OBJECTIVETo investigate the roles of protease-activated receptors (PARs) in thrombin-induced brain injury and neurogenesis in rats.

METHODSNinety male SD rats were randomly assigned to receive intra-hippocampus injection of NS, thrombin or specific agonists of 3 protease-activated receptors (PAR-1, PAR-3 and PAR-4), respectively. At 1,3 and 7 d after injection, the area of the hippocampus was determined with HE staining, the density and morphology of astrocyte were detected with GFAP staining, degenerated neurons were detected with Fluoro-Jade C staining, and the neurogenesis was examined with DCX staining.

RESULTSCompared to NS injection, the area of the hippocampus significantly increased at 1-3 d and decreased at 7 d after the injection of thrombin and PAR-1 agonist (P<0.05). In addition, injection of thrombin and PAR-1 agonist significantly increased the density of astrocyte and Fluoro-Jade C positive cells at 1-7 d after injection (P<0.05), and significantly increased the density of DCX positive cells at 3-7 d after injection(P<0.05). The injection of PAR-3 agonist and PAR-4 agonist had no affect on the area of the hippocampus, the density of astrocyte, Fluoro-Jade C positive cells and DCX positive cells.

CONCLUSIONThe activation of protease-activated receptor-1 may be related to the thrombin-induced brain injury and neurogenesis in rat hippocampus.

Animals ; Brain Injuries ; chemically induced ; metabolism ; pathology ; Hippocampus ; pathology ; Male ; Neurogenesis ; drug effects ; Rats ; Rats, Sprague-Dawley ; Receptor, PAR-1 ; agonists ; physiology ; Receptors, Thrombin ; agonists ; Thrombin ; toxicity

Objective To analyze the differences in total corneal astigmatism(TCA)and vectors in different regions centered on the corneal apex or pupil.Methods This cross-sectional study enrolled 102 patients(102 eyes)with age-re-lated cataracts who underwent phacoemulsification combined with intraocular lens implantation at the Weifang Eye Hospital from October 2021 to June 2022.Before surgery,anterior segment biometrical examinations were performed using Penta-cam to collect the TCA and axes at 2 mm,4 mm,and 6 mm diameter rings and zones with the corneal apex or pupil as the center,and vector analysis was made.Results In the ring mode,a significant difference was observed between the cor-neal apex-centered and pupil-centered astigmatism values for the 6 mm diameter(P＜0.05).In the zone mode,there were statistically significant differences between the corneal apex-centered and pupil-centered astigmatism values for the 2 mm,4 mm,and 6 mm diameters(all P＜0.05).The analysis of the zone and ring modes centered on the corneal apex showed that there were statistically significant differences in astigmatism values for the 2 mm and 6 mm diameters(both P＜0.05).The analysis of the zone and ring modes centered on the pupil showed that there were statistically significant differences in astigmatism values for the 2 mm,4 mm,and 6 mm diameters(all P＜0.05).In the same center,there were no statistically significant differences in astigmatism axes for 2 mm,4 mm,and 6 mm diameters under the ring and zone modes(all P＞0.05).In the same mode,there were no statistically significant differences in astigmatism axes for 2 mm,4 mm,and 6 mm diameters centered on the corneal apex and pupil(all P＞0.05).Vector analysis showed that in the ring mode,the apex-centered to pupil-centered TCA difference of 4 mm on the Y axis was statistically significant(P＜0.05).The comparison between the zone and ring centered on the pupil showed that the TCA difference of 4 mm on the Y axis was statistically sig-nificant(P＜0.05),whereas the other differences were not statistically significant(all P＞0.05).Conclusion The TCA shows a mild difference between the corneal apex-centered and pupil-centered modes and between the ring and zone modes,but the astigmatism axis has no obvious difference.There are some differences between vector analysis and con-ventional analysis of TCA.

Objective:To observe the effect of in‐utero exposure to isoflurane on apoptosis of hippocampal neuron in fetal rats . Methods:SD rats at gestational day 19 were randomly assigned into the isoflurane anesthesia group(group I) and the control group(group C) .The rats in group I were exposed to 1 .3% isoflurane for 3 h ,while group C were exposed to air .The Apoptosis status of neurons in hippocampal CA1 region of fetal brains were observed by using TdT mediated dUTP nick end labeling(TUNEL) 0 h ,3 h ,and 9 h after exposure to isoflurane .Results:There were a certain amount of apoptotic neurons in hippocampal CA1 region in both group I and group C 0 h ,3 h ,and 9 h after the exposure .There were significant differences regarding apoptosis index(AI) 0 h and 3 h after the exposure between the two groups (P< 0 .05) .However ,there was no significant difference regarding the AI between the two groups 9 h after the exposure (P>0 .05) .Conclusions:The in‐utero exposure to 1 .3% isoflurane does not increase the apoptosis of neurons in hippocampal CA1 region of fetal rats .Furthermore , it may alleviate the apoptosis during the early period .The result suggests that fetus period may not be the vulnerable period for isoflurane‐induced neurotoxicity .

Objective To explore the key initiatives and effective methods for preparing the constructions of emergency-oriented hospitals under COVID-19 pandemic. Methods The wartime mechanism was strengthened by adhering to unified leadership, trengthening the top-level design and clarifying the division of responsibilities. Objective management was used as a means to take into account the key of personnel allocation and training, prevention and control of hospital infection, transformation of contagious ward, logistic support, equipment and material supply and construction of system and process. Results The preparations and constructions of the emergency-oriented hospitals were completed in 72 hours，which passed the acceptance and inspections from infection control experts，who appraised our work to be “the highest in difficulty, the fastest in project progress and the highest in quality". Totally, upon to the preparations，14 medical teams were set up and the layout process reestablishment of 14 wards was completed, the installation and preparation of nearly 10000 sets/pieces of medical equipment and medical materials were completed as well and more than 80 work systems and process systems for 9 major modules were established. Conclusion The preparations and constructions of emergency-oriented hospitals should be performed upon the thorough implementation of the decisions and arrangements by the municipal Party committee and the municipal government, insisting on the wartime thinking and establishment of high-quality management team and effective goal management focusing on details and actual needs of medical staff.

Proteases are enzymes that cleave and hydrolyse the peptide bonds between two specific amino acid residues of target substrate proteins. Protease-controlled proteolysis plays a key role in the degradation and recycling of proteins, which is essential for various physiological processes. Thus, solving the substrate identification problem will have important implications for the precise understanding of functions and physiological roles of proteases, as well as for therapeutic target identification and pharmaceutical applicability. Consequently, there is a great demand for bioinformatics methods that can predict novel substrate cleavage events with high accuracy by utilizing both sequence and structural information. In this study, we present Procleave, a novel bioinformatics approach for predicting protease-specific substrates and specific cleavage sites by taking into account both their sequence and 3D structural information. Structural features of known cleavage sites were represented by discrete values using a LOWESS data-smoothing optimization method, which turned out to be critical for the performance of Procleave. The optimal approximations of all structural parameter values were encoded in a conditional random field (CRF) computational framework, alongside sequence and chemical group-based features. Here, we demonstrate the outstanding performance of Procleave through extensive benchmarking and independent tests. Procleave is capable of correctly identifying most cleavage sites in the case study. Importantly, when applied to the human structural proteome encompassing 17,628 protein structures, Procleave suggests a number of potential novel target substrates and their corresponding cleavage sites of different proteases. Procleave is implemented as a webserver and is freely accessible at http://procleave.erc.monash.edu/.