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Objective:To investigate the effect of aucubin on behaviors and excessive activation of astrocytic in attention deficit/hyperactivity disorder (ADHD) model mice.Methods:Twelve wild-type C57BL/6 pregnant mice (female, clean grade) were intraperitoneally administered with esketamine (15 mg/kg) to establish an ADHD model in offspring mice. The offspring mice were divided into control+ saline group, control+ aucubin group, Ketamine+ saline group and Ketamine+ aucubin group according to the nest matching principle with 15 in each group.At 14 days after birth, mice in the control+ aucubin group and Ketamine+ aucubin group were administered with aucubin (5 mg/kg, once a day) by gavage for 5 days. Mice in control+ saline group and Ketamine+ saline group were administered with equal volume of 0.9% sodium chloride solution. The offspring mice were housed with their mothers in the same cage until 21 days after birth. Twenty-one days after birth, the offspring mice were evaluated by open field test and elevated plus maze tests. Immunofluorescence assay was used to detect the expression of glutamate decarboxylase 2 (GAD2), γ- aminobutyric acid (GABA) and glial fibrillary acidic protein (GFAP) in the amygdala. The morphological changes of astrocytes were quantitatively analyzed by Sholl analysis. GraphPad Prim 9.0.1 software was used for statistical analysis. The comparison of multiple groups was conducted by one-way ANOVA or Kruskal-Wallis test.Results:(1)The results of behavioral experiments showed that the total distance traveled in the open field test and the residence time in open arm of the elevated plus maze were statistically significant ( F=236.90, H=39.92, both P<0.001). The total distance ((7 044±249)mm, (22 891±2 175)mm, P<0.05) and the residence time in open arm(12.69(9.86, 17.24)s, 2.72(0.57, 3.87)s, P<0.05) of mice in Ketamine+ saline group were both higher than those in control+ saline group.The total distance((22 891±2 175)mm, (8 252±839)mm, P<0.05) and the the residence time in open arm(5.45(1.13, 10.99)s, 12.69(9.86, 17.24)s, P<0.05) of Ketamine+ aucubin group were both lower than those of Ketamine+ saline group.(2)The immunofluorescence results showed that the levels of GAD2, GABA and GFAP intensity in amygdala of mice in the four groups were statistically significant ( F=145.50, 50.08, 53.83, all P<0.05). Compared with control+ saline group, the fluorescence intensities of GAD2 ((100.00±9.60)%, (24.86±4.14)%, P<0.05) and GABA ((100.00±16.84))%, (25.48±5.70)%, P<0.05) of Ketamine+ saline group were down-regulated, and the GFAP((100.00±18.02)%, (223.80±25.85)%, P<0.05) was up-regulated. Compared with Ketamine+ saline group, the fluorescence intensities of GAD2 ((24.86±4.14)%, (56.08±6.55)%, P<0.05) and GABA((25.48±5.70)%, (52.59±15.74)%, P<0.05) in Ketamine+ aucubin group were up-regulated, but the fluorescence intensity of GFAP ((223.80±25.85)%, (157.10±22.10)%, P<0.05) was down-regulated.(3)Sholl analysis indicated that the number of the intersections between the astrocyte processes or the branches of astrocyte processes was statistically significant in the 4 groups ( F=12.47, P<0.05). Compared with control+ saline group, the number of the intersections in Ketamine+ saline group((2.07±0.48), (1.67±0.72), P<0.05) increased. While the number of the intersections in Ketamine+ aucubin group was lower than that of Ketamine+ saline group ((1.20±0.78), (2.07±0.48), P<0.05). Conclusion:Aucubin administration can alleviate ADHD-like behaviors in offspring mice, and the mechanism may be associated with the inhibition of excessive astrocytic activation.
