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 mechanism of inhibiting invasion and epithelial mesenchymal transformation of esophageal squamous cell carcinoma cells by chidamide (CHI) through long noncoding RNA (LncRNA) VPS9D1-AS1.

Human normal esophageal epithelial cells (HEEC) group (HEEC were cultured normally without any treatment), human esophageal squamous cell carcinoma KYSE-450 cells were divided into KYSE-450 group (normal culture), CHI group (treated with 20 μmol·L^-1 CHI for 48 h), CHI+oe-NC group (transfected with oe-NC, treated with 20 μmol·L^-1 CHI for 48 h), CHI+oe-LncRNA VPS9D1-AS1 group (transfected with oe-LncRNA VPS9D1-AS1, treated with 20 μmol·L^-1 CHI for 48 h). The positive expression of LncRNA VPS9D1-AS1 in the cells was detected by fluorescence in situ hybridization, the invasion ability of the cells was detected by Transwell, and the epithelial mesenchymal transformation and mitogen-activated protein kinase (MEK)/extracellular signal-related protein kinase (ERK) signaling pathway related protein expression levels were detected by protein Western blot.

The positive expression levels of LncRNA VPS9D1-AS1 in HEEC group, KYSE-450 group and CHI group were 1.00±0.06, 4.58±0.84 and 1.93±0.37, respectively. Compared with HEEC group and KYSE-450 group, compared with CHI group and KYSE-450 group, the positive expression levels of LncRNA VPS9D1-AS1 were significantly different (P<0.05). The invasion numbers of cells in KYSE-450 group, CHI group, CHI+oe-NC group, CHI+oe-LncRNA VPS9D1-AS1 group were 89.57±15.61, 22.49±5.18, 27.04±5.95 and 57.82±10.73, respectively; the relative expression levels of N-cadherin were 1.00±0.07, 0.52±0.12, 0.59±0.09 and 0.91±0.16, respectively; the relative expression levels of E-cadherin were 1.00±0.11, 1.81±0.35, 1.79±0.30 and 1.24±0.22, respectively; the relative expression levels of MEK1 were 1.00±0.08, 0.64±0.11, 0.69±0.13 and 0.93±0.17, respectively; p-ERK1/ERK1 levels were 1.00±0.05, 0.61±0.07, 0.55±0.10 and 0.95±0.15, respectively; p-ERK2/ERK2 levels were 1.00±0.12, 0.43±0.09, 0.42±0.08 and 0.89±0.14, respectively. Compared between KYSE-450 group and CHI group, between CHI+oe-LncRNA VPS9D1-AS1 group and CHI+oe-NC group, there were statistical significance in the levels of the above indexes (P<0.05).

CHI can inhibit esophageal squamous cell invasion and epithelial mesenchymal transformation, which may be related to the inhibition of MEK/ERK signaling pathway activation by LncRNA VPS9D1-AS1 down-regulated by CHI.

To observe the clinical efficacy and safety of bevacizumab injection combined with paclitaxel injection and carboplatin injection in the treatment of patients with advanced ovarian cancer.

Patients with advanced ovarian cancer were randomly divided into control group and treatment group. The control group was given 175 mg·m^-2 paclitaxel once every 3 weeks, the intravenous infusion was not less than 3 h + 0.3 - 0.4 g·m^-2 carboplatin once every 3 weeks, intravenous infusion. On the basis of control group, the treatment group was given 15 mg·kg^-1 bevacizumab once every 3 weeks, intravenous infusion. Two groups were treated for 6 courses with 3 weeks per course. The clinical efficacy, tumor markers, vascular related factors, T lymphocyte and miRNA-30 levels, survival during treatment and safety were compared between two groups.

Treatment group was enrolled 71 cases, 10 cases dropped out, and 61 cases were finally included in the statistical analysis. Control group was enrolled 70 cases, 10 cases dropped out, and 60 cases were finally included in the statistical analysis. After treatment, the disease remission rates of treatment and control groups were 60.66% (37 cases/61 cases) and 41.67% (25 cases/60 cases) with statistically significant difference (P<0.05). After treatment, the cluster of differentiation 133 levels were (11.44±2.46) and (26.77±5.41) U·mL^-1, the DEAD-box helicase 4 levels were (13.55±3.48) and (33.16±5.46) U·mL^-1, the relative expression levels of miRNA-30b were 1.03±0.07 and 1.15±0.08, the relative expression levels of miRNA-30c were 1.09±0.05 and 1.22±0.06, the differences were statistically significant (all P<0.05). During follow-up, all-cause deaths of treatment and control groups were 8 and 11 cases, the survival rates were 86.89% and 81.67% (all P>0.05). The adverse drug reactions in both groups were mainly gastrointestinal reactions, alopecia, allergies and liver dysfunction. The total incidences of adverse drug reactions in the treatment and control groups were 55.74% and 43.33%, without significant difference (P>0.05).

