To evaluate the bioequivalence of domestic duloxetine hydrochloride enteric-coated tablets and original enteric-coated capsules in Chinese healthy subjects.

In a random, open, two periods, two sequence, self-crossover study, 40 cases healthy subjects in fasting test and 48 cases healthy subjects in fed test were given single oral test preparation and reference preparation 20 mg of duloxetine hydrochloride. The concentrations of duloxetine hydrochloride in plasma were determined by high performance liquid chromatography tandem mass spectrometry. The pharmacokinetic parameters were calculated using Phonenix WinNolin 8.0 software, and the bioequivalence of the test and the reference duloxetine hydrochloride was evaluated.

The main pharmacokinetic parameters of the test and the reference duloxetine hydrochloride in fasting test were as follows: C_max were (16.70±5.94) and (16.70±7.10) ng·mL^-1; AUC_0-t were (217.28±98.82) and (222.42±117.98) ng·h·mL^-1; AUC_0-∞ were (225.91±100.35) and (229.40±119.34) ng·h·mL^-1. The main pharmacokinetic parameters of the test and the reference duloxetine hydrochloride in fed test were as follows: C_max were (20.10±9.56) and (21.30±10.90) ng·mL^-1; AUC_0-t were (266.99±146.66) and (273.22±168.09) ng·h·mL^-1; AUC_0-∞ were (277.83±154.73) and (283.51±174.63) ng·h·mL^-1. The 90% confidence intervals of the main pharmacokinetic parameters of the test and reference preparations in fasting and fed tests were between 80.00%-125.00%.

The test and the reference duloxetine hydrochloride were bioequivalent under fasting and fed conditions.

To evaluate the pharmacokinetic characteristics and safety of delafloxacin, a new fluoroquinolone drug, in Chinese healthy subjects, and to evaluate the expected microbiological efficacy of delafloxacin in treating infections caused by Staphylococcus aureus and Streptococcus pneumoniae through pharmacokinetic/pharmacodynamic analysis.

This trial consists of two parts. The first part is a randomized, double-blind, placebo-controlled, single-dose/multiple-dose administration trial with a dose range of 150-450 mg. The second part is a randomized, open-label, double-period, self-crossover trial comparing the pharmacokinetic similarities between a 300 mg intravenous infusion of the test drug and the reference drug. Combined with the in vitro pharmacodynamic data of delafloxacin against Staphylococcus aureus and Streptococcus pneumoniae clinically isolated in China, the Monte Carlo simulation method was used to analyze the probability of target attainment and cumulative fraction of response of the 300 mg q12 h intravenous infusion over 60 min and to evaluate the expected microbiological efficacy.

After administering 150, 300 and 450 mg of delafloxacin to Chinese healthy subjects in single doses, the C_max, AUC_0-t and AUC_0-∞ increase proportionally with the dose. The apparent volume of distribution ranged from 45.79 to 144.38 L. The elimination half-life of each dose group ranged from 2.99 to 11.87 h. The cumulative urinary excretion rates of (47.69±8.11)% and (73.71±9.32)% were observed for single doses of 300 and 450 mg, respectively, suggesting that the primary route of excretion was renal. The 90% confidence interval of C_max, AUC_0-t and AUC_0-∞ of test drug over reference drug after single-dose intravenous infusion are all within 80.00%-125.00%. After reaching steady state with multiple-dose administration in the 300 mg group, the plasma exposure level was similar to that of the single-dose administration group.

Single-dose intravenous infusion of 150-450 mg delafloxacin in healthy subjects showed linear pharmacokinetic characteristics, and there was no accumulation after 300 mg q12 h administration. Adverse effects were mild, indicating good safety, and good microbiological efficacy.

To explore the therapeutic effects and mechanisms of Dunhuang Xiexin decoction on mice with ulcerative colitis (UC).

Mice were randomly divided into blank group (0.9% NaCl), model group (0.9% NaCl) and experimental-L, -M, -H groups (2.93, 5.85, 11.70 g·kg^-1 Dunhuang Xiexin decoction water extracts) with 10 cases per group for 7 days. Meanwhile, apart from the blank group, the other four groups of mice were allowed adlibitum access to drinking water containing 3% sodium dextran sulfate for 7 consecutive days to establish the UC model. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 in mouse serum were determined by enzyme-linked immunosorbent assay. The expression levels of occludin, zonula occludens-1 (ZO-1) and phospho nuclear factor kappa B p65 (p-NF-κB p65) in colonic tissues was detected by Western blot.

