The Anesthesiologists' Perception of Malignant Hyperthermia and Availability of Dantrolene in China: A Cross-Sectional Survey.

Background: Malignant hyperthermia (MH) is a hypermetabolic syndrome with high mortality rates. Early detection and prompt intravenous administration of dantrolene are crucial for effective management of MH. However, there is currently a lack of comprehensive nationwide surveys on the availability of dantrolene and anesthesiologists' understanding of MH in China. Methods: A nationwide survey was conducted between January 2022 and June 2022. Online questionnaires on the cognition of MH among anesthesiologists in China were sent through social platforms to anesthesiologists in mainland China. Data regarding participants' perception of MH-related knowledge, availability of domestic dantrolene, and reported MH cases were collected in this study. Results: Responses were collected from a total of 11,354 anesthesiologists representing 31 provinces across the Chinese mainland. Among the 11 scoring questions, the highest accuracy rates were observed for the question regarding therapeutic drugs for MH (99.3%) and the characteristics of MH (98.0%). Conversely, the question pertaining to the earliest clinical signs of MH had the lowest accuracy rate (23.5%). Significant variations were observed in the scores among different professional titles (P=0.003), academic degree (P<0.001), hospital classification (P<0.001), and urban hierarchy (P<0.001). Of the respondents, 919 (8.1%) anesthesiologists reported dantrolene availability in their hospitals, and 631 (5.6%) indicated unclear. A total of 136 hospitals in this survey reported at least one previous case of MH. Conclusion: Mainland China faces challenges such as insufficient experience in diagnosing and treating MH, as well as difficulty in obtaining dantrolene. To improve the public awareness of MH, it is imperative to establish and promote a refined MH training system. Additionally, a streamlined and rapid dantrolene linkage emergency system should be implemented to ensure prompt access to the drug.

Water-Stable High-Entropy Metal-Organic Framework Nanosheets for Photocatalytic Hydrogen Production.

Metal-organic frameworks (MOFs) have emerged as promising platforms for photocatalytic hydrogen evolution reaction (HER) due to their fascinating physiochemical properties. Rationally engineering the compositions and structures of MOFs can provide abundant opportunities for their optimization. In recent years, high-entropy materials (HEMs) have demonstrated great potential in the energy and environment fields. However, there is still no report on the development of high-entropy MOFs (HE-MOFs) for photocatalytic HER in aqueous solution. Herein, the authors report the synthesis of a novel p-type HE-MOFs single crystal (HE-MOF-SC) and the corresponding HE-MOFs nanosheets (HE-MOF-NS) capable of realizing visible-light-driven photocatalytic HER. Both HE-MOF-SC and HE-MOF-NS exhibit higher photocatalytic HER activity than all the single-metal MOFs, which are supposed to be ascribed to the interplay between the different metal nodes in the HE-MOFs that enables more efficient charge transfer. Moreover, impressively, the HE-MOF-NS demonstrates much higher photocatalytic activity than the HE-MOF-SC due to its thin thickness and enhanced surface area. At optimum conditions, the rate of H2 evolution on the HE-MOF-NS is ≈13.24 mmol h-1 g-1, which is among the highest values reported for water-stable MOF photocatalysts. This work highlights the importance of developing advanced high-entropy materials toward enhanced photocatalysis.

Joint-GWAS, Linkage Mapping, and Transcriptome Analysis to Reveal the Genetic Basis of Plant Architecture-Related Traits in Maize.

Plant architecture is one of the key factors affecting maize yield formation and can be divided into secondary traits, such as plant height (PH), ear height (EH), and leaf number (LN). It is a viable approach for exploiting genetic resources to improve plant density. In this study, one natural panel of 226 inbred lines and 150 family lines derived from the offspring of T32 crossed with Qi319 were genotyped by using the MaizeSNP50 chip and the genotyping by sequence (GBS) method and phenotyped under three different environments. Based on the results, a genome-wide association study (GWAS) and linkage mapping were analyzed by using the MLM and ICIM models, respectively. The results showed that 120 QTNs (quantitative trait nucleotides) and 32 QTL (quantitative trait loci) related to plant architecture were identified, including four QTL and 40 QTNs of PH, eight QTL and 41 QTNs of EH, and 20 QTL and 39 QTNs of LN. One dominant QTL, qLN7-2, was identified in the Zhangye environment. Six QTNs were commonly identified to be related to PH, EH, and LN in different environments. The candidate gene analysis revealed that Zm00001d021574 was involved in regulating plant architecture traits through the autophagy pathway, and Zm00001d044730 was predicted to interact with the male sterility-related gene ms26. These results provide abundant genetic resources for improving maize plant architecture traits by using approaches to biological breeding.

