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Optical artificial synapses possess several advantages, including high bandwidth, strong interference immunity, and ultra-fast signal transmission, overcoming the limitations of electrically stimulated synapses. Among various functional materials, 2D materials exhibit exceptional optical and electrical properties. By utilizing van der Waals heterostructures formed by these materials through rational design, synaptic devices can mimic the information perception ability of biological systems. This lays the foundation for low-energy artificial vision systems and neuromorphic computing. This study introduces an inhibitory artificial synapse based on photoelectric co-modulation of graphene/WSe2van der Waals heterojunctions. By synergistically applying gate voltage and light pulses, we simulate memory and logic functions observed in the brain's visual cortex. We achieve the construction of inhibitory synapses, enabling properties such as postsynaptic current response, short-term and long-term plasticity, and paired-pulse facilitation. Additionally, we accomplish the inverse recovery of device conductivity through separate gate voltage stimulation. Through bidirectional modulation of the artificial synaptic conductance, we construct an artificial hardware neural network that achieves 92.5% accuracy in recognizing handwritten digital images from the MNIST dataset. The network also has good recognition accuracy for handwritten digital images with different standard deviation Gaussian noise applied and other datasets. Furthermore, we successfully mimic the neural behavior of aversive learning for alcohol withdrawal in alcoholic patients using the device properties. The promising capabilities of artificial synapses constructed through electrical and optical synergistic modulation make them suitable for wearable electronics and artificial vision systems.
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Alcoolismo , Grafite , Síndrome de Abstinência a Substâncias , Humanos , Sinapses/fisiologia , Redes Neurais de ComputaçãoRESUMO
Sevoflurane inhalation is prone to initiate cognitive deficits in infants. The early growth response-2 (Egr-2) gene is DNA-binding transcription factor, involving in cognitive function. In this study we explored the molecular mechanisms underlying the vulnerability to cognitive deficits after sevoflurane administration. Six-day-old (young) and 6-week-old (early adult) mice received anesthesia with 3% sevoflurane for 2 h daily for 3 days. We showed that multiple exposures of sevoflurane induced significant learning ability impairment in young but not early adult mice, assessed in Morris water maze test on postnatal days 65. The integrated differential expression analysis revealed distinct transcription responses of Egr family members in the hippocampus of the young and early adult mice after sevoflurane administration. Particularly, Egr2 was significantly upregulated after sevoflurane exposure only in young mice. Microinjection of Egr2 shRNA recombinant adeno-associated virus into the dentate gyrus alleviated sevoflurane-induced cognitive deficits, and abolished sevoflurane-induced dendritic spins loss and BDNF downregulation in young mice. On the contrary, microinjection of the Egr2 overexpression virus in the dentate gyrus aggravated learning ability impairment induced by sevoflurane in young mice but not early adult mice. Furthermore, we revealed that sevoflurane markedly upregulated the nuclear factors of activated T-cells NFATC1 and NFATC2 in young mice, which were involved in Egr2 regulation. In conclusion, Egr2 serves as a critical factor for age-dependent vulnerability to sevoflurane-induced cognitive deficits.
