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1.
J Hematol Oncol ; 13(1): 52, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32414392

RESUMO

Human leukocyte antigen (HLA) haploidentical stem cell transplantation (haplo-SCT) as a postremission treatment for standard risk Philadelphia chromosome-negative acute lymphoblastic leukemia (SR Ph-ALL) in the first complete remission (CR1) has not been defined. In this multicenter, phase 3 study (NCT02042690), of the 131 consecutive Ph-ALL young adult patients (YA, aged 18-39 years) without high-risk features who achieved CR1, 114 patients without HLA-matched donors received consolidation with an adult chemotherapy regimen (n = 55) or haplo-SCT (n = 59). In the landmark analysis, haplo-SCT resulted in a lower 2-year cumulative incidence of relapse (CIR, 12.8% vs 46.7%, P = 0.0017) and superior 2-year leukemia-free survival (LFS, 80.9% vs 51.1%, P = 0.0116) and 2-year overall survival (OS, 91.2% vs 75.7 [64.8-93.2] %, P = 0.0408) than chemotherapy. In the time-dependent multivariate analysis with propensity score adjustment, postremission treatment (haplo-SCT vs chemotherapy) was an independent risk factor for the CIR (HR 0.195, 95% CI 0.076-0.499, P = 0.001), LFS (HR 0.297, 95% CI 0.131-0.675, P = 0.003), and OS (HR 0.346, 95% CI 0.140-0.853, P = 0.011). In all subgroups, CIR was lower in haplo-SCT. Myeloablative haplo-SCT with ATG+G-CSF might be one of the preferred therapies for YA patients with standard-risk Ph-ALL. TRIAL REGISTRATION: ClinicalTrials.gov. Registered on 23 January 2014, https://clinicaltrials.gov/ct2/show/NCT02042690.

2.
Stem Cell Res Ther ; 11(1): 163, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32345350

RESUMO

BACKGROUND: Human embryonic stem cells represent a potentially unlimited source of insulin-producing cells for diabetes therapy. While tremendous progress has been made in directed differentiation of human embryonic stem cells into IPCs in vitro, the mechanisms controlling its differentiation and function are not fully understood. Previous studies revealed that lysine-specific demethylase 1(LSD1) balanced the self-renewal and differentiation in human induced pluripotent stem cells and human embryonic stem cells. This study aims to explore the role of LSD1 in directed differentiation of human embryonic stem cells into insulin-producing cells. METHODS: Human embryonic stem cell line H9 was induced into insulin-producing cells by a four-step differentiation protocol. Lentivirus transfection was applied to knockdown LSD1 expression. Immunofluorescence assay and flow cytometry were utilized to check differentiation efficiency. Western blot was used to examine signaling pathway proteins and differentiation-associated proteins. Insulin/C-peptide release was assayed by ELISA. Statistical analysis between groups was carried out with one-way ANOVA tests or a student's t test when appropriate. RESULTS: Inhibition or silencing LSD1 promotes the specification of pancreatic progenitors and finally the commitment of functional insulin-producing ß cells; Moreover, inhibition or silencing LSD1 activated ERK signaling and upregulated pancreatic progenitor associated genes, accelerating pre-maturation of pancreatic progenitors, and conferred the NKX6.1+ population with better proliferation ability. IPCs with LSD1 inhibitor tranylcypromine treatment displayed enhanced insulin secretion in response to glucose stimulation. CONCLUSIONS: We identify a novel role of LSD1 inhibition in promoting IPCs differentiation from hESCs, which would be emerged as potential intervention for generation of functional pancreatic ß cells to cure diabetes.

