Efficacy and safety of subanesthetic doses of esketamine combined with propofol in painless gastrointestinal endoscopy: a prospective, double-blind, randomized controlled trial.

BACKGROUND: Painless gastrointestinal endoscopy is widely used for the diagnosis and treatment of digestive diseases. At present, propofol is commonly used to perform painless gastrointestinal endoscopy, but the high dose of propofol often leads to a higher incidence of cardiovascular and respiratory complications. Studies have shown that the application of propofol combined with ketamine in painless gastrointestinal endoscopy is beneficial to reduce the dosage of propofol and the incidence of related complications. Esketamine is dextrorotatory structure of ketamine with a twice as great anesthetic effect as normal ketamine but fewer side effects. We hypothesized that esketamine may reduce the consumption of propofol and to investigate the safety of coadministration during gastrointestinal endoscopy. METHODS: A total of 260 patients undergoing painless gastrointestinal endoscopy (gastroscope and colonoscopy) were randomly divided into P group (propofol + saline), PK1 group (propofol + esketamine 0.05 mg/kg), PK2 group (propofol + esketamine 0.1 mg/kg), and PK3 group (propofol + esketamine 0.2 mg/kg). Anesthesia was achieved by 1.5 mg/kg propofol with different doses of esketamine. Propofol consumption per minute was recorded. Hemodynamic index, pulse oxygen saturation, operative time, induction time, awakening status, orientation recovery time, adverse events, and Mini-Mental State Examination (MMSE) were also recorded during gastrointestinal endoscopy. RESULTS: Propofol consumption per minute was 11.78, 10.56, 10.14, and 9.57 (mg/min) in groups P, PK1, PK2, and PK3, respectively; compared with group P, groups PK2 and PK3 showed a decrease of 13.92% (P = 0.021) and 18.76% (P = 0.000), respectively. In all four groups, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), but not pulse oxygen saturation (SpO2) significantly decreased (P = 0.000) immediately after administration of induction, but there were no significant differences between the groups. The induction time of groups P, PK1, PK2, and PK3 was 68.52 ± 18.394, 64.83 ± 13.543, 62.23 ± 15.197, and 61.35 ± 14.470 s, respectively (P = 0.041). Adverse events and psychotomimetic effects were observed but without significant differences between the groups. CONCLUSIONS: The combination of 0.2 mg/kg esketamine and propofol was effective and safe in painless gastrointestinal endoscopy as evidenced by less propofol consumption per minute, shorter induction time, and lower incidence of cough and body movement relative to propofol alone. The lack of significant differences in hemodynamic results, anesthesia-related indices, adverse events, and MMSE results showed the safety to apply this combination for painless gastrointestinal endoscopy. Trial registration This study was registered with China Clinical Trial Registration on 07/11/2020 (registration website: chictr.org.cn; registration numbers: ChiCTR https://clinicaltrials.gov/ct2/show/2000039750 ).

Dantrolene Ameliorates Impaired Neurogenesis and Synaptogenesis in Induced Pluripotent Stem Cell Lines Derived from Patients with Alzheimer's Disease.

BACKGROUND: Overactivation of ryanodine receptors and the resulting impaired calcium homeostasis contribute to Alzheimer's disease-related pathophysiology. This study hypothesized that exposing neuronal progenitors derived from induced pluripotent stems cells of patients with Alzheimer's disease to dantrolene will increase survival, proliferation, neurogenesis, and synaptogenesis. METHODS: Induced pluripotent stem cells obtained from skin fibroblast of healthy subjects and patients with familial and sporadic Alzheimer's disease were used. Biochemical and immunohistochemical methods were applied to determine the effects of dantrolene on the viability, proliferation, differentiation, and calcium dynamics of these cells. RESULTS: Dantrolene promoted cell viability and proliferation in these two cell lines. Compared with the control, differentiation into basal forebrain cholinergic neurons significantly decreased by 10.7% (32.9 ± 3.6% vs. 22.2 ± 2.6%, N = 5, P = 0.004) and 9.2% (32.9 ± 3.6% vs. 23.7 ± 3.1%, N = 5, P = 0.017) in cell lines from sporadic and familial Alzheimer's patients, respectively, which were abolished by dantrolene. Synapse density was significantly decreased in cortical neurons generated from stem cells of sporadic Alzheimer's disease by 58.2% (237.0 ± 28.4 vs. 99.0 ± 16.6 arbitrary units, N = 4, P = 0.001) or familial Alzheimer's disease by 52.3% (237.0 ± 28.4 vs.113.0 ± 34.9 vs. arbitrary units, N = 5, P = 0.001), which was inhibited by dantrolene in the familial cell line. Compared with the control, adenosine triphosphate (30 µM) significantly increased higher peak elevation of cytosolic calcium concentrations in the cell line from sporadic Alzheimer's patients (84.1 ± 27.0% vs. 140.4 ± 40.2%, N = 5, P = 0.049), which was abolished by the pretreatment of dantrolene. Dantrolene inhibited the decrease of lysosomal vacuolar-type H-ATPase and the impairment of autophagy activity in these two cell lines from Alzheimer's disease patients. CONCLUSIONS: Dantrolene ameliorated the impairment of neurogenesis and synaptogenesis, in association with restoring intracellular Ca homeostasis and physiologic autophagy, cell survival, and proliferation in induced pluripotent stem cells and their derived neurons from sporadic and familial Alzheimer's disease patients.

