1.Strategies of lowering relapse after allogeneic hematopoietic stem cell transplantation for high-risk myelodysplastic syndrome
Ran ZHANG ; Xuan LU ; Han YAN ; Huafang WANG ; Yong YOU ; Zhaodong ZHONG ; Linghui XIA ; Wei SHI
Chinese Journal of Organ Transplantation 2021;42(4):197-202
		                        		
		                        			
		                        			Objective:To explore the strategies of reducing relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with high-risk myelodysplastic syndrome (MDS) from the perspectives of optimizing the conditioning regimen and pre-transplant cytoreductive therapy.Methods:A total of 84 patients with high-risk MDS undergoing allo-HSCT between January 2013 and September 2019 were retrospectively analyzed. Based upon preparative regimens, they were divided into two groups of decitabine intensified BUCY2 ( n=49) and BUCY2 regimen ( n=35), based upon whether or not pre-treatment prior to allo-HSCT: cytoredutive treatment ( n=34) and none ( n=50). Two groups were compared with regards to hematopoietic reconstitution, graft-versus-host disease (GVHD), relapse rate, transplant-related mortality (TRM) and survival. Results:No significant inter-group differences existed in hematopoietic reconstitution or acute/chronic GVHD. The relapse rate was significantly lower in decitabine intensified group than that in BUCY2 group (18.7% vs 40.0%, P=0.025). Survival was significantly better in decitabine intensified group than that in BUCY2 group (3-year OS: 71.3% vs 51.2%, P=0.038; 3-year DFS: 65.3% vs 45.2%, P=0.033). Moreover, the incidence of recurrence was markedly lower in pre-transplant treatment group than that in non-treatment group (20.7% vs 38.9%, P=0.035). The inter-group incidence of TRM was not different. Three-year OS/DFS of treatment group were remarkably superior to those of non-treatment group (71.2% vs 50.8%, P=0.024; 64.7% vs 45.9%, P=0.044). Conclusions:As an optimal conditioning regimen for high-risk MDS, decitabine intensified BUCY2 regimen could better eliminate tumor burden, remarkably lower relapse rate and improve OS after allo-HSCT. In addition, pre-transplant treatment significantly reduces relapse and offers benefit for OS after allo-HSCT. Therefore intensified conditioning regimen and pre-transplant treatment may be promising strategies of reducing relapse and improving survival for high-risk MDS. However, it still needs further confirmation from prospective randomized controlled trials.
		                        		
		                        		
		                        		
		                        	
2.Optimization of ATG dose in haploid hematopoietic stem cell transplantation for hematologic malignancies
Xi ZHOU ; Xuan LU ; Liang TANG ; Han YAN ; Wenlan CHEN ; Wei SHI ; Zhaodong ZHONG ; Yong YOU ; Linghui XIA ; Yu HU ; Huafang WANG
Chinese Journal of Hematology 2020;41(7):557-563
		                        		