Bevacizumab injection combined with paclitaxel injection and carboplatin injection has better clinical efficacy in the treatment of patients with advanced ovarian cancer than paclitaxel injection combined with carboplatin injection, the former can significantly reduce the levels of tumor markers, improve immune function, without increasing the incidence of adverse drug reactions.

To establish a qualification evaluation system for primary investigators (PI) in clinical trials.

Based on the preliminary determination of PI qualification evaluation indicators in accordance with laws and regulations, 19 experts engaged in clinical trials or clinical trial management fields were selected for 2 rounds of Delphi expert consultation, and the weights of each indicator were calculated using principal component analysis.

The positive coefficients for the two rounds of expert consultation were 100.00% and 94.74%, and the expert authority coefficients were 0.940 and 0.933, the coordination coefficients of expert opinions were 0.318 and 0.613. After 2 rounds of expert consultation, the PI qualification evaluation indicators were determined, including 3 primary indicators and 17 secondary indicators. The results of principal component analysis showed that the weight range of each index was 0.037 9 to 0.080 3.

The preliminary construction of the PI qualification evaluation system based on the "PI Qualification Evaluation Form" has strong scientificity and applicability, and can provide references for the evaluation and selection of clinical trial PI.

To explore the effect of Wuzi Yanzong pill on testicular dysfunction in subacute aging rats through metabolomics.

Forty-two rats were subcutaneously injected with 200 mg·kg^-1 D-galactose (D-Gal) to induce a subacute aging model. After successful modeling, the rats were randomly divided into four groups: model group, control group, exprimental-L group, exprimental-H group, each with 9 rats. Eight normal rats without D-Gal treatment were used as the normal group. The exprimental-L,-H groups were administered Wuzi Yanzong pill at doses of 0.54 and 2.16 g·kg^-1 by gavage, respectively, while the control group was given 300 mg·kg^-1 metformin by gavage. The normal and model groups were treated with an equal volume of distilled water by gavage. All rats were dosed once daily for 4 weeks. During this period, the each group (except for the normal group) was continued injected 200 mg·kg^-1 D-Gal injections. The levels of testosterone (T), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in serum were measured using enzyme-linked immunosorbent assay (ELISA). The relative expression of proteins involved in testicular secretory function [hydroxysteroid 17-beta dehydrogenase 3 (HSD17B3), cytochrome P450, family 11, subfamily A, polypeptide 1 (CYP11A1), steroidogenic acute regulatory protein (STAR)] was determined by Western blot. Metabolomics analysis was performed to study metabolic changes in the testicular tissue.

The serum T levels in the normal, model, control, experimental-L, and experimental-H groups were (8.67±1.71), (1.95±0.46), (6.50±1.15), (2.45±0.49) and (5.81±0.96) pg·mL^-1, respectively; the FSH levels were (28.53±4.16), (46.73±3.72), (30.18±5.17), (35.35±1.90) and (30.31±4.35) mU·mL^-1, respectively; the LH levels were (22.66±3.97), (37.89±4.16), (24.28±3.75), (37.09±3.98) and (28.35±4.38) mU·mL^-1, respectively; the relative protein expression levels of HSD17B3 were 1.04±0.05, 0.29±0.14, 0.78±0.18, 0.71±0.13 and 0.85±0.18; the relative protein expression levels of CYP11A1 were 1.23±0.15, 0.62±0.08, 1.01±0.05, 0.77±0.15 and 1.24±0.09; the relative protein expression levels of STAR were 0.97±0.12, 0.21±0.05, 0.79±0.19, 0.62±0.23 and 0.96±0.25, respectively. The model group showed significant differences in these indicators when compared with the control and experimental-H groups (all P<0.05). Metabolomics analysis identified six differential metabolites in the experimental-H group compared to the model group. These metabolites were mainly involved in steroid hormone biosynthesis, ovarian steroidogenesis, lipid metabolism, and biotin metabolism.

In vivo and metabolomics studies show that Wuzi Yanzong pill improves antioxidant capacity in the testes, reduces oxidative stress damage, delays aging, and effectively treats testicular dysfunction, thereby improving testicular function.

To investigate the effect of pyrotinib on ferroptosis in gastric cancer cells through the regulation of the tumor protein 53 (p53)/solute carrier family 7 member 11 (SLC7A11) axis by the long noncoding RNA small nucleolar RNA host gene 16 (LncRNA SNHG16).

Human gastric cancer cells (NCI-N87) were selected and divided into NCI-N87 group (NCI-N87 cells were cultured normally without treatment), experimental group (NCI-N87 cells treated with 0.5 μmol·L^-1 pyrotinib for 72 h), and oe-NC group (based on the transfection of oe-NC in experimental group), LncRNA SNHG16 group (based on experimental group transfected with oe-LncRNA SNHG16). Real-time fluorescence quantitative polymerase chain reaction and fluorescence in situ hybridisation were used to determine the expression level of LncRNA SNHG16, cell viability was detected by cell counting kit-8; invasive ability was detected by Transwell assay; reactive oxygen species (ROS) fluorescence level was detected by fluorescent probe staining of dihydroethidium (DHE); malondialdehyde (MDA) level and glutathione (GSH) activity were detected by kits; and the expression level of p53 and SLC7A11 protein was detected by Western blot.

