Safety and tolerability of anti-diabetic drugs should be among the most concern when it comes to management of Type 2 Diabetes.With the understanding of functions of incretin and degrading enzyme dipeptidepeptidase (DPP-4),several DPP-4 inhibitors with different chemical structures are now available.They are welltolerated with few weight gain,hypoglycemia or adverse effects.Therefore,DPP-4 inhibitors are considered to be among the ideal anti-hyperglycemic agents.

The prevalence of prediabetes is increasing rapidly in China, and with higher prevalence in coronary heart disease and hypertension patients. Diabetes can be controlled and prevented, previous studies have confirmed that lifestyle interventions and drug interventions can delay the progression of prediabetes to diabetes, and acarbose can be used for the primary prevention of cardiovascular events in impaired glucose tolerance(IGT) and diabetic patients, but benefits of drug intervention for secondary prevention of cardiovascular disease in IGT population are uncertain. The Acarbose Cardiovascular Evaluation(ACE) Study is a multicentre, randomized, placebo-controlled, double-blind study, with the aim of assessing the use of acarbose to reduce the risk of cardiovascular events and the onset of diabetes in IGT patients with cardiovascular disease in China , the results will be very meaningful and valuable for the prevention and treatment of diabetes. We will predict the results of ACE Study based on previous evidences.

Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant inherited disease,and may be related to the mutation of CDH1 or CTNNA1 genes.Microscopically,signet-ring cell carcinoma is suggested frequently in endoscopic biopsy or gastrectomy specimens.Some patients may have concomitant extra-stomach tumor (frequently breast cancer in females).Detection of CDH1 gene mutation should be performed in high-risk individuals,and diagnosis and treatment should be carried out by a multidisciplinary team.Prophylactic gastrectomy is recommended for those with pathogenic CDH1 mutation.Endoscopic surveillance is an option for those with CDH1 mutation of undetermined significance and those without germline CDH1 mutation.This review discussed the concept,genetic characteristics,clinicopathological features and genetic screening of HDGC for providing a reference for clinicians.

Caveolae is a specified micro-domain of plasma membrane, which consists of caveolin and many lipid molecules and membrane proteins. Caveolae plays important roles in internalization of extra-membrane molecules, transmembrane signal transdution and transport of cholesterin. Recent studies indicated that caveolae and its components were up-regulated in multidrug resistant tumor cells and might participate the development of multidrug resistance of tumor cells. This paper concentrated on the role of caveolae in tumor multidrug resistance.

By molecular cloning technique, the expressing plasmids pDOR-SV40-Bcl-2 cDNA were successfully constructed. The reconstructed plasmids with lipofectamine were transduced into gastric cancer cell line SGC7901 and then the positive clones which contained the reconstructed plasmids were choosed by G418. Circa 150 positive clones were choosed from 2 x 10_5 gene transduced cells, which suggested that the transducing efficiency was more than 1%o; 2 positive clones were expanded and passage, then 1 drug-resistance cell strain (SGC7901 anBcl-2 cells) was obtained. The bloting results suggested, Bcl-2 cDNA were expressed in both gene transduced and not transduced cell strains, but the expressing level of mRNA and protein in gene transduced cell strain was very low than that in gene not transduced cell strain were positive by the means of Southern blot, Northern blot and Western blot. This results showed that normally in gastric cancer cells the expressing level of Bcl-2 gene was very high, and the cDNA fragment of antisense Bcl-2 were successfully transduced into gastric cancer cells, and in gene transduced cell strains the expressing of Bcl-2 gene was effi-cientlv blocked.

