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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.
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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.
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Objective To test the the reliability and validity of the Chinese version of the adult haemophilia activities list (HAL).Methods A Chinese version of the HAL was prepared by translation,back-translation and revision.Adult hemophilia patients were used to test it and a short-form arthritis impact measurement scale (AIMS-SF) simultaneously.A total of 98 valid questionnaires were collected.The internal consistency,reliability,split-half reliability,content validity,construct validity and convergent validity were tested.Results The Cronbach's α coefficients for the total questionnaire and its dimensions were all 0.7 or more.The half-reliability test produced a Spearman.correlation coefficient of 0.97.The Pearson correlation coefficients relating each dimension score with the total score and each dimension's entry score with the dimension score were all greater than 0.6.The correlation coefficient between the dimensions of the two questionnaires was smaller than the correlation coefficients relating each dimension with the total scale.There was relatively good correlation between the HAL sum score and the AIMS2-SF sum score (r=0.640,P≤0.01),as well as between the HAL sum score and the AIMS2-SF physical score (r=0.576,P≤0.01).Conclusion The Chinese version of the adult HAL has good reliability and validity.
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Under the available data gathered from a coronary study questionnaires with 10 792 cases,this article constructs a Bayesian network model based on the tabu search algorithm and calculates the conditional probability of each node,using the Maximum-likelihood.Pros and cons of the Bayesian network model are evaluated to compare against the logistic regression model in the analysis of coronary factors.Applicability of this network model in clinical study is also investigated.Results show that Bayesian network model can reveal the complex correlations among influencing factors on the coronary and the relationship with coronary heart diseases.Bayesian network model seems promising and more practical than the logistic regression model in analyzing the influencing factors of coronary heart disease.
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Under the available data gathered from a coronary study questionnaires with 10 792 cases,this article constructs a Bayesian network model based on the tabu search algorithm and calculates the conditional probability of each node,using the Maximum-likelihood.Pros and cons of the Bayesian network model are evaluated to compare against the logistic regression model in the analysis of coronary factors.Applicability of this network model in clinical study is also investigated.Results show that Bayesian network model can reveal the complex correlations among influencing factors on the coronary and the relationship with coronary heart diseases.Bayesian network model seems promising and more practical than the logistic regression model in analyzing the influencing factors of coronary heart disease.
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Objective To compare the planning quality and acute toxicity between RapidArc and fixed gantry angle dynamic intensity modulated radiotherapy (IMRT) in the postoperative radiotherapy for cervical cancer patients.Methods All 35 patients with cervical cancer who had received postoperative radiotherapy were studied,including 17 patients with RapidArc and 18 patients with IMRT.All plans were prescribed 50 Gy in 25 fractions.The dose-volume histogram data,the conformity index and homogeneity index of the targets,the monitor units (MUs) and delivery time were compared.During the treatment,the incidence of acute intestinal and bladder side effects were also compared.Results Compared to IMRT,the conformity index of RapidArc was better(t =3.13,P ＜ 0.05),but the homogeneity index was slightly worse (t =-4.25,P ＜ 0.05).The V20 and V30 of femoral head planned by RapidArc was significantly lower than that by IMRT (t =2.56,2.34,P ＜ 0.05).The mean MU for RapidArc was reduced by 52.1％ compared with IMRT.The mean treatment time for RapidArc was decreased by 46.8％ compared with IMRT.There was no difference in the incidence of acute intestinal and bladder toxicity between the two groups.Conclusion For patients with cervical cancer who need prophylactic postoperative radiotherapy,both RapidArc and IMRT plan can achieve equal target coverage and organs at risk(OAR) sparing.There is no significant difference in dosimetric parameters and acute toxicity between the two groups.Compared with IMRT,RapidArc plan has fewer MUs and less treatment time and significantly improves the treatment efficiency.
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This study examined the association of a common polymorphic allele (25G) of the low-density lipoprotein receptor-related protein1 (LRP1) gene with myocardial infarction (MI). The genotypes of LRP1 25CG (rs35282763) were determined in 347 MI patients and 347 age- and sex-frequency-matched controls from an unrelated Chinese Han population. Factor VIII (FVIII) levels were measured in the MI patients and controls by chromogenic assay and enzyme-linked immunosorbent assay (ELISA). The results showed that LRP1 25CG (rs35282763) genotype distribution did not differ significantly between patients (n=206 for 25CC, n=122 for 25CG) and controls (n=191 for 25CC, n=126 for 25CG; P>0.05). The 25G allele was not associated with a reduced risk of MI (P>0.05). Further stratifications for age, sex, and other cardiovascular risk factors did not affect the negative findings. It was concluded that the presence of the G allele at the 25CG (rs35282763) polymorphism of the LRP1 is not associated with a reduced risk of MI, and genotyping for LRP1 25CG (rs35282763) polymorphism is not useful in assessing the individual risk of MI.
