1.CD4+CD25+regulatory T cells and graft-versus-host disease after hematopoietic stem cell transplantation
Zhi GUO ; Chun TONG ; Huiren CHEN
Chinese Journal of Tissue Engineering Research 2017;21(9):1456-1462
BACKGROUND: Autoreactive T cells are a group of specialized cells that exert a peripheral immunosuppressive effectthrough certain mechanisms ensuring self-tolerance within the adaptive immune system. The discovery of the latestsurface markers for natural CD4+CD25+ regulatory T cells has re-emphasized the concept of peripheral regulation orsuppression of T cells. Several groups have begun to investigate the role of regulatory T cells in animal models ofallogeneic hematopoietic stem cell transplantation.OBJECTIVE: To review the recent results regarding protection from graft-versus-host disease by adoptively transferredCD4+ CD25+ regulatory T cells in mice and to discuss the latest findings from clinical studies on hematopoietic stem celltransplantation.METHODS: We retrieved CNKI, PubMed and Medline databases for articles concerning CD4+CD25+ regulatory T cellsand graft-versus-host disease published from 2000 to 2015. According to inclusion and exclusion criteria, 46 paperswere included in result analysis.RESULTS AND CONCLUSION: CD4+CD25+ regulatory T cells expressing the transcriptional repressor FOXP3 mediateimmunoregulatory functions and are critical for the prevention of autoimmune diseases. As peripheral tolerance inductionis a prerequisite for successful allogeneic hematopoietic stem cell transplantation, the role of CD4+CD25+ regulatory Tcells in transplantation models and clinical trials is now under investigation in many laboratories. CD4+CD25+ regulatoryT cells play an important role in the development of graft-versus-host disease after allogeneic hematopoietic stem celltransplantation. CD4+CD25+ regulatory T cells not only effectively prevent and treat graft-versus-host disease but alsoretain graft-versus-leukemia effect.
2.Perioperative cardiovascular abnormality in elder patients with silent coronary heart disease.
Xiao-Qi ZHAO ; Chun-Guang WANG ; Guo-Li LI ; Tong YAO ; Zhi-Guang SUN
Chinese Journal of Applied Physiology 2014;30(2):127-131
OBJECTIVETo explore the perioperative cardiovascular dysfunction and its relevance to age in patients with silent coronary heart disease (or silent myocardial ischemia), and explore the clinical treatment and recovery of perioperative arrhythmias.
METHODSOne hundred and eighty cases were selected from selective surgery patients with silent myocardial ischemia (SMI). Among the cases, 130 patients older than 51 years old were divided into 51 - 60 year-old group, 61- 70 year-old group and 71 - 80 year-old group. Control group was set up by other 50 patients younger than 51 years old. Electrocardiogram data of 24 h before the operation, 24 h after the operation and 48 h after the operation were continuously monitored by dynamic electrocardiogram (DCG). The electrocardiogram data of ST shifting, arrhythmia incidences of different type and at different time were analyzed by professional doctors. At the same time, the treatment and recovery of perioperative arrhythmia were recorded.
RESULTSAs the age increase, the magnitude and duration of ST shifting appeared upward trend compared to the control group (P < 0.05, P < 0.01). The incidence of ST elevation in 71 - 80 year-old group was higher than the control group (P < 0.05). The ST depression duration in 61 - 70 and 71 - 80 year-old group and ST elevation magnitude in 71 - 80 year-old group were higher than 51 - 60 year-old group (P < 0.05). Compared to the control group, the incidence of accelerated idioventricular rhythm (AIR) in 61 - 70 year-old group and the incidence of sinus bradycardia (SB), ventricular premature beat (VPB), ventricular tachycardia (VT) in 71 - 80 year-old group were higher (P < 0.05, P < 0.01). Compared to the 51 - 60 year-old group, the incidence of atrial fibrillation (AF) in 61 - 70 year-old group and the incidence of VP, VT, AF in 71 - 80 year-old group were higher (P < 0.05, P < 0.01). The arrhythmia incidences in 24 h after operation were higher than 48 h after operation and 24 h before operation (P < 0.01). As the age increase, the recovery incidence by removing inducement was decreased, but the recovery incidences by drug and electric-shock treatment were increased (P < 0.05).