3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(2): 595-601, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32319402

RESUMO

OBJECTIVE: To investigate the cause, diagnosis and therapeutic method of the neurological complication with the main manifestation of paraplegia after the hematopoietic stem cell transplantation (HSCT). METHODS: The clinical features, the process of diagnosis and treatment and the prognosis follow-up of 9 cases, who received HSCT in our department during January 2014 and January 2017 and had the neurological complication with the main symptom of paraplegia after the transplantation, were summarized. RESULTS: The incidence rate of paraplegia was 2.96% (9/304). The median onset time was 245 days (50 days-772 days) after transplantation. The cause of paraplegia determined by examination was extramedullary recurrence of leukemia in 3 cases, cyclosporin neurotoxicity in 1 case, GBS in 1 case, CIDP in 2 cases and autoimmune myeleterosis in 2 cases. One patient abandoned the treatment. The rest 8 patients received empirical or targeted treatment. The median follow-up period was 11 months. There were 5 dead cases and 4 survival cases. CONCLUSION: Paraplegia is a serious post-HSCT complication. The cause of paraplegia should be determined as early as possible to perform targeted treatment. Empirical preemptive treatment should be given if necessary, so as to improve the survival rate and the quality of life of HSCT patients.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Paraplegia/terapia , Humanos , Leucemia , Qualidade de Vida , Recidiva , Estudos Retrospectivos
4.
Leuk Res ; 91: 106333, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32109757

RESUMO

B-cell acute lymphoblastic leukemia (B-ALL) with MLL-rearrangements (MLL-r) is rare in pediatric patients (aged >1 year), and optimal treatment strategies remain unclear. This study aimed to retrospectively evaluate the clinical characteristics, outcomes, and effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) of 37 non-infant children with t(v;11q23)/MLL-r B-ALL. Their 4-year overall survival (OS), event-free survival (EFS), and cumulative incidence of relapse (CIR) were 69.8 %, 58.2 %, and 39.1 %, respectively, and differed significantly between patients receiving allo-HSCT (18/19 cases received haploidentical [haplo]-HSCT) at the first complete remission (HSCT at CR1, n = 19; 87.4 %, 89.5 % and 5.3 %) and those continuing consolidation therapy (Non-HSCT at CR1, n = 18; 52.2 %, 25.9 %, and 74.1 %, respectively), and the p values were 0.022, <0.001 and <0.001, respectively. Of the 13 patients experiencing relapse during consolidation chemotherapy, the five continuing with chemotherapy only died within 44 months, and the eight patients opting for allo-HSCT after CR2 had a 4-year OS of 57.1 %. Multivariate analysis revealed HSCT at CR1 as the only independent protective factor for OS, EFS, and CIR. The present results indicate that allo-HSCT (especially haplo-HSCT) at CR1 may decrease the relapse rate and improve the prognosis of non-infant children with t(v;11q23)/MLL-r B-ALL.

5.
Sci China Life Sci ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32086670

RESUMO

Prophylactic/preemptive donor lymphocyte infusion (p/pDLI) and intensified conditioning have shown promising results in experimental studies of refractory/relapsed acute leukemia (RRAL), but real-world data remain scarce. We conducted a multicenter, population-based analysis of 932 consecutive patients. The three-year leukemia-free survival (LFS) rates were 56% for patients receiving both p/pDLI and intensified myeloablative conditioning (MAC) (intenseMAC) and 30% for those who received neither therapy per landmark analysis. Multivariable analyses were run separately for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), and p/pDLI treatment was linked to significantly higher LFS than non-DLI for both AML and ALL patients without increasing the nonrelapse mortality. IntenseMAC was associated with significantly lower relapse and higher LFS than nonintensified MAC despite higher nonrelapse mortality rates in ALL, while there was no impact of intenseMAC observed in AML. p/pDLI achieved superior outcomes in both matched-sibling donor (MSD) and haploidentical donor transplantation, while intenseMAC only influenced MSD outcomes. Data suggest that RRAL patients receiving "total therapy" by way of p/pDLI and intensified conditioning treatment have an improved chance for LFS, with p/pDLI being safer with a more extensive impact relative to intenseMAC. Patients with RRAL can tolerate both interventions and achieve a reasonable outcome.