Comparative genomics of 84 Pectobacterium genomes reveals the variations related to a pathogenic lifestyle.

BACKGROUND: Pectobacterium spp. are necrotrophic bacterial plant pathogens of the family Pectobacteriaceae, responsible for a wide spectrum of diseases of important crops and ornamental plants including soft rot, blackleg, and stem wilt. P. carotovorum is a genetically heterogeneous species consisting of three valid subspecies, P. carotovorum subsp. brasiliense (Pcb), P. carotovorum subsp. carotovorum (Pcc), and P. carotovorum subsp. odoriferum (Pco). RESULTS: Thirty-two P. carotovorum strains had their whole genomes sequenced, including the first complete genome of Pco and another circular genome of Pcb, as well as the high-coverage genome sequences for 30 additional strains covering Pcc, Pcb, and Pco. In combination with 52 other publicly available genome sequences, the comparative genomics study of P. carotovorum and other four closely related species P. polaris, P. parmentieri, P. atrosepticum, and Candidatus P. maceratum was conducted focusing on CRISPR-Cas defense systems and pathogenicity determinants. Our analysis identified two CRISPR-Cas types (I-F and I-E) in Pectobacterium, as well as another I-C type in Dickeya that is not found in Pectobacterium. The core pathogenicity factors (e.g., plant cell wall-degrading enzymes) were highly conserved, whereas some factors (e.g., flagellin, siderophores, polysaccharides, protein secretion systems, and regulatory factors) were varied among these species and/or subspecies. Notably, a novel type of T6SS as well as the sorbitol metabolizing srl operon was identified to be specific to Pco in Pectobacterium. CONCLUSIONS: This study not only advances the available knowledge about the genetic differentiation of individual subspecies of P. carotovorum, but also delineates the general genetic features of P. carotovorum by comparison with its four closely related species, thereby substantially enriching the extent of information now available for functional genomic investigations about Pectobacterium.

The Effect of Lidocaine-Prilocaine Cream Combined with or Without Remimazolam on VAS and APAIS Anxiety Score in Patient Undergoing Spinal Anesthesia.

Purpose: This study aimed to investigate patients' expectative pain of spinal anesthesia puncture and anxiety pre-anesthesia, and to examine the effect of lidocaine-prilocaine cream and remimazolam prior to spinal anesthesia puncture on pain relief and anxiety release. Methods: Patients undergoing spinal anesthesia were divided into control, lidocaine-prilocaine cream, and lidocaine-prilocaine cream with remimazolam groups. A questionnaire consisting of The Amsterdam Preoperative Anxiety and Information Scale (APAIS) and patient's concerns and Visual Analog Scale (VAS) was used to evaluate patient's anxiety and pain. The primary outcomes were differences in VAS and anxiety scores. Patient's spinal anesthesia-related concerns, advent events and hemodynamic index were also recorded. Results: The expected spinal anesthesia puncture pain was 5.34±0.27 and anxiety scores before spinal anesthesia was 10.88 ± 0.64. A statistically significant positive correlation of 31.3% was detected between VAS and APAIS scores (r = 0.313; P=0.003). The VAS score at the time of puncture decreased by 29.7% (3.78±0.40, P=0.001) in lidocaine-prilocaine cream group and 29.2% (3.75±0.39, P=0.001) in lidocaine-prilocaine cream with remimazolam group compared with the expected VAS score. Lidocaine-prilocaine cream combined with or without remimazolam reduced the percentage of moderate pain (21.4% and 31.3% vs 50.0%, P=0.0001) and increased mild pain (60.7% vs 59.4% vs 22.7%, P=0.03). Anxiety score in lidocaine-prilocaine cream group was reduced by 2.84 (8.04±0.76 vs 10.88 ± 0.46, P=0.05) when compared with pre-anesthesia. Concerns about postoperative pain (P=0.03) and fear of the needle or intervention (P=0.000) both decreased post-anesthesia among groups. Conclusion: Approximately half of the patients scheduled for spinal anesthesia experienced a moderate level of preoperative anxiety. The patient's pain expectation from the spinal anesthesia puncture was moderate, which was higher than the actual pain. Lidocaine-prilocaine cream with or without remimazolam sedative before spinal anesthesia puncture reduced the patient's pain and anxiety scores after surgery.

