This article aims to provide a reference for the dynamic regulatory oversight of clinical trials of stem cell drugs and the enhancement of pharmacovigilance practices.

Using data from the Drug Clinical Trial Registration and Information Disclosure Platform and the Pharmacovigilance Database of the Center for Drug Evaluation of the National Medical Products Administration, we conducted a retrospective analysis of the progress of domestic registered clinical trials for stem cell drugs and of individual case safety reports on suspected unexpected serious adverse reactions (SUSAR).

As of June 30, 2025, a total of 134 Investigational New Drug (IND) applications for stem cell drugs have been approved in China, and 113 registered clinical trials are recorded on the registration platform. From January 2021 to June 2025, a total of 29 domestic SUSAR reports were received, with adverse reactions mainly involving systemic disorders and administration site reactions, as well as respiratory disorders.

Registered clinical trials of stem cell drugs in China have shown a steady development trend in recent years. Sustained attention must be paid to the long-term potential safety risks of stem cells to safeguard the safety of clinical trials.

To systematically explore the antidepressant multi-target mechanism of Shenge Bushen Capsules, and evaluate its direct effect on dopamine (DA) and norepinephrine (NE) system, as well as the inhibition of monoamine oxidase A (MAO-A) activity and the protective effect on glucose-deficient and hypoxic neurons.

The effects of yohimbine on DA and NE systems were evaluated by apomorphine-induced mouse stereotyped behavior model and yohimbine-enhanced toxicity test, respectively. Its effect on MAO-A activity in mouse brain was studied by in vitro fluorescence assay. The model of oxygen-glucose deprivation injury was established by primary cultured mouse cortical neurons, and the neuroprotective activity was evaluated by detecting the leakage rate of lactate dehydrogenase (LDH).

Shenge Bushen Capsules had no significant effect on apomorphine-induced stereotyped behavior and did not enhance the lethal toxicity of yohimbine. In vitro experiments showed that the drug had a significant inhibitory effect on MAO-A at a concentration of 4×10^-4 g·mL^-1. In the neuroprotective experiment, Shenge Bushen Capsules could significantly reduce the LDH leakage rate of glucose-deficient hypoxic neurons at a low concentration of 10×10^-6 g·mL^-1 in a concentration-dependent manner.

The antidepressant effect of Shenge Bushen Capsules is not achieved by directly regulating the DA or NE system. The mechanism is related to the inhibition of MAO-A activity to reduce the degradation of monoamine neurotransmitters and the direct protection of neurons from damage.

To analyze the current situation and causes of protocol violations in pediatric drug clinical trials, develop strategies to prevent and reduce them, and provide a reference for standardized implementation of pediatric drug clinical trials.

Cases of protocol violations in pediatric drug clinical trials at a Grade Ⅲ Level A specialized women and children's hospital from January 2022 to June 2025 were collected. A retrospective analysis of the types of protocol violations, responsible entities, and specific causes was performed, and targeted improvement measures were formulated accordingly.

Across 24 pediatric drug clinical trials, a total of 186 occurrences of protocol violations were recorded. The primary types included sample-related violations, visit-related violations, medication-related violations, and examination/test-related violations. When classified by the responsible entity and ranked by frequency of occurrence, the order was: subjects/guardians, investigators, clinical research coordinators, sponsors, and other factors.

Throughout the entire process of pediatric drug clinical trials, continuous summary and optimization work should be carried out, and corresponding strategies should be formulated for each responsible entity to effectively reduce the incidence of protocol violations, thereby providing practical reference for improving the quality of pediatric clinical trials.

To investigate the clinical efficacy of Longmu Ningxin Formula (LMNXF) in treating children with attention deficit hyperactivity disorder (ADHD) and to explore its potential mechanism of action through animal experiments and proteomics.

A total of 80 children with ADHD were randomly divided into a western medicine group (n=40) and a Chinese medicine group (n=40). The western medicine group was treated with methylphenidate hydrochloride extended-release tablets (MPH), while the Chinese medicine group received LMNXF. The treatment lasted for 12 weeks. The scores of the Swanson, Nolan, and Pelham-Ⅳ Rating Scale (SNAP-Ⅳ, parent version), the Weiss Functional Impairment Rating Scale (WFIRS, parent version), the Conners' Parent Rating Scale (CPRS), and the Chinese medicine syndrome scores were compared between the two groups before and after treatment. Safety was also evaluated. For the animal experiment, the spontaneously hypertensive rat (SHR), a classic ADHD model, was used. A total of 18 4-week-old male SHRs were randomly divided into a model group, a Chinese medicine group, and a western medicine group. A total of 6 Wistar-Kyoto rats served as the control group. The Chinese medicine group received LMNXF at 38.00 g·kg^-1·d^-1, the western medicine group received MPH at 4.22 mg·kg^-1·d^-1, and the control and model groups were administered an equal volume of saline by gavage. Treatment lasted for 4 weeks. Behavioral tests were conducted to assess the rats' performance. After the experiment, prefrontal cortex tissues were collected for quantitative proteomic analysis, and Western Blot analysis was performed to validate differentially expressed proteins.

After treatment, the scores of the SNAP-Ⅳ, WFIRS, CPRS, and the primary and secondary Chinese medicine syndrome scores in the Chinese medicine group were significantly decreased compared to those before treatment (all P<0.001). The improvements in the WFIRS and CPRS scores and the Chinese medicine syndrome scores in the Chinese medicine group were greater than those in the western medicine group (all P<0.05). No serious adverse reactions related to the study drugs were observed in any child during the treatment period. LMNXF significantly ameliorated hyperactivity/impulsivity and spatial learning/memory deficits in SHRs (all P<0.05). Proteomic analysis of the prefrontal cortex identified 273 differentially expressed proteins between the model group and the Chinese medicine group. These proteins were primarily involved in seven pathways, including the NOD-like receptor signaling pathway, FoxO signaling pathway, and intestinal immune network for IgA production. Western Blot results showed that LMNXF reversed the upregulation of Ripk2, Tab1, and IL-6 in the prefrontal cortex of SHRs.

