Objective To study the effect of myocardial ischemic preconditioning on activity of ATPase and creatine kinase(CK) in high blood fat rat. Methods High blood fat rat mode was established from SD rats.The rats were randomly divided into three groups: ischemic preconditioning(IPC), ischemic/reperfusion(I/R) and control group.The activity of CK in coronary outflow,the activity of malonyldialdehyde(MDA),superoxide dismutase(SOD),glutathione perodxidase(GSH-Px) and ATPase in myocardium were dectected. Results CK and MDA were significantly less in IPC group than those in I/R group.In IPC group,the activity of SOD,GSH-Px,Na~(+)-K~(+)-ATPase,Ca~(2+)-ATPase and Ca~(2+)-Mg~(2+)-ATPase were much higher than those in I/R group. Conclusion Myocardial ischemic preconditioning can protect high blood fat rat from ischemic/reperfusion injury.

OBJECTIVESTo block the synthesis of ryanodine receptor 2 (RyR2) in myocardial cells by RNA interference and to investigate its biological impact on ischemia-reperfusion (I/R) in rat myocardial cells.

METHODSRat myocardial cells were isolated and cultured for an I/R model in vitro. RNA interference technique was used to block the synthesis of RyR2 in myocardial cells. Changes of LDH level, apoptosis, RyR2 mRNA expression and cytosolic Ca(2+) concentration were analyzed accordingly.

RESULTSMyocardial cells after I/R manipolation were severely injuried (LDH leakage, 125 IU/L vs 12 IU/L, P < 0.05), apoptosis (60.1% vs 5.5%, P < 0.05), significant cytosolic Ca(2+) overload (21.2 vs 7.6, P < 0.05) and remarkable mitochondrial membrane potential loss (37.2 vs 85.1, P < 0.05). However, no visible change of RyR2 was observed (20.1 vs 22.7, P > 0.05). Pre-treatment with RyR2 specified siRNA demonstrated suppressed expression of RyR2 (6.8 vs 20.1, P < 0.05), increased mitochondrial membrane potential (55.8 vs 37.2, P < 0.05), attenuated cytosolic Ca(2+) overload (8.6 vs 21.2) and cellular apoptosis (31.2% vs 60.1%, P < 0.05).

CONCLUSIONRyR2 gene silencing enables to protect myocardial cells from I/R injury in vitro.

Animals ; Apoptosis ; drug effects ; genetics ; Cells, Cultured ; Gene Silencing ; immunology ; physiology ; Membrane Potential, Mitochondrial ; drug effects ; immunology ; Myocardial Reperfusion Injury ; immunology ; pathology ; Myocytes, Cardiac ; drug effects ; pathology ; Oxygen ; metabolism ; RNA Interference ; RNA, Small Interfering ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; immunology ; pathology ; Ryanodine Receptor Calcium Release Channel ; drug effects ; genetics

To investigate the protective effects of recombinant human tumor necrosis factor receptor II: IgG Fc fusion protein (rhu TNFR: Fc) against the lipopolysaccharide (LPS) induced intestinal damage of rats and its underlying mechanism. SD rats were randomly divided into four groups: control group, rhuTNFR: Fc group, LPS group and rhu TNFR: Fc + LPS group. Mean arterial pressure (MAP) was continuously monitored and the mortality rates were assessed. The levels of TNF-alpha and its bioactivity in the serum were assessed by ELISA and flow cytometry respectively. Pathologic changes of intestinal tissue were observed by HE staining. The rats of control and rhu TNFR: Fc group all survived with stable MAP, and the low level and bioactivity of TNF-alpha in the serum were maintained. While 83% of the rats in LPS group died by 6 h with the levels and bioactivity of TNF-alpha increasing significantly. In rhu TNFR: Fc + LPS group, the mortality rate of rats dropped to 33%. The TNF-alpha level increased compared with control group but its bioactivity decreased significantly compared with LPS group. The MPO activity and content of MDA decreased significantly. The status of pathological manifestation in the intestine was also ameliorated. These data suggest that rhu TNFR: Fc could protect rats from the acute intestine injury induced by LPS through ablating the rise in serum TNF-alpha level and bioactivity as well as anti-oxidation.
Animals ; Disease Models, Animal ; Etanercept ; Female ; Humans ; Immunoglobulin G ; pharmacology ; Intestines ; drug effects ; metabolism ; pathology ; Lipopolysaccharides ; adverse effects ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Tumor Necrosis Factor ; Receptors, Tumor Necrosis Factor, Type II ; pharmacology ; Recombinant Fusion Proteins ; pharmacology ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVEThis study was aimed to investigate whether incorporation of rituximab into high-dose chemotherapy with autologous peripheral blood stem cell transplantation (auto-PBSCT)could improve the survival of patients with diffuse large B-cell lymphoma (DLBCL), and evaluate the safety of this regimen.

