To explore the key elements in the evaluation and selection of sites for multicenter clinical trials, providing references for standardizing clinical trial site selection practices.

By integrating the practical experience of multiple sponsors, contract research organizations (CROs), and research sites, a standardized framework for site evaluation and selection was constructed.

A three-phase standardized process was proposed, encompassing pre-assessment preparation, formal evaluation, and outcome assessment. This study systematically categorized common and specific evaluation criteria, including 5 core dimensions and 17 key indicators covering site and personnel qualifications, hardware conditions, patient resources and quality systems, management processes, and special considerations.

This study constructed a comprehensive site evaluation system encompassing standardized procedures, structured dimensions, and core indicators. It achieves a transformation in evaluation practices from an experience-driven approach to a framework-guided methodology, providing an operable tool for the scientific selection of sites in multicenter clinical trials.

To analyze the characteristics of adverse drug reactions (adverse drug reaction, ADRs) of oral riluzole in patients with amyotrophic lateral sclerosis (amyotrophic lateral sclerosis, ALS), and to provide references for clinical safe medication.

Data of ALS patients treated with riluzole at Peking Union Medical College Hospital from May 2018 to August 2023 were collected. Patients with ADRs were retrospectively analyzed regarding demographic information, medication details, clinical manifestations, time of onset, management, and outcomes. Causality assessment was performed according to China’s Measures for Reporting and Monitoring of Adverse Drug Reactions, severity was evaluated using CTCAE V5.0, and ADRs were coded using MedDRA terms.

A total of 67 ALS patients were included, among whom 22 experienced ADRs (32.8%). The incidence of ADRs was higher in females (44.0%) than in males (26.2%). A total of 54 ADR episodes were recorded. The most common ADRs involved the nervous system (20 cases/54 cases, 37.0%), followed by gastrointestinal system disorders (13 cases/54 cases, 24.1%), general disorders and administration site conditions (7 cases/54 cases, 13.0%), and various laboratory investigations (6 cases/54 cases, 11.1%). One patient (1.5%) experienced a grade 3 serious ADR (interstitial lung disease). Seventeen patients (77.3%) developed ADRs within the first three months of treatment. Sixteen patients (72.7%) tolerated the ADRs without specific intervention, while six (27.3%) improved after drug discontinuation, dose reduction, or symptomatic treatment.

The most common ADRs of riluzole in ALS patients involve the nervous system, gastrointestinal tract, and elevated liver enzymes (all not higher than twice the normal value), mostly occurring early in the treatment course. Clinicians should remain vigilant for respiratory ADRs and potential heightened inflammatory responses, with close monitoring recommended during the first six months of treatment.

To investigate the effect of wogonin on hypoxia/reoxygenation (H/R)-induced neuronal injury based on the C-C chemokine ligand 2-C-C chemokine receptor 2 (CCL2-CCR2) pathway.

PC12 cells were cultured and divided into five groups, control group (normal culture), model group (H/R injury), experimental group (H/R+50 μmol·L^-1 wogonin pretreatment for 1 h), antagonist group (H/R+10 μmol·L^-1 CCR2 antagonist RS102895 pretreatment for 1 h), and agonist group (H/R+50 μmol·L^-1 wogonin+20 μmol·L^-1 CCL2 recombinant protein pretreatment for 1 h). Cell viability and cytotoxicity were assessed using the cell counting kit-8 (CCK-8) and lactate dehydrogenase (LDH) assay kits. Apoptosis was detected by Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) double staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. Oxidative stress and inflammatory responses were evaluated by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (RT-qPCR). Protein expression levels related to the CCL2-CCR2 signaling pathway were measured by Western blot.

The viability of PC12 cells in control group, model group, experimental group, antagonist group and agonist group were 0.89±0.06, 0.32±0.04, 0.69±0.05, 0.65±0.07 and 0.46±0.04, respectively; the SOD activities were (45.11±3.02), (10.05±1.05), (33.62±3.15), (30.15±2.87) and (21.05±2.17) U·mL^-1, respectively; the Annexin V FITC/PI double staining apoptosis rates were (3.21±0.68)%, (29.65±1.59)%, (8.99±0.82)%, (9.87±0.85)% and (18.65±1.06)%, respectively; the TUNEL positive rates were (5.66±0.89)%, (33.65±2.42)%, (13.25±1.05)%, (11.66±1.87)% and (24.06±1.16)%, respectively; the relative expression levels of tumor necrosis factor-alpha(TNF-α) mRNA were 1.02±0.15, 3.05±0.32, 1.59±0.16, 2.98±0.24 and 2.66±0.20, respectively; the relative expression levels of interleukin-6 (IL-6) mRNA were 1.05±0.12, 4.54±0.39, 1.87±0.15, 1.75±0.14 and 3.08±0.32, respectively; the relative expression levels of CCL2 mRNA were 1.01±0.07, 3.99±0.32, 1.64±0.15, 3.90±0.33 and 2.84±0.23, respectively; the relative expression levels of CCR2 mRNA were 1.03±0.10, 5.21±0.51, 2.03±0.26, 2.11±0.20 and 3.85±0.32, respectively; the relative expression levels of phosphorylation (p)p65/p65 were 0.12±0.02, 0.75±0.06, 0.24±0.03, 0.22±0.01 and 0.52±0.05, respectively; the leakage rates of LDH were (18.32±1.15)%, (58.64±5.16)%, (29.02±2.16)%, (26.98±3.02)% and (40.24±3.54)%, respectively; the malondialdehyde (MDA) contents were (50.16±5.24), (169.65±10.16), (91.32±7.12), (86.21±5.16) and (134.16±11.87) nmol·mL^-1, respectively. The differences of above indicators between model group and control group, between experimental group and model group, and between the antagonist, agonist group and experimental group were all statistically significant (all P<0.05).

