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.

To explore and analyze the efficacy of propranolol combined with Radiopharmaceutical iodine-131 in treating hyperthyroidism, its impact on thyroid function.

Patients with hyperthyroidism were collected and assigned into treatment group and control group. The control group was treated with iodine-131 alone; the treatment group was treated with a combination of propranolol and iodine-131. The efficacy, anxiety (self-rating anxiety scale, SAS) scores and depression (self-rating depression scale, SDS) scores, thyroid hormone levels, cardiac function indicators, and adverse reactions were compared between the two groups.

A total of 160 patients were enrolled, with 80 cases in each group. There was no significant difference in efficacy between the treatment group and the control group (P>0.05). There was no significant difference in adverse reactions between the two groups (P>0.05). After treatment, the SAS score, SDS score, free triiodothyronine (FT3) level, free thyroxine (FT4) level, left ventricular ejection fraction (LVEF) level, stroke volume (SV) level, heart rate level in both groups decreased, and the treatment group was lower than the control group (all P<0.05); the TSH level increased, and the treatment group was higher than the control group (P<0.05).

Compared with the use of iodine-131 alone, the combined treatment of propranolol and iodine-131 for hyperthyroidism can effectively improve thyroid function and cardiac function, and reduce anxiety and depression in patients.

To investigate the efficacy of tranexamic acid combined with phloroglucinol in fetal protection for threatened abortion and its impact on pregnancy outcome.

Patients with threatened abortion were divided into control group and treatment group according to the treatment methods. Both groups received routine fetal protection treatment. The control group was given intravenous infusion of tranexamic acid on the basis of routine treatment. The patients in the treatment group were additionally given intravenous infusion of phloroglucinol on the basis of the treatment of the control group. The clinical efficacy, remission time of clinical symptoms, uterine hemodynamics, sex hormone levels, pregnancy outcomes, and safety evaluation of the two groups were assessed.

A total of 82 cases were enrolled in this study, including 39 cases in the control group and 43 cases in the treatment group. The fetal protection success rates were 71.79% and 90.70% in the control and treatment groups, respectively, with statistically significant difference (P<0.05). The waist soreness relief time was (3.64±0.71) d in the control group and (3.26±0.62) d in the treatment group; the lower abdominal dragging pain relief time was (2.90±0.50) d and (2.65±0.53) d, respectively; and the vaginal bleeding relief time was (3.00±0.61) d and (2.72±0.59) d, respectively. After treatment, the resistance index (RI) was 0.83±0.16 and 0.76±0.14; the pulsatility index (PI) was 2.46±0.65 and 2.12±0.41, respectively; and the systolic/diastolic ratio (S/D) was 3.24±0.54 and 2.98±0.48 in the control and treatment groups, respectively. The progesterone (P) levels were (99.40±8.63) and (104.11±8.97) nmol·L^-1, respectively; the estradiol (E₂) levels were (982.73±82.77) and (1 027.18±79.41) pmol·L^-1, respectively; and the β-human chorionic gonadotropin (β-hCG) levels were (77 695.54±10 728.91) and (85 684.63±11 755.83) mIU·mL^-1 in the control and treatment groups, respectively. The abortion rates were 23.08% and 6.98%, and the term delivery rates were 61.54% and 88.37% in the two groups, respectively. The differences in the above indicators between the two groups were statistically significant (all P<0.05). During the treatment period, headache or diarrhea occurred in both groups, with total incidence rates of 7.69% and 4.65%, respectively, and the difference was not statistically significant (P>0.05).

The combined use of tranexamic acid and phloroglucinol in patients with threatened abortion can accelerate the relief of clinical symptoms, improve the success rate of fetal protection, and improve pregnancy outcomes, with no significant increase in adverse events observed.

To explore the clinical effect of insulin lispro combined with balanced salt solution in the treatment of adult emergency patients with diabetic ketoacidosis (DKA).

