Comparative transcriptome analysis of PBMC from HIV patients pre- and post-antiretroviral therapy

Infections of the human immunodeficiency virus (HIV) trigger host immune responses, but the virus can destroy the immune system and cause acquired immune deficiency syndrome (AIDS). Highly active antiretroviral therapy (HAART) can suppress viral replication and restore the impaired immune function. To understand HIV interactions with host immune cells during HAART, the transcriptomes of peripheral blood mononuclear cells (PBMC) from HIV patients and HIV negative volunteers before and two weeks after HAART initiation were analyzed using RNA sequencing (RNA-Seq) technology. Differentially expressed genes (DEGs) in response to HAART were firstly identified for each individual, then common features were extracted by comparing DEGs among individuals and finally HIV-related DEGs were obtained by comparing DEGs between the HIV patients and HIV negative volunteers. To demonstrate the power of this approach, minimum numbers of patients (one HIV alone; one HIV + tuberculosis, TB; one HIV + TB with immune reconstitution inflammatory syndrome during HAART) and two HIV negative volunteers were used. More than 15,000 gene transcripts were detected in each individual sample. Fourteen HAART up-regulated and eleven down-regulated DEGs were specifically identified in the HIV patients. Among them, nine up-regulated (CXCL1, S100P, AQP9, BASP1, MMP9, SOD2, LIMK2, IL1R2 and BCL2A1) and nine down-regulated DEGs (CD160, CD244, CX3CR1, IFIT1, IFI27, IFI44, IFI44L, MX1 and SIGLEC1) have already been reported as relevant to HIV infections in the literature, which demonstrates the credibility of the method. The newly identified HIV-related genes (up-regulated: ACSL1, GPR84, GPR97, ADM, LRG1; down-regulated: RASSF1, PATL2) were empirically validated using qRT-PCR. The Gene Set Enrichment Analysis (GSEA) was also used to determine pathways significantly affected by HAART. GSEA further confirmed the HAART relevance of five genes (ADM, AQP9, BASP1, IL1R2 and MMP9). The newly identified HIV-related genes, ADM (which encodes Adrenomedullin), a peptide hormone in circulation control, may contribute to HIV-associated hypertensions, providing new insights into HIV pathology and novel strategies for developing anti-HIV target. More importantly, we demonstrated that comparative transcriptome analysis is a very powerful tool to identify infection related DEGs using a very small number of samples. This approach could be easily applied to improve the understanding of pathogen-host interactions in many infections and anti-infection treatments

Knowledge, attitude, and practice of nephrologists on the decision for renal replacement therapy

Abstract Background This study aimed to investigate the Knowledge, Attitude, and Practice (KAP) of nephrologists on the decision of renal replacement therapy (RRT), including peritoneal dialysis, hemodialysis, and kidney transplantation. Methods This multicenter cross-sectional study was conducted on qualified nephrologists who volunteered to participate between July and August 2022 by using a self-administered questionnaire. Results Among 327 nephrologists, the total knowledge, attitude, and practice scores were 12.03 ± 2.11/16, 58.39 ± 6.62/75, and 27.15 ± 2.74/30, respectively. Multivariate logistic regression analysis showed that the attitude score (peritoneal dialysis: OR = 1.19, 95%CI: 1.13–1.25, P  50 years of age (peritoneal dialysis: OR = 0.27, 95%CI: 0.08–0.84, P = 0.024; hemodialysis: OR = 0.45, 95%CI: 0.20–0.97, P = 0.042; kidney transplantation: OR = 0.24, 95%CI: 0.08–0.77, P = 0.016) were independently associated with the consideration score of peritoneal dialysis, hemodialysis, and kidney transplantation. Conclusion Better attitudes may lead to more consideration by nephrologists when choosing between peritoneal dialysis, hemodialysis, and kidney transplantation and relatively less consideration by senior physicians when making decisions; in addition, having good knowledge and good attitudes may lead to better practice