To investigate the mechanism of Dioscorea bulbifera L. against non-small cell lung cancer (NSCLC) by network pharmacology and molecular docking.

The active components and corresponding targets of Dioscorea bulbifera L. were retrieved by the traditional Chinese medicine systems pharmacology database and analysis platform. NSCLC targets were obtained and intersected. Protein-protein interaction (PPI) network analysis was performed using STRING database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of intersection targets were performed. Molecular docking techniques were used to predict the binding of core components to key targets.

Fifteen possible active components and 203 targets of active components were screened out. There were 1 653 targets for NSCLC and 120 intersection targets. The key targets were tumor antigen p53 (TP53), RAC-alpha serine/threonine-protein kinase (AKT1), transcription factor Jun (JUN), tumor necrosis factor (TNF) and interleukin-6 (IL-6) by PPI network analysis. GO and KEGG enrichment analysis showed that the key targets were mainly in transcription regulator complex, and through response to inorganic substance, played DNA-binding transcription factor binding function, and anti-NSCLC by regulating in cancer pathways. Molecular docking results showed that diosgenin and diosbulbin B were better bound to key targets.

The anti-NSCLC effect of Dioscorea bulbifera L. may be related to the regulation of cancer pathways by the action of diosgenin and diosbulbin B on TP53, AKT1, JUN, TNF and IL-6.

To investigate the effects and mechanism of Polygonum orientale flower (POR) extract on exercise arrhythmia (EA) in rats after exhaustive exercise.

The EA rat model was induced by 8 weeks of exhaustive weight-bearing swimming exercise and was randomly divided into model group and experimental -L, -M, -H groups, with 12 rats per group. Twelve normal rats were selected as the normal group. On the modeling day, normal and model groups were given pure water by intragastric administration. Experimental -L, -M, -H groups were given 50, 100 and 200 mg·kg^-1 POR extract solution by intragastric administration, respectively. Five groups were administrated with once a day for 8 weeks. The latent time and duration of arrhythmia in rats were detected by electrocardiograph. The contents of adenosine triphosphate (ATP), the activities of Na⁺/K⁺ATP and the contents of superoxide dismutase (SOD) in myocardial tissue were measured by corresponding kit. The transcriptional levels of calmodulin (CaM) and calmodulin dependent protein kinase Ⅱ (CaMK Ⅱ) in rat myocardium were measured by real-time fluorescence quantitative polymerase chain reaction.

The latent time of arrhythmia in experimental -M, -H groups and model group were (9.77±1.48), (10.61±1.61) and (7.44±2.12) min; the duration were (33.25±6.39), (20.01±3.89) and (71.44±13.68) min. The ATP contents in experimental -M, -H groups, model group and normal group were (26.45±2.96), (29.44±1.89), (10.38±1.22) and (34.50±4.24) ng·g prot^-1; the Na⁺/K⁺ ATP activities were (17.27±0.92), (19.57±1.33), (5.14±0.80) and (20.00±2.11) U·g prot^-1; SOD contents were (89.22±9.07), (86.29±7.22), (73.62±7.36) and (89.43±8.85) U·mg prot^-1; the relative expression levels of CaM mRNA in myocardial tissue were 1.28±0.08, 1.06±0.08, 2.34±0.30 and 1.00±0.10; the relative expression levels of CaMK Ⅱ mRNA in myocardial tissue were 1.46±0.09, 1.15±0.09, 2.80±0.19 and 1.00±0.11, respectively. Compared with model group, the differences of above indexes in experimental -M, -H groups were statistically significant (all P<0.05).

POR extract can effectively treat the rats with EA, and the mechanism is related to the increase of ATP contents, Na⁺/K⁺ ATP and antioxidant activities, and inhibition of Ca²⁺/CaM/CaMK Ⅱ signaling pathway.

To observe the clinical efficacy of medroxyprogesterone acetate and dinogestrel in the treatment of endometriosis (EMs) respectively.

