Effects of opioid drugs on immune function in cancer patients.

Opioid receptor agonists are often used when cancer patients undergo surgery or analgesic treatment. As analgesics in clinical care, opioids can provide intraoperative or to chronic cancer pain relief. Immune function plays an important role in anti-cancer therapy, with cellular immunity, comprised principally of T-lymphocytes and natural killer cells, representing the primary anti-cancer immune response. However, it remains unclear whether immune function is further affected with the use of opioids in already immunocompromised cancer patients. This article provides a review of the effects of commonly used clinical opioids, including morphine, oxycodone, fentanyl and tramadol, on immune function in cancer patients. It provides a summary of current evidence regarding the immunomodulatory effects of opioids in the cancer setting and mechanisms underlying these interactions.

Case report: Successful anesthesia management of noncardiac surgery in a patient with single atrium.

Background: Single atrium is very rare congenital cardiac anomaly in adults. The prognosis of patients with single atrium is very poor, with 50% of patients dying owing to cardiopulmonary complications in childhood. Herein, we focused on anesthesia management for noncardiac surgery in patients with single atrium. Case presentation: A 58-year-old male with a history of bilateral varicocele underwent laparotomy for high-position ligation of the spermatic vein. The patient also had a history of single atrium, atrial fibrillation, chronic heart failure, pulmonary hypertension (PH), and complete right bundle branch block (CRBBB). Given the significant complications associated with general anesthesia in patients with PH, we preferred to use low-dose epidural anesthesia for this patient. Transthoracic echocardiography was used to assess cardiac function before and during surgery and guide perioperative fluid therapy. To limit the stress response, we used a regional nerve block for reducing postoperative pain. Furthermore, we used norepinephrine to appropriately increase the systemic vascular resistance in response to the reduction of systemic vascular resistance caused by epidural anesthesia. Conclusion: Low-dose epidural anesthesia can be safely used in patients with single atrium and PH. The use of perioperative transthoracic echocardiography is helpful in guiding fluid therapy and effectively assessing the cardiac structure and function of patients. Prophylactic administration of norepinephrine before epidural injection may make it easier to maintain the patient's BP.

The potential anti-tumor effect of anesthetics on cancer by regulating autophagy.

Autophagy is a conserved, cellular self-degradation system that is essential for maintaining intracellular homeostasis. Increasing evidence suggests that autophagy plays an important dual regulatory role in the development of many human diseases, such as cancer. Recent studies have shown that the autophagy process in tumor cells can be regulated by various stimuli from both intracellular and extracellular environments, including the effects of anesthesia. Anesthetics have been shown to not only have clinical anesthetic and sedative effects but also play important roles in the progression of tumors. The effects of different types of anesthetics on tumors differ. In this review, we summarize the basic information on autophagy, the regulatory function of autophagy in cancer, currently used autophagy-targeted tumor therapy, and the effects of different types of anesthetics on tumor progression. We focus on the molecular mechanisms by which anesthetics exert tumor-inhibiting effects by activating or inhibiting autophagy. Herein, we also explore the potential application of the anesthetic/autophagy system in clinical tumor treatment. These findings provide a theoretical basis for the use of anesthetics during the perioperative period to suppress tumor development and provide insights for autophagy-targeted cancer treatment and drug development.

Phase III clinical trial comparing the efficacy and safety of adamgammadex with sugammadex for reversal of rocuronium-induced neuromuscular block.

BACKGROUND: Preliminary clinical trials of adamgammadex, a new cyclodextrin-based selective reversal agent, have demonstrated its efficacy in reversing neuromuscular block by rocuronium. METHODS: This multicentre, randomised, double-blind, positive-controlled, non-inferiority phase III clinical trial compared the efficacy and safety of adamgammadex and sugammadex. We randomised 310 subjects to receive adamgammadex (4 mg kg-1) or sugammadex (2 mg kg-1) at reappearance of the second twitch of the train-of-four (TOF), and standard safety data were collected. RESULTS: For the primary outcome, the proportion of patients with TOF ratio ≥0.9 within 5 min was 98.7% in the adamgammadex group vs 100% in the sugammadex group, with a point estimate and 95% confidence interval (CI) of 1.3% (-4.6%, +1.3%); the lower limit was greater than the non-inferiority margin of -10%. For the key secondary outcome, the median (inter quartile range) time from the start of administration of adamgammadex or sugammadex to recovery of TOF ratio to 0.9 was 2.25 (1.75, 2.75) min and 1.75 (1.50, 2.00) min, respectively. The difference was 0.50 (95% CI: 0.25, 0.50); the upper limit was lower than the non-inferiority margin of 5 min. In addition, there were no inferior results observed in secondary outcomes. Adamgammadex had a lower incidence of adverse drug reactions compared with sugammadex (anaphylactic reaction, recurarisation, decreased heart rate, and laryngospasm; P=0.047). CONCLUSIONS: Adamgammadex was non-inferior to sugammadex with a possible lower incidence of adverse drug reactions compared with sugammadex. Adamgammadex may have a potential advantage in terms of its overall risk-benefit profile. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000039525. Registered October 30, 2020. https://www.chictr.org.cn/showproj.html?proj=56825.