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Anestésicos Inalatórios , Disfunção Cognitiva , Proteína 2 de Resposta de Crescimento Precoce , Éteres Metílicos , Animais , Camundongos , Anestésicos Inalatórios/toxicidade , Animais Recém-Nascidos , Cognição , Disfunção Cognitiva/induzido quimicamente , Proteína 2 de Resposta de Crescimento Precoce/genética , Proteína 2 de Resposta de Crescimento Precoce/metabolismo , Hipocampo/metabolismo , Aprendizagem em Labirinto , Sevoflurano/efeitos adversosRESUMO
BACKGROUND: Surgical resection is considered to be the primary and most effective therapy for breast cancer, postoperative pain is an issue gaining significant attention. In recent years, erector spinae plane block (ESPB) has attracted much attention in postoperative analgesia, but its effectiveness is still controversial. This meta-analysis was implemented to verify the clinical analgesic efficacy and safety of erector spinae plane block in patients undergoing breast cancer surgery. METHODS: We searched PubMed, EMBASE, Web of Science, the Cochrane Library and ClinicalTrials.gov for randomized controlled trials (RCTs) comparing ESPB with general anesthesia (GA) in breast cancer surgery that were published before December 25, 2020. The primary outcome was opioid consumption at the first 24 h after surgery, while secondary outcomes included pain scores at 1, 6,12 and 24 h after surgery, opioid consumption at 1, 6 and 12 h after surgery, intraoperative opioid consumption, number of patients who need for rescue analgesia, and the incidence of postoperative nausea and vomiting (PONV). RESULTS: Eleven randomized controlled trials involving 679 patients met the study inclusion criteria and were included in this study. In comparison to GA group, the ESPB group showed a significant reduction in morphine consumption at the first 24 h after surgery by a mean difference (MD) of - 7.67 mg [95% confidence interval (CI) - 10.35 to - 5.00] (P < 0.01). In addition, the ESPB group showed lower pain scores than the GA group in the four time periods (1, 6, 12 and 24 h after surgery). ESPB group significantly reduce the intraoperative consumption of fentanyl, the need for postoperative rescue analgesia, and the incidence of PONV. CONCLUSIONS: Ultrasound-guided ESPB is an effective approach for reducing morphine consumption and pain intensity within the first 24 h after breast cancer surgery, compared with GA alone.
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Analgesia/métodos , Neoplasias da Mama/cirurgia , Mastectomia/métodos , Bloqueio Nervoso/métodos , Dor Pós-Operatória/tratamento farmacológico , Adulto , Mama/cirurgia , Feminino , Humanos , Músculos Paraespinais/efeitos dos fármacosRESUMO
BACKGROUND: The aim of this study was twofold: (i) to investigate the intrarater reliability of acromiohumeral distance measurement; (ii) to assess the level of association between acromiohumeral distance measured by ultrasonography, and the degree of supraspinatus tendon tear, in patients suffering from chronic shoulder pain. METHODS: A cross-sectional, case-control study was carried out. A convenience sample comprising 59 patients with a unilateral supraspinatus tendon tear was assessed. Both shoulders of each patient were scanned by ultrasound, with the contralateral asymptomatic shoulders serving as the control group for comparison. Acromiohumeral distances of each shoulder were measured and analysed. RESULTS: Intrarater reliability was excellent for the ultrasound method of acromiohumeral distance measurement. The acromiohumeral distance of shoulders with full-thickness supraspinatus tendon tear was significantly smaller than that of joints with partial-thickness supraspinatus tendon tear and an intact supraspinatus tendon. There was a significant positive correlation between reduced acromiohumeral distance and the severity of a supraspinatus tendon tear. CONCLUSIONS: Ultrasound is a reliable tool to measure acromiohumeral distance. A positive relationship was found between a narrowed acromiohumeral distance and the severity grading of a supraspinatus tendon tear. Reduced acromiohumeral distance can be considered a predictive parameter for a full-thickness supraspinatus tendon tear. TRIAL REGISTRATION: The study was prospectively registered with the Chinese Clinical Trial Registry. Registration number: ChiCTR-ROC-17013550. Date of registry: 26 November 2017.
