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INTRODUCTION: In recent years, the correlation between CD117 antigen and the prognosis of hematological malignancies has been demonstrated. However, there is limited literature on the clinical significance of CD117 antigen in acute promyelocytic leukemia (APL). The aim of this study was to retrospectively analyze the clinical features and prognostic significance of CD117 in APL. METHODS: In this study, we retrospectively investigated the clinicopathological characteristics, outcome, and prognostic impact of negative CD117 expression (CD117-) in 169 APL patients treated with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) containing regimen. RESULTS: The median follow-up period was 63.0 months. CD117- was detected in 13 APL patients (7.7%). No significant differences were found in baseline characteristics between CD117+ and CD117- subgroups. However, compared to CD117+ APL, the incidence of early death (ED) was significantly higher in CD117- APL (p = 0.023). By multivariate analysis, CD117- was an independent adverse prognostic factor for overall survival (OS) and progression-free survival (PFS) (p = 0.022 and p = 0.014, respectively). CONCLUSIONS: To sum up, CD117- is associated with greater risk of ED and has the statistical power to predict inferior OS and PFS, this marker may be considered to build prognostic scores for risk-adapted therapeutic strategies in APL management.
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BACKGROUND AND OBJECTIVES: Blood services manage the increasingly tight balance between the supply and demand of blood products, and their role in health research is expanding. This review explores the themes that may define the future of blood banking. MATERIALS AND METHODS: We reviewed the PubMed database for articles on emerging/new blood-derived products and the utilization of blood donors in health research. RESULTS: In high-income countries (HICs), blood services may consider offering these products: whole blood, cold-stored platelets, synthetic blood components, convalescent plasma, lyophilized plasma and cryopreserved/lyophilized platelets. Many low- and middle-income countries (LMICs) aim to establish a pool of volunteer, non-remunerated blood donors and wean themselves off family replacement donors; and many HICs are relaxing the deferral criteria targeting racial and sexual minorities. Blood services in HICs could achieve plasma self-sufficiency by building plasma-dedicated centres, in collaboration with the private sector. Lastly, blood services should expand their involvement in health research by establishing donor cohorts, conducting serosurveys, studying non-infectious diseases and participating in clinical trials. CONCLUSION: This article provides a vision of the future for blood services. The introduction of some of these changes will be slower in LMICs, where addressing key operational challenges will likely be prioritized.
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Bancos de Sangue , Doadores de Sangue , Humanos , Doadores de Sangue/provisão & distribuição , Países em DesenvolvimentoRESUMO
BACKGROUND: The innovative combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has established a new chapter of curative approach in acute promyelocytic leukemia (APL). The disease characteristics and prognostic influence of additional cytogenetic abnormalities (ACA) in APL with modern therapeutic strategy need to be elucidated. METHODS: In the present study, we retrospectively investigated disease features and prognostic power of ACA in 171 APL patients treated with ATRA-ATO-containing regimens. RESULTS: Patients with ACA had markedly decreased hemoglobin levels than that without ACA (p = 0.021). Risk stratification in the ACA group was significantly worse than that in the non-ACA group (p = 0.032). With a median follow-up period of 62.0 months, worse event-free survival (EFS) was demonstrated in patients harboring ACA. Multivariate analysis showed that ACA was an independent adverse factor for EFS (p = 0.033). By further subgroup analysis, in CD34 and CD56 negative APL, patients harboring ACA had inferior EFS (p = 0.017; p = 0.037). CONCLUSIONS: To sum up, ACA remains the independent prognostic value for EFS, we should build risk-adapted therapeutic strategies in the long-term management of APL when such abnormalities are detected.
