Objective To identify the association of thyroid stimulating hormone receptor ( TSHR ) gene intron 1 susceptible loci and 4p14 susceptible locus rs6832151 polymorphisms with Graves’ disease ( GD) in Han Chinese population in Bengbu, Anhui, China. The gene-gene interaction among TSHR intron 1 susceptible loci and 4p14 susceptible locus rs6832151 was also investigated. Methods The genotypes of the single-nucleotide polymorphisms ( SNPs) were analyzed by Taqman probe technique on Fluidigm EP1 platform in 611 patients with GD and 555 control subjects, and linkage analysis, correlation analysis, haplotype analysis, and epistasis analysis with them were performed. Results Six SNPs in two candidate genes(rs12101261, rs4903964,rs179247, rs2284722 and rs17111394 in TSHR, rs6832151 in 4p14) were associated with GD (all P<0. 05). The frequency distributions of haplotypes of SNPs in TSHR intron 1 ( AGTA, GGCG, AATA, and CC) were significantly different between GD and control groups(all P<0. 01). There existed the interactions between rs179247 and rs12101261 in TSHR(P=0. 001) and among rs179247(TSHR),rs4903964(TSHR) and rs6832151(4p14) (P=0. 001). Conclusions rs683215 in 14p14 and rs12101261, rs4903964, rs179247, rs2284722 and rs17111394 in TSHR intron 1 were susceptible loci of GD in the Chinese Han population from Bengbu. The haplotypes in TSHR intron 1 were associated with GD. There exists the interaction between the SNPs in TSHR and 4p14,which may change the risk of GD.

Objective To explore the application value of Z-scores in evaluating growth of aorta (AO) and pulmonary artery (PA) diameter.Methods AO and PA diameters in 332 normal fetuses were measured twice using fetal echocardiography.Z-scores of AO and PA were obtained based on a simple linear equation using gestational age (GA),biparietal diameter (BPD) and femur length (FL) as independent variables.The difference of Z-scores calculated by twice examinations was evaluated.Results The gestation ages of the first and the second examinations of fetal echocardiography were (25.82± 2.27) weeks (range 18-35 weeks) and (30.61± 2.28) weeks (range 23-39 weeks).There were statistical significant differences of AO and PA diameters between the first and the second examinations (both P＜0.05).AO and PA diameters increased with the growth of GA in all fetuses obtained using two examinations,whereas there was no obvious change of Zscores of AO and PA with increasing GA,BPD and FL in individual pregnant woman.No statistical significant difference was found for Z-scores of AO and PA between the first and the second examinations (both P＞0.05).Conclusion The growth of AO and PA diameters are positively correlated with the growth of biological parameters in normal fetuses,while Z-scores of AO and PA remain constant in second and late trimesters.

Objective:To explore the clinical application value of fetal heart quantification (fetal HQ) in the analysis of 24-segment spherical index (SI) of fetal heart in normal second and third trimestries.Methods:In July 2019, sixty-five normal singletons with gestational age (GA) of 28(24, 31) weeks were examined by echocardiography in Sir Run Run Shaw Hospital. The global spherical index (GSI) of the heart was measured and the dynamic images of the standard four chamber view were collected. Twenty-four-segment SI of the left and right ventricles were measured by using the fetal HQ analysis system and the correlation between SI and gestational age was analyzed.Results:There were no significant correlations between GSI, SI of left and right ventricles and gestational age ( r s=-0.22-0.14, all P>0.05). The SI of the first segment of left ventricle was lower than those of the other 23 segments (all P<0.05). There were no significant differences of SI among the second to the eleventh segments of the left ventricle (all P>0.05). In the 13th to the 24th segments of the left ventricle, the closer to the apex of the heart, the greater the SI of the segment were noted (all P<0.05). For the right ventricle, the closer to the apex of the heart, the greater the SI of the 4th to the 24th segments were found (all P<0.05), and there were no significant differences in SI among the first to third segment( P>0.05). The success rate of fetal HQ software was 95.4%. Conclusions:The 24-segment SI of RV and LV provides a feasible and reliable quantitative method which allows for the assessment of fetal heart function from the four-chamber view.

Animals ; Bone Marrow Transplantation ; Busulfan ; Disease Models, Animal ; Drug Combinations ; Graft vs Host Disease ; Mice ; Transplantation Conditioning ; Vidarabine ; analogs & derivatives

The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury-repair process following lung injury. Pulmonary fibrosis (PF) is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells. In this study, we report that P21 expression was increased in alveolar epithelial type 2 cells (AEC2s) in a time-dependent manner following multiple bleomycin-induced PF. Repeated injury of AEC2s resulted in telomere shortening and triggered P21-dependent cell senescence. AEC2s with elevated expression of P21 lost their self-renewal and differentiation abilities. In particular, elevated P21 not only induced cell cycle arrest in AEC2s but also bound to P300 and β-catenin and inhibited AEC2 differentiation by disturbing the P300-β-catenin interaction. Meanwhile, senescent AEC2s triggered myofibroblast activation by releasing profibrotic cytokines. Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF. The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development, which suggests a potential strategy for the treatment of fibrotic lung diseases.