Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 34
Filtrar
1.
BMC Geriatr ; 24(1): 21, 2024 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-38178002

RESUMEN

BACKGROUND: Malnutrition is a common geriatric syndrome and can be targeted preoperatively to decrease the risk of postoperative delirium (POD) in older adult patients. To analyze the value of the prognostic nutritional index (PNI) to predict the incidence of POD in older adult patients with hip fractures. METHODS: This was a prospective, observational, cohort study of older adult patients with hip fractures. Preoperative PNI was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (/µL) using preoperative laboratory results. Patients were divided into POD and non-POD groups using the Confusion Assessment Method (CAM). The risk factors associated with POD as well as the relationship between PNI values and the incidence of POD were analyzed using univariate and multivariate logistic regression analyses. The predictive value of PNI for POD was assessed using receiver operating characteristic curve analysis. RESULTS: In this cohort of 369 patients who underwent hip fracture surgery, 67 patients (18.2%) were diagnosed with POD by the CAM results. Low PNI increased the risk of POD (odds ratio (OR) = 0.928, 95% confidence interval (CI): 0.864-0.997). General anesthesia (OR = 2.307, 95% CI: 1.279-4.162) and Mini-Mental State Examination (MMSE) score (OR = 0.956, 95% CI: 0.920-0.994) were also identified as risk factors for POD. Receiver operating characteristic curve analysis suggested that PNI combined with the anesthetic method and MMSE score may be used as a potential predictive indicator of POD after hip fracture surgery. CONCLUSION: Preoperative PNI value is related to POD in older adult patients with hip fractures. TRIAL REGISTRATION: This secondary analysis study was approved by the Peking University Third Hospital Medical Science Research Ethics Committee (approval No. M2022578) and registered in the Chinese Clinical Trial Registry (ChiCTR2300070569).


Asunto(s)
Delirio , Delirio del Despertar , Fracturas de Cadera , Humanos , Anciano , Evaluación Nutricional , Delirio/diagnóstico , Delirio/epidemiología , Delirio/etiología , Pronóstico , Estudios Prospectivos , Estudios de Cohortes , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Fracturas de Cadera/complicaciones , Fracturas de Cadera/epidemiología , Fracturas de Cadera/cirugía , Factores de Riesgo
2.
J Ultrasound Med ; 42(10): 2215-2232, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37129170

RESUMEN

Low-intensity ultrasound (LI-US) is a non-invasive stimulation technique that has emerged in recent years and has been shown to have positive effects on neuromodulation, fracture healing, inflammation improvement, and metabolic regulation. This study reports the conclusions of a bibliometric analysis of LI-US. Input data for the period between 1995 and 2022, including 7209 related articles in the field of LI-US, were collected from the core library of the Web of Science (WOS) database. Using these data, a set of bibliometric indicators was obtained to gain knowledge on different aspects: global production, research areas, and sources analysis, contributions of countries and institutions, author analysis, citation analysis, and keyword analysis. This study combined the data analysis capabilities provided by the WOS database, making use of two bibliometric software tools: R software and VOS viewer to achieve analysis and data exploration visualization, and predicted the further development trends of LI-US. It turns out that the United States and China are co-leaders while Zhang ZG is the most significant author in LI-US. In the future, the hot spots of LI-US will continue to focus on parameter research, mechanism discussion, safety regulations, and neuromodulation applications.


Asunto(s)
Bibliometría , Curación de Fractura , Humanos , Ultrasonografía , China , Bases de Datos Factuales
3.
Inflamm Res ; 71(7-8): 911-922, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35731253

