To provide practical references for all participants in drug clinical trials on drug safety risk management and promote the construction of a more efficient clinical trial safety management system.

Based on the regulatory practice of 40 clinical trial safety risk control cases from the Center for Drug Evaluation in 2024, this paper uses classified statistics and correlation analysis methods to analyze the characteristics of safety risk information from multiple dimensions such as drug types and indications, and systematically sorts out the response logic of regulatory measures.

Among the 40 cases where risk management procedures were initiated, distinct risk characteristics were observed across different drug types and indications. The regulatory measures reflected the principle of matching the intensity of control with the risk characteristics.

Regulatory authorities have adopted differentiated regulatory requirements in accordance with the logic of risk classification and bottom-line thinking. The regulatory initiatives have gradually evolved into focusing on the optimization and full-chain improvement of sponsors’ risk management systems, providing crucial support for the protection of subjects’ rights and interests as well as the high-quality development of pharmaceutical innovation..

This study aimed to evaluate analyze the current quality status of investigator-initiated trials (IITs) conducted in a hospital, analyze key influencing factors, explore targeted improvement measures, and provide references for enhancing the design level of IITs.

IITs registered in the Medical Research Registration and Filing Information System by the hospital from January 2020 to April 2025 were selected as the research objects. The research compliance, scientificity, and value were assessed, and then followed by statistical analysis.

Among the 124 IITs, 76% were initiated by investigators with associate senior titles or above. The median scores of the standardization and scientificity dimensions were both 8 points, while the median score of the research value dimension was 6 points. The total scores of interventional studies and observational studies were 23 and 21, respectively (P<0.01), and the total scores of multi-center studies and single-center studies were 23 and 20, respectively (P<0.001). Except for the correlation between funding support and the scientificity score, which the difference was not statistially signifccant (P>0.05), funding support showed a significant positive correlation with both the research compliance and research value dimensions (correlation coefficients ranging from 0.300 to 0.346, all P<0.001); disciplinary strength, and investigator title were significantly positively correlated with all three dimensions of research quality (correlation coefficients ranging from 0.213 to 0.380, P<0.01, P<0.001) and disciplinary strength had the greatest impact on research value.

Medical institutions still need to strengthen the standardization and scientificity of IITs, and there is great room for improvement in research value. Disciplinary strength, investigator background, and funding support are key factors affecting the research quality. From the perspective of institutional management, the quality of IITs can be effectively improved by constructing a systematical management system that integrates scientific review, methodological support and resource guarantee.

To investigate the effect of daratumumab on the levels of serum micro ribonucleic acid (miR) miR-140-5p, miR-17-3p and miR-29c in patients with relapsed and refractory multiple myeloma (RRMM).

In this study, 92 RRMM patients included in the study were divided into control and study groups by random number table method, 46 cases in each group. All cases were admitted to the Affiliated Hospital of Nantong University from January 2022 to January 2025. The control group was treated with VRD regimen (bortezomib, dexamethasone, lenalidomide), and the study group was treated with DVD regimen (daratumumab, bortezomib, dexamethasone). Both groups were treated for 21 d as a course of treatment, a total of 4 courses of treatment. The efficacy after 4 course of treatment, T lymphocyte subsets, inflammation-related indicators, serum miR-140-5p, miR-17-3p, miR-29c levels before and after 4 course of treatment, and safety were compared between the two groups.

Compared with the control group (65.22%), the total remission rate (84.78%) of the study group after 4 course of treatment was higher (P<0.05). Compared with before treatment, the levels of peripheral blood CD3⁺, CD4⁺, CD4⁺/CD8⁺ and serum interferon-γ (IFN-γ), miR-140-5p and miR-29c increased after 4 course of treatment in the two groups, and the study group were higher; the levels of peripheral blood CD8⁺, serum C-reactive protein (CRP), transforming growth factor-β (TGF-β) and miR-17-3p decreased, and the study group were lower (all P<0.05). No significant difference was observed between the two groups in terms of safety (P>0.05).

Daratumumab could effectively regulate T lymphocyte subsets, inflammation-related indicators and serum levels of miR-140-5p, miR-17-3p and miR-29c in RRMM patients, improve the immune function of the body, reduce the inflammatory response of the body. The curative effect was significant and the safety was good.

To explore the efficacy of ceftazidime/avibactam (CAZ/AVI) combined with polymyxin in the treatment of carbapenem-resistant Gram-negative bacteria (CRO) pulmonary infections.

