Objective To explore the expression of breast cancer susceptibility gene 1 (BRCA1) in human colorectal cancer and its correlation with the efficacy of platinum-based chemotherapy.Methods Seventy-eight cases of colorectal cancer patients treated with platinum-based chemotherapy after surgery were collected.The surgical specimens of them were taken.Fourteen normal colonic mucosa specimens and 12 non-cancerous tissues of colorectal cancer specimens were obtained.The expression of BRCA1 in tissues was detected by immunohistochemistry and analyzed by x2 test.The colorectal cancer patients were followed up for survival time.Comparison of survival analysis was performed by Kaplan-Meier survival curves and Log-rank test.Results The positive rate of the BRCA1 expression in colorectal cancer tissue (52.6 ％,41/78) was lower than that of para-cancer tissue (11/12,x2 =6.518,P=0.011) and normal colonic mucosa tissue (13/14,x2 =7.949,P=0.005).The poorer the differentiation of colorectal cancer,the lower the positive rate of BRCA1 (x2=14.160,P=0.001).The median disease-free survival time of BRCA1 negative colorectal cancer patients was 51.0 months (95 ％ CI:47.7 to 54.4 months),which was longer than that of BRCA1 positive patients (45.0 months,95 ％CI:36.6 to 53.4 months,x2 =4.367,P=0.032).Conclusions Receiving oxaliplatin based chemotherapy may be a survival benefit for BRCA1 negative colorectal cancer patients.The expression of BRCA1 may be an index for chemotherapy options and prognosis evaluation for colorectal cancer patients after surgery.

AIM:Vascular smooth muscle cell (SMC) proliferation and migration from the arterial wall media into the intima are believed to play a critical role in the pathogenesis of restenosis. Several studies have demonstrated that phosphothioate (PS) oligodeoxynucleotides targeted against genes involved in SMC proliferation inhibits in vitro SMC proliferation and migration. However, the therapeutic effect of antisense ODN on the individual who receives the treatment of delivery of the agent depends on the efficacy of this agent in great degree. We investigated the inhibition effect of a novel agent, insulin-antisense-c-myb-PS-ODN on SMC proliferation in vitro.　METHODS：The rat aortic artery SMCs were cultured in Dulbecco's modified Eagel's medium. The passage 8 to 13 were used as the experiment. Cell surface receptor binding assay was quantified through counting gamma particles emitted from 125　　　　I labeled insulin. SMC rapid proliferation was brought by stimulation of high concentration of fetal bovine serum (FBS). The novel agent of insulin conjugated to the antisense-c-myb-PS-ODN was obtained via incubation of both in condition of certain reagents, pH, temperature, and ion concentration. The characterization and purification of the agent was performed through HPLC. Inhibition of SMC proliferation was reflected by incorporation rate of trillium labeled thymidine deoxyribonucleotide.RESULTS：The binding efficacy of insulin to the receptor was remarkably increased in SMC cultured in supplement of 20% FBS. The inhibition effect of conjugator insulin-c-myb-antisense-PS-ODN was stronger than that of the simple c-myb-antisense-PS-ODN. The inhibition rate of conjugator and simple form on SMC proliferation were 48.34% and 29.54%, respectively. CONCLUSION：The binding efficacy and specificity of c-myb-antisense-PS-ODN to SMC may be enhanced by the insulin receptor mediation through the insulin-insulin receptor interaction. The insulin-receptor targeted method may be a potential and specific therapeutic pathway for restenosis.

Objective To investigate the value of Cytochrome P450 (CYP3A5) * 3 gene polymorphism in providing individualized administration for the use of tacrolimus (Tac) in renal transplantation recipients.Method Pyrophosphate sequencing method was used to determine the CYP3A5 * 3 genotype of renal transplant patients in the first day after surgery.Sixty recipients were divided into experiment group and control group.Both groups of patients were routinely given the initial dose of Tac-4.0 mg/day in the first day after surgery.The experiment group of patients were given different doses of Tac based on the different CYP3A5 * 3 genotypes at the third day after surgery [for AA:0.12 mg/(kg· day),and for GG:0.06 mg/(kg· day)],and the control group of patients were given different dosages of Tac according to drug concentration.Different parameters were compared between two groups of patients:percentage of patients reaching the target concentration (3-8 μg/L) at the fifth day after surgery,days required to reach the target concentration level,times needed to adjust the dosage of Tac within two weeks.Result The percentage of patients reaching the target concentration in experiment group and control group was 90％ and 46.67％,respectively (P＜ 0.05).Days required to reach the target concentration were (3.67 ± 1.32) and (7.57 ± 3.42) on average,respectively (P ＜ 0.05).Times of adjusting the Tac dose in experiment group was significantly less than those in the control group (P＜0.05).In the experiment group,the target concentration was obtained even without dosage adjustment (70％).Conclusion Individualized adjustment of Tac doses for patients according to recipients' different CYP3A5 * 3 genotypes is beneficial for reaching target concentration as soon as possible,which is superior to traditional dosage regimen.

