptured fibrous caps and thrombus attached to the surface, which is a potential cause of sudden cardiac death. The prognosis of acute coronary syndrome caused by calcified nodule is poor, and the incidence of perioperative myocardial infarction, cardiac death, and target lesion revascularization is high. This article reviews the progress in the diagnosis and treatment of atherosclerotic calcified nodule in coronary artery.