OBJECTIVETo explore the clinical usage of the methods and tools of the 10-year's risk estimation of ischemic cardiovascular disease (ICVD) in Chinese.

METHODSThe risk of ICVD in 2287 middle-aged Qingdao people was evaluated by the methods and tools of the 10-year's risk estimation of ICVD in Chinese, which was developed by Cardiovascular Institute, Chinese Academy of Medical Sciences.

RESULTS(1) 98.16% of male and 99.39% of female had a 10-year absolute risk of ICVD less than 10%. 0.19% of male and 0.15% of female had a 10-year absolute risk of ICVD higher than 20%. (2) In the low risk group (absolute risk < 10%) detection rate of abnormal SBP, FBG, TC, BMI was 100%, 20.8%, 75%, 87.5% respectively. While in the high risk group (absolute risk > or = 20%) detection rate of abnormal SBP, FBG, TC, BMI was 7.31%, 3.4%, 37.74%, 59.26% respectively.

CONCLUSIONSThe prediction models and simplified tools for estimating 10-year-risk of ICVD in Chinese can predict satisfactorily the occurrence of cardiovascular disease in Qingdao area.

Adult ; Asian Continental Ancestry Group ; China ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Models, Biological ; Myocardial Ischemia ; epidemiology ; prevention & control ; Risk Assessment ; methods

OBJECTIVETo investigate the antifibrotic effect of the Chinese herbs Modified Danggui Buxue Decoction (, MDBD) on adraimycin-induced nephropathy in rats.

METHODSThirty-two male Sprague Dawley albino rats were randomly divided into 4 groups: the control, model, and two treatment groups, with 8 in each group. Nephropathy was induced in the latter 3 groups by intravenous injection of adriamycin. Rats in the two treatment groups received intragastric administration of benazepri (a positive control) or MDBD, which is composed of extracts of Radix Angelicae sinensis, Astragalus membranaceus (Fisch.) Bge and Rhizoma chuanxiong. Serum albumin, blood lipids, 24-h urine protein and urine N-acetyl-b-D-glucosaminidase (NAG) were measured every 2 weeks. The ratio of kidney to body weight was measured. The expressions of extracellular matrix proteins in the renal cortex, including colleagen IV (Col-IV) and fibronectin (FN), were examined by immunohistochemistry, and the transcription of genes encoding transforming growth factor β1 (TGF-β1), the tissue inhibitors of matrix metalloproteinase 1 (TIMP-1) and matrix metalloproteinase 9 (MMP-9) were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) at the end of the 8-week treatment.

RESULTSCompared with the untreated rats in the model group, MDBD significantly increased serum albumin, lowered the blood lipids and decreased the ratio of kidney to body weight. MDBD significantly reduced the excretion levels of urinary protein and NAG as well as the accumulation of extracellular matrix (ECM), including Col-IV and FN, in the renal cortex. Further, MDBD decreased TIMP-1 and TGF-β1 gene expressions and increased MMP-9 gene expression in the kidney.

CONCLUSIONSMDBD was effective in treating the rat model of nephropathy. The clinical benefit was associated with reduction of renal fibrosis. The antifibrotic effect of MDBD may be mediated through the regulation of TIMP-1, MMP and TGF-β1 gene expressions.

Acetylglucosaminidase ; urine ; Animals ; Body Weight ; drug effects ; Collagen Type IV ; metabolism ; Doxorubicin ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Fibronectins ; metabolism ; Fibrosis ; Gene Expression Regulation ; drug effects ; Immunohistochemistry ; Kidney Cortex ; drug effects ; enzymology ; pathology ; physiopathology ; Kidney Diseases ; blood ; drug therapy ; physiopathology ; urine ; Kidney Function Tests ; Male ; Matrix Metalloproteinase 9 ; genetics ; metabolism ; Organ Size ; drug effects ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Serum Albumin ; metabolism ; Time Factors ; Tissue Inhibitor of Metalloproteinase-1 ; genetics ; metabolism ; Tissue Inhibitor of Metalloproteinase-2 ; genetics ; metabolism ; Transforming Growth Factor beta1 ; genetics ; metabolism ; Triglycerides ; blood

OBJECTIVETo investigate the feasibility of prevention and treatment of early scar through observing the effect of feeding immunosuppressive drug cyclophosphamide on rabbit ears hypertrophic scar tissue in early stage.