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Acrômio/diagnóstico por imagem , Cabeça do Úmero/diagnóstico por imagem , Vigilância da População , Lesões do Manguito Rotador/diagnóstico por imagem , Lesões do Manguito Rotador/epidemiologia , Índice de Gravidade de Doença , Adulto , Idoso , Estudos de Casos e Controles , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ultrassonografia de Intervenção/métodos , Ultrassonografia de Intervenção/normasRESUMO
BACKGROUND: The safety and efficiency of intravenous administration of tranexamic acid (TXA) in coronary artery bypass grafting (CABG) remains unconfirmed. Therefore, we conducted a meta-analysis on this topic. METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PUBMED and EMBASE for randomized controlled trials on the topic. The results of this work are synthetized and reported in accordance with the PRISMA statement. RESULTS: Twenty-eight studies met our inclusion criteria. TXA reduced the incidence of postoperative reoperation of bleeding (relative risk [RR], 0.46; 95% confidence interval [CI]; 0.31-0.68), the frequency of any allogeneic transfusion (RR, 0.64; 95% CI, 0.52-0.78) and the postoperative chest tube drainage in the first 24 h by 206 ml (95% CI - 248.23 to - 164.15). TXA did not significantly affect the incidence of postoperative cerebrovascular accident (RR, 0.93; 95%CI, 0.62-1.39), mortality (RR, 0.82; 95%CI, 0.53-1.28), myocardial infarction (RR, 0.90; 95%CI, 0.78-1.05), acute renal insufficiency (RR, 1.01; 95%CI, 0.77-1.32). However, it may increase the incidence of postoperative seizures (RR, 6.67; 95%CI, 1.77-25.20). Moreover, the subgroup analyses in on-pump and off-pump CABG, the sensitivity analyses in trials randomized more than 99 participants and sensitivity analyses that excluded the study with the largest number of participants further strengthened the above results. CONCLUSIONS: TXA is effective to reduce reoperation for bleeding, blood loss and the need for allogeneic blood products in patients undergoing CABG without increasing prothrombotic complication. However, it may increase the risk of postoperative seizures.
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Ponte de Artéria Coronária/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Ácido Tranexâmico/efeitos adversos , Ácido Tranexâmico/uso terapêutico , Administração Intravenosa , Antifibrinolíticos/efeitos adversos , Antifibrinolíticos/uso terapêutico , China/epidemiologia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Ácido Tranexâmico/administração & dosagemRESUMO
AIM: The inhaled anesthetic sevoflurane may induce cognitive impairment in both animals and humans. Previous study has shown that sevoflurane triggers ER stress and may lead to apoptosis in rat hippocampal neurons. In this study, we examined whether sevoflurane caused autophagy and its contributions to sevoflurane induced neuronal cell injury. METHODS: H4 human neuroglioma cells were exposed to 4.1% sevoflurane for 6 h. Cell viability and apoptosis ratio were assessed using a CCK8 kit and flow cytometry, respectively. Autophagosomes in the cells were detected using GFP-LC3 plasmid transfection or transmission electronic microscopy. The expression of LC3B, p62/SQSTM, C/EBP homologous protein (CHOP) and glucose-related protein 78 (GRP78) was assessed with Western blotting. RESULTS: Sevoflurane treatment induced apoptosis and markedly increased the LC3-II level and GFP-LC3 puncta number, decreased p62 expression in H4 cells. Activation of autophagy by rapamycin (1 µmol/L) significantly reduced sevoflurane-induced apoptosis and increased cell viability, whereas inhibition of autophagy with 3-MA (5 mmol/L) caused the opposite effects. Furthermore, sevoflurane treatment markedly increased the expression of CHOP and GRP78, two hallmark proteins of ER stress. Inhibition of ER stress by 4-phenylbutyrate (500 µmol/L) abrogated sevoflurane-induced autophagy and apoptosis, and improved the viability. Moreover, sevoflurane-stimulated expression of CHOP and GRP78 was inhibited by rapamycin, but further enhanced by 3-MA. CONCLUSION: Sevoflurane treatment induces ER stress and activates autophagy, which antagonizes sevoflurane-induced apoptosis in H4 human neuroglioma cells. The results suggest that autophagy may be a potential therapeutic target in preventing sevoflurane-induced neurotoxicity.
