Design and synthesis of a novel chiral photoacoustic probe and accurate imaging detection of hydrogen peroxide in vivo.

Nanocatalytic medicine, which aims to accurately target and effectively treat tumors through intratumoral in situ catalytic reactions triggered by tumor-specific environments or markers, is an emerging technology. However, the relative lack of catalytic activity of nanoenzymes in the tumor microenvironment (TME) has hampered their use in biomedical applications. Therefore, it is crucial to develop a highly sensitive probe that specifically responds to the TME or disease markers in the TME for precision diagnosis and treatment of diseases. In this work, a chiral photoacoustic (PA) nanoprobe (D/L-Ce@MoO3) based on the H2O2-catalyzed TME activation reaction was constructed in a one-step method using D-cysteine (D-Cys) or L-cysteine (L-Cys), polymolybdate, and cerium nitrate as raw materials. The designed and synthesized D/L-Ce@MoO3 chiral nanoprobe can perform in situ, non-invasive, and precise imaging of pharmacological acute liver injury. In vivo and in vitro experiments have shown that the D/L-Ce@MoO3 probe had chiral properties, the CD signal decreased upon reaction with H2O2, and the absorption and PA signals increased with increasing H2O2 concentration. This is because of the catalytic reaction between Ce ions doped in the nanoenzyme and the high expression of H2O2 caused by drug-induced liver injury to produce ·OH, which has a strong oxidizing property to kill tumor cells and destroy the Mo-S bond in the probe, thus converting the chiral probe into an achiral polyoxometalate (POM) with PA signal.

A Novel Fluorescent Aptamer Sensor with DNAzyme Signal Amplification for the Detection of CEA in Blood.

Carcinoembryonic antigen (CEA) is a tumor-specific biomarker; however, its low levels in the early stages of cancer make it difficult to detect. To address the need for analysis of ultra-low-level substances, we designed and synthesized a fluorescent aptamer sensor with DNAzyme signal amplification and used it for the detection of CEA in blood. In the presence of the target protein, the aptamer sequence in the recognition probe binds to the target protein and opens the hairpin structure, hybridizes with the primer and triggers a polymerization reaction in the presence of polymerase to generate double-stranded DNA with two restriction endonuclease Nb.BbvCl cleavage sites. At the same time, the target protein is displaced and continues to bind to another recognition probe, triggering a new round of polymerization reaction, forming a cyclic signal amplification triggered by the target. The experimental results show that the blood detection with CEA has a high sensitivity and a wide detection range. The detection range: 10 fg/mL~10 ng/mL, with a detection limit of 5.2 fg/mL. In addition, the sensor can be used for the analysis of complex biological samples such as blood.

Fabrication of Ag-CaCO3 Nanocomposites for SERS Detection of Forchlorfenuron.

In this study, Ag-CaCO3 nanocomposites were synthesized using silver nitrate as the precursor solution based on calcium carbonate nanoparticles (CaCO3 NPs). The synthesis involved the reaction of calcium lignosulphonate and sodium bicarbonate. The properties of Ag-CaCO3 nanocomposites were studied by various technologies, including an ultraviolet-visible spectrophotometer, a transmission electron microscope, and a Raman spectrometer. The results showed that Ag-CaCO3 nanocomposites exhibited a maximum UV absorption peak at 430 nm, the surface-enhanced Raman spectroscopy (SERS) activity of Ag-CaCO3 nanocomposites was evaluated using mercaptobenzoic acid (MBA) as the marker molecule, resulting in an enhancement factor of 6.5 × 104. Additionally, Ag-CaCO3 nanocomposites were utilized for the detection of forchlorfenuron. The results demonstrated a linear relationship in the concentration range of 0.01 mg/mL to 2 mg/mL, described by the equation y = 290.02x + 1598.8. The correlation coefficient was calculated to be 0.9772, and the limit of detection (LOD) was determined to be 0.001 mg/mL. These findings highlight the relatively high SERS activity of Ag-CaCO3 nanocomposites, making them suitable for analyzing pesticide residues and detecting toxic and harmful molecules, thereby contributing to environmental protection.

Validation and derivation of short-term prognostic risk score in acute decompensated heart failure in China.

