To observe the influence of propofol injection emulsion combined with esketamine injection on hemodynamics and postoperative recovery quality in elderly patients after lower limb arthroplasty.

The elderly patients undergoing lower limb joint replacement were divided into low-dose group (0.25 mg·kg^-1 esketamine), high-dose group (0.50 mg·kg^-1 esketamine) and control group (equal volume of 0.9% NaCl) according to the cohort method. Hemodynamics [heart rate (HR), mean arterial pressure (MAP)], postoperative recovery quality scale-15 (QoR-15) scores, dosages of anesthetic drugs, Ramsay sedation score, recovery quality and adverse reactions were compared among the three groups.

In this study, 39 cases were enrolled in the low-dose group, 40 cases in the high-dose group and 42 cases in the control group. The HR of patients in low-dose group, high-dose group and control group immediately after operation (T1) was (76.39±5.77), (77.16±5.24) and (73.21±4.79) beat·min^-1, respectively; MAP values were (85.11±5.22), (85.21±5.37) and (82.79±4.86) mmHg, respectively; at 15 min after operation, the HR of T2 were (78.36±5.11), (78.24±5.02) and (80.67±4.57) beat·min^-1; the MAP were (85.75±5.11), (85.39±4.97) and (87.93±3.67) mmHg, respectively; the QoR-15 scores 24 h after operation were (108.19±10.29), (109.56±10.12) and (99.66±10.21) points, respectively; the dosage of propofol were (220.66±25.19), (211.66±27.88) and (283.37±26.28) mg, respectively; the dosage of remifentanil were (2.37±0.42), (2.24±0.38) and (2.89±0.35) mg, respectively; Ramsay sedation scores were (1.56±0.27), (1.61±0.22) and (1.58±0.24) points at T0; and (3.18±0.33), (3.29±0.34) and (2.67±0.29) points at T3, respectively. Compared with the control group, there were statistically significant differences in the above indexes between the low-dose group and the high-dose group (all P<0.05), while there were no statistically significant differences in the above indexes between the low-dose group and the high-dose group (all P>0.05). Adverse drug reactions included respiratory depression, nausea/vomiting, dizziness, restlessness, hypotension, etc. The total incidence of adverse drug reactions were 2.56% (1 case /39 cases) in the low-dose group, 15.00% (6 cases/40 cases) in the high-dose group, and 26.19% (11 cases /42 cases) in the control group. The total incidence of adverse drug reactions of low-dose group was significantly lower than the control group, and the difference was statistically significant (P<0.05).

The application of propofol combined with esketamine can reduce the intraoperative dosages of propofol and remifentanil in elderly patients undergoing knee arthroplasty, enhance the sedation effect, improve the hemodynamics, and promote the postoperative recovery.

To study the effect of tazemetostat on the stemness of diffuse large B-cell lymphoma and the related mechanism of action.

OCI-LY3 cells were divided into blank group, tazemetostat group and microRNA-378a-3p (miR-378a-3p) mimics group. Blank group cell conventional culture; tazemetostat group was treated with 5 μmol·L^-1 tazemetostat; miR-378a-3p mimics group was transfected with miR-378a-3p mimics. The relative expression level of miR-378a-3p was detected by fluorescence in situ hybridization. mRNA expression levels of dryness related factors were detected by quantitative real time polymerase chain reaction; the expression of signal pathway-related proteins was detected by Western blot.