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Objective:To explore whether esketamine (ESK) can inhibit the proliferation and induce apoptosis of breast cancer cells, and explore the mechanism.Methods:CCK-8 assay was used to detect the inhibitory effect of ESK on the proliferation of breast cancer cells. Annexin V/PI staining was used to detect the morphological changes of cells; Apoptosis and reactive oxygen species were detected by flow cytometry. Western blot was used to detect apoptosis and pathway expression.Results:CCK-8 experiment results proved that ESK could inhibit the proliferation of breast cancer cells in a time-dependent manner. The survival rate of MDA-MB-468 cells treated with ESK at 20 μM was (35.47±2.61) %, which was statistically different from that treated with vinorelbine at the same concentration ( P<0.05). The IC50 value of ESK on MDA-MB-468 cells was (14.54±2.12) μM. After treatment with ESK, the mitochondrial membrane potential was significantly reduced. In the protein level, the expression of Cytochrome C, Bax and Caspase-3 was up-regulated, and the expression of Bcl-2 was down regulated, which induced the mitochondrial dependent apoptosis of MDA-MB-468 cells. ESK could up regulate the level of reactive oxygen species in MDA-MB-468 cells and regulate the expression of PI3K/AKT signaling pathway. Conclusions:ESK can inhibit the proliferation and migration of breast cancer cells and induce them to play a mitochondrial dependent apoptosis. Its mechanism is achieved by up regulating the level of ROS in breast cancer cells, thereby regulating the PI3K/AKT signaling pathway, which provides a theoretical basis for the development and utilization of Aln.
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OBJECTIVE To observe the effects of low-dose esketamine on analgesia and inflammatory factors after thoracoscopic surgery. METHODS Totally 120 patients who underwent thoracoscopic lobectomy in our hospital from October 2021 to March 2022 were selected and randomly divided into low-dose group （group A）， conventional-dose group （group B）， normal saline group （group C） by using the random number table method， with 40 patients in each group. All the patients were anesthetized with traditional general intravenous anesthesia， group A and B were anesthetized with low dose or normal dose （0.2 or 0.5 mg/kg） of Esketamine hydrochloride injection， and group C was given normal saline intravenously. The visual analog scale （VAS） score 0， 6， 24， 48 h after operation and the consumption of sufentanil 24 h after operation were compared among 3 groups. The levels of white blood cell count （WBC）， neutrophil percentage， C-reactive protein （CRP）， tumor necrosis factor-α （TNF-α）， interleukin-1 （IL-1） and IL-6 were compared 30 min before and 24 h after surgery. The Pittsburgh sleep quality index （PSQI） score and the Beck depression inventory （BDI） score were compared before operation and 0， 1， 2 d after operation， and the occurrence of adverse reaction was also recorded. RESULTS At 0， 6 and 24 h after operation， VAS scores and the consumption of sufentanil within 24 h after operation in group A and B were significantly lower than group C； VAS score 6 h after operation in group A was significantly lower than that in group B （P＜0.05）. The levels of WBC， neutrophil percentage， CRP， TNF-α， IL-1 and IL-6 in the 3 groups 24 h after surgery were significantly increased， compared with 30 min before surgery； the levels of above indexes in group A and B were significantly lower than those in group C （P＜0.05）. PSQI score and BDI score 0， 1 and 2 days after operation in group A and B were significantly lower than those in group C， while BDI score 0 day after operation in group A was significantly lower than that in group B （P＜0.05）. The total incidence of adverse reaction in group A， B and C were 5.0%， 10.0% and 17.5%， without statistical significance （P＞0.05）. CONCLUSIONS The low-dose esketamine has significant analgesic effect after thoracoscopic surgery， can reduce the levels of inflammatory factors after surgery and improve sleep quality and depression， with good safety.
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Objective:To evaluate the optimization efficacy of low-dose esketamine combined with propofol in the patients with major depressive disorder undergoing modified electroconvulsive therapy (MECT).Methods:Fifty-six American Society of Anesthesiologists physical statusⅠor Ⅱ patients, aged 18-64 yr, scheduled for MECT for the first time, were assigned into esketamine plus propofol group (group EP, n=28) and propofol group (group P, n=28) according to a ratio of 1∶1 by the random number table method.Esketamine 0.25 mg/kg was intravenously injected before anesthesia induction in group EP, while the equal volume of normal saline was given instead in group P. Propofol and succinylcholine were then intravenously injected to perform MECT in two groups.The primary outcomes were the remission rate and response rate, and the secondary outcomes included the number of MECT required for response and remission, the seizure duration, energy inhibition index and consumption of propofol for each MECT, and the occurrence of therapy-related adverse reactions and relapse. Results:Compared with group P, the remission rate and response rate were significantly increased, and the number of MECT required for response and remission was decreased, the seizure duration was prolonged, and energy inhibition index was increased, the consumption of propofol was reduced ( P<0.05), and no significant change was found in the incidence of therapy-related adverse reactions and relapse in group EP ( P>0.05). Conclusions:Low-dose esketamine combined with propofol can enhance the efficacy of MECT and shorten the course of therapy without increasing therapy-related adverse reactions in the patients with major depression.
