To investigate the effect of Rocaglamide (Roc-A) on paclitaxel (PTX) resistance in breast cancer MCF-7/PTX cell line and its mechanism.

With breast cancer MCF-7 cells as the research object, PTX resistant MCF-7/PTX cell line was obtained by continuous induction with low concentration of PTX. Methyl thiazolyl tetrazolium (MTT) method was used to determine the drug resistance index of MCF-7/PTX cell line, the effect of Roc-A on the proliferation activity of MCF-7/PTX cell line and the drug resistance reversal multiple. MCF-7/PTX cell lines were divided into control group (normal cultured cells), PTX group (40.8 nmol·L^-1 PTX), PTX+Roc-A-L group (40.8 nmol·L^-1 PTX+25 nmol·L^-1 Roc-A), PTX+Roc-A-M group (40.8 nmol·L^-1 PTX+50 nmol·L^-1 Roc-A) and PTX+Roc-A-H group (40.8 nmol·L^-1 PTX+100 nmol·L^-1 Roc-A). The apoptosis level of each group was detected by flow cytometry; the relative expression levels of cell autophagy related protein LC3 were detected by immunofluorescence assay; Western blotting was used to detect the relative expression levels of cell apoptosis related proteins, such as B cell lymphoma-2 associated X protein (Bax) and autophagy associated protein autophagy microtubule associated protein light chains 3 (LC3).

The PTX resistant cell line MCF-7/PTX of breast cancer was successfully constructed with a drug resistance index of 5.49; Roc-A could inhibit the proliferation activity of MCF-7/PTX cell lines in a concentration dependent manner, while the reversal multiples of PTX resistance of MCF-7/PTX cell lines to Roc-A at different concentrations (25, 50, 100 nmol·L^-1) were 1.57, 2.68 and 6.16, respectively. The apoptosis rates of the control group, PTX group, PTX+Roc-A-L group, PTX+Roc-A-M group and PTX+Roc-A-H group were (4.75±2.10)%, (21.79±3.61)%, (32.54±3.43)%, (39.82±3.26)% and (55.61±4.22)%, respectively; the relative expression levels of LC3 fluorescence were 1.00±0.08, 0.77±0.06, 0.60±0.06, 0.41±0.04 and 0.26±0.03, respectively; the relative expression levels of Bax protein were 0.12±0.04, 0.25±0.09, 0.48±0.10, 0.86±0.12 and 1.10±0.13, respectively; the LC3Ⅱ/LC3Ⅰ protein ratio were 6.52±0.27, 3.75±0.23, 1.76±0.17, 1.31±0.10 and 1.02±0.06, respectively. Compared with the control group, the PTX group, PTX+Roc-A-L group, PTX+Roc-A-M group, PTX+Roc-A-H group showed statistically significant differences in the above indicators (all P<0.05); the above indicators in the PTX+Roc-A-L group, PTX+Roc-A-M group and PTX+Roc-A-H group were compared with those in the PTX group, and the differences were statistically significant (all P<0.05), showing a dose-dependent relationship.

Roc-A can reverse the resistance of breast cancer drug resistant cell line MCF-7/PTX to PTX, and the mechanism may be related to the reduction of autophagy.

To observe clinical effect and safety of dapagliflozin tablets combined with metformin tablets in the treatment of patients with diabetic kidney disease (DKD).

According to cohort method, DKD patients were divided into control group and treatment group. The control group was given oral metformin tablets (0.5 g per time, twice a day), while treatment group was given oral dapagliflozin tablets (10 mg per time, once a day) on basis of control group. All patients were treated for 12 weeks. The clinical curative effect, glucose metabolism indexes [glycated hemoglobin (HbA1c), fasting blood glucose (FPG), 2 h postprandial blood glucose (2 h PG)], renal function [urine albumin/creatinine (UACR), serum creatinine (SCr), estimated glomerular filtration rate (eGFR)], renal vascular function [resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV), end-diastolic velocity (EDV)], urine α-smooth muscle actin (SMA), membrane protein, transforming growth factor (TGF)-β1 and inflammatory factors [interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α] in the two groups were compared, and the safety was evaluated.

