To conduct data mining on tepotinib-associated adverse drug events (ADEs) using the US FDA Adverse Event Reporting System (FAERS) database, providing evidence for its clinical safety.

ADE reports for tepotinib from FAERS (Q1 2021 to Q4 2024) were analyzed. Signal detection methods included the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Multi-item Gamma Poisson Shrinker (MGPS). Sex-based differences in ADE signals were assessed using Fisher’s exact test with Bonferroni correction.

A total of 523 ADE reports identified tepotinib as the primary suspect drug, revealing 37 positive Preferred Terms (PT) across 14 System Organ Classes (SOCs). Notably, ADEs involving the ear and labyrinth disorders, infections and infestations, and nervous system disorders were not documented in the drug label. Several PTs—including malignant pleural effusion, infectious pleural effusion, central nervous system metastasis, pneumothorax, deafness, pericardial effusion, and dysgeusia—were newly identified as potential risks. Sex-stratified analysis showed higher diarrhea risk in women and a stronger appetite loss association in men. Importantly, interstitial lung disease (ILD) exhibited a significant signal in men (ROR=16.28, ROR025=8.71) but not in women, suggesting sex may be a key risk factor for tepotinib-induced ILD.

Clinicians should prioritize monitoring high-frequency, high-signal, and newly detected ADEs during tepotinib therapy. The drug label should be updated to include sex-specific ILD risk warnings.

To explore the efficacy of eravacycline combined with colistimethate sodium in treating sepsis caused by carbapenem-resistant Escherichia coli producing New Delhi metallo-β-lactamase (NDM) secondary to complex intra-abdominal infection.

The anti-infection regimen was dynamically adjusted according to abdominal-pelvic enhanced MRI, laboratory tests, changes in main inflammatory indicators (peripheral blood white blood cell count and procalcitonin), and drug sensitivity test results.

After 13 days of treatment with eravacycline (50 mg, q12h) and colistimethate sodium (150 mg, q12h), the patient's condition and inflammatory indicators improved significantly, with no drug-related adverse reactions during hospitalization.

The combination is safe and effective for the above-mentioned sepsis, providing crucial technical support for clinical treatment of NDM-producing carbapenem-resistant Escherichia coli infections.

To investigate the role of the phosphatidyqinositol-3 kinase / protein kinase B / nuclear factor-erythroid 2 related factor 2 (PI3K/Akt/Nrf2) pathway in remifentanil postconditioning-induced protection against myocardial ischemia-reperfusion (IR) injury in rats.

Establishing a rat model of myocardial ischemia-reperfusion injury (MIRI) by left anterior descending coronary artery ligation. Subsequently, the rats were randomly assigned to the following groups: control (only threading was performed without ligation), model (ischemia was induced for 30 minutes followed by 30 minutes of reperfusion), experimental (remifentanil was continuously infused by at a dose of 10 μg·kg^-1·min^-1 from 25 minutes of ischemia to 5 minutes before reperfusion), LY294002 (while receiving remifentanil intervention, 0.3 mg·kg^-1 LY294002 was administered), and ML385 (while receiving remifentanil intervention, 30 mg·kg^-1 ML385 was administered). Serum levels of interleukin-6 (IL-6), IL-1β and tumor necrosis factor-alpha (TNF-α) were measured using enzyme-linked immunosorbent assay (ELISA). Apoptosis index (AI) of myocardial cells in each group was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). The expression levels of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) were measured using real-time quantitative polymerase chain reaction.

The measured parameters for the control, model, experimental, LY294002, and ML385 groups were as follows. Serum interleukin-6 (IL-6) were 0.76±0.15, 3.44±0.35, 1.46±0.37, 3.17±0.28 and 3.07±0.18. IL-1β were 0.34±0.08, 1.18±0.21, 0.66±0.28, 0.94±0.13 and 0.81±0.25, respectively. Serum tumor necrosis factor-α (TNF-α) were 0.98±0.17, 2.38±0.27, 1.17±0.21, 2.27±0.26 and 2.66±0.16, respectively. Apoptosis index (AI) were 0.95±0.67, 20.73±1.63, 10.20±2.48, 15.69±2.41 and 16.31±1.55, respectively. PI3K mRNA relative expression level were 1.00±0.08, 1.69±0.15, 1.90±0.12, 0.98±0.14 and 1.78±0.13, respectively. Akt mRNA relative expression level were 1.00±0.09, 1.56±0.22, 1.85±0.13, 0.87±0.21 and 1.69±0.31, respectively. Nrf2 mRNA relative expression level were 1.00±0.08, 2.62±0.16, 3.11±0.28, 1.37±0.25 and 1.03±0.14, respectively. Statistically significant differences were observed for all the above parameters when comparing the experimental group with the model group, and when comparing the LY294002 and ML385 groups with the experimental group (P<0.05, P<0.01, P<0.001, P<0.0001).

