To investigate the influence of augmented renal clearance (ARC) on the steady-state serum concentration and pharmacodynamics of meropenem in patients with severe infections and to analyze the linear relationship between them.

A retrospective analysis was conducted on the inpatients who received meropenem treatment and underwent therapeutic drug monitoring (TDM) at the Fifth Medical Center of the General Hospital of the PLA from June 2021 to September 2024. Serum drug concentration data were collected, and pharmacokinetic parameters were calculated using a one-compartment model. The steady-state serum concentrations and pharmacodynamic parameters were compared between patients with normal renal function and those with ARC. Multiple linear regression analysis was performed to explore the factors influencing meropenem serum concentrations and pharmacodynamic parameters.

When meropenem was administered at a dose of 1.0 g three times daily, the blood concentrations in patients with ARC at 3 hours and 0.5 hours before the last administration were (4.78±2.34) mg·L^-1 and (2.44±1.60) mg·L^-1, respectively. In contrast, the corresponding concentrations in patients with normal renal function were (14.08±10.45) mg·L^-1 and (8.40±7.07) mg·L^-1, respectively. The blood concentrations of meropenem were significantly lower in ARC patients compared to those with normal renal function (P<0.05). For the pharmacodynamic target of f%T>4MIC≥40%, the target attainment rates in ARC patients were 81.25%, 25.00%, 0.00%, and 0.00% at MIC values of 1, 2, 4, and 8 μg·mL^-1, respectively. In comparison, the rates in patients with normal renal function were 92.31%, 76.92%, 53.85%, and 7.69%, respectively, indicating significantly lower target attainment in the ARC group. Multiple linear regression analysis revealed that creatinine clearance rate and serum albumin level significantly influenced both the plasma concentration and pharmacodynamic target attainment of meropenem.

ARC significantly reduces the steady-state serum concentration of meropenem and the rate of achieving pharmacodynamic targets, leading to the failure of anti-infective therapy. For patients with severe infections and ARC, attention should be paid to the effects of creatinine clearance, serum albumin on serum drug concentrations and therapeutic efficacy. TDM should be performed to adjust the dosing regimen in a timely manner.

To investigate the effects of gastrodin (GAS) on diabetes-induced cardiomyopathy (DCM) and its underlying mechanisms.

Fifty C57BL/6J mice were divided into control group (n=10, normal diet) and high-fat high-sucrose (HFD) group [n=40, HFD diet combined with intraperitoneal streptozotocin (STZ) injection to establish the DCM model]. Successfully modeled HFD mice were randomly assigned to the model group, GAS low-dose group (50 mg·kg^-1, qd), GAS high-dose group (100 mg·kg^-1 qd), and positive control metformin group (250 mg·kg^-1，qd). The control and model groups were administered saline via gavage, while the other three groups received their respective drugs via gavage for three consecutive months. Cardiac ultrasound was used to measure left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-systolic volume (LVESV), and left ventricular internal diameter at end-systole (LVIDs). Serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were quantified using assay kits. Cardiac tissue levels of malondialdehyde (MDA) and glutathione (GSH) were measured. Protein expression was analyzed via Western blotting.

The LVEF of the model group and high-dose group were (62.54±3.24)% and (80.20±3.29)%, respectively, and the LVFS were (25.87±4.75)% and (42.97±4.75)%, respectively LVESVs were (55.00±4.08) and (23.75±4.79) μL, LVIDs were (2.63±0.16) and (1.67±0.21) mm, TG was (1.17±0.18) and (0.51±0.09) mmol·L^-1, TC was (5.58±0.76) and (1.93±0.58) mmol·L^-1, HDL-C was (1.69±0.50) and (4.86±0.48) mmol·L^-1, LDL-C was (3.84±0.70) and (1.17±0.65) mmol·L^-1, respectively. The MDA content was (6.10±0.38) and (3.02±0.16) nmol· mgprot^-1, the GSH content was (20.90±10.30) and (39.49±15.70) μmol·gprot^-1, the relative expression levels of oxidative stress protein Kelch like ECH associated protein 1 (Keap1) were 1.75±0.22 and 1.07±0.03, the relative expression levels of nuclear factor-E2-related factor 2 (Nrf2) were 0.51±0.09 and 0.96±0.13, and the relative expression levels of peroxidase-1 (PRDX-1) were 0.43±0.08 and 0.93±0.18, respectively, and the relative expression levels of heme oxygenase-1 (HO-1) were 0.42±0.08 and 0.94±0.14, respectively. Compared with the model group, the above indicators in the high-dose group showed statistically significant differences (P<0.01，P<001).

GAS can improve the myocardial function of DCM mice, and its mechanism of action may be related to the inhibition of oxidative stress and the regulation of the Keap1/Nrf2 signaling pathway.

To evaluate the bioequivalence of the test preparation and the reference preparation in a single dose of vortioxetine hydrobromide tablets under fasting and fed conditions in healthy volunteers.