METHODSThirty-two Rabbit ears were used to establish animal models for hypertrophic scar and randomly divided into four groups: group of distilled water (A), group of cyclophosphamide 5 mg x kg(-1) x d(-1) (B), group of 10 mg x kg(-1) x d(-1) (C), group of 30 mg x kg(-1) x d(-1) (D). Before animal models were built and after administration for 14 days, 28 days, leukocytes and lymphocytes were detected. After 28 days, specimens were harvested and underwent HE staining and VG staining in order to assess HI, NA, AA value changes. The data (HI, NA, AA) from each group were compared by analysis of variance, and the variance for the rank sum test when missing.

RESULTSOn the 14th day, the number of leukocytes in group A, B, C, D were (8.62 +/- 0.58) x 10(9)/L, (4.48 +/- 0.41) x 10(9)/L, (2.7 +/- 0.26) x 10(9)/L, (1.33 +/- 0.27) x 10(9)/L; the number of lymphocytes in group A, B, C, D were (3.11 +/- 0.21) x 10(9)/L, (1.67 +/- 0.16) x 10(9)/L, (0.42 +/- 0.10) x 10(9)/L, (0.40 +/- 0.09) x 10(9)/L. On the 28th day, the number of leukocytes in group A, B, C, D was (8.63 +/- 0.53) x 10(9)/L, (5.10 +/- 0.27) x 10(9)/L, (3.10 +/- 0.26) x 10(9)/L, (1.98 +/- 0.20) x 10(9)/L; the number of lymphocytes A, B, C, D was (3.06 +/- 0.16) x 10(9)/L, (2.08 +/- 0.14) x 10(9)/L, (0.96 +/- 0.19) x 10(9)/L, (0.14 +/- 0.07) x 10(9)/L. On the 14th day and 28th day, the number of leukocytes and lymphocytes in experimental groups was reduced, showing a negative relation with cyclophosphamide dose (P < 0.05). The HI in group of A, B, C, D was 3.02 +/- 0.24, 2.59 +/- 0.43, 2.06 +/- 0.19, 1.63 +/- 0.11; the AA was 40.49 +/- 2. 07, 35.29 +/- 1.99, 28.36 +/- 1.87, 24.99 +/- 1.82; the NA was 4570.5 +/- 259.3, 4222.5 +/- 199.6, 3540.3 +/- 170.3, 3341.4 +/- 228.8. The difference in HI, AA, NA between control group and any of the experimental groups was statistically significant (P < 0.01). Each group, with the dose increased, except NA content of group C and D, the HI, AA, NA was more smaller, negative correlation, the difference was statistically significant (P < 0.05).

CONCLUSIONSFeeding cyclophosphamide can inhibit leukocytes and lymphocytes number, so as to inhibit the proliferative activity of hypertrophic scar. It has significant effect on prevention of hypertrophic scar on rabbit ears in early stage.

Animals ; Cicatrix, Hypertrophic ; drug therapy ; prevention & control ; Cyclophosphamide ; pharmacology ; Ear ; pathology ; Female ; Leukocyte Count ; Leukocytes ; drug effects ; Lymphocyte Count ; Lymphocytes ; drug effects ; Male ; Rabbits

Based our previous work, twelve purine derivatives were designed and synthesized as dual modulators of GPR119 and DPP-4by conjugating the GPR119 activating and DPP-4 inhibiting fragments with the position 6 and 9 of purine core via an approach of merged pharmacophores. Compound 11, bearing 2-fluoro-4-methylsulphonyl anilide and cyanopyrrolidine moieties, exhibited the most potent GPR119 agonistic activities (EC₅₀ = 0.33 μmol·L^-1, IA = 71.1%) and DPP-4 inhibitory (58.4% inhibition at 10 μmol·L^-1, 21.2% inhibition at 1 μmol·L^-1) activities in the in vitro antidiabetic study. Subsequently, we performed studies on structure activity relationships and molecular docking to guide the further drug design.

OBJECTIVETo isolate and purify a new phospholipase A2 (PLA2) homologue from Agkistrodon blomhoffii siniticus and investigate its effects on the gene expression profile of Hep3B cells.

