The Influencing Factors of Frailty and Quality of Life in Elderly Patients After Spinal Surgery.

Background: To study the related factors of frailty and quality of life in elderly patients after spinal surgery. Methods: The anxiety, depression, frailty, and quality of life of all patients were assessed by the Anxiety screening scale (GAD-7), Depression screening scale (PHQ-9), Frailty screening scale (FRAIL), and European five-dimensional health scale (EQ-5D-5L) 1 day before surgery (DAY-0). A numeric rating scale (NRS) was used to evaluate patients' pain during activities on the 1st day (POD-1), 3rd day (POD-3), and 30th day (POD-30) after operation. FRAIL scale and EQ-5D-5L were used to evaluate patients' frailty and quality of life on POD-30 and 90th day (POD-90) after the operation. Results: There were significant differences in age, body mass index (BMI), preoperative serum albumin level (ALB), and NRS score on POD-1 between the two groups (P<0.05). Age and PHQ-9 score were positively correlated with EQ-5D-5L score (P<0.05, r Age=0.245, rPHQ-9=0.217), and preoperative ALB level was negatively correlated with EQ-5D-5L score (P<0.05, r ALB=-0.274). Conclusion: The older the age, the larger the BMI and the higher the NRS score on the first day after surgery, the more prone to frailty in elderly patients after spinal surgery; The older age and the lower the preoperative ALB level, the worse the quality of life in elderly patients after spinal surgery.

Association Between Preoperative Sleep Disturbance and Postoperative Delirium in Elderly: A Retrospective Cohort Study.

Purpose: Postoperative sleep disturbance, characterized by diminished postoperative sleep quality, is a risk factor for postoperative delirium (POD); however, the association between pre-existing sleep disturbance and POD remains unclear. This study aimed to evaluate the association between preoperative sleep disturbance and POD in elderly patients after non-cardiac surgery. Patients and methods: This retrospective cohort study was conducted at a single center and enrolled 489 elderly patients who underwent surgery between May 1, 2020, and March 31, 2021. Patients were divided into the sleep disorder (SD) and non-sleep disorder (NSD) groups according to the occurrence of one or more symptoms of insomnia within one month or sleep- Numerical Rating Scale (NRS)≥6 before surgery. The primary outcome was the incidence of POD. Propensity score matching analysis was performed between the two groups. Multiple logistic regression analysis was performed to identify the risk factors for POD. Results: In both the unmatched cohort (16.0% vs 6.7%, P=0.003) and the matched cohort (17.0% vs 6.2%, P=0.023), the incidence of POD was higher in the SD group than in the NSD group. In addition, the postoperative sleep quality and the VAS score at postoperative 24 h were significantly lower in the SD group than in the NSD group. Multivariate logistic regression analysis indicated that age (Odds Ratio, 1.13 [95% CI: 1.04-1.23], P=0.003) and preoperative sleep disturbance (Odds Ratio, 3.03 [95% CI: 1.09-9.52], P=0.034) were independent risk factors for the development of POD. Conclusion: The incidence of POD was higher in patients with pre-existing sleep disturbance than those without it. Whether improving sleep quality for preoperative sleep disturbance may help prevent POD remains to be determined.

The Safety and Efficacy of Remimazolam Compared to Dexmedetomidine for Awake Tracheal Intubation by Flexible Bronchoscopy: A Randomized, Double-Blind, Controlled Trial.