METHODSTwenty-five patients (age, 17 - 61 yrs) with DLBCL were treated with a sequential chemotherapy for remission induction, intensive chemotherapy for mobilization of stem cells, and high-dose chemotherapy followed by auto-PBSCT. Among 25 patients, 22 cases were at IV Ann Arbor stage, 60% cases with B symptom, and 10 cases with intermediate-high risk and 2 cases with high risk when evaluated by International Prognostic Index (IPI). The high-dose chemotherapy included BEAM regimen for 21 patients, and TBI conditioning regimen for 4 patients. Each patient received infusion of rituximab at a dose of 375 mg/m(2) for 2 times, each at peripheral blood stem cell mobilization and peripheral stem cell infusion.

RESULTS20 patients achieved complete remission (CR) before transplantation. After high-dose chemotherapy and auto-PBSCT, 92% patients achieved CR. At a median follow-up of 45 months, the estimated 3-year overall survival (OS) and progression-free survival (PFS) were 78.9% and 75.9%, respectively, for all patients; while those were 87.4% and 82.4% for patients achieved CR before auto-PBSCT. Multivariate analysis by Cox regression revealed that failure to achieving CR before auto-PBSCT was an independent prognostic factor affecting OS, while factor affecting PFS was IPI scores. Rituximab was generally well tolerated with few side-effects.

CONCLUSIONOur results suggested that the addition of rituximab to high-dose chemotherapy followed by auto-PBSCT was effective and safe for patients with DLBCL.

Adolescent ; Adult ; Aged ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Combined Modality Therapy ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse ; therapy ; Male ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; Rituximab ; Transplantation, Autologous ; Young Adult

OBJECTIVETo monitor blood cells EBV-DNA copies by quantitative Epstein-Barr virus (EBV) polymerase chain reaction after hematopoietic stem cell transplantation (HSCT) and to evaluate its implication.

METHODSEBV-DNA copies of peripheral blood mononucleated cells (PBMNCs) were detected by fluorescence quantitative PCR once a week since conditioning regimen from fifty one patients received HSCT. Correlation between development of lymphoproliferative disorders (LPD) and EBV-DNA copies and influence factors of EBV reactivation were analyzed.

RESULTSThe cumulative incidence of EBV viremia was 58.8%. EBV reactivation occurred (39.6 +/- 23.5) days after HSCT, later than that of cytomegalovirus (CMV) reactivation (25.0 +/- 15.1) days (P < 0.01). HLA mismatch (P < 0.01), use of antithymocyte globulin (ATG) (P < 0.01), age less than twenty (P < 0.001) were factors for EBV reactivation, (93.3% vs 48.1%, 92.3% vs 18.7%, and 100% vs 53.1%, respectively). EBV related post-transplant lymphoproliferative disorders (EBV-PTLD) occurred only in 4 out of 30 (13.3%) EBV reactivation patients, whose EBV DNA load maintained over 10(6) copies/ml for at least two weeks (4 out of 13 cases). The median survival time of EBV-PTLD patients was 19.5 (11 - 75) days.

CONCLUSIONSEBV reactivation occurs frequently after HSCT, especially in those received HLA mismatch grafts, used antithymocyte globulin or aged under twenty. Patients with EBV loads over 10(6) copies/ml, especially lasting over two weeks, appear to have an increased risk for PTLD, and pre-emptive therapy may be of clinical useful.

DNA, Viral ; blood ; Epstein-Barr Virus Infections ; Hematopoietic Stem Cell Transplantation ; Herpesvirus 4, Human ; genetics ; Humans ; Lymphoproliferative Disorders

OBJECTIVETo analyze the impact of the time to hematopoietic reconstitution on the prognosis of hematological malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODS173 patients with hematological malignancies treated with allo-HSCT (excluding umbilical cord blood transplantation) at Peking University first Hospital between 2003 and 2011 were analyzed retrospectively. According to the median time to neutrophil and platelet engraftment, the patients were divided into tow groups. The 5-year overall survival (OS), transplant-related mortality (TRM), relapse rate (RR) and prognostic factors were analyzed.

RESULTSThe quicker neutrophil engraftment group with an estimated 5-year OS rate of 66.63%, 5-year TRM of 21.58% and 5-year RR of 18.65%. The slower neutrophil engraftment group with OS of 61.84%, TRM of 24.14% and RR of 23.57%. Univariate analysis demonstrated that no relationship was found between time to neutrophil engraftment and OS, TRM and RR (P = 0.462, P = 0.893, P = 0.545, respectively). There seems to be a trend toward increasing incidence of OS in quicker platelet engraftment group(OS were 69.44% and 54.31%, respectively), but no significant difference (P = 0.065). TRM were 19.13% and 25.45%, respectively (P = 0.424), RR were 17.36% and 24.71%, respectively (P = 0.251). Multivariate analyses showed that the time to neutrophil engraftment was not a significant risk factor for prognosis, the time to platelet engraftment was an independent risk factor for OS and TRM, but not a significant risk factor for RR. Pre-transplantation disease status was the only independent prognostic factor for RR.