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Arsenicais , Leucemia Promielocítica Aguda , Humanos , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/genética , Intervalo Livre de Progressão , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tretinoína/uso terapêutico , Aberrações Cromossômicas , Óxidos/uso terapêutico , Arsenicais/uso terapêutico , Resultado do TratamentoRESUMO
3D metamaterials have gained considerable attention owing to their extraordinary optical properties and promising applications beyond natural materials. However, fabricating 3D metamaterials with high resolution and reliable controllability is still a significant challenge. Here, a novel approach to manufacturing various 3D freestanding plasmonic nanostructures on elastic substrates is demonstrated using the shadow metal-sputtering and plastic deformations. A critical step is constructing a freestanding "Γ-shape" gold structural array in poly(methyl methacrylate) (PMMA) hole array via the shadow metal-sputtering and following a multifilm transfer procedure. This "Γ-shape" structural array undergoes plastic deformation to form 3D freestanding metamaterials for removing the PMMA resist by the oxygen plasma. The approach allows accurate manipulations of the morphology, size, curvature, and bend orientation of 3D nanostructures. The spectral response of the 3D cylinder array was experimentally confirmed and understood by the simulations based on the finite element method (FEM). Moreover, the bulk refractive index (RI) sensitivity of up to 858 nm RIU-1 was achieved theoretically for this cylinder array. The proposed approach provides a new possibility to realize the fabrication of 3D freestanding plasmonic metamaterials with high resolution and compatible planar lithography procedures.
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An important puzzle for tea consumers is which type of tea is effective in treating metabolic syndrome (MS). In this study, the effects of six types of tea extracts (TEs) on high-fat diet (HFD)-induced MS, as well as chemical components of six TEs, were investigated and compared. Each TE consisted of representative tea originated from different places in China to avoid one-sidedness of sampling. All six TEs were found to attenuate MS and ameliorate intestinal barrier function in HFD-fed rats. Further, white tea performed better in body weight control, while dark tea had more advantages in protecting intestinal barrier. Moreover, all six TEs alleviated the gut microbiota dysbiosis, which was manifested by decreased Firmicutes/Bacteroidetes ratio and enriched beneficial bacteria, such as Akkermansia, Bacteroides, and Bifidobacterium. Together, all six TEs attenuate HFD-induced MS although their efficiency varies, and this therapeutic effect is related to the modulation of gut microbiota.
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Microbioma Gastrointestinal , Síndrome Metabólica , Animais , Dieta Hiperlipídica/efeitos adversos , Síndrome Metabólica/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , CháRESUMO
Objective: This study aimed to summarize the effectiveness of rhythmic auditory stimulation (RAS) for the treatment of gait and motor function in Parkinson's disease (PD) through a systematic review and meta-analysis. Methods: All studies were retrieved from eight databases. The effects of RAS on PD were determined using the following indicators: gait parameters including step length, stride width, step cadence, velocity, stride length; motor function including 6 min walk test (6MWT) and timed up-and-go test (TUGT); the Unified Parkinson's Disease Rating Scale (UPDRS); and the Berg Balance Scale (BBS). The risk map of bias of the quality of the studies and the meta-analysis results of the indicators was prepared with RevMan 5.2 software. Results: Twenty-one studies were included in the systematic review, and 14 studies were included in the meta-analysis. In the meta-analysis, the results of gait parameters, namely, velocity, step length, and stride length, were statistically significant (P < 0.05), whereas the results of cadence and stride width were not statistically significant (P ⧠0.05). The results of 6MWT and TUGT for motor function as well as UPDRS-II, UPDRS-III, and BBS were statistically significant (P < 0.05). Conclusions: RAS could improve gait parameters, walking function, balance function, and daily living activities of individuals with PD. The application of RAS in conventional rehabilitation approaches can enhance motor performance in PD. Future studies should use a large sample size and a rigorous design to obtain strong conclusions about the advantages of RAS for the treatment of gait and motor function in PD.