RESUMEN

BACKGROUND: The aim of this study is to investigate role of Visfatin, one of the pro-inflammatory adipokines, in sepsis-induced intestinal injury and to clarify the potential mechanism. METHODS: C57BL/6 mice underwent cecal ligation and puncture (CLP) surgery to establish sepsis model in vivo. Intestinal epithelial cells were stimulated with LPS to mimic sepsis-induced intestinal injury in vitro. FK866 (the inhibitor of Visfatin) with or without XMU-MP-1 (the inhibitor of Hippo signaling) was applied for treatment. The expression levels of Visfatin, NF-κB and Hippo signaling pathways-related proteins were detected by western blot or immunohistochemistry. The intestinal cell apoptosis and intestinal injury were investigated by TUNEL staining and H&E staining, respectively. ELISA was used to determine the production of inflammatory cytokines. RESULTS: The expression of Visfatin increased in CLP mice. FK866 reduced intestinal pathological injury, inflammatory cytokines production, and intestinal cell apoptosis in sepsis mice. Meanwhile, FK866 affected NF-κB and Hippo signaling pathways. Additionally, the effects of FK866 on inflammatory response, apoptosis, Hippo signaling and NF-κB signaling were partly abolished by XMU-MP-1, the inhibitor of Hippo signaling. In vitro experiments also revealed that FK866 exhibited a protective role against LPS-induced inflammatory response and apoptosis in intestinal cells, as well as regulating NF-κB and Hippo signaling, whereas addition of XMU-MP-1 weakened the protective effects of FK866. CONCLUSION: In short, this study demonstrated that inhibition of Visfatin might alleviate sepsis-induced intestinal injury through Hippo signaling pathway, supporting a further research on Visfatin as a therapeutic target.


Asunto(s)
Nicotinamida Fosforribosiltransferasa , Sepsis , Animales , Citocinas/metabolismo , Vía de Señalización Hippo , Lipopolisacáridos , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Sepsis/metabolismo
4.
BMC Anesthesiol ; 21(1): 186, 2021 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-34215213

RESUMEN

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.


Asunto(s)
Trastornos Neurocognitivos , Publicaciones Periódicas como Asunto/estadística & datos numéricos , Bibliometría , Humanos , Factor de Impacto de la Revista , Periodo Perioperatorio , Estudios Retrospectivos
5.
BMC Anesthesiol ; 18(1): 149, 2018 10 24.
Artículo en Inglés | MEDLINE | ID: mdl-30352555

RESUMEN

BACKGROUND: The effects of the intravenous anesthetics propofol and etomidate on circulation are significantly different; however, their differing effects on miRNA expression in the cardiovascular system are not clearly understood. The purpose of this study is to investigate the effects of these two anesthetics on miRNA expression profiles in the heart and blood vessels. METHODS: Rats were randomly divided into a propofol group and an etomidate group. Spontaneous breathing was maintained throughout the anesthesia process and the rats' oxygen supply was ensured. Heart and thoracic aorta tissue was harvested 3 h after induction. The expression profiles of cardiovascular miRNAs were detected by microarray 4.0 analysis. Twelve representative miRNAs were selected for qRT-PCR validation, and their target genes were predicted using bioinformatics methods. RESULTS: Microarray analysis showed 16 differentially expressed miRNAs in heart tissue from the propofol group compared with the etomidate group (10 up-regulated and 6 down-regulated), while in the blood vessels there were 25 altered miRNAs (10 up-regulated, 15 down-regulated). After verifying 12 representative miRNAs via qRT-PCR, the results showed no significant difference in the expression of miRNAs in the heart tissue, but a significant difference in the expression of 5 miRNAs in vessel tissue between the two groups. Bioinformatics analysis predicts that the target genes of the 5 differentially expressed miRNAs are associated with chemical synapse signaling pathways. CONCLUSIONS: Propofol and etomidate have different effects on the expression of cardiovascular miRNAs, and further research is needed to elucidate the functional consequences of these differentially expressed miRNAs.


Asunto(s)
Anestésicos Intravenosos/farmacología , Etomidato/farmacología , MicroARNs/genética , Propofol/farmacología , Animales , Sistema Cardiovascular/efectos de los fármacos , Sistema Cardiovascular/metabolismo , Biología Computacional , Regulación hacia Abajo , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Regulación hacia Arriba
6.
CNS Neurosci Ther ; 30(3): e14436, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-37736695

