Background An ongoing outbreak of pneumonia associated with a novel coronavirus was reported in Wuhan city, Hubei province, China. Affected patients were geographically linked with a local wet market as a potential source. No data on person-to-person or nosocomial transmission have been published to date. MethodsIn this study, we report the epidemiological, clinical, laboratory, radiological, and microbiological findings of five patients in a family cluster who presented with unexplained pneumonia after returning to Shenzhen, Guangdong province, China, after a visit to Wuhan, and an additional family member who did not travel to Wuhan. Phylogenetic analysis of genetic sequences from these patients were done.Findings From Jan 10, 2020, we enrolled a family of six patients who travelled to Wuhan from Shenzhen between Dec 29, 2019 and Jan 4, 2020. Of six family members who travelled to Wuhan, five were identified as infected with the novel coronavirus. Additionally, one family member, who did not travel to Wuhan, became infected with the virus after several days of contact with four of the family members. None of the family members had contacts with Wuhan markets or animals, although two had visited a Wuhan hospital. Five family members (aged 36-66 years) presented with fever, upper or lower respiratory tract symptoms, or diarrhoea, or a combination of these 3-6 days after exposure. They presented to our hospital (The University of Hong Kong-Shenzhen Hospital, Shenzhen) 6-10 days after symptom onset. They and one asymptomatic child (aged 10 years) had radiological ground-glass lung opacities. Older patients (aged >60 years) had more systemic symptoms, extensive radiological ground-glass lung changes, lymphopenia, thrombocytopenia, and increased C-reactive protein and lactate dehydrogenase levels. The nasopharyngeal or throat swabs of these six patients were negative for known respiratory microbes by point-of-care multiplex RT-PCR, but five patients (four adults and the child) were RT-PCR positive for genes encoding the internal RNA-dependent RNA polymerase and surface Spike protein of this novel coronavirus, which were confirmed by Sanger sequencing. Phylogenetic analysis of these five patients' RT-PCR amplicons and two full genomes by nextgeneration sequencing showed that this is a novel coronavirus, which is closest to the bat severe acute respiatory syndrome (SARS)-related coronaviruses found in Chinese horseshoe bats.Interpretation Our findings are consistent with person-to-person transmission of this novel coronavirus in hospital and family settings, and the reports of infected travellers in other geographical regions.

Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) plays a pivotal role in regulating T cell activation, which is believably critical for the outcome of hepatitis B virus (HBV) infection. The expression and function of CTLA-4 may be affected by gene polymorphisms. This study investigated the influence of CTLA-4 polymorphisms on disease susceptibility in Chinese Han patients with chronic HBV infection. CTLA-4 +49A/G and -318C/T polymorphisms were evaluated by DNA amplification with polymerase chain reaction followed by the restriction fragment length polymorphism analysis. The patients with chronic HBV infection had higher frequencies of genotype AA and allele A of CTLA-4 +49A/G polymorphism. The haplotype +49A-318C was significantly over-represented (P < 0.001) and haplotype +49G-318C under-represented (P = 0.006) in the patients. The +49GG genotype was more frequent (P = 0.009) and +49A allele was less frequent in patients with lower ALT levels (P = 0.012) in HBeAg positive chronic hepatitis B. It is indicated that CTLA-4 +49A/G polymorphism alone and in a haplotype with -318C allele may confer susceptibility to chronic HBV infection in Chinese Han patients.

Accumulating evidence indicates that dysregulation of miRNAs could contribute to tumor growth and metastasis of chondrosarcoma by infuencing cell proliferation and invasion. In the current study, we are interested to examine the role of miRNAs in the carcinogenesis and progression of chondrosarcoma. Here, using comparative miRNA profiling of tissues and cells of chondrosarcoma and cartilage, we identified miR-494 as a commonly downregulated miRNA in the tissues of patients with chondrosarcoma and chondrosarcoma cancer cell line, and upregulation of miR-494 could inhibit proliferation and invasion of chondrosarcoma cancer cells in vivo and in vitro. Moreover, our data demonstrated that SOX9, the essential regulator of the process of cartilage differentiation, was the direct target and functional mediator of miR-494 in chondrosarcoma cells. And downregulation of SOX9 could also inhibit migration and invasion of chondrosarcoma cells. In the last, we identified low expression of miR-494 was significantly correlated with poor overall survival and prognosis of chondrosarcoma patients. Thus, miR-494 may be a new common therapeutic target and prognosis biomarker for chondrosarcoma.

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in China. Recently, a shift in molecular epidemiology from hepatitis E genotype 1 (HEV-1) to hepatitis E genotype 4 (HEV-4) has been observed in Northern China, marking a switch from human-to-human transmission to zoonosis. However, similar data from cities in Southern China are lacking. This observational study of human hepatitis E cases in Shenzhen, a metropolitan city in the Pearl River Delta region, aimed to describe the clinical features and molecular epidemiology of hepatitis E in Southern China. Over a 55-month period, we identified 20 patients with acute hepatitis E. Most were middle-aged men, and 50% of patients had concomitant liver disease, of whom 70% were identified to have non-alcoholic fatty liver disease; such patients had a trend toward higher liver enzymes. Quantitative real-time RT-PCR using archived serum samples showed that 12 patients had hepatitis E viremia at presentation. Sequencing of the RNA-dependent RNA polymerase gene was performed for five of these patients, and phylogenetic analysis revealed that these five HEV isolates belonged to subgenotype 4b and were clustered with swine HEV isolates from Southern China. Combined with other studies showing similar findings, this suggests that the molecular epidemiology of hepatitis E in China is evolving toward low-level endemicity driven by foodborne transmission from seafood or pork products. The importance of concomitant liver disease, in particular non-alcoholic fatty liver disease, as a risk factor for severe hepatitis E requires further study.

Interleukin (IL)-17A plays important roles in hepatitis B virus (HBV)-induced liver diseases. This study aims to investigate IL17A single nucleotide polymorphisms (SNPs) and the predispositions to chronic HBV infection and hepatocellular carcinoma (HCC) risk and the correlations to IL-17A and IgE levels. Three hundred ninety-five chronic HBV patients, 75 HBV infection resolvers, and 174 healthy controls were included. IL17A SNPs rs8193036 (C/T) and rs2275913 (A/G) and serum IL-17A and IgE levels were determined. HBV infection resolvers had higher rs8193036 allele T and allele T-containing genotypes than HBV patients or controls. Compared with chronic hepatitis, HCC patients had more frequent rs2275913 genotype GG (odds ratios [OR] 3.317, 95% confidence interval [CI] 1.663-6.617, P = 0.001) and allele G (OR 1.844, 95% CI 1.311-2.595, P < 0.001), and more frequent haplotypes CG (OR 1.868, 95% CI 1.256-2.778, P = 0.002) and TG (OR 1.788, 95% CI 1.031-3.101, P = 0.037) of rs8193036 and rs2275913. Comparison of HCC patients with cirrhosis yielded similar findings. Apart from male gender and older ages, IL-17A level (OR 1.020, 95% CI 1.003-1.036, P = 0.019) and rs2275913 genotypes AG and GG (OR 1.704, 95% CI 1.214-2.390, P = 0.006) were factors significantly associated with HCC risk in multivariate analysis in comparison with HBV patients without HCC. These factors remained significant in multivariate analysis in relation to cirrhosis. IL17A rs2275913 genotype GG was associated with significantly increased IL-17A and IgE levels. IL17A polymorphisms may influence HCC risk in chronic HBV infection via regulating IL-17A production.