1.Protective effects of trimetazidine on bone marrow mesenchymal stem cells viability in an ex vivo model of hypoxia and in vivo model of locally myocardial ischemia.
Hongxin, XU ; Gangyan, ZHU ; Yihao, TIAN
Journal of Huazhong University of Science and Technology (Medical Sciences) 2012;32(1):36-41
Bone marrow mesenchymal stem cells (MSCs) have shown potential for cardiac repair following myocardial injury, but this approach is limited by their poor viability after transplantation. The present study was to investigate whether trimetazidine (TMZ) could improve survival of MSCs in an ex vitro model of hypoxia, as well as survival, differentiation, and subsequent activities of transplanted MSCs in rat hearts with acute myocardial infarction (AMI). MSCs at passage 3 were examined for their viability and apoptosis under a transmission electron microscope, and by using flow cytometry following culture in serum-free medium and exposure to hypoxia (5% CO(2), 95% N(2)) for 12 h with or without TMZ. Thirty Wistar rats were divided into 3 groups (n=10 each group), including group I (AMI control), group II (MSCs transplantation alone), and group III (TMZ+MSCs). Rat MSCs (4×10(7)) were injected into peri-infarct myocardium (MSCs group and TMZ+MSCs group) 30 min after coronary artery ligation. The rats in TMZ+MSCs group were additionally fed on TMZ (2.08 mg·kg(-1)·day(-1)) from day 3 before AMI to day 28 after AMI. Cardiac structure and function were assessed by echocardiography at 28th day after transplantation. Blood samples were collected before the start of TMZ therapy (baseline), and 24 and 48 h after AMI, and inflammatory cytokines (CRP, TNF-α) were measured. Then the survival and differentiation of transplanted cells in vivo were detected by immunofluorescent staining. The cellular apoptosis in the peri-infarct region was detected by using TUNEL assay. Furthermore, apoptosis-related proteins (Bcl-2, Bax) within the post-infarcted myocardium were detected by using Western blotting. In hypoxic culture, the TMZ-treated MSCs displayed a two-fold decrease in apoptosis under serum-free medium and hypoxia environment. In vivo, cardiac infarct size was significantly reduced, and cardiac function significantly improved in MSCs and TMZ+MSCs groups as compared with those in the AMI control group. Combined treatment of TMZ with MSCs implantation demonstrated further decreased MSCs apoptosis, further increased MSCs viability, further decreased infarct size, and further improved cardiac function as compared with MSCs alone. The baseline levels of inflammatory cytokines (CRP, TNF-α) had no significant difference among the groups. In contrast, all parameters at 24 h were lower in TMZ+MSCs group than those in MSCs group. Furthermore, Western blotting indicated that the expression of anti-apoptotic protein Bcl-2 was up-regulated, while the pro-apoptotic protein Bax was down-regulated in the TMZ+MSCs group, compared with that in the MSCs group. It is suggested that implantation of MSCs combined with TMZ treatment is superior to MSCs monotherapy for MSCs viability and cardiac function recovery.
2.A study for the time course of cerebral infarction with diffusion kurtosis imaging
Shun ZHANG ; Yihao YAO ; Shuixia ZHANG ; Jingjing SHI ; Yan ZHANG ; Suiqiang ZHU ; Wenzhen ZHU
Chinese Journal of Radiology 2014;(6):443-447
Objective To investigate the time course of cerebral infarction with diffusion kurtosis imaging-related parameters.Methods According to the time interval from symptom onset to MRI examination, 114 cases of cerebral infarction were divided into five groups:8 cases of hyperacute phase(less than 6 hours), 14 cases of acute(>6-24 h), 60 cases of early subacute(>24 h-7 d), 20 cases of late subacute(>7-14 d), and 12 cases of chronic phase ( >14 d-2 months).They underwent routine diffusion weighted imaging (DWI) and diffusion kurtosis imaging (DKI) scanning, and apparent diffusion coefficient ( ADC) and DKI-derived parameters were obtained from them.The derived diffusion parameters were compared among different phases in the patients , and the percent of changes in the infarcted regions were calculated.Paired t-test was used to compare the difference of each parameter between the infarcted region and contralateral normal region , and their correlation with time interval was tested using Pearson correlation analysis.Results Except for chronic phase , mean kurtosis ( MK) , axial kurtosis ( K∥) , radial kurtosis (K⊥)map showed uneven high signal in the infarcted regions , while mean diffusion(MD), axial diffusion(D∥), radial diffusion(D⊥) showed uniform low signal.MK values in the infarcted regions of hyperacute, acute, early subacute and late subacute phase (1.331 ±0.357,1.578 ±0.453,1.519 ±0.455, 1.403 ±0.275 ) increased significantly , compared with the contralateral normal mirror regions ( 0.850 ± 0.236,0.827 ±0.194,0.865 ±0.144,0.939 ±0.212) (t values were 5.242,6.907,12.416,5.629, respectively.P values were all less than 0.01 ).MK, K∥, K⊥ achieved a peak in the acute and early subacute phase , and showed more amplitude than the decrease of MD , D∥, D⊥.Then they gradually reduced, and tended to normalize.MK, MD, ADC had a significant correlation with the time onset of cerebral infarction ( r was 0.354, 0.747, 0.723, respectively, P values were all less than 0.05 ).Conclusion Diffusion kurtosis imaging can provide more diffusion information than conventional DWI , which can better reflect the microstructure changes in tissue.
