Mathematical models for devising the optimal Ebola virus disease eradication.

BACKGROUND: The 2014-2015 epidemic of Ebola virus disease (EVD) in West Africa defines an unprecedented health threat for human. METHODS: We construct a mathematical model to devise the optimal Ebola virus disease eradication plan. We used mathematical model to investigate the numerical spread of Ebola and eradication pathways, further fit our model against the real total cases data and calculated infection rate as 1.754. RESULTS: With incorporating hospital isolation and application of medication in our model and analyzing their effect on resisting the spread, we demonstrate the second peak of 10,029 total cases in 23 days, and expect to eradicate EVD in 285 days. Using the regional spread of EVD with our transmission model analysis, we analyzed the numbers of new infections through four important transmission paths including household, community, hospital and unsafe funeral. CONCLUSIONS: Based on the result of the model, we find out the key paths in different situations and propose our suggestion to control regional transmission. We fully considers Ebola characteristics, economic and time optimization, dynamic factors and local condition constraints, and to make our plan realistic, sensible and feasible.

The enrichment of HBV immune-escape mutations during nucleoside/nucleotide analogue therapy.

BACKGROUND: Drug-resistant HBV mutants frequently arise during nucleoside/nucleotide analogue (NA) therapy, while the resistance mutations on polymerase also have consequent changes in the S protein. The enrichment of immune-escape mutations was negatively correlated with hepatitis B surface antigen (HBsAg) clearance under NA therapy. This study aims to characterize the variability of HBV polymerase and surface antigen in patients with virological breakthrough under NA therapy. METHODS: From 2012 to 2014, serum samples were collected from 156 patients with chronic hepatitis B infection, who had experienced NA therapy for at least 24 weeks and displayed virological breakthrough, while 165 HBV carriers without NA treatment were also enrolled. HBV DNA was quantified and polymerase reverse transcriptase domain was amplified and sequenced. RESULTS: A total of 97 patients in the NA treatment group had resistance mutations, with rtM204I/V/S being the most common substitution (78 of 97), while no resistance mutations were detected in the treatment-naive group. Various escape mutations were detected, and the detection rate was significantly higher in the NA treatment group (38, 24.4%) than that of treatment-naive group (18, 10.9%; P<0.05). Except for the combination of sP120T+sA128V, other double combinations (n=11) were only detected in the NA treatment group, and nine of these combinations in the treatment group were detected in HBV variants without antiviral resistance mutations. CONCLUSIONS: Antiviral resistance mutations were selected by a long duration of NA therapy. Virological breakthrough was not only attributed to the emergence of resistance mutations, but may also be associated with the enrichment of immune-escape mutations.

Molecular analyses of prostate tumors for diagnosis of malignancy on fine-needle aspiration biopsies.

Prostate cancer (PCa) is a common cancer and remains the second-leading cause of cancer-associated mortality in men, but diagnosis of PCa remains a main clinical challenge. To investigate the involvement of differentially expressing genes in PCa with deregulated pathways to allow earlier diagnosis of the disease, transcriptomic analyses of differential expression genes in fine-needle aspiration (FNA) biopsies helped to discriminate PCa from benign prostatic hyperplasia (BPH). We identified 255 genes that were deregulated in prostate tumors compared with BPH tissues. qRT-PCR was conducted to examine the expression levels of the four genes in FNA biopsies and confirmed that ITGBL1 was significantly up-regulated and HOXA7, KRT15 and TGM4 were down-regulated in the PCa compared to the BPH, with a sensitivity of 87.1% and a specificity of 87.8%; the area under the receiver operating characteristic curve was estimated at 0.94, which was significantly improved compared with PSA alone (AUC = 0.82). Moreover, the increased expression of ITGBL1 correlated with total cholesterol, triglyceride and PSA. Our results demonstrated that transcriptomic analyses in FNA biopsies could facilitate rapid identification of potential targets for therapy and diagnosis of PCa.

A novel norovirus GII.17 lineage contributed to adult gastroenteritis in Shanghai, China, during the winter of 2014­2015.

Norovirus (NoV) is now recognized as a leading cause of nonbacterial acute gastroenteritis; however, the NoV GII.17 genotype has rarely been reported as the predominant genotype in clinical diarrhea cases. During the winter of 2014­2015, the GII.17 genotype, together with the NoV GII.4 genotype, dominated in sporadic adult patients with gastroenteritis in Shanghai. Phylogenetic analysis based on full-length VP1 amino acid sequences showed that the GII.17 strains that emerged in Shanghai have close evolutionary relationships with strains recently collected in the Hong Kong area, Guangdong province of China, and Japan during the same period. This cluster in the phylogenetic tree may represent a novel NoV GII.17 lineage recently circulating in East Asia. Pairwise distances between clusters also revealed the evolution of the NoV GII.17 genotype in previous decades. Our study emphasizes the importance of combined surveillance of NoV-associated infections.