Objective To study the risk factors for in-hospital mortality in patients with acute myocardial infarction(AMI)undergoing emergency percutaneous coronary intervention(EPCI).Methods Nine hundred and eight patients with acute myocardial infarction(AMI)who underwent EPCI at Beijing Jingmei Group General Hospital between September 2016 and December 2022 were enrolled and divided into an in-hospital death group(36 cases)and a survival group(872 cases)based on in-hospital outcomes.The basic information,clinical indicators,results of coronary angiography,outcomes of EPCI,and complications were compared between the two groups.Multiple logistic regression analysis was conducted to identify the risk factors for in-hospital mortality during EPCI.Results The age and serum creatinine levels of the death group were higher than those of the survival group(P＜0.05),and the estimated glomerular filtration rate(eGFR)and hemoglobin(Hb)levels were lower than those of the survival group(P＜0.05).The proportion of diabetes mellitus,cerebral infarction,cardiogenic shock,left main culprit lesion,rapid ventricular arrhythmia,TIMI flow grade＜3 after EPCI for culprit vessel,and intra-aortic balloon pump(IABP)implantation in the death group were higher than those of the survival group(P＜0.05).The results of multiple logistic regression analysis showed that age,cardiogenic shock,TIMI flow grade＜3 after culprit vessel intervention,and rapid ventricular arrhythmia had a statistically significant impact on in-hospital mortality in EPCI(P＜0.05).Conclusion Age,cardiogenic shock,TIMI flow grade＜3 after PCI for culprit vessels,and rapid ventricular arrhythmia are independent risk factors for in-hospital mortality in EPCI patients with AMI.

Objective:To evaluate the effect of selective inhibitor of caspase-1 VX-765 on cognitive function in a rat model of hemorrhage shock and resuscitation (HSR).Methods:Forty-eight clean-grade healthy male Sprague-Dawley rats, aged 9-10 weeks, weighing 350-400 g, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (S group), HSR group (H group), VX-765 group (V group), and solvent control group (C group). The rats in H, V and C groups were subjected to hemorrhage by bleeding from femoral vein to achieve mean arterial pressure of 25-35 mmHg which was maintained at this level for 60 min followed by resuscitation with shed blood within 15 min to restore blood pressure, and normal saline was infused when needed.VX-765 1 mg/kg and 0.4% polyethylene glycol 1 mg/kg were intravenously injected via the femoral vein immediately after the end of resuscitation in V and C groups, respectively.Six rats in each group were selected and sacrificed at 12 h after the end of resuscitation, and the cerebral cortex was removed for determination of neuronal pyroptosis (by immunofluorescence) and degree of cortical edema (using T2-weighted imaging). Cognitive function was measured by open field test on day 7 after resuscitation in the rest 6 rats in each group. Results:Compared with S group, the pyroptosis rate in cortical neurons at 12 h after resuscitation and degree of cortical edema were significantly increased, the distance in the central square and the number of standing on the back legs were decreased on day 7 after resuscitation, and the time spent in the central square was shortened in H, V and C groups ( P<0.05). Compared with H and C groups, the pyroptosis rate in cortical neurons at 12 h after resuscitation and degree of cortical edema were significantly decreased, the distance in the central square and the number of standing on the back legs were increased on day 7 after resuscitation, and the time spent in the central square was prolonged in V group ( P<0.05). Conclusion:VX-765 can improve the cognitive function, and the mechanism may be associated with inhibiting pyroptosis in cortical neurons in a rat model of HSR.

