Objective To evaluate the effects of dexmedetomidine (DEX) on cell apoptosis induced by endoplasmic reticulum stress and c-Jun N-terminal kinase (JNK) pathway during one-lung ventilation (OLV) in rats.Methods Sixty male Sprague-Dawley rats were randomly allocated into 6 groups (n =10 each):sham operation group (Sham group),OLV group,OLV + atipamezole (α2 receptor antagonist) group (AD group),OLV + atipamezole + DEX group (DEX+AD group),OLV + low-dose DEX group (DEX-L group) and OLV + high-dose DEX group (DEX-H group).The animals were anesthetized with 10％ chloral hydrate 4.5 ml/kg,tracheostomized and mechanically ventilated.Bilateral lungs were ventilated for 2.5 h in Sham group.The right lung was ventilated for 2.0 h followed by 0.5 h two-lung ventilation in OLV group.In DEX-L and DEX-H groups,DEX was infused intravenously for 1 h at a rate of 2.5 μg · kg-1 · h-1 and 5.0 μg · kg-1 · h-1,respectively,starting from 1 h prior to OLV.Atipamezole 250 μg/kg was injected intravenously at 1 h prior to OLV in AD group.Atipamezole 250 μg/kg was injected intravenously at the onset of DEX infusion (5.0 μg · kg-1 · h-1) in DEX+AD group.The rats were sacrificed and left lungs were removed for determination of weight to dry lung weight ratio (W/D),cell apoptosis in lung tissues (by TUNEL),and expression of glucose-regulated protein 78 (GRP78) mRNA and protein,JNK mRNA and phosphorylated JNK (p-JNK) protein (by RT-PCR and Western blot).Pathological changes of lungs were examined and the injured alveolus rate (IAR) was counted under light microscope.The changes in ultrastructure of lung tissues were observed under transmission electron microscope.Apoptosis index (AI) was calculated.Results W/D,AI and IAR were significantly higher in OLV,AD and DEX+AD group than in Sham group,while lower in DEX-L and DEX-H groups than in OLV,AD and DEX+AD groups.The pathological changes of the structure of lung tissues were observed in OLV,AD and DEX+AD groups,while the pathological changes were significantly alleviated in DEX-L and DEX-H groups.In OLV,AD and DEX + AD groups,there was apoptosis in lots of pulmonary vascular endothelial cells and alveolar epithelial cells,while cell apoptosis was significantly reduced after administration of DEX.The expression of GRP78 mRNA and protein,JNK mRNA and p-JNK protein was significantly higher in OLV,AD and DEX+AD groups than in Sham group,and lower in DEX-L and DEX-H groups than in OLV,AD and DEX +AD groups.Conclusion DEX pretreatment can protect lungs during OLV,and inhibited JNK signaling pathway and reduced cell apoptosis induced by endoplasmic reticulum stress may be involved in the mechanism.

Objective To evaluate the effects of dexmedetomidine on perioperative inflammatory response and cellular immune function in patients undergoing posterior lumbar interbody fusion. Methods Eighty American Society of Anesthesiologists physical statusⅠorⅡpatients of either sex, aged 40-60 yr, scheduled for elective posterior lumbar interbody fusion, were divided into dexmedetomidine group(group Dex)and control group(group C)using a random number table with 40 patients in each group. In group D, dexmedetomidine at a loading dose of 0.5 μg∕kg was intravenously infused starting from 10 min before anesthesia induction, followed by continuous infusion of 0.5 μg·kg-1·h-1until 15 min before the end of operation. The equal volume of normal saline was given at the same time points in group C. Before induc?tion, at 30 min after beginning of operation and at 1 h and 1, 3 and 5 days after the end of operation (T1?6), arterial blood samples were collected for determination of the plasma CD42a+∕CD14+ratio, HLA?DR+∕CD14+ratio, concentration of C?reactive protein(CRP)and white blood cell(WBC)count. Re?sults Compared with the baseline at T1, the plasma CD42a+∕CD14+ratio was significantly increased at T2?6, the HLA?DR+∕CD14+ratio was decreased at T3?6, the plasma CRP concentrations were increased at T4?6, and the WBC count was increased at T3?5in group C, and the plasma CD42a+∕CD14+ratio was signifi?cantly increased at T6, the HLA?DR+∕CD14+ratio was decreased at T3?5, and the plasma CRP concentra?tions were increased at T2?5in group D(P<0.05). Compared with group C, the plasma CD42a+∕CD14+ra?tio was significantly decreased at T2?4, the HLA?DR+∕CD14+ratio was increased at T4?5, and the plasma CRP concentrations and WBC count were decreased at T2?5in group D(P<0.05). Conclusion Dexme?detomidine can decrease perioperative inflammatory response and improve cellular immune function in the patients undergoing posterior lumbar interbody fusion.