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The binding function of EGF1 domain peptide with tissue factor (TF) and its ability of triggering coagulation were explored. The TF expression model in vitro was established by lipopolysaccharide induction. The affinity of EGFP-EGF1 and TF expressing cells was analyzed by fluorescence microscopy and flow cytometry (FCM). The affinity of EGFP-EGF1 and rat soluble TF was quantitated by surface plasmon resonance (SPR). The ability of EGFP-EGF1 in triggering coagulation was tested by prothrombin time assay. The FCM results showed recombinant factor VII (rFVII) could definitely depress the integration of EGFP-EGF1 with recombinant TF (rTF) (68.65%+/-3.86% vs 57.98%+/-4.71%, P<0.01). The SPR results indicated the association constant ka of EGFP-EGF1 proteins was higher than rFVII (8.29+/-1.39 vs 3.75+/-0.32, P<0.01). However, the EGFP-EGF1 protein lost the activity of triggering coagulation as compared with blood plasma of normal SD rats (56.8+/-3.2 s vs 17.8+/-3.4 s, P<0.01). It was concluded that the rat EGF1 peptide could specifically bind to TF without the ability of triggering coagulation. EGF1 peptide may be a good target head for delivering drugs to TF in anticoagulation therapy.
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OBJECTIVE To deepen the understanding of the hospital infection in the operating room and the importance of the work,do a good job for operating room disinfection and isolation work. METHODS Via self-inspection and detection of departments combined with randomized and selected inspection from the Office of infection,the deficits and their causes were found out to overcome. RESULTS For the operating room,infection control measures was developed ensure that all allegations of indicators in the normal range. CONCLUSIONS Only deepening the understanding of hospital infection and the importance of the work,the hospital can do a good job of systematic work to elevate the level of management in the operating room.
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Objective To observe the changes of coagulation function in patients with acute lowerlimb deep venous thrombosis(DVT)and evaluate the risk factors for DVT. Methods Plasma APTT.PT,TT,D-dimer and fibrinogen(Fbg)were detected by an automated coagulation analyzer in 62 acute lower-limb DVT patients and 70 controls:Retrospective studies on the clinical data of all patients were done by binary logistic regression analysis.Results (1)In DVT group,plasma APTT,PT and TT,the levels of D-dimer and fibrinogen.and D-dimer/fibrinogen ratio(D/F ratio)were higher when compared with control group(au P＜0.01);(2)There were positive correlations between D-dimer and fibrinogen both in DVT and control groups(r=0.475,P＜0.01;r=0.564,P＜0.01,respectively);(3)Logistic analysis indicated that acute lower-limb DVT was associated with the presence of hypertension and increased plasma level of fibrinogen(OR=24.99,P＜0.01: OR=4.346.P＜0.01,respectively).Conclusions Hypertension and elevated plasma level of fibrinogen are independent risk factors for acute lower-limb DVT.
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The effects of fenofibrate on plasminogen activator inhibitor-1 (PAI-1) expression in human umbilical endothelial cell-derived transformed cell line--ECV 304 cells were investigated. ECV 304 cells were incubated with different concentrations of fenofibrate (0, 10, 50, 100 micromol/L) for 24 h. PAI-1 mRNA and protein was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot respectively. PAI-1 antigenic content of endothelial cells was measured by using ELISA. Fenofibrate could inhibit the PAI-1 mRNA and protein expression and reduce PAI-1 antigenic content dependently. After treatment with fenofibrate (10 micromol/L), the expression levels of PAI-1 mRNA and protein were 0.65 +/- 0.05 and 0.96 +/- 0.11 respectively, significantly lower than in the control group (0.78 +/- 0.03 and 1.21 +/- 0.15, respectively, P<0.05). PAI-1 antigenic contents (24.52 +/- 8.39) in ECV304 cells treated with 10 micromol/L fenofibrate were significantly lower than those in the control group (6.98 +/- 5.12, P<0.05). It was concluded that fenofibrate inhibited the expression of PAI-1 mRNA in ECV304 cells, and reduce the protein expression and the antigenic content of PAI-1, suggesting that fenofibrate may have an antiatherosclerotic effect on endothelial cells by PAI-1 pathway.
