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Postoperative cognitive dysfunction (POCD) is a common brain function-related complication after surgery. In addition to old age being an independent risk factor, anesthetics are also important predisposing factors. Among them, propofol is the most commonly used intravenous anesthetic in clinical practice. It has a rapid onset, short half-life, and high recovery quality. Many studies report that propofol can attenuate surgery-induced cognitive impairment, however, some other studies reveal that propofol also induces cognitive dysfunction. Therefore, this review summarizes the effects of propofol on the cognition, and discusses possible related mechanisms, which aims to provide some evidence for the follow-up studies.

Mitochondria damage and apoptosis were found associated with sevoflurane induced neurotoxicity in developing brains of rodent and neuro cell lines. The detailed upstream mechanism remains unclear. This study explored whether sevoflurane induces neurotoxicity by activating a GSK3β (glycogen synthase kinase 3β)/Drp1 (dynamin-related protein-1)-dependent mitochondrial fission and apoptosis. Our results showed that sevoflurane exposure promoted mitochondria fission in hippocampus of neonatal mice, resulted in a prolonged escape latency from P32 (32-day-postnatal) to P35, and decreased platform crossing times on P36 as compared to the control treatment. Additionally, sevoflurane upregulated GSK3β stability and activation, promoted phosphorylation of Drp1 at Ser

A single-domain protein catenane refers to two mechanically interlocked polypeptide rings that fold synergistically into a compact and integrated structure, which is extremely rare in nature. Herein, we report a single-domain protein catenane of dihydrofolate reductase (cat-DHFR). The design was achieved by rewiring the connectivity between secondary motifs to introduce artificial entanglement and the synthesis was readily accomplished by a series of programmed streamlined post-translational processing events in cells without any additional in vitro reactions. The target molecule contains few exogenous motifs and has been thoroughly characterized by combined techniques of LC-MS, SDS-PAGE, protease cleavage experiment, and ion mobility mass spectrometry. Compared to the linear control, cat-DHFR retains the catalytic capability and exhibits enhanced stability against thermal or chemical denaturation due to conformational restriction. The results suggest that linear proteins may be converted into concatenated single-domain counterparts with almost identical chemical composition, well-preserved function, and elevated stability, which represents an entirely new horizon in protein science.

BACKGROUND Mechanical ventilation can lead to cardiopulmonary complications in elderly patients undergoing abdominal surgery plus general anesthesia. The cardiopulmonary exercise test (CPET) is a dynamic and noninvasive evaluation method for assessing the cardiopulmonary system function under rest and stress. Positive end-expiratory pressure (PEEP) titration guided by electrical impedance tomography (EIT) can individualize lung protection strategies and may be beneficial in postoperative cardiopulmonary exercise capacity for these patients. MATERIAL AND METHODS This study is a prospective, single-center, randomized, and controlled trail that will include 80 elderly patients scheduled for major abdominal surgery. The patients will be divided into 2 groups: (1) intervention group: using individualized PEEP ventilation; and (2) control group: using fixed PEEP ventilation (3-5 cmH₂O). RESULTS The primary outcome is the change of postoperative cardiopulmonary exercise capacity. CONCLUSIONS In this study, we will evaluate if EIT-guided PEEP titration can improve postoperative cardiopulmonary exercise capacity and reduce postoperative complications in elderly patients undergoing open abdominal surgery plus general anesthesia. If the result is in accordance with the hypothesis, it would provide evidence to aid the perioperative management for these patients.

Application of a certain concentration of local anesthetics during tumor resection inhibits the progression of tumor. The effects of ropivacaine in bladder cancer (BC) have never been explored. We explored the effects of ropivacaine on the progression of BC in vitro and in vivo. CCK8 assay and EDU staining was conducted to examine cell proliferation. Flow cytometry and transwell assay were performed to evaluate apoptosis and invasion, respectively. Expression of light chain 3 (LC3) was observed through immunofluorescence. Furthermore, the xenograft tumor model of BC was built to detect the effects of ropivacaine in vivo. IHC and TUNEL assay were conducted to detect cell proliferation and apoptosis in vivo. Ropivacaine inhibited the proliferation of T24 and 5639 cells with the 50% inhibitory concentration (IC50) of 20.08 and 31.86 µM, respectively. Ropivacaine suppressed the invasion ability and induces the apoptosis of cells. Besides, ropivacaine triggers obvious autophagy in BC cells. Moreover, ropivacaine blocks the PI3K/AKT signal pathway in BC cells. The impact of ropivacaine on cell viability, motility, and autophagy was reversed by 740 Y-P, the activator of PI3K/AKT signal pathway. The in vivo experiments demonstrated that ropivacaine inhibited the proliferation and mobility of BC. Ropivacaine has anti-carcinoma effects in BC via inactivating PI3K/AKT pathway, providing a new theoretical reference for the use of local anesthetics in the treatment of BC.