LMNXF demonstrates favorable efficacy and a high safety profile in treating children with ADHD. Its mechanism of action may involve modulating Ripk2, Tab1, and IL-6 expression in the prefrontal cortex, thereby inhibiting NOD-like receptor signaling pathway-mediated neuroinflammation.

To optimize the extraction and formulation processes for paediatric appetite-enhancing Gel (PAG).

The content of forsythoside, dry extract yield, and total flavonoid content in PAG were used as evaluation indicators. The analytic hierarchy process (AHP) combined with the criteria importance through intercriteria correlation (CRITIC) method was employed to calculate the comprehensive weighting coefficients for each indicator. The factors considered were water-to-raw-material ratio, extraction time, and extraction number. A multi-indicator comprehensive scoring method combined with the Box-Behnken design-response surface methodology (BBD-RSM) was used to design the experiment, aiming to determine the optimal water extraction process for PAG. The formulation process of PAG was optimized based on evaluation criteria including appearance and adhesiveness.

The optimal process for PAG was determined to be a water-to-raw-material ratio of 10-fold, extraction for 1.5 h, and three extraction cycles. Validation experiments confirmed that the extraction process for PAG is stable and feasible. The optimal formulation process for PAG was determined to be: carrageenan∶barley β-glucan∶sucrose∶water (2 g∶1 g∶1 g∶30 mL).

Based on the quality-by-design principle, the extraction process for PAG was optimized through a combined approach of multi-criteria evaluation and the Box-Behnken response surface methodology. Subsequently, the formulation process for the gel was refined using evaluation criteria such as appearance and adhesiveness. This study provides reference data for the modern extraction research on this formulation and for the development of pediatric preparations.

To develop an extemporaneous oral vehicle suitable for dose-splitting administration in special populations and to evaluate its clinical feasibility.

Based on analysis of reference product and formulation screening, an oral vehicle was prepared and evaluated for critical quality attributes (CQAs) and stability. Using spironolactone tablets as a model drug, the solubility, content stability, and dispersion uniformity of the drug in the vehicle were investigated. A preliminary subjective assessment of palatability was also performed.

The prepared vehicle met the specifications for appearance, pH, relative density, preservative content, and microbial limits. It remained stable under accelerated and long-term storage conditions, enabling a 24-month shelf life for routine stocking in medical institutions. Spironolactone was uniformly dispersed in the vehicle and remained physicochemically stable for 60 days, with drug content maintained above 90% and a dispersion uniformity relative standard deviation (RSD=1.29%). Subjective palatability evaluation showed improved palatability.

The developed oral vehicle demonstrates robust control of critical quality attributes and system stability, enabling the model drug to maintain uniform dispersion and physicochemical stability during dose-splitting compounding. It holds promise for providing a feasible approach for individualized dose-splitting administration in special populations.

To compare the cost-effectiveness of recombinant human follicle-stimulating hormone alfa (follitropin alfa, GONAL-f^®) versus other recombinant human follicle-stimulating hormone injections (Jinsaheng^®, Fangleshu^®, and Anxinbao^®) for controlled ovarian stimulation (COS) in infertile women undergoing assisted reproductive technology (ART).

A decision tree model was developed, simulating the treatment pathway of patients undergoing one ART cycle including one fresh embryo transfer cycle and three frozen embryo transfer cycles following a single COS treatment. Clinical parameters were derived from three independent randomized controlled trials and expert interviews. Drug utilization data for cost parameters came from the same trials, while drug prices were sourced from Yaozh.com. Costs of other medical services were obtained from provincial/city medical price lists and expert opinions. The base-case analysis used cumulative live birth rate (CLBR) as the effectiveness measure to calculate the incremental cost-effectiveness ratio (ICER). The robustness of the results was tested through one-way sensitivity analysis and probabilistic sensitivity analysis (PSA).

Although the total cost of the GONAL-f strategy was higher than that of Jinsaheng, Anxinbao, and Fangleshu (incremental cost: ￥1 219.44, ￥643.19, and ￥250.61, respectively), it also yielded higher CLBRs (incremental CLBRs: 3.91%, 3.13%, and 3.84%, respectively). The average cost per live birth was ￥44 238.72 vs ￥44 844.00 (GONAL-f vs Jinsaheng), ￥52 701.11 vs ￥54 096.63 (GONAL-f vs Anxinbao), and ￥44 028.08 vs ￥45 775.20 (GONAL-f vs Fangleshu). The corresponding ICERs were ￥31 174.32, ￥13 795.07, and ￥6 530.83 per additional live birth, respectively. Sensitivity analyses supported the base-case findings. In the PSA, as the willingness-to-pay (WTP) threshold increased to over ￥100 000, the probability of GONAL-f being cost-effective stabilized at approximately 92.9%, 69.9%, and 81.9% compared to Jinsaheng, Anxinbao, and Fangleshu, respectively. At a WTP of ￥35 000, these probabilities were 58.0%, 71.9%, and 77.8%, respectively.

This study indicates that for COS in ART, GONAL-f incurs higher costs but also achieves higher CLBRs compared to Jinsaheng, Anxinbao, and Fangleshu. GONAL-f is the more cost-effective option when the WTP exceeds ￥31 174.32 per additional live birth.