Objective: To investigate the association of polymorphisms of related genes in folic acid metabolic pathway and the tumor candidate genes with the survival of gastric cancer patients treated with capecitabine combined with paclitaxel. Methods: Ninety-three patients with pathological diagnosis of gastric cancer were treated with capecitabine plus paclitaxel-based chemotherapy. The gene polymorphisms of tumor necrosis factor ( TNF) A308G (rs1800629), methylenetetrahydrofolate reductase ( MTHFR) C677T (rs1801131) and A1298C (rs1801133), methionine synthase ( MTR) A2756G (rs1805087) and methionine synthase reductase ( MTRR) A66G (rs1801394) were detected by TaqMan-MGB probe typing method. The median survival time (MST) of patients with different genotypes was compared, and the effects of various factors on the prognosis were evaluated. Results: The median follow-up period was 29.6 months. The MST of 93 patients was 34.93 months. The MST of patients with MTHFR 1298CA and 1298CC were 47.50 and 22.91 months, respectively. The log-rank test revealed that the polymorphism of MTHFR 1298C/A had marginally significant correlation with the survival of patients (χ2=3.447, P=0.062), and other gene polymorphisms were not associated with the survivals. The gender, drinking and operation were the major prognostic factors for gastric cancer patients receiving chemotherapy. Conclusion: Detection of MTHFR 1298CA polymorphism may predict the survival of gastric cancer patients receiving chemotherapy of capecitabine combined with paclitaxel.

Objective To study the expression of sex hormone-binding globulin(SHBG),insulin signaling pathway and glucose transporter in placenta of pregnant women with gestational diabetes mellitus(GDM),and to explore its role in the pathogenesis of GDM. Methods A total of 10 full-term and non-obese(BMI<25 kg/m2)pregnancy women diagnosed with GDM and 10 normal pregnant cases were recruited for the study. Placental tissues were collected respectively. The expression of protein and mRNA of SHBG and insulin signal transduction(IRS-1,ISR-2,PI3K p85α)and glucose transporter proteins(GLUT-1,GLUT-3,GLUT-4)in placental tissue were detected by real-time PCR and Western blotting. Pearson and linear regression analysis were used to evaluate the correlation among the related indicators. Results In the placental tissue of non-obese women,there existed a decrease(P<0.05)in the expression of protein and mRNA of SHBG with a concurrent a decrease(P<0.05)in the expression of protein and mRNA of GLUT-4 in GDM women compared with normal controls. Furthermore ,a decrease(P<0.05)of GLUT-3 and IRS-1 protein expression with lower(P<0.05)IRS-2 mRNA expression was also observed in placental tissue from GDM patients. No changes were found in PI3K p85α and GLUT-1 at both protein and mRNA levels(P>0.05). Results of linear correlation analysis showed that there were positive correlations between SHBG mRNA and IRS-2 mRNA(P<0.05),SHBG mRNA and PI3K p85α mRNA(P<0.05),and SHBG mRNA and GLUT-4 mRNA(P<0.05). There was also a remarkable positive correlation between IRS-2 mRNA and GLUT-4 mRNA(P<0.01). There existed negative correlations between IRS-1 mRNA and PI3K p85α mRNA(P<0.05),and IRS-1 mRNA and GLUT-3 mRNA(P<0.05). There existed a remarkable positive correlation between IRS-2 mRNA and GLUT-1 mRNA(P<0.01). Conclusion The defective receptors of insulin signaling pathway are present in GDM placental tissue. Decreased expression of SHBG may be involved in the regulation insulin signaling ,leading to a concomitant decrease expression of relevant insulin signaling components in placental tissue ,implying insulin resistance and developing GDM finally.

Objective To develop a high-resolution melting ( HRM ) assay for rapidly screening Gilbert syndrome ( GS) and Crigler-Najjar syndrome ( CNS) associated with UGT1A1 defects.Method Methodology was developed .Then, we applied the established method to analyze 61 clinical samples from neonatal patients with severe unexplained unconjugated hyperbilirubinemia .Neonates with known risk factors for developing hyperbilirubinemia , such as ABO hemolysis, G6PD deficiency, sepsis, hypoxic ischemic encephalopathy were excluded .Five pairs of PCR primers were designed to detect the five common mutations (G211A, C686A, C1091T, C1352T and T1456G) in Asia population.PCR and HRM Assay conditions were optimized.UGT1A1 genotyping in clinical samples was performed by using the established HRM analysis , and all results were subsequently confirmed by direct DNA sequencing .Results The mutants were readily differentiated by using HRM analysis .In this study, 42 neonates were identified with UGT1A1 mutation, and 4 different known variants were detected .Conclusion HRM analysis in this study was economical, convenient, rapid, effective for screening UGT1A1 gene mutations, which can serve as an reliable method for the clinical diagnosis of GS and CNS and the large-scale molecular epidemiological research of UGT1A1 gene-related diseases.

