RESUMEN
To investigate the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on chemokine receptors and explore the potential mechanism of rhG-CSF inducing immune tolerance, ninety-seven donor and recipient pairs undergoing family-donor allogeneic hematopoietic stem cell transplantation were studied. The results indicated that different donors showed great disparities in expression changes after mobilization. Multivariate analysis revealed that both HLA mismatching and CCR7 downregulation on donors' CD4+ T cells after mobilization were independent risk factors for acute graft-versus-host disease (GVHD). In contrast, CCR5 downregulation on CD4+ T cells was associated with reduced incidence of acute GVHD. In conclusion, rhG-CSF mobilization could lead to differential regulation of chemokine receptors expression on T cell subsets in different donors. Downregulation of CCR5 and upregulation of CCR7 expression on donor CD4+ T cells might protect recipients from acute GVHD. This finding may provide a promising new strategy for the prevention and treatment of acute GVHD.
Asunto(s)
Donantes de Sangre , Enfermedad Injerto contra Huésped/etiología , Factor Estimulante de Colonias de Granulocitos/farmacología , Movilización de Célula Madre Hematopoyética , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Receptores CCR5/análisis , Receptores CCR7/análisis , Subgrupos de Linfocitos T/inmunología , Enfermedad Aguda , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/farmacología , Adulto JovenRESUMEN
Polysialic acid (PSA) is a carbohydrate polymer of repeating α-2,8 sialic acid residues that decorates multiple targets, including neural cell adhesion molecule (NCAM). PST and STX encode the two enzymes responsible for PSA modification of target proteins in mammalian cells, but despite widespread polysialylation in embryonic development, the majority of studies have focused strictly on the role of PSA in neurogenesis. Using human pluripotent stem cells (hPSCs), we have revisited the developmental role of PST and STX and show that early progenitors of the three embryonic germ layers are polysialylated on their cell surface. Changes in polysialylation can be attributed to lineage-specific expression of polysialyltransferase genes; PST is elevated in endoderm and mesoderm, while STX is elevated in ectoderm. In hPSCs, PST and STX genes are epigenetically marked by overlapping domains of H3K27 and H3K4 trimethylation, indicating that they are held in a "developmentally-primed" state. Activation of PST transcription during early mesendoderm differentiation is under control of the T-Goosecoid transcription factor network, a key regulatory axis required for early cell fate decisions in the vertebrate embryo. This establishes polysialyltransferase genes as part of a developmental program associated with germ layer establishment. Finally, we show by shRNA knockdown and CRISPR-Cas9 genome editing that PST-dependent cell surface polysialylation is essential for endoderm specification. This is the first report to demonstrate a role for a glycosyltransferase in hPSC lineage specification. Stem Cells 2016;34:1742-1752.
Asunto(s)
Estratos Germinativos/metabolismo , Células Madre Pluripotentes/citología , Células Madre Pluripotentes/metabolismo , Ácidos Siálicos/metabolismo , Sialiltransferasas/metabolismo , Diferenciación Celular , Línea Celular , Linaje de la Célula , Membrana Celular/metabolismo , Endodermo/citología , Endodermo/metabolismo , Humanos , Especificidad por Sustrato , Factores de Transcripción/metabolismo , Transcripción GenéticaRESUMEN
CONTEXT: The buds of Coreopsis tinctoria Nutt (Compositae) are used in the treatment of hypertension in the Uyghur folk medicine in China. OBJECTIVE: To investigate vasorelaxant properties of extracts and some flavonoids from C. tinctoria (CT) and their underlying mechanisms in isolated rat thoracic aortic rings. MATERIALS AND METHODS: Vasorelaxant effects of ethanol extracts of CT (CTA) and its flavonoids as well as water-ethanol eluates from CTA by AB-8 resins (CTAAâ¼CTAF) were evaluated on rat aortic rings pre-contracted with phenylephrine (PE, 1 µM) or high KCl (60 µM). We evaluated the effect of CTA, CTAD and CTAE on PE-induced contraction in a Ca²âº-free medium and a dose-effect curve of Ca²âº in pre-contracted ring with high KCl. RESULTS: Endothelial removal did not modify the effect of CTAD and CTAE (3.00 g/L) neither on PE-pre-contracted rings (164.78 ± 21.44 and 191.47 ± 16.75%) nor on KCl-pre-contracted rings (75.68 ± 10.76 and 125.14 ± 17.41%) compared with intact-endothelium rings pre-contracted with high KCl (100.49 ± 17.30 and 110.81 ± 16.33%). CTAD and CTAE (3.00 g/L) down-regulated the dose-effect curve of Ca²âº in pre-contraction with high KCl, and inhibited the pre-contraction with PE in a Ca²âº-free medium (p < 0.05). Seven flavonoids were obtained from CTAD, of which luteolin (5) and quercetin (6) were found to be the most effective relaxation in rings precontracted with PE (EC50: 0.006 and 0.039 g/L, p < 0.05) or high KCl (EC50: 0.023 and 0.045 g/L, p < 0.05). DISCUSSION AND CONCLUSION: These data demonstrated the vasorelaxant effect of CT, and its mechanism is likely due to an inhibitory effect on calcium movements through cell membranes.
