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Insufficient angiogenic stimulation and dysregulated glycolipid metabolism in senescent vascular endothelial cells (VECs) constitute crucial features of vascular aging. Concomitantly, the generation of excess senescence-associated secretory phenotype (SASP) and active immune-inflammatory responses propagates within injured vessels, tissues, and organs. Until now, targeted therapies that efficiently rectify phenotypic abnormalities in senescent VECs have still been lacking. Here, we constructed a Pd/hCeO2-BMS309403@platelet membrane (PCBP) nanoheterostructured capsule system loaded with fatty acid-binding protein 4 (FABP4) inhibitors and modified with platelet membranes and investigated its therapeutic role in aged mice. PCBP showed significant maintenance in aged organs and demonstrated excellent biocompatibility. Through cyclic tail vein administration, PCBP extended the lifespan and steadily ameliorated abnormal phenotypes in aged mice, including SASP production, immune and inflammatory status, and age-related metabolic disorders. In senescent ECs, PCBP mediated the activation of vascular endothelial growth factor (VEGF) signaling and glycolysis and inhibition of FABP4 by inducing the synthesis of hypoxia-inducible factor-1α, thereby reawakening neovascularization and restoring glycolipid metabolic homeostasis. In conclusion, the PCBP nanocapsule system provides a promising avenue for interventions against aging-induced dysfunction.
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Envelhecimento , Nanocápsulas , Animais , Camundongos , Envelhecimento/metabolismo , Nanocápsulas/química , Humanos , Camundongos Endogâmicos C57BL , Glicolipídeos/química , Glicolipídeos/metabolismo , Senescência Celular/efeitos dos fármacos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , AngiogêneseRESUMO
BACKGROUND: Reversible loss of consciousness is the primary therapeutic endpoint of general anesthesia; however, the drug-invariant mechanisms underlying anesthetic-induced unconsciousness are still unclear. This study aimed to investigate the static, dynamic, topological and organizational changes in functional brain network induced by five clinically-used general anesthetics in the rat brain. METHOD: Male Sprague-Dawley rats (n = 57) were randomly allocated to received propofol, isoflurane, ketamine, dexmedetomidine, or combined isoflurane plus dexmedetomidine anesthesia. Resting-state functional magnetic resonance images were acquired under general anesthesia and analyzed for changes in dynamic functional brain networks compared to the awake state. RESULTS: Different general anesthetics induced distinct patterns of functional connectivity inhibition within brain-wide networks, resulting in multi-level network reorganization primarily by impairing the functional connectivity of cortico-subcortical networks as well as by reducing information transmission capacity, intrinsic connectivity, and network architecture stability of subcortical regions. Conversely, functional connectivity and topological properties were preserved within cortico-cortical networks, albeit with fewer dynamic fluctuations under general anesthesia. CONCLUSIONS: Our findings highlighted the effects of different general anesthetics on functional brain network reorganization, which might shed light on the drug-invariant mechanism of anesthetic-induced unconsciousness.
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Anestésicos Gerais , Encéfalo , Dexmedetomidina , Isoflurano , Ketamina , Imageamento por Ressonância Magnética , Propofol , Ratos Sprague-Dawley , Animais , Masculino , Ratos , Encéfalo/efeitos dos fármacos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Anestésicos Gerais/farmacologia , Ketamina/farmacologia , Propofol/farmacologia , Dexmedetomidina/farmacologia , Isoflurano/farmacologia , Rede Nervosa/efeitos dos fármacos , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia , Vias Neurais/efeitos dos fármacos , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiologiaRESUMO
Perioperative anaesthesia management has an important significance for kidney transplantation; however, the related consensus remains limited. An electronic survey with 44 questions was developed and sent to the chief anaesthesiologist at 115 non-military medical centres performing kidney transplantation in China through WeChat. A response rate of 81.7% was achieved from 94 of 115 non-military medical centres, where 94.4% of kidney transplants (10404 /11026) were completed in 2021. The result showed an overview of perioperative practice for kidney transplantations in China, identify the heterogeneity, and provide evidence for improving perioperative management of kidney transplantation. Some controversial therapy, such as hydroxyethyl starch, are still widely used, while some recommended methods are not widely available. More efforts on fluid management, hemodynamical monitoring, perioperative anaesthetics, and postoperative pain control are needed to improve the outcomes. Evidence-based guidelines for standardizing clinical practice are needed.