3.Protective Effects of Trimetazidine on Bone Marrow Mesenchymal Stem Cells Viability in an ex vivo Model of Hypoxia and in vivo Model of Locally Myocardial Ischemia
XU HONGXIN ; ZHU GANGYAN ; TIAN YIHAO
Journal of Huazhong University of Science and Technology (Medical Sciences) 2012;32(1):36-41
Bone marrow mesenchymal stem cells (MSCs) have shown potential for cardiac repair following myocardial injury,but this approach is limited by their poor viability after transplantation.The present study was to investigate whether trimetazidine (TMZ) could improve survival of MSCs in an ex vitro model of hypoxia,as well as survival,differentiation,and subsequent activities of transplanted MSCs in rat hearts with acute myocardial infarction (AMI).MSCs at passage 3 were examined for their viability and apoptosis under a transmission electron microscope,and by using flow cytometry following culture in serum-free medium and exposure to hypoxia (5% CO2,95% N2) for 12 h with or without TMZ.Thirty Wistar rats were divided into 3 groups (n=10 each group),including group Ⅰ (AMI control),group Ⅱ (MSCs transplantation alone),and group Ⅲ (TMZ+MSCs).Rat MSCs (4×107) were injected into peri-infarct myocardium (MSCs group and TMZ+MSCs group) 30 min after coronary artery ligation.The rats in TMZ+MSCs group were additionally fed on TMZ (2.08 mg·kg-1·day-1) from day 3 before AMI to day 28 after AMI.Cardiac structure and function were assessed by echocardiography at 28th day after transplantation.Blood samples were collected before the start of TMZ therapy (baseline),and 24 and 48 h after AMI,and inflammatory cytokines (CRP,TNF-α) were measured.Then the survival and differentiation of transplanted cells in vivo were detected by immunofluorescent staining.The cellular apoptosis in the peri-infarct region was detected by using TUNEL assay.Furthermore,apoptosis-related proteins (Bcl-2,Bax) within the post-infarcted myocardium were detected by using Western blotting.In hypoxic culture,the TMZ-treated MSCs displayed a two-fold decrease in apoptosis under serum-free medium and hypoxia environment.In vivo,cardiac infarct size was significantly reduced,and cardiac function significantly improved in MSCs and TMZ+MSCs groups as compared with those in the AMI control group.Combined treatment of TMZ with MSCs implantation demonstrated further decreased MSCs apoptosis,further increased MSCs viability,further decreased infarct size,and further improved cardiac function as compared with MSCs alone.The baseline levels of inflammatory cytokines (CRP,TNF-α) had no significant difference among the groups.In contrast,all parameters at 24 h were lower in TMZ+MSCs group than those in MSCs group.Furthermore,Western blotting indicated that the expression of anti-apoptotic protein Bcl-2 was up-regulated,while the pro-apoptotic protein Bax was down-regulated in the TMZ+MSCs group,compared with that in the MSCs group.It is suggested that implantation of MSCs combined with TMZ treatment is superior to MSCs monotherapy for MSCs viability and cardiac function recovery.
