Glutamine supplementation alleviated aortic atherosclerosis in mice model and in vitro.

This study aimed to clarify the role of glutamine in atherosclerosis and its participating mechanism. Forty C57BL/6J mice were divided into wild control (wild Con), ApoE- /- control (ApoE- /- Con), glutamine + ApoE- /- control (Glut + ApoE- /- Con), ApoE- /- high fat diet (ApoE- /- HFD), and glutamine + ApoE- /- HFD (Glut + ApoE- /- HFD) groups. The degree of atherosclerosis, western blotting, and multiomics were detected at 18 weeks. An in vitro study was also performed. Glutamine treatment significantly decreased the degree of aortic atherosclerosis (p = 0.03). O-GlcNAcylation (O-GlcNAc), IL-1ß, IL-1α, and pyruvate kinase M2 (PKM2) in the ApoE- /- HFD group were significantly higher than those in the ApoE- /- Con group (p < 0.05). These differences were attenuated by glutamine treatment (p < 0.05), and aggravated by O-GlcNA transferase (OGT) overexpression in the in vitro study (p < 0.05). Multiomics showed that the ApoE- /- HFD group had higher levels of oxidative stress regulatory molecules (guanine deaminase [GUAD], xanthine dehydrogenase [XDH]), proinflammatory regulatory molecules (myristic acid and myristoleic acid), and stress granules regulatory molecules (caprin-1 and deoxyribose-phosphate aldolase [DERA]) (p < 0.05). These differences were attenuated by glutamine treatment (p < 0.05). We conclude that glutamine supplementation might alleviate atherosclerosis through downregulation of O-GlcNAc, glycolysis, oxidative stress, and proinflammatory pathway.

Precise Metabolomics Defines Systemic Metabolic Dysregulation Distinct to Acute Myocardial Infarction Associated With Diabetes.

BACKGROUND: Acute myocardial infarction (AMI) is a leading cause of death and disability. Diabetes is an important risk factor and a common comorbidity in AMI patients. The higher mortality risk of diabetes-AMI relative to nondiabetes-AMI indicates a need for specific treatment to improve clinical outcome. However, the global metabolic dysregulation of AMI complicated with diabetes is still unclear. We aim to systematically interrogate changes in the metabolic microenvironment immediate to AMI episodes in the absence or presence of diabetes. METHODS: In this work, quantitative metabolomics was used to investigate plasma metabolic differences between diabetes-AMI (n=59) and nondiabetes-AMI (n=59) patients. A diverse array of perturbed metabolic pathways involving carbohydrate metabolism, lipid metabolism, glycolysis, tricarboxylic acid cycle, and amino acid metabolism emerged. RESULTS: In all, our omics-oriented approach defined a metabolic signature of afflicted mitochondrial function aggravated by concurrent diabetes in AMI patients. In particular, our analyses uncovered N-lactoyl-phenylalanine and lysophosphatidylcholines as key functional metabolites that skewed the metabolic picture of diabetes-AMI relative to nondiabetes-AMI. N-lactoyl-phenylalanine was strongly associated with metabolic indicators reflective of mitochondrial overload and negatively correlated with HbA1c (glycosylated hemoglobin, type A1C) specifically in hyperglycemic AMI, suggestive of its central role in glucose utilization and mitochondrial energy production instrumental to the clinical outcome of diabetes-AMI. Reductions in lysophosphatidylcholines, which were negatively correlated with blood glucose and inflammatory markers, might further compromise glucose expenditure and aggravate inflammation leading to poorer prognosis in diabetes-AMI. CONCLUSIONS: As circulating metabolite levels are amenable to therapeutic intervention, such shifts in metabolic signatures provide new clues and potential therapeutic targets specific to the treatment of diabetes-AMI.

Activation of macrophage TBK1-HIF-1α-mediated IL-17/IL-10 signaling by hyperglycemia aggravates the complexity of coronary atherosclerosis: An in vivo and in vitro study.