LncRNA CHROMR/miR-27b-3p/MET axis promotes the proliferation, invasion, and contributes to rituximab resistance in diffuse large B-cell lymphoma.

Long non-coding RNAs (LncRNAs) could regulate chemoresistance through sponging microRNAs (miRNAs) and sequestering RNA binding proteins. However, the mechanism of lncRNAs in rituximab resistance in diffuse large B-cell lymphoma (DLBCL) is largely unknown. Here, we investigated the functions and molecular mechanisms of lncRNA CHROMR in DLBCL tumorigenesis and chemoresistance. LncRNA CHROMR is highly expressed in DLBCL tissues and cells. We examined the oncogenic functions of lncRNA CHROMR in DLBCL by a panel of gain-or-loss-of-function assays and in vitro experiments. LncRNA CHROMR suppression promotes CD20 transcription in DLBCL cells and inhibits rituximab resistance. RNA immunoprecipitation, RNA pull-down, and dual luciferase reporter assay reveal that lncRNA CHROMR sponges with miR-27b-3p to regulate mesenchymal-epithelial transition factor (MET) levels and Akt signaling in DLBCL cells. Targeting the lncRNA CHROMR/miR-27b-3p/MET axis reduces DLBCL tumorigenesis. Altogether, these findings provide a new regulatory model, lncRNA CHROMR/miR-27b-3p/MET, which can serve as a potential therapeutic target for DLBCL.

Preoperative prognostic nutritional index value as a predictive factor for postoperative delirium in older adult patients with hip fractures: a secondary analysis.

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

Identification of difficult laryngoscopy using an optimized hybrid architecture.

BACKGROUND: Identification of difficult laryngoscopy is a frequent demand in cervical spondylosis clinical surgery. This work aims to develop a hybrid architecture for identifying difficult laryngoscopy based on new indexes. METHODS: Initially, two new indexes for identifying difficult laryngoscopy are proposed, and their efficacy for predicting difficult laryngoscopy is compared to that of two conventional indexes. Second, a hybrid adaptive architecture with convolutional layers, spatial extraction, and a vision transformer is proposed for predicting difficult laryngoscopy. The proposed adaptive hybrid architecture is then optimized by determining the optimal location for extracting spatial information. RESULTS: The test accuracy of four indexes using simple model is 0.8320. The test accuracy of optimized hybrid architecture using four indexes is 0.8482. CONCLUSION: The newly proposed two indexes, the angle between the lower margins of the second and sixth cervical spines and the vertical direction, are validated to be effective for recognizing difficult laryngoscopy. In addition, the optimized hybrid architecture employing four indexes demonstrates improved efficacy in detecting difficult laryngoscopy. TRIAL REGISTRATION: Ethics permission for this research was obtained from the Medical Scientific Research Ethics Committee of Peking University Third Hospital (IRB00006761-2015021) on 30 March 2015. A well-informed agreement has been received from all participants. Patients were enrolled in this research at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn , identifier: ChiCTR-ROC-16008598) on 6 June 2016.

Melatonin regulates the circadian rhythm to ameliorate postoperative sleep disorder and neurobehavioral abnormalities in aged mice.

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

Epidemiological and clinical features of malignant hyperthermia: A scoping review.

Malignant hyperthermia (MH) is a potentially fatal inherited pharmacogenetic disorder related to pathogenic variants in the RYR1, CACNA1S, or STAC3 genes. Early recognition of the occurrence of MH and prompt medical treatment are indispensable to ensure a positive outcome. The purpose of this study was to provide valuable information for the early identification of MH by summarizing epidemiological and clinical features of MH. This scoping review followed the methodological framework recommended by Arksey and O'Malley. PubMed, Embase, and Web of science databases were searched for studies that evaluated the epidemical and clinical characteristics of MH. A total of 37 studies were included in this review, of which 26 were related to epidemiology and 24 were associated with clinical characteristics. The morbidity of MH varied from 0.18 per 100 000 to 3.9 per 100 000. The mortality was within the range of 0%-18.2%. Identified risk factors included sex, age, disorders associated with MH, and others. The most frequent initial clinical signs included hyperthermia, sinus tachycardia, and hypercarbia. The occurrence of certain signs, such as hypercapnia, delayed first temperature measurement, and peak temperature were associated with poor outcomes. The epidemiological and clinical features of MH varied considerably and some risk factors and typical clinical signs were identified. The main limitation of this review is that the treatment and management strategies were not assessed sufficiently due to limited information.

