Based on the previously established competency model for clinical investigators in drug clinical trials, this study aims to evaluate the effectiveness of a targeted training program, clarify the role of this model in improving investigators’ professional competence, operational skills, and ethical awareness, and provide evidence-based basis for the precise optimization of clinical trial training models.

Investigators from tertiary Grade A hospitals in Beijing who had participated in at least one clinical trial in the past three years were selected as the research subjects. The training content was designed based on the core elements of the competency model. A pre-training and post-training paired design was adopted to evaluate the improvement of knowledge and skills through standardized Good Clinical Practice (GCP) simulation tests; online questionnaire surveys were conducted to collect trainees’ satisfaction feedback on training content, teaching quality, organizational management and other dimensions. Wilcoxon signed-rank test was used to compare scores before and after training. Stratified by gender, the Mann-Whitney U test was used to compare the inter-group differences in post-training competency scores of investigators of different genders. Stratified by educational background, professional title and working years of clinical trial practice, the Kruskal-Wallis H test was adopted to analyze the inter-group differences in post-training scores among investigators with different educational levels, different professional titles, and different working years.

A total of 81 clinical investigators were included, with a median age of 34 (31.00, 44.00) years. The proportions of males and females were 27.16% and 72.84%, respectively. Among the participants, 62.96% held doctoral degrees, and 32.10% had senior professional titles. The median pre-training total score (Q1, Q3) was 35.00 (31.00, 39.00) scores, while the median post-training total score (Q1, Q3) was 43.00 (40.00, 46.00) scores, indicating a significant improvement in the trainees’ total scores (Z=-7.30, P<0.001). The scores for all competency sub-dimensions increased significantly compared to those before training. Among them, the differences in scores before and after training for ethical awareness and subject protection, GCP implementation capability, study design and protocol execution, and data quality control were all statistically significant (all P<0.001). Subgroup analysis showed that the total competency scores of investigators with different genders, professional titles, and years of experience in clinical trials significantly improved after training, with no statistically significant differences in the magnitude of improvement between groups. Participants with master’s or doctoral degrees showed significant improvements in post-training scores (all P<0.001), while those with bachelor’s degrees showed no significant difference between pre- and post-training scores (P>0.05). Furthermore, 85.19% of the trainees rated the overall performance of the training as very satisfied.

The training program designed based on the competency model could improve the GCP theoretical level and practical knowledge reserve of clinical investigators in clinical trials, and has good trainee acceptance and practicality. By accurately matching the core competency needs of clinical investigators, this training model provides a replicable practical path for the optimization of the clinical trial talent training system.

To compare the clinical efficacy of daratumumab injection combined with lenalidomide capsules and dexamethasone injection in the treatment of multiple myeloma (MM).

Patients with MM were divided into control group and treatment group according to the treatment method. Patients in the control group received the bortezomib for injection, lenalidomide capsules and dexamethasone injection (VRd) regimen; patients in the treatment group received the daratumumab injection, lenalidomide capsules and dexamethasone injection (DRd) regimen. The VRd regimen: Within each 28-day cycle, bortezomib for injection at 1.3 mg·m^-2, lenalidomide capsules at 25 mg·d^-1 and dexamethasone injection at 20 mg·d^-1 were administered according to the standard protocol. The DRd regimen: Based on lenalidomide capsules and dexamethasone injection , daratumumab injection at 16 mg·kg^-1 was added (once weekly in cycles 1-2, once every 2 weeks in cycles 3-6, and once every 4 weeks thereafter). Efficacy was evaluated after 3 cycles of treatment in both groups. Clinical efficacy, MM-related biomarkers and adverse reactions were compared between the two groups.

The study enrolled 88 patients, with 45 cases in the control group and 43 cases in the treatment group. Post-treatment evaluation revealed objective response rates (ORR) of 77.78% (35 cases/45 cases) and 90.70% (39 cases/43 cases) for the control and treatment groups, respectively, demonstrating no statistically significant intergroup difference (P>0.05). After treatment, the levels of hemoglobin of control group and treatment group were (102.85±15.87) and (109.71±16.24) g·L^-1, respectivley; the levels of β2-microglobulin (β2-MG) were (4.29±1.12) and (3.67±1.03) mg·L^-1, respectivley; the levels of lactate dehydrogenase (LDH) were (167.29±30.92) and (152.32±29.67) U·L^-1, respectivley; the levels of monoclonal protein (M protein) were (17.42±3.87) and (15.39±3.42) g·L^-1, respectivley; bone marrow plasma cells were (10.25±2.13)% and (8.92±2.06)%, respectivley; cluster of differentiation 3 positive (CD3⁺) were (62.45±8.74)% and (67.06±9.12)%, respectivley; CD4⁺ levels were (34.26±5.12)% and (37.68±5.33)%, respectivley; CD4⁺/CD8⁺ ratios were 1.16±0.24 and 1.28±0.22, respectivley. Compared the control group with treatment group, the differences of above indexes were all statistically significant (all P<0.05). The total incidence of peripheral neuropathy of control group and treatment group were 22.22% (10 cases/45 cases) and 2.33% (1 case/43 cases), respectivley; myelosuppression were 15.56% (7 cases/45 cases) and 37.21% (16 cases/43 cases), respectivley; infection were15.56% (7 cases/45 cases) and 34.88% (15 cases/43 cases), respectivley, all with statistically significant differences (P<0.05, P<0.01).

While ensuring clinical efficacy, the DRd regimen exerts more significant effects in improving immune function, levels of MM-related biomarkers, and quality of life, and significantly reduces the incidence of peripheral neuropathy. However, it is associated with increased risks of myelosuppression and infection.