Asunto(s)
Aorta Torácica/efectos de los fármacos , Señalización del Calcio/efectos de los fármacos , Coreopsis/química , Medicamentos Herbarios Chinos/farmacología , Flavonoides/farmacología , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacología , Animales , Antihipertensivos/química , Antihipertensivos/aislamiento & purificación , Antihipertensivos/farmacología , China , Coreopsis/crecimiento & desarrollo , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Endotelio Vascular/fisiología , Etnofarmacología , Flavonoides/química , Flavonoides/aislamiento & purificación , Flores/química , Flores/crecimiento & desarrollo , Técnicas In Vitro , Luteolina/química , Luteolina/aislamiento & purificación , Luteolina/farmacología , Masculino , Fenilefrina/antagonistas & inhibidores , Fenilefrina/farmacología , Quercetina/química , Quercetina/aislamiento & purificación , Quercetina/farmacología , Ratas , Ratas Wistar , Vasoconstrictores/antagonistas & inhibidores , Vasoconstrictores/farmacología , Vasodilatadores/química , Vasodilatadores/aislamiento & purificaciónRESUMEN
Reproductive strategies and spawning habits play key roles in the evolution of endemic East Asian cyprinids. However, the molecular mechanisms underlying the regulation of spawning habits are not well understood. We recently identified zona pellucida (Zp) as the top differentially expressed protein between East Asian cyprinids that produce adhesive and semi-buoyant eggs, suggesting that Zp protein may play important roles in the regulation of egg type. In this work, we generated transgenic zebrafish in which oocyte-specific expression of zp genes from rare minnow ( Gobiocypris rarus), an East Asian cyprinid laying adhesive eggs, was driven by a zebrafish zp3.2 gene promoter. We found that the transgenic eggs obtained partial adhesiveness and exhibited alteration in hydration and buoyancy. Abnormal metabolism of vitellogenin (VTG) may contribute to enhanced hydration and/or buoyancy. Our work shows that expression of the exogenous zp3a gene from an adhesive-egg producing fish is sufficient to induce changes in both egg adhesiveness and buoyancy in zebrafish, emphasizing the important role of zp genes in the regulation of spawning habits. Our results thus provide new insights into how endemic East Asian cyprinids may have adapted to the Yangtze river-lake system via changes in spawning habits.
Asunto(s)
Cyprinidae , Pez Cebra , Animales , Pez Cebra/genética , Glicoproteínas de la Zona Pelúcida/genética , Glicoproteínas de la Zona Pelúcida/metabolismo , Proteínas del Huevo/genética , Proteínas del Huevo/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Secuencia de Aminoácidos , Adhesividad , Receptores de Superficie Celular/genética , Animales Modificados Genéticamente/genéticaRESUMEN
OBJECTIVE: To investigate the risk factor for cytomegalovirus (CMV) viremia and its impact on the survival of patients after allogeneic hematological stem cell transplantation (allo-HSCT). METHODS: Quantitative fluorescence PCR was used to examine the quantity of CMV in mononuclear cells. All patients were tested weekly after allo-HSCT within 3 months. Univariate and multivariate analysis were used to determine the risk factors of CMV viremia. Five-year overall survival rate was compared and analyzed between the patients with or without CMV viremia. RESULTS: The incidence of CMV viremia was 72.1% (132/183). Of which, 59.1% (78/132) occurred post one month after transplantation, 40.9% (54/132) occurred within one month and 27.9% (51/183) sustained negative within three months. Two cases were clearly diagnosed as CMV disease with a incidence of 1.1%. Both univariate and multivariate analysis indicated that transplant methods and blood cyclosporine A (CsA) concentration were significantly correlated with CMV viremia. When pairwise compared the results between the different transplant methods, significant differences of CMV viremia were found between human leukocyte antigen (HLA) matched sibling and HLA mismatched relatives, unrelative donor or cord blood (all P values < 0.05). There was no significant difference between HLA mismatched relatives and unrelative donor or cord blood. Further analysis showed that the incidence of CMV viremia was much higher in those who had used antithymocyte globulin (ATG) then those not used ATG. The Kaplan-Meier survival curve showed there was no significant difference between the groups with and without CMV viremia. CONCLUSIONS: The incidence of CMV viremia after allo-HSCT is 72.1%. Administration of ATG during conditioning regimen and blood CsA concentration > 300 µg/L are the main risk factors for CMV viremia. There is no significant effect of CMV viremia on the cumulative overall survival, while prompt treatment of CMV viremia is a crucial way to prevent CMV disease.