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Anestésicos Inalatórios/toxicidade , Autofagia/efeitos dos fármacos , Éteres Metílicos/toxicidade , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Sevoflurano , Sirolimo/farmacologiaRESUMO
BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication with its pathophysiological mechanisms not been fully elucidated. Pyroptosis is a novel type of pro-inflammatory cell death and considered to be associated with cognitive dysfunction. Therefore, our study aimed to examine the effect of pyroptosis on sevoflurane-induced cognitive impairment in aged mice as well as its underlying mechanism. METHODS: A mice model of cognitive impairment was established by sevoflurane exposure and the levels of reactive oxygen species (ROS), N-GSDMD, cleaved caspase-1, ASC, IL-1ß and IL-18, and NLRP3 in hippocampus was determined. To explore the underlying mechanism, a pyroptosis inhibitor, necrosulfonamide (NSA), and a ROS scavenger, N-acetylcysteine (NAC), were administrated before sevoflurane exposure both in vitro and in vivo. Neurobehavioral tests, western blot, transmission electron microscope (TEM) observation, and immunofluorescence staining were performed. RESULTS: Sevoflurane induced hippocampal pyroptosis in the cognitive impairment model. NSA effectively inhibited the pyroptosis and improved cognitive function. Co-labeled immunofluorescence staining suggested sevoflurane induces microglial pyroptosis. Sevoflurane induced pyroptosis accompanied with ROS accumulation in a dose-independent manner in BV2 cells, and NAC effectively reduce the levels of ROS and pyroptosis through NLRP3 inflammasome pathway in both vitro and vivo. Furthermore, NAC could also alleviate sevoflurane-induced cognitive dysfunction. CONCLUSIONS: Microglial pyroptosis in hippocampus mediates sevolfurane-induced cognitive impairment in aged mice via ROS-NLRP3 inflammasome pathway. Both pyroptosis inhibition and ROS scavenging might be potential approaches to ameliorate sevoflurane-induced neurocognitive dysfunction.
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Disfunção Cognitiva , Inflamassomos , Piroptose , Sevoflurano , Animais , Camundongos , Caspase 1/metabolismo , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Hipocampo/metabolismo , Inflamassomos/metabolismo , Microglia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sevoflurano/efeitos adversosRESUMO
It is common for elderly patients to develop postoperative cognitive dysfunction (POCD), but the pathophysiological mechanisms have not yet been fully explored. NLRP3 inflammasome activation and mitophagy impairment was involved in neurodegenerative disease. This study investigated the interaction of NLRP3 inflammasome and mitophagy in sevoflurane-induced cognitive dysfunction. We found that sevoflurane induced cleaved caspase-1 level, IL-1ß and IL-18 maturation, and activated NLRP3 inflammasome in aged mice and the primary hippocampus neuron. The cleaved caspase-1 was demonstrated in microglia of hippocampus. Ac-YVAD-cmk, a selected caspase-1 inhibitor, reduced the expression of cleaved caspase-1, IL-1ß, IL-18 and NLRP3 inflammasome activation induced by sevoflurane. Ac-YVAD-cmk ameliorated learning ability impairment in aged mice induced by sevoflurane using Morris water maze. Moreover, Ac-YVAD-cmk reversed the mitophagy flux dysfunction induced by sevoflurane in aged mice by western blotting, immunostaining and mt-Keima reporters. For the first time, we found caspase-1 inhibitor mitigated mitochondria dysfunction and revised mitophagy impairment induced by sevoflurane.
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Disfunção Cognitiva , Doenças Neurodegenerativas , Camundongos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-18 , Sevoflurano , Mitofagia , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Caspase 1/metabolismoRESUMO
Serotonin 3 receptor antagonists, a commonly used drug for preventing postoperative nausea and vomiting, have recently been reported to decrease the incidence of hypotension and the need for vasoactive drugs after spinal anaesthesia in obstetric surgery. However, it remains unknown whether they could also prevent hypotension after induction of general anaesthesia. In the current study, we aimed to investigate the effect of intravenous granisetron on prophylactic ephedrine for preventing hypotension after general anaesthesia induction in elderly patients. Sixty elderly patients were randomly assigned to receive granisetron or saline control 30 min before induction of general anaesthesia. The first patient in each group received a prophylactic dose of ephedrine (0.15 mg kg-1) to prevent hypotension. The prophylactic dose for each patient was increased or decreased by 0.05 mg/kg based on the efficacy results of the previous patient. The up-down sequential allocation analysis and probit regression was used to calculate the effective dose for 50% of patients (ED50) with prophylactic ephedrine. In the up-down sequential allocation analysis, the ED50 of ephedrine was significantly lower in group granisetron (0.08 mg kg-1 [95% CI, 0.06-0.11 mg kg-1]) when compared with group control (0.14 mg kg-1 [95% CI, 0.13-0.16 mg kg-1]) (P < 0.001). The conclusion was further supported by probit regression analysis (0.09 mg kg-1 [95% CI, 0.05-0.12 mg kg-1] in group granisetron and 0.14 mg kg-1 [95% CI, 0.12-0.16 mg kg-1] in group control). Intravenous granisetron reduced the requirement of prophylactic ephedrine in preventing hypotension after general anaesthesia induction in elderly patients.