The relative expression levels of miR-378a-3p in blank group and tazemetostat group were 1.00±0.14 and 0.52±0.08, respectively, the difference was statistically significant (P<0.001). The relative expression of octamer binding transcription factor 4 mRNA in blank group, tazemetostat group and miR-378a-3p mimics group were 1.00±0.16, 0.21±0.06 and 0.49±0.08, respectively; the relative expression of sex determining region Y box protein 2 mRNA were 1.00±0.09, 0.39±0.05 and 0.85±0.11, respectively; the relative expression of Nanog homeobox mRNA were 1.00±0.13, 0.17±0.03 and 0.65±0.10, respectively; the relative expressions of Kruppel like factor 4 mRNA were 1.00±0.10, 0.28±0.05 and 0.86±0.14, respectively; the relative expressions of Yes associated protein were 1.00±0.19, 3.46±0.52 and 2.14±0.36, respectively; the relative expression of transcriptional coactivator with PDZ-binding motif protein were 1.00±0.14, 1.90±0.35 and 1.51±0.33, respectively. The above indexes of tazemetostat group were compared with those of blank group, and the above indexes of miR-378a-3p mimics group were compared with those of tazemetostat group, the differences were statistically significant (P<0.001, P<0.05).

Tazemetostat can inhibit the stemness of OCI-LY3 cells by down-regulating the level of miR-378a-3p, which may be achieved through the Yes associated protein/transcriptional coactivator with PDZ-binding motif signaling pathway.

To investigate the effects of almonertinib on the proliferation, invasion, epithelial-mesenchymal transition (EMT), and stemness of non-small-cell lung cancer (NSCLC) cells by regulating microRNA-22 (miR-22) targeting ubiquitin-conjugating enzyme E2O (UBE2O).

Human lung adenocarcinoma cell line NCI-H1975 was randomly divided into control group (normal culture with no treatment), medium-dose group (4 μmol·L^-1 almonertinib), inhibitor negative control (NC inhibitor) group (4 μmol·L^-1 almonertinib + miR-22 inhibition negative control), miR-22 inhibitor group (4 μmol·L^-1 almonertinib + miR-22 inhibition), miR-22 inhibitor+short hairpin negative control (sh-NC) group (4 μmol·L^-1 almonertinib + miR-22 inhibition + short hairpin negative control), and miR-22 inhibitor+short hairpin UBE2O (sh-UBE2O) group (4 μmol·L^-1 almonertinib + miR-22 inhibition + short hairpin UBE2O). The expression of miR-22 was detected by quantitative real-time polymerase chain reaction (qRT-PCR) ; Western blot analysis was performed to detect the expression of octamer-binding transcription factor 4 (OCT4), SRY-Box transcription factor 2 (SOX2), and Nanog; the cell proliferation rate was assessed using the 5-ethynyl-2-deoxyuridine (EdU) assay; and Transwell assays were conducted to evaluate cell invasion ability.

The expression levels of miR-22 in the control group, medium-dose group were 1.00±0.16, 2.07±0.34. The expression levels of OCT4 in the control group, medium-dose group, NC inhibitor group, and miR-22 inhibitor group were 1.00±0.16, 0.63±0.09, 0.67±0.08 and 0.94±0.12, respectively; SOX2 expression levels were 1.00±0.14, 0.48±0.06, 0.54±0.07 and 0.81±0.11; and Nanog expression levels were 1.00±0.18, 0.45±0.08, 0.52±0.11 and 0.89±0.15. The cell proliferation rates in the control group, medium-dose group, NC inhibitor group, miR-22 inhibitor group, miR-22 inhibitor+sh-NC group, and miR-22 inhibitor+sh-UBE2O group were (87.29±10.73)%, (41.65±7.82)%, (48.47±6.54)%, (79.31±10.26)%, (84.50±11.98)% and (36.82±6.79)%, respectively. The numbers of invading cells were (156.92±24.81), (72.53±9.06), (64.41±10.75), (143.27±26.19), (137.58±21.46) and (75.23±11.94), respectively. Compared between the control group and medium-dose group, NC inhibitor and miR-22 inhibitor groups, as well as miR-22 inhibitor+sh-NC and miR-22 inhibitor+sh-UBE2O groups showed statistically significant differences (all P<0.05).

Almonertinib can inhibit the proliferation and invasion of NSCLC NCI-H1975 cells, likely by regulating miR-22 to target UBE2O.