Preoperative radiological indicators for prediction of difficult laryngoscopy in patients with atlantoaxial dislocation.

Background: Difficult airway remains a great challenge in patients with atlantoaxial dislocation (AAD). Preoperative evaluation and reliable prediction are required to facilitate the airway management. We aimed to screen out reliable radiological indicators for prediction of difficult laryngoscopy in patients with AAD. Methods: A retrospective nested case-control study within a single center longitudinal AAD cohort was conducted to investigate the radiological indicators. All the patients with difficult laryngoscopy from 2010 to 2021 were enrolled as the difficult laryngoscopy group. Others in the cohort without difficult laryngoscopy were randomly selected as the non-difficult laryngoscopy group by individually matching with the same gender, same surgery year, and similar age (±5 years) at a ratio of 6:1. Radiological data on preoperative lateral X-ray images between the two groups were compared. Bivariate logistic regression model was applied to screen out the independent predictive indicators and calculate the odds ratios of indicators associated with difficult laryngoscopy. Receiver operating characteristic curve and area under the curve (AUC) were used to describe the discrimination ability of indicators. Results: A total of 154 patients were finally analyzed in this study. Twenty-two patients with difficult laryngoscopy and matched with 132 controls. Four radiological parameters showed significant difference between the two groups. Among which, ΔC1C2D (the difference of the distance between atlas and axis in the neutral and extension position), owned the largest AUC. Conclusions: ΔC1C2D could be a valuable radiologic predictor for difficult laryngoscopy in patients with AAD.

Evaluation of brain function in adult patent ductus arteriosus surgery: A multimodal monitoring approach.

Adult patent ductus arteriosus (PDA) repair surgery often involves hypothermic cardiopulmonary bypass (CPB) and is associated with postoperative neurological complications. Our study evaluates brain function during PDA surgery using regional cerebral oxygen saturation (rSO2) and bispectral index (BIS) monitoring to mitigate these complications. Patients were categorized into moderate (26-31 â„ƒ) and mild (32-35 â„ƒ) hypothermia groups. Findings indicate a positive correlation between PDA diameter and pulmonary artery systolic blood pressure, and a strong correlation between delirium and average rSO2-AUC. The mild hypothermia group had longer extubation and hospitalization times. During CPB, rSO2 levels fluctuated significantly, and EEG analysis revealed changes in brain wave patterns. One case of nerve injury in the mild hypothermia group showed incomplete recovery after a year. Our results advocate for moderate hypothermia during CPB in adult PDA repair, suggesting that combined rSO2 and BIS monitoring can reduce neurological complications post-surgery.

Effect of cerebral oxygen saturation monitoring in patients undergoing superficial temporal anterior-middle cerebral artery anastomosis for ischemic Moyamoya disease: a prospective cohort study.

Objective: Regional cerebral oxygen saturation (rSO2) is linked with blood pressure. This study evaluated the influence of perioperative rSO2 monitoring on the prognosis of ischemic Moyamoya disease (MMD) patients undergoing anastomosis surgery. Methods: In this prospective cohort, patients with unilateral ischemic MMD of Suzuki stage ≥3 were included. The decision of rSO2 was made by the clinician and the patient. The rSO2 group maintained intraoperative rSO2 levels through the modulation of blood pressure, inhaled oxygen concentration, carbon dioxide in arterial blood, and red blood cell transfusion. The non-rSO2 group used conventional anesthesia practices. Perioperative mean arterial pressure (MAP), rSO2 values, neurological complications, and postoperative results were assessed. Results: A total of 75 eligible patients were categorized into a rSO2 monitoring group (n = 30) and a non-rSO2 monitoring group (n = 45). For the rSO2 group, the preoperative rSO2 was significantly lower on the affected side (P < 0.05). After anastomosis, this value notably increased (P = 0.01). A moderate relationship was observed between perioperative rSO2 and MAP before, during, and after surgery, with correlation coefficients (r) of 0.536, 0.502, and 0.592 (P < 0.05). Post-surgery MAP levels differed between the groups, with the rSO2 group showing decreased levels compared to pre-surgery and the non-rOS2 group displaying elevated levels. Notably, the rSO2 group reported shorter hospitalizations and decreased neurological complications. Patients with a hypertension history found postoperative MAP influencing hospital stay duration. Conclusion: Perioperative rSO2 surveillance enhanced cerebral perfusion and minimized postoperative complications in ischemic MMD patients. Thus, rSO2 monitoring is advocated for MMD patients undergoing vascular anastomosis.