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Anestésicos , Transplante de Rim , Humanos , Transplante de Rim/métodos , Anestésicos/uso terapêutico , Inquéritos e Questionários , Derivados de Hidroxietil Amido , Complicações Pós-Operatórias , Assistência PerioperatóriaRESUMO
The rapid reversal of deep neuromuscular blockade (NMB) is important but remains challenging. This study aimed to evaluate the efficacy and safety of adamgammadex versus sugammadex in reversing deep rocuronium-induced NMB. This multicenter, randomized, phase IIb study included 80 patients aged 18-64 years, American Society of Anesthesiologists (ASA) grade 1-2, undergoing elective surgery under general anesthesia with rocuronium. Patients were randomized to the adamgammadex 7, 8, and 9 mg/kg group or the sugammadex 4 mg/kg group. The primary efficacy variable was the time to recovery of train-of-four ratio (TOFr) to 0.9. The secondary efficacy variables were the time to recovery of TOFr to 0.7, antagonistic success rate of the recovery of TOFr to 0.9 within 5 min, and incidence rate of recurarization within 30 min after drug administration. The explorative efficacy variable was the time to recovery of the corrected TOFr to 0.9 (actual/baseline TOF ratio). Adamgammadex 7, 8, and 9 mg/kg and sugammadex 4 mg/kg groups did not significantly differ in all efficacy variables. Importantly, adamgammadex 9 mg/kg permitted reversal within a geometric mean of 2.9 min. According to the safety profile, adamgammadex achieved good tolerance and low incidence of drug-related adverse events compared with the 4 mg/kg sugammadex. Adamgammadex 7, 8, and 9 mg/kg facilitated rapid reversal of deep rocuronium-induced NMB and had good tolerance and low incidence of drug-related adverse events. Therefore, adamgammadex is a potential and promising alternative to sugammadex.
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Bloqueio Neuromuscular , Humanos , Bloqueio Neuromuscular/efeitos adversos , Rocurônio/efeitos adversos , Sugammadex/efeitos adversos , Tolerância a Medicamentos , Tolerância ImunológicaRESUMO
BACKGROUND: Remimazolam, an ultra-short-acting benzodiazepine, may provide adequate sedation for endoscopy while causing less cardiovascular or respiratory disturbance than propofol. Although fixed-dose administration is suggested, body weight affects the volume of the central chamber and thus affects the sedation depth that can be achieved by the first dose. This study aimed to compare the efficacy and safety of different doses of remimazolam and propofol by body weight for sedation during gastroscopy. METHODS: This multicenter, randomized, single-blind, parallel-controlled noninferiority trial recruited patients from five centers between March 2021 and July 2022. A total of 1,883 patients scheduled to undergo gastroscopy were randomized to groups receiving 0.15 mg/kg remimazolam, 0.2 mg/kg remimazolam, or 1.5 mg/kg propofol. The noninferiority margin was set to 5%. The primary outcome was the success rate of sedation. Adverse events were recorded to evaluate safety. RESULTS: The sedation success rate of the 0.2 mg/kg remimazolam group was not inferior to that of the 1.5 mg/kg propofol group (98.7% vs. 99.4%; risk difference, -0.64%; 97.5% CI, -2.2 to 0.7%, meeting criteria for noninferiority). However, the sedation success rate of the 0.15 mg/kg remimazolam group was 88.5%, and that of the 1.5 mg/kg propofol group was 99.4% (risk difference, -10.8%; 97.5% CI, -14.0% to -8.0%), demonstrating inferiority. Simultaneously, the overall adverse events rate of remimazolam was lower than that of propofol, and the incidence of bradycardia, hypotension, subclinical respiratory depression, and hypoxia in the remimazolam groups was significantly lower than that in the propofol group. CONCLUSIONS: This trial established the noninferior sedation success rate of remimazolam (0.2 mg/kg but not 0.15 mg/kg) compared with propofol (1.5 mg/kg), with a superior safety profile.
