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Purpose: To compare the impact of erector spinae plane block (ESPB) and paravertebral block (PVB) on the quality of postoperative recovery (QoR) of patients following laparoscopic sleeve gastrectomy (LSG). Methods: A total of 110 patients who underwent elective LSG under general anesthesia were randomly assigned to receive either ultrasound-guided bilateral ESPB or PVB at T8 levels. Before anesthesia induction, 40 mL of 0.33% ropivacaine was administered. The primary outcome was the QoR-15 score at 24 hours postoperatively. Results: At 24 hours postoperatively, the QoR-15 score was comparable between the ESPB and PVB groups (131 (112-140) vs. 124 (111-142.5), P = 0.525). Consistently, there was no significant difference in QoR-15 scores at 48 hours postoperatively, numerical rating scale (NRS) pain scores at any postoperative time points, time to first ambulation, time to first anal exhaust, postoperative cumulative oxycodone consumption, and incidence of postoperative nausea and vomiting (PONV) between the two groups (all P > 0.05). No nerve block-related complications were observed in either group. Conclusion: In patients undergoing LSG, preoperative bilateral ultrasound-guided ESPB yields comparable postoperative recovery to preoperative bilateral ultrasound-guided PVB.
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Gastrectomía , Laparoscopía , Bloqueo Nervioso , Dolor Postoperatorio , Humanos , Femenino , Bloqueo Nervioso/métodos , Masculino , Gastrectomía/efectos adversos , Gastrectomía/métodos , Laparoscopía/efectos adversos , Adulto , Dolor Postoperatorio/prevención & control , Persona de Mediana Edad , Anestésicos Locales/administración & dosificación , Anestésicos Locales/uso terapéutico , Ropivacaína/administración & dosificación , Ropivacaína/uso terapéutico , Ultrasonografía Intervencional/métodos , Dimensión del Dolor , Músculos Paraespinales/inervación , Músculos Paraespinales/diagnóstico por imagen , Resultado del Tratamiento , Obesidad Mórbida/cirugía , Náusea y Vómito Posoperatorios/epidemiología , Anestesia General/efectos adversosRESUMEN
Objective: Insulin attaches insulin receptor to activate the PI3-kinase/Akt signaling to maintain glucose homeostasis and inhibit apoptosis. This study determined whether preconditioning with insulin and glucose protects the kidney against ischemia-reperfusion injury (IRI). Methods: Kidney IRI was performed in C57BL/6 mice by clamping the renal vessels for 30 min, followed by reperfusion for 24 h. A total subcutaneous 0.1 unit of insulin along with 10% glucose in drinking water was treated on the mice for 24 h before kidney IRI. The kidney function and injuries were investigated through the determination of BUN and Cr in blood plasma, as well as the apoptosis and the expression of P-AKT, BAX, and caspase-3 in the kidneys. The role of P-AKT in insulin-treated IRI kidneys was tested using an AKT inhibitor. The effects of the preconditional duration of insulin and glucose on IRI kidneys were investigated by expanding the treatment duration to 1, 3, and 6 days. Results: Preconditioning with insulin and glucose protected the kidney against IRI as manifested by a decrease in creatinine and BUN and a reduction of kidney tubular injury. The protection effect was mediated by P-AKT-BAX-caspase-3 signaling pathway resulting in suppression of apoptotic cell death. An AKT inhibitor partially reversed the protective effects of preconditional insulin. The preconditional duration for 1, 3, and 6 days had no differences in improving kidney functions and pathology. Conclusion: A short-term preconditioning with insulin and glucose protected the kidney from IRI through the activation of p-AKT and subsequent reduction of BAX-caspase-3-induced apoptosis. The short-term precondition provides a practicable strategy for protecting the kidney against predictable IRI, such as kidney transplant and major surgical operations with high risk of hypotension.