Objective To evaluate the effect of multimodal warming regimen on the postoperative outcomes and cost-effectiveness in the patients undergoing resection of liver cancer.Methods Sixty Ameri-can Society of Anesthesiologists physical status ⅠorⅡ patients of both sexes, aged 35-64 yr, with body mass index of 18-24 kg∕m2, of liver function Child-Pugh grade A, scheduled for elective resection of liver cancer, were divided into 2 groups(n=30 each)using a random number table: routine warming group (group R)and multimodal warming group(group M). Quilts were covered on the body exposed before in-duction of anesthesia, and the abdominal cavity was washed with the room-temperature peritoneal lavage flu-id during operation in group R.In group M, the lower body was covered using the forced-air warming system at 30 min before induction of anesthesia, and the temperature was maintained at 38℃ until the end of oper-ation; the solution used for infusion was warmed to 42 ℃ using a fluid-warming device during operation;the abdominal cavity was washed with 0.9% sodium chloride injection which was prewarmed to 37℃ during operation.The rectal temperature was recorded after anesthesia induction and before tracheal intubation (T1), at 30, 60, 90, 120 and 150 min after anesthesia and at the end of operation(T2-7). The parame-ters of thrombelastogram were measured before induction of anesthesia(T0), at T7and at 12 h after opera-tion(T8).At T0, T7, T8and 24 and 48 h after operation(T9,10), blood samples were taken from the in-ternal jugular vein for determination of plasma interleukin-6 concentrations by enzyme-linked immunosorbent assay.The extubation time, duration of post-anesthesia care unit stay, intraoperative blood loss, blood transfusion, requirement for allogeneic blood transfusion, length of hospitalization, occurrence of postoper-ative shivering, occurrence of hypothermia, volume of drainage on 1st and 3rd days after operation, neu-trophil count, cost of general anesthesia and total cost of hospitalization were recorded.Results Compared with group R, the extubation time and duration of post-anesthesia care unit stay were significantly short-ened, the intraoperative blood loss, volume of blood transfused, and volume of drainage on 1st day after operation were reduced, length of hospitalization was shortened, the requirement for allogeneic blood trans-fusion and incidence of postoperative shivering and hypothermia were decreased, the body temperature was increased at T2-7, R and K were shortened at T7, α angle was enlarged, the neutrophil count on 1st day af-ter operation was reduced, the concentration of plasma interleukin-6 was decreased at T8and T9, the cost of anesthesia was increased, and the total cost of hospitalization was reduced in group M(P<0.05). Con-clusion Multimodal warming regimen can not only promote postoperative outcomes but also improve the cost-effectiveness in the patients undergoing resection of liver cancer.

Objective: To evaluate the effect of dexmedetomidine on pyroptosis during lung ischemia-reperfusion (I/R) in rats. Methods: Adult male Sprague-Dawley rats, weighing 250-320 g, were used in this study.The model of isolated lung perfusion was established using an IL-2 Isolated Perfused Rat or Guinea Pig Lung System after the rats were anesthetized.Thirty lungs in which an ex vivo lung perfusion model was successfully established were divided into 3 groups (n=10 each) by a random number table method: control group (C group), I/R group and dexmedetomidine group (DEX group). The lungs were continuously perfused with K-H solution for 150 min in C group.After 15 min of perfusion, lungs were subjected to 60-min suspension of ventilation and perfusion, followed by 75 min of reperfusion and ventilation to establish the model of lung I/R injury in I/R and DEX groups.In DEX group, dexmedetomidine 10 nmol/L was added to K-H solution at the beginning of reperfusion.Lung tissues were obtained for determination of wet/dry weight ratio (W/D ratio) and for examination of pathological changes (with a light microscope) and ultrastructure (using an electron microscope), and the alveolar damage rate (IAR) was calculated.The expression of pyroptosis-related factors including NOD-like receptor family protein 3 (NLRP3), caspase-1, interleukin-1β (IL-1β), IL-18 and gasdermin D (GSDMD) protein and mRNA was detected by Western blot or by real-time polymerase chain reaction. Results: Compared with C group, the W/D ratio and IAR in lung tissues were significantly increased, and the expression of NLRP3, caspase-1, IL-1β, IL-18 and GSDMD protein and mRNA was up-regulated in I/R and DEX groups (P<0.05). Compared with I/R group, the W/D ratio and IAR in lung tissues were significantly decreased, the expression of NLRP3, caspase-1, IL-1β, IL-18 and GSDMD protein and mRNA was down-regulated (P<0.05), and the pathological changes were significantly attenuated in DEX group. Conclusion The mechanism by which dexmedetomidine reduces isolated rat lung I/R injury may be related to inhibiting pyroptosis.