Our purpose was to study the effect of hyperglycemia on macrophage TBK1-HIF-1α-mediated IL-17/IL-10 signaling and its correlation with coronary atherosclerosis. A total of 135 patients with coronary heart disease (CHD) were divided into a stable CHD (SCHD) group (n = 30) and an acute myocardial infarction (AMI) group (n = 105) [nondiabetes mellitus (non-DM)-AMI, n = 60; DM-AMI, n = 45] from January to September 2020. The SYNTAX score and metabolic and inflammatory markers were quantified and compared. THP-1 cell studies and an animal study of coronary intimal hyperplasia were also carried out. We found that the DM-AMI group showed a higher SYNTAX score than the non-DM-AMI group (P < .05). The DM-AMI group showed the highest expression levels of TANK-binding kinase 1 (TBK1), hypoxia-inducible factor 1α (HIF-1α), and interleukin (IL)-17 and the lowest expression level of IL-10, followed by the non-DM-AMI group and the SCHD group (P < .05). THP-1 cell studies showed that BAY87-2243 (a HIF-1α inhibitor) reversed the increase in IL-17 and decrease in IL-10 expression induced by hyperglycemia. Amlexanox (a TBK1 inhibitor) reversed the increase in HIF-1α expression induced by hyperglycemia. Amlexanox treatment resulted in lower coronary artery intimal hyperplasia and a larger lumen area in a diabetic swine model. We conclude that hyperglycemia might aggravate the complexity of coronary atherosclerosis through activation of TBK1-HIF-1α-mediated IL-17/IL-10 signaling. Thus, TBK1 may be a novel drug therapy target for CHD complicated with DM.

Dynamic Changes in Plasma Urotensin II and Its Correlation With Plaque Stability.

ABSTRACT: Urotensin II (UII) is involved in the formation of atherosclerosis, but its role in the stability of atherosclerotic plaques is unknown. The purpose of this study was to observe the dynamic changes in plasma UII and analyze its relationship to the stability of atherosclerotic plaques. One hundred thirty-five consecutive patients with acute coronary syndrome (ACS) were enrolled. The plasma UII levels were measured immediately after admission and during three-month follow-up. A vulnerable plaque model was established using local transfection of a recombinant P53 adenovirus into plaques in rabbits fed with a high-cholesterol diet and subjected to balloon arterial injury. The levels of plasma UII were measured weekly. The changes in plasma UII during the formation of atherosclerotic plaques and before and after plaque transfection were observed. The morphology of the plaques and the expression, distribution, and quantitative expression of UII in the plaques also were observed. Our results showed that the levels of plasma UII in patients with ACS at admission were lower than levels observed at the three-month follow-up. UII dynamic changes and its correlation with plaque stabilities were further verified in rabbits with atherosclerotic vulnerable plaques. The UII levels in rabbits were significantly decreased immediately after the P53 gene transfection, which led to plaque instability and rupture. These results suggested that UII expression was down-regulated in ACS, which may be related to its ability to modulate mechanisms involved in plaque stability and instability.

Glucose Variability and Coronary Artery Disease.

Fasting blood glucose, postprandial blood glucose and glycated haemoglobin are considered three important indicators for diabetes treatment. There is increasing evidence that glucose variability has more detrimental effects on the coronary arteries than does chronic sustained hyperglycaemia. This overview summarises recent findings in the field of glucose variability and its possible relationship with coronary artery disease. Glucose variability may be a marker of increased progression of coronary disease and plaque vulnerability. It might be a potential new therapeutic target for secondary prevention of coronary artery disease. Future studies will focus on the early detection and control of glucose variability to improve the clinical outcomes in patients with coronary artery disease.

The correlation between glucose fluctuation from self-monitored blood glucose and the major adverse cardiac events in diabetic patients with acute coronary syndrome during a 6-month follow-up by WeChat application.