DKA patients were divided into a control group and an experimental group according to the treatment method. Both groups were given intravenous infusion of balanced salt solution for rehydration at the same time. The control group was given insulin aspart, and the experimental group was given insulin lispro. The blood glucose control efficacy, improvement of acidosis, and safety were compared between the two groups.

There were 44 patients enrolled in the control group and 48 patients in the experimental group. After treatment, the fasting blood glucose (FBG) of the control group was (5.77±1.08) mmol·L^-1, the 2-hour postprandial glucose (2 h PG) was (12.11±4.27) mmol·L^-1, the mean amplitude of glycemic excursions (MAGE) was (3.48±1.04) mmol·L^-1, the 24-hour mean blood glucose (24 h MBG) was (7.84±1.57) mmol·L^-1, the beta-hydroxybutyrate (β-HB) was (0.35±0.11) mmol·L^-1, the carbon dioxide combining power (CO₂CP) was (20.06±6.43) mmol·L^-1, and the potential of hydrogen (pH) value was 7.58±1.13. For the experimental group, the FBG was (5.36±1.26) mmol·L^-1, the 2 h PG was (10.22±2.52) mmol·L^-1, the MAGE was (3.32±0.92) mmol·L^-1, the 24 h MBG was (7.60±1.44) mmol·L^-1, the β-HB was (0.30±0.14) mmol·L^-1, the CO₂CP was (21.34±6.54) mmol·L^-1, and the pH was 7.55±1.07. The experimental group had significantly lower levels of FBG, 2 h PG, MAGE, and 24 h MBG compared to the control group(all P<0.05). There was no significant difference in β-HB, CO₂CP, and pH value between the two groups (all P>0.05). There was 1 case of hypoglycemia in the control group and 3 cases of hypoglycemia in the experimental group. There were no gastrointestinal adverse reactions such as abdominal distension in both groups, and there was no significant difference in the total incidence of adverse reactions between the two groups (P>0.05).

Insulin lispro combined with balanced salt solution can effectively control blood glucose, improve acidosis and electrolyte levels, exert no significant adverse effects on renal function, and has good safety in the treatment of adult emergency DKA patients.

To observe the clinical efficacy and safety of tenecteplase bridging endovascular thrombectomy versus direct thrombectomy in the treatment of acute basilar artery occlusion stroke.

Patients with acute basilar artery occlusion stroke were collected and divided into a control group and an experimental group based on different treatment methods. Compared the differences in clinical efficacy, vascular recanalization rate, thrombectomy-related indicators, infarct-related parameters, cerebral hemodynamic indicators, serum biomarkers, neurological function, 90-day prognosis, and adverse reactions between the two groups.