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Gastroscopia , Propofol , Humanos , Método Simples-Cego , Benzodiazepinas , Peso Corporal , Hipnóticos e SedativosRESUMO
Background: Sleep is an important biological process and has been linked to many diseases; however, very little is known about which and how genes control and regulate sleep. Although technology has seen significant development, this issue has still not been adequately resolved. Therefore, we conducted a bibliometric analysis to assess the progress in research on sleep quality and associated genes over the past 2 decades. Through our statistical data and discussions, we aimed to provide researchers with better research directions and ideas, thus promoting the advancement of this field. Methods: On December 29, 2022, we utilized bibliometric techniques, such as co-cited and cluster analysis and keyword co-occurrence, using tools such as CiteSpace, VOSviewer, and the Online Analysis Platform of Literature Metrology (http://bibliometric.com/), to conduct a thorough examination of the relevant publications extracted from the Web of Science Core Collection (WoSCC). Our analysis aimed to identify the emerging trends and hot spots in this field while also predicting their potential development in future. Results: Cluster analysis of the co-cited literature revealed the most popular terms relating to sleep quality and associated genes in the manner of cluster labels; these included genome-wide association studies (GWAS), circadian rhythms, obstructive sleep apnea (OSA), DNA methylation, and depression. Keyword burst detection suggested that obstructive sleep apnea, circadian clock, circadian genes, and polygenic risk score were newly emergent research hot spots. Conclusion: Based on this bibliometric analysis of the publications in the last 20 years, a comprehensive analysis of the literature clarified the contributions, changes in research hot spots, and evolution of research techniques regarding sleep quality and associated genes. This research can provide medical staff and researchers with revelations into future directions of the study on the pathological mechanisms of sleep-related diseases.
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Purpose: The need for anaesthesia or analgesia for performing hysteroscopy remains debatable. This study aimed to conduct an overview of the situation of anaesthesia for hysteroscopy in mainland China. Methods: Two questionnaires were separately designed for anaesthesiologists and gynaecologists and distributed to every medical institution that performed hysteroscopic procedures on patients with infertility in mainland China. Electronic questionnaires were distributed via WeChat, and data on anaesthesia regimen, monitoring parameters, procedure number, and other information were collected. Results: Reproductive technology is conducted by 536 institutions in mainland China. The survey received 491 responses from anaesthetists (91.6%) and 436 from gynaecologists (81.3%). In 2021, 552,225 hysteroscopies were conducted in 268 medical centres. The average percentage of hysteroscopy under anaesthesia is 63.8% in 2021, wherein 47.3% of institutions have an anaesthesia percentage of >75%. Propofol and opioid analgesics, such as fentanyl and sufentanil, were the most commonly used intravenous anaesthetics. All sedations were performed by anaesthesiologists. Monitoring parameters included pulse oxygen saturation (98.9%), electrocardiogram (91.6%) and noninvasive blood pressure (91.3%). An anaesthesiologist-to-operating room ratio of <1 was observed in 31.3% of medical institutions. Surprisingly, 52.4% of medical institutions performing hysteroscopy had no postanaesthesia care unit (PACU). Most institutions with PACU were equipped with independent oxygen sources, suction and monitors. Both rigid and flexible hysteroscopes (rigid hysteroscope, 45.1%; flexible hysteroscope, 4.5%; both types, 50.4%) were used, and the hysteroscopic diameter was ≤5 mm in 60.3% of medical centres. Conclusions: China performs a large number of hysteroscopies, and sedation is the most frequently used anesthesia regimen. However, issues such as inadequate emergency support devices, insufficient personnel and weak resuscitation management after anaesthesia, have been observed.
