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 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 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 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 effect of inhibition of mitochondrial pyruvate carrier on Okada-induced cuprotosis in SH-SY5Y cells.

SH-SY5Y cells were induced by okada acid (OA) to establish a model of Alzheimer’s disease (AD). The cells were divided into control group (complete medium), model group (20 nmol·L^-1 OA) and experimental group [20 nmol·L^-1 OA+1 μmol·L^-1 2-cyano-3 -(1-phenyl-1H-indole-3-yl) -2-acrylic acid (UK-5099)]. Copper ion content was detected by cell cupric colorimetric kit. Pyruvate content was detect by pyruvate detection kit, and the expressions of phosphorylated Tau (AT8) and ferredoxin 1 (FDX1) in each group were detected by immunofluorescence staining. The expression levels of mitochondrial pyruvate carrier (MPC1/MPC2) and dihydrolipoyl transacetylase (DLAT) were detected by Western blot.

The contents of copper ions in experimental group, model group and control group were (0.36±0.01), (0.90±0.05) and (0.23±0.04) μmol·g prot^-1; the pyruvate content were (0.55±0.04), (0.33±0.03) and (0.44±0.04) μmol·10⁸ cell^-1; the AT8 expression levels were 91.46±14.53, 125.02±14.43 and 72.57±19.81; the FDX1 expression levels were 98.93±7.40, 147.83±18.63 and 79.18±8.06; the relative expression levels of MPC1 protein were 0.59±0.11, 1.01±0.14 and 0.55±0.13; the relative expression levels of MPC2 protein were 0.54±0.05, 1.31±0.07 and 0.43±0.07; the relative expression levels of DLAT protein were 0.72±0.04, 0.92±0.07 and 0.53±0.14, respectively. The above indexes in the experimental group were statistically significant compared with those in the model group (P<0.05, P<0.01, P<0.001).

Inhibition of mitochondrial pyruvate carrier can alleviate Okada-induced cuprotosis of SH-SY5Y cells.

To achieve overexpression of phosphoglycerate kinase 1 (PGK1) in HEK-293T cells and screen the key site of its succinylation through constructing PGK1 overexpression vector (PGK1-WT) and four lysine site succinylation mutation vectors.

GEPIA2 database was used to analyze the expression of PGK1 mRNA in normal breast tissue (291 cases) and breast cancer tissue (135 cases) and the relationship between PGK1 expression level and the overall survival rate of breast cancer patients. Protein modification proteomics was used to detect the levels of protein succinylation in four triple negative breast cancer (TNBC) cell lines (MDA-MB-436, MDA-MB-468, MDA-MB-231, BT-549) and normal breast epithelial cells (MCF-10A); the succinylated positive and negative mutation vectors of K11, K131, K323, K361 were contructed with point mutation kit. The experiment was divided into NC, shPGK1-496, shPGK1-220, PGK1-WT groups and positive and negative mutant groups of K11, K131, K323 and K361. Real-time fluorescence quantitative polymerase chain reaction was used to detect the level of expression of PGK1 mRNA in NC, shPGK1-496 and shPGK1-220 groups. The expression levels of PGK1 proteins in NC, shPGK1-496 and shPGK1-220 groups, and the expression levels of Flag proteins in NC, PGK1-WT and four sites in positive and negative mutant groups were detected by Western blot. The key site of PGK1 succinylation was detected by co-immunoprecipitation.

Compared with normal breast tissues, the level of PGK1 mRNA was highly expressed in breast cancer tissue, and the survival time of breast cancer patients with high PGK1 expression was shorter. Four lysine sites of PGK1 in TNBC cells were hypersuccinylated. The relative expression levels of PGK1 mRNA in NC, shPGK1-496 and shPGK1-220 groups were 1.03±0.23, 0.15±0.11 and 1.42±0.69, respectively; the relative expression levels of PGK1 protein were 1.08±0.05, 0.49±0.05 and 1.28±0.01 respectively; compared with NC group, the above indexes in shPGK1-496 group were statistically different (all P<0.01). The relative expression levels of Flag protein in NC group, PGK1-WT group and positive and negative mutant groups of K11, K131, K323 site were 0, 3.43±0.09, 3.28±0.10, 2.28±0.11, 3.03±0.03, 2.79±0.11, 3.29±0.09 and 2.98±0.04, respectively; compared with the NC group, PGK1-WT group and the positive and negative mutant groups of K11, K131 and K323 had statistical differences (all P<0.01). The relative expression levels of Flag protein in NC group, PGK1-WT group and K361 positive and negative mutant group were 0, 2.58±0.11, 3.04±0.02 and 4.04±0.10, respectively; compared with NC group, PGK1-WT group and K361 positive and negative mutant group had statistical significance (all P<0.01). The levels of lysine succinylation in IgG group, PGK1-WT group and negative mutant groups of K11, K131, K323, K361 were 0, 1.53±0.12, 1.30±0.18, 1.29±0.09, 1.23±0.03 and 0.89±0.16, respectively; compared with PGK1-WT group, the negativ mutant group of K361 had statistical significance (P<0.01).