Asunto(s)
Infecciones por Citomegalovirus/prevención & control , Citomegalovirus , Complicaciones Posoperatorias/prevención & control , Viremia/prevención & control , Adolescente , Adulto , Niño , Preescolar , Infecciones por Citomegalovirus/epidemiología , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/virología , Trasplante Homólogo/efectos adversos , Viremia/epidemiología , Viremia/virología , Adulto JovenRESUMEN
Objective: Previous studies showed that hypomethylating agents (HMAs) could alleviate acute graft-versus-host disease (aGvHD), but affect engraftment after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The combination of two different HMAs in lower doses might overcome this problem. This study aimed to evaluate the treatment effect of the combination of two HMAs-azacitidine (5-Aza) and histone H3K27 methyltransferase inhibitor 3-deazaneplanocin (DZNep)-for the prophylaxis of aGvHD after allo-HSCT and to explore the possible mechanisms. Methods: We first optimized the concentrations of individual and combinational 5-Aza and DZNep treatments to ensure no obvious toxicities on activated T cells by evaluating T-cell proliferation, viability, and differentiation. A mouse model of aGvHD was then established to assess the prophylactic efficacy of 5-Aza, DZNep, and their combination on aGvHD. The immunomodulatory effect on T cells and the hematopoietic reconstruction were assessed. Additionally, RNA sequencing (RNA-seq) was performed to identify the underlying molecular mechanisms. Results: Compared with single treatments, the in vitro application of 5-Aza with DZNep could more powerfully reduce the production of T helper type 1 (Th1)/T cytotoxic type 1 (Tc1) cells and increase the production of regulatory T cells (Tregs). In an allo-HSCT mouse model, in vivo administration of 5-Aza with DZNep could enhance the prophylactic effect for aGvHD compared with single agents. The mechanism study demonstrated that the combination of 5-Aza and DZNep in vivo had an enhanced effect to inhibit the production of Th1/Tc1, increase the proportions of Th2/Tc2, and induce the differentiation of Tregs as in vitro. RNA-seq analysis revealed the cytokine and chemokine pathways as one mechanism for the alleviation of aGvHD with the combination of 5-Aza and DZNep. Conclusion: The combination of 5-Aza and DZNep could enhance the prophylactic effect for aGvHD by influencing donor T-cell differentiation through affecting cytokine and chemokine pathways. This study shed light on the effectively prophylactic measure for aGvHD using different epigenetic agent combinations.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Adenosina/análogos & derivados , Animales , Citocinas/metabolismo , Modelos Animales de Enfermedad , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/prevención & control , Hematopoyesis , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Histona Metiltransferasas , RatonesRESUMEN
OBJECTIVE: To analyze clinical effectiveness of myelodysplastic syndrome (MDS) patients treated by allogeneic hematopoietic stem cell transplantation (allo-HSCT), and to investigate new therapy strategy for the treatment of relapse after allo-HSCT. METHODS: 72 MDS patients treated by HSCT in our hospital from April 2013 to November 2019 were enrolled and analyzed retrospectively. The effect of allo-HSCT was summarized. The risk factors affecting the survival and relapse of the patients were investigated. RESULTS: Among 72 patients, the median follow up was 37(12-111) months. 57 patients survivedï¼79.2%ï¼ï¼while 15 patients diedï¼20.8%ï¼. The 5-year overall survival (OS) rate and 5-year disease-free survival (DFS) rate were 76.6% and 62.3%, respectively. IPSS-R, TP53 mutation and chronic graft versus-host-disease (cGVHD) were the risk factors affecting the OS of the MDS patients after treated by allo-HSCT. IPSS-R, TP53 mutation and â ¢-â £° acute graft versus-host-disease (aGVHD) were the risk factors affecting the DFS of the MDS patients after treated by allo-HSCT. After transplanted, 19 patients (26.4%) emerged aGVHD, and 5 patients (6.9%) emerged â ¢-â £° aGVHD, 25 patients (34.7%) emerged cGVHD, while 4 patients (5.6%) emerged extensive cGVHD. 