The relative expression levels of LncRNA SNHG16 in the NCI-N87 group, the experimental group, the oe-NC group and the LncRNA SNHG16 group were 1.00±0.18, 0.39±0.06, 0.41±0.07 and 0.80±0.15, respectively; the relative fluorescence intensities of LncRNA SNHG16 were 1.00±0.16, 0.27±0.05, 0.23±0.04 and 0.81±0.17, respectively; the number of cell invasion was (82.16±14.67), (29.03±4.75), (31.82±5.69) and (74.98±11.34) pieces, respectively; the relative fluorescence levels of ROS were 1.00±0.15, 4.57±0.86, 3.95±0.61 and 1.54±0.33, respectively; MDA levels were (5.49±1.08), (11.27±1.93), (10.85±1.64) and (6.73±0.95) μmol·mg^-1, respectively; GSH relative activities were 1.00±0.00, 0.54±0.09, 0.56±0.07 and 0.83±0.14, respectively; the relative expression levels of p53 protein were 1.00±0.17, 2.26±0.38, 1.98±0.32 and 1.24±0.19, respectively; the relative expression levels of SLC7A11 protein were 1.00±0.13, 0.34±0.05, 0.41±0.09 and 0.79±0.11, respectively. The differences in the above indicators between the NCI-N87 group and the experimental group, as well as between the oe-NC group and the LncRNA SNHG16 group, were all statistically significant (P<0.001).

Pyrotinib can regulate the p53/SLC7A11 signaling pathway by inhibiting the expression of LncRNA SNHG16 to induce ferroptosis of gastric cancer cells and inhibit the proliferation and invasion of gastric cancer cells.

To study the effects of carbocisteine on airway inflammation and airway remodeling in mice with Mycoplasma pneumoniae pneumonia and its mechanism.

Mice were randomly divided into control group, model group, experimental group, negative transfection group and positive transfection group, with 12 mice in each group. The control group were inoculated with 0.9% NaCl by nasal drip, the other groups were inoculated with Mycoplasma pneumoniae suspension to establish Mycoplasma pneumoniae pneumonia model. After successful modeling, the experimental group was given 10 mg·kg^-1 carbocisteine by intragastric administration; the negative transfection group was given 10 mg·kg^-1 carbocisteine by gavage + 1.0×10⁹ PFU of adenovirus containing tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) blank control plasmid in the tail vein, the positive transfection group was given 10 mg·kg^-1 carbocisteine by intragastrial + 1.0×10⁹ PFU containing sh-TIPE2 plasmid was injected into the tail vein, the control and model groups were given 0.9% NaCl by intragastric administration. Five groups were treated for 2 weeks with once a day. The levels of inflammatory factors in lung tissue were detected by enzyme-linked immunosorbent assay. Airway remodeling index and p38 mitogen activated protein kinase (p38MAPK) /activated protein-1 (AP-1) signaling pathway related protein expression were detected by Western blot.

The levels of tumor necrosis factor-α in control, model, experimental, negative transfection and positive transfection groups were (9.18±1.92), (134.32±24.56), (42.20±8.61), (39.95±7.77) and (74.03±13.59) pg·mL^-1; the levels of interleukin-6 were (5.80±1.21), (65.12±11.81), (22.94±4.47), (26.11±5.08) and (42.67±7.97) pg·mL^-1; the relative protein expression levels of matrix metallopeptidase 9 were 1.00±0.16, 3.64±0.62, 1.45±0.22, 1.39±0.20 and 2.16±0.38; the relative protein expression levels of tissue inhibitor of metalloproteinases 1 were 1.00±0.14, 0.52±0.11, 0.89±0.16, 0.84±0.15 and 0.65±0.13; the phospho-p38MAPK/p38MAPK ratios were 1.00±0.16, 2.74±0.48, 1.57±0.29, 1.54±0.27 and 2.31±0.36; the relative protein expression levels of cellular proto-oncogene Jun were 1.00±0.14, 2.25±0.38, 1.34±0.21, 1.37±0.22 and 1.98±0.32; the relative protein expression levels of cellular proto-oncogene Fos were 1.00±0.18, 3.07±0.56, 1.86±0.32, 1.91±0.35 and 2.51±0.44, respectively. The above indexes in the model group were compared with the experimental and control groups, the above indexes in the positive transfection group were compared with the negative transfection group, and the differences were statistically significant (all P<0.05).

Carbocisteine inhibits airway inflammation and airway remodeling in mice with Mycoplasma pneumoniae pneumonia by inhibiting the p38MAPK/AP-1 signaling pathway.