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Caspasa 3 , Glucosa , Insulina , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas c-akt , Daño por Reperfusión , Transducción de Señal , Proteína X Asociada a bcl-2 , Animales , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/prevención & control , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratones , Transducción de Señal/efectos de los fármacos , Insulina/farmacología , Masculino , Caspasa 3/metabolismo , Glucosa/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Riñón/efectos de los fármacos , Riñón/patología , Riñón/metabolismo , Apoptosis/efectos de los fármacosRESUMEN
Objective: This study aimed to estimate the effects of the volume of preperitoneal balloon (PPB) on arterial and venous hemorrhage in a swine pelvic fracture model. Methods: Twenty-four swine were randomized into 0-mL, 500-mL, 800-mL, and 1000-mL intra-hematoma PPB groups. They were subjected to open-book pelvic fracture and reproducible injuries in the external iliac artery and vein. The pelvic binder and IH-PPBs with different volumes of fluid were applied to control the active hemorrhage after arterial and venous injuries. The survival time and rate during 60-min observation and digital subtraction angiography (DSA) images were the primary endpoints in this study. Secondary endpoints included survival rate within 70 min, peritoneal pressure, hemodynamics, blood loss, infusion fluid, blood pH, and lactate concentration. Results: Our results indicated that the 800-mL and 1000-mL groups had a higher survival rate (0%, 50%, 100% and 100% for 0, 500, 800, and 1000-mL groups respectively; p < 0.0001) and longer survival time (13.83 ± 2.64, 24.50 ± 6.29, 55.00 ± 6.33, and 60.00 ± 0.00 min for 0, 500, 800, and 1,000 groups respectively; p < 0.0005) than the 0-mL or 500-mL groups during the 60 min observation. Contrastingly, survival rate and time were comparable between 800-mL and 1000-mL groups during the 60-min observation. The IH-PPB volume was associated with an increase in the pressure of the balloon and the preperitoneal pressure but had no effect on the bladder pressure. Lastly, the 1000-mL group had a higher mean arterial pressure and systemic vascular resistance than the 800-mL group. Conclusion: IH-PPB volume-dependently controls vascular bleeding after pelvic fracture in the swine model. IH-PPB with a volume of 800 mL and 1000 mL efficiently managed pelvic fracture-associated arterial and venous hemorrhage and enhanced survival time and rate in the swine model without evidences of visceral injury.
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OBJECTIVE: Heart disease poses a significant global health challenge. Transesophageal echocardiography (TEE) has gained prominence in clinical practice because of advancements in visual medicine. The present bibliometric analysis provides an overview of TEE research, identifies trends, and highlights emerging topics. METHODS: A comprehensive search of TEE-related literature from the establishment of the Web of Science Core Collection (WOSCC) until 2022 was conducted. Utilizing the CiteSpace software, we performed an in-depth analysis of the literature data encompassing disciplines, publication years, countries, institutions, authors, journals, cited references, and keywords. RESULTS: A total of 17 032 TEE-related articles were included in this study. The most active disciplines in TEE research were Cardiac & Cardiovascular Systems, Anesthesiology, and Respiratory System. The number of publications displayed a consistent upward trajectory over the years. Notably, research contributions predominantly originated from developed countries, mainly Europe and North America, with the United States, Germany, Italy, and Japan leading the way. Analysis of institutions, authors, and journals revealed the United States' significant role in TEE research. Furthermore, the analysis of cited references and keywords identified the treatment of patent foramen ovale and its association with stroke as emerging hot topics in recent years. CONCLUSIONS: This study highlights that TEE remains a research hotspot, with the United States at the forefront. Future research should investigate the relationship between heart disease and brain function.
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Ecocardiografía Transesofágica , Cardiopatías , Humanos , Corazón , Bibliometría , Europa (Continente)RESUMEN