A total of 80 patients with CRO pulmonary infections admitted to our hospital from December 2019 to December 2024 were selected and divided into a control group (n=37) and a CAZ/AVI group (n=43) based on treatment methods. The control group received colistimethate sodium combined with meropenem, while the CAZ/AVI group received CAZ/AVI combined with colistimethate sodium. The clinical efficacy, bacterial clearance rate, and prognosis were compared between the two groups. Based on treatment efficacy, patients were classified into an effective group and an ineffective group, and logistic analysis was performed to identify factors influencing treatment outcomes in CRO pulmonary infections.

The clinical efficacy and bacterial clearance rate in the CAZ/AVI group were higher than those in the control group (P<0.05); there was no statistically significant difference in 28-day mortality between the two groups (P>0.05). The levels of WBC, CRP, PCT, TNF-α, IL-6, and IL-10 in the CAZ/AVI group were lower than those in the control group (P<0.05). In the effective group, age, APACHE Ⅱ score, SOFA score, and the proportion of patients receiving continuous renal replacement therapy (CRRT) were lower than those in the ineffective group, while treatment duration and the proportion receiving CAZ/AVI combined with polymyxin were higher (P<0.05). Logistic analysis indicated that APACHE Ⅱ score, SOFA score, CRRT, treatment duration, and CAZ/AVI combined with polymyxin were influencing factors for treatment outcomes in CRO pulmonary infections (P<0.05).

CAZ/AVI combined with polymyxin shows significant efficacy in the treatment of CRO pulmonary infections.

To observe the clinical efficacy and safety of alirocumab injection combined with ticagrelor tablets in treating patients with moderate coronary artery stenosis accompanied by angina pectoris.

Patients exhibiting moderate coronary artery stenosis and angina pectoris were categorized into two groups according to their treatment methods: treatment group and control group. Both groups received basic treatment. The control group received additional ticagrelor tablets, starting with a dose of 180 mg, followed by 90 mg twice daily. The treatment group added alirocumab injection at an initial dose of 75 mg, subcutaneously injected every two weeks, with dose adjustments made from weeks 4-8 based on lipid levels. Both groups continued treatment for 12 weeks. The clinical efficacy, angina attack frequency, use of nitroglycerin tablets, echocardiographic parameters, lipid levels, coagulation and myocardial injury markers, Seattle Angina Questionnaire scores, 6-minute walk distances and safety evaluation were compared between the two groups. Safety was also evaluated.

A total of 92 patients were enrolled in this study, with 45 and 47 patients assigned to the control group and the treatment group, respectively. After treatment, the total effective rates were 75.56% (34 cases/45 cases) for the control group and 91.49% (43 cases/47 cases) for the treatment group. The corrected QTc intervals were (387.38±18.62) and (379.29±17.54) ms, respectively; QRS durations were (98.38±7.27) and (97.45±6.74) ms; cardiac outputs were (4.82±0.63) and (5.17±0.68) L·min^-1; cardiac indexes were (3.17±0.42) and (3.39±0.48) L·(min·m²)^-1; total cholesterol levels were (4.11±0.82) and (3.58±0.71) mmol·L^-1; triglyceride levels were (3.42±0.63) and (3.05±0.57) mmol·L^-1; low-density lipoprotein cholesterol levels were (3.42±0.54) and (2.95±0.40) mmol·L^-1; free fatty acid levels were (0.54±0.07) and (0.48±0.08) mmol·L^-1. The differences in the above indicators between the treatment group and the control group were all statistically significant (all P<0.05). The incidence rates of adverse reactions in control group and treatment group were 11.11% (5 cases/45 cases) and 14.89% (7 cases/47 cases), with no statistically significant difference (P>0.05).

Both alirocumab injection combined with ticagrelor tablets and ticagrelor tablets alone can treat moderate coronary artery stenosis associated with angina pectoris, however, the combination therapy more significantly improves efficacy, reduces the frequency of angina attacks and blood lipid levels, enhances overall cardiac function and quality of life, with good safety.

To explore the effect of hyperoside on insulin resistance in polycystic ovary syndrome rats by regulating adenosine monophosphate activated protein kinase (AMPK)/glycogen synthase kinase 3β (GSK3β) signaling pathway.

Nine female SD rats were randomly selected from 45 as the normal (NC) group (equal amount of distilled water), while the rest were used to construct a polycystic ovary syndrome model and grouped into model group (equal amount of distilled water), experimental-L group (0.7 mg·kg^-1·d^-1 hyperoside), experimental-H group (1.5 mg·kg^-1·d^-1 hyperoside), and inhibitor group (1.5 mg·kg^-1·d^-1 hyperoside and 0.2 mg·kg^-1·d^-1 Compound C), with nine rats in each group. The blood glucose meter was used to measure fasting blood glucose (FBG) in rats. Enzyme linked immunosorbent assay (ELISA) method was used to measure fasting insulin (FINS), testosterone (T), luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), triglycerides (TG), cholesterol (CHO), low-density lipoprotein (LDL), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. Hematoxylin-eosin (HE) staining was used to detect pathological changes in ovarian tissue. Western blot was used to measure AMPK/GSK3β signaling pathway proteins in ovarian tissue.

