To investigate the clinical efficacy and safety of atorvastatin tablets combined with bivalirudin injection in patients with acute ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI).

Patients with acute STEMI were divided into control group and treatment group according to whether combined medication was used. The control group was given an intravenous continuous bolus of bivalirudin for injection at a dose of 0.75 mg·kg^-1 during the operation, and after the operation, intravenous pumping of bivalirudin was continued at a dose of 1.75 mg·(kg·h)^-1 until 6 hours postoperatively. The treatment group was treated with atorvastatin combined with bivalirudin, where the administration method of bivalirudin was the same as that in the control group, and atorvastatin calcium tablets were administered orally at a dose of 20 mg each time, bid. Both groups received a 30-day treatment course, and relevant reexaminations were conducted after the course. The efficacy, myocardial function indicators, blood coagulation indicators, blood lipid indicators, and inflammatory factor indicators were compared between the two groups.

The trial recruited 118 patients, with 54 assigned to the control group and 64 to the treatment group. At 30 days postoperatively, the efficacy rates of the control group and the treatment group were 74.07% and 89.06%, respectively. At 30 days after surgery, the cardiac troponin T levels in the control group and the treatment group were (7.58±1.27) and (7.01±1.38) μg·L^-1, respectively; the global longitudinal strain values were (16.87±1.05)% and (16.34±1.01)%, respectively; the fibrinogen degradation product levels were (4.09±0.80) and (3.82±0.51) μg·mL^-1 , respectively; the D-dimer levels were (0.97±0.42) and (0.82±0.33) mg·L^-1, respectively; the low-density lipoprotein cholesterol levels were (2.26±0.77) and (1.97±0.61) mmol·L^-1, respectively; the β2-microglobulin levels were (2.45±0.12) and (2.36±0.14) mg·L^-1, respectively; and the macrophage inflammatory protein-1α levels were (26.22±3.90) and (24.20±4.33) pg·mL^-1, respectively. The differences in the above indicators between the treatment group and the control group were all statistically significant (all P<0.05). The incidence of adverse reactions was 7.41% (4 cases/54cases) in the control group and 4.69% (3 cases/64cases) in the treatment group, and the incidence of major adverse cardiovascular events was 5.56% (3 cases/54 cases) and 1.56% (1 case/64 cases), respectively, with no statistically significant differences (all P>0.05).

Atorvastatin tablets combined with bivalirudin injection have a significant efficacy in STEMI patients after PCI. It can achieve the goals of improving myocardial function and coagulation function, effectively controlling the patient′s blood lipid level, reducing the inflammatory response, and exhibit good safety.

To reveal the association between the vanM gene and different glycopeptide resistance phenotypes in Enterococcus faecium, drug susceptibility testing and sequencing analysis were conducted on four E. faecium strains carrying the vanM gene.

The broth microdilution method was employed to determine the susceptibility of four E. faecium strains to glycopeptide antibiotics. Polymerase chain reaction (PCR) was performed to detect the vancomycin-resistant genotypes, while population analysis profiling (PAP) was used to identify the presence of heteroresistant strains among vancomycin-susceptible isolates. Quantitative real-time PCR (qRT-PCR) was conducted to analyze the relative expression level of the vanM gene in E. faecium, and genomic sequencing was carried out for alignment of the resistance gene cluster.

All four E. faecium strains carried the vanM gene. Strain SZD1 was susceptible to vancomycin, whereas SZD2 was identified as a vancomycin-heteroresistant strain. Strain SZD3 exhibited a high relative expression level of the vanM gene and showed resistance to vancomycin. In addition, strain SZD4 harbored both vanA and vanM genotypes, conferring high-level resistance to vancomycin.

E. faecium strains harboring the vanM gene can exhibit diverse glycopeptide resistance phenotypes, and such variations may be associated with the structure, copy number, and expression level of the vanM gene cluster, as well as the coexistence of other resistance genes.