4.FILLING VEIN WITH TWO NEURAL SEGMENTS TO BRIDGE NERVE DEFECT:AN EXPERIMENTAL AND CLINICAL STUDY
Bin CAO ; Chengqi WANG ; Zhenhua ZHAI ; Qishen FAN ; Chunzhi JIANG ; Zuoyong ZHANG ; Yaoguang LIANG ; Yihao ZHU ; Changjin PANG
Medical Journal of Chinese People's Liberation Army 1981;0(04):-
Twenty-one rabbits were randomly divided into three groups: experimental group-filling vein with two neural segments being 0.3cm long to bridge 4cm defect of common peroneal nerve, control group-bridging vein directly to the 4cm defect of common peroneal nerve, auto-nerve-grafting group-cutting off a segment (4cm long) from common peroneal nerve and grafting it inversely.After 25 weeks, morphological, electrophysiological and histological examinations were undertaken, which revealed that the experimental group was most similar to the auto-nerve-grafting group in recovery of motion of the limbs, action potential of muscle, nerve conductive velocity, and regenerating density of nerve fibers and axons. It was a failure in control group. Satisfactory results were also achieved in 2 patients with defect of ulnar nerve treated by filling vein with two neural segments. It suggests that our method is feasible.
5.Three-dimensional arterial spin labeling PWI in evaluating postoperative cerebral perfusion changes in patients with Moyamoya disease
Wenjie ZHU ; Shun ZHANG ; Yihao YAO ; Zhenxiong WANG ; Li PENG ; Hanxiong GUAN ; Wenzhen ZHU
Chinese Journal of Medical Imaging Technology 2018;34(4):495-498
Objective To observe the value of three-dimensional arterial spin labeling (3D-ASL) PWI in evaluating postoperative cerebral perfusion changes in patients with Moyamoya disease.Methods Totally 19 patients of Moyamoya disease confirmed with DSA were enrolled.All the patients received revascularization.Before and after operation,3D-ASL PWI and dynamic susceptibility contrast perfusion weighted imaging (DSC-PWI) were performed.ROI was located in the region with obvious perfusion changes supplied by middle cerebral artery on the operating side.Then the cerebral blood flow (CBF) was measured on 3D-ASL images,and time to peak (TTP) was measured on DSC-PWI images before and after operation.The differences of CBF and TTP before and after operation were compared,as well as the improvement rate of CBF,TTP and clinical symptoms.Results Before and after operation,CBF was (41.40±11.36) ml/(100 g · min) and (54.10±16.69) ml/(100 g · min),respectively,and the difference was statistically significant (t=-4.273,P<0.01).TTP was (28.66 ± 3.21) s and (26.44 ± 3.93) s,respectively,and the difference was also statistically significant (t =-2.936,P<0.01).The improvement rate of clinical symptoms was 84.21% (16/19),of CBF was 78.95% (15/19) and of TTP was 68.42% (13/19),the differences of improvement rate had no statistically significant (P=0.625).Conclusion 3D-ASL PWI is noninvasive,no contrast agent need to be used,and can be used to evaluate perfusion changes after operation of revascularization in patients with Moyamoya disease.
6.Relationship between preoperative pain threshold and chronic postsurgical pain in patients undergoing thoracoscopic pneumonectomy
Yihao ZHU ; Tao ZHU ; Xuechao HAO ; Fei WANG
Chinese Journal of Anesthesiology 2023;43(9):1037-1041
Objective:To evaluate the relationship between preoperative pain threshold and chronic postsurgical pain (CPSP) in the patients undergoing thoracoscopic pneumonectomy.Methods:One hundred patients of both sexes, aged 18-75 yr, with body mass index of 18-35 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, scheduled for thoracoscopic pneumonectomy at West China Hospital of Sichuan University from December 2019 to February 2020, were selected. The pain threshold was measured using Pain Vision at 1 day before surgery. Telephone follow-up was implemented by a pain questionnaire to assess CPSP (numerical rating scale score ≥1) at 3 months after surgery. Multivariate logistic regression was used to identify the risk factors for CPSP, and the receiver operating characteristic curve was used to evaluate the accuracy of preoperative pain threshold in predicting CPSP. Results:Ninety-four patients were finally enrolled, of which 38 cases (40%) developed CPSP. The results of multivariate logistic regression analysis showed that low preoperative pain threshold was an independent risk factor for CPSP ( OR=0.899, 95% confidence interval 0.854-0.946, P<0.001). The area under the receiver operating characteristic curve was 0.882 (95% confidence interval 0.804-0.960), Youden Index was 0.673, the sensitivity was 0.816, and the specificity was 0.857. Conclusions:Low preoperative pain threshold is an independent risk factor for CPSP, and preoperative pain threshold can predict the occurrence of CPSP in the patients undergoing thoracoscopic pneumonectomy.
