1.Attentional Connectivity-based Prediction of Autism Using Heterogeneous rs-fMRI Data from CC200 Atlas
Yaya LIU ; Lingyu XU ; Jun LI ; Jie YU ; Xuan YU
Experimental Neurobiology 2020;29(1):27-37
Autism spectrum disorder (ASD) is a developmental syndrome characterized by obvious drawbacks in sociality and communication. It has crucial significance to exactly discern the individuals with ASD and typical controls (TC). Previous imaging studies on ASD/TC identification have made remarkable progress in the exploration of objective as well as crucial biomarkers associated with ASD. However, glaring deficiency is manifested by the investigation on solely homogeneous and small datasets. Thus, we attempted to unveil some replicable and robust neural patterns of autism using a heterogeneous multi-site brain imaging dataset from ABIDE (Autism Brain Imaging Data Exchange). Experiments were carried out with an attention mechanism based on Extra-Trees algorithm, taking the study object of brain connectivity measured with the resting-state functional magnetic resonance imaging (fMRI) data of CC200 atlas. With cross-validation strategy, our proposed method resulted in a mean classification accuracy of 72.2% (sensitivity=68.6%, specificity=75.4%). It raised the precision of ASD prediction by about 2% and specificity by 3.2% in comparison with the most competitive reported effort. Connectivity analysis on the optimal model highlighted informative regions strongly involved in the social cognition as well as interaction, and manifested lower correlation between the anterior and posterior default mode network (DMN) in autistic individuals than controls. This observation is concordant with previous studies, which enables our proposed method to effectively identify the individuals with risk of ASD.
2.Cohort Study on the Effectiveness and Safety of Tiapride Combined with Clonidine versus Tiapride and Clonidine Alone for Children with Tic Disorders
Chunsong YANG ; Lingli ZHANG ; Dan YU ; Yaya YANG ; Xiaofang WU
China Pharmacy 2021;32(20):2514-2519
OBJECTIVE:To compa re the effectiveness and safety of three regimens of tiapride ,clonidine and tiapride combined with clonidine in the treatment of tic disorder (TD)in children. METHODS :A sequential collection of 312 children with TD from the outpatient department of West China Second Hospital of Sichuan University were conducted during Jan.-Dec. 2019. They were divided into clonidine group ,tiapride group ,tiapride combined with clo nidine group ,with 104 cases in each group. Tiapride group was given Tiapride hydrochloride tablets with initial dose of 50-100 mg per day ,and the dose was gradually increased to 150-500 mg per day according to tolerance and clinical experience. Clonidine group was given Clonidine transdermal patches ,once a week ,with initial dose of 1 mg each week ,maintenance dose of 1-2 mg each week ,once a week. Tiapride combined with clonidine group was given Tiapride hydrochloride tablets (same usage and dosage as tiapride group )+ Clonidine transdermal patches (same usage and dosage as clonidine group ). The treatment course of 3 groups was 3 months. After the treatment ,they were followed up every 3 months(the following were expressed as 24,36 and 48 weeks after treatment ). Yale global tie severity scale (YGTSS)scores of 3 groups were observed before treatment ,after 4,8,12,24,36,48 weeks of treatment,and the occurrence of ADR was recorded at different follow up time points. RESULTS :Before treatment ,there was no statistical significance in YGTSS scores among 3 groups(P>0.05). After 4,8,12,24,36 and 48 weeks of treatment ,YGTSS scores of 3 groups were significantly lower than those before treatment (P<0.05). After 4,8 and 12 weeks of treatment ,YGTSS scores of tiapride combined with clonidine group were significantly lower than tiapride group and clonidine group (P<0.05),while there was no statistical significance between tiapride group and clonidine group (P>0.05). At 24 weeks of treatment ,YGTSS score of children in tiopride combined with clonidine group was significantly lower than tiopride group (P<0.05),but there were no significant differences between tiopride combined with clonidine group and tiopride group ,and between tiopride group and clonidine group (P>0.05). After 36 and 48 weeks of treatment ,there was no significant difference in YGTSS scores among 3 groups(P>0.05). After 12 weeks of treatment ,the results of P value corrected by Bonferroni method showed that YGTSS score of tiopride combined with clonidine group was significantly lower than those of tiopride group and clonidine group (P<0.016 7), while there was no statistical significance in the difference between tiopride group and clonidine group (P>0.016 7). There was no statistically significant difference in the total incidence of ADR among 3 groups(P>0.05). CONCLUSIONS :Clonidine,tiapride and tiapride combined with clonidine can significantly improve the tic symptoms of TD children with good safety .
