In addition to kill tumor cells through direct cytotoxicity, the immunomodulatory activity is another facet of chemotherapy. The major molecular mechanisms of immunogenicity of cytotoxic drugs are elimination of CD_4~+ CD_(25)~+ regulatory T cells or Myeloid-Derived Suppressor Cells, and sensitization of tumor cells to immune effectors through modulation of death receptor expression. These studies provide scientific evidence for combinatorial treatments including vaccines and Traditional Chinese Medicine for cancer therapy.

Objective To investigate the association of HLA DRB1 alleles with gastric carcinoma and H. pylori infection. Methods HLA DRB1 alleles polymorphism in 63 patients with gastric adenocarcinoma and 136 normal controls were tested with the polymerase chain reaction/sequence specific primer(PCR/SSP) technique. The status of H. pylori infection was determined by histology of gastric biopsy specimens and /or by ELISA. Results Both HLA DRB1 0901 and HLA DRB1 12 were positively associated, and HLA DRB1 15 was negatively associated with gastric adenocarcinoma, but no significant associations were found between patients with and without above HLA DRB1 alleles with regard to patients' age at presentation, sex ratio, tumor site (distal vs proximal), TNM staging, histological grading of tumor or status of H. pylori infection. Conclusions Our results suggest that HLA DRB1 0901, DRB1 12 and DRB1 15 are associated with gastric adenocarcinoma, but are not associated with the clinical features of gastric adenocarcinoma and the status of H. pylori infection.

Cardiomyopathy, Dilated ; genetics ; Lamin Type A ; genetics

ObjectiveTo determine the diversity of outer membrane protein expression of Leptospira interrogans during infection of human THP-1 monocytes,and protein antigen candidates for developing leptospiral genetically engineering vaccines.MethodsThe outer membrane proteins(OMPs) of Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai strain Lai before or after infection of human THP-1 monocyte line were extracted using Triton X-114 method.The OMPs extracts were separated by two-dimensional gel electrophoresis(2-DGE) and then detected using silver staining method.Four up-regulated and four down-regulated OMPs were selected for hydrolysis by trypsin and then identified by using liquid chromatography-tandem mass(LC-MS/MS) method.The transmembrane regions and signal peptides in the eight target OMPs were analyzed using bioinformatic software.Several real-time fluorescent quantitative RT-PCRs were performed to determine the mRNA level changes of the eight target genes of L.interrogans strain Lai before or after infection of THP-1 cells.The prokaryotic expression systems of target genes were generated and the immunoprutection of target recombinant proteins was determined using leptospire-infected guinea pigs model.ResultsAfter a 60 min infection of THP-1 cells,four OMPs( Loa22,GroEL,F0F1 ATP synthase alpha- and beta-subunits) of L interrogans strain Lai were noticeably up-regulated ( P＜0.05 ),while the other four OMPs( FlaB2,LigB,OmpA family protein and OmpA) were significantly down-regulated (P＜0.05).The results of real-time fluorescent quantitative RT-PCRs were coincident with those confirmed by the 2-DGE phus silver staining.The bioinformatic analysis indicated that among the eight OMPs,OmpA and OmpA family protein belonged transmembrane proteins,while the rest had no membrane structure.Loa22,LigB and OmpA family protein contained a signal peptide in their sequences.200 μg of the recombinant proteins rLoa22 and rGroEL presented 75.0％ immunoprotective rates in the infected guinea pigs.Conclusion An obvious change of the OMP expression map of L.interrogans strain Lai occurs during infection of host cells.The up-regulated leptospiral OM Ps during infection,especially for the GroEL and Loa22 proteins,can be used as the immunogen candidates for developing leptospiral genetically engineering vaccines.

The methyl group plays an important role in the rational drug design. Introducing methyl into small molecules has become an important strategy of lead compound optimization. The application of methyl in drug design is reviewed in this paper. Methyl can modulate the physicochemical, pharmacodynamic, and pharmacokinetic properties by ortho effect, inductive effect, and conformational effect. It also improves the metabolic stability as a soft metabolic point. In addition, introducing methyl into drug molecules can also be applied as a strategy in new uses of old drugs and generate me-too drugs.

