To investigate the effect of epifriedelanol (Epi) on gene expression of P-glycoprotein (P-gp) in human colorectal adenocarcinoma cell line LS174T and its mechanism.

LS174T cells were divided into control group and experimental -L, -M, -H groups. Experimental -L, -M, -H groups were treated with 5, 10, 20 μmol·L^-1 Epi, respectively. Control group was treated with 0.1% dimethyl sulfoxide. Polymerase chain reaction was used to detect the mRNA expression level of P-gp. The effect of Epi on multidrug resistance protein 1 (MDR1/P-gp) luciferase activity was investigated by pregnane X receptor (PXR)-MDR1/P-gp dual luciferase reporter gene assay. In addition, Western Blot was used to detect the protein expression level of P-gp and the nuclear factor-κB (NF-κB) pathway related proteins.

The relative expression levels of P-gp mRNA in experimental -M, -H groups and control group were 52.24±5.19, 23.00±3.52 and 100.00±9.00; the relative expression levels of P-gp protein were 86.37±9.96, 74.85±15.92 and 100.00±12.91; the relative activities P-gp luciferase were 230.19±41.32, 203.10±52.84 and 279.67±19.20; the relative expression levels of p65 (RelA/p65) in nucleus were 132.36±23.93, 145.96±25.15 and 100.00±10.88; the relative expression levels of phosphorylation NF-κB inhibits protein kinase α/β (p-IKKα/β) in cytoplasm were 184.00±54.82, 290.10±49.59 and 100.00±15.34; the relative expression levels of phosphorylated NF-κB inhibitory protein α (p-IκBα) in cytoplasm were 125.73±18.77, 133.69±20.25 and 100.00±8.12; the relative expression levels of IκBα in cytoplasm were 78.36±14.83, 70.44±14.57 and 100.00±22.82, respectively. The above indexes of experimental -M and experimental -H groups were compared with control group, and the differences were statistically significant (P<0.05, P<0.01, P<0.001).

Epi can down-regulate the gene expression of P-gp in human colorectal adenocarcinoma cell line LS174T, and the mechanism may be related to activation of NF-κB and suppression of PXR.

To investigate the effect of subanesthetic dose esketamine hydrochloride injection combined with midazolam injection on hip replacement in elderly patients.

The elderly patients undergoing hip replacement were divided into control group and treatment group. The control group was given 0.02 mg·kg^-1 midazolam injection; the treatment group was given 0.02 mg·kg^-1 midazolam injection combined with 0.25 mg·kg^-1 esketamine hydrochloride injection. Anesthesia (sedation, analgesic effect), hemodynamic indexes, and safety evaluation.

There were 90 cases in the treatment group and 90 cases in the control group. The scores of sedation in the treatment group and the control group were (1.54±0.28) and (1.67±0.35) points, respectively; the scores of pain simulation at 2 h after operation were (3.16±0.47) and (3.38±0.59) points, respectively; at the end of the operation, the mean arterial pressure of the treatment group and the control group were (83.06±2.47) and (82.15±2.94) mmHg, respectively; the heart rate were (82.04±3.25) and (80.75±3.32) time·min^-1, respectively, and the difference was statistically significant (all P<0.05). The total incidence of adverse drug reactions in the treatment group and the control group was 8.89% (8 cases /90 cases) and 13.33% (12 cases /90 cases), respectively, with no statistical significance (P>0.05).

The subanesthetic dose of esketamine hydrochloride injection combined with midazolam hydrochloride injection can effectively stabilize the hemodynamic level of the body and reduce postoperative pain in elderly patients with hip replacement with good safety.

To study the expression characteristics of osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL)/receptor activator of nuclear factor-κB (RANK) system and the relationship with fibrosis in myocardial tissues of rats with chronic heart failure.

SD rats were randomly divided into sham-operation group (12 rats) and model group. In sham-operation group, surgical thread was passed through the abdominal aorta without constricting it after laparotomy; in model group, establish the heart failure model by abdominal aorta coarctation. The successful model rats were randomly divided into model 1 week (12 rats), model 2 weeks (11 rats), model 4 weeks (11 rats), model 8 weeks (11 rats) and model 12 weeks groups (11 rats). The end point of the study is at week 12. The contents of hydroxyproline (HYP), total myocardial collagen and collagen volume fraction (CVF) were compaired in all proups. The expression levels of OPG, RANKL and RANK proteins in cardiomyocytes were determined by Western blot.