17 patients (23.3%) relapsed, and the 5-year cumulative incidence of relapse (CIR) rate was 27.5%. IPSS-R, TP53 mutation and cGVHD were the risk factors affecting the relapse of the patients. The median survival time after relapse was 9 months. There were 7 out of 17 relapsed patients survived without disease, while 10 patients died. The OS rate of patients treated with maintained hypomethylation agents(HMA) combined with G-CSF mobilized donor lymphocyte infusion (DLI) was significantly higher than the patients without HMA (80.0% vs 10.0%, P=0.002). CONCLUSION: Allo-HSCT is an effective therapy for intermediate and high risk MDS patients. But relapse after HSCT is still a major problem that affecting the survival of the patients. Maintenance treatment of HMA combined with DLI may improve the long-time survival of MDS patients with relapsed after treated by allo-HSCT.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Síndromes Mielodisplásicos , Humanos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: To explore the efficacy of low-dose rabbit antithymocyte globulin (rATG) in matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) for patients with acute leukemia or myelodysplastic syndrome. PATIENTS AND METHODS: We performed a retrospective study of 79 patients with hematologic malignancies who received MSD-HSCT. All patients received standard graft-versus-host disease (GVHD) prophylaxis comprising cyclosporine, mycophenolate mofetil and short-term methotrexate. Among them, 38 were administered 5 mg/kg rATG as part of GVHD prophylaxis. Clinical outcomes including overall survival (OS), GVHD and relapse were analyzed. RESULTS: No graft failure occurred in the antithymocyte globulin (ATG) or non-ATG group. The cumulative incidences of grade 2-4 and 3-4 acute GVHD at day +100 were 13.3% versus 19.5% (p=0.507) and 5.7% versus 15.2% (p=0.196), respectively. The 2-year cumulative incidences of chronic GVHD (cGVHD) were 35.4% and 60.4% (p=0.039), and those of extensive cGVHD were 12.9% and 40.0% (p=0.015), respectively. In a multivariate analysis, the use of low-dose rATG was an independent protective factor for extensive cGVHD (hazard ratio [HR] 0.256; 95% confidence interval [CI], 0.080 to 0.822, p=0.022). The 2-year OS was 88.1% and 68.4% (p=0.038), respectively, and the use of low-dose rATG was the only protective factor in the multivariate analysis (HR 0.216; 95% CI, 0.059 to 0.792, p=0.021). There was no significant difference between the two groups in terms of the 2-year cumulative incidence of relapse, leukemia-free survival or GVHD-free and relapse-free survival. CONCLUSION: Low-dose rATG used in MSD-HSCT as part of the conditioning regimen results in a reduced incidence of cGVHD and improves survival outcomes.
RESUMEN
OBJECTIVE: To analyze risk factors that affect survival and relapse of AML patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and to investigate the therapy choices after AML relapse. METHODS: Clinical data of 180 AML patients achieved complete remission (CR) before HSCT from January 2009 to December 2018 treated in our center were analyzed retrospectively. Risk factors for survival and relapse after allo-HSCT were analyzed by COX regression. RESULTS: Among 180 AML patients, 134 survived (74.4%), 46 patients died (25.6%), and 40 patients relapsed (22.2%). The rate of overall survival (OS), event-free survival (EFS) and cumulative rate of relapse in 5-years was 74.3%ã42.5% and 25.0%, respectively. High-risk, adverse cytogenetics, CR2 at HSCT and no cGvHD were independent risk factors that affect OS. CR2 at HSCT, high-risk were independent risk factors that affect EFS. High-risk, MRD+ after one course of induction therapy, adverse cytogenetics and no cGVHD were independent risk factors that affect relapse. The OS rate of relapse patients could be improved by the usage of hypomethylation agents combined with G-CSF mobilized donor lymphocyte infusion (DLI), and 2-year OS rate was 62.5%. CONCLUSION: The survival rate of AML is greatly improved by allo-HSCT, but relapse is still one of the most important factors that influence survival of the AML patients. The maintenance therapy of hypomethylation agents combined with DLI may be a new effective treatment option for patients who relapse after HSCT.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Supervivencia sin Enfermedad , Humanos , Recurrencia Local de Neoplasia , Inducción de Remisión , Estudios RetrospectivosRESUMEN
