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Malignant hyperthermia (MH) is a potentially fatal inherited pharmacogenetic disorder related to pathogenic variants in the RYR1, CACNA1S, or STAC3 genes. Early recognition of the occurrence of MH and prompt medical treatment are indispensable to ensure a positive outcome. The purpose of this study was to provide valuable information for the early identification of MH by summarizing epidemiological and clinical features of MH. This scoping review followed the methodological framework recommended by Arksey and O'Malley. PubMed, Embase, and Web of science databases were searched for studies that evaluated the epidemical and clinical characteristics of MH. A total of 37 studies were included in this review, of which 26 were related to epidemiology and 24 were associated with clinical characteristics. The morbidity of MH varied from 0.18 per 100 000 to 3.9 per 100 000. The mortality was within the range of 0%-18.2%. Identified risk factors included sex, age, disorders associated with MH, and others. The most frequent initial clinical signs included hyperthermia, sinus tachycardia, and hypercarbia. The occurrence of certain signs, such as hypercapnia, delayed first temperature measurement, and peak temperature were associated with poor outcomes. The epidemiological and clinical features of MH varied considerably and some risk factors and typical clinical signs were identified. The main limitation of this review is that the treatment and management strategies were not assessed sufficiently due to limited information.
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Hipertermia Maligna , Humanos , Hipertermia Maligna/diagnóstico , Hipertermia Maligna/epidemiologia , Hipertermia Maligna/genética , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Fatores de Risco , Medição de RiscoRESUMO
BACKGROUND: Identification of difficult laryngoscopy is a frequent demand in cervical spondylosis clinical surgery. This work aims to develop a hybrid architecture for identifying difficult laryngoscopy based on new indexes. METHODS: Initially, two new indexes for identifying difficult laryngoscopy are proposed, and their efficacy for predicting difficult laryngoscopy is compared to that of two conventional indexes. Second, a hybrid adaptive architecture with convolutional layers, spatial extraction, and a vision transformer is proposed for predicting difficult laryngoscopy. The proposed adaptive hybrid architecture is then optimized by determining the optimal location for extracting spatial information. RESULTS: The test accuracy of four indexes using simple model is 0.8320. The test accuracy of optimized hybrid architecture using four indexes is 0.8482. CONCLUSION: The newly proposed two indexes, the angle between the lower margins of the second and sixth cervical spines and the vertical direction, are validated to be effective for recognizing difficult laryngoscopy. In addition, the optimized hybrid architecture employing four indexes demonstrates improved efficacy in detecting difficult laryngoscopy. TRIAL REGISTRATION: Ethics permission for this research was obtained from the Medical Scientific Research Ethics Committee of Peking University Third Hospital (IRB00006761-2015021) on 30 March 2015. A well-informed agreement has been received from all participants. Patients were enrolled in this research at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn , identifier: ChiCTR-ROC-16008598) on 6 June 2016.
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Laringoscopia , Espondilose , Humanos , Vértebras Cervicais , Hospitais Universitários , Espondilose/cirurgiaRESUMO
In this paper we investigated lipid and metabolite changes in diabetic neuropathy, using untargeted lipidomics and metabolomics analyses of the spinal cords from streptozotocin-treated diabetic rats.170 metabolites and 45 lipids were dysregulated in the painful diabetic neuropathy (PDN) phase. Pathway enrichment analysis revealed perturbations in starch and sucrose, tryptophan, pyrimidine, cysteine and methionine, thiamine, tyrosine, and nucleotides. The disturbance of tyrosine, tryptophan, methionine, triacylglycerol, and phosphatidylethanolamine metabolism indicated that pathological mechanisms in the PDN involved energy metabolism, oxidative stress, and neural reparative regeneration. These revelations offered potential biomarkers for PDN and enriched the comprehension of the complex molecular mechanisms characterizing PDN, establishing a solid foundation for subsequent inquiries into neural convalescence and recovery after PDN.
