ObjectiveTo apply different machine learning menthods in screening of core autophagy genes in vulnerable plaques and investigate their association with immune infiltration.MethodsStable and unstable plaque samples from gene expression omnibus (GEO) datasets (GSE163154, GSE41571, GSE111782) were integrated, and through intersection of differentially expressed genes with the Human Autophagy Database, 14 candidate genes were obtained. Core autophagy genes were screened using least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination (SVM-RFE). Diagnostic value of core autophagy genes for unstable plaques were evaluated by receiver operating characteristic (ROC) curve analysis. A nomogram model was constructed to analyze the predictive value of core autophagy genes for unstable plaques, the predictive efficacy was verified using calibration curves and decision analysis curves. The CIBESORT algorithm was used to analyze the immune infiltration characteristics in stable plaque samples and unstable plaque samples. Correlations between core autophagy genes and different immune cells was analyzed by Pearson's method.ResultsFour core autophagy genes (CX3CL1, CTSD, MTMR14, and NRG1) were identified using two different machine learning methods. ROC curve analysis demonstrated their diagnostic value for unstable plaques, with area under the curve (AUC) values of 0.874, 0.876, 0.866, and 0.733, respectively. Calibration curve analysis indicated strong predictive performance of the nomogram model based on these core autophagy genes, showing high concordance with the ideal curve. Decision analysis curve confirmed favorable net benefits for predicting unstable plaques using the core autophagy gene nomogram model. Immune infiltration analysis revealed significant differences in immune cell composition between stable and unstable plaques and unstable plaques exhibited increased M0 macrophage infiltration (P < 0.05), but with a non-significant decreasing trend in M2 macrophages. The expression level of core autophagy genes had a strong correlation with the infiltration degree of various immune cells. The expression of some core autophagy genes showed significant correlations with M1 macrophage (P < 0.05).ConclusionMachine learning identified four core autophagy genes (CX3CL1, CTSD, MTMR14, and NRG1) that demonstrate significant diagnostic and predictive value for unstable plaques. The expression levels of these core autophagy genes are correlated with infiltration of macrophage.

ObjectiveTo explore the efficacy and safety of off-label use of domestically produced tenecteplase (TNK) for intravenous thrombolysis in the treatment of acute ischemic stroke (AIS) in the real world.MethodsA retrospective analysis was conducted on 350 AIS patients who received intravenous thrombolysis with domestically produced TNK or recombinant tissue plasminogen activator (rt-PA) within 4.5 hours of symptom onset at the First People's Hospital of Zhaoqing from April 2017 to January 2024. Patients were divided into the TNK group with 44 cases and the rt-PA group with 306 cases based on the medication. Baseline clinical data of patients were collected and compared, and the inverse probability weighting method based on propensity score (IPTW) method was employed to balance the differences of baseline clinical data between the TNK group and the rt-PA group. Symptomatic intracerebral hemorrhage (sICH) and early neurological deterioration (END) were used to evaluate the safety of intravenous thrombolysis. Patients were followed up for 3 months after thrombolysis, and the modified Rankin Scale (mRS) was employed to assess treatment efficacy. Differences in good prognosis, mRS scores, END, and sICH were compared between the TNK and rt-PA groups. Multivariate logistic regression analysis was performed to validate the robustness of the findings.ResultsAfter IPTW adjustment, no statistically significant differences were observed in baseline data (e.g., age, sex) between the two groups (all P > 0.05). The door-to-needle time (DNT) was significantly shorter in the TNK group than in the rt-PA group (Z=-2.602, P < 0.01). Comparisons of good prognosis, mRS scores, END, and sICH between the two groups showed no statistically significant differences (2/Z=0.949, -0.343, 0.395, 4.899; all P > 0.05). Multivariate Logistic regression analysis revealed no significant differences in the risks of good prognosis, END, or sICH between the TNK and rt-PA groups (OR=1.154, 0.729, 6.089; all P > 0.05).ConclusionFor AIS within 4.5 hours of onset, domestically produced TNK demonstrates comparable efficacy, safety, and cost-effectiveness to rt-PA for intravenous thrombolysis, suggesting TNK as a viable alternative treatment option.

