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Objective:To evaluate the effect of ultrasound-guided single fascia iliaca compartmentblock (FICB) combined with esketamine on postoperative delirium (POD) in elderly patients undergoing hip fracture surgery.Methods:Sixty-two patients of either sex, aged 60-85 yr, with body mass index of 18-30 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, undergoing hip fracture surgery under subarachnoid anesthesia, were divided into 2 groups ( n=31 each) using a random number table method: single FICB group (group FICB) and single FICB combined with esketamine group (group FICB+ E). Ultrasound-guided FICB was performed on the operated side at 30 min before subarachnoid anesthesia. In FICB+ E group, esketamine was intravenously injected as a bolus of 0.3 mg/kg at 5 min before skin incision followed by an infusion of 0.25 mg·kg -1·h -1 until 30 min before the end of procedure. Patient-controlled intravenous analgesia was used for postoperative analgesia, and tramadol 1 mg/kg was given for rescue analgesia. The pressing times of patient-controlled analgesia, the number of rescue analgesia, and consumption of tramadol were recorded within 48 h after operation. The Ramsay sedation score was used to assess the degree of sedation at skin incision, 30 min after the start of surgery, 30 min before the end of surgery, at the end of surgery, and at discharge from the post-anesthesia care unit. Postoperative delirium (POD) occurred within 7 days after surgery was assessed using the Confusion Assessment Method. The serum concentrations of tumor necrosis factor-alpha, interleukin-6, S100β and glial fibrillary acidic protein (GFAP) were detected by enzyme-linked immunosorbent assay on admission to the operating room and at 3 and 7 days after surgery. The occurrence of adverse drug reactions (respiratory depression, nausea and vomiting, dizziness, somnolence, urinary retention) was recorded. Results:Compared with group FICB, the incidence of POD was significantly decreased within 3 days after surgery, the consumption of tramadol, pressing times of patient-controlled analgesia and the number of rescue analgesia were reduced, Ramsay sedation score was increased at each time point, and the serum concentrations of tumor necrosis factor-alpha, interleukin-6, S100β and glial fibrillary acidic protein were decreased after surgery ( P<0.05), and no significant change was found in the total incidence of POD at 7 days after surgery in group FICB+ B ( P>0.05). Conclusions:Ultrasound-guided single FICB combined with esketamine can provide adequate analgesia and sedation in the perioperative period for elderly patients with hip fractures, reducing the risk of early postoperative (within 3 days) POD.
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Objective:To evaluate the efficacy of ultrasound-guided superior laryngeal nerve block(SLNB) combined with intravenous anesthesia for improving pediatric fiberoptic bronchoscopy.Methods:Forty pediatric patients of either sex, aged 3-6 yr, of American Society of Anesthesiologists Physical Status classificationⅠor Ⅱ, with body mass index of 18-24 kg/m 2, undergoing fiberoptic bronchoscopy in Cangzhou Central Hospital in 2022, were divided into 2 groups ( n=20 each) by a random number table method: ultrasound-guided SLNB plus intravenous anesthesia group (group A) and topical anesthesia plus intravenous anesthesia group (group B). After sedation with dexmedetomidine and esketamine, ultrasound-guided bilateral SLNB was performed with 1% lidocaine 0.5 ml (for each side)in group A, and topical anesthesia was performed with 1% lidocaine in nasal and pharyngeal cavities in group B. After completion of the surgery procedure, propofol was continuously infused at 5 mg·kg -1·h -1 until completion of diagnosis and treatment. An increment of propofol 1 mg/kg was intravenously given if severe bucking or body movement occurred during operation. Mean arterial pressure (MAP), heart rate (HR) and SpO 2 were recorded on admission to the operating room (T 0), immediately after sedation (T 1), immediately after bronchoscopy entering the glottis (T 2), 5 min after start of treatment (T 3) and at the end of examination (T 4). The occurrence of intraoperative hypoxemia, HR <60 bpm, and MAP <50 mmHg were recorded, and the additional dose of propofol was recorded. The venous blood samples were collected at T 0 and T 4 to determine plasma cortisol concentrations by chemiluminescence.The surgeon′s satisfaction score was recorded. The complications of SLNB were also recorded within 2 h after operation in group A. Results:Compared with group B, HR was significantly decreased at T 2 and T 3, SpO 2 was increased, the intraoperative additional dosage of propofol and incidence of hypoxemia were decreased, and the surgeon′s satisfaction score was increased, and the concentrations of cortisol were decreased at T 4 in group A ( P<0.05). No HR<60 bpm and MAP<50 mmHg were found in two groups. No SLNB-related complications were observed after operation in group A. Conclusions:Ultrasound-guided SLNB combined with intravenous anesthesia is safer for pediatric fiberoptic bronchoscopy and can improve the analgesic effect and is more helpful in inhibiting intraoperative stress responses when compared with conventional anesthesia.
