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 establish and validate a highly sensitive and selective high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the determination of lurasidone, which was used subsequently to clinical lurasidone blood drug concentration monitoring.

Tadalafil was used as internal standard. Following a deproteinization procedure, lurasidone and the internal standard (tadalafil) were isostatically eluted using a mobile phase composed of methanol and 0.1% aqueous formic acid (50：50, v/v) at a flow rate of 0.70 mL·min^-1. The chromatographic separation was achieved within 4.0 min on an Agilent ZORBAX Eclipse plus C₈(4.6 mm×100.0 mm，3.5 μm). Quantification was performed using a triple-quadrupole mass spectrometer operating in positive electrospray ionization (ESI) mode with multiple reaction monitoring (MRM). The method was validated for selectivity, linearity (calibration curve), precision and accuracy, matrix effect, extraction recovesise, stability and dilutive integrity. The concentrations of 14 clinical samples were measured after this method was validated.

The calibration curve for lurasidone in human plasma demonstrated linearity over the concentration range of 0.50-500.00 ng·mL^-1. The precision data (both intra- and inter-day) for the three QC levels ranged from 2.87% to 10.03%. Accuracy (relative error) was within±15% of the nominal values. The plasma samples maintained stability for 28 h at room temperature, for 85 days at -20 ℃ and through five freeze-thaw cycles. The measured concentrations of clinical samples were within the range of the standard curve, with concentrations ranging from 2.63 to 21.17 ng·mL^-1.

The validated method is proved to be convenient, accurate, and sensitive for the quantification of lurasidone in human plasma. The method is proved to be suitable for the monitoring of plasma concentration and pharmacokinetics study of lurasidone.

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 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 explore the potential of anti-programmed cell death ligand 1 (PD-L1) immunotherapy in giant congenital melanocytic nevus (GCMN) treatment.

GCMN cells were divided into four groups: GCMN group (GCMN cells alone), unactivated peripheral blood mononuclear cells (PBMC)+GCMN group (GCMN cells with unstimulated PBMCs), activated PBMC+GCMN group (GCMN cells with CD3/CD28 antibody-stimulated PBMCs), and activated PBMC+GCMN+PD-L1 inhibitor group (the activated PBMC +GCMN group treated with 10 μg·mL^-1 PD-L1 inhibitor atezolizumab). After 72 hours of culture, cell cytotoxicity and confluence were assessed. Cell viability was measured using the cell counting kit (CCK-8) assay, and apoptosis was evaluated via flow cytometry. Additionally, a humanized immune system was established in C-NKG severely immunodeficient mice by intraperitoneal injection of human PBMCs. A GCMN patient-derived xenograft (PDX) model was constructed in these humanized mice, divided into two groups: control group [phosphate buffer saline (PBS)] and experimental group (intraperitoneal injection of 10 mg·kg^-1 atezolizumab), administered every 3 days for 2 weeks, to evaluate in vivo efficacy.

Cell confluence rates for the GCMN, unactivated PBMC+GCMN, activated PBMC+GCMN, and activated PBMC+GCMN+PD-L1 inhibitor groups were (93.14±3.25)%, (85.29±2.40)%, (68.29±3.68)% and (22.55±4.28)%, respectively. Cell viability rates were (100.00±1.48)%, (80.35±2.60)%, (52.17±2.37)% and (15.61±1.82)%, respectively. Apoptotic cell proportions were (0.64±0.14)%, (9.32±0.91)%, (19.29±3.98)% and (28.43±0.33)%, respectively. Compared to the GCMN group, the activated PBMC+GCMN+PD-L1 inhibitor group showed statistically significant differences in all measured parameters (all P<0.05). In GCMN-PDX model, dermal cell density in experimental group and control group were (580±183) and (3 658±532) cells·mm^-2, respectively. And the difference of the above index between the two groups was statistically significant (all P<0.05).

This study demonstrates that PD-L1 inhibitors effectively target GCMN cells by activating the immune system, offering a promising new strategy for the clinical treatment of GCMN.

To evaluate the bioequivalence and safety of colchicine tablets under fasting and fed conditions in Chinese healthy participants.

A single-center, randomized, open, single-dose, two-formulation, two-period, two-sequence crossover design was adopted, enrolling 72 healthy participants, with 36 healthy participants in each group for fasting and fed conditions. Single oral dose 0.5 mg of test formulation (T) or the reference formulation (R) was taken across two periods，respectively. Plasma concentration of colchicine was determined using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The pharmacokinetic parameters were calculated and the bioequivalence was evaluated using the non-compartmental model in Phoenix WinNonlin 8.2 software.

The main pharmacokinetic parameters of a single oral colchicine tablet under fasting condition for T and R were as follows: C_max were (2.70±0.88) and (2.54±0.87) ng·mL^-1，t_max were 0.98 (0.48, 2.00) and 0.98 (0.73, 2.48) h，t_1/2 were (29.54±5.46) and (29.67±4.86) h，AUC_0-t were (18.40±5.30) and (18.00±5.10) h·ng·mL^-1，AUC_0-∞ were (21.80±5.90) and (20.70±4.90) h·ng·mL^-1, respectively. The main pharmacokinetic parameters under fed condition for T and R were as follows: C_max were (2.49±0.84) and (2.58±1.00) ng·mL^-1，t_max were 1.48 (0.73, 3.98) and 1.48 (0.73, 4.00) h，t_1/2 were (31.79±4.69) and (30.65±4.91) h，AUC_0-t were (19.80±4.30) and (19.90±5.00) h·ng·mL^-1，AUC_0-∞ were (23.20±5.00) and (23.10±5.20) h·ng·mL^-1, respectively. The geometric mean ratios of C_max, AUC_0-t and AUC_0-∞ of the T and R formulations under fasting and fed conditions with a 90% confidence interval ranged from 80.00% to 125.00%.

Under both fasting and fed conditions, the colchicine tablet test formulation and reference formulation were bioequivalent in Chinese healthy subjects, and both were shown to be safe.