To explore the effects and mechanism of resveratrol on the proliferation, migration and glycolysis of breast cancer cells by regulating the liver kinase B1 (LKB1)/AMP activated protein kinase (AMPK) pathway.

Human breast cancer MDA-MB-231 cells were divided into four groups: control group, low-concentration experimental group (25 μmol·L^-1 resveratrol), high-concentration experimental group (50 μmol·L^-1 resveratrol) and inhibitor group (50 μmol·L^-1 resveratrol + 4 μmol·L^-1 AMPK inhibitor BML-275). The cell proliferation of each group was detected by thiazolyl blue (MTT) assay and Edu staining; the cell migration was detected by scratch test; the cell apoptosis was detected by flow cytometry; the glucose consumption and lactic acid production of cells in each group were measured by glucose content kit and lactic acid content kit, respectively; the protein expressions of glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), hexokinase 2 (HK2), LKB1 and AMPK in each group were detected by Western blot.

The cell proliferation inhibition rates of control group, low-concentration experimental group, high-concentration experimental group and inhibitor group were (0±0)%, (32.27±3.68)%, (56.75±5.82)% and (24.41±3.06)%, respectively; the Edu-positive rates were (52.64±6.95)%, (30.72±4.21)%, (18.86±2.54)% and (41.37±4.88)%, respectively; the scratch healing rates were (34.24±3.82)%, (23.67±2.74)%, (14.85±2.03)% and (29.74±3.42)%, respectively; the cell apoptosis rates were (3.04±0.32)%, (21.81±2.64)%, (34.43±3.86)% and (12.67±1.93)%, respectively; the glucose consumption levels were (31.74±3.52), (23.18±2.64), (14.33±1.67) and (28.27±3.12) μmol·L^-1, respectively; the lactic acid production levels were (48.12±4.43), (31.27±3.75), (18.85±2.14) and (42.36±4.19) μmol·L^-1, respectively; the relative expression levels of GLUT1 were 1.14±0.12, 0.76±0.08, 0.41±0.04 and 0.94±0.09, respectively; the relative expression levels of LDHA were 1.32±0.14, 0.89±0.09, 0.47±0.05 and 1.13±0.12, respectively; the relative expression levels of HK2 were 0.97±0.09, 0.61±0.06, 0.34±0.04 and 0.86±0.09, respectively; the relative expression levels of LKB1 were 0.93±0.10, 1.38±0.14, 1.75±0.17 and 1.12±0.11, respectively; the relative expression levels of AMPK were 1.02±0.11, 1.56±0.16, 2.04±0.23 and 1.18±0.13, respectively. Compared with control group, the above indicators in the low- and high-concentration experimental groups were statistically significantly different (all P<0.05); compared with the high-concentration experimental group, the above indicators in the inhibitor group were statistically significantly different (all P<0.05).

Resveratrol may inhibit the proliferation, migration and glycolysis of breast cancer cells by activating the LKB1/AMPK pathway.

To investigate the effects of abatacept (ABT)-mediated micro ribonucleic acid-16-5p (miR-16-5p) in rats with acute myocardial infarction (AMI) based on the neurogenic locus notch homolog protein 1 (Notch1)/hypoxia inducible factor 1α (HIF-1α) signaling pathway.

AMI rat model was established using the left anterior descending coronary artery ligation method. A total of 50 rats were randomly divided into the sham-operation group (thoracotomy without ligation), model group, experimental group (5 mg·kg^-1 ABT), Ad-scramble group (tail vein injection of adenovirus-coated NC-mimic) and Ad-miR-16-5p group (tail vein injection of adenovirus-coated miR-16-5p mimic), with 10 rats in each group. Cardiac function indicators in each group were detected by echocardiography. Fluorescence in situ hybridization was used to detect miR-16-5p relative expression levels in rat myocardial tissue. Enzyme-linked immunosorbent assay was used to detect serum lactate dehydrogenase and creatine phosphohykinase levels, as well as inflammatory factor and oxidative stress factor levels in myocardial tissue. Immunofluorescence was used to detect Notch1 and HIF-1α protein expression in rat myocardial tissue.

