To compare the effects of different doses of budesonide and formoterol fumarate powder for inhalation combined with montelukast sodium tablet in the treatment of cough variant asthma (CVA) and the improvement of airway function and inflammatory factors.

Elderly patients with cough variant asthma were randomly divided into group A and group B. Both groups of patients received budesonide and formoterol fumarate powder for inhalation combined with montelukast sodium tablet. Group A was given budesonide and formoterol fumarate powder for inhalation(Ⅱ), 2 inhalation per time, twice a day; Group B was given budesonide and formoterol fumarate powder for inhalation, 4 inhalation per time, twice a day; budesonide fumatrol inhalation powder mist for continuous treatment for 6 months, and montelukast sodium tablet 10 mg once a day for at least 3 months. The nighttime cough scores of the two groups were compared before treatment and after treatment. The percentage of forced expiratory volume in one second (FEV₁) in the predicted value, the maximum mid expiratory flow (MMEF), the fractional exhaled nitric oxide (FeNO), interleukin-5 (IL-5) and eosinophils were compared between the two groups. The incidence of adverse drug reactions and the recurrence rate within 1 year were compared between the two groups.

A total of 45 cases were enrolled in both the group A and the group B. At 9 months after treatment, the nocturnal cough scores of the group A and the group B were (0.93±0.42) and (0.65±0.29) points, respectively; the percentage of FEV₁ in the predicted value were (97.75±9.67)% and (100.93±11.06)%, respectively; the MMEF values were (2.81±1.04) and (3.08±1.09) L·s^-1, respectively; the FeNO values were (18.94±9.75) and (15.94±7.96) ppb, respectively; the IL-5 levels were (10.88±7.06) and (8.11±5.56) pg·mL^-1, respectively. The above indicators in group B showed statistically significant differences compared to group A (all P<0.05). The total incidence of adverse drug reactions in group A and group B were 8.89% (5 cases/45 cases) and 13.33% (6 cases/45 cases), respectively. The recurrence rates was 15.56% (7 cases/45 cases) and 13.33% (6 cases/45 cases), respectively. There was no statistically significant difference in the above indicators between group B and group A (all P>0.05).

For elderly patients with CVA, higher dose of budesonide and formoterol fumarate powder for inhalation combined with montelukast sodium tablet can better improve cough symptoms, reduce the level of airway hyperresponsiveness and inflammatory factors, reduce the recurrence rate, and the patients are well tolerated.

To observe the clinical efficacy and safety of vericiguat tablets combined with sacubitril valsartan sodium (Sac/Val) tablets in the treatment of patients with heart failure with reduced ejection fraction (HFrEF).

The HFrEF patients were divided into control group and treatment group according to the cohort method. The control group was treated with Sac/Val tablets 200 mg per time, bid, orally. On the basis of control group, the treatment group was treated with vericiguat tablets 2.5 mg per time, qd, taken with meal. Two groups were treated for 3 months. The clinical efficacy, left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD) and end-systolic diameter (LVESD), levels of high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), nitric oxide (NO), N-terminal pro-brain natriuretic peptide (NT-proBNP), blood urea nitrogen (BUN) and serum creatinine (SCr), and safety were compared between the two groups. During follow-up, the heart failure rehospitalization rates and major adverse cardiovascular events were compared between the two groups.

Treatment group was enrolled 53 patients, control group was enrolled 53 patients. After treatment, the total effective rates of treatment and control groups were 94.34% (50 cases / 53 cases) and 81.13% (43 cases / 53 cases) with statistical significant difference (P<0.05). After treatment, the LVEF of treatment and control groups were (48.02±5.20)% and (43.02±4.33)%, the LVEDDs were (52.85±6.30) and (55.63±6.88) mm, the LVESDs were (41.64±6.40) and (44.22±5.85) mm, the levels of hs-CRP were (10.22±2.63) and (14.60±2.98) mg·L^-1, the levels of IL-6 were (14.48±2.40) and (17.36±2.52) pg·mL^-1, the levels of NO were (102.60±20.16) and (92.16±16.33) μmol·L^-1, the levels of NT-proBNP were (898.74±102.20) and (1315.60±182.64) ng·L^-1, the levels of BUN were (12.02±2.28) and (13.45±2.33) mmol·L^-1, the levels of SCr were (82.22±5.89) and (85.64±6.03) μmol·L^-1, the heart failure rehospitalization rates were 5.66% and 13.21%, respectively; the differences were statistical significant between two groups (all P<0.05). The adverse drug reactions of treatment group were hyperkalemia, hypotension, renal dysfunction, dizziness and headache, while those in control group were renal dysfunction, hyperkalemia, and hypotension. The major adverse cardiovascular events of treatment group were angina pectoris and acute myocardial infarction, while those in control group were angina pectoris, acute myocardial infarction and atrial fibrillation. The incidences of total adverse drug reactions in treatment and control groups were 13.21% and 7.55%, the incidences of major adverse cardiovascular events were 5.66% and 13.21%, respectively, without statistically significant differences (all P>0.05).

Vericiguat tablets combined with Sac/Val tablets have a definitive clinical efficacy in the treatment of HFrEF patients, which can improve cardiac and endothelial function, reduce inflammatory response and readmission times, without increasing the incidences of adverse drug reactions.

To explore the cardiovascular protective effect of dapagliflozin on patients with heart failure with preserved ejection fraction (HFpEF) complicated with type 2 diabetes mellitus (T2DM).