BACKGROUND: Few prognostic risk scores (PRSs) have been routinely used in acute decompensated heart failure (ADHF). We, therefore, externally validated three published PRSs (3A3B, AHEAD, and OPTIME-CHF) and derived a new PRS to predict the short-term prognosis in ADHF. METHODS: A total of 4550 patients from the Heb-ADHF registry in China were randomly divided into the derivation and validation cohorts (3:2). Discrimination of each PRS was assessed by the area under the receiver operating characteristic curve (AUROC). Logistic regression was exploited to select the predictors and create the new PRS. The Hosmer-Lemeshow goodness-of-fit test was used to assess the calibration of the new PRS. RESULTS: The AUROCs of the 3A3B, AHEAD, and OPTIME-CHF score in the derivation cohort were 0.55 (95% CI 0.53-0.57), 0.54 (95% CI 0.53-0.56), and 0.56 (95% CI 0.54-0.57), respectively. After logistic regression analysis, the new PRS computed as 1 × (diastolic blood pressure < 80 mmHg) + 2 × (lymphocyte > 1.11 × 109/L) + 1 × (creatinine > 80 µmol/L) + 2 × (blood urea nitrogen > 21 mg/dL) + 1 × [BNP 500 to < 1500 pg/mL (NT-proBNP 2500 to < 7500 pg/mL)] or 3 × [BNP ≥ 1500 (NT-proBNP ≥ 7500) pg/mL] + 3 × (QRS fraction of electrocardiogram < 55%) + 4 × (ACEI/ARB not used) + 1 × (rhBNP used), with a better AUROC of 0.67 (95% CI 0.64-0.70) and a good calibration (Hosmer-Lemeshow χ2 = 3.366, P = 0.186). The results in validation cohort verified these findings. CONCLUSIONS: The short-term prognostic values of 3A3B, AHEAD, and OPTIME-CHF score in ADHF patients were all poor, while the new PRS exhibited potential predictive ability. We demonstrated the QRS fraction of electrocardiogram as a novel predictor for the short-term outcomes of ADHF for the first time. Our findings might help to recognize high-risk ADHF patients.

Comparison of myocardial microcirculatory perfusion after catheter-administered intracoronary thrombolysis with anisodamine versus standard thrombus aspiration in patients with ST-elevation myocardial infarction.

OBJECTIVE: To evaluate efficacy, safety and feasibility of targeted intracoronary injection using pro-urokinase combined with anisodamine (TCA) versus thrombus aspiration (TA) in ST-elevation myocardial infarction (STEMI) patients with high thrombus loads. BACKGROUND: The best method of avoiding thrombus detachment and stroke in PCI patients with high thrombus loads has not yet been established. METHODS: STEMI patients receiving coronary artery angiography or percutaneous coronary intervention (CAG/PCI) with thrombus grade ≥ 3 from January 1, 2017 to June 30, 2018 were randomly assigned to targeted intracoronary thrombolysis (pro-urokinase and anisodamine via catheter (TCA) group), or the TA group which followed the standard thrombus aspiration procedure. Parameters compared included thrombus grade, index of microcirculatory resistance (IMR), postoperative myocardial SPECT, thrombosis in myocardial infarction (TIMI) scores including flow grade, corrected TIMI frame counts (CTFCs), and TIMI myocardial perfusion grade (TMPG). Adverse events were followed up within 3 months. RESULTS: Thirty-nine patients were finally enrolled. In primary CAG/PCI, the TCA group had higher percentages of TIMI 3 flow and lower IMR values compared with the TA group. The ratio of TMPG 3 grade in the TCA group was higher in repeat CAG, and the perfusion descending area (PDA) presented by SPECT was lower than in the TA group. No significant difference was seen in major adverse coronary events (MACEs) or bleeding events at follow-up. CONCLUSIONS: TCA appears to be effective, safe, and feasible for repatency and reduction of high thrombus burden in primary PCI and may protect myocardial microcirculation with improved outcomes.

Synthesis of MBA-Encoded Silver/Silica Core-Shell Nanoparticles as Novel SERS Tags for Biosensing Gibberellin A3 Based on Au@Fe3O4 as Substrate.