Objective:To evaluate the effect of esmolol on the expression of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) during cerebral ischemia-reperfusion (I/R) in rats.Methods:Forty-eight clean-grade healthy adult male Sprague-Dawley rats, were allocated into 3 groups ( n=16 each) using a random number table method: sham operation group (Sham group), cerebral I/R group (I/R group) and esmolol group (E group). Cerebral I/R was induced by 3 cycles of 20-min occlusion of bilateral common carotid arteries followed by 10-min reperfusion in anesthetized rats.Esmolol 200 g·kg -1·min -1 was intravenously infused for 1 h starting from 30 min before ischemia, and the model was established after 30-min infusion in E group.The equal volume of normal saline was given at 30 min before ischemia in I/R group.Bilateral common carotid arteries were only isolated but not clamped, and the equal volume of normal saline was given after isolating bilateral common carotid arteries in Sham group.Learning and memory function was tested by Morris water maze test before ischemia and at 1, 3 and 7 days of reperfusion.Rats were sacrificed after Morris water maze test, and the hippocampus was excised for determination of wet to dry weight ratio (W/D ratio), permeability of blood-brain barrier (using Evans blue method), expression of ERK1/2 mRNA (by real-time polymerase chain reaction ), and expression of p-ERK1/2 (by Western blot). Results:Compared with Sham group, the escape latency and swimming distance were significantly prolonged at 1, 3 and 7 days of reperfusion, the W/D ratio and EB content in brain tissues were increased, and the expression of ERK1/2 mRNA and p-ERK1/2 was up-regulated in I/R and E groups ( P<0.05). Compared with I/R group, the escape latency and swimming distance were significantly shortened at 1, 3 and 7 days of reperfusion, the W/D ratio and EB content in brain tissues were decreased, and the expression of ERK1/2 mRNA and p-ERK1/2 was down-regulated in E group ( P<0.05). Conclusion:The mechanism by which esmolol alleviates cerebral I/R injury and improves cognitive function is related to inhibiting the up-regulated expression of ERK1/2 in rats.

Objective To evaluate the effect of sevoflurane on unfolded protein response-related cell apoptosis during acute lung injury in rats undergoing cardiopulmonary bypass ( CPB) . Methods For-ty-eight clean-grade healthy adult male Sprague-Dawley rats, aged 6-8 weeks, weighing 250-300 g, were allocated into 3 groups ( n=16 each) using a random number table method: sham operation group ( Sham group) , CPB group and sevoflurane group ( Sev group) . Left common carotid artery and right internal jugu-lar vein were only cannulated in group Sham. After establishing CPB, the flow rate was gradually adjusted to the maximum (100 ml·kg-1·min-1) and maintained for 60 min in group CPB. Two percent sevoflurane was inhaled for 30 min, and 15 min later the model of CPB was established in Sev group. Rats were sacri-ficed at 1 h after the end of CPB, lungs were removed and lung tissues were obtained. The pathological changes and ultrastructure of lung tissues were examined with a light microscope and with an electron micro-scope, respectively. The wet to dry weight ratio ( W∕D ratio) , apoptosis in lung cells ( by TUNEL assay) , expression of glucose-regulated protein 78 ( GRP78) , CCAAT∕enhancer-binding protein homologous protein (CHOP), c-Jun N-terminal kinase (JNK) and caspase-12 mRNA was determined by real-time polymerase chain reaction. The expression of GRP78, CHOP, phosphorylated JNK (p-JNK) and caspase-12 was de-tected by Western blot. The index of quantitative assessment of histologic lung injury ( IQA) was measured, and apoptotic index ( AI) was calculated. Results Compared with Sham group, the W∕D ratio, IQA and AI were significantly increased, the expression of GRP78, CHOP, JNK and caspase-12 was up-regulated ( P<0. 05) , and the pathological changes of lung tissues were accentuated in CPB group. Compared with CPB group, the W∕D ratio, IQA and AI were significantly decreased, the expression of GRP78, CHOP, JNK and caspase-12 was down-regulated ( P<0. 05) , and the pathological changes of lung tissues were sig-nificantly attenuated in Sev group. Conclusion The mechanism by which sevoflurane mitigates acute lung injury induced by CPB is related to inhibiting unfolded protein response related cell apoptosis in lung tissues of rats.