A randomized, open-ended, single-dose, two-cycle, double-cross bioequivalence trial design was adopted, and 28 subjects were enrolled in the fasting group and the fed group, respectively, and 1 tablet of the test preparation and the reference preparation were taken in the fasting or fed state each cycle. The concentration of vortioxetine in plasma was determined by liquid chromatography-tandem mass spectrometry （LC-MS/MS） method. The main pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.1, and the bioequivalence was evaluated.

The t_1/2 for the fasting single oral administration of the test preparation and the reference preparation were （61.74±23.90） and （58.22±18.61）h, the median T_max were （7.33±2.15） and （7.61±3.89） h, the C_max were （7.32±1.90） and （7.46±1.98） ng·mL^-1, and the AUC_{0-72 h} were （312.61±92.95） and （310.00±93.84） h·ng·mL^-1, respectively. The statistical results of the 90% confidence intervals of the main pharmacokinetic parameters C_max and AUC_{0-72 h} were 92.75%-103.71% and 97.47%-104.43%, respectively, all of which were within the range of 80.00%-125.00%, and the safety of the tested preparation and the reference preparation was good when taken orally on an empty stomach. The t_1/2 of single oral administration after prandial administration of the tested preparation and the reference preparation were （77.60±33.87） and （81.61±45.24） h, the median T_max were （8.06±3.02） and （7.77±2.45）h, the C_max were （7.54±2.08） and （7.76±2.00） ng·mL^-1, and the AUC_{0-72 h} were （319.75±87.71） and （326.03±86.64） h·ng ·mL^-1, respectively. The 90% confidence intervals of C_max, AUC_{0-72 h} were 89.00%-105.32% and 92.21%-102.72%, respectively, which were in the range of 80.00%-125.00%.

In the state of fasting and fed single oral administration, the two kinds of vortioxetine hydrobromide tablets have good bioequivalence.

To investigate the effect of emodin (Emo) on chemotherapy resistance of human leukemia K562/adriamycin-resistant (K562/ADR) cells and its mechanism.

K562/ADR cells were assigned to control group and experimental -L, -M, -H groups. Experimental -L, -M, -H groups were incubated with Emo at concentrations of 5, 10, and 20 μmol·L^-1, respectively. Control group was treated with 0.1% dimethyl sulfoxide. Methyl thiazolyl tetrazolium (MTT) assay was used to detect the effect of Emo on chemotherapy resistance in K562/ADR cells. Fluorescence analysis was used to detect the intracellular accumulation of adriamycin. Flow cytometry was used to detect the cell cycle and apoptosis. Polymerase chain reaction was used to detect the mRNA expression level of P-glycoprotein (P-gp). In addition, Western blot was used to detect the protein expression level of P-gp and nuclear factor-kappa B (NF-κB) pathway related proteins.

The half maximal inhibitory concentrations (IC₅₀) of K562/ADR cells to adriamycin in experimental -M, -H groups and control group were (20.91±2.03), (11.79±0.89) and (38.00±2.61) μg·ml^-1; the intracellular adriamycin-associated mean fluorescence intensities (×10⁴) were (5.22±0.66), (7.47±0.77) and (2.69±0.69); the proportions of G₀/G₁ phase cells were (37.81±3.47)%, (28.05±2.86)% and (51.18±5.06)%; the proportions of S phase cells were (19.89±2.98)%, (15.24±2.21)% and (32.15±3.20)%; the proportions of G₂/M phase cells were (40.65±3.33)%, (55.75±4.55)% and (13.63±2.29)%; the cell apoptosis rates at 48 hours were (39.91±3.51)%, (46.26±4.06)% and (21.45±1.92)%; the relative expression levels of P-gp mRNA were 68.10±9.61, 31.01±8.90 and 100.00±12.22; the relative expression levels of P-gp protein were 77.01±8.31, 63.65±7.72 and 100.00±7.07; the relative expression levels of p65 (RelA/p65) in nucleus were 126.10±8.17, 157.58±11.87 and 100.00±8.55; the relative expression levels of phosphorylated-inhibitor of nuclear factor κB protein α (p-IκBα) in cytoplasm were 132.45±13.46, 150.97±9.47 and 100.00±7.35; the relative expression levels of IκBα in cytoplasm were 82.10±5.95, 73.20±6.39 and 100.00±5.84; the relative expression levels of phosphorylated-inhibitor of kappa B kinase α/β (p-IKKα/β) in cytoplasm were 126.23±6.63, 120.61±7.70 and 100.00±7.96, respectively. Compared the above indexes of the experimental -M and experimental -H groups with those of the control group, and the differences were statistically significant (P<0.05, P<0.01, P<0.001).

Emo can inhibit adriamycin chemotherapy resistance in K562/ADR cells by activating the NF-κB pathway and subsequently down-regulating the expression of P-gp.

To study the efficacy and safety of allisartan isoproxil tablet combined with indapamide tablet in the treatment of patients with mild to moderate essential hypertension and coronary heart disease.

Patients with mild to moderate essential hypertension and coronary heart disease were divided into treatment group and control group using the cohort method. The control group was given oral indapamide tablets 2.5 mg once a day based on the conventional treatment regimen. The treatment group was given allisartan isoproxil tablets 240 mg once a day in addition to the control group’s regimen for a total of 12 weeks. The clinical efficacy, 24-hour blood pressure variability, cardiac function, vascular endothelial function and safety evaluation of the two groups were compared.