6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(6): 1973-1978, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31839069

RESUMO

OBJECTIVE: To explore the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed or refractory peripheral T-cell lymphoma(PTCL). METHODS: The clinical data of 6 patients with relapsed or refractory PTCL undergoing allo-HSCT from Sep. 2014 to Sep. 2018 in the department of hematology, aerospace center hospital were retrospectively analyzed. Complications and disease-free survival after HSCT were observed. RESULTS: All the patients could well tolerate the conditioning regimen and acquired hematopoietic recon-struction. Following up till December 2018, with a median time of 11.5 months (1-51); acute GVHD developed in 2 cases and chronic GVHD developed in 5 cases, Among 6 cases one case died of viral pheumonia and the other 5 patients remained disease-free survival. The longest disease-free survival time has reached 51 months. CONCLUSION: allo-HSCT is a safe and effective method for relapsed or refractory peripheral T-cell lymphoma, which can be chosen as salvage treatment method for patients with primary resistance. Optimization of the conditioning regimen may result in better efficacy of allo-HSCT.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/terapia , Estudos Retrospectivos , Condicionamento Pré-Transplante , Transplante Homólogo
7.
Blood Adv ; 3(21): 3406-3418, 2019 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-31714962

RESUMO

Thrombocytopenia is associated with life-threatening bleeding and is common in myelodysplastic syndromes (MDS). Robust molecular prognostic biomarkers need to be developed to improve clinical decision making for patients with MDS with thrombocytopenia. Wilms tumor 1 (WT1) and preferentially expressed antigen in melanoma (PRAME) are promising immunogenic antigen candidates for immunotherapy, and their clinical effects on patients with MDS with thrombocytopenia are still not well understood. We performed a multicenter observational study of adult patients with MDS with thrombocytopenia from 7 different tertiary medical centers in China. We examined bone marrow samples collected at diagnosis for WT1 and PRAME transcript levels and then analyzed their prognostic effect for patients with MDS with thrombocytopenia. In total, we enrolled 1110 patients diagnosed with MDS with thrombocytopenia. Overexpression of WT1 and PRAME was associated with elevated blast percentage, worse cytogenetics, and higher Revised International Prognostic Scoring System (IPSS-R) risk. Further, both WT1 and PRAME overexpression were independent poor prognostic factors for acute myeloid leukemia evolution, overall survival, and progression-free survival. Together, the 2 genes overexpression identified a population of patients with MDS with substantially worse survival. On the basis of WT1 and PRAME transcript levels, patients with MDS with IPSS-R low risk were classified into 2 significantly divergent prognostic risk groups: a low-favorable group and a low-adverse group. The low-adverse group had survival similar to that of patients in the intermediate-risk group. Our study demonstrates that the evaluation of WT1/PRAME transcript analysis may improve the prognostication precision and better risk-stratify the patients.

8.
Cancer Commun (Lond) ; 39(1): 43, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307548

RESUMO

Lung cancer is the leading cause of cancer mortality worldwide. Dendritic cells (DCs) are the key factors providing protective immunity against lung tumors and clinical trials have proven that DC function is reduced in lung cancer patients. It is evident that the immunoregulatory network may play a key role in the failure of the immune response to terminate tumors. Lung tumors likely employ numerous strategies to suppress DC-based anti-tumor immunity. Here, we summarize the recent advances in our understanding on lung tumor-induced immunosuppression in DCs, which affects the initiation and development of T-cell responses. We also describe which existing measures to restore DC function may be useful for clinical treatment of lung tumors. Furthering our knowledge of how lung cancer cells alter DC function to generate a tumor-supportive environment will be essential in order to guide the design of new immunotherapy strategies for clinical use.