ObjectiveTo explore the causal relationship between different types of drug poisoning and different types of stroke using Mendelian randomization (MR).MethodsDrug poisoning types included anticonvulsant and anti-Parkinsonism drug poisoning, as well as poisoning from analgesics, antipyretics, and antirheumatic drugs. The types of strokes encompassed ischemic stroke, large artery atherosclerotic ischemic stroke, small-vessel ischemic stroke, cardiogenic ischemic stroke, lacunar stroke, transient ischemic attack, intracerebral hemorrhage, and subarachnoid hemorrhage. The above data is sourced from the genome-wide association study (GWAS) public database. Bidirectional MR analysis was performed using six methods, including inverse variance weighted (IVW). Multiple sensitivity analyses were employed to test the results for pleiotropy and heterogeneity. The MRlap function was used to correct for causality in the presence of sample overlap, and Meta-analysis was utilized to deal with bias due to different outcome sources. Finally, reverse MR analyses were performed for drug intoxication types that were found to be causally associated with stroke in the forward MR analyses.ResultsAnticonvulsant and anti-Parkinsonism drug poisoning were protective factors for intracerebral hemorrhage (source from European Molecular Biology Laboratory) [OR(95%CI)=0.969(0.945-0.995), P < 0.05], while Meta-analysis showed anticonvulsant and anti-Parkinsonism drug poisoning had no protective effect on intracerebral hemorrhage [OR(95%CI)=0.938(0.845-1.042), P > 0.05]. Analgesics, antipyretics, and antirheumatic drugs poisoning were risk factors for small-vessel ischemic stroke and lacunar stroke[OR(95%CI)=1.074(1.011-1.142), 1.094(1.031-1.162); P < 0.05]. All results were free of heterogeneity and horizontal pleiotropy. In addition, there was no reverse causality between drug poisoning and stroke.ConclusionInappropriate use of different types of drugs can affect the risk of stroke.

ObjectiveTo explore the predictive value of combined detection of serum glucose regulated protein 78 (GRP78), insulin-like growth factor binding protein-6 (IGFBP-6), and clusterin for poor prognosis in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI).MethodsThis study selected 360 AMI patients who were treated at North China Medical Health Group Fengfeng General Hospital from January to December, 2023. All patients underwent one year of follow-up after PCI. Based on their prognosis during the follow-up period, patients were grouped into a good prognosis group (265 cases) and a poor prognosis group (95 cases). Enzyme-linked immunosorbent assay (ELISA) was applied to detect serum levels of GRP78, IGFBP-6, and clusterin. Color Doppler echocardiography was applied to detect left ventricular ejection fraction (LVEF) level in all patients. Chemiluminescence immunoassay was used to detect the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), and glycated hemoglobin (HbA1c). Multivariate Logistic regression analysis was used to analyze the influencing factors of poor prognosis in AMI patients after PCI. Pearson correlation analysis was used to analyze the correlation between serum GRP78, IGFBP-6, and clusterin levels in the poor prognosis group. Receiver operating characteristic (ROC) curve analysis was used to analyze the diagnostic value of serum GRP78, IGFBP-6, and clusterin levels for poor prognosis in AMI patients after PCI.ResultsThe heart rate and LVEF in the poor prognosis group were lower than those in the good prognosis group, while the serum levels of HbA1c, NT-proBNP, cTnI, CK-MB, GRP78, IGFBP-6, and clusterin were higher than those in the good prognosis group (P < 0.05). cTnI, GRP78, IGFBP-6, and clusterin were risk factors for poor prognosis in AMI patients after PCI [OR(95%CI)=1.473(1.040-2.088), 1.346(1.079-1.680), 1.742(1.121-2.708), 1.624(1.061-2.485); all P < 0.05]. There was a positive correlation between GRP78 and IGFBP-6, GRP78 and clusterin, and IGFBP - 6 and clusterin (r=0.426, 0.571, 0.551; P < 0.05) in the poor prognosis group. The areas under the curve (AUCs) of serum GRP78, IGFBP-6, and clusterin for predicting poor prognosis in AMI patients after PCI were 0.794, 0.742, and 0.790, respectively. The AUC of the combined diagnosis of the three was 0.913, which was better than the individual diagnosis (Z=4.695, 6.237, 5.241;P < 0.05).ConclusionSerum levels of GRP78, IGFBP-6, and clusterin are upregulated in AMI patients with poor prognosis after PCI. Each is a risk factor for poor post-PCI prognosis in AMI patients and demonstrates predictive value for poor prognosis in AMI patients after PCI. The combination of all three biomarkers shows superior predictive value.

