RESUMO
Spinal cord injury (SCI) is a highly disabling neurological disorder that is difficult to treat due to its complex pathophysiology and nerve regeneration difficulties. Hence, effective SCI treatments are necessary. Olfactory ensheathing cells (OECs), glial cells derived from the olfactory bulb or mucosa, are ideal candidates for SCI treatment because of their neuroprotective and regenerative properties, ample supply, and convenience. In vitro, animal model, and human trial studies have reported discoveries on OEC transplantation; however, shortcomings have also been demonstrated. Recent studies have optimized various OEC transplantation strategies, including drug integration, biomaterials, and gene editing. This review aims to introduce OECs mechanisms in repairing SCI, summarize the research progress of OEC transplantation-optimized strategies, and provide novel research ideas for SCI treatment.
Assuntos
Edição de Genes , Traumatismos da Medula Espinal , Animais , Humanos , Regeneração Nervosa , Neuroglia , Neuroproteção , Traumatismos da Medula Espinal/terapiaRESUMO
BACKGROUND: Lung cancer remains a major global health concern due to its high incidence and mortality rates. With advancements in medical treatments, an increasing number of early-stage lung cancer cases are being detected, making surgical treatment the primary option for such cases. However, this presents challenges to the physical and mental recovery of patients. Peplau known as the "mother of psychiatric associations" has formulated a theory of interpersonal relationships in nursing. Through effective communication between nurses and patients over four periods, she has established a good therapeutic nurse-patient relationship. Therefore, this study aimed to explore the effect of perioperative multimodal nursing based on Peplau's interpersonal relationship theory on the rehabilitation of patients with surgical lung cancer. METHODS: We retrospectively analyzed 106 patients with non-small cell lung cancer who underwent thoracoscopic lobectomy at our department between June 2021 and April 2022. Patients were categorized into two groups according to the different nursing intervention techniques. The Peplau's group comprised 53 patients who received targeted nursing interventions, and the control group comprised 53 patients who received conventional nursing care. We observed the patients' illness uncertainty, quality of life, and clinical symptoms in both groups. RESULTS: Patients in the Peplau's group had significantly lower illness uncertainty scores and a significantly higher quality of recovery than those in the control group. However, there were no significant differences in length of post-anesthesia care unit stay, complication rates, and visual analog scores between both groups. CONCLUSION: The multimodal perioperative nursing based on Peplau's interpersonal relationship theory not only reduces the illness uncertainty of patients with lung cancer surgery and improves their QoR but also expands the application of this theory in clinical practice, guiding perioperative nursing of patients with lung cancer. IMPLICATIONS: These findings provide practical information for standardized care in a hectic anesthetic care setting. IMPACT: The assessed anesthesia nursing model helps reduce uncertainty and promote early recovery in patients with cancer at various stages of their disease, which expands the scope of therapeutic practice and existing theories. It also serves as a guide for care in the anesthesia recovery room. REPORTING METHOD: We adhered to the relevant Equator guidelines and the checklist of items in the case-control study report. PATIENT OR PUBLIC CONTRIBUTION: Patients cooperated with medical staff to complete relevant scales.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Feminino , Humanos , Teoria de Enfermagem , Estudos Retrospectivos , Estudos de Casos e Controles , Neoplasias Pulmonares/cirurgia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Qualidade de VidaRESUMO
The latest clinical trials have reported conflicting outcomes regarding the effectiveness of xenon anesthesia in preventing postoperative neurocognitive dysfunction; thus, this study assessed the existing evidence. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases from inception to April 9, 2023, for randomized controlled trials of xenon anesthesia in postoperative patients. We included English-language randomized controlled studies of adult patients undergoing surgery with xenon anesthesia that compared its effects to those of other anesthetics. Duplicate studies, pediatric studies, and ongoing clinical trials were excluded. Nine studies with 754 participants were identified. A forest plot revealed that the incidence of postoperative neurocognitive dysfunction did not differ between the xenon anesthesia and control groups (P = 0.43). Additionally, xenon anesthesia significantly shortened the emergence time for time to opening eyes (P < 0.001), time to extubation (P < 0.001), time to react on demand (P = 0.01), and time to time and spatial orientation (P = 0.04). However, the Aldrete score significantly increased with xenon anesthesia (P = 0.005). Postoperative complications did not differ between the anesthesia groups. Egger's test for bias showed no small-study effect, and a trim-and-fill analysis showed no apparent publication bias. In conclusion, xenon anesthesia probably did not affect the occurrence of postoperative neurocognitive dysfunction. However, xenon anesthesia may effectively shorten the emergence time of certain parameters without adverse effects.