Accidents, Occupational ; statistics & numerical data ; Adolescent ; Adult ; Factor Analysis, Statistical ; Humans ; Male ; Middle Aged ; Occupational Injuries ; epidemiology ; Risk Factors ; Young Adult

Oxaliplatin, the third generation of the platinum based chemotherapy agent, is effective in the treatment of multiple solid tumors and is also quite safe. However, there is a high incidence of peripheral neurotoxiciy, which is dose-limiting. Oxaliplatin induces two distinct forms of neurotoxicity: an acute syndrome that is triggered or aggravated by exposure to cold, and chronic cumulative sensory neurotoxicity which in nature resembles characteristics of cisplatin associated neurotoxicity. In this article, the clinical manifestations, electrophysiologic abnormalities, mechanism of neurotoxicity and therapy are reviewed.

Clinical medicine and its teaching patterns put forward the new demand to the teaching of laboratory diagnostics. According to the teaching objectives and development tendency of laboratory diagnostics, a novel teaching pattern based on organ-system diseases was established through systematical reform measures. The course content system was reconstructed and focused on the diseases. And the professional teacher group carefully orchestrated, applied new teaching methods,such as case-based learning and problem-based learning. The independent learning on a resource sharing network platform was encouraged, and the evaluation system was innovated. The novel teaching pattern has obtained gratifying achievement, and showed a bright prospect of development.

Objective To analyze the image and histological results of the combined use of allograft/extracorporeally frozen tumor-bearing bone and vascularized fibular flap for the reconstruction of bony defects following tumor resection,guiding clinical practice.Methods From March 2007 to June 2013,we enrolled 63 patients who had combinative biological reconstruction after bone tumor resection (11 in humerus,22 in femur,21 in tibia,4 in calcaneus).There were 36 male and 27 female in this series.The average age at time of operation was 20 years,ranging from 9 to 48 years.The follow-up ranged from 16 to 102 months with average of 48 months.We investigated the X-ray and CT images for all patients and histological findings of two patients.Patients were assessed functionally with the Musculoskeletal Tumor Society 93 score.Results Three patients with local soft tissue recurrence and one patient with infection underwent amputation.The survival of construct was 93.6％.Bone union achieved in all cases with the average MSTS score of 92.8％.Bone union ranged from 11 to 28 months in allograft group and 9 to 14 months in devitalized tumor bearing bone group.Significant difference of bone union time was found between two groups (Z=-3.638,P=0.000).Viability of the fibular grafts was verified in 58 of 63 patients (92％).Three types of images were observed in complex.Osteopenia and spongy change in fibula were found in 51 patients (81％) with stable fixation of the complex.Five complexes with failed blood supply of fibula and stable fixation revealed no density change of fibula,small amount of callous formation and relative delayed union.In seven complexes (11％) with unstable complex due to patients' incompliance,fibula reacted with dense hypertrophy and microfracture.Fusion of grafts with amount of callus was obviously observed.Union at allograft-host bone junctions occurred by residual host bone-derived external callus and fibular-derived internal callus that bridged the junction and filled the gap between abutting cortices.Callus from fibular graft was mature than that from periosteum of residual host bone.Internal repair was observed at the internal surface of the allografts.Fibula showed significant spongy changes.Conclusion Recycled tumor-bearing bone in combined with fibular flap is a reliable reconstruction as an alternative to traditional Capanna technique.The survival of the fibula is a cornerstone in success of complex reconstruction.Sponginess of fibula and internal repair of allograft compromise the intensity of complex,necessitating the strong instrumentation during reconstruction.

