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Objective:To evaluate the efficacy of esketamine for patient-controlled intravenous analgesia (PCIA) in elderly patients undergoing modified radical mastectomy for breast cancer.Methods:Ninety elderly female patients, aged 65-78 yr, weighing 46-75 kg, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, undergoing elective modified radical surgery for breast cancer under general anesthesia, were divided into 2 groups ( n=45 each) using a random number table method: esketamine PCIA group (group E) and sufentanil PCIA group (group S). Anesthesia was induced with target-controlled infusion of propofol, intravenous atracurium besylate and sufentanil and maintained with target-controlled infusion of propofol and remifentanil and intermittent intravenous boluses of cis-benzenesulfonic acid atracurium.The patients were connected to an analgesic pump for PCIA at 10 min before completion of operation.The PCIA solution in group E contained esketamine 2 mg/kg, ketorolac tromethamine 90 mg and tropisetron 5 mg in 100 ml of normal saline.The PCIA solution in group S contained sufentanil 1 μg/kg, ketorolac tromethamine 90 mg and tropisetron 5 mg in 100 ml of normal saline.The PCA pump was set up with a 1.5 ml bolus dose, a 15 min lockout interval and background infusion at a rate of 1.5 ml/h, and the analgesia was performed until 48 h after operation.When numeric rating scale score ≥ 4 points and the efficacy of patient-controlled analgesia was not good, tramadol 100 mg was intravenously injected for rescue analgesia.Steward recovery scores were recorded at 4, 8, 24 and 48 h after operation.The requirement for rescue analgesia, effective pressing times of analgesic pump and time to first flatus were recorded within 48 h after operation.The nausea and vomiting, respiratory depression, dizziness and pruritus within 48 h after operation and delirium within 7 days after operation were recorded.The 40-item Quality of-Recovery scale was used to evaluate the early postoperative recovery of patients at 24 and 48 h after operation. Results:Compared with group S, the 40-item Quality of Recovery scale score was significantly increased at each time point, postoperative time to first flatus was shortened, the incidence of postoperative nausea and vomiting and pruritus was decreased ( P<0.05), and no significant change was found in the Steward recovery score at each time point after operation, effective pressing times of PCA and requirement for rescue analgesia in group E ( P>0.05). Conclusions:Esketamine provides better efficacy than sufentanil when used for PCIA in elderly patients undergoing modified radical mastectomy for breast cancer.
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Objective:To evaluate the relationship between long-term learning and memory impairment induced by sevoflurane anesthesia and postsynaptic density protein-95 (PSD-95)/Kalirin-7/Ras-related C3 botulinum toxin substrate 1 (Rac1) signaling pathway in neonatal rats.Methods:Sixty SPF male Wistar rats, aged 7 days, weighing 12-18 g, were divided into 5 groups ( n=12 each) using a random number table method: control group (group C), 1% sevoflurane anesthesia for 2 h group (group S 1), 1% sevoflurane anesthesia for 4 h group (group S 2), 2% sevoflurane anesthesia for 2 h group (group S 3) and 2% sevoflurane anesthesia for 4 h group (group S 4). Morris water maze test was performed at 4, 8 and 12 weeks after anesthesia.The rats were sacrificed after the last Morris water maze test, and the hippocampal tissues were obtained for microscopic examination of the pathological changes (using HE staining), neuron apoptosis (by TUNEL staining), and expression of PSD-95, Kalirin-7 and Rac1 protein and mRNA (by Western blot and quantitative real-time polymerase chain reaction). The apoptosis rate was calculated. Results:Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the time of stay in the target quadrant was shortened, and the apoptosis rate of hippocampal neurons was increased at 4th, 8th and 12th weeks after anesthesia, phosphorylated Rac1/Rac1 ratio was decreased, and the expression of PSD-95 and Kalirin-7 protein and mRNA was down-regulated in S 1, S 2, S 3 and S 4 groups ( P<0.05). Compared with group S 4, the escape latency was significantly shortened, the number of crossing the original platform was increased, the time of stay in the target quadrant was prolonged, and the apoptosis rate of hippocampal neurons was decreased, phosphorylated Rac1/Rac1 ratio was increased, the expression of PSD-95 and Kalirin-7 protein and mRNA was up-regulated, and the histopathological changes of hippocampal tissues were attenuated in S 1, S 2 and S 3 groups ( P<0.05). Conclusions:The mechanism by which sevoflurane anesthesia induces long-term learning and memory impairment may be related to inhibition of activity of PSD-95/Kalirin-7/Rac1 signaling pathway in hippocampi of neonatal rats.
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Objective:To evaluate the effect of operation duration on the pharmacokinetics of desflurane in the patients undergoing tumor resection.Methods:One hundred and fifty patients of both sexes, aged 18-75 yr, with body mass index of 19-25 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, in whom abnormal preoperative lung function was not found, undergoing elective surgery with general anesthesia from November 2019 to March 2020, were enrolled in this study.Anesthesia was induced with intravenous injection of sufentanil 0.3 μg/kg, cisatracurium besylate 0.2 mg/kg and propofol 2 mg/kg.The patients were tracheally intubated after mechanical ventilation.Anesthesia was maintained with inhalation of desflurane, the vaporizer dial was adjusted to 6% with fresh gas flow rate of 2 L/min, and sufentanil and cisatracurium besylate were intermittently injected intravenously according to the changes in hemodynamics and degree of muscle relaxation during operation.The duration required for the end-tidal concentration of desflurane reaching 0.5 minimum alveolar concentration (MAC), time when the ratio of the end-tidal concentration of desflurane to the pre-set concentration of the vaporizer reached 1/2, time when the ratio of the end-tidal concentration of desflurane to the inhaled concentration reached 1/2, time for the end-tidal concentration of desflurane to decrease to 0.5 MAC and time for the end-tidal concentration to decrease from 0.5 MAC to 0.2 MAC immediately after closing the volatile tank were recorded.The patients were divided into 3 groups according to the operation time: operation time <2 h group (group S), operation time 2-4 h group (group M), and operation time >4 h group (group L). Results:There were no significant differences among the 3 groups in the duration required for the end-tidal concentration of desflurane reaching 0.5 MAC, time when the ratio of the end-tidal concentration of desflurane to the pre-set concentration of the vaporizer reached 1/2, time when the ratio of the end-tidal concentration of desflurane to the inhaled concentration reached 1/2, time for the end-tidal concentration of desflurane to decrease to 0.5 MAC and time for the end-tidal concentration to decrease from 0.5 MAC to 0.2 MAC immediately after closing the vaporizer ( P>0.05). Conclusion:Operation duration does not affect the pharmacokinetics of desflurane in the patients undergoing tumor resection.