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BACKGROUND: Airway management is one of the most important techniques in anesthesia practice and inappropriate airway management is related with airway injury, brain hypoxia, and even death. The patients with cervical spondylosis are often confronted with difficult laryngoscopy who are more prone to appear difficult airway, so it is important to figure out valuable predictors of difficult laryngoscopy in these patients. METHODS: We randomly enrolled 270 patients undergoing elective cervical spine surgery and analyzed the cervical mobility data in predicting difficult laryngoscopy. The preoperative X-ray radiological indicators were measured by an attending radiologist. Cormack-Lehane scales were assessed during intubation, and patients with a class III or IV view were assigned to the difficult laryngoscopy group. RESULTS: Univariate analysis showed that the hyomental distance (HMD, the distance between the hyoid bone and the tip of the chin) and the hyomental distance ratio (HMDR, the ratio between HMD in the extension position and the one in the neutral position) might not be suitable indicators in patients with cervical spondylosis. Binary multivariate logistic regression (backward-Wald) analyses identified two independent correlative factors from the cervical mobility indicators that correlated best as a predictor of difficult laryngoscopy: modified Mallampati test (MMT) and C2C6AR (the ratio of the angle between a line passing through the bottom of the second cervical vertebra and a line passing through the bottom of the sixth cervical vertebra in the extension position and the one in the neutral position). The odds ratio (OR) and 95 % CI were 2.292(1.093-4.803) and 0.493 (0.306-0.793), respectively. C2C6AR exhibited the largest area under the curve (0.714; 95 % CI 0.633-0.794). CONCLUSIONS: C2C6AR based on preoperative X-ray images may be the most accurate predictor of cervical mobility indicators for difficult laryngoscopy in patients with cervical spondylosis. TRIAL REGISTRATION: The study was registered at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn ; identifier: ChiCTR-ROC-16,008,598) on June 6, 2016.
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Manuseio das Vias Aéreas , Vértebras Cervicais/diagnóstico por imagem , Laringoscopia , Espondilose/diagnóstico por imagem , Espondilose/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Raios XRESUMO
BACKGROUND: In line with aging populations and increased application of anesthesia and surgery, perioperative neurocognitive disorder (PND) has received growing attention worldwide. Considerable researches into PND are being conducted; however, the quantity and quality of such researches have not been reported. Through a retrospective bibliometric analysis, this study aims to identify and characterize the top 100 cited publications on PND. METHODS: We searched the Web of Science database to find the top 100 cited articles focusing on PND. We collected bibliographic information, including year of publication, country of origin, article type, published journal, citation count, and authorship. To determine changes with time, we compared older and newest articles. RESULTS: The top 100 cited articles were published between 1955 and 2016; the number of citations ranged from 111 to 1248. The United States had the most published papers; clinical trial was the most common article type. The specialty journals of Anesthesiology and Anesthesia & Analgesia were the two most cited journals. Newest articles had a comparable number of citations to older articles, but the former had higher annual citation rates, greater funding disclosures, more focus on basic research, and more open access publications. CONCLUSIONS: This study provides a comprehensive overview of the most cited articles and highlights the increasing attention on PND. High-quality clinical trials with a greater journal impact factor receive more citations. However, there has been a growth in the number of basic science studies as an area of research with respect to the pathogenesis of PND.
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Transtornos Neurocognitivos , Publicações Periódicas como Assunto/estatística & dados numéricos , Bibliometria , Humanos , Fator de Impacto de Revistas , Período Perioperatório , Estudos RetrospectivosRESUMO
BACKGROUND: Preoperative airway assessment help anticipate a difficult airway. We hypothesized that a close association existed between difficult laryngoscopy and the neck circumference/inter-incisor gap ratio (RNIIG). Our aim was to determine its utility in predicting difficult laryngoscopy in cervical spondylosis patients. METHODS: Two hundred thirteen consecutive patients, aged 20-70 years, scheduled to undergo cervical spine surgery under general anesthesia, were recruited. Preoperative assessments included inter-incisor gap (IIG), thyromental distance (TMD), neck circumference (NC), NC/IIG ratio (RNIIG), NC/TMD ratio (RNTMD) and modified Mallampati test (MMT). Cormack-Lehane scales were assessed during intubation. The anesthesiologist was blinded to the airway assessments. RNIIG's ability to predict difficult laryngoscopy was compared with that of established predictors. RESULTS: Difficult laryngoscopy incidence was 16.4%. Univariate analysis showed that male gender, increased age, weight, NC, RNIIG and RNTMD, decreased IIG and TMD, and MMT 3 and 4 were associated with difficult laryngoscopy. Binary multivariate logistic regression analyses identified only one factor that was independently associated with difficult laryngoscopy: RNIIG. The odds ratio and 95% confidence interval (95% CI) were 1.932 (1.504-2.482). RNIIG (≥9.5) exhibited the largest area under the curve (0.80; 95% CI 0.73-0.86) and the highest sensitivity (88.6%; 95% CI 78.1-99.1) and negative predictive value (96.6%; 95% CI 94.0-99.2), confirming its better predictive ability. CONCLUSIONS: RNIIG is a new and simple predictor with a higher level of efficacy, and could help anesthetists plan for difficult laryngoscopy management in cervical spondylosis patients. TRIAL REGISTRATION: ChiCTR-OON-16008320 (April 19th, 2016).