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OBJECTIVES: Prospect theory categorizes message framing according to whether it emphasizes a possible loss or a possible gain. Promotions of blood donation worldwide mainly focus on gain-framed appeal. The objective of the current study is to examine the effects of message framing on recruiting Rh-D-negative blood donors (RDNBDs) in an emergency situation. DESIGN: Two randomized trials. METHODS: In Study 1, 813 group O and 500 group B RDNBDs were randomly assigned to three groups receiving three different recruitment text messages: (1) gain-framed, (2) loss-framed, and (3) information messages. In addition, 613 group A and 148 group AB RDNBDs were marked as (4) no message group. In Study 2, 758 RDNBDs were randomly provided one of two versions of materials focusing on either the possible survival (gain-framed) or the death (loss-framed) of a Rh-D-negative patient needed a blood transfusion. These participants then completed a questionnaire to examine the possible mechanisms underlying the observed effects. RESULTS: Compared to not receiving any message, significantly more RDNBDs re-donated within 14 days after they received a loss-framed message. Study 2 found that RDNBDs who read the loss-framed material expressed more willingness to donate immediately than those who read the gain-framed material. RDNBDs with high-risk perception expressed a greater blood donation intention in the loss-framed group. The loss-framed message made participants perceive others' needs more strongly, which generated more empathy, and thus increased blood donation intention. CONCLUSIONS: The results suggested that recruiting RDNBDs using a loss-framed message is suitable under an emergency.
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Doadores de Sangue , Intenção , Promoção da Saúde/métodos , Humanos , Comunicação Persuasiva , Ensaios Clínicos Controlados Aleatórios como Assunto , Inquéritos e QuestionáriosRESUMO
Graphene, combined with plasmonic nanostructures, shows great promise for achieving desirable photodetection properties and functionalities. Here, we theoretically proposed and experimentally demonstrated a graphene photodetector based on the metamaterial absorber in the visible and near-infrared wavebands. The experimental results show that the metamaterial-based graphene photodetector (MGPD) has achieved up to 3751% of photocurrent enhancement relative to an antennasless graphene device at zero external bias. Furthermore, the polarization-independent of photoresponse has resulted from the polarization-insensitive absorption of symmetric square-ring antennas. Moreover, the spectral-dependent photocurrent enhancement, originated from the enhanced light-trapping effect, was experimentally confirmed and understood by the simulated electric field profiles. The design contributes to the development of high-performance graphene photodetectors and optoelectronic devices.
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Yellow tea, a rare type tea from China, has a rich breadth of functional ingredients and benefits the gastrointestinal tract. However, it is not clear whether the yellow tea extract can alleviate constipation. Therefore, we used loperamide-induced constipation in mice to evaluate the effects of yellow tea extract. Fifty Kunming mice were randomly divided into five groups: normal, model, low-dose yellow tea extract, low-dose yellow tea extract prevention group, and high-dose yellow tea extract prevention group. Mice were administered yellow tea extract for 5 weeks followed by loperamide-induced constipation for the final 2 weeks. The results showed that yellow tea extract alleviated constipation symptoms by improving the fecal water content, defecation weight, and gastrointestinal transit rate. Yellow tea extract intervention also protected colon tissue, regulated serum neurotransmitters, and decreased the vasoactive intestinal peptide level. Furthermore, qRT-PCR indicated that yellow tea extract regulated genes associated with the constipation state, raised 5-HT3 and 5-HT4 and reduced AQP3 and AQP4 mRNA expression. Moreover, we found that yellow tea extract changed the gut microbiota composition. Community diversity and richness were increased and principal co-ordinate analysis demonstrated that the yellow tea extract prophylaxis groups differed from the model group. Difference analysis indicated that yellow tea extract increased Roseburia, Lachnospiraceae_UCG-006, and Bifidobacterium and decreased norank_f_Clostridiales_vadinBB60_group, unclassified_o_Bacteroidales, and Bacteroides, which are correlated with constipation. Based on these results, we believe that regular yellow tea consumption can effectively alleviate constipation.
