To evaluate the effects of repeated-dose toxicity of the candidate drug HYH2002 injection in Sprague-Dawley (SD) rats, thereby providing a basis for its use in clinical trials.

A total of 120 SD rats (half male, half female) were randomly divided into four groups. Group 1 (vehicle control) received the blank formulation solution. Groups 2, 3, and 4 were administered HYH2002 injection at doses of 0.60, 3.00, and 9.00 mg·kg^-1, respectively. The test article was administered once daily via tail vein infusion for 2 weeks, followed by a 2-week recovery period. Parameters including clinical observations, body weight, food consumption, body temperature, ophthalmological examinations, hematology, coagulation parameters, clinical biochemistry, and urinalysis were assessed at scheduled intervals. Necropsy, gross observations, and histopathological examinations were conducted at the end of the dosing period and the recovery period.

Animals in the 9.00 mg·kg^-1 group exhibited decreases in body weight and food consumption. Hematological changes included decreases in red blood cell (RBC) count, hemoglobin (HGB), hematocrit (HCT), and lymphocyte count (Lymph), alongside increases in neutrophil count (Neut), mean corpuscular volume (MCV), and reticulocyte count (Retic). Clinical biochemistry showed a decrease in albumin (Alb). These changes were reversible after the 2-week recovery period. No test article-related adverse effects were observed in the 0.60 and 3.00 mg·kg^-1 groups. Under the conditions of this study, the no-observed-adverse-effect level (NOAEL) was determined to be 3.00 mg·kg^-1, which is 50 times the effective dose (0.06 mg·kg^-1) in a rat model of gastric ulcer.

HYH2002 injection demonstrates a favorable safety profile within the anticipated therapeutic dose range, suggesting a low risk for clinical trials.

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 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 study the bioequivalence of efavirenz, lamivudine and tenofovir disoproxil fumarate tablets (I) from two different manufacturers in healthy Chinese participants under fasting conditions.

A randomized, single-center, open-label, single-dose, two-sequence, two-period, two-way crossover design. Forty-two eligible healthy subjects were enrolled. In each period, subjects received a single oral dose of the test or reference formulation of efavirenz lamivudine tenofovir tablets (specification: each tablet contains 0.4 g efavirenz, 0.3 g lamivudine and 0.3 g tenofovir disoproxil fumarate) under fasting conditions. The plasma concentrations of efavirenz, lamivudine and tenofovir was performed using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method that had been fully validated. Pharmacokinetic parameters were calculated and the bioequivalence and safety of the two efavirenz lamivudine tenofovir tablets were evaluated.

For efavirenz, the key pharmacokinetic parametersderived from the test and reference formulations were as follows: C_max were (1 710.25±430.44) and (1 851.26±505.57) ng·mL^-1, AUC_{0-72 h} were (37 571.38±8 747.34) and (39 391.65±8 746.77) ng·mL^-1·h, t_max were [3.23±1.13 (1.00, 3.17, 5.00)] and [3.12±1.30 (1.25, 3.00, 6.03)] h, and t_1/2 were (77.08±61.79) and (71.11±39.45) h, respectively. For lamivudine: C_max were (2 397.22±689.34) and (2 388.23±618.71) ng·mL^-1, AUC_0-t were (12 134.48±2 526.28) and (12 324.11±2 891.50) ng·mL^-1·h, t_max were [1.97±0.70 (0.67, 1.88, 4.00)] and [2.04±0.90 (0.67, 2.00, 4.51)] h, and t_1/2 were (11.07±11.10) and (11.46±11.90) h, respectively. For tenofovir: C_max were (287.40±86.07) and (304.71±91.49) ng·mL^-1, AUC_0-t were (2 516.91±583.47) and (2 507.40±573.45) ng·mL^-1·h, t_max were [1.40±0.74 (0.50, 1.13, 3.00)] and [1.39±0.84 (0.33, 1.25, 4.00)] h, and t_1/2 were (22.95±4.26) and (21.88±2.99) h, respectively. Under fasting conditions, the 90% confidence intervals of the main PK parameters of the test and reference formulations were all within 80.00% to 125.00%.

The test and reference formulations are bioequivalent under fasting conditions.

To establish a population pharmacokinetic-pharmacodynamic (PK-PD) model of a novel glucagon-like peptide-1 (GLP-1) analogue in patients with type 2 diabetes mellitus (T2DM), using HbA1c levels after 52 weeks of treatment as the efficacy endpoint and based on a nonlinear mixed-effects model (NLME).