A surface-enhanced Raman scattering (SERS) tag is proposed for high-sensitivity detection of gibberellin A3 (GA3). Silver nanoparticles (AgNPs) were synthesized using citrate reduction. 4-Mercaptobenzoic acid (MBA) was used for the Raman-labeled molecules, which were coupled to the surface of the AgNPs using sulfydryls. MBA was coated with silica using the Stöber method to prevent leakage. GA3 antibodies were attached via the active functional groups N-Hydroxysuccinimide (NHS) and N-Ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) to construct a novel immuno-AgNPs@SiO2 SERS tags. The captured SERS substrates were fabricated through Fe3O4 nanoparticles and gold nanoparticles (AuNPs) using chemical methods. These nanoparticles were characterized using ultraviolet-visible spectroscopy (UV-Vis), dynamic light scattering, Raman spectroscopy, transmission electron microscope (TEM), and X-ray diffraction (XRD). This immuno-AgNPs@SiO2 SERS tags has a strong SERS signal based on characterizations via Raman spectroscopy. Based on antigen-antibody reaction, the immuno-Au@Fe3O4 nanoparticles can capture the GA3 and AgNPs@SiO2 SERS tags. Due to the increasing number of captured nanoprobes, the SERS signal from MBA was greatly enhanced, which favored the sensitive detection of GA3. The linear equation for the SERS signal was y = -13635x + 202211 (R2 = 0.9867), and the limit of detection (LOD) was 10-10 M. The proposed SERS tags are also applicable for the detection of other food risk factors.

Preventive effect of oral nicorandil on contrast-induced nephropathy in patients with renal insufficiency undergoing elective cardiac catheterization.

This study aims to investigate the preventive effect of oral nicorandil on contrast-induced nephropathy (CIN) in patients with renal insufficiency undergoing elective cardiac catheterization. A total of 240 patients with an estimated glomerular filtration rate (eGFR) of 60 mL/min or less, who were undergoing elective cardiac catheterization, were randomly assigned to nicorandil group (n = 120, 10 mg nicorandil, three times daily from 2 days before to 3 days after procedure) or control group (n = 120, matching placebo as the same method). The primary endpoint was the incidence of CIN defined as 25 % increase in serum creatinine (SCr) from baseline or 44 µmol/L (0.5 mg/dL) increase in absolute value within 72 h after exposure to contrast medium. The secondary endpoints were: (1) the changes of SCr, Cystatin-C (Cys-C) and eGFR within 72 h; (2) major adverse events (MACE) occurring within 30 days. Baseline characteristics of the patients in the two groups were similar. The incidence of CIN was significantly lower in nicorandil group compared with control group (6.67 vs. 17.5 %, P = 0.017). Compared with the control group, nicorandil group tended to have a lower SCr and Cys-C levels as well as a higher eGFR at 48 h after the procedure (all P < 0.05). There was no difference about the incidence of MACE within 30 days between nicorandil group and control group (4.16 vs. 5.83 %, P = 0.767). Multivariate logistic analysis showed that nicorandil was an independent protective factor against CIN (OR = 0.260, 95 % CI = 0.1-0.676, P = 0.006). Therefore, we concluded that oral nicorandil was associated with a decline in the incidence of CIN in patients with renal insufficiency undergoing elective cardiac catheterization.

[Study on the Hydrothermal Synthesis and Fluorescence of LaF3 : Tb3+, Ce3+ Nanocrystals].

LaF3 : Tba3+, Ce3+ nanocrystals were prepared with hydrothermal method with the help of cetyltrimethyl ammonium bromide (CTAB). The effects of pH values of the solution, Ce3+/Tb+ ratio value and reaction time on the luminescent properties were investigated. XRD analysis shows that the as-prepared samples possess hexagonal phase and their main diffraction peaks of samples are similar to the standard card (JCPDS 32-0483). Compared with pure LaF3, the main diffraction peaks of the doped samples have a slight shift, showing existing isomorphous substitution between La3+ and the doped rare earth ions in parent lattice of LaF3. It is found from TEM results that the as-prepared samples have good crystallinity and their average grain sizes change in the range of 20-50 nm. The excitation spectra indicate that the stronger excitation spectrum peaks exist at 250 nm, which is assigned to the transition of 4f --> 5d from Ce3+. When activated at 250 nm, all LaF3 : Tb3+, Ce3+ nanocrystals possess weak blue emission at 490 nm (electric dipole transition, 5D4 --> 7F6) and good green emission at 543 nm (magnetic dipole transition, 5D4 -->7F5). As the Ce3+/Tb+ ratio increases, the fluorescence intensities increase at first and then weaken, and reach the strongest green emission at n(Ce)3+ /n(Tb)3+ = 4. The pH values have some influence on the colors and intensities of the LaF3 : Tb3+, Ce3+ nanocrystals. The sample prepared at pH 9 presents the best color, while the one at pH 7 exhibits the strongest green emission. Besides, increasing reaction time is helpful to improve color purity of sample and enhance its green emission.

A Novel Medical Treatment for Lipid Control in Patients with Unstable Angina Pectoris and Statin-Induced Liver Dysfunction.