7.Clinical research progress on brain natriuretic peptide and amino-terminal pro-brain natriuretic peptide
Yihao ZHU ; Fei WANG ; Tao ZHU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2022;29(12):1665-1670
Brain natriuretic peptide (BNP) and amino-terminal pro-brain natriuretic peptide (NT-proBNP) were the main members of the natriuretic peptide family. BNP has the effects of diuretic sodium, reducing sympathetic nervous system activity, dilating blood vessels, and improving the pathological remodeling of heart. Plasma BNP/NT-proBNP levels have been widely used in the diagnosis, severity assessment, prognosis prediction and treatment guidance of heart failure. In recent years, BNP/NT-proBNP has become a research hotspot in the diagnosis and and prognosis judgment of atrial fibrillation, recurrence of atrial fibrillation after radiofrequency ablation and cardioversion and congenital heart disease in infants and children, prediction of postoperative complications, and drug development. This article reviews the latest advances in clinical application and research progress on BNP/NT-proBNP.
8.Correlation between malignant tumors and serum N-terminal pro-brain natriuretic peptide: a cross-sectional study
Yihao WANG ; Shaoning ZHU ; Mingzhuang SUN ; Xiaolong LI ; Zhijun SUN ; Shunying HU
Chinese Journal of Clinical Medicine 2024;31(4):551-558
Objective To explore the correlation between malignant tumors and serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Methods A total of 336 patients with malignant tumors (cancer group) who were admitted to the Department of Cardiology, Chinese PLA General Hospital and underwent coronary angiography from January 1, 2009 to December 31, 2020, and were newly diagnosed and had not received any anti-tumor treatment were selected. They were matched with 1 008 patients (non-cancer group) in a 1∶3 ratio using propensity score matching based on gender and age. Clinical data of the patients were collected, including age, gender, serum NT-proBNP, left ventricular ejection fraction (LVEF), SYNTAX score, serum creatinine, and tumor diagnosis information. The patients were divided into 4 groups based on the quartiles of NT-proBNP levels: low-level group (NT-proBNP≤61.80 pg/mL), medium-level group (61.80 pg/mL<NT-proBNP≤152.95 pg/mL), high-level group (152.95 pg/mL<NT-proBNP≤470.10 pg/mL), and very high-level group (NT-proBNP>470.10 pg/mL). Ordered logistic regression analysis was used to analyze the correlation between malignant tumors and serum NT-proBNP. Results A total of 1 344 patients were included, with an average age of (65.78±9.18) years old, 1 003 males (74.63%), LVEF of 60.00% (55.00%, 64.00%) , SYNTAX score of (13.84±11.63) points, and creatinine level of 76.60 (66.50, 88.88) μmol/L. Among the 336 cancer patients, the top 3 types of cancer were lung cancer (84 cases, 25.00%), colorectal cancer (58 cases, 17.26%), and gastric cancer (52 cases, 15.48%). The NT-proBNP levels in the cancer group were significantly higher than those in the non-cancer group (208.45[85.75, 601.83] pg/mL vs 134.35[57.18, 430.23] pg/mL, P<0.001). Ordered logistic regression analysis showed that in the unadjusted model, malignant tumors were significantly associated with higher NT-proBNP levels (OR=1.561, 95% CI 1.538-1.584, P<0.001); after adjusting for relevant factors, malignant tumors remained significantly associated with higher serum NT-proBNP levels (OR=1.384, 95% CI 1.070-1.791, P=0.013). Conclusions NT-proBNP in malignant tumor patients is higher than that in non-malignant tumor patients, and there is a significant correlation between malignant tumors and serum NT-proBNP levels.
10.Discovery of novel heteroaryl alkynes for highly potent KITD816V cells inhibition to treat gastrointestinal stromal tumors.
Zhicheng XIE ; Lin LI ; Yihao GUO ; Mi ZHANG ; Taiwen CHEN ; Yongpeng LI ; Xin LI ; Xi ZHU ; Yu ZHANG ; Liguang LOU ; Youhong HU
Acta Pharmaceutica Sinica B 2022;12(10):4004-4007