BACKGROUND: Oxidative stress is known as a hallmark of cerebral ischaemiaâreperfusion injury and it exacerbates the pathologic progression of ischaemic brain damage. Vialinin A, derived from a Chinese edible mushroom, possesses multiple pharmacological activities in cancer, Kawasaki disease, asthma and pathological scarring. Notably, vialinin A is an inhibitor of ubiquitin-specific peptidase 4 (USP4) that shows anti-inflammatory and antioxidative properties. However, the precise effect of vialinin A in ischaemic stroke, as well as its underlying mechanisms, remains largely unexplored. PURPOSE: The present research focuses on the impacts of vialinin A on oxidative stress and explores the underlying mechanisms involved while also examining its potentiality as a therapeutic candidate for ischaemic stroke. METHODS: Mouse ischaemic stroke was conducted by MCAO surgery. Vialinin A was administered via lateral ventricular injection at a dose of 2 mg/kg after reperfusion. Subsequent experiments were meticulously conducted at the appropriate time points. Stroke outcomes were evaluated by TTC staining, neurological score, Nissl staining and behavioural analysis. Co-IP assays were operated to examine the protein-protein interactions. Immunoblot analysis, qRT-PCR, and luciferase reporter assays were conducted to further investigate its underlying mechanisms. RESULTS: In this study, we initially showed that administration of vialinin A alleviated cerebral ischaemiaâreperfusion injury-induced neurological deficits and neuronal apoptosis. Furthermore, vialinin A, which is an antioxidant, reduced oxidative stress injury, promoted the activation of the Keap1-Nrf2-ARE signaling pathway and increased the protein degradation of Keap1. The substantial neuroprotective effects of vialinin A against ischaemic stroke were compromised by the overexpression of USP4. Mechanistically, vialinin A inhibited the deubiquitinating enzymatic activity of USP4, leading to enhanced ubiquitination of Keap1 and subsequently promoting its degradation. This cascade caused the activation of Nrf2-dependent antioxidant response, culminating in a reduction of neuronal apoptosis and the amelioration of neurological dysfunction following ischaemic stroke. CONCLUSIONS: This study demonstrates that inhibition of USP4 to activate Keap1-Nrf2-ARE signaling pathway may represent a mechanism by which vialinin A conferred protection against cerebral ischaemiaâreperfusion injury and sheds light on its promising prospects as a therapeutic intervention for ischaemic stroke.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Daño por Reperfusión , Accidente Cerebrovascular , Compuestos de Terfenilo , Ratones , Animales , Antioxidantes/farmacología , Antioxidantes/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Isquemia Encefálica/tratamiento farmacológico , Factor 2 Relacionado con NF-E2/metabolismo , Accidente Cerebrovascular/tratamiento farmacológico , Estrés Oxidativo , Daño por Reperfusión/metabolismoRESUMEN
PURPOSE: Previous research has not evaluated the potential effect of erector spinae plane block (ESPB) on quality of recovery (QoR) after laparoscopic sleeve gastrectomy. Therefore, we investigated the effect of an ultrasound-guided ESPB performed on patients with obesity who have undergone laparoscopic sleeve gastrectomy, measured using the 15-item QoR (QoR-15) scale. METHODS: A total of 172 patients were enrolled in the study who were aged 18 to 65 years, had a body mass index ≥30 kg/m², were classified as having American Society of Anaesthesiologists physical status â ¡ to â ¢, and had undergone laparoscopic sleeve gastrectomy. The patients were randomly divided into an ESPB group and a sham group (treated with normal saline). The primary outcome was the QoR-15 score, measured using the questionnaire 24 and 48 hours after surgery. The secondary outcomes were postoperative pain score, postoperative cumulative analgesic drug consumption, number of patient-controlled analgesia (PCA) requests, rate of rescue analgesia required at 48 hours, incidence of respiratory complications, and nerve block-related complications. The time of discharge from the postanesthesia care unit, postoperative activity, and length of stay at the hospital were also recorded. FINDINGS: There was no significant difference in the global QoR-15 scores 24 and 48 hours after the operation. However, the groups' subdimension scores for the emotional state in QoR-15 at 24 and 48 hours after surgery were statistically different (P < 0.05). Meanwhile, patients in the ESPB group who indicated they were "feeling rested" at 24 and 48 hours after surgery and "having a feeling of general well-being" at 24 hours after surgery were significantly better than those in the sham group (P < 0.05). Compared with the sham group, participants in the ESPB group had lower resting pain scores at 6 and 12 hours after surgery and lower movement pain scores at 6, 12, 24, and 36 hours after surgery (P < 0.05). There was no statistical difference between the groups in postoperative cumulative analgesic drug consumption, number of PCA requests, incidence of respiratory complications, time of discharge from the postanesthesia care unit, or postoperative activity. IMPLICATIONS: Our results indicate that a single ESPB does not improve the global QoR-15 scores after laparoscopic sleeve gastrectomy. However, the visual analog scale score for postoperative pain is reduced.