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Objective:To evaluate the efficacy of sugammadex for the reversal of residual neuromuscular blockade after laparoscopic radical gastrectomy in elderly patients.Methods:Sixty patients of both sexes, aged 65-85 yr, with body mass index of 20-26 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ-Ⅲ, undergoing elective laparoscopic radical gastrectomy under general anesthesia, were divided into 2 groups ( n=30 each) by a random number table method: sugammadex group (S group) and neostigmine group (N group). Rocuronium 0.3-0.6 mg·kg -1·h -1 was intravenously infused during operation, and the muscle relaxation was monitored by a Veryark-TOF monitor, maintaining TOF ratio=0 and counting 1 or 2 after tonic stimulation.Rocuronium was discontinued when the peritoneum was closed.The patients were admitted to the PACU after operation.When the muscle relaxation monitoring T 2 appeared, sugammadex 2 mg/kg was intravenously injected in S group, and neostigmine 0.03 mg/kg plus atropine 0.015 mg/kg was intravenously injected in N group.The tracheal tube was removed after the patient′s consciousness and spontaneous breathing recovered.Before anesthesia (T 1) and 5 and 30 min after tracheal extubation (T 2, 3), arterial blood samples were collected for blood gas analysis, PaO 2 and PaCO 2 were recorded, and ultrasound was used to measure the diaphragm end-inspiratory thickness, end-expiratory thickness and mobility of diaphragm muscle at the above time points.The diaphragm thickening fraction was calculated.The time of T 2 appeared, time of extubation, time of postanesthesia care unit (PACU) stay, postoperative hospital stay, and residual neuromuscular blockade (TOF ratio <0.9) and hypoxemia occurred within 30 min after extubation were recorded.The pulmonary complications within 7 days after operation were recorded. Results:Compared with group N, PaO 2 was significantly increased and PaCO 2 was decreased at T 2, 3, the mobility of diaphragm muscle and diaphragm thickening fraction were increased at T 2, the tracheal extubation time, time of PACU stay and postoperative hospital stay were shortened, the residual neuromuscular blockade and hypoxemia occurred after extubation and incidence of pulmonary complications after operation were decreased ( P<0.05), and no significant change was found in the time of T 2 appeared in group S ( P>0.05). Conclusion:Sugammadex can quickly and effectively reverse the residual neuromuscular blockade after laparoscopic radical gastrectomy, which is helpful for early postoperative recovery in elderly patients.
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Objective:To evaluate the role of histone deacetylase 6 (HDAC6) in spinal dorsal horn in dexmedetomidine-induced reduction of neuropathic pain (NP) in rats.Methods:Forty clean-grade healthy male Sprague-Dawley rats, aged 7-9 weeks, weighing 190-240 g, were divided into 5 groups ( n=8 each) using a random number table method: control group (group C), sham operation group (group SH), group NP, dexmedetomidine group (group D), and specific HDAC6 inhibitor ACY-1215 plus dexmedetomidine group (group AD). The animals were commonly fed without any treatment in group C. The sciatic nerve was only isolated but not ligated in group SH.The animals were anesthetized with intraperitoneal 10% chloral hydrate 350 mg/kg.NP was induced by chronic constrictive injury (CCI). The right sciatic nerve was exposed, and 4 loose ligatures were placed on the sciatic nerve at 1-mm intervals with 4-0 silk thread in NP and D groups.In group D, dexmedetomidine 40 μg/kg was intraperitoneally injected once a day starting from the end of operation until the animals were sacrificed.In group AD, ACY-1215 25 mg/kg was intraperitoneally injected every day immediately before CCI, and dexmedetomidine 40 μg/kg was intraperitoneally injected daily after CCI until 15 days after CCI.The equal volume of solvent was given instead of dexmedetomidine in S and NP groups.The mechanical paw withdrawal threshold to von Frey filament stimulation (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before CCI (baseline, T 0) and 3, 6, 9, 12 and 15 days after CCI (T 1-5). The rats were then sacrificed, and the dorsal horn tissues of L 4-6 spinal cord were obtained for determination of the expression of myeloid differentiation factor 88 (MyD88) and nuclear factor kappa B (NF-κB) p65 by Western blot. Results:Compared with group C and group SH, the MWT was significantly decreased, and the TWL was shortened at T 1-5, and the expression of MyD88 and NF-κB p65 in the spinal dorsal horn was up-regulated in NP, D and AD groups ( P<0.05). Compared with group NP, the MWT was significantly increased, and the TWL was prolonged at T 1-5, the expression of MyD88 and NF-κB p65 in the spinal dorsal horn was down-regulated in group D ( P<0.05), and no significant change was found in the parameters mentioned above in group AD ( P>0.05). Compared with group D, MWT was significantly decreased, and TWL was shortened at T 1-5, and the expression of MyD88 and NF-κB p65 was up-regulated in the dorsal horn of the spinal cord in group AD ( P<0.05). Conclusion:HDAC6 in spinal dorsal horn is involved in dexmedetomidine-induced reduction of NP in rats, which is related to inhibiting MyD88/NF-κB signaling pathway.