RESUMEN

BACKGROUND: Postoperative sleep disorder (PSD) and delirium, which may be associated with surgery and inhalational anesthetics, induce adverse effects in old adults. Emerging evidence indicates that circadian rhythm contributes to various neuropathological diseases, including Alzheimer's disease. Thus, we analyzed the potential role of circadian rhythm in PSD and delirium-like behavior in aged mice and determined whether exogenous melatonin could facilitate entrainment of the circadian rhythm after laparotomy under sevoflurane anesthesia. METHODS: We selected old C57BL/6J mice which receiving laparotomy/sevoflurane anesthesia as model animals. We employed buried food, open field, and Y maze test to assess delirium-like behavior, and electroencephalography/electromyography (EEG/EMG) were used to investigate sleep changes. We analyzed the transcription rhythm of clock genes in superchiasmatic nucleus (SCN) to explore the effects of surgery and melatonin pretreatment on the circadian rhythm. Then, we measured melatonin receptor levels in SCN and ERK/CREB pathway-related proteins in hippocampus and prefrontal cortex to assess their role in PSDs and delirium-like behavior. RESULTS: Laparotomy under sevoflurane anesthesia had a greater influence than sevoflurane alone, leading to sleep disorder, a shift in sleep-wake rhythm, and delirium-like behavior. Bmal1, Clock, and Cry1 mRNA expression showed a peak shift, MT1 melatonin receptor expression level was increased in the SCN, and p-ERK/ERK and p-CREB/CREB were decreased in hippocampus and prefrontal cortex of aged mice 1 day after laparotomy. Melatonin showed significant efficacy in ameliorating PSD and delirium-like behavior and restoring the circadian rhythm, reversing melatonin receptor and ERK/CREB pathway expression abnormalities. In addition, most of the beneficial effect of melatonin was antagonized by luzindole, a melatonin receptor antagonist. CONCLUSIONS: Melatonin receptors in SCN, circadian rhythm, and ERK/CREB signaling pathway participate in the pathophysiological processes of PSD and delirium-like behavior. Melatonin intervention could be a potential preventative approach for PSD and delirium.


Asunto(s)
Delirio , Melatonina , Trastornos del Sueño-Vigilia , Animales , Ratones , Melatonina/farmacología , Melatonina/uso terapéutico , Receptores de Melatonina , Sevoflurano/farmacología , Ratones Endogámicos C57BL , Ritmo Circadiano/fisiología , Trastornos del Sueño-Vigilia/tratamiento farmacológico , Trastornos del Sueño-Vigilia/etiología
7.
Heliyon ; 10(1): e23435, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38148803

RESUMEN

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.

8.
Biochem Pharmacol ; 224: 116261, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38705534

RESUMEN

Delayed neurocognitive recovery (dNCR) is a common complication in geriatric surgical patients. The impact of anesthesia and surgery on patients with neurodegenerative diseases, such as Parkinson's disease (PD) or prion disease, has not yet been reported. In this study, we aimed to determine the association between a pre-existing A53T genetic background, which involves a PD-related point mutation, and the development of postoperative dNCR. We observed that partial hepatectomy induced hippocampus-dependent cognitive deficits in 5-month-old A53T transgenic mice, a model of early-stage PD without cognitive deficits, unlike in age-matched wild-type (WT) mice. We respectively examined molecular changes at 6 h, 1 day, and 2 days after partial hepatectomy and observed that cognitive changes were accompanied by weakened angiotensin-(1-7)/Mas receptor [Ang-(1-7)/MasR] axis, increased alpha-synuclein (α-syn) expression and phosphorylation, decreased methylated protein phosphatase-2A (Me-PP2A), and prompted microglia M1 polarization and neuronal apoptosis in the hippocampus at 1 day after surgery. Nevertheless, no changes in blood-brain barrier (BBB) integrity or plasma α-syn levels in either A53T or WT mice. Furthermore, intranasal administration of selective MasR agonist AVE 0991, reversed the mentioned cognitive deficits in A53T mice, enhanced MasR expression, reduced α-syn accumulation and phosphorylation, and attenuated microglia activation and apoptotic response. Our findings suggest that individuals with the A53T genetic background may be more susceptible to developing postoperative dNCR. This susceptibility could be linked to central α-syn accumulation mediated by the weakened Ang-(1-7)/MasR/methyl-PP2A signaling pathway in the hippocampus following surgery, independent of plasma α-syn level and BBB.