CONCLUSIONOld SMI patients have high levels of perioperative myocardial ischemia and arrhythmia, and 24 h after operation is the period of high incidence.
Aged ; Aged, 80 and over ; Cardiovascular System ; physiopathology ; Coronary Disease ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Perioperative Period
3.Preoperative plasmic D-dimer levels predict the response to first-line chemotherapy and the prognosis of serous ovarian cancer
Ping LIU ; Zhi GUO ; Wenxin LIU ; Ying WANG ; Lina TONG ; Hong NI
Chinese Journal of Clinical Oncology 2015;(18):916-920
Objective:To investigate the correlation of plasma D-dimer levels with the response to first-line chemotherapy and the prognosis of patients with serous ovarian cancer (SOC). Methods:The preoperative plasmic D-dimer levels of 143 patients with prima-ry SOC were retrospectively evaluated. The patients were admitted to Tianjin Medical University Cancer Institute and Hospital between January 2008 and May 2010. The patients were divided into two groups on the basis of plasmic D-dimer levels. Group A consisted of 100 patients with a normal plasmic D-dimer level of≤0.3 mg/L. Group B included 43 patients with an increased plasmic D-dimer level of>0.3 mg/L. The correlations of the different plasmic D-dimer levels with clinicopathological features, therapeutic effects, and surviv-al outcomes were further analyzed. Results:The plasmic D-dimer levels were positively correlated with the staging of the Federation of International Gynecology and Obstetrics, residual tumor size, presence of malignant ascites, preoperative serum CA125 level, and neo-adjuvant chemotherapy. Group B exhibited a significantly lower (P<0.001) complete response (CR) rate of 34.88%(15/43) than group A, which yielded a CR rate of 73.00%(73/100). The progression-free survival and overall survival rates of group B were significantly lower than those of group A (25.58%vs. 50.00%and 32.56%vs. 65.00%;P<0.05). Multivariate analysis revealed that the plasmic D-di-mer level is an independent prognostic factor associated with unfavorable prognosis. Conclusion:Increased preoperative plasmic D-di-mer levels may be a potential biomarker of weak responses to first-line chemotherapy and poor clinical outcomes in patients with SOC.
4.The levels and clinical significances of hepatocyte growth factor in the hepatic tissue and serum of hepatocellular carcinoma
Wenxia SHI ; Yingtang GAO ; Weili WANG ; Li JING ; Tong LIU ; Hua GUO ; Bin YANG ; Zhi DU
Chinese Journal of Laboratory Medicine 2012;35(7):598-603
ObjectiveTo investigate hepatocyte growth factor (HGF) levels in the tissue and serum of patients with chronic hepatitis,cirrhosis or hepatocellular carcinoma (HCC),and analyze the clinical significances of HGF for HCC.MethodSurgical specimens from 97 patients were collected during Dec.2003 to Aug.2008 in the Third Central Hospital.The patients were prospectively enrolled and categorized into four groups:normal subjects ( n =11 ),chronic hepatitis B or C ( n =6=,cirrhosis ( n =20)and HCC ( n =60 ) including well-differentiated ( n =21 ),moderately differentiated ( n =23 ),poorly differentiated (n =16) specimens.N0 (n =24),N1 (n =21 ),N2 (n =54) and N3 (n =43) were tissues respectively removed from liver at 0,1,2 or 3 cm beyond the margin of tumor.HGF mRNA expression in liver tissues was determined by real-time quantitative reverse transcription- (RT)-PCR.Serum HGF levels in the other cases of normal subjects ( n =20),chronic hepatitis B or C ( n =20),cirrhosis ( n =20) and HCC (n =57) were measured by ELISA.The Kaplan-Meier method with log-rank test was employed for survival analysis.Univariate and multivariate analyses were performed to identify prognostic factors in each group.ResultsThe HGF mRNA in normal subjects,chronic hepatitis,cirrhosis,N3,N2,N1,N0 and HCC were0.99(0.78-1.66),2.15(1.06-3.40),1.78(1.18-2.73),4.59(2.67 -8.63),3.86 ( 2.25 - 6.45 ),3.12 ( 1.59 - 5.74 ),2.92 ( 0.88 - 5.99 ) and 0.48 ( 0.19 - 1.06 ) respectively.The serum concentration of HGF in the normal subjects,chronic hepatitis,cirrhosis and HCC patients were (0.31 ± 0.05 ),(0.65 ± 0.07 ),( 1.27 ± 0.30 ) and ( 2.06 ± 0.66) μg/L respectively.The highest level of HGF mRNA was found in N3,while the HGF mRNA expression in HCC was [ (2.14 ± 0.52 ) μg/L] lower than that not only in the non-tumor