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 investigate the effect and mechanism of methyl oxofulnonone A (META) on high glucose (HG)-induced H9c2 cell injury.

H9c2 cells were divided into control group (normal culture), model group (55 mmol·L^-1 glucose) and experimental -L, -M, -H groups (55 mmol·L^-1 glucose+12.5, 25.0, 50.0 μmol·L^-1 META). Cell viability was detected by cell counting kit-8; intracellular reactive oxygen species (ROS) level was detected by DCFH-DA fluorescent probe; intracellular adenosine triphosphate (ATP) content was detected by luciferase; and autophagy-related protein expression was detected by Western blotting.

The optical density values of 72-hour cells in the control group, model group and experimental -M, -H groups were 0.91±0.03, 0.61±0.01, 0.69±0.02 and 0.72±0.03; the ROS levels were (40.75±1.53)%, (43.73±1.30)%, (30.87±1.27)% and (28.28±1.43)%; the ATP contents were (8.16±0.71), (4.03±0.29), (5.29±0.31) and (5.83±0.31) nmol·mg^-1; the relative expression levels of autophagy-related gene 5 protein were 1.05±0.06, 1.46±0.09, 0.98±0.11 and 0.89±0.09; the relative expression levels of ubiquitin-binding protein were 1.05±0.10, 0.55±0.13, 0.89±0.04 and 0.98±0.04; the ratios of microtubule-associated protein 1 light chain 3 Ⅱ/Ⅰ protein were 1.09±0.09, 1.82±0.05, 1.67±0.29 and 1.09±0.15, respectively. Among the above indicators, there were statistically significant differences between the model group and the control and experimental -M, -H groups (P<0.05, P<0.01).

META significantly ameliorates H9c2 cardiomyocyte damage caused by high glucose, ameliorates oxidative stress, protects mitochondrial respiration and inhibits autophagy.

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 whether O6-methylguanine-DNA methyltransferase (MGMT) interference combined with temozolomide (TMZ) could enhance the therapeutic effect of temozolomide on human drug-resistant melanoma cells A375/TMZ.

A375/TMZ cells were randomly divided into 4 groups, control group (normal culture), MGMTsiRNA group (200 nmol·L^-1 MGMTsiRNA), experimental group (1 600 μmol·L^-1 TMZ) and combined group (transfection of MGMTsiRNA followed by addition of 1 600 μmol·L^-1 TMZ). After 24 h of culture, the proliferation of cells in each group was analyzed by cell counting kit-8 method. Western blotting was used to detect the expression levels of poly ADP-ribose polymerase (PARP), cleaved PARP(cleaved-PARP), DNA-dependent protein kinase catalytic subunit(DNA-PKcs) and nuclear factor kappa-B(NF-κB) proteins in the cells. The expression and distribution of NF-κB proteins in the cells were detected by immunofluorescence.

Cell inhibition rates of control, MGMTsiRNA, experimental and combined groups were 0, (3.45±1.53)%, (51.24±2.73)% and (70.69±4.48)%; the relative expression levels of PARP protein were 0.45±0.08, 0.47±0.06, 0.33±0.04, 0.14±0.03; the relative expression levels of the cleaved-PARP protein were 0.01±0.02、0.01±0.01、0.18±0.03 and 0.36±0.04; the relative expression levels of DNA-PKcs protein were 0.09±0.03, 0.07±0.02, 0.32±0.02 and 0.39±0.04; the relative expression levels of NF-κB protein were 0.35±0.04, 0.36±0.05, 0.20±0.02 and 0.15±0.02. Compared with experimental group or control group, the differences of above indexes were all statistically significant (all P<0.05). Immunofluorescence analysis showed that the average fluorescence intensity of NF-κB in control group, MGMTsiRNA group, experimental group and combined group were (5.26±1.05)%, (7.58±1.18)%, (10.56±1.99)% and (15.47±2.61)%; and compared with the cells in control group and MGMTsiRNA group, combined group showed NF-κB was significantly increased in the nucleus of tumor cells, and the difference was statistically significant (all P<0.01).

MGMTsiRNA combined with TMZ further promotes proliferation inhibition and apoptosis of drug-resistant melanoma A375/TMZ cells by TMZ.

To investigate the protective effect of astaxanthin (ASTA) on gouty chondrocyte injury induced by monosodium urate crystal (MSU) and its mechanism.

