Aim To investigate apoptosis induced by 3,3'-diethyl-9-methylthia-carbocyanine iodide(DMTCCI) , an inhibitor of DNA primase found in our previous study, and the mechanism of DMTCCI in human myelogenous leukemia HL-60 cells. Methods HL-60 cells were cultured in RPMI-1640 medium and treated with different concentrations of DMTCCI. MTT assay was used to detect growth inhibition.Flow cytometry and DNA ladders were used to detect apoptosis. Western blotting was used to observe the expression of survivin, Bcl-xL, Bad, Bax, Bcl-2, caspase-9, caspase-3, caspase-6, PARP, DFF45 and lamin B protein. Caspase-3 activity was measured by ApoAlert Caspase-3 Assay Kit. Results DMTCCI inhibited proliferation of human leukemia HL-60 cells with IC50 value of 0. 24 μmol · L-1. The results of flow cytometry and DNA ladders showed that DMTCCI could induce apoptosis of HL-60 cells. The expression levels of protein survivin and Bcl-xL were down-regulated, Bad and Bax were up-regulated,while Bcl-2 protein had no change in response to DMTCCI treatment in HL-60 cells. Treatment of HL-60cells with DMTCCI induced the proteolytic cleavage of caspase-9, caspase-3, caspase-6, PARP, DFF45and lamin B protein. Caspase-3 activity apparently increased at 3 h and reached a peak at 12 h after exposure to 1 μmol · L-1 of DMTCCI in HL-60 cells. Conclusion DMTCCI inhibited proliferation and induced apoptosis of human leukemia HL-60 cells. Bcl-2 family proteins, survivin and caspases family proteins might playa role in the apoptosis process induced by DMTCCI.

OBJECTIVETo make a comparative study on wild and cultivated Astragali Radix in Wuchuan, Neimenggu where is one of the geo-authentic producing areas of Astragalus membranaceus var. mongholicus.

METHODThis comparative study focus on shapes and properties, microscopic features of transverse section and powder of roots, qualitative evaluation of wild and cultivated Astragali Radix.

RESULTWild Astragali Radix had a cylindrical main root, 2 or 3 root branches, dark brown color and many lenticels on the root bark. Cultivated Astragali Radix had a long cylindrical root, few root branches, yellowish white or light brown and fewer lenticels on the root bark. The differences of microscopic features were that the number of cork cells layers in wild Astragali Radix was bigger than that in cultivated Astragali Radix; stone cells were only observed in wild Astragali Radix; distinct annual rings in the xylem were only existed in cultivated Astragali Radix. The results of qualitative evaluation reveal that the contents of major active isoflavonoids and saponins in wild Astragali Radix are higher than those in cultivated Astragali Radix.

CONCLUSIONThere are some diagnostic differences in the main microscopic features of transverse section and powder between wild and cultivated Astragali Radix. The contents of major active isoflavonoids and saponins in wild Astragali Radix are higher than those in cultivated Astragali Radix. Our study provides important scientific evidence for reasonable and effective uses of wild and cultivated Astragali Radix in Wuchuan, and also provides a reliable basis for the quality control of Astragali Radix.

Astragalus Plant ; chemistry ; growth & development ; Plant Roots ; chemistry ; growth & development

Objective To analyse the relationships between islet β-cell function and infection,inflammation and major organ function in multiple organ dysfunction syndrome (MODS) patients with severe traumatic hemorrhage.Methods A total of 187 cases of MODS patients hospitalized in the 94th Hospital of PLA from January 2013 to January 2016 were selected,and were divided into the MODS survival group (MODS-S group,104 cases) and MODS dead group (MODS-D group).Other 100 healthy subjects were selected as the control group.The fasting blood glucose (GLU0) and insulin (INS0) levels,blood glucose (GLU30) and insulin (INS30) levels after 30 min of glucose loading,and levels of soluble triggering receptor expressedon myeloid cells-1 (sTREM-1),tumor necrosis factor-α (TNF-a),interleukin-6 (IL-6),alanine aminotransferase (ALT),creatinine (Cre) and creatine kinase isoenzyme (CK-MB) in different groups were determined.The insulin-β-cell function was evaluated by homeostasis model assessment of β-cell function (HOMA-β) index and ratio of insulin increment and blood glucose increment after 30 min of glucose loading (ΔINS30/ΔGLU30),and their relationships to other indexes,including sTREM-1,TNF-α,IL-6,GLU0,ALT,Cre and CK-MB,in MODS patients with severe traumatic hemorrhage were analysed.Results The HOMA-β and AINS30/AGLU30 ratio in the MODS-D group were lower than those in the MODS-S group,and levels of sTREM-1,TNF-α,IL-6,ALT,Cre and CK-MB in the MODS-D group were higher than those in the MODS-S group,there were statistically significant differences (P＜0.01).In MODS patients with severe traumatic hemorrhage,HOMA-β and ΔINS30/AGLU30 was both negatively correlated with sTREM-1,TNF-α,IL-6,GLU0,ALT,CreandCK-MB (r=-0.356 4,-0.532 1,-0.345 8,-0.772 1,-0.762 5,-0.684 8,-0.606 4;r=-0.428 5,-0.567 8,-0.487 0,-0.743 6,-0.781 7,-0.717 6,-0.640 1,P＜0.01).Conclusion MODS patients with severe traumatic hemorrhage have islet β-cell dysfunction which may be used as a prognostic and diagnostic indicator.