tissues,but also in the normal control ( U =196.50,P =0.03 ).The serum concentration of HGF was significantly higher in patients with chronic hepatitis,cirrhosis or HCC than in normal subjects.The serum HGF level of HCC was bounced after hepatectomy (t =2.70,P <0.01 ).On the logistic regression analysis,the tumor numbers and Child-pugh were related with the levels of the tissue HGF mRNA and serum HGF of HCC,OR were0.15 (95%CI:0.03-0.72,P<0.05) and0.13 (95%CI:0.27 -0.89,P <0.05 ),respectively.Univariate analysis using the Cox proportional hazards model in the complication groups revealed that the levels of the tissue HGF mRNA and serum HGF were significant risk factors of death for HCC,OR were 0.02 (95% CI:0.00 - 0.52,P < 0.05 ) and 10.01 (95% CI:1.16 -86.23,P < 0.05 ),respectively.On the Log-rank analysis,no statistically difference in the cumulative survival was found between the two groups categorized by median (0.49) of tissue HGF mRNA 2 - AACT (X2 =0.13,P =0.72).While the HCC patients were dichotomized by their the median(0.69 μg/L) of serum HGF concentration,the death risk for the patients with higher levels of HGF was increased 2.84 fold than those with lower levels (95% CI:1.03 - 7.92,P < 0.05 ).ConclusionHGF mRNA expression is decreased in tumor tissues,while its level in tumor adjacent live and serum is significantly elevated and is in association with shortened postoperative survival of HCC patients.
5.Multiple imaging evaluation on the therapeutic efficacy of coronary artery bypass graft combined with autologous stem cell transplantation for myocardial infarction
xiu Guo LU ; hu Shan HAO ; guo Zhi WANG ; Tong ZHANG ; shan Hui WANG ; xu Guo ZHANG
Chinese Journal of Tissue Engineering Research 2017;21(33):5332-5338
BACKGROUND: Stem cells are still controversial for the treatment of old myocardial infarction. Multimodal imaging evaluation is one of the key points in the study of stem cell transplantation, which can evaluate the therapeutic efficacy of stem cell transplantation from the perspective of molecular imaging. OBJECTIVE: To evaluate the therapeutic efficacy of coronary artery bypass graft (CABG) with different stem cell transplantation in patients with old myocardial infarction using multimodal imaging technology. METHODS: Sixty patients with old myocardial infarction were enrolled and randomly divided into three groups to receive CABG, CABG+autologous bone marrow stem cell transplantation (CABG+BMC) or CABG+autologous peripheral blood stem cell transplantation (CABG+PBSC), respectively. All the patients were scanned with gated PET/CT (13N-NH3?H2O/18F-FDG), echocardiography and coronary angiography at different time points orderly (at baseline, 1, 12 and 24 months after treatment). We compared the degree of coronary stenosis (%), left ventricular ejection fraction (LVEF), percentage of defect size with myocardial perfusion/metabolic abnormal radioactive distribution (A) and the ratio of defect area (R).RESULTS AND CONCLUSION: In the diagnosis of survival myocardial segments, the sensitivity, specificity, positive predictive value and negative predictive value for the gated PET/CT were 92.1%, 85.6%, 93.4% and 78.4%, respectively. After the above treatments, the extent of coronary stenosis decreased significantly in the three groups (P < 0.05), which was improved most at 1 month after treatment (P < 0.05). In the CABG+BMC and CABG+PBSC groups, the LVEF value increased significantly after treatment (P < 0.05). In the CABG+BMC group, the A value decreased significantly at 1 and 24 months after treatment as compared with the baseline (P < 0.05), and the A value was further decreased, indicating a significant difference at 12 and 24 months after treatment (P < 0.05). In the CABG+BMC group, the R value significantly decreased at 1 month after treatment compared with the baseline (P=0.019). To conclude, the multimodal imaging is better to evaluate the prognosis of patients undergoing CABG with different stem cell transplantation, which is beneficial for the selection of treatment and therapeutic evaluation in myocardial infarction patients. CABG combined with stem cell transplantation can improve the left ventricular function of patients in a short time, and CABG+BMC is superior to CABG+PBSC to improve the survived myocardial function in patients.
