Paclitaxel (Taxol) is a powerful chemotherapy drug used in breast cancers, but it often causes neuropathic pain, leading to the early cessation of therapy and poor treatment outcomes. Approaches for the management of paclitaxel-induced neuropathic pain are urgently needed. The involvement of spinal astrocytes in the pathogenesis of paclitaxel-induced neuropathy has been reported, but little is known about the role of fluorocitrate (FC), a selective inhibitor of astrocyte activation, during neuropathic pain related to paclitaxel treatment. In this study, we investigated the effects of FC on paclitaxel-induced neuropathic pain. Glial fibrillary acidic protein (GFAP) expression was determined to assess astrocyte activation. To explore the mechanisms involved, the expression of glial glutamate transporter 1 (GLT-1) and the activation of mitogen-activated protein kinases in the spinal dorsal horn were analyzed. The results showed that paclitaxel decreased the mechanical nociceptive thresholds and increased GFAP expression, leading to spinal astrocyte activation. After paclitaxel treatment, GLT-1 was significantly down-regulated, and the phosphorylation of ERK1/2 and JNK were obviously up-regulated. However, paclitaxel treatment did not increase p38 phosphorylation. Additional studies showed that paclitaxel-evoked mechanical hypersensitivity was reduced by FC treatment. Moreover, FC treatment inhibited the activation of astrocytes and reversed the changes in GLT-1 expression and MAPK phosphorylation. Further study indicated that FC did not influence the antitumor effect of paclitaxel, suggesting that FC blocked paclitaxel-induced neuropathic pain without antagonizing its antitumor effect. Together, these results suggested that paclitaxel induced astrocyte-specific activation, which may contribute to mechanical allodynia and hyperalgesia, and that FC could be a potential therapeutic agent for paclitaxel-induced neuropathic pain.

The A(H7N9) virus strain that emerged in 2013 was associated with a high fatality rate and may become a long-term threat to public health. A(H7N9) disease incidence is disproportionate to viral exposure, suggesting that host genetic factors may significantly influence susceptibility to A(H7N9) infection. Human genome variation in conferring risk for A(H7N9) infection in Chinese populations was identified by a two-stage investigation involving 121 A(H7N9) patients and 187 healthy controls using next generation sequencing followed by functional analysis. As a result, a low frequency variant (rs189256251; P = 0.0303, OR = 3.45, 95% CI 1.05-11.35, chi-square test) and three HLA alleles (DQB1*06:01, DQA1*05:05 and C*12:02) were identified in A(H7N9) infected volunteers. In an A549 cell line carrying the rs189256251 variant CT genotype, A(H7N9) infection incidence was elevated 6.665-fold over control cells carrying the CC genotype. Serum levels of interferon alpha were significantly lower in patients with the CT genotype compared to the CC genotype (P = 0.01). The study findings of genetic predisposition to A(H7N9) in the Chinese population may be valuable in systematic investigations of A(H7N9) disease etiology. Since the first reported human infection by the novel avian influenza A virus H7N9 [A(H7N9)] in 2013 more than 1,564 laboratory-confirmed human cases were reported up to 27 May 2018, with a fatality rate of 39.25%. Five large epidemic waves of human infection have been reported 1. Multiple regionally distinct viral genotypes and expanded geographical range suggest that A(H7N9) virus may become a long-term threat to public health 2. The role of host genetic background in determining susceptibility to viral diseases has been studied intensively for several pathogens including human immunodeficiency virus 3 , hepatitis B virus 4 , hepatitis C virus 5 and respiratory syncytial virus 6. It is clear that the genetic make-up of the host has a major influence on the response

Recent genome-wide association studies (GWAS) have identified eleven leukocyte telomere length (LTL)-related single nucleotide polymorphisms (SNPs). Since LTL has been associated with risk of many malignancies, LTL-related SNPs may contribute to cancer susceptibility. To test this hypothesis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), we genotyped these eleven LTL-related SNPs in a case-control set including 1186 HBV-related HCC cases, 508 chronic HBV carriers and 1308 healthy controls at the discovery stage. The associations of HCC risk with these SNPs were further confirmed in an independent case-control set. We found that 1p34.2 rs621559 and 14q21 rs398652 were significantly associated with HBV-related HCC risk (both P<0.005 after Bonferroni corrections). There was no significant difference of either rs621559 or rs398652 genotypes between chronic HBV carriers and healthy controls, demonstrating that the association was not due to predisposition to HBV infection. In the pooled analyses (1806 HBV-related HCC cases and 1954 controls), we observed a decreased HCC risk, 0.72-times, associated with the 1p34.2 rs621559 AA genotype compared to the GG genotype (P = 1.6×10−6). Additionally, there was an increased HCC risk, 1.27-fold, associated with the rs398652 GG genotype (P = 3.3×10−6). A statistical joint effect between the rs621559 GG and rs398652 GG genotypes may exist in elevating risk of HBV-related HCC. We show, for the first time, that rs398652 and rs621559 might be marker genetic variants for risk of HBV-related HCC in the Chinese population.