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Objective:To evaluate the efficacy of preoperative interview with humanistic care in patients undergoing resection of tumor.Methods:Two hundred patients, aged 35-64 yr, with body mass index of 18-28 kg/m 2, of American Society Anesthesiologists physical status Ⅰ or Ⅱ, undergoing elective laparoscopic gastrointestinal tumor resection, were divided into 2 groups ( n=100 each) by a random number table method: conventional preoperative interview group (group C) and preoperative interview with humanistic care group (group H). Pre-interview anxiety was assessed using the Self-Rating Anxiety Scale (SAS) at 1 day before the interview (T 0), and pre-interview heart rate (HR) and mean arterial pressure (MAP) were recorded, followed by a preoperative interview.Conventional preoperative interview was given in group C, and preoperative interview with humanistic care was given in group H. Anxiety was assessed again after interview (T 1) and HR and MAP were recorded at 24 h. Venous blood samples were collected for determination of plasma norepinephrine (NE) and cortisol (Cor) concentrations by enzyme-linked immunosorbent assay at T 0 and T 1. Results:Compared with group C, the MAP, HR and SAS scores were significantly decreased at T 1, the incidence and degree of anxiety and plasma NE and Cor concentrations were decreased at T 1, and the incidence of abnormalities of MAP, HR and plasma Cor concentrations were decreased in group H ( P<0.05). Conclusion:Preoperative interview with humanistic care can alleviate the post-interview anxiety and reduce the over-stress response in patients undergoing resection of tumor.
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Objective:To evaluate the effect of remimazolam pretreatment on brain injury following thalamic hemorrhage in mice.Methods:Sixty clean-grade healthy adult CD1 male mice, weighing 25-30 g, aged 7-8 weeks, were divided into 3 groups ( n=20 each) by using a random number table method: sham operation group (Sham group), brain injury group (BI group) and remimazolam pretreatment group (Rem group). Remimazolam 25 mg/kg was intravenously injected via the tail vein in group Rem.and the equal volume of normal saline was given instead in Sham group and BI group.Ten min later, type Ⅳ collagenase 0.01 U/10 nl was microinjected into unilateral ventroposterolateral nucleus and ventromedial nucleus to develop a mouse model of brain jury induced by thalamic hemorrhage.The rats were sacrificed at 6 h after developing the model, brain tissues were taken for measurement of the wet/dry weight (W/D) ratio, and hippocampal tissues were taken and stained with haematoxylin and eosin for determination of the count of the viable neurons in the hippocampal dentategyrus area, count of apoptotic neurons in the hippocampal CA1 region (by TUNEL), expression of CCAAT/enhancer-binding protein homologous protein (CHOP), activating transcription factor 4 (ATF4) and X-box binding protein-1 (XBP1) mRNA (by real-time polymerase chain reaction) and expression of CHOP, Bcl-2, Bax and caspase-3 (by Western blot) and for microscopic examination of ultrastructure of hippocampal tissues (with a transmission electron microscope). Results:Compared with group Sham, the W/D ratio of brain tissues and count of apoptotic neurons in the hippocampal CA1 area were significantly increased, the count of viable neurons in the hippocampal dentate gyrus was decreased, the expression of CHOP, ATF4 and XBP1 mRNA in hippocampal tissues was up-regulated, the expression of CHOP, caspase-3 and Bcl-2 was up-regulated, and the expression of Bax was down-regulated in BI and Rem groups ( P<0.05). Compared with group BI, the W/D ratio of brain tissues and count of apoptotic neurons in the hippocampal CA1 area were significantly decreased, the number of viable neurons in the hippocampal dentate gyrus was increased, the expression of CHOP, ATF4 and XBP1 mRNA in hippocampal tissues was down-regulated, the expression of CHOP, caspase-3 and Bcl-2 was down-regulated, and the expression of Bax was up-regulated in group Rem ( P<0.05). Conclusion:Remimazolam pretreatment can reduce the brain injury following thalamic hemorrhage in mice, and the mechanism may be related to inhibition of cell apoptosis induced by endoplasmic reticulum stress in hippocampus.
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OBJECTIVE：To investigate the effects of d exmedetomidine on postoperative delirium （POD） in liver tumor resection elderly patients with sleep disorder （SD）. METHODS ：Totally 80 patients undergoing liver tumor resection with preoperative Pittsburgh sleep quality index （PSQI）score ≥7 were selected from the Affiliated Cancer Hospital of Zhengzhou University from Jan. 1st，2020 to Oct. 31st，2020. They were randomly divided into group SD and group Dex according random number table ，with 40 cases in each group. At the same time ，40 patients with preoperative PSQI score ＜7 were selected as group C. Thirty min before anesthesia induction ，Dexmedetomidine hydrochloride injection 0.4 μg/kg was injected intravenously in group Dex. Etomidate emulsion injection ，Sufentanil citrate injection and Rocuronium bromide injection were used for anesthesia induction in 3 groups，and Ropofol medium/long chain fat emulsion injection + Remifentanil hydrochloride for injection was used to maintain anesthesia. The drug use ，operation time ，PACU stay time and postoperative hospital stay were recorded in 3 groups. The cognitive function was evaluated 2 h before operation and 1，3，5，7 days after operation. The occurrence of POD was observed. The plasma levels of IL- 6 and S 100β were measured 2 h before operation ，2 h after operation ，1，3，5 days after operation. The occurrence of ADR was recorded. RESULTS ：There was no statisti cal significance in intraoperativ e drug use and operation time among 3 groups （P＞0.05）. The PACU stay time ， the incidence of POD and the duration of POD in group SD an d lixxi18@126.com group Dex were significantly higher or longer than group C ， while the Dex group was significantly lower or shorter thangroup SD （P＜0.05）. The postoperative hospitalization stay ofgroup SD was significantly longer than group C and group Dex （P＜0.05），and there was no statistical significance between group Dex and group C （P＞0.05）. Before operation ，there was no statistical significance in MMSE scores or plasma levels of IL- 6 and S100β among 3 groups（P＞0.05）. MMSE scores of group C 1，3 days after operation ，those of group SD and group Dex 1，3，5 and 7 days after operation were significantly lower than those before operation. MMSE scores of group SD and group Dex 1，3，5 and 7 days after operation were significantly lower than group C at corresponding period ；the group Dex was significantly higher than the group SD at corresponding period （P＜0.05）. The plasma levels of IL- 6 and S 100 β at different time points were significantly higher than before operation ，and the group SD and group Dex were significantly higher than the group C ，and the group Dex was significantly lower than group SD at corresponding period （P＜0.05）. There was no statistical significance in the total incidence of ADR among 3 groups（P＞0.05）. CONCLUSIONS ：SD can promote the occurrence of POD in liver tumor resection elderly patients. Dexmetomidine can reduce the incidence of POD in elderly patients with preoperative SD ，the mechanism of which may be associated with the inhibition of IL- 6 and S 100β expression and the alleviation of brain injury with good safety.
