AIM:To compare the mutant prevention concentration(MPC)of linezolid and vancomycin against methicillin resistant staphylococcus aureus(MRSA)and study the correlation between minimal inhibitory concentration(MIC)and MPC.METHODS:MICs and MPCs of two drugs against 35 MRSA clinical stains were determined by agar plates dilution method.The correlations between MIC and MPC were determined by linear regression.The ability to restrict the resistance was evaluated according the pharmacokinetics of two drugs.RESULTS:The MPCs of two drugs against MRSA were 16 and 8 ?g/mL and the MPC/MIC was 8.MPCs and MICs correlated poorly(R2 were 0.32 and 0.008,respectively).According to pharmacokinetics of two drugs,the concentration of linezolid was inside the MSW(mutant selective window)for the entire dosage interval,while the concentration of vancomycin exceeded the MPC for the most dosage interval.CONCLUSION:The capacity of vancomycin for restricting the selection of MRSA resistant mutants is stronger than that of linezolid.There is low correlation between MPC and MIC.

Objective To study the prenatal genetic diagnostic methods for hemophilia A fetus.Methods From 2002 to 2006,19 hemophilia A families were diagnosed either by long distance-polymerase chain reaction(LD-PCR)for factor Ⅷ intron 22 inversion or by the DNA polymorphism genetic linkage analysis of factorⅧin the Beijing Chaoyang Hospital.Results (1)Totally 19 women,with 22pregnancies received the prenatal diagnosis of fetal hemophilia A.The average week at diagnosis was 23(17-34)weeks.All the direct fetal blood sampling(DFBS)were successful.There was no fetal-loss caused by the procedures.(2)Of the 19 hemophilia A families,14 appeared to be factorⅧintron 22inversion,in which 16 prenatal diagnoses were done,10 fetuses were diagnosed as genetical hemophilia A patients,and 6 fetuses were normal.(3)Using combined polymorphism genetic linkage analysis 6 prenatal diagnoses were done,including one woman's two pregnancies,in which both her fetuses were diagnosed as genetical hemophilia A patients.(4)Factor Ⅷ levels of 16 fetuses were measured,and 6 fetuses were unmeasured either because the pregnancy weeks were lower than 20 weeks or the parents refused.Factor Ⅷlevel ranged from 0 to 198%.There were 11 fetuses whose factor Ⅷ levels were lower than 10%.Ten of them were diagnosed to be genetical hemophilia A patients,and in only one boy the factorⅧlevel was 2%,but the genetic diagnosis was normal and for one year's follow up he was doing normal.Conclusion LDPCR combined with polymorphism genetic linkage analysis enables a quick and correct detection ofhemophilia A carrier.For a carrier pregnancy.prenatal diagnosis could be done for the male fetus.Factor Ⅷ deficiency of the fetus could help make the diagnosis but the final diagnosis should be based on genetic evidence.

Objective To investigate the clinical characteristics, the antenatal management, the outcome and prognosis of chronic myeloproliferative disorders (CMPD) complicating pregnancy. Methods Retrospectively analyze the clinical data of eleven patients with CMPD complicating pregnancy hospitalized in Peking University People' s Hospital from 2000 to 2009, including five patients with essential thrombocythemia, one with primary myelofibrosis and five with chronic myeloid leukemia. Results (1)Five pregnancies had periodic antenatal care and laboratory monitorings like full blood count. Reasonable anti-coagulation therapy was given to prevent the complications. One patient with PMF diagnosed before conception had her first pregnancy ended with mild pre-eclampsia and intrauterine death at the gestational age of 32 weeks. During the first trimester of her second pregnancy two years later, the test for anti-β2 glycoprotein antibody was positive. She received low-dose aspirin and low-molecular-weight heparin as anticoagulants. An uneventful course was obtained and she delivered a healthy term infant. (2) Five pregnancies had occasional antenatal examination, including two patients with ET and three patients with CML One patient with ET developed severe pre-eclampsia at the gestational age of 25 weeks. Umbilical artery Doppler showed reversed end-diastolic velocity. The management with anti-convulsants, antihypertensives and anti-coagulants showed no effect. An emergency cesarean section had to be performed because of the aggressive hypertension and placental abruption, with still birth as a result. Two pregnancies never had an antenatal care. Both of them were admitted on labor and the diagnoses of CML were made. (3)Four pregnancies developed oligohydramnios and three developed preelampsia(two severe pre-eclampsia and one mild pre-eclampsia). There was no other hemorrhage and thrombosis event. (4) Eight pregnancies reached full-term with four cesarean sections and four vaginal births. Two preterm cesarean sections were performed because of a progressive oligohydramnios. The ten live neonates weighed 1820 - 3600 g. All were appropriate for gestational age, except one fetal growth retardation (FGR) developed in one patient with severe pre-eclampsia. (5) As for the CMPD, the eleven patients were all in stable conditions. Three patients with CML received hydroxyurea in the third trimester, four with ET and one with CML had plateletpheresis before delivery with favorable effect. All patients were uneventful postpartum, except one with CML who died in 5 months after childbirth. Conclusions The pregnancy outcomes for patients with CMPD are mostly good. However, antenatal care should pay more attention to the complications such as thromboembolic accidents, pre-eclampsia, still birth and fetal growth retardation. Management including reasonable anticoagulation therapy should be considered, which may help improve the prognosis.