The four lysine sites of PGK1 in TNBC cells are highly succinylated, and K361 site is critical to their succinylation.

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 explore the effects of ginsenoside Rh2 on the development of colon cancer through microRNA-128-3p(miR-128-3p)/growth differentiation factor 15(GDF15) mediated wingless-type MMTV integration site family member (Wnt)/β-catenin signaling pathway.

SW620 colorectal cancer cells were randomly divided into the following groups: Control group (standard culture), experimental group (treated with ginsenoside Rh2 at 20 μmol·L^-1), NC inhibitor group (transfected with NC inhibitor), miR-128-3p inhibitor group (transfected with miR-128-3p inhibitor), ginsenoside Rh2 + miR-128-3p inhibitor group (treated with ginsenoside Rh2 at 20 μmol·L^-1 and transfected with miR-128-3p inhibitor), and ginsenoside Rh2+miR-128-3p inhibitor+si-GDF15 group (treated with ginsenoside Rh2 at 20 μmol·L^-1, transfected with miR-128-3p inhibitor and si-GDF15). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative expression levels of miR-128-3p and GDF15 mRNA. Cell proliferation was assessed using 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay. Western blotting was employed to detect the protein relative levels of myelocytomatosis oncogene (Myc) and β-catenin.

The relative expression levels of miR-128-3p in the control group and experimental group were 1.00±0.16 and 1.56±0.25, respectively; the relative expression relative levels of GDF15 mRNA were 1.00±0.12 and 0.43±0.05, respectively; the proliferation rates were (88.76±8.56)% and (35.89±4.05)%, respectively; the v-myc avian myelocytomatosis viral oncogene homolog (Myc) protein levels were 1.00±0.21 and 0.45±0.06, respectively; and the β-catenin protein relative levels were 1.00±0.23 and 0.52±0.07, respectively. Compared with the control group, the above indicators in the experimental group showed statistically significant differences (all P<0.05). In the ginsenoside Rh2+miR-128-3p inhibitor group and ginsenoside Rh2+miR-128-3p inhibitor+si-GDF15 group, the cell proliferation rates were (68.56±7.12)% and (50.56±5.18)%, respectively; the Myc protein relative levels were 0.86±0.12 and 0.61±0.08, respectively; and the β-catenin protein relative levels were 0.71±0.09 and 0.58±0.08, respectively. The above indicators in the ginsenoside Rh2+miR-128-3p inhibitor group compared with the experimental group, and those in the ginsenoside Rh2+miR-128-3p inhibitor+si-GDF15 group compared with the ginsenoside Rh2+miR-128-3p inhibitor group, all showed statistically significant differences (all P<0.05).

Ginsenoside Rh2 can inhibit the proliferation and migration of colon cancer SW620 cells, and promote the apoptosis, which may be related to the regulation of ginsenoside Rh2 on the miR-128-3p/GDF15 to inhibit Wnt/β-catenin signaling pathway.

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 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 investigate the effects of paeoniflorin on insulin resistance and myocardial injury in rats with gestational diabetes mellitus and its mechanism.

Female rats were randomly divided into control group (normal diet), model group [male rats fed with high-fat diet and intraperitoneally injected 30 mg·kg^-1 streptozotocin (STZ) after close cages], experimental group (after modeling, 50 mg·kg^-1 paeoniflorin was given by gavage), si-NC group (50 mg·kg^-1 paeoniflorin + si-NC plasmid injected into tail vein after modeling), si-IGFBP2 group (50 mg·kg^-1 paeoniflorin + si-IGFBP2 plasmid injected into tail vein after modeling), each group of 10 rats. After 2 weeks of continuous treatment, fasting blood glucose (FBG) was measured with a glucose meter. Serum insulin-like growth factor binding protein 2 (IGFBP2), fasting insulin (FINS), cardiac troponin Ⅰ (cTnⅠ), creatine kinase isoenzyme MB (CK-MB) related factors were detected by enzyme-linked immunosorbent assay (ELISA), insulin resistance index (HOMA-IRI) was calculated, and the expression of signal pathway-related proteins was detected by Western blot assay.

