The nationwide distribution and trends of hepatitis C virus genotypes in mainland China

Comprehensive data on hepatitis C virus (HCV) genotypes distribution is critical for treatment regimen selection, vaccine design, and drug development. This study aimed to understand the dynamic distribution of HCV genotypes in Mainland China. Three hundred sixty-two studies published from January 1993 to December 2017 involving 64 891 samples (5133 injecting drug users, 2748 volunteer blood donors, 1509 former paid plasma donors, 160 sexually encounters, and 1992 human immunodeficiency virus (HIV)/HCV coinfection patients) were eligible for the quantitative synthesis estimation. Pooled proportion of HCV genotypes (and 95% confidence intervals [CIs]) was estimated through the Freeman-Tukey double arcsine transformation by period, region, and risk group. A sharp decline of the subtype 1b was observed in all regions except in northwestern and central regions. The genotypes 3 and 6 showed an obvious increase in southern and southwestern regions and have already spread nationwide. After 2010, subtype 1b was the most dominant variant in all regions and risk groups, accounting for 54.0% (95% CI, 51.9-56.1) of all national infections. Subtype 2a was the second most prevalent strain in all regions except in the south and southwest, with 15.4% (95% CI, 13.1-17.8) national infections. The subtype 6a in southern region and 3b and 3a in southwestern region had a higher proportion of infections than that in other regions. In addition, the genotypes 3 and 6 are already prevalent in almost all risk groups. The distribution of HCV genotypes were sharply shifting in China in the past three decades. The HCV subtype 1b posed a sharp decline, whereas genotypes 3 and 6 played an increasing role in the regional and populational HCV pandemic.     

T follicular regulatory cells suppress Tfh-mediated B cell help and synergistically increase IL-10-producing B cells in breast carcinoma

T follicular regulatory (Tfr) cell is a recently discovered subset of T regulatory (Treg) cells. The main function of Tfr cells is thought to suppress germinal cancer reaction and inhibit B cell proliferation and Ig production. However, recent studies demonstrate that Tfr cells may be required for high-affinity Ig formation during acute virus infections. The role of Tfr cells in breast cancer is not thoroughly investigated. In this study, total circulating CD4 T cells were sorted into CD25⁺CXCR5⁻ Treg-like, CD25⁺CXCR5⁺ Tfr-like, and CD25⁻CXCR5⁺ Tfh-like subsets. Data showed that the Tfr-like subset presented intermediate levels of both Foxp3 and Bcl-6, while the Treg-like subset was high in Foxp3 and low in Bcl-6, and the Tfh-like was high in Bcl-6 and low in Foxp3. Of note, the frequencies of Tfr-like and Treg-like cells were significantly elevated in breast cancer (BC) patients than in non-cancer (NC) controls. Tfr-like cells in BC patients also expressed significantly higher levels of Foxp3 than those in NC controls. Neither Treg-like nor Tfr-like cells could support Ig production from naive B cells, while Tfh-like cells potently supported Ig production from naive B cells. Tfr-like cells increased the availability of IL-10, both by directly producing IL-10 and by increasing IL-10 production from B cells. Interestingly, Tfr-like cells increased IL-10 production from B cells synergistically with Tfh cells, but at the same time, significantly reduced Ig production in the Tfh-B cell coculture. These Tfr-mediated effects on Tfh cells were not found in canonical Treg cells. Overall, this study demonstrates several distinctive features in circulating Tfr cells and suggests that Tfr cells may promote the formation of IL-10-producing B cells in BC.

