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 investigate the improving effect of ginseng (GS) on metoprolol（meto） induced bradycardia in mice with chronic heart failure（CHF）and its molecular mechanism.

The CHF model in C57BL/6J mouse was established through left anterior descending coronary artery ligation. Mice were randomly divided into 6 groups, including sham group（underwent the same surgical procedure without coronary artery ligation）, model group, control group（26 mg·kg^-1·d^-1 metoprolol）, experimental-low group（26 mg·kg^-1·d^-1 metoprolol + 1.3 g·kg^-1·d^-1 GS）, experimental-midium group（26 mg·kg^-1·d^-1 metoprolol + 2.6 g·kg^-1·d^-1 GS）and experimental-high group（26 mg·kg^-1·d^-1 metoprolol + 5.2 g·kg^-1·d^-1 GS）. Each group contained 9 mice. After continuous administration for 8 weeks, heart rate changes were monitored using non-invasive blood pressure monitors in small animals; transcriptome sequencing was employed to analyze differentially expressed genes in cardiac tissues with functional enrichment analysis; calcium ion concentration in myocardial tissue was measured using a calorimetric assay; Western blot analysis was used to detect relative expression levels of sarcoplasmic reticulum calcium ATPase 2a（SERCA2a）, phosphorylated phospholamban（p-PLB）and sodium-calcium exchanger 1（NCX1）in myocardial tissue.

The heart rates of sham group, model group, control group and experimental-L, -M, -H groups were（528.61±60.86），（448.67±84.58）,（260.07±74.97）,（352.84±40.47）,（436.27±90.84）and（501.91±43.11）beats·min^-1, respectively. Control group was compared with model group, experimental-L, -M, -H groups were compared with control group, the differences showed statistical significance in heart rates（P<0.05，P<0.01）. Transcriptome gene ontology（GO）analysis revealed that differentially expressed genes were significantly enriched in pathways related to myocardial contraction and calcium ion transmembrane transport（all P<0.05）. The myocardial tissue calcium ion concentrations in sham group, model group, control group and experimental-L, -M, -H groups were（30.09±2.36）,（35.97±1.15）,（16.15±2.37）,（19.59±1.04）, （23.64±0.54）and（28.54±2.82）mmol·L^-1，respectively. Compared with control group, experimental-L, -M, -H groups all showed significantly increase（P<0.01, P<0.05）. The relative expression levels of SERCA2a in sham group, model group, control group and experimental-L, -M, -H groups were 1.00±0.14, 0.83±0.05, 1.23±0.12, 1.00±0.03, 0.98±0.05 and 0.90±0.11, respectively; the relative expression levels of p-PLB were 1.38±0.24, 1.05±0.19, 2.12±0.35, 1.08±0.24, 0.54±0.57,and 0.52±0.13; while the relative expression levels of NCX1 were 1.00±0.13, 1.08±0.20, 1.69±0.34, 1.06±0.35, 1.15±0.22 and 0.81±0.21. Compared with model group, the relative expression levels of all 3 proteins in control group showed significant increases. Except for SERCA2a in experimental -L group and NCX1 in experimental -M group, the relative expression levels of the above three proteins in the experimental group were significantly lower than that in the control group (P<0.01, P<0.05).

Meto may induce bradycardia adverse drug reaction by increasing the p-PLB/PLB ratio and elevating the expression levels of SERCA2a and NCX1 proteins, which reduces intracellular free calcium ion concentration in cardiomyocytes. Ginseng could significantly down regulate the p-PLB/PLB ratio, increase the protein expression levels of SERCA2a and NCX1, and up regulate the concentration of intracellular free calcium ion, so as to improve Meto induced bradycardia, suggesting that it may antagonize the negative frequency effect of Meto by remodeling the calcium cycle homeostasis.

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 explore the roles of oxidative stress and apoptosis in the renal deficiency and blood stasis type oligoasthenozoospermia（OAS） model, and to investigate the mechanism of the intervention by the Qi-supplementing, Blood-activating and Essence-nourishing formula.

The rat model of renal deficiency and blood stasis type oligoasthenozoospermia was established by intragastric administration of Gentiana macrophylla polysaccharides (GTW). The rats were randomly divided into the model group, the levocarnitine group, the low, medium and high doses of the Qi-supplementing, Blood-activating and Essence-nourishing formula groups; another 8 rats were randomly selected as the normal control group. The levocarnitine group was intragastrically administered 1.8 mL·kg^-1 levocarnitine oral liquid; the low, medium and high doses of the Qi-supplementing, Blood-activating and Essence-nourishing formula groups were given 7.87, 15.75 and 31.50 g·kg^-1，respectively; the blank group and the model group were intragastrically administered the same amount of 0.9% NaCl. All 6 groups of rats were administered the drugs once daily and continuously for 28 days. The general conditions of the rats were observed; the testicular and epididymal indices were measured; the sperm quality was detected; the pathological morphology of the testicular tissue was observed by hematoxylin-eosin staining (HE); the activity of reactive oxygen species (ROS), catalase (CAT) and superoxide dismutase (SOD) in the testicular tissue was detected by enzyme-linked immunosorbent assay (ELISA); the mRNA expression levels of Caspase-3, Bcl-2 and Bax in the testicular tissue were detected by real-time fluorescence quantitative polymerase chain reaction (q-PCR).

