Aim To explore the effect of genetic poly-morphisms of POR on the stable warfarin maintenance doses in Han Chinese patients receiving mechanical heart valve replacement. Methods The association between POR gene polymorphisms and warfarin doses of 185 Han Chinese patients were investigated through ANOVA or t test. SNPs of POR and VKORC1 were de-tected by Sequenom? DNA MassArray genotyping method. CYP2C9*3 was genotyped by polymerase chain reaction-restriction fragment length polymorphism method ( PCR-RFLP ) . Patients ’ clinical characteris-tics, INR value and daily dose were obtained from their medical records. Statistical analysis was performed by SPSS 21. 0 software. Results No mutant carriers of POR rs17148944 , POR rs56256515 and rs72553971 were found in this study. The genotype frequencies of other SNPs were in accordance with Hardy-Weinberg e-quilibrium. In the group of patients with CYP2C9*1*1 , the mutant type carriers ( T carriers ) of POR rs17685 had a significantly higher dose than CC carri-ers(3. 50 ± 1. 07) mg·d-1 vs (3. 14 ± 0. 94) mg· d-1,P =0. 03. Also, in the group of patients with CYP2 C9*1*1 and VKORC1 rs9934438 G allele carri-ers, the mutant type carriers ( T carriers ) of POR rs17685 had a significantly higher dose than CC carri-ers(4. 76 ± 0. 90) mg·d-1 vs (4. 08 ± 1. 03) mg· d-1 ,P=0. 04. No significant difference was found in different genotypes of POR rs2868177 . Conclusion These results illustrate that POR rs17685 T carrier is closely associated with a higher warfarin maintenance dose, suggesting that this SNP is useful for clinical guidance of warfarin.

Objective To study the changes of gastrointestinal movement function in rats with chronic unpredictable mild stress(CUMS) and explore the mechanisms underlying it.Methods The rats were divided into stress model group and control group.The stress model rats were induced by 21-day chronic unpredictable mild stress as well as social-isolated fed.The rate of ink propulsion of gastrointestinal tract and the contraction of intestinal canal in rats were observed.Immunohistochemistry was adopted to detect the expression of OT in rats.Results (1) After the models were induced,weight-gain and sucrose preference of model group ((69.97 ± 9.81) g,(49.05± 5.98) g) were lower than those in control group ((116.27 ± 13.60) g,(83.51 ± 3.08) g) (P ＜ 0.001),and both the crossing-score and rearing-score ((24.00 ± 13.52),(3.90 ± 2.51)) were lower than those in control group ((53.60 ± 27.98),(11.50 ± 8.85)) in the open-field test.(2) The rate of ink propulsion of model group ((67.33 ± 6.24) ％) was decreased when compared to the control group ((76.83 ± 10.00) ％) (P ＜ 0.05),and the intestinal canal contraction amplitude and contraction frequency ((1.37 ± 0.18) g,(0.58 ± 0.02) S-1) were lower than those in control group ((1.88 ± 0.13) g),(0.62 ± 0.04) S-1) (P ＜ 0.05).(3) Compared with the control group (6.07 ± 3.71),OT immunoreactive substance was increased in model group (59.17 ± 16.08) of rats (P＜0.001).Conclusion Chronic stress can cause the decrease in gastrointestinal movement function of rats.These changes may be related to the increased expression of OT in paraventricular nucleus.