EMs patients were divided into control group and treatment group according to cohort methods. Control group was given oral treatment with medroxyprogesterone acetate tablets, 10 mg each time, tid. Treatment group was given oral treatment with dinorgestrel tablets, 2 mg each time, qd. Patients in both groups continued to take the drug for 6 menstrual cycles. The levels of clinical efficacy, basal follicle-stimulating hormone (bF-SH), basal estradiol (bE₂), anral follicle count (AFC) and anti-mullerian hormone (AMH) before and after treatment were compared between the two groups.

In this trial, 38 cases were enrolled in the control group and 42 cases in the treatment group. After treatment, the total effective rates of the treatment group and the control group were 90.48% (38 cases / 42 cases) and 71.05% (27 cases / 38 cases), respectively, and the difference was statistically significant (P<0.05). After treatment, the levels of bF-SH in the treatment group and control group were (11.25±3.02) and (13.41±3.56) IU·L^-1, respectively; the bE₂ levels were (2.14±0.63) and (2.58±0.87) pmol·L^-1, respectively; the AFC levels were 7.80±1.69 and 6.97±1.63, respectively; the AMH levels were (1.12±0.14) and (1.03±0.21) ng·mL^-1, respectively; the above indexes were statistically significant (P<0.01,P<0.001). The adverse drug reactions of the treatment group mainly included abnormal vaginal bleeding, hot flashes and increased body weight, while the adverse drug reactions of the control group mainly included bleeding and hot flashes. The incidence of total adverse drug reactions in the treatment group and the control group was 11.90% (5 cases/42 cases) and 7.89% (3 cases/38 cases), respectively, and the difference was not statistically significant (P>0.05).

Dienogest tablets has a good effect in the treatment of EMs patients, which can effectively relieve pain symptoms, inhibit estrogen expression, improve uterine artery blood flow, and reduce the level of inflammation in the body, with low adverse drug reactions.

To observe the clinical efficacy of ulinastatin injection and thymalfasin for injection in the treatment of sepsis patients and their effects on peripheral blood T lymphocyte subsets.

Sepsis patients were divided into control group and treatment group according to the cohort method. The control group was treated with ulinastatin injection in addition to initial resuscitation, hemoperfusion, and antimicrobial therapy. The treatment regimen was intravenous infusion, 2.0×10⁵ U bid for 4 days, followed by intravenous pump infusion, 1.0×10⁵ U bid for 6 days. The treatment group received thymalfasin for injection on base of the control group’s treatment, subcutaneous injection, 1.6 mg twice a week, for 2 weeks. The clinical efficacy, Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ score, peripheral blood procalcitonin (PCT), lactate (Lac), D-dimer (D-D), and levels of T lymphocyte subsets were compared between the two groups, as well as 28-day mortality rate and safety were evaluated.

A total of 43 patients were enrolled in the control group and 37 patients in the treatment group. After treatment, the total effective rates in the treatment group and the control group were 94.59% (35 cases/37 cases) and 86.05% (37 cases/43 cases), respectively, with no significant difference statistically (P>0.05). After treatment, the SOFA scores in the treatment group and the control group were (5.46±1.20) and (6.71±1.33) points; the APACHE Ⅱ scores were (16.17±3.49) and (18.63±3.82) points; the peripheral blood PCT levels were (1.51±0.33) and (1.88±0.42) μg·L^-1; the Lac levels were (2.73±0.52) and (5.06±1.19) nmol·L^-1; the D-D levels were (0.85±0.27) and (1.02±0.33) mg·L^-1; the CD3⁺ levels were (38.98±4.36)% and (34.42±4.14)%; the CD4⁺ levels were (18.66±2.47)% and (13.17±1.96)%; the CD8⁺ levels were (12.35±1.42)% and (13.01±1.39)%; and the CD4⁺/CD8⁺ ratio were 1.49±0.24 and 1.04±0.22, respectively, all showing statistically significant differences (all P<0.05). The 28-day mortality rates in the treatment group and the control group were 18.92% (7 cases/37 cases) and 23.26% (10 cases/43 cases), respectively, with no significant difference statistically (P>0.05). No drug-related adverse reactions were observed in either group.

