ABSTRACT
Background@#Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. @*Methods@#In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. @*Results@#Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. @*Conclusions@#We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.
ABSTRACT
Zeolite supportedα-cyano-4-hydroxycinnamic acid ( CHCA) as novel composite matrix was applied in matrix assisted laser desorption ionization time-of-flight mass spectrometry ( MALDI-TOF-MS ) analysis of substance P and small molecular compounds of fluoroquinolones. In the experiment, this new matrix was examined and compared with conventional organic matrix CHCA. The results indicated that the novel composite matrix was capable of suppressing the alkali metal related peaks and interference fragments, simplifying mass spectra in low-molecular-weight region, and promoting ionization efficiency. The influence of SiO2/Al2 O3 ratio of ZSM-5 and porous diameter of ZSM-5 and Beta zeolites on performance of MALDI-TOF-MS analysis of substance P was also investigated under the same conditions. In contrast, it was regarded that the strong surface acidity and sufficient cavity for loading CHCA were beneficial for interference fragments suppression and peak intensity enhancement. Additionally, it was successfully applied in the detection of enrofloxacin and ciprofloxacin in complex samples.
ABSTRACT
Zeolite supportedα-cyano-4-hydroxycinnamic acid ( CHCA) as novel composite matrix was applied in matrix assisted laser desorption ionization time-of-flight mass spectrometry ( MALDI-TOF-MS ) analysis of substance P and small molecular compounds of fluoroquinolones. In the experiment, this new matrix was examined and compared with conventional organic matrix CHCA. The results indicated that the novel composite matrix was capable of suppressing the alkali metal related peaks and interference fragments, simplifying mass spectra in low-molecular-weight region, and promoting ionization efficiency. The influence of SiO2/Al2 O3 ratio of ZSM-5 and porous diameter of ZSM-5 and Beta zeolites on performance of MALDI-TOF-MS analysis of substance P was also investigated under the same conditions. In contrast, it was regarded that the strong surface acidity and sufficient cavity for loading CHCA were beneficial for interference fragments suppression and peak intensity enhancement. Additionally, it was successfully applied in the detection of enrofloxacin and ciprofloxacin in complex samples.
ABSTRACT
<p><b>OBJECTIVE</b>To improve the accuracy and efficiency of pulmonary nodule segmentation of thoracic CT image for computer-aided diagnostic (CAD) system, especially for those nodules adhering to the pleural or blood vessels.</p><p><b>METHODS</b>We proposed the automatic process of pulmonary nodule segmentation, and using region growing method based on the contrast and gradient, the pulmonary nodule images were acquired. A self-adapted morphologic segmentation algorithm was presented for the unsuccessful nodule segmentation using region growing.</p><p><b>RESULTS AND CONCLUSIONS</b>Experiments on clinical 2D pulmonary images showed that the solitary pulmonary nodules and those adhering to the pleural or blood vessels could all be segmented. This pulmonary nodule segmentation algorithm is feasible for automated segmentation of the thoracic CT images.</p>