Objective To construct the targeting vector for conditional gene knockout of sex hormone?binding globulin(Shbg)in mice. Methods Based on Red/ET,two LoxP were inserted into both sides of extron 4 and extron 7 for conditional gene knockout of murine Shbg. Firstly,the Shbg gene and its upstream,downstream genes obtained from BAC DNA by PCR were cloned into plasmid pBR322?MK,which was named pBR322?MK?AB. The retrieve plasmid(pBR322?Shbg?Re)was obtained by homologous recombination between the plasmid and BAC.Then a great quantity of Neo fragments obtained from PL452 and PL451 were inserted into the targeting vector after another round of Red/ET and then the final targeting vec?tor(pBR322?MK?SHBG?cko)was achieved. Results The correct structures of the targeting vectors such as pBR322?MK?AB,pBR322?Shbg?Re, SHBG?Ln and pBR322?MK?Shbg?cko were confirmed by restriction enzyme digestion and sequencing analysis. Conclusion The targeting vector for conditional knockout of murine SHBG was successfully constructed. The construction of targeting vector paved the way for conditional knockout mouse strain generated by targeted mutation of Shbg.

Objective To evaluate the feasibility of composite material of bone morphogenetic protein (BMP) and PLGA/TCP in repair of peri-porous-titanium bone defects in adult rabbits.Meth- otis The composite of PLGA/TCP scaffold with bovine BMP was made and implanted in distal bone de- fects peri-porous-titanium in femur of adult rabbits.The effect of BMP with PLGA/TCP on peri-prosthesis was evaluated by means of scanning electron microscope (SEM),energy dispersive X-ray analysis (EDX) and biomechanics.Results BMP with PLGA/TCP showed obvious peak of Ca and P of EDX in the pores of titanium in experiment group six weeks after operation and higher than that in control group (P＜0.05).Push-out test demonstrated that the bonding strength between the composite of HA coating/ porous titanium and bone was increased significantly with time (P＜0.05).In experiment group,at 6 and 12 weeks,peri-porous-titanium had higher shearing force compared with control group (P＜0.05). Conclusion BMP loaded with PLGA/TCP is a promising bone graft for bone defects in revision arthro- plasty,as indicates that bone induction of BMP plays an important role in biological stabilizaiton.

BACKGROUND: Osteoblasts derived from bone marrow stromal stem cells are the main force of the cells In bone marrow cavity.In the artificial joint replacement cases, their life situation is closely related to conductive pressure of prosthesis.OBJECTIVE: To observe the continuous pressure on the proliferation of rabbit's bone marrow stromal stem cells, and to reveal the biomechanism of continuous pressure causing loosening and sinking of prosthesis and its activity after replacement.DESIGN, TIME AND SE'I-I'ING: A randomized study based on cytology was performed at the Institute of Othorpaedics, the Fourth Military Medical University of Chinese PLA from February 2004 to October 2007.MATERIALS: One New Zealand rabbit aging 1 month and weighing 0.5 kg was used to extract the bone marrow stromal calls.METHODS: The third-passaged bone marrow stromal stem cells were inoculated in seven 24-well culture plates at the density of 1 × 104 cells/well. After 14 hours, cells were adherent completely and cultured in DMEM culture media containing 10% fetal bovine serum. Thereafter, the four culture plates were randomly divided into 4 experimental groups, including control group without any pressure, and continuous pressure (20, 60, and 100 kPa) groups. The continuous pressure was performed for 3 hours every day.MAIN OUTCOME MEASURES: Absorbance was detected at day 1, 3, 5, and 7 after culture using MTT assay.RESULTS: Absorbance of the three pressure groups after 3, 5 and 7 days was significantly lower than the control group (P < 0.01). There was no significant difference in absorbance between 20 kPa continuous pressure group and 60 kPa continuous pressure group on the third day (P >0.05); but the absorbance was significantly higher than 100 kPa continuous pressure group (P < 0.05). On the fifth day, there was significant difference in absorbance between paired continuous pressure groups (P < 0.05),i.e., the higher the continuous pressure was, the lower the absorbance was. On the seventh day, the absorbance of the 100 kPa continuous pressure group was significantly lower than 20 kPa continuous pressure group (P < 0.05).CONCLUSION: Patients with eady post-joint replacement had better not stand on the ground; otherwise, a continuous stress will be caused so as to induce the restrain of bone marrow stromal stem calls in the bone marrow cavity, which is not helpful for bone healing and easily causes subsidence and loosening of prosthesis.