Objective:Mutations in epidermal growth factor receptor (EGFR) can predict tumor response to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). However, not all cases of NSCLC with EGFR mutations can respond well;thus, discovering the heterogeneity of NSCLC at the molecular level is necessary. This study aimed to determine the discrepancy in EGFR mutations in primary tumors, N2 lymph nodes, and plasma samples. Methods:Primary tumors, N2 lymph nodes, and plasma samples obtained from 49 patients with stageⅢA-N2 NSCLC were analyzed for EGFR mutations in exons 19 and 21 by using mutant-enriched liquidchip technology. Results:In 49 patients, we detected 18 (36.7%) EGFR mutations in primary tumors, 11 (22.4%) mutations in N2 lymph nodes, and 2 (4.1%) mutations in plasma samples. Eleven (22.4%) cases showed discordance in EGFR mutations between primary tu-mors and N2 lymph nodes. In nine cases, EGFR mutations were detected only in primary tumors, whereas EGFR mutations were de-tected only in N2 lymph nodes in two cases. In addition, EGFR mutations were detected in the plasma samples of two patients, who al-so carry mutations in their primary tumors. Conclusion:A considerable proportion of NSCLC cases showed discrepancy in EGFR muta-tions between primary tumors and N2 lymph nodes. In addition, the detection rate of EGFR mutations was lower in plasma samples obtained from patients with stage IIIA-N2 NSCLC. All of the results indicated tumor heterogeneity at the molecular level during metas-tasis, and this heterogeneity may have implications during treatment with TKIs.

OBJECTIVESTo evaluate the effects of different dosages of cyclosporine A (CsA) on the main semen parameters and sperm morphology of the patients after renal transplantation.

METHODSThe semen of 18 patients after renal transplantation treated with different dosages of CsA was analyzed and the semen parameters and sperm morphology were compared with those of 12 normal volunteers.

RESULTSThere was not significant difference between the main parameters of the patients treated with 1.5-3.0 mg.Kg-1.d-1 of CsA and 3.1-5.5 mg.Kg-1.d-1 of CsA and those of the volunteers (P > 0.05), but the rate of normal sperm morphology was significantly different between the two groups(P < 0.05).

CONCLUSIONSDifferent therapeutic dosages of CsA did not have any effect on most of the semen parameters of the patients after renal transplantation, but did affect the sperm morphology.

Adult ; Cyclosporine ; pharmacology ; Dose-Response Relationship, Drug ; Humans ; Immunosuppressive Agents ; pharmacology ; Kidney Transplantation ; Male ; Semen ; drug effects ; Sperm Count ; Sperm Motility ; drug effects ; Spermatozoa ; drug effects

OBJECTIVETo investigate the relationship between serum resistin level and acute coronary syndrome (ACS) or stable angina pectoris (SAP).

METHODSSixty-five patients, with coronary artery disease, were enrolled and divided into three subgroups: acute myocardial infarction (AMI), unstable angina pectoris (UAP) and SAP, and 26 healthy people were recruited as controls in the cross-sectional study. Serum resistin levels were determined by ELISA (enzyme-linked immunosorbent assay), and WBC (white blood cell count), hsCRP (high sensitive C-reaction protein), CK(max) (maximum of creatinkinase), CK-MB(max) (maximum of isozyme of creatinkinase) and cTnI(max) (maximum of troponin) were measured by standard laboratory methods.

RESULTSThe serum resistin levels were 4 folds higher in AMI patients, 2.43 folds in UAP patients and 1.12 folds in SAP patients than in the healthy controls (P<0.05). The resistin levels were also significantly different between AMI [(8.16+/-0.79) ng/ml], UAP [(5.59+/-0.75) ng/ml] and SAP [(3.45+/-0.56) ng/ml] groups (P<0.01); WBC, hsCRP, CK(max), CK-MB(max) and cTnI(max) were significantly increased in AMI patients over UAP and SAP patients. Spearman analysis showed that serum resistin levels were positively correlated with WBC (r=0.412, P=0.046), hsCRP (r=0.427, P=0.037), CK(max), CK-MB(max) and cTnI(max) (r=0.731, 0.678, 0.656; P<0.01).

CONCLUSIONSerum resistin levels increased with inflammatory factors and myocardial impairment. The results suggest that human resistin might play an important role in the pathogenesis of atherosclerosis and AMI as an inflammatory factor.

Acute Coronary Syndrome ; blood ; Angina Pectoris ; blood ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; blood ; Resistin ; blood

OBJECTIVETo investigate the effect of testosterone on neointimal proliferation and blood lipids after balloon-induced aorta injury in male rabbits.

