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In clinic, perioperative neurocognitive disorder is becoming a common complication of surgery in old patients. Neuroinflammation and blood-brain barrier (BBB) disruption are important contributors for cognitive impairment. Atorvastatin, as a strong HMG-CoA reductase inhibitor, has been widely used in clinic. However, it remains unclear whether atorvastatin could prevent anesthesia and surgery-induced BBB disruption and cognitive injury by its anti-inflammatory property. In this study, aged C57BL/6J mice were used to address this question. Initially, the mice were subject to atorvastatin treatment for 7 days (10 mg/kg). After a simple laparotomy under 1.5% isoflurane anesthesia, Morris water maze was performed to assess spatial learning and memory. Western blot analysis, immunohistochemistry, and enzyme-linked immunosorbent assay were used to examine the inflammatory response, BBB integrity, and cell apoptosis. Terminal-deoxynucleotidyl transferase mediated nick end labeling assay was used to assess cell apoptosis. The fluorescein sodium and transmission electron microscopy were used to detect the permeability and structure of BBB. The results showed that anesthesia and surgery significantly injured hippocampal-dependent learning and memory, which was ameliorated by atorvastatin. Atorvastatin could also reverse the surgery-induced increase of systemic and hippocampal cytokines, including IL-1β, TNF-α, and IL-6, accompanied by inhibiting the nuclear factor kappa-B (NF-κB) pathway and Nucleotide-Binding Oligomerization Domain, or Leucine Rich Repeat and Pyrin Domain Containing 3 (NLRP3) inflammasome activation, as well as hippocampal neuronal apoptosis. In addition, surgery triggered an increase of BBB permeability, paralleled by a decrease of the ZO-1, occludin, and Claudin 5 proteins in the hippocampus. However, atorvastatin treatment could protect the BBB integrity from the impact of surgery, by up-regulating the expressions of ZO-1, occludin, and Claudin 5. These findings suggest that atorvastatin exhibits neuroprotective effects on cognition in aged mice undergoing surgery.

To study whether ropivacaine inhibits the proliferation and migration of colon cancer cells through ITGB1 (Integrin beta-1). First, the effect of ropivacaine on cell proliferation and migration was detected by MTT and Transwell. DAPI staining, annexin V staining and Western blot were used to detect the expression of apoptosis-related proteins to investigate the effect of ropivacaine on cell apoptosis. Using bioinformatics software to predict the potential drug targets of ropivacaine. RT-PCR, Western blot and immunofluorescence verify the distribution and expression of the drug target ITGB1, and detect its downstream-related proteins to further prove that ropivacaine affects colon cancer cells by acting on ITGB1 protein. 1. Ropivacaine significantly inhibited the proliferation of colon cancer cells and promoted their apoptosis 2. Ropivacaine could interact with ITGB1 protein, and inhibited the expression of ITGB1 protein in colon cancer cells, thereby affecting its downstream signaling pathway. Ropivacaine regulates the function of colon cancer cells by targeting the expression of ITGB1 protein and affecting the activation of its downstream signaling pathways. Abbreviation: Integrin beta-1 (ITGB1); 3-(45)-dimethylthiahiazo (-z-y1)-35-di- phenytetrazoliumromide (MTT); 4. 6-diamimo-2-phenyl indole (DAPI); Reverse transcrption PCR (RT-PCR); Colorectal cancer (CRC); Local anesthetics (LA); voltage-gated sodium channel (VGSC); dulbecco s modifed eade medium (DMEM); propidium iodide (PI); dodecyl sulf ate, sodium salt-Polyacrylamide gel electrophoresis (SDS-PAGE); Polyvinylidene Fluoride (PVDF); BCL2 associated X (Bax); Focal Adhesion Kinase (FAK); extracellular signal-regulated kmase (ERK); alpha serme threcnime-proteim kinase (AKT); Glyceraldehyde-3-phosphate dehydrogenase (GAPDH); Tris-buffered salme with 0.1% Tween 20 (TBST); Similarty ensemble approach (SEA), Graphical abstract

Background Rectus sheath block (RSB) is known to attenuate postoperative pain and reduce perioperative opioid consumption. Thus, a retrospective study was performed to examine the effects of bilateral rectus sheath block (BRSB) in cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Methods A total of 178 patients undergoing CRS/HIPEC at our hospital were included. Patient information and anaesthesia-related indicators were collected from the electronic medical record (EMR) system. All subjects were divided into the following two groups: the G group (general anaesthesia) and the GR group (RSB combined with general anaesthesia). Patients in the GR group received 0.375% ropivacaine for BRSB before surgery. The primary outcomes included the total amount of remifentanil and rocuronium, the total consumption of dezocine after surgery, the visual analogue scale (VAS) score and the patient-controlled intravenous analgesia (PCIA) input dose at 1 h (T6), 6 h (T7), 12 h (T8), 24 h (T9) and 48 h (T10) after surgery. Other outcomes were also recorded, such as patient demographic data, the intraoperative heart rate (HR) and mean arterial pressure (MAP), and postoperative complications. Results Compared with the G group, the GR group showed a shorter time to tracheal extubation (P P P P > 0.05). Moreover, the incidence of hypertension, emergence agitation, delayed recovery, hypercapnia, and nausea and vomiting was lower in the GR group than in the G group (P P > 0.05). No complications associated with nerve block occurred. Conclusion BRSB could provide short-term postoperative analgesia, reduce perioperative opioid consumption and reduce the incidence of postoperative complications. It is an effective and safe procedure in CRS/HIPEC.

BackgroundCytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment choice for peritoneal cancer. However, patients commonly suffer from severe postoperative pain. The pathophysiology of postoperative pain is considered to be from both nociceptive and neuropathic origins.Main bodyThe recent advances on the etiology of postoperative pain after CRS + HIPEC treatment were described, and the treatment strategy and outcomes were summarized.ConclusionConventional analgesics could provide short-term symptomatic relief. Thoracic epidural analgesia combined with opioids administration could be an effective treatment choice. In addition, a transversus abdominis plane block could also be an alternative option, although further studies should be performed.