CONCLUSIONSThe time to platelet engraftment was a significant predictor after allo-HSCT. Early platelet engraftment increased OS, which this may be due to decreasing TRM.

Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Hematologic Neoplasms ; diagnosis ; therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Transplantation, Homologous ; Treatment Outcome ; Young Adult

OBJECTIVETo study the chronic health conditions (CHC) in long-term survival recipient after hematopoietic stem cell transplantation (HSCT).

METHODSThe CHC of 101 cases survived for more than 1 year after HSCT were collected according to Bone Marrow Transplant Survivor Study (MBMTSS) questionnaire. The differences of the incidence and severity of CHC between auto-HSCT and allo-HSCT, HLA-matched and HLA-mismatched family donors HSCT were compared, and risk factors related to chronic health conditions were analyzed retrospectively in family donor HSCT.

RESULTSOf the 101 HSCT survivors, 48.5% reported one or more chronic health conditions, and 83.7% of which were mild to moderate. The CHC in HLA-matched related donors HSCT were more serious than in HLA-mismatched related donors HSCT. The percentage of CHC total score above 3 in allo-HSCT recipients (32.1%) was higher than that in auto-HSCT ones (10.0%). The percentage of CHC total score 1-2, 3-4, and above 5 in HLA-matched family donors HSCT were 23.5%, 29.4%, and 14.7%, respectively, being significantly higher than those in HLA-mismatched ones (15.6%, 15.6%, and 6.2%, respectively). CHC was mainly related to chronic graft-versus-host disease (cGVHD). Single variable analysis showed that younger age at time of transplantation, HLA fully matched, the use of antithymocyte globulin (ATG) in the conditioning regimens were favorable for CHC. COX-regression Model showed that age was the only independent risk factor for predicting the CHC in family donor HSCT.

CONCLUSIONThe chronic health conditions after HSCT is mild to moderate, these complications in HLA-matched related donor HSCT are more serious than those in HLA-mismatched related donor HSCT. The age at transplantation is the only independent risk factor for chronic health conditions.

Adolescent ; Adult ; Child ; Child, Preschool ; Chronic Disease ; epidemiology ; Female ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Tissue Donors ; Transplantation Conditioning ; Young Adult

OBJECTIVETo investigate the treatment of primary amyloidosis with high-dose melphalan and autologous hematopoietic stem cell transplantation to further examine the survival, hematologic response, and improvement of amyloid-related organ dysfunction.

METHODSRetrospective analysis of 20 patients with primary amyloidosis treated with autologous hematopoietic stem cell transplantation. The status of major organ function before transplantation, mobilization programs and conditioning regimen as possible risk factors for survival were also investigated.

RESULTSOf 20 cases, 11 out of 15 evaluable cases achieved hematologic response, among them, 6 got complete remission (CR, 40%) and 5 partial remission (PR, 33%). The median onset time was 3.0 months (1.5 - 4.0 months) and 4 months (3 - 5 months), respectively after transplantation. The overall hematologic response was 73%. The 11 hematologic responders also had kidney responses. The median time to achieve kidney response was 3 months (2 - 6 months). The 3-year overall survival of the cohort of cases was 71.4%. The major causes of death were heart failure, renal dysfunction and gastrointestinal bleeding. G-CSF alone could obtain satisfactory mobilization results and most of patients well tolerated to the conditioning regimen of melphalan doses from 140 mg/m(2) to 200 mg/m(2).

CONCLUSIONTreatment of primary amyloidosis with high-dose melphalan followed by autologous peripheral blood stem cell transplantation produced high efficacy. The cardiovascular system involvement, renal dysfunction and the abnormality of coagulation function before transplantation may be the risk factors for survival.

Adult ; Aged ; Amyloidosis ; drug therapy ; mortality ; surgery ; Cardiovascular System ; physiopathology ; Female ; Gastrointestinal Hemorrhage ; physiopathology ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunoglobulin Light-chain Amyloidosis ; Kidney ; physiopathology ; Male ; Melphalan ; therapeutic use ; Middle Aged ; Retrospective Studies ; Risk Factors ; Survival Rate ; Transplantation, Autologous ; Treatment Outcome

