An effective blood-based method for the diagnosis and prognosis of hepatocellular carcinoma (HCC) has not yet been developed. Circulating tumour DNA (ctDNA) carrying cancer-specific genetic and epigenetic aberrations may enable a noninvasive 'liquid biopsy' for diagnosis and monitoring of cancer. Here, we identified an HCC-specific methylation marker panel by comparing HCC tissue and normal blood leukocytes and showed that methylation profiles of HCC tumour DNA and matched plasma ctDNA are highly correlated. Using cfDNA samples from a large cohort of 1,098 HCC patients and 835 normal controls, we constructed a diagnostic prediction model that showed high diagnostic specificity and sensitivity (P < 0.001) and was highly correlated with tumour burden, treatment response, and stage. Additionally, we constructed a prognostic prediction model that effectively predicted prognosis and survival (P < 0.001). Together, these findings demonstrate in a large clinical cohort the utility of ctDNA methylation markers in the diagnosis, surveillance, and prognosis of HCC.

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Proteomics was used to identify a protein encoded by ORF 3a in a SARS-associated coronavirus (SARS-CoV). Immuno-blotting revealed that interchain disulfide bonds might be formed between this protein and the spike protein. ELISA indicated that sera from SARS patients have significant positive reactions with synthesized peptides derived from the 3a protein. These results are concordant with that of a spike protein-derived peptide. A tendency exists for co-mutation between the 3a protein and the spike protein of SARS-CoV isolates, suggesting that the function of the 3a protein correlates with the spike protein. Taken together, the 3a protein might be tightly correlated to the spike protein in the SARS-CoV functions. The 3a protein may serve as a new clinical marker or drug target for SARS treatment.

ObjectiveDiabetes mellitus (DM) is associated with an increased fracture risk; however, the impact of DM and subsequent fracture at different sites and the associations according to patient characteristics remain unknown.DesignMeta-analysisData sourcesThe PubMed, EMBASE and Cochrane Library databases were searched from inception to March 2018.Eligibility criteriaWe included prospective and retrospective cohort studies on the associations of DM and subsequent fracture risk at different sites.Data extraction and synthesisTwo authors independently extracted data and assessed the study quality. Relative risks (RRs) with 95% CIs were calculated using a random-effects model, and the heterogeneity across the included studies was evaluated using I2 and Q statistics.ResultsOverall, DM was associated with an increased risk of total (RR: 1.32; 95% CI 1.17 to 1.48; p<0.001), hip (RR: 1.77; 95% CI 1.56 to 2.02; p<0.001), upper arm (RR: 1.47; 95% CI 1.02 to 2.10; p=0.037) and ankle fractures (RR: 1.24; 95% CI 1.10 to 1.40; p<0.001), whereas DM had no significant impact on the incidence of distal forearm (RR: 1.02; 95% CI 0.88 to 1.19; p=0.809) and vertebral fractures (RR: 1.56; 95% CI 0.78 to 3.12; p=0.209). RR ratios suggested that compared with patients with type 2 DM (T2DM), patients with type 1 DM (T1DM) had greater risk of total (RR: 1.24; 95% CI 1.08 to 1.41; p=0.002), hip (RR: 3.43; 95% CI 2.27 to 5.17; p<0.001) and ankle fractures (RR: 1.71; 95% CI 1.06 to 2.78; p=0.029). Although no other significant differences were observed between subgroups, the association of DM with upper arm or ankle, vertebrae and total fracture differed according to sex, study design and country, respectively.ConclusionsPatients with DM had greater risks of total, hip, upper arm and ankle fractures, with T1DM having a more harmful effect than T2DM.