Objective To examine whether tissue inhibitor of metalloproteinases-1 (TIMP-1) is involved in arterial calcification of chronic renal failure (CRF) rats. Methods CRF model was induced in male Wistar rats by garage daily with 2% adenine 250 mg/kg. The calcification of aorta, femoral artery, renal artery and coronary artery was evaluated histomorphometrically by van Kossa-stained sections at 2-, 4-, 6- and 8-week respectively. RT-PCR and Western blot were used to observe the expressive levels of TIMP-1 mRNA and protein. Expressions of TIMP-1, osteopentin (OPN) and core binding factor α1 (Cbfα-1) protein were analyzed by immunhistochemistry. Results Serum urea nitrogen, creatinine, inorganic phosphate, calcium-phosphorus product and intact parathyroid hormone (iPTH) increased significantly in the model animals compared with control group after 2 weeks (P<0.01). Medial calcification was found in above four arteries of model groups after 6 weeks. RT-PCR and Western blot showed that TIMP-1 expression of model group was significantly higher than that of control group (P< 0.05), and obviously elevated in a time-dependent manner. The expression of TIMP-1 and OPN in calcified aortic smooth muscle cells increased obviously (P<0.05), and positive immunostaining of Cbfα-1 was found. The expression of TIMP-1 was positively correlated with OPN and Cbfα-1 (r=0.317, P=0.000; r=0.485, P=0.000). Conclusions The pathology of arterial calcification in CRF rats induced by adenine is similar to CRF patients, which may serve as a useful model of CRF with arterial calcification. The up-regulation of TIMP-1 seems to participate in the formation and development of vascular calcification in CRF.

Objective To observe the changes of renal function in elderly patients with heart failure but normal ejection fraction,and explore its clinical significance. Methods A total of 145 cases diagnosed as coronary artery disease from Department of Geriatric Cardiology in The First Affili?ated Hospital of China Medical University were enrolled in the study. All of the cases were divided into HFPEF group(65 cases)and non HFPEF group(80 cases). All patients underwent cardiac ultrasound,BNP and renal function examination,and the glomerular filtration rate(GFR)was cal?culated. Results The average age of patients in HFPEF group was significantly higher than non HFPEF group(P<0.001),and the incidence of hypertension,diabetes,coronary heart disease,atrial fibrillation,or concomitant incidence of two or more kinds of these disease in HFPEF group was significantly higher than non HFPEF group(P1=0.046,P2<0.001,P3=0.002,P4=0.021,P5<0.001);the GFR of two groups of patients were lower than normal level,but the GFR of HFPEF group was significantly lower than non HFPEF group(P=0.046);E/Em was significantly higher (P<0.001),Em was significantly lower(P=0.002),left atrial diameter was significantly higher(P<0.001),LVEF was significantly lower(P=0.012),BNP values were significantly higher(P=0.001)in HFPEF group than in the non?HFPEF group;There were significant linear correlation between GFR and E/Em(r=-0.428,P=0.001),GFR and the BNP(r=-0.435,P=0.001),E/Em and BNP(r=0.392,P=0.002)in HFPEF group. Conclusion Elderly patients with heart failure but normal ejection fraction were older,and more of them were complicated with hyperten?sion,diabetes,coronary heart disease,atrial fibrillation,or concurrency of these diseases. Glomerular filtration rate was significantly decreased in el?derly patients with HFPEF,which has a significant correlation with diastolic function parameters.

Objective To investigate MR findings and analysis of misdiagnosis of atypical invasive pituitary adenoma.Methods The MR findings of twenty cases of atypical invasive pituity adenomas confirmed by pathology were reviewed ,which were misdiag-nosed as chordomas or meningiomas.Results All the twenty cases showed iso-or slightly hypo-signal on T1 WI,iso-or slightly hy-per-signal on T2 WI;Enhanced scan displayed heterogeneous enhancement.The dynamic enhancement curve showed rapid enhance-ment phase.The bilateral cavernous sinuswere infringed in nine cases,in which the pituity and pituity stalk were not well seen. Among the twenty cases,twelve cases with suprasellar and anterior cranial fossa extension were misdiagnosed as meningiomas;eight cases with clival destruction were misdiagnosed as chordomas.Conclusion The MR features of atypical invasive pituity adenomas are various.In order to avoid misdiagnosis,a comprehensive analysis should be based on a variety of signs.

Objective: Xiaoliu Granule (XLG) is based on the principle of Yiqi Huayu Decoction, this experiment was to study the treating point of XLG on the hysteromyoma rats. Methods: The hysteromyoma rats models was established in rats by loading estrogen and progesterone, to observe the effect of XLG on pathological condition of uterus, and the content of PR , ER, Bcl-2/Bax. Results: The experiments proved that XLG was effective in reducing the proliferation, reversing the proliferative abnormalities of uterus smooth muscle. The XLG also can significantly reduce the content of PR, ER and Bcl-2/Bax. Conclusion: Therefore, XLG was a good approach in treating hysteromyoma. The mechanism of XLG in treating hystermyoma was probably by reducing ER, PR, lowering the E, P sensitivity; reducing expression of Bcl-2, increasing the expression of Bax, and promoting cell apoptosis, etc.

PCR/ASO probes were applied to analyse the T-786C polymorphisms in 5′-flanking region of endothelial nitric oxide synthase(eNOS)gene in type 2 diabetic patients with or without nephropatby and healthy individuals.The results showed that the T-786C polymorphisms of eNOS gene seemed to be related to diabetic nephropathy in type 2 diabetes.