Remnant cholesterol, iron status and diabetes mellitus: a dose-response relationship and mediation analysis.

BACKGROUND: Remnant cholesterol (RC) is recognized as a risk factor for diabetes mellitus (DM). Although iron status has been shown to be associated with cholesterol metabolism and DM, the association between RC, iron status, and DM remains unclear. We examined the relationship between RC and iron status and investigated the role of iron status in the association between RC and DM. METHODS: A total of 7308 patients were enrolled from the China Health and Nutrition Survey. RC was calculated as total cholesterol minus low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Iron status was assessed as serum ferritin (SF) and total body iron (TBI). DM was ascertained by self-reported physician diagnosis and/or antidiabetic drug use and/or fasting plasma glucose ≥ 126 mg/dL and/or glycated haemoglobin ≥ 6.5%. General linear models were used to evaluate the relationships between RC and iron status. Restricted cubic splines were used to assess the association between RC and DM. Mediation analysis was used to clarified the mediating role of iron status in the association between the RC and DM. RESULTS: The average age of the participants was 50.6 (standard deviation = 15.1) years. Higher RC was significantly associated with increased SF (ß = 73.14, SE = 3.75, 95% confidence interval [CI] 65.79-80.49) and TBI (ß = 1.61, SE = 0.08, 95% CI 1.44-1.78). J-shape relationships were found in the association between RC levels with DM, as well as iron status with DM. Significant indirect effects of SF and TBI in the association between RC and DM were found, with the index mediated at 9.58% and 6.37%, respectively. CONCLUSIONS: RC has a dose-response relationship with iron status. The association between RC and DM was mediated in part by iron status. Future studies are needed to confirm these findings and further clarify the underlying mechanism.

Effects of atorvastatin and rosuvastatin on dysfunctional coronary circulation in patients with ST-segment elevation myocardial infarction.

OBJECTIVE: Evidence of therapy for dysfunctional coronary circulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) is limited. This study was performed to compare the effects of atorvastatin and rosuvastatin on dysfunctional coronary circulation. METHODS: This retrospective study enrolled 597 consecutive patients with STEMI who underwent pPCI in 3 centers from June 2016 to December 2019. Dysfunctional coronary circulation was defined by the thrombolysis in myocardial infarction (TIMI) grade and the TIMI myocardial perfusion grade (TMPG). Logistic regression analysis was used to evaluate the impact of different statin types on dysfunctional coronary circulation. RESULTS: The incidence of TIMI no/slow reflow did not differ between the two groups, but the incidence of TMPG no/slow reflow was significantly lower in the atorvastatin than rosuvastatin group (44.58% vs. 57.69%, respectively). After multivariate adjustment, the odds ratio with 95% confidence interval of rosuvastatin was 1.72 (1.17-2.52) for after pretreatment TMPG no/slow reflow and 1.73 (1.16-2.58) for after stenting TMPG no/slow reflow. Atorvastatin and rosuvastatin showed no significant differences in clinical outcomes during hospitalization. CONCLUSIONS: Compared with rosuvastatin, atorvastatin was associated with better coronary microcirculatory perfusion in patients with STEMI who underwent pPCI.

Fluorescent "AND" logic gates for simultaneous detection of thiols and protons: photophysical properties, mechanism and bioimaging of living cells.

Five fluorescent probes TP1-5 were demonstrated as two-input "AND" molecular logic gates for the detection of thiols and protons. The molecules were designed based on "thiol receptor-spacer1-fluorophore-spacer2-proton receptor" mode. The logic gates were constructed by employing maleimide, naphthalimide and morpholine (TP1-3)/N-methyl piperazine (TP4-5) as the thiol receptor, fluorophore and proton receptor, respectively. All probes show significant fluorescence enhancements upon addition of both protons and thiols. However, much weaker spectral responses were observed with the addition of only one single analyte. The fluorescence outputs, based on photoinduced electron transfer (PET) and (twisted) intramolecular charge transfer (TICT/ICT), were modulated by the proton receptor and linker. The length of spacer1 affects the responses toward thiols, whereas spacer2 influences the sensing performance toward protons. The difference between the pKa values of morpholine (∼5.80) and N-methyl piperazine (∼7.10) enables us to detect thiols in divergent pH circumstances. TP1-3 exhibit an excellent "AND" logic function for simultaneous detection of protons and thiols as well as bioimaging thiols in weakly acidic living cells. However, TP4 and TP5 are not good candidates for executing "AND" logic operation possibly due to the stronger electron donating properties and steric effect of N-methyl piperazine.

D-Dimer Is Associated With Coronary Microvascular Dysfunction in Patients With Non-obstructive Coronary Artery Disease and Preserved Ejection Fraction.

