ER, and least marked when IR

Objective To evaluate the efficacy and safety of dipeptidyl peptidase-4 inhibitor,linagliptin,in subjects aged 60 years or older with type 2 diabetes mellitus (T2DM).Methods Data from eight 24-week,multinational,multicenter,randomized,double-blind,placebo-controlled,parallel-group studies were analyzed.Patients aged 60 years or older with T2DM were received oral linagliptin (5 mg/d) or placebo in combination with mefformin,or metformin plus sulfonylurea.Efficacy was assessed by the changes in glycosylated hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) from baseline to 24 weeks of treatment.Safety endpoint included the frequency and intensity of adverse events.Results A total of 1 421 patients (placebo 429,linagliptin 992) were included in the full analysis set (FAS).Mean ages of the subjects were (67.4 ± 5.6) years in the linagliptin group and (66.7-± 5.6) years in the placebo group.Baseline HbA1c was (8.0 ±0.8) ％ in the linagliptin group and (8.1 ±0.9) ％ in the placebo group.At the end of 24-week,placebo-adjusted reduction in HbAlc in subjects with linagliptin was (0.7 ±0.1)％ (95％ CI 0.6-0.8,P ＜0.000 1),and placebo-adjusted reduction in FPG in subjects with linagliptin was (0.88 ±0.12) mmol/L(95％ CI 0.65-1.11,P ＜0.000 1).Overall safety and tolerability in the two groups were similar.Adverse events occurred in 57.1％ of patients in the placebo group and 61.1％ of patients in the linagliptin group,and the incidence of adverse events leading to discontinuation was 3.2％ in the placebo group and 3.8％ in the linagliptin group.Serious adverse events occurred in 1.6％ of patients in the placebo group and 2.8％ of patients in the linagliptin group.Investigator-defined hypoglycaemia occurred in 7.3％ of patients in the placebo group and 11.9％ of patients in the linagliptin group.Among them,most were mild or moderate hypoglycaemia,and severe hypoglycaemia only occurred in 0.2％ of patients in the placebo and 0.5％ in the linagliptin groups.Overall incidence of hypoglycaemia in linagliptin group was slightly higher than that in placebo group,which might be due to the fact that more patients were taking sulfonylureas in linagliptin group than in placebo group (26.8％ linagliptin;18.4％ placebo).No difference could be viewed in hypoglycaemia between the two groups in patients without sulfonylureas (1.2％ linagliptin,1.1％ placebo)Moreover,no severe hypoglycaemia was reported in subjects without sulfonylureas.The incidences of other adverse events were similar in both groups.Conclusion Linagliptin was efficacious in lowering glucose with a safety profile similar to placebo in type 2 diabetic patients aged 60 years or older.

Objective To evaluate the effect of tissue factor (TF), tissue factor pathway inhibitor-1,2 (TFPI-1,2) on cancer metastases and thrombosis complicated with cancer. Methods Blood samples from 292 cancer patients were collected and were divided into different teams according to cancer types,complicated with or without thrombosis; TF, TFPI-1, TFPI-2, plasma concentrations were measured by ELISA;Tissue expression of TF, TFPI-1, TFPI-2 were observed by immunohistochemical method. Results Plasma concentrations of TF and TFPI-1 in all kinds of cancers were higher than the control and lung cancer was the highest; TFPI-2 plasma concentrations had no statistics differences among all these teams. Tissue expression of TF of all kinds of cancer were higher than the adjacent tissues, lung cancer was higher than the other types of cancer. There were no statistics differences for TFPI-1 and TFPI-2. Both TF and TFPI-1 plasma concentrations of cancer with-or without-thrombosis were higher than control. TF was even higher in cancer with thrombosis team, TFPI-1 had no statistic difference between these two teams. TFPI-2 concentrations had no differences among all these teams. Conclusion Many kinds of tumor have higher expression of TF, it is expressed with different intensity according to different types of cancer. TFPI-1 has no clear effect in cancer growing and metastases. Unbalance of TF and TFPI-1 in plasma may relate to high coagulation state of cancer and may accelerate the thrombosis formation in cancer.

Objective To investigate the correlation between exhaled nitric oxide and lung function (FEV1)in asthmatic children.Methods Fifty three stable asthmatic children aged 5 to 14 years old were recruited from ShengJing Hospital of China Medical University.According to whether the patients were treated with inhaled corticosteroid(ICS)therapy regularly,they were divided into two groups:steroid group and non-steroid group,then fraction of exhaled nitric oxide(FeNO)and lung function were measured.Results In non-steroid group,the levels of FeNO(mean 40.450±25.428 part by billion)were significantly higher than those in the steroid group(mean 19.879±13.845 part by billion),and they were statistically significant.(P = 0.003).The mean FEVI in non-steroid group was(95.152±8.993)%,and the mean FEVI in non-steroid group was(91.350±11.690)%,and there were no significant differences between two groups (P =0.189).Significantly negative correlation was found between FeNO and FEV1 in steroid group(r =-0.465,P = 0.039),but there was no significant correlation between them in steroid group(r = 0.058,P =0.747).Conclusion The levels of FeNO were higher in non-steroid group than those of the steroid group in the stable asthmatic children.FeNO is a good biomarker to evaluate the airway inflammation of asthmatic children.