9.
Chin Med J (Engl) ; 132(13): 1563-1571, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31058667

RESUMO

BACKGROUND: Nasopharyngeal carcinoma (NPC) is sensitive to radiotherapy (RT). However, neurocognitive complications such as memory loss and learning and attention deficits emerge in the survivors of NPC who received RT. It remains unclear how radiation affects patient brain function. This pilot study aimed at finding cerebral functional alterations in NPC patients who have received RT. METHODS: From September 2014 to December 2016, 42 individuals, including 22 NPC patients and 20 normal volunteer controls in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, were recruited in this study. All patients received resting-state functional magnetic resonance imaging scans and neurocognitive tests 1 day before the initiation of RT (baseline) and 1 day after the completion of RT; the 20 normal controls were also subjected to the same scans and tests. The amplitude of the low-frequency fluctuations (ALFF) in blood oxygen level-dependent signals and functional connectivity (FC) were used to characterize cerebral functional changes. Independent t test, paired t test, and analysis of variances were used to obtain statistical significance across groups. RESULTS: After RT, NPC patients showed significantly decreased ALFF values in the calcarine sulcus, lingual gyrus, cuneus, and superior occipital gyrus and showed significantly reduced FC mainly in the default mode network (P < 0.05, corrected by AlphaSim). Relative to the controls, ALFF was decreased in the lingual gyrus, calcarine sulcus, cingulate cortex, medial prefrontal gyrus (P < 0.05, corrected by AlphaSim), and FC reduction was found in multiple cerebellar-cerebral regions, including the cerebellum, parahippocampus, hippocampus, fusiform gyrus, inferior frontal gyrus, inferior occipital gyrus, precuneus, and cingulate cortex (P < 0.001, corrected by AlphaSim). CONCLUSIONS: Cerebral functional alterations occur immediately after RT. This study may provide an explanation for the cognitive deficits in the morphologically normal-appearing brains of NPC patients after RT and may contribute to the understanding of the complex mechanism of RT.


Assuntos
Imagem por Ressonância Magnética/métodos , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/patologia , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos da radiação , Mapeamento Encefálico , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Cerebelo/efeitos da radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/radioterapia , Projetos Piloto
10.
Ann Hematol ; 98(7): 1733-1742, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31053879

RESUMO

Hepatic sinusoidal obstruction syndrome (SOS) has been rarely studied after haploidentical donor (HID) allogeneic hematopoietic stem cell transplantation (allo-HSCT). We performed a retrospective multicentre study on patients with SOS after allo-HSCT in China. The incidence, risk factors, and outcomes were compared between HID HSCT and matched related donor (MRD) HSCT. SOS developed in 0.4% of patients (HIDs: 0.4%, MRDs: 0.5%, p = 0.952) at a median time of 21.50 days (range, 1-55) after allo-HSCT (HIDs: 24 days, MRDs: 20 days, p = 0.316). For patients diagnosed with SOS, the 2-year cumulative incidence of relapse was 22.7% and 22.4% in patients receiving HID and MRD transplantation, respectively (p = 0.584). Overall survival (OS) at 2 year was 10.4% and 38.5% in the two groups (p = 0.113). The transplant-related mortality (TRM) at 100 days was 60.9% in the HID group and 38.5% in the MRD group (p = 0.178). According to the multivariate analyses, significant independent risk factors for the occurrence of SOS were delayed platelet engraftment (p = 0.007) and advanced disease status at the time of HSCT (p = 0.009). The outcomes of SOS after HID HSCT are similar to those after MRD HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Hepatopatia Veno-Oclusiva , Doadores de Tecidos , Condicionamento Pré-Transplante , Adolescente , Adulto , Aloenxertos , Criança , China/epidemiologia , Feminino , Seguimentos , Hepatopatia Veno-Oclusiva/epidemiologia , Hepatopatia Veno-Oclusiva/etiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
11.
Curr Gene Ther ; 19(1): 40-53, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30444200

RESUMO

INTRODUCTION: Recent studies on CD19-specific chimeric antigen receptor (CAR)-modified T cells (CARTs) have demonstrated unprecedented successes in treating refractory and relapsed B cell malignancies. The key to the latest CART therapy advances can be attributed to the improved costimulatory signals in the CAR design. METHODS: Here, we established several novel CARs by incorporating T cell signaling domains of CD28 in conjunction with intracellular signaling motif of 4-1BB, CD27, OX40, ICOS, and IL-15Rα. These novel CARs were functionally assessed based on a simple target cell killing assay. RESULTS: The results showed that the CD28/IL-15Rα co-signaling (153z) CAR demonstrated the fastest T cell expansion potential and cytotoxic activities. IL-15 is a key cytokine that mediates immune effector activities. The 153z CARTs maintained prolonged killing activities after repetitive rounds of target cell engagement. Consistent with the enhanced target killing function, the 153z CARTs produced increased amount of effector cytokines including IFN-γ, TNFα and IL-2 upon interaction with the target cells. CONCLUSION: In a follow-up clinical study, an acute lymphoblastic leukemia (ALL) patient, who experienced multiple relapses of central nervous system leukemia (CNSL) and failed all conventional therapies, was enrolled to receive the CD19-specific 153z CART treatment. The patient achieved complete remission after the 153z CART cell infusion. The translational outcome supports further investigation into the safety and enhanced therapeutic efficacy of the IL-15Rα-modified CART cells in cancer patients.


