HIV-1 Elimination in Humanized Mice

Human immunodeficiency virus type one (HIV-1) exclusively infects humans and chimpanzees. Therefore, animal models are required for all investigations of viral pathogenesis, therapy and cure. Immunodeficient mice transplanted with human hematopoietic stem cells, termed humanized mice, support the development of multiple human cell lineages throughout the cell’s life span. To this end, we used humanized mice to evaluate the dynamic changes of host immunologic and viral profiles during both acute and chronic HIV-1 infection. We identified the temporal and spatial distribution of HIV-1 cell and tissue compartment infections and outlined correlations made between viral progression and host immunity by comparing two different humanized mouse models. Based on the discovery of early viral set-points, we developed a paradigm for a potential ‘HIV-1 cure’ by sequential administration of long-acting slow-effective release antiretroviral therapy (LASER ART) and CRISPR-Cas9 treatments. HIV-1 elimination was achieved in a third of dual-treated humanized mice after exhaustive works to detect HIV-1 and its gene products in peripheral blood, brain, lung, liver, spleen, kidney, gut, and bone marrow (BM). This was done by sensitive nested and digital-droplet PCR and RNAscope tests. Immune function was preserved in animals where HIV-1 was eliminated. In vivo viral outgrowth assay (VOA) was employed to confirm HIV-1 elimination by adoptive transfer of donor splenocytes and BM cells into naïve humanized mice. While virus was successfully recovered from HIV-1 control, LASER ART or CRISPR-Cas9 alone treated animals virus could not be recovered in recipients transplanted from a third of the dual-treated “cured” animals. We further characterized the impact of humanized mice-based VOA in viral isolation assay by expanding the sample sizes. We observed that replication-competent HIV-1 persisted in multiple tissues even when plasma viral load was undetectable and virus can be readily recovered from naïve humanized mice. We demonstrate that in vivo VOA using humanized mice is a sensitive assay system to interrogate replication competent HIV-1 and can be employed to determine viral eradication from donor samples. To this end, we used the humanized mouse model to study HIV-1 tissue compartmentalization, interrogate HIV-1 eradication employing innovative technologies, and assess HIV-1 elimination using humanized mice-based VOA, which will facilitate future translational studies

Total quality management influence the logistics performance of pharmaceutical industry in China

One of key issues of china pharmaceutical industry is inefficient logistics. Logistics plays an important role in organization operating. Therefore, organization requires seeking the method to improve logistics performance. The purpose of this study was to investigate the relationship between total quality management and logistics performance in pharmaceutical industry in china. The sample of this study was the 121 employees of Furen pharmaceutical industry in Henan province, China. For this purpose survey method was used by questionnaire as instrument for data collection. In this study, regression analysis method and correlation analysis method are used to analysis the correlation between independent variables and dependent variable. The research results have shown that Furen pharmaceutical industry has high implementation in total quality management at current stage. Meanwhile, employee involvement, customer focus, leadership and continuous improvement as items of total quality management are significantly influence logistics performance. The study faced several limitations such as time constraints and budget constraints which limited this study only have one pharmaceutical industry. The finding of this study has some contributions for future research and organization’s logistics developmen