Objective:To investigate the effect of miRNA-618 (miR-618) on the cell proliferation and apoptosis of acute monocyte leukemia THP-1 cells.Methods:Real-time polymerase chain reaction (PCR) was used to detect the relative expression level of miR-618 in THP-1 cells and monocytes isolated from peripheral blood of the healthy people. Overexpression of miR-618 plasimid vector was constructed and empty vector was treated as the negative control; and then the two vectors were transfected with THP-1 cells; finally, miR-618 overexpression group and negative control group were set. THP-1 cell proliferation and apoptosis of both groups were detected by using CCK-8 method and flow cytometry, respectively. TargetScan was used to predict the target gene of miR-618 and it was verified by using luciferase reporter assay.Western blot was used to detect the protein levels of THP-1 cells in miR-618 overexpression group and negative control group, and predicted miR-618 target gene in peripheral blood monocytes of the healthy people.Results:PCR showed that the expression level of miR-618 was lower in THP-1 cells compared with that in monocytes isolated from peripheral blood of the healthy people ( P < 0.05). CCK-8 assay showed that compared with the negative control group, the proliferation ability of THP-1 cells in miR-618 overexpression group was decreased (the absorbance values at 0, 24, 48 and 72 h after transfection: 0.20±0.03 vs. 0.20±0.03, 0.28±0.02 vs. 0.35±0.03, 0.34±0.03 vs. 0.43±0.04, 0.39±0.02 vs. 0.53±0.05, all P < 0.05), and the late apoptosis rate was increased [(27.1±0.1)% vs. (14.9±0.1)%, t=2.13, P=0.03]. The target gene of miR-618 was ARPP19 predicted by using TargetScan software. Luciferase reporter assay showed that the relative luciferase activity of THP-1 cells in group transfected with wild-type ARPP19 gene plasmid+miR-618 gene plasmid was higher than that in the blank control group and group transfected with wild-type ARPP19 gene plasmid+miR-618 empty vector (0.170±0.003 vs. 0.100±0.004, 0.100±0.001, all P < 0.05). Western blot indicated the expression level of ARPP19 protein in THP-1 cells of miR-618 overexpression group was lower than that of the negative control group, while the expression levels of ARPP19 protein of peripheral blood monocytes of the healthy people in both groups were similar. Conclusion:miR-618 can inhibit the cell proliferation and promote apoptosis of THP-1 cells by inhibiting the expression of of THP-1 cells ARPP19 in acute monocyte leukemia.

0 (P<0.01).Conclusions HERG1 was over expressed in PANC1 cells and tissues of human pancreatic cancer.The HERG1 K+ channel was related to the proliferation,migration and invasion of PANC1.

Objective To explore the activity of thioredoxin reductase (TrxR) in chronic myeloid leukemia cell line K562 and the anti-leukemia effect of BBSKE (a novel inhibitor of TrxR) in vitro. Methods The activity of TrxR on K562 cell lineage and fresh bone marrow cell from healthy adult was analyzed by insulin reduction assay. The inhibition of proliferation was measured by CCK-8 assay. The anti-leukemia effect of BBSKE was detected by laser scanning confocal microscope,agarose gel electrophoresis and flow cytometry with Annexin V -FITC/PI staining. Results TrxR activity of K562 cell lineage was significantly higher than that of normal bone marrow mononuclear cells. The apoptosis of K562 cells could be induced at concentrations of 10 μmol/L BBSKE after treated for 24 hours. The typical DNA ladder bans were observed by agarose gel electrophoresis. The apoptotic rates of K562 cells were (10.28±2.74) %. Application of 10 μmol/L BBSKE for 48 hours could also induce apoptosis of fresh bone marrow cell from chronic myeloid leukemia patients, and the apoptotic rates were (5.70±0.48) %. Conclusion TrxR activity in chronic myeloid leukemia cells was significantly higher than that of normal cells. BBSKE inhibits the TrxR activity and the proliferation of K562 by inducing apoptosis.It might be a potential medication for chronic myeloid leukemia.