There were 40 cases in control group and 40 cases in treatment group. After treatment, difference in total response rate between treatment group and control group was statistically significant [92.50% (37 cases/40 cases) vs 72.50% (29 cases/40 cases), P<0.05]. After treatment, HbA1c levels in treatment group and control group were (6.52±0.76)% and (7.44±0.98)%; FPG levels were (7.11±1.05) and (8.05±1.21)mmol·L^-1; 2 h PG levels were (9.32±1.08) and (10.57±1.35) mmol·L^-1; UACR levels were (104.76±13.85) and (138.41±16.07)mg·g^-1; SCr levels were (82.27±10.38) and (101.68±13.54) μmol·L^-1; eGFR levels were (88.06±8.37) and (80.52±7.64) mL·min^-1·1.73 m^-2; RI levels were 0.51±0.10 and 0.65±0.13; PI were 1.15±0.24 and 1.49±0.31; PSV were (38.30±5.29) and (34.59±4.71) cm·s^-1; EDV were (15.73±2.49) and (13.41±2.02) cm·s^-1; levels of urine SMA were (26.31±2.39) and (30.47±2.86)kU·L^-1; levels of urine membrane protein were (528.41±50.78) and (581.65±57.22) μg·L^-1; levels of urine TGF-β1 were (85.01±9.82) and (102.94±13.57) μg·L^-1; levels of serum IL-1β were (26.93±3.36) and (40.14±4.57)ng·L^-1; levels of serum IL-6 were (14.36±1.59) and (17.94±2.01) ng·L^-1; levels of serum TNF-α were (30.22±3.37) and (43.81±4.06) ng·L^-1, and differences of all the above indexes between the two groups were statistically significant (all P<0.05). The adverse drug reactions were mainly on loss of appetite, diarrhea, fatigue and nausea in treatment group, while which were mainly on loss of appetite, headache and nausea in control group. There was no significant difference in total incidence of adverse drug reactions between treatment group and control group [12.50% (5 cases/40 cases) vs 7.50% (3 cases/40 cases), P>0.05].

Dapagliflozin combined with metformin can improve glucose metabolism, promote recovery of renal function and renal vascular function, regulate levels of SMA, membrane protein and TGF-β1, relieve inflammatory response and improve clinical curative effect in DKD patients.

To investigate the protective effects and potential mechanisms of 6-gingerol against acute respiratory distress syndrome (ARDS) in juvenile mice through nerve growth factor-induced clone B (Nur77).

The juvenile mouse model of ARDS was established by tracheal instillation of lipopolysaccharide. After modeling, 48 juvenile mice were randomly divided into the model group, the 6-gingerol group (intraperitoneal injection of 30 mg·kg^-1 6-gingerol), the 6-gingerol+sh-NC group (intranasal instillation of sh-NC negative control adenovirus+intraperitoneal injection of 30 mg·kg^-1 6-gingerol), and the 6-gingerol+sh-Nur77 group (intranasal instillation of sh-Nur77 adenovirus+intraperitoneal injection of 30 mg·kg^-1 6-gingerol). Another 12 normal juvenile mice were given an equal volume of sterile 0.9% NaCl by tracheal instillation as the sham operation group. Detected the lung wet/dry (W/D) ratio of young mice in each group. The immunohistochemistry method was used to detect the positive expression of collagen Ⅲ in lung tissues. The kit was used to detect apoptosis in the lung tissues of young mice. The expressions of pathway-related proteins were detected by Western blotting.

The W/D ratios of the sham operation group, the model group, the 6-gingerol group, the 6-gingerol+sh-NC group and the 6-gingerol+sh-Nur77 group were 2.20±0.26, 6.65±0.92, 3.89±0.52, 3.72±0.44 and 5.55±0.78, respectively; the positive levels of collagen Ⅲ were 1.00±0.22, 3.99±0.54, 1.85±0.28, 1.76±0.29 and 2.79±0.34, respectively; the apoptosis rates were (4.65±0.66)%, (39.62±5.03)%, (18.63±2.33)%, (17.82±2.12)% and (33.65±5.03)%, respectively; the levels of phosphorylated phosphatidylinositol 3-kinase/phosphatidylinositol 3-kinase (p-PI3K/PI3K) were 1.00±0.13, 1.66±0.22, 1.23±0.17, 1.21±0.14 and 1.58±0.24, respectively; the levels of phosphorylated protein kinase B/protein kinase B (p-Akt/Akt) were 1.00±0.16, 1.78±0.26, 1.33±0.21, 1.38±0.19 and 1.60±0.22, respectively. Compared with the sham operation group, the differences in the above indicators of the model group were statistically significant (all P<0.05); compared with the model group, the differences in the 6-gingerol group were statistically significant (all P<0.05); compared with the 6-gingerol+sh-NC group, the differences in the 6-gingerol+sh-Nur77 group were also statistically significant (all P<0.05).