OBJECTIVE: To investigate the clinical efficacy, related side-effectt and long-term survival condition of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) patients treated with second generation TKI dasatinib and chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Clinical data of 19 newly diagnosed as Ph+ ALL patients treated by dasatinib, chemotherapy and allo-HSCT from January 2012 to September 2018 were collectd and analyzed. RESULTS: There were 10 males and 9 females with median age of 29 years old. 14 patients were BCR/ABL P190 positive while 5 with BCR/ABL P210 positive. Three patients had complex karyotype, and 3 cases were confirmed to have central nervous system leukemia. All the patients received treatment with the induction chemotherapy regimen of VDCLP and consolidation regimens such as HD-MTX and MAE. 11 patients (57.9%) received dasatinib during induction chemotherapy, 3 patients (15.8%) received dasatinib after remission and 5 patients (26.3%) received dasatinib to replace imatinib. Side-effect appeared in 3 patients including rash, edema and nausea. All the patients got morphological remission and 7 patients(63.6%) got MMR after 4 weeks of induction chemotheraphy. 17 patients (89.5%) got MMR and 15 patients(78.9%) got CMR before allo-HSCT. All the patients received related bone marrow and peripheral hematopoietic stem cell transplantation from related donors, the median time of WBC and platelet engraftment were 12 d and 14 d after transplantation, respectively. The incidence rate of aGVHD and cGVHD were 42.1% and 57.9% respectivety. 13 patients received therapy of dasatinib after HSCT but 7 patients discontinued because of severe headache, vomiting and serious effusions. All the patients were followed-up for the median time of 42 months, the 3-year and 5-year OS both were 94.4%, and 3-year and 5-year RFS of 81.9% and 71.6%, respectively. CONCLUSION: First-line administration of dasatinib and chemotherapy followed by allo-HSCT for treatment of Ph+ALL is effective and patients can well-tolerate, the patients long-tern survival maybe superior to that of the patients treated with first generation TKI.
Asunto(s)
Dasatinib/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Femenino , Humanos , Masculino , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Inhibidores de Proteínas Quinasas , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: An association between admission plasma glucose levels and an increased risk of no-reflow has been well documented. Although HMG-CoA reductase inhibitor (statin) therapy can reduce no-reflow, little is known about its effect on no-reflow in patients with hyperglycemia. In the present study, we investigated whether pretreatment with a statin could reduce no-reflow in patients with hyperglycemia, who underwent primary coronary intervention for acute myocardial infarction (AMI). METHODS: A total of 259 consecutive patients who underwent primary angioplasty for a first AMI were studied. Blood glucose and creatinine kinase levels were measured on admission. All patients underwent 2-dimensional echocardiography and electrocardiographic analysis just after admission. No-reflow was defined as a Thrombolysis in Myocardial Infarction (TIMI) flow grade <3. Hyperglycemia was defined as a blood glucose level >or=10 mmol/L. Statin administration prior to admission was determined by detailed interview or information in the medical records. RESULTS: Hyperglycemia was diagnosed in 154 patients on admission. The no-reflow phenomenon was found in 31 of the 154 patients with hyperglycemia. The incidence of no-reflow was significantly greater in patients with hyperglycemia compared with no hyperglycemia. A multivariable logistic regression analysis showed that hyperglycemia on admission was an independent predictor of no-reflow. Among the 154 patients with hyperglycemia, there were no significant differences in baseline clinical characteristics between patients who received statin pretreatment and those who did not; however, hyperlipidemia occurred in a greater number of the patients who did not receive statin pretreatment. The 40 patients with hyperglycemia who received statins before admission had a lower incidence of no-reflow than those who did not receive statin pretreatment (5% and 25.4%; p < 0.05). Multivariable logistic regression analysis revealed that absence of statin pretreatment was a significant predictor of no-reflow in patients with hyperglycemia, along with ejection fraction on admission, initial TIMI 0 flow, number of Q waves, and anterior AMI. CONCLUSION: The results of our study show that pretreatment with statins could attenuate no-reflow after AMI in patients with acute hyperglycemia.
