Transforming growth factor-?(TGF-?) is a kind of multifunctional cytokine that regulates cell growth,differentiation,cellular senescence,apoptosis,wound healing and embryo development.As a tumor suppressor,deregulated or aberrant TGF-? signaling has been strongly implicated in human solid tumors,as well as in normal and malignant hematopoiesis.TGF? exerts an inhibitory role during the whole procedure of hematopoiesis.As a cell cycle inhibitor,it maintains cells in a quiescent state and can downregulate expression of hematopoiesis activators and oncoproteins.In malignant hematopoiesis,altered expression of coactivators or corepressors involve in TGF-?-induced transcriptional responses and loss/disruption of TGF-? target gene expression.Then malignant cells grow and differentiate abnormally.In acute promyelocytic leukemia,PML-RAR? may inhibit TGF-? signaling through inhibition of cPML and nPML.Degradation of PML-RAR? by ATRA restores this signaling pathway.

The metabolism study of radiolabeled drugs plays an important role in the development of new drugs. It provides information on drug absorption, metabolism, tissue distribution and excretion, and plays an irreplaceable role in the metabolite safety evaluation and mass balance of new drugs. The new guidance draft on clinical trials of radiolabeled drugs recently released by the US FDA puts forward higher standards and has been widely concerned by the industry. In recent years, in the research and development of new drugs in China, ¹⁴C labeled drugs have been used to carry out clinical metabolism studies, which has overcome key technical bottlenecks and accumulated experience. This paper summarizes the above research progress, analyzes the existing problems, and preliminarily looks forward to the future technological development and application.

Objective To investigate the effect of serum-deprivation on the changes of [ Ca2+ ] i and the protein release of S100A13 and fibroblast growth factor 1 ( FGF-1 ) in thyroid cancer TT cell,and to reveal the role of Ca2+in the protein release of S100Al3 and FGF-1.Methods The protein expressions of FGF-1 and S100A13 in TT cells under serum-deprivation were detected by Western blot.The released FGF-1 protein from TT cells in the supernatant fluid was detected by ELISA.Realtime dynamic examinations on the change of 1 h [ Ca2+ ] i in TT cells under serum-deprivation were detected by confocal laser scanning microscopy.Then,the effect of EGTA( 2.5 mmol/ L),BAPTA-AM (2.5 μmol/L)on distributions of the fluorescence of S100AI 3 and FGF-1 in TT cells under serumdeprivation for6 h were detected by indirect immunofluorescence.Results The expressions of FGF-1 and S100A13 in TT cells after serum-deprivation for4 h and 6 h were reduced( P＜0.05 or P＜0.01 ),but the released FGF-1 protein from TT cells in the supernatant fluid was elevated ( P＜0.05 or P＜0.01).Confocal laser scanning of Ca2+ imaging indicated that [ Ca2+ ] i of serum-deprivation TT cells maintained the relative stabilization within 23 win,but the rapid rise of [ Ca2+ ] i achieved peak value 1.6 μmol/L after 30 min,and remained stable for about 17 win,and thereafter 40 win slowly dropped to a low level From 40 win to 60 win the [ Ca2+ ] i was about 0.3-0.6 μ mol/L.The average [ Ca2+ ] i was higher than that in normal group,EGTA group,and BAPTA-AM group within 1 h.The protein expressions of S100A13 and FGF-1 did not drop obviously in EGTA group and BAPTA-AM group.Conlusion The release of S100A13 and FGF-1 from TT cell under serum-deprivation is possibly related with the change of [ Ca2+ ]i.Both Ca2+-chelating agents EGTA and BA PTA-AM are able to inhibit the rise of [ Ca2+ ] i and release of S100A 13 and FGF-1 from TT cells under serum-deprivation.