It has been reported that morphine pretreatment (MP) can exert neuroprotective effects, and that protein kinase C (PKC) participates in the initiation and development of ischemic/hypoxic preconditioning in the brain. However, it remains unknown whether PKC is involved in MP-induced neuroprotection. The aim of the present study, which included in vivo and in vitro experiments, was to determine whether the conventional γ isoform of PKC (cPKCγ) was involved in the protective effects of MP against cerebral ischemic injury. The present study included an in vivo experiment using a mouse model of middle cerebral artery occlusion and an in vitro experiment using neuroblastoma N2a cells with oxygen-glucose deprivation (OGD). Furthermore, a cPKCγ antagonist, Go6983, was used to determine the involvement of cPKCγ in the protective effects of MP against cerebral ischemic injury. In the in vivo experiment, neurological deficits, ischemic infarct volume, neural cell damage, apoptosis and caspase-3 activation were evaluated. In the in vitro experiment, flow cytometry was used to determine the activation of caspase-3 in N2a cells with OGD. It was found that MP protected against cerebral ischemic injury. However, intracerebroventricular injection of the cPKCγ antagonist before MP attenuated the neuroprotective effect of MP and increased the activation of cleaved caspase-3. These findings suggested that MP may provide protection against cerebral ischemic injury via a cPKCγ-mediated anti-apoptosis pathway.

Objective: To investigate the residual effects of cis-atracurium with different administrations in patients with hyperthermic intraperitoneal chemotherapy.Methods: 60 patients undergoing hyperthermic intraperitoneal chemotherapy were randomly divided into two groups with 30 cases in each group. All patients were induced with sufentanil 0.4ug/kg, propofol 2.0mg/kg and cis atracurium 0.2mg/kg. During the operation, sevoflurane and remifentanil were used to maintain anesthesia. BIS value was 45-55. The control group intermittently received cis-atracurium injection with 0.1mg/kg/h. The experimental group received continuous injection of cis-atracurium at a rate of 1.5ug/kg/min. Cis-atracurium was discontinued 30min before the end of the operation, sevoflurane inhalation was stopped 20min before the end of the surgery and remifentanil was discontinued 10min before the end. At the end of the operation, no muscle relaxant antagonism were applied. General information of patients was recorded. Mean arterial pressure (MAP), heart rate (HR), tidal volume (VT), respiratory rate (F), and blood oxygen saturation (SpO2) were recorded before anesthesia (T1) , at the time of tracheal catheter extraction (T2).Besides, the total amount of cis-atracurium, the time of recovery of spontaneous tidal volume to 6ml/kg (t1), the time of continuous lifting of the head for 5 s (t2), and the time from the withdrawal of muscle relaxant to the removal of the tracheal catheter (t3) were recorded. Blood gas analysis was also performed to record PaO2 and PaCO2 before anesthesia, when leaving the operating room and SICU. Moreover, relevant adverse reactions were recorded.Results: 1) general situation: there was no difference in body weight, operation time, ASA classification and other indicators between the two groups (P>0.05). 2) comparison of residual effects of muscle relaxants: the values of t1, t2 and t3 in the experimental group were significantly shorter than those in the control group (P0.05). 3) hemodynamic comparison: there were no statistically significant differences in mean arterial pressure, heart rate, tidal volume, respiratory rate and blood oxygen saturation between the two groups at time points T1 and T2 (P>0.05). 4) comparison of adverse events: no adverse events occurred in either group.Conclusion: Compared with intermittent infusion, continuous infusion of cis-atracurium did not result in significant residual muscle relaxation and no significant histamine release. Therefore, continuous infusion is more suitable for long-term surgery.

Isoflurane, a widely used volatile anesthetic, induces neuronal apoptosis and memory impairments in various animal models. However, the potential mechanisms and effective pharmacologic agents are still not fully understood. The p38MAPK/ATF-2 pathway has been proved to regulate neuronal cell survival and inflammation. Besides, atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, exerts neuroprotective effects. Thus, this study aimed to explore the influence of atorvastatin on isoflurane-induced neurodegeneration and underlying mechanisms. Aged C57BL/6 mice (20 months old) were exposed to isoflurane (1.5%) anesthesia for 6 h. Atorvastatin (5, 10, or 20 mg/kg body weight) was administered to the mice for 7 days. Atorvastatin attenuated the isoflurane-induced generation of ROS and apoptosis. Western blotting revealed a decrease in cleaved caspase-9 and caspase-3 expression in line with ROS levels. Furthermore, atorvastatin ameliorated the isoflurane-induced activation of p38MAPK/ATF-2 signaling. In a cellular study, we proved that isoflurane could induce oxidative stress and inflammation by activating the p38MAPK/ATF-2 pathway in BV-2 microglia cells. In addition, SB203580, a selected p38MAPK inhibitor, inhibited the isoflurane-induced inflammation, oxidative stress, and apoptosis. The results implied that p38MAPK/ATF-2 was a potential target for the treatment of postoperative cognitive dysfunction.

Background The peri-operative effectiveness of ultrasound-guided great auricular nerve block (GANB) in patients, especially in adult patients undergoing middle ear microsurgery remains unclear. We hypothesized that ultrasound-guided GANB would decrease the hemodynamic responsiveness to incision and opioid consumption in middle ear microsurgery as well as the post-operative analgesia requirement. Methods Sixty patients undergoing middle ear microsurgery were randomized into two equal groups to receive either a GANB with 2 ml of 0.25% ropivacaine under ultrasound guidance (GANB group) or to receive a blank control intervention (without any performed injection) before general anesthesia inductions. The primary outcomes were hemodynamic changes of MAP (mean artery pressure) and HR (heart rate) to skin incision. The secondary endpoints were to determine the consumptions of propofol and remifentanil during the operation and the incidence of remedial analgesia 48 h post-operation to maintain VAS ≤ 3. Results The MAP post incision in GANB group was significantly lower than that in control group (GANB group 93.83 ± 11.72 mmHg vs. control group 100.87 ± 12.65 mmHg, P = 0.029). The increases for MAP and HR post incision were also lower in GANB group (∆MAP GANB group 11.90 ± 8.32 mmHg vs. control group 19.83 ± 10.37 mmHg, P = 0.002; ∆HR GANB group 3.67 ± 5.30 beat min− 1 vs. control group 8.23 ± 8.56 beat min− 1, P = 0.016). Remifentanil consumption was significantly decreased in GANB group (GANB group 401.55 ± 100.51 μg h− 1 vs. control group 697.34 ± 215.45 μg h− 1, P = 0.000). The incidence of remedial analgesia post-operation in GANB group (5/30) was significantly lower than that in control group (20/30, P = 0.000). Conclusion Ultrasound-guided GANB decreases the hemodynamic responsiveness to incision and remifentanil consumption in middle ear microsurgery as well as the post-operative analgesia requirement. Trial registration This trial was retrospectively registered at http://www.chictr.org.cn with the registration number of ChiCTR1800014333 on 6 January, 2018.