Asunto(s)
Angiotensina I , Hipocampo , Ratones Transgénicos , Fragmentos de Péptidos , Receptores Acoplados a Proteínas G , alfa-Sinucleína , Animales , Humanos , Masculino , Ratones , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Angiotensina I/metabolismo , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Ratones Endogámicos C57BL , Mutación , Fragmentos de Péptidos/metabolismo , Complicaciones Cognitivas Postoperatorias/metabolismo , Complicaciones Cognitivas Postoperatorias/genética , Complicaciones Posoperatorias/metabolismo , Complicaciones Posoperatorias/genética , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética
9.
Brain Sci ; 13(4)2023 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-37190563

RESUMEN

Delayed neurocognitive recovery (dNCR) is a common complication that occurs post-surgery, especially in elderly individuals. The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex plays an essential role in various membrane fusion events, such as synaptic vesicle exocytosis and autophagosome-lysosome fusion. Although SNARE complex dysfunction has been observed in several neurodegenerative disorders, the causal link between SNARE-mediated membrane fusion and dNCR remains unclear. We previously demonstrated that surgical stimuli caused cognitive impairment in aged rats by inducing α-synuclein accumulation, inhibiting autophagy, and disrupting neurotransmitter release in hippocampal synaptosomes. Here, we evaluated the effects of propofol anesthesia plus surgery on learning and memory and investigated levels of SNARE proteins and chaperones in hippocampal synaptosomes. Aged rats that received propofol anesthesia and surgery exhibited learning and memory impairments in a Morris water maze test and decreased levels of synaptosome-associated protein 25, synaptobrevin/vesicle-associated membrane protein 2, and syntaxin 1. Levels of SNARE chaperones, including mammalian uncoordinated-18, complexins 1 and 2, cysteine string protein-α, and N-ethylmaleimide-sensitive factor, were all significantly decreased following anesthesia with surgical stress. However, the synaptic vesicle marker synaptophysin was unaffected. The autophagy-enhancer rapamycin attenuated structural and functional disturbances of the SNARE complex and ameliorated disrupted neurotransmitter release. Our results indicate that perturbations of SNARE proteins in hippocampal synaptosomes may underlie the occurrence of dNCR. Moreover, the protective effect of rapamycin may partially occur through recovery of SNARE structural and functional abnormalities. Our findings provide insight into the molecular mechanisms underlying dNCR.

10.
Clin Neurol Neurosurg ; 226: 107631, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36805349

RESUMEN

BACKGROUND: Postoperative delirium (POD) is a common postoperative neurocognitive complication, especially in older patients. However, satisfactory biomarkers for predicting individual risks of POD have not been confirmed. D-ribose involvement in protein glycation and aggregation plays a pivotal role in age-related neurodegenerative disorders such as Alzheimer's disease. OBJECTIVES: This study aimed to determine whether serum D-ribose concentrations contribute to the early diagnosis of POD. We also discuss the probable mechanisms underlying the development of POD. METHODS: 110 older patients with hip fracture who had undergone internal fixation or hip replacement under general anesthesia and had completed our assessments were selected. Preoperative venous blood (4 ml) was collected before the induction of anesthesia. Postoperative venous blood was obtained at 07:00 and 20:00 h on postoperative day 1 and at 20:00 h on postoperative day 2. On the first 2 postoperative days, the patients were assessed twice daily (at 8:00 and 20:00 h on each day) using the Confusion Assessment Method-Chinese Revision. RESULTS: 15 patients were finally diagnosed with POD. We also included 15 patients without POD who were matched with the recruited patients with POD (1:1) on the basis of age, sex, body mass index and the Mini-Mental State Examination score. Serum ribose concentrations were measured by high-performance liquid chromatography. The demographic characteristics of the groups were matched. Preoperative serum ribose concentrations were significantly higher in patients with POD than in those without POD (p < 0.05) and were also an independent risk factor for POD. Moreover, when the preoperative serum ribose concentration doubled, the risk of POD increased by 1.672 times. CONCLUSIONS: These results indicate that the serum D-ribose concentration may be a potential predictive molecular biomarker for POD, and provide useful information for further pathological mechanism studies.


Asunto(s)
Delirio , Delirio del Despertar , Fracturas de Cadera , Humanos , Anciano , Delirio del Despertar/complicaciones , Ribosa , Delirio/diagnóstico , Delirio/etiología , Fracturas de Cadera/complicaciones , Fracturas de Cadera/cirugía , Complicaciones Posoperatorias , Biomarcadores
11.
Brain Sci ; 13(4)2023 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-37190622