Wogonin exerts a protective effect against H/R-induced neuronal injury by inhibiting the CCL2-CCR2 signaling pathway.

To analyze the characteristics of patient subgroups and temporal patterns of adverse events (AE) associated with efgartigimod treatment for generalized myasthenia gravis (gMG), based on the U.S. FDA Adverse Event Reporting System (FAERS) database, providing evidence for personalized clinical use and long-term drug safety monitoring.

Individual case safety reports (ICSRs) in which efgartigimod was the primary suspect drug were extracted from the FAERS database covering Q1 2020 to Q4 2023. After deduplication and MedDRA standardization, binary logistic regression was used to assess the impact of age, sex, and body weight on symptom recurrence risk; K-means clustering identified high-risk patient subgroups; and descriptive analysis characterized the distribution of AE onset times (TTO).

A total of 788 ICSRs were included, of which 321 had complete time information. Logistic regression revealed that low body weight (OR=0.97, P=0.021) and younger age (OR=0.96, P=0.014) were risk factors for symptom recurrence. Clustering analysis divided patients into three groups: older and heavier individuals (mainly cardiovascular or procedure related AEs), younger and lighter individuals (primarily immune or hypersensitivity related AEs), and a heterogeneous group. The overall TTO distribution of AEs was right-skewed, with 68% occurring within 30 days. Median TTO for serious AEs (73 days) was longer than for non-serious AEs (54 days), indicating a clear delayed risk (>180 days).

Efgartigimod related AE risks exhibit heterogeneity across populations and time dependency. Younger, lower weight patients require close monitoring for immune related AEs, while older, higher weight patients should be monitored for cardiovascular risks. A comprehensive, long-term monitoring strategy throughout the treatment cycle is warranted clinically. The integrated framework proposed here "risk stratification-subgroup identification-temporal monitoring" can be directly applied to other neonatal Fc receptor (FcRn) targeted drugs, offering an innovative model for post-marketing evaluation of biologics in China.

Explore the correlation between tacrolimus trough concentration (C₀) and clinical efficacy in children with lupus nephritis (LN), and identify key factors affecting the efficacy of tacrolimus treatment in LN patients..

A total of 120 children with LN who took tacrolimus in our hospital from March 2021 to December 2024 and were monitored for blood drug concentration were retrospectively selected. According to the treatment effect, they were divided into effective group (n=78) and ineffective group (n=42). The basic information, laboratory indicators and other data of the children were collected to explore the influencing factors of the efficacy of the children.

The daily dose of tacrolimus, trough concentration C₀, 24 h urinary protein and albumin in the effective group were higher than those in the ineffective group (all P<0.001), while the glomerular filtration rate was significantly lower than that in the ineffective group (P<0.001). After collinearity diagnosis, the indexes were included in Logistic regression analysis. The daily dose of tacrolimus, trough concentration C₀, glomerular filtration rate and albumin were all protective factors affecting the efficacy of children with LN (P<0.05), while 24 h urine protein quantification was a risk factor (P<0.05). The receiver operating characteristic curve was drawn. The AUC of glomerular filtration rate, 24-hour urinary protein quantification, and albumin in predicting the efficacy of children with LN was 0.882 [95% CI: 0.809-0.956], 0.861 [ 95 % CI: 0.790-0.932], 0.897 [95% CI: 0.837-0.956]. The AUC and optimal cut-off value of tacrolimus daily dose and trough concentration C₀ in predicting the efficacy of children with LN were 0.750 [95% CI : 0.649-0.851 ], 1.45 mg and 0.772 [ 95 % CI: 0.691-0.853 ], 4.05 ng·mL^-1.

The trough concentration of tacrolimus (C₀) is significantly correlated with the clinical efficacy of LN in children, and the daily dose and trough concentration C₀ are key factors affecting the efficacy.

To establish a population pharmacokinetic (PPK) model of duloxetine (DLXT) in hospitalized patients with depression, to investigate its influencing factors, and to provide reference for individualized medication.

A total of 325 patients who were hospitalized and received oral DLXT treatment at Shenzhen Kangning Hospital from January 2022 to October 2025 were retrospectively included, and their medication information, plasma concentrations, and other clinically relevant data were collected. Nonlinear mixed-effects modeling (NONMEM) was used to establish a PPK model of DLXT concentrations. Goodness-of-fit (GOF) plots, visual predictive check (VPC) and Bootstrap were used to evaluate the stability and predictive performance of the model, respectively. Based on the significant covariates identified in the final model, the steady-state plasma concentrations (C_ss) of DLXT over time were simulated under different dosage regimens in various populations.