Background: Coronary microvascular dysfunction (CMVD), an important etiology of ischemic heart disease, has been widely studied. D-dimer is a simple indicator of microthrombosis and inflammation. However, whether an increase in D-dimer is related to CMVD is still unclear. Materials and Methods: This retrospective study consecutively enrolled patients with myocardial ischemia and excluded those with obstructive coronary artery. D-dimer was measured at admission and the TIMI myocardial perfusion grade (TMPG) was used to distinguish CMVD. Patients were divided into the two groups according to whether the D-dimer was elevated (>500 ng/ml). Logistic models and restricted cubic splines were used to explore the relationship between elevated D-dimer and CMVD. Results: A total of 377 patients were eventually enrolled in this study. Of these, 94 (24.9%) patients with CMVD had older age and higher D-dimer levels than those without CMVD. After full adjustment for other potential clinical risk factors, patients with high D-dimer levels (>500 ng/ml) had a 1.89-times (95% CI: 1.09-3.27) higher risk of CMVD than patients with low D-dimer levels. A non-linear relationship was found between concentrations of D-dimer and CMVD. With increased D-dimer level, the incidence of CMVD increased and then remained at a high level. Stratified analysis was performed and showed similar results. Conclusion: Elevated D-dimer level is associated with the incidence of CMVD and potentially serves as a simple biomarker to facilitate the diagnosis of CMVD for patients with angina.

Indomethacin-induced spectral responses of naphthalimide-based dyes to serum albumin: effects of substituent and spacer.

Four indomethacin-naphthalimide binaries with different proton receptors at 4-position of naphthalimide were designed and synthesized. N,N-Dimethylethylenediamine and N-methyl piperazine were served as proton receptors as well as solubility regulators. Indomethacin, an inhibitor for cyclooxygenase-2 overexpressed on cancer cells, was connected at the imine N through different spacers. The attachment of indomethacin significantly quenched the fluorescence of all compounds with obvious red-shift in the absorption maxima due to the strong photo-induced electron transfer process of the folded-state. Human serum albumin (HSA) triggered about 15-fold fluorescence enhancements of DMN-IMC-5 with 30 nm blue-shift. However, it caused much smaller fluorescence increments of other compounds, suggesting that indomethacin, the linker and proton receptor play critical roles in HSA identification. Fluorescence bioimaging results show that indomethacin enables the naphthalimide-based compounds to fluorescent imaging living cells. Molecular docking reveals that the introduction of indomethacin improved the binding affinity of the dyes to HSA.

Predictive effect of different blood lipid parameters combined with carotid intima-media thickness on coronary artery disease.

Background: Blood lipids disorder and atherosclerosis are closely related to coronary artery disease (CAD). This study aims to compare different blood lipid parameters combined with carotid intima-media thickness (cIMT) in predicting CAD. Methods: This was a retrospective study including patients who underwent coronary angiography for highly suspected CAD. Blood samples were taken for lipid profile analysis and cIMT was evaluated by carotid ultrasound. Logistic analysis was used to establish different models of different lipid parameters in predicting CAD. The area under the receiver operating characteristic curve (AUC) was used to examine the predictive value. The optimal lipid parameter was also used to explore the relationship with multi-vessel CAD. Results: Patients were classified into two groups based on whether CAD existed. Compared with non-CAD patients, the CAD group had higher lipoprotein (a) [Lp (a)], apolipoprotein B/apolipoprotein A, total cholesterol/high-density lipoprotein cholesterol (HDL-C), triglyceride/HDL-C and LDL-C/HDL-C. According to the AUCs, Lp (a) combined with cIMT (AUC: 0.713, P < 0.001) had the best performance in predicting CAD compared to other lipid parameters. High level of Lp (a) was also associated with multi-vessel CAD (odds ratio: 1.41, 95% confidence interval: 1.02-1.95, P = 0.036). Conclusion: For patients with highly suspected CAD, Lp (a) better improved the predictive value of CAD rather than most of blood lipid indices, especially in the absence of high levels of LDL-C. Lp (a) also can be used to predict the multi-vessel CAD.

Effect of GP IIb/IIIa inhibitor duration on the clinical prognosis of primary percutaneous coronary intervention in ST-segment elevation myocardial infarction with no-/slow-reflow phenomenon.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) accompanied by the no-/slow-reflow phenomenon, the maintenance duration of GP IIb/IIIa inhibitor (GPI) is controversial. We compare the efficacy and safety of short- and long-term GPI infusion in STEMI patients with the no-/slow-reflow phenomenon. METHODS: From June 2016 to December 2019, we continuously included patients with on-set STEMI who underwent pPCI, accompanied by the no-/slow-reflow, during interventional procedures at Guangdong Provincial People's Hospital and Zhuhai Golden Bay Hospital. The hemorrhage events, heart function, and major adverse cardiovascular events (MACE) were compared between < 24 h and ≥ 24 h GPI duration groups. The Kaplan-Meier curve was used to estimate the 1-year MACE-free survival at different GPI utility times. RESULTS: In total, 127 patients were divided into two groups based on the duration of tirofiban use (less and more than 24 h). There was no significant difference between two groups in terms of baseline characteristics, plaque condition, and coronary physiological function. The two groups showed similar in-hospital MACE (1 [1.85%] vs. 4 [5.48%], p = 0.394) and 1-year MACE-free survival (log-rank test p = 0.9085). The 1-year MACE remained consistent between the two groups in all subgroups of different risk factors of no-/slow-reflow. There was no significant difference in heart function and in-hospital hemorrhage events (3.7% vs. 1.37%, p = 0.179). CONCLUSION: In the real world, prolonging the duration of GPI may not significantly improve the clinical outcome in patients with STEMI with no-/slow-reflow.