Targeting the opioid remifentanil: Protective effects and molecular mechanisms against organ ischemia-reperfusion injury.

Opioids are widely used in clinical practice by activating opioid receptors (OPRs), but their clinical application is limited by a series of side effects. Researchers have been making tremendous efforts to promote the development and application of opioids. Fortunately, recent studies have identified the additional effects of opioids in addition to anesthesia and analgesia, particularly in terms of organ protection against ischemia-reperfusion (I/R) injury, with unique advantages. I/R injury in vital organs not only leads to cell dysfunction and structural damage but also induces acute and chronic organ failure, even death. Early prevention and appropriate therapeutic targets for I/R injury are crucial for organ protection. Opioids have shown cardioprotective effects for over 20 years, especially remifentanil, a derivative of fentanyl, which is a new ultra-short-acting opioid analgesic widely used in clinical anesthesia induction and maintenance. In this review, we provide current knowledge about the physiological effects related to OPR-mediated organ protection, focusing on the protective effect and mechanism of remifentanil on I/R injury in the heart and other vital organs. Herein, we also explored the potential application of remifentanil in clinical I/R injury. These findings provide a theoretical basis for the use of remifentanil to inhibit or alleviate organ I/R injury during the perioperative period and provide insights for opioid-induced human organ protection and drug development.

Mindfulness, mortality, disability rates, physical and mental health among the oldest old.

OBJECTIVES: Due to the population aging, there is an urgent need to focus on how to help the oldest old (people age 80 years or older) to reach successful aging and improve their life quality. In this study, a longitudinal design spanning 1 year was used to explore the relationship between trait mindfulness and the physical and mental health of the oldest old and the mediating role of attitude toward one's own aging (ATOA). METHOD: A total of 437 older adults from Jiangsu, China, participated in this study and completed questionnaires about trait mindfulness and ATOA at baseline, and their death, disability, negative affect (NA), and health-related quality of life (HRQoL) were collected after 1 year. RESULTS: The results indicated that trait mindfulness in the oldest old was negatively associated with their mortality, disability rate, and NA and positively associated with individual HRQoL. The results of structural equation modeling analyses indicated that ATOA mediated the association of trait mindfulness with mortality, disability rate, anxiety, and three HRQoL subdimensions: role limitations because of emotional problems, vitality, and mental health. CONCLUSIONS: This study confirmed the positive longitudinal relationships between trait mindfulness and ATOA on physical health (especially mortality and disability rates), mental health, and emotional aspects of HRQoL in the oldest old population. The findings highlight the potential significance of promoting trait mindfulness and ATOA as interventions to enhance successful aging among the oldest old, which is of particular relevance in the context of the global trend of population aging. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Computing tensor Z-eigenpairs via an alternating direction method.

Tensor eigenproblems have wide applications in blind source separation, magnetic resonance imaging, and molecular conformation. In this study, we explore an alternating direction method for computing the largest or smallest Z-eigenvalue and corresponding eigenvector of an even-order symmetric tensor. The method decomposes a tensor Z-eigenproblem into a series of matrix eigenproblems that can be readily solved using off-the-shelf matrix eigenvalue algorithms. Our numerical results show that, in most cases, the proposed method converges over two times faster and could determine extreme Z-eigenvalues with 20-50% higher probability than a classical power method-based approach.

Endothelial Glycocalyx in Aging and Age-related Diseases.

The worldwide population is aging exponentially, creating burdens to patients, their families and society. Increasing age is associated with higher risk of a wide range of chronic diseases, and aging of the vascular system is closely linked to the development of many age-related diseases. Endothelial glycocalyx is a layer of proteoglycan polymers on the surface of the inner lumen of blood vessels. It plays an important role in maintaining vascular homeostasis and protecting various organ functions. Endothelial glycocalyx loss happens through the aging process and repairing the endothelial glycocalyx may alleviate the symptoms of age-related diseases. Given the important role of the glycocalyx and its regenerative properties, it is posited that the endothelial glycocalyx may be a potential therapeutic target for aging and age-related diseases and repairing endothelial glycocalyx could play a role in the promotion of healthy aging and longevity. Here, we review the composition, function, shedding, and manifestation of the endothelial glycocalyx in aging and age-related diseases, as well as regeneration of endothelial glycocalyx.

