OBJECTIVETo determine the effect of butylphthalide on the expressions of protein disulfide isomerase (PDI) and P53 in the brain tissue of rats with Alzheimer's disease (AD).

METHODSSixty male adult rats were randomly divided into AD model group, butylphthalide group and control group (n = 20). AD models were established by injecting beta-amyloid protein 1-42 into the hippocampus of rats. Sixty days later, the learning and memory abilities of the rats were evaluated using Y-maze test, and the expressions of PDI and P53 in the brain tissue of the rats were measured by immunohistochemistry.

RESULTSCompared with the control group, the rats in AD model group exhibited significantly reduced learning and memory abilities, lowered expressions of PDI in the hippocampus and increased expression of P53 in the cortex (P > 0.01). In comparison with the model group, the rats in the butylphthalide group showed significantly increased PDI-positive cells in the hippocampus and decreased expression of P53 in the cortex (P < 0.01).

CONCLUSIONButylphthalide improves the learning and memory abilities of rats with experimental AD, the mechanism of which may involve inhibition of P53 expression and enhancement of PDI expression in the brain tissues.

Alzheimer Disease ; physiopathology ; Animals ; Apoptosis ; drug effects ; Benzofurans ; pharmacology ; Brain ; enzymology ; metabolism ; Disease Models, Animal ; Learning ; drug effects ; Male ; Memory ; drug effects ; Protein Disulfide-Isomerases ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tumor Suppressor Protein p53 ; metabolism

To investigate the influence of the thalidomide on the growth of multiple myeloma cells from untreated, relapsed or refractory patients and summarize its mechanisms, thalidomide influence on colony growth of untreated, relapsed or refractory multiple myeloma cells cultured by semisolid methylcellulose was observed. The level of interleukin-6 (IL-6) autosecreted by myeloma cells was tested by IL-6-dependent cell line when myeloma cells were treated with thalidomide at 200 microgram/ml, and in the same concentration of thalidomide the expression of IL-6 receptor were tested by flow cytometry. Results showed that colony growths of myeloma cell from untreated and relapsed or refractory patients were all colonies were inhibited when treated by thalidomide up to 75 microgram/ml or 100 microgram/ml concentration. The inhibition was concentration-dependent, higher concentration cause more inhibition. After treatment with thalidomide at 200 microgram/ml, the concentrations of IL-6 secreted by myeloma cells were (148.5 +/- 96.7) microgram/ml, and the levels of IL-6 receptor expressed on the cell surface were 16.7% and 20.2% in untreated and relapsed or refractory patients, respectively, and those were significantly lower than those levels in the cells before exposure to thalidomide. It was concluded that thalidomide can inhibit growth of both relapsed or refractory cells and untreated myeloma cells in vitro. Therefore, it can be used to treat untreated multiple myeloma patients. Inhibiting tumor cells secreting level of IL-6 and reducing the expression of IL-6 receptor on myeloma cell surface is one of the mechanisms for thalidomide to remedy multiple myeloma patients
Angiogenesis Inhibitors ; pharmacology ; Cell Division ; drug effects ; Dose-Response Relationship, Drug ; Humans ; Interleukin-6 ; metabolism ; Multiple Myeloma ; metabolism ; pathology ; Receptors, Interleukin-6 ; biosynthesis ; Thalidomide ; pharmacology ; Tumor Cells, Cultured

