Type 2 diabetes mellitus (T2DM) is a common chronic metabolic disorder,it results from an interaction of environmental as well as genetic factors.There were several kinds of oral antidiabetic drugs (OADs),including biguanides,sulfonylureas,thiazolidinediones,and meglitinides,etc.Several genes have been identified to be associated with disease development and therapeutic outcomes.Inter-individual variations in the human genome affect both,risk of T2DM development and personalized response to identical drug therapies.Pharmacogenomics approaches focus on single nucleotide polymorphisms and their influence on individual drug response,efficacy and toxicity.Therefore,pharmacogenomics in T2DM is of great importance towards precision medicine which will greatly improve the efficacy of diabetes treatment.In this paper,antidiabetic drugs and related gene polymorphism researches are reviewed.

Post stroke depression (PSD) is a common complication after senile cerebrovascular diseases. It influences both physical and mental health of the elderly severely. So, the attention should be paid to not only the medical cares but also the function and mental rehabilitation, in order to improve the qualities of PSD patients' lives and decrease the death rate.

Objective To investigate the cause of high cardiovascular lethality in patients with diabetics mellitus. Methods Sections from autopsied coronary arteries and myocardium of dead patients with non-insulin-dependent diabetics mellitus and 12 dead control subjects were used for histomorphometric studies. Results The coronary atherosclerotic lesion in diabetics patients was not different in severity from those in controls. Nor was there difference in number of myofibers or diameters of myocardic fibers and capillaries.But the capillary density and the ratio of capillary number to myocardic fiber number in diabetics group were significeantly reduced compared with control group(P<0.0 l),and the capillary basement membrane in the former was significantly thicker than in the latter(P<0.01).Conclision The decrease in number of capillaries and the thickening of basement membrane enhance myocardiac vulnerability to further ischemia and hypoxia,which may undelie high lethality of myocardiopathy in diabetic patients.

40 cases(control group)with aggressive periodontitis (AgP)received scaling and root planning (SRP)and 38 cases(test group)received SRP followed by oral administration of amoxicillin plus metronidazole for 7 d.Gingival crevicular fluid samples were exam-ined for the levels of MMP-1,MMP-8 and tissue TIMP-1 by ELISA before therapy,3 and 6 months after therapy,TIMP-1 /MMP-1 and TIMP-1 /MMP-8 ratios were calculated.The levels of MMP-1 and MMP-8 were decreased in both groups (P <0.05)at 3 and 6 months after therapy.TIMP-1 /MMP-1 and TIMP-1 /MMP-8 ratios were increased in the 2 groups(P <0.05)after treatment,3 months after therapy the ratio in test group was higher than that in control group(P <0.05).

Objective CD44, a cell surface glycoprotein, plays an important role in tumor growth and glycolysis.The aim of this study was to investigate the effects of neutralizing CD44 antibodies on the growth and glycolytic metabolism of B16 cells in melanoma in vitro.Methods B16 cells were treated with control antibodies (50 μg/mL) or different concentrations of CD44 antibodies (2, 10, and 50 μg/mL) for 24 hours, followed by examination of the activation of the AKT pathway in the B16 cells by Western blot.Then the tumor cells were also treated with control antibodies (50 μg/mL) or CD44 antibodies (50μg/mL) after pretreated with API-2 (4 μmol/L) in a parallel test.After 48 hours of treatment, the expression of lactate dehydrogenase A (LDHA) in the B16 cells and the level of lactate in the culture supernatant were detected by immunofluorescence and colorimetry, respectively.Lastly, the B16 cells were treated with control antibodies (50μg/mL), API-2 (4 μmol/L), CD44 antibodies (50μg/mL), or API-2 + CD44 antibodies for 96 hours, followed by measurement of the proliferation of the cells by MTT and their apoptosis by AO/EB and AnnexinV staining.Results In comparison with the control antibody group, the level of AKT phosphorylation (p-AKT) in the B16 cells showed a concentration-dependent increase in the 2, 10, and 50 μg/mL CD44 antibody groups (1.00±0.25 vs 2.51±0.32, 3.89±0.46, and 4.07±0.42, P<0.01), and the expression of LDHA was increased by (2.13±0.24) times, with the lactate level in the culture supernatant significantly elevated from (35.32±3.24) to (56.34±8.19) mmol/L (P<0.01) after 96 hours of treatment with 50 μg/mL CD44 antibodies.Treatment with API-2+CD44 antibodies, however, suppressed the increase in the LDHA expression and reduced the level of lactate.Compared with the control antibody group, the proliferation rate of the B16 cells was markedly decreased in the API-2, CD44 antibody, and API-2+CD44 antibody groups ([103±12.91] vs [84.87±19.35], [71.35±16.23], and [41.16±9.15]%, P<0.05), while the apoptosis rate remarkably increased ([5.23±0.96] vs [13.65±4.27], [19.21±3.53], and [43.21±7.87]%, P<0.01).Conclusion Neutralizing the function of CD44 in the B16 cells in vitro can inhibit the growth of the cells and promote AKT-mediated glycolytic metabolism, while suppressing the AKT pathway may enhance the antitumor activity of the CD44 antibody.