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Constipação Intestinal/tratamento farmacológico , Loperamida/efeitos adversos , Extratos Vegetais/farmacologia , Chá/química , Animais , Aquaporina 3/metabolismo , Aquaporina 4/metabolismo , China , Colo/efeitos dos fármacos , Constipação Intestinal/induzido quimicamente , Modelos Animais de Doenças , Microbioma Gastrointestinal/efeitos dos fármacos , Trânsito Gastrointestinal/efeitos dos fármacos , Masculino , CamundongosRESUMO
The first complete chloroplast genome (cp) of Sinosenecio jishouensis D.G. Zhang, Ying Liu & Q. E. Yang (Asteraceae) was sequenced and assembled in this study. The cp genome was 151,257 bp in length, including a large single-copy(LSC) region of 83,373 bp, a small single-copy (SSC) region of 18,178 bp, and a pair of inverted repeat (IR) regions of 24,853 bp each. These sequences encoded 134 genes, including 89 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The phylogenetic analysis based on 18 complete cp sequences revealed that S. jishouensis was closely related to Eclipta prostrata.
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High-performance strain sensors, composed of various artificial sensing materials on/in stretchable substrates, show great promise for applications in flexible electronic devices. Here, we demonstrated a highly sensitive and durable strain sensor consisting of a ribbon of close-packed sea-urchin-shaped silver nanoparticles (SUSNs) sandwiched between two layers of poly(dimethylsiloxane) (PDMS). Each of SUSNs possesses high-density and spherically distributed sharp spines over the body, which promotes electron transduction and further improves signal detection. This SUSN-based sensor possesses a desirable integration of high sensitivity (a gauge factor of 60) and large stretchability (up to 25%) at tensile sensing, broadening its application in wearable devices. Moreover, it also shows fast response (48 ms), good reproducibility, and long-term stability (>2500 cycles at 20% strain). It can also be used to detect compressing (sensitivity up to 31.5) and folding-type bending deformations. The sensing mechanism, the resistance of the sensors varying as the deformation load, results from the inter-spine contacts change and the microcracks evolution caused by variation in the gap between SUSNs. The sensor's sensitivity at different degrees of strain was also achieved by controlling the width of the close-packed SUSNs ribbon. For practical demonstration, the SUSN-based sensors could be used as wearable devices for monitoring human activities ranging from subtle deformations to substantial movements.
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Dimetilpolisiloxanos/química , Nanopartículas Metálicas/química , Prata/química , Dispositivos Eletrônicos Vestíveis , Fenômenos Biomecânicos , Técnicas Biossensoriais/instrumentação , Força Compressiva , Desenho de Equipamento , Humanos , Nanopartículas Metálicas/ultraestrutura , Movimento , Pressão , Estresse MecânicoRESUMO
BACKGROUND: Arthroscopic repair is recommended for young patients with full-thickness rotator cuff tears (RCTs), but the healing rates have raised concerns. The Southern California Orthopedic Institute (SCOI) row method has been developed based on greater than 3 decades of experience with excellent clinical outcomes; however, studies with a focus on the younger patient population are limited in number. The current study assessed the short-term clinical outcome and the initial tendon-to-bone healing in a young cohort after repair of a full-thickness RCT using the SCOI row method. METHODS: A retrospective cohort study was performed. Patients < 55 years of age who had a full-thickness RCT and underwent an arthroscopic repair using the SCOI row method were reviewed. Clinical outcomes were assessed at baseline, and 3 and 6 months post-operatively. The visual analog scale (VAS), University of California at Los Angeles (UCLA) scale, and Constant-Murley score were completed to assess pain and function. Active range of motion was also examined, including abduction and flexion of the involved shoulder. A preoperative MRI was obtained to assess the condition of the torn tendon, while 3- and 6-month postoperative MRIs were obtained to assess tendon-to-bone healing. Repeated measurement ANOVA and chi-square tests were used as indicated. RESULTS: Eighty-nine patients (57 males and 32 females) with a mean age of 44.1 ± 8.6 years who met the criteria were included in the study. Compared with baseline, clinical outcomes were significantly improved 3 and 6 months postoperatively based on improvement in the VAS, UCLA score, and Constant-Murley score, as well as range of motion. Greater improvement was also noted at the 6-month postoperative assessment compared to the 3-month postoperative assessment. Three- and six-month postoperative MRIs demonstrated intact repairs in all shoulders and footprint regeneration, which supported satisfactory tendon-to-bone healing. The mean thickness of regeneration tissue was 7.35 ± 0.76 and 7.75 ± 0.79 mm as measured from the 3- and 6-month MRI (P = 0.002). The total satisfactory rate was 93.3 %. CONCLUSIONS: Arthroscopic primary rotator cuff repair of a full-thickness RCT using the SCOI row method in patients < 55 years of age yields favorable clinical outcomes and early footprint regeneration.