BACKGROUND: The application of coronary stents, especially drug-eluting stents (DESs), has made percutaneous coronary intervention (PCI) one of important therapeutic methods for CHD. DES has reduced the in-stent restenosis to 5％–9％ and signifi cantly improved the long-term prognosis of patients with CHD. The study aimed to investigate the long-term efficacy and safety of domestic drug-eluting stents (DESs) in patients with acute coronary syndrome (ACS). METHODS: All patients with ACS who had undergone successful percutaneous coronary intervention (PCI) in the First Affiliated Hospital of Zhengzhou University from July 2009 to December 2010 were included in this study. Patients were excluded from the study if they were implanted with bare metal stents or different stents (domestic and imported DESs) simultaneously. The included patients were divided into two groups according to different stents implanted: domestic DESs and imported DESs. RESULTS: In the 1683 patients of this study, 1558 (92.6％) patients were folowed up successfuly for an average of (29.1±5.9) months. 130 (8.3％) patients had major adverse cardiovascular events (MACEs), including cardiac death in 32 (2.1％) patients, recurrent myocardial infarction in 16 (1％), and revascularization in 94 (6％). The rates of cardiac death, recurrent myocardial infarction, revascularization, in-stent restenosis, stent thrombosis and other MACEs were not significantly different between the two groups (allP>0.05). Multivarite logistic regression revealed that diabetes mellitus (OR=1.75, 95％CI: 1.09–2.82,P=0.021), vascular numbers of PCI (OR=2.16, 95％CI: 1.22–3.83, P=0.09) and PCI with left main lesion (OR=9.47, 95％CI: 2.96–30.26,P=0.01) were independent prognostic factors of MACEs. The Kaplan-Meier method revealed that there was no significant difference in cumulative survival rates and survival rates free from clinical events between the two groups (allP>0.05). CONCLUSIONS: The incidences of clinical events and cumulative survival rates are not statistically different between domestic DESs and imported DESs. Domestic DES is effective and safe in the treatment of patients with ACS.

Glucose Transport Proteins, Facilitative ; deficiency ; Humans ; Syndrome

OBJECTIVETo investigate the quantitative and qualitative changes of TCRVα24(+)Vβ11(+) natural killer T (NKT) cells from bone marrow (BM) of aplastic anemia (AA) after in vitro stimulation of α-galactosylceramide (α-Galcer).

METHODSNKT cells in the bone marrow mononuclear cells (BMMNCs) from either AA patients or healthy controls were enumerated with flow cytometry. BMMNCs were cultured in RPMI1640 medium supplemented with either α-Galcer and rhIL-2 or α-Galcer, rhIL-2 and rhG-CSF. The proliferative capacity of NKT cells was determined by NKT cell numbers before and after in vitro culture. Expression of intracellular IFNγ and IL-4 in activated NKT cells was analyzed with flow cytometry.

RESULTSIn AA group, the percentage of NKT cells in BMMNCs was (0.19 ± 0.09)%. Addition of rhG-CSF into the α-Galcer/rhIL-2 culture medium resulted in significantly reduced expansion of NKT cells (67.45 ± 29.42-fold vs 79.91 ± 40.56 fold, P < 0.05). Meanwhile, addition of rhG-CSF reduced IFNγ positive NKT cells \[(37.45 ± 7.89)% vs (62.31 ± 14.67)%, P < 0.01\] and increased IL-4 positive NKT cells \[(55.11 ± 12.13)% vs (27.03 ± 9.88)%, P < 0.01\]. In healthy control group, the percentage of NKT cells in BMMNCs was (0.25 ± 0.12)%. Addition of rhG-CSF into the α-Galcer/rhIL-2 culture medium also significantly reduced expansion of NKT cells (97.91 ± 53.22-fold vs 119.58 ± 60.49-fold, P < 0.05), reduced IFNγ positive NKT cells \[(28.65 ± 10.63)% vs (50.87 ± 12.66)%, P < 0.01\], and increased IL-4 positive NKT cells \[(66.53 ± 14.96)% vs (31.11 ± 10.07)%, P < 0.01\].

CONCLUSIONCompared to those from healthy controls, BMMNCs from AA patiants have a reduced fraction of NKT cells, which possesses a decreased potential to expand in vitro in response to α-Galcer stimulation, and produce more IFNγ(+) NKT1 cells. rhG-CSF, in combination with α-Galcer, confers polarization of NKT cells towards IL-4(+) NKT2 subpopulation.

Anemia, Aplastic ; metabolism ; Bone Marrow ; metabolism ; Humans ; Interleukin-4 ; metabolism ; Killer Cells, Natural ; cytology ; Natural Killer T-Cells

Objective：This study was designed to investigate the outcome of double autologous hematopoietic stem cell transplantation(Double AHSCT) in hematological malignancies. Methods: The clinical data of 12 patients who underwent Double AHSCT between January 1995 and January 1999 were analyzed retrospectively and the outcome were compared with that of 17 patients who received single autologous hematopoietic stem cell transplantation (Single AHSCT) in the same period. Results: The duration of continuous remission in 12 patients undergoing Double AHSCT ranged from 6 to 68 months(mean 27 months). Among them, eight patients (66.7％ ) were still alive without relapse up to now. While one patient had relapsed 6 months after second grafting. Three patients died from diseases related to graft. The patients who received Single AHSCT had a continuous remission of 1－ 36 months after graft (mean 12 months). Six of the 17 patients were still alive in good condition. Eight patients relapsed and 3 patients died from diseases related to graft. Conclusion: Good outcome were showed in Double AHSCT for the treatment of hematological malignancies. The 18 month survival rate in Double AHSCT tended to be better than that in Single AHSCT.

