Identification of Key Candidate Genes and Chemical Perturbagens in Diabetic Kidney Disease Using Integrated Bioinformatics Analysis.

Globally, nearly 40 percent of all diabetic patients develop serious diabetic kidney disease (DKD). The identification of the potential early-stage biomarkers and elucidation of their underlying molecular mechanisms in DKD are required. In this study, we performed integrated bioinformatics analysis on the expression profiles GSE111154, GSE30528 and GSE30529 associated with early diabetic nephropathy (EDN), glomerular DKD (GDKD) and tubular DKD (TDKD), respectively. A total of 1,241, 318 and 280 differentially expressed genes (DEGs) were identified for GSE30258, GSE30529, and GSE111154 respectively. Subsequently, 280 upregulated and 27 downregulated DEGs shared between the three GSE datasets were identified. Further analysis of the gene expression levels conducted on the hub genes revealed SPARC (Secreted Protein Acidic And Cysteine Rich), POSTN (periostin), LUM (Lumican), KNG1 (Kininogen 1), FN1 (Fibronectin 1), VCAN (Versican) and PTPRO (Protein Tyrosine Phosphatase Receptor Type O) having potential roles in DKD progression. FN1, LUM and VCAN were identified as upregulated genes for GDKD whereas the downregulation of PTPRO was associated with all three diseases. Both POSTN and SPARC were identified as the overexpressed putative biomarkers whereas KNG1 was found as downregulated in TDKD. Additionally, we also identified two drugs, namely pidorubicine, a topoisomerase inhibitor (LINCS ID- BRD-K04548931) and Polo-like kinase inhibitor (LINCS ID- BRD-K41652870) having the validated role in reversing the differential gene expression patterns observed in the three GSE datasets used. Collectively, this study aids in the understanding of the molecular drivers, critical genes and pathways that underlie DKD initiation and progression.

Case Report: Rhizopus arrhizus Rhino-Orbital-Cerebral Mycosis and Lethal Midline Granuloma: Another Fungal Etiological Agent.

Objective: Both rhino-orbital-cerebral mycosis and lethal midline granuloma (LMG) may result in midline destruction. LMG has now been generally considered as a natural killer/T cell lymphoma, nasal type (ENKTL-NT) with an association of EBV. Fungi have been detected from the diseased tissues now and then but are often considered as lymphoma-associated infections. We previously reported an ENKTL-NT case with Mucor irregularis, which played a causal role in the disease and was involved in the overexpression of Ki67 and CD56 in the mouse experiment. The present study describes a chronic Rhizopus arrhizus infection with immunological parameters that are closely similar to LMG. We aim to explore the relationship of another Mucorales fungus, R. arrhizus, and LMG in a patient and in mice. Methods: Case study and mouse infection modules were designed for our observation. A 35-year-old man with midline face ulcers which was clinically suspected as LMG was selected. Biopsy specimens were sent for lymphoma diagnosis and microbiological detection. The isolated fungus was tested in an ICR mouse model for mycological and histological analyses. Results: Five tissue samples yielded Rhizopus arrhizus. In the pathology, characteristic inflammation, necrosis, and granulation with thin-walled hyphae are observed. Immunohistochemistry showed NK/T cell infiltration (CD3+, CD8+, TIA1+, GZMB+, PRF+, individual CD56+) with hyperplasia (Ki67+) and angioinvasion. The patient recovered completely with amphotericin B. In the murine experiment, R. arrhizus caused angioinvasion with NK/T cell infiltration (CD3+, CD56+, TIA1+, GZMB +, PRF+) with proliferation (Ki67+) and was re-isolated from the infected host. Conclusions: We here describe a mid-face destruction patient, which was diagnosed by the top pathologists in China according to the current criteria of NK/T cell lymphoma, with a negative result for EBV and positive result for R. arrhizus. With a then developed mouse experiment, the R. arrhizus in the diseased lesions was responsible for the NK/T cell infiltration (CD3+, CD8+, CD56+, TIA1+, GZMB+, PRF+), proliferation (Ki67+), and angioinvasion, suggesting another fungal etiological agent for LMG, which could be eradicated with amphotericin B. Limitations: The sample size is not sufficient for statistical analysis. However, our findings are suggestive for the role fungus plays in LMG.

Retention-Aware DRAM Auto-Refresh Scheme for Energy and Performance Efficiency.

Dynamic random access memory (DRAM) circuits require periodic refresh operations to prevent data loss. As DRAM density increases, DRAM refresh overhead is even worse due to the increase of the refresh cycle time. However, because of few the cells in memory that have lower retention time, DRAM has to raise the refresh frequency to keep the data integrity, and hence produce unnecessary refreshes for the other normal cells, which results in a large refresh energy and performance delay of memory access. In this paper, we propose an integration scheme for DRAM refresh based on the retention-aware auto-refresh (RAAR) method and 2x granularity auto-refresh simultaneously. We also explain the corresponding modification need on memory controllers to support the proposed integration refresh scheme. With the given profile of weak cells distribution in memory banks, our integration scheme can choose the most appropriate refresh technique in each refresh time. Experimental results on different refresh cycle times show that the retention-aware refresh scheme can properly improve the system performance and have a great reduction in refresh energy. Especially when the number of weak cells increased due to the thermal effect of 3D-stacked architecture, our methodology still keeps the same performance and energy efficiency.

Low calcium dialysate combined with CaCO3 in hyperphosphatemia in hemodialysis patients.

This aim of this study was to observe the effects of the application of low calcium dialysate (LCD) combined with oral administration of CaCO3 in the treatment of hyperphosphatemia, as well as blood Ca2+, calcium-phosphate product (CPP), parathyroid hormone (PTH) and blood pressure in patients undergoing hemodialysis. Thirty-one maintenance hemodialysis (MHD) patients with hyperphosphatemia, but normal blood Ca2+, underwent dialysis with an initial dialy-sate Ca2+ concentration (DCa) of 1.50 mmol/l for six months and then with 1.25 mmol/l for six months. The patients who underwent dialysis with a DCa of 1.25 mmol/l were treated orally with 0.3 g CaCO3 tablets three times a day. In the third and sixth months [observation end point (OEP)] of the dialysis, the concentrations of Ca2+, phosphorus and intact PTH (iPTH) were measured; blood pressure and side-effects prior to and following dialysis were also observed. The Ca2+, CPP and iPTH levels increased (P<0.05) in the sixth month of treatment with a DCa of 1.50 mmol/l. However, the Ca2+ concentration declined to a certain degree, CPPs decreased significantly (P<0.05) and the iPTH concentration increased following treatment with a DCa of 1.25 mmol/l for six months. The incidence rate of adverse effects of LCD was 12.9% (4/31); the effects were mainly muscle spasms, hypotension and elevated PTH. The periodic application of LCD combined with the oral administration of CaCO3 effectively reduced serum phosphorus and CPPs among MHD patients with hyperphosphatemia, indicating that the treatment may be used clinically.