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Incisivo/anatomia & histologia , Laringoscopia , Pescoço/anatomia & histologia , Espondilose/complicações , Adulto , Idoso , Manuseio das Vias Aéreas/métodos , Anestesia Geral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Cuidados Pré-Operatórios , Espondilose/cirurgia , Adulto JovemRESUMO
BACKGROUND: Postoperative cognitive dysfunction (POCD) is a frequent complication in elderly patients undergoing major non-cardiac surgery, but its etiology is still unclear. Cerebral oxygen saturation (ScO2) represents the balance of cerebral oxygen supply and demand. The aim of present study was to evaluate the relationship between perioperative ScO2 and POCD, and to verify the hypothesis that the value of ScO2 after multiple perioperative influential factors could predict POCD in elderly patients undergoing total knee arthroplasty (TKA). METHODS: Seventy eight Patients aged more than 65 years undergoing elective TKA with intrathecal anesthesia were enrolled. Cognitive functions were assessed one day before and 6 days after surgery, and POCD were defined according to ISPOCD. Demographics were recorded. Perioperative ScO2, blood pressure (BP), blood gas analysis and other clinical data were monitored and recorded, then the decrease of ScO2, BP and PaO2 after influential factors were calculated. RESULTS: POCD occurred in 15 patients (19.2 %). BP decreased after anesthesia induction and tourniquet deflation, and PaO2 decreased after cement implantation was higher in POCD group. ScO2 of POCD group is significantly lower than non-POCD group (P < 0.05), and the absolute value and percentage decrease of ScO2 became significant between two groups after multiple influential factors. ScO2 after all influential factors (anesthesia induction, cement implantation and tourniquet deflation) had the best predictive performance for POCD (AUC = 0.742), and the optimal threshold was 66.5 %. CONCLUSIONS: Perioperative ScO2 of patients with POCD is lower than patients without POCD. ScO2 after multiple perioperative influential factors could be an effective predictor for POCD, which reveal an important role of ScO2 decrease in the development of POCD and provide possible treatment target.
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Artroplastia do Joelho/métodos , Transtornos Cognitivos/epidemiologia , Oxigênio/metabolismo , Complicações Pós-Operatórias/epidemiologia , Fatores Etários , Idoso , Raquianestesia/métodos , Gasometria , Encéfalo/metabolismo , Cognição , Transtornos Cognitivos/etiologia , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/etiologiaRESUMO
Exploring the neural mechanisms of awareness is a fundamental task of cognitive neuroscience. There is an ongoing dispute regarding the role of the prefrontal cortex (PFC) in the emergence of awareness, which is partially raised by the confound between report- and awareness-related activity. To address this problem, we designed a visual awareness task that can minimize report-related motor confounding. Our results show that saccadic latency is significantly shorter in the aware trials than in the unaware trials. Local field potential (LFP) data from six patients consistently show early (200-300ms) awareness-related activity in the PFC, including event-related potential and high-gamma activity. Moreover, the awareness state can be reliably decoded by the neural activity in the PFC since the early stage, and the neural pattern is dynamically changed rather than being stable during the representation of awareness. Furthermore, the enhancement of dynamic functional connectivity, through the phase modulation at low frequency, between the PFC and other brain regions in the early stage of the awareness trials may explain the mechanism of conscious access. These results indicate that the PFC is critically involved in the emergence of awareness.