RESUMEN

Postoperative neurocognitive impairment is an urgent problem with global aging accelerating. The prevention and treatment of postoperative neurocognitive impairment have been widely investigated but lack effective strategies. Low-intensity pulsed ultrasound (LIPUS), a non-invasive tool, has shown an effect on neuroprotection, but whether it could attenuate the postoperative neurocognitive impairment and the underlying mechanisms remains unknown. An experimental setup for LIPUS stimulation of the hippocampus was well established. A laparotomy model in aged mice was applied, and a Morris water maze was used to assess cognitive function. RT-qPCR and western blotting were used to detect levels of Piezo1, synapse-associated proteins in the hippocampus, respectively. Immunofluorescent staining was also used to determine the neural activation and Piezo1 expression. The results showed that LIPUS increased synapse-related proteins of the hippocampus and attenuated cognitive impairment in aged mice. Meanwhile, LIPUS suppressed the overexpression of Piezo1 in the hippocampus. We further found that LIPUS promoted Calpain1 activity and increased extracellular regulated protein kinases (Erk) phosphorylation. Our results suggested that LIPUS could improve cognitive impairment and increase hippocampal synaptogenesis through the Piezo1-mediated Calpain1/ Erk pathway. LIPUS could be used as an effective physical intervention to alleviate postoperative cognitive dysfunction in the aged population.

12.
CNS Neurosci Ther ; 29(11): 3322-3338, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37208948

RESUMEN

INTRODUCTION: Emerging evidence suggests that mitochondrial dysfunction plays a crucial role in the pathogenesis of postoperative delayed neurocognitive recovery (dNCR). Mitochondria exist in a dynamic equilibrium that involves fission and fusion to regulate morphology and maintains normal cell function via the removal of damaged mitochondria through mitophagy. Nonetheless, the relationship between mitochondrial morphology and mitophagy, and how they influence mitochondrial function in the development of postoperative dNCR, remains poorly understood. Here, we observed morphological alterations of mitochondria and mitophagy activity in hippocampal neurons and assessed the involvement of their interaction in dNCR following general anesthesia and surgical stress in aged rats. METHODS: Firstly, we evaluated the spatial learning and memory ability of the aged rats after anesthesia/surgery. Hippocampal mitochondrial function and mitochondrial morphology were detected. Afterwards, mitochondrial fission was inhibited by Mdivi-1 and siDrp1 in vivo and in vitro separately. We then detected mitophagy and mitochondrial function. Finally, we used rapamycin to activate mitophagy and observed mitochondrial morphology and mitochondrial function. RESULTS: Surgery impaired hippocampal-dependent spatial learning and memory ability and caused mitochondrial dysfunction. It also increased mitochondrial fission and inhibited mitophagy in hippocampal neurons. Mdivi-1 improved mitophagy and learning and memory ability of aged rats by inhibiting mitochondrial fission. Knocking down Drp1 by siDrp1 also improved mitophagy and mitochondrial function. Meanwhile, rapamycin inhibited excessive mitochondrial fission and improved mitochondrial function. CONCLUSION: Surgery simultaneously increases mitochondrial fission and inhibits mitophagy activity. Mechanistically, mitochondrial fission/fusion and mitophagy activity interact reciprocally with each other and are both involved in postoperative dNCR. These mitochondrial events after surgical stress may provide novel targets and modalities for therapeutic intervention in postoperative dNCR.


Asunto(s)
Dinaminas , Mitofagia , Ratas , Animales , Mitofagia/fisiología , Dinámicas Mitocondriales , Sirolimus
13.
Exp Ther Med ; 26(1): 317, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38895540

RESUMEN

Postoperative delirium (POD), which occurs in hospital up to 1-week post-procedure or until discharge, is a common complication, especially in older adult patients. However, the pathogenesis of POD remains unclear. Although damage to blood-brain barrier (BBB) integrity is involved in the neuropathogenesis of POD, the specific role of the BBB in POD requires further elucidation. Anaesthesia using 2% isoflurane for 4 h results in the upregulation of hippocampal receptor for advanced glycation end-products (RAGE) expression and ß-amyloid accumulation in aged rats. The present study investigated the role of RAGE in BBB integrity and its mechanisms in POD-like behaviours. The buried food, open field and Y maze tests were used to evaluate neurobehavioural changes in aged mice following 2.5% sevoflurane anaesthesia administration with exploratory laparotomy. Levels of tight junction proteins were assessed by western blotting. Multiphoton in vivo microscopy was used to observe the ultrastructural changes in the BBB in the hippocampal CA1 region. Anaesthesia with surgery decreased the levels of tight junction proteins occludin and claudin 5, increased matrix metalloproteinases (MMPs) 2 and 9, damaged the ultrastructure of the BBB and induced POD-like behaviour. FPS-ZM1, a specific RAGE antagonist, ameliorated POD-like behaviour induced by anaesthesia and surgery in aged mice. Furthermore, FPS-ZM1 also restored decreased levels of occludin and claudin 5 as well as increased levels of MMP2 and MMP9. The present findings suggested that RAGE signalling was involved in BBB damage following anaesthesia with surgery. Thus, RAGE has potential as a novel therapeutic intervention for the prevention of POD.