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Objective:To observe the effect of esketamine on cardiac index in patients undergoing lumbar surgery in prone position under general anesthesia.Methods:Forty-five patients with prone lumbar surgery after general anesthesia in Hunan Provincial People′s Hospital from March to July 2021 were divided into observation group (24 cases, group A) and control group (21 cases, group B) according to random number table method. Group A received 0.5 mg/kg esketamine intravenously during induction, and 0.15 mg/(kg·h) esketamine intravenously for 2 h after prone position. Group B received the same amount of normal saline. Both groups were given sevoflurane and remifentanil during operation to maintain anesthesia, and sufentanil was given intermittently during operation. The mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic pressure (DBP), cardiac index (CI), and heart rate (HR) before induction (T 0), during endotracheal intubation (T 1), 5 minutes after intubation (T 2), 5 minutes after prone position (T 3), 10 minutes after prone position (T 4), 30 minutes after prone position (T 5), 45 minutes after prone position (T 6), 60 minutes after prone position (T 7), 90 minutes after prone position (T 8), and 120 minutes after prone position (T 9) were recorded; The total dosage of norepinephrine 2 hours after anesthesia to prone position and extubation time after operation were also recorded. The Visual Analogue Scale (VAS) was performed 15 minutes after extubation, 6 and 24 hours after operation. Results:There was no significant difference in CI between T 3-T 9 and T 2 in group A ( P>0.05); the CI of group B at T 3-T 7 was significantly lower than that at T 2 (all P<0.05); there was no significant difference in CI between T 8-T 9 and T 2 in group B (all P>0.05); There was no significant difference in CI between group A and group B at T 0-T 2 (all P>0.05). The CI of group A at T 3-T 9 was significantly higher than that of group B (all P<0.05); The dosage of norepinephrine in group A was significantly lower than that in group B ( P<0.05); There was no significant difference in HR, MAP, SBP and DBP between the two groups at different time points (all P>0.05); there was also no significant difference in extubation time and VAS scores at 15 minutes, 6 hours and 24 hours after extubation between the two groups (all P>0.05). Conclusions:Intraoperative application of esketamine can increase CI after prone position and reduce the amount of norepinephrine during lumbar surgery.
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Objective:To investigate the effects of esketamine on the behavior of post-traumatic stress disorder(PTSD).Methods:Thirty-six adult male SD rats were randomly divided into three groups. The mouse craniocerebral trauma model was established by cortical impact injury method. The Sham group ( n=12) only opened the bone window without craniocerebral trauma. The TBI group( n=12) and the TBI+ ES group( n=12) were subjected to cortical trauma; Immediately after trauma, the TBI+ ES group was intraperitoneally injected with esmketamine (10 mg/kg, once every two hours, three times in total), and the TBI group and Sham group were intraperitoneally injected with equal volume 0.9% sodium chloride solution. The results of sugar water preference test, open field test on day 16 and elevated cross maze test on day 17 were collected to analyze PTSD like behavior changes, and Morris water maze test was used to evaluate the learning and memory ability of rats in each group from day 18 to 23 after craniocerebral trauma. After the experiment, the rats were euthanized and the brain tissues were taken. The expression levels of brain-derived neurotrophic factor (BDNF), synaptic protein PSD95 and synaptophysin (Syp) were analyzed by Western blot. The measurement data of normal distribution were expressed as mean ± standard deviation ( ± s). One way ANOVA was used for multi group comparison, SNK- q test was used for post pairwise comparison, and LSD method was used for