The potential regulatory role of the lncRNA-miRNA-mRNA axis in teleost fish.

Research over the past two decades has confirmed that noncoding RNAs (ncRNAs), which are abundant in cells from yeast to vertebrates, are no longer "junk" transcripts but functional regulators that can mediate various cellular and physiological processes. The dysregulation of ncRNAs is closely related to the imbalance of cellular homeostasis and the occurrence and development of various diseases. In mammals, ncRNAs, such as long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), have been shown to serve as biomarkers and intervention targets in growth, development, immunity, and disease progression. The regulatory functions of lncRNAs on gene expression are usually mediated by crosstalk with miRNAs. The most predominant mode of lncRNA-miRNA crosstalk is the lncRNA-miRNA-mRNA axis, in which lncRNAs act as competing endogenous RNAs (ceRNAs). Compared to mammals, little attention has been given to the role and mechanism of the lncRNA-miRNA-mRNA axis in teleost species. In this review, we provide current knowledge about the teleost lncRNA-miRNA-mRNA axis, focusing on its physiological and pathological regulation in growth and development, reproduction, skeletal muscle, immunity to bacterial and viral infections, and other stress-related immune responses. Herein, we also explored the potential application of the lncRNA-miRNA-mRNA axis in the aquaculture industry. These findings contribute to an enhanced understanding of ncRNA and ncRNA-ncRNA crosstalk in fish biology to improve aquaculture productivity, fish health and quality.

Childhood trauma and aggression among Chinese college students: The mediation of self-compassion and moderation of left-behind experience.

OBJECTIVE: Previous studies have found that college students with left-behind experience presented high levels of aggression, and childhood trauma may be one of the contributors. This study aimed to examine the relationship between childhood trauma and aggression in Chinese college students, and to explore the mediating role of self-compassion and the moderating role of left-behind experience. METHOD: 629 Chinese college students completed the questionnaires at two time points: childhood trauma and self-compassion were assessed at baseline, and aggression was assessed at baseline and 3-month follow-up. RESULTS: Among these participants, 391 (62.2%) had left-behind experience. Emotional neglect of college students with left-behind experience in childhood was significantly higher than that of college students without such experience. Childhood trauma predicted aggression after 3 months among college students. Self-compassion mediated the predictive effect of childhood trauma on aggression after controlling for gender, age, only-child status, and family residential status. However, no moderating effect of left-behind experience was found. CONCLUSIONS: These findings indicated that childhood trauma is an important predictor of aggression among Chinese college students regardless of their left-behind experience. The reason for the higher aggression of left-behind college students may be that their left-behind situation increased the possibility of childhood trauma. In addition, whether in college students with left-behind experience or without such experience, childhood trauma may increase aggression by reducing the level of self-compassion. Furthermore, interventions incorporating components to improve self-compassion could be effective in decreasing aggression of college students who perceived high childhood trauma. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Design, synthesis, and mechanism of action of novel µ-conotoxin KIIIA analogues for inhibition of the voltage-gated sodium channel Nav1.7.

µ-Conotoxin KIIIA, a selective blocker of sodium channels, has strong inhibitory activity against several Nav isoforms, including Nav1.7, and has potent analgesic effects, but it contains three pairs of disulfide bonds, making structural modification difficult and synthesis complex. To circumvent these difficulties, we designed and synthesized three KIIIA analogues with one disulfide bond deleted. The most active analogue, KIIIA-1, was further analyzed, and its binding pattern to hNav1.7 was determined by molecular dynamics simulations. Guided by the molecular dynamics computational model, we designed and tested 32 second-generation and 6 third-generation analogues of KIIIA-1 on hNav1.7 expressed in HEK293 cells. Several analogues showed significantly improved inhibitory activity on hNav1.7, and the most potent peptide, 37, was approximately 4-fold more potent than the KIIIA Isomer I and 8-fold more potent than the wildtype (WT) KIIIA in inhibiting hNav1.7 current. Intraperitoneally injected 37 exhibited potent in vivo analgesic activity in a formalin-induced inflammatory pain model, with activity reaching ∼350-fold of the positive control drug morphine. Overall, peptide 37 has a simplified disulfide-bond framework and exhibits potent in vivo analgesic effects and has promising potential for development as a pain therapy in the future.

Relationship Between Post-Traumatic Stress Symptoms and Caregiver Burden In Breast Cancer Patients: The Mediating Role of Anxiety and Depression.