BACKGROUND: This study aims to evaluate the safety and efficacy of Xuezhikang in the treatment of unstable angina pectoris (UAP) in patients with elevated liver enzymes caused by statins. METHODS: Ninety UAP patients with elevated liver enzymes (higher than 3-fold the upper limits of normal caused by statins) were randomly divided into 3 groups: withdrawal of simvastatin (group A), continued taking of simvastatin (group B) and switching to Xuezhikang capsules (group C). RESULTS: Blood lipids and high-sensitivity C-reactive protein (hs-CRP) were measured before and after treatment, and liver enzymes were measured every two weeks. As the liver enzymes of the patients in group A returned to normal, they could again undertake administration of simvastatin. If the liver enzyme levels remained abnormal at four weeks, polyene phosphatidylcholine would be added. The endpoint events of each group were followed-up. After treatment for 4 weeks, the liver enzymes decreased in all of the three groups and there was a significant difference (p < 0.05). However, at 8 weeks the liver enzymes showed no significant difference among the three groups (p > 0.05). The blood lipids and hs-CRP were both reduced in group B and C. The decreased triglyceride and hs-CRP levels and increased high-density lipoprotein cholesterol level in group C were more remarkable than those in group B (p < 0.05). The incidence rate of endpoint events in group A was the highest (p < 0.05) among the three groups. CONCLUSIONS: Xuezhikang is safe and effective in the treatment for UAP patients with elevated liver enzymes caused by statins. KEY WORDS: Liver enzymes; Simvastatin; Unstable angina pectoris; Xuezhikang capsules.

Development and Validation of a Nomogram for Predicting the Severity of Coronary Artery Disease Based on Cardiopulmonary Exercise Testing.

As a major global health concern, coronary artery disease (CAD) demands precise, noninvasive diagnostic methods like cardiopulmonary exercise testing (CPET) for effective assessment and management, balancing the need for accurate disease severity evaluation with improved treatment decision-making. Our objective was to develop and validate a nomogram based on CPET parameters for noninvasively predicting the severity of CAD, thereby assisting clinicians in more effectively assessing patient conditions. This study analyzed 525 patients divided into training (367) and validation (183) cohorts, identifying key CAD severity indicators using least absolute shrinkage and selection operator (LASSO) regression. A predictive nomogram was developed, evaluated by average consistency index (C-index), the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA), confirming its reliability and clinical applicability. In our study, out of 25 variables, 6 were identified as significant predictors for CAD severity. These included age (OR = 1.053, P < .001), high-density lipoprotein (HDL, OR = 0.440, P = .002), hypertension (OR = 2.050, P = .007), diabetes mellitus (OR = 3.435, P < .001), anaerobic threshold (AT, OR = 0.837, P < .001), and peak kilogram body weight oxygen uptake (VO2/kg, OR = 0.872, P < .001). The nomogram, based on these predictors, demonstrated strong diagnostic accuracy for assessing CAD severity, with AUC values of 0.939 in the training cohort and 0.840 in the validation cohort, and also exhibited significant clinical utility. The nomogram, which is based on CPET parameters, was useful for predicting the severity of CAD and assisted in risk stratification by offering a personalized, noninvasive diagnostic approach for clinicians.

Associations between serum electrolyte and short-term outcomes in patients with acute decompensated heart failure.