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STUDY OBJECTIVE: Videolaryngoscopes are widely used to visualize difficult airways. Our aim was to compare the GlideScope and C-MAC D-blade videolaryngoscopes for double-lumen tube (DLT) intubation in patients with difficult airways. DESIGN: A multi-center, prospective, randomized controlled trial. SETTING: Three comprehensive tertiary, high-volume hospitals from 5 December 2020 to 4 November 2021. PATIENTS: We included 348 adult patients with anticipated difficult airways who underwent elective thoracic surgery. INTERVENTIONS: Patients were randomized into two groups: GlideScope and C-MAC D-blade. Following anesthesia induction, DLT intubation was performed using different videolaryngoscopes. MEASUREMENTS: The primary outcome was the first-pass success rate of DLT intubation. All other results were recorded as secondary outcomes. MAIN RESULTS: No significant differences were observed in the first-pass success rate of DLT intubation between the GlideScope and C-MAC D-blade (86.21% and 89.66%, respectively; P = 0.323). However, compared with the GlideScope, the C-MAC D-blade provided a lower Cormack-Lehane grade (P < 0.001), lower rates of external laryngeal pressure (48 vs. 15, P < 0.001), and postprocedure sore throat (26 vs. 8, P < 0.001). The numerical rating score for difficulty of videolaryngoscope insertion into the oral cavity, delivery to the glottis, and intubation into the main bronchus were significantly lower when using the C-MAC D-blade (P < 0.001). Moreover, the duration of DLT intubation was shorter in the C-MAC D-blade group (81 s [70-97 s] vs. 95 s [78-115 s], P < 0.001). In each group, two patients underwent fiberoptic intubation after three attempts with a videolaryngoscope failed. CONCLUSIONS: In patients with difficult airways, the GlideScope and C-MAC D-blade provided a similar success rate on the first DLT intubation attempt; however, the C-MAC D-blade offers a better glottic view, easier and faster intubation, and lower incidence of sore throat.
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Laringoscópios , Faringite , Adulto , Humanos , Intubação Intratraqueal/efeitos adversos , Intubação Intratraqueal/métodos , Laringoscopia/efeitos adversos , Laringoscopia/métodos , Estudos Prospectivos , Laringoscópios/efeitos adversos , Faringite/epidemiologia , Faringite/etiologia , Gravação em VídeoAssuntos
Delírio , Estimulação Magnética Transcraniana , Humanos , Delírio/etiologia , Delírio/terapiaRESUMO
Introduction: Blood-brain barrier (BBB) breakdown is closely associated with cognitive dysfunction. This study aimed to categorize and summarize research topics on the correlation between BBB breakdown and its effects on cognitive function. Methods: Bibliometric analysis methods were used to quantitatively and qualitatively assess research progress and predict future research hotspots. Relevant publications from the Web of the Science Core Collection were extracted on November 5, 2022 and analyzed to predict trends and hotspots in the field. Results: We identified 5518 articles published from 2000 to 2021 about the BBB and cognition. The number of manuscripts on this topic increased steadily during this time period, especially after 2013. We found that the number of articles published in China increased gradually and is in second place behind the United States of America (USA). In the research field of BBB breakdown and cognitive function, the USA is still far ahead. Keyword burst detection suggested that cognitive impairment, neurodegeneration disease and neuroinflammation are emerging research hotspots. Discussion: The mechanisms of BBB integrity breakdown and its effects on the deterioration of cognitive function are complex, and clinical treatment of the affected diseases has been a hot topic in the field over the past 22 years. Looking forward, this body of research is aimed at improving or maintaining patients' cognitive abilities, by finding preventive measures and to provide a basis for finding new treatments of cognitive disorders.
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BACKGROUND: Vocal cord polyp is common otorhinolaryngological disease, traditionally treated by vocal cord polypectomy under a supporting laryngoscope with general anaesthesia. Although it is safe and controllable, it would cause some anaesthesia complications. Moreover, the complex process of general anaesthesia may significantly reduce surgical efficiency. Avoiding these problems remains an important issue. METHODS: All patients were subjected to the standard non-intubated deep paralysis (NIDP) protocol consisting of four phases. An emergency plan was launched when NIDP cannot be implemented successfully. Patient characteristics, blood gas and monitoring data were collected during NIDP. Data concerning satisfaction, complications and duration of anaesthesia and recovery were collected to assess its effectiveness. RESULT: Among 20 enrolled patients, the success rate of NIDP was 95%. Only one patient failed in completing NIDP. Blood gas analysis revealed that the partial pressure of oxygen and carbon dioxide was maintained at safe levels. Monitoring during NIDP revealed fluctuations in mean arterial pressure between 110 and 70 mmHg, and the heart rate was stable at 60-100 beats per minute. The duration of anaesthesia and postoperative recovery were 13.0 ± 2.84 and 5.47 ± 1.97 min, respectively. All patients and surgeons were satisfied with NIDP, and no complications were detected before discharge. CONCLUSION: NIDP can be safely applied to patients and can replace general anaesthesia in vocal cord polypectomy. It can significantly reduce the duration of anaesthesia and postoperative recovery. No anaesthesia complications occurred without intubation, and patients and surgeons were satisfied with NIDP. TRIAL REGISTRATIONS: This single-centre, prospective study was registered on clinicaltrial.gov (NCT04247412) on 30th July 2020.