Assuntos
Anestésicos , Delírio , Adulto , Humanos , Criança , Xenônio/farmacologia , Período Pós-Operatório , Anestesia por Inalação/efeitos adversos , Delírio/induzido quimicamenteRESUMO
BACKGROUND: HSK3486 (ciprofol) is a 2,6-disubstituted phenol derivative that acts like propofol as an agonist at the gamma-aminobutyric acid-A (GABA A ) receptor. OBJECTIVE: To investigate the efficacy and safety of HSK3486 for general anaesthesia induction and maintenance. DESIGN: A single-blinded, randomised, parallel-group, phase 3 trial. SETTING: Involving 10 study centres, from November 24, 2020 to January 25, 2021. PATIENTS: A total of 129 patients undergoing nonemergency, noncardiothoracic, and nonneurosurgical elective surgery. INTERVENTION: Patients were randomly assigned at a 2:1 ratio into HSK3486 or propofol groups, to receive HSK3486 (0.4âmg kg -1 ) or propofol (2.0âmg kg -1 ) for induction before a maintenance infusion at initial rates of 0.8 and 5.0âmg kg -1 h -1 , and were adjusted to maintain a bispectral index (BIS) of 40-60 until the end of surgery. MAIN OUTCOME MEASURES: Noninferiority between the drugs was evaluated as the lower limit of the 95% confidence interval (CI) for the between-group difference in the success rate of anesthetic maintenance (primary outcome) >-8%. Secondary outcomes included successful anaesthetic induction, full alertness and spontaneous breathing recovery, time until leaving the postanaesthesia care unit and changes in BIS. Safety profiles were also measured. RESULTS: Of 129 enrolled patients, 128 completed the trial, with 86 in the HSK3486 group and 42 in the propofol group. The success rate for the maintenance of general anaesthesia was 100% for both groups, and noninferiority of HSK3486 was confirmed (95% CI -4.28% to 8.38%). No significant differences were found between the two groups of patients with regard to secondary outcomes (all Pâ >â0.05). There appeared to be a comparable incidence of treatment for emergency adverse events (TEAEs) (80.2% vs. 81.0%, P â=â1.000) and drug-related TEAEs (57.0% vs. 64.3%, P â=â0.451) in the HSK3486 and propofol groups. CONCLUSION: HSK3486 had a noninferior efficacy profile compared to propofol, exhibiting excellent tolerance. TRIAL REGISTRATION: Clinicaltrials.gov, identifier: NCT04511728.
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Anestésicos , Propofol , Humanos , Propofol/efeitos adversos , Método Simples-Cego , Anestesia Geral/efeitos adversos , Procedimentos Cirúrgicos Eletivos , Anestésicos Intravenosos/efeitos adversosRESUMO
Postoperative neurocognitive disorder (PND) is a disease that frequently develops in older patients during the perioperative period. It seriously affects the quality of life of the affected patients. Despite advancements in understanding PND, this disorder's mechanisms remain unclear, including pathophysiological processes such as central synaptic plasticity and function, neuroinflammation, excitotoxicity, and neurotrophic support. Growing evidence suggests that microenvironmental changes are major factors for PND induction in older individuals. Exosomes are carriers for transporting different bioactive molecules between nerve cells in the microenvironment and maintaining intercellular communication and tissue homeostasis. Studies have shown that exosomes and microRNAs (miRNAs) are involved in various physiological and pathological processes, including neural processes related to PND, such as neurogenesis and cell death, neuroprotection, and neurotrophy. This article reviews the effects of exosomes and miRNAs on the brain microenvironment in PND and has important implications to improve PND diagnosis, as well as to develop targeted therapy of this disorder.
