Objective To observe the effects of Yiqi Huoxue Prescription in regulating METTL3/HAND2/TGF-β1 signaling axis on rats with qi deficiency and blood stasis syndrome of coronary heart disease.Methods Totally 48 male SD rats were randomly divided into sham-operation group,model group,Yiqi Huoxue Prescription group and Western medicine(isosorbide mononitrate)group,with 12 rats in each group.Except for the sham-operation group,the animal models of coronary heart disease with qi deficiency and blood stasis syndrome were prepared by the method of ligation of the left anterior descending branch of coronary artery combined with swimming exhaustion.After modeling,Yiqi Huoxue Prescription group and the Western medicine group were gavaged for 28 d.The general conditions of the rats were observed,and electrocardiograms and echocardiograms were collected to detect the cardiac function of the rats,blood rheology was used to detect the degree of blood stasis,HE staining was used to observe the morphology of myocardial tissue,immunohistochemistry was used to detect the expression of METTL3,TGF-β1,Smad2 and Smad3 in myocardial tissue,RT-PCR and Western blot were used to detect the expression of METTL3,HAND2,TGF-β1,Smad2 and Smad3 mRNA and protein in myocardial tissue.Results Compared with the sham-operation group,the model group rats showed symptoms of qi deficiency such as mental lethargy,slow movement,drowsiness,and decreased body mass,significant elevation of ST segment on electrocardiogram,the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)decreased(P＜0.01),the left ventricular end diastolic volume(LVEDV),left ventricular end systolic volume(LVESV),left ventricular end diastolic diameter(LVEDd)and left ventricular end systolic diameter(LVEDs)increased(P＜0.01),the red blood cell aggregation index,Carcasson viscosity and whole blood viscosity increased(P＜0.01);with enlargement and necrosis of myocardial cells,disordered arrangement of myocardial fibers,and infiltration of inflammatory cells into myocardial tissue,the mRNA and protein expressions of METTL3,TGF-β1,Smad2 and Smad3 in myocardial tissue increased(P＜0.05,P＜0.01),while the mRNA and protein expression of HAND2 decreased(P＜0.01).Compared with the model group,the Yiqi Huoxue Prescription group and the Western medicine group showed significant improvement in the mental state of rats,significant ST segment regression on electrocardiogram,LVEF and LVFS increased(P＜0.01),LVEDV,LVESV,LVEDd and LVEDs decreased(P＜0.05,P＜0.01),with red blood cell aggregation index,Carcasson viscosity and whole blood viscosity decreased(P＜0.01);the arrangement of myocardial fibers was neat,the structure and morphology of myocardial cells were improved,the infiltration of inflammatory cells was reduced,the mRNA and protein expressions of METTL3,TGF-β1,Smad2 and Smad3 in myocardial tissue decreased(P＜0.05,P＜0.01),and the mRNA and protein expression of HAND2 increased(P＜0.05,P＜0.01).Conclusion Yiqi Huoxue Prescription can alleviate the pathological damage of myocardial tissue in rats with coronary heart disease of qi deficiency and blood stasis syndrome,improve heart function and inhibit inflammatory response.Its mechanism may be related to the regulation of the METTL3/HAND2/TGF-β1 signaling axis.