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To study the variation and significance of plasma coagulation factor VII (FVII) in different kinds of ischemia heart disease (IHD) and examine its relation with plasma lipid and gene polymorphism. FVIIa was determined with one stage clotting assay by using a recombinant soluble tissue factor (rsTF). FVIIc was measured with one stage clotting assay. FVIIag was quantified with an enzyme-linked immunosorbent assay (ELISA). Polymorphism was analyzed with PCR-urea-polyacrylamide gel electrophoresis. Our results showed that FVIIa in stable angina (SA), unstable angina (UA), obsolete and acute myocardial infraction (OMI, AMI) patients was higher than those of normal group with the differences being significant within any two groups. FVIIag in UA, OMI and AMI was higher than those in SA and normal groups. There were positive correlations between FVIIa and serum triglycerides, FVIIa and FVIIc, FVIIc and FVIIag. FVII-323 0/10 bp polymorphism analysis was performed in 60 patients and 0/10 bp polymorphism was found in 5 cases. FVIIc and FVIIag were much lower in cases of 0/10 bp groups than those in cases of 0/0 bp groups. It is concluded that there was activation of extrinsic coagulation pathway in every kind of IHD to different extent. FVIIa was the risk factor in the development of IHD, and more sensitive in reflecting the severity of cardiovacutar disease than FVIIc or FVIIag. FVIIa was higher in OMI, which may be one of the risk factors of re-infraction. Serum triglyceride may indirectly lead to the development of IHD by increasing the level of FVIIa. FVII-323 0/10 bp polymorphism was present in Chinese patients with IHD and it was correlated with the level of FVIIc, FVIIag in plasma. 10 bp allelomorphic gene was a protective factor against thrombogenesis.
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To study the variation and significance of plasma coagulation factor Ⅶ (FⅦ) in differ ent kinds of ischemia heart disease (IHD) and examine its relation with plasma lipid and gene polymorphism. FⅦa was determined with one stage clotting assay by using a recombinant soluble tissue factor (rsTF). FⅦc was measured with one stage clotting assay. FⅦag was quantified with an enzyme-linked immunosorbent assay (ELISA). Polymorphism was analyzed with PCR-urea-polyacrylamide gel electrophoresis. Our results showed that FⅦa in stable angina (SA),unstable angina (UA), obsolete and acute myocardial infraction (OMI, AMI) patients was higher than those of normal group with the differences being significant within any two groups. FⅦag in UA, OMI and AMI was higher than those in SA and normal groups. There were positive correlations between FⅦa and serum triglycerides, FⅦa and FⅦc, FⅦc and FⅦag. FⅦ-323 0/10 bp polymorphism analysis was performed in 60 patients and 0/10 bp polymorphism was found in 5 cases. FⅦc and FⅦag were much lower in cases of 0/10 bp groups than those in cases of 0/0 bp groups. It is concluded that there was activation of extrinsic coagulation pathway in every kind of IHD to different extent. FⅦa was the risk factor in the development of IHD, and more sensitive in reflecting the severity of cardiovacutar disease than FⅦc or FⅦag. FⅦa was higher in OMI, which may be one of the risk factors of re-infraction. Serum triglyceride may indirectly lead to the development of IHD by increasing the level of FⅦa. FⅦ-323 0/10 bp polymorphism was present in Chinese patients with IHD and it was correlated with the level of FⅦc, FⅦag in plasma. 10 bp allelomorphic gene was a protective factor against thrombogenesis.
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The effects of fenofibrate on plasminogen activator inhibitor-1 (PAI-1) expression in human umbilical endothelial cell-derived transformed cell line-ECV 304 cells were investigated. ECV 304 cells were incubated with different concentrations of fenofibrate (0, 10, 50, 100 μmol/L) for 24 h. PAI-1 mRNA and protein was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Westernblot respectively. PAI-1 antigenic content of endothelial cells was measured by using ELISA. Fenofibrate could inhibit the PAI-1 mRNA and protein expression and reduce PAI-1 antigenic content dependently. After treatment with fenofibrate (10 μmol/L), the expression levels of PAI-1 mRNA and protein were 0.65±0.05 and 0.96±0.11 respectively, significantly lower than in the control group (0.78±0.03 and 1.21±0.15, respectively, P＜0.05). PAI-1 antigenie contents (24.52±8.39) in ECV304 cells treated with 10 μmol/L fenofibrate were significantly lower than those in the control group (6.98±5.12, P＜0.05). It was concluded that fenofibrate inhibited the expression of PAI-1 mRNA in ECV304 cells, and reduce the protein expression and the antigenic content of PAI-1, suggesting that fenofibrate may have an antiatherosclerotic effect on endothelial cells by PAI-1 pathway.