		                        			
		                        			Objective:To compare the clinical efficacy of different doses of rabbit antithymocyte globulin (rATG) in haplo-HSCT in the treatment of hematologic malignancies.Methods:Malignant hematological patients treated at our hospital from March 2013 to December 2018 were retrospectively analyzed. These patients were divided into three groups as per three doses of ATG (6 mg/kg, 7.5 mg/kg, and 9 mg/kg) in the conditioning regimens. The transplant outcomes were compared in terms of the occurrence of acute graft versus host disease (GVHD) , infection, and survival.Results:①Total 288 patients were enrolled in the study, including 182 men and 106 women, with a median age of 18 (6-62) years. Total 110 patients were diagnosed with acute lymphoblastic leukemia (ALL) , 128 with acute myelogenous leukemia (AML) , 8 with chronic myeloid leukemia (CML) , 28 with myelodysplastic syndrome (MDS) , and 14 with mixed cell leukemia (MAL) . There were 159 patients in the ATG-6 group, 72 in the ATG-7.5 group, and 57 in the ATG-9 group. The median follow-up time of post transplantation was 14 (0.2-74) months. ②The incidence of neutrophil engraftment (96.9% , 97.2% , and 96.5% , respectively) and platelet engraftment (92.5% , 87.5% , and 86% , respectively) did not significantly differ among the ATG-6, ATG-7.5, and ATG-9 groups ( P=0.972, P=0.276) . The incidence of grades 2-4 acute GVHD was 14.5% , 11.1% , and 8.8% in the three groups, respectively ( P=0.493) , chronic GVHD incidence in the three group was 8.8% , 14.3% and 12.0% , respectively ( P=0.493) . The infection rates of CMV and EBV in the ATG-9 group (77.2% and 12.5% ) were significantly higher than those in the ATG-6 (43.3% and 3.5% ) , and ATG -7.5 group (44.4% and 1.5% ) ( P<0.001 and P=0.033, respectively) . ③Among the three groups, there were no significant difference in the 3-year overall survival [68.5% (95% CI 60.3% -77.9% ) , 60.1% (95% CI 48.3% -74.8% ) , 64.7% (95% CI 51.9% -80.7% ) ], cumulative incidences of relapse [34.6% (95% CI 34.3% -35.1% ) , 38.0% (95% CI 37.3% -38.7% ) , 20.6% (95% CI 20.0% -21.3% ) ], disease-free survival [53.3% (95% CI 44.9% -63.4% ) , 51.9% (95% CI 41% -65.8% ) , 63.9% (95% CI 51.9% -78.7% ) ] and non-relapse mortality [24.2% (95% CI 23.8% -24.5% ) , 26.0% (95% CI 25.4% -26.6% ) , 23.6% (95% CI 26.3% -28.2% ) ] ( P=0.648, P=0.165, and P=0.486 and P=0.955) . Conclusion:Low dose (6 mg/kg) of rATG may increase the risk of grade Ⅱ-Ⅳ aGVHD, and a high dose (9 mg/kg) of ATG could significantly increase the risk of CMV and EBV infection. Median dose (7.5 mg/kg) of ATG is expected to reduce the incidence of moderate to severe aGVHD and viral infections without increasing the mortality.
		                        		
		                        		
		                        		
		                        	
3.Role of cerebrospinal fluid chimerism in predicating central nervous relapse surveillance for patients of acute leukemia after allogeneic hematopoietic stem cell transplantation
Junying LI ; Zhaodong ZHONG ; Yong YOU ; Liang TANG ; Xuan LU ; Han YAN ; Huafang WANG ; Linghui XIA ; Yu HU ; Wei SHI
Chinese Journal of Organ Transplantation 2019;40(3):138-143
		                        		
		                        			
		                        			Objective To explore the role of cerebrospinal fluid chimerism in central nervous relapse surveillance for patients of acute leukemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods The follow-up data were retrospectively collected and analyzed in 104 patients with acute leukemia after allo-HSCT.Comparisons were made between patients with complete chimerism and mixed chimerism in cerebrospinal fluid.The role of recipient DNA percentage and its changing trend in predicting central nervous relapse were also explored.Analysis was conducted for determining the risk factors of central nervous relapse.And the effectiveness of prophylaxis with intrathecal injection was also examined.Results The incidence of relapse was higher in patients with mixed chimerism (P<0.001),high percentage of recipient DNA (P<0.05) and higher mixed chimerism (P<0.001).Hyperleukocytosis at an initial diagnosis was a risk factor of central nervous relapse.Whether or not intrathecal injection prophylaxis was applied showed no significant difference in relapsing rate.Conclusions Monitoring cerebrospinal fluid chimerism can effectively help predict central nervous relapse among patients of acute leukemia after allo-HSCT.Yet intrathecal injection prophylaxis failed to benefit recipients.
		                        		
		                        		
		                        		
		                        	
4.Construction of prostate cancer diagnosis model based on high throughput sequencing data
Funeng JIANG ; Xin ZHANG ; Chao CHEN ; Zhaodong HAN ; Yongding WU ; Weide ZHONG ; Yuxiang LIANG
Chinese Journal of Urology 2017;38(z1):61-63
		                        		
		                        			
		                        			Objective We used the dataset base on high throughput sequencing data to construct a diagnosis model by ANN and GA.Methods We screened the Taylor_prostate datasets from GEO according to,then we used the GA to screen the datas further. Finally we used the ANN to analyze the datas and construct a diagnosis model. To validate the model,we used 10-folds crossvalidation as the inner validation and the datas from Grasso dataset( GPL6480 and GPL6848) were used as the outter validation.Results We got 5 genes ACADL,ACTG2, CACNA2D1,PCP4 and SPARCL1.And we used spss to get the AUC of the model which is 94.62.The result of validation is good.Conclusion The performance of the model is good because the AUC is larger than 0.5.
		                        		
