Association among ß2-adrenergic receptor autoantibodies and proximal left anterior descending artery lesions in patients with initial ST-segment elevation myocardial infarction.

BACKGROUND: ß2 -adrenergic receptor autoantibody (ß2 -AA) are widely present in patients with many different types of cardiovascular diseases. Proximal left anterior descending (LAD) artery lesions are associated with adverse prognostic events in patients with ST-segment elevation myocardial infarction (STEMI). HYPOTHESIS: ß2 -AA is associated with the presence of proximal LAD lesions in patients with STEMI. METHODS: A cohort of 153 patients with STEMI who underwent primary percutaneous coronary intervention (PPCI) was enrolled in the study. Baseline characteristics were compared between the proximal LAD group (n = 62) and the nonproximal LAD group (n = 91). Admission serum of patients was collected to detect the level of ß2 -AA. Data for echocardiogram within 24 hours after PPCI and at the 6-month follow-up were recorded. RESULTS: The optical density values and positive rates of ß2 -AA in the proximal LAD group were higher than those in the nonproximal LAD group (p < 0.05). ß2 -AA positively correlated with high sensitivity C-reactive protein and peak N-terminal pro-B type natriuretic peptide levels in the proximal LAD group, but those were not relevant in the nonproximal LAD group. Multivariate logistic regression analysis revealed that high ß2 -AA levels was independently associated with the presence of proximal LAD lesions in patients with STEMI. Furthermore, a receiver operating characteristic curve was used to show the efficiency of ß2 -AA levels to detect proximal LAD lesions, and the AUC of the ß2-AA OD value was 0.658 (95% confidence interval 0.568-0.749; p = 0.001). CONCLUSIONS: The STEMI patients with high ß2 -AA levels had a greater possibility having proximal LAD lesions.

12,13-diHOME and noradrenaline are associated with the occurrence of acute myocardial infarction in patients with type 2 diabetes mellitus.

BACKGROUND: Acute myocardial infarction (AMI) is the most prevalent cause of mortality and morbidity in patients with type 2 diabetes mellitus (T2DM). However, strict blood glucose control does not always prevent the development and progression of AMI. Therefore, the present study aimed to explore potential new biomarkers associated with the occurrence of AMI in T2DM patients. METHODS: A total of 82 participants were recruited, including the control group (n = 28), T2DM without AMI group (T2DM, n = 30) and T2DM with initial AMI group (T2DM + AMI, n = 24). The untargeted metabolomics using liquid chromatography-mass spectrometry (LC-MS) analysis was performed to evaluate the changes in serum metabolites. Then, candidate metabolites were determined using ELISA method in the validation study (n = 126/T2DM group, n = 122/T2DM + AMI group). RESULTS: The results showed that 146 differential serum metabolites were identified among the control, T2DM and T2DM + AMI, Moreover, 16 differentially-expressed metabolites were significantly altered in T2DM + AMI compared to T2DM. Amino acid and lipid pathways were the major involved pathways. Furthermore, three candidate differential metabolites, 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME), noradrenaline (NE) and estrone sulfate (ES), were selected for validation study. Serum levels of 12,13-diHOME and NE in T2DM + AMI were significantly higher than those in T2DM. Multivariate logistic analyses showed that 12,13-diHOME (OR, 1.491; 95% CI 1.230-1.807, P < 0.001) and NE (OR, 8.636; 95% CI 2.303-32.392, P = 0.001) were independent risk factors for AMI occurrence in T2T2DM patients. The area under receiver operating characteristic (ROC) curve (AUC) were 0.757 (95% CI 0.697-0.817, P < 0.001) and 0.711(95% CI 0.648-0.775, P < 0.001), respectively. The combination of both significantly improved the AUC to 0.816 (95% CI 0.763-0.869, P < 0.001). CONCLUSIONS: 12,13-diHOME and NE may lead to understanding the possible metabolic alterations associated with AMI onset in T2DM population and serve as promising risk factors and therapeutic targets.

Pretreatment lymphocyte-monocyte ratio (LMR) as a superior predictor of short-term progression outcomes in patients with gastric cancer receiving second- and later-line apatinib regimens.

