BACKGROUNDAdaptor proteins containing PH domain, PTB domain, and leucine zipper motif 1 and 2 (APPL1/2) play a key role in cell proliferation in many tissues. APPL1 or APPL2 as an adaptor for adiponectin receptors mediates the signaling pathway of adiponectin which acts as an anti-atherosclerotic adipokine. This study aimed to investigate whether genetic variations in the APPL1/2 genes affect the risk of coronary artery disease (CAD) in Chinese patients with type 2 diabetes mellitus (T2DM).

METHODSSeven haplotype-tagging single nucleotide polymorphisms (tag-SNPs) were selected from CHB HapMap database (Phase II) and total 203 CAD-positive cases and 106 CAD-negative controls with T2DM were genotyped for the 7 tag-SNPs by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay.

RESULTSThe minor allele G of rs4640525 at APPL1 locus was protective from CAD in patients with T2DM, with the carriers of genotype CC at higher risk of CAD compared with non-carriers (OR = 2.830, 95%CI 1.285 - 6.230, P = 0.010; OR' = 4.992, 95%CI = 1.758 - 14.173, P' = 0.003, after adjustment for the other known CAD risk factors); the homozygotes of AA at rs11112412 in APPL2 gene had higher risk of CAD compared with those of GG (adjusted OR' = 5.697, 95%CI 1.006 - 32.257, P' = 0.049).

CONCLUSIONGenetic variation(s) in APPL1/2 may be associated with CAD risk in T2DM in Chinese population.

Adaptor Proteins, Signal Transducing ; genetics ; Aged ; Asian Continental Ancestry Group ; Coronary Artery Disease ; genetics ; Diabetes Mellitus, Type 2 ; genetics ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide

OBJECTIVETo investigate the function and mechanism of 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) on activity of VEGF and GPI genes in human pancreatic cancer PC-3 cells incubated under hypoxic conditions.

METHODSHuman pancreatic cancer PC-3 cells were incubated under hypoxic culture conditions. Immunocytochemical staining was used to detect HIF-1alpha protein expression in hypoxic and normoxic PC-3 cells. Semi-quantitative RT-PCR was used to detect the effect of YC-1 on the expression of VEGF and GPI mRNA and HIF-1alpha protein in PC-3 cells. Effect of YC-1 on the expression of HIF-1alpha protein was examined by Western blotting. MTF assay was used to detect proliferation of hypoxicPC-3 cells.

RESULTSHIF-1alpha expression was mainly located in nuclei in hypoxic PC-3 cells. The mRNA synthesis of VEGF and GPI and the protein expression of HIF-1alpha were significantly decreased in the group treated with the highest concentration of YC-1 (100 micromol/L). Compared to placebo, YC-1 inhibited the proliferation of hypoxic PC-3 cells greatly when it was increased to 100 micromol/L.

CONCLUSIONYC-1 inhibited the transcription of VEGF and GPI in hypoxic human pancreatic cancer PC-3 cells. It was induced by down-regulation of HIF-1alpha protein. YC-1 inhibites the proliferation of PC-3 cells exposed to hypoxic conditions.

Blotting, Western ; Cell Hypoxia ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Enzyme Activators ; pharmacology ; Gene Expression Regulation, Neoplastic ; drug effects ; Glucose-6-Phosphate Isomerase ; genetics ; metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Indazoles ; pharmacology ; Pancreatic Neoplasms ; metabolism ; pathology ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription, Genetic ; drug effects ; Vascular Endothelial Growth Factors ; genetics ; metabolism

AIM To establish a UPLC method for the simultaneous content determination of glycosides,rutinoside,myricitrin,hyperoside,isoquercitrin,guaijaverin,astragalin,quercitrin and afzelin in the shoots of Toona sinensis Roemer.METHODS The analysis of 60％ methanol extract of T.sinensis shoots was performed on a 35 ℃ thermostatic Waters XBridge Shield RP18 column (2.1 mm × 150 mm,1.7 μm),with the mobile phase comprising of acetonitrile-water flowing at 0.35 mL/min in a gradient elution manner,and the detection wavelength was set at 350 nm.RESULTS Eight flavonol glycosides showed good linear relationships within their own ranges (r≥ 0.9992),whose average recoveries were 98.3％-103.5％ with the RSDs of 0.46％-3.36％.CONCLUSION This accurate,stable and reproducible method can be used for the quality control of T.sinensis shoots.

OBJECTIVETo determine the effect of laparoscopic radiofrequency ablation of T1aN0M0 renal cell carcinoma (RCC) with regular follow-up.

METHODSAll patients underwent surgery from March 2006 to March 2009. Eight cases were solitary kidney. Twenty-two cases of left RCC and 18 cases of right RCC were diagnozed by ultrasonography and CT scanning.All of the cases were T1aN0M0 stage. No metastasis was found by iconography test. By ultrasound positioning, laparoscopic radiofrequency were performed on the renal tumor. All patients were followed up with eGFR and enhanced-CT.