BACKGROUND: In the field of intervertebral disc tissue engineering, seed cells primarily consist of nucleus pulposus cells (NPCs) and mesenchymal stem cells (MSCs). NPCs have been known to have several shortcomings: limited source, inconvenient collection, poor proliferative capacity, and difficult in vitro culture.OBJECTIVE: To investigate the proliferation of MSCs after co-culture with NPCs in alginate beads-simulated three-dimensional environment.DESIGN, TIME AND SETTING: A cell observation was performed at the Laboratory of Orthopedics, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology between December 2007 and October 2008.MATERIALS: Six healthy New Zealand rabbits of 4 months old were provided by the Laboratory Animal Center, Tongji Medical College of Huazhong University of Science and Technology and were used for the present study.METHODS: Rabbit MSCs were isolated and purified using density gradient centrifugation and adherence methods. Rabbit NPCs were isolated and purified using collagenase Ⅱ digestion and adherence methods. Following liposome-mediated green fluorescent protein tranfection and G418 screening, MSCs of passage 3 were cultured either alone (control group) or with NPCs at a ratio of 1:1 (co-culture group) in alginate beads. After 14 days of culture, alginate beads were dissolved and MSCs were collected by flow cytometry sorting.MAIN OUTCOME MEASURES: The expression of collagen Ⅱ and aggrecan in MSCs was detected by RT-PCR and Western blot techniques.RESULTS: mRNA and protein expression of collagen Ⅱ and aggrecan was observed in the co-culture group, but not in the control group, after 14 days of culture.CONCLUSION: MSC differentiation towards nucleus pulposus-like cells can be induced by co-culture with NPCs in a three-dimensional environment.

Objective To investigate the prognostic values of serum lactate dehydrogenase(LDH) and beta-2 microglobulin(?2-MG) levels in patients with acute myeloid leukemia(AML). Methods The associations of serum LDH and ?2-MG levels at diagnosis,remission and relapse with treatment and prognosis in 68 patients with AML were retrospectively analysed. Results There were no difference in LDH and ?2-MG between AML subtypes patients.The level of serum LDH and ?2-MG at diagnosis and relapse were much higher than those at remission.Patients with lower level of LDH and ?2-MG got higher CR rate and longer term overall survival and disease-free survival.Patients with higher level of both LDH and ?2-MG got lower CR rate,shorter term of overall survival and disease-free survival than those with higher level of LDH or ?2-MG or those with normal level of LDH and ?2-MG. Conclusion LDH and ?2-MG is a singificant prognostic indicator for AML.While combined LDH and ?2-MG are more definite for the treatment and diagnosis.

An analysis method has been established to test 27 elements (Li, Be, B, Mg, Al, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, As, Sr, Mo, Cd, Sn, Sb, Ba, La, Hg, Pb, Bi) in Maca nationality's medicine with microwave digestion-ICP-MS. Sample solutions were analyzed by ICP-MS after microwave digestion, and the contents of elements were calculated according to their calibration curves, and internal standard method was adopted to reduce matrix effect and other interference effects. The experimental results showed that the linear relations of all the elements were very good; the correlation coefficient (r) was 0.9994-1.0000 (Hg was 0.9982) ; the limits of detection were 0.003-2.662 microg x L(-1); the relative standard deviations for all elements of reproducibility were lower than 5% (except the individual elements); the recovery rate were 78.5%-123.7% with RSD lower than 5% ( except the individual elements). The analytical results of standard material showed acceptable agreement with the certified values. This method was applicable to determinate the contents of multi-elements in Maca which had a high sensitivity, good specificity and good repeatability, and provide basis for the quality control of Maca.
Lepidium ; chemistry ; Mass Spectrometry ; methods ; Microwaves ; Reproducibility of Results ; Trace Elements ; chemistry ; isolation & purification

Objective To explore the underlying relationship between hyperglycemic factors in type 2 diabe- tes.Methods Fifty seven type 2 diabetes with obesity (DM-OB)and 64 without obesity(DM-NOB)were recruited. Age,body mass index(BMI),hemoglobin A1c (HbA1c),homeostasis model assessment-2 insulin resistance (HO- MA-IR),high-sensitivity C-reactive protein (hsCRP),fasting plasma glucose,postprandial plasma glucose (PPG), postprandial glucose excursion(PPGE),lipid profile,blood pressure were determined.Results DM-OB subjects had significantly higher HOMA-IR,BMI,DBP,TC,hsCRP,HbAlc,LDL-C when compared with DM-NOB sub- jects.Pearson correlation analysis,in DM-OB subjects,BMI,FBG,FPG,HOMA-IR,hs-CRP were all the posi- tive relative factors(P all

