To analyze the requirements of different sponsors for serious adverse event (SAE) reporting in clinical trials and the existing problems of suspected unexpected serious adverse reaction (SUSAR) report submission after the implementation of new edition of GCP thus to give possible suggestions to guide the trial parties in drug trial safety alert work and clinical trial risk control and improve the management of SAE/SUSAR.

SAE reports of 60 applicants and SUSAR reports of 64 applicants from July 1, 2020 to December 31, 2020 were collected. Taking the report submitted by the same sponsor in the same format as one valid study sample, 62 valid original SAE reports and 87 SUSAR reports were included for the analysis.

In the submitted SAE forms, 61.3% used the template designed by the sponsors, 32.3% used the original CFDA SAE report template, 6.4% used SAE reports derived directly from EDC. Differences existed in SAE forms provided by different sponsors. For the design of these SAE forms, there were problems such as field duplicate, unreasonable setting of field options, logistic problems, missing necessary fields, handwritten filling out, unclear fonts, and so on. Among the SUSAR reports received by the institute, 38 applicants reported individual SUSAR cases, 5 out of which (13.116%) used self-made form templates, 10 out of which used the original CFDA form template (26.31%), and 23 sponsors using the CIOMS form template (60.53%), showing that CIOMS template was the most commonly used for case reports. The 49 sponsors who submitted the column matrix used different formats, fields, and varied in time of submission.

There is no unified template for the SAE report form in the industry. Sponsors need to strengthen the normative design and filling guidelines for the SAE report form, so that the researchers can fill out the SAE report more efficiently and ensure the data quality of individual case safety reports. There are significant differences in the SUSAR reports submitted to institutions and ethics committees among different applicants. Some forms are not sufficient to meet the requirements of security information review, and the time limit and frequency of submitting SUSAR reports are different. Under the above-mentioned situation institutions and ethics committees may not be able to accurately determine the risk levels of the clinical trials and subjects. So the SAE/SUSAR report forms need to be further unified and standardized.

To optimize the preparation process of Qiwei Chanshen Capsules (QCC) and conduct quality standard research.

Using the comprehensive scores of molding rate, drying weight loss, moisture absorption rate, solid density and angle of repose as characteristic index, the preparation technology of QCC was optimized using Box-Behnken design-response surface method combined with G1-entropy weight method with regard to the factors such as drug dosage, wetting agent (ethanol) concentration and drying time. Moisture, volume difference, disintegration time limit were checked. TLC method was used for qualitative identification. HPLC wavelength switching method was used to simultaneously determine the contents of 3 components with anti-tumor effect, such as epicatechin, camptothecin, and ginsenoside Rb₁.

The best preparation process was as following: the dosage ratio of drug to adjuvant was 1∶1.15, the wetting agent (ethanol) concentration was 91%, and drying time was 117 min. The moisture, volume difference and disintegration time limit of the capsule were in line with Chinese Pharmacopoeia. TLC identification is highly specific. The linear ranges of the 3 components with anti-tumor effect were 0.52~16.74 μg·mL^-1 (r=0.999 6), 0.68~21.68 μg·mL^-1 (r=0.999 9), 6.70~214.49 μg·mL^-1 (r=0.999 7), respectively. RSDs of precision, stability and reproducibility tests were lower than 3%. The average recoveries were 97.11% (RSD=1.73%, n=6), 99.33% (RSD=1.68%, n=6), 99.18% (RSD=2.21%, n=6), respectively. The content of them were 0.158 8, 0.196 7, 3.091 3 mg·g^-1.

The preparation process of QCC is stable and feasible. The quality control method is comprehensive and systematic.

To explore the protective effects of metformin plus berberine against diabetes-induced cognitive dysfunction in db/db mice.

Mice were randomly divided into model, metformin, berberine, and metformin plus berberine (MB) groups. Db/m mice born in the same litter were used as the control group. Metformin (300 mg·kg^-1) and berberine (135 mg·kg^-1), either alone or in combination, were administered orally for 10 weeks. Body weight, blood glucose and related indices, and behavioral, oxidative stress-related, and inflammatory factor-related indexes of db/db mice were measured. Brain tissue sections were subjected to hematoxylin-eosin (HE) staining, and pathological changes were observed via light microscopy. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was used to observe changes in the levels of small molecules in the brain tissue.

Fasting blood glucose levels were significantly lower in the MB group than in the model, metformin, and berberine groups after 8 and 10 weeks of dosing. In the Morris water maze test, escape latency and time to find the platform from the contralateral quadrant were significantly shorter in the MB group than in the model group. The number of target crossings in 90 s and residence time in the target quadrant significantly increased in the metformin plus berberine group. According to ELISA, glycated hemoglobin, 8-hydroxydeoxyguanosine, protein carbonyl, tumor necrosis factor-α, NLRP3, and interleukin-1β levels were significantly lower in the MB group than in the model group, whereas interleukin-6 levels significantly increased. In HE staining experiments, compared with the model group, the neurons in the hippocampal region in the metformin plus berberine group were arranged neatly, with more complete shape, clear nuclear staining, and clear cell boundaries. In mass spectrometry imaging experiments, brain aspartate, N-acetyl-aspartate, and glutamate levels were significantly higher in the MB group than in the model group, whereas taurine and glucose levels significantly decreased.

Oral administration of MB has protective effects on diabetes-induced cognitive dysfunction and stronger effects than using either drug alone. The mechanism of action may be related to anti-inflammatory and antioxidative stress effects and increase in excitatory amino acids levels.

To analyze the correlation between blood drug concentration and kidney injury in children with medulloblastoma treated with high-dose methotrexate (HD-MTX) chemotherapy.

A total of 139 children with medulloblastoma treated with high-dose methotrexate chemotherapy were selected and their 782 blood drug concentrations, basic data, and laboratory examination results before and after treatment were retrospectively collected to analyze the correlation between changes in kidney function indicators and blood drug concentration.

Serum MTX concentrations at 24 h post medication were positively correlated with uric acid level, negatively correlated with creatinine clearance, but not with serum creatinine and blood urea nitrogen levels. Serum concentrations of MTX at 42 h post medication were positively correlated with serum creatinine and blood urea nitrogen levels, negatively correlated with creatinine clearance and blood urea nitrogen level.

Monitoring of MTX serum concentration can predict the kidney damage caused by MTX chemotherapy.