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Exossomos , MicroRNAs , Humanos , Idoso , Exossomos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Qualidade de Vida , Comunicação Celular , Transtornos Neurocognitivos/genética , Transtornos Neurocognitivos/metabolismoRESUMO
Spinal cord injury (SCI) is a severe traumatic disease of the central nervous system, with a global prevalence of 236-4187 per million people. This meta-analysis aimed to evaluate the safety and efficacy of mesenchymal stem cells (MSCs) in treating patients with SCI as well as the optimal source and transplantation method of MSCs. PubMed, OVID, Cochrane, Web of Science, and China Biomedical Database were searched up until April 01, 2021. The study was conducted for five endpoints: American Spinal Injury Association (ASIA) motor and sensory score, ASIA grade improvement, Barthel Index (BI), and adverse reactions. Standard meta-analysis and network meta-analysis were performed using Stata 14.0. Eighteen studies with a total of 949 patients, were included in the meta-analysis. Standard meta-analysis showed that MSCs significantly improved ASIA motor score (P < 0.001), sensory score (P < 0.001), ASIA grade (P < 0.001), and BI (P < 0.001) compared to rehabilitation. In addition, in the network meta-analysis, autologous MSCs significantly improved the ASIA motor [MD = 8.01, 95% CI (4.27, 11.76)], sensory score [MD = 17.98, 95% CI (10.04, 25.91)], and BI [MD = 7.69, 95% CI (2.10, 13.29)] compared to rehabilitation. Similarly, compared to rehabilitation, intrathecal injection (IT) of MSCs significantly improved the ASIA motor [MD = 7.97, 95% CI (4.40, 11.53)] and sensory score [MD = 19.60, 95% CI (9.74, 29.46)]. Compared to rehabilitation, however, only the IL of MSCs was associated with more adverse reactions [OR = 17.82, 95% CI (2.48, 128.22)]. According to the results of SUCRA, both autologous MSCs and IT transplantation approaches most improved the neurological function in SCI patients. Cell transplantation using MSCs is effective in patients with SCI and IT of autologous MSCs may be more beneficial.
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Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Traumatismos da Medula Espinal , China , Humanos , Metanálise em Rede , Medula Espinal , Traumatismos da Medula Espinal/terapiaRESUMO
Esophageal cancer is one of the fatal cancers around the world. Dexmedetomidine (DEX) is widely used during anesthesia of esophageal cancer surgery. Nevertheless, the role of DEX in the progression of esophageal cancer remains barely known. The proliferation, apoptosis and metastasis of esophageal cancer cells were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, transwell migration and invasion assays and Western blot assay. The expression of miR-143-3p was measured by quantitative real-time PCR in esophageal cancer tissues and cells. The binding sites between miR-143-3p and epidermal growth factor receptor pathway substrate 8 (EPS8) were predicted by Starbase online software, and the combination was verified by dual-luciferase reporter assay. The murine xenograft model was established using KYSE150 cells to verify the function of DEX in vivo. DEX inhibited the proliferation and metastasis while accelerated the apoptosis of esophageal cancer cells. The abundance of miR-143-3p was lower in esophageal cancer tissues and cells than that in paring normal tissues and normal esophageal mucosal cells Het-1A. MiR-143-3p could be induced by DEX treatment in esophageal cancer cells, and miR-143-3p also suppressed the development of esophageal cancer. EPS8 was a functional target of miR-143-3p, and it played an oncogenic role in esophageal cancer. DEX inhibited the growth of tumor via miR-143-3p/EPS8 in vivo. DEX suppressed the growth and metastasis while facilitated the apoptosis of esophageal cancer cells through upregulating the abundance of miR-143-3p and reducing the level of EPS8 in vivo and in vitro, providing promising target for the treatment of esophageal cancer.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Dexmedetomidina/farmacologia , Neoplasias Esofágicas/tratamento farmacológico , MicroRNAs/metabolismo , Analgésicos não Narcóticos/farmacologia , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Processos de Crescimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Progressão da Doença , Regulação para Baixo/efeitos dos fármacos , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Humanos , Camundongos , Metástase Neoplásica , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
CONTEXT: Thoracic trauma results in multiple rib fractures (MRF), and surgical stabilisation of rib fractures (SSRF) can relieve fracture pain. Epigallocatechin-3-gallate (EGCG) is reported to exhibit beneficial effects in bone-related metabolic and differentiation processes. OBJECTIVE: To study the clinical effect of EGCG on regional analgesia for pain relief in MRF patients after SSRF. MATERIALS AND METHODS: Ninety-seven MRF patients (61 males, 36 females) who were on epidural catheter analgesia after SSRF were recruited. They were randomly divided into: oral EGCG 100 mg (oral grade) twice daily for 10 days and placebo groups. Pain scores, incentive spirometry (IS) volumes, respiratory rate and oxygen saturation (SpO2) were assessed day 10 after SSRF. RESULTS: Comparing results from the placebo and EGCG group, in the 10-day intervention course, oral EGCG reduced pain score (8 at base line vs. 4 at end of intervention in EGCG group, p < 0.05; 4 in EGCG group vs. 6 in placebo group at end of intervention, p < 0.05), improved IS volume (713 at base line vs. 1072 at end of intervention in EGCG group, p < 0.05; 1072 in EGCG group vs. 953 in placebo group at end of intervention, p < 0.05) and respiratory rate (24 at base line vs. 15 at end of intervention in EGCG group, p < 0.05; 15 in EGCG group vs. 19 in placebo group at end of intervention, p < 0.05). However, no further enhancing effect on SpO2 was observed in the EGCG group (0.98 in EGCG group vs. 0.98 in placebo group at end of intervention, p > 0.05). DISCUSSION AND CONCLUSIONS: Although the study is limited by a relatively small sample size and lack of serum factor analysis, the key results and the study design, for the first time, nevertheless pave the way for trials with larger number of patients to understand the effect of EGCG in MRF patients that are undergoing SSRF.