Advanced colorectal cancer (CRC) is a significant cause of cancer mortality, with a poor prognosis. Here, we identified a novel prognostic signature for predicting survival of advanced CRC. Advanced CRC data were used (training set: n = 267 and validation set: n = 264). The survival analyses were investigated. The functional analysis of the prognostic signature was examined. In this study, our 15-gene signature was established and was an independent prognostic factor of advanced CRC. Stratification analyses also showed that this signature was still powerful for survival prediction in each stratum of age, gender, stage, and metastasis status. In mechanism, our signature involved in DNA replication, DNA damage, and cell cycle. Therefore, our findings suggested that this 15-gene signature has prognostic and predictive value in advanced CRC, which could be further used in personalized therapy for advanced CRC., Graphical Abstract

Background Hypoglycemia is one of the most fatal complications during the perioperative period. General anesthesia or sedation can mask a hypoglycemia-altered mental status. Acute hypoglycemia might result in permanent brain injury. There is no way to detect hypoglycemia during general anesthesia, except for intermittent blood glucose monitoring. Case presentation Hypoglycemia is associated with changes in electroencephalogram readings. Here, we report two cases of patients with an abnormally low Bispectral Index (BIS) associated with diabetic retinopathy surgery, one in the recovery stage of general anesthesia and the other in the maintenance of general anesthesia. Hemodynamics were stable. Severe hypoglycemia (1.6 mmol/L and 2.2 mmol/L) was then detected. BIS increased with the correction of severe hypoglycemia. Conclusions For diabetic patients, when the intraoperative BIS value is abnormally low, hypoglycemia should be considered. Severe hypoglycemia may be presented in BIS monitoring during general anesthesia.

Background: We conducted a meta-analysis of published literature to identify the correlation between leptin receptor gene polymorphisms and the risk of obstructive sleep apnea syndrome (OSAS). Methods: Five different single nucleotide polymorphisms (SNPs) were studied. Only Gln223Arg and Pro1019Pro had multiple studies. Nine studies focused on the correlation between Gln223Arg and Pro1019Pro polymorphisms and OSAS risk. Fixed-effects model or random-effects model was used to calculate the pooled odds ratio (ORs) and its corresponding 95% confidence interval (95% CI). The Begg's, Egger's, Perter's and Harbord tests were used to measure publication bias. Sensitivity analysis was also performed to ensure the robustness of the findings. Results: Six studies on Gln223Arg polymorphisms (661 cases and 498 controls) and three studies on Pro1019Pro polymorphisms (561 cases and 561 controls) were extracted. There was no correlation between the leptin receptor Gln223Arg polymorphism and the risk of OSAS (odd ratio = 0.86, 95% CI = 0.68â1.10, P = 0.23). However, Caucasian OSAS patients had a higher Arg allele frequency; whereas Chinese population with G genotype were more susceptible to OSAS (odd ratio = 1.28, 95% CI = 1.04â1.57, P = 0.02) in the studies on Pro1019Pro polymorphisms. Conclusion: The Gln223Arg polymorphisms in the Caucasian population and the Pro1019Pro polymorphisms in the Chinese population are risk factors for OSAS. Keywords: Leptin receptor gene polymorphism, rs1137101, Obstructive sleep apnea syndrome, Risk, Meta-analysis

Clinical application of local anesthetic reagent, liposomal bupivacaine (BUP), may cause irreversible damage to human nerve system. In this study, we explored the functional role of long non-coding RNA (lncRNA) small nucleolar RNA host gene 16 (SNHG16) in BUP-induced neurotoxicity in SH-SY5Y cells. SH-SY5Y cells were treated with BUP in vitro, whose dose-dependent effects on cell viability and SNHG16 expression were explored. SNHG16 was upregulated in SH-SY5Y cells. The protection of SNHG16 upregulation on BUP-induced neurotoxicity was examined by viability assay, apoptosis assay, and caspase activity assay, respectively. The endogenously competing target of SNHG16, human mature microRNA-132-3p (hsa-miR-132-3p), was explored by dual-luciferase assay and quantitative real-time PCR (qRT-PCR). Hsa-miR-132-3p was then further overexpressed in SNHG16-upregulated SH-SY5Y cells to explore its functional role in BUP-induced neurotoxicity. BUP induced dose-dependent cell death and SNHG16 downregulation in SH-SY5Y cells. Inversely, lentivirus-mediated SNHG16 upregulation mitigated cell death. In addition, SNHG16 upregulation rescued BUP-induced apoptosis and caspase 3/7 augmentation. Hsa-miR-132-3p was found to be reversely expressed with SNHG16 in BUP-treated SH-SY5Y cells. Overexpressing hsa-miR-132-3p reduced the protection of SNHG16 on BUP-induced neurotoxicity. We demonstrated that epigenetic axis of SNHG16/hsa-miR-132-3p had a functional role in regulating anesthesia-induced neurotoxicity in human lineage neural cells.

Highlights • Rich club of the brain functional network was reorganized during propofol-induced unconsciousness. • Rich-club nodes were switched among high-order cognitive function networks (DMN and FPN), sensory networks (ON) and cerebellum network (CN) from wakefulness to propofol-induced unconsciousness. • There existed the similar pattern of rich-club reorganization with propofol-induced unconsciousness during the process of natural sleep. • The characterizations of rich-club organization might underlie the common neurological mechanism of pharmacological and physiological unconsciousness., Background General anesthesia (GA) provides an invaluable experimental tool to understand the essential neural mechanisms underlying consciousness. Previous neuroimaging studies have shown the functional integration and segregation of brain functional networks during anesthetic-induced alteration of consciousness. However, the organization pattern of hubs in functional brain networks remains unclear. Moreover, comparisons with the well-characterized physiological unconsciousness can help us understand the neural mechanisms of anesthetic-induced unconsciousness. Methods Resting-state functional magnetic resonance imaging was performed during wakefulness, mild propofol-induced sedation (m-PIS), and deep PIS (d-PIS) with clinical unconsciousness on 8 healthy volunteers and wakefulness and natural sleep on 9 age- and sex-matched healthy volunteers. Large-scale functional brain networks of each volunteer were constructed based on 160 regions of interest. Then, rich-club organizations in brain functional networks and nodal properties (nodal strength and efficiency) were assessed and analyzed among the different states and groups. Results Rich-clubs in the functional brain networks were reorganized during alteration of consciousness induced by propofol. Firstly, rich-club nodes were switched from the posterior cingulate cortex (PCC), angular gyrus, and anterior and middle insula to the inferior parietal lobule (IPL), inferior parietal sulcus (IPS), and cerebellum. When sedation was deepened to unconsciousness, the rich-club nodes were switched to the occipital and angular gyrus. These results suggest that the rich-club nodes were switched among the high-order cognitive function networks (default mode network [DMN] and fronto-parietal network [FPN]), sensory networks (occipital network [ON]), and cerebellum network (CN) from consciousness (wakefulness) to propofol-induced unconsciousness. At the same time, compared with wakefulness, local connections were switched to rich-club connections during propofol-induced unconsciousness, suggesting a strengthening of the overall information commutation of networks. Nodal efficiency of the anterior and middle insula and ventral frontal cortex was significantly decreased. Additionally, from wakefulness to natural sleep, a similar pattern of rich-club reorganization with propofol-induced unconsciousness was observed: rich-club nodes were switched from the DMN (including precuneus and PCC) to the sensorimotor network (SMN, including part of the frontal and temporal gyrus). Compared with natural sleep, nodal efficiency of the insula, frontal gyrus, PCC, and cerebellum significantly decreased during propofol-induced unconsciousness. Conclusions Our study demonstrated that the rich-club reorganization in functional brain networks is characterized by switching of rich-club nodes between the high-order cognitive and sensory and motor networks during propofol-induced alteration of consciousness and natural sleep. These findings will help understand the common neurological mechanism of pharmacological and physiological unconsciousness.

