Changes in expression levels of erythrocyte and immune-related genes are associated with high altitude polycythemia.

BACKGROUND: As a chronic mountain sickness(CMS) with the highest incidence and the greatest harm, the pathogenesis of high altitude polycythemia (HAPC) is still not fully understood. METHODS: 37 HAPC patients and 42 healthy subjects were selected from plateau, and peripheral venous blood samples were collected for transcriptome sequencing on Illumina NovaSeq platform. The sequenced data were analyzed by bioinformatics and phenotypic association analysis. RESULTS: The results showed significant differences in multiple clinical indicators including RBC and HGB et al. existed between HAPC and control. Based on the RNA-seq data, 550 genes with significant differential expression were identified in HAPC patients. GO and KEGG pathway enrichment analysis showed that the up-regulated genes were mainly enriched in processes such as erythrocyte differentiation and development and homeostasis of number of cells, while the down-regulated genes were mainly enriched in categories such as immunoglobulin production, classical pathway of complement activation and other biological processes. The coupling analysis of differential expression genes(DEGs) and pathological phenotypes revealed that 91 DEGs were in close correlation with in the phenotype of red blood cell volume distribution (width-CV and width-SD), and they were all up-regulated in HAPC and involved in the process of erythrocyte metabolism. Combined with the functional annotation of DEGs and literature survey, we found that the expression of several potential genes might be responsible for pathogenesis of HAPC. Besides, cell type deconvolution analysis result suggested that the changes in the number of some immune cell types was significantly lower in HAPC patients than control, implying the autoimmune level of HAPC patients was affected to a certain extent. CONCLUSION: This study provides an important data source for understanding the pathogenesis and screening pathogenic genes of HAPC. We found for the first time that there was a significant correlation between HAPC and the pathological phenotype of width-CV and width-SD, wherein the enriched genes were all up-regulated expressed and involved in the process of erythrocyte metabolism. Although the role of these genes needs to be further studied, the candidate genes can provide a starting point for functionally pinning down the underlying mechanism of HAPC.

Reusable ring-like Fe3O4/Au nanozymes with enhanced peroxidase-like activities for colorimetric-SERS dual-mode sensing of biomolecules in human blood.

Peroxidase-like nanozymes have led to important progress in biosensing, but most of nanozyme sensing systems are currently established by a single-signal output mode, which is susceptible to environmental and operational factors. Thus construction of a dual-signal output nanozyme sensing system is essential for obtaining reliable and robust performance. In this study, a novel peroxidase mimicking nanozyme was developed by decorating magnetic ring-like Fe3O4 with gold nanoparticles (R-Fe3O4/Au) for the colorimetric and surface-enhanced Raman scattering (SERS) dual-mode detection of biomolecules in human serum. The R-Fe3O4/Au nanozymes served as mimetic peroxidase which can catalyze the oxidation of colorless 3,3',5,5'-tetramethylbenzidine by hydrogen peroxide, and concomitantly as SERS substrates for detecting the Raman signals of oxidized products, providing an effective approach to investigate the reaction kinetics of enzymes. Based on the redox reactions, the nanozymes achieved colorimetric-SERS dual-mode sensing of glutathione (GSH) and cholesterol with detection limits as low as 0.10 µM and 0.08 µM, respectively. Furthermore, the nanozymes enabled rapid detection of GSH and cholesterol in serum without any complicated sample pretreatment. The R-Fe3O4/Au catalyst still displayed excellent peroxidase activity even after repeated use for 5 times. The proposed colorimetric-SERS dual-mode sensors exhibited good accuracy and reproducibility, which provides a new avenue for exploiting multifunctional sensors and has a great application prospect in biosensing.

Mineral and bone disorder in hemodialysis patients in the Tibetan Plateau: a multicenter cross-sectional study.

Background: Mineral and bone disorder (MBD) in hemodialysis patients is associated with increased morbidity and mortality. Studies on the MBD status of hemodialysis patients at high altitudes are extremely limited. Methods: A total of 146 hemodialysis patients from 5 local hospitals across all districts with hemodialysis centers in the Tibetan Plateau were enrolled in this cross-sectional study. Parameters related to MBD, including serum phosphorus (P), calcium (Ca), and intact parathyroid hormone (iPTH) levels, were measured. The achievement of MBD goals was compared with the achievement in the Dialysis Outcomes and Practice Study (DOPPS) 3, DOPPS 4 and a multicenter study of MBD in China. Factors associated with hyperphosphatemia were examined. Results: Altogether, 146 hemodialysis patients were recruited from the Tibetan Plateau. According to the K/DIGO guidelines, there were low achievement rates for serum Ca (40.4%), P (29.7%), and iPTH (47.1%). As for the (KDOQI) guidelines, the rates of achievement of defined targets were 38.4%, 33.7% and 16.4% for serum Ca, P and iPTH, respectively. The percentages of patients reaching the KDOQI targets for corrected Ca, P, and iPTH were significantly lower for Tibetan patients than the percentages found in DOPPS 3 (38.4% vs. 50.4%, 33.7% vs. 49.8%, and 16.4% vs. 31.4%, respectively, all p < .001) and DOPPS 4 (38.4% vs. 56.0%, 33.7% vs. 54.5%, and 16.4% vs. 35.3%, respectively, all p < .001). The percentage of patients reaching the KDOQI targets for iPTH was significantly lower in Tibet than in the plain areas of China (16.4% vs. 26.5%, p < .001). The proportion of patients with hypocalcemia was higher in Tibet than in the plain areas (44.5% vs. 19.4%, p < .001). The percentage of local patients with optimal P was significantly higher for patients with an activated vitamin D prescription than for patients without an activated vitamin D prescription (45.3% vs. 19.3%, p < .001). Age and the activated vitamin D prescription were independently associated with hyperphosphatemia. Conclusion: The MBD status of hemodialysis patients in Tibet is far from the ideal level. High altitude is one of the possible causes of the differences found, but not the principal one. It is necessary for medical staff in Tibet to improve the detection and treatment of MBD.