The contents of HYP in sham-operation, model 1 week, model 2 weeks, model 4 weeks, model 8 weeks and model 12 weeks group were (0.25±0.04), (0.37±0.05), (0.45±0.04), (0.60±0.05), (0.82±0.10) and (1.03±0.07) μg·mg^-1; the total myocardial collagen contents were (1.87±0.31), (2.73±0.38), (3.36±0.31), (4.47±0.37), (6.08±0.74) and (7.67±0.49) μg·mg^-1; the CVF were (1.95±0.23)%, (2.40±0.25)%, (3.65±0.25)%, (5.43±0.29)%, (6.97±0.36)% and (9.38±0.49)%; the relative expression levels of OPG protein were 0.64±0.07, 0.80±0.07, 1.02±0.07, 1.32±0.11, 2.13±0.12 and 2.84±0.16; the relative expression levels of RANKL protein were 0.71±0.08, 1.06±0.07, 1.53±0.07, 2.62±0.12, 4.46±0.14 and 6.11±0.16; the relative expression levels of RANK protein were 0.30±0.05, 0.45±0.05, 0.63±0.06, 0.98±0.07, 1.43±0.10 and 1.63±0.10. With the extention of time, the above indexs of all model groups were significantly higher than those in the sham-operation group (all P<0.05). There were positive linear correlation between the relative expression levels of OPG, RANKL, RANK protein and the levels of CVF and total contents in cardiomyocytes of rats with chronic heart failure (all P<0.01).

In the process of chronic heart failure, the expression of OPG/RANKL/RANK axis is obviously enhanced, in which the up-regulation of RANKL level is most obvious. The expression level of OPG/RANKL/RANK is positively correlated with CVF and total myocardial collagen content.

To observe the clinical efficacy and safety of vericiguat tablets combined with sacubitril valsartan sodium (Sac/Val) tablets in the treatment of patients with heart failure with reduced ejection fraction (HFrEF).

The HFrEF patients were divided into control group and treatment group according to the cohort method. The control group was treated with Sac/Val tablets 200 mg per time, bid, orally. On the basis of control group, the treatment group was treated with vericiguat tablets 2.5 mg per time, qd, taken with meal. Two groups were treated for 3 months. The clinical efficacy, left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD) and end-systolic diameter (LVESD), levels of high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), nitric oxide (NO), N-terminal pro-brain natriuretic peptide (NT-proBNP), blood urea nitrogen (BUN) and serum creatinine (SCr), and safety were compared between the two groups. During follow-up, the heart failure rehospitalization rates and major adverse cardiovascular events were compared between the two groups.

Treatment group was enrolled 53 patients, control group was enrolled 53 patients. After treatment, the total effective rates of treatment and control groups were 94.34% (50 cases / 53 cases) and 81.13% (43 cases / 53 cases) with statistical significant difference (P<0.05). After treatment, the LVEF of treatment and control groups were (48.02±5.20)% and (43.02±4.33)%, the LVEDDs were (52.85±6.30) and (55.63±6.88) mm, the LVESDs were (41.64±6.40) and (44.22±5.85) mm, the levels of hs-CRP were (10.22±2.63) and (14.60±2.98) mg·L^-1, the levels of IL-6 were (14.48±2.40) and (17.36±2.52) pg·mL^-1, the levels of NO were (102.60±20.16) and (92.16±16.33) μmol·L^-1, the levels of NT-proBNP were (898.74±102.20) and (1315.60±182.64) ng·L^-1, the levels of BUN were (12.02±2.28) and (13.45±2.33) mmol·L^-1, the levels of SCr were (82.22±5.89) and (85.64±6.03) μmol·L^-1, the heart failure rehospitalization rates were 5.66% and 13.21%, respectively; the differences were statistical significant between two groups (all P<0.05). The adverse drug reactions of treatment group were hyperkalemia, hypotension, renal dysfunction, dizziness and headache, while those in control group were renal dysfunction, hyperkalemia, and hypotension. The major adverse cardiovascular events of treatment group were angina pectoris and acute myocardial infarction, while those in control group were angina pectoris, acute myocardial infarction and atrial fibrillation. The incidences of total adverse drug reactions in treatment and control groups were 13.21% and 7.55%, the incidences of major adverse cardiovascular events were 5.66% and 13.21%, respectively, without statistically significant differences (all P>0.05).

Vericiguat tablets combined with Sac/Val tablets have a definitive clinical efficacy in the treatment of HFrEF patients, which can improve cardiac and endothelial function, reduce inflammatory response and readmission times, without increasing the incidences of adverse drug reactions.

To explore the cardiovascular protective effect of dapagliflozin on patients with heart failure with preserved ejection fraction (HFpEF) complicated with type 2 diabetes mellitus (T2DM).