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Lesões do Manguito Rotador , Adulto , Artroscopia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Manguito Rotador/diagnóstico por imagem , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/diagnóstico por imagem , Lesões do Manguito Rotador/cirurgia , Tendões , Resultado do TratamentoRESUMO
BACKGROUND: The coronavirus disease 2019 (COVID-19) epidemic affected blood collection in Guangzhou, China. STUDY DESIGN AND METHODS: This paper includes three studies. The observational study reported the trends of blood collection during the epidemic in Guangzhou, China. The cross-sectional survey investigated factors influencing blood donation during the COVID-19 epidemic, and a self-administered questionnaire was given to 1584 street whole blood donors (SWBDs) who donated during the epidemic. The randomized controlled trial involved 19 491 SWBDs who donated in 2019 but did not donate during the epidemic. Trial participants were randomly assigned to two intervention groups: Group 1 completed Questionnaire 1, which contained precautionary measures in response to COVID-19 and other messages about blood donation during the epidemic; Group 2 completed Questionnaire 2, which did not include this information. A control group did not receive any questionnaire. RESULTS: As measures were implemented, the number of blood donors increased accordingly. Both first-time and repeat SWBDs perceived the same level of blood need and donated blood because it would save lives. SWBDs who completed Questionnaire 1 expressed a greater intention to donate during the epidemic. Enabling blood donors to perceive a higher level of blood need and a lower level of COVID-19 infection risk related to blood donation mobilized experienced SWBDs to donate within 3 weeks. Intention-to-treat analyses and average-treatment-effect-on-the-treated estimations confirmed that Questionnaire 1 could motivate SWBDs to actually donate blood. CONCLUSION: Various measures could ease blood shortage during the COVID-19 epidemic. Administration of Questionnaire 1 could increase blood donations during the epidemic.
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Doadores de Sangue/provisão & distribuição , COVID-19/epidemiologia , Seleção de Pacientes , Adulto , Doadores de Sangue/estatística & dados numéricos , COVID-19/sangue , COVID-19/virologia , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/fisiologia , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Recruiting of sufficient numbers of donors of blood products is vital worldwide. In this study we assessed the efficacy and cost-effectiveness of telephone calls and SMS reminders for re-recruitment of inactive blood donors. METHODS: This single-centre, non-blinded, parallel randomised controlled trial in Guangzhou, China included 11,880 inactive blood donors whose last donation was between January 1 and June 30, 2014. The donors were randomly assigned to one of two intervention groups (telephone call or short message service [SMS] communications) or to a control group without intervention. SMS messages with altruistic appeal were adopted in the SMS group; in addition to altruistic appeal, reasons for deferral of blood donation were also asked in the telephone group. All participants were followed up for 1 year. The primary outcome was re-donation rate, and rates in different groups were compared by intention-to-treat (ITT) analysis and estimation of the average treatment effect on the treated (ATT). Secondary outcomes were the self-reported deterrents. Other outcomes included the re-donation interval, and the incremental cost-effectiveness ratio (ICER) of telephone calls and SMS reminders on re-recruitment. RESULTS: ITT analysis revealed no significant differences in the re-donation rate among the three groups. ATT estimations indicated that among compliers, telephone calls significantly increased re-donation compared to both SMS reminders and no intervention. Donor return behaviour was positively associated with receiving reminders successfully, being male, older age, and previous donation history. The SMS reminder prompted donors to return sooner than no reminder within 6 months, and according to ICER calculations, SMS reminders were more cost-effective than telephone calls. Donors reported time constraints as the most main causes of self-deferral in the telephone group, and altruistic appeal had a positive effect on these donors. CONCLUSIONS: Interventions to reactivate inactive blood donors can be effective, with telephone calls prompting more donors to return but at a greater cost than SMS messages. SMS reminder with altruistic appeal can urge donors to re-donate sooner within 6 months than no reminder. TRIAL REGISTRATION: NCT03366441 (Reactivation of Inactive Blood Donors). Retrospectively registered 4 December 2017.