Objective To assess the clinical significance of detecting the immune markers in idiopathic thrombocytopenic purpura (ITP). Methods The frequencies of circulating B cells secreting platelet-specific antibody, platelet-specific antibody, the percentage of T lymphocyte subsets, the percentage of reticulated platelet and the level of thrombopoietin in 64 ITP patients and 31 healthy controls were measured with enzyme-linked immunospot assay (ELISPOT),modified monoclonal antibody immunobilization of platelet antigens assay (MAIPA), flow cytometry and sandwich enzyme-linked innnunosorbent assay respectively. Results Compared with the controls[1.3 ± 0. 5/105 peripheral blood mononuclear cell (PBMC), (0.33±0.06,0.41±0.03), (22.08±4.54)% and (8.19±2.46)%], the frequencies of circulating B cells secreting platelet-specific antibody (7.6±4.6/105 PBMC in acute ITP group, 5.3±3.0/105 PBMC in chronic ITP group), platelet-specific antibody (including the anti-GP Ⅱ b/Ⅲa antibody, anti-GP Ⅰ b/X antibody) (0.51 ±0.11, 0.48±0.06 in acute ITP group; 0.49±0.10,0.46±0.09 in chronic ITP group), the percentage of CD8+ T Lymphocyte (27.09±9.86 ) %, the percentage of reticulated platelet in ITP patients[the megakaryocyte cytosis group (24. 85 ± 19. 18)%, the normal megakaryocyte group (23.89±18.90)%]were significantly increased ( all P＜0.05).The frequencies of circulating B cells secreting platelet-specific antibody in acute ITP patients were notably increased (P＜0.05) compared to the chronic ITP patients. In T lymphocyte subsets, the percentage of CD3+T lymphocyte and CD4+ T lymphocyte and the ratio of CD4+/CD8+ in the patients with ITP[(60.88±14.59)%, (28.41±10.55)%, 1.18±0.59]were notably decreased than those in the healthy controls [(69.89±6.43)%, (35.38±5.05) %, 1.64±0.29, P＜0.05]. There was no apparent difference of the level of thrombopoietin between ITP patients with megakaryocyte cytosis (72. 09 ± 41.64 ) and health controls (75.37± 26. 32, P ＞ 0. 05 ), however, the level of thrombopoietin of ITP patients with normal megakaryocyte apparently increased (118.60±70.72, P＜0.05). Conclusion Detecting the frequencies of circulating B cells secreting platelet-specific antibody, platelet-specific antibody, the percentage of T lymphocyte subsets, the percentage of reticulated platelet and the level of thrombepoietin in the patients with ITP may improve the diagnosis and guide clinical therapy.

[ ABSTRACT] AIM:To investigate the expression relevance of transcription factors GATA-1 and GATA-2 in the bone marrow CD71 +cells of a high-altitude polycythemia (HAPC) rat model.METHODS:Male SD rats (n=48) were randomly divided into normal control group and HAPC model group .HAPC model was established at an altitude of 4 300 m in the natural environment and verified by the morphology and quantity of the bone marrow cells and hematologic parameters detection .A relative change in the trend of bone marrow CD 71 +cell numbers was detected by flow cytometry analysis .The expression of GATA-1 and GATA-2 at mRNA and protein levels in the CD 71 +cells was examined by RT-qPCR and West-ern blot .CD71 +cells were cultured under hypoxic condition and transfected with the optimal interference sequence of GA -TA-1shRNA1 for 96 h.The expression of GATA-1 and GATA-2 at mRNA and protein levels was detected by RT-qPCR and Western blot .RESULTS:The establishment of the animal model with HAPC was successful as the bone marrow smears and the hematologic parameters showed compared with the control .The quantity of the bone marrow CD 71 +cells of HAPC rats were significantly increased and the expression of GATA-1 at mRNA and protein levels in the CD 71 +cells were higher than those of the control .The expression of GATA-2 at mRNA and protein levels was similar to that of the control .The correla-tion analysis showed that the expression of GATA-1 was negatively correlated with that of GATA-2 in the control, while no obvious correlation between them was observed in the HAPC rats .The expression of GATA-1 at mRNA and protein levels in HAPC group was lower than that in control group after interfered by GATA-1 shRNA1 for 96 h, but no obvious diversity of GATA-2 expression between the 2 groups was observed .CONCLUSION:GATA-1 and GATA-2 are abnormally expressed and their negative correlation is destroyed in HAPC , which may be one of the pathogenesis of HAPC .

Objective To comprehensively evaluate the curative effect and adverse effects of rituximab plus cyclophosphamide, vincristine, doxoruhicin and prednisone(R-CHOP) chemotherapy and CHOP chemotherapy alone on the treatment for low and moderate malignant B cell non-Hodgkin lymphoma (NHL). Methods By the application of the systematic review method of Cochrance International Collaboration, the world-wide randomized controlled trials (RCT) on the comparison between different curative effects of R-CHOP and CHOP chemotherapy alone on the treatment low and moderate malignant B cell NHL was collected and the study results was evaluated systematically. Results Seven RCT studies involving 1569 patients and had no heterogeneity between themselves (χ=5.31,P=0.50). The baseline of patients characteristics was comparable in all the studies. By comparing complete response (CR) rate and adverse effects through fixed effect analysis model, the results showed that R-CHOP was better than CHOP chemotherapy on the treatment for low and moderate malignant B cell NHL(OR =2.22, 95 %CI 1.72-2.85, P ＜0.000 01), and adverse events of R-CHOP had no significant difference compared with CHOP chemotherapy alone (P＞0.05). Conclusion With good curative effect on the treatment low and moderate malignant B cell NHL and without obvious differences from the CHOP chemotherapy alone in adverse effects, R-CHOP chemotherapy should be recommended as the best treatment method for low and moderate malignant B cell NHL And much more well-designed clinical RCT should be made to further prove its clinical effect.