Background: Remimazolam is a novel ultra-short-acting benzodiazepine sedative that has the potential to be an alternative for procedural sedation due to its rapid sedation and recovery, no accumulation effect, stable hemodynamics, minimal respiratory depression, anterograde amnesia effect, and specific antagonist. Here, we aimed to compare the safety and efficacy of remimazolam with dexmedetomidine for awake tracheal intubation by flexible bronchoscopy (ATI-FB). Methods: Ninety patients scheduled for ATI-FB were randomly divided into three groups, each consisting of 30 cases: dexmedetomidine 0.6 µg/kg + sufentanil (group DS), remimazolam 0.073 mg/kg + sufentanil (group R1S), or remimazolam 0.093 mg/kg + sufentanil (group R2S). The primary outcome was the success rate of sedation. Secondary outcomes were MOAA/S scores, hemodynamic and respiratory parameters, intubation conditions, intubation time, tracheal intubation amnesia, and adverse events. Results: The success rates of sedation in groups R2S and DS were higher than that in group R1S (93.3%, 86.7%, respectively, vs 58.6%; P = 0.002), and intubation conditions were better than those in group R1S (P < 0.05). Group R2S had shorter intubation times than groups R1S and DS (P = 0.003), and a higher incidence of tracheal intubation amnesia than group DS (P = 0.006). No patient in the three groups developed hypoxemia or hypotension, and there were no significant differences in oligopnea, PetCO2, or bradycardia (P > 0.05). Conclusion: In conclusion, both DS and R2S had higher success rates of sedation, better intubation conditions, and minor respiratory depression, but R2S, with its shorter intubation time, higher incidence of anterograde amnesia, and ability to be antagonized by specific antagonists, may be a good alternative sedation regimen for patients undergoing ATI-FB.

Remimazolam Attenuates LPS-Derived Cognitive Dysfunction via Subdiaphragmatic Vagus Nerve Target α7nAChR-Mediated Nrf2/HO-1 Signal Pathway.

Sepsis-induced neuroinflammation is significantly associated with sepsis-related brain dysfunction. Remimazolam is a novel ultra-short-acting benzodiazepine anesthetic with multiple organ protective effects. However, it is unknown whether remimazolam can ameliorate LPS-induced brain impairment. In this study, Lipopolysaccharide (5 mg/kg, LPS) severely impaired Sprague-Dawley rats spatial learning ability, memory, and cognitive function. However, remimazolam treatment showed a protective effect on LPS-induced cognitive dysfunction. Remimazolam partly reversed LPS-induced splenomegaly, decreased serum cytokine expression, suppressed hippocampal M1 microglial activation, and mitigated oxidative stress injury and neuroinflammation. Electroacupuncture (EA) or PNU282987 treatment improved LPS-induced cognitive dysfunction and also significantly inhibited neuroinflammation and systemic inflammation. However, MLA, ML385, or subdiaphragmatic vagus nerve (SDV) treatment abolished the protective effects of remimazolam. Further mechanistic studies showed that remimazolam induces protective effects by activating subdiaphragmatic vagus nerve target α7nAChR-mediated Nrf2/HO-1 signaling pathway. These results demonstrate that remimazolam can up-regulate α7nAChR, Cyto-Nrf2, HO-1, and cognitive-related (CREB, BDNF, PSD95) protein expressions, suppress M1 microglia, ameliorate neuroinflammation or systemic inflammation, and reverse cognitive dysfunction. Therefore, this study provides insight into a new therapeutic target for the treatment of sepsis-induced cerebral dysfunction.

Association of peripheral B cells and delirium: combined single-cell sequencing and Mendelian randomization analysis.

Background: Delirium seriously affects the prognosis of patients and greatly reduces the ability to work and live. Peripheral inflammatory events may contribute to the development of delirium, the mechanism of which is still unclear. There is a lack of effective diagnostic and treatments for delirium in clinical practice. The study aims to investigate alterations in peripheral immune cell subsets under inflammatory stress and to explore causal associations with delirium. Methods: Single-cell transcriptional sequencing data of human peripheral blood mononuclear cells (PBMC) before and after lipopolysaccharide (LPS) intervention were processed by the Seurat package in R software. PBMC subsets and cellular markers were defined after downscaling and clustering by the Harmony algorithm to identify characteristic subsets in the context of inflammatory stress. Subsequently, a two-sample Mendelian randomization (MR) study was used to explore the causal associations of these inflammation-related PBMC subsets and their molecular phenotypes with delirium. Based on publicly available genetic data, the study incorporated 70 PBMC-associated immune traits, including 8 types of circulating immune cells, 33 B cell subsets and molecular phenotypes, 13 T cell subsets, and 16 B cell-associated cytokines. The results were also validated for robustness, heterogeneity, and horizontal pleiotropy. Results: Under LPS-induced inflammatory stress, B cells, T cells, monocytes, and dendritic cells in human PBMC showed significant activation and quantitative changes. Of these, only lymphocyte and B cell counts were causally associated with delirium risk. This risk link is also seen in the TNF pathway. Further studies of B cells and their subsets revealed that this association may be related to unswitched memory B cells and CD27 expressed on memory B cells. Annotation of the screened SNPs revealed significant polymorphisms in CD27 and CD40 annotated by rs25680 and rs9883798, respectively. The functions of the key annotated genes may be related to the regulation of immune responses, cell differentiation, proliferation, and intercellular interactions. Conclusion: The present study revealed the potential possibility that B cell, memory B cell subset, and TNF-related molecules may be involved in the development of delirium due to peripheral inflammation, which can provide clues for further investigation of delirium prevention and treatment strategies.

