Defining a critical period in calvarial development for Hedgehog pathway antagonist-induced frontal bone dysplasia in mice / 国际口腔科学杂志·英文版

The Hedgehog (Hh) signalling pathway is essential for cellular proliferation and differentiation during embryonic development. Gain and loss of function of Hh signalling are known to result in an array of craniofacial malformations. To determine the critical period for Hh pathway antagonist-induced frontal bone hypoplasia, we examined patterns of dysmorphology caused by Hh signalling inhibition. Pregnant mice received a single oral administration of Hh signalling inhibitor GDC-0449 at 100 mg•kg or 150 mg•kg body weight at preselected time points between embryonic days (E)8.5 and 12.5. The optimal teratogenic concentration of GDC-0449 was determined to be 150 mg•kg. Exposure between E9.5 and E10.5 induced frontal bone dysplasia, micrognathia and limb defects, with administration at E10.5 producing the most pronounced effects. This model showed decreased ossification of the frontal bone with downregulation of Hh signalling. The osteoid thickness of the frontal bone was significantly reduced. The amount of neural crest-derived frontal bone primordium was reduced after GDC-0449 exposure owing to a decreased rate of cell proliferation and increased cell death.

Hedgehog pathway antagonist-induced oromandibular limb hypogenesis in mouse / 中华口腔医学杂志

Objective@#To analysis teratogenic effect of GDC-0449 to fetus and set up the animal model of GDC-0449 induced oromandibular limb hypogenesis in mouse for further research of its pathogenesis.@*Methods@#Twenty-seven pregnant Institute of Cancer Research (ICR) mice were randomly divided into: control group, embryonic day 8.5 (E8.5) exposed groups, E9.5 exposed groups, E10.5 exposed groups, E11.5 exposed groups, E12.5 exposed groups, E13.5 exposed groups, E14.5 exposed groups and E15.5 exposed groups. Each group had 3 mice. Exposed groups were treated with the Hedgehog pathway antagonist GDC-0449 at a single dose 150 mg/kg by oral gavage from E8.5 to E15.5. At E16.5, embryonic phenotypes were analyzed in detail by stereo microscope and histology. After establish an optimal dysmorphogenic concentration, 6 pregnant ICR mice were randomly divided into control group and the optimal group, embryonic phenotypes were analyzed by whole-mount skeletal staining and micro-computed tomography at E18.5.@*Results@#The mice were exposed to GDC-0449 on E11.5 and E12.5 had a high incidence of cleft palate. GDC-0449 exposed between E9.5 and E10.5 caused craniofacial and limb dysmorphology, including micrognathia, microglossia, ectrodactylia, partial anodontia and cleft palate. Most interestingly, these are extremely similar to oromandibular limb hypogenesis syndrome.@*Conclusions@#The results of this study indicate that GDC-0449 can be used to induce micrognathia, microglossia, ectrodactylia, partial anodontia and cleft palate. This work established a novel mouse model for oromandibular limb hypogenesis.

Value of acute renal injury associated biomarkers for patients in intensive care unit / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the early predictive and diagnostic significance of the acute kidney injury (AKI) associated biomarkers for patients in the intensive care unit (ICU).
@*METHODS@#From January to June, 2014, relevant clinical data of participants were collected upon admission to the intensive care unit (ICU) in Affiliated Hospital of Zunyi Medical College. Levels of serum cystatin C (sCys C), neutrophil gelatinase-associated lipocalin (sNGAL), urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary kidney injury molecule-1 (uKIM-1), interleukin-18 (uIL-18), and N-acetyl-beta-D-glucosaminidase (uNAG) were detected by enzyme linked immune sorbent assay (ELISA), and compared between AKI and non-AKI patients. Diagnostic significance of these biomarkers was evaluated by a receiver operating characteristic (ROC) curve and the area under the ROC curve.
@*RESULTS@#A total of 176 patients were enrolled in this study. Among them, 71 patients were diagnosed as AKI, in which 57 patients hospitalized with AKI and 14 developed AKI after 24 h hospitalization. The renal replacement therapy ratio was increased with the progress of clinical stage for AKI. AKI mortality rate was 18.8% (46.5% of the total number of deaths). The levels of sCys C, sNGAL, uNGAL, and uIL-18 in AKI patients were increased compared with those in the non-AKI patients (P<0.05). With the progress of AKI, sCys C, and uNGAL levels were also elevated. In 14 patients who suffered from AKI 24 h after hospitalization, the average levels of sCys C, uNGAL, uIL-18, and uKIM-1 were significantly increased (P<0.05). Sensitivity and specificity of the uNGAL, sCys C, and uIL-18 in AKI diagnosis were 97.2%, 76.1%, 54.9% and 93.3 %, 96.2%, 78.1%, respectively. The areas under the ROC curve of uNGAL, sCys C, and uIL-18 were 0.99, 0.90, and 0.69, respectively.
@*CONCLUSION@#uNGAL, sCys C and uIL-18 can be used to predict and diagnose AKI, and to evaluate the AKI clinical stage.

The value of MR imaging in the diagnosis of colonic carcinoma / 中华放射学杂志

Objective To investigate the MR imaging findings of colonic carcinoma and the diagnostic value of MRI. Methods Multi-planar and multi-sequence MRI scanning, before and after contrast enhancement, were performed in 40 patients with colonic cancer. The patients were fasted for 12 hours, prepared with clean clysis or senna at night before study, given 10 mg of anisodamine 10 minutes before study, and then infused with 800～1 000 ml physiological saline immediately before study by anus. Dukes staging and resectability evaluation were made in 32 patients before surgery and meanwhile the results were compared with pathology. Results Colonic anatomy and surrounding organs were clearly demonstrated on MRI in 40 patients with colonic cancer, particularly in recta and sigmoid flexure. The tumours showed iso-intensity on T 1WI, iso-intensity or slight high-intensity signal on T 2WI, and high-intensity signal on SPIR. Remarkable enhancement was seen in 35/40 (87.5%). Invasion of surrounding organs occurred in 8/40(20.0%)and MRI revealed 6; Meanwhile, MRI revealed lymph node metastasis in 8 out of 12 cases. 32 patients were regarded as resectable before surgery, and 8 patients as unresectable. Four patients were overestimated, the accuracy of preoperative evaluation for the resectability was 87.5%, and the detecting rate of colonic cancer was 100.0%. Conclusion MRI can clearly show the colonic wall thickness, anatomic structure and surrounding anatomy. For the diagnosis of colonic cancer, MRI can not only demonstrate all its morphologic features, such as mass, thickened wall, and invasion of adjacent organs, but also swollen lymph node and metastasis in abdominal cavity. MRI is very helpful in the diagnosis, staging, and respectability evaluation of colonic cancer.