Mortality and Attrition Rates within the First Year of Antiretroviral Therapy Initiation among People Living with HIV in Guangxi, China: An Observational Cohort Study

Objective. To assess the mortality and attrition rates within the first year of antiretroviral therapy (ART) initiation among people living with human immunodeficiency virus (PLHIV) in rural Guangxi, China. Design. Observational cohort study. Setting. The core treatment indicators and data were collected with standard and essential procedures as per the Free ART Manual guidelines across all the rural health care centers of Guangxi. Participants. 58,115 PLHIV who were under ART were included in the study. Interventions. The data collected included sociodemographic characteristics that consist of age, sex, marital status, route of HIV transmission, CD4 cell count before ART, initial ART regimen, level of ART site, and year of ART initiation. Primary and Secondary Outcome Measures. Mortality and attrition rate following ART initiation. Results. The average mortality rate was 5.94 deaths, and 17.52 attritions per 100 person-years within the first year of ART initiation among PLHIV. The mortality rate was higher among intravenous drug users (Adjusted Hazard Ratio (AHR) 1.27, 95% Confidence Interval (CI) 1.14-1.43), prefecture as a level of ART site (AHR 1.14, 95% CI 1.02-1.28), and county as the level of ART site (AHR 2.12, 95% CI 1.90-2.37). Attrition was higher among intravenous drug users (AHR 1.87, 95% CI 1.75-2.00), the first-line ART containing AZT (AHR 1.09, 95% CI 1.03-1.16), and first-line ART containing LVP/r (AHR 1.34, 95% CI 1.23-1.46). Conclusion. The mortality and attrition rates were both at the highest level in the first year of post-ART; continued improvement in the quality of HIV treatment and care is needed

Effects of high CD4 cell counts on death and attrition among HIV patients receiving antiretroviral treatment: an observational cohort study

Current WHO guidelines recommend initiating ART regardless of CD4+ cell count. In response, we conducted an observational cohort study to assess the effects of pre-ART CD4+ cell count levels on death, attrition, and death or attrition in HIV treated patients. This large HIV treatment cohort study (n = 49,155) from 2010 to 2015 was conducted in Guangxi, China. We used a Cox regression model to analyze associations between pre-ART CD4+ cell counts and death, attrition, and death or attrition. The average mortality and ART attrition rates among all treated patients were 2.63 deaths and 5.32 attritions per 100 person-years, respectively. Compared to HIV patients with 500 CD4+ cells/mm 3 at ART initiation had a significantly lower mortality rate (Adjusted hazard ratio: 0.56, 95% CI: 0.40-0.79), but significantly higher ART attrition rate (AHR: 1.17, 95% CI: 1.03-1.33). Results from this study suggest that HIV patients with high CD4+ cell counts at the time of ART initiation may be at greater risk of treatment attrition. To further reduce ART attrition, it is imperative that patient education and healthcare provider training on ART adherence be enhanced and account for CD4 levels at ART initiation

Vegetation history and its links to climate change during the last 36 ka in arid Central Asia: Evidence from a loess-paleosol sequence in the Eastern Ili Valley

Detailed vegetation history response to complex influencing factors of arid Central Asia (ACA) is crucial to understanding ecological sustainability. Here, we present the first pollen record in the Ili Valley during the Last Glacial Maximum (LGM) using the Jirentai (JRT) loess-paleosol sequence. Combining the results of multi-climate proxies and optically stimulated luminescence (OSL) dating, we aim to reconstruct the vegetative response to climate change during the last 36 ka. Our results show that rapid loess accumulation in the JRT section began in the Late MIS3 (Marine isotope stage 3), and a thin paleosol layer developed in the Late LGM and Post Glacial. The pollen concentrations in the loess are significantly lower than in the paleosol, but the pollen assemblages are richer. Artemisia and Asteraceae are the dominant non-arboreal types in the loess, and abundant arboreal species are present (e.g., Pinus, Picea, Quercus, Betulaceae). The percentage of Artemisia remains high in the paleosol, and typical drought-tolerant plants are an important component (e.g., Orthomorphic, Ephedra). We suggest that the rich variety of pollen in loess is transported by frequent and intense dust activities, and these pollen may come from regional vegetation. Less diverse pollen assemblages in paleosol respond to the vegetation surrounding the JRT section. The vegetation history obtained from the JRT section shows that the lowlands of the Ili Valley were typical desert or desert-steppe vegetation for the past 36 ka. The surrounding mountains are dominated by Pinus and Picea forests. During the Early LGM, vegetation conditions deteriorated in both of mountainous and lowland. The above phenomena coincide with the pollen records from lakes in the ACA. Our results further suggest that mountain forests reappear and the lowland environment improves in response to increased insolation in the Northern Hemisphere at high latitudes in the Late LGM. This point in time is earlier by about 5–10 ka compared to previous records. We attribute it to the fact that pollen assemblages from the loess-paleosol sequence are more sensitive to vegetation and climate change during the transition from the glacial to interglacial and propose a simple model to characterize them

Upregulation of MIAT Regulates LOXL2 Expression by Competitively Binding MiR-29c in Clear Cell Renal Cell Carcinoma

Background/Aims: MIAT is a long noncoding RNA (lncRNA) involved in cell proliferation and the development of tumor. However, the exact effects and molecular mechanisms of MIAT in clear cell renal cell carcinoma (ccRCC) progression are still unknown. Methods: We screened the lncRNAs’ profile of ccRCC in The Cancer Genome Atlas database, and then examined the expression levels of lncRNA MIAT in 45 paired ccRCC tissue specimens and in cell lines by q-RT-PCR. MTS, colony formation, EdU, and Transwell assays were performed to examine the effect of MIAT on proliferation and metastasis of ccRCC. Western blot and luciferase assays were performed to determine whether MIAT can regulate Loxl2 expression by competitively binding miR-29c in ccRCC. Results: MIAT was up-regulated in ccRCC tissues and cell lines. High MIAT expression correlated with worse clinicopathological features and shorter survival rate. Functional assays showed that knockdown of MIAT inhibited renal cancer cell proliferation and metastasis in vitro and in vivo. Luciferase and western blot assays further confirmed that miR-29c binds with MIAT. Additionally, the correlation of miR-29c with MIAT and Loxl2 was further verified in patients' samples. Conclusion: Our data indicated that MIAT might be an oncogenic lncRNA that promoted proliferation and metastasis of ccRCC, and could be a potential therapeutic target in human ccRCC

Mudskipper genomes provide insights into the terrestrial adaptation of amphibious fishes

Mudskippers are amphibious fishes that have developed morphological and physiological adaptations to match their unique lifestyles. Here we perform whole-genome sequencing of four representative mudskippers to elucidate the molecular mechanisms underlying these adaptations. We discover an expansion of innate immune system genes in the mudskippers that may provide defence against terrestrial pathogens. Several genes of the ammonia excretion pathway in the gills have experienced positive selection, suggesting their important roles in mudskippers’ tolerance to environmental ammonia. Some vision-related genes are differentially lost or mutated, illustrating genomic changes associated with aerial vision. Transcriptomic analyses of mudskippers exposed to air highlight regulatory pathways that are up- or down-regulated in response to hypoxia. The present study provides a valuable resource for understanding the molecular mechanisms underlying water-to-land transition of vertebrates