Construction of a predictive model for blood transfusion in patients undergoing total hip arthroplasty and identification of clinical heterogeneity.

A precise forecast of the need for blood transfusions (BT) in patients undergoing total hip arthroplasty (THA) is a crucial step toward the implementation of precision medicine. To achieve this goal, we utilized supervised machine learning (SML) techniques to establish a predictive model for BT requirements in THA patients. Additionally, we employed unsupervised machine learning (UML) approaches to identify clinical heterogeneity among these patients. In this study, we recruited 224 patients undergoing THA. To identify factors predictive of BT during the perioperative period of THA, we employed LASSO regression and the random forest (RF) algorithm as part of supervised machine learning (SML). Using logistic regression, we developed a predictive model for BT in THA patients. Furthermore, we utilized unsupervised machine learning (UML) techniques to cluster THA patients who required BT based on similar clinical features. The resulting clusters were subsequently visualized and validated. We constructed a predictive model for THA patients who required BT based on six predictive factors: Age, Body Mass Index (BMI), Hemoglobin (HGB), Platelet (PLT), Bleeding Volume, and Urine Volume. Before surgery, 1 h after surgery, 1 day after surgery, and 1 week after surgery, significant differences were observed in HGB and PLT levels between patients who received BT and those who did not. The predictive model achieved an AUC of 0.899. Employing UML, we identified two distinct clusters with significantly heterogeneous clinical characteristics. Age, BMI, PLT, HGB, bleeding volume, and urine volume were found to be independent predictors of BT requirement in THA patients. The predictive model incorporating these six predictors demonstrated excellent predictive performance. Furthermore, employing UML enabled us to classify a heterogeneous cohort of THA patients who received BT in a meaningful and interpretable manner.

Transfer of massive mitochondria from astrocytes reduce propofol neurotoxicity.

Studies have shown that propofol-induced neurotoxicity is mediated by disruption of mitochondrial fission and fusion, leading to an imbalance in energy supply for developing neurons. Healthy mitochondria released from astrocytes migrate to compromised neurons to mitigate propofol-induced neurotoxicity, yet the precise mechanisms involved require further clarification. In our investigation, primary neurons were incubated with propofol, which decreased ATP synthesis and mitochondrial membrane potential, increased ROS generation and neuronal apoptosis. Notably, astrocytes did not respond to the deleterious effects of propofol. The culture medium of neurons or astrocytes incubated with propofol was collected. It was found that mitochondrial ratio was decreased and mitochondrial function was impaired. Non-contact co-culture of neuro-astrocytes facilitated transcellular mitochondrial transfer in both physiological and propofol interventions, but failed to reverse propofol-induced neurotoxicity. The more pronounced damage to neuronal mitochondria induced by propofol compared to that in astrocytes alludes to secondary injury. Damaged neurons incubated with large, functional extracellular mitochondria derived from astrocytes demonstrates transfer of mitochondria to neurons, effectively reversing propofol-induced neurotoxicity. This discovery presents a novel mitochondrial transfer of neuro-astrocytes crosstalk that contributes to neuroprotection and neurological recovery in neurotoxicity.

Peripheral inflammation and neurocognitive impairment: correlations, underlying mechanisms, and therapeutic implications.