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BACKGROUND: Hypoxia is a very common adverse event that occurs during gastrointestinal endoscopy under sedation, especially in older patients, owing to limited reservation of heart, brain, lung, and other organs. Prolonged or severe hypoxia can cause ischemia of the coronary artery and permanent nervous system damage, and even result in death. Hence, it is imperative to reduce or prevent hypoxia during gastrointestinal endoscopy under sedation in older patients. Although several oxygen delivery methods would reduce hypoxia during this procedure, early detection of respiratory depression and early administration of intervention would be the best method to reduce or even confirm the hypoxia. Capnographic monitoring is reportedly more sensitive for detecting respiratory depression before the onset of hypoxia than the current clinical routine monitoring of pulse oxygen saturation; however, its effect is controversial. Therefore, in this study, we aimed to improve the safety of gastrointestinal endoscopy under sedation in older patients. METHODS: A multicenter, randomized, single-blind, two-arm parallel-group, controlled with an active comparator, interventional superiority clinical trial will be conducted to evaluate the impact of an additional capnographic monitoring-based intervention on the incidence of hypoxia in older patients. Patients (n = 1800) scheduled for gastrointestinal endoscopy with propofol sedation will be randomly assigned to either a control or interventional arm, wherein standard or capnographic monitoring is implemented, respectively. DISCUSSION: This study primarily aims to examine whether an additional capnographic monitoring-based intervention can reduce the incidence of hypoxia in older patients during gastrointestinal endoscopy under propofol and sufentanil sedation. The results of this study may extensively impact gastrointestinal endoscopy under sedation and the development of associated guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT05030870. Registered on September 1, 2021.
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Propofol , Insuficiência Respiratória , Humanos , Idoso , Propofol/efeitos adversos , Hipnóticos e Sedativos/efeitos adversos , Incidência , Método Simples-Cego , Capnografia/efeitos adversos , Capnografia/métodos , Endoscopia Gastrointestinal/efeitos adversos , Hipóxia/diagnóstico , Hipóxia/epidemiologia , Hipóxia/etiologia , Insuficiência Respiratória/etiologia , Sedação Consciente/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
INTRODUCTION: So far, the recovery quality after general anesthesia is still unsatisfied. Nalmefene is a drug to treat opioid overdose and reverse opioid actions. We aim to investigate the efficacy of nalmefene on optimizing the recovery quality of patients after general anesthesia. METHODS: It is a prospective, placebo-controlled, two-arm parallel groups, multicentre, double-blind, randomized (PPPMDR) clinical trial. The participants (n = 520) will be randomly assigned into two groups. Each patient will receive either: a single dose of nalmefene 0.25 µg/kg in the intervention group, or the same volume of 0.9% NaCl solution in the control group at the end of the surgery. The primary outcome will be the time interval between the end of anaesthesia and recovery endpoints achieved (Aldrete recovery score ≥ 9) in post-anesthesia care unit (PACU). The other variables are the time interval from the end of operation to extubation; Richmond Agitation Sedation Scale (RASS) score at extubation; the time at Montreal Cognitive Assessment Scale (MoCA) orientation score ≥ 5; visual analog scale (VAS) score and adverse effects including postoperative nausea and vomiting (PONV), and pruritus in PACU and 24 h postoperatively. ANALYSIS: This trial aims to study whether small dose of nalmefene can shorten the time from the end of surgery to Aldrete score ≥ 9 and improve opioid-induced side effects.This trial focuses on providing the reliable clinical evidence for satisfactory quality of recovery. ETHICS AND DISSEMINATION: This clinical trial has been approved and supported by the ethics committee of the Renji Hospital, Shanghai Jiaotong University, School of Medicine (KY2020-150); Shanghai Tongren Hospital (2021-030-01);The First Affiliated Hospital of Guangxi Medical University (2021-032); and The First Affiliated Hospital of Zhengzhou University(2021-KY-0495-003). Analysis of the study results will be submitted to a peer-reviewed journal for publication. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04713358, Registered on September 23, 2021.