Breast cancer impacts not only the physical and mental health of patients but also the people around them-especially their caregivers. This study examined the relationship between post-traumatic stress symptoms (PTSS) and caregiver burden in breast cancer patients through the mediating pathway of anxiety and depression. METHODS: A total of 236 breast cancer patients from China completed the Chinese Version of the Posttraumatic Stress Disorder Symptom Scale (PSS), the Chinese version of the Patient Health Questionnaire (PHQ-9), the Chinese version of the General Anxiety Symptoms Scale (GAD-7). In addition, caregivers of these breast cancer patients were surveyed by the Caregiver Self-Assessment Questionnaire (CSAQ). RESULTS: Structural equation model showed that our model fitted well [χ2 /df = 1.966, TLI = 0.959, CFI = 0.994, RMSEA (90% CI) = 0.065 (0-0.12)] and revealed that anxiety, but not depression, mediated the relationship between PTSS in breast cancer patients and caregiver burden. CONCLUSION: The level of PTSS was positively correlated with anxiety and depression in breast cancer patients, and the level of anxiety and depression was positively related to caregiver burden. The PTSS of patients positively predicted caregiver burden and this relationship appears to be mediated by the patient's anxiety.

Non-coding RNA-related antitumor mechanisms of marine-derived agents.

In the last two decades, natural active substances have attracted great attention in developing new antitumor drugs, especially in the marine environment. A series of marine-derived compounds or derivatives with potential antitumor effects have been discovered and developed, but their mechanisms of action are not well understood. Emerging studies have found that several tumor-related signaling pathways and molecules are involved in the antitumor mechanisms of marine-derived agents, including noncoding RNAs (ncRNAs). In this review, we provide an update on the regulation of marine-derived agents associated with ncRNAs on tumor cell proliferation, apoptosis, cell cycle, invasion, migration, drug sensitivity and resistance. Herein, we also describe recent advances in marine food-derived ncRNAs as antitumor agents that modulate cross-species gene expression. A better understanding of the antitumor mechanisms of marine-derived agents mediated, regulated, or sourced by ncRNAs will provide new biomarkers or targets for potential antitumor drugs from preclinical discovery and development to clinical application.

Comparison of the Efficacy and Safety of Adamgammadex with Sugammadex for Reversal of Rocuronium-Induced Neuromuscular Block: Results of a Phase II Clinical Trial.

This current phase II clinical trial was to compare the effect and safety of adamgammadex, a new cyclodextrin-based selective relaxant binding agent, with sugammadex to reverse rocuronium-induced neuromuscular block. Patients were randomised to receive adamgammadex (4 or 6 mg kg-1) or sugammadex (2 mg kg-1, as a positive control group) at the reappearance of the second twitch (T2) in response to TOF stimulation. The standard safety data were collected. The 4 mg kg-1 (n = 16) and 6 mg kg-1 (n = 20) adamgammadex- and 2 mg kg-1 (n = 20) sugammadex-induced recovery time of TOF ratio to 0.9 were 2.3, 1.6, and 1.5 min, respectively (p = 0.49). The 4 mg kg -1 adamgammadex-induced median recovery time was longer than that of 2 mg kg-1 sugammadex (p = 0.01), and there was no difference between the 6 mg kg -1 adamgammadex group and 2 mg kg-1 sugammadex group (p = 0.32). Then, the number of patients who experienced adverse events (AEs) was 6, 11, and 14 for adamgammadex at 4, 6 mg kg-1 and sugammadex at 2 mg kg-1, respectively. The treatment emergent AEs that occurred more than twice were detailed as follows: incision site pain, hypotension, emesis, fever, throat pain, blood bilirubin increase, abnormal T-wave of ECG, dizziness, incision site swelling, postoperative fever, expectoration, and nausea. For drug-related AEs, the increased urine acetone bodies and first-degree atrioventricular block were observed in two patients from sugammadex group. Then, the previously reported AEs were not observed in this study, including anaphylaxis, haemorrhage, recurarization, abnormal basic vital signs, or lengthened QRS intervals and QT intervals. Adamgammadex was found to be effective for reversal of rocuronium-induced neuromuscular block as sugammadex.

Effects of propofol on macrophage activation and function in diseases.

