Objective To analyze the related risk factors of postoperative delirium(POD)in patients with Stanford type A aortic dissection, and to guide clinical practices. Methods The clinical data of 118 cases [81 males and 37 females, average age (55.0 ± 10.3) years] with Stanford type A aortic dissection in Tianjin Chest Hospital from January 2016 to December 2017 were analysed in this study. According to whether developed delirium after surgery, the patients were divided into POD group(n=56)and Non-POD group(n=62).The preoperative,perioperative,and postoperative clinical data were collected.The univariate and multivariate Logistic regression analysis was used to investigate the risk factors of POD in patients with the Stanford type A aortic dissection. Results Single factor analysis showed that the proportions of drinking and cerebrovascular history significantly increased,the proportions of early electrolyte disorder and hypoxemia significantly increased, the levels of granulocytes / lymphocytes, circulatory time and blood volume during operation increased significantly, and the duration from onset to operation was decreased, but fibrinogen level decreased significantly in POD group than those of Non-POD group (P < 0.05). Multivariate Logistic analysis indicated that the more intraoperative consumption of blood (OR=1.733, 95% CI:1.409-2.129) and early postoperative electrolyte disorder (OR=10.500, 95% CI:2.930-37.622)were independent risk factors of POD,while the higher level of preoperative fibrinogen(OR=0.157,95% CI:0.050-0.635) and longer time from onset to surgery (OR=0.871, 95% CI:0.808-0.943) were protective factors of POD in patients with Stanford type A aortic dissection.Conclusion The early identification of risk factors of POD,and the active intervention of POD have a positive significance to reduce the occurrence of POD.

OBJECTIVETo explore the role of autophagy in doxorubicin (DOX)-induced resistance of human myeloma cell line RPMI8226.

METHODSWe established doxorubicin induced resistant subline of myeloma cell line RPMI8226/DOX by drug concentration step-elevation method. Resistant index of DOX was measured by MTT assay. Autophagy of myeloma cell lines RPMI8226/s and RPMI8226/DOX was detected by transmission electron microscopy, immunofluorescence (LC3-FITC) and western blot respectively. Apoptosis of RPMI8226/DOX cells induced by DOX combined with autophagic inhibitor hydroxychloroquine or 3-MA was identified by AnnexinV-FITC/PI double fluorescence dyeing.

RESULTSResistant index of RPMI8226/DOX was approximately 10.8 fold of that of RPMI8226/S. Electron microscopic studies revealed that most of RPMI8226/DOX cells displayed viable attributes and contained numerous autophagic vacuoles. Fluorescent images of RPMI8226/DOX cells showed a punctuate distribution in LC3 protein. Increased LC3-II protein in RPMI8226/DOX cells was determined by immunoblotting. There were no differences among 8 μmol/L HCQ (3.24±1.08)%, 10 mmol/L 3-MA (2.81±0.80)% or control \[(2.12±1.24)%\] (P>0.05) in terms of AnnexinV-FITC/PI double fluorescence dyeing; Compared with apoptosis of (9.75±2.15)%, (24.36±2.16)% and (40.51±3.14)% of RPMI8226/DOX cells under 2, 4 and 6 μmol/L DOX, apoptosis increased significantly after 24 h incubation under 2, 4 and 6 μmol/L DOX combined with 8 μmol/L HCQ as of \[(16.56±1.89)%, (36.44±2.91)% and (62.68±3.75)%, respectively\], or under 2, 4 and 6 μmol/L DOX combined with 10 mmol/L 3-MA as of \[(15.47±1.85)%, (39.28±3.06)% and (55.46±4.07)%, respectively\] (P<0.05).

CONCLUSIONAutophagy was involved in doxorubicin-induced resistance of myeloma cell line RPMI8226, DOX resistance in myeloma cells was reversed partly by autophagy inhibitor hydroxychloroquine or 3-MA, and autophagy may be one of mechanisms for drug resistance.

Autophagy ; drug effects ; Cell Line, Tumor ; Doxorubicin ; pharmacology ; Drug Resistance, Neoplasm ; Humans ; Multiple Myeloma

OBJECTIVETo investigate the autophagy in human bone marrow mesenchymal stem cells (hBMMSC) exposed to irradiation.