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Granisetron , Hipotensão , Gravidez , Feminino , Humanos , Idoso , Granisetron/uso terapêutico , Efedrina , Hipotensão/etiologia , Náusea e Vômito Pós-Operatórios/prevenção & controle , Náusea e Vômito Pós-Operatórios/tratamento farmacológico , Anestesia Geral/efeitos adversos , Método Duplo-CegoRESUMO
The incidence rate of anxiety and depression is significantly higher in patients with inflammatory bowel diseases (IBD) than in the general population. The mechanisms underlying dextran sulfate sodium (DSS)-induced depressive-like behaviors are still unclear. We clarified that IBD mice induced by repeated administration of DSS presented depressive-like behaviors. The paraventricular thalamic nucleus (PVT) was regarded as the activated brain region by the number of c-fos-labeled neurons. RNA-sequencing analysis showed that lipocalin 2 (Lcn2) was upregulated in the PVT of mice with DSS-induced depressive behaviors. Upregulating Lcn2 from neuronal activity induced dendritic spine loss and the secreted protein induced chemokine expression and subsequently contributed to microglial activation leading to blood-brain barrier permeability. Moreover, Lcn2 silencing in the PVT alleviated the DSS-induced depressive-like behaviors. The present study demonstrated that elevated Lcn2 in the PVT is a critical factor for DSS-induced depressive behaviors.
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Doenças Inflamatórias Intestinais , Núcleos da Linha Média do Tálamo , Camundongos , Humanos , Animais , Lipocalina-2/genética , Encéfalo , Proteínas Proto-Oncogênicas c-fos , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: A direct comparison of phenylephrine, metaraminol, and norepinephrine in preventing hypotension during spinal anaesthesia for elective caesarean section has never been made. PATIENTS AND METHODS: Seventy-five parturients scheduled for elective caesarean section were randomly assigned into the three groups. After spinal anaesthesia induction, patients received a bonus dose of vasopressor (norepinephrine 4ug, phenylephrine 50ug, or metaraminol 250ug) combined with continuous infusion (norepinephrine 8ug/mL, phenylephrine 100ug/mL, or metaraminol 500ug/mL) at a rate of 30 mL/h to prevent hypotension. The primary outcome was umbilical arterial (UA) pH and other intraoperative data were also recorded. RESULTS: The UA pH was 7.32±0.03 for metaraminol, 7.31±0.03 for phenylephrine, and 7.31±0.03 for norepinephrine. The 95% CI of MD was -0.011 to 0.026 comparing metaraminol with norepinephrine and 0.0181 to 0.0182 comparing phenylephrine with norepinephrine. Both lower bounds of the 95% CI of MD were above the predetermined lower boundary of clinical non-inferiority of -0.03, indicating both metaraminol and phenylephrine were non-inferior to norepinephrine. Moreover, the incidence of hypotension was lower in metaraminol compared with norepinephrine (P = 0.01). However, the incidence of hypertension was significantly lower in both phenylephrine and metaraminol compared with norepinephrine. CONCLUSION: Both metaraminol and phenylephrine were non-inferior to norepinephrine with respect to neonatal UA pH when used as a bolus and continuous infusion to prevent hypotension during combined spinal-epidural anaesthesia for elective caesarean section.