?AlM: To evaluate the clinical effects and security of posterior chamber implantable Collamer lens ( lCL ) implantation in patients with extreme highly myopia.
?METHODS:ln this study, 18 patients ( 32 eyes ) with extreme highly myopic patients who had undergone posterior chamber lCLs implantation from July 2010 to July 2013 were evaluated. Diopter -10. 5 ~ 19. 0D, and astigmia -0. 5 ~4. 5DC. Changes in intraocular pressure ( lOP ) , refraction, visual acuity and corneal endothelium, anterior chamber depth, iris, high arch, lens were noted at 1d, 1wk, 1, 3mo and 1a after surgery respectively, and follow-up was of 1a.
? RESULTS: Before surgery, the uncorrected visual acuity (UCVA) were 0. 01~0. 05, and the best spectacle-corrected visual acuity ( BSCVA) were 0. 4 ~ 1. 0. One month after surgery, the UCVA were 0. 5~1. 2. The mean vault were 547±222 μm (95%CI 442~672μm) and 528±268μm (95%CI 354 ~635μm) for 1mo and 1a, respectively (P = 0. 81), and there was no significant difference. Anterior subcapsular opacities in 1 eye, mild and transient increase in lOP in 3 eyes, and chronic pigment dispersion in 2 eyes were observed. There was no serious complication.
?CONCLUSlON: Posterior chamber phakic intraocular lens implantation is an effective and safe method for correcting patients with extreme highly myopia.

Objective To investigate the influencing factors of strain ratio(SR) value in differential diagnosis of benign and malignant thyroid nodules by using real-time tissue elastosonography (RTE).Methods One hundred and seventy-one patients with a total of 171 thyroid nodules were analyzed retrospectively.Their images,including 2D ultrasound,color Doppler flow imaging (CDFI) and RTE were reviewed and conventional ultrasonic features (including the maximum diameter,composition,shape,magin,calcification,intranodular blood flow,depth) and SR value were recorded.Receiver-operating characteristic (ROC) curve was employed to assess the diagnostic efficiency of SR value in differentiating malignant nodules from benign ones.Firstly,the correlation between the aforementioned factors and SR value was assessed by using malignant lesions as the research subjects.And then,the multiple linear regressions (MLR) was employed to evaluate the influence of particular features which turned out to be an important disturbing factor affecting SR value of the lesion in the first step of analysis and pathological type in all nodules (benign and malignant) on SR value.Results With a cut-off point of SR value 3.67,the sensitivity and specificity of SR value in differential diagnosis of benign and malignant thyroid nodules was 85.6％ and 81.1 ％,respectively,and the area under ROC curve was 0.891.Correlation between the maximum diameter and calcification and SR value was significant(r =0.345 and 0.261 respectively,P ＜0.05).However,there was no significant correlation between other features(5 factors) and SR value(P ≥0.05).MLR indicated that the maximum diameter,calcification and the type of pathology of the nodule were associated with SR value (P ＜ 0.05).Among them,pathological nature was the most significant impact factor with a standardized coefficient 0.494).Conclusions SR value can be used to evaluate the hardness of thyroid nodules semi-quantitatively.Its value mainly depends on the pathological nature of the nodules.The maximum diameter and calcification are also the influencing factors of SR value.However,the composition,shape,margin,intranodular blood flow and depth have no obvious effect on SR value.

Objective To investigate the antibacterial effect of grape peel residue procyanidins on common clinical bacteria ,inclu‐ding E .coli ,Pseudomonas aeruginosa ,Acinetobacter baumannii ,Enterococcus and methicillin‐resistant Staphylococcus aureus (M R‐SA) .Methods By the means of agar plate method ,we detected the minimum inhibitory concentration (MIC) of 30 strains of E .co‐li ,28 strains of Pseudomonas aeruginosa ,15 strains of Acinetobacter baumannii ,32 strains of Feces Enterococcus ,25 strains of E . faecalis and 70 strains of MRSA ,then calculate the MIC50 and MIC90 .The result was analyzed with SPSS software 16 .0 .Results The concentration of procyanidins at 3 -8 mg/mL had no inhibitory effect on E .coli ,Pseudomonas aeruginosa and Acinetobacter baumannii;there was no inhibitory effect on E .faecalis at 3-8 mg/mL ,but the inhibition rate to Feces Enterococcus was 6 .3% .By measuring the inhibitory effect of procyanidins on 70 MRSA ,the inhibition rate at 4 mg/mL was 65 .7% ,at 8 mg/mL was 95 .7% , MIC50 was 4 .221 mg/mL and MIC90 was 6 .260 mg/mL .Conclusion There are no inhibitory effects of grape peel residue procya‐nidins on Gram‐negative bacilli such as E .coli ,Pseudomonas aeruginosa ,Acinetobacter baumannii ,and there are certain inhibitory effects on Gram‐positive bacteria such as MRSA ,enterococci ,especially on MRSA (P<0 .05) .