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Doadores de Sangue/psicologia , Sistemas de Alerta , Telefone , Envio de Mensagens de Texto , Adulto , Altruísmo , Doadores de Sangue/estatística & dados numéricos , China , Análise Custo-Benefício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistemas de Alerta/economia , Telefone/economia , Envio de Mensagens de Texto/economia , Adulto JovemRESUMO
OBJECTIVE: To evaluate the efficacy and safety of thrombopoietin (TPO) on platelet engraftment in hematological malignancies patients after allogeneic haematopoietic stem cell transplantation (allo-HSCT). METHODS: One hundred and twenty patients were enrolled in a multicenter, open-label, randomized, controlled clinical trial, and were randomized into 4 treatment groups following allo-HSCT. Group A was the control arm without TPO, while group B, C and D were trial arms with received 300 U×kg(-1)×d(-1) of TPO starting from day +1, +4 and +7, respectively. A total of 89 cases were evaluated, of which 22 cases in group A, 23 in group B, 20 in group C and 24 in group D. Efficacy evaluation (the time of platelet engraftment, the number of platelet transfusion) and safety evaluation \[adverse events, routine blood tests, liver and renal function, coagulation function and occurrence of graft-versus-host disease (GVHD)\] were observed. RESULTS: The median platelet engraftment time in experimental groups (groups B, C and D) were on day (13.17 ± 2.89), day (12.15 ± 2.08), day (12.33 ± 1.76), respectively, and that in control group was on day (14.82 ± 5.05). There was statistically significant difference between two groups (P = 0.029), There were no statistically significant difference in the average amount of platelet transfusion, platelet engraftment time, and platelet nadir value among the 3 experimental groups. No significant adverse events were observed in experimental groups. CONCLUSIONS: TPO administration following allo-HSCT for patients with hematologic malignancies appears to shorten platelet engraftment time. TPO given starting from day +7 is effective and safe.
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Neoplasias Hematológicas/cirurgia , Transplante de Células-Tronco Hematopoéticas , Transfusão de Plaquetas/métodos , Trombopoetina/uso terapêutico , Adolescente , Adulto , Plaquetas , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Homólogo , Adulto JovemRESUMO
BACKGROUND: There has been little literature about leukemia epidemiology in Nanjing in recent years. We aimed to explore the incidence rate, gender and age distribution of leukemia in Nanjing using the leukemia database of the city. RESULTS: The average yearly incidence rate of leukemia was 3.68/105 during 2003 - 2007 in Nanjing. There were no significant difference in gender (x2 = 3.266, p > 0.05) or seasons (x2 = 11.36, p > 0.05). The incidence rate was the highest in group aged 80~ years (18.64/105). AML accounted for approximately 36.8% of all leukemias. CONCLUSIONS: The incidence rate of leukemia, especially in the aged population, was relatively high in Nanjing. Leukemia is the major malignant tumor in children. Therefore, more attention should be paid to leukemia in children and the aged people.