The levels of FBG in control group, model group, experimental group, si-NC group and si-IGFBP2 group were: (5.62±0.56), (18.10±1.76), (9.81±1.46), (10.02±1.38) and (16.32±1.87) mmol·L^-1, respectively; IGFBP2 levels were (39.47±2.64), (20.65±1.86), (27.18±1.85), (27.95±1.74) and (15.28±1.22) ng·mL^-1, respectively; FINS levels were (8.72±0.75), (21.11±2.50), (16.88±1.86), (16.06±1.39) and (20.01±2.94) mU·L^-1, respectively; cTnⅠ levels were (406.04±29.98), (788.11±84.43), (513.70±57.62), (526.85±38.03) and (756.51±63.88) pg·mL^-1, respectively; CK-MB levels were (7.98±0.07), (15.15±1.26), (11.59±1.23), (11.37±1.79) and (13.49±1.54) U·L^-1, respectively; HOMA-IRI levels were 2.17±0.26, 16.92±2.12, 6.24±0.95, 6.60±1.10 and 12.83±1.68, respectively; the relative expression levels of phosphorylate-phosphatidylinositol 3-kinase (p-PI3K) protein were 0.68±0.11, 0.39±0.04, 0.53±0.05, 0.51±0.06 and 0.43±0.04, respectively; the above indexes in the model group were compared with the control group, the experimental group were compared with the model group, and the si-IGFBP2 group were compared with the si-NC group, the differences were statistically significant (all P<0.05).

Paeoniflorin may improve insulin resistance and myocardium injury in gestational diabetes mellitus rats by up-regulating IGFBP2 expression.

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 whether the supplemented Buyang Huanwu tang can improve the kidney injury in diabetic kidney disease (DKD) mice through regulating mitochondrial dynamics.

The db/db mice were randomized into the model group (0.2 mL·d^-1 distilled water), low and high-dose experimental groups (16.0, 32.0 g·kg^-1 supplemented Buyang Huanwu tang), with 8 mice in each group. Another 8 db/m mice were included in the normal group (0.2mL·d^-1 distilled water). The four groups were orally administered once a day for 8 consecutive weeks. Then, the levels of fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), blood urea nitrogen (BUN), serum creatinine (SCr), and urinary microalbumin (mALB) were detected at the end of the experiment. The expression of mitofusin 1 (Mfnl), mitofusin 2 (Mfn2), optic atrophy 1 (Opa1), dynamin-related protein 1 (Drp1), fission protein 1 (Fis1), sirtuin 3 (SIRT3), transforming growth factor-β₁ (TGF-β₁), α-smooth muscle actin (α-SMA), collagen type Ⅲ (Col-Ⅲ) and fibronectin (FN) was measured by Western blotting.

The levels of TG in the experimental-L, -H groups, model group and normal group were (1.98±0.13), (1.69±0.13), (3.38±0.59) and (1.25±0.16) mmol·L^-1; the levels of TC were (3.86±0.14), (3.19±0.15), (5.41±0.61) and (1.46±0.19) mmol·L^-1; the levels of BUN were (10.04±2.21), (8.79±1.75), (16.92±4.57) and (4.78±1.07) mmol·L^-1; the levels of SCr were (19.17±2.25), (17.16±2.03), (27.92±4.13) and (13.37±1.77) μmol·L^-1; the levels of mALB were (26.92±4.61), (20.54±2.31), (46.78±7.32) and (6.14±1.13) mg·L^-1; the relative expression levels of TGF-β1 were 0.73±0.09, 0.59±0.05, 1.01±0.14 and 0.48±0.05; the relative expression levels of α-SMA were 0.79±0.09, 0.56±0.05, 1.12±0.11 and 0.55±0.04; the relative expression levels of FN were 0.61±0.03, 0.55±0.05, 0.83±0.09 and 0.22±0.03; the relative expression levels of Col-Ⅲ were 0.53±0.06, 0.35±0.05, 0.73±0.09 and 0.17±0.03; the relative expression levels of SIRT3 were 0.65±0.07, 0.41±0.14, 0.23±0.12 and 0.91±0.04; the relative expression levels of Drp1 were 0.54±0.08, 0.49±0.09, 0.98±0.11 and 0.37±0.03; the relative expression levels of Fis1 were 0.71±0.05, 0.51±0.03, 1.14±0.11 and 0.35±0.05; the relative expression levels of Mfn1 were 0.61±0.04, 0.95±0.05, 0.43±0.05 and 1.02±0.07; the relative expression levels of Mfn2 was 0.67±0.06, 0.89±0.09, 0.52±0.03 and 1.08±0.05; the relative expression levels of OPA1 were 0.77±0.06, 0.79±0.09, 0.52±0.03 and 1.13±0.11, respectively. Significant differences were found between the model group and experimental-L, -H groups (P<0.05, P<0.01). Simultaneously, the renal pathological and mitochondrial damage was significantly improved.

