Objective:To investigate the effect of aucubin(AU)on mitochondrial autophagy in the hippocampus of ischemic stroke(IS)rats by regulating the pten-induced kinase protein 1(PINK1)/cytoplasmic E3-ubiquitin ligase(Parkin)signaling pathway.Methods:The IS rat model was established by middle cerebral artery occlusion(MCAO),and was randomly divided into IS group,low-dose AU group(AU-L),medium-dose AU group(AU-M),high-dose AU group(AU-H),and high-dose AU combined with 3-MA group(AU-H+3-MA).The rats without liga-tion were used as the Sham surgery group.Zea Longa score was used to evaluate the neurological function of rats.TTC staining was used to detect the percentage of cerebral infarction volume.The microstructures of mitochondria were observed by transmission electron microscopy,and the changes of autophagy protein-microtubule associated protein light chain 3B(LC3B)and p62 were detected by immunohistochemistry.Hippocampal apoptosis was detected by TUNEL.PINK1/Parkin-related protein expression in hippocampus was detected by Western blot.Results:Neurological function score of IS rats was increased(P＜0.05),cerebral infarction was observed by TTC staining,the expression of mito-chondrial autophagy protein p62 in hippocampus was up-regulated(P＜0.05),the expression of LC3B was down-regu-lated(P＜0.05),the number of autophagosomes was decreased(P＜0.05),and apoptosis in hippocampus was in-creased(P＜0.05),the expression of PINK1 and ARKIN protein in hippocampus was down-regulated(P＜0.05).After AU intervention,the neural function score of rats was decreased,the percentage of cerebral infarction volume was reduced,the positive expression of p62 in hippocampus was down-regulated(P＜0.05),the positive expression of LC3B was up-regulated(P＜0.05),and the number of autophagosomes was increased(P＜0.05),the apoptosis of hippocampus was decreased(P＜0.05),and the expression of PINK1 and ARKIN protein in hippocampus was in-creased(P＜0.05).3-MA blocked the therapeutic effect of AU and aggravated the nerve injury in rats.Conclusion:AU promotes hippocampal mitochondrial autophagy and improves neurological damage in IS rats by activating the PINK1/Parkin signaling pathway.

Objective:To investigate the effect of aucubin(AU)on mitochondrial autophagy in the hippocampus of ischemic stroke(IS)rats by regulating the pten-induced kinase protein 1(PINK1)/cytoplasmic E3-ubiquitin ligase(Parkin)signaling pathway.Methods:The IS rat model was established by middle cerebral artery occlusion(MCAO),and was randomly divided into IS group,low-dose AU group(AU-L),medium-dose AU group(AU-M),high-dose AU group(AU-H),and high-dose AU combined with 3-MA group(AU-H+3-MA).The rats without liga-tion were used as the Sham surgery group.Zea Longa score was used to evaluate the neurological function of rats.TTC staining was used to detect the percentage of cerebral infarction volume.The microstructures of mitochondria were observed by transmission electron microscopy,and the changes of autophagy protein-microtubule associated protein light chain 3B(LC3B)and p62 were detected by immunohistochemistry.Hippocampal apoptosis was detected by TUNEL.PINK1/Parkin-related protein expression in hippocampus was detected by Western blot.Results:Neurological function score of IS rats was increased(P＜0.05),cerebral infarction was observed by TTC staining,the expression of mito-chondrial autophagy protein p62 in hippocampus was up-regulated(P＜0.05),the expression of LC3B was down-regu-lated(P＜0.05),the number of autophagosomes was decreased(P＜0.05),and apoptosis in hippocampus was in-creased(P＜0.05),the expression of PINK1 and ARKIN protein in hippocampus was down-regulated(P＜0.05).After AU intervention,the neural function score of rats was decreased,the percentage of cerebral infarction volume was reduced,the positive expression of p62 in hippocampus was down-regulated(P＜0.05),the positive expression of LC3B was up-regulated(P＜0.05),and the number of autophagosomes was increased(P＜0.05),the apoptosis of hippocampus was decreased(P＜0.05),and the expression of PINK1 and ARKIN protein in hippocampus was in-creased(P＜0.05).3-MA blocked the therapeutic effect of AU and aggravated the nerve injury in rats.Conclusion:AU promotes hippocampal mitochondrial autophagy and improves neurological damage in IS rats by activating the PINK1/Parkin signaling pathway.

ObjectiveTo analyze the drop-out rate of participants in antidepressant clinical trials and to explore the related influencing factors. MethodsA retrospective analysis was carried out on the participants of 9 antidepressant clinical trials conducted at the Affiliated Brain Hospital of Guangzhou Medical University from 2013 to 2020. A self-compiled questionnaire was used to collect the subjects' demographic data， disease characteristics and the final completion of the trial， thereafter， the participant drop-out rate and related influencing factors were discussed. ResultsA total of 157 cases were enrolled， including 120 cases completed and 37 cases dropped out the trail. The causes of drop-out were poor efficacy in 13 cases （35.14%）， presence of adverse reactions in 12 cases （32.43%）， withdrawal of informed consent in 8 cases （21.62%） and loss of follow-up in 4 cases （10.81%）. Correlation analysis showed that participant drop-out was positively correlated with the level of anxiety （r=0.224， P<0.01） and presence of adverse events （r=0.158， P<0.05）， meantime， negatively correlated with the level of education （r=-0.209， P<0.01） and overall efficacy （r=-0.545， P<0.01）. Binary Logistic regression analysis showed that education level （β=-0.611， OR=0.543， P<0.05）， number of visits （β=-1.831， OR=0.160， P<0.01） and overall efficacy （β=-2.286， OR=0.102， P<0.01） were the influencing factors of participant drop-out. ConclusionLow education level， first visit， poor outcome， high level of anxiety， and adverse events are the factors affecting participant drop-out in antidepressant clinical trials.

To investigate the effect of multiple factors, including breast-feeding and modes of birth, on gastrointestinal (GI) symptoms of children with autism spectrum disorder (ASD). Methods This was a cross-sectional study. A total of 92 children, aged 2 to 10 years, with a diagnosis of ASD by DSM-5 criteria, along with 84 age-matched typical developing (TD) children as control, were enrolled in this study. The six-item gastrointestinal symptom index (6-GSI) was used for symptomatic survey. The self-made questionnaires were used to collect information on dietary preferences, sleep problems and breast-feeding. Results Constipation from 6-GSI was higher in ASD group than in TD group (P＜0.01). Stratified analysis revealed that total GI symptom scores (P=0.030), fecal odor (P=0.028) and abdominal pain (P=0.022) were higher in ASD children born by c-section than ASD children born vaginally whereas only abdominal pain was higher in TD children born by C-section than TD children born vaginally (P=0.016). ASD children with pick eating had higher scores in diarrhea (P=0.048) and abdominal pain (P=0.013) than those without. ASD children with sleep disorders had higher scores in constipation (P=0.008), diarrhea (P=0.020) and fecal odor (P=0.027) than those without. There was also a significant difference in constipation from 6-GSI between mainly breast-fed children and mainly formula-fed children among all subjects (P=0.026). Conclusion ASD children have more severe constipation than TD children. ASD children with pick eating or with sleep disorders tend to have more GI symptoms, including diarrhea, fecal odor, and abdominal pain, while breastfeeding can alleviate these symptoms.