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.

BACKGROUND Electrical impedance tomography (EIT) is a new test that has been widely used by clinicians in recent years at bedside or in ICU wards. Studies and publications on EIT increased quickly and the hotspot trends changed; however, the overview and characteristics of such studies have not yet been reported. Therefore, we have attempted to interpret the evolution of EIT and to anticipate its possible future clinical use by conducting a statistical analysis of EIT articles over the past 20 years. MATERIAL AND METHODS We analyzed EIT-related articles from 2020 and the 20 years prior, sourced from the Web of Science database. The data collected included the number of articles published, the classification of the articles, basic information, and author affiliation. RESULTS Our study retrieved a total of 1427 EIT-related articles through screening, with the most articles published from Chinese authors and the Chinese Air Force Military Medical University, and the most cited article type being EIT-related basic research. Most articles on EIT have been published in the journal Physiological Measurement. Furthermore, the hotspots and research trends of EIT have changed from basic innovation development to clinical application in the past 20 years. CONCLUSIONS This paper presents a statistical analysis of articles on EIT over the last 20 years, focusing on trends from the mechanisms of EIT to its clinical use.

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.

Jiaojiao Yang, Huihui Miao, Hui Qiao, Tianzuo Li Department of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of ChinaCorrespondence: Huihui Miao; Tianzuo LiDepartment of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, 10th Tieyi Road, Haidian District, Beijing, 100038, People’s Republic of China, Email miaohuihui@bjsjth.cn; litz@bjsjth.cn View the original paper by Dr Yang and colleagues

BackgroundKetamine is an intravenous anesthetic with analgesic effects that has a rapid onset and short duration of action. Many studies have been conducted on the use of ketamine; however, the quantity and quality of such studies have not been reported. Therefore, we aimed to conduct a bibliometric analysis of research on ketamine from 2001 to 2020.MethodsWe used the Web of Science database to get publications on ketamine from January 2001 to December 2020. Various bibliographic information was collected, including the number of publications, year of publication, country of origin, journal name, research hotspots, citation count, and author information.ResultsA total of 5,192 articles were included in the analysis. The United States published the highest number of papers on ketamine and the United States participated in publishing the most papers and disclosure funds. The types of articles in clinical trials were cited more frequently. Most articles on ketamine were published in the journal Anesthesia and Analgesia. Furthermore, the antidepressant effect of ketamine has been a research hotspot for the last 20 years.ConclusionThis study provided a comprehensive analysis of research on ketamine and highlighted the growing interest in ketamine and its antidepressant effects.

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.

Hypobaric hypoxia exposure leads to brain edema, followed by neuropsychological disorders. However, the related mechanism and effective treatments are still unclear. The study aimed to discuss the neuroprotective effects of Cordycepin on hypobaric hypoxia-induced cognitive impairment.The study contained two parts. In the first part, rats underwent hypobaric hypoxia (HH) exposure for 7 days, with or without Cordycepin (10 mg/kg) or lipopolysaccharide (LPS,10 mg/kg) treatment once a day. In the second part, rats underwent HH exposure for 7 days, with or without TAK242 (3 mg/kg) and Cordycepin (10 mg/kg) once a day. Open field and Morris water maze test were performed one day after the 7days treatment. The BBB permeability was detected by the uptake of NaF. Western bloting was used to detect the levels of TLR4/MyD88/NF-κB pathway related proteins in the hippocampus. The hippocampal and serous levels of cytokines were detected by ELISA. The structure of tight junctions in the hippocampus was observed under the transmission electron microscopy.Both acute HH and LPS exposure could activate the TLR4 pathway and neuroinflammation, further induced BBB disruption and cognitive injury. Cordycepin could inhibit the activation of theTLR-4/NF-κB/MMP-9 pathway, which further attenuated cognitive dysfunction, and disruption of the blood-brain barrier (BBB) in HH and LPS exposed rats. Furthermore, TAK242, a TLR4 antagonist, also inhibited the activation of theTLR-4/NF-κB/MMP-9 pathway and BBB disruption, as well as attenuated HH induced cognitive impairment.Cordycepin could ameliorate HH-induced neuroinflammation, BBB disruption, and cognitive damage partly by inhibiting the TLR-4/NF-κB/MMP-9 pathway.

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.

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: 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.