ObjectiveTo investigate the effects of sacubitril/valsartan on myocardial energy metabolism and the expression of Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-B) mRNA in elderly patients with congestive heart failure (CHF) complicated by rapid atrial fibrillation (AF).MethodsA total of 150 elderly patients with CHF admitted to Xingtai Central Hospital from August 2022 to January 2024 were selected and randomly divided into a control group and an observation group. Patients who did not meet the inclusion and exclusion criteria were excluded. Eventually, 145 patients were included, including 71 in the control group and 74 in the observation group. The control group received conventional treatment, while the observation group was treated with additional sacubitril/valsartan. The following parameters were compared between the two groups: clinical efficacy, cardiac function parameters[ left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), and left ventricular ejection fraction (LVEF)], myocardial injury markers[ creatine kinase-MB(CK-MB), cardiac troponin I (cTnI), and N-terminal pro-B-type natriuretic peptide (NT-proBNP)], heart rate variability (HRV) indexes [standard deviation of NN intervals (SDNN), standard deviation of average NN intervals (SDANN), percentage of successive NN intervals differing by more than 50 ms (pNN50), and root mean square of successive differences (RMSSD)], myocardial energy metabolism markers [phosphocreatine to adenosine triphosphate (PCr/ATP) ratio, inorganic phosphate to phosphocreatine (Pi/PCr) ratio, and Pi/ATP ratio], mRNA expression levels of TLR4 and NF-B, and adverse events.ResultsThe total effective rate in the observation group was significantly higher than that in the control group (2=7.097, P < 0.01). After treatment, the observation group showed significant reduction in LVEDD and LVESD, and increase in LVEF (t=3.070, 3.903, 5.831; P < 0.05). Compared to the control group, CK-MB, cTnI, NT-proBNP in the observation group were significantly lower (t=2.475, 4.005, 16.011; P < 0.05), while SDNN, SDANN, PNN50, RMSSD were higher (t=14.236, 6.835, 8.243, 3.292; P < 0.05). Compared to the control group, Pi/PCr and Pi/ATP were lower in the observation group, while PCr/ATP were higher (t=2.601, 5.015, 3.593; P < 0.05). The mRNA expressions of TLR4 and NF-B in the observation group were lower than the control group (t=15.267, 10.855; P < 0.05). No statistically significant difference in adverse events was observed between the two groups (2=0.445, P > 0.05).ConclusionSacubitril/valsartan improves cardiac function and myocardial energy metabolism in elderly patients with CHF and rapid AF, while inhibiting TLR4 and NF-B expressions, demonstrating a favorable safety profile.

ObjectiveTo investigate the relationship between coronary collateral circulation status and Adropin level in patients with acute myocardial infarction.MethodsA total of 274 patients with acute myocardial infarction who underwent percutaneous coronary intervention (PCI) at the First Affiliated Hospital of Hebei North University from March, 2023 to April, 2024 were selected as the research object. All patients underwent coronary angiography. According to their coronary collateral circulation status, the patients were divided into a good circulation group (46 cases) and a poor circulation group (228 cases). General data, clinical parameters, and admission Adropin levels of patients from the two groups were compared. Pearson correlation analysis was used to evaluate the association between the coronary collateral circulation status and Adropin levels. Multivariate Logistic regression was applied to analyze the influencing factors of poor coronary collateral circulation.ResultsThe proportion of acute myocardial infarction patients with good coronary collateral circulation prior to PCI was 16.79%. There were statistically significant differences between the good and poor circulation groups in angina pectoris duration, white blood cell count, adrenaline and Adropin level, infarct location, and symptom-to-treatment time (2/t/U=8.668, 3.968, 7.392, 7.791, 6.500, 2.666; all P < 0.05). Pearson correlation analysis showed that Rentrop classification was positively correlated with Adropin level (r=0.683, P < 0.05). Multivariate Logistic regression analysis revealed that angina pectoris duration (OR=0.314), symptom-to-treatment time (OR=0.567), white blood cell count (OR=1.278), adrenaline (OR=0.948) and Adropin level (OR=0.902) were influencing factors for coronary collateral circulation status (P < 0.05).ConclusionAcute myocardial infarction patients with good coronary collateral circulation status have higher admission Adropin levels. Adropin level is identified as an influencing factor for the coronary collateral circulation status.

Bradyarrhythmia is a common clinical disease characterized by a marked decrease in heart rate. The etiology and pathogenesis of this disease are complex, and conditions such as coronary heart disease, various types of cardiomyopathies, cardiac degeneration, hypothyroidism, and others may contribute to its development. Some patients may show no obvious symptoms of discomfort, while others may experience symptoms such as shortness of breath and palpitations. In severe cases, patients may even faint, and the condition can become life-threatening. In recent years, with the continuous development of science and technology, there has been an increasing research focus on the etiology, pathogenesis, and diagnosis and treatment of bradyarrhythmia. This article summarizes the latest research progress on the etiology and treatment of bradyarrhythmia from the past decade, both domestically and internationally, aiming to provide guidance for clinical practice.