Assuntos
Imunoterapia/métodos , Subunidade alfa de Receptor de Interleucina-15/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/transplante , Receptor Toll-Like 9/imunologia , Adulto , Estudos de Casos e Controles , Células Cultivadas , Citocinas/metabolismo , Humanos , Subunidade alfa de Receptor de Interleucina-15/genética , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T/imunologia , Receptor Toll-Like 9/genética
12.
Medicine (Baltimore) ; 97(42): e12696, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30334953

RESUMO

RATIONALE: Surgical intervention may be not a contraindication for acute invasive fungal rhinosinusitis (AIFR) during the pre-engraftment period of allogeneic hematopoietic stem cell transplantation (allo-HSCT). PATIENT CONCERNS: We present 2 cases involving patients with AIFR in the pre-engraftment phase of allo-HSCT. DIAGNOSES: Both patients received surgical debridement combined with systemic antifungal treatment. The biopsies identified the diagnosis of AIFR in these 2 cases. OUTCOMES: The 2 patients obtained normal hematopoiesis without recurrence of AIFR. LESSON: Our experience with these 2 cases suggests that prompt endoscopic surgical debridement is not an absolute contraindication for allo-HSCT recipients with AIFR during the pre-engraftment period. If permitted, urgent, radical, and aggressive but careful endoscopic debridement should be performed together with systemic antifungal treatment once AIFR has been diagnosed or suspected.


Assuntos
Desbridamento/métodos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções Fúngicas Invasivas/cirurgia , Rinite/cirurgia , Sinusite/cirurgia , Antifúngicos/uso terapêutico , Feminino , Humanos , Hospedeiro Imunocomprometido , Infecções Fúngicas Invasivas/diagnóstico , Rinite/complicações , Rinite/microbiologia , Sinusite/complicações , Sinusite/microbiologia , Tomografia Computadorizada por Raios X , Adulto Jovem
13.
J Comp Eff Res ; 7(10): 1001-1008, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30270641

RESUMO

AIM: We conducted this meta-analysis for comparing the efficacy and safety in proximal humeral fractures by treatment minimally invasive plate osteosynthesis and open plating. METHODS: The potential academic literature were identified from the Cochrane Library, Springer, PubMed, Embase and ScienceDirect. Pooled data were analyzed by RevMan 5.1. RESULTS: Seven studies marched with the inclusion criteria. Meta-analysis showed the significant differences in terms of blood loss, operative time, length of hospital stays and constant score between two groups. No significant differences were found in time to union, the union rate and complications. CONCLUSION: Minimally invasive plate osteosynthesis in proximal humeral fractures provided significantly shorter operative times, length of hospital stays, less blood loss and better clinical outcomes without increasing complications.


Assuntos
Placas Ósseas , Fixação Interna de Fraturas/instrumentação , Procedimentos Cirúrgicos Minimamente Invasivos/instrumentação , Fraturas do Ombro/cirurgia , Idoso , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Feminino , Fixação Interna de Fraturas/métodos , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Resultado do Tratamento
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(5): 1515-1522, 2018 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-30295277