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Neurociência Cognitiva , Córtex Pré-Frontal , Humanos , Estado de Consciência , Movimentos SacádicosRESUMO
Background: Difficult airway remains a great challenge in patients with atlantoaxial dislocation (AAD). Preoperative evaluation and reliable prediction are required to facilitate the airway management. We aimed to screen out reliable radiological indicators for prediction of difficult laryngoscopy in patients with AAD. Methods: A retrospective nested case-control study within a single center longitudinal AAD cohort was conducted to investigate the radiological indicators. All the patients with difficult laryngoscopy from 2010 to 2021 were enrolled as the difficult laryngoscopy group. Others in the cohort without difficult laryngoscopy were randomly selected as the non-difficult laryngoscopy group by individually matching with the same gender, same surgery year, and similar age (±5 years) at a ratio of 6:1. Radiological data on preoperative lateral X-ray images between the two groups were compared. Bivariate logistic regression model was applied to screen out the independent predictive indicators and calculate the odds ratios of indicators associated with difficult laryngoscopy. Receiver operating characteristic curve and area under the curve (AUC) were used to describe the discrimination ability of indicators. Results: A total of 154 patients were finally analyzed in this study. Twenty-two patients with difficult laryngoscopy and matched with 132 controls. Four radiological parameters showed significant difference between the two groups. Among which, ΔC1C2D (the difference of the distance between atlas and axis in the neutral and extension position), owned the largest AUC. Conclusions: ΔC1C2D could be a valuable radiologic predictor for difficult laryngoscopy in patients with AAD.
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Background: Malignant hyperthermia (MH) is a hypermetabolic syndrome with high mortality rates. Early detection and prompt intravenous administration of dantrolene are crucial for effective management of MH. However, there is currently a lack of comprehensive nationwide surveys on the availability of dantrolene and anesthesiologists' understanding of MH in China. Methods: A nationwide survey was conducted between January 2022 and June 2022. Online questionnaires on the cognition of MH among anesthesiologists in China were sent through social platforms to anesthesiologists in mainland China. Data regarding participants' perception of MH-related knowledge, availability of domestic dantrolene, and reported MH cases were collected in this study. Results: Responses were collected from a total of 11,354 anesthesiologists representing 31 provinces across the Chinese mainland. Among the 11 scoring questions, the highest accuracy rates were observed for the question regarding therapeutic drugs for MH (99.3%) and the characteristics of MH (98.0%). Conversely, the question pertaining to the earliest clinical signs of MH had the lowest accuracy rate (23.5%). Significant variations were observed in the scores among different professional titles (P=0.003), academic degree (P<0.001), hospital classification (P<0.001), and urban hierarchy (P<0.001). Of the respondents, 919 (8.1%) anesthesiologists reported dantrolene availability in their hospitals, and 631 (5.6%) indicated unclear. A total of 136 hospitals in this survey reported at least one previous case of MH. Conclusion: Mainland China faces challenges such as insufficient experience in diagnosing and treating MH, as well as difficulty in obtaining dantrolene. To improve the public awareness of MH, it is imperative to establish and promote a refined MH training system. Additionally, a streamlined and rapid dantrolene linkage emergency system should be implemented to ensure prompt access to the drug.
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BACKGROUND: Cervical haemorrhage due to spontaneous rupture of a parathyroid adenoma is a rare complication that may cause life-threatening acute airway compromise. CASE SUMMARY: A 64-year-old woman was admitted to the hospital 1 day after the onset of right neck enlargement, local tenderness, head-turning difficulty, pharyngeal pain, and mild dyspnoea. Repeat routine blood testing showed a rapid decrease in the haemoglobin concentration, indicating active bleeding. Enhanced computed tomography images showed neck haemorrhage and a ruptured right parathyroid adenoma. The plan was to perform emergency neck exploration, haemorrhage removal, and right inferior parathyroidectomy under general anaesthesia. The patient was administered 50 mg of intravenous propofol, and the glottis was successfully visualised on video laryngoscopy. However, after the administration of a muscle relaxant, the glottis was no longer visible and the patient had a difficult airway that prevented mask ventilation and endotracheal intubation. Fortunately, an experienced anaesthesiologist successfully intubated the patient under video laryngoscopy after an emergency laryngeal mask placement. Postoperative pathology showed a parathyroid adenoma with marked bleeding and cystic changes. The patient recovered well without complications. CONCLUSION: Airway management is very important in patients with cervical haemorrhage. After the administration of muscle relaxants, the loss of oropharyngeal support can cause acute airway obstruction. Therefore, muscle relaxants should be administered with caution. Anaesthesiologists should pay careful attention to airway management and have alternative airway devices and tracheotomy equipment available.