This study was purposed to investigate the role of NK-alloreactivity and donor-inhibiting or activating KIR gene in predicting prognosis under unmanipulated allogeneic blood and marrow transplantation. A modified polymerase chain reaction sequence specific primers (PCR-SSP) method was used to typing KIR and HLA genotype of donors and recipients. The relationship between donor activating or inhibitory KIR and recipient HLA genotypes on event free survival (EFS), cumulative incidence of malignant relapse and transplant-related mortality (TRM) were investigated retrospectively in 67 patients undergoing hematopoietic stem cell transplantation. The results showed that no effect of 'KIR/HLA mismatched' was detected on acute graft-versus-host disease (aGVHD) and relapse. The EFS of KIR/HLA mismatched group was lower, especially KIR2DL1/HLA-C2 mismatched group (44.8% vs 69.2%, P = 0.043). However, EFS was better for the presence of donor-activating KIR2DS2 (81.3% vs 52.6%, P = 0.052), and the relapse rate was significantly lower for the presence of this genotype (7.7% vs 34.2%, P = 0.05). EFS was worse in patients homozygous for group 1 HLA-C (C1) when donor carries the activating KIR2DS1 (KIR2DS1 positive/HLA-C2-negative group, P = 0.028), and the incidence of aGVHD in this group was significantly higher than that in any other groups (P = 0.028). In multivariate analysis, advanced disease stage, more than two donor-activating KIR, donor KIR2DS2-negative genotype were associated with an reduced disease-free survival (HR = 3.34, 2.19, 3.18;and P = 0.005, 0.053, 0.066). Donor KIR2DS2-negative genotype were also associated with an increased risk of relapse (HR = 6.72, 9.43; and P = 0.019, 0.047). And donor KIR2DS1 positive/recipient HLA-C2 negative group was the only risk factor of TRM (HR = 3.27, 95% CI 1.78 - 9.06, P = 0.023). It is concluded that missing ligand for the donor inhibitory KIR has weak effect on the outcome of unmanipulated HSCT. The activating KIR play an important role in the EFS, relapse and TRM after HSCT. Donor KIR2DS1-positive/recipient HLA-C2-negative group and donor KIR2DS1 gene negative predict poor prognosis. Analysis of KIR genotype and its ligand is important for the selection of best donor and prognostic evaluation in unmanipulated allogeneic HSCT.
Adolescent ; Adult ; Child ; Child, Preschool ; DNA Fingerprinting ; Female ; Genotype ; HLA Antigens ; genetics ; Hematopoietic Stem Cell Transplantation ; methods ; mortality ; Humans ; Male ; Middle Aged ; Prognosis ; Receptors, KIR ; genetics ; metabolism ; Retrospective Studies ; Survival Rate ; Transplantation, Homologous ; Young Adult

This study was purposed to analyze the clinical characteristics and prognostic factors in patients with primary gastrointestinal non-Hodgkin's lymphoma (PGI-NHL). The pathological data of 101 PGI-NHL patients admitted in our hospital in the past 15 years were analyzed retrospectively. The results showed that 101 patients with PGI-NHL accounted for 14.49% of NHL in the same period, there were 64 males, 37 females, the range of ages was from 18 to 87 years old, median age was 61 years old; in disease distribution, the stomach PGI-NHL accounted for 58.42%, intestine PGI-NHL accounted for 39.60%, multiple GI involvements (MGI) accounted for 1.98%; in pathological type, diffuse large B cell lymphoma (DLBCL) accounted for 66.34%, mucosa-associated lymphoid tissue (MALT) lymphoma accounted for 17.82%, mantle cell lymphoma (MCL) accounted for 3.96%, enteropathy-associated T cell lymphoma (EATL) accounted for 7.92%, extra-nodal nasal type NK/T cell lymphoma accounted for 1.98%, follicular lymphoma (FL) accounted for 0.99%, small lymphocyte lymphoma (SLL) accounted for 0.99%. Eighty-nine out of 101 patients were followed up (49 cases live, 40 cases dead), data of the 12 patients were lost; the median survival time was 29 months (1 - 173). The three-year OS and five-year OS were 58.4% and 52.6% respectively. Univariate analysis revealed that the factors affecting OS included sex (P = 0.004), lesion site (P = 0.002), tumor size (P = 0.011), clinical Lugano staging for gastrointestinal non-Hodgkin's lymphoma (P = 0.003), IPI score (P = 0.000), pathological cell phenotype (P = 0.001), and pathological type (P = 0.006), their differences were statistically significant (P < 0.05). Multivariate Cox regression analysis indicated that clinical Lugano staging for gastrointestinal non-Hodgkin's lymphoma, IPI score, pathological type were independent prognostic risk factors affecting OS. It is concluded that clinical Lugano staging for gastrointestinal non-Hodgkin's lymphoma, IPI score and pathological type are independent risk factors affecting OS.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Gastrointestinal Neoplasms ; diagnosis ; mortality ; pathology ; Humans ; Lymphoma, Non-Hodgkin ; diagnosis ; mortality ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Survival Rate ; Young Adult