Objective:To investigate the clinical characteristics of acute ischemic stroke with anterior circulation large vessel occlusion caused by cardioembolism (CE) and large artery atherosclerosis (LAA) and the efficacy of endovascular treatment.Methods:Patients with acute ischemic stroke caused by large vessel occlusion in anterior circulation and received endovascular treatment in the Stroke Center of the 971 st Hospital of the PLA Navy from April 2014 to April 2021 were retrospectively enrolled. The etiological classification of stroke was CE or LAA. According to the modified Rankin Scale score at 90 d after onset, the patients were divided into good outcome group (0-2) and poor outcome group (>2). The demographic and clinical data between the groups were compared. Multivariate logistic regression analysis was used to determine the independent influencing factors of clinical outcome. Results:A total of 106 patients were enrollded. Their age was 61.39±13.73 years and 70 (66.0%) were males. Seventy-four patients (69.8%) were in the CE group and 32 (30.2%) were in the LAA group. Sixty-six patients (62.3%) had good outcomes. Univariate analysis showed that there were significant differences in gender, age, smoking, systolic blood pressure, diastolic blood pressure, baseline National Institutes of Health Stroke Scale (NIHSS) score, time from onset to femoral artery puncture, time from puncture to vascular recanalization, and the number of retrieval attempts between the CE group and the LAA group (all P<0.05), and there were no significant differences in the incidences of poor outcome, hemorrhagic transformation, and symptomatic intracranial hemorrhage. There were significant differences in systolic blood pressure, diastolic blood pressure, baseline NIHSS score, time from onset to femoral artery puncture, and blood perfusion grade after treatment between the good outcome group and the poor outcome group (all P<0.05). Multivariable logistic regression analysis showed that higher systolic blood pressure (odds ratio [ OR] 1.046, 95% confidence interval [ CI] 1.014-1.078; P=0.004), higher baseline NIHSS score ( OR 1.117, 95% CI 1.037-1.203; P=0.003), longer time from onset to femoral artery puncture ( OR 1.008, 95% CI 1.001-1.015; P=0.019) and poor blood perfusion after treatment ( OR 8.042, 95% CI 1.532-42.215; P=0.014) were significantly and independently associated with the poor outcomes. Conclusions:Compared with LAA, CE do not increase the risks of hemorrhagic transformation and symptomatic intracranial hemorrhage. The safety and efficacy of the two are similar.

Objective:To evaluate the role of NOD-like receptor protein 3 (NLRP3) inflammasomes in curcumin-induced reduction of sevoflurane-induced postoperative cognitive dysfunction in rats.Methods:Forty SPF healthy male Sprague-Dawley rats, aged 17-18 months, with body mass index of 580-600 g, were divided into 4 groups ( n=10 each) by a random number table method: control group (C group), postoperative cognitive dysfunction group (P group), curcumin group (CU group), and curcumin+ NLRP3 inflammasome activator group (CN group). The rat model of postoperative cognitive dysfunction was prepared by inhaling 1.5% sevoflurane to explore the abdominal cavity. Curcumin suspension 300 mg/kg was given by intragastric administration in CU group and CN group, and the rats received intragastric administration of nidrisin sodium 5 mg/kg simultaneously in CN group, once a day for 6 consecutive days. Rats received the equal volume of normal saline instead in C group and P group. The frequency of crossing the original platform and time spent in the target quadrant were measured by the Morris water maze test. The histopathological changes of hippocampus were observed by HE staining, neuronal apoptosis was detected by TUNEL staining, and the expression of NLRP3, Bcl-2 and Bax was detected by Western blot. Results:Compared with C group, the frequency of crossing the original platform was significantly reduced, the time spent in the target quadrant was shortened, the apoptosis rate of neurons was increased, and the expression of NLRP3 and Bax was up-regulated, and the expression of Bcl-2 was down-regulated in P group ( P<0.05). Compared with P group, the frequency of crossing the original platform was significantly increased, the time spent in the target quadrant was prolonged, the apoptosis rate of neurons was decreased, and the expression of NLRP3 and Bax was down-regulated, and the expression of Bcl-2 was up-regulated in CU group ( P<0.05). Compared with CU group, the frequency of crossing the original platform was significantly reduced, the time spent in the target quadrant was shortened, the apoptosis rate of neurons was increased, and the expression of NLRP3 and Bax was up-regulated, and the expression of Bcl-2 was down-regulated in CN group ( P<0.05). Conclusions:The NLRP3 inflammasome is involved in curcumin-induced reduction of postoperative cognitive dysfunction in sevoflurane-anesthetized rats.