INTRODUCTION: There is a dearth of comprehensive studies on the association between serum electrolyte and adverse short-term prognosis of Chinese patients with acute decompensated heart failure (ADHF). PATIENTS AND METHODS: A total of 5166 patients with ADHF were divided into four serum electrolyte-related study populations (potassium (n = 5145), sodium (n = 5135), chloride (n = 4966), serum total calcium (STC) (n = 4143)) under corresponding exclusions. Different logistic regression models were utilized to gauge the association between these electrolytes or the number of electrolyte abnormalities and the risk of a composite of all-cause mortality or 30-day heart failure (HF) readmission. RESULTS: In multivariable adjusted analysis, patients with potassium below 3.5 mmol/L (odds ratios (ORs) 1.45; 95% confidence interval (CI):1.07-1.95), 4.01-4.50 mmol/L (OR: 1.29, CI: 1.02-1.62), 4.51-5.00 mmol/L (OR: 1.43, CI: 1.08-1.90) and above 5.00 mmol/L (OR: 1.74, CI: 1.21-2.51) had an increased risk of outcome when compared with potassium at 3.50-4.00 mmol/L. Sodium levels were inversely related to the risk of a composite outcome (<130 mmol/L: OR: 2.73 (95% CI, 1.81-4.12); 130-134 mmol/L: OR, 1.97 (CI, 1.45-2.68); 135-140 mmol/L: OR, 1.45 (CI, 1.17-1.81); p for trend < 0.001) in comparison with sodium at 141-145 mmol/L. Chloride < 95 mmol/L corresponded to a higher risk of a composite outcome with an OR of 1.65 (95% CI, 1.16-2.37) in contrast to chloride levels at 101-105 mmol/L. In addition, the adjusted ORs (95% CI) for a composite outcome comparing the STC < 2.00 and 2.00-2.24 vs. 2.25-2.58 mmol/L were 0.98 (0.69-1.43) and 1.13 (0.89-1.44), respectively. Besides that, the number of electrolyte abnormalities was positively related to the risk of a composite outcome (N = 1, OR 1.40, 95% CI: 1.13-1.73; N = 2, OR 2.51, 95% CI: 1.85-3.42; N = 3, OR 2.47, 95% CI: 1.45-4.19; p for trend < 0.001) in comparison with N = 0. CONCLUSIONS: A deviation of potassium levels from 3.50 to 4.00 mmol/L, lower sodium levels and hypochloremia were associated with poorer short-term prognosis of ADHF. Furthermore, the number of electrolyte abnormalities positively correlated with adverse short-term prognosis of patients with ADHF. Key MessagesADHF patients with baseline serum potassium at first half part of normal range (3.50-4.00 mmol/L) may herald the lowest risk of recent cardiovascular events.Serum sodium and chloride levels exhibit discrepancies in terms of risk of short-term adverse events of ADHF patients.The number of electrolyte abnormalities is a significant predictor of poor short-term prognosis in patients with ADHF. CLINICAL TRIAL REGISTRATION URL: http://www.chictr.org.cn/showproj.aspx?proj=23139. Unique identifier: ChiCTR-POC-17014020.

[Solvothermal synthesis and optical properties of LiVO4 : Dy3+ nanorod].

Using La2O3, Dy2O3, NH4VO3, HNO3 as materials, solvothermal synthesis method was adopted to prepare LaVO4 : Dy3+ nanorods through adjusting the pH values of ethanol-water mixing solution. The as-prepared samples were characterized by X-ray diffraction, transmission electron microscope, infrared spectrum, UV-Vis absorption spectra and fluorescence spectra. The results show that the phase transition from m- to t -LaVO4 : Dy3+ can be found when the pH value changes from 2 to 4. With the increase of the pH value of the mixing solution, the grain size of the sample becomes smaller and the shape of LaVO4 : Dy3+ crystal changes from irregular nanoparticle to one dimension nanorod. Besides, the band gap of the sample decrease from 3.68 (pH 2) to 3.43 eV (pH 10). It is found from FL that the excitation spectra of LaVO4 : Dy3+ nanorods have a little red shift in comparison with irregular nanoparticle. Furthermore, the LaVO4 : Dy3+ nanorod exhibits the strongest yellow emission (4F9/2-6 H13/2) and blue emission(4F9/2-6H15/2), and it possesses the largest Y/B value (1.039).

Discovery of thirteen cobalt(II) and copper(II) salicylaldehyde Schiff base complexes that induce apoptosis and autophagy in human lung adenocarcinoma A549/DDP cells and that can overcome cisplatin resistance in vitro and in vivo.

In this study, 13 transition metal complexes, namely, [Cu(L1H)(H2O)2]·(H2O)·NO3 (1), [Cu(LnH2)2]·(NO3)·(H2O)2 (2, n = 2; 3, n = 3; 4, n = 4; 5, n = 5), [Co(LnH)2]2·(H2O)0.5 (6, n = 2; 7, n = 3; 8, n = 4; 9, n = 5), [Cu(L6H)0.5(L10H)0.5(phen)]·(CH3OH)0.25 (10), [Cu(L11H) (phen)]4·(H2O)9 (11), [Cu(L8H)0.27(L12H)0.73(phen)]4·(H2O)5.5(CH3OH) (12), and [Cu(L9H) (phen)]3·(H2O)7·(CH3OH) (13), were synthesized using Schiff base ligands and characterized by elemental analysis (EA), infrared spectroscopy (IR), and single-crystal X-ray diffraction (SC-XRD). Compared with complexes 1-9, complexes 10-13 displayed stronger cytotoxic activities against the tested A549/DDP cancer cells (IC50 = 0.97-3.31 µM), with differences greater than one order of magnitude. Moreover, complexes 11 and 13 could induce apoptosis and autophagy in A549/DDP cells via the mitochondrial dysfunction pathway that affects the regulation of autophagy- and mitochondrial-related proteins. Importantly, the results indicate that the two novel salicylaldehyde Schiff base analogs, 11 and 13, exhibited pronounced and selective activity against A549/DDP xenografts in vivo.