Asunto(s)
Angioplastia Coronaria con Balón , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hiperglucemia/tratamiento farmacológico , Fenómeno de no Reflujo/prevención & control , Enfermedad Aguda , Glucemia/metabolismo , Angiografía Coronaria , Circulación Coronaria/efectos de los fármacos , Ecocardiografía , Electrocardiografía , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Hiperglucemia/complicaciones , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/terapia , Fenómeno de no Reflujo/complicaciones , Valor Predictivo de las PruebasRESUMEN
PURPOSE: To evaluate the role of Decitabine in the allo-HSCT conditioning regimen for intermediate- and high-risk patients with MDS or AML. PATIENTS AND METHODS: Retrospective analysis of data pertaining to 76 intermediate- and high-risk patients with MDS or AML who underwent allo-HSCT between December 2005 and June 2018 at the Peking University First Hospital. Forty patients received Decitabine-containing conditioning regimen before transplantation, while thirty-six patients received regimen without Decitabine. RESULTS: Over a median follow-up of 40 months (range, 1 to 155), the cumulative incidence of grade II to IV acute graft versus host disease was 12.4% [95% confidence interval (CI) 4.9-30.9%] in the Decitabine group and 41.5% (95% CI 28.1-61.2%) in the non-Decitabine group (P=0.005). On multivariate analysis, Decitabine-containing conditioning regimen was found to protect against grade II to IV aGVHD (HR=0.279, 95% CI 0.102-0.765, P=0.013). Incidence of respiratory infection in the Decitabine and non-Decitabine groups was 22.5% and 52.78%, respectively (P=0.012). No significant between-group difference was observed with respect to 3-year OS, DFS, or RR (P=0.980, 0.959, and 0.573, respectively), while the median relapse time was longer in the Decitabine group [7 months (range, 2-12) versus 3 months (range, 2-4), P=0.171]. Decitabine-containing conditioning showed a tendency for lower relapse rate among higher risk patients, as assessed by IPSS R; however, the between-group difference was not statistically significant (P=0.085). CONCLUSION: Inclusion of Decitabine in the conditioning regimen for allo-HSCT in intermediate- and high-risk patients may lower the incidence of aGVHD and respiratory infections, and contribute to longer median relapse time.
RESUMEN
OBJECTIVE: To investigate the clinical manifestations pathologic features, treatment options and prognosis of patients with bone lymphoma. METHODS: The clinical characteristics, pathologic features, treatment and prognosis of 34 BL patients diagnosed by histopathologic method or/and PET-CT and treated in first hospital of peking university from January 2004 to April 2018 were analyzed retrospectively. RESULTS: The median age of 34 BL patients was 56 years old, the male and female ratio was 1.43â¶1 (24 /10). Among 34 patients, the patients with primary bone lymphoma(PBL) were 8 cases, the patients with secondary bone lymphoma(SBL) was 26 cases, the PBL and SBL ratio was 0.31â¶1. Bone lymphoma lacks typical systemic symptoms, and its onset began mostly from bone pain and pathologic bone fracture. The most frequent pathological type of bone lymphoma in our study was diffuse large B-cell lymphoma (DLBCL), accounting for 55.88%. At present, the conventional treatment for bone lymphoma includes chemotherapy, or chemotherapy combined with radiotherapy and surgery, as well as hematopoietic stem cell transplantation. The average and median OS time of BL patients were 3î49 years and 3 years respectively, meanwhile the OS rate for three years and two years were 56.25% and 78.16%, respectively. Factors that affect survival of BL patients were PBL and SBL classification, pathological type, blood LDH level, and treatment methods. CONCLUSION: Bone lymphoma is usually concealed onsetï¼an adequate and adequate combination therapy can improve the survival rate and transplantation therapy plays an important role. Primary bone lymphoma is rare, the prognosis of patients with primary bone lymphoma is good, whereas the prognosis of patients with secondary bone lymphoma is poor.
Asunto(s)
Neoplasias Óseas , Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B Grandes Difuso , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Pronóstico , Estudios RetrospectivosRESUMEN
UNLABELLED: It has been verified that adenosine can attenuate myocardial no-reflow. However, the effects of adenosine on adenosine triphosphate-sensitive K+ (KATP) channel and endothelin-1 (ET-1) are unknown. METHODS: Forty mini-swines were randomized into 5 study groups: 8 in the control group, 8 in the adenosine pretreatment group, 8 in the glibenclamide (K(ATP) channel blocker)-treated group, 8 in the adenosine and glibenclamide-pretreated group and 8 in the sham-operated group. An acute myocardial infarction and reperfusion model was created with three-hour occlusion of the left anterior descending coronary artery followed by a one-hour reperfusion. RESULTS: Compared with the control group, adenosine significantly decreased the area of no-reflow (myocardial contrast echocardiography: from 78.5 +/- 4.5% to 20.7 +/- 4.1%, pathological means: from 82.3 +/- 1.9% to 21.5 +/- 4.3% of ligation area, respectively; all P < 0.01), reduced necrosis size from 98.5 +/- 1.3% to 75 +/- 4.7% of ligation area, P < 0.05). It also decreased plasma ET-1 and myocardial tissue ET-1. However, glibenclamide abrogated the protective effect of adenosine. CONCLUSION: The beneficial effect of adenosine on myocardial no-reflow could be due to its effect on ET-1 via the activation of K(ATP) channel.