Patients with HFpEF complicated with T2DM were divided into treatment group and control group according to cohort method. The control group was given 0.5 g of metformin hydrochloride tablet orally twice a day, while the treatment group was given 10 mg of dapagliflozin tablet orally once a day on the basis of treatment in the control group. Patients in both groups were continuously treated for 6 months. The clinical efficacy after treatment and blood glucose indicators [fasting blood glucose (FBG), 2 hours postprandial blood glucose (2 h PBG), glycosylated hemoglobin (HbA1c)], echocardiographic left ventricular parameters [left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left ventricular remodeling index (LVRI), left ventricular mass index (LVMI)] and serum N-terminal pro-brain natriuretic peptide (NT-proBNP), serum myocardial fibrosis indicators [matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1)] before and after treatment were compared between both groups, and the safety evaluation was performed.

Seventy-five cases in treatment group and 72 cases in control group were included. After treatment, the total effective rates in treatment group and control group were 93.33% (70 cases/75 cases) and 81.94% (59 cases/72 cases), respectively (P<0.05). After treatment, the levels of FBG, 2 h PBG, HbA1c, LVEF and LVEDD revealed no statistical differences between treatment group and control group (all P>0.05). After treatment, LVRI values in treatment group and control group were (2.17±0.41) and (2.54±0.46) g·mL^-2; LAMI values were (102.47±10.32) and (113.84±15.52) g·m^-2; serum NT-proBNP levels were (652.38±208.26) and (993.24±302.69) pg·mL^-1; MMP-9 levels were (142.52±21.67) and (168.73±25.88) mg·L^-1; TIMP-1 levels were (3.68±0.84) and (3.12±0.91) μg·L^-1, respectively (all P<0.05). The total incidence rates of adverse reactions in treatment group and control group were 14.67% (11 cases/75 cases) and 12.50% (9 cases/72 cases), respectively (P>0.05).

Dapagliflozin can improve ventricular remodeling and enhance cardiac function in patients with HFpEF complicated with T2DM, and it has a significant cardiovascular protective effect.

To observe the clinical efficacy and safety of dexamethasone injection combined with tranexamic acid injection in the treatment of patients with hyperfibrinolysis caused by bleeding after prostatic hyperplasia.

Patients with hyperfibrinolysis caused by hemorrhage after prostatic hyperplasia were randomly divided into control group and treatment group. The control group was given 1 g·d^-1 tranexamic acid intravenously. On the basis of the control group, the treatment group was given dexamethasone 10 mg, intravenous injection, q12 h. Both groups were treated continuously for 5 days. The clinical efficacy, coagulation factor level, quality of life (QOL) score, international prostate symptom score (IPSS), and safety were compared between the two groups.

In the treatment group, 52 cases were enrolled, 2 cases fell off, and finally 50 cases were included in the statistical analysis. In the control group, 51 cases were enrolled, 1 case fell off, and finally 50 cases were included in the statistical analysis. After treatment, the total effective rates of treatment group and control group were 94.00% (47 cases /50 cases) and 72.00% (36 cases /50 cases), respectively, and the difference was statistically significant (P<0.05). After treatment, the partial thromboplastin time of treatment group and control group were (35.12±4.38) and (49.14±5.61)s; the prothrombin time were (12.78±1.67) and (16.10±1.94) s; D-dimer levels were (350.42±25.90) and (380.90±37.10) μg·L^-1; QOL scores were (1.16±0.37) and (2.26±0.78) points, IPSS were (4.48±1.22) and (16.12±3.67) points, respectively. The differences of above indexes were statistically significant between two groups (all P<0.05). The adverse drug reactions of two groups were mainly abdominal pain, anemia and headache. The incidences of total adverse drug reactions in treatment group and control group were 6.00% and 16.00%, respectively, without statistical significance (P>0.05).

Dexamethasone injection combined with tranatemylic acid injection has a definitive clinical efficacy in the treatment of patients with bleeding induced hyperfibrinolytic hyperplasia after prostatic hyperplasia, which can significantly improve the coagulation function of patients, relieve symptoms, without increasing the incidence of adverse drug reactions.

To observe the clinical effect of live vaginal Lactobacillus capsule for vaginal use combined with nifuratel nystatin vaginal soft capsule on patients with recurrent vulvovaginal candidiasis (RVVC) and its influence on vaginal microecological environment of patients.

The RVVC patients were divided into the control group and the treatment group according to the cohort method. The patients in the control group were treated with one grain of vaginal embolization before going to bed with nifuratel nystatin vaginal soft capsule. The patients in the treatment group were treated with 0.25 g of vaginal live Lactobacillus capsule in the morning combined with one grain of vaginal embolization before going to bed with nifuratel nystatin vaginal soft capsule. The initial treatment time of the two groups lasted for 7 days. Initial treatment lasted for 7 days in both groups. Pathogenic bacteria culture was performed after 7 days of drug withdrawal. The negative patients were cured, and the cured patients were treated with nifuratel nysfungin vaginal suppository for consolidation treatment once a week for 6 months. The clinical therapeutic effect in the two groups was recorded. The changes in vaginal microecology and human β-defensin (HβD)-3, interleukin (IL)-1β and IL-8 in vaginal secretions were compared between the two groups before treatment and after 7 days of treatment, and the safety evaluation was carried out.