Objective To investigate the effects of in vivo electroporation on plasmid mediated reporter gene expression and immunogenicity of DNA vaccine. Methods Luciferase expression plasmid was administered intramuscularly to BALB/c mice at 8μg and 40μg dosage level through injection with or without eletroporation Luciferase expression level in murine muscle was detected by IVIS imaging system 24 h after injection. DNA vaccine plasmid p1.0-gp1455m carrying codon-optimized env gene of CN54 strain ( HIV-1 CRF07_BC) was administered to mice at dosages of 8μg and 40μg through the two approaches mentioned above. Mice were immunized at week 0,2 and 4. Env-specific immune responses were detected at two weeks post the second and the third vaccinations. Env-specific antibody immune responses were determined by ELISA. Euv-specific cellular immune responses were determined by IFN-γ ELISPOT. Results Luciferase expression level in murine muscle was significantly increased as much as 35 folds through in vivo eletroporation. Results of ELISA and ELISPOT revealed that in vivo eletroporation could significantly enhance both the humoral and cellular immune responses induced by DNA vaccination. The responses induced by electrodelivered p1.0-gp1455m at 8 μg dosage were better than those induced by simple intramuscular injection with 40 μg of plasmid DNA. On the other hand, 2 injections followed by electroporation elicited comparable level of humoral and cellular immune responses with those induced by 3 injections without electroporation. Conclusion In vivo electroporation was capable of enhancing both the plasmid-mediated gene expression and immunogenicity of DNA vaccine.

Objective To investigate the clinical effect of active immunotherapy combined with endometrial local injury in women with recurrent spontaneous abortion( RSA) caused by negative-blocking antibodies.Methods 112 patients diagnosed RSA with negative -blocking antibodies were randomly divided into the treatment group (62 patients) and control group (50 patients).The patients in treatment group were treated by active immunotherapy combined with endometrial local injury.The patients in the control group were treated by active immunotherapy.The pregnancy outcomes were observed.Results The rate of pregnancy was 93.54%in treatment group,and 80.00%in the control group.The success pregnancy rate in the treatment group was significant higher than that in the control group (χ2 =4.65,P<0.05).The rate of abortion was 3.44% in the treatment group and 12.50% in the control group.It was significant lower than the control group(χ2 =4.90,P<0.05).After active immunotherapy,the pregnan-cy rate was 90.58%in positive-blocking antibodies group and 77.77%in negative-blocking antibodies group.The success pregnancy rate in positive-blocking antibodies group was significant higher than that in negative-blocking antibodies group (χ2 =4.27,P<0.05).The abortion rate in positive-blocking antibodies group was 2.60% and 19.05%in negative-blocking antibodies group.It was significant lower than that in negative-blocking antibodies group (χ2 =6.14,P<0.05).Conclusion It can significantly improve pregnant outcome and reduce the abortion rate with active immunotherapy combined with endometrial local injury in women with recurrent spontaneous abortion ( RSA) caused by negative-blocking antibodies.

Objective To summarize the reasons of bleeding complications and the prevention methods in stenting for intracranial arterial stenosis.Methods The clinical data of 366 patients underwent stent-assistant angioplasty of intracranial artery stenosis from July 2006 to December 2011were analyzed retrospectively.Among them,14 patients with bleeding complications were found.The initial 100 patients were categorized as early stage group and the rest as mature stage group.The reasons of bleeding and the methods for preventing this complication were summarized.Results The overall incidence of bleeding complication was 3.8％ (14/366).In the early stage group and mature stage group,the rates was 10％(10/100) and 1.5％ (4/266).Six cases were related to the operational manipulation and 8 cases secondary to hyperperfusion injury.Death was found in 6 patients,severe disability in 3,mild paralysis in 2,and no neurological deficits in 3.Conclusions The bleeding complications in stent-assisted angioplasty of intracranial artery stenosis have a high disability and mortality.The improvement of operative techniques and the more strict indications decrease the bleeding complications rate effectively.

Objective In the context of worldwide shortage of amytal,explore the intracarotidpropofol test for lateralizing language area and assessing hemispheric memory function.Methods Fourteen patients with refractory partial epilepsy who were candidates for surgical intervention were included in the study.With guide under a digital subtraction angiography,propofol was injected in bilateral intracarotidsequentially.Muscle power deceasing to level 0 at the contralateral limb and eyes gazing to contralateral side were used as the mark of hemispheric anesthesia completely.The immediate language alterations were recorded.To evaluate the bilateral language and memory functions,the visual and auditory memory tasks were performed sequentially once patient could concentrate his attention ; and after limb muscle power recovering to normal level,patients were required to perform a free recall test.Any abnormal responses were recorded.Results Language dominant hemisphere was determined in 14 patients.Nine patients were confirmed as left language dominance,2 patients were right language dominance.The remained 3 patients were considered as bilateral language dominance.Meanwhile,the hemispheric memory function was able be evaluated in 13 patients.More than 67％ memory function was sustained in hemisphere contralateral to mesial temporal lesions.Transient responses including eye pain,facial muscle spasms,laughers and involuntary movements were observed.Conclusion Hemispheric language and memory functions can be assessed with direct intracarotidpropofol injection,and propofol could be an alternative drug to amobarbital used in the Wada test.

OBJECTIVETo assess a minipig model of acute myocardial infarction (AMI) established by percutaneous balloon occlusion using delayed-enhanced magnetic resonance imaging (DE-MRI).

METHODSA minipig model of AMI was established by placement of a 2.0 mm×15.0 mm percutaneous transluminal coronary angioplasty balloon in the middle left anterior descending artery (LAD) through a percutaneous femoral puncture in the right inguinal region. The left anterior descending coronary artery (LAD) was occluded for 90 min, followed by assessment of the infarct size and cardiac function with DE-MRI, and the results were confirmed by pathological examination.

RESULTSDE-MRI showed a mean infarcts size of 10.2∓2.9 cm3 in the minipig models. Compared to the control group, the minipigs with AMI had significantly increased end-diastolic and end-systolic volumes (P<0.05) with a decreased stroke volume, ejection fraction and cardiac output (P<0.001). These DE-MRI values were matched with the microsphere values obtained from short-axis slices in pathological examination.

CONCLUSIONWe have established a feasible approach for evaluating minipig models of AMI as a platform for assessing the therapeutic effect of stem cell transplantation for AMI.