Cognitive impairments, such as learning and memory deficits, may occur in susceptible populations including the elderly and patients who are chronically ill or have experienced stressful events, including surgery, infection, and trauma. Accumulating lines of evidence suggested that peripheral inflammation featured by the recruitment of peripheral immune cells and the release of pro-inflammatory cytokines may be activated during aging and these conditions, participating in peripheral immune system-brain communication. Lots of progress has been achieved in deciphering the core bridging mechanism connecting peripheral inflammation and cognitive impairments, which may be helpful in developing early diagnosis, prognosis evaluation, and prevention methods based on peripheral blood circulation system sampling and intervention. In this review, we summarized the evolving evidence on the prevalence of peripheral inflammation-associated neurocognitive impairments and discussed the research advances in the underlying mechanisms. We also highlighted the prevention and treatment strategies against peripheral inflammation-associated cognitive dysfunction.

Quantum storage of entangled photons at telecom wavelengths in a crystal.

Quantum storage and distribution of entanglement are the key ingredients for realizing a global quantum internet. Compatible with existing fiber networks, telecom-wavelength entangled photons and corresponding quantum memories are of central interest. Recently, 167Er3+ ions have been identified as a promising candidate for an efficient telecom quantum memory. However, to date, no storage of entangled photons, the crucial step of quantum memory using these promising ions, 167Er3+, has been reported. Here, we demonstrate the storage and retrieval of the entangled state of two telecom photons generated from an integrated photonic chip. Combining the natural narrow linewidth of the entangled photons and long storage time of 167Er3+ ions, we achieve storage time of 1.936 µs, more than 387 times longer than in previous works. Successful storage of entanglement in the crystal is certified using entanglement witness measurements. These results pave the way for realizing quantum networks based on solid-state devices.

Causal association between adiposity and hemorrhoids: a Mendelian randomization study.

Background: Hemorrhoids are a very common anorectal disorder affecting a large number of individuals throughout the world. This study aimed to evaluate the causal effects of four adiposity traits including body mass index (BMI), body fat percentage, waist circumference, and waist-to-hip ratio on hemorrhoids by Mendelian randomization (MR). Methods: We used summary statistics of BMI (N = 461,460), body fat percentage (N = 454,633), waist circumference (N = 462,166), waist-to-hip ratio (N = 212,244), and hemorrhoids (N = 337,199) from large-scale genome wide association studies of European ancestry. Univariable and multivariable MR were carried out to infer causality. The MR Steiger directionality test was used to test the causal direction. Results: The primary MR analysis using the inverse variance weighted (IVW) method showed that there were positive effects of genetically determined BMI [odds ratio (OR) = 1.005, 95% confidence interval (CI): 1.003-1.008, per standard deviation (SD), p = 7.801 × 10-5], body fat percentage (OR = 1.005, 95% CI: 1.001-1.008, per SD, p = 0.008), waist circumference (OR = 1.008, 95% CI: 1.005-1.011, per SD, p = 1.051 × 10-6), and waist-to-hip ratio (OR = 1.010, 95% CI: 1.003-1.017, per SD, p = 0.003) on hemorrhoids. These findings were robust in multivariable MR adjusting for physical activity. The Steiger directionality test showed evidence against reverse causation. Conclusion: Our MR study supports a causal role of adiposity in the development of hemorrhoids. Adiposity prevention may be an important strategy for reducing hemorrhoids risk.

Ultrasonographic Assessment of Gastric Volume in Fasted Patients Undergoing Gastrointestinal Endoscopy Under Sedation.

Purpose: In this prospective observational study, an ultrasonographic measurement of antral cross-sectional area (ACSA) was conducted to evaluate the gastric content and volume as well as to identify high-risk stomach in non-pregnant adult surgical patients adhering to preanesthetic fasting guidelines. Patients and Methods: Fasted patients undergoing gastrointestinal endoscopy under sedation were included. Ultrasonographic measurements of ACSA were conducted in both semi-recumbent and right lateral decubitus positions before endoscopic procedures. Gastroscopy was employed to guide the measurement of suctioned gastric volume (GV). Ultrasonography was performed to assess gastric contents and identify patients with high-risk stomach. The relationship between ACSA and suctioned GV was also evaluated. Results: ACSA was evaluated in 736 out of 782 patients. A significant positive correlation was discovered between ACSA in the right lateral decubitus position and suctioned GV, which was more reliable than in the semi-recumbent position. To analyze high-risk stomach with a GV > 100 mL, the cutoff value of ACSA in the right lateral decubitus was found to be 7.5 cm2, with the AUC, sensitivity and specificity of 0.80 (95% CI, 0.76-0.82; P<0.001), 82.4% and 67.3%, respectively. A novel mathematical model based on ACSA to estimate GV in non-pregnant fasted adults was presented. Conclusion: Ultrasonographic measurement of ACSA can assist anesthesiologists in estimating the risk of pulmonary aspiration of gastric contents during general anesthesia and sedation.