6.The preliminary research of immune function monitoring before and after allogeneic hematopoietic stem cell transplantation in children with aplastic anemia
Chun TONG ; Zhi GUO ; Jinxing LOU ; Xiaodong LIU ; Kai YANG ; Xuepeng HE ; Yuan ZHANG ; Peng CHEN ; Huiren CHEN
Chinese Journal of Applied Clinical Pediatrics 2016;(3):199-202
Objective To explore the clinical significance of the relationship between the immune function and the pathogenesis of aplastic anemia in children with aplastic anemia(AA),along with the incidence of graft versus host disease (GVHD)by monitoring the changes of T lymphocyte subsets dynamically in +1 ,+3,+6,+1 2 months for blood disease patients after allogeneic hematopoietic stem cell transplantation.Methods Twelve AA patients re-ceived allogeneic hematopoietic stem cell transplantation in Department of Hematology,the Affiliated General Hospital of Beijing Military Region of Anhui Medical University,from January 201 3 to January 201 4,including 4 male and 8 fe-male,with average age of 7.92 years old(3 -1 4 years old)with 5 cases of human leukocyte antigen(HLA)matched and 7 cases of HLA mismatched.The level of T lymphocyte subsets including CD3 +,CD4 +,CD8 +,CD4 +/CD8 +, CD56 +,CD4 +CD25 high +FOXP3 +were monitored with flow cytometry before transplantation and in +1 ,+3,+6,+1 2 months after transplantation dynamically in the peripheral blood.While in the same period the level of T lymphocyte subsets was monitored in 1 2 cases of healthy children at the same period as the healthy control group.Results Fol-lowed up to March 201 5,1 0 cases had abnormal cellular immunity (CD4 +/CD8 + ratio inversion)in the 1 2 AA pa-tients.Compared with the control group,in the AA group,CD3 + was slightly higher,(66.79 ±7.35)% and (62.74 ± 5.58)% respectively(P =0.043),CD4 + was decreased by (33.73 ±7.26)% and (39.54 ±3.46)% respectively (P =0.037),CD8 + was increased by (35.69 ±6.78)% and (25.34 ±4.36)%,respectively (P =0.000),CD4 +/CD8 + decreased by 1 .23 ±0.56 and 1 .78 ±0.34 respectively(P =0.001 )and CD56 + was decreased by (7.46 ± 2.80)% and (1 6.73 ±3.70)% respectively(P =0.000),CD4 +CD25 high +FOXP3 + was decreased by (3.3 ± 1 .5)% and (8.1 ±1 .3)% respectively (P =0.003),whose difference was statistically significant (P <0.05).The lever of CD3 +,CD4 +,CD8 +,CD4 +/CD8 +,CD56 +,CD4 +CD25 high +FOXP3 + had a different degree of recovery after transplantation for all cases and returned to normal in +1 2 months basically.In +1 ,+3,+6,+1 2 months after transplantation,the levels of CD4 +CD25 high +FOXP3 + in GVHD positive group and negative group were (0.4 ± 0.6)% and (1 .6 ±0.7)% respectively,(0.7 ±0.3)% and (2.7 ±0.4)% respectively,(1 .1 ±0.5 )% and (2.9 ±0.7)% respectively,(1 .4 ±0.3)% and (3.6 ±0.2)% respectively,which had statistical significance (P <0.05).Conclusions There was abnormal cell immune function in some cases with AA.After transplantation,the level of CD4 +CD25 high +FOXP3 + is closely related to the acute GVHD,which can be used to predict the occurrence of GVHD.