Background This study aimed to investigate the correlation between glucose fluctuation from self-monitored blood glucose (SMBG) and the major adverse cardiac events (MACE) in diabetic patients with acute coronary syndrome (ACS) during a 6-month follow-up period using the WeChat application. Methods From November 2016 to June 2017, 262 patients with ACS were discharged in a stable condition and completed a 6-month follow-up period. SMBG was recorded using the WeChat application. The patients were divided to a high glucose fluctuation group (H group; n=92) and a low glucose fluctuation group (L group; n=170). The 6-month incidence of MACE, lost-to-follow-up rate and satisfaction rate were measured through the WeChat follow-up. Results MACE occurred in 17.4% of patients in the H group and in 8.2% of patients in the L group (p=0.04). Multivariable analysis suggested that high glucose fluctuation conferred an 87% risk increment of MACE in the 6-month follow-up period (odds ratio: 2.1, 95% confidence interval 1.95-4.85; p=0.03). The lost-to-follow-up rate was lower and the satisfaction rate was higher in the patients using the WeChat application during follow-up than those of the regular outpatient follow-up during the same period (p<0.05). Conclusions The trial demonstrates that higher glucose fluctuation from SMBG after discharge was correlated with a higher incidence of MACE in diabetic patients with ACS. WeChat follow-up might have the potential to promote a good physician-patient relationship.

A 6-Month Follow-Up Study of the Relation between Apolipoprotein E Gene Polymorphism and Major Adverse Cardiovascular Events in Patients with Acute Coronary Syndrome.

OBJECTIVES: This study aimed to investigate the relation between ApoE gene polymorphisms and major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS) during a 6-month follow-up. METHODS: From October 2016 to July 2017, 211 patients were admitted to a cardiology clinic with a diagnosis of ACS. Blood samples were obtained from all patients on the first day. The primary end point was a 6-month incidence of MACE. ApoE gene polymorphism was genotyped by real-time PCR using TaqMan® SNP Genotyping Assay. RESULTS: The patients with the E4 allele were associated with higher low-density lipoprotein (LDL) cholesterol and total cholesterol (TC) levels compared with the patients without the E4 allele (p = 0001 and p = 0.001). The patients with the E4 allele were associated with a higher rate of MACE compared with the patients without the E4 allele (ApoE4 allele(+) 23.1% vs. ApoE4 allele(-) 9.3%; p = 0.03). Multivariable analysis suggested that E4 allele carriers showed an 85% risk increment of 6-month MACE (odds ratio 2.48, 95% confidence interval 2.37-5.95; p = 0.01). CONCLUSIONS: The trial shows that E4 allele carriers were correlated with not only higher LDL cholesterol and TC levels, but also with a higher incidence of MACE during a 6-month follow-up.

Effect of novel bioresorbable scaffold composed of poly-L-lactic acid and amorphous calcium phosphate nanoparticles on inflammation and calcification of surrounding tissues after implantation.

To study the effect of novel bioresorbable scaffold composed of poly-L-lactic acid (PLLA) and amorphous calcium phosphate (ACP) nanoparticles on inflammation and calcification of surrounding tissues after implantation. Ninety six PLLA/ACP scaffolds and 96 PLLA scaffolds were randomly implanted in the back muscle tissue of 48 SD rats. At the 1st, 2nd, 4th, and 12th weeks after implantation, the calcium, phosphorus, and alkaline phosphatase levels in the blood serum and the contents of calcium and alkaline phosphatase in the tissue surrounding the scaffolds were measured. Hematoxylin-eosin staining was performed to count the inflammatory cells. Von kossa staining was performed to observe calcification of the surrounding tissue around the scaffold. NF-κB staining was performed by immunohistochemistry to calculate the positive expression index of inflammatory cells. Western blot was used to detect the expression of IL-6 and BMP-2 in the tissues surrounding the scaffolds. At the 1st, 2nd, 4th, and 12th weeks after scaffold implantation, there were no significant difference in the serum concentration of calcium, phosphorus, alkaline phosphatase and in the tissue homogenate concentration of alkaline phosphatase between the two groups (P > 0.05). The level of calcium in tissue homogenates was lower in the PLLA/ACP group than in the PLLA group at 12-week (P < 0.05). The hematoxylin-eosin staining results showed that the inflammatory cell count in the PLLA/ACP group was lower than the PLLA group at 4-week and 12-week (P < 0.05). The results of NF-kB positive expression index showed that the PLLA group was significantly more than the PLLA/ACP group at 4-week and 12-week (P < 0.01). Western blot results showed that IL-6 expression levels in the PLLA/ACP group scaffolds were significantly lower than those in the control group at the 2-week, 4-week and 12-week (P < 0.05). The expression of BMP-2 in the PLLA group was significantly lower than that in the control group at 4-week and 12-week (P < 0.05). The PLLA/ACP composite material has good histocompatibility. The integration of nanoscale ACPs reduces the inflammatory response induced by acidic metabolites of PLLA material and may inhibit tissue calcification by reducing the amount of calcification factors in the body.

