PD-L1 Expression Correlates With Tumor Infiltrating Lymphocytes And Response To Neoadjuvant Chemotherapy In Cervical Cancer.

Programmed death-ligand 1 (PD-L1) has been reported to be expressed in many types of tumor cells, and bind to PD-1 on T lymphocytes to inhibit immune response. Immunologic checkpoint blockade with antibodies that target the PD1/PD-L1 pathway has demonstrated to have impressive antitumor effects on many malignancies. However, the significance of PD1/PD-L1 pathway in cervical cancer remains unclear. Here we studied PD-L1, PD-1, CD8 and HPV expression in cervical cancer and normal cervix by immunohistochemical staining. Our results showed that there was more frequently positive for PD-L1, PD-1 and CD8 in cervical cancer tissues compared to normal tissues, especially those strongly stained HPV. Additionally, PD-L1, PD-1 and CD8 were more frequently stained in tissues from advanced tumor and tumor with lymphoid nodes or vascular invasion respectively. Tissues from patients with chemotherapy history had over expression of PD-L1 in tumor cells and more PD-1 and CD8 in stromal mononuclear cells, which were identified as tumor infiltrated lymphocytes (TILs). These findings point to a key role of PD-L1 in immune escape of cervical cancer, and provide a rationale for therapeutic targeting of the PD-1/PD-L1 pathway.

Expansion of genotypic diversity and establishment of 2009 H1N1 pandemic-origin internal genes in pigs in China.

UNLABELLED: Two-way transmission of influenza viruses between humans and swine has been frequently observed, and the occurrence of the 2009 H1N1 pandemic influenza virus (pdm/09) demonstrated that swine-origin viruses could facilitate the genesis of a pandemic strain. Although multiple introductions to and reassortment in swine of the pdm/09 virus have been repeatedly reported in both Eurasia and the Americas, its long-term impact on the development of swine influenza viruses (SIVs) has not been systematically explored. Our comprehensive evolutionary studies of the complete genomes of 387 SIVs obtained from 2009 to 2012 by influenza virus surveillance in China revealed 17 reassortant genotypes with pdm/09-origin genes. Even though the entire 2009 pandemic virus and its surface genes cannot persist, its internal genes have become established and are now the predominant lineages in pigs in the region. The main persistent pdm/09-origin reassortant forms had at least five pdm/09-origin internal genes, and their surface genes were primarily of European avian-like (EA) or human H3N2-like SIV origin. These findings represent a marked change in the evolutionary patterns and ecosystem of SIVs in China. It is possible that the pdm/09-origin internal genes are in the process of replacing EA or triple-reassortant-like internal genes. These alterations in the SIV gene pool need to be continually monitored to assess changes in the potential for SIV transmission to humans. IMPORTANCE: Shortly after the emergence of the 2009 pandemic H1N1 (pdm/09) influenza virus, it was transmitted from humans to pigs and this continues to occur around the world. Many reassortants between pdm/09-origin viruses and enzootic swine influenza viruses (SIVs) have been detected. However, the long-term impact of pdm/09-origin viruses on the SIV gene pool, which could lead to the generation of influenza viruses with the potential to infect humans, has not been systematically examined. From extensive surveillance of SIVs over a 38-month period in southern China, it was found that although neither complete pdm/09 viruses nor their surface genes could persist in pigs, their internal genes did persist. Over the survey period, these internal genes became predominant, potentially replacing those of the enzootic SIV lineages. The altered diversity of the SIV gene pool needs to be closely monitored for changes in the potential for SIV transmission to humans.

The genesis and source of the H7N9 influenza viruses causing human infections in China.

A novel H7N9 influenza A virus first detected in March 2013 has since caused more than 130 human infections in China, resulting in 40 deaths. Preliminary analyses suggest that the virus is a reassortant of H7, N9 and H9N2 avian influenza viruses, and carries some amino acids associated with mammalian receptor binding, raising concerns of a new pandemic. However, neither the source populations of the H7N9 outbreak lineage nor the conditions for its genesis are fully known. Using a combination of active surveillance, screening of virus archives, and evolutionary analyses, here we show that H7 viruses probably transferred from domestic duck to chicken populations in China on at least two independent occasions. We show that the H7 viruses subsequently reassorted with enzootic H9N2 viruses to generate the H7N9 outbreak lineage, and a related previously unrecognized H7N7 lineage. The H7N9 outbreak lineage has spread over a large geographic region and is prevalent in chickens at live poultry markets, which are thought to be the immediate source of human infections. Whether the H7N9 outbreak lineage has, or will, become enzootic in China and neighbouring regions requires further investigation. The discovery here of a related H7N7 influenza virus in chickens that has the ability to infect mammals experimentally, suggests that H7 viruses may pose threats beyond the current outbreak. The continuing prevalence of H7 viruses in poultry could lead to the generation of highly pathogenic variants and further sporadic human infections, with a continued risk of the virus acquiring human-to-human transmissibility.

Determination of forsythiaside in rat plasma by high-performance liquid chromatography and its application to pharmacokinetic studies.

A simple high-performance liquid chromatographic method was developed to study the pharmacokinetics of forsythiaside in rat plasma after intravenous administration. Hesperidin was used as the internal standard. The drugs were separated on a reversed-phase C(18) column and detected at 332 nm. Good linearity was achieved in the range of 0.067-26.667 microg/mL. The intra- and inter-assay variation coefficients for this analysis were no more than 10.94 and 14.56%, respectively. The average recovery for forsythiaside was 87.42% from plasma. The analytical sensitivity and accuracy of this assay were adequate for characterization of the pharmacokinetics of intravenous administration of forsythiaside to rats and the assay has been successfully applied to provide pharmacokinetic data. The mean t(1/2Z) was 20.36, 19.40 and 23.62 min for 2, 5 and 20 mg/kg for forsythiaside after i.v. administration, respectively. The AUC(0-t) increased linearly from 40.64 to 624.14 microg min/mL after administration of the three doses.