Long-term abuse of caffeine sodium benzoate induces endothelial cells injury and leads to coagulation dysfunction.

Our hospital admitted a patient who had difficulty in coagulation even after blood replacement, and the patient had abused caffeine sodium benzoate (CSB) for more than 20 years. Hence, we aimed to explore whether CSB may cause dysfunction in vascular endothelial cells and its possible mechanism. Low, medium, and high concentrations of serum of long-term CSB intake patients were used to treat HUVECs, with LPS as the positive control. MTT and CCK8 were performed to verify CSB's damaging effect on HUVECs. The expression of ET-1, ICAM-1, VCAM-1, and E-selectin were measured by ELISA. TUNEL assay and Matrigel tube formation assay were carried out to detect apoptosis and angiogenesis of HUVECs. Flow cytometry was applied to analyze cell cycles and expression of CD11b, PDGF, and ICAM-1. Expression of PDGF-BB and PCNA were examined by western blot. The activation of MAPK signaling pathway was detected by qRT-PCR and western blot. Intracellular Ca2+ density was detected by fluorescent probes. CCK8 assay showed high concentration of CSB inhibited cell viability. Cell proliferation and angiogenesis were inhibited by CSB. ET-1, ICAM-1, VCAM-1, and E-selectin upregulated in CSB groups. CSB enhanced apoptosis of HUVECs. CD11b, ICAM-1 increased and PDGF reduced in CSB groups. The expression level and phosphorylation level of MEK, ERK, JUN, and p38 in MAPK pathway elevated in CSB groups. The expression of PCNA and PDGF-BB was suppressed by CSB. Intracellular Ca2+ intensity was increased by CSB. Abuse of CSB injured HUVECs and caused coagulation disorders.

A review of genetic risk in systemic lupus erythematosus.

INTRODUCTION: Systemic Lupus Erythematosus (SLE) is a complex multisystem autoimmune disease with a wide range of signs and symptoms in affected individuals. The utilization of genome-wide association study (GWAS) technology has led to an explosion in the number of genetic risk factors mapped for autoimmune diseases, including SLE. AREAS COVERED: In this review, we summarize the more recent genetic risk loci mapped in SLE, which bring the total number of loci mapped to approximately 200. We review prioritization analyses of the associated variants and experimental validation of the putative causal variants. This includes the implementation of new bioinformatic techniques to align genomic and functional data and the use of transcriptomics with single-cell RNA-sequencing, CRISPR genome editing, and Massive Parallel Reporter Assays to analyze non-coding regulatory genetics. EXPERT OPINION: Despite progress in identifying more genetic risk loci and variant-gene pairs for SLE, understanding its pathogenesis and applying findings clinically remains challenging. The polygenic risk score (PRS) has been used as an application of SLE genetics, but with limited performance in non-EUR populations. In the next few years, advancements in proteomics, post-translational modification estimation, and whole-genome sequencing will enhance disease understanding.

COVID-19 and systemic lupus erythematosus genetics: A balance between autoimmune disease risk and protection against infection.

Genome wide association studies show there is a genetic component to severe COVID-19. We find evidence that the genome-wide genetic association signal with severe COVID-19 is correlated with that of systemic lupus erythematosus (SLE), having formally tested this using genetic correlation analysis by LD score regression. To identify the shared associated loci and gain insight into the shared genetic effects, using summary level data we performed meta-analyses, a local genetic correlation analysis and fine-mapping using stepwise regression and functional annotation. This identified multiple loci shared between the two traits, some of which exert opposing effects. The locus with most evidence of shared association is TYK2, a gene critical to the type I interferon pathway, where the local genetic correlation is negative. Another shared locus is CLEC1A, where the direction of effects is aligned, that encodes a lectin involved in cell signaling, and the anti-fungal immune response. Our analyses suggest that several loci with reciprocal effects between the two traits have a role in the defense response pathway, adding to the evidence that SLE risk alleles are protective against infection.

Comprehensive Risk Assessment of High Temperature Disaster to Kiwifruit in Shaanxi Province, China.

In recent years, the main kiwifruit producing region, central-south Shaanxi Province, has often suffered from the threat of extreme high temperatures. Assessing the risk of high-temperature disasters in the region is essential for the rational planning of agricultural production and the development of resilience measures. In this study, a database was established to assess the risk of a high-temperature disaster to kiwifruit. Then, four aspects, hazard, vulnerability, exposure and disaster prevention and mitigation capacity, were taken into account and 19 indexes were selected to make an assessment of the risk of a high-temperature disaster. At the same time, 16 indexes were selected for the assessment of the climatic suitability of kiwifruit in terms of light, heat, water, soil and topography, and were used as one of the indexes for exposure assessment. The analytic hierarchy process and the entropy weighting method were combined to solve the weights for each index. The results reveal that: (1) The Guanzhong Plain has a high climatic suitability for kiwifruit, accounting for 15.14% of the study area. (2) The central part of the study area and southern Shaanxi are at high risk, accounting for 22.7% of the study area. The major kiwifruit producing areas in Shaanxi Province (e.g., Baoji) are at a low risk level, which is conducive to the development of the kiwifruit industry. Our study is the first to provide a comprehensive assessment of the risk of a high-temperature disaster to the economic fruit kiwifruit, providing a reference for disaster resilience and mitigation.

The effect of donor-recipient body surface area ratio on donor age and donor glomerular filtration rate in Chinese patients undergoing a living-donor kidney transplant.

OBJECTIVES: The purpose of this study was to evaluate the effect of donor-recipient body surface area ratio on donor age and donor glomerular filtration rate in living-donor kidney transplant. MATERIALS AND METHODS: This retrospective study included 254 rejection-free patients who underwent their first living-donor kidney transplant at our center between April 2007 and April 2011. We performed multivariate linear regression and receiver operating characteristic curve analyses to determine independent associations and the cumulative effects on posttransplant graft function and outcomes in persons in China who had a living-donor kidney transplant. RESULTS: In multivariate linear regression, donor age, donor estimated glomerular filtration rate, and donor-recipient body surface area ratio were independent predictors of 1-year graft function. Linear regression showed that correcting donor age by donor-recipient body surface area ratio increased the strength of the correlation between donor age and 1-year graft function. In the older group (donor age ≥ 45 y), the effect of donor-recipient body surface area ratio on graft function was stronger. By considering the 1-year donor estimated glomerular filtration rate in 2 groups (< 60 or ≥ 60 mL/min/1.73 m(2)), the cutoff values for corrected donor age was 55 years and donor estimated glomerular filtration rate before surgery was 113 mL/min/1.73 m(2). CONCLUSIONS: By correcting for donor-recipient body surface area ratio, donor age accurately predicted and correlated better with 1 year graft function. During preoperative evaluation donor and recipient body surface area matching may be useful.