Objective To evaluate renal hemodynamic changes in hydronephrosis children with no image on intravenous urography by color doppler flow image(CDFI). Methods The resistance indexes(RIs)in main renal arteries(MRAs),interlobar renal arteries(IRAs)and arcuate renal arteries(ARAs)were measured in 48 children with hydronephrosis with no image on intravenous urography.The thickness and area were also measured in hydronephrotic kidneys.Resistive index ration(RIR=hydronephrotic kidneys RI/contralateral RI)was calculated. And pathological changes of kidneys were graded in these cases.Spearman's correlation test was used to compare RIR and pathological grades in these kidneys. Results In healthy and hydronephrotic kidneys,the relevant parameters were as fol1.13±0.14,1.14±0.09,respectively in MRAs,IRAs,ARAs in hydronephrotic kidneys(P＞ness,area of hydronephrotic kidneys(P＜0.05),also between RIR and thickness,araa(P＜0.05),MRAs,IRAs,ARAs and pathologic grades(P＜0.05),especially in IRP(s(r=0.795,P＜0.01).Conclusions RIR of IRA could be an ideal parameter of renal hemodynamics to evaluate renal damage in children with congenital hydronephrosis with no image on intravenous urography.

Objective To investigate the influencing factors of low birth weight infants (LBWI) in China in order to provide evidence for lowering the incidence of LBWI and improving the perinatal outcomes.Methods Clinical data were obtained from 14 different provinces, municipalities or autonomous regions in Northeastern, Northwestern, Northern, Central, Eastern, Southern and Southwestern of China, covering 39 hospitals of different levels.A total of 112 441 newborns were collected from January 1 to December 31 in 2011.After exclusion of those cases with incomplete information, miscarriage before 28 weeks of gestation, induction due to fetal malformation or intrauterine fetal death, 103 678 cases were restrospectively analyzed.Questionnaires were filled out and all data were recorded in computer network databases.Clinical data included maternal age, education background, height, weight, parity, histories of abnormal pregancy and comorbidities and complication.Independent sample t-test, Chi-square test, unvariate and ultivariate unconditional Logistics regression analysis were performed.Results The incidence of LBWI in mainland China was 7.21％ (7 474/103 678), 61.43％ (5 260/8 562) for preterm babies, and 2.33％ (2 214/95 116) for full-term babies.Univariate analysis showed that LBWI were associated with maternal age, education background, height, pregestational body mass index (BMI), weight gain during pregnancy, cord length, smoking, parity, histories of abnormal pregancy, gestational diabetes mellitus (GDM), preterm birth, hypertensive disorders in pregnancy, anemia, premature rupture of membranes and abnormal amniotic fluid volume.The following unconditional binary logistic regression analysis for those factors with P ＜ 0.3 in unvariate analysis showed that preterm birth (OR=46.246, 95％CI: 41.484-51.555), hypertensive disorders during pregnancy (OR=5.031, 95％CI: 4.325-5.853), histories of intrauterine fetal death ≥ 1 times (OR=2.446, 95％CI: 1.479-4.044), oligohydramnios (OR=2.068, 95％CI:1.659-2.578), pregestational BMI ＜ 18.5 (OR=1.637, 95％CI: 1.415-1.893), spontaneous abortion ≥ 1 times (OR=1.362, 95％CI: 1.043-1.777), age ≤ 20 (OR=1.332, 95％CI: 1.046 1.695), anemia (OR=1.230, 95％CI: 1.017-1.488) and premature rupture of membranes (OR=1.154, 95％CI:1.016-1.311) were risk factors for LBWI.The higher the maternal education level, weight gain, BMI and height, the lower the LBWI incidence.The risk factors of LBWI in premature small for gestational age (SGA) infants were hypertensive disorders during pregnancy and histories of intrauterine fetal death ≥ 1 times.The higher the maternal height and weight gain during pregnancy, the lower the incidence of LBWI in premature SGA infants.Conclusions The main influencing factors for LBWI are preterm birth and hypertensive disorders during pregnancy.In addition, LBWI is also associated with socioeconomic and genetic factors.