Macrophages work with monocytes and dendritic cells to form a monocyte immune system, which constitutes a powerful cornerstone of the immune system with their powerful antigen presentation and phagocytosis. Macrophages play an essential role in infection, inflammation, tumors and other pathological conditions, but these cells also have non-immune functions, such as regulating lipid metabolism and maintaining homeostasis. Propofol is a commonly used intravenous anesthetic in the clinic. Propofol has sedative, hypnotic, anti-inflammatory and anti-oxidation effects, and it participates in the body's immunity. The regulation of propofol on immune cells, especially macrophages, has a profound effect on the occurrence and development of human diseases. We summarized the effects of propofol on macrophage migration, recruitment, differentiation, polarization, and pyroptosis, and the regulation of these propofol-regulated macrophage functions in inflammation, infection, tumor, and organ reperfusion injury. The influence of propofol on pathology and prognosis via macrophage regulation is also discussed. A better understanding of the effects of propofol on macrophage activation and function in human diseases will provide a new strategy for the application of clinical narcotic drugs and the treatment of diseases.

An Integrative Bioinformatics Analysis of the Potential Mechanisms Involved in Propofol Affecting Hippocampal Neuronal Cells.

The aim of this study is to probe the possible molecular mechanisms underlying the effects of propofol on HT22 cells. HT22 cells treated with different concentrations were sequenced, and then the results of the sequencing were analyzed for dynamic trends. Expression pattern clustering analysis was performed to demonstrate the expression of genes in the significant trend modules in each group of samples. We first chose the genes related to the trend module for WGCNA analysis, then constructed the PPI network of module genes related to propofol treatment group, and screened the key genes. Finally, GSEA analysis was performed on the key genes. Overall, 2,506 genes showed a decreasing trend with increasing propofol concentration, and 1,871 genes showed an increasing trend with increasing propofol concentration. WGCNA analysis showed that among them, turquoise panel genes were negatively correlated with propofol treatment, and genes with Cor R >0.9 in the turquoise panel were selected for PPI network construction. The MCC algorithm screened a total of five key genes (CD86, IL10RA, PTPRC, SPI1, and ITGAM). GSEA analysis showed that CD86, IL10RA, PTPRC, SPI1, and ITGAM are involved in the PRION_DISEASES pathway. Our study showed that propofol sedation can affect mRNA expression in the hippocampus, providing new ideas to identify treatment of nerve injury induced by propofol anesthesia.

Evaluation on the generalization of a learned convolutional neural network for MRI reconstruction.

Recently, deep learning approaches with various network architectures have drawn significant attention from the magnetic resonance imaging (MRI) community because of their great potential for image reconstruction from undersampled k-space data in fast MRI. However, the robustness of a trained network when applied to test data deviated from training data is still an important open question. In this work, we focus on quantitatively evaluating the influence of image contrast, human anatomy, sampling pattern, undersampling factor, and noise level on the generalization of a trained network composed by a cascade of several CNNs and a data consistency layer, called a deep cascade of convolutional neural network (DC-CNN). The DC-CNN is trained from datasets with different image contrast, human anatomy, sampling pattern, undersampling factor, and noise level, and then applied to test datasets consistent or inconsistent with the training datasets to assess the generalizability of the learned DC-CNN network. The results of our experiments show that reconstruction quality from the DC-CNN network is highly sensitive to sampling pattern, undersampling factor, and noise level, which are closely related to signal-to-noise ratio (SNR), and is relatively less sensitive to the image contrast. We also show that a deviation of human anatomy between training and test data leads to a substantial reduction of image quality for the brain dataset, whereas comparable performance for the chest and knee dataset having fewer anatomy details than brain images. This work further provides some empirical understanding of the generalizability of trained networks when there are deviations between training and test data. It also demonstrates the potential of transfer learning for image reconstruction from datasets different from those used in training the network.

Propofol protects against the neurotoxicity of 1­methyl­4­phenylpyridinium.

Parkinson's disease (PD) is a progressive and degenerative disorder of the central nervous system, characterized by the loss of dopaminergic neurons and muscular rigidity. Treatment with propofol (2,6­diisopropylphenol) has been observed to attenuate oxidative stress injury via inhibition of programmed cell death. Results from the present study indicate that propofol treatment attenuates 1­methyl­4­phenylpyridinium (MPP+)­induced oxidative stress, which was demonstrated by increased levels of reactive oxygen species, 4­hydroxy­2­nonenal and protein carbonyls. Furthermore, it was demonstrated that propofol may ameliorate MPP+­induced mitochondrial dysfunction by increasing the level of ATP and the mitochondrial membrane potential. MTT and lactate dehydrogenase assays indicated that propofol treatment reduces cell vulnerability to MPP+­induced insult. Propofol was also observed to prevent apoptotic signals by reducing the ratio of Bcl­2­associated X protein to B­cell lymphoma 2, reducing the expression level of cleaved caspase­3 and attenuating cytochrome c release. Thus, propofol may present as a novel therapeutic strategy for the treatment of PD.