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Background: Anorectal diseases are common in the population and include internal, external, and mixed hemorrhoids. Although hemorrhoid surgery is a brief operation, anesthesia, anesthetic drugs, drug concentrations, and anesthesia level control are closely related to postoperative uroschesis. For hemorrhoid surgery, a single spinal block with ropivacaine is commonly used that blocks the S2-S4 parasympathetic nervous system, which in turn governs the voiding reflex, causing postoperative urinary retention; this affects the recovery of patients. This study was performed to investigate the effects of two doses ropivacaine that provided satisfactory analgesia and muscle relaxation and inhibited adverse reflexes on urinary retention after hemorrhoidectomy. Methods: The study included 200 male patients who underwent anorectal surgery with American Society of Anesthesiologists (ASA) grade I-II single elective spinal anesthesia between March 2021 and March 2022. Patients were randomly assigned to 2 groups using a random number table: Group A (n = 100) received 10â mg 0.5% ropivacaine (1.5â ml 1% ropivacaine + 1.5â ml 10% glucose = 3â ml), and Group B (n = 100) received 15â mg 0.5% ropivacaine (1.5â ml 1% ropivacaine + 1.5â ml 10% glucose = 3â ml). Results: The anal sphincter exhibited good relaxation, and no obvious traction pain or significant difference in the time of muscle strength recovery was observed between the 10â mg and 15â mg 0.5% ropivacaine groups (P > 0.05). The 10â mg 0.5% ropivacaine group had shorter time of micturition exceeding 100â ml and lower voiding International Prostate Symptom Score than the 15â mg 0.5% ropivacaine group (P < 0.01). Conclusions: Single spinal anesthesia with 10â mg 0.5% ropivacaine not only provides satisfactory anesthetic effect for hemorrhoidectomy but also has less influence on postoperative uroschesis and is worthy of clinical application. Trial registration: The study was registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn; identifier: ChiCTR2,100,043,686) on February 27, 2021.
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Difficult laryngoscopy is associated with airway injury, and asphyxia. There are no guidelines or gold standards for detecting difficult laryngoscopy. There are many opinions on which predictors to use to detect difficult laryngoscopy exposure, and no comprehensively unified comparative analysis has been conducted. The efficacy and accuracy of deep learning (DL)-based models and machine learning (ML)-based models for predicting difficult laryngoscopy need to be evaluated and compared, under the circumstance that the flourishing of deep neural networks (DNN) has increasingly left ML less concentrated and uncreative. For the first time, the performance of difficult laryngoscopy prediction for a dataset of 671 patients, under single index and integrated multiple indicators was consistently verified under seven ML-based models and four DL-based approaches. The top dog was a simple traditional machine learning model, Naïve Bayes, outperforming DL-based models, the best test accuracy is 86.6%, the F1 score is 0.908, and the average precision score is 0.837. Three radiological variables of difficult laryngoscopy were all valuable separately and combinedly and the ranking was presented. There is no significant difference in performance among the three radiological indicators individually (83.06% vs. 83.20% vs. 83.33%) and comprehensively (83.74%), suggesting that anesthesiologists can flexibly choose appropriate measurement indicators according to the actual situation to predict difficult laryngoscopy. Adaptive spatial interaction was imposed to the model to boost the performance of difficult laryngoscopy prediction with preoperative cervical spine X-ray.