Objectives To investigate the delivery mode and perinatal outcomes of low birth weight infants in mainland China, and to explore the appropriate delivery mode and timing of delivery. Methods Clinical data of 103 678 babies delivered from Jan 1st to Dec 31th, 2011 in 39 hospitals in mainland China were analyzed retrospectively. The 39 hospitals located in 7 administrative regions, including Northeast, Northwest, North, Central, East, South and Southwest China. Result (1) The average birth weight of the newborns was (3 263 ± 540) g. Among them, 7 474 cases were diagnosed low birth weight infants, with the incidence of 7.209%(7 474/103 678). There were 2.328%(2 214/95 116 ) full-term low birth weight infants and 61.434% (5 260/8 562 ) preterm low birth weight infants. (2) From week 28 to week 36, the cesarean section rate of low birth weight infants increased with the increasing of gestational weeks. The cesarean section rate of full-term low birth weight infants were 61.14%(1 139/1 863) , which was higher than that of normal birth weight infants (52.947%, 45 108/85 195). The differences were statistically significant (P<0.01). (3) The constitution of the indication of cesarean section showed that social factor and maternal factor were 10.73%(443/4 128) and 48.91%(2 019/4 128) for low birth weight infants, respectively. While for the normal birth weight infants, they were 27.70%(12 495/45 108) and 38.60%(17 412/45 108), respectively. There was statistically significant difference(P<0.01). (4) The emergency cesarean section rate of full-term low birth weight infants was 41.09%(468/1 139), which was higher than that of normal birth weight infants (31.09%, 14 024/45 108). The difference was statistically significant (P<0.01). (5) The rates of stillbirth, neonatal asphyxia and the mortality of full-term low birth weight infants were 2.36%(44/1 863), 6.12%(114/1 863), and 3.17%(59/1 863), respectively. Those of normal birth weight infants were 0.11%(94/85 195), 1.41%(1 201/85 195), and 0.14%(119/85 195), respectively. The differences were statistically significant (P<0.01). (6) The stillbirth rate and mortality of low birth weight infants born by cesarean delivery were significantly lower than those born by vaginal delivery. The rate of neonatal asphyxia (17.95%) and other morbidity (3.61%) among low birth weight infants born by cesarean section in week 28 to week 33+6 were significantly lower than those born by vaginal delivery (30.09%, 6.62%, respectively). (7) With the increase of gestational age, the incidence of neonatal asphyxia and stillbirth decreased. The incidence of neonatal asphyxia(39.22%) and stillbirth(23.28%) was most seen in 28 to 29 gestational weeks, which decreased to 9.08% and 2.88% in 34 gestation weeks. Conclusions Low birth weight is one of the leading causes of adverse perinatal outcomes and cesarean section. To decrease the incidence of low birth weight, individualized management should be performed according to the gestational age and fetal condition. Extending the gestational age to at least 34 weeks may avoid iatrogenic preterm labor and improve the neonatal survival rate.

To observe the effects of diabetogenic (high fat high sucrose, lacking choleserol) diet on atherogenesis in New Zealand white rabbits. Two groups of New Zealand white rabbits received regular rabbit chow (the normal control), or high fat high sucrose diet for 4 months. The levels of plasma total cholesterol, HDL cholesterol, triglycerides, insulin, and glucose were investigated, the areas of fatty streak of the aortae were measured after staining with Sodan IV, and the aortic, coronary specimens were observed with light and electron microscopies. The plasma glucose, triglycerides, and total cholesterol were increased significantly by high fat high sucrose feeding. At the end of 4 months, the early charateristics of atherosclerosis were present in the animals' vascular specimens. Our findings suggest that high fat high sucrose feeding can induce hyperglycemia, hypertriglyceridemia and atherosclerosis in New Zealand white rabbits, and this could be a potential animal model for studying the mechanisms of diabetes-accelerated atherosclerosis. This study raised a question: What is the mechanism by which high fat high sucrose feeding induces atherosclerosis?. The related hypothesis was given in this article.

