Objectives:To estimate the basic reproduction number of the Wuhan novel coronavirus (2019-nCoV). Methods:Based on the susceptible-exposed-infected-removed (SEIR) compartment model and the assumption that the infectious cases with symptoms occurred before 26 January, 2020 are resulted from free propagation without intervention, we estimate the basic reproduction number of 2019-nCoV according to the reported confirmed cases and suspected cases, as well as the theoretical estimated number of infected cases by other research teams, together with some epidemiological determinants learned from the severe acute respiratory syndrome (SARS). Results:The basic reproduction number fall between 2.8 and 3.3 by using the real-time reports on the number of 2019-nCoV-infected cases from People's Daily in China and fall between 3.2 and 3.9 on the basis of the predicted number of infected cases from international colleagues. Conclusions:The early transmission ability of 2019-nCoV is close to or slightly higher than SARS.It is a controllable disease with moderate to high transmissibility. Timely and effective control measures are needed to prevent the further transmissions. K E Y W O R D S2019 novel coronavirus (2019-nCoV), basic reproduction number, epidemiology

ObjectiveT cell receptor (TCR) diversity determines the autoimmune responses in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and is closely associated with autoimmune diseases prognosis and prevention. However, the characteristics of variations in TCR diversity and their clinical significance is still unknown. Large series of patients must be studied in order to elucidate the effects of these variations.MethodsPeripheral blood from 877 SLE patients, 206 RA patients and 439 healthy controls (HC) were amplified for the TCR repertoire and sequenced using a high-throughput sequencer. We have developed a statistical model to identify disease-associated TCR clones and diagnose autoimmune diseases.ResultsSignificant differences were identified in variable (V), joining (J) and V-J pairing between the SLE or RA and HC groups. These differences can be utilised to discriminate the three groups with perfect accuracy (V: area under receiver operating curve > 0.99). One hundred ninety-eight SLE-associated and 53 RA-associated TCRs were identified and used for diseases classification by cross validation with high specificity and sensitivity. Disease-associated clones showed common features and high similarity between both autoimmune diseases. SLE displayed higher TCR heterogeneity than RA with several organ specific properties. Furthermore, the association between clonal expansion and the concentration of disease-associated clones with disease severity were identified, and pathogen-related TCRs were enriched in both diseases.ConclusionsThese characteristics of the TCR repertoire, particularly the disease-associated clones, can potentially serve as biomarkers and provide novel insights for disease status and therapeutical targets in autoimmune diseases.

The cross talk of CD40/CD40 ligand (CD40L) plays a key role in CD4+ T cell priming, B-cell terminal maturation, and immunoglobulin (Ig) class-switch recombination. Genetic defects in the CD40L lead to a disorder characterized by elevated concentrations of serum IgM and immunodeficiency. Patients with Primary Biliary Cirrhosis (PBC) characteristically show circulating anti-mitochondrial antibodies (AMAs), liver infiltrating autoreactive T lymphocytes against mitochondrial antigens, and high levels of IgM. We hypothesized that CD40L may play a key role in the pathogenesis of the elevated serum IgM and analyzed genetic and epigenetic modifications of the gene coding for CD40L in CD4+ and CD8+ T cells isolated from circulating mononuclear cells from PBC patients and healthy controls. We herein demonstrate significantly lower levels of DNA methylation of the CD40L promoter in CD4+ T cells from PBC patients as compared with controls, and this decreased methylation was inversely correlated with levels of serum IgM in PBC patients. In conclusion, the findings of an absence of genetic modifications of the CD40L gene in concert with decreased DNA methylation of the CD40L promoter in PBC patients suggests that environmental factors rather than genetics must play a major role in the pathogenesis of elevated serum IgM in PBC.