Objective:To evaluate the effect of exogenous carbon monoxide (CO) on cell apoptosis during acute renal injury induced by hemorrhagic shock and resuscitation (HSR) in rats.Methods:Forty-eight clean-grade healthy male Sprague-Dawley rats, aged 9-10 weeks, weighing 350-400 g, were divided into 4 groups ( n=12 each) by a random number table method: sham operation group (S group), HSR group (H group), HSR plus CORM-3 group (HC group) and HSR plus iCORM-3 group (HiC group). Mean arterial pressure was maintained at 30-35 mmHg for 45 min by withdrawing blood from the femoral vein, and the shed blood was re-transfused within 15 min to reach the initial blood pressure for resuscitation.Normal saline was infused when necessary, and the model of HSR was established.CORM-3 4 mg/kg and iCORM-3 4 mg/kg were added during resuscitation in HC group and HiC group, respectively.Only femoral vein and artery puncture was performed in S group.Blood samples were obtained from the tail vein at 3 h after resuscitation for measurement of serum urea nitrogen (BUN) and creatinine (Scr) concentrations.Rats were sacrificed at 12 h after resuscitation, and renal tissues were obtained for determination of the expression of Bcl-2 and Bak protein and cleaved caspase-3 (by Western blot) and cell apoptosis (by TUNEL). The damage to the renal tubules was assessed by paller assay after HE staining.Bcl-2/Bak ratio and apoptosis rate were calculated. Results:Compared with group S, the serum BUN and Scr concentrations, paller scores, and apoptosis rate were significantly increased, Bcl-2/Bak ratio was decreased, and the expression of cleaved caspase-3 was up-regulated in H, HC and HiC groups ( P<0.05). Compared with group H, the serum BUN and Scr concentrations, paller scores, and apoptosis rate were significantly decreased, Bcl-2/Bak ratio was increased, and the expression of cleaved caspase-3 was down-regulated in group HC ( P<0.05). Compared with group HC, the serum BUN and Scr concentrations, paller scores, and apoptosis rate were significantly increased, Bcl-2/Bak ratio was decreased, and the expression of cleaved caspase-3 was up-regulated in group HiC ( P<0.05). There was no significant difference in the indexes mentioned above between group H and group HiC ( P>0.05). Conclusion:The mechanism by which exogenous CO improves acute kidney injury may be related to inhibiting cell apoptosis in a rat model of HSR.

Objective:To evaluate the effect of VX-765 on cognitive function in acute rapid eye movement (REM) sleep-deprived juvenile rats.Methods:Thirty-six clean-grade healthy male Sprague-Dawley rats, aged 3-4 weeks, weighing 52-101 g, were divided into 3 groups ( n=12 each) using a random number table method: control group (group C), acute REM group (group AREM) and VX-765 group (group V). Sleep deprivation model was established by modified multi-platform water environment method.In group V, VX-765 solution 10 mg/kg was intravenously injected via the tail vein at 9: 00 a. m.every day for 4 consecutive days.The equal volume of normal saline was given instead in C and AREM groups.Morris water maze and novel object recognition tests were performed for 4 consecutive days during sleep deprivation.The rats were then sacrificed after the end of Morris water maze and novel object recognition tests on 5th day, and hippocampi were removed for determination of the expression of interleukin-1beta (IL-1β) and IL-18 by Western blot. Results:Compared with group C, the latency of novel object recognition was significantly prolonged, the percentage of novel object exploration was shortened, and the number of head exploration was decreased, the percentage of novel object exploration and discrimination index were decreased, the number of crossing the original platform in Morris water maze test was reduced, the time of staying at the target quadrant was shortened, and the expression of IL-1β and IL-18 was up-regulated in AREM and V groups ( P<0.05). Compared with group AREME, the latency of novel object recognition was significantly shortened, the percentage of novel object exploration was prolonged, and the number of head exploration was increased, the percentage of novel object exploration and discrimination index were increased, the number of crossing the original platform in Morris water maze test was increased, the time of staying at the target quadrant was prolonged, and the expression of IL-1β and IL-18 was down-regulated ( P<0.05). Conclusion:VX-765 can improve the cognitive function in acute REM sleep-deprived juvenile rats, which is related to inhibiting hippocampal inflammatory responses.