The serum TNF-α levels in the experimental- M, - H groups, model group and blank group were (397.57±33.05), (389.41±22.57), (472.19±18.70) and (355.92±31.86) pg·mL^-1; the IL-1β levels were (73.06±18.38), (62.60±9.80), (98.94±27.50) and (55.26±18.14) ng·mL^-1; the IL-6 levels were (153.23±32.96), (148.12±23.53), (239.35±50.99) and (131.36±27.58) pg·mL^-1; the relative expressions levels of occludin protein in colon tissues were 0.80±0.13, 1.03±0.24, 0.57±0.15 and 1.10±0.03; the relative expressions levels of ZO-1 protein were 0.90±0.21, 1.09±0.10, 0.73±0.16 and 1.29±0.03; the relative expressions levels of p-NF-κB p65 protein were 0.75±0.12, 0.53±0.08, 1.15±0.19 and 0.43±0.21, respectively. There were significant differences between the experimental- H group and the model group (P<0.05).

Dunhuang Xiexin decoction may improve ulcerative colitis in mice by repairing the intestinal barrier and inhibiting the NF-κB signaling pathway to reduce the release of inflammatory factors.

To investigate the mechanism of action of harmine (HM) in anti-Echinococcus granulosus (E.g) based on non-targeted metabolomics.

The aseptically cultured fine-grained E.g was divided into blank group (KB group, conventional culture), solvent group (DMSO group, DMSO 2 μL) and administration group (HM group, 20 mmoL·L^-1 HM solution 2 μL). Survival rate was observed by eosin staining after 48 h of intervention and the ultrastructural changes were observed by scanning electron microscopy, respectively. Meanwhile, non-targeted metabolomics analysis was performed based on ultra performance liquid chromatography-mass spectrometry (UPLC-MS/MS) technology on each group of E.g to screen the differential metabolites and explore the effect of harmine on the metabolic profile of E.g.

Eosin staining and scanning electron microscopy results showed that harmine had a significant inhibitory effect on E.g in vitro. Metabolomics results showed that there were a total of 15 metabolites with significant differences between the harmine and blank groups (all P<0.05). Enrichment of the differential metabolites by Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that harmine mainly affected the metabolic pathways of amino acid metabolism, fatty acid metabolism and nucleotide metabolism in E.g.

Harmine had a significant inhibitory effect on E.g, the mechanism of which may be related to the regulation of amino acid metabolism, fatty acid metabolism and nucleotide metabolism pathways, which can provide a new way of thinking for the development of the subsequent anti-cystic echinococlosis drug targets.

To investigate the effect and mechanism of loganin on retinopathy in diabetic retinopathy (DR) rats.

DR rats were established by injection of streptozotocin and high glucose and high fat. They were randomly grouped into model group (0.9% NaCl), experimental -L group, experimental-H group (50, 100 mg·kg^-1 loganin), combined group [100 mg·kg^-1 loganin+10 mg·kg^-1 lysophosphatidic acid (LPA)] and 10 normal rats were taken as control group (0.9% NaCl). After the intervention, retinal histomorphology, the levels of inflammatory factors and oxidative stress, apoptosis of ganglion cells, and the expression of Ras homologous gene family member A (RhoA) and Rho associated coiled coil-forming kinase (ROCK) proteins in retinal tissue were measured in turn.