Remifentanil postconditioning exerts a protective effect on myocardial IR injury by reducing IR-induced cardiomyocyte apoptosis and inflammatory response in rats, and may be related to the PI3K / Akt / Nrf2 signaling pathway.

To observe the clinical efficacy and safety of porcine pulmonary surfactant injection combined with budesonide suspension in premature infants with respiratory distress syndrome (RDS).

Infants with RDS were divided into control group and treatment group based on treatment methods. The control group received endotracheal administration of poractant alfa injection at 200 mg·kg^-1, with a supplemental dose of 100 mg·kg^-1 after 12 h. The treatment group additionally received inhaled budesonide suspension at 0.25 mg·kg^-1, twice daily. Both groups continued treatment for 3 d. The clinical symptoms and respiratory support parameters, blood gas analysis parameters, serum inflammatory and stress markers, clinical efficacy and safety evaluation were compared between the two groups.

A total of 136 were enrolled, with 59 cases in treatment group and 65 cases in control group. After treatment, the total efficacy rates in treatment group and control group were 89.83% (53 cases /59 cases) and 78.46% (49 cases /65 cases), respectively; time to disappearance of tachypnea were (36.85±5.62) and (39.52±7.15) h, respectively; time to disappearance of retractions were (40.58±7.93) and (43.88±8.61) h, respectively; time to disappearance of lung rales were (49.34±7.96) and (54.18±9.63) h, respectively; duration of mechanical ventilation were (4.15±0.78) and (4.45±0.87) d, respectively; total duration of oxygen therapy were (7.56±1.32) and (8.12±1.13) d, respectively; duration of neonatal intensive care unit (NICU) stay were (17.42±2.55) and (18.66±3.28) d, respectively; partial pressure of oxygen (PaO₂) levels were (65.24±9.24) and (61.58±9.85) mmHg, respectively; partial pressure of carbon dioxide (PaCO₂) levels were (41.85±6.61) and (44.92±7.13) mmHg, respectively; oxygenation indexes (OI) were 8.44±0.95 and 8.92±1.16, respectively; interleukin-6 (IL-6) levels were (45.78±5.42) and (48.74±7.25) pg·mL^-1, respectively; C-reactive protein (CRP) levels were (11.63±1.56) and (12.65±3.04) mg·L^-1, respectively; cortisol (Cor) levels were (296.54±36.87) and (315.16±45.32) nmol·L^-1, respectively; adrenocorticotropic hormone (ACTH) levels were (61.23±7.65) and (65.20±9.48) pg·mL^-1, respectively. There were statistically significant differences in the above indexes between treatment group and control group (all P<0.05). During treatment, the main adverse drug reactions in treatment group included air leak syndrome, pulmonary hemorrhage, decreased blood oxygen saturation, hyperglycemia and bradycardia; the control group included pulmonary hemorrhage, decreased oxygen saturation, hyperglycemia and bradycardia. The total incidence of adverse drug reactions in treatment group and control group were 13.56% (8 cases/59 cases) and 13.85% (9 cases/65 cases), respectively, with no statistically significant difference (P>0.05).

Poractant alfa injection combined with budesonide suspension can improve the total effective rate of treatment for RDS in preterm infants, accelerate symptom relief, inhibit inflammatory response and oxidative stress, without increasing the risk of additional adverse drug reactions.

To analyze adverse drug event (ADE) signals associated with dupilumab based on the date from the U.S. Food and Drug Administration Adverse Event Reporting System(FAERS), and to provide insights for rational medication use in clinical settings.