Objective To study the effect of ribosomal protein S13(RPS13) encoding genes on the development of mutidrug resistance (MDR) in human gastric cancer cell line. Methods RPS13 cDNA was amplified by RT-PCR. The sense and antisense eukaryotic expression vectors were constructed by DNA recombination. Gastric cancer cell line SGC7901 and Vincristine-resistant SGC7901/VCR cells were transfected with the sense and antisense recombinant vectors respectively using liposome-mediated method. RNA dot blotting assay was used to verify the changes of mRNA level in stable clones. To investigate effects of the sense, antisense vector transfection on the chemotherapeutic drug sensitivity, thiazolyl blue (MTT) cytotoxicity assay was used. Cell cycle was detected by flow cytometry (FCM). Results Whole length of RPS13 cDNA gene was amplified by RT-PCR. The sense, antisense eukaryotic expression vectors were constructed by the directed cloning of the target genes into eukaryotic expression vector pcDNA 3.1(+). RNA dot blotting assay suggested that mRNA level of the RPS13 was up-regulated in the sense recombinant vector transfected cells, and down-regulated in the antisense recombinant vector transfected cells. By MTT cytotoxicity assay, the enhanced resistance to adriamycin, 5-fluorouracil and vincristine was found in the RPS13 sense recombinant vector transfected SGC7901 cells. RPS13 antisense recombinant vector rendered SGC7901/VCR cells partially sensitive to mitomycin and vincristine. Cell cycle analysis suggested that the proportion of G1, S, and G2 cells was 47.0%, 33.2% and 19.8% respectively in up-regulated RPS13 cells; the proportion of G1, S and G2 cells was 62.9%, 1.0% and 36.1% respectively in down-regulated RPS13 cells. Conclusions RPS13 may take part in the mediation of MDR in gastric cancer cells.

Elderly agrypnia patients were given with different doses of melatonin. Patients′ falling a sleep time, coming into effect time, sleep lasting time and adverse effect of melatonin were observed to study the effect and safety of melatonin on elderly agrypnia patients. The results showed melatonin could effectively improve the agrypnia suffered by elderly patients. Patients′ falling a sleep time was shortened and sleep lasting time prolonged after taking melatonin. The effect of melatonin increased along with increase of its dose.There were no adverse effects observed. Our study indicates that melatonin has a good safety profile and significant effects on agrypnia suffered by elderly patients.

In order to detect and localize melatonin receptor and its mRNA expression in the human skin, human skin was obtained from healthy volunteers. Immunohistochemistry and RT-PCR were applied to detect MR in human skin and to identify its subcellular distribution. Electrophoresis of RT-PCR product showed positive band of mt 1 subtype in human skin. The subtype of MR, mt 1was present in the membrane, cytosol and nucleus of skin cells as shown by immunohistochemistry. It is suggested that skin is the target organ of melatonin.

To study the role of a novel MDR-related gene MGr1-Ag in the multidrug resistant (MDR) gastric cancer. The whole length MGr1-Ag gene was cloned, and eukaryotic vectors carrying the full length of MGr1-Ag cDNA and its antisense expression vector were constructed. The sense vector and anti-sense were then transfected into MGC803 cells and SGC7901/VCR cells respectively by lipofectamine. The result showed that a 1.0kb fragment was successfully amplified by RT-PCR and cloned into pUCm-T vector. DNA sequencing suggested that the fragment was the properly encoded MGr1-Ag gene. Recombinant eukaryotic plasmids harboring MGr1-Ag and its antisense expression vector were also obtained by subcloning the gene into pCDNA3.1/V5-His, which was confirmed by endonuclease digestion. As confirmed by Western blot, stable cell strains with up and down-regulated MGr1-Ag expression were constructed. Those cell strains provided the basis for further study on the MGr1-Ag in MDR of gastric cancer.

Objective To study the expression of 9 delayed rectifier potassium channel subunits in human gastric cancer cell line AGS, as well as the effect of down-regulation of the expression of Kv1.5 on AGS cells proliferation. Methods RT-PCR technique was employed to detect the mRNA expression of Kv1.1, Kv1.2, Kv1.3, Kv1.5, Kv1.6, Kv2.1, Kv2.2, Kv3.1 and Kv3.2 in AGS cells. Once the expression of Kv1.5 protein was confirmed by immunofluorescence, small interference RNA (siRNA) was applied to down-regulate the Kv1.5 protein expression, then MTT assay and flow cytometry were used to observe the cell proliferation and the cell cycle distribution. Results Totally 7 delayed rectifier potassium channel subunits were detected in AGS cells, among them the mRNA levels of Kv1.3, Kv1.5 and Kv2.1 were much higher than that of the others. It was confirmed by immunofluorescence that the Kv1.5 protein was expressed mainly in AGS cytomembrane. After the endogenous Kv1.5 expression in AGS cells was down regulated by siRNA, the cell proliferation obviously slowed down and the cell growth stopped in G1 period. Conclusion Multiform expression of delayed rectifier potassium channel subunits existed in AGS cells, and Kv1.5 may be involved in the regulation of gastric carcinoma cell proliferation by modulating the cell cycle.