Optical Coherence Tomography Assessment of Glucose Fluctuation Impact on the Neointimal Proliferation After Stent Implantation in a Diabetic/Hypercholesterolemic Swine Model.

The aim of the present study was to investigate the effects of glucose fluctuation on neointimal proliferation after stent implantation by optical coherence tomography (OCT) in a diabetic/hypercholesterolemic (DM/HC) swine model.A total of 24 everolimus-eluting stents (EES) were implanted in the right coronary artery (RCA) of the animals using a 20% overstretch ratio. The 24 swines were divided into a DM-high glucose fluctuation (HGF) group (n = 8), DMlow glucose fluctuation (LGF) group (n = 8), and a control group (n = 8). Percent diameter stenosis (%DS), late loss (LL), percent area stenosis (%AS), and neointimal thickness (NIT) were analyzed. The differences in neointimal characteristics and circulating oxidative stress and inflammation biomarkers were assessed and measured.At 28 days, the highest values of %DS, LL, %AS, and NIT were achieved in the HGF group followed by the LGF group (P < 0.05) and the control group (P < 0.05). The highest frequency of the heterogeneous pattern was in the HGF group followed by the LGF group (P < 0.05) and the control group (P < 0.05). This was also the case for the oxidative stress and inflammation biomarkers.DM might have a deleterious impact on neointimal proliferation after EES implantation in this DM/HC swine model. The extent of glucose fluctuation may be related to the degree of neointimal proliferation and this needs to be further confirmed by long-term follow-up and histology.

Efficacy of High-Intensity Atorvastatin for Asian Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Statins have proven cardioprotective effects, but higher doses are accompanied by various concerns and may not lead to superior clinical outcomes in Chinese/Asian populations. OBJECTIVE: We designed a trial to test the efficacy of high-intensity statin therapy for the reduction of periprocedural myocardial infarction (MI) and 1-year major adverse cardiovascular events (MACEs, including cardiovascular death, spontaneous MI, unplanned revascularization) in an Asian population. METHODS: A total of 798 Chinese patients with stable angina or acute coronary syndrome (ACS) were randomized to high-intensity atorvastatin (80 mg/d before percutaneous coronary intervention [PCI] and 40 mg/d thereafter for 1 year, n = 400) or moderate-intensity atorvastatin (20 mg/d for 1 year, n = 398). The primary end point was 1-year incidence of MACEs. RESULT: In patients with stable angina, 1-year MACE rates were not significantly different between moderate- and high-intensity groups (7.6% vs 5.7%, P = 0.53). In contrast, in patients with ACS, the 1-year MACE rate was significantly higher in the moderate- than in the high-intensity atorvastatin group (16.8% vs 10.1%, P = 0.021; adjusted hazard ratio = 1.71, 95% CI = 1.08 to 2.77, P = 0.021). CONCLUSIONS: Whereas stable angina patients derive similar benefit from moderate- and high-intensity atorvastatin therapy over the duration of 1 year after PCI, high-intensity statin therapy is superior in ACS patients.

Preoperative rosuvastatin protects patients with coronary artery disease undergoing noncardiac surgery.