The left ventricular ejection fractions (EF) in the sham-operation group, model group and experimental group were (64.72±6.15)%, (42.70±5.26)% and (59.51±6.61)%, respectively; the relative fluorescence intensities of miR-16-5p were 1.00±0.11, 2.53±0.33 and 1.37±0.19, respectively; the lactate dehydrogenase (LDH) levels in the sham-operation group, model group, experimental group, Ad-scramble group and Ad-miR-16-5p group were (154.64±27.48), (347.14±48.67), (173.42±28.45), (179.75±29.83) and (336.47±41.35) IU·L^-1, respectively; the creatine phosphohykinase (CPK) levels were (161.37±29.14), (425.43±52.34), (201.67±31.23), (197.74±30.48) and (413.46±49.78) IU·L^-1, respectively; the interleukin-1β (IL-1β) levels in myocardial tissue were (35.48±6.93), (129.64±19.51), (52.52±8.48), (51.62±7.32) and (118.42±19.51) pg·mg^-1 prot, respectively; the superoxide dismutase levels in myocardial tissue were (83.45±13.42), (34.54±5.61), (76.63±15.63), (75.87±14.23) and (41.75±5.92) U·mg^-1 prot, respectively; the relative fluorescence intensities of Notch1 were 1.00±0.16, 1.86±0.22, 1.36±0.19, 1.29±0.25 and 1.71±0.28, respectively; the relative fluorescence intensities of HIF-1α were 1.00±0.13, 2.41±0.37, 1.64±0.24, 1.57±0.29 and 2.10±0.38, respectively; the above indicators showed statistically significant differences between the sham-operation group and the model group, between the model group and the experimental group, and between the Ad-scramble group and the Ad-miR-16-5p group (P<0.01, P<0.001).

ABT may protect cardiac function in AMI rats, improve myocardial tissue pathological damage and fibrosis, and reduce oxidative stress and inflammatory responses by mediating miR-16-5p expression to regulate the Notch1/HIF-1α signaling pathway.

To investigate the effect and mechanism of quercetin on the recovery of pelvic floor function in a rat model of stress urinary incontinence (SUI) by regulating the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway.

Female SD rats were selected and assigned into the control (NC) group, SUI group, low-, medium-, and high-dose quercetin (L, M, H-quercetin) groups, and H-quercetin+JAK2-STAT3 activator RO8191 (H-quercetin+RO8191) group according to the criteria of 12 rats in each group. Each administration group was administered daily according to the dose, for 5 consecutive weeks. Subsequently, the urodynamics, intravesical pressure, pelvic floor function-related parameters of rats and the surface electrical signals of pelvic floor muscles were detected. The oxidative stress indexes were detected by ELISA and DCFH-DA fluorescent probe. HE staining was used to observe the pathological changes of urethral tissue. Moreover, protein expression was detected by Western blot.