Herkinorin is an opiate analgesic with limited adverse effects, functioning as a primary selective atypical opioid µ agonist. The present study aimed to identify whether herkinorin has a positive effect on ischemic/reperfusion (I/R) injury. Adult male C57BL/6 mice were randomly divided into five groups: i) Naive, ii) sham, iii) I/R, iv) I/R with dimethyl sulfoxide (I/R+D) and v) I/R with herkinorin (I/R+H). The I/R injury model was induced by occluding the middle cerebral artery for 1 h followed by 24 h or 7 days of reperfusion. Neurobehavioral scores and sensorimotor functions were examined 24 h and 7 days following reperfusion. In addition, infarct volumes were examined at these time points using a 2,3,5‑triphenyltetrazolium chloride assay. Herkinorin treatment improved neurobehavioral and sensorimotor functional recovery from I/R‑induced brain injury. There was a significant decrease in infarct volume in the I/R+H group at 24 h or 7 days following reperfusion compared with the I/R and I/R+D groups. Western blotting suggested that the decrease in conventional protein kinase C γ (cPKCγ) membrane translocation in the peri‑infarct region may be attenuated by herkinorin pretreatment. These results indicated that herkinorin may be beneficial in I/R‑induced mouse brain injury, and this may be attributed to the membrane translocation of cPKCγ following activation.

Background Elderly patients receive propofol at regular intervals for sedation during gastrointestinal endoscopy. However, the link between cognition and intermittent propofol exposure remains unclear. Thus, we used aged rats to investigate the effect of propofol on cognition. Methods The study included two parts. In the first part, aged (18–20 months old) male Sprague-Dawley rats underwent intermittent intraperitoneal injection of propofol (200 mg/kg) or intralipid, every 9 days or once a day. In the second part, some aged rats received intraperitoneal injection of Bay 11-7082 (1 mg/kg), a specific inhibitor of NF-κB, 30 min before propofol injection. Memory tests were performed to evaluate cognition 24 h after the entire treatment. The hippocampal neuronal damage was assessed by TUNEL staining. The hippocampal levels of p-NF-κB p65, NLRP3, caspase-1 p20, and cleaved caspase-3 were detected by western blotting. The hippocampal and serum levels of IL-1β, IL-6, and TNF-α were evaluated using ELISA. Results There were no differences in the behavioral tests, hippocampal neuronal damage, and neuroinflammation between groups given intralipid and propofol treatment every 9 days. However, repeated propofol treatment once a day promoted activation of NF-κB and the NLRP3 inflammasome, inducing cognitive impairment and neuroinflammation. Interestingly, pretreatment with Bay-11-7082 not only inhibited NF-κB/NLRP3 inflammasome activation, but also attenuated neuronal damage and cognitive dysfunction in aged rats exposed to daily propofol treatment. Conclusions Intermittent propofol treatment every 9 days may be safe for aged rats. However, propofol treatment once a day could impair the cognition of aged rats, partly through the activation of the NF-κB pathway and NLRP3 inflammasome, which may be a potential targets for the treatment of cognitive impairment in elderly patients.

Postoperative pain may lead to poor wound healing, insomnia, and increased postoperative hospitalization. The objective of the study was to explore the effect of local infiltration of the surgical wound with levobupivacaine, dexibuprofen, and norepinephrine in postoperative pain. A randomized, parallel experimental design was applied in 40, 9-11-week-old Wister albino rats. A laparotomy was performed in all groups of 10 rats each. During surgery, the sutured muscle was infiltrated with 40μL of a normal saline (vehicle group), a normal saline containing 0.25% v/v levobupivacaine, 0.2mg/mL dexibuprofen, and 0.1mg/mL norepinephrine (treatment group) before skin closure. The same combination (negative control group) and a 10-fold higher dose (positive control group) were administered systematically. Rat Grimace Scale scores, based on facial expression, 24h after suturing of the tissues, histopathology and tensile strength of the surgical wound, two weeks after suturing of the tissues were measured. The one-way ANOVA and the two-tailed paired t-test/the Dunnett multiple comparisons test were used to compare the Rat Grimace Scale scores for pain within the group and between groups. The Kruskal-Wallis test and the one-way ANOVA/the Dunnett multiple comparisons test were used to compare the histopathology study and the tensile strength. The difference for statistical analysis was considered significant at the 95% of confidence level. The mean Rat Grimace Scale score at 24h for the treatment, negative control, and positive control groups was 1.945 (p=0.0025; q=3.257), 1.1 (p=0.1), and 1.95 (p=0.0021 q=3.547) respectively. The reduction in postoperative pain started within 1h after the suturing of the tissues in the treatment group. There were significant difference for epidermal and dermal regeneration (p=0.043), granulation tissue thickness (p=0.025), and angiogenesis (p=0.002) between treatment group and vehicle group. Tensile strength for the treatment group was 0.82±0.013N/cm2(p=0.003; q=5.231). The rapid infiltration of surgical wounds with a low-dose levobupivacaine, dexibuprofen, and norepinephrine may reduce postoperative pain and increase the wound regeneration process.