Objective To observe the effects of Yiqi Huoxue Prescription in regulating METTL3/HAND2/TGF-β1 signaling axis on rats with qi deficiency and blood stasis syndrome of coronary heart disease.Methods Totally 48 male SD rats were randomly divided into sham-operation group,model group,Yiqi Huoxue Prescription group and Western medicine(isosorbide mononitrate)group,with 12 rats in each group.Except for the sham-operation group,the animal models of coronary heart disease with qi deficiency and blood stasis syndrome were prepared by the method of ligation of the left anterior descending branch of coronary artery combined with swimming exhaustion.After modeling,Yiqi Huoxue Prescription group and the Western medicine group were gavaged for 28 d.The general conditions of the rats were observed,and electrocardiograms and echocardiograms were collected to detect the cardiac function of the rats,blood rheology was used to detect the degree of blood stasis,HE staining was used to observe the morphology of myocardial tissue,immunohistochemistry was used to detect the expression of METTL3,TGF-β1,Smad2 and Smad3 in myocardial tissue,RT-PCR and Western blot were used to detect the expression of METTL3,HAND2,TGF-β1,Smad2 and Smad3 mRNA and protein in myocardial tissue.Results Compared with the sham-operation group,the model group rats showed symptoms of qi deficiency such as mental lethargy,slow movement,drowsiness,and decreased body mass,significant elevation of ST segment on electrocardiogram,the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)decreased(P＜0.01),the left ventricular end diastolic volume(LVEDV),left ventricular end systolic volume(LVESV),left ventricular end diastolic diameter(LVEDd)and left ventricular end systolic diameter(LVEDs)increased(P＜0.01),the red blood cell aggregation index,Carcasson viscosity and whole blood viscosity increased(P＜0.01);with enlargement and necrosis of myocardial cells,disordered arrangement of myocardial fibers,and infiltration of inflammatory cells into myocardial tissue,the mRNA and protein expressions of METTL3,TGF-β1,Smad2 and Smad3 in myocardial tissue increased(P＜0.05,P＜0.01),while the mRNA and protein expression of HAND2 decreased(P＜0.01).Compared with the model group,the Yiqi Huoxue Prescription group and the Western medicine group showed significant improvement in the mental state of rats,significant ST segment regression on electrocardiogram,LVEF and LVFS increased(P＜0.01),LVEDV,LVESV,LVEDd and LVEDs decreased(P＜0.05,P＜0.01),with red blood cell aggregation index,Carcasson viscosity and whole blood viscosity decreased(P＜0.01);the arrangement of myocardial fibers was neat,the structure and morphology of myocardial cells were improved,the infiltration of inflammatory cells was reduced,the mRNA and protein expressions of METTL3,TGF-β1,Smad2 and Smad3 in myocardial tissue decreased(P＜0.05,P＜0.01),and the mRNA and protein expression of HAND2 increased(P＜0.05,P＜0.01).Conclusion Yiqi Huoxue Prescription can alleviate the pathological damage of myocardial tissue in rats with coronary heart disease of qi deficiency and blood stasis syndrome,improve heart function and inhibit inflammatory response.Its mechanism may be related to the regulation of the METTL3/HAND2/TGF-β1 signaling axis.

Objective     To construct a radiomics model for identifying clinical high-risk carotid plaques. Methods     A retrospective analysis was conducted on patients with carotid artery stenosis in China-Japan Friendship Hospital from December 2016 to June 2022. The patients were classified as a clinical high-risk carotid plaque group and a clinical low-risk carotid plaque group according to the occurrence of stroke, transient ischemic attack and other cerebrovascular clinical symptoms within six months. Six machine learning models including eXtreme Gradient Boosting, support vector machine, Gaussian Naive Bayesian, logical regression, K-nearest neighbors and artificial neural network were established. We also constructed a joint predictive model combined with logistic regression analysis of clinical risk factors. Results    Finally 652 patients were collected, including 427 males and 225 females, with an average age of 68.2 years. The results showed that the prediction ability of eXtreme Gradient Boosting was the best among the six machine learning models, and the area under the curve (AUC) in validation dataset was 0.751. At the same time, the AUC of eXtreme Gradient Boosting joint prediction model established by clinical data and carotid artery imaging data validation dataset was 0.823. Conclusion     Radiomics features combined with clinical feature model can effectively identify clinical high-risk carotid plaques.

An auxiliary dining robot is designed in this paper, which implements the humanoid feeding function with theory of inventive problem solving (TRIZ) theory and aims at the demand of special auxiliary nursing equipment. Firstly, this robot simulated the motion function of human arm by using the tandem joints of the manipulator. The end-effector used a motor-driven spoon to simulate the feeding actions of human hand. Meanwhile, the eye in hand installation style was adopted to instead the human vision to realize its automatic feeding action. Moreover, the feeding and drinking actions of the dining robot were considered comprehensively with the flexibility of spatial movement under the lowest degree of freedom (DOF) configuration. The structure of the dining robot was confirmed by analyzing its stresses and discussing the specific application scenarios under this condition. Finally, the simulation results demonstrate high-flexibility of the dining robot in the workspace with lowest DOF configuration.
Computer Simulation ; Equipment Design ; Hand ; Humans ; Movement ; Robotics/methods*

Objective To explore the effect of angiogenesis in carotid atherosclerotic plaque.Methods From Jan 2016 to Aug 2016,Carotid artery plaque was abtained in 52 cases after carotid endarterectomy at the Department of Cardiovascular Surgery of China-Japan Friendship Hospital.Patients were divided into symptomatic group and asymptomatic group.Specimens were stained with HE and Movat,and the density,size,distribution and morphology of neovascularization were counted.Results The density of neovascularization in the symptomatic group and the asymptomatic group were 5.27 ± 0.46 and 2.30 ±0.29,respectively (P ＜ 0.001),the average cross-sectional area of neovascularization in the symptomatic group was (2.26±0.21) mm2 and (1.00 ±0.48) mm2 in the asymptomatic group (P=0.02).In the distribution,the symptomatic group and the asymptomatic group were 3.37 ± 0.46/ mm2,1.32 ±0.16/mm2 in basal part,3.71 ±0.42/mm2,1.56 ±0.20/mm2 in the shoulder part,3.48 ±0.44/mm2,1.55 ± 0.21/ mm2 in the fibrous cap,respectively (P ＜ 0.001).Conclusion The density and cross-sectional area of neovascularization in the symptomatic group were larger than those in the asymptomatic group,irregular branching vessels were dominant.