Assuntos
Analgésicos/farmacologia , Catequina/análogos & derivados , Dor/tratamento farmacológico , Fraturas das Costelas/complicações , Adulto , Idoso , Analgesia Epidural/métodos , Analgésicos/administração & dosagem , Catequina/administração & dosagem , Catequina/farmacologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/metabolismo , Dor/etiologia , Medição da Dor , Estudos Prospectivos , Taxa Respiratória , Fraturas das Costelas/cirurgia , Espirometria , Adulto JovemRESUMO
Neuropathic pain is caused by somatosensory nervous system disorder which happens in patients with different diseases. Akt3 regulates innate immune function and plays a role in neuropathic pain pathogenesis in rats. MiR-20b-5p is a microRNA which has been suggested to inhibit Akt3 expression through directly targeting Akt3 mRNA. This research focused on miR-20b-5p function in neuropathic pain by Akt3 expression inhibition. Chronic constriction injury (CCI) was employed to induce neuropathic pain in rats. Paw withdrawal thresholds and paw withdrawal latency were examined to show neuropathic pain development. Expression levels of relative genes or microRNA were checked using qRT-PCR and western blot. Inflammation cytokine levels were measured by enzyme-linked immunosorbent assay kits. In CCI rat model, miR-20b-5p level was declined and Akt3 mRNA level was upregulated. MiR-20b-5p mimics suppressed the enhanced neuropathic pain, neuroinflammation, and Akt3 expression. MiR-20b-5p directly targeted Akt3 mRNA and downregulated the Akt3 expression in rat primary microglial cells. MiR-20b-5p inhibitory function in neuropathic pain was suppressed by the upregulation of Akt3 expression. This research illustrated that miR-20b-5p alleviated neuropathic pain through the inhibition of Akt3 expression in CCI rat model.
Assuntos
MicroRNAs/metabolismo , Microglia/metabolismo , Neuralgia/metabolismo , Traumatismos dos Nervos Periféricos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Regulação para Baixo , MicroRNAs/genética , Neuralgia/etiologia , Neuralgia/genética , Medição da Dor , Limiar da Dor/fisiologia , Traumatismos dos Nervos Periféricos/complicações , Traumatismos dos Nervos Periféricos/genética , Ratos , Ratos Sprague-Dawley , Regulação para CimaRESUMO
BACKGROUND: Microglial activation and the subsequent inflammatory response in the central nervous system play important roles in secondary damage after traumatic brain injury (TBI). High-mobility group box 1 (HMGB1) protein, an important mediator in late inflammatory responses, interacts with transmembrane receptor for advanced glycation end products (RAGE) and toll-like receptors (TLRs) to activate downstream signaling pathways, such as the nuclear factor (NF)-κB signaling pathway, leading to a cascade amplification of inflammatory responses, which are related to neuronal damage after TBI. Omega-3 polyunsaturated fatty acid (ω-3 PUFA) is a commonly used clinical immunonutrient, which has antioxidative and anti-inflammatory effects. However, the effects of ω-3 PUFA on HMGB1 expression and HMGB1-mediated activation of the TLR4/NF-κB signaling pathway are not clear. METHODS: The Feeney DM TBI model was adopted to induce brain injury in rats. Modified neurological severity scores, brain water content, and Nissl staining were employed to determine the neuroprotective effects of ω-3 PUFA supplementation. Assessment of microglial activation in lesioned sites and protein markers for proinflammatory, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, interferon (IFN)-γ, and HMGB1 were used to evaluate neuroinflammatory responses and anti-inflammation effects of ω-3 PUFA supplementation. Immunofluorescent staining and western blot analysis were used to detect HMGB1 nuclear translocation, secretion, and HMGB1-mediated activation of the TLR4/NF-κB signaling pathway to evaluate the effects of ω-3 PUFA supplementation and gain further insight into the mechanisms underlying the development of the neuroinflammatory response after TBI. RESULTS: It was found that ω-3 PUFA supplementation inhibited TBI-induced microglial activation and expression of inflammatory factors (TNF-α, IL-1ß, IL-6, and IFN-γ), reduced brain edema, decreased neuronal apoptosis, and improved neurological functions after TBI. We further demonstrated that ω-3 PUFA supplementation inhibited HMGB1 nuclear translocation and secretion and decreased expression of HMGB1 in neurons and microglia in the lesioned areas. Moreover, ω-3 PUFA supplementation inhibited microglial activation and the subsequent inflammatory response by regulating HMGB1 and the TLR4/NF-κB signaling pathway. CONCLUSIONS: The results of this study suggest that microglial activation and the subsequent neuroinflammatory response as well as the related HMGB1/TLR4/NF-κB signaling pathway play essential roles in secondary injury after TBI. Furthermore, ω-3 PUFA supplementation inhibited TBI-induced microglial activation and the subsequent inflammatory response by regulating HMGB1 nuclear translocation and secretion and also HMGB1-mediated activation of the TLR4/NF-κB signaling pathway, leading to neuroprotective effects.