METHODSTwenty-five male white rabbits were randomly divided into five groups with 5 in each. G1 underwent sham castration served as control group, rabbits in remaining 4 groups were castrated. One week after the castration, rabbits in G3, G4, G5 groups received 3 mg/kg, 6 mg/kg, 12 mg/kg testosterone undecanoate i.m, respectively, G2 was not received. Two weeks after the castration, deendothelializing balloon-induced injury in right iliac artery was performed in all animals. Two weeks after the injury, blood samples were drawn for measurement of plasma testosterone and lipids, and the right iliac arteries were excised for computer imagining analysis.

RESULTCompared with G1, plasma levels of total cholesterol(TC), triglycerides(TG), low density lipoprotein(LDL) in G3, G4 and G5, gradually decreased, plasma levels of high density lipoprotein(HDL)gradually increased. There were most significant differences of plasma TC, TG and LDL(P<0.05) between G2 and G1. There were not significant differences of plasma TC, TG, HDL and LDL among all groups before endothelial denudation and 2 weeks after endothelial denudation (P>0.05). In G3, G4 and G5 the intimal area and radio of intima/media gradually decreased, there were significant differences between G2, G3, G4 and G1(P<0.05), the differences between G1 and G2 were most significant, and those of G5 were close to G1. Endothelial cell repair was observed with electron microscope. Endothelial cells from G2 to G5 became smoother gradually, which in G5 were very close to G1.

CONCLUSIONTestosterone inhibits the intima proliferation induced by balloon-induced injury and improves blood lipids levels. The effects are enhanced by the dose increasing.

Animals ; Aorta ; pathology ; Catheterization ; adverse effects ; Cholesterol ; blood ; Hyperplasia ; Lipids ; blood ; Lipoproteins ; blood ; Male ; Orchiectomy ; Rabbits ; Random Allocation ; Testosterone ; pharmacology ; Triglycerides ; blood ; Tunica Intima ; pathology

OBJECTIVETo observe the relation of androgen levels and atherosclerosis (AS) in elderly males.

METHODSBoth carotid arteries and arteries of lower extremity were examined with Doppler ultrasonography. Those with arteriosclerosis and much atheromatous plaque were designated as case group, and those with normal results formed control group. Total testosterone (TT), free testosterone (FT) and estradiol (E2) were measure by radioimmunoassay, HDL-C, LDL-C, TC and TG were assayed by colorimetry, vascular endothelium growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), intercellular adhesion molecule (sICAM-1) were determined by ELISA.

RESULTFT was significantly lower in case group than in control group (P<0.01), no differences were found in TT, E2. HDL-C in control group was higher than that in case group (P<0.01), TC and TG were higher in case group than those in control group (P<0.05). HDL-C was correlated positively and LDL-C was negatively with FT level, while both TC and TG in case group had negative relation with FT. VEGF was higher in case group (P<0.05), and it had negative relation with FT in both groups. TNF-alpha and IL-6 were significantly higher in case group (P<0.05), and they had negative relation with FT. sICAM-1 was significantly lower in control group than it in case group (P<0.01).

CONCLUSIONThe normal androgen levels, especially FT, have beneficial effect in AS development in elderly males. Low FT level may be an independent risk factor in AS development.

Aged ; Androgens ; blood ; Atherosclerosis ; blood ; diagnostic imaging ; Carotid Arteries ; diagnostic imaging ; Humans ; Male ; Middle Aged ; Risk Factors ; Testosterone ; blood ; Ultrasonography, Doppler

OBJECTIVETo explore the relationship between androgen levels and pathological changes of coronary artery in elderly males.

METHODSOne hundred and twenty-eight in-patients who received coronary angiography were divided into four groups: single vessel lesion group (SV group), double vessel lesion group (DV group), three vessel lesion group (TV group) and control group. The levels of serum total testosterone (TT) and sex hormone binding globulin (SHBG) were assayed by ELISA, and free testosterone (FT) calculated with the Vermeulen formula.

RESULTSThere was significant difference in FT levels among these four groups, while there was no statistical difference in TT levels. FT level in TV group was lower than that in DV group and SV group.

CONCLUSIONSerum levels of free testosterone may be correlated with pathological degree of coronary artery.