Objective To explore the influencing factors of blood concentration of tacrolimus in pediatric living donor liver transplant recipients and provide rationales for individualized administration of tacrolimus .Methods Trough concentrations (C0 ) , doses of tacrolimus , recipient age , gender , body weight ,donor and recipient CYP3A5 genotypes ,hematocrit (HCT ) and liver/kidney function related indicators at 3 ,5 ,7 ,14 days ,1 month , 2 months and 3 months post living donor liver transplantation were collected from a total of 100 pediatric recipients .Taking ratio of concentration to dose (C0 /D) as a dependent variable ,the influencing factors of blood concentration of tacrolimus were analyzed by multivariate stepwise regression .Results The influencing factors of blood tacrolimus concentration at 3d post-transplantation were recipient CYP3A5 genotyp , donor CYP3A5 genotype and weight of recipients . The major influencing factors at 5d post-transplantation were recipient & donor CYP3A5 genotypes , recipient weight and HCT . The major relevant factors at 7d posttransplantation were CYP3A5 of recipients ,age and HCT .The influencing factors at 14 days were the same as those at 2 months ,i .e .CYP3A5 genotype and weight of recipients .At 1 month the major influencing factors were weight of recipients ,CYP3A5 of recipients and alkaline phosphatase (ALP) ; CYP3A5 genotype and weight of recipients at 3 months . Further study on CYP3A5 genotype of donors and recipients , the C0 /D ratio of CYP3A5 genotype non-expression group was significantly higher than that of expression group in recipients and C0 /D ratio of donor CYP3A5 genotype nonexpression group was significantly higher than that of expression group .Conclusions The influencing factors of concentration of tacrolimusvary at different timepoints after liver transplantation . Paying close attention to the changes of CYP3A5 genotype , weight of recipients and related biochemical indexes and considering various influencing factors facilitate individualized dosing for improving the prognosis of pediatric recipients .

Objective To investigate the mechanism of miRNA-129-5p in epithelial-mesenchymal transition (EMT)of biliary atresia.Methods Constructed bile duct epithelial EMT cell model (the experimental group) induced by TGF-β1,detected the expressions of EMT related markers and miRNA-129-5p.While miRNA-129-5p precursor was transfected,the expressions of EMT related markers and extracellular matrix were contrasted between the original and the renovated biliary epithelial cells.Results In the experimental group,extrahepatic bile duct showedEMT,the expression of miRNA-129-5p was decreased (P＜0.05),overexpression of miRNA-129-5p could inhibit the progression of EMT (P＜0.05).Conclusion miRNA-129-5p may relate to EMT by regulating the expression of TGF-β1.

Objective To provide a reference for the individualized medication of tacrolimus in children after living related liver transplantation,according to the effect of CYP3A5 genotyping on the concentration/dose ratio of tacrolimus in children with living related liver transplantation.Methods Peripheral blood samples were collected from children with living related liver transplantation in the transplant center.The CYP3A5 genotype was determined by polymerase chain reaction (PCR)pyrosequencing.Related indicators such as tacrolimus dose and concentration in children with living related liver transplantation were collected within 3 months after operation.According to the donor/receptor genotype,the donor/receptor expression group,the donor/receptor single expression group,and the donor/receptor non-expression group were set up.Tacrolimus concentration/dose (C0/D) ratio was statistically analyzed at 5th day,7th day,14th day,28th day,2nd month and 3rd month after administration.Results Among the 76 patients,there were 21 patients (27.63％) in CYP3A5 donor/receptor non-expression group,27 patients (35.53％) in donor/receptor single expression group,and 28 patients (36.84％) in the donor/receptor expression group.The time to the target concentration range (C0＞8 ng/mL) in CYP3A5 donor/receptor expression group was longer than in donor/receptor single expression group and donor/receptor non-expression group.Except for the individual time points,there were significant differences between CYP3A5 donor/receptor expression group and donor/receptor non expression group,or between donor/receptor non-expression group and donor/receptor single expression group,or between donor/receptor expression group and donor/receptor single expression group at rest time points (P＜0.05 for all).Conclusion In the CYP3A5 donor/receptor gene expression group,the higher dose was needed to reach the target concentration range than the gene single expression group and the donor/receptor non-expression group.Except for individual time points,there were significant differences in C0/D at rest different time points.Regardless of whether the donor or recipient contained the CYP3A5* 1 allele,C0/D was lower than the non-expressed type of the gene.Considering the polymorphism of the donor/receptor CYP3A5 gene,it was worthful for children with living related liver transplantation to allow the drug concentration to reach the therapeutic window as soon as possible and reduce organ rejection and adverse reactions.

