To explore the pharmacokinetic (PK) characteristics of desloratadine tablets and reference drugs in healthy subjects, and evaluate their bioequivalence and safety.

The random, open, two-period, cross-over pharmacokinetic study method was adopted, each subject received a single oral dose of desloratadine tablets test drug(T) or reference drug(R) for 5 mg. The concentrations of desloratadine and 3-hydroxy desloratadine in plasma were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS); and the PK parameters were calculated by WinNonlin 8.1 software to evaluate the bioequivalence.

The main PK parameters of T and R of desloratadine were as follows: the fasting condition C_max were respectively (3 809.82±1 016.54) and (3 642.36±777.07) pg·mL^-1; AUC_0-120h were respectively (5.75×10⁴±5.03×10⁴) and (5.51×10⁴±4.00×10⁴) pg·h·mL^-1; AUC_0-∞ were respectively (6.85×10⁴±1.03×10⁴) and (6.37×10⁴±7.92×10⁴) pg·h·mL^-1. The fed condition C_max were respectively (4 398.98±1 191.22) and (4 744.40±1 511.97) pg·mL^-1; AUC_{0-120 h} were respectively(5.25×10⁴±1.82×10⁴) and (5.55×10⁴±1.98×10⁴) pg·h·mL^-1; AUC_0-∞ were respectively(5.37×10⁴±1.86×10⁴) and (5.68×10⁴±2.04×10⁴) pg·h·mL^-1. The 90% confidence interval of C_max, AUC_0-t and AUC_0-∞ of desloratadine were all within 80.00%~125.00%.

There was no significant difference in the main PK parameters between T and R under fasting or high-fat postprandial conditions, and desloratadine tablets were bioequivalent, safe and well tolerated.

To investigate the expression of microRNA-508-3p (miR-508-3p) in epithelial ovarian cancer (EOC) tissue, its impact on the migration and invasion of ovarian cancer cells, and its regulatory relationship with zinc-finger E-box-binding homeobox 1 (ZEB1).

The surgical resection of EOC cancer tissues and paired adjacent normal tissues were collected. SKOV3 cells were divided into the NC mimic group (transfected with NC mimic), miR-508-3p mimic group (transfected with miR-508-3p mimic), si-NC group (transfected with si-NC), si-ZEB1 group (transfected with si-ZEB1) and co-transfection group (co-transfected with si-ZEB1 and miR-508-3p mimic). The mRNA expression levels of miR-508-3p and ZEB1 in EOC cancer tissues, adjacent normal tissues and five groups of cells were measured by real-time quantitative polymerase chain reaction. The Transwell assay was used to detect the cell migration and invasion abilities.

The relative expression levels of miR-508-3p in EOC tissues and adjacent normal tissues were 0.77±0.36 and 1.07±0.40, the relative expression levels of ZEB1 mRNA in EOC tissues and adjacent normal tissues were 2.10±1.21 and 1.29±0.95, and the differences were statistically significant (all P<0.01). The migration cell number of the NC mimic, miR-508-3p mimic, si-NC, si-ZEB1 and co-transfection groups was 633.00±32.49, 319.20±19.89, 650.40±25.85, 375.00±17.25 and 129.40±17.10; the invasion cell number was 527.20±25.01, 288.60±16.68, 520.00±25.83, 293.40±18.37 and 76.60±8.76; the relative expression levels of miR-508-3p were 1.05±0.37, 3.94±1.21, 1.01±0.21, 1.26±0.34 and 3.40±0.41; the relative expression levels of ZEB1 mRNA were 1.00±0.04, 0.58±0.05, 1.00±0.08, 0.54±0.07 and 0.29±0.03, respectively. The above indicators showed statistically significant differences between the miR-508-3p mimic group and the NC mimic group, between the si-NC group and the co-transfection group (P<0.01, P<0.05).

MiR-508-3p is lowly expressed in EOC cancer tissue, and it may inhibit the migration and invasion of ovarian cancer cells by targeting ZEB1 expression.

To investigate the effects of γ-glutamyl hydrolase (GGH) rs11545078 C>T polymorphisms on serum concentrations, chemotherapy toxicities of methotrexate (MTX), and prognosis in children with intracranial tumors.

Peripheral blood samples were obtained from children with intracranial tumors to extract genome DNA. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry was used to detect the genotypes of GGH rs11545078 C>T polymorphisms. Fluorescence polarization immunoassay was employed to determine the serum concentrations of MTX. The incidences of toxicities, relapse, and metastasis were recorded after chemotherapy with MTX. The associations of GGH rs11545078 C>T polymorphisms with concentration-to-dose ratios (C/D ratios), chemotherapy toxicities of MTX, relapse, and metastasis of tumors were analyzed.

A total of 75 children were included in the present study. The frequencies of rs11545078 CC and CT genotypes were 82.67% and 17.33%, respectively. The frequencies of C and T alleles were 91.33% and 8.67%, respectively. There were no statistically significant differences for these frequencies among the children with intracranial tumors, the children with acute lymphoblastic leukemia, and the health population in Beijing. Children with the CC genotype had higher median C/D ratios of MTX in 24 and 42 h (25.19 and 0.14 μmol·L^-1 per g·m^-2, respectively), higher metastasis rates (46.77%), and lower relapse rates (17.74%) than those in CT genotype carriers (22.01 and 0.11 μmol·L^-1 per g·m^-2, 38.46%, and 30.77%, respectively), and the differences were no statistically significant (all P>0.05). The incidences of gastrointestinal disorders (76.92%) in children with the CT genotype were significantly higher than those in CC genotype carriers (45.16%, P<0.05). There were no statistically significant differences in the incidences of other adverse events between patients with the CC genotype and patients with the CT genotype (all P>0.05).