A total of 112 patients with acute basilar artery occlusion stroke were enrolled, including 57 cases in the control group and 55 cases in the experimental group. After treatment, the overall effective rate of the experimental group was 52.73% (29 cases/55 cases), which was higher than that of the control group 33.33%,(19 cases/57 cases) (P<0.05). At the time of treatment, the effective recanalization rates in the experimental group and the control group were 85.45% (47 cases/55 cases) and 80.70% (46 cases/57 cases), respectively, while the complete recanalization rates were 56.36% (31 cases/55 cases) and 49.12% (28 cases/57 cases), respectively. There was no statistically significant difference in the above indicators between the two groups (P>0.05). The first-pass effect (FPE) rates in the experimental group and the control group were 72.73% (40 cases/55 cases) and 52.63% (30 cases/57 cases), respectively, and the number of thrombectomy procedures was 1.91±0.48 and 2.11±0.52, respectively, with statistically significant differences (P<0.05). The thrombectomy time in the experimental group and the control group was (64.29±10.29) and (66.37±12.32) min, respectively, and the residual stenosis rates were 10.91% (6 cases/55 cases) and 21.05% (12 cases/57 cases), respectively, with no statistically significant differences (P>0.05). At 24 hours after the operation, the ischemic area volume of the experimental group and the control group was (82.66±15.21) and (93.61±18.65) mL. respectively, the ischemic core volume was (60.19±8.52) and (65.15±9.10) mL, respectively, the ischemic penumbra volume was (22.47±5.18) mL and (28.46±7.22) mL, respectively, the final infarct growth volume was (30.47±8.16) and (35.04±9.04) mL, respectively, the salvage rates of the ischemic penumbra were (69.93±8.11)% and (64.71±7.52)%, respectively, and the peak systolic velocity was (119.86±28.79) and (105.24±24.35) cm·s^-1, respectively, the end-diastolic velocity was (44.44±7.16) and (34.89±8.05) cm·s^-1, respectively; the resistance index (RI) was 0.63±0.04 and 0.67±0.05, respectively; the pulsatility index (PI) was 0.70±0.07 and 0.74±0.06, respectively; The serum neurofilament light chain (NfL) levels were (345.26±30.15) and (372.34±54.19) pg·mL^-1, respectively, and the glial fibrillary acidic protein (GFAP) levels were (526.37±74.91) and (566.42±82.21) pg·mL^-1, respectively. There were statistically significant differences in the above indicators between the two groups (P<0.05). At 7 days, 30 days postoperatively, the NIHSS scores of the experimental group were (10.42±2.13), (7.47±1.92) points, respectively, all of which were lower than those of the control group [(11.56±2.29), (8.37±2.04) points]. During the follow-up period, 11 bleeding events occurred in the experimental group, including 4 cases of symptomatic intracerebral hemorrhage (sICH), 6 cases of asymptomatic intracerebral hemorrhage (aICH), and 1 case of upper gastrointestinal bleeding; 9 bleeding events occurred in the control group, including 4 cases of sICH and 5 cases of aICH. The difference was not statistically significant (P>0.05). The rate of favorable prognosis at 90 days was 54.55% (30 cases/55 cases) in the experimental group, which was higher than the 33.33% (19 cases/57 cases) in the control group (P<0.05). There were no significant differences between the two groups in all-cause mortality or re-infarction rate (P>0.05). The overall incidence of adverse reactions was 9.09% (5 cases/55 cases) in the experimental group and 10.53% (6 cases/57 cases) in the control group, with no statistically significant difference between the groups (P>0.05).

For patients with acute basilar artery occlusion stroke with onset <6 hours, ASA grade ≤Ⅲ, and baseline mRS 0-2, tenecteplase bridging endovascular thrombectomy and direct thrombectomy achieve similar recanalization outcomes in the treatment of acute basilar artery occlusion stroke. The bridging approach reduces the number of thrombectomy attempts required, further improves cerebral blood flow perfusion, promotes neurological function and prognosis, while maintaining a safety profile comparable to that of direct thrombectomy.

To evaluate the clinical efficacy and safety of β-lactam antibiotics (BLAs) combined with tigecycline (TGC) in the treatment of complicated urinary tract infections (cUTIs) in perimenopausal women, and to provide evidence-based data for optimizing clinical treatment regimens in this population.

A retrospective study was conducted on the clinical data of 102 perimenopausal women with cUTI admitted to our hospital from March 2023 to March 2025. The patients were divided into a experimental group (52 cases) and a control group (50 cases) based on treatment regimens. The control group received BLAs (cefoperazone-sulbactam) monotherapy, while the treatment group received BLAs combined with TGC therapy. Both groups underwent continuous treatment for 14 days. Changes in various indicators before and after treatment were recorded.