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OBJECTIVE：To c ompare the effects o f intravenous anesthesia with remimazolam and propofol on perioperative cellular immune function in patients underwent radical mastectomy. METHODS ：Eighty patients underwent selective radical mastectomy were collected ，and then randomly divided into remimazolam group （group R ）and propofol group （group P ）. During anesthesia induction ，group R was intravenously injected with remimazolam 0.2 mg/kg+sufentanil 0.3 μg/kg+cisatracurium 0.2 mg/kg；group R was intravenously injected with propofol 2 mg/kg+sufentanil 0.3 μg/kg+cisatracurium 0.2 mg/kg. During anesthesia maintenance，group R was intravenously pumped with remimazolam 0.4-1.2 mg/（kg·h）+remifentanil 0.1-0.2 μg（/ kg·min）；group P was intravenously pumped with propofol 4-10 mg/（kg·h）+remifentanil 0.1-0.2 μg（/ kg·min）. Both groups were given intravenous injection of cisatracurium intermittently. The anesthesia depth was monitored during the operation and the pumping speed of remimazolam，propofol and remifentanil was adjusted accordingly. The intraoperative infusion volume ，blood loss ，operation time ， opioid dosage ，and visual analogue scale （VAS）scores at 24 and 72 hours after operation were recorded in 2 groups；at the same time，the levels of T lymphocyte CD 3+，CD4+，CD8+ and NK cells were measured 30 min before anesthesia induction ，24 h and 72 h after operation ；CD4+/CD8+ was also calculated. The incidence of ADR was recorded in 2 groups. RESULTS ：There was no statistical significance in intraoperative infusion volume ，blood loss ，operation time ，opioid dosage ，VAS score at 24，72 hours after operation and the incidence of ADR between 2 groups（P＞0.05）. Compared with 30 min before anesthesia induction ，the levels of CD 3+，CD4+，NK cells and CD 4+/CD8+ ratio in 2 groups at 24 hours after operation were significantly decreased （P＜ 0.05）；compared with group P ，the levels of CD 3+，CD4+ and NK cells as well as CD 4+/CD8+ ratio in group R increased significantly in group R （P＜0.05）. CONCLUSIONS ：For anesthesia maintenance ，the inhibitory effects of remimazolam on perioperative cellular immunity in patients underwent radical mastectomy are poorer than propofol.
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Objective:To investigate the effect of postsynaptic density-95(PSD-95)on long-term learning and memory impairment in neonatal rats induced by sevoflurane anesthesia.Methods:A total of 54 SD rats aged 7 days of SPF grade were randomly divided into 3 groups: control group (exposed to air), model group (exposed to 2.1% sevoflurane, 4 h/d, consecutive 3 days) and PSD-95 inhibitor group (inhaled sevoflurane+ intraperitoneal injection NA-1, consecutive 5 days), with 18 rats in each group.Morris water maze test and new object recognition test were used to detect the ability of visuospatial learning and memory and recognition memory of rats in each group.RT-qPCR was used to detect the mRNA levels of kalirin, Rac1 and PSD-95 in rat hippocampus.The expressions of kalirin, Rac1, PSD-95 and apoptosis related proteins Caspase-3, Bcl-2 and Bax in rat hippocampus were detected by Western blot.The expression levels of kalirin and Rac1 in hippocampus were detected by immunohistochemistry.SPSS 23.0 software was used for statistical analysis.Repeated measurement ANOVA and one-way ANOVA was used for comparing among groups.Results:Repeated measurement ANOVA showed that in the water maze test, the interaction between time and group of platform seeking latency and swimming distance of the three groups were significant ( Ftime×group=36.539, 41.548, both P<0.01). Simple effect analysis showed that the platform latency and swimming distance in the model group from day 2 to 6 were longer than those in the control group (platform latency from day 2 to 6: t=14.039, 17.147, 13.155, 13.831, 27.247, all P<0.01; swimming distance from day 2 to 6: t=10.122, 20.987, 7.267, 10.011, 8.121, all P<0.01). Compared with the model group, from day 2 to 6, the platform latencies of PSD-95 inhibitor group were prolonged( t=7.948, 14.768, 11.582, 12.832, 24.346, all P<0.01) and the swimming distances were increased( t=8.235, 24.325, 11.234, 12.031, 7.036, all P<0.01). The new object recognition test found that the new object exploration time in the model group was significantly longer than that in the control group ((21.30±2.27)s, (19.21±1.42)s, t=1.843, P<0.01), and the new object exploration time in the PSD-95 inhibitor group was significantly longer than that in the model group ((26.83±2.13)s, t=4.844, P<0.01). The difference index of novel objects in the model group was significantly lower than that in the control group ((0.41±0.12), (0.59±0.10), t=3.416, P<0.01), and the difference index of novel objects in the PSD-95 inhibitor group was significantly lower than that in the model group ((0.37±0.08), t=0.696, P<0.05). The qRT-PCR results showed that the expressions of Rac1, kalirin and PSD-95 mRNA in the model group were significantly lower than those in the control group ( t=9.969, 3.954, 6.561, P<0.05), and the expressions of Rac1, kalirin and PSD-95 mRNA in the PSD-95 inhibitor group were significantly lower than those of the model group ( t=2.132, 2.251, 3.502, all P<0.05). Immunohistochemistry results showed that the kalirin in the hippocampus CA1 area of the model group was significantly lower than that in the control group((8.18±1.94) vs (15.47±3.35), t=11.47, P<0.01), and kalirin in the PSD-95 inhibitor group was significantly lower than that in the model group((4.98±1.53), t=10.28, P<0.01); Rac1 in the model group was significantly lower than that in the control group ((3.72±1.53), (8.17±2.91), t=6.76, P<0.01), and the Rac1 in the PSD-95 inhibitor group(2.73±0.37) was significantly lower than the model group ( t=4.72, P<0.05). Western blot results showed that Caspase-3((1.37±0.16) vs (0.54±0.01), t=5.71, P<0.01) and Bax((1.87±0.31) vs (1.23±0.25), t=12.01, P<0.01) protein levels in the model group were significantly higher than those in the control group.Caspase-3 and Bax protein levels in the PSD-95 inhibitor group were significantly higher than those in model group (Caspase-3: (1.79±0.17), t=9.87, P<0.01; Bax: (2.19±0.21), t=16.19, P<0.01). The Bcl-2 protein level in the model group was significantly lower than that of the control group ((1.22±0.21) vs (1.96±0.38), t=11.92, P<0.01). And the Bcl-2 protein level in the PSD-95 inhibitor group (1.01±0.19) was significantly lower than that in the model group ( t=10.73, P<0.01). Conclusion:Sevoflurane anesthesia can damage the long-term learning and memory function and reduce the expression of PSD95 protein in neonatal rats.Inhibiting the expression of PSD95 can aggravate this damage, which may be related to the synaptic plasticity and apoptosis of neurons involved in PSD95.