To analyze the clinical efficacy and safety of salmeterol fluticasone propionate combined with cetirizine hydrochloride and montelukast sodium tablet in the treatment of children with cough variant asthma.

The children with cough variant asthma were divided into control group and treatment group by random number table method. The control group was treated with oral montelukast sodium chewable tablets and cetirizine hydrochloride oral solution, both 10 mg every time, qd; the treatment group was treated with salmeterol fluticasone propionate inhalation powder inhalation, 1 inhalation/time, bid on the basis of the control group. Children in both groups continued treatment for 3 weeks. The clinical efficacy, pulmonary function, airway reaction status, immune function index, inflammatory index and adverse drug reactions were compared between the two groups.

In the treatment group, 50 cases were enrolled, 1 case was lost, and 49 cases were finally included in the statistical analysis. In the control group, 52 cases were enrolled, 3 cases were lost, and finally 49 cases were included in the statistical analysis. After treatment, the total effective rate of the control group and the treatment group were 77.55% (38 cases/49 cases) and 93.88% (46 cases/49 cases), respectively, and the difference were statistically significant (P<0.05). After treatment, the maximum expiratory flow were (4.68±0.56) and (5.07±0.62) L·s^-1 in the control and treatment groups; the vital capacity were (0.98±0.05) and (1.02±0.07) L; the forced expiratory volume in the first second were (75.72±7.24)% and (80.03±8.36)%; the forced vital capacity were (75.49±7.68)% and (79.97±6.72)%; the initial airway resistance were (7.33±0.75) and (7.01±0.73) cm H₂O·L^-1·s^-1; the minimum induced cumulative dose were (1.89±0.14) and (2.01 ± 0.25) mg·L^-1; the 35th percentile of specific airway conduction decrease were (5.24±0.52)% and (5.59±0.68)%. 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 adverse drug reactions of the control group and the treatment group were headache, palpitation and sleep difficulty, and the incidence of the total adverse drug reactions of the treatment group and the control group were 6.12% (3 cases /49 cases) and 12.24% (6 cases /49 cases), respectively, with no statistical significance (P>0.05).

Salmeterol fluticasone propionate, cetirizine hydrochloride and montelukast sodium tablet are effective and safe in the treatment of children with cough variant asthma.

Acute lung injury (ALI)/acute respiratory distress syndrome is a life-threatening acute diffuse inflammatory lung injury characterised by increased pulmonary vascular permeability, inflammatory cell infiltration, pulmonary oedema, diffuse alveolar damage and reduced respiratory output. Its pathogenesis is complex, and oxidative stress is a key mechanism leading to ALI exacerbated by alveolar epithelial cell dysfunction. The Kelch-like ECH associated protein 1 /nuclear factor -E2-related factor 2 (Keap1/Nrf2) signalling pathway is an important signalling pathway of traditional Chinese medicine in the treatment of ALI by regulating oxidative stress. This paper analyses and summarizes the relevant Chinese medicine formulas and active ingredients for the treatment of ALI, and finds that a large number of antioxidant active ingredients can regulate oxidative stress through the Keap1/Nrf2 signaling pathway and play a role in improving ALI, which also provides a basis for the prevention and treatment of ALI disease and further drug development.

To establish a high performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method for the determination of nicorandil concentrations in human plasma and for pharmacokinetic studies in healthy subjects.

Human plasma samples were pretreated with acetonitrile extraction. Chromatographic cdumn: Acquity HPLC BEH C₁₈ (1.7 μm, 2.1 mm×50.0 mm), mobile phase: methanol (0.1% formic acid)-5 mmoL· L^-1 ammonium acetate (with 0.1% formic acid). Flow rate: 0.2 mL·min^-1, column temperature: 40 ℃, injection volume: 5 μL. Gradient elution, electrospray ion source, multiple reaction monitoring, positive ion scanning, nicorandil-d4 isotope as internal standard. The specificity of the method, the standard curve and the lower limit of quantification, the carryover effect and dilution reliability, the precision and recovery, the matrix effect, and the stability of the method were investigated.