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Laparoscopía , Bloqueo Nervioso , Humanos , Obesidad , Analgesia Controlada por el Paciente , Gastrectomía/efectos adversos , Dolor Postoperatorio/tratamiento farmacológico , Ultrasonografía Intervencional , Laparoscopía/efectos adversos , Analgésicos OpioidesRESUMEN
Purpose: This study aims to compare the conventional lung protective ventilation strategy (LPVS) with driving pressure-guided ventilation in obese patients undergoing laparoscopic sleeve gastrectomy (LSG). Methods: Forty-five patients undergoing elective LSG under general anesthesia were randomly assigned to the conventional LPVS group (group L) or the driving pressure-guided ventilation group (group D) using random numbers generated by Excel. The primary outcome was the driving pressure of both groups 90 min after pneumoperitoneum. Results: After 30 min of pneumoperitoneum, 90 min of pneumoperitoneum, 10 min of closing the pneumoperitoneum, and restoring the supine position, the driving pressure of group L and group D were 20.0 ± 2.9 cm H2O vs 16.6 ± 3.0 cm H2O (P < 0.001), 20.7 ± 3.2 cm H2O vs 17.3 ± 2.8 cm H2O (P < 0.001), and 16.3 ± 3.1 cm H2O vs 13.3 ± 2.5 cm H2O (P = 0.001), respectively; the respiratory compliance of groups L and D were 23.4 ± 3.7 mL/cm H2O vs 27.6 ± 5.1 mL/cm H2O (P = 0.003), 22.7 ± 3.8 mL/cm H2O vs 26.4 ± 3.5 mL/cm H2O (P = 0.005), and 29.6 ± 6.8 mL/cm H2O vs 34.7 ± 5.3 mL/cm H2O (P = 0.007), respectively. The intraoperative PEEP in groups L and group D was 5 (5-5) cm H2O vs 10 (9-11) cm H2O (P < 0.001). Conclusion: An individualized peep-based driving pressure-guided ventilation strategy can reduce intraoperative driving pressure and increase respiratory compliance in obese patients undergoing LSG.
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INTRODUCTION: Acute postoperative pain is a major concern among surgical patients. Thus, this study established a new acute pain management model and compared the effects of the acute pain service (APS) model in 2020 and the virtual pain unit (VPU) model in 2021 on postoperative analgesia quality. METHODS: This retrospective, single-center clinical study involved 21,281 patients from 2020 to 2021. First, the patients were grouped on the basis of their pain management model (APS and VPU). The incidence of moderate to severe postoperative pain (MSPP) [numeric rating scale (NRS) score ≥ 5], postoperative nausea and vomiting (PONV), and postoperative dizziness were recorded. RESULTS: The VPU group recorded significantly lower MSPP incidence (1-12 months), PONV, and postoperative dizziness (1-10 months and 12 months) compared with the APS group. In addition, the annual average incidence of MSPP, PONV, and postoperative dizziness in the VPU group was significantly lower than in the APS group. CONCLUSIONS: The VPU model reduces the incidence of moderate to severe postoperative pain, nausea, vomiting, and dizziness; hence, it is a promising acute pain management model.
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ABSTRACT: Objective: This study evaluated the feasibility of a combination of pelvic binder and rectal balloon compression in managing fatal venous hemorrhage in a canine model of pelvic fracture. Methods: Rectums from humans (rectal cancer patients), swine, and canines were retrieved to determine their elasticity by measuring their stress and strain. Canines were selected as the animal model in this study because their rectum demonstrated more reversible strain than swine rectum. Doppler ultrasound was used to assess the effect of rectal balloon volume on the blood flow of pelvic iliac blood vessels in three canines. A rectal balloon of 250 mL was chosen to control pelvic venous bleeding as it could provide a peak effect in reducing the blood flow of bilateral internal iliac veins. Then, the open-book pelvic fracture with fatal bleeding of both internal iliac veins animal model was built. The animals were divided into four groups after the modeled surgery to undergo no treatment, pelvic binder, rectal balloon compression, or a combination of pelvic binder and rectal balloon compression. The treatment efficacy was evaluated based on their survival time, survival rate, blood loss, bleeding rate, infusion rate, blood pH, lactate concentration, the stability of hemodynamics, blood loss, and fluid infusion volume. Results: Our results showed that after the reproducible injuries in both internal iliac veins, the combination of pelvic binder and rectal balloon compression was associated with the best survival rate and survival time compared with the other treatment groups. In addition, the combination of pelvic binder and rectal balloon compression exhibited more stable hemodynamics than the pelvic binder or rectal balloon compression treatment alone. Conclusions: This study demonstrated the potential feasibility of using pelvic binder combined with rectal balloon compression to manage the fatal venous bleeding in pelvic fractures.
