Genotype-phenotype landscape of pituitary adrenocorticotroph hormone adenoma / 中华内分泌代谢杂志

Objective:Cushing′s disease(CD) is caused by the pituitary adrenocorticotroph hormone(ACTH) secreting adenomas, leading to increased serum cortisol levels and various abnormal metabolic processes. Untreated CD is linked to high mortality, thus it is critical to elucidate its pathogenesis. This study aims to explore the pathogenesis of pituitary ACTH adenomas using whole-genome sequencing analysis.Methods:Fresh tumor tissues and peripheral blood samples were collected in 9 confirmed cases of pituitary ACTH adenomas who underwent surgery. Whole genome sequencing was then performed, followed by analysis and verification of single nucleotide mutations, copy number variation(CNV) and chromosome structure variations.Results:Somatic USP8 mutations(p.Ser718del, p. Ser718Pro, p. Pro720Arg, p. Pro720Gln) were found in 5 patients, with a rate of 55.6%; CNV of USP8 was detected in 1 patient; TP53(p.Cys135Tyr), NF1(p.Val1049Glufs*11) and KMT2C(c.3323+ 1G>A) mutations were identified in 1 patient harboring wild-type USP8. CNV analysis showed a loss of heterozygosity in multiple chromosomes in a wild-type USP8 patient. Structural variations were found in 2 with unknown significance. No germline gene mutations were detected in this study.Conclusion:Somatic USP8 mutations, increased copy number of USP8, variations of tumor-related genes such as TP53 and extensive somatic CNV all contribute to pathogenesis of CD. Chromosomal structure variations may suggest high-risk pituitary ACTH adenomas, and call for frequent follow-up and aggressive treatment.

Investigation of image quality and radiation dose of coronary CT angiography in a single cardiac cycle with different heart rate / 中华放射医学与防护杂志

Objective To investigate the image quality and radiation dose of coronary computed tomography argiograply(CCTA) with wide-body detector CT in single cardiac cycle with different heart rate.Methods A total of 821 patients with clinically suspected coronary artery lesions were performed CCTA examination continuously.They were divided into six groups:group A (＜65 bpm) with 132 cases,group B (66-75 bpm) with 244 cases,group C (76-85 bpm) with 145 cases,group D (86-95 bpm) with 101 cases,group E (96-105 bpm) with 101 cases and group F (106-135 bpm) with 98 cases.The CT values of the aorta root and the middle segment of LAD and RCA,the signal to noise ratios (SNRs),the contrast noise ratios (CNRs),the effective doses (E),the diagnostic rates and scores were compared among six groups of CCTA images.Results There was no significant difference in objective quality between the six groups (P＞0.05).There was no significant difference in the diagnostic rates of LAD,LCX and RCA (all P＞0.05).However,there were significant differences in LAD,LCX and RCA with 4 points (excellent) among the six groups (x2 =27.614,58.475,39.571,P ＜ 0.05).There were significant differences in radiation dose among the 6 groups (F=37.32,P＜0.05).The radiation dose of group B was highest,and that of group D,group E and group F was the lowest.Conclusions The CCTA images with wide-body detector CT in single heart cycle with different heart rate can meet the clinical diagnostic requirements,but image quality declined with heart rate increasing.The higher heart rate groups (heart rate ＞ 85 beats/min) had lower radiation doses.

Detection of drug resistance mutation in HBV using matrix assisted laser desorption/ionization time-of-flight mass spectrometry / 中华检验医学杂志

Objective To establish a rapid method for detection of drug-resistance mutation in HBV, based on PCR-MALDI-TOF MS, and to explore the influential factors on this method. Methods One hundred blood serum samples, which were collected from chronic HBV patients with single drug-resistance or multiple drug-resistance of Lamivudin, Adefovi, Entecavir and Telbivudine, and 10 kinds of mutant HBV plasmids were analyzed using PCR-MALDI-TOF MS and confirmed by PCR-based sequencing. Results Of 100 samples detected, thirty-one samples were positive for drug-resistance and 69 samples were negative. The PCR-MALDI-TOF MS results of 94 samples were completely consistent with PCR-based sequencing. Six samples were inconsistent , of which three samples were positive by the two methods, but more mutation loci were detected by PCR-MALDI-TOF MS than sequencing. The consistent rate of two methods was 94%,detection sensitivity was up to 100 copies/μl, and the cut off value of detectable mutation level was 5%.Conclusion PCR-MALDI-TOF MS could be used for rapid and simple analysis of the drug resistance for the clinical application with features of high sensitivity and accuracy, high throughput and automation.