Nitrogen-containing bisphosphonates exert antitumor activity through induction of apoptosis or inhibition of proliferation, invasion and migration in tumor cells, inhibition of angiogenesis and promotion of immune surveillance. Animal models show that bisphosphonates delay visceral metastasis progression. Both ABCSG-12 and ZOFAST trial have demonstrated that Zoledronate reduced breast cancer recurrence risks. Bisphosphonates are synergistic with a variety of chemotherapeutics, and sequential dosing is more effective, which may be attributable to increased uptake of bisphosphonates by tumor cells after pretreatment with chemotherapeutics. Metronomic administration of bisphophonates after chemotherapy provides bisphosphonates the promising antineoplatic potential.

Background:Vitamin D receptor( VDR)is a member of the steroid hormone receptor superfamily,which plays roles in various biological processes including cell proliferation,differentiation,apoptosis and immune responses,and is low expressed in many malignant tumors. Aims:To evaluate the expression and regulation mechanism of VDR in colorectal cancer. Methods:A total of 30 patients with colorectal cancer admitted from February 2010 to December 2012 at Ren Ji Hospital,School of Medicine,Shanghai Jiao Tong University were enrolled. Expression of VDR in cancerous tissue and para-cancer noncancerous tissue was determined by immunohistochemistry. Clinical data of 224 patients with colorectal cancer were collected from Gene Expression Omnibus( GEO)for analyzing the correlation between VDR expression in cancerous tissue and clinicopathological characteristics as well as survival time. Expression of VDR in human colon cancer cell lines HCT116 and SW620 transfected with enhancer of zeste homolog 2( EZH2 )-siRNA or treated with 5-azacytidine (5-AZA)was determined by real-time PCR,and methylation level of VDR promoter was determined by methylation-specific PCR( MSP). Results:Positivity rate of VDR was significantly lower in colorectal cancer tissue than that in para-cancer noncancerous tissue( 26. 7% vs. 70. 0%,P < 0. 001 ). Expression of VDR was negatively correlated with histological staging,distant metastasis,vascular metastasis and lymph node metastasis of colorectal cancer(P<0. 05). Survival time was significantly longer in patients with high expression of VDR than patients with low expression of VDR (P=0. 032). Compared with cells transfected with control-siRNA,expression of EZH2 mRNA and methylation level of VDR promoter in HCT116 and SW620 cells transfected with EZH2-siRNA were significantly decreased(P<0. 05),and expression of VDR mRNA was significantly increased(P<0. 05). Compared with negative control group,methylation level of VDR promoter in HCT116 and SW620 cells treated with 5-AZA was significantly decreased(P<0. 05),and expression of VDR mRNA was significantly increased(P<0. 05). Conclusions:Expression of VDR in colorectal cancer is down-regulated and positively correlated with a favourable prognosis. Transcriptional repression of VDR in colorectal cancer is co-regulated by histone methylation and DNA methylation.

BACKGROUND:Although there is no report of adipose-derived stem cells in ureteral repair, but with the deepening of the research of adipose stem cells, the differentiation conditions of adipose-derived stem cells to the vascular endothelial cells, smooth muscle cells and urothelial cells are more mature, and the experimental research of adipose-derived stem cells in the repair and reconstruction of kidney and bladder is also increasing.
OBJECTIVE:To summarize the adipose-derived stem cells research and its application in damage and repair of urinary system in recent years.
METHODS:The first author retrieved PubMed database and CNKI databases for articles relevant to adipose-derived stem cells in the repair of urinary system published between January 2001 to September 2013 using the keywords of“adipose tissue-derived stem cel/adipose tissue-derived stromal cells/ADSCs;tissue engineering;kidney;ureter;ureathra;bladder;urology”in English and Chinese, respectively. Final y, 52 articles were included for further analysis.
RESULTS AND CONCLUSION:Adipose-derived stem cells which can be found easily and have the unique advantages of multi-directional differentiation ability have been used for repairing and constructing the urinary system. Adipose-derived stem cells provide a new model of treatment for the urinary tract, which solves the traditional problems, including immune rejection, source of organs and ethical issues, and become an ideal cellsource in repair of urinary system. Accumulated data related to adipose-derived stem cells and its experiment and clinical application in repair of urinary system injuries have been reported. But before the cells are widely used in clinic, the fol owing problems need to be solved:its specific surface marker identification, specific conditions and control of celldifferentiation, mechanisms of action.

Objective To find the characteristics of stress distribution on condyle during different vertical distances of edentulous jaw.Methods Three dimensional finite element models of the mandible and temporomandibular joint were established with the complete dentures in different heights by helix-CT scanned transverse sections.The stress distribution of the condyle was analyzed under load.Results The compressive stress and tensile stress coexisted on the whole condyle with the different vertical distances.The trend of distribution was consistent practically,but the stress presented a large difference on different locum.With the decrease of the vertical distance(from H-2 to H-6),the stress presented a decreasing trend but an increasing trend at H-8.Conclusion Changes in the vertical distance produce different effects of stress on edentulous jaw under the same load.