Patients with HFpEF complicated with T2DM were divided into treatment group and control group according to cohort method. The control group was given 0.5 g of metformin hydrochloride tablet orally twice a day, while the treatment group was given 10 mg of dapagliflozin tablet orally once a day on the basis of treatment in the control group. Patients in both groups were continuously treated for 6 months. The clinical efficacy after treatment and blood glucose indicators [fasting blood glucose (FBG), 2 hours postprandial blood glucose (2 h PBG), glycosylated hemoglobin (HbA1c)], echocardiographic left ventricular parameters [left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left ventricular remodeling index (LVRI), left ventricular mass index (LVMI)] and serum N-terminal pro-brain natriuretic peptide (NT-proBNP), serum myocardial fibrosis indicators [matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1)] before and after treatment were compared between both groups, and the safety evaluation was performed.

Seventy-five cases in treatment group and 72 cases in control group were included. After treatment, the total effective rates in treatment group and control group were 93.33% (70 cases/75 cases) and 81.94% (59 cases/72 cases), respectively (P<0.05). After treatment, the levels of FBG, 2 h PBG, HbA1c, LVEF and LVEDD revealed no statistical differences between treatment group and control group (all P>0.05). After treatment, LVRI values in treatment group and control group were (2.17±0.41) and (2.54±0.46) g·mL^-2; LAMI values were (102.47±10.32) and (113.84±15.52) g·m^-2; serum NT-proBNP levels were (652.38±208.26) and (993.24±302.69) pg·mL^-1; MMP-9 levels were (142.52±21.67) and (168.73±25.88) mg·L^-1; TIMP-1 levels were (3.68±0.84) and (3.12±0.91) μg·L^-1, respectively (all P<0.05). The total incidence rates of adverse reactions in treatment group and control group were 14.67% (11 cases/75 cases) and 12.50% (9 cases/72 cases), respectively (P>0.05).

Dapagliflozin can improve ventricular remodeling and enhance cardiac function in patients with HFpEF complicated with T2DM, and it has a significant cardiovascular protective effect.

To analyze the efficacy and safety of different doses of esketamine for laparoscopic high hernia sac ligation in school-age children.

The school-age children who underwent laparoscopic high ligation of hernia sac were divided into small-dose group and conventional-dose group according to cohort method. The conventional-dose group was given intravenous 0.75 mg·kg^-1 esketamine hydrochloride injection to prepare for induction; the small-dose group was given intravenous 0.50 mg·kg^-1 esketamine hydrochloride injection to prepare for induction, and the two groups were given the same anesthesia induction, anesthesia maintenance and postoperative analgesia. The recovery time, laryngeal mask removal time, anesthesia recovery room residence time, children face, legs, activity, cry, consolability behavioral tool (FLACC) score of the children in the two groups were observed, the hemodynamic indexes were recorded at the time of entry (T1), before anesthesia induction (T2), immediately after laryngeal mask placement (T3), and the safety was evaluated.

A total of 39 cases and 43 cases children were included in the conventional-dose group and the small-dose group, respectively. After treatment, the recovery time of conventional-dose group and small-dose group were (26.36±3.91) and (23.21±3.55) min; the time of removing laryngeal mask were (13.02±2.15) and (12.24±2.30) min; the retention time of postanesthesia care unit (PACU) were (37.23±5.64) and (32.11±5.36) min; the scores of FLACC were (2.08±0.45) and (2.16±0.51) points, respectively. At T1, T2 and T3, the heart rate (HR) of the conventional-dose group were (99.23±15.78), (102.19±17.20) and (118.30±14.96) beat·min^-1; that of the small-dose group were (99.93±16.27), (103.28±16.75) and (120.19±15.39) beat·min^-1, respectively. The mean arterial pressure (MAP) of the conventional-dose group were (84.56±7.22), (85.92±6.96) and (89.89±7.02) mmHg; that of the small-dose group were (84.88±6.87), (86.16±6.45) and (91.12±7.31) mmHg, respectively. There were statistically significant differences in the recovery time and PACU retention time between the small-dose group and the conventional-dose group (all P<0.05). The adverse drug reactions in the two groups mainly included nausea and vomiting, increased secretions and transient hypertension. The incidence of total adverse drug reactions in the conventional-dose group and the small-dose group were 10.26% and 4.65%, respectively, with no statistical significance (P>0.05).

Small-dose esketamine hydrochloride injection can effectively maintain hemodynamic stability in the preoperative intravenous administration of school-age children undergoing laparoscopic high ligation of hernia sac, and the effect of reducing postoperative pain and inhibiting agitation during the recovery period is comparable to that of conventional-dose, with good safety.