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Objective:To evaluate the efficacy of esketamine combined with fascia iliaca compartment-subarachnoid block in optimizing anesthesia in elderly patients undergoing hip fracture surgery.Methods:Sixty-two American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ elderly patients of either sex, aged 60-85 yr, with body mass index of 18.5-30.0 kg/m 2, were divided into 2 groups ( n=31 each) using a random number table method: fascia iliaca compartment-subarachnoid block group (FS group) and esketamine combined with fascia iliaca compartment-subarachnoid block group (ES group). In FS group, patients underwent ultrasound-guided fascia iliaca compartment block at 30 min before the operation of subarachnoid anesthesia on the surgical side. In ES group, esketamine 0.25 mg/kg was intravenously administered at 5 min before skin incision based on the fascia iliaca compartment-subarachnoid block. Patient-controlled intravenous analgesia was used for postoperative analgesia, and tramadol 1 mg/kg was intravenously given for rescue analgesia when numerical rating scale score > 4. The pressing times of patient-controlled analgesic pump, the number of rescue analgesia and consumption of tramadol were recorded within 48 h after operation. The occurrence of postoperative adverse reactions (respiratory depression, nausea and vomiting, dizziness, drowsiness, pruritus, illusion, nightmares) was recorded. Results:Compared with FS group, the consumption of postoperative tramadol was significantly decreased, and the pressing times of patient-controlled analgesic pump and the number of rescue analgesia were reduced in ES group ( P<0.05). There were no significant differences in the incidence of postoperative adverse reactions between the two groups ( P>0.05). Conclusions:Combination of esketamine with fascia iliaca compartment-subarachnoid block for hip fracture surgery can raise postoperative analgesia and optimize clinical management strategies in elderly patients.
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Objective:To evaluate the role of stimulator of interferon genes (STING) signaling pathway in carbon monoxide (CO)-releasing molecule-3 (CORM-3)-induced reduction of hepatocyte pyroptosis and apoptosis in a rat model of hepatic ischemia-reperfusion.Methods:Forty-eight clean-grade healthy male Sprague-Dawley rats, aged 9-11 weeks, weighing 320-380 g, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (S group), ischemia-reperfusion group (IR group), CORM-3 group (C group) and STING agonist ADU-S100 group (A group).Hepatic ischemia-reperfusion injury models were developed by reversible ligation of left middle hepatic artery, portal vein and bile duct branches for 45 min, followed by reperfusion in anesthetized animals in IR, C and A groups.In group C, CORM-3 4 mg/kg was injected into the femoral vein immediately after reperfusion.The equal volume of normal saline containing dimethyl sulfoxide was injected into the femoral vein in S, IR and A groups.At 1.5 h after injection into the femoral vein, ADU-S100 10 mg/kg was intraperitoneally injected in A group, and the equal volume of normal saline was given instead in S, IR and C groups.The serum alanine transaminase (ALT) and aspartate transaminase (AST) concentrations were determined at 3 h of reperfusion.The rats were sacrificed at 12 h of reperfusion, and liver tissues were collected for determination of the content of CO (by colorimetry), expression of interleukin-1beta (IL-1β), IL-18, Bcl-2, Bax, interferon regulatory factor 3 (IRF3), phosphorylated IRF3 (p-IRF3), STING, NOD-like receptor protein 3 (NLRP3), aspirin D (GSDMD) and activated caspase-1 (by Western blot), and pyroptosis and apoptosis rates of hepatocytes (by immunofluorescence staining).The liver injury was scored. Results:Compared with group S, the serum ALT and AST concentrations, liver injury score, CO content, and pyroptosis and apoptosis rates of hepatocytes were significantly increased, and