Lurasidone is a new atypical antipsychotic drug, it was approved by the Food and Drug Administration ( FDA ) for treatment of schizophrenia on october 28,2010.The article is to provide an review about pharmacological effects, clinical applications, pharmacokinetics, dosage, drug interactions, adverse reactions of Lurasidone.

Objective To construct the recombinant adenovirus vector containing ubiquinol-cytochrome C reductase core protein 1(UQCRC1) and to investigate the protective role of UQCRC1 against hypoxia/reoxygenation injury in H9c2 cardiac myocytes . Methods UQCRC1 gene was obtained from the cDNA library by PCR ,then was double-digested with restriction endonucleases SalⅠand XbaⅠand inserted into pAd Track-CMV .The identified plasmid of pAd Track-UQCRC1 was transfected into BJ 5183 contai-ning pAdEasy-1 .After screening the positive clone ,the plasmid was transfect into 293T cells with liposome to integrate and package the recombinant adenovirus .Finally ,these adenoviruses were transfected into H9c2 cardiac myocytes .The expressions of green fluo-rescence protein(GFP) ,UQCRC1 gene and protein were observed by RT-PCR and Western blot analysis .The cell viability and the LDH release were detect .Results The recombinant adenovirus-UQCRC1 was constructed successfully .The overexpression of UQCRC1 increased the cell viability(P<0 .05) and decreased the LDH release(P<0 .05) from H9C2 cardiac myocytes after suf-fering hypoxia/reoxygenation injury .Conclusion UQCRC1 has the protective effect on hypoxia/reoxygenation injury in H9c2 car-diac myocytes ,and the construction of recombinant adenovirus vector will lay the foundation for further studying the role of UQCRC1 in cardioprotection .

Objective The immature platelet fraction (IPF) could be detected quantificationally in Sysmex XE-2100 with the software of XE-pro and IPF master.The study aimed to perform the methodological evaluation of IPF detection and investigate the clinical significance for the monitoring for bone marrow hyperplasia in cancer chemotherapy patients.Methods The high-level, middle-level and low-level whole blood samples were randomly chosen for detection repeatly 20 times to obtain interrun coefficient of variation (CV) for evaluation of the precision and reproducibility. Integrated quality controls were determined for continuous 20 days to obtain intrarun CV, and the stability and carryover was investigated.Furthermore, the correlation between results from Sysmex XE-2100 and results from flow cytometry was assessed.182 healthy subjects and 130 cancer patients undergoing chemotherapy were selected and the latter were divided into two groups according to platelet counts after therapy, one was normal PLT group, the other was decreased PLT group.The IPF of either group was measured and was compared with each other.Results The precision of IPF for high-level, middle-level and low-level were 4.71%, 4.33% and 4.95%, respectively, they were less than 5%.The interrun CV of IPF detection for middle-level and low-level were less than 5%.The interrun CV of IPF detection for high-level were less than 10%.The carryover ranged from 0.6% to 2.7%,and the average rate was 1.2%.A good correlation for IPF detection was shown between results from Sysmex XE-2100 and flow cytometry(r = 0.880 9,P ＜ 0.01).Regarding clinical utility of IPF detection in treatment monitoring for chemotherapy effect, the median of IPF levels in decreased PLT group, normal PLT group,control group were 14.45% ,7.35% and 15.68%, respectively.There was significant difference among the three groups (H =49.032,P ＜0.01 ).The IPF level was higher in decreased PLT group than normal PLT group (t = -5.681, P ＜ 0.O1 ), and was lower in normal PLT group after chemotherapy than the control group (t = -6.662 ,P ＜0.01 ).Conclusions The determination of IPF by the Sysmex XE-2100 owns high precision and good stability. IPF is an effective marker for evaluation of thrombopoietic condition in the cancer chemotherapy patients.

Objective To study activation effect of a natural compound baicalein on cystic fibrosis transmembrane conductance regulator(CFTR) chloride channel.Methods A cell-based fluorescence assay was used to determine CFTR-mediate iodide influx rate/dt(mmol?L-1?s-1)] activated by baicalein(the concentrations were 0.18,0.55,1.65,5,15,44,133 and 400 ?mol?L-1).Results The Ka of flavonoid baicalein stimulating CFTR was about 16 ?mol?L-1.The half of maximal activity was reached in ten minutes and the activation disappeared in 20 min after baicalein was washed out.The activation of baicalein was not affected obviously under different concentrations of Forsklin(0,20,50 and 100 nmol?L-1)and the activation could be totally inhibited by CFTRinh-172.Conclusion Baicalein can stimulate CFTR-mediated iodide influx in a dose-dependent way and its activity manifests a rapid and reversible characteristic.It might work in both elevating CFTR protein phosphorylation and direct binding way.