The clinical efficacy of thymalfasin for injection in the treatment of sepsis is more ideal than that of ulinastatin alone, as it can better reduce the levels of peripheral PCT, Lac, and D-D, regulate T lymphocyte subsets, demonstrating definite efficacy and safety.

To observe the anesthetic effect of esketamine injection combined with remimazolam injection in radical prostatectomy for prostate cancer.

The patients were divided into the control group and the treatment group according to cohort method. The control group was given anesthesia induction with remimazolam injection at 0.2 mg·kg^-1 combined with propofol injection at 1 mg·kg^-1. The treatment group was given anesthesia induction with esketamine injection at 0.5 mg·kg^-1 combined with remimazolam injection at 0.1 mg·kg^-1. Both groups underwent maintenance of anesthesia with propofol injection at 4-8 mg·kg^-1·h^-1 combined with remifentanil injection at 5-10 μg·kg^-1·h^-1. The analgesic effect, sedative effect, hemodynamics [before anesthesia (T0), tracheal intubation (T1), 30 min after the beginning of surgery (T2), 2 h after surgery (T3)], stress (T0~T3) and safety were compared between the two groups.

The control group and the treatment group were enrolled in 44 cases and 42 cases, respectively. At 3 h, 6 h, 12 h and 24 h after surgery, the Numerical Rating Scale (NRS) scores of the treatment groups were 2.71±0.46, 2.52±0.43, 2.24±0.32 and 2.25±0.29; the dosage of patient-controlled intravenous analgesia (PCIA) was (52.38±6.67) mL. At 3 h, 6 h, 12 h and 24 h after surgery, NRS scores of the control group were 3.49±0.52, 3.27±0.44, 2.73±0.41 and 2.54±0.39; the dosage of PCIA was (64.79±7.45) mL. For the treatment group, heart rate (HR) were (105.48±3.34), (102.67±3.45) and (100.29±1.93) beat·min^-1 from T1, T2, T3; serum cortisol (Cor) levels at T1 and T2 were (257.68±29.18) and (303.75±31.52) nmoL·L^-1; serum superoxide dismutase (SOD) levels at T2 and T3 were (425.85±50.45) and (422.96±50.21) U·L^-1. For the control group, HR were (95.38±2.26), (91.52±2.68) and (87.15±1.40) beats·min^-1 from T1, T2, T3; serum Cor levels at T1 and T2 were (307.36±32.11) and (322.38±33.45) nmoL·L^-1; serum SOD levels at T2 and T3 were (401.23±46.21) and (388.24±45.87) U·L^-1. The differences were statistically significant (all P<0.05). Adverse drug reactions in the treatment group mainly included emergence agitation, nausea and vomiting. Adverse drug reactions in the control group mainly included diplopia, emergence agitation, nausea and vomiting. The total incidence rates of adverse drug reactions in the treatment group and the control group were 13.64% (6 cases/44 cases) and 16.67% (7 cases /42 cases), without statistically significant difference (P>0.05).

Esketamine injection combined with remimazolam injection can achieve good anesthetic effect on patients undergoing radical prostatectomy for prostate cancer, which can effectively alleviate postoperative pain and physiological stress, and facilitate postoperative early functional recovery, with good safety.

To develop a high performance liquid chromatographic method for determination of epinephrine in epinephrine hydrochloride injection.

The separation was carried out on a Waters XBridge C₁₈ column (150.0 mm×4.6 mm, 5 μm) with isocratic elution . The mobile phase consisted of 5.0 g·L^-1 potassium dihydrogen phosphate and 2.6 g·L^-1 octanesulfonic acid sodium solution (adjusting pH to 3.7 by phosphoric acid) -acetonitrile (85∶15) with the flow rate of 1.0 mL·min^-1, the column temperature of 40 ℃, the detection wavelength of 280 nm and the injection volume of 10 μL. The specificity, standard curve and lower limit of quantitation (LLOQ), system suitability, stability, precision and recovery were investigated.