The gout cell model by sodium urate crystals was established. C-28I2 cells were randomly divided into blank group (conventional culture), model group (200 μg·mL^-1 MSU), experimental-L group (200 μg·mL^-1 MSU+20 μmol·mL^-1 ASTA), experimental-H group (200 μg·mL^-1 MSU+40 μmol·L^-1 ASTA), experimental-H+Vector group (transfected with Vector +200 μg·mL^-1 MSU+40 μmol·L^-1 ASTA), experimental-H+NLRP3 group (transfected with NLRP3 plasmid +200 μg·mL^-1 MSU+40 μmol·L^-1 ASTA). Cell counting kit-8 (CCK-8) assay was used to detect the cell proliferation rate; Western blot assay was used to detect the expression of related proteins; the levels of Hyp and GAG were detected by enzyme-linked immunosorbent assay (ELISA).

The cell proliferation rate of blank group, model group, experimental-L group and experimental-H group were (100.00±5.40)%, (67.41±4.52)%, (72.69±5.05)% and (81.47±7.73)%, respectively. The above indicators showed statistically significant differences between the model group and the blank group, between the experimental-L, experimental-H groups and the model group (all P<0.05). Nucleotide binding oligomeric domain-like receptor protein 3 (NLRP3) protein expression levels in blank group, model group, experimental-L group, experimental-H group, experimental-H+Vector group and experimental-H+NLRP3 group were 0.44±0.04, 0.86±0.06, 0.72±0.10, 0.52±0.03, 0.51±0.03 and 1.13±0.10, respectively; the expression levels of cleaved Caspase-1 (Cl-caspase-1) protein were 0.33±0.05, 0.73±0.08, 0.61±0.07, 0.42±0.04, 0.39±0.04 and 0.70±0.06, respectively; the mature interleukin (m-IL)-1β protein expression levels were 0.26±0.03, 0.91±0.05, 0.70±0.11, 0.57±0.08, 0.58±0.06 and 0.79±0.08, respectively; the Hyp levels were (1.95±0.22), (3.33±0.25), (2.53±0.18), (2.22±0.21), (2.24±0.20) and (3.25±0.38) μg·mL^-1, respectively; the GAG levels were (2.30±0.20), (3.71±0.26), (3.29±0.33), (2.90±0.16), (2.97±0.24) and (3.50±0.34) ng·mL^-1, respectively. The above indicators showed statistically significant differences between the model group and the blank group, between the experimental-L, experimental-H groups and the model group, between the experimental-H+NLRP3 group and the experimental-H+Vector group (all P<0.05).

Astaxanthin can regulate NLRP3 to play an anti-inflammatory role and has a protective effect on MSU-induced gouty cartilage injury.

Based on nuclear factor E2 associated factor 2 (NRF2) /PTEN induced hypothesized kinase 1 (PINK1) pathway, explored the ameliorating effect of rutaecarpine on chronic obstructive pulmonary disease (COPD) rats and its repairing effect on airway epithelial barrier.

COPD rat model were established by smoke combined with airway infusion of lipopolysaccharide; and were randomly divided into model group, control group, and experimental -L group, experimental -M group, experimental-H group, 10 rats per group. Another 10 normal rats were selected as the normal group. Experimental -L, -M, -H groups were intraperitoneally injected 15, 30 and 60 mg·mL^-1 rutaecarpine at the dose of 10 mL·kg^-1, respectively. The control group was received 4.05×10^-2 mg·mL^-1 prednisone acetate at the dose of 10 mL·kg^-1 by gavage. The normal and model groups were given 0.9% NaCl by intraperitoneal injection. Six groups were treated for 28 days with once a day. The first second forced expiratory volume (FEV1) and forced vital capacity (FVC) of rats were measured by minor animal lung function tester. The levels of interleukin (IL) and interferon-γ (INF-γ) in alveolar lavage fluid were determined by enzyme-linked immunosorbent assay method. The expression levels of PINK1 and NRF2 proteins in the lung tissue were determined by Western blot.

The levels of FEV1 in the experimental -M group, experimental -H group, control group, model group and normal group were (5.17±0.16), (6.36±0.12), (5.06±0.07), (2.24±0.20) and (6.84±0.11) mL; the levels of FVC were (6.71±0.13), (7.56±0.12), (6.81±0.07), (4.46±0.14) and (7.92±0.11) mL; the levels of IL-12 in alveolar lavage fluid were (7.08±0.51), (9.03±0.54), (7.92±0.79), (3.61±1.01) and (10.15±0.82) pg·mL^-1; the levels of IL-9 in alveolar lavage fluid were (22.49±2.27), (15.02±1.41), (17.47±1.84), (38.72±1.28) and (11.78±0.94) pg·mL^-1; the levels of INF-γ in alveolar lavage fluid were (13.18±0.54), (16.25±0.60), (15.23±0.43), (6.97±0.89) and (17.22±1.15) pg·mL^-1; the relative expression levels of PINK1 protein were 1.10±0.06, 1.30±0.09, 1.18±0.15, 0.42±0.03 and 1.61±0.05; the relative expression levels of NRF2 protein were 0.91±0.05, 1.46±0.03, 1.35±0.07, 0.53±0.07 and 1.64±0.11, respectively. The differences of above indexes were statistically significant between the experimental -M group, experimental -H group, control group and the model group (all P<0.05).