Background and objective Intravenous lidocaine infusion has been shown to facilitate postoperative recovery after major abdominal surgery. The current randomized controlled study was performed to assess the effect of perioperative intravenous lidocaine infusion on pain intensity, bowel function and cytokine response after larparoscopic cholecystectomy. Methods Eighty patients undergoing laparoscopic cholecystectomy were randomly allocated to receive intravenous lidocaine (bolus injection of 1.5 mg/kg lidocaine at induction of anesthesia, then a continuous infusion of 2 mg/kg/h until the end of surgery) or an equal volume of saline. Patients, anesthesiologists, and study personnel were blinded, and anesthesia and multimodal perioperative analgesia were standardized. Blood cytokines were measured at scheduled times within 48 h. Pain scores, opioid consumption, time to first flatus and time to first bowel movement were also measured after surgery. Results Seventy-one of the 80 patients who were recruited completed the study protocol. Patient demographics were similar in the two groups. Lidocaine significantly reduced pain intensity [visual analogue scale (VAS), 0–10 cm] at 2 h (lidocaine 3.01 ± 0.65 cm vs. placebo 4.27 ± 0.58 cm, p = 0.01) and 6 h (lidocaine 3.38 ± 0.42 cm vs. placebo 4.22 ± 0.67 cm, p = 0.01) and total fentanyl consumption 24 h after surgery (lidocaine 98.27 ± 16.33 μg vs. placebo 187.49 ± 19.76 μg, p = 0.005). Time to first flatus passage (lidocaine 20 ± 11 h vs. placebo 29 ± 10 h, p = 0.01) and time to first bowel movement (lidocaine 41 ± 16 h vs. placebo 57 ± 14 h, p = 0.01) were also significantly shorter in patients who received lidocaine. Intravenous lidocaine infusion experienced less cytokine release than the control group. Conclusions This study indicates that perioperative systemic lidocaine improves postoperative recovery and attenuates the initiation of excessive inflammatory response following laparoscopic cholecystectomy.

Background It has been demonstrated that κ-opioid receptor agonists can reduce hypoxia–ischemia brain injury in animal models. However, it is unclear how the κ-opioid receptor responds to hypoxia–ischemia. In the current study, the authors used an in vitro model of oxygen–glucose deprivation and reoxygenation to explore how κ-opioid receptors respond to hypoxia and reoxygenation. Methods Mouse neuroblastoma Neuro2A cells were stably transfected with mouse κ-opioid receptor–tdTomato fusion protein or Flag-tagged mouse κ-opioid receptor, divided into several groups (n = 6 to 12), and used to investigate the κ-opioid receptor movement. Observations were performed under normal oxygen, at 30 min to 1 h after oxygen–glucose deprivation and at 1 h after reoxygenation using high-resolution imaging techniques including immunoelectronmicroscopy in the presence and absence of κ-opioid receptor antagonist, dynamin inhibitors, potassium channel blockers, and dopamine receptor inhibitor. Results Hypoxic conditions caused the κ-opioid receptor to be internalized into the cells. Inhibition of dynamin by Dyngo-4a prevented the receptor internalization. Interestingly, a specific κ-opioid receptor antagonist norbinaltorphimine blocked internalization, suggesting the involvement of activation of a specific κ-opioid receptor. κ-Opioid receptor internalization appears to be reversed by reoxygenation. Quantities of intracellular κ-opioid receptor-associated gold particles as demonstrated by immunoelectron microscopy were increased from 37 to 85% (P < 0.01) after oxygen–glucose deprivation. Potassium channel blockers and dopamine receptor inhibitor failed to block hypoxia-induced κ-opioid receptor internalization. Conclusions Hypoxia induces reversible κ-opioid receptor internalization, which was inhibited by selective κ-opioid receptor antagonists or dynamin inhibitor, and can be reversed by reoxygenation in neuroblastoma cells, indicating the modulating effects between κ-opioid receptor and hypoxia via κ-opioid receptor activation and the dynamin-dependent mechanism.

Background Simulation-based training (SBT) has become a standard for medical education. However, the efficacy of simulation based training in airway management education remains unclear. Methods The aim of this study was to evaluate all published evidence comparing the effectiveness of SBT for airway management versus non-simulation based training (NSBT) on learner and patient outcomes. Systematic review with meta-analyses were used. Data were derived from PubMed, EMBASE, CINAHL, Scopus, the Cochrane Controlled Trials Register and Cochrane Database of Systematic Reviews from inception to May 2016. Published comparative trials that evaluated the effect of SBT on airway management training in compared with NSBT were considered. The effect sizes with 95% confidence intervals (CI) were calculated for outcomes measures. Results Seventeen eligible studies were included. SBT was associated with improved behavior performance [standardized mean difference (SMD):0.30, 95% CI: 0.06 to 0.54] in comparison with NSBT. However, the benefits of SBT were not seen in time-skill (SMD:-0.13, 95% CI: −0.82 to 0.52), written examination score (SMD: 0.39, 95% CI: −0.09 to 0.86) and success rate of procedure completion on patients [relative risk (RR): 1.26, 95% CI: 0.96 to 1.66]. Conclusion SBT may be not superior to NSBT on airway management training.

The inhalation anesthetic isoflurane has been reported to induce caspase activation and apoptosis, which may lead to learning and memory impairment. However, the underlying mechanisms of these effects are largely unknown. Isoflurane has been shown to induce elevation of cytosol calcium levels, accumulation of reactive oxygen species (ROS), opening of the mitochondrial permeability transition pore, reduction in mitochondria membrane potential, and release of cytochrome c. The time course of these effects, however, remains to be determined. Therefore, we performed a pilot study to determine the effects of treatment with isoflurane for various times on ROS levels in HEK-293 cells. The cells were treated with 2% isoflurane plus 21% O2 and 5% CO2 for 15, 30, 60, or 90 min. We then used fluorescence imaging and microplate fluorometer to detect ROS levels. We show that 2% isoflurane for 60 or 90 min, but not 15 or 30 min, induced ROS accumulation in the cells. These data illustrated that isoflurane could cause time-dependent effects on ROS levels. These findings have established a system to further determine the time course effects of isoflurane on cellular and mitochondria function. Ultimately, the studies would elucidate, at least partially, the underlying mechanisms of isoflurane-induced cellular toxicity.

Postoperative pain management remains a significant challenge after abdominal surgery.The aim of this meta-analysis was to evaluate the efficacy of systemic lidocaine for postoperative pain management and recovery after abdominal surgery.Data were derived from Medline (1966-2010), CINAHL, The Cochrane Central Register of Controlled Trials, and Scopus.Randomized controlled trials of systemic administration of lidocaine for postoperative analgesia and recovery after abdominal surgery in adults, ie,18 years, were considered.Combined data were analyzed with use of a random-effects model.Data on opioid consumption, postoperative pain intensity, opioid-related side effects, time to first flatus, time to first bowel movement, and length of hospital stay were extracted.Twenty-one trials comparing systemic lidocaine with placebo or blank control for postoperative analgesia and recovery after abdominal surgery were included in this meta-analysis. Weighted mean difference for cumulative analgesic opioid (morphine) consumption 48 hours after surgery was -7.04 mg (95% CI: -10.40, -3.68, I2= 46.1%).Systemic lidocaine also significantly reduced postoperative pain intensity(visual analog scale, 0-100 mm) 6 hours after surgery at rest (weighted mean difference: -8.07 mm (95% CI: -14.69, -1.49); I2 = 90.6%) and during activity (weighted mean difference: -10.56 mm (95% CI: -16.89, -4.23), I2 = 82%). The time to first flatus and bowel movement was significantly shortened with lidocaine intervention by 6.92 hours (95% CI: -9.21, -4.63, I2 = 62.8%) and 11.74 hours (95% CI:-16.97, -6.51, I2 = 0). Moreover, systemic lidocaine also reduced hospital length of stay following the open procedure (weighted mean difference: -0.71 days (95% CI: -1.35, -0.07); I2 = 37.3%).Heterogeneity of study results is the main limitation of this meta-analysis.Perioperative systemic lidocaine may be a useful adjunct for postoperative pain management by decreasing postoperative pain intensity, reducing opioid consumption, facilitating GI function, and shortening length of hospital stay.

