The hyperglycemia of maternal diabetes suppresses the glucose transporter-1 (GLUT1) facilitative glucose transporter 49 -66% in preimplantation embryos. Glucose uptake is reduced and apoptosis is activated. We hypothesized that the reduction of embryonic GLUT1 may play a key role in the malformations of diabetic embryopathy. Therefore, we produced GLUT1-deficient transgenic mice [i.e., antisense-GLUT1 (GT1AS)] to determine whether GLUT1 deficiency alone could reproduce the growth defects. Early cell division of fertilized mouse eggs injected with GT1AS was markedly impaired, P < 0.001 vs. controls. Two populations of preimplantation embryos obtained from GT1AS ؋ GT1AS heterozygote matings exhibited reduction of the 2-deoxyglucose uptake rate: one by 50% (presumed heterozygotes, P < 0.001 vs. control) and the other by 95% (presumed homozygotes, P < 0.001 vs. heterozygotes). Embryonic GLUT1 deficiency in the range reported with maternal diabetes was associated with growth retardation and developmental malformations similar to those described in diabetes-exposed embryos: intrauterine growth retardation (31.1%), caudal regression (9.8%), anencephaly with absence of the head (6.6%), microphthalmia (4.9%), and micrognathia (1.6%). Reduced body weight (small embryos, <70% of the nontransgenic body weight) was accompanied by other malformations and a 56% reduction of GLUT1 protein, P < 0.001 vs. nonsmall embryos (body weight >70% normal). The heart, brain, and kidneys of embryonic day 18.5 GT1AS embryos exhibited 24 -51% reductions of GLUT1 protein. The homozygous GT1AS genotype was lethal during gestation. Reduced embryonic GLUT1 was associated with the appearance of apoptosis. Therefore, GLUT1 deficiency may play a role in producing embryonic malformations resulting from the hyperglycemia of maternal diabetes. Late gestational macrosomia was absent, apparently requiring a different mechanism.embryo ͉ antisense ͉ transgenic ͉ development ͉ apoptosis

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A stable clone of rat mesangial cells expressing antisense GLUT-1 (i.e., MCGT1AS cells) was developed to protect them from high glucose exposure. GLUT-1 protein was reduced 50%, and the 2-deoxy-[(3)H]glucose uptake rate was reduced 33% in MCGT1AS. MCLacZ control cells and MCGT1 GLUT-1-overexpressing cells were used for comparisons. In MCLacZ, 20 mM D-glucose increased GLUT-1 transcription 90% vs. no increase in MCGT1AS. Glucose (8 mM) and 12 mM xylitol [a hexose monophosphate (HMP) shunt substrate] did not stimulate GLUT-1 transcription. An 87% replacement of the standard 8 mM D-glucose with 3-O-methylglucose reduced GLUT-1 transcription 80%. D-Glucose (20 mM) increased fibronectin mRNA and protein by 47 and 100%, respectively, in MCLacZ vs. no increases in MCGT1AS. Fibronectin synthesis was elevated 48% in MCGT1 and reduced 44% in MCGT1AS. We conclude that 1) transcription of GLUT-1 in response to D-glucose depends on glucose metabolism, although not through the HMP shunt, and 2) antisense GLUT-1 treatment of mesangial cells blocks D-glucose-induced GLUT-1 and fibronectin expression, thereby demonstrating a protective effect that could be beneficial in the setting of diabetes.

We have analysed the reasons for the low reported incidence of prostate cancer in China and argue for early diagnosis and treatment of this disease. According to the 2002 database of the International Agency for Research on Cancer (IARC), the age-standardized incidence of prostate cancer in China is 1.6/10 5 person years (PY), with a mortality rate of 1.0/10 5 PY and mortality-to-incidence rate ratio (MR/IR) = 0.63. The MR/IR ratio of prostate cancer in China was found to be higher than the average in Asia (MR/IR = 0.57) and much higher than that in North America (MR/IR = 0.13). These data indicate that in China most prostate cancers were in the advanced stages at the time of diagnosis, and that patients had a short survival time thereafter. In 2004, Stamey et al. reported a retrospective American study of prostate cancer for the years 1983-2003. It was shown that most cases of prostate cancer detected by prostate-specific antigen (PSA) screening were in the advanced stage at the start of this 20-year period. These early follow-up data are quite similar to the results obtained from mass PSA screening of elderly men in Changchun, China. However, after the American programmes for early diagnosis and treatment of prostate cancer were accepted, tumours were diagnosed at earlier stages. On the basis of these findings, mass screening should be performed in the whole of China using serum PSA to facilitate early diagnosis and treatment of prostate cancer.