Effects of penehyclidine hydrochloride combined with dexmedetomidine on pulmonary function in patients undergoing heart valve surgery: a double-blind, randomized trial.

AIM: To investigate the effects of penehyclidine hydrochloride combined with dexmedetomidine on pulmonary function in patients undergoing heart valve surgery with cardiopulmonary bypass (CPB). METHODS: A total of 180 patients undergoing elective heart valve surgery with CPB were randomly divided into four groups: 45 in group P (intravenous penehyclidine hydrochloride 0.02 mg/kg 10 min before anesthesia induction and at the beginning of CPB, total 0.04 mg/kg); 43 in group D (dexmedetomidine 0.5 µg/kg/h after induction of anesthesia until the end of anesthesia); 44 in group PD ( penehyclidine hydrochloride 0.04 mg/kg combined with dexmedetomidine 0.5 µg/kg/h intravenously during anesthesia); and 43 in group C (same amount of normal saline 10 min before and after anesthesia induction, to the end of anesthesia, and at the beginning of CPB). The main outcomes were the incidence and severity of postoperative pulmonary complications (PPCs). The secondary outcomes were: (1) extubation time, length of stay in intensive care, and postoperative hospital stay, and adverse events; and (2) pulmonary function evaluation indices (oxygenation index and respiratory index) and plasma inflammatory factor concentrations (tumor necrosis factor-α, interleukin-6, C-reactive protein and procalcitonin) during the perioperative period. RESULTS: The incidence of PPCs in groups P, D and PD after CPB was lower than that in group C (P < 0.05), and the incidence in group PD was significantly lower than that in groups P and D (P < 0.05). The scores for PPCs in groups P, D and PD were lower than those in group C (P < 0.05). CONCLUSION: Combined use of penehyclidine hydrochloride and dexmedetomidine during anesthesia reduced the occurrence of postoperative pulmonary dysfunction, and improved the prognosis of patients undergoing heart valve surgery with CPB. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry on 3/11/2020 (Registration No.: ChiCTR2000039610).

Causal effects of opioids on postpartum depression: a bidirectional, two-sample Mendelian randomization study.

Background: Postpartum depression is the most common psychiatric disorder in pregnant women during the postpartum period and requires early detection and treatment. Previous studies have found that opioids use affects depression and anxiety disorders. Although it has long been suspected that opioids may contribute to the development of postpartum depression, observational studies are susceptible to confounding factors and reverse causality, making it difficult to determine the direction of these associations. Methods: To examine the causal associations between opioids and non-opioid analgesics with postpartum depression, we utilized large-scale genome-wide association study (GWAS) genetic pooled data from two major databases: opioids, salicylate analgesic, non-steroidal anti-inflammatory drugs (NSAIDs), and aniline analgesics GWAS data from the United Kingdom Biobank database. GWAS data for postpartum depression were obtained from the FinnGen database. The causal analysis methods used random-effects inverse variance weighting (IVW), and complementary sensitivity analyses using weighted median, MR-Egger method, and MR-PRESSO test. Results: In the IVW analysis, Mendelian randomization (MR) analysis showed that opioids increased the risk of postpartum depression (OR, 1.169; 95% CI, 1.050-1.303; p = 0.005). Bidirectional analysis showed a significant causal relationship between genetically predicted postpartum depression and increased risk of opioids and non-opioid analgesics use (opioids OR, 1.118; 95% CI, 1.039-1.203; p = 0.002; NSAIDs OR, 1.071; 95% CI, 1.022-1.121; p = 0.004; salicylates OR, 1.085; 95% CI, 1.026-1.146; p = 0.004; and anilides OR, 1.064; 95% CI, 1.018-1.112; p = 0.006). There was no significant heterogeneity or any significant horizontal pleiotropy bias in the sensitivity analysis. Conclusion: Our study suggests a potential causal relationship between opioids use and the risk of postpartum depression. Additionally, postpartum depression is associated with an increased risk of opioids and non-opioid analgesics use. These findings may provide new insights into prevention and intervention strategies for opioids abuse and postpartum depression.