RESULTSAll patients underwent laparoscopic radiofrequency ablation surgery successfully. The mean operation time was (101 ± 19) minutes and the mean blood loss was (90 ± 14) ml (no blood transfusion pre- and post-operation). During postoperative follow-up, enhanced CT revealed complete ablation in 39 cases (the success rate was 97.5%), and 1 residue tumor was confirmed by enhanced CT 7 days post operation. This patient was under close surveillance because of solitary kidney. No progression of the residue tumor was found during the follow-up. One case of recurrence was confirmed by enhanced CT in 6 month after operation. The 3-year recurrence rate was 2.5%. No further intervation was performed on this patient and no change was found in the recurrence area during the follow-up. Both 3-year total survival rate and 3-year cancer specific survival rate were 100%. The mean eGFR was (72 ± 9) ml/(min·1.73 m(2)) in 3 years after surgery. There was no significant difference between pre-and post-operation (P > 0.05).

CONCLUSIONMid-term follow-up results show the effectiveness and safety of laparoscopic radiofrequency ablation in the treatment for T1aN0M0 RCC and have no negative influence on the renal function.

Carcinoma, Renal Cell ; mortality ; surgery ; Catheter Ablation ; methods ; Female ; Follow-Up Studies ; Humans ; Kidney Neoplasms ; mortality ; surgery ; Laparoscopy ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; epidemiology ; Treatment Outcome

Objective To evaluate the role of new strategy in the transmission control of schistosomiasis in Poyang Lake re-gion. Methods The information and epidemic data of schistosomiasis control were collected and analyzed in Poyang Lake re-gion from 2005 to 2016. Results After eleven years of carrying out the new strategy,thirteen counties achieved the objective of transmission control in Poyang Lake region. In 2016,the number of schistosomiasis cases and human infection rate were 10301 and 0.03％,decreased by 89.64％and 99.45％compared with those in 2005,respectively. The number of cattle and schistosome-infected cattle were 68152 and 5,decreased by 50.84％and 99.83％compared with those in 2005,respectively. The average density of Oncomelania hupensis snails was decreased by 61.52％. No schistosome-infected snails were found since 2014. Con-clusion The new strategy accurately locates the key points and targets of schistosomiasis transmission chain ,which has con-trolled the human and animal's fecal eggs from polluting grassland,and cut off the transmission chain,reduced both the infec-tion rates of human and animal and the re-infection risk,and promoted to achieve the target of schistosomiasis transmission con-trol in Poyang Lake region.

UNLABELLEDTo study the clinical significance of the expression of antiapoptosis gene, survivin and bcl-2, and proapoptosis gene, Fas and bax, in acute myeloid leukemia (AML), RT-PCR was used to examine the expression of survivin and flow cytometry (FCM) to detect the expression of Fas, bcl-2, bax and bcl-2/bax ratio in 68 cases of AML. The results demonstrated that: (1) The positivity of survivin mRNA expression was significantly higher in AML compared to control (70.6% vs 30%, P < 0.05). (2) The expression of Fas and bcl-2 in AML before treatment was significantly higher than that in control (P < 0.001), but the bax expression did not (P > 0.05). (3) The survivin-positive AML cases showed a significantly lower Fas and higher bcl-2 expression in comparison with survivin-negative ones (P < 0.01 and P < 0.001, respectively), but the bax did not (P > 0.01). (4) Survivin-positive AML cases had a lower CR rate as compared with survivin-negative cases (64.6% vs 90%, P < 0.05). (5) The survivin-positive CR cases showed a decreased expression of Fas and bcl-2 after treatment in comparison with pretreatment expression (P < 0.001), but the bax expression remained unchanged before and after therapy. The survivin-positive NR cases showed a significantly decreased Fas and increased bcl-2 expression as compared with pretreatment expression (P < 0.001). bcl-2/bax ratio was also significantly higher in NR cases.

IN CONCLUSION70.6% AML cases showed positive for survivin expression with a lower CR rate, the survivin-positive AML showed a low Fas with high bcl-2 expression and bcl-2/bax ratio as compared to the survivin-negative cases.

Adolescent ; Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Biomarkers, Tumor ; biosynthesis ; genetics ; Bone Marrow Cells ; drug effects ; metabolism ; Female ; Flow Cytometry ; Gene Expression Regulation, Neoplastic ; Humans ; Inhibitor of Apoptosis Proteins ; Leukemia, Myeloid, Acute ; drug therapy ; genetics ; metabolism ; Male ; Microtubule-Associated Proteins ; genetics ; Middle Aged ; Neoplasm Proteins ; Proto-Oncogene Proteins ; biosynthesis ; Proto-Oncogene Proteins c-bcl-2 ; biosynthesis ; RNA, Messenger ; drug effects ; genetics ; metabolism ; bcl-2-Associated X Protein ; fas Receptor ; biosynthesis

OBJECTIVETo analyze the clinical features and prognostic factors of primary gastric diffuse large B-cell lymphoma (PG-DLBCL) and to evaluate the staging system and treatment modality of PG-DLBCL.

METHODSThe clinicopathological data of 69 patients with PG-DLBCL were retrospectively analyzed. Event-free survival (EFS) and overall survival (OS) were the primary endpoints.