OBJECTIVES: We explored whether preoperative rosuvastatin could protect the cardiac health of patients with coronary artery disease undergoing emergency, noncardiac surgery. METHODS: We randomized 550 noncardiac emergency surgery patients with stable coronary artery disease on long-term statin therapy to treatment with and without preoperative rosuvastatin. All patients received rosuvastatin after surgery. We evaluated the incidence of myocardial necrosis and major adverse cardiovascular and cerebrovascular events (MACCE) 30 days and 6 months after surgery. RESULTS: Creatinine kinase-myocardial band (CK-MB) isoform elevations occurred less frequently 12 and 24 h after noncardiac emergency surgery in the experimental group than in the control group (p = 0.029). After surgery, the incidence of MACCE was also lower in the experimental group than in the control group (p = 0.019). The difference was mainly due to the incidence of perioperative myocardial infarction (p = 0.029). Multivariable analysis found that rosuvastatin reload reduced the incidence of MACCE 52% 6 months after surgery (p = 0.03). CONCLUSIONS: Preoperative rosuvastatin reload therapy decreases the incidence of myocardial necrosis and MACCE after noncardiac emergency surgery in patients with stable coronary artery disease on long-term statin therapy.

[Midterm follow-up outcomes of ticagrelor on acute ST segment elevation myocardial infarction undergoing emergency percutaneous coronary intervention].

OBJECTIVE: To evaluate the safety and efficacy of antiplatelet therapy of ticagrelor on patients suffering from acute ST segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. METHODS: In the study, 96 patients suffering from acute ST segment elevation myocardial infarction onset within 12 h undergoing primary percutaneous coronary intervention from May to October in 2013 were randomly divided into ticagrelor group (n=48) and clopidogrel group (n=48) by using the method of random number table. Ticagrelor and clopidogrel antiplatelet treatment were used before and after operation. Their baseline data, coronary artery disease characteristics, platelet count, adenosine diphosphate(ADP)-induced platelet inhibition rate by thrombelastograph after 5 days of treatment, the major adverse cardiovascular events of the follow up for 6 months and bleeding complications were observed and compared in the two groups. RESULTS: The differences between the two groups of patients with their baseline data, the features of coronary artery lesions, platelet count before and after 5 days of treatment had no statistical significance (P>0.05). ADP induced platelet inhibition rate [(80.2±10.7)%] after 5 days of treatment in ticagrelor group was significantly higher than that in clopidogrel group [(75.3±12.1)%, P<0.05]. The two groups of patients were followed up for 6 months, 8 cases of major adverse cardiovascular events occurred in clopidogrel group, 2 cases of major adverse cardiovascular events occurred in ticagrelor group, and there was significant difference between the two groups (P<0.05). The two groups (7 cases of 48 patients in ticagrelor group vs. 3 cases of 48 patients in clopidogrel group) had no statistically significant difference in bleeding complications (P>0.05). CONCLUSION: Antiplatelet therapy of ticagrelor on patients suffering from acute ST segment elevation myocardial infarction undergoing emergency PCI has good efficacy and safety.

Patients with stable coronary artery disease receiving chronic statin treatment who are undergoing noncardiac emergency surgery benefit from acute atorvastatin reload.

OBJECTIVE: This study was designed to investigate whether patients with stable coronary artery disease (CAD) receiving chronic statin treatment who are undergoing noncardiac emergency surgery benefit from acute atorvastatin reload. METHODS: A total of 500 patients with stable CAD and regular administration of statin before noncardiac emergency surgery were randomized to atorvastatin reload (n = 250) or placebo (n = 250). All patients received atorvastatin treatment thereafter. The primary end point was a 30-day incidence of major adverse cardiac events (MACE). Secondary end points were the incidence of atrial fibrillation (AF) during hospitalization and length of hospital stay. RESULTS: The primary end point occurred in 2.4% of patients treated with atorvastatin reload and in 8% in the placebo arm (p = 0.0088). The incidence of AF during hospitalization was 6.8% in patients treated with atorvastatin reload and 17% in the placebo arm (p = 0.0003). Compared with the placebo arm, the atorvastatin reload arm shortened the length of stay (9.8 ± 3.3 vs. 10.6 ± 3.5 days, p = 0.009). Multivariable analysis suggested that atorvastatin reload conferred a 65% risk reduction of 30-day MACE (odds ratio 0.35, 95% confidence interval 0.18-0.86; p = 0.005). CONCLUSION: The trial suggests that atorvastatin reload may improve the clinical outcome of patients with stable CAD receiving chronic statin treatment who are undergoing noncardiac emergency surgery.

[Cardioprotective effect and mechanism of intensive lipid modulation on patients with coronary artery disease undergoing noncardiac surgery].