PURPOSE: Lymphocyte-monocyte ratio (LMR) has previously been used as a prognostic predictor in various solid tumors. This research aims in comparing the prognostic predictive Please check and conability of several inflammatory parameters and clinical parameters to validate further the excellent prognostic value of LMR in patients with gastric cancer treated with apatinib. METHODS: Monitor inflammatory, nutritional parameters and tumor markers. Cutoff values of the parameters concerned were identified with the X-tile program. Subgroup analysis was made via Kaplan-Meier curves, and univariate and multivariate Cox regression analyses were used to find independent prognostic factors. The nomogram of logistic regression models was constructed according to the results. RESULTS: A total of 192 patients (115 divided into training group and 77 into validation group) who received the second- or later-line regimen of apatinib were retrospectively analyzed. The optimal cutoff value for LMR was 1.33. Patients with high LMR (LMR-H) were significantly longer than those with low LMR (LMR-L) in progression-free survival (median 121.0 days vs. median 44.5 days, P < 0.001). The predictive value of LMR was generally uniform across subgroups. Meanwhile, LMR and CA19-9 were the only hematological parameters with significant prognostic value in multivariate analysis. The area under the LMR curve (0.60) was greatest for all inflammatory indices. Adding LMR to the base model significantly enhanced the predictive power of the 6-month probability of disease progression (PD). The LMR-based nomogram showed good predictive power and discrimination in external validation. CONCLUSION: LMR is a simple but effective predictor of prognosis for patients treated with apatinib.

Independent and joint associations between the triglyceride-glucose index and NT-proBNP with the risk of adverse cardiovascular events in patients with diabetes and acute coronary syndrome: a prospective cohort study.

BACKGROUND: Elevated triglyceride-glucose (TyG) index and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are independently associated with increased risk of major adverse cardio-cerebral events (MACCEs) in diabetic patients with the acute coronary syndrome (ACS), but have not been evaluated jointly. We sought to investigate the independent and joint association of the TyG index and NT-proBNP with MACCEs risk. METHODS: Data from 5046 patients with diabetes and ACS were recorded in the Cardiovascular Center Beijing Friendship Hospital Database Bank between 2013 and 2021, including measurements of fasting triglycerides, plasma glucose, and NT-proBNP. The TyG index was calculated as Ln (fasting triglycerides [mg/dL] × fasting plasma glucose [mg/dL]/2). Associations of the TyG index and NT-proBNP with MACCEs risk were assessed using flexible parametric survival models. RESULTS: During 13589.9 person-years of follow-up, 985 incident MACCEs of the 5046 patients (65.6 years of age and 62.0% men) were observed. Elevated TyG index (HR: 1.18; 95% CI 1.05‒1.32 per 1 unit increase) and NT-proBNP categories (HR: 1.95; 95% CI: 1.50‒2.54 for > 729 pg/ml compared to < 129 pg/ml) were independently associated with MACCEs risk in the fully adjusted model. According to the joint categories of the TyG index and NT-proBNP, patients with the TyG index > 9.336 and NT-proBNP > 729 pg/ml were at the highest risk of MACCEs (HR: 2.45; 95% CI 1.64‒3.65) than the ones with TyG index < 8.746 and NT-proBNP < 129 pg/ml. The test for interaction was not significant (P interaction = 0.49). Incorporating these two biomarkers into the established clinical model, the Global Registry of Acute Coronary Events (GRACE) risk score, resulted in a significant improvement in risk stratification. CONCLUSIONS: The TyG index and NT-proBNP were independently and jointly associated with the risk of MACCEs in patients with diabetes and ACS, suggesting that patients with both markers elevated should be aware of the higher risk in the future.

Analysis of individualized antiplatelet therapy for patients of acute coronary syndrome after percutaneous coronary intervention under the guidance of platelet function: A one-center retrospective cohort study.