RESUMO

OBJECTIVE: To investigate the efficiency and safety of treating Epstein-Barr virus (EBV) infection of acute graft versus host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) by EBV specific cytotoxic T lymphocytes (EBV-CTL). METHODS: The Clinical characteristics, therapeutic efficacy and safety of 12 patients with EBV infection treated by EBV-CTL infusion after allo-HSCT in Department of Hemahlogy of Aero Space Center Hospital between Jan 2015 and May 2017 were analyzed retrospectioely. RESULTS: Our of 12 cases received EBV-CTL infusion after transplantation, 9 did not received Rituximab therapy due to the active infection, 4 cases including 3 received Ritaximab progressed into posttransplantation lymphoroliferetive disease (PTLD). The median time of EBV infection was 47 (22-71) days, median time of antivirus therapy before tramplantation was 10 (8-33) days, median time of first CTL infusion was 59(34-86) days after transplatation. The 43 cases-time CTL infusion was performed smoothly, no related harmful evnts occoured, no progression of GVHD was observed. After the first course of infusion, complete remission (CR), Partial remssion (PR) and no remssion (NR) were obtained in 9, 1 and 2 patients respectively, the relapse was observed in 4 patients who then received the socond course of infusion and all reached CR, the patient in PR did not reathed CR finally and died of GVGD at 5 months after transpplantation . Only 1 out of 2 cases of NR obtained CR, another 1 still was in NR, and died of transplantation related infection at 5 months after transplantation. 4 cases of PTLD were all cared. CONCLUSION: Preliminary results of this study suggest that EBV-CTL infusion is safe for the EBV infection combined with acute GVHD after all-HSCT. However, a further larger scale clinical studies are needed to prove the efficiency.


Assuntos
Infecções por Vírus Epstein-Barr , Doença Enxerto-Hospedeiro , Herpesvirus Humano 4 , Transplante de Células-Tronco Hematopoéticas , Humanos , Linfócitos T Citotóxicos
15.
World J Gastroenterol ; 24(29): 3273-3280, 2018 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-30090007

RESUMO

AIM: To detect the expression of type I inositol 1,4,5-trisphosphate receptor (IP3RI) in the kidney of rats with hepatorenal syndrome (HRS). METHODS: One hundred and twenty-five Sprague-Dawley rats were randomly divided into four groups to receive an intravenous injection of D-galactosamine (D-GalN) plus lipopolysaccharide (LPS; group G/L, n = 50), D-GalN alone (group G, n = 25), LPS alone (group L, n = 25), and normal saline (group NS, n = 25), respectively. At 3, 6, 9, 12, and 24 h after injection, blood, liver, and kidney samples were collected. Hematoxylin-eosin staining of liver tissue was performed to assess hepatocyte necrosis. Electron microscopy was used to observe ultrastructural changes in the kidney. Western blot analysis and real-time PCR were performed to detect the expression of IP3RI protein and mRNA in the kidney, respectively. RESULTS: Hepatocyte necrosis was aggravated gradually, which was most significant at 12 h after treatment with D-galactosamine/lipopolysaccharide, and was characterized by massive hepatocyte necrosis. At the same time, serum levels of biochemical indicators including liver and kidney function indexes were all significantly changed. The structure of the renal glomerulus and tubules was normal at all time points. Western blot analysis indicated that IP3RI protein expression began to rise at 3 h (P < 0.05) and peaked at 12 h (P < 0.01). Real-time PCR demonstrated that IP3RI mRNA expression began to rise at 3 h (P < 0.05) and peaked at 9 h (P < 0.01). CONCLUSION: IP3RI protein expression is increased in the kidney of HRS rats, and may be regulated at the transcriptional level.


Assuntos
Síndrome Hepatorrenal/patologia , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Rim/patologia , Animais , Modelos Animais de Doenças , Galactosamina/toxicidade , Hepatócitos/patologia , Síndrome Hepatorrenal/induzido quimicamente , Humanos , Receptores de Inositol 1,4,5-Trifosfato/genética , Rim/irrigação sanguínea , Rim/citologia , Rim/ultraestrutura , Lipopolissacarídeos/toxicidade , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Microscopia Eletrônica , Músculo Liso Vascular/citologia , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Miócitos de Músculo Liso/ultraestrutura , Necrose , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Organismos Livres de Patógenos Específicos
16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(3): 880-885, 2018 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-29950237