Assuntos
Lesões Encefálicas Traumáticas/patologia , Encefalite/dietoterapia , Ácidos Graxos Ômega-3/administração & dosagem , Proteína HMGB1/metabolismo , Microglia/efeitos dos fármacos , Neuroprostanos/administração & dosagem , Animais , Edema Encefálico/etiologia , Lesões Encefálicas Traumáticas/complicações , Proteínas de Ligação ao Cálcio/metabolismo , Córtex Cerebral/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Encefalite/etiologia , Encefalite/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Proteínas dos Microfilamentos/metabolismo , Microglia/patologia , Proteínas do Tecido Nervoso/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo , Fatores de TempoRESUMO
The protective effect of tetrahydrocurcumin (THC) after experimental traumatic brain injury (TBI) has been demonstrated, as demonstrated by the inhibition of oxidative stress, mitochondrial dysfunction, and apoptosis. However, the mechanisms underlying this effect are still not well understood. This study was to investigate the neuroprotective effects of THC, and its potential mechanisms, in a rat model of TBI. To this end, rats were divided into 4 groups: the sham group, the TBI group, the TBI + vehicle (V) group, and the TBI + THC group. THC or V was administered via intraperitoneal injection to rats in the TBI + V and TBI + THC groups 30 min after TBI. After euthanasia (24 h after TBI), neurological scores, brain water content, and neuronal cell death in the cerebral cortex were recorded. Brain samples were collected after neurological scoring for further analysis. THC treatment alleviated brain edema, attenuated TBI-induced neuronal cell apoptosis, and improved neurobehavioral function. In addition, NFE2-related factor 2 (Nrf2) expression was upregulated following TBI. These results suggest that THC improves neurological outcome after TBI, possibly by activating the Nrf2 signaling pathway.
Assuntos
Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/prevenção & controle , Curcumina/análogos & derivados , Fator 2 Relacionado a NF-E2/biossíntese , Fármacos Neuroprotetores/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Animais , Curcumina/farmacologia , Curcumina/uso terapêutico , Masculino , Fator 2 Relacionado a NF-E2/agonistas , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologiaRESUMO
Chronic postsurgical pain may have a substantial impact on patient's quality of life, and has highly heterogenous presentation amongst sufferers. We aimed to explore the risk factors relating to chronic pain and the related miRNA phenotypes in patients with lung adenocarcinoma after video-assisted thoracoscopic lobectomy to identify potential biomarkers. Our prospective study involved a total of 289 patients with early invasive adenocarcinoma undergoing thoracoscopic lobotomy and a follow-up period of 3 months after surgery. Blood was collected the day before surgery for miRNA detection and patient information including operation duration, duration of continuous drainage of the chest, leukocyte count before and after operation, and postoperative pain scores were recorded. Using clinical and biochemical information for each patient, the risk factors for chronic postsurgical pain and related miRNA phenotypes were screened. We found that chronic postsurgical pain was associated with higher body mass index; greater preoperative history of chronic pain; longer postoperative drainage tube retention duration; higher numerical rating scale scores one, two, and three days after surgery; and changes in miRNA expression, namely lower expression of miRNA 146a-3p and higher expression of miRNA 550a-3p and miRNA 3613-3p in peripheral blood (p < 0.05). Of these factors, patient body mass index, preoperative history of chronic pain, average numerical rating scale score after operation, and preoperative peripheral blood miRNA 550a-3P expression were independent risk factors for the development of chronic postsurgical pain. Identification of individual risk markers may aid the development and selection of appropriate preventive and control measures.