3.Effect of Reduning Injection, Shenfu Injection Combined with Gefitinib on Proliferation, Stemness Characteristics and Metabolism of Non-small Cell Lung Cancer Cells
Zhenzhen XIAO ; Yanjuan ZHU ; Yaya YU ; Lina DING ; Changju MA ; Chenjing LEI ; Yihong LIU ; Xuesong CHANG ; Yadong CHEN ; Haibo ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(18):45-53
ObjectiveTo compare and observe the effect of Reduning injection (mainly clearing heat), Shenfu injection (mainly warming Yang) combined with gefitinib on the proliferation, apoptosis, stemness characteristics and metabolism of lung cancer cells. MethodDifferent non-small cell lung cancer (NSCLC) cell lines were selected and intervened with gefitinib (5, 10, 20 μmol·L-1), Reduning injection (0.6%, 0.9%), Shenfu injection (0.6%, 0.9%), gefitinib combined with Reduning injection, and gefitinib combined with Shenfu injection. Cell proliferation in each group was detected by cell counting kit-8 (CCK-8) assay, and cell apoptosis was detected by flow cytometry. The mRNA and protein expressions of lung cancer stem cell markers sex determining region Y-box 2 (Sox2) and aldehyde dehydrogenase family 1 member A1 (ALDH1A1) were determind by real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot, respectively. The redox ratio of lung cancer cells was observed by femtosecond label-free imaging (FLI) and energy metabolism instrument was used to determine the glycolysis level in cells. ResultCompared with the blank group, Reduning injection reduced the survival rate of lung cancer cells (P<0.05), increased the apoptosis rate (P<0.05), down-regulated the mRNA and protein expressions of Sox2 and ALDH1A1 (P<0.05), and up-regulated the redox ratio of cells (P<0.05), while Shenfu injection exerted no remarkable effect on the above indexes. In addition, compared with gefitinib alone, Reduning injection combined with gefitinib inhibited the survival rate of lung cancer cells (P<0.05), promoted the cell apoptosis (P<0.05), down-regulated the mRNA and protein expressions of Sox2 and ALDH1A1 (P<0.05), up-regulated the redox ratio of cells (P<0.05), and lowered the proton efflux rate of glycolysis (P<0.05), while Shenfu injection combined with gefitinib failed to affect these indexes of lung cancer cells significantly. ConclusionReduning injection may inhibit stemness characteristics of tumor cells by regulating their metabolism to enhance the proliferation-inhibiting and pro-apoptotic effects of gefitinib on lung cancer cells, while Shenfu injection had no significant enhancing effect on gefitinib. This indicates that epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) should be used in combination with heat-clearing Chinese medicines.
4.High degree of pharmacokinetic compatibility exists between the five-herb medicine XueBiJing and antibiotics comedicated in sepsis care.