ADE reports of dupilumab as the primary suspected drug were obtained by collecting the data of FAERS database from the first quarter 2017 to the third quarter 2024. ADE signals were analyzed by joint reporting odds ratio (ROR) method and bayesian confidence interval progressive neural network (BCPNN) method.

After data cleaning, 669 761 reports of dupilumab-related ADEs were collected, involving 264 882 patients. A total of 461 ADE signals were detected across 18 system-organ classes (SOC), which had a good coincidence with the adverse reactions in the current Chinese and English drug instructions, and also found some new high-intensity positive signals that were not included in the instructions. Including ocular hyperaemia, erythema of eyelid, eyelid exfoliation, periorbital irritation, skin fissures, neurodermatitis, injection site exfoliation, cutaneous T-cell lymphoma, etc. The median time to onset of ADE reported by patients <18 years old, 18-65 years old, and ≥65 years old was 75 days, 98 days, and 110.5 days, respectively (P<0.000 1 according to Log-rank test). Weibull distribution test was performed on time to onset of 20 ADE signals that were not included in the manual. It was found that cutaneous T-cell lymphoma, hyposmia, parosmia, and sinus headache, occurred continuously over time, and the incidence of the others decreased gradually over time.

When clinically using dupriumab, it is essential to controll the indications and conduct a thorough medication assessment. Monitoring should be strengthened near the time window of adverse events. The latent ADEs that are not mentioned in the instructions should be noticed to ensure safe medication.

To investigate the impact of application site on the evaluation of formulation differences of flurbiprofen cataplasms based on pharmacokinetic parameters in Chinese subjects.

An open label, randomized, single-dose, two-sequence, two-period cross-over study under fasting condition was conducted. 12 subjects were randomized to A-B group or B-A group, with 6 subjects in each group, and 3 subjects in each group were applied to the leg and back respectively. The concentration of flurbiprofen in plasma was determined by methodologically validated liquid chromatography-mass spectrometry (LC-MS/MS), and the main pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.1.

The median t_max of flurbiprofen in plasma were 8.50 (4.00, 24.00) and 19.50 (4.00, 24.00) h respectively in 12 subjects (n=12; applied to leg : n=6; applied to back: n=6) after applying flurbiprofen cataplasms A and B, and the main pharmacokinetic parameters of flurbiprofen were as followed, C_max were (66.26±62.84) and (32.68±23.32) ng·mL^-1, AUC_0-t were (1 215.19±749.72) and (771.72±394.14) h·ng·mL^-1, AUC_0-∞ were (1 286.57±720.36) and (870.24±351.99) h·ng·mL^-1, respectively, and the geometric mean ratios and 90% CI (A/B) of the main pharmacokinetic parameters (C_max, AUC_0-t, AUC_0-∞) were 170.59% (139.21%-209.04%)、152.05% (135.60%-170.48%)、145.47% (126.21%-167.67%), respectively. The median t_max of flurbiprofen in plasma were 17.50 (10.00, 24.00) and 24.00 (24.00, 24.00) h respectively in 6 subjects (applied to leg) after applying flurbiprofen cataplasms A and B, and the main pharmacokinetic parameters of flurbiprofen in plasma were as followed, C_max were (20.56±7.76) and (15.30±6.79) ng·mL^-1, AUC_0-t were (727.03±267.78) and (500.59±186.09) h·ng·mL^-1, AUC_0-∞ were (845.73±288.00) and (636.69±166.74) h·ng·mL^-1 respectively, and the geometric mean ratios and 90% CI (A/B) of the main pharmacokinetic parameters (C_max, AUC_0-t, AUC_0-∞) were 139.60% (123.24%-158.13%), 146.70% (124.74%-172.51%), 130.61% (100.76%-169.30%) respectively. The median t_max of flurbiprofen in plasma were 4.00 (4.00, 7.00) and 9.00 (4.00, 15.00) h respectively in 6 subjects (Applied to back) after applying flurbiprofen cataplasms A and B, and the main pharmacokinetic parameters of flurbiprofen in plasma were as followed, C_max were (111.95±60.14) and (50.05±20.64) ng·mL^-1, AUC_0-t were (1 703.35±770.04) and (1 042.86±361.53) h·ng·mL^-1, AUC_0-∞ were (1 727.41±769.57) and (1 064.87±354.32) h·ng·mL^-1 respectively, and the geometric mean ratios and 90% CI (A/B) of the main pharmacokinetic parameters (C_max, AUC_0-t, AUC_0-∞) were 208.46% (139.61%-311.25%), 157.59% (123.51%-201.08%), 156.24% (122.10%-199.93%) respectively, compared to leg application, greater formulation difference was observed in back application.