Assuntos
Adenocarcinoma de Pulmão , Dor Crônica , Neoplasias Pulmonares , MicroRNAs , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/complicações , MicroRNAs/genética , Estudos Prospectivos , Dor Crônica/genética , Dor Crônica/complicações , Qualidade de Vida , Cirurgia Torácica Vídeoassistida/efeitos adversos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/cirurgia , Adenocarcinoma de Pulmão/complicações , Dor Pós-Operatória/genética , Dor Pós-Operatória/prevenção & controle , Fenótipo , Pneumonectomia/efeitos adversosRESUMO
PURPOSE: Esketamine, the S(+) enantiomer of ketamine, exhibits good anesthetic efficacy and controllability; however, its potential clinical applications, particularly in sepsis-associated encephalopathy (SAE), remain underexplored. SAE involves the development of diffuse brain dysfunction after sepsis, leading to markedly increased sepsis-related disability and mortality. In this study, we investigated the effects of esketamine pretreatment on acute SAE. METHODS: Mice were randomly divided into four groups: control (C, n = 22), acute SAE (L, n = 22), esketamine pretreatment + acute SAE (EL, n = 22), and nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor (ML385) + esketamine pretreatment + acute SAE (N + EL, n = 22). Acute SAE was established using intraperitoneal (i.p.) injection of lipopolysaccharide (LPS; 10 mg/kg), while controls received equal amounts of saline. The EL group received daily i.p. injections of esketamine (10 mg/kg) for 5 consecutive days, followed by LPS on day 6. The N + EL group received i.p. injections of ML385 (30 mg/kg) 1 h before esketamine pretreatment. The remainder of treatment followed the same protocol as the EL group. Behavioral tests were performed 24 h post-LPS injection, and whole blood and brain tissues were collected for further analysis. RESULTS: Esketamine improved sepsis symptoms, 7-day survival, and spatial cognitive impairment, without altering locomotor activity. Moreover, esketamine reversed the LPS-induced increase in serum S100 calcium-binding protein ß and neuron-specific enolase levels and reduced hippocampal neuroinflammation, oxidative stress, and neuronal apoptosis in the EL group. However, these neuroprotective effects of esketamine were reversed by ML385. CONCLUSION: The results of our study suggest that esketamine pretreatment mitigates acute SAE, highlighting the involvement of the Nrf2/heme oxygenase-1 pathway in mediating its neuroprotective effects.
Assuntos
Ketamina , Fármacos Neuroprotetores , Encefalopatia Associada a Sepse , Sepse , Camundongos , Animais , Encefalopatia Associada a Sepse/tratamento farmacológico , Ketamina/farmacologia , Ketamina/uso terapêutico , Lipopolissacarídeos/toxicidade , Fator 2 Relacionado a NF-E2 , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Sepse/complicações , Sepse/tratamento farmacológicoRESUMO
Background: Sepsis-associated encephalopathy (SAE) is one of the most ubiquitous complications of sepsis and is characterized by cognitive impairment, poor prognosis, and a lack of uniform clinical diagnostic criteria. Therefore, this study investigated the early diagnostic and prognostic value of serum neuron-specific enolase (NSE) in SAE. Methods: This systematic review and meta-analysis systematically searched for clinical trials with serum NSE information in patients with sepsis in the PubMed, Web of Science, Embase, and Cochrane databases from their inception to April 10, 2023. Included studies were assessed for quality and risk of bias using The Quality Assessment of Diagnostic Accuracy-2 tool. The meta-analysis of the included studies was performed using Stata 17.0 and Review Manager version 5.4. Findings: Eleven studies were included in this meta-analysis involving 1259 serum samples from 947 patients with sepsis. Our results showed that the serum NSE levels of patients with SAE were higher than those of the non-encephalopathy sepsis group (mean deviation, MD,12.39[95% CI 8.27-16.50, Z = 5.9, p < 0.00001]), and the serum NSE levels of patients with sepsis who died were higher than those of survivors (MD,4.17[95% CI 2.66-5.68, Z = 5.41, p < 0.00001]). Conclusion: Elevated serum NSE levels in patients with sepsis are associated with the early diagnosis of SAE and mortality; therefore, serum NSE probably is a valid biomarker for the early diagnosis and prognosis of patients with SAE. Systematic review registration: This study was registered in PROSPERO, CRD42023433111.
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Neurocognitive disorders, such as Alzheimer's disease, vascular dementia, and postoperative cognitive dysfunction, are non-psychiatric brain syndromes in which a significant decline in cognitive function causes great trauma to the mental status of the patient. The lack of effective treatments for neurocognitive disorders imposes a considerable burden on society, including a substantial economic impact. Over the past few decades, the identification of resveratrol, a natural plant compound, has provided researchers with an opportunity to formulate novel strategies for the treatment of neurocognitive disorders. This is because resveratrol effectively protects the brain of those with neurocognitive disorders by targeting some mechanisms such as inflammation and oxidative stress. This article reviews the status of recent research investigating the use of resveratrol for the treatment of different neurocognitive disorders. By examining the possible mechanisms of action of resveratrol and the shared mechanisms of different neurocognitive disorders, treatments for neurocognitive disorders may be further clarified.