A total of 268 patients were enrolled in this study, including 136 in the treatment group and 132 in the control group. The mycological cure rates of initial treatment in the treatment group and the control group were 84.56% (115 cases/136 cases) and 73.48% (97 cases/132 cases), respectively; the mycological cure rates of consolidation treatment were 82.61% (95 cases/115 cases) and 70.10% (68 cases/97 cases), respectively; the differences were statistically significant (all P<0.05). The proportions of vaginal cleanliness grade Ⅲ-Ⅳ in treatment group and control group after 7 days of treatment were 24.26% and 36.36%; the proportions of vaginal flora density grade Ⅱ-Ⅲ were 79.41% and 68.18%; the proportions of vaginal flora diversity grade Ⅱ-Ⅲ were 77.94% and 65.91%; the proportions of dominant bacteria of Lactobacillus were 82.35% and 68.18%; the levels of HβD-3 in vaginal secretions were (129.65±11.51) and (135.87±10.46) pg·mL^-1; IL-1β levels were (65.48±9.27) and (72.46±10.38) pg·mL^-1; IL-8 levels were (159.36±12.50) and (176.30±13.19) pg·mL^-1 , and the differences were statistically significant (all P<0.05). The total incidence rates of adverse drug reactions in the treatment group and control group were 23.53% (32 cases/136 cases) and 18.38% (25 cases/132 cases), respectively (P>0.05).

Compared with nifuratel nysfungin vaginal soft capsule therapy, the combination of vaginal live Lactobacillus capsule can improve the vaginal microecology of RVVC patients, and the cure rate of vaginal fungal infection is higher, with better safety.

To explore the clinical efficacy and safety of alendronate sodium tablet combined with injection of recombinant teriparatide and calcium carbonate D₃ tablet in the treatment of postmenopausal osteoporosis (PMDP).

The patients with postmenopausal osteoporosis were divided into control group and treatment group according to the cohort method according to the treatment regimen. The control group was treated with calcium carbonate D₃ tablet (600 mg, 1 tablet a day) and alendronate sodium tablet (70 mg, once a week), while the treatment group was given injection of reacombinant teriparatide (200 U/20 μg, 20 μg every day) on the basis of the control group. Both groups were continuously treated for 6 months. The clinical efficacy was compared after 6 months of treatment. The bone mineral density (BMD) of lumbar spine, total hip and femoral neck and levels of bone metabolism indicators [osteocalcin (OCN), tartrate-resistant acid phosphatase-5b (TRAP-5b), procollagen type Ⅰ amino-terminal propeptide (PINP), C-terminal cross-linked peptide of type Ⅰ collagen (CTX-Ⅰ)]before treatment and after 6 months of treatment and bone pain [visual analogue scale (VAS)]and quality of life [European Foundation Osteoporosis Quality of Life Questionnaire (ECOS-16)]before treatment and after 3 and 6 months of treatment were recorded, and the adverse drug reactions within 6 months of treatment were compared.

Fifty-two cases in treatment group and 64 cases in control group were enrolled. After treatment, the total effective rates in treatment group and control group were 87.80% (36 cases/41 cases) and 68.29% (28 cases/41 cases), respectively (P<0.05). The BMD values of lumbar spine in treatment group and control group after treatment were (0.69±0.15) and (0.79±0.18) g·cm^-2; the BMD values of total hip were (0.70±0.11) and (0.77±0.15) g·cm^-2; the BMD values of femoral neck were (0.79±0.19) and (0.87±0.15) g·cm^-2, respectively; the OCN levels were (7.42±1.53) and (5.37±1.16) μg·L^-1; the PINP levels were (85.31±5.66) and (76.30±5.49) ng·mL^-1; the TRAP-5b levels were (3.27±0.46) and (5.16±0.72) U·L^-1; the CTX-I levels were (3.37±0.54) and (5.08±0.70) ng·mL^-1; the VAS scores were (1.48±0.13) and (2.07±0.24) points; the ECOS-16 scores were (24.84±4.62) and (32.71±6.07) points, and there were statistical differences in the above indicators between treatment group and control group (all P<0.05). The main adverse drug reactions in treatment group were rash, dizziness and limb pain, and the main adverse drug reactions in control group were rash, dizziness, nausea, and limb pain, and the total incidence rates of adverse reactions in treatment group and control group were 12.20% (5 cases/41 cases) and 19.51% (8 cases/41 cases) (P>0.05).

Alendronate sodium tablet combined with injection of recombinant teriparatide and calcium carbonate D₃ tablet has a significant short-term efficacy on PMOP patients, and it can help to enhance the bone mineral density, reduce the symptoms of bone pain, and relieve the osteoporosis.

To explore the clinical effects and influencing factors of recombinant human growth hormone (rhGH) treatment in pediatric patients with growth hormone deficiency.

The study subjects were pediatric patients with growth hormone deficiency, all of whom received a combination therapy of stanozolol tablets 2 mg (qd) and 0.1 U·kg^-1·d^-1 of recombinant human growth hormone injection for a continuous period of one year. After one year, the patients were divided into active group and invalid group based on clinical outcomes. Comparisons were made between the two groups in terms of height, annual growth velocity (GV) and height standard deviation score (HtSDS) before and after treatment, and safety evaluations were conducted. Multivariate Logistic regression analysis was used to identify factors that influenced the treatment outcomes in pediatric patients with growth hormone deficiency.