Development of a Brief Cognitive Screening Tool for Predicting Postoperative Delirium in Patients with Parkinson's Disease: A Secondary Analysis.

Background: A simple, rapid, and effective cognitive screening test appropriate for fast-paced settings with limited resources and staff is essential, especially preoperatively. This study aimed to develop and validate the short versions of Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) for predicting postoperative delirium (POD) in patients with Parkinson's disease (PD) who were scheduled for surgery. Methods: The current study was a secondary analysis of data collected from 128 inpatients scheduled for deep brain stimulation of the subthalamic nuclei (STN-DBS) lasting >60 min, at Tsinghua University Yuquan Hospital, China. Preoperative cognitive screening was performed during the preoperative visit using the MMSE and MoCA. The optimal MMSE and MoCA cut-off scores for detecting PD-MCI was 27 and 23 respectively. The POD was assessed twice a day on the first postoperative day until discharge by the confusion assessment method. The backward conditional logistic regression analysis was used to organize the reduced versions of the MMSE or MoCA. Also, the areas under the receiver operating characteristic curves (AUCs) were examined using the DeLong test. Results: 125/128 PD patients were included in the analysis, and 27 (21.6%) developed POD. The MMSE reduced version (orientation to time, attention and calculation, and comprehension) demonstrated performance similar to the original MMSE in predicting POD (z=0.820, p=0.412). The AUC of the original MoCA and the short MoCA (visuospatial and executive attention and orientation) were 0.808 and 0.826, respectively. There was no significantly difference in the AUC values between the tests (z=0.561, p=0.575). Conclusion: Our simplified MMSE and MoCA could be efficiently used to identify patients at risk for POD. Also, short cognitive tests could be considered while predicting POD in fast-paced preoperative settings with limited resources and staff.

Chalcogen-bridged coordination polymer for the photocatalytic activation of aryl halides.

The ability to deliver electrons is vital for dye-based photocatalysts. Conventionally, the aromatic stacking-based charge-transfer complex increases photogenerated electron accessibility but decreases the energy of excited-state dyes. To circumvent this dilemma, here we show a strategy by tuning the stacking mode of dyes. By decorating naphthalene diimide with S-bearing branches, the S···S contact-linked naphthalene diimide string is created in coordination polymer, thereby enhancing electron mobility while simultaneously preserving competent excited-state reducing power. This benefit, along with in situ assembly between naphthalene diimide strings and exogenous reagent/reactant, improves the accessibility of short-lived excited states during consecutive photon excitation, resulting in greater efficiency in photoinduced electron-transfer activation of inert bonds in comparison to other coordination polymers with different dye-stacking modes. This heterogeneous approach is successfully applied in the photoreduction of inert aryl halides and the successive formation of CAr-C/S/P/B bonds with potential pharmaceutical applications.

Integrated IBD Analysis, GWAS Analysis and Transcriptome Analysis to Identify the Candidate Genes for White Spot Disease in Maize.

Foundation parents (FPs) play an irreplaceable role in maize breeding practices. Maize white spot (MWS) is an important disease in Southwest China that always seriously reduces production. However, knowledge about the genetic mechanism of MWS resistance is limited. In this paper, a panel of 143 elite lines were collected and genotyped by using the MaizeSNP50 chip with approximately 60,000 single nucleotide polymorphisms (SNPs) and evaluated for resistance to MWS among 3 environments, and a genome-wide association study (GWAS) and transcriptome analysis were integrated to reveal the function of the identity-by-descent (IBD) segments for MWS. The results showed that (1) 225 IBD segments were identified only in the FP QB512, 192 were found only in the FP QR273 and 197 were found only in the FP HCL645. (2) The GWAS results showed that 15 common quantitative trait nucleotides (QTNs) were associated with MWS. Interestingly, SYN10137 and PZA00131.14 were in the IBD segments of QB512, and the SYN10137-PZA00131.14 region existed in more than 58% of QR273's descendants. (3) By integrating the GWAS and transcriptome analysis, Zm00001d031875 was found to located in the region of SYN10137-PZA00131.14. These results provide some new insights for the detection of MWS's genetic variation mechanisms.