The supplemented Buyang Huanwu tang can maintain the balance of mitochondrial dynamics, thereby reducing urinary protein, alleviating renal injury and fibrosis. Its potential mechanism may be related to the regulation of SIRT3 protein expression.

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.

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 evaluate the bioequivalence of test preparation (T) and reference preparation (R) of diphenidol hydrochloride tablets taken orally in a single fasting/postprandibular state in healthy Chinese subjects.

This protocol was designed as random, open, single-center, single-dose, double-cycle and double-cross experiment was selected in this study. A total of 66 healthy male and female subjects were enrolled, including 24 subjects in the test group and 42 subjects in the reference group. All subjects took the test preparation and the reference preparation 25 mg in each cycle. The plasma concentration of diphenidol hydrochloride was determined by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and the pharmacokinetic (PK) data collected was analyzed and processed statistically.

The PK parameters of diphenidol hydrochloride tablets and reference preparations in fasting group were as follows: C_max were (75.90±34.60) and (67.96±19.90) ng·mL^-1, respectively; AUC_0-t were (387.67±198.48) and (341.57±137.05) ng·h·mL^-1, respectively; AUC_0-∞ were (413.00±228.39) and (361.70±161.19) ng·h·mL^-1, respectively. Main PK parameters of diphenidol hydrochloride tablets and reference preparations orally taken by subjects after meals: C_max were (92.60±33.60) and (85.30±31.96) ng·mL^-1, respectively; AUC_0-t were (511.90±206.87) and (498.33±197.78) ng·h·mL^-1, respectively; AUC_0-∞ were (543.21±236.90) and (513.98±203.92) ng·h·mL^-1, respectively. Under fasting and postprandial conditions, subjects took diphenidol hydrochloride tablet and reference preparation orally, one tablet 25 mg each time. The geometric mean of the main pharmacokinetic parameters of difenidol in plasma (C_max, AUC_0-t, AUC_0-∞) and the ratio of their corresponding parameters ranged from 80.00% to 125.00% with 90% confidence interval, and no serious adverse events occurred in both groups.

Diphenidol hydrochloride tablets show bioequivalence and good safety evaluation under fasting and postprandial conditions

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 evaluate the impact of stage assessment nursing mode on the psychological state of healthy participants in Phase I clinical trials of new drugs based on psychological questionnaire.

This was a randomized, single blind, controlled clinical research. Healthy participants were randomly divided into treatment and control group. According to the impact of anxiety and depression on healthy participants, the treatment group was given a stage evaluation nursing model, while the control group received routine nursing measures. Both groups were evaluated using the self rating depression scale (SDS) and self rating anxiety scale (SAS) questionnaires before administration, on the day of administration, after administration (mid-term of the trial), on the day of discharge, and on the day of withdrawal, and their effectiveness was observed.

A total of 159 healthy participants were included in the study, with 83 cases in the treatment group and 76 cases in the control group. SDS scores of treatment group and control group were (54.93±4.62) and (54.87±4.89) points before administration, (52.17±6.55) and (53.95±7.03) points on the administration day, (49.94±7.35) and (51.69±9.16) points at the mid-term of the trial, (52.13±6.70) and (53.85±6.76) points on the discharge day, (51.33±7.99) and (52.60±7.39) points on the day of withdrawal, respectively. Compared with before administration, there was statistically significant difference in treatment group during administration day and the day of withdrawal, as well as in the mid-term of trial in the control group (all P<0.01). SAS scores for treatment group and control group were (36.08±6.45) and (37.04±6.87) points before administration, (36.18±7.79) and (37.43±8.53) points on administration day, (35.04±7.09) and (36.86±9.55) points at the mid-term of the trial, (35.82±7.75) and (37.68±8.78) points on discharge day, (39.29±9.17) and (36.47±7.91) points on the day of withdrawal, respectively. No statistical significance of SAS scores was observed (all P>0.05).

Use of psychological questionnaires and stage nursing assessment forms for evaluation and nursing intervention can alleviate the levels of depression and anxiety in healthy participants.

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.