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Cesárea , Hipotensão/prevenção & controle , Metaraminol/administração & dosagem , Norepinefrina/administração & dosagem , Fenilefrina/administração & dosagem , Simpatomiméticos/administração & dosagem , Adulto , Anestesia Epidural , Raquianestesia , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Gravidez , Estudos ProspectivosRESUMO
BACKGROUND: Difficult airway is a significant cause of anesthesia-associated death and disability. Currently, physical examinations of thyromental distance, mouth opening, Mafampaii classification, etc. combined with X-ray, computed tomography (CT), and other imaging technologies are mainly used to evaluate difficult airways. However, in many special cases, i.e., emergency surgery, imaging examinations cannot be completed preoperatively. Such patients' airway can only be evaluated through general physical examination, which inevitably increases the likelihood of an unexpected difficult airway during anesthesia. CASE SUMMARY: We report a rare case of difficult intubation because of severe upper trachea distortion after induction. Emergency holmium laser lithotripsy was performed under transurethral ureteroscopy because the patient had anuria for 4 d and a creatinine level of 890 µmol/L. Due to the urgency of the condition, chest radiography or chest CT was not examined before surgery and the anesthesiologist did not evaluate the airway adequately, resulting in an unexpected difficult airway. CONCLUSION: The incidence of tracheal malformation and tracheal stenosis is extremely low, but the risk of hypoxia and even death due to difficult airways is extremely high for such patients. It is recommended to complete preoperative imaging examinations of the airway. For life-threatening emergency patients, a pre-anesthesia reassessment should be performed and surgeons should be prepared to prevent and manage the difficult airway.
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The aim of this study was to assess the analgesic efficacy of QLB versus controls in women undergoing cesarean section (CS). We systematically searched Cochrane Library, PUBMED, EMBASE, VIP, WANFANG, and China National Knowledge Infrastructure. Trials were eligible if parturients received QLB during CS. GRADE system was used to assess the certainty of evidence and Trial sequential analyses (TSA) were performed to determine whether the results are supported by sufficient data. Thirteen studies involving 1269 patients were included. Compared to controls, QLB significantly reduced the cumulative postoperative intravenous opioid consumption (in milligram morphine equivalents) at 24 h (MD, - 11.51 mg; 95% CI - 17.05 to - 5.96) and 48 h (MD, - 15.87 mg; 95% CI - 26.36 to - 5.38), supported by sufficient data confirmed by TSA. The postoperative pain scores were significantly reduced by QLB at 4 h, 6 h, 12 h, 24 h, and 48 h postoperatively by QLB compared with control. Moreover, the time to first request for rescue analgesic and the incidence of PONV were also significantly reduced by QLB. The quality of evidence of most results were low and moderate assessed by GRADE.
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Músculos Abdominais/efeitos dos fármacos , Analgesia , Cesárea , Bloqueio Nervoso , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/terapia , Músculos Abdominais/inervação , Analgesia/métodos , Cesárea/efeitos adversos , Feminino , Humanos , Bloqueio Nervoso/métodos , Manejo da Dor , Gravidez , Viés de Publicação , Ensaios Clínicos Controlados Aleatórios como Assunto , Tempo para o Tratamento , Resultado do TratamentoRESUMO
Postoperative cognitive dysfunction (POCD) is a common disorder following surgery, which seriously threatens the quality of patients' life, especially the older people. Accumulating attention has been paid to POCD worldwide in pace with the popularization of anesthesia/surgery. The development of medical humanities and rehabilitation medicine sets higher demands on accurate diagnosis and safe treatment system of POCD. Although the research on POCD is in full swing, underlying pathogenesis is still inconclusive due to these conflicting results and controversial evidence. Generally, POCD is closely related to neuropsychiatric diseases such as dementia, depression and Alzheimer's disease in molecular pathways. Researchers have come up with various hypotheses to reveal the mechanisms of POCD, including neuroinflammation, oxidative stress, autophagy disorder, impaired synaptic function, lacking neurotrophic support, etc. Recent work focused on molecular mechanism of POCD in older people has been thoroughly reviewed and summed up here, concerning the changes of peripheral circulation, pathological pathways of central nervous system (CNS), the microbiota-gut-brain axis and the related brain regions. Accordingly, this article provides a better perspective to understand the development situation of POCD in older people, which is conductive to uncover the pathological mechanism and exploit reasonable treatment strategy of POCD.