6-gingerol intervention can improve lung injury in young ARDS mice, up-regulate the expression of Nur77, inhibit lung tissue inflammatory response, reduce lung tissue apoptosis, and promote coagulation/fibrinolytic balance, and its mechanism of action may be related to the inhibition of PI3K/Akt pathway.

To establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of propofol medium/long chain fat milk in Beagle dogs plasma, and to investigate the pharmacokinetics and bioequivalence of the reference preparation of propofol medium/long chain fat milk injection and the subject preparation after intravenous injection in Beagle dogs.

The protein precipitation method was used for pretreatment, and the chromatographic column was Inert Sustain AQ-C₁₈ column (50.0 mm×2.1 mm, 5 μm). Mobile phase: 0.1% ammonia-ammonium acetate aqueous solution, flow rate: 0.4 mL·min^-1, column temperature: 40 ℃; the injection volume was 10 μL; ion source: electrospray ion source, negative ion mode, multi-reaction detection. The specificity, standard curve and lower limit of quantitation, precision and recovery, stability and reproducibility of the method were investigated.

The linear range of propofol was 0.05-10.00 μg·mL^-1, the lower limit of quantitation was 0.05 μg·mL^-1, the accuracy was 94.2%-105.0%, the intra-day and inter-day precision was less than 20%, and the stability was good. The C_max of the reference preparation and the test preparation were (8.75±2.66) and (8.15±2.78)μg·mL^-1 and the AUC_last were (1.71±0.45) and (1.88±0.42) h·μg·mL^-1, respectively.

A simple, sensitive and accurate LC-MS/MS method is established for the determination of propofol.

To explore the effects of rapamycin (RAP) combined with cyclosporine A (CsA) on the hematopoietic function and the levels of bone marrow vascular endothelial growth factor (VEGF), thrombopoietin (TPO), and vascular cell adhesion molecule-1 (VCAM-1) in aplastic anemia mice by regulating the T-box transcription factor (T-bet)/interferon-gamma (IFN-γ) signaling pathway.

Female Kunming mice of pure line were randomly divided into control group (without any treatment), model group (subcutaneously injected with 50 mg·kg^-1 cyclophosphamide, once every other day for a total of 4 times; meanwhile, inhaling 30 mg·L^-1 toluene once a day for 8 consecutive days), CsA group (intraperitoneally injected with 5 mg·kg^-1 CsA on the basis of the model group), RAP-L combined with CsA group (intraperitoneally injected with 5 mg·kg^-1 CsA and 0.1 mg·kg^-1 RAP on the basis of the model group), RAP-M combined with CsA group (intraperitoneally injected with 5 mg·kg^-1 CsA and 0.5 mg·kg^-1 RAP on the basis of the model group), RAP-H combined with CsA group (intraperitoneally injected with 5 mg·kg^-1 CsA and 1 mg·kg^-1 RAP on the basis of the model group), and RAP-H group (intraperitoneally injected with 1 mg·kg^-1 RAP on the basis of the model group), with 10 mice in each group. Except for the control group, the aplastic anemia model was established in the other groups. A biochemical analyzer was used to detect the levels of peripheral blood red blood cells (RBC), white blood cells, hemoglobin and platelets. Hematoxylin-eosin staining was used to observe the bone marrow morphology and conduct pathological injury scoring. The enzyme-linked immunosorbent assay method was used to detect the levels of VEGF, VCAM-1, TPO, IFN-γ and tumor necrosis factor-α in the bone marrow supernatant. Immunohistochemistry was used to detect the expression of TPO. Real-time fluorescence quantitative polymerase chain reaction and Western blotting were used to detect the messenger ribonucleic acid (mRNA) and protein expressions of T-bet in bone marrow mononuclear cells.

