Ultrasound scoring in combination with ultrasound elastography for differentiating benign and malignant thyroid nodules.

OBJECTIVE: The aim of this study was to evaluate the value of ultrasound scores obtained by conventional ultrasonography and ultrasound elastography in the differentiation of benign and malignant thyroid nodules in Chinese patients. METHODS: This study included 297 patients who were referred for surgery for compressive symptoms or suspicion of malignancy. Five hundred and twelve thyroid nodules were examined by ultrasonography. The final diagnosis was based on histological findings. A seven-point ultrasound scoring system based on conventional ultrasonography and a five-point scoring system based on ultrasound elastography were applied independently or in combination. The receiver operating characteristic (ROC) curves were graphed, and the areas under the curves (AUCs) were compared using the χ(2) -test. RESULTS: Solid composition, hypo-echoic appearance, an irregular or blurred margin, an aspect ratio ≥1, intranodular blood flow and presence of microcalcifications were significant predictors of malignant thyroid nodules. The AUC (95% CI) was 0·9067 (0·8817-0·9318) for the ultrasound scores based on conventional ultrasonography and 0·9080 (0·8842-0·9317) for the elasticity scores. The combination of these two scoring systems provided good accuracy with an AUC (95% CI) of 0·9415 (0·9223-0·9606), which was significantly higher than that obtained with the conventional ultrasound scores (χ(2)  = 36·03, P < 0·001) or the elasticity scores (χ(2)  = 12·80, P < 0·001) individually. When we set the cut-point to ≥5, the sensitivity and specificity were 85·22% and 87·38%, respectively. CONCLUSIONS: Elastography in combination with conventional ultrasonography is a promising imaging-based approach that can assist in the differential diagnosis of thyroid cancer.

Obesity-associated gene FTO rs9939609 polymorphism in relation to the risk of tuberculosis.

BACKGROUND: Obesity is known to affect cell-mediated immune responses. Recent studies have revealed that genetic polymorphisms in the fat mass and obesity associated (FTO) gene are related to human obesity. We hypothesize that this gene may also play a role in the risk of immune-related infectious diseases such as tuberculosis. METHODS: This case-control study included 1625 pulmonary tuberculosis cases and 1570 unaffected controls recruited from the Jiangsu province in China. Single nucleotide polymorphisms (SNPs), rs9939609 and rs8050136, in the FTO gene were genotyped using TaqMan allelic discrimination assays. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the unconditional logistic regression model. RESULTS: We observed a significant association between the genetic polymorphism rs9939609 and tuberculosis risk. Compared with the common genotype TT, individuals carrying AA had a significantly increased risk, with an OR of 3.77 (95% CI: 2.26-6.28). After adjusting for potential confounders, the relationship remains significant. An additive model showed that carriers of an allele A had a 26% increased risk of tuberculosis compared with the T allele (OR: 1.26, 95% CI: 1.08-1.48). Compared with the common haplotype rs9939609T-rs8050136C, the haplotype rs9939609A-rs8050136C was related to an increased risk of tuberculosis (OR = 6.09, 95% CI: 3.27-12.34). CONCLUSIONS: The FTO polymorphism rs9939609 is associated with a risk of pulmonary tuberculosis in the Chinese population.

[Correlation between acoustic immittance and ETS in eustachian tube function test].

Objective:To investigate the correlation between acoustic immittance and eustachian tube score（ETS） in eustachian tube function test. Methods:124 ears eustachian tube function with tympanic tension perforation of 107 patients with chronic suppurative otitis media were measured by acoustic immittance positive pressure balance method and ETS. According to the positive pressure balance test results of acoustic immittance, the ear eustachian tube open pressure between 100 and 200 daPa is assigned 2, the ear with open pressure between 200 and 300 daPa is assigned 3, the ear with open pressure betwween 300 and 400 daPa is assigned 4, the ear open pressure is greater than 400 daPa but eustachian tube open after swallowing is assigned 5, and the ear which eustachian tube open pressure is greater than 400 daPa and cannot open after swallowing is assigned 6. Then compare the results. Results:In the acoustic immittance test, there was no ears whose eustachian tube opening pressure less than 100 daPa, 10 ears（8.1%） open pressure between 100 and 200 daPa, 16 ears（12.9%） open pressure between 200 and 300 daPa, 46 ears（37.1%） open pressure between 300 and 400 daPa, 19 ears（15.3%） whose eustachian tube don't open pressure at 400 daPa but open after swallowing, and the cumulative percentage of the above was 73.4%. There were 33 ears（26.6%） whose eustachian tubes not opening after receiving maximum pressure（400 daPa） and repeated swallowing. The score of acoustic immittance eustachian tube function test was significantly correlated with the scores of ETS, eustachian tube manometry（TMM） and subjective part of ETS（P<0.05）. The result of acoustic immittance was moderately negatively correlated with ETS（r=-0.439） and TMM（r=-0.425）, and weakly negatively correlated with subjective part of ETS（r=-0.249）. The scores of 2-5 points （the affected ears with open eustachian tube in all acoustic impedance test methods） were defined as the normal group, and the scores of 6 point were defined as the abnormal group. The results of acoustic immittance between the normal group and the abnormal group showed that there were significant differences with the subjective scores of ETS, TMM and ETS. The consistency compared the results of acoustic immittance eustachian tube test with the results of ETS was poor（kappa value was negative）, and the difference was statistically significant. Conclusion:The open pressure of acoustic immittance positive pressure balance method is a good predictor of the subjective scores of ETS, TMM and ETS. The smaller the open pressure is, the better the subjective scores of ETS, TMM and ETS may be. This two methods results are inconsistent and cannot be replaced. More consideration should be given to the middle ear. The open pressure, equilibrium pressure and the difference between them need to be paid attention to at the same time.