The number of retinal ganglion cells in experimental -L, -H groups, combined group, model group and control group were 19.75±1.90, 24.32±2.15, 17.80±1.94, 15.44±1.65 and 28.30±2.02; the levels of interleukin-6 were (85.67±8.61), (68.88±6.91), (98.52±9.88), (108.24±10.83) and (62.08±6.22) ng·L^-1; the levels of tumor necrosis factor -α were (150.24±15.11), (110.38±11.06), (186.94±18.77), (200.05±20.08) and (105.34±10.55) ng·L^-1; the levels of malondialdehyde were (7.52±0.78), (4.76±0.48), (9.52±0.96), (10.85±1.09) and (4.58±0.46) μmol·mg^-1; the superoxide dismutase activities were (62.05±6.21), (78.22±7.83), (52.11±5.23), (50.21±5.04) and (79.61±7.98) U·mg^-1; the apoptosis rates of ganglion cells were (12.71±1.06)%, (6.98±0.93)%, (14.69±1.30)%, (19.50±1.42)% and (2.15±0.38)%; the relative expression levels of RhoA protein were 0.81±0.09, 0.42±0.05, 1.08±0.11, 1.16±0.12 and 0.38±0.04; the relative expression levels of ROCK protein were 1.28±0.13, 0.77±0.08, 1.72±0.18, 1.85±0.19 and 0.63±0.07, respectively. Compared with the model group, the above indexes of the control group, experimental -H group and combination group had statistical significance (all P<0.05).

Loganin may improve retinopathy in DR rats by inhibiting the activation of RhoA/ROCK pathway, inhibiting inflammation and oxidative stress response.

To compare the clinical efficacy and safety of sodium bicarbonate ringer’s injection and 0.9% NaCl as resuscitation fluid in the treatment of patients with diabetic ketoacidosis (DKA).

Patients with DKA were randomly divided into treatment group and control group. After enrollment, the treatment group was immediately given sodium bicarbonate ringer’s , and the control group was given 0.9% NaCl for fluid resuscitation. Other treatment protocols for DKA were the same in two groups. The incidence of hyperchloremia in 96 hour the change value of chloride in 96 hours (with the maximum value minus the baseline value), the total volume of fluid administered over 24 hours, the volume of urine produced over 24 hours, and the incidence of acute kidney injury(AKI) were compared between the two groups. Additionally, the incidence of hypokalemia in the two groups during the 96-hour observation period was recorded, and the safety of the intervention was evaluated.

The study cohort comprised 20 cases in the treatment group, of whom two were dislodged, finally 18 cases were included in the statistical analysis. In the control group, 20 cases were enrolled, with one case being dislodged, leaving 19 cases included in the statistical analysis. The incidence of 96 hour hyperchloraemia in the treatment group and the control group was 27.78% (5 cases/18 cases) and 73.68% (14 cases/19 cases), respectively. Furthermore, the change values of chloride in 96 hour were 11.05(9.30, 13.13) and 19.10(14.10, 29.10) mmol·L^-1, respectively. Notably, the differences between the two groups were statistically significant(all P<0.05). The total fluid volume was 3 410.00 and 3 600.00 mL, the 24 hour urine output was 2 075.00 and 2 950.00 mL, and the incidence of AKI was 0% (0 cases/18 cases) and 5.26% (1 cases/19 cases) in the treatment group and the control group, respectively. No statistically significant differences were observed in any of the statistical comparisons(all P>0.05). However, the incidence of hypokalaemia in the treatment group(22.22%) was lower than that in the control group(57.89%), and this difference was statistically significant (P<0.05).

The administration of sodium bicarbonate ringer’s injection for the resuscitation of patients with diabetic ketoacidosis has been demonstrated to reduce the incidence of hyperchloremia at 96 hours, and have good safety.

To investigate the effect of circRNA_0044556 on the resistance of triple-negative breast cancer (TNBC) to paclitaxel (PTX) and the mechanism of drug resistance.

PTX resistant TNBC cells (MDA-MB-231/PTX) were obtained by exposing the human TNBC cell (MDA-MB-231) to increasing concentrations of PTX. MDA-MB-231 and MDA-MB-231/PTX cells in logarithmic growth phase were treated with circRNA_0044556 short hairpin RNA (sh-circRNA_0044556) and negative control (sh-NC), respectively. The groups were finally divided into MDA-MB-231-NC, MDA-MB-231-circRNA_0044556, MDA-MB-231/PTX-NC and MDA-MB-231/PTX-circRNA_0044556 groups. The expression level of circRNA_0044556 in cells was determined by real-time quantitative polymerase chain reaction (RT-qPCR); methyl thiazolyl tetrazolium assay and colony formation assay were used to observe cell proliferation; flow cytometry was used to observe cell apoptosisand; Western blot was used to observe the expression of cell proliferation and apoptosis-related proteins.