Objective To establish a HPLC-MS/MS method for simultaneous determination of the concentration of simvastatin, simvastatin acid and rivaroxaban in rats plasma. Methods The plasma samples were determined after secondary extraction with ethyl acetate. Ticagrelor and lovastatin were used as internal standards. Simvastatin, simvastatin acid and rivaroxaban in rats plasma were separated by Waters C18 (150. 0 mm × 4. 6 mm, 3. 5 μm) with mobile phase consisting of acetonitrile?ammonium (75: 25, pH = 4. 5) . Electrospray ionization source was applied and operated in positive multiple reaction monitoring mode. Polarlity switch (negative-positive mode) was performed. The detector was operated in multiple reaction-monitoring mode at m/z 436. 0→144. 9 for simvastatin, m/z 452. 9 → 162. 3 for simvastatin acid, m/z 324. 1 →127. 2 for rivaroxaban, m/z 521. 1→361. 2 for Ticagrelor and m/z 405. 3→199. 0 for lovastatin. The specificity, standard curve and lower limit ofquantification, precision and recovery, stability and matrix effect of the method were investigated. Results The linear ranges of simvastatin, simvastatin acid and rivastatin in plasma were 1-100, 5-400 and 1-100 ng·m L-1, standard curve were y = 0. 78 x + 7. 00 × 10-4 (r = 0. 992 8) , y = 0. 59 x + 2. 57 × 10-2 (r = 0. 997 2) and y = 1. 09 x + 1. 79 ×10-2 (r = 0. 996 4) , and the lower limit of quantitation were 1, 5 and 1 ng·m L-1, respectively. The intra-day and inter-day standard deviation were less than 15％, and the recovery rate reached more than 70％. The plasma samples had a good stability with freezing-thawing for three times, -80 ℃ for 5 days and 4 ℃ for 24 h. And there was no obvious matrix effect. Conclusion The method was simple, specific and sensitive, suitable to detect a number of samples for pharmacokinetic study.

OBJECTIVETo analyze the measles immunity level of persistent population in Beijing.

METHODSA total of 2125 objects from 10 age groups, who had been living in Beijing for over 6 months, were selected from urban and rural areas in Beijing in 2012. Demographic characteristics, history of measles and vaccine immunization were investigated by questionnaire. 5 ml blood sample of each subject was collected, and the Measles IgG antibody was measured by ELISA assay.

RESULTSPositive rate of measles antibody was 84.71% (1800/2125) and standardized positive rate was 88.07% . Median of antibody was 960.46 IU/L. Positive rate and median of measles antibody were significantly different between population from different age groups (χ(2) = 341.60, P < 0.01; H = 216.27, P < 0.01). Antibody positive rate and median were lowest in the <1 year age group, which were separately 43.06% (90/209) and 185.80 IU/L; and highest in the 1-4 (97.31% (181/186) and 2448.81 IU/L) and 5-9 years age group (96.46% (218/226) and 1910.72 IU/L). The range of antibody positive rate and median in adults of ≥ 15 years were 81.98%-90.14% and 744.38-1474.84 IU/L. Antibody positive rate and median in persistent population, which were separately 82.45% (883/1071) and 899.82 IU/L, were lower than those in migrant population, which were 87.00% (917/1054) and 166.19 IU/L, respectively (χ(2) = 8.51, P < 0.01;U = 538 704.00, P < 0.01). Antibody positive rate and median in population with vaccination history, which were separately 91.95% (891/969) and 1443.11 IU/L, were higher than those population without vaccination history and people whose history unknown (32.95% (57/173) , 127.33 IU/L; 86.67% (852/983) , 923.73 IU/L). The difference showed statistical significance (χ(2) = 399.92, P < 0.01; H = 202.11, P < 0.01).

CONCLUSIONAmong the persistent population in China, measles antibody level among the children aging 1-9 years old was high enough to prevent outbreak and epidemic of measles. However, we should try our best to strengthen the measles antibody level among the babies younger than 1 year old and the migrant population aging between 15 and 40 years old.