		                        		
		                        		
		                        	
5.The value of retinoblastoma binding protein 4 in the diagnosis of prostate cancer
Jun ZOU ; Funeng JIANG ; Zhaodong HAN ; Yanru CHEN ; Yongding WU ; Weide ZHONG
Chinese Journal of Urology 2016;37(9):703-706
		                        		
		                        			
		                        			Objective To explore the value of retinoblastoma binding protein 4 ( RBBP4 ) in diagnosing prostate cancer ( PCa).Methods From January 2015 to December 2015, the prostate tissue after prostatectomy were collected and the differentially expressed degree of RBBP4 protein was analyzed in PCa and adjacent tissues by 2D-DIGE technology.The RBBP4 score of prostate tissue chip which contains 3 normal prostate tissues, 7 cancer adjacent normal prostate tissues, 50 adenocarcinoma and 20 hyperplasia tissue was checked by immunohistochemistry( IHC).In 50 patients with PCa, 4 cases were less than 60 years old and 46 cases were more than 60 years.In those patients, the Gleason scores were less than 7 scores in 18 cases, and more than 7 scores in 30 cases.22 cases were confirmed less than Ⅱ stage, and 28 cases were confirmed more than Ⅲ stage.Finally, the RBBP4 IHC score and the clinic-pathological parameters such as age, Gleason score and clinical stage of PCa patients were analyzed together.Results We found that the protein of RBBP4 increased by 2.15 times in PCa tissues compared to adjacent tissues by using 2D-DIGE technology( P=0.008).The expression of RBBP4 was higher than that in benign tissues by IHC ( F=43.972,P=0.000).And the expression of RBBP4 was positive correlation with Gleason score( t=5.589, P=0.000) and clinical stage(t=5.620,P=0.000), but was negative correlation with age(t=1.125,P=0.266).Conclusions The detection of RBBP4 can help to separate PCa from benign tissues.The overexpression of RBBP4 might result in the rapid growth of malignant cells.It may have certain value in determine the clinical staging and pathological grading of PCa.
		                        		
		                        		
		                        		
		                        	
6.Effects of narrow-band ultraviolet B on expression of IL-23/IL-17 axis and efficacy in patients with psoriasis vulgaris
Zhongyong WANG ; Lei MA ; Huifen QIU ; Zhaodong HAN
Chinese Journal of Physical Medicine and Rehabilitation 2013;35(7):564-567
		                        		
		                        			
		                        			Objective To observe clinical efficacy of NB-UVB in treating psoriasis vulgaris and its effects on expression of serum interleukin-17 (IL-17),interleukin-23 (IL-23) and interleukin-22 (IL-22) in patients with psoriasis vulgaris,and to study the underlying mechanisms of NB-UVB.Methods Ninety patients were recruited and treated with NB-UVB therapy for 8 weeks.Before and after treatment,the serum level of IL-17,IL-23,IL-22,interleukin-l0(IL-10) and transforming growth factor(TGF-β) were tested by use of ELISA method,meanwhile Psoriasis Area and Severity Index (PASI) were used to evaluate clinical efficacy.Fifty healthy volunteers were selected as control group.Results Compared to healthy controls,the level of serum IL-17,IL-23 and IL-22 was significantly higher in patients with psoriasis vulgris (P < 0.01),and IL-10,TGF-β shown lower expression in psoriasis patients (P < 0.01).After 8 weeks of treatment with NB-UVB,serum levels of IL-17,IL-23 and IL-22 in psoriasis patients decreased significantly (P < 0.01),while IL-10,TGF-βelevated significantly (P < 0.01) in contrast.The Psoriasis Area and Severity Index (PASI) results indicated significantly clinical improvement after therapy,and the total effective rate was 87.78%.Conclusion NB-UVB could down-regulate serum IL-17,IL-23,IL-22 and up-regulate IL-10,TGF-β,which may help regulate imbalance of T lymphocytes cells of psoriasis patients.The clinical data demonstrate that the treatment of NB-UVB is a safe,effective method for psoriasis vulgaris.
		                        		