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Anestesiologia , Anestésicos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Analgésicos Opioides , Estudos Prospectivos , China , Anestesia Geral , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND: Postoperative cognitive dysfunction (POCD) refers to a neurological dysfunction after a major surgery and anesthesia. It is common in elderly patients and is characterized by impairment in consciousness, orientation, thinking, memory, and executive function after surgical anesthesia. However, at present, there is no definite preventive or treatable strategy for it. Previous animal experiments showed that giving probiotics to mice before operation can prevent POCD, but there is a lack of clinical evidence. This study aims to intervene with the intestinal flora imbalance using probiotics during the perioperative period to reduce the incidence of POCD in elderly patients after orthopedic surgery and to provide new ideas and methods for the clinical prevention and treatment of POCD. METHODS: A multicenter, double-blind, placebo-controlled clinical trial will be performed to evaluate the efficacy of probiotics in elderly patients undergoing orthopedic surgery. Participants (n = 220) will receive probiotics (Peifeikang, Live Combined Bifidobacterium, 210 mg per capsule, twice a day, four capsules each time, which contains Bifidobacterium longum, Lactobacillus acidophilus and Streptococcus faecalis no less than 1.0 × 107 CFU viable bacteria respectively) or placebo from 1 day before surgery to 6 days after surgery. Neuropsychological tests will be performed 1 day before surgery and 1 week and 1 month after surgery. The main outcome of this study is the incidence of POCD 7 days after surgery. Our secondary objective is to assess the incidence of POCD 1 month after surgery; the cognitive status will be determined based on a telephone interview and will be evaluated via TICS-m; postoperative delirium will be assessed 7 days after surgery using the Confusion Assessment Method (CAM). DISCUSSION: Discovering the correlation between the intestinal microbiota and POCD is an important breakthrough. Based on the key role of the intestinal microbiota in other cognitive disorders, we hope that probiotics can reduce its incidence in elderly orthopedic patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04017403. Registered on August 15, 2019.
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Transtornos Cognitivos , Disfunção Cognitiva , Procedimentos Ortopédicos , Complicações Cognitivas Pós-Operatórias , Probióticos , Animais , Camundongos , Complicações Cognitivas Pós-Operatórias/etiologia , Disfunção Cognitiva/prevenção & controle , Procedimentos Ortopédicos/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND: µ-opioid receptor agonists (MORAs) are indispensable for analgesia in bladder cancer (BC) patients, both during surgery and for chronic pain treatment. Whether MORAs affect BC progression and metastasis remains largely unknown. This study focused on the effects of MORAs on the formation of circulating tumor cells (CTCs) in BC and aimed to provide potential therapeutic targets, which would retain the pain-relieving effects of MORAs in BC patients without sacrificing their long-term prognosis. METHODS: Different preclinical models were used to identify the effects of MORAs on the progression of BC. A novel immunocapture microfluidic chip was utilized to analyze whether MORAs affected the number of CTCs in mouse models and clinical BC patients. Bioinformatic analyses, total transcriptome sequencing, and molecular biology methods were then used to investigate the underlying mechanisms in these models and in BC cell lines. RESULTS: Mouse models of hematogenous metastasis and in situ BC demonstrated that tumor metastasis was significantly increased after MORA treatment. A significant increase in the number of mesenchymal and/or epithelial CTCs was detected after MORA treatment in both the mouse models and clinical trial patients. Mechanistically, MORAs facilitated the formation of CTCs by activating the MOR/PI3K/AKT/Slug signaling pathway, hereby promoting the epithelial-mesenchymal transition (EMT) of BC cells, as knockdown of MOR, Slug or blockade of PI3K inhibited the EMT process and CTC formation. CONCLUSION: MORAs promoted BC metastasis by facilitating CTC formation. The EMT-CTC axis could be targeted for preventive measures during MORA treatment to inhibit the associated tumor metastasis or recurrence in BC patients.