The RBC levels of the control group, model group, CsA group, RAP-H combined with CsA group and RAP-H group were (8.48±0.89)×10¹², (2.14±0.25)×10¹², (3.54±0.54)×10¹², (6.12±0.74)×10¹² and (3.26±0.61) ×10¹²·L^-1, respectively; the pathological injury scores were (0.20±0.04), (2.50±0.25), (1.10±0.10), (1.00±0.11) and (1.20±0.16) points, respectively; the TPO levels were (195.48±28.15), (145.81±15.24), (169.76±20.26), (190.54±22.37) and (165.52±20.29) pg·mL^-1, respectively; the VCAM-1 levels were (213.46±32.33), (132.81±21.94), (185.49±19.65), (204.19±19.82) and (183.67±20.87) ng·mL^-1, respectively; the IFN-γ levels were (132.04±18.10), (232.46±25.29), (205.98±21.26), (183.67±20.20) and (209.05±19.82) pg·mL^-1, respectively; the relative expression levels of T-bet mRNA were 1.00±0.10, 3.98±0.69, 2.18±0.21, 1.95±0.20 and 2.24±0.23, respectively; the relative expression levels of T-bet protein were 1.00±0.10, 2.46±0.29, 1.98±0.21, 1.67±0.20 and 2.01±0.22, respectively. When the above-mentioned indicators of the model group were compared with those of the control group, the above-mentioned indicators of the CsA group, the RAP-H combined with CsA group, and the RAP-H group were compared with those of the model group, and the above-mentioned indicators of the RAP-H combined with CsA group were compared with those of the CsA group and the RAP-H group, all the differences were statistically significant (all P<0.05).

CsA combined with RAP can significantly improve the hematopoietic function and cellular immune function of aplastic anemia model mice, which may be related to increasing the levels of bone marrow TPO and VCAM-1 and regulating the T-bet/IFN-γ signaling pathway.

To explore the protective effects of orphan nuclear receptor subfamily 2 group E member 1 (NR2E1) overexpression on nerve regeneration in dentate gyrus (DG) of diabetic rats complicated with depression.

The rat model of diabetes complicated with depression was established by injecting streptozotocin into the tail vein combined with chronic unpredictable mild stimulation. The successful rats were randomly divided into model, control and experimental groups, with 8 rats per group; another 8 normal rats were set as normal group. Control group was injected adeno-associated control virus 4 μL. Experimental group was injected with adeno-associated virus of overexpress NR2E1 4 μL; model and normal groups were injected with 0.9% NaCl. After 14 days, the depression-like behavior of rats was detected by Morris water maze, the fasting blood glucose level was detected by blood glucose meter, and the serum insulin (INS), interleukin -1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels in DG area were detected by enzyme-linked immunosorbent assay. The expression of thymidine analogue bromodeoxyuridine (Brdu) in DG region was detected by immunofluorescence method, and the signal transduction expression levels of microRNA-let-7d (miRNA-let-7d)/NR2E1/silencing information regulatory factor 1 (SIRT1) gene were detected by real-time fluorescence quantitative polymerase chain reaction.

The space exploration time of experimental, control, model and normal groups was (31.25±9.94), (25.50±8.02), (19.75±5.82) and (43.87±12.77) s; the fasting blood glucose were (19.28±3.60), (25.26±5.25), (23.71±4.13) and (4.45±0.40) mmoL·L^-1; the insulin levels were (77.15±3.03), (80.53±4.93), (83.31±5.77) and (48.15±5.18) ng·mL^-1; the IL-1β levels were (28.15±4.68), (36.83±6.97), (40.18±4.40) and (19.15±2.67) pg·mL^-1; the TNF-α levels were (281.15±25.15), (324.06±16.85), (337.08±23.11) and (219.06±27.68) pg·mL^-1; the integrated optical density of Brdu were 1.70±1.19, 0.89±0.12, 0.93±0.14 and 2.14±0.15; the relative expression levels of miRNA-let-7d were 2.02±0.18, 2.67±0.54, 2.88±0.30 and 1.11±0.16; the relative expression levels of NR2E1 mRNA were 2.87±0.39, 0.96±0.09, 1.07±0.12 and 3.29±0.35; the relative expression levels of SIRT1 mRNA were 1.62±0.37, 0.99±0.08, 1.04±0.10 and 2.30±0.34, respectively. Compared with the model group, the above indexes in experimental group have statistical significance (all P<0.05).