14.
Front Neurosci ; 16: 938874, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35873828

RESUMEN

Postoperative cognitive dysfunction (POCD) is commonly observed during the postoperative period and significantly affects the prognosis of patients. Neuroinflammation plays a vital role in the pathogenesis of POCD. Despite laboratory and clinical research over the past decades, practical pharmacological strategies for the treatment and prevention of POCD are not yet available currently. Nobiletin (NOB) is a natural polymethoxylated flavone. As an enhancer of the clock protein retinoic acid receptor-related orphan receptors (RORs), NOB has been shown to attenuate inflammation and improve cognitive decline. We speculate that NOB is a candidate for the treatment and prevention of POCD. In this study, we investigated whether and how NOB affected surgery-induced neuroinflammation and POCD in adult CD1 mice. NOB pretreatment suppressed exploratory laparotomy-induced systemic inflammation and neuroinflammation in a dose-dependent manner (< 50 mg/kg), and attenuated POCD. Moreover, NOB dose-dependently reversed the decrease of brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1, also known as Arntl) and Rors expression induced by exploratory laparotomy. The expression of Bmal was negatively correlated with tumor necrosis factor-α (TNF-α). Our results suggest that NOB attenuated POCD, possibly via preserving the expression of Bmal and Rors and inhibiting inflammation.

15.
Neurosci Lett ; 784: 136740, 2022 07 27.
Artículo en Inglés | MEDLINE | ID: mdl-35738457

RESUMEN

Postoperative cognitive impairment is more likely to occur in elderly patients and in those with neurodegenerative diseases. The mechanisms underlying this impairment include neuroinflammation and oxidative stress. The increase in reactive oxygen species during oxidative stress causes cellular and molecular injury to neurons, including DNA damage, which aggravate brain dysfunction. Vitamin C has antioxidant effects and improves cognitive function in patients with Alzheimer's disease. However, it is unclear whether it can ameliorate surgery-induced cognitive impairment by inhibiting oxidative stress. In this study, 6-month-old mice overexpressing mutant amyloid precursor protein and presenilin-1 (APP/PS1) were subjected to laparotomy. The open field and fear conditioning tests were used to assess cognitive function. Mice that underwent surgery showed cognitive impairment without changes in spontaneous locomotor activity. Oxidative stress, DNA damage and inflammatory mediators were increased in the hippocampus after surgery. The expression levels of non-homologous end-joining DNA repair-associated proteins, including Ku heterodimer, DNA-dependent protein kinase catalytic subunit, X-ray repair cross complementing 4 (XRCC4) and XRCC4-like factor, were increased after surgery. Vitamin C pretreatment effectively attenuated cognitive dysfunction induced by surgery and reduced oxidative stress and DNA damage. Our findings suggest that DNA damage plays an important role in surgery-induced cognitive dysfunction, and that vitamin C pretreatment may have therapeutic potential as a preventative approach for the cognitive impairment.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Ácido Ascórbico/farmacología , Ácido Ascórbico/uso terapéutico , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Daño del ADN , Modelos Animales de Enfermedad , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Presenilina-1/genética , Presenilina-1/metabolismo
16.
Front Oncol ; 12: 873729, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35619905