After one year of treatment, a total of 93 cases pediatric patients were included in the analysis, with 62 cases in the active group and 31 cases in the invalid group. The heights of the patients before and after treatment were (119.40±2.48) and (129.08±2.37) cm, respectively; the GV were (3.08±0.39) and (7.34±1.02) cm·year^-1, respectively; the HtSDS were -2.45±0.49 and -1.68±0.35, respectively, with statistically significant differences observed for all comparisons (all P<0.05). In the active and invalid groups, the proportions of patients with GV<3.0 cm·year^-1 before treatment were 32.26% and 58.06%, respectively; the proportions of patients with peak growth hormone (GH) levels <5.0 ng·mL^-1 before treatment were 30.65% and 54.84%, respectively; the average maternal heights were (158.83±5.76) and (155.48±6.58) cm, respectively, with statistically significant differences observed for all comparisons (all P<0.05). The results of the Logistic regression model showed that GV<3.0 cm·year^-1 before treatment, peak GH levels <5.0 ng·mL^-1 before treatment, and a shorter maternal height were independent risk factors for poor treatment outcomes with rhGH in pediatric patients with growth hormone deficiency (all P<0.05). No severe adverse reactions occurred during the treatment of any patient; seven patients experienced pain at the injection site, one patient had a slight increase in blood glucose, and five patients had mild decreased appetite. The total incidence of adverse drug reactions were 13.98% (13 cases/93 cases).

Treatment with rhGH for pediatric patients with growth hormone deficiency can significantly improve height development and has good safety, but it is influenced by factors such as growth velocity, peak GH levels, and maternal height.

To investigate the effect of subanesthetic dose esketamine hydrochloride injection combined with midazolam injection on hip replacement in elderly patients.

The elderly patients undergoing hip replacement were divided into control group and treatment group. The control group was given 0.02 mg·kg^-1 midazolam injection; the treatment group was given 0.02 mg·kg^-1 midazolam injection combined with 0.25 mg·kg^-1 esketamine hydrochloride injection. Anesthesia (sedation, analgesic effect), hemodynamic indexes, and safety evaluation.

There were 90 cases in the treatment group and 90 cases in the control group. The scores of sedation in the treatment group and the control group were (1.54±0.28) and (1.67±0.35) points, respectively; the scores of pain simulation at 2 h after operation were (3.16±0.47) and (3.38±0.59) points, respectively; at the end of the operation, the mean arterial pressure of the treatment group and the control group were (83.06±2.47) and (82.15±2.94) mmHg, respectively; the heart rate were (82.04±3.25) and (80.75±3.32) time·min^-1, respectively, and the difference was statistically significant (all P<0.05). The total incidence of adverse drug reactions in the treatment group and the control group was 8.89% (8 cases /90 cases) and 13.33% (12 cases /90 cases), respectively, with no statistical significance (P>0.05).

The subanesthetic dose of esketamine hydrochloride injection combined with midazolam hydrochloride injection can effectively stabilize the hemodynamic level of the body and reduce postoperative pain in elderly patients with hip replacement with good safety.

To analyze the efficacy and safety of different doses of esketamine for laparoscopic high hernia sac ligation in school-age children.

The school-age children who underwent laparoscopic high ligation of hernia sac were divided into small-dose group and conventional-dose group according to cohort method. The conventional-dose group was given intravenous 0.75 mg·kg^-1 esketamine hydrochloride injection to prepare for induction; the small-dose group was given intravenous 0.50 mg·kg^-1 esketamine hydrochloride injection to prepare for induction, and the two groups were given the same anesthesia induction, anesthesia maintenance and postoperative analgesia. The recovery time, laryngeal mask removal time, anesthesia recovery room residence time, children face, legs, activity, cry, consolability behavioral tool (FLACC) score of the children in the two groups were observed, the hemodynamic indexes were recorded at the time of entry (T1), before anesthesia induction (T2), immediately after laryngeal mask placement (T3), and the safety was evaluated.

A total of 39 cases and 43 cases children were included in the conventional-dose group and the small-dose group, respectively. After treatment, the recovery time of conventional-dose group and small-dose group were (26.36±3.91) and (23.21±3.55) min; the time of removing laryngeal mask were (13.02±2.15) and (12.24±2.30) min; the retention time of postanesthesia care unit (PACU) were (37.23±5.64) and (32.11±5.36) min; the scores of FLACC were (2.08±0.45) and (2.16±0.51) points, respectively. At T1, T2 and T3, the heart rate (HR) of the conventional-dose group were (99.23±15.78), (102.19±17.20) and (118.30±14.96) beat·min^-1; that of the small-dose group were (99.93±16.27), (103.28±16.75) and (120.19±15.39) beat·min^-1, respectively. The mean arterial pressure (MAP) of the conventional-dose group were (84.56±7.22), (85.92±6.96) and (89.89±7.02) mmHg; that of the small-dose group were (84.88±6.87), (86.16±6.45) and (91.12±7.31) mmHg, respectively. There were statistically significant differences in the recovery time and PACU retention time between the small-dose group and the conventional-dose group (all P<0.05). The adverse drug reactions in the two groups mainly included nausea and vomiting, increased secretions and transient hypertension. The incidence of total adverse drug reactions in the conventional-dose group and the small-dose group were 10.26% and 4.65%, respectively, with no statistical significance (P>0.05).

Small-dose esketamine hydrochloride injection can effectively maintain hemodynamic stability in the preoperative intravenous administration of school-age children undergoing laparoscopic high ligation of hernia sac, and the effect of reducing postoperative pain and inhibiting agitation during the recovery period is comparable to that of conventional-dose, with good safety.

To investigate the effect and mechanism of methyl oxofulnonone A (META) on high glucose (HG)-induced H9c2 cell injury.

H9c2 cells were divided into control group (normal culture), model group (55 mmol·L^-1 glucose) and experimental -L, -M, -H groups (55 mmol·L^-1 glucose+12.5, 25.0, 50.0 μmol·L^-1 META). Cell viability was detected by cell counting kit-8; intracellular reactive oxygen species (ROS) level was detected by DCFH-DA fluorescent probe; intracellular adenosine triphosphate (ATP) content was detected by luciferase; and autophagy-related protein expression was detected by Western blotting.