Comparison of long-term radial artery occlusion following trans-radial coronary intervention using 6-french versus 7-french sheaths.

BACKGROUND: The aim of this study was to explore the impact of 6-Fr and 7-Fr sheaths on the incidence of long-term radial artery occlusion (RAO) after trans-radial coronary intervention (TRI). METHODS: From September 2013 to January 2016, patients with ischemic heart disease including acute myocardial infarction and true bifurcation lesions were randomly assigned to 6-Fr group and 7-Fr group immediately after coronary angiography in a 1:1 ratio. The radial artery diameters were observed by ultrasound examination one day prior to TRI as well as at 30 days and 1 year after TRI. The primary endpoint was the incidence of RAO at 1-year after TRI. The secondary endpoints were the incidence of local vascular complications during hospitalization and changes of radial artery diameters within 1-year after TRI between the two groups. Additionally, multivariate logistic regression analysis was used to explore potential factors related to the incidence of long-term RAO after TRI. RESULTS: A total of 214 patients were enrolled and randomly assigned to 6-Fr group (n = 105) or 7-Fr group (n = 109). There was no significant difference in the incidence of RAO at 1-year after TRI (8.57% vs. 12.84%, p = 0.313). Moreover, no significant difference was observed in the incidence of local vascular complications during hospitalization (20% vs. 24.77%, p = 0.403). After 1-year follow-up, no significant difference was found in radial artery diameters (2.63 ± 0.31 mm vs. 2.64 ± 0.27 mm, p = 0.802). Multivariate logistic analysis revealed that repeated TRI was an independent risk factor of long-term RAO 1 year after TRI (OR = 10.316, 95% CI 2.928-36.351, p = 0.001). CONCLUSIONS: Compared to 6-Fr sheath, 7-Fr sheath did not increase short-term or long-term incidence of RAO after TRI.

Effects of metoprolol on serum inflammatory factors and myocardial ischemia in rats modeled with coronary heart disease.

OBJECTIVE: This study was designed to observe the effects of metoprolol on serum inflammatory factors, cardiac function and oxidative stress response in rats modeled with coronary heart disease (CHD). METHODS: Thirty clean SD rats aged 6-8 weeks were randomized into a control group (CG), treatment group (TG) and model group (MG), with 10 in each group. Rats in the CG were fed regular chow, while those in the MG and TG were fed a high-fat diet. After successful CHD modeling, those in the TG were given metoprolol every day, 10 mg/kg once a day. The effects of cardiac function indexes, myocardial injury indexes, blood lipids, inflammatory factors and oxidative stress indexes, myocardial apoptosis-related factors and apoptosis rate were observed and recorded before and after treatment. RESULTS: Compared with the CG, the cardiac function indexes of the MG decreased significantly, while the myocardial injury indexes increased markedly. After metoprolol treatment, the cardiac function and myocardial injury of the TG were significantly improved. Also, the expression of serum lipid indexes in the MG increased obviously, and the hyperlipidemia in the TG was improved after metoprolol treatment. Besides, the expression of inflammatory factors in serum of the MG increased remarkably, and metoprolol could reduce the inflammatory state in rats. Furthermore, MDA in serum of the MG increased, SOD, CAT, GSH-Px decreased; revealing that metoprolol can improve oxidative stress in rats. Finally, the apoptosis rate of cardiomyocytes in the MG increased dramatically. Metoprolol treatment can reduce the apoptosis rate and improve the expression of apoptosis related proteins. CONCLUSION: Metoprolol reduces the degree of myocardial injury, inhibits inflammatory reaction and oxidative stress in vivo, reduces myocardial apoptosis and improves myocardial ischemia in CHD modeled rats.

Comparative Toxicity, Biodistribution and Excretion of Ultra-Small Gold Nanoclusters with Different Emission Wavelengths.