During the perinatal period, the pharmacokinetics and pharmacodynamics of drugs may be altered. Data about the neurotoxicity of intrathecal local anesthetics in the peripartum period are lacking. So we hypothesized that the neurotoxicity of intrathecal lidocaine during perinatal period may be changed. Therefore, we designed the present study to determine whether the neurotoxicity of intrathecal lidocaine in postpartum rats would be different from that in nonpregnant, virgin rats. Postpartum and nonpregnant rats randomly received an intrathecal infusion of lidocaine 50 mg/mL in saline, lidocaine 20 mg/mL in saline, or saline for 1 h at a rate of 1 μL/min. Four days after drug infusion, the rats were assessed for persistent impairment of sensory and motor function (MF) using the tail-flick (TF) test, paw pressure test, and MF score. Spinal cords and nerve roots were obtained for light and electron microscopic examinations, and the injury scores were compared between groups. The TF latencies and the mean nerve injury scores of the postpartum group were significantly higher than those of nonpregnant group. Lidocaine induced a dose-dependent impairment in TF latencies and nerve injury scores. There was no significant interaction between postpartum and the drug. Our results suggest that the neurotoxicity of intrathecal lidocaine is enhanced in rats during the early postpartum period compared with nonpregnant, virgin rats.

Propofol and ketamine may provide certain degree of neuroprotection, but the underlying mechanism remains unclear to date. The cAMP response element-binding protein (CREB) was proposed that its phosphorylation at Ser133 (P-CREB) constituted a convergence point involved in neuroprotection. The purpose of this study was to determine whether different dosages of propofol and ketamine could provide neuroprotection against permanent middle cerebral artery occlusion (MCAO)-induced ischemic injuries and the involvement of P-CREB. Eighty adult male BALB/c mice that underwent 6 h MCAO were randomly divided into eight groups: Sham-operation; MCAO + saline; MCAO + 25, 50, 100 mg/kg propofol; and MCAO + 25, 50, 100 mg/kg ketamine (intraperitoneal injection 30 min following MCAO). We found that 50, 100 (not 25) mg/kg propofol, and 25 (not 50 and 100) mg/kg ketamine could significantly reduce the infarct volume, edema ratio and neurological deficit (n = 10 per group) as well as inhibit the decrease of P-CREB level in peri-infarct region when compared with that of MCAO + saline group (n = 6 per group). In addition, the results of double-labeled immunofluorescent staining showed that P-CREB co-localized with neuron-specific marker, NeuN, in the peri-infarct region of 50 mg/kg propofol and 25 mg/kg ketamine treated 6 h MCAO mice (n = 4 per group). These results suggested that inhibition of neuron-specific P-CREB dephosphorylation in the peri-infarct region is involved in high dose propofol and low dose ketamine-induced neuroprotection of 6 h MCAO mice.

Adenosine monophosphate-activated protein kinase (AMPK) orchestrates the regulation of energy-generating and -consuming pathways, and protects the heart against ischemic injury and apoptosis. Recent progress shed light on various factors, including adiponectin, MIF, H11K, and metformin in the activation of AMPK. It is uncertain whether the activation of AMPK is contributed to cardioprotection of opioids. Here we show that morphine, an exogenous non-peptide opioid receptor agonist, can modulate the activation of the cardioprotective AMPK pathway during ischemia and exert anti-apoptotic effects through AMPK.Isolated rat hearts were perfused on a constant pressure Langendorff system and subjected to 30 min of global ischemia followed by 60 min of reperfusion. The hearts received vehicles, morphine, a combination of morphine and compound C, a combination of morphine and STO609, a combination of morphine and BAPTA-AM at the onset of ischemia. Hemodynamics parameters, infarct size, release of intracellular creatine kinase, expression of AMPK, and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining were analyzed.Morphine significantly increased phosphorylation level of Thr172 site on AMPK, left ventricular function, and reduced infarct size as a percentage of the area at risk (IS/AAR from 63% ± 7% to 40% ± 5%), release of intracellular creatine kinase (from 319 ± 46 to 156 ± 42IU/60 min/gdw), apoptosis ratio (from 16% ± 2% to 5% ± 1.4%) during reperfusion in comparison with the control group. A inhibitor of AMPK, compound C abrogated phosphorylation of AMPK induced by morphine, the improvement in myocardial function, and the reduction of IS/AAR (58% ± 6%), release of intracellular creatine kinase (270 ± 40IU/60 min/gdw), apoptosis ratio (13% ± 1.5%). A Ca(2+)/calmodulin-dependent protein kinase kinase inhibitor STO609 and a chelator of intracellular Ca(2+) stores BAPTA-AM also abolished the cardioprotection of morphine.Morphine can ameliorate myocardial contractile dysfunction and limit infarct size following ischemia and reperfusion by a mechanism involving activation of AMPK, and activate AMPK by Ca(2+)-CaMKKβ-dependent phosphorylation.

β-Amyloid protein (Aβ) accumulation, caspase activation, apoptosis, and hypoxia-induced neurotoxicity have been suggested to be involved in Alzheimer disease neuropathogenesis. Aβ is produced from amyloid precursor protein through proteolytic processing by the aspartyl protease β-site amyloid precursor protein-cleaving enzyme (BACE) and γ-secretase. Inhaled anesthetics have long been considered to protect against neurotoxicity. However, recent studies have suggested that the inhaled anesthetic isoflurane may promote neurotoxicity by inducing caspase activation and apoptosis, and by increasing levels of BACE and Aβ. We therefore sought to determine whether isoflurane can induce concentration-dependent dual effects on hypoxia-induced caspase-3 activation and increases in BACE levels: protection versus promotion.H4 human neuroglioma cells were treated with hypoxia (3% O(2)) alone, different concentrations of isoflurane (0.5% and 2%), and the combination of hypoxia and 0.5% or 2% isoflurane. The levels of caspase-3 cleavage (activation), BACE, and Bcl-2 were determined by Western blot analysis.We show for the first time that treatment with 0.5% isoflurane for 8 hours attenuated, whereas treatment with 2% isoflurane for 8 hours enhanced, hypoxia-induced caspase-3 activation and increases in BACE levels. The 2% isoflurane treatment also enhanced a hypoxia-induced decrease in Bcl-2 levels.These results suggest a potential concept that isoflurane has dual effects (protection versus promotion) on hypoxia-induced toxicity, which may act through Bcl-2 family proteins. These findings could lead to more systematic studies to determine the potential dual effects of anesthetics on Alzheimer disease-associated neurotoxicity.

