ABSTRACT
RNA binding proteins (RBPs) have the potential for transcriptional regulation in sepsis-induced liver injury, but precise functions remain unclear. Our aim is to conduct a genome-wide expression analysis of RBPs and illuminate changes in the regulation of alternative splicing in sepsis-induced liver injury. RNA-seq data on "sepsis and liver" from the publicly available NCBI data set was analyzed, and differentially expressed RBPs and alternative splicing events (ASEs) in the healthy and septic liver were identified. Co-expression analyses of sepsis-regulated RBPs and ASEs were performed. Models of sepsis were established to validate hepatic RBP gene expression patterns with different treatments. Pairwise analysis of gene expression profiles of sham, cecum ligation puncture (CLP), and CLP with dichloroacetate (CLPDCA) mice allowed 1208 differentially expressed genes (DEGs), of which 800 were up-regulated and 408 down-regulated, to be identified. DEGs were similar in both Sham and CLPDCA mice. The KEGG analysis showed that up-regulated genes as being involved in cytokine-cytokine receptor interaction and IL-17 signaling pathway and down-regulated genes in metabolic pathways. Differences in lipid metabolism-related alternative splicing events, including A3SS, were also found in CLP and CLPDCA compared with sham mice. Thirty-seven RBPs, including S100a11, Ads2, Fndc3b, Fn1, Ddx28, Car2, Cisd1, and Ptms, were differentially expressed in CLP mice and the regulated alternative splicing genes(RASG) with the RBP shown to be enriched in lipid metabolic and oxidation-reduction-related processes by GO functional analysis. In KEEG analysis the RASG mainly enriched in metabolic pathway. The models of sepsis were constructed with different treatment groups, and S100a11 expression in the CLP group found to be higher than in the sham group, a change that was reversed by DCA. The alternative splicing ratio of Srebf1 and Cers2 decreased compared with the sham group increased after DCA treatment. Abnormal profiles of gene expression and alternative splicing were associated with sepsis-induced liver injury. Unusual expression of RBPs, such as S100a11, may regulate alternative splicing of lipid metabolism-associated genes, such as Srebf1 and Cers2, in the septic liver. RBPs may constitute potential treatment targets for sepsis-induced liver injury.
ABSTRACT
Objective To collect the data of present basic constructive situation of intensive care units (ICUs) in second and tertiary grade hospitals in Xinjiang Uygur Autonomous Region and to provide a data base beneficial to the construction of ICUs in the whole region.Methods The information including basic situation of ICUs in a total of 49 second and tertiary grade hospitals as samples in Xinjiang Uygur Autonomous Region were investigated by questionnaire survey from December 2012 to April 2013. The contents of questionnaire chiefly included the basic situations of hospitals, ICU constructions, ICU human resources and allocation of equipments.Results Forty-nine questionnaires were sent out, and all of them gave answers, the recovery rate being 100%. In the whole region of Xinjiang, there were 49 second and tertiary grade hospitals with establishment of 66 various types of ICUs. ① Medical unit basic situation: the second grade A hospitals accounted for 59.2%, and the tertiary grade A hospitals, 34.7%. There was a larger proportion of local hospitals (67.3%); most of the hospitals had beds over 500 (57.14%), the designed hospital bed number was 41 403, and 35 442 beds were open up for service (85.60%). ② The ICU basic construction situation: the construction of ICUs concentrated mainly after the year 2000, from 2000 to 2010, a total of 37 units, and from 2010 to 2012, 12 units were constructed; when they opened to the public, the beds were relatively few, and the ICUs containing less than 10 beds occupied 79.00%. In the 66 ICUs surveyed, there were 43 general ICUs, accounting the largest proportion, followed by 7 emergency ICUs, and the least were 1 neurosurgery and 1 cardiac surgery ICU. In the 66 ICUs, all together 765 beds were prepared, but actually 808 beds were opening up to public; most of ICUs had 5 - 20 beds, accounting for 71% in all the ICUs. At present, in the whole Xinjiang region, the rate of beds in ICUs in various grades of hospitals opening to the outside for use accounted for more than 80% of which 56% ICUs were almost turning round fully. ③ ICU human resources situation: totally, there were 484 doctors in ICUs in the whole region, the ratio of full-time doctor to nurses was 1:3.50, the ratio for bed to physician 1:0.55 and the ratio for bed to nurse 1:0.92. The title of doctor was primarily resident, and the various title gradient levels were good. Most doctors graduated from a regular medical college, and the doctors having obtained a master degree were few. The physician professional backgrounds were mainly critical disease medicine, emergency medicine and respiratory medicine, the professional relevance being good; the chief way of ICU physicians to engage in advanced study of their professional training was in China, and generally they joined professional continuing education programs poorly, mostly joining once a year or non at all. The physicians who obtained the identification of Chinese critical care medicine specialist accounted only for 23.56%. ④ ICU equipment allocation situation: according to the requirements of ICU construction guidelines, the equipments must be allocated including bedside monitors (703 units), ventilators (516 units) and infusion pumps (702 units), occupying the highest proportion. In the optional equipments, there were enteral nutritional pump (89 stations), blood glucose monitoring device (57 units) and anti-decubitus mattresses (54 units), the proportion being the largest, bispectral index monitor (2 units), extracorporeal membrane oxygenation (ECMO, 1 table) and gastric mucosal carbon dioxide tension pHi meter (0 unit), the proportion being the least or non at all.Conclusions In the whole Xinjiang region, the construction of ICUs is still at the developing stage, and needs to further strengthen the standardized construction. The human resources, equipments, etc. are not distributed in balance, and it is necessary to move forward the adjustment to benefit the development of ICUs in the whole region.