repeated measurement data. Results:In the TBI group, the preference rate of sugar water, the number of moving grids, the number of standing upright, the residence time of open arm, the number of open arm entry, the escape latency and the number of crossing platform [(75.8±4.9)%, (30.9±4.1) grids, (12.4±2.6) times, (40.3±8.5) s, (6.8±2.3) times, (30.0±4.6) s and (7.0±2.5) times] were significantly lower than Sham group [(85.3±4.4)%, (40.5±5.4) grid, (17.3±2.7) times, (95.8±12.4) s, (15.3±3.1) times, (18.3±7.8) s, (15.7±2.6) times] ( P< 0.05); In TBI+ ES group, the sugar water preference rate, the number of moving grids, the number of upright times, the time of open arm stay, the number of open arm entry, the number of escape latency and the number of crossing platform position [(82.9±5.5)%, (35.5±5.5) grids, (15.1±2.4) times, (68.4±9.7) s, (12.1±3.2) times, (22.3±8.8) s and (12.5±4.1) times] were significantly higher than those in TBI group ( P<0.05). The expression levels of BDNF, PSD95 and Syp in TBI+ ES Group [0.43±0.08), (0.22±0.02), (0.31±0.04)] were higher than those in TBI group [0.19±0.02), (0.20±0.02), (0.24±0.01)], the difference was significant ( P<0.05), and they were lower than those in Sham group [0.89±0.11), (0.45±0.12), (0.57±0.15)], and the difference was significant ( P<0.05). Conclusion:Esticketamine significantly reduce PTSD-like behavior in TBI rats and play a neuroprotective role, which may be a potential medicinefor PTSD treatment.
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Objective:To evaluate the effect of pectoral nerve block type Ⅱ combined with esketamine on anxiety and depression in the patients with breast cancer undergoing modified radical mastectomy under general anesthesia.Methods:Eighty-four female patients, aged 18-64 yr, of American Society of Anesthesiologists physical status Ⅰor Ⅱ, with body mass index of 18-25 kg/m 2, undergoing elective first-time modified radical mastectomy for unilateral breast cancer, were divided into 2 groups ( n=42 each) using a random number table method: routine group (R group) and pectoral nerve block type Ⅱ combined with esketamine group (PS group). Sufentanil was used for anesthesia induction and postoperative patient-controlled intravenous analgesia (PCIA) in group R, esketamine was used for anesthesia induction and postoperative PCIA, and type Ⅱ thoracic nerve block was performed under ultrasound guidance after anesthesia induction in group PS, and the rest of the drugs used were the same in both groups.The observer′s assessment of awareness/sedation scale score was recorded at the end of surgery, 30 min after the end of surgery, and at 6, 12 and 24 h after surgery.The Hospital Anxiety and Depression Scale was used to assess patients′ anxiety and depression at 1 day before surgery and at discharge.The intraoperative consumption of anesthetics, emergence time, postanesthesia care unit stay time, pressing times of PCIA, requirement for rescue analgesia, hospital costs, length of postoperative hospital stay, satisfaction scores of surgeons and patients were recorded at discharge.The occurrence of adverse reactions was also recorded after operation. Results:Compared with group R, the observer′s assessment of awareness/sedation scale score were significantly increased at the end of surgery and 30 min after surgery, the consumption of propofol and remifentanil was decreased, the emergence time and postanesthesia care unit stay time were shortened, the incidence of nausea and vomiting was decreased, the Hospital Anxiety and Depression Scale score was decreased at discharge, the incidence of anxiety and depression was decreased, the satisfaction scores of surgeons and patients were increased, and the length of postoperative hospital stay was shortened in group PS ( P<0.05). Conclusions:Pectoral nerve block type Ⅱ combined with esketamine can optimize the efficacy of anesthesia and relieve early postoperative anxiety and depression in the patients undergoing modified radical mastectomy for breast cancer under general anesthesia.