Adolescent ; Adult ; Antibodies, Viral ; blood ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Infant ; Male ; Measles ; epidemiology ; immunology ; prevention & control ; Measles virus ; Young Adult

OBJECTIVETo retrospectively analyze the curative effects and prognostic factors of HLA-matched sibling donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) for chronic myelogenous leukemia patients (CML).

METHODSOf the 35 CML patients, 26 were males and 9 were females, with a median age of 32 (12 - 50) years. 30 patients were in chronic phase of CML, 5 patients were in accelerated phase. Allo-HSCT from HLA identical siblings was performed for 35 patients, of whom 11 received bone marrow transplantation (BMT) and 24 peripheral blood stem cell transplantation (PBSCT). Conditioning regimens was TBI (total-body irradiation) + CY (CTX) protocol in 8 patients and BU/CY protocol in 27 patients. The average follow-up was 48 months (range 7 - 108 months).

RESULTS34 (97.1%) patients were successfully engrafted. Among them, 21 patients (60.0%) had three years disease-free (DFS) survival. The overall 5-year survival (OS) was 57.1%. Two patients (5.7%) relapsed. Transplant-related mortality occurred in 12 patients. Hemorrhagic cystitis (HC) occurred in 5 patients and HVOD was observed in 1 patient. Acute graft-versus-host disease (aGVHD) occurred in 18 patients (51.4%), among them 7 patients (20.0%) were of grade III-IV. Chronic GVHD was in 17 patients (48.5%). There was no significant difference in 3-years DFS between BMT group and PBSCT group (54.5% vs. 62.5%, P > 0.05). The 3-year disease-free survival (DFS) was 42.9% in TBI/CY group and 55.6% in BU/CY group (P > 0.05). In univariate prognostic analysis model, the DFS at 3 years is 75% and 47.4% for < or =30 years patients and >30 years patients, respectively, P < 0.05. The 3-year DFS of patients with first chronic phase is higher than patients with advanced diseases (61.3% vs. 40%, P < 0. 05). The 3-year DFS in patients of grade I - II GVHD was higher than that in patients of grade III-IV GVHD (81.8% vs. 14.3%, P < 0.05).

CONCLUSIONThe patients who had transplantation done within 1 year after diagnosis during their first chronic phase of disease and who had low-grade GVHD have better prognosis. Those patients who had III-IV acute GVHD are prone to incorporate severe infection, which was a worse prognostic factor of allo-HSCT for chronic myelogenous leukemia.

Adolescent ; Adult ; Age Factors ; Child ; Cystitis ; etiology ; Disease-Free Survival ; Female ; Follow-Up Studies ; Graft vs Host Disease ; etiology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; methods ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; mortality ; therapy ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Siblings ; Survival Rate ; Transplantation Conditioning ; Transplantation, Homologous

This study was aimed to explore changes of platelet function in vitro during storage by thrombelastography (TEG). 12 units plateletpheresis were randomly selected and stored at 20 to 24 degrees C with agitation. Thrombelastography variable parameters R, K values and maximal amplitude (MA) were measured on 1, 2, 3, 4, 5 days of platelet storage. Platelet concentration, mean platelet volume (MPV), hypotonic shock response (HSR), CD62p expression and CD62p reexpression on platelet surface were detected at the same time. Changes of platelet function in virto were systematically evaluated by above-mentioned indexes. The results showed that MPV augmented slightly with prolongation of preserved time (p > 0.05), and CD62p expression on platelet surface increased remarkably (p < 0.01), while CD62p reexpression decreased gradually (p < 0.01). There were no significant differences in HSR level of platelets during storage (p > 0.05). R value increased with prolongation of preserved time (p < 0.01). There were no obvious changes on K value and alpha Angle during storage (p > 0.05). There were no obvious changes in MA from 1 to 4 days, and MA decreased slightly on day 5 (p < 0.05). It is concluded that there was no significant change in MA and HSR which reflects comprehensive coagulation of platelets during storage. Platelets on the end of storage have excellent function of hemostasis; Thrombelastography parameter MA value can be used as a valuable indicator for evaluation of platelet function in vitro during storage.
Blood Platelets ; physiology ; Blood Preservation ; Humans ; Platelet Function Tests ; methods ; Thrombelastography