This study suggested that regardless of application sites (leg or back), flurbiprofen cataplasms A exhibited higher on the rate and extent of absorption than that of flurbiprofen cataplasms B, and back application showed potentially greater drug absorption rate and extent than leg application, the formulation differences based on pharmacokinetic parameters were less pronounced when applied to leg. These findings indicate that back application may provide better discriminatory power for evaluating formulation differences.

To investigate the effect of ciprofibrate on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension (HPH) by regulating the angiopoietin 2 (Ang2)/tyrosine protein kinase (Tie) pathway.

Newborn rats were randomly separated into normal group, HPH group, low concentration ciprofibrate group, medium concentration ciprofibrate group, high concentration ciprofibrate group, and high concentration ciprofibrate + Ang2 activator rat Ang2 recombinant protein (rrAng2) group, with 12 rats in each group. Except for the normal group, newborn rats in all other groups were constructed with HPH models and administered once a day for 2 weeks starting from the first day of hypoxia. The changes in right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index were detected. Hematoxylin-eosin (HE) staining was applied to detect the pathology of lung tissue and the percentage of pulmonary artery middle layer wall thickness to its outer diameter (MT), and the percentage of pulmonary artery middle layer cross-sectional area to its total cross-sectional area (MA) changes. Immunofluorescence staining was applied to detect the relative fluorescence intensity of hypoxia inducible factor-1α (HIF-1α) and endothelin-1 (ET-1) in pulmonary arteries. Enzyme-linked immnosorbent assay (ELISA) was applied to detect levels of tumor necrosis factor-α (TNF-α) and interleukin (IL)-8 in pulmonary arteries. Western blot was applied to detect Ang2 and Tie2 proteins in pulmonary arteries.

Compared with the normal group, the HPH group showed an increase in pulmonary artery wall thickness and narrowing of the lumen, the RVSP, right ventricular hypertrophy index, MA, MT, HIF-1α, ET-1 relative fluorescence intensity, TNF-α, IL-8 levels, and Ang2 and Tie2 proteins in the pulmonary artery increased (P<0.05). Compared with the HPH group, the pulmonary artery wall thickening and luminal stenosis in rats in the low, medium, and high concentration ciprofibrate groups were improved, the RVSP, right ventricular hypertrophy index, MA, MT, HIF-1α, ET-1 relative fluorescence intensity, TNF-α, IL-8 levels, and Ang2 and Tie2 proteins in the pulmonary artery reduced (P<0.05). Compared with the high concentration ciprofibrate group, the high concentration ciprofibrate +rrAng2 group showed more significant thickening of the pulmonary artery wall and narrowing of the lumen in rats, the RVSP, right ventricular hypertrophy index, MA, MT, HIF-1α, ET-1 relative fluorescence intensity, TNF-α, IL-8 levels, and Ang2 and Tie2 proteins in the pulmonary artery increased (P<0.05).

Ciprofibrate may improve pulmonary vascular remodeling in neonatal rats with HPH by inhibiting the Ang2/Tie pathway, thereby suppressing the expression of HIF-1α and ET-1 as well as the inflammatory response.

To observe the clinical efficacy and safety of vitamin D and calcium tablets combined with calcitriol soft capsules in the treatment of type 2 diabetic osteoporosis.

Patients with type 2 diabetic osteoporosis were divided into control group and treatment group using a random number table. The control group received oral vitamin D and calcium tablets, each dose containing 750 mg of calcium carbonate and 2.5 μg of vitamin D3, administered once daily. The treatment group received oral calcitriol soft capsules at 0.25 μg per dose, once daily, in addition to the same treatment as the control group. Both groups continued treatment for 6 months. Glycometabolic indices, bone mineral density (BMD), bone metabolism indices, serological indices and clinical efficacy were compared between the two groups, and safety evaluation was conducted.