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Doença de Alzheimer , Disfunção Cognitiva , Demência Vascular , Humanos , Resveratrol/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Doença de Alzheimer/tratamento farmacológico , Demência Vascular/tratamento farmacológico , EncéfaloRESUMO
Postoperative cognitive dysfunction (POCD) is a neurological complication associated with surgery and anesthesia that is commonly observed in older patients, and it can significantly affect patient prognosis and survival. Therefore, predicting and preventing POCD is important. Regional cerebral oxygen saturation (rSO2) reflects cerebral perfusion and oxygenation, and decreased intraoperative cerebral oxygen saturation has been reported to increase the risk of POCD. In this review, we elucidated the important relationship between the decline in rSO2 and risk of POCD in older patients. We also emphasized the importance of monitoring rSO2 during surgery to predict and prevent adverse perioperative cognitive outcomes. The findings reveal that incorporating intraoperative rSO2 monitoring into clinical practice has potential benefits, such as protecting cognitive function, reducing perioperative adverse outcomes, and ultimately improving the overall quality of life of older adults.
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Circulação Cerebrovascular , Complicações Cognitivas Pós-Operatórias , Humanos , Complicações Cognitivas Pós-Operatórias/etiologia , Idoso , Saturação de Oxigênio , Encéfalo/metabolismo , Qualidade de Vida , Oxigênio/metabolismo , Oxigênio/sangue , Disfunção Cognitiva/etiologiaRESUMO
Intestinal-type gastric adenocarcinoma (IGA) is a common phenotype of gastric cancer. Currently, few studies have constructed nomograms that may predict overall (OS) and cancer-specific survival (CSS) probability after surgery. This study is to establish novel nomograms for predicting the survival of IGA patients who received surgery. A total of 1814 IGA patients who received surgery between 2000 and 2018 were selected from Surveillance, Epidemiology, and End Results database and randomly assigned to the training and validating sets at a ratio of 7:3. Then univariate and multivariate cox regression analyses were performed to screen significant indictors for the construction of nomograms. The calibration curve, the area under the receiver operating characteristic (receiver operating characteristic, ROC) curve (the area under curve, AUC), C-index, net reclassification index (NRI), integrated discrimination improvement (IDI) and decision curve analysis (DCA) curves were applied to assess the performance of the model. The significant outcomes of multivariate analysis revealed that ten variables (age, sex, race, surgery type, summary stage, grade, AJCC TNM stage, radiotherapy, number of regional nodes examined, number of regional nodes positive) were demonstrated to construct the nomogram for OS and ten variables (age, sex, race, surgery type, summary stage, grade, AJCC TNM stage, chemotherapy, number of regional nodes examined, number of regional nodes positive) for CSS. The calibration and AUC uncovered their favorable predictive performance. Subsequently, C-index, NRI, IDI and DCA curves further validated the predicative superiority of nomograms over 7th AJCC Stage System. The validated nomogram provides more reliable OS and CSS predictions for postoperative IGA patients with good accuracy, which can help surgeons in treatment decision-making and prognosis evaluation.
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Adenocarcinoma , Neoplasias Gástricas , Humanos , Nomogramas , Neoplasias Gástricas/cirurgia , Adenocarcinoma/cirurgia , Calibragem , Imunoglobulina A , Prognóstico , Programa de SEERRESUMO
The pathology of spinal cord injury (SCI), including primary and secondary injuries, primarily involves hemorrhage, ischemia, edema, and inflammatory responses. Cell transplantation has been the most promising treatment for SCI in recent years; however, its specific molecular mechanism remains unclear. In this study, bioinformatics analysis verified by experiment was used to elucidate the hub genes associated with SCI and to discover the underlying molecular mechanisms of cell intervention. GSE46988 data were downloaded from the Gene Expression Omnibus dataset. In our study, differentially expressed genes (DEGs) were reanalyzed using the "R" software (R v4.2.1). Functional enrichment and protein-protein interaction network analyses were performed, and key modules and hub genes were identified. Network construction was performed for the hub genes and their associated miRNAs. Finally, a semi-quantitative analysis of hub genes and pathways was performed using quantitative real-time polymerase chain reaction. In total, 718 DEGs were identified, mainly enriched in immune and inflammation-related functions. We found that Cd4, Tp53, Rac2, and Akt3 differed between vehicle and transplanted groups, suggesting that these genes may play an essential role in the transplantation of olfactory ensheathing cells, while a toll-like receptor signaling pathway was significantly enriched in Gene set enrichment analysis, and then, the differences were statistically significant by experimentally verifying the expression of their associated molecules (Tlr4, Nf-κb, Ikkß, Cxcl2, and Tnf-α). In addition, we searched for upstream regulatory molecules of these four central genes and constructed a regulatory network. This study is the first to construct a regulatory network for olfactory ensheathing cell transplantation in treating SCI, providing a new idea for SCI cell therapy.