RESUMO

OBJECTIVE: To make through introduction of Wernicke's encephalopathy (WE) following hematopoietic stem cell transplantation (HSCT) in terms of clinical characteristics, diagnostic process and treatment. METHODS: The clinical charactaristics, diagnostic and therapeutic process and prognostic follow-up in 4 patients diagnosed of WE following HSCT between January 2016 to January 2017 at Department of Hematology, Chinese Aerospace Center Hospital were retrospectively analyzed. RESULTS: Four patients included 2 ALL and 2 AML, and 3 males and 1 female, their age ranged from 8 to 20 years old. 4 patients accouted for about 3% of all petients who received HSCT at that time. Typical triad syndrome consisting of ocular motility disorders, ataxia, global confusion was seen in only 1 patient. However, confusion and heterophthongia as onset of this complication were seen in all patients. Cerebral computed tomograph scan was universally unremarkable and useless. Cerebral MRI scan disclosed that typical involvement including thalamus, fourth ventricle, third ventricle, middle cerebral aqueduct was seen in 3, while untypical site including mamillary body was in the remaining 1 patient. All received vitamin B1 supplement therapy by intramuscular injection at a dose of 100 mg each day. Initial response was observed at 2, unknown, 3, 4 days after treatment and all obtained complete remission within 2 weeks without any event of relapse after median follow-up period of 8 (7-12) months. CONCLUSION: Any recipient of HSCT with clinical signs or symptoms of central nervous system should receive vitamin B1 supplementary therapy immediately to decrease risk of mortality of WE even if the diagnosis of WE is uncertain.


Assuntos
Encefalopatia de Wernicke , Adolescente , Criança , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Imagem por Ressonância Magnética , Masculino , Estudos Retrospectivos , Tiamina , Adulto Jovem
17.
Spectrochim Acta A Mol Biomol Spectrosc ; 200: 93-101, 2018 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-29674244

RESUMO

Oil-field wastewaters contain high level of polycyclic aromatic hydrocarbons (PAHs), which have to be analyzed to assess the environmental effects before discharge. In this work, a green fluorimetric detection method that combines excitation-emission matrix (EEM) fluorescence with parallel factor analysis (PARAFAC) algorithm was firstly developed to achieve the direct and simultaneous determination of six U.S. EPA PAHs in two different kinds of complex oil-field wastewaters. Due to the distinctive "second-order advantage", neither time-consuming sample pretreatments nor toxic organic reagents were involved in the determination. By using the environment-friendly "mathematical separation" of PARAFAC, satisfactory quantitative results and reasonable spectral profiles for six PAHs were successfully extracted from the total EEM signals of oil-field wastewaters without need of chromatographic separation. The limits of detection of six PAHs were in the range of 0.09-0.72ngmL-1, and the average spiked recoveries were between (89.4±4.8)% and (109.1±5.8)%, with average relative predictive errors <2.93%. In order to further confirm the accuracy of the proposed method, the same batch oil-field wastewater samples were analyzed by the recognized GC-MS method. t-test demonstrated that no significant differences exist between the quantitative results of the two methods. Given the advantages of green, fast, low-cost and high-sensitivity, the proposed method is expected to be broadened as an appealing alternative method for multi-residue analysis of overlapped PAHs in complex wastewater samples.

18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(1): 239-244, 2018 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-29397851

RESUMO

OBJECTIVE: To investigate the value of flow cytometry (FCM) detection in prognostic evaluation of minimal residual disease (MRD) of acute myeloid leukemia (AML) patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Eighty-two cases of AML (except M3) after allo-HSCT who accord to enrolled condition (no MRD positive after allo-HSCT confirmed by regular flow cytometry detection and followed-up for 2 years) from April 2012 to September 2016 in our department were selected. Among 82 cases males were 50 and females were 32 with average age of 27.27 (2-57) years old. According to FAB classification, 2 cases were classified as M0/M1, 51 cases as M2, 24 cases as M4/M5 and 5 cases as M6. The antibody panels were selected accordingly to the initial leukemia associated immunophentype(LAIP) of patients. RESULTS: Twenty patients (24.39%) were identified as MRD+ (0.10%-4.91%, mean 1.64%) in 82 AML patients after allo-HSCT (all the patients were in complete remission phase based on bone marrow morphology). During follow-up, 16 cases relapsed (relapse rate 80%)in 20 MRD+ cases, including 1 case with extramedullary relapse; 4 out of 62 MRD- cases relapsed (relapse rate 6.45%)in bone marrow, and 2 cases extramedullary relapsed. The average survival time of leukemia- free survival (LFS) in group MRD+ was 15.19 ± 3.99 months, median LFS was 10± 3.84 months. The average LFS time was 53.50 ± 1.69 months in MRD- group (P<0.001). The average overall survival (OS) of the MRD+ group was 22.52 ± 5.72 months, the median OS was 18 ± 3.27 months; the average OS time was 42.86 ± 2.83 months in MRD- group(P=0.008). CONCLUSION: For the patients with morphologically complete remission after allo-SCT, the FCM regular monitoring of bone marrow MRD closely relates with its relapse rate, LFS and OS. Compared with the MRD- group, the relapse rate of MRD+ group is significantly increases, and the LFS and OS significantly decreases.