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OBJECTIVE：To observe the a nesthetic effect and safety of dexmedetomidine combined with butorphanol for laparoscopic radical resection of colorectal cancer. METHODS ：Totally 180 patients undergoing elective laparoscopic radical resection of colorectal cancer were selected from our hospital during Apr. 2019-May 2020. They were randomly divided into control group（group C ），dexmedetomidine group （group D ），butorphanol group （group B ），dexmedetomidine+butorphanol group （group E），with 45 cases in each group. Group C received rountine anesthesia of Etomidate emulsion injection+Sufentanil citrate injection+ Cisatracurium besylate for injection. Group D was given Dexmedetomidine injection 0.5 μg/kg by pumping 15 min before induction ， and received rountine anesthesia indution performed in group C. Group B was given intravenous injection of Butorphanol tartrate injection 0.02 mg/kg when anesthesia indution ，and received rountine anesthesia performed in group C. Anesthesia induction in group E was the same as that in group D+B. The dosage of sufentanil and the maintenance concentration of sevoflurane were observed；average arterial pressure （MAP）and heart rate （HR）at the time of entering the room （T0），1 min after intubation （T1）， 1 min after skin incision （T2），and 5 min after extubation （T3），extubation time ，Ramsay sedation score 5 min after extubation and VAS score ，the occurrence of ADR were recorded. RESULTS ：One patient in group C and two patients in Group E were excluded due to the conversion of laparoscopic surgery to open surgery. The rest of the patients completed the study. At T 1-T3，MAP and HR in group C ，D and B were significantly higher than those at T 0（P＜0.05），while there was no significant difference in MAP or HR in group E at T 1-T3，compared with those at T 0（P＞0.05）. MAP of group D and B at T 1-T2 as well as MAP of group E at T 1-T3 were significantly lower than that of group C ，the order was group E ＜group B ＜Group D （except for group B compared with group D at T 3）；HR of group D and E at T 1-T3 as well as that of group B at T 1-T2 were significantly lower than group C ，and the order was group E ＜group B ＜Group D （except for group B compared with group D at T 3）（P＜0.05）. The amount of sufentanil and VAS score of group B ，D，E were significantly lower than that of group C ，and the order was group E ＜group B ＜group D ， VAS score of group E ＜group D ，B（P＜0.05）. The maintenance concentration ，extubation time ，nausea and vomiting ，the incidence of agitation during recovery period in group E were significantly lower or shorter than group C ，D，B. Ramsay sedation score was significantly higer than group C ，D and B. The nausea and vomiting ，the incidence of emergence agitation in group E ＜ group D ，B（P＜0.05）. There was no statistical significance in the maintenance concentration of sevoflurane ，Ramsay sedation score or extubation time among group C ，D and B ，VAS score ，the incidence of nausea and vomiting ，the incidence of agitation during recovery period between group D and B （P＞0.05）. CONCLUSIONS ：Dexmedetomidine combined with butorphanol can effectively reduce the amount of intraoperative anesthetics and the occurrence of stress reaction ，improve the quality of resuscitation，and reduce the incidence of postoperative ADR.
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Objective:To evaluate the optimized efficacy of thoracic paravertebral nerve block and subcostal transversus abdominis plane block combined with general anesthesia for elderly patients undergoing thoracic combined with laparoscopic radical resection of esophageal cancer.Methods:Eighty American Society of Anesthesiologists physical status Ⅰ orⅡ patients of both sexes, aged 66-78 yr, weighing 46-80 kg, undergoing elective thoracoscopic combined with laparoscopic radical resection of esophageal cancer, were divided into 2 groups ( n=40 each) using a random number table method: general anesthesia group (group G) and thoracic paravertebral nerve block and subcostal transversus abdominis plane block combined with general anesthesia group (TSG group). Both groups received target-controlled infusion of propofol and remifentanil and intravenous injection of cisatracurium besilate for anesthesia induction and maintenance, with BIS value maintained at 45-60 during operation.Thoracic paravertebral nerve block on the affected side was performed under ultrasound guidance after the end of anesthesia induction, and 0.5% ropivacaine 15 ml was injected in TSG group.The patients were turned to the supine position after the thoracic operation was completed, and the bilateral subcostal approach to the transversus abdominis plane block was performed under ultrasound guidance, and 0.3% ropivacaine 20 ml was injected into each side.Sufentanil was used for patient-controlled intravenous anesthesia (PCIA) after operation.The background infusion rate was 0.05 μg·kg -1·h -1, PCA was 0.04 μg/kg, and the lockout interval was 10 min in group G. The background infusion rate was 0.03 μg·kg -1·h -1, PCA was 0.025 μg/kg, the lockout interval was 10 min in group TSG.Both groups received analgesia until 48 h after operation, and VAS score was maintained ≤3.When VAS score ≥ 4, tramadol 100 mg was intravenously injected for rescue analgesia.At 1 day before operation (T 0), immediately before anesthesia induction (T 1), at 1 h after emergence from anesthesia (T 2), and 4, 8, 12, 24 and 48 h after operation (T 3-7), venous blood samples were collected for determination of serum norepinephrine, epinephrine and cortisol concentrations (by enzyme-linked immunosorbent assay). The intraoperative consumption of remifentanil and occurrence of cardiovascular events were recorded.The pressing times of PCA, consumption of sufentanil and requirement for rescue analgesia within 48 h after operation were recorded.The occurrence of nerve block-related complications (hematoma at the puncture site, infection, local anesthetic poisoning, etc.) and adverse reactions such as nausea and vomiting, respiratory depression and pruritus were recorded within 48 h after the operation. Results:Compared with group G, the concentrations of serum epinephrine, norepinephrine and cortisol were significantly decreased, the consumption of intraoperative remifentanil and postoperative sufentanil and pressing times of PCA were reduced, the rate of rescue analgesia was decreased, scores of satisfaction with analgesia were increased, and the incidence of intraoperative cardiovascular events and postoperative adverse reactions such as nausea and vomiting, pruritus and respiratory depression were decreased in group TSG ( P<0.05). Conclusion:Thoracic paravertebral nerve block and subcostal transversus abdominis plane block combined with general anesthesia can reduce the perioperative consumption of opioids and inhibit perioperative stress responses and postoperative hyperalgesia with fewer adverse reactions when used for the elderly patients undergoing thoracic combined with laparoscopic radical resection of esophageal cancer.
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Objective:To evaluate the modified efficacy of thoracic paravertebral block (TPVB) combined with general anesthesia in the patients undergoing laparoscopic radical nephrectomy.Methods:Eighty patients, aged 38-64 yr, with body mass index of 18-24 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, scheduled for elective laparoscopic radical nephrectomy, were selected and randomly divided into 2 groups ( n=40 each) using a random number table method: general anesthesia group (group GA) and TPVB combined with general anesthesia group (group TPVB+ GA). A paravertebral catheter was placed at T 8 and T 10 under ultrasound guidance before induction of anesthesia, and 0.5% ropivacaine 10 ml was administered via the catheter in group TPVB+ GA.Anesthesia was induced with propofol, sufentanil, etomidate and rocuronium and maintained by intravenous infusion of propofol and remifentanil.Patient-controlled intravenous analgesia was performed with sufentanil, ketorolac tromethamine and tropisetron at the end of surgery.When postoperative visual analog scale score≥4, tramadol 50 mg was intravenously injected as rescue analgesic.Immediately before anesthesia induction (T 0), at 5 min after establishing pneumoperitoneum (T 1), at 2 h of pneumoperitoneum (T 2), and immediately after the end of pneumoperitoneum (T 3), and at 24 h after operation (T 4), venous blood samples were collected for determination of plasma norepinephrine concentrations (by enzyme-linked immunosorbent assay), plasma cortisol level (using radioimmunoassay), and blood glucose concentrations were measured.The intraoperative consumption of sufentanil and remifentanil was recorded.The intraoperative hypertension, hypotension, and bradycardia were recorded, and the nausea and vomiting, pruritus, and requirement for rescue analgesia occurred within 24 h after surgery were recorded. Results:Compared with group GA, the plasma concentrations of norepinephrine, cortisol and blood glucose were significantly decreased at T 1-4, the intraoperative consumption of sufentanil and remifentanil was reduced, and the postoperative requirement for rescue analgesia was decreased in group TPVB+ GA ( P<0.05). There was no significant difference in the incidence of intraoperative and postoperative adverse reactions between the two groups ( P>0.05). Conclusion:TPVB combined with general anesthesia is helpful in carrying out the anesthetic model of low-consumption opioids and is more helpful in inhibiting intraoperative and postoperative stress responses and postoperative pain responses than general anesthesia alone when used for laparoscopic radical nephrectomy.
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Objective:To evaluate the effect of midazolam on sevoflurane anesthesia-induced cortical abnormal electroencephalogram waves in neonatal rats.Methods:Ten male Sprague-Dawley rats, aged 7 days, weighing 12-16 g, were used in this study.After the electrodes were correctly implanted, the electroencephalogram was continuously monitored, and 6% sevoflurane was inhaled for 3 min to induce anesthesia.The experiment was carried out in three phases.In 1st phase, 2.1% sevoflurane was inhaled for 30 min.In 2nd phase, midazolam 3 μg/g was intraperitoneally injected.In 3rd phase, flumazenil 10 μg/g was intraperitoneally injected at 60 min of 2.1% sevoflurane inhalation.Each phase lasted 30 min.The total time of convulsion wave in each phase and frequency of spike wave in the last 3 min of each phase were recorded.Results:There was no significant difference in the rate of convulsion wave and spike wave developed and total duration of convulsion wave among the three phases ( P>0.05). The frequency of spike wave was significantly decreased in 2nd phase compared with that in 1st and 3rd phases ( P<0.05). Conclusion:Midazolam can decrease the frequency of cortical spike waves induced by sevoflurane anesthesia, but produces no inhibitory effect on convulsion waves in the neonatal rats.
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Objective:To investigate the effects of bumetanide on changes of NKCC1 and KCC2 mRNA expression in hypothalamus and anxiety in adulthood induced by multiple sevoflurane exposure in neonatal rats.Methods:Eighty-one healthy male Sprague-Dawley rats, at postnatal 5 days (P5), were randomly divided into 3 groups ( n=27 in each group): control group (group C), multiple sevoflurane group (group MS) and bumetanide group (group B). The rats were commonly reared in the cage and received no anesthesia in group C. Animals were exposed to 2.1% sevoflurane for 2 h on P5, P7, P9 in group MS and group B. In group B, animals received intraperitoneal injection of 1.82 mg/kg bumetanide(Na + -K + -2Cl - cotransporter 1 blocker, NKCC1 blocker)at 30 min before every anesthesia.The animals in group C and group MS received the same dose of dimethyl sulfoxide subcutaneously at the same time as group B. The rats were observed for 30 minutes after recovery from anesthesia, and then breastfed normally.On the 9th day after birth, six rats were taken from each group immediately at the end of anesthesia and the blood was collected by left ventricular puncture for blood gas analysis.At 30 min after anesthesia, 6 animals in each group were decapitated and the hypothalamus part of brain tissue was collected.Then the expression level of IL-6 mRNA, NKCC1 mRNA and KCC2 mRNA were detected by RT-PCR.The other rats in each group were raised to 60 days for the elevated plus maze (EPM) test. Results:Compared with group C, the expression of IL-6 mRNA and NKCC1 mRNA in hypothalamus of MS group was up-regulated (IL-6: (1.000±0.207) vs (1.782±0.231); t=6.899, P<0.01; NKCC1: (1.000±0.255) vs (1.639±0.290); t=3.518, P<0.01), the KCC2 mRNA expression was down-regulated ((1.000±0.140) vs (0.733±0.115); t=3.017, P<0.001) and the NKCC1/KCC2 mRNA ratio increased ((1.000±0.276) vs (2.054±0.521); t=5.078, P<0.001) and the differences were statistically significant.Compared with MS group, the expression of IL-6 mRNA and NKCC1 mRNA in hypothalamus of group B was down-regulated (IL-6: (1.147±0.140); t=5.635, P<0.01; NKCC1: (1.038±0.385); t=3.310, P=0.01), KCC2 mRNA expression was up-regulated((0.988±0.194); t=2.880, P<0.05), NKCC1 / KCC2 mRNA ratio was decreased((1.027±0.200); t=4.950, P<0.001), and the differences were statistically significant.EPM behavioral test showed that compared with group C, the open arm residence time in MS group was significantly shorter than that in group C ((18.4±10.1)s vs (4.3±3.1)s; P<0.01); compared with group MS, the open arm residence time in group B was significantly prolonged((16.6±7.6)s, P<0.05). Conclusion:Bumetanide can reduce the up-regulation of NKCC1 level and the down-regulation of KCC2 level in neonatal rats after sevoflurane anesthesia, and alleviate the anxiety state of adult rats.
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Objective@#To evaluate the effect of penehyclidine hydrochloride (PHC) on Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway in non-ventilated lung injury in the patients undergoing radical operation for lung cancer.@*Methods@#A total of 100 patients, aged 40-64 yr, with body mass index 18-27 kg/m2, of American Society of Anesthesiology physical status Ⅱ or Ⅲ, undergoing radical operation for lung cancer, were divided into 2 groups (n=50 each) according to the random number table method: control group (group C) and PHC group.PHC 0.01 mg/kg was intravenously injected at 10 min before anesthesia induction in group PHC, while the equal volume of normal saline was given instead in group C. The peripheral tissues of the removed lung tissues were obtained for determination of wet/dry weight ratio (W/D ratio). The pathological changes and ultrastructure of lung tissues were observed under light microscope, and lung injury was assessed and scored.The expression of TLR4 and NF-κB protein and mRNA was detected by Western blot and real-time polymerase chain reaction, respectively.Before administration (T0), at the onset of one-lung ventilation (T1), at 60 min of one-lung ventilation (T2), immediately after the end of one-lung ventilation (T3), at the end of operation (T4) and at 24 h after operation (T5), blood samples were collected from the internal jugular vein for determination of serum tumor necrosis factor-alpha, interleukin-6 (IL-6) and IL-8 concentrations by enzyme-linked immunosorbent assay.@*Results@#Compared with group C, the W/D ratio and lung injury scores were significantly decreased, the expression of TLR4 and NF-κВ protein and mRNA was down-regulated, and the concentrations of tumor necrosis factor-alpha, IL-6 and IL-8 were decreased at T2-T5 in group PHC (P<0.05). The pathological changes and damage to ultrastructure of lung tissues were significantly attenuated in group PHC as compared with group C.@*Conclusion@#The mechanism by which PHC attenuates non-ventilated lung injury is related to blocking TLR4/NF-κВ signaling pathway and reducing inflammatory responses in the patients undergoing radical operation for lung cancer.
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Objective To evaluate the effect of penehyclidine hydrochloride (PHC) on Toll-like receptor 4 (TLR4) /nuclear factor kappa B (NF-κB) signaling pathway in non-ventilated lung injury in the patients undergoing radical operation for lung cancer.Methods A total of 100 patients,aged 40-64 yr,with body mass index 18-27 kg/m2,of American Society of Anesthesiology physical status Ⅱ or Ⅲ,undergoing radical operation for lung cancer,were divided into 2 groups (n=50 each) according to the random number table method:control group (group C) and PHC group.PHC 0.01 mg/kg was intravenously injected at 10 min before anesthesia induction in group PHC,while the equal volume of normal saline was given instead in group C.The peripheral tissues of the removed lung tissues were obtained for determination of wet/dry weight ratio (W/D ratio).The pathological changes and ultrastructure of lung tissues were observed under light microscope,and lung injury was assessed and scored.The expression of TLR4 and NF-κB protein and mRNA was detected by Western blot and real-time polymerase chain reaction,respectively.Before administration (T0),at the onset of one-lung ventilation (T1),at 60 min of one-lung ventilation (T2),immediately after the end of one-lung ventilation (T3),at the end of operation (T4) and at 24 h after operation (T5),blood samples were collected from the internal jugular vein for determination of serum tumor necrosis factor-alpha,interleukin-6 (IL-6) and IL-8 concentrations by enzyme-linked immunosorbent assay.Results Compared with group C,the W/D ratio and lung injury scores were significantly decreased,the expression of TLR4 and NF-κB protein and mRNA was down-regulated,and the concentrations of tumor necrosis factor-alpha,IL-6 and IL-8 were decreased at T12-T5 in group PHC (P＜0.05).The pathological changes and damage to ultrastructure of lung tissues were significantly attenuated in group PHC as compared with group C.Conclusion The mechanism by which PHC attenuates non-ventilated lung injury is related to blocking TLR4/NF-κB signaling pathway and reducing inflammatory responses in the patients undergoing radical operation for lung cancer.
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Objective To evaluate the effect of sevoflurane preconditioning on high-mobility group box 1 protein ( HMGB1) ∕Toll-like receptor 4 ( TLR4) ∕nuclear factor kappa B ( NF-κB) signaling pathway during lung ischemia-reperfusion ( I∕R) in rats. Methods Thirty-six clean-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 200-250 g, were divided into 3 groups ( n=12 each) using a random number table method: sham operation group ( group S) , lung I∕R group ( group I∕R) and sevoflu-rane preconditioning group ( group SP ) . The right pulmonary hilum was only isolated but not ligated in group S. Lung I∕R was induced by clamping the right pulmonary hilum for 60 min followed by 120 min of reperfusion in anesthetized rats in group I∕R. In group SP, 2. 1％ sevoflurane was inhaled for 30 min to per-form sevoflurane preconditioning, and the lung I∕R model was established at 10 min after the end of inhala-tion. The rats were sacrificed at 120 min of reperfusion, and the lungs were removed for examination of the pathological changes which were scored and for determination of wet to dry weight ratio ( W∕D ratio) , con-tent of tumor necrosis factor-alpha ( TNF-α) in lung tissues ( by enzyme-linked immunosorbent assay) and expression of HMGB1, TLR4 and NF-κB protein in lung tissues (by Western blot). Results Compared with group S, the pathological scores, W∕D ratio and content of TNF-α were significantly increased, and the expression of HMGB1, TLR4 and NF-κB was up-regulated in I∕R and SP groups ( P<0. 05) . Compared with group I∕R, the pathological scores, W∕D ratio and content of TNF-αwere significantly decreased, and the expression of HMGB1, TLR4 and NF-κB was down-regulated ( P<0. 05) , and the pathological changes of lung tissues were significantly attenuated in group SP . Conclusion Sevoflurane preconditioning reduces lung I∕R injury probably through inhibiting HMGB1∕TLR4∕NF-κB signaling pathway in rats.
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Objective To evaluate the effect of curcumin on the mammalian target of rapamyein (mTOR) signaling pathway during ischemia-reperfusion (I/R) injury in isolated rat lungs.Methods Sixty-four clean-grade healthy male Sprague-Dawley rats,aged 3-4 months,weighing 250-320 g,were divided into 4 groups (n=16 each) using a random number table method:sham operation group (S group),I/R group,low-dose curcumin group (LC group) and high-dose curcumin group (HC group).The rats only received in vitro perfusion without ischemia in S group.Isolated rat lungs were subjected to 60 min of ischemia followed by 75-min reperfusion to establish the lung I/R injury model in I/R group.Curcumin 5 and 10 μmol/L were added to perfusion fluid from the beginning of reperfusion in LC and HC groups,respectively.Airway resistance (Res),lung compliance,perfusion flow (Flow) and pulmonary venous partial pressure of oxygen (PaO2) were recorded at 10 min of first perfusion (T0) and 15,45 and 75 min of reperfusion (T1-3).Wet/dry lung weight ratio (W/D ratio) was measured at the end of reperfusion.The morphological structure and ultrastructure of lung tissues were observed by using a light microscope and a transmission electron microscope,respectively.The expression of mTOR,Tau protein,nuclear factor kappa B (NF-κB) and tumor necrosis factor-alpha (TNF-α) mRNA in lung tissues was detected by real-time polymerase chain reaction.The expression of mTOR,phosphorylated Tau protein (pS396 Tau protein),NF-κB and TNF-α protein in lung tissues was determined by Western blot.Results Compared with S group,Res at T1-3 and W/D ratio at T3 were significantly increased,lung compliance,Flow and PaO2 were decreased at T1-3,and the expression of mTOR,NF-κB and TNF-α protein and mRNA,Tau protein mRNA and pS396 Tau protein was up-regulated at T3 in I/R,LC and HC groups (P＜0.05).Compared with I/R group,Res at T1-3 and W/D ratio at T3 were significantly decreased,lung compliance,Flow and PaO2 were increased at T1-3,and the expression of mTOR,NF-κB and TNF-α protein and mRNA,Tau protein mRNA and pS396 Tau protein was down-regulated at T3 in LC and HC groups (P＜0.05).Compared with LC group,Res at T1-3 and W/D ratio at T3 were significantly decreased,lung compliance,Flow and PaO2 were increased at T1-3,and the expression of mTOR,NF-κB and TNF-α protein and mRNA,Tau protein mRNA and pS396 Tau protein was down-regulated at T3 in HC group (P＜0.05).The microscopic examination showed that the injury to lung tissues was significantly attenuated in LC and HC groups as compared with I/R group.Conclusion The mechanism by which curcumin reduces I/R injury in isolated rat lungs is related to inhibiting mTOR signaling pathway.
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Objective To evaluate the effect of ulinastatin on postoperative outcomes in elderly patients undergoing thoracoscopic radical operation for lung cancer.Methods Sixty patients of both sexes,aged 65-80 yr,weighing 40-85 kg,of American Society Anesthesiologists physical status Ⅱ or Ⅲ,scheduled for thoracoscopic radical operation for lung cancer,were divided into 2 groups (n =30 each) using a random number table method:ulinastatin group (group UTI) and normal saline group (group NS).Ulinastatin 0.5× 104 U/kg was intravenously infused within 1 h before skin incision in group UTI,while the equal volume of normal saline was given instead in group NS.Central venous blood samples were collected at 30 min before skin incision (T0),30 min after start of surgery (T1),and 1 h and 1,3 and 5 days after surgery (T2-5) for determination of the expression of CD42a+,HLADR+ and CD14+ in monocytes (using the flow cytometry),plasma concentrations of interleukin-6 (IL-6),IL-8 and tumor necrosis factoralpha (TNF-α) (by enzyme-linked immunosorbent assay),and the plasma C-reactive protein (CRP) concentration (by immunoturbidimetry).The ratios of monocyte-platelet adhesion (CD42a+/CD14+) and monocyte activation function (HLADR+/CD14+) were calculated.Cognitive function was assessed and scored on day 1 before operation and day 7 after operation,and the incidence of postoperative cognitive dysfunction (POCD) was calculated using Z score.Results Compared with group NS,the CD42a+/CD14+ ratio was significantly decreased at T1-3,the HLADR+/CD14+ ratio was increased at T3,4,the concentrations of plasma IL-6,IL-8,TNF-α and CRP were decreased at T1-5,and the incidence of POCD was decreased in group UTI (P＜0.05).Compared with the baseline value at T0,the HLADR+/CD14+ ratio was significantly decreased at T2-4 in group UTI,the HLADR+/CD14+ ratio was decreased at T2-5,and the CD42a+/CD14+ ratio was increased at T1,2 and T4,5 in group NS,and the concentrations of plasma IL-6,IL-8,TNF-α and CRP were increased at T1-5 in the two groups (P＜0.05).Conclusion Ulinastatin can promote postoperative outcomes in the elderly patients undergoing thoracoscopic radical operation for lung cancer.