Objective: To perform a meta-analysis and literature review regarding the diagnostic accuracy of MRI for pre-operative tumour depth invasion (T) and regional lymph node invasion (N) staging of gastric carcinoma (GC). Methods: Articles were identified through systematic search of Medline, PubMed, Cochrane Library, Web of Science, Springerlink and several Chinese databases. The study quality was assessed by the quality assessment for studies of diagnostic accuracy. 2 reviewers independently extracted and assessed the data from 11 eligible studies. A meta-analysis was then carried out. Subgroup and sensitivity analyses were also performed. Results: 11 studies (439 patients) were finally included in the current review. Among these studies, the significant evidence of heterogeneity was only discovered for Subgroup analyses showed that diffusion-weighted imaging was more helpful for T staging. Conclusion:The present systematic review suggests that MRI has a good diagnostic accuracy for pre-operative T staging of GC and should be widely used in clinical work. However, the ability for N staging is relatively poor on MRI. Advances in knowledge:In the pre-operative staging of GC, MRI was a useful tool and may enhance accuracy for the T staging of advanced GC.Gastric carcinoma (GC) is the fourth most common cancer and the second leading cause of cancer-related death with a 5-year survival rate of ,20% around the world. 1 The disease is more common in Asian countries, especially China, Japan and Republic of Korea.2,3 Accurate assessment of local tumour depth invasion (T) and regional lymph node invasion (N) plays an essential role in predicting prognosis and determining the most appropriate treatment planning. 4,5The pre-operative staging of GC has been based on a multimodality approach, such as endoscopic ultrasonography (EUS), CT, MRI and positron emission tomography (PET).6,7 EUS and CT have been widely used for GC staging in previous years.8 Of course, different imaging modalities have themselves relative merits. CT with ionized radiation requires the injection of iodine contrast medium.9 EUS is an invasive technique requiring sedation 1 and is highly operator dependent.10 PET highly depends upon the standardized uptake value and the pathological subtype of the cancer. 11MRI is a powerful imaging method with high soft-tissue contrast, with technical versatility for sequence selection and modification, and without ionizing radiation. However, it was unsuitable for the staging of GC owing to its long acquisition time and susceptibility to motion artefacts in previous years. With technology improved and shorter imaging time, these limitations have recently been partially overcome. 12Recently, there has been much research using MRI to assess pre-operative staging of GC. Nevertheless, the number of patients in each study has been insufficient, and the results varied among the articles. Also, the limited imaging field of view of MRI in a single session makes it difficult to stage the distant metastasis (M). 13Therefore, the o...

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Aims: This study aimed to prepare swim bladder hydrolysate (SBH) with M n < 4000 Da, and investigate its effects on cyclophosphamide (CTX)-mediated ovarian injury in mice. Methods: Hydrolysates were prepared by heating extraction, enzymatic hydrolysis and ultrafiltration. M n and distribution of SBH were analyzed via gel filtration chromatography and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Changes in the mouse oestrus cycle were determined by cytological examination. The number of follicles was examined using histopathology. Enzyme-linked immunosorbent assays (ELISAs) were used to determine the serum sex hormone levels.Results: The M n of SBH, prepared by heating extraction, enzymatic hydrolysis, ultrafiltration, and from different batches, was below 4000 Da, and the preparation process was stable. Compared with the control group, the low-, middle-, and high-dose SBH treatment groups showed different trends in oestrus duration, serum sex hormone levels, and the number of primordial and secondary follicles. The oestrus cycle duration of the high-dose SBH group was longer than that of the model group. The serum luteinizing hormone, follicle-stimulating hormone, and anti-Müllerian hormone levels in the middle-dose group were the closest to those of control group. The number of primordial and secondary follicles in the medium-dose group was significantly higher than that in the model group and closest to those of control group. Conclusion: After heating extraction, trypsin/Flavourzyme hydrolysis and ultrafiltration, a hydrolysate with M n below 4000 Da could be prepared. We found that a moderate (400 mg/kg) SBH dose resulted in the greatest effect on ovarian injury remission in mice.