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Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/terapia , Terapia Baseada em Transplante de Células e Tecidos , Biologia Computacional , Quinase I-kappa B , InflamaçãoRESUMO
Sevoflurane, commonly administered to children as anesthesia, often leads to emergence delirium (ED). Currently, a consensus is lacking among clinicians regarding pharmacological interventions to improve recovery. To determine an effective approach, we compared the effects of several drugs in lowering the incidence of ED after sevoflurane anesthesia in children.We searched online databases for relevant randomized controlled trials (59 studies selected; 5199 NMA-eligible participants) and performed a frequentist network meta-analysis (NMA). This study was registered on PROSPERO (number CRD: 42022329939).All included studies had a low to moderate risk of overall bias. The incidence of ED after sevoflurane anesthesia in children differed according to other drugs administered, and were ranked from high to low according to the surface under the cumulative ranking curve (SUCRA).Sufentanil (91.2%) and dexmedetomidine (77.6%) were more likely to reduce the incidence (SUCRA value) of ED, whereas the placebo (6.5%), ramelteon (11.1%), and magnesium (18%) were less likely to reduce the incidence of ED. Remifentanil (89.3%) ranked first in shortening emergence time, followed by placebo (82.4%) and ketamine (69.7%). Placebo shortened extubation time, followed by remifentanil (66.5%) and alfentanil (61.4%).Sufentanil and remifentanil lowered sevoflurane-induced ED incidences among children and shortened the emergence time more effectively than other drugs. Most adjuvant drugs that are combined with sevoflurane either do not change or may even prolong extubation time. Further research and clinical trials are required to support and update these conclusions.
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Anestesia , Anestésicos Inalatórios , Delírio do Despertar , Éteres Metílicos , Humanos , Criança , Sevoflurano/farmacologia , Sevoflurano/uso terapêutico , Sufentanil , Remifentanil , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Anestésicos Inalatórios/farmacologia , Anestésicos Inalatórios/uso terapêutico , Éteres Metílicos/uso terapêutico , Anestesia GeralRESUMO
INTRODUCTION: Determining the prevalence of chronic postsurgical pain (CPSP) after video-assisted thoracoscopic surgery (VATS) and identifying CPSP predictors should improve the prognosis of patients undergoing VATS. Although several studies have investigated predictors of CPSP after VATS, there were significant dissimilarities in the findings due to the confounding of predictors. METHODS: PubMed, Cochrane, MEDLINE, Web of Science, Chinese Biomedical Literature, and China National Knowledge Infrastructure databases were comprehensively searched using the Medical Subject Headings terms "pain, postoperative," "thoracic surgery, video-assisted," and all related free terms from inception until March 27, 2022. The Stata metaprop package was used to comprehensively analyze the incidence of CPSP following VATS. Furthermore, the pooled odds ratios (OR) or the standardized mean differences (SMD) and their corresponding 95% confidence intervals (95% CI) were calculated, and qualitative analyses were performed for predictors that could not be assessed quantitatively to evaluate the effects of the included risk factors on the occurrence of CPSP. Unadjusted odds ratios were utilized to consider the impact of non-significant estimates if the original study did not report them. RESULTS: Of the 4302 studies, 183 were considered eligible, and 17 were finally included in this study. The overall incidence of CPSP after VATS was 35.3% (95% CI 27.1-43.5%). The qualitative synthesis results revealed that female sex, age, and acute postoperative pain were definite predictors of CPSP after VATS. The number of ports, operation time, duration of drainage, and insufficient analgesia were also considered predictors. Consistent, quantitative synthesis results also showed that the aforementioned predictors were closely related to the occurrence of CPSP after VATS. Only by quantitative analysis, postoperative chemotherapy and an educational level less than junior school were also risk factors for CPSP. Other predictors displayed no evidence or unclear evidence of association with CPSP after VATS. CONCLUSION: This study preliminarily determined the incidence of CPSP after VATS based on the existing literature. Female sex, age, and acute pain were identified as risk factors for CPSP after VATS, and other potential risk factors were also identified and analyzed. However, as a result of the inclusion of retrospective studies and inevitable limitations in this systematic review and meta-analysis, the results of this study still need to be verified by large-scale prospective clinical studies. TRIAL REGISTRATION: CRD42022323179.