ABSTRACT: There is controversy in clinical application of antiplatelet drugs by monitoring platelet function. Therefore, we explored whether early and dynamic medication could bring better clinical outcomes for patients under the guidance of platelet function tests (PFT).In this retrospective cohort study, we analyzed the prognostic events of 1550 patients with acute coronary syndrome (ACS) at Tianjin People's Hospital in China. They received dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) from January 2017 to December 2018. The primary endpoint was based on the Bleeding Academic Research Consortium (BARC) 3 or 5 major bleeding. Secondary endpoints included MACCE (all-cause death, nonfatal myocardial infarction, stroke, stent thrombosis, and unplanned target vessel reconstruction) and BARC 1 to 2 minor bleeding. The endpoint events within 1 year after PCI were recorded. Patients were divided into a guided group and a control group according to the drug adjustment by PFT results. After the propensity scores matched, the end points of 2 groups were compared, and subgroup analysis was performed on major bleeding events.After propensity score matching, there were 511 cases in the guided group and the control group, respectively. The primary endpoint events occurred in 10 patients (1.96%) in the guided group and 23 patients (4.5%) in the control group (HR: 0.45; 95% CI, 0.21-0.95; P = .037). After the guided group adjusted drug doses, the risk of major bleeding was lower than standard DAPT of the control group. Although some patients in the guided group reduced doses earlier, the incidence of MACCE events did not increase in the guided group compared with the control group (4.89% vs 6.07%; P = .41). There was no statistical difference in BARC 1 to 2 minor bleeding (P = .22). Subgroup analysis showed that PFT was more effective in patients with diabetes and multivessel disease.Early observation of dynamic PFT in ACS patients after PCI can guide individualized antiplatelet therapy to reduce the risk of major bleeding without increasing the risk of ischemia.

Evaluation of the inhibition of chlorophenols towards human cytochrome P450 3A4 and differences among various species.

Chlorophenols (CPs) are important pollutants detected frequently in the environment. This study intended to detect the inhibitory effects of fourteen CPs (2-CP, 3-CP, 4-CP, 4C2AP, 4C3MP, 2.4-DCP, 2.3.4-TCP, 2.4.5-TCP, 2.4.6-TCP, 3.4.5-TCP, 2.3.4.5-TECP, 2.3.4.6-TECP, 2.3.5.6-TECP and PCP) towards human liver cytochrome P450 3A4 (CYP3A4). Throughout the tests, testosterone was used as the probe substrate and CPs were used as inhibitors. A series of experiments (enzyme activity assays, preliminary screening tests, inhibition kinetics determination) were conducted to determine the inhibition of CPs towards human liver CYP3A4. CPs with the inhibitory effect >80% were selected for the inhibition evaluation in liver microsomes from different animal species (monkey, rat, dog, pig). The results showed that 2.3.4-TCP, 3.4.5-TCP, and 2.3.4.5-TECP inhibited the activities of CYP3A4 by 80.3%, 93.4%, 91.6%, respectively. Inhibition kinetics type were non-competitive and inhibition kinetics constant (Ki) values were 26.4 µM, 13.5 µM, and 8.8 µM for the inhibition of 2.3.4-TCP, 3.4.5-TCP, and 2.3.4.5-TECP towards human CYP3A4, respectively. Inhibition kinetics type was competitive and Ki value was 4.9 µM for the inhibition of 2.3.4-TCP towards CYP3A4 in Monkey liver microsomes (MyLMs). Inhibition kinetic types were non-competitive and Ki values were 8.1 µM and 28.7 µM for the inhibition of 3.4.5-TCP and 2.3.4.5-TECP towards CYP3A4 in MyLMs. Inhibition kinetic types were non-competitive and Ki values were 13.8 µM, 0.6 µM, and 6.1 µM for the inhibition of 2.3.4-TCP, 3.4.5-TCP, and 2.3.4.5-TECP towards CYP3A4 in Dog liver microsomes (DLMs), respectively. By comparing Ki values and inhibition kinetic types, the dog was the most suitable model to assess the inhibition of 2.3.4-TCP and 2.3.4.5-TECP towards CYP3A4, and monkey was the most suitable model to assess the inhibition of 3.4.5-TCP towards CYP3A4. In conclusion, our recent study on the inhibition of CPs towards CYP3A4 and species differences was important for further toxicological studies of CPs in human bodies.