OBJECTIVE: To explore the protective effect and possible mechanism of intensive lipid modulation on the perioperative period of patients with stable coronary artery disease undergoing noncardiac surgery. METHODS: In the study, 60 patients with stable coronary artery disease undergoing elective noncardiac surgery were randomly divided into intensive lipid modulation group (n = 30) and conventional group (n = 30). In intensive lipid modulation group, the patients were given atorvastatin 40 mg every night before surgery, 80 mg 12 h before surgery, and 40 mg 2 h before surgery, and 40 mg every night after noncardiac surgery. In conventional group, the patients were given atorvastatin 20 mg every night before surgery and also after the surgery. The occurrence of perioperative major adverse cardiac events (including sudden cardiac death, acute myocardial infarction, unplanned revascularization) were compared in the two groups. Preoperative and 48 h postoperative changes of lipid levels and inflammatory markers were also compared in the two groups. RESULTS: In conventional group, one patient suffered myocardial infarction with acute anterior ST-segment elevation and was given emergency left anterior descending artery interventional reperfusion therapy, and 7 patients suffered asymptomatic myocardial infarction. In intensive lipid modulation group, one patient suffered asymptomatic myocardial infarction, and the incidence rate of perioperative acute myocardial infarction reduced significantly compared with conventional group (P < 0.05). There was no significant difference in preoperative and postoperative changes of lipid levels in the two groups (P > 0.05), and compared with conventional group, there was significantly lower levels of inflammatory markers in intensive lipid modulation group (P < 0.05). CONCLUSION: The intensive lipid modulation group significantly reduced the incidence of perioperative major adverse cardiac events especially asymptomatic myocardial infarction, and the inhibition of the inflammatory response may be one of the protective mechanisms, which still needs to be further confirmed by large multicenter randomized controlled clinical trials.

Phenome-Wide Investigation of the Causal Associations Between Pre-Pregnancy Obesity Traits and Gestational Diabetes: A Two-Sample Mendelian Randomization Analyses.

Pre-pregnancy obesity was associated with gestational diabetes in observational studies, but whether this relationship is causal remains to be determined. To evaluate whether pre-pregnancy obesity traits causally affect gestational diabetes risk, a two-sample Mendelian randomization (MR) analysis was performed utilizing summary-level statistics from published genome-wide association studies (GWAS). Obesity-related traits included body mass index (BMI), overweight, obesity, obesity class 1, obesity class 2, obesity class 3, childhood obesity, waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), percent liver fat, visceral adipose tissue volume, abdominal subcutaneous adipose tissue volume. Effect estimates were evaluated using the inverse-variance weighting method. Weighted median, MR-Egger, simple mode, and weighted mode were performed as sensitivity analyses. Genetically predicted pre-pregnancy BMI [odds ratio (OR) = 1.68; 95% confidence interval (CI): 1.45-1.95; P = 9.13 × 10-12], overweight (OR = 1.49; 95% CI: 1.21-1.85; P = 2.06 × 10-4), obesity (OR = 1.25; 95% CI: 1.18-1.33; P = 8.01 × 10-13), obesity class 1 (OR = 1.31; 95% CI: 1.17-1.46; P = 1.49 × 10-6), obesity class 2 (OR = 1.26; 95% CI: 1.16-1.37; P = 5.23 × 10-8), childhood obesity (OR = 1.33; 95% CI: 1.23-1.44; P = 4.06 × 10-12), and WHR (OR = 2.35; 95% CI: 1.44-3.83; P = 5.89 × 10-4) were associated with increased risk of gestational diabetes. No significant association was observed with obesity class 3, WC, HC, percent liver fat, visceral adipose tissue volume, or abdominal subcutaneous adipose tissue volume. Similar results were observed in sensitivity analyses. Therefore, genetically predicted pre-pregnancy obesity traits may increase the risk of gestational diabetes. Weight control before pregnancy may be beneficial to prevent gestational diabetes.

Lipidomic analyses reveal potential biomarkers for predicting death and heart failure after acute myocardial infarction.