RESUMEN

Background: This study aims to report the surgical management, complications, and outcomes for patients with retroperitoneal tumor and venous thrombus. Methods: We retrospectively analyzed 19 cases of retroperitoneal tumor with venous tumor thrombus from August 2015 to March 2021. A new tumor thrombus PUTH-RT grading system was proposed on the basis of the characteristics of the surgical techniques. Results: Two cases of PUTH-RT-1a, two cases of PUTH-RT-1b, six cases of PUTH-RT-2, six cases of PUTH-RT-3, and three cases of PUTH-RT-4 were included. Surgeries were successfully performed in all 19 patients. Among them, five cases (26.3%) were operated via a completely laparoscopic approach and 13 cases (68.4%) via an open approach. One case (5.3%) was converted from laparoscopic to open approach. Five cases (26.3%) experienced postoperative complications. All patients were followed for a median of 14 months. Cancer-associated death occurred in three cases. Distant metastases occurred in seven cases. Conclusions: We propose a new tumor thrombus grading system based on the anatomical characteristics of retroperitoneal tumors with venous tumor thrombus. Retroperitoneal tumor resection and removal of venous tumor thrombi are safe and effective for the treatment of such diseases.

17.
Brain Sci ; 12(7)2022 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-35884759

RESUMEN

(1) Background: Previous evidence demonstrates that tight glycemic control and good physical function could reduce the risk of delirium. This study aimed to investigate whether the occurrence of postoperative delirium (POD) in older hip fracture surgery patients is associated with preoperative glycemic control factors or pre-injury physical performance. (2) Methods: Three-hundred and nine individuals aged over 65 years and scheduled for hip fracture surgery were included at a single center. Glycemic control factors and pre-injury physical performance were assessed preoperatively. The presence of delirium was assessed using the Confusion Assessment Method on postoperative hospitalization days. Univariate and multivariable logistic regression models and a risk prediction model of POD were established. (3) Results: Among the 309 patients, 52 (16.83%) experienced POD during the hospital stay. The numbers of pre-injury physical performance and type 2 diabetes mellitus (T2DM) patients were significantly different in the POD and non-POD groups. The multivariable model showed that development of delirium was significantly explained by preoperative fasting blood glucose (FBG) (OR 0.804, p = 0.004), stair climbing (OR 0.709, p = 0.003), T2DM (odds ratio (OR) 3.654, p = 0.001), and age-adjusted Charlson comorbidity index (ACCI) (OR 1.270, p = 0.038). The area under the receiver operating characteristic curve (AUROC) of the risk prediction model including those covariates was 0.770. (4) Conclusions: More older T2DM patients develop POD after hip fracture surgery than patients without T2DM. A simple assessment of preoperative FBG and pre-injury stair climbing capacity may identify those at high risk for the development of POD. Higher preoperative FBG and good pre-injury stair climbing capacity are protective factors for POD.

18.
Front Med (Lausanne) ; 9: 828867, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35402462

RESUMEN

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.

19.
Front Aging Neurosci ; 13: 741263, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34658843

RESUMEN

Postoperative neurocognitive disorders (po-NCD), including postoperative delirium (POD) and delayed neurocognitive recovery (dNCR), are common in geriatric surgical patients. However, the ideal diagnostic biomarkers to predict individual risks of po-NCDs have not been identified. In this study, proteomic analysis was used to detect dysregulated proteins in three cognitive-related brain regions, the hippocampus, prefrontal cortex, and temporal lobe, of aged dNCR rats. The common affected proteins in these three brain regions were further verified by real-time polymerase chain reaction and western blotting. Furthermore, serum samples from aged rats with dNCR and elderly hip fracture patients with POD were also assessed with enzyme linked immunosorbent assays to investigate the biomarker potential of these dysregulated proteins. The increased expression levels of haptoglobin, caseinolytic protease (ClpP), and alpha-2 macroglobulin (A2M) as well as decreased expression levels of 14-3-3ß/α and biliverdin reductase-A (BVR-A) were validated by proteomic analysis in the hippocampus, prefrontal cortex, and temporal lobe of aged dNCR rats. The increased expression of haptoglobin and decreased expression of 14-3-3ß/α were further demonstrated in the three brain regions by western blotting. Moreover, increased levels of S100A6 and BVR-A in the hippocampus, S100A6 in the prefrontal cortex, and A2M in the temporal lobe were also observed. More intriguingly, both decreased serum 14-3-3ß/α and increased A2M in geriatric POD patients as well as decreased serum ClpP in aged dNCR rats were verified. These results not only indicate potential diagnostic biomarkers for po-NCD but also provide directions for further pathological investigations. Clinical Trial Registration: www.ClinicalTrials.gov, identifier [ChiCTR1900027393].

20.
Front Mol Biosci ; 8: 739227, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34746231

RESUMEN

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.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA