To evaluate the bioequivalence and safety profile of ezetimibe and atorvastatin calcium tablets (10 mg/10 mg) in healthy subjects.

This study utilized a single-center, randomized, open-label, four-period replicate crossover design. A total of 36 participants were enrolled for both fasting and fed state evaluations. Subjects, following a randomization plan, were administered orally either a single tablet of the test (T) or reference (R) formulation on the designated dosing day of each period. An 8-day washout interval separated treatment periods. Quantification of plasma levels for free ezetimibe, total ezetimibe (sum of free ezetimibe and its glucuronide conjugates) and atorvastatin were performed employing validated high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters were analyzed using Phoenix WinNonlin 8.2 software, and the bioequivalence evaluation was conducted.

Fasting state was as following: pharmacokinetic metrics C_max of ezetimibe for T and R formulations were (6.35±3.22) and (7.04±3.20) ng·mL^-1; AUC_0-t were (107.10±46.61) and (109.67±50.23) ng·h·mL^-1; AUC_0-∞ were (114.88±49.96) and (117.14±50.74) ng·h·mL^-1. The 90% confidence intervals for the geometric mean ratio of C_max, AUC_0-t and AUC_0-∞ were 84.11%-98.34%, 94.60%-106.44% and 93.52%-105.82%, respectively, all in the range of 80.00%-125.00%. Pharmacokinetic metrics C_max of total ezetimibe for T and R formulations were (67.01±35.70) and (71.82±30.91) ng·mL^-1; AUC_0-t were (605.29±255.51) and (615.90±270.21) ng·h·mL^-1; AUC_0-∞ were (655.81±268.02) and (676.04±279.18) ng·h·mL^-1. The 90% confidence intervals for the geometric mean ratio of C_max, AUC_0-t and AUC_0-∞ were 85.32%-97.52%, 92.35%-103.46% and 91.43%-102.13%, all in the range of 80.00%-125.00%. Pharmacokinetic metrics C_max of atorvastatin for T and R formulations were (4.28±2.50) and (4.06±2.40) ng·mL^-1; AUC_0-t were (24.24±18.91) and (22.12±10.80) ng·h·mL^-1; AUC_0-∞were (23.86±12.05) and (23.44±10.98) ng·h·mL^-1. The individual coefficient of variation for C_max with the one-sided 95% upper confidence limit below the zero boundary value. The geometric mean ratio for C_max was 1.06, falling within the acceptance range 0.80-1.25. The 90% confidence intervals for the geometric mean ratios of AUC_0-t and AUC_0-∞ were 97.11%-109.14% and 97.24%-104.00%, all in the range of 80.00%-125.00%. The pharmacokinetic parameters of active ingredients in the fed group were as follows: for ezetimibe, the C_max values of the test and reference preparations were (12.50±8.43) and (12.10±10.20) ng·mL^-1, respectively; the AUC_0-t values were (115.66±61.86) and (114.91±61.10) ng·h·mL^-1, respectively; and the AUC_0-∞ values were (127.40±66.49) and (128.37±66.73) ng·h·mL^-1, respectively. The one-sided 95% upper confidence limit for ezetimibe C_max was <0, with a GMR of 1.09, within the range of 0.80-1.25. The 90% confidence intervals for the geometric mean ratios of AUC_0-t and AUC_0-∞ were 93.63%-107.27% and 91.07%-108.13%, respectively, both within 80.00%-125.00%. For total ezetimibe, the C_max values of the test and reference preparations were (102.02±50.21) and (95.10±48.31) ng·mL^-1, respectively; the AUC_0-t values were (660.62±342.67) and (645.43±290.84) ng·h·mL^-1, respectively; the AUC_0-∞ values were (728.80±356.15) and (711.88±301.04) ng·h·mL^-1, respectively. The one-sided 95% upper confidence limit for total ezetimibe C_max was <0, with a GMR of 1.08, within the range of 0.80-1.25. The 90% confidence intervals for the geometric mean ratios of AUC_0-t and AUC_0-∞ were 95.12%-106.95% and 95.27%-107.60%, respectively, both within 80.00%-125.00%. For atorvastatin, the C_max values of the test and reference preparations were (1.79±0.80) and (1.83±0.87) ng·mL^-1, respectively; the AUC_0-t values were (19.09±6.85) and (18.24±6.29) ng·h·mL^-1, respectively; and the AUC_0-∞ values were (21.25±6.97) and (20.34±6.84) ng·h·mL^-1, respectively. The 90% confidence intervals for the geometric mean ratios of C_max, AUC_0-t and AUC_0-∞ were 91.25%-106.96%, 99.81%-108.09% and 100.22%-108.73%, respectively, all falling within the range of 80.00%-125.00%.

The test formulation of ezetimibe and atorvastatin calcium tablets met bioequivalence criteria relative to the reference product in healthy subjects under both fasting and fed (high-fat meal) conditions.

To explore the prescription rationality of compound dextromethorphan hydrobromide syrup and the review effectiveness of the rational drug use system in pediatric outpatient and emergency departments, clarify the key medication risk points and system shortcomings, and provide data support and practical evidence for optimizing the safety prevention and control process of pediatric medication.

A retrospective study was conducted to collect prescriptions of compound dextromethorphan hydrobromide syrup in the outpatient and emergency departments of our hospital from January to December 2024. The mode of system screening combined with manual review was adopted, and an age-weight dual-dimensional evaluation criteria was established with reference to drug instructions and relevant clinical guidelines. The irrational prescriptions were classified and analyzed, and statistical analysis was performed using Excel 2010 and SPSS 23.0 software.

A total of 74 905 prescriptions of this preparation were issued throughout the year. System screening identified 527 positive irrational prescriptions, among which 357 were confirmed as true positive irrational prescriptions after manual review, with a system precision rate of 67.74% (357 prescriptions /527 prescriptions) and a false positive rate of 32.26% (170 prescriptions /527 prescriptions), and the overall irrational prescription rate was 0.48% (357 prescriptions /74 905 prescriptions). The core issues of irrational prescriptions primarily include drug interactions, duplicate medication, inappropriate dosage and administration, and unsuitable indications, accounting for 29.41% (105 prescriptions/357 prescriptions), 26.05% (93 prescriptions /357 prescriptions), 29.41% (105 prescriptions /357 prescriptions) and 16.81% (60 prescriptions /357 prescriptions), respectively. 98.24% (167 prescriptions /170 prescriptions) of false positive prescriptions were from overweight patients, indicating defects in the single-dimensional judgment logic of the system; the true positive rate of nighttime prescriptions 75.56% (250 prescriptions /357 prescriptions) was higher than 65.05% (255 prescriptions/392 prescriptions) of daytime prescriptions.

The medication risks of compound dextromethorphan hydrobromide syrup in children are characterized by age concentration and vary among different age groups, and the rational drug use system has efficiency shortcomings. It is necessary to optimize the age-weight dual-dimensional judgment system, implement hierarchical prevention and control, source intervention and system upgrading, so as to effectively improve the level of pediatric medication safety, and provide reference for the clinical standardized management of this preparation and the optimization of rational drug use system.

To investigate the effects of bicalutamide (BIC) on the malignant biological behavior of prostate cancer LNCaP cells through cadherin 7 (CDH7), and to explore its possible mechanism of action.

This study was divided into two parts, animal experiment and cell experiment. In animal experiment, 30 Balb/c male nude mice were randomly divided into animal blank control group (daily gavage of 10 mL·kg^-1 0.5% carboxymethyl cellulose sodium solution), animal positive control group (daily gavage of 10 mL·kg^-1 enzalutamide) and animal experimental group (daily gavage of 25 mg·kg^-1 BIC), with 10 nude mice in each group. All mice were treated with subcutaneous injection of LNCaP cell suspension to establish a xenograft model and each group was continuously treated for 28 days. The tumor volume of nude mice in each group was recorded every 7 days; tumor tissues were collected 24 h after drug withdrawal; the expression of proliferating cell nuclear antigen (PCNA) protein was detected by immunohistochemistry. In cell experiment, LNCaP cells were divided into cell blank control group (normal culture, no treatment), cell positive control group (treated with enzalutamide 1 μM), cell experimental group (treated with BIC 50 μM), oe-NC group (transfected with oe-NC plasmid and then treated with BIC 50 μM), and oe-CDH7 group (transfected with oe-CDH7 plasmid and then treated with BIC 50 μM). The relative expression levels of CDH7 mRNA in cells was detected by real-time fluorescence quantitative polymerase chain reaction method. The cell invasion ability and apoptosis rate were detected by Transwell assay and terminal-deoxynucleotidyl transferase mediated nick end labeling method, respectively. The activities of superoxide dismutase (SOD) and the levels of malondialdehyde (MDA) were detected by enzyme-linked immunosorbent assay. The relative expression levels of CDH7 and proteins related to relevant pathways were detected by Western blot.

In animal experiments, the tumor volume on day 21 of animal blank control group, animal positive control group and animal experimental group were (622.30±131.15), (411.90±72.07) and (467.40±63.92) mm³, respectively; the tumor volumes on day 28 were (1 189.50±225.95), (729.40±142.90) and (688.60±89.07) mm³, respectively; and the relative expression levels of PCNA protein were 1.00±0.11, 0.28±0.09 and 0.33±0.07, respectively. There were statistically significant differences compared animal positive control group or animal experimental group with the control group (all P<0.001). In cell experiments, the relative expression levels of CDH7 mRNA in the cell blank control group, cell positive control group, cell experimental group, oe-NC group and oe-CDH7 group were 1.00±0.16, 0.35±0.07, 0.40±0.05, 0.37±0.05 and 3.12±0.34, respectively; the number of cell invasions were (134.26±24.97), (57.63±11.53), (66.34±11.84), (61.17±9.12) and (98.08±15.88) pieces, respectively; the MDA levels were (126.94±20.81), (257.63±46.19), (239.21±29.32), (244.35±38.46) and (187.79±25.35) pg·mL^-1, respectively; the apoptosis rates were (4.54±0.87)%, (53.27±6.14)%, (47.13±7.15)%, (51.76±9.59)% and (17.49±3.48) %, respectively; the relative expression levels of extracellular signal-regulated kinase 1/2 (ERK1/2) protein were 1.00±0.12, 0.44±0.06, 0.39±0.05, 0.41±0.03 and 0.67±0.11, respectively. Compared cell positive control group, or cell experimental group with cell blank control group, compared oe-CDH7 group with oe-NC group, the above indicators were all statistically significantly different (all P<0.001).

BIC could inhibit the invasion of prostate cancer LNCaP cells and promote their apoptosis through CDH7, and the mechanism of action may be related to the inhibition of mitogen-activated protein kinase (MAPK)-ERK signaling pathway activation.

To observe the clinical efficacy and safety of optimized clinical procedures combined with N-acetylcysteine (NAC) tablets in the diagnosis and treatment of testicular torsion.

Patients diagnosed with testicular torsion in our hospital from January 2020 to January 2022 were enrolled as control group and received routine diagnosis and treatment. Patients treated from January 2023 to January 2024 who underwent optimized clinical procedures combined with postoperative oral NAC tablets were enrolled as treatment group. The treatment group implemented optimized clinical procedures (including health education, fast track pathway, simplified evaluation and surgical preparation, etc.) and started oral NAC tablets on the second day after surgery (200 mg each time, 3 times daily, for 1 consecutive week). The two groups were compared in terms of time from symptom onset to hospital arrival (T1), time from hospital arrival to surgery start (T2), total ischemia time (T3), orchiectomy rate and testicular atrophy rate at 6 months postoperatively.

T1 in treatment group and control group were 8.00 (5.00, 12.00) and 62.00 (51.00, 72.00) min, respectively; T2 were 52.00 (48.00, 57.00) and 109.00 (85.00, 135.50) min, respectively; and T3 were 60.00 (56.00, 64.00) and 171.50 (149.00, 199.00) min, respectively. The differences in the above indicators between the two groups were statistically significant (all P<0.001). The orchiectomy rate was 65.00% in treatment group and 82.00% in control group, with a statistically significant difference (P<0.001, RR=0.78, 95%CI: 0.66-0.91). At 6 months postoperatively, among patients who underwent testicular salvage, the testicular atrophy rate was 11.43% in treatment group and 33.33% in control group, with a statistically significant difference (P<0.05, RR=0.30, 95%CI: 0.10-0.94). Multivariate logistic regression analysis showed that the combined intervention was an independent protective factor for reducing orchiectomy rate (P=0.001, OR=0.31, 95%CI: 0.15-0.64). In terms of safety, only 3 (3.00%) patients in treatment group reported mild nausea, with no serious adverse drug reactions; no related adverse reactions occurred in control group.

The application of optimized clinical procedures combined with N-acetylcysteine tablets shows significant clinical benefits in the treatment of testicular torsion, helping to shorten treatment time, reduce testicular injury, improve testicular survival rate, and exhibits a favorable safety profile.

To investigate the effects and mechanism of nobiletin (NOB) on slow transit constipation (STC) in rats through dopamine receptor D2 (DRD2).

A total of 70 SD rats were randomly divided into blank group, model group, experimental-L, M, H group, AAV9-NC group and AAV9-DRD2 group, with 10 rats in each group. STC model was established with 15 mg·kg^-1 compound diphenoxylate by intragastric administration except in blank group. In experimental-L, M, H group, 0.1, 0.2, 0.4 g·kg^-1 NOB was administered intragastricly. On the basis of experimental-M group, AAV9-NC group and AAV9-DRD2 group were given AAV9-NC and AAV9-DRD2 100 μL, respectively. Weight and fecal indexes of rats were detected. The expression levels of DRD2 was detected by quantitative real time polymerase chain reaction. Vasoactive intestinal peptide (VIP) and nitric oxide (NO) levels were detected by enzyme-linked immunosorbent assay. Levels of AMP-activated protein kinase (AMPK)/endothelial nitric oxide synthase (eNOS) signaling pathway related proteins were detected by Western blot.

The fecal water content in blank, model, and experimental-L, M, H groups were (35.24±5.25)%, (24.76±3.47)%, (28.38±2.77)%, (32.76±3.49)% and (33.32±4.34)% , respectively; the fecal quantity were (53.20±5.25), (42.40±4.55), (47.10±5.36), (49.50±5.10) and (50.10±5.04) grains, respectively. Compared model group with blank group, and compared experimental-L, -M, -H groups with model group, the above indicators showed statistically significant differences (P<0.05, P<0.01, P<0.001). The relative expression levels of DRD2 mRNA in blank, model and experimental-L, M, H groups were 1.00±0.12, 2.95±0.47, 2.73±0.49, 2.17±0.35 and 2.08±0.32, respectively. The relative expression levels of DRD2 mRNA in the experimental-M and experimental-H groups were significantly lower than those in the model group (all P<0.001), with no significant difference between the two groups (P>0.05); therefore, experimental-M was selected for subsequent experiments. The VIP levels of blank group, model group, experimental-M group, AAV9-NC group and AAV9-DRD2 group were (43.15±4.52), (64.42±7.64), (51.68±5.37), (49.25±4.44) and (56.84±6.41) ng·L^-1, respectively; NO levels were (6.84±0.71), (11.68±1.37), (9.28±0.93), (9.35±0.97) and (10.45±1.03) μmol·L^-1, respectively; the relative expression levels of AMPK protein were 1.00±0.15, 2.42±0.34, 1.68±0.17, 1.55±0.18 and 1.94±0.21, respectively; the relative expression levels of eNOS protein were 1.00±0.11, 3.18±0.35, 2.28±0.23, 2.35±0.27 and 2.95±0.33, respectively. Compared model group with blank group, compared experimental-M group with model group, and compared AAV9-DRD2 group with AAV9-NC group, the above indicators all showed statistically significant differences (all P<0.05).

NOB can improve STC in rats, possibly by down-regulating DRD2 expression, regulating VIP and NO levels, and inhibiting the AMPK/eNOS signaling pathway.

To explore the effects and mechanism of shionone on ulcerative colitis in rats based on the extracellular regulated protein kinase (ERK)/NOD-like receptor protein 3 (NLRP3)/interleukin (IL)-1β signaling pathway.

A total of 60 rats were randomly divided into normal group, model group, experimental-L group, experimental-H group and activator group by random number table method, with 12 rats in each group. The normal group was given drinking water without dextran sulfate sodium, while the other groups were fed with drinking water containing 5% dextran sulfate sodium for 10 days to establish ulcerative colitis rat models. After modeling, rats were administered for 7 days. The experimental-L and -H groups were intragastrically given 50 and 100 mg·kg^-1 shionone daily, respectively; the activator group was intragastrically given 100 mg·kg^-1 shionone daily combined with intraperitoneal injection of 4 mg·kg^-1 ERK activator RO 67-7476; the normal group and model group were intragastrically given and intraperitoneally injected with equal volumes of normal saline daily. Disease activity index was analyzed; the levels of IL-17 and IL-23 in colon tissue were detected by enzyme-linked immunosorbent assay (ELISA); colonic histopathological changes were observed by hematoxylin-eosin (HE) staining; intestinal mucosa was detected by Alcian blue-periodic acid-Schiff (AB-PAS) staining; the relative expression levels of phosphorylated (p)-ERK, NLRP3 and IL-1β proteins were determined by Western blot.

Rats in the model group showed severe colonic tissue damage, characterized by disappearance of intestinal mucosa, blurred epithelial cell structure, gland atrophy, inflammatory cell infiltration, lamellar necrosis of the colonic mucosal layer and decreased number of goblet cells. The disease activity index scores in the normal group, model group, experimental-L group, experimental-H group and activator group were (0.12±0.02), (2.98±0.34), (1.76±0.19), (0.55±0.07) and (2.69±0.29) points, respectively; the levels of IL-17 in colon tissue were (24.64±2.74), (39.78±4.27), (32.92±3.65), (26.13±2.85) and (37.85±3.98) pg·mL^-1, respectively; the levels of IL-23 in colon tissue were (14.25±1.73), (28.47±3.04), (22.14±2.42), (15.96±1.87) and (26.95±2.94) pg·mL^-1, respectively; the histopathological scores of colon tissue were (0±0), (3.73±0.39), (2.49±0.28), (1.24±0.15) and (3.61±0.38) points, respectively; the p-ERK/ERK in colon tissue were 0.32±0.04, 0.81±0.09, 0.58±0.07, 0.36±0.05 and 0.77±0.08, respectively; the relative expression levels of NLRP3 protein were 1.03±0.11, 2.05±0.23, 1.64±0.18, 1.24±0.14 and 1.95±0.22, respectively; the relative expression levels of IL-1β protein were 1.05±0.11, 1.96±0.22, 1.58±0.17, 1.21±0.13 and 1.91±0.21, respectively. Statistical significance was observed in the above indicators when comparing the normal group with the model group, comparing the model group with the experimental-L, H groups and comparing the experimental-H group with the activator group (all P<0.05).

Shionone has protective effects on rats with ulcerative colitis by inhibiting the ERK/NLRP3/IL-1β signaling pathway.

To extract severe cutaneous adverse reactions (SCAR) associated with commonly used anti-influenza virus drugs from the US Food and Drug Administration (FDA) adverse event reporting system (FAERS) database, analyze the epidemiological characteristics of SCAR to provide a reference for safe clinical medication, and explore the underlying molecular mechanisms using network pharmacology.

Reports from January 2004 to December 2024 in FAERS database were collected, in which oseltamivir, peramivir, zanamivir and baloxavir marboxil were the primary suspected drugs and SCAR was the preferred term (PT). The reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) methods were used to mine and analyze adverse drug event (ADE) signals. Targets of commonly used anti-influenza virus drugs and SCAR were extracted, a protein-protein interaction network was constructed, and enrichment analysis was performed.

A total of 263 cases (1.90%) of SCAR related to commonly used anti-influenza virus drugs were collected. Females (55.13%) accounted for a higher proportion than males (35.36%). Positive signals were detected for all drugs except peramivir, with the association strength in descending order, baloxavir marboxil [n=42, ROR 1.75, information component(IC)0.8], zanamivir (n=53, ROR 1.61, IC 0.68) and oseltamivir (n=208, ROR 1.34, IC 0.42). The top 5 PT by frequency were blister, erythema multiforme, drug eruption, toxic epidermal necrolysis and acute generalized exanthematous pustulosis. Network pharmacology analysis showed that the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway may be a key pathway underlying SCAR induced by commonly used anti-influenza virus drugs.

Baloxavir marboxil, oseltamivir and zanamivir carry a risk of SCAR, with baloxavir marboxil and zanamivir showing higher signal intensity, while oseltamivir had the highest number of reports. Close monitoring of skin symptoms in female patients is recommended from 3 days after administration to guard against the occurrence of SCAR. Anti-influenza virus drugs may induce SCAR by regulating the JAK-STAT signaling pathway, which provides insights for further research.

To analyze the therapeutic effects and safety of ticagrelor tablets combined with aspirin enteric-coated tablets on young patients with first-onset atherosclerotic acute cerebral infarction.

According to different treatment plans, the patients with first-onset atherosclerotic acute cerebral infarction were divided into the treatment group and the control group. The treatment group was treated with aspirin enteric-coated tablets combined with ticagrelor tablets (initial dose: aspirin enteric-coated tablets 100 mg·d^-1 and ticagrelor tablets 180 mg·d^-1, maintenance dose: aspirin enteric-coated tablets 100 mg·d^-1 and ticagrelor tablets 90 mg·d^-1). The control group was treated with aspirin enteric-coated tablets combined with clopidogrel tablets (initial dose: aspirin enteric-coated tablets 100 mg·d^-1 and clopidogrel tablets 300 mg·d^-1, maintenance dose: aspirin enteric-coated tablets 100 mg·d^-1 and clopidogrel tablets 75 mg·d^-1). The courses of treatment for both groups were 3 months. After 3 months of treatment, the efficacy, National Institutes of Health stroke scale (NIHSS) scores, cerebral hemodynamics, Barthel index, platelet aggregation rate, modified Rankin scale (mRS) scores, adverse cardiovascular events, and adverse reactions were observed.

A total of 103 patients were enrolled, with 53 cases in treatment group and 50 patients in control group. After 3 months of treatment, the total effective rates in the treatment group and the control group were 92.45% (49 cases/53 cases) and 88.00% (44 cases/50 cases), with no statistically significant difference between groups (P>0.05). After 3 months of treatment, the mean blood flow velocities (Vmean) of the middle cerebral artery (MCA) in the treatment group and the control group were (56.73±11.05) and (50.50±10.33) cm·s^-1, respectively; the Vmean of the anterior cerebral artery (ACA) were (45.92±9.83) and (41.28±8.22) cm·s^-1, respectively; the Vmean of the posterior cerebral artery (PCA) were (50.11±10.33) and (45.59±9.12) cm·s^-1, respectively; the Vmean of the vertebral artery (VA) were (52.67±10.49) and (47.81±9.63) cm·s^-1, respectively; the Vmean of basilar artery (BA) were (53.75±10.28) and (48.29±9.60) cm·s^-1, respectively; the platelet aggregation rates were (22.71±7.33)% and (26.47±7.35)%, respectively; the above indexes in the treatment group were significantly different from those in the control group (P<0.05, P<0.01). After 3 months of treatment, the NIHSS scores of the treatment group and the control group were (1.23±0.47) and (1.38±0.49) points, respectively, and the Barthel indexes were (92.17±5.17) and (90.08±6.37) points, respectively. There was no statistically significant difference in the NIHSS score and Barthel index between the treatment group and the control group (all P>0.05). The incidences of adverse cardiovascular events in treatment group and control group were 0% and 8.00% (4 cases/50 cases), respectively, with no statistically significant difference (P>0.05). Adverse drug reactions in the treatment group included gastrointestinal reactions, bleeding tendency, hyperuricemia, and bradycardia, with a total incidence of 13.21% (7 cases/53 cases); adverse drug reactions in the control group included gastrointestinal reactions and bleeding tendency, with a total incidence of 10.00% (5 cases/50 cases); there was no statistically significant difference between groups (P>0.05).

Applying ticagrelor tablets to treat young patients with first-onset atherosclerotic acute cerebral infarction can significantly improve cerebral hemodynamics, with more advantages.