Background Acute myocardial infarction (AMI) and postmyocardial infarction heart failure (pMIHF) have high mortality rates worldwide. This study aimed to explore lipidomic profiles and identify potential biomarkers for the prediction of death and heart failure (HF) after AMI. Methods All serum samples were collected at Xuanwu Hospital, Capital Medical University, and their clinical characteristics and lipidomic profiles were analyzed in different groups. LC-MS/MS was used for lipidomic analyses, and underlying biomarkers were screened by receiver operating characteristic (ROC) curve analysis. Results Lipidomic analyses of the survival and nonsurvival groups revealed that the decrease of the content of SM (d18:1/22:0), PE (P-20:1/18:0), PC (18:2), LPE (18:2), PE (P-20:0/18:0), LPC (18:0) and PC (20:0/20:3) while increase of the content of PG (18:1/18:1) could increase the risk of death after AMI. In parallel, the lipidomic analysis of the HF and non-HF groups revealed that the decrease of the content of PC (20:3/20:4), LPC (20:3), LPC (18:0), LPC (18:2), LPC (20:0), LPC (18:3), LPE (16:1) and PC (18:2/20:3) could increase the risk of HF after AMI. Conclusion Several lipids could be potential biomarkers for the prediction of death and HF after AMI.

Identification of molecular markers for predicting the severity of heart failure after AMI: An Olink precision proteomic study.

BACKGROUND: Acute myocardial infarction (AMI) still has a high incidence of varying degrees of heart failure (HF). The aim of this study is to identify new molecular markers for predicting the severity of HF after AMI. METHODS: We analyzed demographic indicators, past medical history, clinical indicators, major adverse cardiac events (MACEs) and molecular markers in patients with different Killip classifications after AMI. Olink proteomics was used to explore new molecular markers for predicting different severity of HF after AMI. RESULTS: Neutrophil count was the independent risk factors for in-hospital MACEs. Nineteen differentially expressed proteins (DEPs) increased significantly with increasing Killip classification. Five DEPs were also found to have an AUC (95 % CI) value greater than 0.8: GDF-15, NT-pro BNP, TNF-R2, TNF-R1 and TFF3. CONCLUSIONS: Neutrophil count, GDF-15, TNF-R2, TNF-R1 and TFF3 were closely related to the Killip classification of HF after AMI, which suggests that the inflammatory response plays an important role in the severity of HF after AMI and that regulating inflammation might become a new target for controlling HF.

Knowledge, Attitude and Practice Toward COVID-19: A Cross-Sectional Study of Staff in China-Guinea Friendship Hospital, Guinea.

Background: The purpose of this study was to assess the level of knowledge, attitude and practice of COVID-19 among staff in China-Guinea Friendship Hospital, and to confirm the effect of nosocomial infection management. Methods: This cross-sectional study was conducted in December 2021. Information on socio demographic data, knowledge, attitude and practices related to COVID-19 was collected through a self-administered questionnaire. Results: A total of 143 employees participated in the survey, with a response rate of 99.31% and a vaccination rate of 95.10%. The average knowledge score of COVID-19 was 8.39 ± 1.3 points (10 points in total), without significant differences between subgroups with different demographic variables (P > 0.05); more than 80% of the participants had a positive attitude, and 72.03-93.01% of the participants could take appropriate preventive practices in different environments such as hospital, outdoor or home. Conclusion: The staff of the China-Guinea Friendship Hospital has good knowledge of COVID-19, a positive attitude and appropriate preventive practices. It can be concluded that the current nosocomial infection management is active and effective. Therefore, this study suggests that comprehensive activities such as training, promotion and supervision of COVID-19-related knowledge and countermeasures should be widely and continuously implemented in healthcare facilities, which will continuously improve the overall KAP level of hospital staff and play an important role in curbing the COVID-19 pandemic.

A GLP-1 Analog Liraglutide Reduces Intimal Hyperplasia After Coronary Stent Implantation via Regulation of Glycemic Variability and NLRP3 Inflammasome/IL-10 Signaling in Diabetic Swine.