		                        		
		                        		
		                        	
7.The effects of narrow-band ultraviolet B on the expression of the CC subfamily of chemokines and its efficacy in treating patients with atopic dermatitis
Zhongyong WANG ; Zhaodong HAN ; Lei MA ; Jianming ZHANG ; Yujie ZHANG ; Yu GAO
Chinese Journal of Physical Medicine and Rehabilitation 2012;34(3):186-189
		                        		
		                        			
		                        			Objective To observe the clinical efficacy of narrow-band ultraviolet B (NB-UVB) in the treatment of the patients with atopic dermatitis (AD) and the effects of NB-UVB on the expression of the CC subfamily of chemokines in AD patients. Methods Fifty-five AD patients were treated with NB-UVB with a starting dose of 50% of the minimal erythma dose.ELISA was used to measure the serum levels of thymus and activation-regulated chemokine ( TARC),cutaneous T cell-attracting chemokine ( CTACK),macrophage-derived chemokine (MDC) and eotaxin in all of the patients before and after treatment,and the clinical efficacy was evaluated.The scores on an atopic dermatitis index (SCORAD) and a visual analogue scale were used for the clinical evaluation.Thirty healthy persons were recruited and served as normal controls. Results The serum levels of TARC,CTACK and MDC were significantly higher in patients with AD than in the normal controls.There was no significant difference between the patients and controls with regard to the average serum level of eotaxin.After treatment with NB-UVB,the serum levels of TARC,CTACK and MDC,but not eotaxin,significantly decreased in the patients.The total clinical effectiveness rate was 76.36%,and the accumulated SCORAD points and VAS scores decreased significantly. Conclusions NB-UVB is able to down-regulate significantly the serum levels of TARC,CTACK and MDC.It can affect immune function and regulate any imbalance of Th1/Th2 cells.This might be one of the mechanisms of NB-UVB treatment for AD.The clinical data demonstrate that NB-UVB is a safe and effective treatment for AD.
		                        		
		                        		
		                        		
		                        	
8.Effects of RNA interference targeting HOXA9 on the proliferation and apoptosis of human acute monocytic leukemia U937 cells
Liping ZHU ; Xiuhong JIA ; Jianchang LI ; Zhaodong HAN
Cancer Research and Clinic 2012;24(8):533-536
		                        		
		                        			
		                        			Objective To investigate the effects of small interference RNA (siRNA) targeting HOXA9 on the proliferation and apoptosis of human acute monocytic leukemia U937 cell line.Methods Effective and specific siRNA oligo targeting HOXA9 was designed and compounded.It was transfected transiently into U937 cells by cationic liposome.The cells was divided into three groups:experimental group(siRNA targeting HOXA9 was transfected by liposome),negative control group (negative siRNA was transfected by liposome) and cell control group (add equal cells and medium).The expression of HOXA9 mRNA and protein were detected by reverse transcription PCR and Western blot.The cell proliferation was assessed by MTT.The apoptosis of each group were measured by Annexin V-FITC.Results Aftcr transfected by siRNA targeting HOXA9,the relative mRNA expression levels of HOXA9 in the experimental group,negative control group and cell control group were (22.980±0.548) %,(82.371±1.517) % and (84.637±2.252) %,respectively (P < 0.05),and the relative protein expression levels were (50.377±2.773).%,(105.500±3.900) % and (111.392±3.905) %,respectively (P < 0.05).The inhibitory rates of cell proliferation and the apoptosis rates of the experimental group were significantly increased.The inhibitory rates of cell proliferation of 24 h,48 h and 72 h were (41.909±4.333) %,(54.470±3.756) % and (65.835±1.024) %,respectively,and the apoatosis rate was (26.800±2.081) %.Compared with 2 controls,the experimental group differences had statistically significance (P < 0.05).Conclusion siRNA targeting HOXA9 can effectively silence HOXA9 gene expression in U937 cell,suppress cell proliferation and induce cell apoptosis obviously,which providing experimental basis for clinical lenkemia therapy by targeting HOXA9 gene.
		                        		