Jian LI ; Olajide E OLALEYE ; Xuan YU ; Weiwei JIA ; Junling YANG ; Chuang LU ; Songqiao LIU ; Jingjing YU ; Xiaona DUAN ; Yaya WANG ; Kai DONG ; Rongrong HE ; Chen CHENG ; Chuan LI
Acta Pharmaceutica Sinica B 2019;9(5):1035-1049
Managing the dysregulated host response to infection remains a major challenge in sepsis care. Chinese treatment guideline recommends adding XueBiJing, a five-herb medicine, to antibiotic-based sepsis care. Although adding XueBiJing further reduced 28-day mortality modulating the host response, pharmacokinetic herb-drug interaction is a widely recognized issue that needs to be studied. Building on our earlier systematic chemical and human pharmacokinetic investigations of XueBiJing, we evaluated the degree of pharmacokinetic compatibility for XueBiJing/antibiotic combination based on mechanistic evidence of interaction risk. Considering both XueBiJing‒antibiotic and antibiotic‒XueBiJing interaction potential, we integrated informatics-based approach with experimental approach and developed a compound pair-based method for data processing. To reflect clinical reality, we selected for study XueBiJing compounds bioavailable for drug interactions and 45 antibiotics commonly used in sepsis care in China. Based on the data of interacting with drug metabolizing enzymes and transporters, no XueBiJing compound could pair, as perpetrator, with the antibiotics. Although some antibiotics could, due to their inhibition of uridine 5'-diphosphoglucuronosyltransferase 2B15, organic anion transporters 1/2 and/or organic anion-transporting polypeptide 1B3, pair with senkyunolide I, tanshinol and salvianolic acid B, the potential interactions (resulting in increased exposure) are likely desirable due to these XueBiJing compounds' low baseline exposure levels. Inhibition of aldehyde dehydrogenase by 7 antibiotics probably results in undesirable reduction of exposure to protocatechuic acid from XueBiJing. Collectively, XueBiJing/antibiotic combination exhibited a high degree of pharmacokinetic compatibility at clinically relevant doses. The methodology developed can be applied to investigate other drug combinations.
5.Study on the Medication Compliance of Children with Tic Disorder Based on the Theory of Protective Motivation
Chunsong YANG ; Lingli ZHANG ; Jiayuan LI ; Dan YU ; Yaya YANG ; Xiaofang WU
China Pharmacy 2021;32(19):2415-2420
OBJECTIVE:To study the current status and influencing factors of medication compliance in children with tic disorder(TD),and to provide reference for improving medication compliance in TD children. METHODS:The questionnaire was designed according to the protection motivation theory. The cross-sectional study was adopted to conduct questionnaire survey among TD children in West China Second Hospital of Sichuan University from Jan. 2018 to Dec. 2019. The structural equation model was established according to the theoretical assumptions,and the maximum likelihood method was used to estimate the model;multiple linear regression analysis was carried out for the factors with significant influence in the single factor analysis,and path analysis and intermediary effect test were carried out. RESULTS:A total of 317 patients with TD were included,the mean age was(8.38±2.54)years,and the mean course of disease was(3.19±2.46)years. Average medication compliance scores was (5.70±1.69),among which 15.1% was low compliance,37.5% moderate compliance,and 47.3% high compliance. Multivariate linear regression analysis showed that comorbidities(β=0.124,SE=0.167,P=0.011),education level of the main guardian(β= 0.236,SE=0.110,P<0.001),quality of life(β=0.399,SE=0.112,P<0.001)and the types of drugs taken(β=0.166,SE= 0.047,P=0.001)were the factors affecting medication compliance of children with TD. Structural equation model analysis showed that severity(β=0.295,95%CI:0.103-0.493),external return(β=0.830,95%CI:0.662-1.002),self-efficacy(β=0.200,95%CI: 0.057-0.353),susceptibility(β=0.220,95%CI:0.084-0.352)and quality of life(β=0.353,95%CI:0.211-0.500)had a direct positive impact on medication compliance. Quality of life mediated between external returns and compliance variables(intermediary effect accounted for 13.9% of the total effect value). CONCLUSIONS:Children with TD have low medication compliance. It is recommended that pediatricians in medical institutions at all levels to manage the medication compliance of patients with TD from the severity,susceptibility,external returns and self-efficacy,so as to improve patients and guardians’awareness of the severity and susceptibility of disease and medication non-adherence,weaken external returns and increase self-efficacy,and ultimately improve medication compliance of patients