The optical density values of 72-hour cells in the control group, model group and experimental -M, -H groups were 0.91±0.03, 0.61±0.01, 0.69±0.02 and 0.72±0.03; the ROS levels were (40.75±1.53)%, (43.73±1.30)%, (30.87±1.27)% and (28.28±1.43)%; the ATP contents were (8.16±0.71), (4.03±0.29), (5.29±0.31) and (5.83±0.31) nmol·mg^-1; the relative expression levels of autophagy-related gene 5 protein were 1.05±0.06, 1.46±0.09, 0.98±0.11 and 0.89±0.09; the relative expression levels of ubiquitin-binding protein were 1.05±0.10, 0.55±0.13, 0.89±0.04 and 0.98±0.04; the ratios of microtubule-associated protein 1 light chain 3 Ⅱ/Ⅰ protein were 1.09±0.09, 1.82±0.05, 1.67±0.29 and 1.09±0.15, respectively. Among the above indicators, there were statistically significant differences between the model group and the control and experimental -M, -H groups (P<0.05, P<0.01).

META significantly ameliorates H9c2 cardiomyocyte damage caused by high glucose, ameliorates oxidative stress, protects mitochondrial respiration and inhibits autophagy.

To investigate the effect of epifriedelanol (Epi) on gene expression of P-glycoprotein (P-gp) in human colorectal adenocarcinoma cell line LS174T and its mechanism.

LS174T cells were divided into control group and experimental -L, -M, -H groups. Experimental -L, -M, -H groups were treated with 5, 10, 20 μmol·L^-1 Epi, respectively. Control group was treated with 0.1% dimethyl sulfoxide. Polymerase chain reaction was used to detect the mRNA expression level of P-gp. The effect of Epi on multidrug resistance protein 1 (MDR1/P-gp) luciferase activity was investigated by pregnane X receptor (PXR)-MDR1/P-gp dual luciferase reporter gene assay. In addition, Western Blot was used to detect the protein expression level of P-gp and the nuclear factor-κB (NF-κB) pathway related proteins.

The relative expression levels of P-gp mRNA in experimental -M, -H groups and control group were 52.24±5.19, 23.00±3.52 and 100.00±9.00; the relative expression levels of P-gp protein were 86.37±9.96, 74.85±15.92 and 100.00±12.91; the relative activities P-gp luciferase were 230.19±41.32, 203.10±52.84 and 279.67±19.20; the relative expression levels of p65 (RelA/p65) in nucleus were 132.36±23.93, 145.96±25.15 and 100.00±10.88; the relative expression levels of phosphorylation NF-κB inhibits protein kinase α/β (p-IKKα/β) in cytoplasm were 184.00±54.82, 290.10±49.59 and 100.00±15.34; the relative expression levels of phosphorylated NF-κB inhibitory protein α (p-IκBα) in cytoplasm were 125.73±18.77, 133.69±20.25 and 100.00±8.12; the relative expression levels of IκBα in cytoplasm were 78.36±14.83, 70.44±14.57 and 100.00±22.82, respectively. The above indexes of experimental -M and experimental -H groups were compared with control group, and the differences were statistically significant (P<0.05, P<0.01, P<0.001).

Epi can down-regulate the gene expression of P-gp in human colorectal adenocarcinoma cell line LS174T, and the mechanism may be related to activation of NF-κB and suppression of PXR.

To investigate whether O6-methylguanine-DNA methyltransferase (MGMT) interference combined with temozolomide (TMZ) could enhance the therapeutic effect of temozolomide on human drug-resistant melanoma cells A375/TMZ.

A375/TMZ cells were randomly divided into 4 groups, control group (normal culture), MGMTsiRNA group (200 nmol·L^-1 MGMTsiRNA), experimental group (1 600 μmol·L^-1 TMZ) and combined group (transfection of MGMTsiRNA followed by addition of 1 600 μmol·L^-1 TMZ). After 24 h of culture, the proliferation of cells in each group was analyzed by cell counting kit-8 method. Western blotting was used to detect the expression levels of poly ADP-ribose polymerase (PARP), cleaved PARP(cleaved-PARP), DNA-dependent protein kinase catalytic subunit(DNA-PKcs) and nuclear factor kappa-B(NF-κB) proteins in the cells. The expression and distribution of NF-κB proteins in the cells were detected by immunofluorescence.

Cell inhibition rates of control, MGMTsiRNA, experimental and combined groups were 0, (3.45±1.53)%, (51.24±2.73)% and (70.69±4.48)%; the relative expression levels of PARP protein were 0.45±0.08, 0.47±0.06, 0.33±0.04, 0.14±0.03; the relative expression levels of the cleaved-PARP protein were 0.01±0.02、0.01±0.01、0.18±0.03 and 0.36±0.04; the relative expression levels of DNA-PKcs protein were 0.09±0.03, 0.07±0.02, 0.32±0.02 and 0.39±0.04; the relative expression levels of NF-κB protein were 0.35±0.04, 0.36±0.05, 0.20±0.02 and 0.15±0.02. Compared with experimental group or control group, the differences of above indexes were all statistically significant (all P<0.05). Immunofluorescence analysis showed that the average fluorescence intensity of NF-κB in control group, MGMTsiRNA group, experimental group and combined group were (5.26±1.05)%, (7.58±1.18)%, (10.56±1.99)% and (15.47±2.61)%; and compared with the cells in control group and MGMTsiRNA group, combined group showed NF-κB was significantly increased in the nucleus of tumor cells, and the difference was statistically significant (all P<0.01).