Sedation induces changes in electroencephalography (EEG) dynamics. However, the distinct EEG dynamic characteristics at comparable sedation levels have not been well studied, resulting in potential interpretation errors in EEG monitoring during sedation. We aimed to analyze the EEG dynamics of dexmedetomidine and propofol at comparable sedation levels and to explore EEG changes with increased sedation levels for each agent. We measured the Bispectral Index (BIS) and 20-channel EEG under dexmedetomidine and propofol sedation from wakefulness, moderate sedation, and deep sedation to recovery in healthy volunteers (n = 10) in a randomized, 2-day, crossover study. Observer's Assessment of Alertness and Sedation (OAA/S) score was used to assess sedation levels. Despite similar changes in increased delta oscillations, multiple differences in the EEG spatiotemporal dynamics were observed between these two agents. During moderate sedation, both dexmedetomidine and propofol induced increased spindle power; however, dexmedetomidine decreased the global alpha/beta/gamma power, whereas propofol decreased the alpha power in the occipital area and increased the global spindle/beta/gamma power. During deep sedation, dexmedetomidine was associated with increased fronto-central spindle power and decreased global alpha/beta/gamma power, but propofol was associated with increased theta/alpha/spindle/beta power, which was maximized in the frontal area. The transition of topographic alpha/spindle/beta power distribution from moderate sedation to deep sedation completely differed between these two agents. Our study demonstrated that there was a distinct hierarchy of EEG changes with increased sedation depths by propofol and dexmedetomidine. Differences in EEG dynamics at the same sedation level might account for differences in the BIS value and reflect the different sedation mechanisms. EEG-based clinical sedation monitoring should consider the effect of drug types on EEG dynamics.

Background The mechanism of general anesthesia (GA) has been explored for hundreds of years, but unclear. Previous studies indicated a possible correlation between NREM sleep and GA. The purpose of this study is to compare them by in vivo human brain function to probe the neuromechanism of consciousness, so as to find out a clue to GA mechanism. Methods 24 healthy participants were equally assigned to sleep or propofol sedation group by sleeping ability. EEG and Ramsay Sedation Scale were applied to determine sleep stage and sedation depth respectively. Resting-state functional magnetic resonance imaging (RS-fMRI) was acquired at each status. Regional homogeneity (ReHo) and seed-based whole brain functional connectivity maps (WB-FC maps) were compared. Results During sleep, ReHo primarily weakened on frontal lobe (especially preoptic area), but strengthened on brainstem. While during sedation, ReHo changed in various brain areas, including cingulate, precuneus, thalamus and cerebellum. Cingulate, fusiform and insula were concomitance of sleep and sedation. Comparing to sleep, FCs between the cortex and subcortical centers (centralized in cerebellum) were significantly attenuated under sedation. As sedation deepening, cerebellum-based FC maps were diminished, while thalamus- and brainstem-based FC maps were increased. Conclusion There’re huge distinctions in human brain function between sleep and GA. Sleep mainly rely on brainstem and frontal lobe function, while sedation is prone to affect widespread functional network. The most significant differences exist in the precuneus and cingulate, which may play important roles in mechanisms of inducing unconciousness by anesthetics. Trial registration Institutional Review Board (IRB) ChiCTR-IOC-15007454.

Background and Objectives Potentially, perioperative regional anesthesia and analgesia (RA) could influence the outcomes of patients with cancer. The aim of this systematic review and meta-analysis was to evaluate the effects of perioperative RA on survival and cancer recurrence after oncologic surgery. Methods The authors searched computerized databases (from inception to December 2014) and reference lists and considered all studies comparing the effects of RA on cancer recurrence or overall survival with that of general anesthesia (GA). Risk estimates were pooled to determine the effects of RA on risks of cancer recurrence and mortality. Twenty eligible studies were included. Results Perioperative RA use was associated with improved overall survival (Hazard ratio [HR] = 0.84, 95% CI, 0.75 − 0.94; I2 =41%), but not with reduced cancer recurrence (HR=0.91, 95% CI, 0.70 − 1.18; I2=83%). Conclusions Our meta-analysis suggests that RA may improve overall survival but not reduce cancer recurrence after oncologic surgery.

To compare paravertebral block under thoracoscopy with wound infiltration at an early stage after video-assisted thoracic lobectomy surgery.A prospective, randomized, triple-blinded, placebo-controlled trial.A single-center university hospital.Patients scheduled for video-assisted thoracic lobectomy surgery between February 20, 2014 and June 1, 2014 randomly were allocated into paravertebral block (PVB) (n = 35) and infiltration (n = 35) groups.In the PVB group, 0.5% ropivacaine was injected into the paravertebral space by the surgeon under direct vision with placebo infiltration of saline in the wounds. In the infiltration group, the wounds were infiltrated with 0.5% ropivacaine by the surgeon with a placebo paravertebral block. Subsequently, patient-controlled intravenous morphine analgesia and paracoxib were administered.The primary endpoints were visual analog scale (VAS) pain scores at rest and on cough 0, 2, 6, and 24 hours after surgery. The secondary endpoints were the total morphine during postoperative 0 hours to 24 hours, adverse events, and patient satisfaction with the analgesia. Sixty-one patients completed the study. VAS score on cough at each time point was significantly lower (p0.05) and median (25th, 75th) morphine consumption was lower in the PVB group than in the infiltration group (26 [10, 35] mg and 42 [29, 58] mg, p0.001, respectively). There was no difference in VAS score at rest. Patients in the PVB group had higher satisfaction with analgesia than in the infiltration group (p = 0.003).As part of the multimodal postoperative analgesia, intraoperative paravertebral block provided better dynamic pain relief and reduced morphine consumption compared with local wound infiltration.