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Fracturas Óseas , Recto , Humanos , Animales , Perros , Porcinos , Hemorragia/complicaciones , Pelvis , Vena Ilíaca/lesiones , Vena Ilíaca/cirugíaRESUMEN
Background: Both epidural and combined spinal-epidural (EA and CSEA) analgesia can induce intrapartum maternal fever. CSEA has a more rapid onset and wider nerve block than EA. Therefore, CSEA might have a different profile of intrapartum maternal fever, including higher temperatures or earlier occurrence. This randomized clinical trial was to determine whether CSEA could cause maternal fever earlier than EA. Methods: A randomized, double-blind, controlled clinical trial was performed on 233 nulliparous full-term pregnant women during vaginal delivery. The pregnant women were randomly allocated into the EA group (n = 113) and the CSEA group (n = 120). The fever latent period, from analgesia start to fever occurrence, was the primary endpoint in this study. The temperature was measured every 30 min using an eardrum thermometer during labor analgesia. The fever was defined as an eardrum temperature of ≥38 °C. Results: No difference was found in the maternal fever rate between the EA and the CSEA groups (10/113 vs. 7/120, P = 0.356). There was no significant difference in the fever latent period between the two groups (4.75 ± 0.86 h vs. 3.79 ± 2.2 h, p = 0.305). The temperatures at all points had no differences between EA and CSEA. Conclusion: CSEA had a similar latent fever period as EA. A further study is warranted to confirm the similar characteristic between CSEA and EA in the development of intrapartum maternal fever. Clinical trial registration: www.chictr.org.cn, identifier ChiCTR2000038793.
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N1-methyladenosine (m1A) is ubiquitous in eukaryotic RNA and regulates mRNA translation. However, little is known about its regulatory role in glioma. Here, we identified 4 m1A modification-related patterns based on m1A regulators in the TCGA (The Cancer Genome Atlas) and CGGA (Chinese Glioma Genome Atlas) cohorts. The differences in survival prognosis between different clusters were striking. In addition, stemness, genomic heterogeneity, tumor microenvironment (TME), and immune cell infiltration were also significantly different between the poor and best prognostic clusters. To reveal the underlying mechanism, differentially expressed genes (DEGs) between the poor and best prognostic clusters were identified, and then were integrated for weighted correlation network analysis (WGCNA). After Univariate Cox-LASSO-Multivariate Cox analyses, DEGs PLEK2 and ABCC3 were screened as the risk-hub genes and were selected to construct an m1A-related signature. Moreover, ABCC3 exacerbated glioma proliferation and was associated with temozolomide (TMZ) resistance. Overall, our study provided new insights into the function and potential therapeutic role of m1A in glioma.
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Neoplasias Encefálicas , Glioma , Regulación Neoplásica de la Expresión Génica , Humanos , Metilación , ARN , Microambiente Tumoral/genéticaRESUMEN
Perioperative cardiac arrest (POCA) is associated with a high mortality rate. This work aimed to study its prognostic factors for risk mitigation by means of care management and planning. A database of 380,919 surgeries was reviewed, and 150 POCAs were curated. The main outcome was mortality prior to hospital discharge. Patient demographic, medical history, and clinical characteristics (anesthesia and surgery) were the main features. Six machine learning (ML) algorithms, including LR, SVC, RF, GBM, AdaBoost, and VotingClassifier, were explored. The last algorithm was an ensemble of the first five algorithms. k-fold cross-validation and bootstrapping minimized the prediction bias and variance, respectively. Explainers (SHAP and LIME) were used to interpret the predictions. The ensemble provided the most accurate and robust predictions (AUC = 0.90 [95% CI, 0.78-0.98]) across various age groups. The risk factors were identified by order of importance. Surprisingly, the comorbidity of hypertension was found to have a protective effect on survival, which was reported by a recent study for the first time to our knowledge. The validated ensemble classifier in aid of the explainers improved the predictive differentiation, thereby deepening our understanding of POCA prognostication. It offers a holistic model-based approach for personalized anesthesia and surgical treatment.