The relative expression levels of circRNA_0044556 in MDA-MB-231/PTX, MDA-MB-231 and MCF-10A cells were 6.08±0.59, 3.36±0.11 and 1.00±0.02, respectively, and the differences were statistically significant (all P<0.001). Proliferation rates of MDA-MB-231-NC and MDA-MB-231-circRNA_0044556 groups were (100.00±0.84)% and (54.38±1.20)%; the apoptosis rates were (2.41±0.34)% and (21.65±0.29)%, respectively, and the differences were statistically significant (all P<0.001). The proliferation rates of MDA-MB-231/PTX-NC and MDA-MB-231/PTX-circRNA_0044556 groups were (112.29±1.19)% and (61.33±1.24)%; the apoptosis rates were (2.08±0.07)% and (14.38±0.16)%, respectively, the differences were all statistically significant (all P<0.001). The relative protein expression level of Ki-67 in MDA-MB-231-NC and MDA-MB-231-circRNA_0044556 groups were 1.00±0.02 and 0.67±0.02; the relative protein expression of Bcl-2-associated X protein (Bax) were 1.00±0.02 and 1.46±0.03; and the differences were statistically significant (all P<0.05). The relative relative protein expression levels of Ki-67 in MDA-MB-231/PTX-NC group and MDA-MB-231/PTX-circRNA_0044556 group were 1.00±0.03 and 0.81±0.01, respectively; the relative expression levels of Bax protein were 1.00±0.02 and 1.55±0.02, respectively; the relative expression levels of Bcl-2 protein were 1.00±0.03 and 0.79±0.01, respectively. The above indexes in MDA-MB-231/PTX-NC group were significantly different from those in MDA-MB-231/PTX-circRNA_0044556 group (all P<0.05).

Knocking down the expression of circRNA_0044556 can inhibit the malignant progression and PTX resistance of TNBC cells.

Probing whether salivary acid-binding immunoglobulin-like agglutinin-15 (Siglec-15) promotes hepatocellular carcinoma proliferation and migration by regulating the signal transducer and activator of transcription 1/3 (STAT1/STAT3) pathway.

SMMC-7721 and BEL-7402 cells were divided into empty vector groups: S-NC and B-NC groups (NC siRNA was transfected into SMMC-7721 and BEL-7402 cell, respectively), Siglec-15 knockdown expression group: S-si-Siglec-15-3 and B-si-Siglec-15-3 groups (Siglec-15-3 siRNA was transfected into SMMC-7721 and BEL-7402 cell, respectively). The proliferation ability of the cells were detected by methyl thiazolyl tetrazolium (MTT); the longitudinal and lateral migration ability of the cells were detected by Transwell and scratch assay; the expression of STAT3, phosphorylation of STAT3 (p-STAT3), STAT1, phosphorylation of STAT1 (p-STAT1), Siglec-15 was detected by Western blot.

Cell viability values at 24 h in the S-NC group, S-si-Siglec-15-3 group, B-NC group and B-si-Siglec-15-3 group were 0.93±0.01, 0.87±0.03, 0.96±0.03 and 0.83±0.02, respectively; the vertical migration rates of cells were 100.00%, 36.40%, 100.00% and 52.20%, respectively; the healing rate of cell scratches at 24 h were (0.76±0.02)%, (0.53±0.02)%, (0.44±0.02)% and (0.36±0.03)%, respectively; STAT3 protein expression levels were 1.11±0.05, 0.66±0.05, 1.07±0.14 and 0.49±0.04, respectively; p-STAT3 protein expression levels were 1.07±0.04, 0.16±0.06, 0.78±0.05 and 0.32±0.03, respectively; STAT1 protein expression levels were 1.32±0.04, 0.71±0.04, 0.91±0.03 and 0.61±0.04, respectively; p-STAT1 protein expression levels were 0.99±0.04, 0.29±0.05, 0.67±0.04 and 0.20±0.06, respectively; Siglec-15 protein expression levels were 1.51±0.04, 0.93±0.05, 0.73±0.02 and 0.12±0.01, respectively. The differences between the S-si-Siglec-15-3 group and the S-NC group, between the B-si-Siglec-15-3 group and the B-NC group were statistically significant in all comparisons (P<0.05, P<0.01, P<0.001).

Siglec-15 promotes the proliferation and migration ability of hepatocellular carcinoma cells through the STAT1/STAT3 pathway.