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Células Neoplásicas Circulantes , Neoplasias da Bexiga Urinária , Animais , Camundongos , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Receptores Opioides , Neoplasias da Bexiga Urinária/patologia , HumanosRESUMO
BACKGROUND: Pediatric liver transplantation is an important modality for treating biliary atresia. The overall survival (OS) rate of pediatric liver transplantation has significantly improved compared with that of 20 years ago, but it is still unsatisfactory. The anesthesia strategy of maintaining low central venous pressure (CVP) has shown a positive effect on prognosis in adult liver transplantation. However, this relationship remains unclear in pediatric liver transplantation. Thus, this study was conducted to review the data of pediatric living-donor liver transplantation to analyze the associations of different CVP levels with the prognosis of recipients. METHODS: This was a retrospective study and the patients were divided into two groups according to CVP levels after abdominal closure: low CVP (LCVP) (≤ 10 cmH2O, n = 470) and high CVP (HCVP) (> 10 cmH2O, n = 242). The primary outcome measured in the study was the overall survival rate. The secondary outcomes included the duration of mechanical ventilation in the intensive care unit (ICU), length of stay in the ICU, and postoperative stay in the hospital. Patient demographic and perioperative data were collected and compared between the two groups. Kaplan-Meier curves were constructed to determine the associations of different CVP levels with the survival rate. RESULTS: In the study, 712 patients, including 470 in the LCVP group and 242 in the HCVP group, were enrolled. After propensity score matching, 212 pairs remained in the group. The LCVP group showed a higher overall survival rate than the HCVP group in the Kaplan-Meier curves and multivariate Cox regression analyses (P = 0.018), and the HCVP group had a hazard ratio of 2.445 (95% confidence interval, 1.163-5.140). CONCLUSION: This study confirmed that a low-CVP level at the end of surgery is associated with improved overall survival and a shorter length of hospital stay.
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Transplante de Fígado , Adulto , Humanos , Criança , Pressão Venosa Central , Doadores Vivos , Estudos Retrospectivos , PrognósticoRESUMO
BACKGROUND: Gastrointestinal endoscopy has been associated with difficult experiences and can leave patients with an unpleasant impression. Propofol and midazolam are the most commonly used intravenous anesthetics for sedation during gastrointestinal endoscopy. However, cardiac and pulmonary adverse events are the primary concerns associated with the use of these sedatives. Remimazolam tosylate is an ultra-short-acting benzodiazepine drug with a mild inhibitory effect on the respiratory and circulatory systems. These properties qualify remimazolam tosylate to be used as a replacement for propofol or midazolam as a sedative during gastrointestinal endoscopy. This study aims to describe the efficacy and safety of remimazolam tosylate as a sedative for upper gastrointestinal endoscopy. METHODS: A multicenter, randomized, single-blind, parallel-controlled, noninferiority clinical study will be conducted to evaluate the efficacy and safety of remimazolam tosylate as a sedative during upper gastrointestinal endoscopy. Participants (n = 1800) will be randomized to receive remimazolam tosylate at 0.15 mg/kg (experimental group 1), remimazolam tosylate at 0.2 mg/kg (experimental group 2), or propofol at 1.5 mg/kg (control group). Procedure success will be assessed and defined as the completion of upper gastrointestinal endoscopy without the administration of a rescue sedative agent or more than two top-up doses of the trial drug in any 5-min period after initial administration. Sedation quality will be evaluated using the Modified Observer's Assessment of Alertness/Sedation score. Adverse events will be recorded to evaluate safety. DISCUSSION: This study will determine the optimal dosage of remimazolam tosylate during upper gastrointestinal endoscopy and will describe its efficacy and safety. These findings may contribute to a more comfortable and safer experience for patients compared with that when the conventional sedative propofol is used. TRIAL REGISTRATION: ClinicalTrials.gov NCT04727034. Registered on February 18, 2021.
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Midazolam , Propofol , Humanos , Método Simples-Cego , Midazolam/efeitos adversos , Benzodiazepinas , Hipnóticos e Sedativos/efeitos adversos , Propofol/efeitos adversos , Endoscopia Gastrointestinal/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
The habenula (Hb) is a small structure of the posterior diencephalon that is highly conserved across vertebrates but nonetheless has attracted relatively little research attention until the past two decades. The resurgent interest is motivated by neurobehavioral studies demonstrating critical functions in a broad spectrum of motivational and cognitive processes, including functions relevant to psychiatric diseases. The Hb is widely conceived as an "anti-reward" center that acts by regulating brain monoaminergic systems. However, there is still no general conceptual framework for habenula research, and no study has focused on uncovering potentially significant but overlooked topics that may advance our understanding of physiological functions or suggest potential clinical applications of Hb-targeted interventions. Using science mapping tools, we quantitatively and qualitatively analyzed the relevant publications retrieved from the Web of Science Core Collection (WoSCC) database from 2002 to 2021. Herein we present an overview of habenula-related publications, reveal primary research trends, and prioritize some key research fronts by complementary bibliometric analysis. High-priority research fronts include Ventral Pallidum, Nucleus Accumbens, Nicotine and MHb, GLT-1, Zebrafish, and GCaMP, Ketamine, Deep Brain Stimulation, and GPR139. The high intrinsic heterogeneity of the Hb, extensive connectivity with both hindbrain and forebrain structures, and emerging associations with all three dimensions of mental disorders (internalizing, externalizing, and psychosis) suggest that the Hb may be the neuronal substrate for a common psychopathology factor shared by all mental illnesses termed the p factor. A future challenge is to explore the therapeutic potential of habenular modulation at circuit, cellular, and molecular levels.