AIM: Anti-atherosclerosis effects of Momordica charantia L was further studied in a New Zealand rabbit atherosclerotic model at the basis of anti-inflammation and antioxidant effects. METHODS: Animals were divided into 3 groups: normal group (normal rabbit diet), atherosclerosis group(diet containing 2% cholesterol), and Momordica charantia L group(diet containing 2% cholesterol and 1 5% sarcocarp of Momordica charantia L ). Ninety days later, all animals were sacrificed. The effect of Momordica charantia L on atherosclerosis was evaluated by measuring serum lipid and total cholesterol content of artery wall, observing fatty liver degree, aorta arteriosclerotic area, and the thickness of intima. RESULTS: The level of total serum cholesterol and LDL-C in Momordica charantia L treatment group were obviously lower than those in atherosclerosis group, so were the total cholesterol content of artery wall, fatty liver degree, atherosclerotic area, intima thickness and I/M ratio, but no significantly difference was found between the two groups in TG level. The level of HDL-C in Momordica charantia L treatment group was evidently lower than that in normal control group. CONCLUSION: Momordica charantia L has an anti-atherosclerosis action in rabbits.

AIM: To investigate the relationship betw een ADRP and the development of atherosclerosis. METHODS: Antisense oligodeoxynucleotide of mouse ADRP was constr ucted. The mouse peritoneum macrophages were cultured with Ox-LDL or Ox-LDL plus the antisense fragment. The cellular cholesterol was measured and the expressio n of ADRP was observed with RT-PCR and western blotting. New Zealand white rabbi ts were fed with high cholesterol chow for 12 weeks. The levels of serum lipid a nd cholesterol content of aortic wall were investigated. The areas of fatty stre ak of the aortas was measured after staining with Sudan Ⅳ. The aortic, and live r specimens with HE and immunohistochemistry staining were observed under light microscopes. RESULTS: Antisense oligodeoxynucleotides of mouse ADRP decreased cellular cholesterol ester, induced cellular lipid droplets and the expression of ADRP. The expression of ADRP was induced by high-cholesterol-diet feeding in rabbit atherosclerotic lesions. The fatty streak of the aorta with immunohistoch emistry staining was strongly positive for ADRP in animals fed with high cholest erol chow, and the liver was negative with or without high cholesterol chow. CONCLUSIONS: The expression of ADRP in vessel walls is related t o the atherosclerosis, and has a potential role in lipid accumulation in macroph ages and pathogenesis of atherosclerosis.

AIM: Based on the finding of adipophilin expression with the increase in cellular cholesterol, the aim of the present study was to look for the active site of adipophilin in cellular cholesteryl metabolism. METHODS: Mouse peritoneal macrophages were incubated with 80 mg/L Ox-LDL (Ox-LDL group) or 80 mg/L Ox-LDL plus 1 mmol/L adipophilin antisense oligonucleotides (Ox-LDL+antisense group), respectively. At the various time points, the incubated cell samples were observed with adipophilin immunofluorescence staining, flow cytometric analysis and cellular cholesterol analysis. RESULTS: The Ox-LDL+antisense group cells contained significantly lower cholesteryl ester (19.9?1.9) mg/g (protein) than that of cells in Ox-LDL group (46.6?3.4) mg/g (protein) at 4 days. From 12 h, expression of adipophilin in Ox-LDL group increased more quickly than that of the cells in Ox-LDL+antisense group. At day 4, the level of adipophilin expression in Ox-LDL group was significantly higher than that in Ox-LDL+antisense group. During the observation, the amount of Ox-r[CL-3H] LDL taking up increased gradually in both groups, however, from day 1 the taking up amount in Ox-LDL+antisense group was less than that in Ox-LDL group. There was a statistical difference between the two groups from day 2 to day 4. From 6 h to day 2, the relative ACAT activity increased in both groups. The relative ACAT activity kept unchanged from day 2 to day 4 in the two groups. At day 2, the relative ACAT activity in Ox-LDL+antisense group was significantly lower than that in Ox-LDL group. Correlative analysis between activity of ACAT and adipophilin expression showed than R2 were 0.6176 and 0.8212 (P