the expression of IL-1β, IL-18, p-IRF3, STING, NLRP3, GSDMD and activated caspase-1 was up-regulated, and the Bcl-2/Bax ratio was decreased in group IR ( P<0.05).Compared with group IR, the serum ALT and AST concentrations, liver injury score, and pyroptosis and apoptosis rates of hepatocytes were significantly decreased, the CO content was increased, the expression of IL-1β, IL-18, p-IRF3, STING, NLRP3, GSDMD and activated caspase-1 was down-regulated, and the Bcl-2/Bax ratio was increased in group C ( P<0.05).Compared with group C, the serum ALT and AST concentrations, liver injury score, and pyroptosis and apoptosis rates of hepatocytes were significantly increased, the CO content was decreased, the expression of IL-1β, IL-18, p-IRF3, STING, NLRP3, GSDMD and activated caspase-1 was up-regulated, and the Bcl-2/Bax ratio was decreased in group A ( P<0.05). Conclusions:The mechanism by which CORM-3 attenuates hepatocyte pyroptosis and apoptosis may be related to the inhibition of activation of STING signaling pathway in a rat model of hepatic ischemia-reperfusion.
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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.
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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.
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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.
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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.
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Objective To evaluate the effect of carbon monoxide (CO) postconditioning on pyroptosis induced by oxygen-glucose deprivation and restoration (OGD/R) in rat hippocampai neurons and the relationship with mitochondrial permeability transition pore (mPTP)/reactive oxygen species (ROS) signaling pathway.Methods Primary hippocampal neurons were cultured in vitro,seed in 6-well or 96-well plates,and divided into 5 groups (n =24 each) using a random number table method:control group (C group),OGD/R group,CO postconditioning group (CO group),specific mPTP opener atractyloside plus CO postconditioning group (ACO group),and specific ROS inducer antimycin A plus CO postconditioning group (KCO group).Neurons were subjected to O2-glucose deprivation (OGD) for 16 h followed by restoration of O2-glucose supply for 24 h to establish the model of OGD/R injury.In group CO,neurons were exposed to 2％ CO-5％ CO2 for 3 h at 37 ℃ starting from the end of OGD,followed by normal culture for 21 h.In ACO and KCO groups,atractyloside 20 μmol/L and antimycin A 50 μmol/L were added at the end of OGD,respectively,and the other treatments were similar to those previously described in group CO.Neuronal pyroptosis rate was determined using double immunofluorescent staining cleaved caspase-1-AlexaFluor 568/DAPI after the end of treatments in each group.The neuronal survival rate was determined by MTT,opening of mPTP by Calcein-AM fluorescence,ROS content by DCFH-DA,and expression of interleukin1beta (IL-1β) and IL-18 by Western blot.Results Compared with C group,neuronal pyroptosis rate,ROS content and opening of mPTP were significantly increased,the neuronal survival rate was decreased,and the expression of IL-1β and IL-18 was up-regulated in the other groups (P＜0.05).Compared with OGD/R group,neuronal pyroptosis rate,ROS content and opening of mPTP were significantly decreased,the neuronal survival rate was increased,and the expression of IL-1β and IL-18 was down-regulated in CO,ACO and KCO groups (P＜0.05).Compared with CO group,neuronal pyroptosis rate and ROS content were significantly increased,the neuronal survival rate was decreased,and the expression of IL-1β and IL-18 was up-regulated in ACO and KCO groups,and opening of mPTP was significantly inctreased in ACO group (P＜0.05).Conclusion CO postconditioning can inhibit OGD/R-induced pyroptosis in rat hippocampal neurons,and the mechanism is related to inhibiting mPTP/ROS signaling pathway.