Evaluating efficacy and safety of sub-anesthetic dose esketamine as an adjuvant to propofol/remifentanil analgosedation and spontaneous respiration for children flexible fibreoptic bronchoscopy: a prospective, double-blinded, randomized, and placebo-controlled clinical trial.

Background: Flexible fiberoptic bronchoscopy (FFB) for children is widely performed under sedation. Currently, the optimal sedation regimen remains unclear. Esketamine is an N-methyl-D-aspartic acid (NMDA) receptor antagonist, which has stronger sedative and analgesic effects and exerts less cardiorespiratory depression than other sedatives. The purpose of this study was to evaluate whether a subanesthetic dose of esketamine as an adjuvant to propofol/remifentanil and spontaneous ventilation compared with control reduces the procedural and anesthesia-related complications of FFB in children. Materials and methods: Seventy-two children ≤ 12 years of age who were scheduled for FFB were randomly assigned, in a 1:1 ratio, to the esketamine-propofol/remifentanil (Group S, n = 36) or to the propofol/remifentanil group (Group C, n = 36). All children were retained spontaneous ventilation. The primary outcome was the incidence of oxygen desaturation (respiratory depression). Perioperative hemodynamic variables, blood oxygen saturation (SPO2), end-tidal partial pressure of carbon dioxide (PetCO2), respiratory rate (R), and the Bispectral index (BIS), induction time, procedural time, recovery time, the time to the ward from the recovery room, consumption of propofol and remifentanil during the procedure and the appearance of adverse events, including paradoxical agitation following midazolam administration, injection pain, laryngospasm, bronchospasm, PONV, vertigo, and hallucination were also compared. Results: The incidence of oxygen desaturation was significantly lower in Group S (8.3%) compared to Group C (36.1%, p = 0.005). The perioperative hemodynamic profile including SBP, DBP, and HR were more stable in Group S than that in Group C (p < 0.05). Consumption of propofol and remifentanil was lower in Group S than in Group C (p < 0.05). Furthermore, PAED scores, cough scores and injection pain were lower in the Group S than in Group C (p < 0.05). The recovery time of Group S was slightly longer than that of Group C (p < 0.05). Nobody happened paradoxical agitation following midazolam administration, PONV, vertigo, and hallucinations in both groups (p > 0.05). Conclusion: Our findings indicate that a subanesthetic dose of esketamine as an adjuvant to propofol/remifentanil and spontaneous respiration is an effective regimen for children undergoing FFB. Our findings will provide a reference for clinical sedation practice during these procedures in children. Clinical Trail Registration: Chinese clinicaltrials.gov registry (identifier: ChiCTR2100053302).

Functional modular networks identify the pivotal genes associated with morphine addiction and potential drug therapies.

BACKGROUND: Chronic morphine usage induces lasting molecular and microcellular adaptations in distinct brain areas, resulting in addiction-related behavioural abnormalities, drug-seeking, and relapse. Nonetheless, the mechanisms of action of the genes responsible for morphine addiction have not been exhaustively studied. METHODS: We obtained morphine addiction-related datasets from the Gene Expression Omnibus (GEO) database and screened for Differentially Expressed Genes (DEGs). Weighted Gene Co-expression Network Analysis (WGCNA) functional modularity constructs were analyzed for genes associated with clinical traits. Venn diagrams were filtered for intersecting common DEGs (CDEGs). Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for functional annotation. Protein-protein interaction network (PPI) and CytoHubba were used to screen for hub genes. Potential treatments for morphine addiction were figured out with the help of an online database. RESULTS: Sixty-five common differential genes linked to morphine addiction were identified, and functional enrichment analysis showed that they were primarily involved in ion channel activity, protein transport, the oxytocin signalling pathway, neuroactive ligand-receptor interactions, and other signalling pathways. Based on the PPI network, ten hub genes (CHN2, OLIG2, UGT8A, CACNB2, TIMP3, FKBP5, ZBTB16, TSC22D3, ISL1, and SLC2A1) were checked. In the data set GSE7762, all of the Area Under Curve (AUC) values for the hub gene Receiver Operating Characteristic (ROC) curves were greater than 0.8. We also used the DGIdb database to look for eight small-molecule drugs that might be useful for treating morphine addiction. CONCLUSIONS: The hub genes are crucial genes associated with morphine addiction in the mouse striatum. The oxytocin signalling pathway may play a vital role in developing morphine addiction.