In the SUI group, the density of cells and cell nuclei in the rat urethral tissue decreased, the cells atrophied and were arranged in a disordered manner with uneven staining, the muscular layer became thinner, the interstitial spaces widened, and intracellular vacuolation was observed. The urinary leakage point pressure, maximum volume, abdominal pressure, urinary leakage point pressure when abdominal pressing, urination time interval, urination efficiency, vaginal systolic pressure, vaginal resting pressure, type Ⅰ and type Ⅱ pelvic floor muscle fiber potentials, supeioxide dismucase (SOD) and glutathione peroxidase (GSH-Px) in the SUI group were lower than those in the NC group, while the residual urine volume, urine output, bladder neck range of motion, urethral rotation angle, malondialdhyde(MDA), reactive oxygen species (ROS) fluorescence intensities, p-JAK2/JAK2, and p-STAT3/STAT3 were higher (P<0.05). The urinary leakage point pressure, maximum volume, abdominal pressure, urinary leakage point pressure when abdominal pressing, urination time interval, urination efficiency, vaginal systolic pressure, vaginal resting pressure, type Ⅰ and type Ⅱ pelvic floor muscle fiber potentials, SOD and GSH-Px in the L, M, and H-quercetin groups were higher than those in the SUI group, while the residual urine volume, urine output, bladder neck range of motion, urethral rotation angle, MDA, ROS fluorescence intensities, p-JAK2/JAK2, and p-STAT3/STAT3 were lower (P<0.05). The urinary leakage point pressure, maximum volume, abdominal pressure, urinary leakage point pressure when abdominal pressing, urination time interval, urination efficiency, vaginal systolic pressure, vaginal resting pressure, type Ⅰ and type Ⅱ pelvic floor muscle fiber potentials, SOD and GSH-Px in the H-quercetin+RO8191 group were lower than those in the H-quercetin group, while the residual urine volume, urine output, bladder neck range of motion, urethral rotation angle, MDA, ROS fluorescence intensities, p-JAK2/JAK2, and p-STAT3/STAT3 were higher (P<0.05).

Quercetin may restore pelvic floor function in SUI rats by inhibiting the JAK2-STAT3 pathway.

To establish a population pharmacokinetic model of amoxicillin and clavulanate potassium tablets in healthy Chinese subjects under fasting condition.

Based on the previously confirmed bioequivalence results, this study retrospectively collected the plasma concentration data of 18 subjects who received the test preparation and 17 subjects who received the reference preparation. The population pharmacokinetic model of amoxicillin was constructed using Phoenix NLME software. The effects of covariates such as gender, age, albumin, serum creatinine, creatine kinase, fasting blood glucose, and total cholesterol on pharmacokinetics were evaluated by forward inclusion and backward elimination methods. Model validation included goodness-of-fit plots, bootstrap method, and visual predictive check (VPC).

The population pharmacokinetic model of amoxicillin in healthy subjects conformed to a two-compartment model with first-order elimination kinetics and lag time, which could well describe the data. Serum creatinine and body mass index (BMI) were significant covariates. The parameters of the final model were as follows: central volume of distribution (V)=51.56 L, peripheral volume of distribution (V₂)=7.65 L; clearance (CL)=39.99 L·h^-1, intercompartmental clearance (CL₂)=1.78 L·h^-1, absorption rate constant (K_a)=1.45 h^-1. Serum creatinine had an impact on CL₂ and K_a, while BMI affected V.

The two-compartment model with first-order elimination kinetics and lag time can better describe the in vivo absorption characteristics of amoxicillin after oral administration of amoxicillin and clavulanate potassium tablets in healthy subjects.

This study used 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) as a derivatization reagent to establish an LC-MS/MS analytical method for the quantitative detection of a class of amine drugs, mesalazine(5-ASA) and two thiol drugs, methimazole (MMI) and captopril (CAP).

Plasma samples were processed using derivatization and protein precipitation methods. Optimal derivatization conditions (derivatization reagent concentration, reaction temperature, and derivatization time) were investigated for different drugs. The analytical columns used were Thermo AccucoreTM C₁₈ (2.4 μm, 30 mm×4.6 mm), Agilent Poroshell 120 EC-C₁₈ (4 μm, 50 mm×4.6 mm) as analytical columns, with 0.1% formic acid-acetonitrile, 0.1% formic acid-methanol, and 5 mM ammonium acetate-methanol: acetonitrile (V∶V=50∶50) as the gradient mobile phase, with flow rates of 0.5 mL·min^-1 and 0.6 mL·min^-1, respectively, using an ESI source for positive/negative ion detection in multiple reaction monitoring (MRM) mode.