GGH rs11545078 CT might be a risk factor for gastrointestinal disorders in children with intracranial tumors treated with MTX.

To observe the long-term survival benefit status of bevacizumab injection combined with chemotherapy in the treatment of advanced ovarian cancer.

The patients with advanced ovarian cancer were classified into control group and treatment group according to cohort method. The control group was treated with 175 mg·m^-2 of paclitaxel injection + area under curve (AUC) 5 intravenous infusion of carboplatin injection once every 3 weeks for 6 cycles, and on the basis of the control group, the treatment group was additionally given intravenous injection of 15 mg·kg^-1 of bevacizumab injection in the second cycle, once every 3 weeks, maintained monotherapy after 6 cycles until disease progression (up to 22 cycles of treatment). The solid tumor efficacy at 6 cycles of treatment and levels of serum tumor markers [carbohydrate antigen (CA) 125, CA199, human epididymis protein 4 (HE4)], vascular endothelial growth factor (VEGF), macrophage migration inhibitory factor (MIF), long term survival status (overall survival time, progression-free survival time) and safety evaluation before treatment and at 6 cycles of treatment were compared.

There were 51 cases in the control group and 31 cases in the treatment group. After 6 cycles of treatment, the total effective rates of the treatment group and the control group was 77.42% (24 cases/31 cases) and 52.94% (27 cases/51 cases), respectively, and the difference was statistically significant (P<0.05). After 6 cycles of treatment, serum CA125 levels in treatment group and control group were (63.71±8.53) and (73.09±9.55) U·mL^-1; the CA199 levels were (58.97±10.87) and (69.39±12.45) U·mL^-1; the HE4 levels were (117.96±22.73) and (155.60±30.92) pmol·L^-1; levels of VEGF were (285.50±60.42) and (377.82±73.31) ng·L^-1; the levels of MIF were (20.26±3.42) and (22.34±3.19) μg·L^-1, the progression-free survival time was 7 (0, 17) and 2 (0, 6) months; there were statistically significant differences in the above indexes between the treatment group and the control group(P<0.05, P<0.01, P<0.001). The overall survival time in treatment group and control group was 10 (6, 20) months and 8 (4, 11) months. The differences were statistically significant(P>0.05). The adverse drug reactions in treatment group were mainly nausea and vomiting, hypertension and bone marrow suppression while the adverse drug reactions in control group were mainly nausea and vomiting and bone marrow suppression, and the total incidences of adverse drug reactions were 45.16% (14 cases/31 cases) and 35.29% (18 cases/51 cases) respectively (P>0.05).

Bevacizumab injection combined with chemotherapy has good clinical efficacy in the treatment of advanced ovarian cancer, and significantly prolong the progression-free survival time of patients.

To observe the clinical efficacy and safety of dexmedetomidine injection combined with esketamine injection in the treatment of patients with oral squamous cell carcinoma radical resection.

Patients with oral squamous cell carcinoma radical resection were randomly divided into treatment and control groups. The treatment group will receive intravenous administration of 0.6 μg·kg^-1 dexmedetomidine 10 minutes before anesthesia induction. Subsequently, anesthesia induction will be performed with intravenous administration of 0.5 mg·kg^-1 esketamine. Anesthesia maintenance will be achieved with intravenous infusion of 0.25 mg·kg^-1·h^-1 esketamine and 0.3 μg·kg^-1·h^-1 dexmedetomidine used an infusion pump. The control group will receive intravenous administration of an equivalent volume of 0.9% NaCl 10 minutes before anesthesia induction. Anesthesia induction will then be performed with intravenous administration of 2.5-5.0 μg·kg^-1 fentanyl. Anesthesia maintenance will involve intravenous infusion of 0.10-0.25 μg·kg^-1·min^-1 remifentanil used an infusion pump. The anesthesia effectiveness, analgesic effectiveness, hemodynamics and safety were compared between the two groups.

Treatment group were enrolled 62 cases, 1 case dropped out, and 61 cases were finally included in the statistical analysis. Control group were enrolled 61 cases, 1 case dropped out, and 60 cases were finally included in the statistical analysis. The recovery room stay time of treatment and control groups was (25.97±4.52) and (18.39±3.64) min, the extubation time was (16.75±4.84) and (10.16±3.18) min, and the differences were statistically significant (all P<0.05). After operation 24 h, visual analogue scores of treatment and control groups were (0.85±0.17) and (1.39±0.25) points, adrenocorticotropin levels were (60.07±7.13) and (72.64±9.81) pg·mL^-1, cortisol levels were (481.20±49.15) and (539.94±57.77) nmol·L^-1, and the differences were statistically significant (all P<0.05). The mean arterial pressure at 30 min after anesthesia induction (T1) and at the end of surgery (T2) in treatment group were (82.34±4.98) and (86.57±4.18) mmHg, while those in control group were (77.25±7.16) and (76.02±6.29) mmHg; the heart rates of T1 and T2 in treatment groups were (64.08±4.19) and (66.45±4.83) time·min^-1, while those in control group were (68.44±6.02) and (72.08±7.27) time·min^-1; and the differences were statistically significant (all P<0.05). The adverse drug reactions in two groups were nausea, vomiting, bradycardia and dizziness. The total incidences of adverse drug reactions in treatment and control groups were 8.20% and 15.00%, without significant difference (P>0.05).

Dexmedetomidine injection combined with esketamine injection has a definitive analgesia efficacy in the treatment of patients with oral squamous cell carcinoma radical resection, which can significantly reduce stress responses, maintain hemodynamic stability, without increasing the incidence of adverse drug reactions.