Antitumor Effects of Hydromorphone on Human Gastric Cancer Cells in vitro.

Introduction: Experimental data indicate that morphine and fentanyl may have antitumor effects in gastric cancer cells (GC). Hydromorphone, as an analgesic, is used against refractory cancer pain in recent years. However, the data on hydromorphone influencing the biological characteristics of human gastric cancer cells are lacking. The aim of this study was to investigate how hydromorphone affected the growth of human gastric cancer in vitro. Material and Methods: Human GC cell lines (HGC-27, MGC-803, AGS and SGC-7901) and human gastric epithelial cells GSE-1 were exposed to various concentrations of hydromorphone (0-800µM). The cell viability, invasion and migration abilities were measured using cell counting kit-8, Transwell and wound healing assays. Apoptosis and cell cycle were evaluated by flow cytometry. Results: Hydromorphone was toxic in GSE-1 cells at the concentration 800µM. It showed enhanced antitumor effects at a longer incubation time and higher concentrations in HGC-27, MGC-803, AGS and SGC-7901 cells. Hydromorphone inhibited the progression of MGC- 803 cells by cell cycle arrest and apoptosis induction. Conclusion: Hydromorphone suppresses the proliferation of human GC cells in a dose- and time-dependent manner. That may provide a theoretical basis for the clinical application of hydromorphone in the safe and effective treatment of GC.

Correlation and influencing factors of preoperative anxiety, postoperative pain, and delirium in elderly patients undergoing gastrointestinal cancer surgery.

BACKGROUND: The correlation and influencing factors of preoperative anxiety, postoperative pain, and delirium in elderly patients undergoing gastrointestinal cancer surgery were explored with the Beck Anxiety Inventory (BAI) scale, 10-point Visual Analogue Scale (VAS), and Confusion Assessment Method Chinese Reversion (CAM-CR) scale. METHODS: A total of 120 patients aged 65 years old who receiving gastrointestinal cancer surgery were enrolled in the study. Perioperative anxiety, pain, and delirium were assessed by the BAI scale, VAS scale, and CAM-CR scale, respectively. The correlation and influencing factors of preoperative high anxiety, postoperative high pain, and postoperative delirium were analyzed. RESULTS: Preoperative high anxiety had a moderate positive correlation with postoperative high pain (P < 0.001, r = 0.410), and had a weak positive correlation with postoperative delirium (P = 0.005, r = 0.281). postoperative high pain had a weak positive correlation with postoperative delirium (P = 0.017, r = 0.236). Type of cancer and surgical approach were considered to be independent risk factors of preoperative high anxiety (P = 0.006 and P = 0.021). Preoperative high anxiety was considered to be an independent risk factor of postoperative high pain (P< 0.001). Age and preoperative high anxiety were considered to be independent risk factors of postoperative delirium (P< 0.001 and P = 0.010). CONCLUSIONS: Elderly patients undergoing gastrointestinal cancer surgery had a higher incidence of preoperative anxiety, as well as first-day postoperative pain and first-day postoperative delirium. Factors such as type of cancer, surgical approach and preoperative anxiety had been identified as influencing preoperative anxiety levels; preoperative anxiety had been linked to postoperative pain; and age and preoperative anxiety have been identified as influencing factors of postoperative delirium. TRIAL REGISTRATION: hiCTR2000032008, 17/04/2020, Title: "Effects of different analgesic methods on postoperative recovery of elderly patients with digestive tract tumor". Website: https://www.chictr.ogr.cn .