Correlation analysis between Raman spectral signature and transcriptomic features of carbapenem-resistant Klebsiella pneumoniae.

The Raman microspectroscopy technology has been successfully applied to evaluate the molecular composition of living cells for identifying cell types and states, but the rationale behind it was not well investigated. In this study, we acquired single-cell Raman spectra (SCRS) of three Klebsiella pneumoniae (K. pneumoniae) strains with different Carbapenem resistant mechanisms and analyzed them with machine learning algorithm. Two carbapenem resistant Klebsiella pneumoniae (CRKP) strains can be successfully distinguished from susceptible strain and CRKP with KPC or IMP carbapenemases can be classified with an overall accuracy achieving 100 %. Furthermore, we performed a correlation analysis between transcriptome and Raman spectra, and found that Raman shifts such as 752 and 1039 cm-1 highly correlated with drug resistance genes expression and could be regarded as Raman biomarkers for CRKP with different mechanisms. The findings of the study provide a theoretical basis for identifying the relationship between Raman spectra and transcriptome of bacteria, as well as a novel method for rapid identification of CRKP and their carbapenemases types.

Path reliability-based graph attention networks.

Self-attention mechanism has been successfully introduced in Graph Neural Networks (GNNs) for graph representation learning and achieved state-of-the-art performances in tasks such as node classification and node attacks. In most existing attention-based GNNs, attention score is only computed between two directly connected nodes with their representation at a single layer. However, this attention score computation method cannot account for its multi-hop neighbors, which supply graph structure information and have influence on many tasks such as link prediction, knowledge graph completion, and adversarial attack as well. In order to address this problem, in this paper, we propose Path Reliability-based Graph Attention Networks (PRGATs), a novel method to incorporate multi-hop neighboring context into attention score computation, enabling to capture longer-range dependencies and large-scale structural information within a single layer. Moreover, path reliability-based attention layer, a core layer of PRGATs, uses a resource-constrain allocation algorithm to compute the reliable path and its attention scores from neighboring nodes to non-neighboring nodes, increasing the receptive field for every message-passing layer. Experimental results on real-world datasets show that, as compared with baselines, our model outperforms existing methods up to 3% on standard node classification and 12% on graph universal adversarial attack.

A cross-sectional study to assess the difference in perception of day surgery information between patients and medical staff in China.

PURPOSE: The development of day surgery in China is still in its infancy. The aim of this study is to examine the difference in perception between patients and medical staff about day surgery and to find out what kind of information should be delivered to patients perioperatively. METHODS: The study was designed as a cross-sectional study using survey questionnaires. Patients undergoing day surgery and medical staff working in the day surgery center received a preoperative teaching questionnaire (PTQ). The PTQ consisted of preoperative, operative, postoperative and anesthesia information. Participants were asked to rate accurately what day surgery information they perceived as important on a five-point Likert-type scale that ranged from very important to not important. The main outcome was the value patients and staff place on perioperative information. RESULTS: For patients, details of anesthesia (82.6%) was the most important day surgery information, while for medical staff, preoperative (58.1%), postoperative (60.7%) and anesthesia (60.0%) information were of the same importance. Patients ranked surgery effect (83.3%) and pain management (82.5%) as two of the top five most important details about day surgery, but these were not listed in the top 5 rankings of staff. Student's t-test results of mean rankings also showed that patients placed more importance on surgery effect (4.8±0.6, 4.6±0.6, P=0.036) and pain management (4.8±0.5, 4.5±0.5, P=0.031) than the medical staff did. CONCLUSION: In China, day surgery is an emerging practice with both patients and medical practitioners still lacking experience, so high-quality perioperative teaching is necessary and important. Our study examining patients and staffs' views on day surgery information should be considered when developing perioperative teaching programs. To increase patient satisfaction of the day surgery experience, delivery of patient-specific information tailored to individual circumstances is necessary.