Rutaecarpine can inhibit inflammation, improve lung function and repair airway epithelial barrier in COPD rats, and its mechanism may be related to regulating NRF2/PINK1 pathway.

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 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 brain damage of SD rats under different time points of hypobaric hypoxia exposure.

A rat high-altitube cerebral edema (HACE) model was constructed by simulating an altitude of 6 000 m in a hypobaric hypoxia animal experimental chamber. Thirty-six SD male rats were randomly divided into the control group and the hypobaric hypoxia exposure 3, 7 and 14 d groups, with 9 rats in each group. Except for the control group, the rats in each group were continuously exposed to hypobaric hypoxia for 3, 7, and 14 d. At the end of the modeling period, serum was collected by blood sampling via the abdominal aorta, and brain tissue samples were taken. The wet-to-dry ratio (W/D) of brain tissue was calculated, and the levels of relevant oxidative enzymes in serum and brain tissue were measured. The expression levels of hypoxia-inducible factor-1α (HIF-1α) and aquaporin 4 (AQP4) mRNAs in brain tissue were detected by real-time fluorescence quantitative polymerase chain reaction.

The W/D of brain tissues in the control group and the group exposed to hypobaric hypoxia for 3, 7 and 14 d were 4.46±0.12, 4.98±0.16, 5.07±0.18 and 4.95±0.07; the superoxide dismutase contents were (111.86±2.45), (90.73±1.48), (79.64±2.56) and (55.33±1.45) U·g^-1; the glutathione contents were (126.91±5.18), (125.26±1.53), (56.20±2.17) and (122.73±1.78) μg·mL^-1; the malondialdehyde contents were (230.94±2.00), (362.65±3.28), (407.34±3.47) and (237.50±1.59) nmol·g^-1; the relative expression levels of HIF-1α mRNA were 1.00±0, 2.99±0.49, 4.72±0.49 and 1.91±0.28; the relative expression levels of AQP4 mRNA were 1.00±0, 2.62±0.34, 8.38±0.84 and 5.27±0.42, respectively. Statistically significant differences were found between the above indexes in the 3, 7 and 14 d of hypobaric hypoxia exposure group compared with the control group (P<0.05, P<0.01).

Different time of hypobaric hypoxia exposure can up-regulate the expression of AQPs proteins in HACE rats and cause the disruption of the blood-brain barrier, and the HACE model constructed in the hypobaric hypoxia chamber with 6 000 m intervention for 7 d was more stable.

To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of propofol injectable emulsion, and to assess the bioequivalence of test and reference formulations in healthy Chinese adult volunteers.

Thirty-two healthy Chinese adult volunteers were recruited and randomly assigned to a fasting. single-dose, two-period and double-crossover study. Propofol was given to eligible subjects at a speed of 30 μg·kg^-1·min^-1 for 30 min. The concentration of propofol in plasma was determined by avalidated high performance liquid chromatography-tandem mass spectrometery (HPLC-MS/MS) method. The PK parameters of the two preparations were calculated. Bispectral index (BIS) was measured to calculate the PD parameters of two formulations. Adverse events during the trial were recorded.

Thirty-one volunteers were included in the pharmacokinetic parameter set. The mean values of PK parameters of test andreference formulations were as follows: C_max were (660.87±110.25) and (683.13±125.75)ng·mL^-1; AUC_0-t were (473.50±86.03) and (478.40±80.25)h·ng·mL^-1; AUC_0-∞ were (500.45±96.49) and (507.84±88.00)h·ng·mL^-1; t_max were 0.47(0.25,0.53) and 0.50(0.40, 0.54)h; t_1/2 were (2.97±1.74) and (3.08±1.82)h. Thirty-one volunteers were included in the bioequivalence set. The 90% confidence intervals (CI) for the geometric mean ratios of C_max, AUC_0-t, AUC_0-∞ were 92.64%-101.39%, 96.43%-101.00%, 95.67%-100.70%, respectively. The mean values of PD parameters of test and reference formulations were as follows: BIS_min were (75.94±13.66) and (74.39±12.32); BIS_{AUC 0-60 min} were 5 569.85±182.78 and 5 575.68±166.19; T-BIS_min were 23.00 and 29.00 min, respectively. There were no serious adverse events.

Two formulations of propofol injectable emulsion were bioequivalent and both of them exhibited good safety.