Objective To observe the influence of IL-12,IL-15 on CIK cell in the normal culture;to observe the anti-tumor effect in the circumstance of different combination of cytokines,and to provide a new insight for preparing high effective and qualified CIK cell in vitro.Methods The optimal concentrations of IL-2,IL-12 and IL-15 were determined,respectively.After the peripheral blood from healthy blood donors was collected,monocytes were selected and co-cultured with different cytokines into different groups,as group A(IL-2 normal culture group),group B(IL-2 and IL-12 group),group C(IL-2 and IL-15 group),group D(IL-2,IL-12 and IL-15 group),and group E(cytokine control group).The monocytes in different groups were calculated by globulimeter,the activity of cells was detected by Trypan blue staining,positive ratio of CD3,CD8,CD56 on the celluar membrane was detected by flow cytometry,and the anti-tumor effect of CIK to SMMC-7721 was detected by MTSmethod,inthedayof0,5,10,15,20 after the culture.Results Statistical analysis indicated that,the proliferation multiplication of CIK cells was significantly higher in group B,group C and group D after 10,15 and 20 days of culture than those in group A(P＜0.05);and group D had higher proliferation multi-plication than that of group C(P＜0.05).The percentage of CD3 + CD8 +,CD3 + CD56+ in CIK cell membrane in group B,C,D was significantly higher than that in group A after 15 and 20 days of culture (P＜0.05).The percentage of CD3+ CD8+,CD3+ CD56+ in CIK cell membrane in group D was significantly higher than that in group B after 15 and 20 days of culture (P＜0.05).The killing rate of CIK cells for liver cancer in each group at 10,15,20 days of culture was significantly higher than that of group A when the target target ratio was 5 ∶ 1 (P＜0.05).The killing rate of CIK cells for liver cancer in group D,C at 10,15,20 days of culture was significantly higher than that of group B(P＜0.05).Conclusion IL-12and IL-15 could improve the proliferation of CIK cells,and IL-15 also has the effect of enhancing CIK cells the tumor-killing to SMMC-7721 activity.

BACKGROUNDEndostar™ (rh-endostatin, YH-16) is a new recombinant human endostatin developed by Medgenn Bioengineering Co. Ltd., Yantai, Shandong, P.R.China. Pre-clinical study indicated that YH-16 could inhibit tumor endothelial cell proliferation, angiogenesis and tumor growth. Phase I and phase II studies revealed that YH-16 was effective as single agent with good tolerance in clinical use.The current study was to compare the response rate , median ti me to progression (TTP) ,clinical benefit andsafety in patients with advanced non-small cell lung cancer ( NSCLC) , who were treated with YH-16 plus vi-norelbine and cisplatin (NP) or placebo plus NP.

METHODSFour hundred and ninety-three histologically or cy-tologically confirmed stage IIIB and IV NSCLC patients , withlife expectancy > 3 months and ECOG perform-ance status 0-2 , were enrolledin a randomized ,double-blind ,placebo-controlled , multicenter trial ,either trialgroup : NP plus YH-16 (vinorelbine 25 mg/m² on day 1 and day 5 ,cisplatin 30mg/m² on days 2 to 4 , YH-167.5mg/m² on days 1 to 14) or control group : NP plus placebo (vinorelbine 25 mg/m² on day 1 and day 5 ,cis-platin 30 mg/m² on days 2 to 4 ,0.9% sodium-chloride 3 .75 ml on days 1 to 14) every 3 weeks for 2-6 cycles .The trial endpoints included response rate ,clinical benefit rate ,time to progression,quality of life and safety .

RESULTSOf 486 assessable patients , overall response rate was 35.4% in trial group and 19.5% in controlgroup (P=0 .0003) . The median TTP was 6 .3 months and 3 .6 months for trial group and control group respectively (P < 0 .001) . The clinical benefit rate was 73 .3 %in trial group and 64.0% in control group (P=0 .035) .In untreated patients of trial group and control group ,the response rate was 40 .0% and 23.9%(P=0 .003) ,the clinical benefit rate was 76 .5 % and 65 .0 % (P=0 .023) ,the median TTP was 6 .6 and 3 .7months (P=0 .0000) ,respectively .In pretreated patients of trial group and control group ,the response ratewas 23.9% and 8.5%(P=0 .034) ,the clinical benefit rate was 65.2% and 61.7%(P=0 .68) ,the median TTP was 5 .7 and 3 .2 months (P=0 .0002) ,respectively . The relief rate of clinical symptoms in trial groupwas higher than that of those in control group ,but no significance existed (P > 0 .05) . The score of quality oflife in trial group was significantly higher than that in control group (P=0 .0155) after treatment . There were no significant differences in incidence of hematologic and non-hematologic toxicity , moderate and severe sideeffects betweentrial group and control group .

CONCLUSIONSThe addition of YH-16 to NP regimen results in significantly and clinically meaningful improvement in response rate , median time to tumor progression,and clinical benefit rate compared with NP alone in advanced NSCLC patients . YH-16 in combination with chemotherapy shows a synergic activity and a favorable toxic profile in advanced cancer patients .