The testicular indices of the blank group, model group, low, medium and high doses of the Qi-supplementing, Blood-activating and Essence-nourishing formula group, and the levocarnitine group were (0.83±0.09)%, (0.55±0.10)%, (0.55±0.07)%,(0.71±0.12)%,(0.81±0.08)%, and (0.67±0.07)%, respectively; the epididymal indices were (0.36±0.05)%, (0.24±0.03)%, (0.25±0.04)%, (0.28±0.02)%,(0.35±0.06)%, and (0.28±0.03)%,respectively; the sperm concentrations were (24.11±11.64, 4.65±2.48, 6.75±3.81, 11.60±7.78, 21.72±7.81, 23.22±8.80)×10⁶ sperm·mL^-1, respectively; the sperm motility was (86.93±12.00)%, (33.46±16.13)%, (53.01±21.71)%, (63.15±24.35)%, (79.97±10.22)%, and (75.83±25.05)%, respectively; the ROS intensity was 597 926.11±87 518.20, 925 239.02±95 539.79, 846 676.84±64 867.76, 784 277.73±81 354.32, 658 228.04±82 768.68, and 725 740.12±87 846.36, respectively; the CAT activity was (1.40±0.11), (0.56±0.09), (0.77±0.11), (0.95±0.13), (1.15±0.12), and (1.03±0.11) U·mgprot^-1, respectively; the SOD activity was (2.41±0.07), (1.65±0.05), (1.79±0.33), (1.90±0.04), and (2.21±0.05), and (2.06±0.04) U·mgprot^-1, respectively. the relative expression levels of Bcl-2 mRNA were 1.00±0.04, 0.26±0.02, 0.39±0.04, 0.49±0.02, 0.87±0.02, and 0.66±0.05, respectively; the relative expression levels of Bax mRNA were 1.00±0.05, 1.78±0.07, 1.50±0.04, 1.39±0.02, 1.12±0.04, and 1.27±0.04, respectively; the relative expression levels of Caspase-3 mRNA were 1.00±0.03, 1.95±0.06, 1.81±0.03, 1.68±0.03, 1.18±0.07, and 1.49±0.08, respectively. The above-mentioned indicators of the model group compared with the blank group, the high-dose group compared with the model group, and the L-carnitine group except for the epididymal index compared with the model group, all showed statistically significant differences (P<0.05，P<0.01).

Oxidative stress and cell apoptosis play multiple regulatory roles in the sperm quality and testicular damage of OAS rats. The Qi-supplementing, activating blood, and tonifying essence formula may improve the sperm quality and testicular function of rats by inhibiting oxidative stress and cell apoptosis.

To investigate the effects of daptomycin (DAP) on the proliferation, apoptosis, and cell cycle of U266 [U266B1] human multiple myeloma cells (U266).

U266 cells were divided into the following groups: normal control group (NC group), DAP 20 μM group (DAP20), DAP 40 μM group (DAP40), DAP 80 μM group (DAP80), BZ 50 nM group (BZ50), and DAP 80 μM + BZ 50 nM group (DAP80+BZ50). U266 cells were treated with varying concentrations of DAP (0, 20, 40, and 80 μM), 50 nM bortezomib (BZ), and combination of DAP (80 μM) plus BZ (50 nM). Effects were assessed using cell counting kit-8 (CCK-8) assays, Western blotting (WB), flow cytometry, and quantitative real-time polymerase chain reaction (qPCR).

At 24 h post-treatment: Cell viability rates were recorded as (97.13±2.51)%, (96.80±3.44)%, (85.48±3.28)%, (81.56±2.09)%, (60.78±2.80)%, and (38.09±2.09)% for DAP alone (0-80 μM), BZ monotherapy, and combinatorial treatment, respectively. Early apoptotic cell proportions measured via flow cytometry showed values of (7.50±0.84)%, (8.20±1.41)%, (9.07±1.22)%, (13.14±2.27)%, (14.51±2.58)%, and (15.17±1.87)% across groups. Proportions of cells in G1 phase were determined to be (33.40±1.48)%, (33.03±2.49)%, (31.50±1.40)%, (38.59±1.54)%, (36.94±1.13)%, and (39.43±1.40)%. Relative expression levels of ribosomal protein S19 (RPS19) mRNA exhibited fold changes of 0.99±0.09, 1.00±0.14, 0.66±0.04, 0.61±0.06, 0.55±0.04, and 0.53±0.07, while corresponding protein levels via WB analysis were 1.08±0.05, 0.97±0.03, 0.90±0.02, 0.87±0.04, 0.89±0.04, and 0.57±0.03. Statistically significant differences (all P<0.001) were observed in BZ50, DAP80, and their combination compared to DAP 0 μM group.

DAP may exert its inhibitory effect on U266 cell proliferation and promote apoptosis by downregulating the expression of RPS19. This study provides a potential therapeutic drug for the treatment of multiple myeloma.