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 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 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.

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 investigate the effects of pitavastatin on lipopolysaccharide (LPS)-induced H9c2 cells and its mechanism.

H9c2 cells were divided into control group, model group (treated with 10 μg·mL^-1 LPS), experimental group (after 1 μmol·L^-1 pitavastatin treatment, 10 μg·mL^-1 LPS treatment), and combination group [treated with 1.28 μmol·L^-1 NLR family pyrin domain containing protein 3 (NLRP3) agonist on the basis of experimental group]. The NLRP3/cysteine-requiring aspartate protease 1 (caspase-1)/gasdermin D (GSDMD) signaling pathway related protein levels were detected by Western blot. The messenger ribonucleic acid (mRNA) relative expression levels related to inflammation and mitochondrial function were detected by quantitative real time polymerase chain reaction.

The relative expression levels of NLRP3 protein in control group, model group, experimental group and combination group were 1.00±0.15, 2.56±0.38, 1.35±0.19 and 2.15±0.31, respectively; the relative expression levels of caspase-1 protein were 1.00±0.18, 1.88±0.22, 1.22±0.20 and 1.75±0.22, respectively; the relative expression levels of GSDMD protein were 1.00±0.14, 2.12±0.32, 1.55±0.21 and 1.99±0.23, respectively; the relative expression levels of tumor necrosis factor-α mRNA were 1.00±0.15, 4.12±0.65, 2.11±0.29 and 3.54±0.48, respectively; the relative expression levels of interleukin-1β mRNA were 1.00±0.18, 3.33±0.39, 1.42±0.25 and 2.23±0.33, respectively; the relative expression levels of interleukin-18 mRNA were 1.00±0.14, 2.28±0.28, 1.33±0.26 and 1.98±0.22, respectively; the relative expression levels of PPAR-γ coactivator 1 alpha (PGC-1α) mRNA were 1.00±0.14, 0.45±0.07, 0.89±0.12 and 0.61±0.08, respectively; the relative expression levels of mitochondrial transcription factor A mRNA were 1.00±0.19, 0.53±0.07, 0.77±0.09 and 0.58±0.08, respectively; the relative expression levels of nuclear respiratory factor-1 mRNA were 1.00±0.17, 0.62±0.08, 0.85±0.13 and 0.65±0.08, respectively; the relative expression levels of uncoupling protein 2 mRNA were 1.00±0.15, 0.34±0.05, 0.92±0.16 and 0.48±0.07, respectively. The above indexes in model group were compared with those in control group, those in experimental group were compared with those in model group, and those in combination group were compared with those in experimental group, the differences were statistically significant (all P<0.05).

Pitavastatin can inhibit inflammation, reduce pyroptosis of H9c2 cells, and protect mitochondrial function, which may be achieved by inhibiting the NLRP3/caspase-1/GSDMD signaling pathway.

To explore the effects of 1% lidocaine on pain threshold in rats with myofascial pain syndrome (MPS) based on cyclic adenosine monophosphate (cAMP) / protein kinase A (PKA)/peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) signaling pathways.

The models of MPS rats were prepared by striking manipulation + fatigue method, and they were randomly divided into model group, combined group, experimental-L group and experimental-H group, 10 rats in each group. Another 10 rats were selected as blank group. After successful molding, experimental-L group and experimental-H group were given injection of 1% lidocaine (0.25 mL, 0.5 mL) at pain trigger site of right medial thigh (once a week), combined group was given intraperitoneal injection of SR-18292 (30 mg·kg^-1, 3 times a week) on basis of experimental-H group, model group and blank group were given injection of normal saline (once a week) at pain trigger site of right medial thigh or at the same site. Five groups were treated for 3 weeks. The pain threshold was detected by mechanical stimulation and thermal stimulation, level of adenosine triphosphate (ATP) in muscle tissues at pain trigger site was detected by the kit, and expressions of cAMP, PKA and PGC-1α proteins were detected by Western blot.

After 3 weeks of intervention, paw withdrawal mechanical threshold (PWMT) values in experimental-H group, combined group, model group and blank group were (51.69±7.22), (37.84±6.29), (20.33±5.83) and (67.88±8.46) g, paw withdrawal latency (PWL) values were (10.58±1.03), (7.89±0.87), (6.33±0.92) and (12.89±1.64) s, ATP levels were (866.37±98.66), (728.81±89.60), (617.52±89.84) and (1 098.45±101.36) μmol·g^-1, relative expression levels of cAMP protein were 0.53±0.08, 0.48±0.07, 0.21±0.06 and 0.68±0.10, relative expression levels of PKA protein were 0.60±0.06, 0.58±0.08, 0.28±0.05 and 0.79±0.09, relative expression levels of PGC-1α protein were 0.78±0.05, 0.59±0.06, 0.41±0.08 and 0.93±0.09, and the differences were statistically significant between experimental-H group, combined group and mode group (all P<0.05).

1% lidocaine can improve pain threshold and mitochondrial energy metabolism in muscle tissues of affected limbs in MPS rats, which may be related to activating cAMP/PKA/PGC-1α signaling pathways.