7.Quantitation of hepatitis B virus total DNA, covalently closed circular DNA and HBsAg in patients with different stages of hepatitis B virus infection
Ying LI ; Tao HAN ; Yingtang GAO ; Zhi DU ; Yijun WANG ; Li JING ; Tong LIU ; Hua GUO ; Xiaoyan MA ; Yanzhen PEI
Chinese Journal of Infectious Diseases 2012;30(8):463-467
Objective To quantitatively analyze total hepatitis B virus (HBV) DNA (HBV tDNA),covalently closed circular DNA (cccDNA) and HBsAg in patients with chronic hepatitis B (CHB),HBV-related liver cirrhosis (LC) and hepatocellular carcinoma (HCC),and to analyze the characteristics.Methods HBV tDNA and HBV cccDNA in the serum and liver biopsy samples were measured in 21 CHB,23 LC and 25 HCC patients by real-time polymerase chain reaction (PCR) assay. HBsAg titer was measured by chemiluminescence. Normally distributed variables among multiple groups were analyzed by ANOVA and t-test.Correlation between two variables was tested using Pearson correlation analysis.Skewed distribution was tested using Rank sum test.Results In CHB,LC and HCC patients,the serum HBV tDNA levels were (5.38±2.08),(4.96± 1.65) and (4.18 ± 0.91) lg copy/mL,respectively; the intrahepatic HBV tDNA levels in three groups were (7.18±1.91),(6.51±1.87) and (5.87± 1.47) lg copy/ug,respectively; the intrahepatic HBV cccDNA levels were (3.53±2.03),(2.63±2.13) and (0.58± 1.40) lg copy/μg,respectively; the serum HBsAg levels were (3.30±0.65),(3.12±0.52) and (2.60± 1.03) lg IU/mL,respectively.In CHB patients,the serum HBV tDNA,intrahepatic HBV tDNA,HBV cccDNA and HBsAg levels were all significantly higher than those of HCC patients (t=2.446,P=0.013; t=2.562,P=0.014;t=5.799,P<0.01 ; t=2.709,P=0.003,respectively).However,only intrahepatic HBV cccDNA and HBsAg levels were statistically different between LC and HCC patients (t=-3.894,P<0.01;t=-2.237,P=0.023,respectively).HBV cccDNA was all negative in the serum of 69 patients.The serum HBsAg level was positively correlated with serum HBV tDNA (r=0.290,P=0.016),intrahepatic HBV tDNA (r=0.372,P =0.002) and intrahepatic HBV cccDNA (r=0.378,P=0.001).Conclusions The levels of HBV tDNA,HBV cccDNA and HBsAg decrease gradually with the disease progression.The serum HBsAg level is positively correlated with serum HBV tDNA,intrahepatic HBV tDNA and intrahepatic HBV cccDNA.
8.Haploidentical allogeneic hematopoietic stem cell transplantation for severe aplastic anemia:a retrospective analysis
Chun TONG ; Zhi GUO ; Jinxing LOU ; Xiaodong LIU ; Kai YANG ; Xuepeng HE ; Yuan ZHANG ; Peng CHEN ; Huiren CHEN
Chinese Journal of Tissue Engineering Research 2015;(36):5821-5826
BACKGROUND:Al ogeneic hematopoietic stem cel transplantation is currently recognized as the first-line therapy for severe aplastic anemia. However, with the popularity of the one-child families, the source of ful y matched hematopoietic stem cel transplantation is limited, so haploidentical hematopoietic stem cel transplantation is favored. OBJECTIVE:To retrospectively compare and analyze the clinical efficacy and safety of haploidentical al ogeneic hematopoietic stem cel transplantation and ful y matched hematopoietic stem cel transplantation for the treatment of severe aplastic anemia. METHODS:Clinical data of 15 patients with severe aplastic anemia (treatment group) who underwent haploidentical al ogeneic hematopoietic stem cel transplantation in the Department of Hematology General Hospital of Beijing Military Region from January 2013 to January 2015 were retrospectively analyzed. Pretreatment regimen was cyclophosphamide, fludarabine, Busulfex, combined with anti-human lymphocyte immune globulin. Donors received granulocyte colony-stimulating factor, and the transplantation method was bone marrow mobilization combined with peripheral blood stem cel transplantation. Combined immunosuppressive agents including cyclosporine A, methotrexate, tacrolimus, were adopted for prevention of graft versus host disease. Another 15 cases of severe aplastic anemia undergoing ful y matched hematopoietic stem cel transplantation served as control group over the same period. Complications and survival of the two groups were statistical y analyzed. RESULTS AND CONCLUSION:By the end of July 2015, the median fol ow-up time of the treatment group was 20.7 months (6-30 months), and hematopoietic reconstruction was achieved in al cases, including four cases of graft versus host disease, five cases of pulmonary infection, three cases of sepsis, and one case died of pulmonary infection, one cases died of sepsis, and two cases died of graft versus host disease. In the control group, the median fol ow-up time was 19.7 months (5-28 months), hematopoietic reconstruction was achieved in al cases. There were three cases of graft versus host disease, four cases of pulmonary infection, one case died of pulmonary infection, and two cases died of graft versus host disease. The total survival rates of the two groups were 73%and 80%respectively, with no significant difference (P=0.67). The haploidentical al ogeneic hematopoietic stem cel transplantation for severe aplastic anemia is safe and effective, and the clinical efficacy is comparable to the ful y matched hematopoietic stem cel transplantation.