MGMTsiRNA combined with TMZ further promotes proliferation inhibition and apoptosis of drug-resistant melanoma A375/TMZ cells by TMZ.

To investigate the protective effect of astaxanthin (ASTA) on gouty chondrocyte injury induced by monosodium urate crystal (MSU) and its mechanism.

The gout cell model by sodium urate crystals was established. C-28I2 cells were randomly divided into blank group (conventional culture), model group (200 μg·mL^-1 MSU), experimental-L group (200 μg·mL^-1 MSU+20 μmol·mL^-1 ASTA), experimental-H group (200 μg·mL^-1 MSU+40 μmol·L^-1 ASTA), experimental-H+Vector group (transfected with Vector +200 μg·mL^-1 MSU+40 μmol·L^-1 ASTA), experimental-H+NLRP3 group (transfected with NLRP3 plasmid +200 μg·mL^-1 MSU+40 μmol·L^-1 ASTA). Cell counting kit-8 (CCK-8) assay was used to detect the cell proliferation rate; Western blot assay was used to detect the expression of related proteins; the levels of Hyp and GAG were detected by enzyme-linked immunosorbent assay (ELISA).

The cell proliferation rate of blank group, model group, experimental-L group and experimental-H group were (100.00±5.40)%, (67.41±4.52)%, (72.69±5.05)% and (81.47±7.73)%, respectively. The above indicators showed statistically significant differences between the model group and the blank group, between the experimental-L, experimental-H groups and the model group (all P<0.05). Nucleotide binding oligomeric domain-like receptor protein 3 (NLRP3) protein expression levels in blank group, model group, experimental-L group, experimental-H group, experimental-H+Vector group and experimental-H+NLRP3 group were 0.44±0.04, 0.86±0.06, 0.72±0.10, 0.52±0.03, 0.51±0.03 and 1.13±0.10, respectively; the expression levels of cleaved Caspase-1 (Cl-caspase-1) protein were 0.33±0.05, 0.73±0.08, 0.61±0.07, 0.42±0.04, 0.39±0.04 and 0.70±0.06, respectively; the mature interleukin (m-IL)-1β protein expression levels were 0.26±0.03, 0.91±0.05, 0.70±0.11, 0.57±0.08, 0.58±0.06 and 0.79±0.08, respectively; the Hyp levels were (1.95±0.22), (3.33±0.25), (2.53±0.18), (2.22±0.21), (2.24±0.20) and (3.25±0.38) μg·mL^-1, respectively; the GAG levels were (2.30±0.20), (3.71±0.26), (3.29±0.33), (2.90±0.16), (2.97±0.24) and (3.50±0.34) ng·mL^-1, respectively. The above indicators showed statistically significant differences between the model group and the blank group, between the experimental-L, experimental-H groups and the model group, between the experimental-H+NLRP3 group and the experimental-H+Vector group (all P<0.05).

Astaxanthin can regulate NLRP3 to play an anti-inflammatory role and has a protective effect on MSU-induced gouty cartilage injury.

Based on nuclear factor E2 associated factor 2 (NRF2) /PTEN induced hypothesized kinase 1 (PINK1) pathway, explored the ameliorating effect of rutaecarpine on chronic obstructive pulmonary disease (COPD) rats and its repairing effect on airway epithelial barrier.

COPD rat model were established by smoke combined with airway infusion of lipopolysaccharide; and were randomly divided into model group, control group, and experimental -L group, experimental -M group, experimental-H group, 10 rats per group. Another 10 normal rats were selected as the normal group. Experimental -L, -M, -H groups were intraperitoneally injected 15, 30 and 60 mg·mL^-1 rutaecarpine at the dose of 10 mL·kg^-1, respectively. The control group was received 4.05×10^-2 mg·mL^-1 prednisone acetate at the dose of 10 mL·kg^-1 by gavage. The normal and model groups were given 0.9% NaCl by intraperitoneal injection. Six groups were treated for 28 days with once a day. The first second forced expiratory volume (FEV1) and forced vital capacity (FVC) of rats were measured by minor animal lung function tester. The levels of interleukin (IL) and interferon-γ (INF-γ) in alveolar lavage fluid were determined by enzyme-linked immunosorbent assay method. The expression levels of PINK1 and NRF2 proteins in the lung tissue were determined by Western blot.

The levels of FEV1 in the experimental -M group, experimental -H group, control group, model group and normal group were (5.17±0.16), (6.36±0.12), (5.06±0.07), (2.24±0.20) and (6.84±0.11) mL; the levels of FVC were (6.71±0.13), (7.56±0.12), (6.81±0.07), (4.46±0.14) and (7.92±0.11) mL; the levels of IL-12 in alveolar lavage fluid were (7.08±0.51), (9.03±0.54), (7.92±0.79), (3.61±1.01) and (10.15±0.82) pg·mL^-1; the levels of IL-9 in alveolar lavage fluid were (22.49±2.27), (15.02±1.41), (17.47±1.84), (38.72±1.28) and (11.78±0.94) pg·mL^-1; the levels of INF-γ in alveolar lavage fluid were (13.18±0.54), (16.25±0.60), (15.23±0.43), (6.97±0.89) and (17.22±1.15) pg·mL^-1; the relative expression levels of PINK1 protein were 1.10±0.06, 1.30±0.09, 1.18±0.15, 0.42±0.03 and 1.61±0.05; the relative expression levels of NRF2 protein were 0.91±0.05, 1.46±0.03, 1.35±0.07, 0.53±0.07 and 1.64±0.11, respectively. The differences of above indexes were statistically significant between the experimental -M group, experimental -H group, control group and the model group (all P<0.05).