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Cognição/fisiologia , Complicações Cognitivas Pós-Operatórias/etiologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Sistema Nervoso Central/patologia , Humanos , Inflamação/complicaçõesRESUMO
Postoperative cognitive dysfunction (POCD) is frequently observed in elderly patients following anesthesia, but its pathophysiological mechanisms have not been fully elucidated. Sevoflurane was reported to repress autophagy in aged rat neurons; however, the role of mitophagy, which is crucial for the control of mitochondrial quality and neuronal health, in sevoflurane-induced POCD in aged rats remains undetermined. Therefore, this study investigated whether mitophagy impairment is involved in sevoflurane-induced cognitive dysfunction. We found sevoflurane treatment inhibited mitochondrial respiration and mitophagic flux, changes in mitochondria morphology, impaired lysosomal acidification, and increased Tomm20 and deceased LAMP1 accumulation were observed in H4 cell and aged rat models. Rapamycin counteracted ROS induced by sevoflurane, restored mitophagy and improved mitochondrial function. Furthermore, rapamycin ameliorated the cognitive deficits observed in aged rats given sevoflurane anesthesia as determined by the Morris water maze test; this improvement was associated with an increased number of dendritic spines and pyramidal neurons. Overexpression of PARK2, but not mutant PARK2 lacking enzyme activity, in H4 cells decreased ROS and Tomm20 accumulation and reversed mitophagy dysfunction after sevoflurane treatment. These findings suggest that mitophagy dysfunction could be a mechanism underlying sevoflurane-induced POCD and that activating mitophagy may provide a new strategy to rescue cognitive deficits.
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Most neurological disorders are caused by abnormal gene translation. Generally, dysregulation of elements involved in the translational process disrupts homeostasis in neurons and neuroglia. Better understanding of how the gene translation process occurs requires detailed analysis of transcriptomic and proteomic profile data. However, a lack of strictly direct correlations between mRNA and protein levels limits translational investigation by combining transcriptomic and proteomic profiling. The much better correlation between proteins and translated mRNAs than total mRNAs in abundance and insufficiently sensitive proteomics approach promote the requirement of advances in translatomics technology. Translatomics which capture and sequence the mRNAs associated with ribosomes has been effective in identifying translational changes by genetics or projections, ribosome stalling, local translation, and transcript isoforms in the nervous system. Here, we place emphasis on the main three translatomics methods currently used to profile mRNAs attached to ribosome-nascent chain complex (RNC-mRNA). Their prominent applications in neurological diseases including glioma, neuropathic pain, depression, fragile X syndrome (FXS), neurodegenerative disorders are outlined. The content reviewed here expands our understanding on the contributions of aberrant translation to neurological disease development.
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BACKGROUND: Controversy still exists regarding the efficiency and safety of ilioinguinal/iliohypogastric nerve (II/IH) block versus transversus abdominis plane (TAP) block for pain management after inguinal hernia repair. The purpose of the current meta-analysis was to perform a relatively credible and comprehensive assessment to compare the efficiency and safety of II/IH versus TAP for pain management after inguinal hernia repair. METHODS: The PUBMED, CENTRAL, and EMBASE were systematically searched. Studies comparing II/IH versus TAP for pain management in adult patients undergoing inguinal herniorrhaphy were included. The results of this study are synthesized and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: Six studies with 632 patients were included in this study. No statistically significant difference was observed between the II/IH and TAP groups in postoperative opioid use, the time to first request for rescue analgesia, the incidence of postoperative nausea and vomiting (PONV), incidence of complication related with nerve blocks and patient satisfaction. The TAP group had a significantly higher pain score at 6 and 8âhours postoperatively (6âhours: mean difference [MD]â=â0.94, 95% confidence interval [CI] 0.67-1.22, Iâ=â0%, Pâ<â.01; 8âhours: MDâ=â1.02, 95% CI 0.3-1.74, Iâ=â59%, Pâ<â.01). However, no statistically significant difference was observed at 1, 2, 4, 12, 24, 48âhours, and 6 months postoperatively. CONCLUSIONS: In general, this meta-analysis revealed that both approaches have similar postoperative opioid consumption and no significant difference in postoperative complication and patient satisfaction. The II/IH block provides excellent analgesic effects at 6 and 8âhours after inguinal herniorrhaphy in compared with the TAP block. However, more high-quality randomized controlled trials with long-term follow-up are still required to make the conclusion.
