Improvement in the clinical outcome of human cancers requires characterization of the genetic alterations underlying their pathogenesis. Large-scale genomic and transcriptomic characterization of papillary thyroid carcinomas (PTCs) in Western populations has revealed multiple oncogenic drivers which are essential for understanding pathogenic mechanisms of this disease, while, so far, the genetic landscape in Chinese patients with PTC remains uncharacterized. Here, we conducted a large-scale genetic analysis of PTCs from patients in China to determine the mutational landscape of this cancer. By performing targeted DNA amplicon and targeted RNA deep-sequencing, we elucidated the landscape of somatic genetic alterations in 355 Chinese patients with PTC. A total of 88.7% of PTCs were found to harbor at least one candidate oncogenic driver genetic alteration. Among them, around 72.4% of the cases carried BRAF mutations; 2.8% of cases harbored RAS mutations; and 13.8% of cases were characterized with in-frame gene fusions, including seven newly identified kinase gene fusions. TERT promoter mutations were likely to occur in a sub-clonal manner in our PTC cohort. The prevalence of somatic genetic alterations in PTC was significantly different between our Chinese cohort and TCGA datasets for American patients. Additionally, combined analyses of genetic alterations and clinicopathologic features demonstrated that kinase gene fusion was associated with younger age at diagnosis, larger tumor size, and lymph node metastasis in PTC. With the analyses of DNA rearrangement sites of RET gene fusions in PTC, signatures of chromosome translocations related to RET fusion events were also depicted. Collectively, our results provide fundamental insight into the pathogenesis of PTC in the Chinese population. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley& Sons, Ltd.

Background Anemia is one of the most common complications of sepsis. Sepsis-related anemia is associated mainly with inflammation. We aimed to observe the changes in the inflammatory anemia-associated parameters of patients with sepsis in the early stage of intensive care unit (ICU) admission and to evaluate their association with 28-day mortality. Methods A total of 198 patients with sepsis were divided into survivor ( n = 110) and non-survivor ( n = 88) groups on the basis of 28-day survival. Healthy volunteers ( n = 20) were enrolled as a control group. Plasma levels of iron, ferritin, erythropoietin (EPO), soluble transferrin receptor (sTfR), hepcidin, interleukin-6 (IL-6), hemoglobin and the red blood cell distribution width (RDW) were measured on days 1, 3 and 7 of ICU admission. Clinical data and laboratory findings were collected, and the Sequential Organ Failure Assessment (SOFA) score was calculated. Results Patients with sepsis showed significant decreases in hemoglobin, plasma iron and sTfR/log ferritin and significant increases in plasma EPO, sTfR, hepcidin, ferritin and IL-6 on days 1, 3 and 7 of ICU admission compared with healthy volunteers. Hemoglobin was correlated negatively with plasma IL-6 and hepcidin. In patients with sepsis, non-survivors had significantly lower plasma iron, EPO and sTfR/log ferritin, but higher plasma hepcidin, ferritin and IL-6 than survivors on days 1, 3 and 7 of ICU admission. Plasma EPO, hepcidin, ferritin, IL-6, sTfR/log ferritin, the RDW and SOFA score were associated significantly with 28-day mortality but to a varying extent. In particular, in predicting 28-day mortality, plasma hepcidin had an area under the receiver operating curve of 0.808 and 87.3% specificity, which was the highest among the inflammatory anemia-associated parameters tested. Conclusions Inflammatory anemia-associated parameters changed significantly in patients with sepsis in the first week of ICU admission. Plasma EPO, hepcidin, ferritin, IL-6, sTfR/log ferritin, the RDW and SOFA score were associated significantly with 28-day mortality. Plasma hepcidin might have a superior predictive value, with high specificity, compared with other inflammatory anemia-associated parameters for 28-day mortality of sepsis patients in the ICU. Electronic supplementary material The online version of this article (10.1186/s13613-019-0542-7) contains supplementary material, which is available to authorized users.

NOD2 gene 3020insC frameshift mutation is not a major contributor to the susceptibility to both Crohn's disease and ulcerative colitis in Chinese Han patients.

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ObjectivesDysbiosis of intestinal microbiota has been implicated in ulcerative colitis (UC). Fucosyltransferase (FUT) 2 and FUT3 determine expression of histo-blood group antigens in the gut and may affect the intestinal microbiota. We investigated the association between FUT2 and FUT3 polymorphisms and UC in Chinese patients.MethodsWe genotyped FUT2 (rs281377, rs1047781 and rs601338) and FUT3 (rs28362459, rs3745635 and rs3894326) in 485 UC patients and 580 healthy controls using SNaPshot. We also evaluated expression of Lewis a and b antigens in the sigmoid colon of 7 UC patients and 7 patients with benign colonic polyps.ResultsThe frequencies of mutant allele (A) and genotype (GA+AA) in FUT3 (rs3745635) were higher in UC patients than controls (P = 0.016, 95%CI: 1.339–1.699; P = 0.038, 95%CI: 1.330–1.742, respectively). Stratified analyses revealed that the frequencies of mutant allele (G) and genotype (TG+GG) of FUT3 (rs28362459) were significantly lower in patients with extensive colitis than those with distal colitis (P<0.001, 95%CI: 0.503–0.742; P = 0.001, 95%CI: 0.567–0.786, respectively). Similar conclusions were drawn for the mutant allele (A) and genotype (GA+AA) of FUT3 (rs3745635) in patients with extensive colitis compared to those with distal colitis (P = 0.006, 95%CI: 0.553–0.845; P = 0.011, 95%CI: 0.621–0.900, respectively). Although expression of Lewis b antigen in the sigmoid colon did not differ between UC patients and controls, Lewis a antigen expression was higher in the cryptic epithelium of both inflammatory and non-inflammatory sigmoid colon of UC patients than controls (P = 0.028).ConclusionsOur findings indicated that polymorphisms in FUT3 and its intestinal expression might be associated with UC pathogenesis.