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Background: Emergence agitation (EA) is a conscious disturbance after general anesthesia in adult patients that can lead to severe respiratory or circulatory complications and serious physical injury to patients and caregivers. However, the pathophysiological mechanisms underlying EA remain unclear. The present study aimed to identify serum metabolites with significant alterations in EA patients after general anesthesia and enable inferences on their associations with EA. Methods: EA patients were identified by Richmond Agitation-Sedation Scale (RASS) ≥ + 2 among a cohort of adult patients who received elective surgery under general anesthesia in Peking University Third Hospital between 01 June 2020 and 30 December 2020. We further selected sex-, age-, and surgery type-matched non-EA control patients at a 1:1.5 ratio. Postoperative serum samples were collected from both groups of patients. An untargeted metabolic method was used to identify differences in serum metabolomic profiles between the EA patients and the non-EA patients. Results: A total of 19 EA patients and 32 matched non-EA patients were included in the study. After screening and mapping with a database, 12 metabolites showed significant postoperative alterations in EA patients compared with non-EA patients, and were mainly involved in lipid, fatty acid and amino acid metabolism pathways. Receiver operating characteristic curve analyses indicated that vanillic acid, candoxatril, tiglylglycine, 5-methoxysalicylic acid, decanoylcarnitine, and 24-epibrassinolide may be involved in EA pathogenesis after general anesthesia. Conclusion: In this study, we found differences in the serum levels of vanillic acid, candoxatril, tiglylglycine, 5-methoxysalicylic acid, decanoylcarnitine, and 24-epibrassinolide involved in fatty acid metabolism, lipid metabolism, and amino acid metabolism pathways in EA patients compared with non-EA patients, which may demonstrate an EA pathogenesis-associated molecular pattern and contribute toward better understanding of EA occurrence.
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Background: Visfatin is considered to be a "novel pro-inflammatory cytokine." Neuroinflammatory response is one of the important mechanisms of postoperative delirium (POD). The relationship between preoperative plasma visfatin and POD is unclear. Objective: To investigate the relationship between preoperative plasma visfatin concentrations and POD (primary outcome) in older hip fracture patients and to explore whether it affects POD through inflammatory factors. Materials and methods: This prospective cohort study enrolled 176 elderly patients who were scheduled for hip fracture surgery. Preoperative plasma was collected on the morning of surgery, and visfatin levels were measured. Interleukin (IL)-1 and IL-6 were measured using patients' plasma collected on the first day after surgery. We used the 3-min diagnostic interview for Confusion Assessment Method-defined delirium (3D-CAM) twice daily within the 2 days after surgery to assess whether POD had occurred. Restricted cubic splines and piecewise regression were used to explore the relationship between preoperative plasma visfatin concentrations and POD, and further mediation analysis was used to verify whether visfatin plays a role in POD through regulating inflammatory factors. Results: The incidence of POD was 18.2%. A J-shaped association was observed between preoperative plasma visfatin levels and POD. The risk of POD decreased within the lower visfatin concentration range up to 37.87 ng/ml, with a hazard ratio of 0.59 per 5 ng/ml [odds ratio (OR) = 0.59, 95% confidence interval (CI) = 0.37-0.95], but the risk increased above this concentration (P for non-linearity < 0.001, with a hazard ratio of 1.116 per 10 ng/ml; OR = 1.10, 95% CI = 1.02-1.23). Mediation effect analysis showed that when the plasma visfatin concentration was higher than 37.87 ng/ml, the effect of visfatin on POD was mediated by IL-6 (p < 0.01). A significant indirect association with postoperative plasma IL-6 was observed between preoperative plasma visfatin and POD (adjusted ß = 0.1%; 95% CI = 4.8â¼38.9%; p < 0.01). Conclusion: Visfatin is the protective factor in POD when the preoperative plasma visfatin concentration is below 37.87 ng/ml, but when it exceeds 37.87 ng/ml, the visfatin concentration is a risk factor for POD, which is mediated by postoperative plasma IL-6. The results suggest that preoperative visfatin may have a dual effect on the POD occurrence. Clinical trial registration: [www.ClinicalTrials.gov], identifier [ChiCTR21 00052674].