9.Influence of TangNaiKang on VEGF protein expression of GK rats thoracic aorta
Xiang-yu GUO ; Ying DUAN ; Zhi-cheng WANG ; Jie NIU ; Li-xia YANG ; Juane LI ; Tong-hua LIU ;
International Journal of Traditional Chinese Medicine 2010;32(3):200-202
Objective To investigated the effect of TangNaiKang (TNK) on VEGF protein expression of GK rats Thoracic aorta. Methods 51 male GK rats were divided into five groups randomly: model group, pioglitazone group, and TNK treatment group (low, immediate and high dose). Another 10 male Wistar rats were served as normal control group. GK rats were fed with high-grease forage, while normal control group was fed with a standard diet. Fasting blood glucose, general HE staining and VEGF protein expression were detected by immunohistochemistry. Results The fasting glucose had a significant decline in TNK treatment groups. HE staining showing TNK can ameliorate intima thickness, reduce hyperplasia of shallow vascular smooth muscle cell, and improve wavy and plexiform arrangement of elastic lamina. Immunohistochemistry also showed that TNK decreased VEGF protein expression of great vessels. Conclusion TangNaiKang can prevent and cure diabetic vascular complication of GK rats.
10.Protective effect of baicalin against rotenone induced injury on PC12 cells.
Hai-Lie JI ; Li-Guo TONG ; Chong-Zhi BAI ; Mei-Qing SONG ; Nai-Hong CHEN ; Ma-Li FENG
China Journal of Chinese Materia Medica 2014;39(15):2947-2951
OBJECTIVETo explore the protective effect of baicalin against rotenone-induced injury on PC12 cells, and the po-tential mechanism of action action was also explored.
METHODPC12 cells were injured by rotenone and were treated with different concentrations (0.1, 1, 10 μmol x L(-1)) of baicalin at the same time. Cell viability was analyzed by MTT, and morphology was observed by phase-contrast microscopy. The cell apoptosis was detected by flow cytometry by Annexin V-FITC/PI staining. The intracellular ROS level was determined by fluorescence microscope with DCF-DA staining. The expression of Bcl-2, Bax and Caspase-3 was analyzed by Western blot.
RESULTThe viability of PC12 cells exposure to rotenone for 24 hour was gradually decreased with dose escalating and 1.5 μmol x L was adopted to do the following experiment. Baicalin increased cell viability, improved cell morphology and decreased intracellular ROS level. Moreover, FACS indicated baicalin attenuated the apoptosis induced by rotenone significantly. Western blot showed that Bcl-2, Bax and Caspase-3 expression in rotenone-induced PC12 cells was reversed by baicalin.
CONCLUSIONThis study has demonstrated that baicalin protects PC12 cells against rotenone-induced apoptosis, at least in part, by scavenging excessive ROS and inhibiting the mitochondrion-dependent apoptotic pathway.
Animals ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Survival ; drug effects ; Cytoprotection ; drug effects ; Flavonoids ; pharmacology ; Gene Expression Regulation ; drug effects ; Intracellular Space ; drug effects ; metabolism ; PC12 Cells ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Reactive Oxygen Species ; metabolism ; Rotenone ; pharmacology ; bcl-2-Associated X Protein ; metabolism