OBJECTIVE: This study aimed to explore whether treatment with the glucagon-like peptide-1 (GLP-1) analog liraglutide reduces intimal hyperplasia after coronary stent implantation via regulation of glycemic variability, the NLRP3 inflammasome, and IL-10 in diabetic swine. METHODS: Fifteen pigs were divided into a diabetes mellitus (DM) group (n = 6), a DM + liraglutide treatment group (L group) (n = 6) and a sham group (n = 3). A total of 24 everolimus-eluting stents were implanted in the left anterior descending and right coronary arteries at 3 weeks. A novel continuous glucose monitoring system (GMS) was used for 2 weeks. The means and standard deviations (SDs) were measured and calculated by the GMS. At 22 weeks, the lumen area (LA), neointimal thickness (NIT), neointimal area (NIA), and percent area stenosis (%AS) were analyzed by optical coherence tomography. Plasma tumor necrosis factor-α, interleukin-6, and interleukin-10 were assayed by ELISA. The intima protein expression levels of NLRP3, interleukin-1ß, interleukin-18 and interleukin-10 were examined using Western blot analysis. Histology was used to evaluate the healing response. In an in vitro study, THP-1 cells were divided into control, high glucose (HG), HG + liraglutide, and HG + liraglutide + Exe(9-39) (a GLP-1 receptor inhibitor) groups. RESULTS: The L group had a lower SD, NIT, NIA, and %AS; a larger LA; reduced inflammation and injury scores; lower expression levels of tumor necrosis factor-α, interleukin-6, NLRP3, interleukin-1ß, and interleukin-18; and higher expression of interleukin-10 compared with those of the DM group (p < 0.05). In the in vitro study, similar results were obtained in the HG + liraglutide group, and Exe(9-39) abolished the effect of liraglutide (p < 0.05). CONCLUSIONS: Liraglutide treatment reduces intimal hyperplasia after stent implantation via regulation of glycemic variability, the NLRP3 inflammasome, and IL-10 in diabetic pigs in a GLP-1 receptor-dependent manner. Reducing the inflammation induced by glycemic variability may be one of the cardioprotective mechanisms of liraglutide.

The impact of hyperglycaemia on PKM2-mediated NLRP3 inflammasome/stress granule signalling in macrophages and its correlation with plaque vulnerability: an in vivo and in vitro study.

BACKGROUND: The mechanism of pyruvate kinase M2 (PKM2)-mediated inflammatory signalling in macrophages when plaques rupture and the impact of hyperglycaemia on the signalling are unclear. The present study aimed to explore the impact of hyperglycaemia on PKM2-mediated NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome/stress granule signalling in macrophages and its correlation with plaque vulnerability in vivo and in vitro. METHODS: From July to December 2019, 80 patients with coronary heart disease (CHD) were divided into acute ST-segment elevation myocardial infarction (STEMI) (n = 57) (DM-STEMI, n = 21; non-DM-STEMI, n = 36) and stable CHD (SCHD) groups (n = 23). Circulating mononuclear cells were isolated. The value of peak troponin I (TnI), the Global Registry of Acute Coronary Events (GRACE) risk score, and the expression levels of the related markers were quantified and compared. In vitro studies on the THP-1 cells were also performed. RESULTS: The DM-STEMI group had a higher value of peak TnI and a higher GRACE risk score than the non-DM-STEMI group (p < 0.05). The highest expression levels of PKM2, NLRP3, interleukin (IL)-1ß, and IL-18 and the lowest expression level of GTPase activating protein (SH3 domain)-binding protein 1 (G3BP1) (a stress granule marker protein) were observed in the DM-STEMI group, and they were followed by the non-DM-STEMI group and the SCHD group (p < 0.05). In vitro studies showed similar results and that TEPP-46 (a PKM2 activator) and 2-deoxy-d-glucose (a toxic glucose analogue) reversed the hyperglycaemia-induced increase in the NLRP3 inflammasome and decrease in G3BP1 expression. CONCLUSION: Hyperglycaemia might increase the activation of PKM2-mediated NLRP3 inflammasome/stress granule signalling and increase plaque vulnerability, associating it with worse prognosis. PKM2 may be a novel prognostic indicator and a new target for the treatment of patients with CHD and DM.