		                        		
		                        		
		                        	
9.A study of the effect of ligustrum quihoui carr (LQC)on the immune function of B lymphocytes and NK iymphocytes in mouse with impaired immune function
Yueqin RUAN ; Zhaodong HAN ; Lejun GAO ; Xianghua KONG
International Journal of Traditional Chinese Medicine 2011;33(9):811-813
		                        		
		                        			
		                        			ObjectiveTo explore the effect and mechanism of LQC on the immune function of B lymphocytes and NK lymphocytes in mouse with impaired immune function. Methods Mice with impaired immune function led by Cyclophosphamide (Cy)were used as experimental animmals, and divided into five groups randomly, twelve mice in every group, which is NS control group, Cy control group, Cy+ LQC minor and major dose group, and Cy + LQC decoction group. NS control group was given NS 0.2 ml/d subcutaneously 10 d, and the rest groups were given Cy 0.8 ml/d subcutaneously (20 mg/kg · d-1) 10d, to establish a mouse model of immune dysfunction. Since the 11th day each group was given NS, Cy, LQC minor dose, major dose and fructus ligustri lucidi decoctoin. Mice of each group were killed after 7 days. The percentage of B lymphocytes (CD3 - CD19 + ) and NK lymphocytes (CD3 - CD 16 + CD56 + ) in the peripheral blood of the experimental mice were detected by flow cytometer. ResultsIn comparison with LQC major dose group [ (20.44± 1.78)and(19.12± 1.70) ], fructus ligustri lucidi group[ (19.90± 1.42) and (20.17± 1.66) ], CD3-CD19+and CD3-CD16+CD56+ cells of LQC minor dose group[ (11.54±0.98) and (12.46±0.08)]were decreased significantly (P<0.01), which were increased significantly compared with Cy group[ (4.53± 1.70) and (5.03 ±1.22) ] (P< 0.01), but they had no significant difference with NS [ ( 11.84 ± 0.99) and ( 12.90± 0.28) ] (P > 0.05).In comparison with Cy group and NS group, CD3-CD19+ and CD3-CD16+CD56+ cells of LQC major dose group were increased significantly (P<0.01), which had no significant difference with fructus lignstri lucidi group (P>0.05). Conclusion The immune functions of the mice with impaired immune function were improved by LQC, it also could increase the quantity ofCD3-CD19+ cell and CD3-CD16+CD56+ cell. The dose of LQC was positively correlated with the modulation effect of LQC on the immune function.
		                        		
		                        		
		                        		
		                        	
10.Effect of Chinese herbal medicine immunomodulator on T lymphocyte immune function in immature rats with obstructive jaundice
Yueqin RUAN ; Zhaodong HAN ; Tingliang FU
International Journal of Traditional Chinese Medicine 2011;33(5):394-396
		                        		
		                        			
		                        			Objective To evaluate the effect of Chinese herbal medicine immunomodulator on T lymphocyte immune function in peripheral blood and intestinal mucosa of immature rats with obstructive jaundice. Methods Three-weeks Wistar rats were randomly divided into four groups. (n= 12, in each): normal control group, sham operation group, obstructive jaundice (OJ) group, OJ + Chinese herbal medicine immunomodulator (OJ+ZY) group. Except for the normal control group, the others' bile duct stones were ligatured to establish rat models with obstructive jaundice. The percentage of CD4+ and CD8+ tlymphocytes and the ratio of CD4+/CD8+ in peripheral blood and intestinal mucosa of immature rats was detected by flow cytometry. Results The percentage of CD4+ cell [(36.2 ±4.2)%, (28.8±1.8)% respectively] and the ratio of CD4+/CD8+ [(1.14±0.39), (1.37±0.34)respectively] in OJ group were lower than those in normal control group [peripheral blood: CD4+(41.5±5.3)%,CD4+/CD8+(1.37±0.19); intestinal mucosa: CD4+(32.3± 2.4)%, CD4+/CD8+ (1.84+0.28) and sham operation group (peripheral blood: CD4+ (41.2±5.5)%, CD4+/CD8+ (1.45±0.27); intestinal mucosa: CD4+(31.5 ± 2.7)%, CD4+/CD8+ (1.63±0.58)] . The difference was statistical significant(P<0.05). The percentage of CD4+ cell [(42.7±6.3)%, (33.6±2.4)% respectively] and the ratio of CD4+/CD8+ [(1.56±0.46), (1.84±0.56)respectively] in OJ+ZY group, were higher than those in OJ group(P<0.05). The difference was statistical significant(P<0.05). Conclusion Chinese herbal medicine immunomodulator can increase T lymphocyte immune function in immature rats with obstructive jaundice, but has no significance in normal control group as well as sham operation group.
		                        		
		                        		
		                        		
		                        	
            
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