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Paro Cardíaco , Medicina de Precisión , Paro Cardíaco/terapia , Humanos , Aprendizaje Automático , Medicina de Precisión/efectos adversos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Previous data have reported that Sentrin/SUMO-specific protease 6 (SENP6) is involved in ischaemic brain injury and induces neuronal apoptosis after cerebral ischaemia, but the role of SENP6 in microglia-induced neuroinflammation and its underlying mechanism remain poorly understood. This research systematically explored the function and potential mechanism of SENP6 in microglia-induced neuroinflammation after ischaemic stroke. RESULTS: We first identified an increased protein level of SENP6 in microglia after cerebral ischaemia. Then, we demonstrated that SENP6 promoted detrimental microglial phenotype polarization. Specifically, SENP6-mediated de-SUMOylation of ANXA1 targeted the IκB kinase (IKK) complex and selectively inhibited the autophagic degradation of IKKα in an NBR1-dependent manner, activating the NF-κB pathway and enhancing proinflammatory cytokine expression. In addition, downregulation of SENP6 in microglia effectively reduced cocultured neuronal damage induced by ischaemic stroke. More importantly, we employed an AAV-based technique to specifically knockdown SENP6 in microglia/macrophages, and in vivo experiments showed that SENP6 inhibition in microglia/macrophages notably lessened brain ischaemic infarct size, decreased neurological deficit scores, and ameliorated motor and cognitive function in mice subjected to cerebral ischaemia surgery. CONCLUSION: We demonstrated a previously unidentified mechanism by which SENP6-mediated ANXA1 de-SUMOylation regulates microglial polarization and our results strongly indicated that in microglia, inhibition of SENP6 may be a crucial beneficial therapeutic strategy for ischaemic stroke.
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Esketamine showed more potency, more rapid recovery from anesthesia, and less psychotomimetic side effects when compared with ketamine. However, the patients still experience psychotomimetic side effects of esketamine. In order to investigate whether midazolam can attenuate the esketamine-induced overactive behaviors and neuronal hyperactivities, midazolam 0, 40, 80, and 120 mg/kg combined with esketamine 50 mg/kg were administrated on Kunming mice to assess the behaviors changes during anesthesia. The indicators, including action time, duration of agitation before the sedation, duration of sedation, duration of loss of pedal withdrawal reaction (PWR), duration of loss of righting reaction (RR), duration of agitation during the recovery, and recovery time, were monitored for up to 3-4 h after intraperitoneal administration. The results demonstrated that midazolam 40, 80, and 120 mg/kg efficiently decreased the esketamine-induced overactive behaviors including ataxia, excitation, and catalepsy before sedation. Midazolam and esketamine synergically improved the anesthesia quality assessed by PWR and RR. However, even high doses of midazolam were not able to suppress the esketamine-induced psychotomimetic effects during the recovery.
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Inflammatory cells contribute to the pathogenesis of renal ischemia-reperfusion injury (IRI). However, the signaling mechanisms underlying the infiltration of inflammatory cells into the kidney are not well understood. In this study, we examined the effects of phosphoinositide 3 kinase γ (PI3Kγ) on inflammatory cells infiltration into the kidney in response to ischemia-reperfusion injury. Compared with wild-type mice, PI3Kγ knockout mice displayed less IRI in the kidney with fewer tubular apoptotic cell. Furthermore, PI3Kγ deficiency decreased the number of infiltrated neutrophils, macrophages, and T cells in the kidney, which was accompanied by a decrease in the expression of pro-inflammatory cytokines in the kidney. Moreover, wild-type mice treated with AS-605240, a selective PI3Kγ inhibitor, displayed less tubular damage, accumulated fewer inflammatory cells, and expressed less proinflammatory molecules in the kidney following IRI. These results demonstrate that PI3Kγ has a critical role in the pathogenesis of kidney damage in IRI, indicating that PI3Kγ inhibition may serve as a potential therapeutic strategy for the prevention of ischemia-reperfusion-induced kidney injury.
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Lesión Renal Aguda , Fosfatidilinositol 3-Quinasa Clase Ib/metabolismo , Daño por Reperfusión , Lesión Renal Aguda/metabolismo , Animales , Ratones , Ratones Endogámicos C57BL , Fosfatidilinositol 3-Quinasa , Fosfatidilinositol 3-Quinasas , Daño por Reperfusión/metabolismoRESUMEN
Introduction: Esketamine (Esk) (S(+)-ketamine) is now used as an alternative to its racemic mixture, i. e., ketamine in anesthesia. Esk demonstrated more powerful potency and rapid recovery in anesthesia and less psychotomimetic side effects comparing with ketamine, but Esk could still induce psychological side effects in patients. This study was to investigate whether dexmedetomidine (Dex) can attenuate the Esk-induced neuronal hyperactivities in Kunming mice. Methods: Dexmedetomidine 0.25, 0.5, and 1 mg/kg accompanied with Esk 50 mg/kg were administrated on Kunming mice to assess the anesthesia quality for 1 h. The indicators, such as time to action, duration of agitation, duration of ataxia, duration of loss pedal withdrawal reaction (PWR), duration of catalepsy, duration of righting reflex (RR) loss, duration of sedation, were recorded for 1 h after intraperitoneal administration. The c-Fos expression in the brain was detected by immunohistochemistry and Western Blot after 1 h of administration. Considering the length of recovery time for more than 1 h in Dex and Dex with Esk groups, other mice were repeatedly used to evaluate recovery time from the administration to emerge from anesthesia. Results: Dexmedetomidine dose-dependently increased recovery time when administrated with Esk or alone. Dex combined with Esk efficiently attenuated the duration of agitation, ataxia, and catalepsy. Dex synergically improved the anesthesia of Esk by increasing the duration of sedation, loss of RR, and loss of PWR. Esk induced the high expression of c-Fos in the cerebral cortex, hippocampus, thalamus, amygdala, hypothalamus, and cerebellum 1 h after administration. Western Blot results indicated that Dex at doses of 0.25, 0.5, and 1 mg/kg could significantly alleviate the Esk-induced c-Fos expression in the mice brain. Conclusion: Dexmedetomidine ranged from 0.25 to 1 mg/kg could improve the anesthesia quality and decreased the neuronal hyperactivities and the overactive behaviors when combined with Esk. However, Dex dose-dependently increased the recovery time from anesthesia. It demonstrated that a small dose of Dex 0.25 mg/kg could be sufficient to attenuate Esk-induced psychotomimetic side effects without extension of recovery time in Kunming mice.
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BACKGROUND: Propofol has been proposed to function as a tumor suppressor in various human cancers. In this study, we aimed to investigate the anti-tumor effect of propofol on cervical cancer (CC). METHODS: Cell Counting Kit-8 (CCK-8) assay, colony formation assay, flow cytometry analysis, transwell assay and wound healing assay were conducted for cell viability, colony formation, apoptosis, invasion and migration, respectively. Western blot assay was used for protein levels. Quantitative real-time polymerase chain reaction (qRT-PCR) was used for HOX antisense intergenic RNA (HOTAIR), miR-129-5p and RPL14 levels. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were executed to verify the interaction between miR-129-5p and HOTAIR or RPL14. Murine xenograft model assay was used for the role of propofol in tumor progression in vivo. RESULTS: Propofol treatment suppressed CC cell viability, colony formation, invasion and migration and facilitated apoptosis. Propofol treatment led to a marked reduction in HOTAIR level in CC cells. HOTAIR overexpression promoted cell colony formation, invasion and migration and repressed apoptosis in CC cells and propofol-treated CC cells. For mechanism analysis, HOTAIR positively regulated RPL14 expression via acting as the sponge of miR-129-5p. MiR-129-5p overexpression reversed the impacts of HOTAIR on the malignant behaviors of propofol-treated CC cells. Furthermore, miR-129-5p inhibition accelerated the progression of CC cells, while RPL14 interference rescued the effect. In addition, propofol treatment restrained tumor growth of CC in vivo. CONCLUSION: Propofol inhibited CC development by modulation of HOTAIR/miR-129-5p/RPL14 axis.
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AIM: To compare the efficacy of cesarean section (CS) combined with intermittent aortic balloon occlusion with that of CS alone for treating patients with placenta previa complicated by placenta accreta. METHODS: Forty-five patients with placenta previa complicated by placenta accreta who underwent CS were retrospectively studied. Twenty-two patients had undergone CS combined with intermittent aortic balloon occlusion (combination group) and 23 patients received conventional hemostatic support only (control group). The postpartum hemorrhage, transfusion requirements, operation time and recovery time, and the ability to preserve the uterus and fertility were analyzed. RESULTS: Intermittent aortic balloon occlusion significantly decreased the volume of blood loss in the combination group relative to the control group (597 ± 359 mL vs 2687 ± 575 mL; P < 0.001), and transfusion requirements were also reduced (498 ±195 mL vs 2390 ±789 mL; P <0.001). We observed shorter operation time in the combination group relative to the control group (63.8 ± 12.3 min vs 118.8 ± 22.4 min; P < 0.001), and fewer patients required uterine cavity stuffing followed by uterine artery embolization (n = 2 vs n = 10; P <0.05), uterine artery ligation (n = 1 vs n = 9; P < 0.05), and hysterectomy (n = 0 vs n =7; P < 0.05). CONCLUSION: Intermittent aortic balloon occlusion may control postpartum hemorrhage in pregnancies complicated by placenta accreta, and improve the postoperative conditions.
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Aorta , Oclusión con Balón/métodos , Evaluación de Resultado en la Atención de Salud , Placenta Accreta/terapia , Placenta Previa/terapia , Hemorragia Posparto/prevención & control , Adulto , Femenino , Humanos , Embarazo , Estudios Retrospectivos , Adulto JovenRESUMEN
Colorectal cancer (CRC) is a common malignant tumor, in which the inflammatory microenvironment plays an important role. STAT3 signaling pathway is regarded as the "bridge" between inflammation and cancer, and involved in the development of CRC. SOCS3 is a key negative feedback regulator of JAK/STAT signaling pathway. Studies about SOCS3 gene in CRC are rarely reported. The purpose of this study is to determine the expression of SOCS3 in CRC tissue and its correlation with the clinical pathological characteristics and prognosis of colorectal cancers. The effects of SOCS3 on biological behavior such as apoptosis, proliferation, migration, invasion and tumor formation in nude mice were studied. We observed that SOCS3 expression was down-regulated in CRC tissues, while IL-6, pSTAT3 were up-regulated. Inflammatory cytokines IL-6 can promote the expression of STAT3 signaling pathways while inhibit the expression of SOCS3 by promoting hypermethylation of SOCS3 gene promoters. 5-Aza-cdR treatment can reverse IL-6/STAT3 signaling pathway mediated down-regulation of SOCS3 in colorectal cancer cells. Low expression of SOCS3 was correlated with lymph node metastasis and advanced clinical stage. Patients with high expression of SOCS3 in colorectal cancers often indicated a relatively good prognosis. Overexpression of SOCS3 inhibited proliferation, migration, invasion and tumorigenic ability of CRC cells while increased cell apoptosis. This study demonstrated that IL-6/STAT3 signaling activation negatively regulated SOCS3 expression, which led to imbalance and sustained activation of STAT3 signaling pathway. Reduced expression of SOCS3 promoted the growth and metastasis of colorectal cancer. Thus, targeting IL-6/STAT3/SOCS3 signaling pathway may become an important treatment strategy of colorectal cancer.
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Neoplasias Colorrectales/diagnóstico , Proteína 3 Supresora de la Señalización de Citocinas/metabolismo , Anciano , Animales , China , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Femenino , Humanos , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Pronóstico , Regiones Promotoras Genéticas , Factor de Transcripción STAT3/análisis , Proteína 3 Supresora de la Señalización de Citocinas/análisis , Proteína 3 Supresora de la Señalización de Citocinas/genéticaRESUMEN
BACKGROUND: Placenta accreta (PA), a severe complication during delivery, is closely linked with massive hemorrhage which could endanger the lives of both mother and baby. Moreover, the incidence of PA has increased dramatically with the increasing rate of cesarean deliveries in the past few decades. Therefore, studies evaluating the effects of different perioperative managements based on different modalities in the treatment of PA are necessary. Among the numerous treatment measures, prophylactic abdominal aortic balloon occlusion (AABO) in combination with cesarean section for PA seems to be more advantageous than others. However, up to now, all studies on AABO were almost retrospective. Current evidence is insufficient to recommend for or against routinely using the AABO technology for control intraoperative hemorrhage in patients with PA. Thus, we hope to carry out a prospective, randomized controlled trial (RCT) study to confirm the effectiveness of the AABO technology in patients with PA. METHODS/DESIGN: This trial is an investigator-initiated, prospective RCT that will test the superiority of AABO in combination with cesarean section compared to the traditional hysterectomy following cesarean section for parturients with PA. A total of 170 parturients with PA undergoing cesarean section will be randomized to receive either AABO in combination with cesarean section or the traditional hysterectomy following cesarean section. The primary outcome is estimated blood loss. The most important secondary outcome is the occurrence of cesarean hysterectomy during delivery; others include blood transfusion volume, operating time, neonate's Apgar scores (collected at 1, 5 and 10 min), length of stay in intensive care unit, total hospital stay, and balloon occlusion-relative data. DISCUSSION: This prospective trial will test the superiority of AABO in combination with cesarean section compared to the traditional hysterectomy following cesarean section for parturients with PA. It may provide strong evidence about the benefits and risks of AABO in combination with cesarean section for parturients with PA. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-INR-16008842 . Registered on 14 July 2016.