METHODSThe PLA2 homologue was isolated and purified by reverse-phase high-performance liquid chromatography (HPLC) and its purity was determined also by HPLC. The relative molecular mass of the homologue was measured by electrospray ionization mass spectrum. The gene expression profile of Hep3B cells was detected with gene chip after exposure of the cells to 139 microg/ml PLA2 homologue for 12 h.

RESULTSThe purity of the PLA2 homologue was 97.2%, whose relative molecular mass was 13,900. After exposure of Hep3B cells to 139 microg/ml PLA2 homologue for 12 h, 19 genes were down-regulated and 20 up-regulated in the cells. The genes showing altered expressions in response to the exposure were mainly involved in cell cycle control and DNA damage repair, cell apoptosis and senescence, production of signal transduction molecules and transcription factors, cell adhesion, angiogenesis, and tumor invasion and metastasis.

CONCLUSIONSThe PLA2 homologue induces alterations in the expression of a wide variety of genes involved in the growth and metastasis of tumor cells. The results of this study provide clues for further study of the possible mechanism for the action of PLA2 homologue on Hep3B cells.

Agkistrodon ; Animals ; Carcinoma, Hepatocellular ; genetics ; Chromatography, High Pressure Liquid ; DNA Damage ; drug effects ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; drug effects ; Hyaluronan Receptors ; biosynthesis ; genetics ; Isoenzymes ; Liver Neoplasms ; genetics ; Phospholipases A ; isolation & purification ; pharmacology ; Phospholipases A2 ; Proto-Oncogene Proteins c-bcr ; biosynthesis ; genetics ; Snake Venoms ; enzymology ; Tumor Cells, Cultured

OBJECTIVETo observe the effect of glucagon-like peptide-1 (GLP-1) on hypoxia-reoxygenation (H/R) induced injury in neonatal rat cardiomyocytes.

METHODSCultured neonatal rat cardiomyocytes were randomly divided into seven groups: normal control group, H/R group, GLP-1 + H/R group, GLP-1 + H/R + UO126 group, GLP-1 + H/R + LY294002 group, H/R + UO126 group, H/R + LY294002 group. LDH activity, apoptosis rate of cardiomyocytes, Caspase-3 activity were detected.

RESULTSCompared with normal control group, the activity of LDH, cardiomyocyte apoptosis rate, Caspase-3 activity were all significantly increased in H/R group (all P < 0.01). However, compared with H/R group, these changes were significantly attenuated in GLP-1 + H/R group [the activity of LDH (128.47 +/- 7.96) U/L vs. (223.96 +/- 22.10) U/L, P < 0.01, and cardiomyocyte apoptosis rate (2.84 +/- 2.56)% vs. (12.58 +/- 6.69)%, P < 0.01, and Caspase-3 activity (36,809 +/- 4750) RLU vs. (57,602 +/- 9161) RLU, P < 0.01], while LY294002 (PI3K inhibitor) and UO126 (MAPK inhibitor) could block the effects of GLP-1 in cardiomyocytes underwent H/R injury.

CONCLUSIONSGLP-1 could protect H/R injury mainly by inhibiting cardiomyocytes apoptosis via activating PI3K/Akt and MAPK signaling pathway.

Animals ; Animals, Newborn ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Hypoxia ; Cells, Cultured ; Glucagon ; metabolism ; Glucagon-Like Peptide 1 ; pharmacology ; Myocardial Reperfusion Injury ; metabolism ; Myocytes, Cardiac ; drug effects ; Rats ; Rats, Wistar

OBJECTIVETo summarize the experience of surgical resection of 103 hilar cholangiocarcinoma.

METHODSOne hundred and three consecutive cases of hilar cholangiocarcinoma who underwent surgical resection at our hospital over the past ten years were reviewed retrospectively. The clinical data and long-term outcome were analyzed.

RESULTSOut of 103 cases, 43 patients underwent radical resection (41.7%), and 60 patients underwent palliative resection. There were 34 patients developed postoperative complications and 8 patients died in hospital. For the radical resection group, the median survival time was 29.9 months and 1-year, 3-year, 5-year survival rate was 69.6%, 42.0%, 20.9%, respectively, which was significant greater than 34.1%, 10.2%, 0 of the palliative resection group (P < 0.05). Over the past five years, 42 cases underwent pre-operative drainage of bile and the rate of combined liver resection reached 53.8%. The tumor radical resection rate has increased to 45.7%, the median survival time have reached 24.7 months (P < 0.05).