To study the effects of Hedysarum polysaccharides polysaccharide (HPS) on the farnesoid X receptor (FXR)-fibroblast growth factor-19(FGF19) signaling pathway of diabetes rats.

Twelve Wistar male rats were randomly selected as the normal group, and the other rats were fed with a single intraperitoneal injection of streptozotocin (50 mg·kg^-1 STZ) and a high sugar and high-fat diet to replicate the diabetes rat model. Model rats were randomly divided into model group, positive control group (given 400 mg·kg^-1·d^-1 suspension of Bifidobacterium quadruplex live bacterial tablets by gavage), experimental-H, -M, -L groups (given 200, 100, and 50 mg·kg^-1·d^-1 doses of HPS suspension by gavage); normal group, and model group were given equal volume of purified water by gavage once a day for 8 consecutive weeks. Glucose (Glu) was detected by a blood glucose meter; and serum total glyceride (TG) and total cholesterol (TC) were detected by enzyme-linked immunosorbent assay reagent kit; the expressions of FXR、fibroblast growth factor receptors 4 (FGFR4) relative mRNA expression level and protein were detected by real-time fluorescence quantitative polymerase chain reaction method and Western blot.

The Glu concentrations in the normal group, model group, positive control group, and experimental-H groups were (7.66±0.61), (29.25±1.64), (23.31±3.02) and (19.31±5.13) mmol·L^-1, respectively; the TG content were (957.00±113.73), (1 345.00±246.44), (958.00±96.53) and (964.00±130.22) μmol·L^-1, respectively; the TC content were (161.65±4.53), (302.19±5.35), (236.09±5.14) and (165.58±2.58) μmol·L^-1, respectively; the expression of FXR relative mRNA expression level were 1.00±0.06, 0.48±0.02, 0.67±0.04 and 0.92±0.04, respectively; the expression of FGFR4 relative mRNA expression level were 1.00±0.04, 0.17±0.01, 0.48±0.04 and 0.41±0.03; respectively. The above indexes of the model group were compared with the control group, and the above indexes of the control group and the experimental-H group were compared with the model group, and the differences were statistically significant (all P<0.01).

HPS improves blood sugar, lowers blood lipids, and protects liver and intestinal tissues, possibly by regulating the FXR-FGF19 signaling pathway in intestinal tissue, and regulating bile acid synthesis.

To explore the clinical effects and influencing factors of recombinant human growth hormone (rhGH) treatment in pediatric patients with growth hormone deficiency.

The study subjects were pediatric patients with growth hormone deficiency, all of whom received a combination therapy of stanozolol tablets 2 mg (qd) and 0.1 U·kg^-1·d^-1 of recombinant human growth hormone injection for a continuous period of one year. After one year, the patients were divided into active group and invalid group based on clinical outcomes. Comparisons were made between the two groups in terms of height, annual growth velocity (GV) and height standard deviation score (HtSDS) before and after treatment, and safety evaluations were conducted. Multivariate Logistic regression analysis was used to identify factors that influenced the treatment outcomes in pediatric patients with growth hormone deficiency.

After one year of treatment, a total of 93 cases pediatric patients were included in the analysis, with 62 cases in the active group and 31 cases in the invalid group. The heights of the patients before and after treatment were (119.40±2.48) and (129.08±2.37) cm, respectively; the GV were (3.08±0.39) and (7.34±1.02) cm·year^-1, respectively; the HtSDS were -2.45±0.49 and -1.68±0.35, respectively, with statistically significant differences observed for all comparisons (all P<0.05). In the active and invalid groups, the proportions of patients with GV<3.0 cm·year^-1 before treatment were 32.26% and 58.06%, respectively; the proportions of patients with peak growth hormone (GH) levels <5.0 ng·mL^-1 before treatment were 30.65% and 54.84%, respectively; the average maternal heights were (158.83±5.76) and (155.48±6.58) cm, respectively, with statistically significant differences observed for all comparisons (all P<0.05). The results of the Logistic regression model showed that GV<3.0 cm·year^-1 before treatment, peak GH levels <5.0 ng·mL^-1 before treatment, and a shorter maternal height were independent risk factors for poor treatment outcomes with rhGH in pediatric patients with growth hormone deficiency (all P<0.05). No severe adverse reactions occurred during the treatment of any patient; seven patients experienced pain at the injection site, one patient had a slight increase in blood glucose, and five patients had mild decreased appetite. The total incidence of adverse drug reactions were 13.98% (13 cases/93 cases).

Treatment with rhGH for pediatric patients with growth hormone deficiency can significantly improve height development and has good safety, but it is influenced by factors such as growth velocity, peak GH levels, and maternal height.