A Bibliometric Analysis for Low-Intensity Ultrasound Study Over the Past Three Decades.

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

Inactivation of the antidiabetic drug acarbose by human intestinal microbial-mediated degradation.

Drugs can be modified or degraded by the gut microbiota, which needs to be considered in personalized therapy. The clinical efficacy of the antidiabetic drug acarbose, an inhibitor of α-glucosidase, varies greatly among individuals for reasons that are largely unknown. Here we identify in the human gut acarbose-degrading bacteria, termed Klebsiella grimontii TD1, whose presence is associated with acarbose resistance in patients. Metagenomic analyses reveal that the abundance of K. grimontii TD1 is higher in patients with a weak response to acarbose and increases over time with acarbose treatment. In male diabetic mice, co-administration of K. grimontii TD1 reduces the hypoglycaemic effect of acarbose. Using induced transcriptome and protein profiling, we further identify an acarbose preferred glucosidase, Apg, in K. grimontii TD1, which can degrade acarbose into small molecules with loss of inhibitor function and is widely distributed in human intestinal microorganisms, especially in Klebsiella. Our results suggest that a comparatively large group of individuals could be at risk of acarbose resistance due to its degradation by intestinal bacteria, which may represent a clinically relevant example of non-antibiotic drug resistance.

Factors associated with euphoria in a large subset of cases using propofol sedation during gastrointestinal endoscopy.

Background: The utilization of Propofol, a widely used intravenous sedative or anesthetic, is characterized by its quick onset, predictable control, and fleeting half-life during both general anesthesia and intensive care unit sedation. Recent evidence, however, has highlighted propofol's propensity to induce euphoria, particularly in patients undergoing painless procedures such as gastrointestinal or gastric endoscopy. Given its widespread use in patients undergoing such procedures, this study aims to investigate the clinical evidence and factors that may influence propofol-induced euphoria in these settings. Methods: The Addiction Research Center Inventory-Chinese Version (ARCI-CV) scale was administered to 360 patients undergoing gastric or gastrointestinal endoscopy using propofol as a sedative. Patient characteristics including past medical history, depression, anxiety, alcohol abuse, and sleep disturbance were recorded through history taking and assessment using various questionnaires prior to the examination. The euphoric and sedative statuses were assessed at 30 min and 1 week post-examination. Results: The experimental results of a survey of 360 patients who underwent gastric or gastrointestinal endoscopy using propofol showed that the mean Morphine-Benzedrine Group (MBG) score before the procedure and after 30 min of the procedure was 4.23 and 8.67, respectively. The mean Pentobarbital-Chlorpromazine-Alcohol Group (PCAG) score before the procedure and after 30 min of the procedure was 3.24 and 6.22, respectively. These results showed that both MBG and PCAG scores increased significantly after the procedure. Certain factors, such as dreaming, propofol dose, duration of anesthesia, and etomidate dose, were all correlated with MBG both at 30 min and 1 week after the examination. In addition, etomidate had an effect of decreasing MBG scores and increasing PCAG scores both at 30 min and 1 week after the examination. Conclusion: Taken together, propofol may elicit euphoria and potentially contribute to propofol addiction. There are several risk factors for the development of propofol addiction, including dreaming, propofol dose, duration of anesthesia, and etomidate dose. These findings suggest that propofol may have a euphoric effect and may have the potential for drug addiction and abuse.

Rapamycin Affects the Hippocampal SNARE Complex to Alleviate Cognitive Dysfunction Induced by Surgery in Aged Rats.

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

Low-Intensity Pulsed Ultrasound Attenuates Postoperative Neurocognitive Impairment and Salvages Hippocampal Synaptogenesis in Aged Mice.

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

Reciprocal interaction between mitochondrial fission and mitophagy in postoperative delayed neurocognitive recovery in aged rats.

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