CONCLUSIONSImprovement of pre-operative management, intraoperative pathology for resection margin, and combined liver resection may help in increasing the radical resection rate. Radical resection can improve postoperative survival, and produce a satisfactory outcome for patient with hepatic hilar cholangiocarcinoma.

Adult ; Aged ; Bile Duct Neoplasms ; mortality ; surgery ; Bile Ducts, Intrahepatic ; Cholangiocarcinoma ; mortality ; surgery ; Digestive System Surgical Procedures ; methods ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Survival Rate

OBJECTIVETo observe the differential expression characteristics of microRNAs (miRNAs) in renal tissues in puromycin aminonucleoside (PAN) nephritic model, and its relationship with key structural molecules of slid diaphragm (SD) nephrin and podocin and expression of skeleton protein synaptopodin; and to explore the in vivo mechanisms of Leizhi capsule (LZC) for ameliorating the expressions of nephrin, podocin and synaptopodin and reducing proteins by regulating the modal rat renal tissues miRNAs.

METHODFifty male Wistar rats were randomly divided into five groups: the control group (A), the model group (B), the LZC-treated group (C), the multi-glycoside of Tripterygium wilfordii (GTW)-treated group (D) and the valsartan-treated group (E). Apart from group A, all of rats in the remaining groups are injected with PAN (100 mg x kg(-1)) through jugular veins to establish the PAN nephropathy model. On the 2nd day after PAN nephropathy model was established, group C was orally administered with LZC (5 mL x kg(-1) x d(-1)) in group C, group DGTW (10 mL x kg(-1) x d(-1)), and E group valsartan (7.5 mL x kg(-1) x d(-1)), while groups A and B were intervened with physiological saline, for 10 days. Body weight and 24 h urinary protein ration (Upro) in all rats were measured at day 0, 3, and 9. All rats were sacrificed at day 11 after the establishment of the model, and their blood and renal tissues were collected to observe such blood biochemical indicators including albumin (Alb), serum creatinine (Scr), blood urea nitrogen (BUN) and glomerular ultrastructure (podocyte foot process form) and expressions of dicer enzyme, nephrin, podocin and synaptopodin in renal tissues. Meanwhile, the differential expressional characteristics of miRNAs in renal cortex were analyzed by biochip assay. Additionally, the differential expressional volumes of rno-miR-23a, rno-miR-300-3p, rno-miR-24 and rno-miR-30c were measured by real-time PCR.

RESULTProteinuria, renal dysfunction, hypoproteinemia and podocyte foot process fusion were investigated in model rats induced by PAN. In renal tissues of PAN nephropathy model rats, dicer enzyme affected the expressions of nephrin, podocin and synaptopodin in podocytes, up-regulated the expressions of rno-miR-23a and rno-miR-300-3p, and down-regulated the expressions of rno-miR-24 and rno-miR-30c. The miRNAs with differential expressions included rno-miR-24, rno-miR-30c, rno-miR-23a and rno-miR-300-3p. LZC could improve the general state, proteinuria, serum BUN and podocyte foot process fusion of PAN nephropathy model rats, reduced the expressions of dicer enzyme, increased the expressions of nephrin, podocin and synaptopodin in podocytes, weakened the up-regulated rno-miR-23a and rno-miR-300-3p, and strengthened the down-regulated rno-miR-24 and rno-miR-30c in renal tissues.

CONCLUSIONPAN in vivo impacts the expressions of miRNAs in renal tissues, intervenes the expressions of nephrin, podocin and synaptopodin in podocytes, damages podocyte structures and functions and generates proteinuria by means of differential expression of dicer enayme/miRNAs. LZC can reduce proteinuria in PAN nephropathy model rats. Its mechanism may intervene dicer enayme/miRNAs differential expression, regulate nephrin, podocin and synaptopodin in podocytes and improve podocyte structures and functions.