     

X-linked hyper-IgM syndrome complicated with interstitial pneumonia and liver injury: a new mutation locus in the CD40LG gene

Immunologic Research -     

基于MRI的认知相关的脑宏观-微观结构变化模式研究综述

阿尔茨海默病(AD)是伴有认知功能障碍的神经退行性疾病,其发病机制复杂且至今不明确,一直是国内外医学研究领域的巨大挑战。而结构和扩散磁共振成像技术的发展,为研究AD大脑宏观形态学-微观结构特性病变的机制研究提供重要技术手段。近年来,研究发现,这种宏观和微观结构的异常改变之间具有的内在联系,对于揭示AD等衰老相关疾病的结构病变机理有非常重要的意义。针对该问题,对近几年MRI的大脑宏-微观结构变化模式及相互关系的研究进行分析,对其重要的分析方法和研究结论进行综述,希望有助于今后对大脑宏-微观病变机理的深入开展。     

Prion neurotoxicity

Although the mechanisms underlying prion propagation and infectivity are now well established, the processes accounting for prion toxicity and pathogenesis have remained mysterious. These processes are of enormous clinical relevance as they hold the key to identification of new molecular targets for therapeutic intervention. In this review, we will discuss two broad areas of investigation relevant to understanding prion neurotoxicity. The first is the use of in vitro experimental systems that model key events in prion pathogenesis. In this context, we will describe a hippocampal neuronal culture system we developed that reproduces the earliest pathological alterations in synaptic morphology and function in response to PrP^Sc. This system has allowed us to define a core synaptotoxic signaling pathway involving the activation of NMDA and AMPA receptors, stimulation of p38 MAPK phosphorylation and collapse of the actin cytoskeleton in dendritic spines. The second area concerns a striking and unexpected phenomenon in which certain structural manipulations of the PrP^C molecule itself, including introduction of N‐terminal deletion mutations or binding of antibodies to C‐terminal epitopes, unleash powerful toxic effects in cultured cells and transgenic mice. We will describe our studies of this phenomenon, which led to the recognition that it is related to the induction of large, abnormal ionic currents by the structurally altered PrP molecules. Our results suggest a model in which the flexible N‐terminal domain of PrP^C serves as a toxic effector which is regulated by intramolecular interactions with the globular C‐terminal domain. Taken together, these two areas of study have provided important clues to underlying cellular and molecular mechanisms of prion neurotoxicity. Nevertheless, much remains to be done on this next frontier of prion science.     

One‐Step Route to Ladder‐Type C–N Linked Conjugated Polymers

A one‐step synthetic method is demonstrated to construct ladder‐type conjugated polymers without the resource to post‐cyclization procedures. The ladder‐type C–N linked conjugated polymers ( P1 and P2 ) and model compounds ( 1 and 2 ) are achieved in high yields. The obtained model compounds and polymers display desirable solubility in commonly used solvents and high thermal stability, which show a promising application in photoelectric material field.     

A Triple‐Shape Memory Material via Thermal Responsive Behavior of Liquid Crystalline Network Incorporating Main‐Chain/Side‐Chain LC Units

In the last several years, multiple‐shape memory liquid crystalline networks (LCNs) have received more and more attention due to the basic theoretical research on them and their wide potential applications. In this article, a novel main‐chain/side‐chain liquid crystalline monomer and its corresponding polymer networks based on the thiol‐ene click reaction are reported. Properties of the synthesized liquid crystalline monomer are well studied with nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) spectra, differential scanning calorimetry (DSC), and polarized optical microscopy (POM). The as‐prepared free‐standing LCN films are investigated well by FTIR, DSC, POM, and X‐ray diffraction (XRD), which show them having good liquid crystalline properties. Tensile test and dynamical mechanical analysis (DMA) results indicate the LCN films have excellent thermal mechanical properties. By adjusting the crosslinking densities, LCN films exhibit two thermal transition temperatures (T_g and T_NI) that can be utilized to trigger the triple‐shape memory behaviors. The cyclic thermal mechanical analysis conducted by DMA reveals that LCN films exhibit good triple‐shape memory properties with high‐shape fixity ratio (R_f (S1→S2) is 99.2% and R_f (S2→S3) is 99.3%) and shape recovery ratio (R_r (S3→S2) is 92.4% and R_r (S2→S1) is 98.5%).