The specificity of the established method was good, nicorandil had a good linear relationship between 0.2-200.0 ng·mL^-1, the standard curve was y=1.08×10^-1x+2.66×10^-2 (r=0.999 7), the lower limit of quantification was 0.2 ng·mL^-1, there was no residual effect, the dilution results were reliable, and the intra-day and inter-day precision of quality control samples were 0.64%-8.70% and 0.91%-8.70%, respectively. The intra-day and inter-day accuracy were 100.00%-115.00% and 98.00%-115.00%, respectively. The extraction recoveries of nicorandil at low, medium and high quality control concentrations were 92.78%-95.35%, with no obvious matrix effect and good stability.

This method is highly specific, accurate, stable, reproducible, and simple to operate, and can be used to determine the concentration of drug in plasma of nicorandil.

To establish an ultra-high performance liquid chromatography tandem high resolution mass spectrometry (UHPLC-HRMS) method for the determination of serum demthylzeylasteral concentration in diabetic nephropathy patients, which treated by tripterygium wilfordii polyglycosides tablets (TGTs), and to apply this method in the exploratory study of clinical pharmacodynamic marker.

Serum samples and ¹⁸O-demethylzeylasteral which was used as the internal standard were processed by solid phase extraction method and took the supernatant for the determination. Chromatographic separation of the analytes was accomplished using a BEH C₁₈ column (2.1 mm×50.0 mm, 1.7 μm) under gradient elution, where the mobile phase consisted of a mixture of 0.1% formic acid aqueous solution and acetonitrile, as well as 0.1% formic acid aqueous solution. The flow rate was set at 0.3 mL·min^-1 and the column temperature at 30 ℃. The mass spectrometer was equipped with an electrospray ionization source with positive multiple reaction monitoring mode. The specificity, standard curve and lower limit of quantification, precision and recovery rate, matrix effect and stability were investigated. This method was applied to determine the serum concentration of demethylzeylasteral from 15 patients with oral TGTs. Receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were utilized to explore the correlation between serum concentration of demethylzeylasteral and efficacy in treating diabetic nephropathy.

The calibration curve of demethylezylasteral was linear over the range of 1-200 ng·mL^-1, and the lower limit of quantification was 1 ng·mL^-1. The precision and accuracy relative standard deviation of intra-day and inter-day was less than 10% and 15%, respectively. The average absolute recovery was more than 89%, no matrix effect has been affected and all stability tests met the acceptance criteria. The AUC of the efficacy of TGTs predicted by serum demethylzeylasteral quantitation was 0.66 (95% confidence interval was 0.53-0.78), the cut-off value was 61.73 ng·mL^-1, the sensitivity was 83.3% and the specificity was 46.7% (P<0.05).

The UHPLC-HRMS method established in this study has the advantages of simple operation, high sensitivity, accurate and reliable results, which can be suitable for determining serum concentration of demethylzsylasteral and studying clinical drug efficacy markers of TGTs.

To investigate the regulatory effects of aloperin on bladder cancer cell growth and endoplasmic reticulum stress-dependent mitochondrial pathway.

253J cells were randomly divided into control group, experimental-L group (25.0 μmoL·L^-1 aloperin), experimental-M group (50.0 μmoL·L^-1 aloperin), experimental-H group (100.0 μmoL·L^-1 aloperin), 4-PBA group [100.0 μmoL·L^-1 aloperin+20 μmoL·L^-1 4-phenylbutyric acid (4-PBA)], si-NC (transfected with si-NC+100.0 μmoL·L^-1 aloperin), si-CHOP group [transfected with si-CCAAT-enhancer-binding protein homologous protein (CHOP)+100.0 μmoL·L^-1 aloperin]. Cell proliferation was detected by 5-ethynyl-2′-deoxyuridine (EdU) assay; protein expression was detected by Western blot assay; apoptosis was detected by flow cytometry; mitochondrial membrane potential (MMP) was detected by JC-1 assay.