The calibration curve of epinephrine was linear in the range of 2.09 - 83.66 μg·mL^-1. The standard curve of epinephrine was y=8.74×10³x-2.72×10³ (r=1.000 0). The LLOQ was 2.09 μg·mL^-1. The system applicability was proved to be good since the relative standard deviation (RSD) of the main peak area was 0.19% and the RSD of retention time was 0.18%. The RSD of the test solution at high, medium and low concentrations was less than 0.5%, and the average recovery rate was 105.09%-107.86%. The test solution was stable within 4 h.

The method validation proveded that the proposed method was stable, recovery, precise and specificity, which could be used for the measurement of epinephrine in epinephrine hydrochloride injection administration preparation.

To establish a hollow fiber centrifugal ultrafiltration (HFCF-UF) coupled with ultra-high performance liquid chromatography (UPLC) method for the analysis of free methotrexate (MTX) concentration in human plasma and apply to clinical therapeutic drug monitoring.

Plasma samples 500 μL were prepared with HFCF-UF. A Waters UPLC BEH C₁₈ column (50.0 mm×2.1 mm, 1.7 μm) was used. The mobile phase consisted of methanol and 0.05 mol·L^-1 phosphate buffer (pH 6.2) (17∶83, v/v) at a flow rate of 0.2 mL·min^-1. The column temperature was maintained at 30 ℃. The detected wavelength was 302 nm. The specificity, linear relationship, lower limit of quantification (LLOQ), precision, recovery rate and stability of this method were investigated, and it was applied to the determination of clinical plasma samples.

The good linear relationship were obtained between concentration of free MTX in human plasma from 0.05-10.00 μmol·L^-1, y=0.297x+0.001 (r²=0.999). The LLOQ of MTX free plasma concentration analysis was 0.05 μmol·L^-1. The method recovery rates of free MTX were 95.77%-100.52%. The absolute recovery rates of free MTX was 84.09%-92.93%. The intra-day and inter-day relative standard deviation (RSD) were all less than 7.0 %. It was successfully used to analyze free MTX concentration in 52 plasma samples from patients with MTX chemotherapy. The average free plasma concentration of MTX in these 52 patients was 0.68 μmol·L^-1, with the maximum value of 9.32 μmol·L^-1 and the minimum value of 0.056 μmol·L^-1.

The developed method is simple, accurate and sensitive, which is suitable for the analysis of free MTX on clinical therapeutic drug monitoring.

To analyze the correlations between topoisomerase Ⅱ alpha (TOP2A) and prognosis and immune infiltration in lung cancer.

The expression difference of TOP2A in lung cancer patients was examined by tumor immune estimation resource (TIMER) database. The prognostic value of TOP2A in lung cancer was evaluated using the Kaplan-Meier Plotter and PrognoScan databases. Additionally, the correlation between immune infiltration related gene marker sets and TOP2A expression was analyzed by TIMER database. The gene-gene and protein-protein interactions were determined using GeneMANIA and STRING for network construction, respectively. The possible regulatory network of TOP2A was explored by miRWalk and DIANA-LncBase v2 databases.

The expression of TOP2A in lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) was significantly upregulated and high expression of TOP2A was significantly associated with reduced overall survival, first progression survival, and post-progression survival in lung cancer patients. TOP2A expression was significantly correlated with the infiltration of immune cells in lung cancer, including monocytes, neutrophils, tumor-associated macrophages, helper T cells 1, regulatory T cells, and exhausted T cells. The majority of genes or proteins associated with TOP2A were involved in the regulation of gene transcription and cell cycle. An lncRNA (ENSG00000279978) was identified as being related to the progression of LUAD and LUSC.

TOP2A is an immune infiltration-related prognostic biomarker for lung cancer and may serve as a potential therapeutic target.