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Objective:To observe the effects of esketamine combined with butorphanol in endotracheal intubation guided by fiberoptic bronchoscopy with spontaneous breathing.Methods:Forty patients suspected of having difficult airways during elective general anesthesia operations in Hunan Provincial People′s Hospital were prospectively selected and divided into control group and observation group by random number table. Propofol plus sufentanil, esketamine plus butorphanol were used for intravenous general anesthesia respectively. At the same time, they were assisted with cricothyroid puncture and surface anesthesia of nasopharynx and larynx, and then trachea intubation with spontaneous breathing was performed through the nose under the guidance of fiberoptic bronchoscope. The changes of heart rate (HR), mean arterial pressure (MAP), arterial partial pressure of oxygen (PaO 2), and the levels of serum cortisol, norepinephrine and adrenaline before and after endotracheal intubation were compared between the two groups. The number of body motions and coughing at the completion of endotracheal intubation was compared between the two groups. Results:In the control group, the HR and MAP at the completion of intubation were higher than those before intubation, and the PaO 2 was lower than those before intubation (all P<0.05); In the observation group, there was no significant difference in HR, MAP and PaO 2 at the completion of intubation and before intubation (all P>0.05). The HR and MAP at the end of intubation in the observation group were lower than those in the control group, and the PaO 2 was higher than that in the control group (all P<0.05). The number of body motion and coughing in the observation group was significantly less than that in the control group at the completion of endotracheal intubation (all P<0.01). At the end of endotracheal intubation, the serum cortisol, norepinephrine and epinephrine level in the observation group were significantly lower than those in the control group (all P<0.01). Conclusions:Esketamine combined with butorphanol has advantages over propofol combined with sufentanil in the application of fiberoptic bronchoscopy guided tracheal intubation in difficult airways that retain spontaneous breathing, and can better control the stress response caused by tracheal intubation.
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Objective:To observe the perioperative rehabilitation of children undergoing lingual frenoplasty under dexmedetomidine nasal drip combined with esketamine anesthesia.Methods:100 children who underwent lingual frenoplasty in Changsha Maternal and Child Health Hospital from 2020 to 2021 were randomly divided into two groups: the esketamine group (E group, 50 cases) and the dexmedetomidine nasal drip combined with esketamine group (DE group, 50 cases). The mean arterial pressure (MAP), heart rate (HR) , blood oxygen saturation (SpO 2) and respiratory rate (RR) were measured, and the patients were admitted to the post anesthesia recovery unit (PACU) after operation. The modified Aldrete score, Visual Analogue Score (VAS), Wake-up Restlessness Score, food intake (clear water) time and hospital leaving time were observed at 10 min, 30 min, 60 min and 120 min after operation. Results:There was no significant difference in SpO 2 and RR, MAP and HR at T 0 and T 6 between the two groups (all P>0.05). The MAP and HR at T 1, T 2, T 3, T 4 and T 5 in DE group were lower than those in E group (all P<0.05). The modified Aldrete score of DE group was higher than that of E group, and the VAS and Wake-up Restlessness Score were lower than that of E group (all P<0.05); The time of food intake (clear water) and leaving hospital were shorter than those in Group E, with statistically significant difference (all P<0.05). Conclusions:In children′s lingual frenoplasty, dexmedetomidine nasal drip combined with esmketamine can more effectively relieve postoperative pain and agitation than esmketamine alone, shorten children′s postoperative eating time, leave the hospital earlier, and enhance recovery of children.
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Objective:To observe the efficacy and safety of different doses of esketamine in the prevention and treatment of shivering after epidural anesthesia during cesarean section.Methods:Ninety women with American Society of Anesthesiologists grade Ⅰ to Ⅱ who underwent cesarean section from February to April 2021 in Dalian Women and Children′s Medical Center (Group) were divided into three groups by random digits table method: 0.9% sodium chloride group (group C, 30 cases); 0.25 mg/kg esketamine group (K1 group, 30 cases); esketamine 0.50 mg/kg group (K2 group, 30 cases). After epidural anesthesia, each group was given the drugs in the trial plan intravenously. General condition, shivering, sedation, Apgar score, psychiatric symptoms, nausea and vomiting were observed and recorded.Results:Finally, 81 cases were completed, including 27 cases in group C, 28 cases in group K1, and 26 cases in group K2. Shivering assessment: there was no grade 2/3 shivering in K1 group and K2 group, but the incidence of grade 2/3 shivering in C group was 25.93% (7/27) and 70.37% (19/27) the difference was statistically significant ( P<0.05). Sedation assessment: in the groups of K1 and K2, incidences of mild/moderate sedation were 92.86% (26/28)/7.14% (2/28) and 3.85% (1/26)/96.15% (25/26), respectively, obviously higher than those of group C, the differences were statistically significant ( P<0.01); there were no significant differences in the incidences of maternal mental symptoms, nausea and vomiting, and Apgar score of newborns among the three groups ( P>0.05). Conclusions:0.25 and 0.50 mg/kg esketamine are effective in preventing and treating shivering after cesarean section with epidural anesthesia without obvious adverse reactions.