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.

To explore the clinical efficacy of recombinant human brain natriuretic peptide (rhBNP) combined with amiodarone on patients with elderly heart failure (HF) complicated with ventricular arrhythmia (VA) and its impact on heart rate variability (HRV).

From January 2023 to January 2025, 220 patients with patients with elderly HF complicated with VA admitted to our hospital were prospectively selected and randomly separated into a control group (amiodarone) and an experimental group (rhBNP+amiodarone), with 110 patients in each group. The clinical outcomes, cardiac function, HRV indicators, serum N-terminal pro brain natriuretic peptide (NT-proBNP), QT interval dispersion (QTd), and adverse events were compared.

After treatment, the total effective rate in the experimental group was significantly higher than that in the control group (P<0.05). The experimental group had lower left ventricular end systolic diameter (LVESD), left ventricular end diastolic diameter (LVEDD), NT-proBNP, and QTd than the control group (P<0.05), and higher left ventricular ejection fraction (LVEF), cardiac output (CO), RMSSD, SDNN, and PNN50 than the control group (P<0.05).

The combination of rhBNP and amiodarone has a conspicuous effect on patients with elderly HF complicated with VA. It can optimize cardiac function and HRV, improve electrophysiological stability, and has good safety.

This study aimed to reassess the antibiotic treatment regimen for invasive community-associated methicillin-resistant Staphylococcus aureus(CA-MRSA) infections at a tertiary children’s hospital.

A retrospective analysis was conducted on cases of invasive clindamycin-resistant MRSA infections in children without underlying diseases between 2021 and 2025. A total of 34 children met the inclusion criteria, with the most common types of diagnosis being osteomyelitis (17 cases) and deep abscess (7 cases).

The median duration of intravenous (IV) antibiotic therapy was 11.5 days (interquartile range [IQR], 6-42 days), and the total treatment duration (IV + oral) was 32 days (IQR, 23-42 days). Overall, 50% of the children were subsequently switched to oral antibiotic therapy. The definitive antibiotics used for treatment included vancomycin (15 cases), TMP-SMX (trimethoprim-sulfamethoxazole, 9 cases), linezolid (7 cases), ceftaroline (2 cases), and doxycycline (1 case). The cure rates of different definitive antibiotic treatment regimens were similar: 73.3% in the vancomycin group, 88.9% in the TMP-SMX group, 50% in the ceftaroline group, and 100% in both the linezolid group and the doxycycline group. Three children died from MRSA infection, among whom 2 were treated with vancomycin and 1 with ceftaroline.

Vancomycin is the most commonly used drug for the treatment of invasive clindamycin-resistant CA-MRSA infections in children. However, in specific cases, TMP-SMX and linezolid may be considered as oral alternative options during the completion phase of treatment. Further research is still needed in the future to optimize the treatment regimen for such infections.

To explore the effect of the Mst1/Nrf2 pathway on myocardial autophagy function in type 2 diabetic mice, and to verify whether Mst1 gene knockout and Nrf2 activation can improve diabetic cardiomyopathy (DCM) by regulating autophagy.

The experimental animals were randomly divided into the following 4 groups, with 8 animals in each group: Control group (6 C57BL/6N mice, standard diet), DCM group (6 C57BL/6N mice), DCM+Mst1^-/- group (6 Mst1 gene knockout mice), high-sugar and high-fat diet, DCM+Mst1^-/-+Nrf2 group (6 diabetic mice with Mst1 gene knockout intervened by Tert-butylhydroquinone(tBHQ)(50 mg/kg/day)(PHR3512, Sigma-Aldrich). Cardiac function was detected by blood pressure, and autophagy was analyzed by Western blot.

The 4w systolic blood pressures of the control group, the high glucose control group, the high glucose Mst1 knockout group, and the high glucose Mst1^-/-±Nrf2 group were (103.6±1.43), (117.23±9.80), (111±7.43) and (109.21±3.22) mmHg, respectively, and the 8w systolic blood pressures were (99.09±1.46), (135.78±5.98), (123.57±8.90) and (119.97±6.97) mmHg, respectively. the 12w systolic blood pressures were (106.67±2.32), (138.90±2.00), (126.68±2.98) and (120.63±3.12) mmHg, respectively. The diastolic blood pressures at 4w were (79.50±1.12), (99.24±3.89), (85.03±1.89) and (82.90±3.22) mmHg, respectively. The diastolic blood pressures at 8w were (76.35±2.12), (106.78±5.98), (94.80±3.90) and (88.90±2.90) mmHg, respectively. The diastolic blood pressure at 12w were (78.79±1.70), (101.32±2.13), (93.62±3.98) and (89.02±1.92) mmHg, respectively. The 4-week mean arterial pressures were (87.51±0.41), (117.23±9.80), (85.56±1.46) and (83.91±2.23) mmHg, respectively. The 8-week mean arterial pressures were (84.24±2.41), (116.46±5.68), (104.80±3.91) and (98.90±2.90) mmHg, respectively. the 12-week mean arterial pressures were (86.09±1.74), (101.32±2.13), (103.60±3.37) and (99.02±1.55) mmHg, respectively. Compared with the mice in the Control group, the systolic blood pressure, diastolic blood pressure and mean arterial pressure of the mice in the DCM group, DCM+Mst1^-/- group and DCM+Mst1^-/-+Nrf2 group were significantly increased (P<0.000 01).

Improved cardiac diastolic function in mice with Mst1/Nrf2 activation. This effect is achieved by reducing the expression of p62 protein, further emphasizing that the Mst1/Nrf2 axis exerts its protective function by regulating autophagy-related proteins.

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 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.