RESULTSThe EFS rates at 1, 3, and 5 years were 83.8%, 71.1%, and 69.0%, respectively, with a mean EFS of 91.3 months. The 1-, 3-, and 5-year OS rates were 91.3%, 80.3%, and 72.4%, respectively, with a mean OS of 98.8 months. Univariate analysis revealed that either EFS or OS was significantly prolonged by the following factors (P < 0.05): modified Ann Arbor stage I(E) or II(E1) disease; normal lactate dehydrogenase (LDH) level; normal hemoglobin level; normal albumin level; International Prognostic Index (IPI) of 0 or 1; tumor size < 5 cm; and less depth of invasion. While gender, age, B symptoms at presentation, performance status and treatment modality were not significantly associated with the prognosis (P > 0.05). Cox regression model revealed that only modified Ann Arbor stage and albumin level were independent prognostic factors for EFS and OS.

CONCLUSIONThe most accurate staging system and the exact role of different therapeutic options for PG-DLBCL are still debated. Further randomized prospective studies with a large number of patients are still needed to establish an optimal management for this disease.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Albumins ; metabolism ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Combined Modality Therapy ; Cyclophosphamide ; therapeutic use ; Disease-Free Survival ; Doxorubicin ; therapeutic use ; Female ; Follow-Up Studies ; Gastrectomy ; methods ; Hemoglobins ; metabolism ; Humans ; L-Lactate Dehydrogenase ; blood ; Lymphoma, Large B-Cell, Diffuse ; blood ; pathology ; therapy ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prednisone ; therapeutic use ; Proportional Hazards Models ; Radiotherapy, High-Energy ; Retrospective Studies ; Rituximab ; Stomach Neoplasms ; blood ; pathology ; therapy ; Survival Rate ; Vincristine ; therapeutic use ; Young Adult

BACKGROUNDPigment epithelium-derived factor (PEDF) is expressed in several normal organs and identified as an inhibitor of neovascularization. In the present study, we investigated the effect of PEDF in an in vitro model of ocular choroidal neovascularization.

METHODSMicrodissection was used to isolate the human choroidal endothelial cells (CECs), followed by the use of superparamagnetic beads (Dynabeads) coated with the CD31 antibody, which selectively binds to the endothelial cell surface. The mitogenic and motogenic effects of vascular endothelial growth factor (VEGF) on cultured choroidal capillary endothelial cells were examined in the presence or absence of PEDF (1, 10, 100, and 1000 ng/ml) using cell counts and migration assays.

RESULTSCells bound to the beads were isolated using a magnetic particle concentrator and they were successfully cultured and characterized to be endothelial cells that possessed greater than 95% immunoreactivity to von Willebrand factor. PEDF suppressed the proliferation and migration of VEGF-induced choroidal capillary endothelial cells. However, the concentration of PEDF which we used has little effect on normal CECs.

CONCLUSIONSPEDF played an important role on the growth and migration of VEGF-stimulated choroidal endothelial cell. These findings suggest that PEDF may be an effective approach to the treatment of choroidal neovascular disorders.

Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Choroid ; blood supply ; drug effects ; Choroidal Neovascularization ; drug therapy ; Endothelial Cells ; cytology ; drug effects ; Eye Proteins ; pharmacology ; Humans ; Nerve Growth Factors ; pharmacology ; Serpins ; pharmacology ; Vascular Endothelial Growth Factor A ; pharmacology

Objective To investigate the distribution of gene polymorphism of CYP450 2C9 and VKORC1-1639A/G in the Chinese population as well as the difference of genetic polymorphism between Chinese Han population and other ethnic populations.Contribution of CYP2C9 and VKORC1 genotype to the maintenance doses on warfarin was also studied.Methods The genotype and allele frequencies were calculated and compared with those in other populations.One hundred and one patients with stable anticoagulation with warfarin under a target international normalized ratio(INR)of 2.0 to 3.0 were enrolled for studying the relationship between the CYP2C9 and VKORC1 gene polymorphism and the warfarin maintaining dosage.Results CYP450 2C9~*3 + 1075C/A allele frequencies were:AA in 449 cases(92.2%),AC in 36 cases(7.4%)and CC in 2 cases(0.4%),respectively.VKORC1-1639A/G allele frequencies were AA in 415 cases(85.2%),GA in 72 cases(14.8%),but GG in no case(0.0%),respectively.When linear stepwise regression analysis was used to identify factors contributing to warfarin stable dose,the final equation was:ln(D)=0.346 + 0.017(weight)-0.376(CYP450 2C9~*3 + 1075C/A)+ 0.148(VKORC1-1639A/G)-0.002(age)(r=0.827,P=0.02).Conclusion There existed significant gene polymorphism CYP450 2C9~*3 + 1075C/A and VKORC1-1639A/G in the Chinese Han population.Both Gene polymorphisms of CYP450 2C9*3 + 1075C/A and VKORC1-1639A/G were significantly affecting the maintaining dose of warfarin in the Chinese population.

Gene Expression ; Hep G2 Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Liver Neoplasms ; genetics ; metabolism