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OBJECTIVE To investigate the effects of esketamine combined with dexmedetomidine used for drug-induced sleep endoscopy in patients with obstructive sleep apnea syndrome. METHODS Totally 60 patients with obstructive sleep apnea syndrome were randomly divided into control group and observation group ，with 30 cases in each group. Anesthesia induction scheme of control group included loading dose of dexmedetomidine 1 μg/kg，pumped for 10 min，maintained at 1 μg（/ kg·h），and intravenous administration of propofol at a constant rate of 3 mg（/ kg·h）until the patient snored. That of observation group included same administration route and dose of dexmedetomidine as control group ，intravenous administration of esketamine 1 mg/kg at a constant rate of 0.5 mg/（kg·h）until the patient snored. Sleep endoscopy was performed when the bispectral index （BIS）was lower than 75 and the alert /sedation（OAA/S）score was higher than 1. The vital signs ，BIS and OAA/S scores of patients in awake state （T0），10 min load dose of dexmedetomidine infusion （T1），at the time of examination （T2）and at the end of examination （T3） were recorded ，as well as the patient ’s medication （including the one-time success rate of examination ，the number of additional drugs due to physical movement during examination ），and the occurrence of adverse events after medication. RESULTS In the comparison between groups ，the pulse oxygen saturation （SpO2）and BIS of patients in the observation group were significantly higher than those in the control group at T1，T2 and T3；the heart rates and mean arterial pressures （MAP）at T2 and T3 were significantly lower than those in the control group ；and the OAA/S score at T1 and T2 were significantly higher than those in the control group （P＜0.05）. Comparison within the group ，the heart rates at T1，T2 and T3 in the observation group were significantly lower than those at T0，and the MAP at T2 and T3 were significantly lower than that at T1（P＜0.05）；in control group ，compared with T0，SpO2 decreased significantly at T1，T2 and T3，heart rate decreased significantly at T1，and MAP increased significantly at T2（P＜0.05）. Sixty patients successfully completed drug-induced sleep endoscopy after medication. The one-time success rate of examination in the observation group was significantly higher （No.191460443） than control group （P＜0.05），and the number of additional drugs due to physical movement during examination was significantly less than control group （P＜0.05）. There was no significant difference in the incidence of adverse events between 2 groups（P＞0.05）. CONCLUSIONS Esketamine combined with dexmedetomidine has less respiratory inhibition and less effect on hypoxia hemodynamics in patients with obstructive sleep apnea syndrome. It has less intervention times in the process of sleep endoscopy ，and has more advantages than propofol.
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The mixture of ketamine and xylazine is widely used for the auditory brainstem response (ABR) measurement. Esketamine is twice as potent as ketamine. Our objective was to assess the influence of esketamine in mice undergoing cochlear function measurement including ABR and distortion product otoacoustic emission (DPOAE) measurement. C57Bl/6J mice were treated with an equivalent dose of analgesia and received either a single intraperitoneal (ip) injection of 100 mg/kg ketamine and 25 mg/kg xylazine or 50 mg/kg esketamine and 25 mg/kg xylazine. Hearing thresholds, peak latencies of waves I and V, and DPOAE thresholds were recorded. Time to loss of righting and time to regain righting were also assessed. We found that hearing thresholds, the peak latencies of waves I and V, and DPOAE thresholds were similar between the two groups (all P>0.05). Time to regain righting was significantly shorter in the esketamine group (P<0.001) than in the ketamine group. We concluded that when using equivalent doses of analgesia, esketamine may be an ideal substitute for ketamine during cochlear function test.