After treatment, the white blood cell (WBC) counts in the control group and the experimental group were (8.21±1.19)×10 and (7.55±1.22)×10/L, respectively; serum amyloid A (SAA) levels were (25.31±4.65) and (22.91±4.12) mg·L^-1, respectively; soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) levels were (22.52±4.18) and (20.85±3.55) pg·mL^-1, respectively; urinary heparin-binding protein (U-HBP) levels were (77.60±8.54) and (74.06±7.43) ng·mL^-1, respectively. The CD4⁺/CD8⁺ ratios were 1.62±0.20 and 1.74±0.25, immunoglobulin M (IgM) levels were (1.57±0.20) and (1.72±0.28) g·L^-1, and immunoglobulin G (IgG) levels were (11.33±1.71) and (12.06±1.46) g·L^-1 in the two groups, respectively. In the visual analogue scale (VAS) assessment, the urgency VAS scores were 1.66±0.48 and 1.44±0.50, dysuria VAS scores were 1.90±0.36 and 1.71±0.50, and frequency VAS scores were 1.76±0.48 and 1.54±0.54 in the control group and the experimental group, respectively. The scores of physiological function, mental health, role-emotional, social functioning, vitality, general health, bodily pain, and role-physical were (82.26±8.29) vs. (86.88±9.10), (77.22±7.12) vs. (80.56±8.60), (79.82±8.49) vs. (83.92±9.83), (79.28±8.12) vs. (82.79±8.70), (81.54±9.50) vs. (85.44±8.63), (79.30±7.97) vs. (83.67±8.94), (79.52±8.10) vs. (84.96±9.15), and (82.96±9.17) vs. (87.04±8.71) in the control and experimental groups, respectively. All the above differences were statistically significant (all P<0.05). The total incidence rates of adverse reactions were 8.00% (4 cases/50 cases) in the control group and 5.77% (3 cases/52 cases) in the experimental group, with no statistically significant difference (P>0.05).

Compared with monotherapy with β-lactam antibiotics, combination therapy with tigecycline further improves urinary bacterial clearance rate and cure rate, as well as enhance inflammatory markers, immune function, clinical symptoms, and quality of life. However, there is no statistically significant difference in overall response rates between the two groups. The combination therapy dose not increase adverse drug reactions.

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.

In November 2025, the US Food and Drug Administration (FDA) officially approved Kygevvi oral solution powder for the treatment of thymidine kinase 2 deficiency (TK2d) in adults and children with onset age ≤ 12 years old. Kygevvi is the first and only targeted therapy approved for the treatment of TK2d, consisting of two types of pyrimidine nucleosides, doxecitine and doxribtimine. Its function is to integrate doxecitine and doxribtimine into skeletal muscle mitochondrial deoxyribonucleic acid (DNA), thereby bypassing defective thymidine kinase 2 (TK2) and helping to repair and increase the quantity of mitochondrial DNA, and fundamentally improving cellular energy supply. Here is an introduction to its mechanism of action, pharmacodynamics, pharmacokinetics, clinical research, and safety.

Enhancing the effectiveness of drug regulation and optimizing resource allocation represent core strategies for advancing drug regulatory modernization. To evaluate the efficiency of drug safety regulation in China during the “14th Five-Year Plan” period (2021–2024), analyze the alignment between regulatory resource allocation and output outcomes, identify trends in efficiency changes and regional disparities, and provide recommendations for optimizing the drug regulatory system by bridging the achievements of the “14th Five-Year Plan” with the developmental needs of the “15th Five-Year Plan”.

Data on drug safety regulatory inputs and outputs from 2021 to 2024 were collected. The super-efficiency SBM (slack-based measure) model and Malmquist index were used to measure and analyze drug safety regulatory efficiency across nine provinces in seven administrative regions.

Significant interprovincial efficiency variations were observed. Liaoning maintained consistently high efficiency, Guangdong showed steady improvement, while Shanghai remained persistently low. Slack variable analysis revealed notable input redundancy and output insufficiency in Beijing and Shanghai. Dynamically, only Guangdong, Guangxi, and Shanxi achieved positive growth in total factor productivity (TFP), primarily driven by technological progress (TC>1). In contrast, regions such as Hunan and Guizhou experienced TFP decline due to decreased technical efficiency (EC<1), highlighting significant regional and technological imbalances in the process of improving regulatory effectiveness.

During the “14th Five-Year Plan” period, the efficiency of drug safety regulation in China has seen overall improvement compared to the “13th Five-Year Plan” period. However, challenges such as regional imbalances, lagging pure technical efficiency, and diminishing returns on scale allocation remain. It is essential to advance the transformation of the drug regulatory system toward precision and intelligence, strengthen the development of regulatory talent, and ensure the alignment of regulatory resources with industrial distribution.