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Most current circulating miRNA biomarkers are derived from peripheral venous blood, whereas miRNA deregulation in arterial blood in disease conditions has been largely ignored. To explore whether peripheral venous blood miRNAs could represent a bona fide specific miRNA deregulation pattern, we selected hypertension, a disease that is particularly associated with vessels, as the model. Circulating miRNA profiles of arterial and venous blood from spontaneously hypertensive (SHR) rats and their corresponding controls (i.e., WKY rats) were investigated by next-generation miRNA sequencing. Little miRNAs were observed between arterial and venous circulating miRNAs in WKY rats. Interestingly, this number was enhanced in SHR hypertensive rats. Bioinformatical analysis of disease association, enriched target genes and the regulatory transcription factors of these differentially expressed miRNAs implied a potential functional link with cardiovascular disease-related functions. Comparisons between arterial and venous miRNAs in hypertension-versus-control conditions also revealed prominent disease association of circulating miRNAs and their target genes in arteries but not in veins. Moreover, a young non-hypertensive animal model in SHR background (i.e. JSHR) was used as a second control for SHR. Additional transcriptomic analysis and droplet digital PCR validation of arterial and venous deregulated miRNAs among SHR and its two controls (WKY, JSHR) revealed a noticeable consensus of artery-deregulated miRNAs in hypertension and two novel arterial circulating signatures (miR-455-3p and miR-140-3p) of hypertension. These results suggest the necessity of re-evaluating the efficacy of certain venous miRNAs identified in previous studies as potential biomarkers in cardiovascular diseases or a wider disease spectrum.
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MicroRNA Circulante/sangue , Perfilação da Expressão Gênica , Hipertensão/sangue , Animais , Artérias , Biomarcadores/sangue , Biologia Computacional , Sequenciamento de Nucleotídeos em Larga Escala , Hipertensão/genética , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , VeiasRESUMO
Delayed neurocognitive recovery (dNCR) is a prevalent complication after surgery in older adults. Neuroinflammation plays a pivotal role in the pathogenesis of dNCR. Recently,compelling evidence suggests that theinvolvement of microglia pyroptosis in the regulation of neuroinflammation in neurologicaldiseases. Nevertheless, the exact role of microglia pyroptosis in dNCR remains elusive. In the study, in vitro and in vivo models of dNCR were used to examine the potential effects of the mitogenactivated protein kinase signaling pathway on Nod-like receptor protein 3 (NLRP3) inflammasome-mediated microglia pyroptosis and cognitive deficits following surgery. In vivo, we observed surgery-induced upregulation of phosphorylated (p)-c-Jun N-terminal kinases (JNK) in microglia and subsequently NLRP3 inflammasome activation, pyroptosis, and inflammatory cytokines release in mice hippocampus. Interestingly, JNK inhibitor SP600125 significantly attenuated surgery-induced cognitive impairments through inhibiting pyroptosis, inflammatory responses, and reducing immunoreactivity of NLRP3 and gasdermin D N terminus (GSDMD-N) in hippocampal microglia. In vitro, NLRP3 inflammasome- and pyroptosis-associated proteins and immunoreactivity of NLRP3, GSDMD-N, and interleukin-1ß were activated in BV2 microglial cells following lipopolysaccharide (LPS) stimulation. These effects were significantly suppressed in BV2 cells by SP600125 treatment. Furthermore, treatment with NLRP3 specific inhibitor, MCC950, attenuated microglia pyroptosis induced by LPS, but did not rescue LPS-induced increased expression of p-JNK. These results indicate that the JNK pathway is largely upstream of the NLRP3 inflammasome, which exerts a crucial regulatory impact on microglia pyroptosis and inflammatory responses, thus providing a promising avenue to prevent dNCR.
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MAP Quinase Quinase 4/antagonistas & inibidores , Microglia/metabolismo , Doenças Neuroinflamatórias/metabolismo , Piroptose/fisiologia , Animais , Modelos Animais de Doenças , Feminino , Humanos , Interleucina-1beta , Lipopolissacarídeos , Sistema de Sinalização das MAP Quinases , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno , Teste do Labirinto Aquático de Morris , Transdução de SinaisRESUMO
AIMS: Delayed neurocognitive recovery (dNCR) is a common postoperative complication in geriatric surgical patients for which there is no efficacious therapy. Cholecystokinin octapeptide (CCK-8), an immunomodulatory peptide, regulates memory and learning. Here, we explored the effects and mechanism of action of CCK-8 on dNCR. METHODS: We applied laparotomy to establish a model of dNCR in aged mice. Morris water maze and fear conditioning tests were used to evaluate cognition. Immunofluorescence was used to detect the density of CCK-8, A1 reactive astrocytes, glutamatergic synapses, and activation of microglia in the hippocampus. Quantitative PCR was performed to determine mRNA levels of synapse-associated factors. A1 reactive astrocytes, activated microglia, and glutamatergic synapse-associated protein levels in the hippocampus were assessed by western blotting. RESULTS: Administration of CCK-8 suppressed the activation of microglia, the induction of A1 reactive astrocytes, and the expression of tumor necrosis factor alpha, complement 1q, and interleukin 1 alpha in the hippocampus. Furthermore, it promoted glutamatergic synaptogenesis and neurocognitive recovery in aged dNCR model mice. CONCLUSION: Our findings indicated that CCK-8 alleviated cognitive impairment and promoted glutamatergic synaptogenesis by inhibiting the induction of A1 reactive astrocytes and the activation of microglia. CCK-8 is, therefore, a potential therapeutic target for dNCR.