METHODSThe apoptosis and necrosis rate were assessed by Annexin V and propidium (PI) staining in hBMMSC at 4h after irradiated with X-ray at 0, 2, 4, 8 and 10 Gy. The autophagy was observed by transmission electron microscopy. The mRNA expression of Beclin1 and microtubule-associated protein 1 light chain 3 (MAPLC3 or LC3) was analyzed by RT-PCR in hBMMSC at 4h after X-ray irradiation at 0, 8 and 10 Gy.

RESULTSThe apoptosis rate of hBMMSC was markedly decreased while the necrosis and death rate were slowly increased with the increase of irradiation dose when under 8 Gy. The apoptosis rate was significantly increased and reached a peak while the necrosis and whole death rate were obviously increased when irradiated with 10 Gy X-rays. In addition, the change of apoptosis rate was more significant than that of necrosis rate. By electron microscopy, a mass of autophagic vacuoles (autophagosome and autolysosome) were observed in irradiation and positive control groups, but were only occasionally seen in normal control group. The proportion of hBMMSC with autophagic vacuoles in 8 Gy irradiation group was higher than that in 10 Gy one. The mRNA expression of Beclin1 and LC3 in irradiation groups and positive control group was significantly higher than in normal control group, and so did in 8 Gy irradiation group than that in 10 Gy group.

CONCLUSIONIrradiation may induce the autophagy in hBMMSC, and autophagy could protect hBMMSC from irradiation injury in a certain dose range.

Apoptosis ; radiation effects ; Autophagy ; radiation effects ; Bone Marrow Cells ; radiation effects ; Cell Line ; Humans ; Mesenchymal Stromal Cells ; radiation effects ; X-Rays

Humans ; Immunoglobulin M ; Lung ; pathology ; Multiple Myeloma ; diagnosis ; pathology

The purpose of this study was to investigate the efficacy of treatment with haploidentical donor's lymphocyte infusion(hiDLI) combined with interleukin-2 (IL-2) after transplantation of autologous peripheral blood stem cells mixed with haploidentical allogeneic bone marrow (mix-HSCT) for acute myeloid leukemia (AML). 49 patients diagnosed as AML were enrolled in this study. After preconditioning with TBI plus VEMAC regimen, all patients received mix-HSCT. Autologous peripheral blood hematopoietic stem cells were mobilized with chemotherapy-combined G-CSF, and haploidentical allogeneic bone marrow cells were not mobilized with G-CSF. 33 patients in test group were treated with hiDLI plus IL-2 for 1-8 times after hematopoietic reconstruction, 16 patients in control group received mix-HSCT only. All the patients were followed-up for more than 3 years. The results showed that all the patients obtained hematopoietic reconstruction, and no graft-versus-host disease (GVHD) was found. In two groups, the median time of absolute neutrophil count (ANC) ≥ 0.5×10(9)/L was 14 (12 - 18) and 14 (11 - 16) days, and WBC count ≥ 4.0×10(9)/L was 17 (16 - 22) and 18(17 - 20) days, Plt count ≥ 50×10(8)/L were 25 (24 - 29) and 25 (23 - 26) days. 9 patients in test group formed mixed chimerism (46XX/46XY) and sustained about 3 - 12 months; disease-free survival (DFS) was 63.6%, 3 patients in control group formed mixed chimerism (46XX/46XY), persistent about 3-6 months; DFS was 50.0%. It is concluded that treatment with hiDLI plus IL-2 after mix-HSCT for AML patients may increase DFS efficiently.
Adolescent ; Adult ; Female ; Hematopoietic Stem Cell Mobilization ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunotherapy, Adoptive ; Leukemia, Myeloid, Acute ; therapy ; Male ; Transplantation, Homologous ; Young Adult