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To study the effect of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) on PC-3M cell line, PC-3M cell line was incubated with gradient concentrations of TRAIL for 4--24 h. Annixin-V fluorescence staining and TUNEL method were employed to detect the apoptosis of PC-3M cells. The morphology of apoptotic PC-3M cells was observed by electron microscopy. The relationship between TRAIL concentrations and the percentage of apoptotic cells was evaluated by flow cytometry. The proliferation inhibitory ratio was calculated by using MTT colorimetry. Our results showed that apoptosis of PC-3M cells could be induced by treatment with TRAIL for at most 4 h. The results of flow cytometry and MTT colorimetry demonstrated a time- and concentration-dependent relationship between cell apoptosis rate and TRAIL concentration. It is concluded that apoptosis of PC-3M cells can be induced by TRAIL. Because of the selective killing effect of TRAIL on tumor cells, it may become a potential alternative for the treatment of advanced prostate cancer.
Subject(s)
Apoptosis/drug effects , Cell Line, Tumor , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , TNF-Related Apoptosis-Inducing Ligand/pharmacologyABSTRACT
In this work, blank polylactic acid (PLA) nanoparticles with unstained surface were prepared by the nano-deposition method. On the basis of the preparation, the effect of surface modification on brain microvascular endothelial cells (BMECs) targeting was examined by in vivo experiments and fluorescence microscopy. The results showed that PLA nanoparticles are less toxic than PACA nanoparticles but their BMECs targeting is similar to PACA nanoparticles. The experiments suggest that drugs can be loaded onto the particles and become more stable through adsorption on the surface of PLA nanoparticles with high surface activity. The surface of PLA nanoparticles was obviously modified and the hydrophilicity was increased as well in the presence of non-ionic surfactants on PLA nanoparticles. As a targeting moiety, polysobate 80 (T-80) can facilitate BMECs targeting of PLA nanoparticles.
Subject(s)
Brain/blood supply , Brain/drug effects , Capillaries/cytology , Capillary Permeability/drug effects , Drug Delivery Systems , Endothelium, Vascular/cytology , Lactic Acid/pharmacology , Mice, Inbred Strains , Microscopy, Fluorescence , Nanoparticles , Polymers/pharmacologyABSTRACT
To study the effect of tumor necrosis factor-related apoptosis inducing ligand (TRAIL)on PC-3M cell line, PC-3M cell line was incubated with gradient concentrations of TRAIL for 4-24h. Annixin-Ⅴ fluorescence staining and TUNEL method were employed to detect the apoptosis of PC-3M cells. The morphology of apoptotic PC-3M cells was observed by electron microscopy. The relationship between TRAIL concentrations and the percentage of apoptotic cells was evaluated by flow cytometry. The proliferation inhibitory ratio was calculated by using MTT colorimetry. Our results showed that apoptosis of PC-3M cells could be induced by treatment with TRAIL for at most 4 h. The results of flow cytometry and MTT colorimetry demonstrated a time- and concentration-dependent relationship between cell apoptosis rate and TRAIL concentration. It is concluded that apoptosis of PC-3M cells can be induced by TRAIL. Because of the selective killing effect of TRAIL on tumor ceils, it may become a potential alternative for the treatment of advanced prostate cancer.
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In this work, blank polylactic acid (PLA) nanoparticles with unstained surface were prepared by the nano-deposition method. On the basis of the preparation, the effect of surface modification on brain microvascular endothelial cells (BMECs) targeting was examined by in vivo experiments and fluorescence microscopy. The results showed that PLA nanoparticles are less toxic than PACA nanoparticles but their BMECs targeting is similar to PACA nanoparticles. The experiments suggest that drugs can be loaded onto the particles and become more stable through adsorption on the surface of PLA nanoparticles with high surface activity. The surface of PLA nanoparticles was obviously modified and the hydrophilicity was increased as well in the presence of non-ionic surfactants on PLA nanoparticles. As a targeting moiety, polysobate 80 (T-80) can facilitate BMECs targeting of PLA nanoparticles.
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AIM: To study the expression of tissue factor (TF) in cerebral microvascular thrombosis and its dynamic changes in rats. METHODS: 50 female SD rats were randomized to control group, 2, 4, 6, and 24 hours after thrombosis groups, 10 rats in each group. The model of cerebral microvascular thrombosis was induced by photo-chemical method. ELISA and immunohistochemistry methods were used to observe the changes of TF contents in blood plasma and the expression of TF in cerebral microvascular in each group. RESULTS: Cerebral thrombosis was induced by photo-chemical method successfully. The TF content in plasma was obviously higher in 4 h and 6 h groups than that in control group (P