The overexpression of NR2E1 receptor in isolated nucleus may protect the dentate gyrus nerve regeneration in diabetic rats with depression by regulating miRNA-let-7d/TLX/SIRT1 signal transduction.

To investigate the influencing factors of the dose-corrected concentration (C/D) of the active metabolite of oxcarbazepine (OXC) [10-hydroxycarbazepine (MHD)] and to provide the reference for the rational clinical use of this drug.

A total of 161 MHD blood concentrations were collected from the therapeutic drug monitoring (TDM) data of inpatients who received OXC treatment, as well as demographic information, comedications, diagnosis, and associated clinical chemistry results. Data analysis was carried out through the SPSS 27.0 software.

The effects of age, body mass index (BMI), comedications and diagnosis on MHD C/D values were statistically significant (all P<0.05). The C/D value of patients under 18 years old was higher than that of patients between 18 to 65 years old. The C/D value of female patients was higher than that of male patients in adults. The C/D value of the underweight group was higher than the normal, overweight and obese groups. The C/D value of patients combined with valproic acid was significantly lower than that of patients who didn’t. The C/D value of epilepsy patients was significantly lower than that of patients who weren’t diagnosed with this disease. Only 11 patients (8.20%) had blood sodium below the normal value range after medication, and there was no significant difference in blood sodium value, serum creatinine value, and glutamic-pyruvic transaminase value before and after treatment (all P>0.05). The results of multiple linear regression analysis showed that BMI had an effect on the C/D of MHD (P<0.05).

OXC has relatively good safety profile, and the effects of gender, age, BMI, comedications and diagnosis should be taken into consideration when OXC is prescribed.

To observe the clinical efficacy and safety of sivelestat sodium for injection combined with atomized ambroxol hydrochloride injection in the treatment of acute respiratory distress syndrome patients.

The patients with acute respiratory distress syndrome were divided into treatment group and control group by block randomization method. All patients received high-flow nasal cannula oxygen therapy. The control group was given ambroxol hydrochloride injection 15 mg on this basis. The treatment group was treated with sivelestat sodium for injection 4.80 mg·kg^-1 on the basis of control group. Both groups were treated for 7 days. Clinical score, respiratory function, pulmonary microvascular resistance index and 28-day mortality were compared between the two groups, and the safety was evaluated.

Treatment group was enrolled 47 cases, 1 case dropped out, and 46 cases were finally included in the analysis; control group was enrolled 48 cases, 2 cases dropped out, and 46 cases were finally included in the analysis. After treatment, the total effective rate of the treatment group and the control group was 89.86% (40 cases / 46 cases) and 67.39% (31 cases / 46 cases), respectively, and the difference was statistically significant (P<0.05). After treatment, the scores of acute physiology and chronic health evaluation Ⅱ in the treatment group and control group were (12.38±2.54) and (14.16±2.79) points, respectively; the Murray lung injury scores were (0.93±0.22) and (1.06±0.27) points, respectively; the scores of sequential organ failure assessment were 5.43±1.22 and 6.14±1.59, respectively; partial pressure of carbon dioxide values were (37.43±3.62) and (39.51±4.11) mmHg, respectively; respiratory rates were (22.43±2.72) and (23.96±3.24) time·min^-1, respectively; extra vascular lung water indexes were (8.54±1.62) and (9.37±1.85) mL·kg^-1, respectively; pulmonary vascular permeability indexes were (2.58±0.52)% and (2.86±0.54)%, respectively; the fatality rates at 28 days were 10.87% (5 cases/46 cases) and 28.26% (13cases /46 cases), respectively. In comparison to the control group, the aforementioned indicators in the treatment group demonstrated notable statistical differences (all P<0.05). Abnormal liver function, indigestion and stomach burn were the main adverse reactions in treatment group and control group. The total incidence of adverse drug reactions in treatment group and control group were 8.70% (4 cases/46 cases) and 10.87% (5 cases/46 cases), respectively, with no statistical significance (P>0.05).

The use of sivelestat sodium for injection combined with atomized ambroxol hydrochloride injection in treating acute respiratory distress syndrome patients yields favorable clinical outcomes, alleviates patient symptoms, enhances respiratory function, lowers 28-day mortality rates, and is considered safe.