Asunto(s)
Adenosina/administración & dosificación , Circulación Coronaria/efectos de los fármacos , Endotelina-1/sangre , Canales KATP/metabolismo , Infarto del Miocardio/tratamiento farmacológico , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Vasodilatadores/administración & dosificación , Animales , Modelos Animales de Enfermedad , Ecocardiografía , Endotelina-1/efectos de los fármacos , Inyecciones Intravenosas , Canales KATP/efectos de los fármacos , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/metabolismo , Daño por Reperfusión Miocárdica/diagnóstico , Daño por Reperfusión Miocárdica/metabolismo , Miocardio/metabolismo , Miocardio/patología , Radioinmunoensayo , Distribución Aleatoria , Porcinos , Porcinos Enanos , Resultado del TratamientoRESUMEN
OBJECTIVE: To analyze the incidence of bone marrow involvement in patients with different pathological types of lymphoma. METHODS: The results of bone marrow tests including bone marrow aspiration(BMA), flow cytometry detection, bone marrow biopsy(BMB) and 18F-FDG PET/CT, were analyzed retrospectively in 702 cases of newly diagnosed lymphoma with bone marrow assessment in our hospital from October 2000 to September 2016. If one of the above-mentioned 4 tests showed positive, the lymphoma patient was judged as bone marrow involved. RESULTS: The incidence of bone marrow involvement (BMI ) in the patients with NHL was much higher than that in patients with HL [32.6 %(201/616) vs 15%(13/86)](P<0.05). For patients with NHL, the incidence of bone marrow involvement in B-cell lymphoma was higher than that in T-cell lymphoma (37.0% vs 22.6%)(P<0.05). According to different pathological types, the incidences of BMI in the patient with mantle cell lymphoma, hepatosplenic T-cell lymphoma, diffuse large B-cell lymphoma (DLBCL) and follical lymphoma (FL) were 88% (25/22), 100% (5/5), 21.8% (56/257), and 38.5% (15/39) , respectively. CONCLUSION: The incidence of bone marrow involvement varies in different pathological types of lymphoma.Bone marrow assessment has significant importance for stading of newly diagnosed lymphoma patients.
Asunto(s)
Médula Ósea , Biopsia , Fluorodesoxiglucosa F18 , Humanos , Incidencia , Linfoma , Tomografía Computarizada por Tomografía de Emisión de Positrones , Estudios RetrospectivosRESUMEN
BACKGROUND: In animal models, pretreatment with angiotensin-converting enzyme inhibitor (ACEI) can reduce no-reflow. In the present study, we investigated whether pretreatment with ACEI may prevent no-reflow in patients who underwent primary coronary intervention for AMI. METHOD AND RESULTS: A total of 259 consecutive patients who underwent primary angioplasty for a first AMI were studied. No-reflow was defined as a TIMI flow grade < 3. The no-reflow phenomenon was found in 33 of 259 patients. There were no significant differences in clinical characteristics between the patients with and without ACEI pretreatment. However, the 47 patients receiving chronic ACEI treatment before admission had lower incidence of the no-reflow than those without it (4.2 and 14.6%, p<0.05). Multivariable logistic regression analysis revealed that absence of ACEI pretreatment was a significant predictor of the no-reflow along with absence of preinfarction angina, complete occlusion of the culprit lesion, high-burden thrombus, ejection fraction on admission, number of Q-waves, absence of statin pretreatment, and anterior AMI. CONCLUSION: Pretreatment with ACEI could preserve the microvascular integrity after acute myocardial infarction in humans.
Asunto(s)
Angioplastia Coronaria con Balón , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Circulación Coronaria/efectos de los fármacos , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/terapia , Adulto , Anciano , Análisis de Varianza , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Captopril/uso terapéutico , Angiografía Coronaria , Electrocardiografía , Enalapril/uso terapéutico , Femenino , Fosinopril/uso terapéutico , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico por imagen , Valor Predictivo de las Pruebas , Proyectos de Investigación , Volumen Sistólico/efectos de los fármacos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Using RT-PCR method, the glutathione transferase Pi cDNAs were cloned from Cyprinus carpio, Hypophthalmichthys molitrix, and Carassius auratus. The open reading frames (ORFs) from the 3 fishes were 627 bp long (encoding for 208 amino acids) with the initial code ATG and the terminal code TGA. The sequence similarity was 50% between fish and mammals, 33% between fish and amphibian, and 15% between fish and arthropoda, respectively. The sequence similarity was big among fishes, and the average value of the 4 cyprinids was about 85%. Phylogenetic tree was constructed for 13 species based on GST Pi amino acid sequences using MP (Maximum Parsimony) method. Two major clusters were recognized: cluster one consisted of Mammals (bootstrap 100) and cluster two consisted of fishes (bootstrap 93). Based on the sequences analyses of N/C domain of GST Pi, we proposed the detoxification mechanism of freshwater fishes that were thought to have stronger tolerance to microcystins.