The exponentially increased use of gold nanoclusters in diagnosis and treatment has raised serious concern about their potential threat to living organisms. However, the mechanisms of toxicity of gold nanoclusters in vitro and in vivo remain poorly understood. In this work, comparative toxicity studies, including biodistribution and excretion, were carried out with mildly and chemically synthesized ultra-small L-histidine-protected and bovine serum albumin (BSA)-protected gold nanoclusters in an all-aqueous process. These nanoclusters did not induce a remarkable impact on cell viability, even at relatively high concentrations (100 µg/mL). The haemolytic assay demonstrated that the gold nanoclusters could not destroy blood cell at 600 µg/mL. After intravenous injection with mice, the biocompatibility, biodistribution, and excretion were determined. Quantitative analysis results showed that accumulation varied in the liver, spleen, kidney, and lung, though primarily in the liver and spleen. They were excreted in urine and faeces, but mainly excreted through urine. In our study, no obvious abnormalities were found in body weight, behavioral changes, blood and serum biochemical indicators, and histopathology. These findings suggested that both gold nanoclusters showed similar effects in vivo and were safe and biocompatible, laying the foundation for safe biomedical application in the future.

Effect of nicorandil combined with trimetazidine on miR-223-3p and NRF2 expression in patients with coronary heart disease.

OBJECTIVE: The aim of this study was to explore the effect of nicorandil (NCR) combined with trimetazidine (TMZ) on miR-223-3p and NRF2 expression in patients with coronary heart disease (CHD). METHODS: This study included 71 CHD patients admitted to our hospital from February 2017 to March 2019, including 33 cases in the control group (CG) treated with NCR and 38 cases in the research group (RG) treated with TMZ combined with NCR. Improvement in clinical efficacy after treatment was observed in the two groups; serum miR-223-3p and NRF2 levels pre- and post-treatment were compared, and the predictive value of the two for curative effect was analyzed. In addition, ST segment depression frequency and total duration, pre- and post-treatment cardiac function levels and blood lipid levels were recorded and compared. RESULTS: RG had statistically more markedly effective cases and notably lower serum miR-223-3p and NRF2 expression than CG after treatment. Through receiver operating characteristic (ROC) curve analysis, it was found that the area under curves (AUCs) of miR-223-3p and NRF2 were 0.716 and 0.712 respectively. The post-treatment ST segment depression frequency and duration were lower in RG than in CG (P<0.05). Cardiac function and blood lipid levels were significantly better in RG as compared to those in CG after treatment (P<0.05). CONCLUSIONS: NCR combined with TMZ is more effective in patients with CHD, and miR-223-3p and NRF2 can be predictors of clinical efficacy.

miR-34a targets PAI-1 to regulate urinary microalbumin and renal function in hypertensive mice.

BACKGROUND: The aim of the study is to investigate the effects of miR-34a targeted at PAI-1 on urinary microalbumin and renal function in hypertensive mice. METHODS: Twenty specific-pathogen-free (SPF) BPN/3J mice were selected in normal group, and 120 SPF BPH/2J mice were evenly divided into model group, negative control group, miR-34a mimic group, miR-34a inhibitor group, Si-PAI-1 group, and miR-34a inhibitor + Si-PAI-1 group. qRT-PCR was used to detect the expression of miR-34a and PAI-1 mRNA. The protein expressions of PAI-1, angiotensin-converting enzyme (ACE) and ACE2 were detected by Western blot. Serum levels of AngII and Ang1-7 were detected by ELISA. RESULTS: miR-34a negatively regulated the expression of PAI-1. Compared with the normal group, mice in the other groups had significantly lower body weight, increased systolic blood pressure and 24-h urinary microalbumin content, decreased miR-34a expression, superoxide dismutase (SOD) and nitric oxide (NO) content, and ACE2 protein expression, and increased PAI-1 expression, serum creatinine (Scr), blood urea nitrogen (BUN) malondialdehyde (MDA), AngII and Ang1-7 levels, and ACE protein expression (all P < 0.05). Compared with the model group, mice in the miR-34a mimic group and Si-PAI-1 group had no significant changes in body weight (all P > 0.05), while they had significantly lower systolic blood pressure and 24-h urinary microalbumin content, increased SOD and NO levels and ACE2 protein expression, and decreased PAI-1 expression, Scr, BUN, MDA, AngII and Ang1-7 levels, and ACE protein expression (all P < 0.05). Compared with the miR-34a inhibitor group, symptoms in miR-34a inhibitor + Si-PAI-1 group were significantly improved (all P < 0.05). CONCLUSIONS: miR-34a can inhibit the expression of PAI-1, thereby reducing urinary microalbumin content in hypertensive mice and protecting their renal function.