Assuntos
Leucemia Mieloide Aguda , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Citometria de Fluxo , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Prognóstico , Transplante Homólogo , Adulto Jovem
19.
Biochem Biophys Res Commun ; 478(4): 1660-6, 2016 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-27614312

RESUMO

Cytochrome c oxidase subunit II (COX II) containing a dual core CuA active site is one of the core subunits of mitochondrial Cytochrome c oxidase (Cco), which plays a significant role in the physiological process. In this report, the full-length cDNA of COXII gene was cloned from Sitophilus zeamais, which had an open reading frame (ORF) of 684 bp encoding 227 amino acids residues. The predicted COXII protein had a molecular mass of 26.2 kDa with pI value of 6.37. multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXII had high sequence identity with the COXII of other insect species. The gene was subcloned into the expression vector pET-32a, and induced by isopropyl ß-d-thiogalactopyranoside (IPTG) in E. coli Transetta (DE3) expression system. Finally the recombinant COXII with 6-His tag was purified using affinity chromatography with Ni(2+)-NTA agarose. Western Blotting (WB) showed the recombinant protein was about 44 kD, and the concentration of fusion protein was 50 µg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that recombinant COXII could catalyze the oxidation of substrate Cytochrome C (Cyt c), and influenced by allyl isothiocyanate (AITC). By using molecular docking method, It was found that a sulfur atom of AITC structure could form a length of 2.9 Å hydrogen bond with Leu-31. These results suggested that tag-free COXII was functional and one of the action sites of AITC, which will be helpful to carry out a point mutation in binding sites for the future research.


Assuntos
Complexo IV da Cadeia de Transporte de Elétrons/genética , Regulação Enzimológica da Expressão Gênica , Proteínas de Insetos/genética , Gorgulhos/genética , Sequência de Aminoácidos , Animais , Biocatálise/efeitos dos fármacos , Western Blotting , Clonagem Molecular , Citocromos c/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/classificação , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Escherichia coli/genética , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Isotiocianatos/metabolismo , Isotiocianatos/farmacologia , Simulação de Acoplamento Molecular , Peso Molecular , Oxirredução , Filogenia , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência de Aminoácidos , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta , Especificidade por Substrato , Gorgulhos/enzimologia
20.
Thorac Cancer ; 7(3): 296-303, 2016 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-27148414

RESUMO

BACKGROUND: To investigate the clinical outcomes and toxicity of hypofractionated radiotherapy for medically inoperable stage I non-small cell lung cancer (NSCLC). METHODS: Patients treated with radiotherapy at a dose of 4-6 Gy per fraction using fixed-field intensity modulated radiotherapy (IMRT) or volumetric-modulated arc therapy (VMAT) at our hospital from June 2005 to December 2013 were analyzed. The total prescription doses ranged from 50-78 Gy with 4-6 Gy per fraction. The median follow-up period was 24 months. RESULTS: A total of 65 patients with stage I NSCLC were analyzed, including 43 primary NSCLC patients and 22 patients with recurrent or second primary NSCLC. An objective response (complete or partial response) was achieved at six months in 84.6% of patients. The three-year local control rate was 90.8%. Kaplan-Meier estimates of local failure-free, progression-free, overall, and cancer-specific survival rates at three years were 90.3%, 64.3%, 68.9%, and 88.8%, respectively. The rate of symptomatic radiation pneumonitis was 16.9%, and no grade 4-5 toxicity was observed. CONCLUSION: Favorable local control and outcome was achieved with hypofractionated radiotherapy in patients with inoperable stage I NSCLC with acceptable toxicity. The most common schedule of 6 Gy × 12 fractions may be a promising regimen, and a prospective study is in process.

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