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Hérnia Inguinal/cirurgia , Herniorrafia/efeitos adversos , Bloqueio Nervoso/métodos , Neuralgia/tratamento farmacológico , Dor Pós-Operatória/tratamento farmacológico , Músculos Abdominais/inervação , Adulto , Idoso , Analgésicos Opioides/uso terapêutico , Feminino , Herniorrafia/métodos , Humanos , Plexo Hipogástrico , Masculino , Pessoa de Meia-Idade , Neuralgia/etiologia , Manejo da Dor/métodos , Dor Pós-Operatória/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Autophagy is associated with regulation of both the survival and death of neurons, and has been linked to many neurodegenerative diseases. Postoperative cognitive dysfunction is commonly observed in elderly patients following anesthesia, but the pathophysiological mechanisms are largely unexplored. Similar effects have been found in aged rats under sevoflurane anesthesia; however, the role of autophagy in sevoflurane anesthesia-induced hippocampal neuron apoptosis of older rats remains elusive. The present study was designed to investigate the effects of autophagy on the sevoflurane-induced cognitive dysfunction in aged rats, and to identify the role of autophagy in sevoflurane-induced neuron apoptosis. We used 20-month-old rats under sevoflurane anesthesia to study memory performance, neuron apoptosis, and autophagy. The results demonstrated that sevoflurane anesthesia significantly impaired memory performance and induced hippocampal neuron apoptosis. Interestingly, treatment of rapamycin, an autophagy inducer, improved the cognitive deficit observed in the aged rats under sevoflurane anesthesia by improving autophagic flux. Rapamycin treatment led to the rapid accumulation of autophagic bodies and autophagy lysosomes, decreased p62 protein levels, and increased the ratio of microtubule-associated protein light chain 3 II (LC3-II) to LC3-I in hippocampal neurons through the mTOR signaling pathway. However, administration of an autophagy inhibitor (chloroquine) attenuated the autophagic flux and increased the severity of sevoflurane anesthesia-induced neuronal apoptosis and memory impairment. These findings suggest that impaired autophagy in the hippocampal neurons of aged rats after sevoflurane anesthesia may contribute to cognitive impairment. Therefore, our findings represent a potential novel target for pro-autophagy treatments in patients with sevoflurane anesthesia-induced neurodegeneration.
Assuntos
Anestésicos Inalatórios/efeitos adversos , Autofagia/efeitos dos fármacos , Transtornos Cognitivos/induzido quimicamente , Éteres Metílicos/efeitos adversos , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Sevoflurano , Sirolimo/farmacologiaRESUMO
OBJECTIVES: A meta-analysis to compare postoperative cognitive function and the time to specific recovery events in elderly patients (aged >65 years) anaesthetized with sevoflurane or desflurane. METHODS: A systematic search of the PubMed(®), Embase(®), Cochrane Library and Chinese Biomedical databases was performed using the keywords 'sevoflurane' and 'desflurane'. Data and characteristics of appropriate randomized controlled trials (RCTs) were extracted. RESULTS: The meta-analysis included five trials (n = 300). The time taken to follow commands (mean difference [MD] -3.27; 95% confidence intervals [CI] -4.95, -1.59), extubation (MD -1.59; 95%CI -2.62, -0.55), orientation (MD -4.31; 95%CI -4.99, -3.62), and recovery room discharge (MD -9.38; 95%CI -13.43, -5.42) were significantly shorter in the desflurane group than in the sevoflurane group. There was no significant between-drug difference in the incidence of postoperative cognitive dysfunction or the time taken to open the eyes. CONCLUSIONS: Desflurane is associated with a faster recovery from general anaesthesia than sevoflurane in elderly patients.