Objective To establish a radioresistant esophageal squamous cancer cell line,and to identify the radioresistant genes and mechanisms.Methods The radioresistant KYSE410-res cell line was established by repeated exposure of cell line KYSE410 to radiation.The proliferation and apoptosis of esophageal squamous cancer cells were evaluated before and after radiation.The changes in gene expression of the esophageal squamous cancer cells after radiation were determined by gene microarray and analyzed by group t test.The genes with significant difference in expression after radiation were validated.Results The KYSE410-res cells had significantly enhanced proliferation and anti-apoptosis than the KYSE410 cells (all P＜0.05).The result of gene microarray showed that compared with the KYSE410 cells,the KYSE410-res cells had the expression of 463 and 251 genes upregulated and downregulated by no less than 4 folds,respectively.Those genes with different expression levels after radiation were mainly responsible for cell proliferation,adhesion,signal transduction,angiogenesis,reactive oxygen metabolism,cell damage repair,and the MAPK/ERK signaling pathway.OAS2 and UBD were key proteins in the network.In the KYSE410-res cells,the expression of HLA-DQBI,MMP1,NCAM1,ZNF521,GPC6,SELENBP1,LCN15,and TFPI-2 genes measured by real-time PCR was consistent with that measured by gene microarray.Conclusions Abnormal activation of the MAPK/ERK signaling pathway,upregulated expression of OAS2 and UBD,downregulated expression of TFPI-2,and upregulated expression of MMPs may play a role in radioresistance of esophageal cancer cells.

Objective To study the safety of enteral nutrition in preoperative bowel preparation for patients with colorectal carcinoma. Methods 68 patients with colorectal carcinoma were randomized into 2 groups.34 patients in the study group were applied with a kind of enteral nutrition in preoperative bowel preparation.34 patients in the control group were applied with the traditional liquid diet. Results In the study group, the change of the total sum of lymphocytes, hemoglobin, the serum total protein, albumin,prealbumin, transferrin and immune parameters CD3+, CD4+, CD8+ and CD4+/CD8+ after operation had no significant difference compared with that before preoperative bowel preparation (P >0.05). But in the control group, the total sum of lymphocytes, hemoglobin and immune parameters CD+3, CD+4, CD+8 after operation had no significant difference compared with that before preoperative bowel preparation, the serum total protein [(65.35±3.02) g/L],albumin [(32.5±1.98) g/L], prealbumin [(221.02±22.45) mg/L], transferrin [(2.12±0.2) g/L] and CD+4/CD+8 (1.14±1.98) were significantly lower after operation than that before preoperative bowel preparation [(69.43±3.21) g/L, (35.43±2.45) g/L, (236.54±18.45) mg/L, (2.31±0.03) g/L, 1.53±2.45] (P ＜0.05). Conclusion Enteral nutrition could be applied to the preoperation bowel preparation and replace the traditional liquid diet. As a simple way, it can make the colon clear, improve the nutrition and immunity status of the patients.

Object To investigate the effect of PPARαactivation on PPARγ-induced fatty liver in the mouse. Methods Wild type mice ( C57BL/6) aged 4 to 5 weeks were used as animal models.All mice were divided into four groups.The mice in the first group were fed with chow diet.The mice in the second group were fed with a diet containing 0.125%Wy-14,643, an agonist of PPARa, for 8 days.The mice in the third group were injected with Ad/PPARγvia tail vein for 5 day.The mice in the fourth group were firstly fed with Wy-14,643 diet for 3 days and then injected with Ad/PPARγvia tail vein for another 5 day.Mouse livers were collected and photographed.The effect of PPARαactivation on PPARγ-induced fatty liver was observed by H&E and Oil red O staining.Results Compared with the controls, wild-type mice treated with Wy-14,643 for 8 days exhibited marked hypertrophy of hepatocytes with increased cytoplasmic eosinophil-ia and proliferation of peroxisomes.The liver size was significantly increased in the wild-type mice treated with Ad/PPARγfor 5 days, and over-expression of PPARγstrongly induced hepatic steatosis.Importantly, the wild-type mice pretreated with Wy-14,643 for 3 days and then given Ad/PPARγinjection exhibited dramatically the increase of liver size, which might be due to the dual function of PPARa and PPARγ.Compared with the Ad/PPARγgroup, the Wy-14,643 pretreat-ment group showed a reduced hepatic steatosis.Conclusions Activation of PPARαby Wy-14,643 effectively improves PPARγ-stimulated hepatic steatosis, which provides a novel target for prevention and therapy of fatty liver.