Objective:To evaluate the effect of carbon monoxide-releasing molecule-3 (CORM-3) on blood transfusion-related acute lung injury in rats with traumatic brain injury (TBI).Methods:Seventy-two clean-grade healthy adult male Sprague-Dawley rats, weighing 300-350 g, were divided into 4 groups ( n=18 each) using the random number table method: sham operation group (group S), TBI group (T group), TBI plus 10 ml/kg plasma transfusion group (TP group), and TBI plus 10 ml/kg plasma transfusion plus CORM-3 group (TPC group). TBI was induced by dropping a 20-g weight from 20 cm height falling freely in anesthetized rats.Plasma 10 ml/kg was infused via the femoral vein after TBI in TP and TPC groups.The rats were sacrificed at 24 h after plasma transfusion, and lung tissues were obtained for determination of wet/dry weight (W/D) ratio, cell apoptosis, and expression of caspase-3, Bid, Bim and Puma (by Western blot). The lung injury score was calculated using the results of HE staining.Lung ultrasonography was performed for assessment of sonographic score, and the apoptosis rate was calculated by the TUNEL staining method. Results:Compared with S group, the W/D ratio, lung injury score, sonographic score and apoptosis rate were significantly increased, and the expression of activated caspase-3, Bid, Bim and Puma was up-regulated in the other three groups ( P<0.05). Compared with T group, the W/D ratio, lung injury score, sonographic score and apoptosis rate were significantly increased, and the expression of activated caspase-3, Bid, Bim and Puma was up-regulated in TP group ( P<0.05). Compared with TP group, the W/D ratio, lung injury score, sonographic score and apoptosis rate were significantly decreased, and the expression of activated caspase-3, Bid, Bim and Puma was down-regulated in TPC group ( P<0.05). Conclusion:CORM-3 can reduce acute lung injury related to blood transfusion in rats with TBI, and the mechanism may be related to inhibiting cell apoptosis in lung tissues.

Objective To explore the role of CORM-3 in alleviating cognitive dysfunction and cortical neuronal pyroptosis of rats exposed to hemorrhage shock and resuscitation. Methods One hundred and sixty-eight male SD rats, weighting 350-400 g, in accordance with random number table, were divided into 4 groups (n=42):sham-operated group, hemorrhage shock and resuscitation (H group), hemorrhage shock and resuscitation plus CORM-3 (CO group), hemorrhage shock and resuscitation plus iCORM-3 (ICO group). The rat hemorrhagic shock resuscitation models were established in H, CO and ICO groups:bleeding from femoral vein was performed to achieve mean arterial pressure of 25-35 mmHg (1 mmHg=0.133 kPa) for 60 min;and then, the collected blood was returned to the body within 15 min to reach the initial blood pressure level as resuscitation, and normal saline was injected if necessary. The rats in CO group were injected CORM-3 (4 mg/kg) via femoral vein after resuscitation, the rats in ICO group were injected iCORM-3 (4 mg/kg), and rats in the sham-operate group and H group were only injected equal amount of normal saline containing DMSO. Rats were sacrificed for cortex 12 h after end of resuscitation;CO content was assessed by gas chromatograph assay; Western blotting was used to detect the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and BTB-CNC homology 1 (Bach1) in the nuclear, and heme oxygenase-1 (HO-1), interleukin (IL)-1β and IL-18 in cytosol; and neuronal pyroptosis rate was detected by cleaved caspase-1-Cy3/neuron-specific nucleoprotein (NeuN)-FITC/DAPI. Thirty d after resuscitation, open field test was used to assess the cognitive ability of the rats. Results At 12 h after resuscitation, as compared with sham-operated group, rats in the H, CO and ICO groups had significantly increased CO content, neuronal pyroptosis, ratio of Nrf2/Bach1, and expressions of HO-1, IL-1β and IL-18, statistically longer time spending in the central square, significantly smaller times crossing the grid and times standing on the back legs (P<0.05). As compared with H and ICO group, CO group had significantly increased CO content, ratio of Nrf2/Bach1, and HO-1 expression, times crossing the grid, times standing on the back legs, but significantly decreased neuronal pyroptosis, expressions of IL-1β and IL-18, and time spending in the central square (P<0.05). Conclusion CORM-3 can reduce the neuronal pyroptosis rate and alleviate cognitive dysfunction in rats with hemorrhagic shock and resuscitation, whose mechanism may be related to the increase of HO-1 expression after up-regulation of Nrf2/Bach1 ratio.