A population PK-PD linkage model was developed via the NLME approach, utilizing 1 967 plasma concentration data points and 1 813 observed HbA1c data points from 409 T2DM subjects enrolled in a Phase Ⅲ clinical trial. Model robustness and predictive performance were comprehensively validated using diagnostic plots, visual predictive check (VPC), and the Bootstrap method.

The PK characteristics were best described by a one-compartment model with first-order absorption and first-order elimination, while the PD model was a plasma concentration-driven indirect response model. Key parameters were estimated as follows: apparent volume of distribution (V/F)=11.28 L, apparent clearance (CL/F)=1.11 L·day^-1, maximum inhibitory effect (I_max)=0.30, and half-maximal inhibitory concentration (IC₅₀)=37.77 ng·mL^-1. Covariate analysis revealed that baseline body weight was a significant factor affecting CL/F, and baseline HbA1c (group 1: HbA1c < 8.5%; group 2: HbA1c ≥ 8.5%) influenced the parameter kin.

The nonlinear mixed-effects model effectively utilizes sparsely sampled data, and the obtained PK-PD parameter estimates are robust and reliable.

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.

This article aims to explore the medication strategy for the treatment of type Ⅱ Crigler-Najjar syndrome (CNS II) during pregnancy with phenobarbital, focusing on the relationship between treatment dosage, treatment duration, and gestational stage of the patient with maternal and neonatal outcomes, providing a reference for the treatment of this rare disease during pregnancy.

: This study systematically searched the PubMed, Embase, Web of Science, and Cochrane Library database using the keywords “Pregnancy” and “Crigler-Najjar syndrome Ⅱ” with the logical connector “and”. The time range covered from the establishment of the database to March 2025. A total of 11 articles were screened.

A total of 11 patients with CNS Ⅱ during pregnancy were included. Among them, 3 cases did not receive drug treatment, and 2 cases had known total bilirubin levels, which were 7 mg·dL^-1 and 8.5 mg·dL^-1, respectively. Among the 3 cases, 1 newborn was healthy, 1 had jaundice that could subside on its own, and 1 had jaundice that required ursodeoxycholic acid treatment. The total bilirubin levels of the remaining 8 cases were between 6.85 and 21.5 mg·dL^-1, and all received phenobarbital treatment, with a dosage of 25-60 mg·d^-1. After treatment, 1 out of 8 newborns was completely healthy, 4 had varying degrees of jaundice, and all received 1-3 days of phototherapy and recovered. Follow-up was conducted for 6 months to 11 years for 3 of the infants, and no neurological damage was observed. During the treatment process, 5 patients received bilirubin level monitoring, once a week in the first month and once a month thereafter.

The current evidence suggests that the maternal bilirubin level may be one of the key factors influencing the neonatal outcome. When the bilirubin level remains above 8-10 mg·dL^-1, some studies recommend considering drug intervention under multidisciplinary assessment. However, due to the extremely small sample size and the lack of controlled studies, the causal relationship between the use of phenobarbital and maternal and infant outcomes cannot be clearly determined. The clinical benefits of phenobarbital use still need to be verified by more research. After thorough assessment by the treatment team, if phenobarbital intervention is chosen, it can be started in the early stage of pregnancy and continued until delivery, with a recommended dose of less than 60 mg·d^-1. During the treatment period, the maternal total bilirubin concentration should be closely monitored, once a week in the first month and once a month thereafter, to ensure the safety of medication.

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.

This study used bibliometric methods to analyze the quality and influence of SCI papers, publication patterns, and funding sources in the cardiovascular field published by a Grade A tertiary hospital in Beijing and its international counterparts from 2015 to 2024, aiming to provide insights for future development.

This study retrieved the cardiovascular-related literature published by 11 medical institutions in the Web of Science Core Collection database from January 1, 2015 to December 31, 2024, and imported it into the InCites database for analysis from three aspects: research paper quality, academic quality, collaborative networks, publication source, and funding agency.

The cardiovascular department of the hospital has room for improvement in terms of the quality and international influence of research papers. The main source of research funds relies on government institutions.

In the future, the cardiovascular department in domestic hospitals needs to further enhance the quality of published papers, expand international cooperation, raise the level of published journals, broaden the research funding system, and continuously enhance its global academic influence.