Rutaecarpine can inhibit inflammation, improve lung function and repair airway epithelial barrier in COPD rats, and its mechanism may be related to regulating NRF2/PINK1 pathway.

To study the expression characteristics of osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL)/receptor activator of nuclear factor-κB (RANK) system and the relationship with fibrosis in myocardial tissues of rats with chronic heart failure.

SD rats were randomly divided into sham-operation group (12 rats) and model group. In sham-operation group, surgical thread was passed through the abdominal aorta without constricting it after laparotomy; in model group, establish the heart failure model by abdominal aorta coarctation. The successful model rats were randomly divided into model 1 week (12 rats), model 2 weeks (11 rats), model 4 weeks (11 rats), model 8 weeks (11 rats) and model 12 weeks groups (11 rats). The end point of the study is at week 12. The contents of hydroxyproline (HYP), total myocardial collagen and collagen volume fraction (CVF) were compaired in all proups. The expression levels of OPG, RANKL and RANK proteins in cardiomyocytes were determined by Western blot.

The contents of HYP in sham-operation, model 1 week, model 2 weeks, model 4 weeks, model 8 weeks and model 12 weeks group were (0.25±0.04), (0.37±0.05), (0.45±0.04), (0.60±0.05), (0.82±0.10) and (1.03±0.07) μg·mg^-1; the total myocardial collagen contents were (1.87±0.31), (2.73±0.38), (3.36±0.31), (4.47±0.37), (6.08±0.74) and (7.67±0.49) μg·mg^-1; the CVF were (1.95±0.23)%, (2.40±0.25)%, (3.65±0.25)%, (5.43±0.29)%, (6.97±0.36)% and (9.38±0.49)%; the relative expression levels of OPG protein were 0.64±0.07, 0.80±0.07, 1.02±0.07, 1.32±0.11, 2.13±0.12 and 2.84±0.16; the relative expression levels of RANKL protein were 0.71±0.08, 1.06±0.07, 1.53±0.07, 2.62±0.12, 4.46±0.14 and 6.11±0.16; the relative expression levels of RANK protein were 0.30±0.05, 0.45±0.05, 0.63±0.06, 0.98±0.07, 1.43±0.10 and 1.63±0.10. With the extention of time, the above indexs of all model groups were significantly higher than those in the sham-operation group (all P<0.05). There were positive linear correlation between the relative expression levels of OPG, RANKL, RANK protein and the levels of CVF and total contents in cardiomyocytes of rats with chronic heart failure (all P<0.01).

In the process of chronic heart failure, the expression of OPG/RANKL/RANK axis is obviously enhanced, in which the up-regulation of RANKL level is most obvious. The expression level of OPG/RANKL/RANK is positively correlated with CVF and total myocardial collagen content.

To study the effects of Hedysarum polysaccharides polysaccharide (HPS) on the farnesoid X receptor (FXR)-fibroblast growth factor-19(FGF19) signaling pathway of diabetes rats.

Twelve Wistar male rats were randomly selected as the normal group, and the other rats were fed with a single intraperitoneal injection of streptozotocin (50 mg·kg^-1 STZ) and a high sugar and high-fat diet to replicate the diabetes rat model. Model rats were randomly divided into model group, positive control group (given 400 mg·kg^-1·d^-1 suspension of Bifidobacterium quadruplex live bacterial tablets by gavage), experimental-H, -M, -L groups (given 200, 100, and 50 mg·kg^-1·d^-1 doses of HPS suspension by gavage); normal group, and model group were given equal volume of purified water by gavage once a day for 8 consecutive weeks. Glucose (Glu) was detected by a blood glucose meter; and serum total glyceride (TG) and total cholesterol (TC) were detected by enzyme-linked immunosorbent assay reagent kit; the expressions of FXR、fibroblast growth factor receptors 4 (FGFR4) relative mRNA expression level and protein were detected by real-time fluorescence quantitative polymerase chain reaction method and Western blot.

The Glu concentrations in the normal group, model group, positive control group, and experimental-H groups were (7.66±0.61), (29.25±1.64), (23.31±3.02) and (19.31±5.13) mmol·L^-1, respectively; the TG content were (957.00±113.73), (1 345.00±246.44), (958.00±96.53) and (964.00±130.22) μmol·L^-1, respectively; the TC content were (161.65±4.53), (302.19±5.35), (236.09±5.14) and (165.58±2.58) μmol·L^-1, respectively; the expression of FXR relative mRNA expression level were 1.00±0.06, 0.48±0.02, 0.67±0.04 and 0.92±0.04, respectively; the expression of FGFR4 relative mRNA expression level were 1.00±0.04, 0.17±0.01, 0.48±0.04 and 0.41±0.03; respectively. The above indexes of the model group were compared with the control group, and the above indexes of the control group and the experimental-H group were compared with the model group, and the differences were statistically significant (all P<0.01).

HPS improves blood sugar, lowers blood lipids, and protects liver and intestinal tissues, possibly by regulating the FXR-FGF19 signaling pathway in intestinal tissue, and regulating bile acid synthesis.

To explore the brain damage of SD rats under different time points of hypobaric hypoxia exposure.

A rat high-altitube cerebral edema (HACE) model was constructed by simulating an altitude of 6 000 m in a hypobaric hypoxia animal experimental chamber. Thirty-six SD male rats were randomly divided into the control group and the hypobaric hypoxia exposure 3, 7 and 14 d groups, with 9 rats in each group. Except for the control group, the rats in each group were continuously exposed to hypobaric hypoxia for 3, 7, and 14 d. At the end of the modeling period, serum was collected by blood sampling via the abdominal aorta, and brain tissue samples were taken. The wet-to-dry ratio (W/D) of brain tissue was calculated, and the levels of relevant oxidative enzymes in serum and brain tissue were measured. The expression levels of hypoxia-inducible factor-1α (HIF-1α) and aquaporin 4 (AQP4) mRNAs in brain tissue were detected by real-time fluorescence quantitative polymerase chain reaction.

