Objective:To analyze the registration status of acute pancreatitis-related clinical studies registered on the Chinese Clinical Trial Registry (ChiCTR) and USA ClinicalTrials.gov database.Methods:The ChiCTR and ClinicalTrials.gov database were searched to collect, sort and analyze the clinical studies related to acute pancreatitis registered from the establishment of the database to December 31, 2020. The clinical trials were manually grouped, and the features of clinical researches were compared based on different registered data (2007-2014 vs 2015-2020) and different financial sources (self-support, enterprise support or public support). Results:A total of 157 registered clinical studies related to acute pancreatitis have been included (ChiCTR n=99; ClinicalTrial.gov n=58). The top three areas with the greatest number of registered clinical studies were Sichuan (28.0%), Shanghai (14.6%) and Jiangsu (12.1%), totally accounting for 54.7%. There were 91 interventional studies, 41 observational studies and 25 other type studies. Masking was performed in 34 studies (21.6%). Randomized parallel controlling was performed in 84 studies (53.5%). 30 trials (19.1%) were at Ⅳ phase, and 7 trials (4.4%) were at Ⅱ or Ⅲ phase. 2007-2014 group tended to use randomized parallel controlled design (68.3% vs 45.4%, P=0.005) and randomization grouping (76.7% vs 47.4%, P=0.001). 2015-2020 group tended to use relatively large sample (72.6% vs 47.4%, P=0.002)and data management committee (53.6% vs 25.0%, P=0.001). The differences between the two groups were statistically significant. Of 92 trials from ChiCTR database, 48 were self-supported, 5 was supported by enterprise, and 38 was supported by the public. The percentage of self-support and public support was 86.9%. Conclusions:The number of acute pancreatitis-related clinical studies registered on ChiCTR was generally on the increase. Most registered studies were funded by public finances or by the researchers' institutions self. There was a lack of phaseⅡ or phase Ⅲ.

BACKGROUND:Numerous basic and clinical trials have confirmed that the low survival rate after bone marrow mesenchymal stem cell transplantation is a serious constraint on its long-term therapeutic effect.Previous studies have shown that apoptosis-related factors play an important role in the apoptosis of bone marrow mesenchymal stem cells,of which apoptosis-inducing factor may be a key factor. OBJECTIVE:Bone marrow mesenchymal stem cells,of which apoptosis-inducing factor was knocked down,were transplanted into infarcted myocardium of mice,aiming to certify the importance of apoptosis-inducing factor in the survival of bone marrow mesenchymal stem cells to further recover cardiac function after infarction. METHODS:Firstly,bone marrow mesenchymal stem cells were infected with LV-AIF-shRNA lentivirus to down-regulate the expression of apoptosis-inducing factor protein.Flow cytometry,western blot assay,and RT-qPCR were used to detect the infection efficiency of lentivirus.CCK-8 assay was used to detect the cell viability of bone marrow mesenchymal stem cells with apoptosis-inducing factor knockdown under hypoxic and ischemic conditions.Then,with the mouse model of acute myocardial infarction constructed,the normal bone marrow mesenchymal stem cells and bone marrow mesenchymal stem cells with apoptosis-inducing factor gene knockdown were transplanted into the model,respectively.The expression of apoptosis-inducing factor was examined by fluorescence immunoassay.Serum brain natriuretic peptide levels were detected by ELISA.Cardiac ultrasound was used to detect cardiac function.Myocardial fibrosis was observed by Masson staining.The expression of SRY gene was detected by RT-qPCR in apoptosis-inducing factor-knocked bone marrow mesenchymal stem cells after transplantation,reflecting cell survival. RESULTS AND CONCLUSION:(1)Bone marrow mesenchymal stem cells with apoptosis-inducing factor gene knockdown were successfully established by LV-AIF-shRNA lentivirus infection,following 97.7%of infection efficiency,and notably decline of the expression of apoptosis-inducing factor(P<0.001).(2)Under ischemia and hypoxia,the cell viability of apoptosis-inducing factor knockdown bone marrow mesenchymal stem cells was significantly increased compared with normal bone marrow mesenchymal stem cells.(3)Compared with normal bone marrow mesenchymal stem cells after transplantation,the survival number of bone marrow mesenchymal stem cells in the infarcted myocardium after apoptosis-inducing factor gene knockdown was significantly increased to 3.71 times(P<0.001),and the apoptosis-inducing factor protein expression and myocardial fibrosis degree in the infarcted area were significantly reduced.(4)Compared with normal bone marrow mesenchymal stem cells,the serum brain natriuretic peptide level of bone marrow stem cells with apoptosis-inducing factor gene knockdown after transplantation was significantly decreased(P<0.05),and left ventricular ejection fraction and left ventricular shortening fraction were significantly improved(P<0.05).(5)These findings confirm that apoptosis-inducing factor gene knockdown can reduce myocardial fibrosis and improve cardiac function after acute myocardial infarction via enhancing the bone marrow mesenchymal stem cell viability and increasing the bone marrow mesenchymal stem cell survival after transplantation in the donor.