Animals ; Drugs, Chinese Herbal ; administration & dosage ; Gene Expression ; drug effects ; Humans ; Kidney Diseases ; chemically induced ; drug therapy ; genetics ; metabolism ; Male ; MicroRNAs ; genetics ; metabolism ; Puromycin Aminonucleoside ; adverse effects ; Rats ; Rats, Wistar

Objective To study the correlation between the deformation and displacement trend of the lumbosacral vertebra (L1-S1) for two typical scoliosis spines under vertical loads,so as to provide the mechanical basis of treatment and prevention of scoliosis in clinic.Methods The X-ray computed tomography (CT) images of two typical scoliosis spines (Lenke-4AN type and Lenke-5CN type) were converted into 3D models,and their finite element models were then established and verified.The internal stress distribution and displacement variation of the models were calculated by the finite element software;the correlation between the lumbosacral vertebral structure and displacement of the spine was analyzed.Results Under the same boundary conditions and load cases,the stress and displacement for two kinds of lumbosacral vertebral models showed different trends.Due to its leftleaning and forward convex bending deformation as well as the relatively large lordosis angle (60°) and smaller left-leaning angle (17.37°),the Lenke-4AN type lumbosacral spine produced slightly small forward convex displacement (8.18 mm) and relatively large left-leaning displacement (0.97 mm).The Lenke-5CN type lumbosacral spine showed left-leaning and forward convex bending deformation as well,with relatively large lordosis angle(59°) and left-leaning angle (26.97°),so it produced more severe left-leaning displacement (20.65 mm) andforward convex displacement (9.22 mm).Conclusions The deformation trend of lumbosacral vertebra is closelyrelated to its structural characteristics,and different scoliosis lumbosacral vertebral structures will cause the corre-sponding deformation trend.The research findings are important for the prevention and treatment of scoliosis.

BACKGROUNDImmune cells within a tumor microenvironment have shown modulatory effects on tumor angiogenic activity. Renal cell carcinoma (RCC) is a hypervascular tumor that reportedly increases the frequency of regulatory T cells (Tregs) in tumor tissues. This study investigated the correlation between Tregs infiltration and angiogenic status in RCC.

METHODSThirty-six patients with RCC were enrolled in the present study, and twenty age-matched healthy donors were included as the control. Tregs were defined as CD4(+)CD25(high)CD127(low/-) T cells. The frequency of Tregs in peripheral blood and tumor infiltrating lymphocytes (TILs) were determined by flow cytometry. The expression of vascular endothelial growth factor (VEGF) in surgical resection specimens were measured with a commercial enzyme-linked immunosorbent assay (ELISA) kit. Microvessel density (MVD) was calculated on slides stained with CD34 antibody. Spearman's rank correlation was performed to evaluate the correlation between the frequencies of Tregs in TILs and VEGF values, as well as between frequencies of Tregs and MVD determinations.

RESULTSCompared to healthy controls, the frequency of peripheral blood Tregs was significantly increased in patients with RCC (P < 0.05). The percentage of tumor-infiltrating Tregs was higher than that of peripheral blood Tregs in patients with RCC (P < 0.01). In addition, the frequency of tumor-infiltrating Tregs was shown to significantly correlate with the pathological stage (P < 0.05) and nuclear grade (P < 0.01). Importantly, a significant positive correlation was observed between the frequency of tumor-infiltrating Tregs and VEGF protein expression (r = 0.51, P < 0.05), as well as between frequencies of Tregs and MVD score (r = 0.39, P < 0.05).

CONCLUSIONSThese observations suggest that the high pro-angiogenic status of RCC may be associated with the accumulation of Tregs in the local microenvironment. Angiogenesis networks may be connected with immune tolerance units and cooperate with each other to facilitate tumor growth and progression.

Adult ; Aged ; Carcinoma, Renal Cell ; immunology ; metabolism ; Cells, Cultured ; Enzyme-Linked Immunosorbent Assay ; Female ; Flow Cytometry ; Humans ; Immunohistochemistry ; Kidney Neoplasms ; immunology ; metabolism ; Lymphocytes, Tumor-Infiltrating ; immunology ; Male ; Middle Aged ; Neovascularization, Pathologic ; immunology ; metabolism ; T-Lymphocytes, Regulatory ; immunology