The W/D of brain tissues in the control group and the group exposed to hypobaric hypoxia for 3, 7 and 14 d were 4.46±0.12, 4.98±0.16, 5.07±0.18 and 4.95±0.07; the superoxide dismutase contents were (111.86±2.45), (90.73±1.48), (79.64±2.56) and (55.33±1.45) U·g^-1; the glutathione contents were (126.91±5.18), (125.26±1.53), (56.20±2.17) and (122.73±1.78) μg·mL^-1; the malondialdehyde contents were (230.94±2.00), (362.65±3.28), (407.34±3.47) and (237.50±1.59) nmol·g^-1; the relative expression levels of HIF-1α mRNA were 1.00±0, 2.99±0.49, 4.72±0.49 and 1.91±0.28; the relative expression levels of AQP4 mRNA were 1.00±0, 2.62±0.34, 8.38±0.84 and 5.27±0.42, respectively. Statistically significant differences were found between the above indexes in the 3, 7 and 14 d of hypobaric hypoxia exposure group compared with the control group (P<0.05, P<0.01).

Different time of hypobaric hypoxia exposure can up-regulate the expression of AQPs proteins in HACE rats and cause the disruption of the blood-brain barrier, and the HACE model constructed in the hypobaric hypoxia chamber with 6 000 m intervention for 7 d was more stable.

To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of propofol injectable emulsion, and to assess the bioequivalence of test and reference formulations in healthy Chinese adult volunteers.

Thirty-two healthy Chinese adult volunteers were recruited and randomly assigned to a fasting. single-dose, two-period and double-crossover study. Propofol was given to eligible subjects at a speed of 30 μg·kg^-1·min^-1 for 30 min. The concentration of propofol in plasma was determined by avalidated high performance liquid chromatography-tandem mass spectrometery (HPLC-MS/MS) method. The PK parameters of the two preparations were calculated. Bispectral index (BIS) was measured to calculate the PD parameters of two formulations. Adverse events during the trial were recorded.

Thirty-one volunteers were included in the pharmacokinetic parameter set. The mean values of PK parameters of test andreference formulations were as follows: C_max were (660.87±110.25) and (683.13±125.75)ng·mL^-1; AUC_0-t were (473.50±86.03) and (478.40±80.25)h·ng·mL^-1; AUC_0-∞ were (500.45±96.49) and (507.84±88.00)h·ng·mL^-1; t_max were 0.47(0.25,0.53) and 0.50(0.40, 0.54)h; t_1/2 were (2.97±1.74) and (3.08±1.82)h. Thirty-one volunteers were included in the bioequivalence set. The 90% confidence intervals (CI) for the geometric mean ratios of C_max, AUC_0-t, AUC_0-∞ were 92.64%-101.39%, 96.43%-101.00%, 95.67%-100.70%, respectively. The mean values of PD parameters of test and reference formulations were as follows: BIS_min were (75.94±13.66) and (74.39±12.32); BIS_{AUC 0-60 min} were 5 569.85±182.78 and 5 575.68±166.19; T-BIS_min were 23.00 and 29.00 min, respectively. There were no serious adverse events.

Two formulations of propofol injectable emulsion were bioequivalent and both of them exhibited good safety.

To establish a method for determining the concentration of contezolid in human cerebro spinal fluid (CSF) using ultra high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS).

Linezolid as the internal standard (IS) and acetonitrile as the protein precipitant. Waters ACQUITY UPLC^® BEH C₁₈ (2.1 mm×50.0 mm, 1.7 μm) chromatographic column was used for separation, with a mobile phase of 0.1% formic acid aqueous solution-0.1% formic acid acetonitrile solution, gradient elution method, flow rate was 0.4 mL·min^-1, column temperature was 40 ℃, automatic sampler temperature was 10 ℃, the analysis time was 4 minutes. Electrospray ion source, positive ion mode, and multi-reaction monitoring scanning mode were used. The monitoring and analysis ion pairs for contezolid were m/z 409.15→269.14, and the monitoring ion pairs for linezolid were m/z 338.14→195.10. The specificity, standard curve and lower limit of quantification (LLOQ), precision and recovery rate, matrix effect, residual effect, dilution effect and stability of the method were investigated.

The endogenous substances in CSF do not interfere with the determination of the analyte contezolid and the internal standard linezolid, and the method has good specificity. Satisfactory linearity was observed within the concentration range of 20-5 000 ng·mL^-1 for contezolid in CSF, the calibration curve was y=8.97×10^-4x+1.95×10^-2 (r=0.999 1), and the LLOQ was 20 ng·mL^-1. Precision of the intra-batch and inter-batch relative standard deviation (RSD)<15%, and the extraction recovery were 90.96%-98.71%. The average normalized matrix effect factor of the quality control CSF sample were 94.39%-100.25%. The RSD of dilution effect<15%. The CSF samples of contezolid were stored at room temperature, in the automatic sampler for 72 hours, -20 ℃ and -80 ℃ for 90 days, and subjected to repeated freezing and thawing three times, were stable with all of which the RSD<10%.

This method is high sensitivity, rapid, simple and accurate, which is very suitable for the therapeutic drug monitoring of contezolid in human CSF.