5-ASA, MMI, and CAP all undergo nucleophilic substitution reactions with NBD-Cl, reacting rapidly and completely under suitable derivatization conditions. The established MMI analytical method has a linear range of 1.00-500 ng·mL^-1, with good linearity (r=0.998 9). The linear ranges of the CAP and 5-ASA analytical methods are both 2.00-1 000 ng·mL^-1, with good linear relationships (CAP: r=0.999 3, 5-ASA: r=0.999 6). The intra- and inter-batch precision (CV) and accuracy (RE) were both less than 15%, making the methods suitable for the analysis of actual samples of the corresponding drug formulations and successfully applied to the pharmacokinetic studies of MMI.

The established NBD-Cl derivatization LC-MS/MS analytical methods for the three drugs exhibit advantages such as high sensitivity, strong specificity, and low background noise, and successfully address the issues of low mass spectrometry response, poor spectral retention, and the tendency of CAP to oxidize. The methods require minimal plasma sample volume and have short analysis times, providing a feasible solution for the analysis of biological samples of the three drugs. They also demonstrate the applicability of NBD-Cl derivatization technology in the analysis of amine- and thiol-containing drugs.

To establish a method for determination of zonisamide in plasma of epileptic children by micro-detection technology combined with high performance liquid chromatography-mass spectrometry (HPLC-MS/MS).

10 μL of plasma samples were pre-treated by precipitation protein method with organic solvent. Reversed-phase chromatographic columns were adopted. Flow phase: 0.075% formic acid-2 mmol·L^-1 ammonium acetate-water (A) and methanol (B), gradient elution; flow speed: 0.45 mL·min^-1; injection volume: 1 μL. The quantitative method adopted the internal standard method, and the isotope internal standard was zonisamide -¹⁵N-D₄. Ion source was electric spray ion (ESI) source, multireaction monitoring (MRM) mode for quantitative analysis, using positive ion monitoring mode. The specificity, standard curve, lower limit of quantitation (LLOQ), residual effect, precision, matrix effects, extraction recovery and stability were investigated.

The retention times of zonisamide and its internal standard were both 1.25 min, and there was no interference from endogenous substances within the retention time. The linear range of zonisamide was 1-62.5 μg·mL^-1 (r=0.999 7), and LLOQ was 1 μg·mL^-1. The intra-day and inter-day precision RSD was equal or less than 4.84%, and the accuracy ranges from 97.75%-107.95%, with good stability, and this method was not affected by common matrix.

This method involves micro-blood collection, which is simple to operate, highly efficient and rapid, and can be used for the monitoring of daily therapeutic drugs in children with epilepsy in clinical practice.

To establish a high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method for analyzing the concentrations of methotrexate (MTX) and its metabolite 7-hydroxymethotrexate (7-OH-MTX) in human plasma, and to use it for clinical drug monitoring, in order to explore the relationship between their concentrations and liver and kidney toxicity.

Acetonitrile precipitation protein method was used to preprocess the samples, combined with HPLC-MS/MS detection. 369 blood samples from pediatric and adult patients who received high-dose methotrexate (HDMTX) chemotherapy were collected for methodological validation, and Spearman correlation analysis between concentration and hepatotoxicity and nephrotoxicity was performed using statistical software SPSS 27.

The linear relationship of MTX in human plasma was good within the concentration range of 0.005-2 μmol·L^-1 (r=0.998 8), and the linear relationship of 7-OH-MTX was good within the concentration range of 0.05-20 μmol·L^-1 (r=0.997 4). The intra batch and inter batch precision were all less than 10%, the extraction recovery rate reached 87.0-106.1%, and the coefficient of variation of matrix effect was less than 7%. The analysis of blood concentration measurements at 42 hours, 72 hours, and after HDMTX infusion showed that the concentration ratio of 7-OH-MTX/MTX was significantly negatively correlated with liver function indicators alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (P<0.01), while there was no significant correlation with renal function indicators creatinine (CR) and creatinine clearance rate (CCR) (P>0.05).

The established method is simple, accurate, and sensitive, and is suitable for clinical drug therapy monitoring. By monitoring 7-OH-MTX/MTX, the occurrence of liver toxicity can be effectively predicted for timely clinical drug rescue.