Asunto(s)
Peces/genética , Gutatión-S-Transferasa pi/clasificación , Gutatión-S-Transferasa pi/genética , Homología de Secuencia de Aminoácido , Secuencia de Aminoácidos , Animales , Clonación Molecular , Glutatión Transferasa/genética , Datos de Secuencia Molecular , Alineación de Secuencia , Análisis de SecuenciaRESUMEN
The thin films of C60 on Ag electrodes were studied by in situ surface-enhanced Raman spectroscopy (SERS) in acetonitrile solution and water solution respectively. The influence of C60 from bulk solution on the SERS of the adsorbed C60 was removed by pre-forming C60 films on the electrode. The results indicate that the split of some relevant Raman bands was attributed to the loss of vibrational degeneracy due to the lowering of the C60 molecular symmetry. Moreover, the surface selection rule was extended because of the influence of the surface electromagnetic field in which some forbidden modes became Raman-active. The results were similar to that of C60 molecules adsorbed on Ag electrode in the solution of C60. A weak band at about 348 and 311 cm(-1) was observed for the C60 films in acetonitrile solution and in aqueous solution respectively, which could be assigned to the interaction of C60 and Ag electrode surface.
RESUMEN
OBJECTIVE: To study the chemical constituents in seeds of Cicer arietinum, so that to find bioactive natural products. METHOD: Dried and sprouted seeds of C. arietinum were extracted with ethanol of various concentrations respectively, then isolated and purified by silica gel, macroreticular resin D 101, Sephadex LH -20 gel column chromatography, and structures of compounds were identified by spectral analysis. RESULT: Nine compounds have been isolated and identified: 3-hydroxy-olean-12-ene (1), biochanin A-7-O-beta-D-glucoside (2), cerebroside (3), 1-ethyl-alpha-L-galactoside (4), uridine (5), adenosine (6), trytophan (7), biochanin A (8), fomononetin (9). CONCLUSION: Compounds 1, 3, 4, 6, 7 were isolated from genus Cicer for the first time.
Asunto(s)
Adenosina/aislamiento & purificación , Cerebrósidos/aislamiento & purificación , Cicer/química , Plantas Medicinales/química , Triterpenos/aislamiento & purificación , Adenosina/química , Cerebrósidos/química , Cromatografía en Gel , Semillas/química , Triterpenos/químicaRESUMEN
The aim of the present study was to explore the effect of different X-ray doses on the proliferation and cytotoxic activity of peripheral blood mononuclear cells (PBMCs), particularly lymphocytes, in order to assess whether this reduces the incidence of graft vs. host disease (GVHD) while preserving the graft vs. tumor (GVT) effect in patients with hematological malignancies following hematopoietic stem cell transplantation (HSCT). PBMCs from healthy donors were irradiated with X-rays at doses of 0, 2.5, 5, 7.5, 10, 15, 25 or 50 Gy, and their proliferative activity was determined using a WST-8 assay kit. The cytotoxic activity of non-irradiated PBMCs and PBMCs irradiated with 7.5 Gy X-rays was tested in the leukemic cell line K562 and its Adriamycin-resistant strain K562A using a lactate dehydrogenase assay. The clinical data of 7 patients who received 7.5 Gy X-ray-irradiated PBMC infusions following autologous HSCT were analyzed. PBMCs irradiated with ≥7.5 Gy X-rays exhibited a complete inhibition of proliferation. PBMCs irradiated with 7.5 Gy X-rays exhibited significantly increased cytotoxic activity towards K562 cells compared with K562A cells (P<0.05). There was no significant difference in cytotoxicity between irradiated and non-irradiated PBMCs, irrespective of the target cell, K562 or K562A (P>0.05). Based on the in vitro data, clinical data from patients who received 7.5 Gy X-ray-irradiated PBMC infusions following HSCT between January 2005 and January 2013 were assessed retrospectively. A total of 7 patients were included in the current study. The majority achieved various degrees of remission following donor lymphocyte infusion (DLI) and none suffered from GVHD. This indicates that 7.5 Gy-irradiated PMBCs have a potential application in DLI for the treatment of patients following HSCT. However, further studies on larger patient cohorts are required to assess the clinical potential of 7.5 Gy-irradiated PBMCs for preserving the GVT effect while avoiding GVHD following HSCT.