Role of ferroptosis in hypoxic preconditioning to reduce propofol neurotoxicity.

Background: An increasing number of studies have reported that neurotoxicity of propofol may cause long-term learning and cognitive dysfunction. Hypoxic preconditioning has been shown to have neuroprotective effects, reducing the neurotoxicity of propofol. Ferroptosis is a new form of death that is different from apoptosis, necrosis, autophagy and pyroptosis. However, it is unclear whether hypoxic preconditioning reduces propofol neurotoxicity associated with ferroptosis. Thus, we aimed to evaluate the effect of propofol on primary hippocampal neurons in vitro to investigate the neuroprotective mechanism of hypoxic preconditioning and the role of ferroptosis in the reduction of propofol neurotoxicity by hypoxic preconditioning. Methods: Primary hippocampal neurons were cultured for 8 days in vitro and pretreated with or without propofol, hypoxic preconditioning, agonists or inhibitors of ferroptosis. Cell counting kit-8, Calcein AM, Reactive oxygen species (ROS), Superoxide dismutase (SOD), Ferrous iron (Fe2+), Malondialdehyde (MDA) and Mitochondrial membrane potential assay kit with JC-1 (JC-1) assays were used to measure cell viability, Reactive oxygen species level, Superoxide dismutase content, Fe2+ level, MDA content, and mitochondrial membrane potential. Cell apoptosis was evaluated using flow cytometry analyses, and ferroptosis-related proteins were determined by Western blot analysis. Results: Propofol had neurotoxic effects that led to decreased hippocampal neuronal viability, reduced mitochondrial membrane potential, decreased SOD content, increased ROS level, increased Fe2+ level, increased MDA content, increased neuronal apoptosis, altered expression of ferroptosis-related proteins and activation of ferroptosis. However, hypoxic preconditioning reversed these effects, inhibited ferroptosis caused by propofol and reduced the neurotoxicity of propofol. Conclusion: The neurotoxicity of propofol in developing rats may be related to ferroptosis. Propofol may induce neurotoxicity by activating ferroptosis, while hypoxic preconditioning may reduce the neurotoxicity of propofol by inhibiting ferroptosis.

Propofol-induced sleep ameliorates cognition impairment in sleep-deprived rats.

PURPOSE: Propofol has been shown to clear sleep debt in rats after sleep deprivation (SD). We examined whether or not propofol-assisted sleep can restore cognitive function in SD rats and explored the possible mechanisms. METHODS: A sleep deprivation model was established by housing 9 to 12 week-old rats to a multiplatform water tank for 96 h. Model rats were then intraperitoneally injected with different concentrations of propofol or 10% fat emulsion (vehicle control). All treatment groups were examined for spatial learning and memory ability in the Morris water maze (MWM). After euthanasia, morphological changes in the hippocampus, hippocampal neurons, and mitochondria were examined by hematoxylin-eosin staining and transmission electron microscopy. Serum and hippocampal levels of IL-1ß, TNF-α, and hippocampal concentrations of ATP and Cyt-c were measured by ELISA (enzyme-linked immunosorbent assay). Immunohistochemistry and Western blotting were performed to assess hippocampal expression of Bcl-2, Bax, and cleaved caspase-3. RESULTS: Results showed that escape latencies in MWM training trials were significantly shorter and target crossings in the memory probe trial significantly greater in propofol-treated SD model rats compared to vehicle-treated SD rats. Propofol also reduced the number of apoptotic bodies in the hippocampal CA1 region. Sleep deprivation reduced IL-1ß and ATP in hippocampus while increasing TNF-α and Cyt-c, and propofol treatment reversed all these changes. There was no significant difference in Bcl-2 expression between propofol- and vehicle-treated SD rats, but pro-apoptotic Bax and cleaved caspase-3 expression levels were significantly reduced by propofol in SD rats. CONCLUSIONS: Propofol-assisted sleep restored cognitive function in SD rats possibly by attenuating mitochondria-mediated neuronal apoptosis in the hippocampus.