This study was purposed to detect the expression of autophagy-related gene Beclin1 and microtubule-associated protein 1 light chain 3 (MAPLC3) in bone marrow mononuclear cells (BMMNC) isolated from acute leukemia (AL) patients, and to explore its significance. Transmission electron microscopy and RT-PCR were used to detect the autophagy activity and the expression level of Beclin1 and MAPLC3 mRNA in BMMNC isolated from 27 AL patients with de novo, refractory or relapse AL and completely remission and 31 normal persons respectively. The results showed that autophagy activity and expression levels of Beclin1 and MAPLC3 mRNA in BMMNC from de novo AL patients were 80%, 0.68 ± 0.18, 0.24 ± 0.06, respectively; those in BMMNC from refractory or relapse AL patients were 100%, 0.79 ± 0.09, 0.30 ± 0.07, respectively; those in BMMNC from CR patients were 40%, 0.52 ± 0.15, 0.16 ± 0.04, respectively, while those in BMMNC from normal persons were 20%, 0.57 ± 0.13, 0.16 ± 0.05, respectively. The autophagic activity and expression levels of Beclin1 and MAPLC3 mRNA in de novo and refractory or relapse AL patients were higher than those in normal persons, with statistical significance (p < 0.05), while the comparison between CR patients and normal control showed no statistical difference (p > 0.05). It is concluded that autophagy activity and Beclin1 and MAPLC3 mRNA expression level of in de novo and refractory or relapse patients are higher than those in normal control, and the up-regulation of autophagy activity and expression of Beclin1 and MAPLC3 mRNA in refractory or relapse patients is especially significant. This may be related to the genesis, development and drug resistance of AL.
Acute Disease ; Adolescent ; Adult ; Aged ; Apoptosis Regulatory Proteins ; metabolism ; Beclin-1 ; Bone Marrow Cells ; metabolism ; Child ; Female ; Humans ; Leukemia ; metabolism ; pathology ; Male ; Membrane Proteins ; metabolism ; Microtubule-Associated Proteins ; metabolism ; Middle Aged ; RNA, Messenger ; genetics ; Young Adult

To evaluate the use of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) for treatment of acute and chronic leukemia, from March 1997 to January 2003, 21 adult patients with malignant hematopoietic diseases underwent allo-PBSCT from HLA-identical siblings (19 patients) and haplo-identical mother (one) and one B point site mismatched sibling (one). All donors were mobilized with G-CSF for 4 days and peripheral blood stem cells were collected by CS-3000 separator. The conditioning regimen included the high dose combination chemotherapy and TBI. Cyclosporine-A (CsA) plus a short course of MTX was used for GVHD prophylaxis in all patients. The results showed that after trans plantation, median time for the recovery of granuocyte > or = 0.5 x 10(9)/L and platelets > or = 20 x 10(9)/L were 12 (10 - 20) and 15 (11 - 35) days, respectively. Acute GVHD was observed in 8/17 patients (47%), of which one transplanted from HLA-haploidentical mother. Chronic GVHD occurred in 12/17 patients (70%). All of four female survivals did not show acute and chronic GVHD. Day 100 transplantation-related mortality was 14% (3/21). Relapse occurred in two patients (9.5%) who underwent allo-PBSCT in stage of non-remission at one and six months. After follow-up of 40 (15 - 70) months, 11 patients (52.4%) are still disease-free survival. These results suggested that peripheral blood stem cells produce a faster hematopoietic recovery and a lower relapse of leukemia. The rate of aGVHD is not increased when using the peripheral blood as source of stem cells; however, cGVHD continues to be a significant problem. Donors tolerated the procurement procedure without complications.
Adolescent ; Adult ; Female ; Graft vs Host Disease ; etiology ; Humans ; Leukemia ; therapy ; Male ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; Transplantation, Homologous ; Treatment Outcome

Adult ; Cladribine/therapeutic use* ; Histiocytosis, Langerhans-Cell/drug therapy* ; Humans

OBJECTIVETo investigate the efficacy of autologous peripheral blood hematopoietic stem cell transplantation(auto-PBHSCT) combined with adoptive immunotherapy for patients with B lymphocyte malignant lymphoma(ML).

METHODSA total of 110 cases of ML treated with adoptive immunotherapy after auto-PBHSCT from January 2000 to December 2009 were enrolled in adoptive immunotherapy group (treated group), while 74 cases of ML treated without adoptive immunotherapy after auto-PBHSCT from January 1995 to December 1999 were used as control group. The efficacy of 2 groups were analyzed and compared, 110 case of ML in treated group included 78 cases of non-Hodgkin's lymphoma(NHL), 32 cases of Hodgkin's lymphoma(HL),74 cases of ML in control group included 52 NHL and 22 HL. All of the patients were treated sequentially with chemotherapy regimens for 6 courses. After that, all the patients received auto-PBHSCT. After hematopoietic reconstruction, the patients in treated group were given 6 courses of adoptive immunotherapy(rhIL-2 100 WU/day for 10 days monthly for each course), while the patients in control group were not given immunotherapy. All the patients were followed-up for more than 5 years.