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Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/psicologia , Glutamatos/fisiologia , Neurogênese/efeitos dos fármacos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/psicologia , Sincalida/uso terapêutico , Animais , Astrócitos/efeitos dos fármacos , Disfunção Cognitiva/etiologia , Complemento C1q/metabolismo , Medo/psicologia , Feminino , Interleucina-1/metabolismo , Laparotomia , Ativação de Macrófagos , Aprendizagem em Labirinto , Camundongos , Camundongos Endogâmicos C57BL , Sinapses , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Background: Emergence agitation (EA) in adult patients under general anesthesia leads to increased postoperative complications and heavy medical burden. Unfortunately, its pathogenesis has not been clarified until now. The purpose of the present study was to explore the relationship between preoperative serum metabolites and EA. Methods: We used an untargeted metabolic analysis method to investigate the different metabolomes in the serum of EA patients and non-EA patients undergoing elective surgical procedures after the induction of general anesthesia. A Richmond Agitation-Sedation Scale score ≥ +2 was diagnosed as EA during postoperative emergence. Non-EA patients were matched with EA patients according to general characteristics. Preoperative serum samples of the two groups were collected to investigate the association between serum metabolites and EA development. Results: The serum samples of 16 EA patients with 34 matched non-EA patients were obtained for metabolic analysis. After screening and alignment with databases, 31 altered metabolites were detected between the two groups. These metabolites were mainly involved in the metabolism of lipids, purines, and amino acids. Analyses of receiver-operating characteristic curves showed that the preoperative alterations of choline, cytidine, glycerophosphocholine, L-phenylalanine, oleamide, and inosine may be associated with adult EA. Conclusion: Multiple metabolic abnormalities (including those for lipids, purines, and amino acids) and other pathological processes (e.g., neurotransmitter imbalance and oxidative stress) may contribute to EA. Several altered metabolites in serum before surgery may have predictive value for EA diagnosis. This study might afford new metabolic clues for the understanding of EA pathogenesis.
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INTRODUCTION: Postoperative delirium (POD) is a common neurological complication after hip fracture surgery and is associated with high morbidity and mortality in elderly patients. Although the specific mechanism of POD remains unclear, circadian rhythm disruptions have recently drawn increased attention. To date, only limited postoperative time points of plasma melatonin level measurements were recorded in previous studies, and such data cannot represent a comprehensive melatonin rhythm. The process of anaesthesia (either general anaesthesia (GA) or regional anaesthesia (RA)) is known to influence the melatonin rhythm. However, how these two anaesthesia methods differently affect the postoperative melatonin rhythm is still unknown. Therefore, we hypothesise that RA may attenuate the disruption of the melatonin rhythm, which might decrease the incidence of POD in elderly patients undergoing hip surgery. METHODS AND ANALYSIS: In this prospective cohort clinical trial, 138 patients scheduled for hip fracture surgery will be divided into two groups to receive either GA or RA. The primary aim is to compare the circadian rhythm of melatonin secretion between the two groups and explore its association with the incidence of POD. ETHICS AND DISSEMINATION: The study has been approved by the Medical Science Research Ethics Committees of Beijing Jishuitan Hospital (JLKS201901-04). The results of the study will be published in peer-reviewed international journals. TRIAL REGISTRATION NUMBER: ChiCTR1900027393.