The EdU positive cell rates in control group, experimental-L group, experimental-M group and experimental-H group were (37.51±2.98)%, (29.52±2.19)%, (23.10±2.58)% and (12.94±2.52)%, respectively; the expression levels of C/EBP homologous protein (CHOP) were 0.29±0.04, 0.53±0.05, 0.71±0.08, 0.90±0.12, respectively. The apoptosis rates in control group, experimental-H group and 4-PBA group were (4.79±0.62)%, (23.01±2.03)% and (13.75±1.14)%, respectively. The expressions of CHOP protein in control group, experimental-H, si-NC and si-CHOP groups were 0.30±0.03, 0.92±0.08, 0.91±0.11 and 0.20±0.02, respectively; the apoptosis rates were (4.39±0.30)%, (22.11±1.82)%, (22.65±2.40)% and (15.32±1.19)%, respectively; mitochondrial cytochrome C (Cyto-C) protein levels were 0.78±0.07, 0.43±0.05, 0.42±0.05 and 0.65±0.06; cytoplasmic Cyto-C protein levels were 0.51±0.06, 0.91±0.10, 0.88±0.05 and 0.61±0.04; MMP levels were (100.00±2.79)%, (57.49±3.34)%, (54.09±4.32)% and (69.91±6.81)%, respectively. The above indexes in the experimental-L, -M, -H groups were compared with the control group, the above indexes in the 4-PBA group were compared with the experimental-H group, and the above indexes in the si-CHOP group were compared with the si-NC group, the differences were statistically significant (all P<0.01).

Aloperin can inhibit the proliferation of 253J cells by up-regulating the endoplasmic reticulum stress-dependent mitochondrial apoptosis pathway mediated by CHOP.

To study the effect of hydroxylsafflower yellow A (HSYA) on epiphyseal injury of tibial in rats through neurotrophic factor-3 (NT-3).

Fifty male SD rats were randomly divided into control group, model group, HSYA group, NC group and sh-NT-3 group, with 10 rats in each group. Except the control group, the injury model of tibial epiphyseal was established in the other 4 groups by high speed dental abrasive drill. The HSYA group was given 10 mg·kg^-1 HSYA by intragastric administration once a day for 6 weeks. NC group and sh-NT-3 group were respectively injected with 1 mg·kg^-1 sh-NC and sh-NT-3 through the tail vein, once every two days for 6 weeks. The control group and model group were given the same amount of normal saline intragastric and caudal intravenous injection. Quantitative real-time polymerase chain reaction was used to detect the expression level of NT-3 mRNA. The expression levels of bone repair markers and Notch receptor 1 (Notch1) signaling pathway related proteins were detected by Western blot.

The mRNA levels of NT-3 in control group, model group and HSYA group were 1.00±0.17, 3.31±0.59 and 5.16±0.84, respectively. The relative expression of runt related transcription factor 2 protein in control group, model group, HSYA group, NC group and sh-NT-3 group were 1.00±0.17, 3.67±0.63, 7.36±1.35, 7.31±1.42, 5.74±1.32, respectively; the relative expressions of osteoblast-specific transcription factor protein were 1.00±0.18, 5.76±1.01, 8.49±1.42, 8.56±1.54, 6.48±1.16, respectively; the relative expressions of Notch1 protein were 1.00±0.18, 1.44±0.23, 1.79±0.34, 1.83±0.35, 1.52±0.27, respectively. The above indexes in the model group were compared with the control group, the HSYA group was compared with the model group, and the sh-NT-3 group was compared with the NC group, and the above indexes were statistically significant (all P<0.05).

HSYA improves tibial epiphyseal injury in rats by promoting NT-3 expression and activating Notch1 signaling pathway.