The serum FBG levels in NC group, model group, experimental-L group, experimental-H group and inhibitor group were (5.54±0.69), (7.32±0.91), (6.65±0.82), (5.97±0.72) and (6.98±0.85) mmol·L^-1, respectively; the serum FINS levels were (9.58±1.39), (15.87±1.96), (13.65±1.62), (11.42±1.57) and (15.04±1.85) mU·L^-1, respectively; HOMA-IR indexes were 2.36±0.43, 5.16±0.71, 4.03±0.47, 3.03±0.52 and 4.67±0.68, respectively; the serum TG levels were (0.68±0.09), (1.58±0.18), (1.27±0.17), (0.98±0.13) and (1.46±0.18) mmol·L^-1, respectively; the serum CHO levels were (0.76±0.09), (1.52±0.18), (1.24±0.16), (1.01±0.14) and (1.41±0.17) mmol·L^-1, respectively; serum LDL levels were (1.62±0.23), (3.59±0.46), (3.06±0.42), (2.54±0.31) and (3.38±0.44) mmol·L^-1, respectively; serum LH levels were (4.21±0.57), (9.48±1.39), (7.86±0.96), (6.25±0.74) and (8.87±1.18) ng·mL^-1, respectively; serum FSH levels were (19.38±2.52), (8.27±1.05), (11.36±1.42), (14.65±1.76) and (9.57±1.48) ng·mL^-1, respectively; the serum T levels were (6.82±0.95), (13.86±1.62), (11.39±1.48), (8.98±1.14) and (12.64±1.53) ng·mL^-1, respectively; serum E2 levels were (1.02±0.14), (0.48±0.07), (0.72±0.09), (0.95±0.13) and (0.61±0.08) ng·mL^-1, respectively; the serum IL-6 levels were (53.46±7.69), (123.58±18.32), (98.39±13.58), (74.58±9.37) and (114.27±14.72) pg·mg^-1, respectively; serum TNF-α levels were (43.74±6.82), (82.19±10.46), (66.39±8.27), (51.72±7.24) and (73.54±1.02) pg·mg^-1, respectively; the relative protein expression levels of p-AMPK/AMPK in ovarian tissues were 0.79±0.11, 0.27±0.04, 0.49±0.07, 0.71±0.09 and 0.38±0.06, respectively; the relative protein expression levels of p-GSK3β/GSK3β were 0.19±0.04, 0.68±0.09, 0.47±0.07, 0.28±0.04 and 0.59±0.08, respectively. Among the above indexes, there were all statistically significant differences between NC group and modell group, model group and experimental-L group, experimental-L group and experimental-H group, experimental-H group and inhibitor group (all P<0.05).

Hyperoside improves insulin resistance in polycystic ovary syndrome rats by regulating AMPK/GSK3β signaling pathway.

To investigate the expression of methyltransferase-like 3 (METTL3) in cerebrospinal fluids (CSF) and its correlation with the prognosis of children with medulloblastoma (MB).

Cerebrospinal fluids were collected from MB children. METTL3 protein levels were quantified using the Enzyme-Linked ImmunoSorbent Assay (ELISA) and its correlations with clinicopathological features were analyzed. The prognostic significance was evaluated via the Kaplan-Meier survival curve and Cox proportional hazards regression. Bioinformatics analysis was conducted to assess the association of METTL3 with chemotherapeutic drug sensitivities and functional enrichment of METTL3 in brain tumors.

Ki-67 index was the only clinicopathological factor significantly correlated with CSF METTL3 levels (P<0.05). METTL3 high expression group showed superior progression-free survival (PFS) (HR=0.376, 95% CI:0.133-1.064, P<0.05). Cox analysis identified METTL3 expression as an independent prognostic factor for PFS (P<0.05). Significant negative correlations between METTL3 expression and 50% inhibitory concentrations (IC₅₀) of methotrexate/vinblastine/etoposide (P<0.001). Gene enrichment revealed METTL3′s involvement in neural development and Notch signaling pathways.

METTL3 might serve as a prognostic biomarker for MB pediatric patients. Further validation with expanded cohorts and mechanistic studies (in vivo/in vitro) is warranted.