A total of 247 cases were screened, and 167 cases were enrolled. In the treatment group, 2 cases withdrew due to incomplete treatment and 3 were lost to follow-up; in the control group, 3 cases withdrew due to incomplete treatment and 2 were lost to follow-up. Finally, 78 and 79 cases were included in control and treatme groups, respectively. After treatment, the fasting plasma glucose (FPG) levels in treatment and control groups were (5.32±0.65) and (6.08±0.79) mmol·L^-1, respectively; femoral neck BMD were (0.85±0.14) and (0.79±0.10) g·cm^-2, respectively; bone-specific alkaline phosphatase (BALP) were (17.38±2.94) and (13.25±2.16) ng·mL^-1, respectively; osteoprotegerin (OPG) were (275.31±29.42) and (238.42±24.56) pg·mL^-1, respectively; insulin-like growth factor binding protein-3 (IGFBP-3) were (4.37±0.72) and (3.19±0.45) μg·mL^-1, respectively; and insulin-like growth factor-1 (IGF-1) were (109.35±12.43) and (94.28±10.31) ng·mL^-1, respectively. The differences in the above indices between treatment group and control group were all statistically significant (all P<0.05). The total effective rates in treatment and control groups were 94.94% (75 cases/79 cases) and 84.62% (66 cases /78 cases), respectively, with a statistically significant difference (P<0.05). The adverse drug reactions in treatment group included low-grade fever, abdominal distension, nausea and vomiting, while the control group experienced abdominal distension, nausea and vomiting. The total incidence of adverse drug reactions in treatment and control groups were 6.33% (5 cases/79 cases) and 5.13% (4 cases /78 cases), respectively, with no statistically significant difference (P>0.05).

Vitamin D and calcium tablets combined with calcitriol soft capsules are effective in the treatment of type 2 diabetic osteoporosis, improving glycometabolism and bone metabolism, increasing BMD, promoting the expression of serum IGFBP-3 and IGF-1, and demonstrate reliable safety.

To evaluate the efficacy and safety of different dose combinations of levamlodipine besilate tablets and bisoprolol fumarate tablets compared with placebo and control.

A multicenter, randomized, double-blind, double-dummy, placebo-positive drug-controlled dose-finding study in which patients with grade 1-2 essential hypertension were randomly divided into 5 groups after 14 days of placebo, namely: group A (placebo group), group B (levamlodipine besilate 2.5 mg/placebo), group C (bisoprolol 5 mg/placebo), group D (levamlodipine besilate 2.5 mg/bisoprolol fumarate 2.5 mg group) and E group (levamlodipine besilate 2.5 mg/bisoprolol fumarate 5 mg group), treated for 56 days. 14 days, 28 days, and 56 days after treatment, the main indicators-diastolic blood pressure, and the secondary indicators-systolic blood pressure, were analyzed, and the efficacy and safety were analyzed.

After 56 days of treatment, the decrease in diastolic blood pressure was 3.26±8.09 mmHg in group A, 8.89±6.97 mmHg in group B, 7.89±6.48 mmHg in group C, 12.64±6.49 mmHg in group D, and 13.46±7.80 mmHg in group E. Compared with group A, groups B, C, D, and E, P<0.001; the reduction of blood pressure between groups D and E (combination treatment group) and group B and C (monotherapy group) was significantly lower than that of group A P<0.01, and P>0.05 between combination treatment groups (D and E) and monotherapy groups (B and C groups). In terms of reducing systolic blood pressure, group B (decrease of 13.39±11.48 mmHg), group D (decrease of 17.55±10.31 mmHg) and group E (decrease of 20.60±13.06 mmHg) and group A (decrease of 5.55±13.19 mmHg) were P<0.001; group E compared with group B and C, P<0.001; compared between group D and C, P<0.01; and P>0.05 between groups D and E of the two combination treatment groups.

The 2.5 mg levamlodipine besilatee tablets combined with 2.5 mg bisoprolol fumarate tablets and 2.5 mg levamlodipine besilate tablets combined with 5 mg bisoprolol fumarate tablets have good efficacy and are better than the single agent levamlodipine besilate or bisoprolol fumarate in reducing diastolic blood pressure, and are well tolerated.