Objective To investigate the role of cancer stem cells in radiation resistance of esophageal cancer and its molecular mechanism, and to provide a theoretical basis for radiotherapy for esophageal cancer.Methods Esophageal cancer cell line TE1 was treated with 8 Gy of radiation. Esophageal cancer cell line with resistance to radiation, TE1-res, was established and screened.Cell counting was used to evaluate cell proliferation.Flow cytometry was used to determine the expression of CD44 (high) CD24(-) CD133(+) and apoptosis in cells.The colony formation assay was used to determine the colony-forming rate and cell survival curve.Bisulfite sequencing PCR was used to determine the methylation status of cancer suppressor genes.Comparison of the data was made by group t test or analysis of variance. Results Compared with TE1 cells, TE1-res cells had significantly enhanced proliferation, a significantly higher proportion of CD44( high) CD24(-) CD133(+) cells, and significantly enhanced resistance to apoptosis (mean value 20.84×105 vs.4.46×105/day, P=0.008;(38.0±2.9)%vs.(10.1±1.3)%, P=0.001;mean value 33.23% vs.10.50%, P=0.003 ) .After treatment with 8 Gy of radiation, TE1-res cells had significantly higher colony-forming rate and D0 value than TE1 cells ((14.3±2.6)%vs.(0.9±0.3)%, P=0.011;3.28 vs.2.19 Gy, P=0.125 ) .Moreover, the promoter methylation in cancer suppressor genes including SPINT2, CDKN1B, DKK1, TP53, and PPP2R1B was significantly enhanced in TE1-res cells than in TE1 cells ((89.7±4.9)%vs.(5.0±0.5)%, P=0.001;(92.3±4.7)%vs.(10.4±0.7)%, P=0.001;(90.7±3.7)%vs.(7.9±0.4)%, P=0.001;(83.4±5.7)%vs.(17.2±1.2)%, P=0.002;(90.2±
6.7)%vs.(4.4±1.2)%, P=0.002).Conclusions Cancer stem cells play an important role in radiation resistance of esophageal cancer. The resistance to radiation is closely associated with promoter hypermethylation in cancer suppressor genes including SPINT2, CDKN1B, DKK1, TP53, and PPP2R1B.

Objective To study the metabolic characteristic of prostate cancer(PCa) in peripheral zone (PZ) with three-dimensional proton MR spectroscopic imaging (3D MRSI),and to evaluate the value of 3D MRSI in the differential diagnosis of prostate cancer in PZ. Methods 3D MRSI findings were reviewed in 18 benign prostatic hyperplasia (BPH) cases and 21 PCa cases.(Cho+Cre)/Cit and Cho/Cre ratios of PCa and PZ of BPH were retrospectively measured,(Cho+Cre)/Cit and Cho/Cre of PCa voxels were compared with BPH voxels. Results PZ of BPH showed dominant Cit,which was markedly higher than Cho and Cre. Significantly higher choline levels and lower citrate levels were observed in PCa compared with that of BPH. It showed statistically significant difference between (Cho+Cre)/Cit ratios of PCa voxels and BPH voxels,PCa voxels had minimal overlap with BPH voxels. It also showed statistically significant differences between Cho/Cre ratio of PCa voxels and BPH voxels,but there was some overlap between two groups. Conclusion 3D MRSI can be successfully applied to the diagnosis of cancer in the PZ on the basis of the elevation of Cho and the reduction Cit in cancerous tissue compared with that of PZ tissue of BPH.

Purpose Many studies have shown that subclinical left ventricular systolic dysfunction is seen in prediabetic patients.However,its relationship with prognosis is unclear.The purpose of this study is to investigate the prognostic value of subclinical left ventricular systolic dysfunction with prediabetes.Materials and Methods This was a prospective clinical cohort study.A total of 98 prediabetes patients with complete medical record and follow up data in the physical exam center and the clinic of Yan'an People's Hospital were chosen between January 2013 and January 2014.The biochemical data,echocardiography and left ventricular global longitudinal strain (GLS) in 2 years of follow up were collected.The subjects were grouped into diabetes if the diagnosis was confirmed during follow up,or non-diabetes group if not diagnosed.After follow up,the baseline parameters were compared to screen for risk factors to develop clinical diabetes.Results During the study,38 participants were diagnosed as clinical diabetes.Cox proportional hazard regression models show that obesity [hazard ratio (HR):2.662,95％ CI 1.374-5.159,P=0.004],waist-hip ratio (HR:1.917,95％ CI:1.012-3.492,P=0.001),mitral E/e'ratio (HR:1.661,95％ CI:1.336-2.065,P＜0.001),HbAlc (HR:2.029,95％ CI:1.047-3.932,P＜0.001),global longitudinal strain (HR:0.786,95％ CI:0.728-0.848,P＜0.001) were significant independent predictors for developing diabetes.Using GLS＜18％ as cutoff value,the area under receiver operating characteristic (ROC) curve to predict development of diabetes was 0.796 (95％ CI:0.704-0.888,P＜0.001),with sensitivity and specificity of 46.7％ and 89.5％,respectively.Conclusion Among modifiable risk factors in patients with prediabetes,subclinical left ventricular systolic dysfunction is an early indicator of progressing to diabetes.Early detection of left ventricular systolic dysfunction in prediabetes can provide the basis for early clinical intervention.