Objective To investigate the relationship between CYP3A5 gene polymorphism and tacrolimus concentration/dose ratio in children living donor liver transplantation and the correlation with clinical efficacy,for the relatives living donor liver transplantation in children tacrolimus individualized medication providing reference indicators.Methods Peripheral blood samples were collected from children with relatives living donor liver transplantation in the center of liver transplantation,the genotype of CYP3A5 was determined by polymerase chain reaction (PCR)/pyrophosphate sequencing,The dosage of tacrolimus and blood concentration,liver and kidney function and other related indicators were measured within 3 months after operation According to genotypes,the children can be divided into gene expression group (CYP3A5 *1/*1 and CYP3A5 *1/*3) and non-expression group (CYP3A5*3/*3).The drug concentration (C0),tacrolimus dose / body weight (D/W) ratio,drug concentration/dose (C0/D) ratio of each genotype at 1 day,3 d,5 d,7 d,14 d,28 d,2 months and 3 months after administration and the genotype at the time point on liver and kidney function was carried out statistics.Results Among the 80 cases,36 cases (45.0％) were CYP3A5*3/*3,37 cases (46.2％) were CYP3A5*1/*3,7 cases (8.8％) were CYP3A5*1/*1.CYP3A5 gene expression group reached a therapeutic concentration range (C0 ＞ 8 μg/L) than the gene non-expression group takes longer time.There was no significant difference in CYP3A5 gene expression group between the non-expression group on the initial dose (P＞ 0.05);CYP3A5 gene expression group than the non-expression group,tacrolimus C0 within 1 month after operation were statistically significant.CYP3A5 gene expression group than the non-expression group,tacrolimus D/ W in addition to the first day after surgery,other time points were statistically significant (P＜0.05).CYP3A5 gene expression group than the non-expression group,C0/D at the above time points were statistically significant (P＜0.05);There were no significant differences in liver and kidney function between the two genotypes (P ＞ 0.05),but there was significant difference in the alkaline phosphatase.Conclusion CYP3A5 gene expression in children than non-expression group of children need higher doses to reach the therapeutic drug concentration;CYP3A5 gene polymorphism had significant effects on early tacrolimus C0,D/W and C0/D values;CYP3A5 gene polymorphism is instructive for the administration of tacrolimus in children with living donor liver transplantation,CYP3A5 gene type tests should be regular,improve efficacy and reduce the incidence of adverse reactions.

Objective To assess the efficacy and safety of extended-release versus standardrelease in kidney transplant recipients.Methods We searched Pubmed,Embase,Medline and Cochrane library databases in English and researched published randomized controlled trials (RCTs)focused on extended-release versus standard-release tacrolimus in renal transplant recipients until March 2016.The risk of bias assessment for RCTs was evaluated using the Cochrane Collaboration's tool,and quality of RCTs was assessed by the modified JADAD scale.Meta-analysis was conducted by Review Manager 5.3 and Stata SE 12.0.Results A total of 12 RCTs were included,involving 3 532 adult kidney transplant recipients.There was no significant difference between the two treatment groups in the endpoints such as acute rejection rate (RR =0.93[0.78 1.11],P =0.40),graft survival (RR=1.04[0.79-1.37],P =0.76),patient survival (RR =1.03[0.67-1.57],P =0.90),patients withdrawn (RR =1.07[0.95-1.22],P =0.26),estimated glomemlar filtration rate (eGFR) (MD =-0.52[-1.95,0.92],P =0.48),creatinine clearance (Ccr) (MD =-0.94 [-1.39,3.28],P =0.43),infection (RR=0.98[0.90-1.06],P =0.57),and new-onset diabetes rate (RR =0.91[0.67-1.23],P =0.53).Meanwhile,subgroup analysis of different patient population (early after transplantation vs.late after transplantation) showed similar results in the protocol.Conclusion The extended-release tacrolimus has similar efficacy and safety to the standard-release in kidney transplantation.