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Leucemia/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Leucemia/classificação , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVE: To study the changes in expression and activity of protein phosphatases type 2A (PP2A ) during differentiation of NB4 and NB4-MR2 cells induced by all-trans retinoic acid (ATRA), and evaluate the role of PP2A in MR2 resistance to ATRA. METHODS: ATRA, okadaic acid (OKA) and ATRA + OKA at the same dosage were incubated with NB4 and MR2 cells respectively. Wright's staining and NBT reduction test were employed to evaluate the change in the cells. The CD11b expression was measured by flow cytometry. The activity of PP2A was evaluated by serine/threonine phosphatase assay system, and the level of PP2A subunits was detected by Western blot. RESULTS: 1) Wright's staining, NBT reduction test and flow cytometry results showed OKA could augment the differentiation of NB4 induced by ATRA, and OKA + ATRA induced slight differentiation of MR2 cells. 2) Phosphatase assay showed a decrease in PP2A phosphatase activity [(534 +/- 43) pmol x min(-1) x microg protein(-1)] in NB4 after ATRA treatment, accompanied with that activity [(959 +/- 83) pmol x min(-1) x microg protein(-1)] in untreated NB4 cells. OKA enhanced the inhibitory effect of ATRA on the activity in NB4. When OKA + ATRA was incubated with MR2, PP2A in the cells was significantly decreased [(229 +/- 23) pmol x min(-1) x microg protein(-1)]. 3) Western blot analysis showed that the level of PP2A catalytic subunit (PP2A/C) was decreased during the course of ATRA-induced NB4 cell differentiation, whereas expressions of every subunits of PP2A in MR2 cells were somewhat unaltered. CONCLUSION: Expression of PP2A/C and activity of PP2A is decreased during differentiation of NB4 induced by ATRA, and no repression of the PP2 activity maybe related to MR2 resistance to ATRA.
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Diferenciação Celular/efeitos dos fármacos , Leucemia Promielocítica Aguda/patologia , Ácido Okadáico/farmacologia , Tretinoína/farmacologia , Linhagem Celular Tumoral , Humanos , Leucemia Promielocítica Aguda/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Proteína Fosfatase 2/antagonistas & inibidores , Proteína Fosfatase 2/metabolismoRESUMO
Systemic lupus erythematosus (SLE) is responsive to treatment with immunosuppressives and steroids, but often pursues a relapsing or refractory course resulting in increasing incapacity and reduced survival. Autologous stem cell transplantation (ASCT) following immunoablative chemotherapy is a newer therapy for autoimmune disease of potential use in severe SLE. A retrospective registry survey was carried out by the European Blood and Marrow Transplant and European League Against Rheumatism (EBMT/EULAR) registry. Data was collected from 53 patients with SLE treated by ASCT in 23 centres. Disease duration before ASCT was 59 (2-155) months (median, range), 44 (83%) were female, and median age was 29 (9-52) years. At the time of ASCT a median of seven American College of Rheumatology (ACR) diagnostic criteria for SLE were present (range 2-10) and 33 (62%) had nephritis. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte colony stimulating factor in 93% of cases. Ex vivo CD34 stem cell selection was performed in 42% of patients. Conditioning regimens employed cyclophosphamide in 84%, anti-thymocyte globulin in 76% and lymphoid irradiation in 22%. The mean duration of follow-up after ASCT was 26 (0-78) months. Remission of disease activity (SLEDAI < 3) was seen in 33/50 (66%; 95%CI 52-80) evaluable patients by six months, of which 10/31 (32%; 95%CI 15-50) subsequently relapsed after six (3-40) months. Relapse was associated with negative anti-double stranded DNA (anti-dsDNA) antibodies before ASCT (P = 0.007). There were 12 deaths after 1.5 (0-48) months, of which seven (12%; 95%CI 3-21) were related to the procedure. Mortality was associated with a longer disease course before ASCT (P = 0.036). In conclusion, this registry study demonstrates the efficacy of ASCT for remission induction of refractory SLE, although mortality appeared high. The safety of this procedure is likely to be improved by patient selection and choice of conditioning regimen. The return of disease activity in one-third of patients might be reduced by long-term immunosuppressive therapy post-ASCT.