RESULTSThere was one patient in each group, who died of liver failure and cerebral hemorrhage respectively within 3 and 2 months, and all the other patients achieved hematopoietic reconstruction. Following-up for 1, 3, 5 years, the disease-free survival (DFS) rate in treated group was 97.3%,93.6%,87.3% while 91.9%, 73.0%, 64.9% in control group. Following-up for 3 and 5 years, there was very significant difference in DFS between 2 groups(P<0.01). The 1,3 and 5 year DFS rate of patients in stage I/II and III/IV in the treated group were 100%,100%,91.7% and 96.5%,91.9%,86.0% respectively while DFS of control group was 100%, 93.3%, 86.7% and 89.8%, 67.8%, 59.3%, there was a significant difference in 3 and 5 years DFS of III/IV stage patients between 2 groups (P<0.01). The 1,3 and 5 year DFS rate of HL patients were 100%, 93.8%,84.4% in treated group and 100%,72.7%,59.1% in control group respectively. There was significant difference in 3 and 5 years DFS of HL between 2 groups (P<0.05). The 1,3 and 5 year DFS rate of stage I/II HL patients were 100%,100%,88.9% in treated group and 100%,100%,80.0% in control group. The 1,3 and 5 year DFS of HL patients in stage III/IV was 100%,91.3%,82.6% and 94.1%,64.7%,52.9% respectively. There was significant difference in 3 and 5 years DFS of III/IV stage of HL patients between 2 groups (P<0.05). The 1,3 and 5 year DFS rate of NHL patients is 96.2%, 93.6%,88.5% in treated group and 90.4%,73.1%,65.4% in control group respectively. There was a significant difference in 3 and 5 years DFS of NHL between 2 groups(P<0.01). The 1,3 and 5 year DFS rate of stage I/II NHL patients was 100%, 100%, 93.3.9% in treated group and 100%, 90%, 90.0% in control group, respectively. The 1,3 and 5 year DFS of NHL patients in stage III/IV is 95.2%, 92.1%,87.3% and 88.1%,69.0%, 59.5% respectively. There was significant difference in 3 and 5 years DFS of III/IV stage NHL patients between 2 groups (P<0.05).

CONCLUSIONTherapeutic efficacy is satisfactory for the patients of B lymphocyte ML treated with adoptive immunotherapy after auto-PBHSCT, especially benefited the patients of stage III/IV significantly.

OBJECTIVETo investigate the correlation between the HLA genes and pathogenesis of aplastic anemia (AA), so as to find the susceptible AA genes.

METHODSPolymerase chain reaction with specific sequence primers (PCR-SSP) method was used to detect the HLA typing of 50 AA patients and 183 normal healthy individuals as controls in Chinese Han population of northwestern plateau.

RESULTSThe frequency of HLA-A* 0201 (45.0%), B* 1501 (11.0%), B* 5501 (9.0%) and DRB1* 0901 (19.0%) gene frequences in AA patients were significantly higher than those in controls (Odds Ratio: OR=1.657, 2.138, 2.314 and 1.932, x2=4.882, 3.876, 3.863 and 4.473 (P<0.05). In contrast, A* 0301 gene frequency (4.0%) in AA was significantly lower than that in controls, OR=0.349, x2=4.154 (P<0.05). The male HLA-A* 0201 gene frequency was lower than that in female (38.2% vs 59.4%), and the difference was statistically significant (P<0.05). Concludsion: The HLA-A* 0201, B* 1501, B* 5501 and DRB1* 0901 genes may be considered as the risk markers while A* 0301 gene as a protective marker of AA, the HLA-A* 0201 also shows the sex differences.

Alleles ; Anemia, Aplastic ; genetics ; Asian Continental Ancestry Group ; genetics ; China ; Female ; Gene Frequency ; HLA-DRB1 Chains ; genetics ; Humans ; Male ; Polymerase Chain Reaction ; Polymorphism, Genetic