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Backgrounds and aims: Pain is the main reason for hysteroscopy failure. In day-surgical settings, hysteroscopy procedures are commonly performed with the patient under sedation. Hypoxia is the most common adverse event during sedation and can lead to severe adverse events. This study aimed to compare the incidence of hypoxia when using high-flow nasal oxygen (HFNO) with that when using regular nasal oxygen in patients undergoing hysteroscopy with sedation. Materials and methods: In this single-center, prospective, randomized, single-blinded study, 960 female patients undergoing elective diagnostic or operative hysteroscopy were randomly enrolled into the following two groups: the regular nasal group [O2 (3-6 L/min) covered by an HFNO] and the HFNO group [O2 (30-60 L/min)] from September 2021 to December 2021. All women were sedated with propofol (1.5 mg/kg) and remifentanil (1.5 µg/kg) in the operating room. The primary outcome was the incidence of hypoxia (75% ≤ SpO2 < 90%, < 60 s). Results: HFNO decreased the incidence of hypoxia (75% ≤ SpO2 < 90%, < 60 s), subclinical respiratory depression (90% ≤ SpO2 < 95%) and severe hypoxia (SpO2 < 75% for any duration or 75% ≤ SpO2 < 90% for ≥ 60 s) from 24.38 to 0.83%, from 11.25 to 1.46% and from 3.75 to 0%, respectively (P < 0.001). Conclusion: In procedures conducted to treat female infertility, HFNO can reduce hypoxia during hysteroscopy in patients sedated with propofol, and it can prevent the occurrence of subclinical respiratory depression and severe hypoxia.
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Purpose: Herpes zoster infection, with its considerable burden to individuals and society, remains a challenge around the world. However, to the knowledge of the authors, little bibliometric quantitative or qualitative analysis has been carried out to evaluate herpes zoster research. This study aimed to use a bibliometric analysis to evaluate current publication trends and hotspots on herpes zoster research worldwide, in order to advance research in this field. Methods: Relevant publications from January 2012 to December 2021 were collected from the Web of Science Core Collection database. Citespace (V5.8.R3) was used to analyze the research points, including publication countries, institutions and authors, cited author, cited reference and their clustering, and keyword co-occurrence, and burst keyword to acquire research trends and hotspots. Results: A total of 9,259 publications were obtained, with a steady increase in the number of annual publications during the decade. Articles were the main type of publication. The United States is the leading country in this research, and the University of Colorado has the highest influence in this field. Oxman is the most representative author, with a main research interest in herpes zoster vaccines. The top five cited authors' publications focused on herpes zoster vaccines, molecular mechanisms, and postherpetic neuralgia. A co-citation map resulted 19 main clusters, and revealed that vaccines, postherpetic neuralgia, treatments, varicella zoster virus and its mechanisms, and epidemiology of herpes zoster were the current research focus after clustering co-cited publications. Human herpesviruses, antiviral prophylaxis, rheumatoid arthritis, recombinant zoster vaccine, varicella vaccination and postherpetic neuralgia were the top clusters after co-occurrence keywords analysis. Moreover, burst keywords detection showed that the subunit vaccine was the new hotspot in the field of herpes zoster. Conclusion: This bibliometric study defined the overall prospects in the field of herpes zoster and provided valuable instruction for the ongoing research. The keyword "subunit vaccine" indicated that a vaccine for herpes zoster prevention was the hotspot. Efforts to prevent varicella zoster virus infection will be essential to improve herpes zoster outcomes.