A total of 105 patients were enrolled, including 54 patients in treatment group and 51 patients in control group. After treatment, the total clinical effective rate of the treatment group was 90.74% (49 cases/54 cases), and that of control group was 72.55% (37 cases/51 cases), which was significantly higher in treatment group than in control group (P<0.05). After treatment, the daytime (d) systolic blood pressure variability (SBPV) levels in treatment group and control group were (11.32±2.13) and (12.48±2.26) mmHg, respectively; the nighttime (n) SBPV levels were (10.03±1.79) and (10.82±2.10) mmHg, respectively; the d diastolic blood pressure variability (DBPV) levels were (8.66±1.51) and (9.36±1.57) mmHg, respectively; the nDBPV levels were (8.05±1.32) and (8.68±1.62) mmHg, respectively; the 24 h SBPV levels were (10.85±2.20) and (11.96±2.05) mmHg, respectively; the 24 h DBPV levels were (9.67±1.93) and (10.66±1.92) mmHg, respectively; the brain natriuretic peptide (BNP) levels were (83.47±10.53) and (89.41±13.19) ng·L^-1, respectively; the endothelin-1 (ET-1) levels were (55.44±9.27) and (60.36±10.86) ng·L^-1, respectively; and the Apelin levels were (36.44±6.41) and (34.22±4.37) ng·mL^-1, respectively. The above metrics showed significant differences between the two groups (P<0.05，P<0.01). The adverse drug reactions in treatment group included diarrhea, fever, fatigue, palpitations, soreness in both knee joints, cough, insomnia, decreased appetite and orthostatic hypotension. The adverse drug reactions in control group included diarrhea, headache, decreased appetite, insomnia and orthostatic hypotension. The total incidence of adverse drug reactions in treatment group was 22.22% (12 cases /54 cases), and that in control group was 17.65% (9 cases /51 cases). There was no statistically significant difference (P>0.05).

The application of allisartan isoproxil combined with indapamide in treatment of patients with mild to moderate essential hypertension and coronary heart disease can achieve significant therapeutic effects, regulate 24-hour blood pressure variability, improve cardiac function, vascular endothelial function, and quality of life, also demonstrate good safety.

To explore the clinical efficacy of fusidic acid ointment in patients with acne vulgaris who underwent non-ablative fractional 1 565 nm laser treatment.

Patients with common acne who received non-peeling fractional 1 565 nm laser treatment were divided into treatment group and control group. Treatment group was treated with fusidic acid ointment, 3 times a day, while control group was not treated with additional treatment.The lesion severity, skin sebum secretion, skin stratum corneum water content, clinical efficacy, matrix metalloproteinase 1 (MMP-1), matrix metalloproteinase tissue inhibitor-1 (TIMP-1), MMP-1/TIMP-1 ratio, skin elasticity indicators (R2, R5, R7), facial acne comprehensive grading system (global acne grading system, GAGS) score and acne-specific quality of life questionnaire (Acne-QOL) score were compared between the two groups.

100 patients with acne vulgaris who received non exfoliative dot matrix 1 565 nm laser were enrolled, including 50 cases in treatment group and 50 cases in control group. After treatment, the total clinical effective rate of treatment group was 96.00% (48 cases/50 cases), and that of control group was 74.00% (37 cases/50 cases), the difference was statistically significant (P<0.05). After 3 months treatment, the skin oil secretion of treatment group and control group were (53.79±7.23) and (69.21±10.67) μg·cm^-2, respectively; the moisture content of cuticle were (34.21±5.15)% and (29.68±3.92)%, respectively; MMP-1 were (1.02±0.28) and (1.24±0.43) μg·mL^-1, respectively; TIMP-1 were (1.62±0.24) and (1.43±0.20) μg·mL^-1, respectively; MMP-1/TIMP-1 were 0.63±0.10 and 0.87±0.15, respectively; the R2 were (53.77±8.75)% and (49.11±7.64)%, respectively; the R5 were (53.88±8.58)% and (49.67±7.69)%, respectively; the R7 were (32.55±6.05)% and (28.39±5.44)%, respectively; the GAGS scores were (13.78±2.69) and (17.83±3.35) points, respectively; the Acne-QOL scores were (105.56±5.58) and (90.21±6.32) points, respectively. After treatment, the above indexes in treatment group were significantly lower than those in control group (all P<0.05). The adverse drug reactions in treatment group and control group were dry, tingling, scaling and flushing. The total incidence of adverse drug reactions in treatment group was 10.00% (5 cases/50 cases) and in control group was 16.00% (8 cases/50 cases). There was no significant difference in the incidence of adverse drug reactions between the two groups (P>0.05).

Fusidic acid ointment could significantly improve the dynamic balance of MMP-1/TIMP-1, skin elasticity and skin physiological indexes in patients with acne vulgaris receiving non-ablative fractional 1 565 nm laser, with good safety.