[Progress on clinical trials of common gastrointestinal cancer drugs in China from 2012 to 2021].

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.

SETD5-AS1 stimulates neuron death in stroke via promoting PTEN expression.

OBJECTIVE: To investigate the specific role of long non-coding RNA (lncRNA) SETD5-AS1 in regulating stroke development, and its underlying mechanism. MATERIALS AND METHODS: Middle cerebral artery occlusion (MCAO) model and OGD/R (oxygen-glucose deprivation/reoxygenation) model were constructed for exploring the mechanism of ischemia-reperfusion injury induced by ischemic stroke. SETD5-AS1 expression in brain tissues of ischemic stroke mice and control mice was detected by quantitative Real-time-polymerase chain reaction (qRT-PCR). Proliferation and apoptosis of N2a cells were detected after transfection of overexpression plasmid or siRNA SETD5-AS1. The downstream gene of SETP5-AS1 was predicted by Starbase and PTEN was screened out. Both mRNA and protein expressions of PTEN in MCAO model and OGD/R model were detected. Furthermore, the binding condition of SETD5-AS1 and PTEN was verified by dual-luciferase reporter gene assay, RNA pull-down assay and RNA binding protein immunoprecipitation (RIP). The regulatory effect of SETD5-AS1 on PI3K/AKT pathway was detected by Western blot. RESULTS: SETD5-AS1 was highly expressed in the ischemia-reperfusion injury model. Overexpression of SETD5-AS1 in N2a cells resulted in increased apoptosis and decreased proliferation. PTEN expression was upregulated in MCAO model and OGD/R model. Dual-luciferase reporter gene assay indicated that SETD5-AS1 can promote PTEN transcription. The binding condition of SETD5-AS1 and PTEN was further verified by RNA pull-down assay and RIP. Overexpression of SETD5-AS1 in N2a cells inhibited PI3K/AKT pathway. CONCLUSIONS: SETD5-AS1 is highly expressed in the ischemia-reperfusion injury model. SETD5-AS1 participates in the development of ischemic stroke by activating PTEN and inhibiting PI3K/AKT pathway.