The commonly used inhaled anesthetic isoflurane has been shown to induce caspase-3 activation. However, the underlying mechanism(s) and targeted intervention(s) remain largely to be determined. Isoflurane may induce caspase-3 activation via causing accumulation of reactive oxygen species (ROS), mitochondrial dysfunction, and reduction in adenosine triphosphate (ATP) levels. Therefore, we performed a hypothesis-generation study to determine whether glucose could attenuate isoflurane-induced caspase-3 activation, ROS accumulation, mitochondrial dysfunction, and ATP reduction in cultured cells.H4 human neuroglioma cells (H4 cells) were treated with 2% isoflurane or the control condition plus saline or 50 mM glucose for 6 or 3 hours. Caspase-3 activation, cell viability, levels of ROS and ATP, and mitochondrial membrane potential were determined at the end of the experiments by Western blot analysis and fluorescence assay.We found that the glucose treatment might attenuate isoflurane-induced caspase-3 activation and reduction of cell viability in H4 cells. Moreover, the glucose treatment mitigated the isoflurane-induced increase in ROS levels and reduction in ATP levels in H4 cells. Unexpectedly, we observed that the glucose treatment might not inhibit the isoflurane-induced decrease in mitochondrial membrane potential in H4 cells.Pending further studies, these results suggested that glucose might attenuate isoflurane-induced caspase-3 activation through a mitochondria-independent reduction in ROS levels and enhancement in ATP levels. These findings have established a system and suggest that it is worth performing more research to further investigate whether glucose can attenuate anesthesia neurotoxicity.

An estimated 234 million patients worldwide undergo anesthesia and surgery each year. Even though the incidence of Alzheimer disease (AD) may not be increased by anesthesia,1 the age of AD onset was reported to be inversely related to cumulative exposure to anesthesia and surgery before the age of 50 yrs.2 Several other studies have also suggested general anesthesia as one of the risk factors for AD.3,4 Opposing findings, however, do exist,5–7 and therefore more research, especially human studies aimed to define the role of anesthesia in AD neuropathogenesis, is necessary.8,9 Excessive production and/or accumulation of β-amyloid protein (Aβ), predominantly including Aβ40 and Aβ42, plays a fundamental role in the neuropathogenesis of AD.10–13 In addition, recent studies have suggested the contribution of Aβ40 in AD neuropathogenesis.14,15 Furthermore, Aβ40 has been shown to induce caspase activation and apoptosis16–18 and to impair synaptic plasticity and memory function..19,20 In addition to Aβ, the accumulation, abnormal aggregation, and deposition of tau play a key role in AD neuropathogenesis.21 As the major protein component of intraneuronal neurofibrillary tangles, elevation of total tau levels (two- to threefold) is seen in the cerebrospinal fluid (CSF) of AD patients compared to nondemented elderly adults.22,23 Moreover, a reduced ratio of Aβ42 to tau in the CSF has been suggested as one of the biomarkers of AD.23,24 Several studies have suggested that the commonly used inhalation anesthetic isoflurane can increase Aβ accumulation in cultured cells, neurons, and animals.9,25–29 The isoflurane has been shown to increase levels of phosphorylated, but not total, tau in brain tissues of mice.30 In contrast, another commonly used inhalation anesthetic desflurane has been shown not to increase Aβ levels in cultured cells.31 However, the in vivo relevance of these acute effects of isoflurane on Aβ levels in humans has not yet been assessed. In this study, we set out to determine the effects of surgery under spinal (S) anesthesia alone, spinal plus desflurane (SD) anesthesia, and spinal plus isoflurane (SI) anesthesia on the acute changes in CSF Aβ levels in human participants. We also assessed the effects of surgery under S, SD, and SI anesthesia on total tau levels in human CSF and calculated the ratios of Aβ40 or Aβ42 to tau. We hypothesized, based on the in vitro and animal studies, that isoflurane, but not desflurane, would increase the human CSF Aβ levels.

The chronic intrathecal catheterization of the subarachnoid space in the rat is a very useful model in the research of neuroscience, anesthesiology, neurotoxicity, and etc. To avoid high postoperative mortality and neurological impairment, the catheterization from the lumbar interspace has been widely used in recent years. But one of the most discouraging disadvantages is that the external portion of the chronic indwelling catheters is easily damaged by rats. Besides, the short length of catheter left in the subarachnoid space in addition to its slimness makes it difficult for proper fixation. To improve the abovementioned situations, we designed a protector to protect the external portion of the catheters and developed a simple method for better fixation. Results suggest that this is an excellent method for protecting and fixing the lumbar catheters placed in the subarachnoid space of rats, and this method did not affect the sensory and motor function of the rat. The general conditions of the rats were unswayed.

Ca/calmodulin-dependent protein kinase II (CaMKII) activation through autophosphorylation at threonine 286 was involved in the modulation of neuronal excitability and neurotransmission. Both propofol and ketamine may affect the intracellular Ca levels through N-methyl-D-aspartate receptors or voltage-dependent Ca channels, but they have different mechanisms in general anesthesia. The purpose of this study was to investigate the effects of propofol and ketamine on CaMKII total protein and phosphorylation (p-CaMKII) levels in the brain of rats. We found that both propofol and ketamine could induce a decrease of p-CaMKII, not CaMKII total protein, in an anesthetic depth-dependent manner, whereas only ketamine caused a dose (50, 100, and 150 mg/kg)-dependent depression of p-CaMKII in hippocampus and frontal cortex of rats after intraperitoneal injections for 30 minutes. The significant depressions of p-CaMKII started at 5 minutes both in hippocampus and frontal cortex of rats after 100 mg/kg propofol treatment, whereas 100 mg/kg ketamine-induced significant depression of p-CaMKII initiated at 30 minutes in hippocampus and 5 minutes (no reduction observed at 15 min) in frontal cortex of rats. The maximum reduction of p-CaMKII with both drugs was at 60 minutes, and then restored to control level at 240 minutes. In addition, we confirmed the depression of p-CaMKII in hippocampus and frontal cortex of rats after 100 mg/kg of propofol or ketamine treatment for 60 minutes by using immunostaining. These results suggested that decreased p-CaMKII levels correlate with anesthetic depths achieved by propofol and ketamine, which may be related to the effects of propofol and ketamine on central nervous system function and their clinical effect.

Background/Objective Inadvertent intraoperative hypothermia (core temperature 2 h (OR = 3.44, 95% CI 1.90–6.22,), and intravenous un-warmed fluid (OR = 2.45, 95% CI 1.45–4.12) significantly increased the risk of hypothermia. Conclusions The incidence of inadvertent intraoperative hypothermia in Beijing is high, and the rate of active warming of patients during operation is low. Concern for the development of intraoperative hypothermia should be especially high in patients undergoing major operations, requiring long periods of anesthesia, and receiving un-warmed intravenous fluids.