Association of myeloperoxidase, homocysteine and high-sensitivity C-reactive protein with the severity of coronary artery disease and their diagnostic and prognostic value.

In the present study, the association between the severity of coronary artery disease (CAD) and myeloperoxidase (MPO), homocysteine (Hcy) and high-sensitivity C-reactive protein (hs-CRP) was assessed and their diagnostic and prognostic value was determined. A total of 112 patients with CAD [patient group (PG)] and 112 healthy participants who visited the hospital for physical examinations [control group (CG)] were enrolled in the present study. The plasma levels of MPO, Hcy and hs-CRP were compared between the two groups. According to the arteriography results, the patients were further divided into the single-vessel disease group (SVG), double-vessel disease group (DVG) and multi-vessel disease group (MVG). The Gensini scores of the three groups were evaluated according to the Gensini score standard. The correlations between the expression of MPO, Hcy or hs-CRP and the Gensini score of the PG were analyzed. The patients' major adverse cardiovascular event (MACEs) were recorded over 6 months and compared, and the predictive values of MPO, Hcy and hs-CRP regarding MACEs were determined by receiver operating characteristics analysis. The results indicated that the levels of MPO, Hcy and hs-CRP in the PG were higher than those in the CG (P<0.05). The Gensini score and the expression of MPO, Hcy and hs-CRP in the MVG were higher than those in the SVG and the DVG, and the Gensini score and the expression of MPO, Hcy and hs-CRP in the DVG were higher than those in the SVG (P<0.05). There was a positive correlation between the Gensini score and the expression of MPO (r=0.814, P<0.05), Hcy (r=0.774, P<0.05) and hs-CRP (r=0.765, P<0.05) in the PG. The total incidence of MACEs in patients with multiple lesions was significantly higher than that in patients with double and single lesions (P<0.05). The total incidence of MACEs in the MVG group was higher than that in the SVG and the DVG, and the total incidence of MACEs in the DVG was higher than that in the SVG (P<0.05). The area under the curve (AUC) and sensitivity for MPO levels to predict MACEs were higher than those of Hcy and hs-CRP (P<0.05); however, there was no significant difference in the AUC and sensitivity of Hcy and hs-CRP for predicting MACEs (P<0.05). The specificity of hs-CRP for predicting MACEs was higher than that of MPO and Hcy (P<0.05). The number of lesions, hypertension, diabetes, MPO, Hys and hs-CRP were determined to be independent risk factors for MACEs. In conclusion, for patients with CAD, elevated plasma levels of MPO, Hcy and hs-CRP were directly correlated with the severity of CAD and the risk of MACEs. Furthermore, MPO, Hcy and hs-CRP may effectively predict MACEs and are of important clinical significance in terms of judging the condition and improving the prognosis for patients with CAD.

Circulating pro-angiogenic micro-ribonucleic acid in patients with coronary heart disease.

OBJECTIVES: Our goal was to evaluate the expressions of 14 selected pro-angiogenic micro-ribonucleic acids in patients with coronary heart disease (CHD) and healthy controls (HCs) and to assess the correlations of those micro-ribonucleic acids with risk and severity of CHD. METHODS: In the exploration stage, 20 patients with CHD were enrolled; in the validation stage, 102 patients with CHD and 92 age- and gender-matched HCs with the same eligibility of those in the exploration stage were recruited. Blood samples were collected from all participants, and plasma levels of micro-ribonucleic acids were measured by the quantitative polymerase chain reaction method. RESULTS: In the exploration stage, the expression of miR-126, miR-17-5p, miR-19a, miR-92a, miR-210 and miR-378 in patients with CHD was down-regulated compared with that of HCs. In the validation stage, miR-126, miR-17-5p, miR-92a, miR-210 and miR-378 levels decreased remarkably in patients with CHD compared with the HCs. Plasma levels of miR-126, miR-17-5p, miR-92a, miR-210 and miR-378 were independent prediction factors for CHD. The combination of miR-126, miR-17-5p, miR-92a, miR-210 and miR-378 was of good diagnostic value for CHD with an area under the curve of 0.756. Additionally, plasma levels of miR-126, miR-210 and miR-378 correlated negatively with Gensini scores. CONCLUSIONS: Circulating miR-126, miR-17-5p, miR-92a, miR-210 and miR-378 could serve as novel, promising biomarkers for risk and severity of CHD. Additionally, miR-126, miR-210 and miR-378 were negatively associated with Gensini scores.