A one-compartment model with first-order absorption and elimination was developed using 450 plasma concentration data points from 325 inpatients. The inter-individual variability of apparent clearance (CL/F) was 42.2%, and the proportional residual variability was 27.1%. Gender was identified as a significant covariate affecting CL/F. The final model was expressed as: CL/F(L·h^-1)=64.6×(1-0.25×Gender), where Gender is an indicator variable (male=0, female=1). The apparent volume of distribution was 1 530 L, and the absorption rate constant was fixed at 0.168 h^-1. Monte Carlo simulations showed that the C_ss in females was higher than that in males at the same doses.

A PPK model for DLXT in hospitalized patients with depression was successfully established. The final model is stable and reliable, and it can be used for individualized dosing regimens in clinical practice.

To establish a high-efficiency and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantitative analysis of cyclosporine A in human whole blood.

Protein precipitation with methanol was employed for sample pretreatment, and cyclosporine A-d₄ was used as the internal standard. Chromatographic separation was performed on a Kinetex C₁₈ column (3.0 mm×50.0 mm, 2.6 μm, 100 Å) with a mobile phase consisting of 0.1% formic acid in water (phase A) and 0.1% formic acid in methanol (phase B) at a flow rate of 0.55 mL·min^-1. The column temperature was maintained at 40 ℃. Quantitative detection was carried out using electrospray ionization in positive ion mode and multiple reaction monitoring (MRM). The method was validated for specificity, calibration curve and lower limit of quantitation (LLOQ), accuracy and precision, matrix effect, and sample stability.

The retention time of cyclosporine A was 1.19 min, with a total run time of 2.0 min per sample. A good linear relationship was observed in the concentration range of 10-1 000 ng·mL^-1 (r=0.998 5), and the LLOQ was 10.0 ng·mL^-1. The recovery rates ranged from 99.53% to 102.83%, with intra-batch precision ≤3.58% and inter-batch precision ≤3.24%. The sample stability was satisfactory, and the matrix effect was negligible.

The established method features short analysis time, high sensitivity, and low sample volume requirement, making it suitable for therapeutic drug monitoring and accurate quantification of cyclosporine A in human whole blood samples.

To evaluate the clinical efficacy and safety of intrathecal nusinersen combined with risdiplam in children with spinal muscular atrophy (SMA).

A total of 75 children with SMA were divided into a control group and an experimental group. The control group received intrathecal nusinersen (12 mg) at loading doses on days 0, 14, 28, and 63, followed by maintenance doses every 4 months for 12 months. The experimental group received additional oral risdiplam once daily, with the dose adjusted according to age and body weight, for 12 months. Clinical efficacy, motor function, pulmonary function, and adverse drug reactions were compared between the two groups.

Following treatment, the overall response rates in the experimental group and control group were 91.67% (33 cases/36 cases) and 82.05% (32 cases/39 cases), respectively, with no statistically significant difference between the two groups. (P>0.05). After treatment, the revised upper extremity module (RULM) scores in the experimental group and control group were 32.69±2.07 and 31.59±1.97, respectively; the Hammersmith Functional Motor Scale Expanded (HFMSE) scores for spinal muscular atrophy were 27.75±6.19 and 24.62±6.08, respectively; the 6-minute walking test (6MWT) results were (323.28±29.99) and (303.18±31.39) meters, respectively; the percentage of predicted forced vital capacity (FVC%pred) was (88.09±7.63)% and (83.85±7.79)%, respectively; the percentage of predicted forced expiratory volume in one second (FEV1%pred) was (97.54±8.69)% and (93.28±8.95)%, respectively; the percentage of predicted peak expiratory flow (PEF%pred) was (84.31±8.14)% and (79.64±8.05)%, respectively. In the PedsQL^TM-SMA Module, the scores for daily activities were 1.97±0.17 and 1.85±0.37, motor function scores were 2.14±0.35 and 2.03±0.28, fatigue/pain scores were 2.06±0.23 and 1.97±0.28, social interaction scores were 1.83±0.38 and 1.72±0.51, treatment worry scores were 1.94±0.23 and 1.85±0.37, and emotional functioning scores were 2.11±0.40 and 1.97±0.28, respectively. Serum neurofilament light chain (NfL) levels were (16.58±2.09) and (17.57±2.14) pg·mL^-1, and serum creatine kinase (CK) levels were (59.72±6.81) and (61.73±7.33) U·L^-1, respectively. Statistically significant differences were observed in the above indicators between the two groups (P<0.05). The overall incidence of adverse drug reactions in the experimental group and control group was 8.33% and 10.26%, respectively, with no statistically significant difference (P=0.775).

Intrathecal nusinersen combined with risdiplam significantly improves motor function in children with SMA compared with nusinersen alone, without increasing adverse drug reactions.