Induction of apoptosis by p110C requires mitochondrial translocation of the proapoptotic BCL-2 family member BAD.

p110C, a 50-kDa isoform of the PITSLRE kinase family, was demonstrated to play an important role in cell apoptosis. However, how p110C exactly promotes apoptosis is unclear. Our previous study showed that p110C interacted with p21-activated kinase 1 (PAK1), an important kinase of the proapoptotic BCL-2 family member BAD, and evidently inhibited its kinase activity. Here, we report that overexpression of p110C leads to decreased phosphorylation of BAD and its subsequent translocation from cytosol to mitochondria, which in turn induces the release of cytochrome c and the onset of apoptosis. Knocking down endogenous BAD expression will inhibit p110C induced apoptosis. Two kinase dead forms of p110C, D149N and K36N, lose the ability to inhibit the kinase activity of PAK1 and fail to induce the translocation of BAD and the BAD and such proapoptotic ability is associated with the kinase activity of p110C.

Genetic polymorphisms of IFNG and IFNGR1 in association with the risk of pulmonary tuberculosis.

OBJECTIVE: Genetic host factors play an important role in controlling individual's susceptibility to the pathogen. This study aims to explore the single and joint effect of genetic polymorphisms of interferon-gamma (IFNG) and its receptor (IFNGR1) in association with the pulmonary tuberculosis in a Chinese Han population. METHODS: This population-based case control study consisted of 1434 pulmonary tuberculosis patients and 1412 healthy controls. Six tag SNPs in IFNG/IFNGR1 were genotyped using TaqMan allelic discrimination technology. The logistic regression model was carried out to analyze the associations between the genotypes and haplotypes and the risk of tuberculosis by calculating the odds ratio (OR) and 95% confidence interval (CI). RESULTS: After the Bonferroni correction for multiple comparisons, three SNPs (rs2234711, rs1327475 and rs7749390) in IFNGR1 gene were observed to be significantly associated with the altered risks of tuberculosis. For the SNP rs2234711, individuals carrying C allele (vs. T) showed a decreased risk, with the adjusted OR(95% CI) of 0.82(0.76-0.91). The additive model revealed that each additional allele contributed about 14% decreased risk (OR: 0.86, 95% CI: 0.77-0.95). Moreover, we observed a strong linkage disequilibrium between rs2234711 and rs3799488. Compared with the common rs2234711C-rs3799488C haplotype, the haplotype rs2234711T-rs3799488C contributed to a significant increase in the risk of tuberculosis (adjusted OR: 1.24, 95% CI: 1.09-1.41). CONCLUSIONS: Our results suggest that genetic polymorphisms in IFNGR1 gene are involved in the risk of tuberculosis in the Chinese population. Future studies should include a comprehensive sequencing analysis to identify the specific causative sequence variants underlying the observed associations.

Identification of dynein light chain 2 as an interaction partner of p21-activated kinase 1.

p21-Activated kinase 1 (PAK1), a member of the evolutionarily conserved PAK family of serine/threonine kinases, is essential for a variety of cellular functions. Our previous studies showed that PAK1 participated in the apoptotic pathway mediated by p110C. To further investigate its functions, we used the yeast two-hybrid system to screen a human fetal brain cDNA library and identified dynein light chain 2 (DLC2)/myosin light chain (MLC) as an interacting partner of PAK1. The association of PAK1 with DLC2 was further confirmed by in vitro binding assay. With the stimulation of EGF, PAK1 interacted with HA-DLC2 in vivo and relocalized in cytoplasm near the perinuclear location in confocal microscope analysis. The deletion analysis showed that the interaction of DLC2 with PAK1 occurred within the residues 210-332 of PAK1. For that studies showed that DLC2 was a subunit of myosin complex, so it is possible that PAK1 binds to DLC2 and transports by myosin complex.

Cyclin D3 interacts with vitamin D receptor and regulates its transcription activity.

D-type cyclins are essential for the progression through the G1 phase of the cell cycle. Besides serving as cell cycle regulators, D-type cyclins were recently reported to have transcription regulation functions. Here, we report that cyclin D3 is a new interacting partner of vitamin D receptor (VDR), a member of the superfamily of nuclear receptors for steroid hormones, thyroid hormone, and the fat-soluble vitamins A and D. The interaction was confirmed with methods of yeast two-hybrid system, in vitro binding analysis and in vivo co-immunoprecipitation. Cyclin D3 interacted with VDR in a ligand-independent manner, but treatment of the ligand, 1,25-dihydroxyvitamin D3, strengthened the interaction. Confocal microscopy analysis showed that ligand-activated VDR led to an accumulation of cyclin D3 in the nuclear region. Cyclin D3 up-regulated transcriptional activity of VDR and this effect was counteracted by overexpression of CDK4 and CDK6. These findings provide us a new clue to understand the transcription regulation functions of D-type cyclins.