Aged ; Coronary Artery Disease ; blood ; pathology ; Enzyme-Linked Immunosorbent Assay ; Humans ; Male ; Middle Aged ; Risk Factors ; Sex Hormone-Binding Globulin ; metabolism ; Testosterone ; blood

OBJECTIVETo evaluate the effect of intensive treatment on the blood sugar, blood lipids and blood pressure levels in incipient diabetes II patients.

METHODSOne hundred and sixty incipient diabetes patients were allocated into two groups according to chronological order: 80 cases received routine treatment and 80 cases received intensive treatment. Fasting blood-glucose (FBG), glycosylated hemoglobin (HbA1C), blood pressure, blood cholesterol (TC), triglyceride (TG), LDL cholesterol-C (LDL-C), alanine aminotransferase (ALT) and aspertate aminotransferase (AST) were tested before treatment. For intensive treatment group blood pressure, blood sugar and blood lipids were regularly tested, and the therapeutic protocols were adjusted according to the test results until the therapeutic target reached. After six months, HbA1C, blood pressure, TC, LDL-C, ALT and AST were tested again and comparison was made between the two groups.

RESULTSThere was a significant decrease in TC and LDL-C in the intensive treatment group compared with those in the routine treatment group (P <0.05).

CONCLUSIONThe intensive treatment on the incipient diabetes II patients facilitate the control of the blood lipids and blood sugar.

Adult ; Aged ; Blood Glucose ; drug effects ; Blood Pressure ; drug effects ; Diabetes Mellitus, Type 2 ; drug therapy ; Female ; Humans ; Hypoglycemic Agents ; therapeutic use ; Lipids ; blood ; Male ; Middle Aged

This study was aimed to analyze the clinical and laboratorial characteristics of patients with chronic lymphocytic leukemia (CLL), as well as their relationship with outcomes of patients. The clinical and laboratorial data of 40 CLL patients admitted from 2004 to 2010 in our hospital were analyzed retrospectively. The results indicated that the most of CLL attacked the elderly male patients with median age 66 (from 42 to 80). Flow cytometric analysis showed that 25 cases were positive for typical immunophenotype of CLL. On the other hand, all the patients clearly expressed CD19 and CD5, 7 cases (17.5%) and 14 cases (35%) were positive for the expression of CD38 and Zap70 respectively. 8 cases harbored a mutated immunoglobulin heavy-chain (VH) gene, among them 4 cases belong to VH3 family. Interphase FISH analysis showed that P53 deletion, RB1 deletion, trisomy 12 and normal chromosome were detected in 6, 3, 1, and 5 cases, respectively. The median PFS in 31 patients received treatment of fludarabine based chemotherapy was 48 months (95%CI: 39 - 57 months), among them 27 cases (87.1%) achieved CR + PR. While PFS was 14 months (95%CI: 10 - 18 months, P < 0.001) in 9 patients received other treatment regimen, out of them only 3 cases (33.3%) achieved CR + PR. Patients with normal level of serum β2-microglobulin at diagnosis showed significantly higher overall survival (78%, 95%CI: 69% - 87%) in 36 months than those with abnormal level of serum β2-microglobulin (47%, 95%CI: 35% - 59%, P = 0.004). Significant difference in the rate of CR + PR was noted in the Zap70 positive group (50%) and in negative group (88.5%, P = 0.006). All of 8 patients with IgVH mutation displayed CR after treatment, while 4 cases (66.7%) archived CR among 6 patients without IgVH mutation. It is concluded that CLL is characterized by high heterogeneity in both clinical features and molecular markers, which are associated with prediction of outcomes for patients. The treatment with fludarabine-based chemotherapy results in a major benefit and long survival for patients with CLL.
ADP-ribosyl Cyclase 1 ; metabolism ; Adult ; Aged ; Aged, 80 and over ; Female ; Flow Cytometry ; Humans ; Immunoglobulin Variable Region ; genetics ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; metabolism ; Male ; Middle Aged ; Mutation ; Retrospective Studies ; ZAP-70 Protein-Tyrosine Kinase ; metabolism