Chiral coordination polymer nanowires boost radiation-induced in situ tumor vaccination.

Radiation-induced in situ tumor vaccination alone is very weak and insufficient to elicit robust antitumor immune responses. In this work, we address this issue by developing chiral vidarabine monophosphate-gadolinium nanowires (aAGd-NWs) through coordination-driven self-assembly. We elucidate the mechanism of aAGd-NW assembly and characterize their distinct features, which include a negative surface charge, ultrafine topography, and right-handed chirality. Additionally, aAGd-NWs not only enhance X-ray deposition but also inhibit DNA repair, thereby enhancing radiation-induced in situ vaccination. Consequently, the in situ vaccination induced by aAGd-NWs sensitizes radiation enhances CD8+ T-cell-dependent antitumor immunity and synergistically potentiates the efficacy immune checkpoint blockade therapies against both primary and metastatic tumors. The well-established aAGd-NWs exhibit exceptional therapeutic capacity and biocompatibility, offering a promising avenue for the development of radioimmunotherapy approaches.

Modulating Synovial Macrophage Pyroptosis and Mitophagy Interactions to Mitigate Osteoarthritis Progression using Functionalized Nanoparticles.

Synovial macrophages play an important role in the progression of osteoarthritis (OA). In this study, we noted that synovial macrophages can activate pyroptosis in a gasdermin D-dependent manner and produce reactive oxygen species (ROS), aberrantly activating the mammalian target of rapamycin complex 1 (mTORC1) pathway and matrix metalloproteinase-9 (MMP9) expression in synovial tissue samples collected from both patients with OA and collagen-induced osteoarthritis (CIOA) mouse model. To overcome this, we constructed rapamycin- (RAPA, a mTORC1 inhibitor) loaded mesoporous Prussian blue nanoparticles (MPB NPs, for catalyzing ROS) and modified the NPs with MMP9-targeted peptides (favor macrophage targeting) to develop RAPA@MPB-MMP9 NPs. The inherent enzyme-like activity and RAPA released from RAPA@MPB-MMP9 NPs synergistically impeded the pyroptosis of macrophages and the activation of the mTORC1 pathway. In particular, the NPs decreased pyroptosis-mediated ROS generation, thereby inhibiting cGAS-STING signaling pathway activation caused by the release of mitochondrial DNA. Moreover, the NPs promoted macrophage mitophagy to restore mitochondrial stability, alleviate pyroptosis-related inflammatory responses, and decrease senescent synoviocytes. After the as-prepared NPs were intra-articularly injected into the CIOA mouse model, they efficiently attenuated synovial macrophage pyroptosis and cartilage degradation. In conclusion, our study findings provide a novel therapeutic strategy for OA that modulates the pyroptosis and mitophagy of synovial macrophage by utilizing functionalized NPs. STATEMENT OF SIGNIFICANCE: Osteoarthritis (OA) presents a significant global challenge owing to its complex pathogenesis and finite treatment options. Synovial macrophages have emerged as key players in the progression of OA, managing inflammation and tissue destruction. In this study, we discovered a novel therapeutic strategy in which the pyroptosis and mitophagy of synovial macrophages are targeted to mitigate OA pathology. For this, we designed and prepared rapamycin-loaded mesoporous Prussian blue nanoparticles (RAPA@MPB-MMP9 NPs) to specifically target synovial macrophages and modulate their inflammatory responses. These NPs could efficiently suppress macrophage pyroptosis, diminish reactive oxygen species production, and promote mitophagy, thereby alleviating inflammation and protecting cartilage integrity. Our study findings not only clarify the intricate mechanisms underlying OA pathogenesis but also present a promising therapeutic approach for effectively managing OA by targeting dysregulation in synovial macrophages.

Muscular Function Recovery from General Anesthesia in 132 Patients Undergoing Surgery with Acceleromyography, Combined Acceleromyography, and Ultrasonography, and without Monitoring Muscular Function.

BACKGROUND Diaphragmatic thickness fraction (DTF), measured by ultrasound, can predict the occurrence of postoperative residual neuromuscular blockade (RNMB). We hypothesized that the utilization of diaphragmatic ultrasound during the postoperative awakening phase of anesthesia in patients offers a successful means of avoiding RNMB in a notably comfortable manner, as compared to the use of acceleromyograph. MATERIAL AND METHODS Patients who underwent elective thyroid cancer radical surgery were enrolled in this prospective clinical study. Eligible participants were randomly assigned to 1 of 3 groups: 1) combined ultrasonography with acceleromyography group (the US+AMG group), 2) the AMG group, or 3) the usual clinical practice group (the UCP group). The primary outcomes of the study were the incidence of RNMB and hypoxemia after tracheal extubation. RESULTS The study included a total of 127 patients (43 in the US+AMG group, 44 in the AMG group, and 40 in the UCP group). The incidence of RNMB and hypoxemia was higher in the UCP group than in the US+AMG and AMG groups at 15 and 30 min after extubation, respectively. The mean area under the receiver operating characteristic curve, and the decision curve of the recovery rate of DTF (DTF) was greater than that of DTF. CONCLUSIONS The use of diaphragm ultrasound during the postoperative awakening phase of anesthesia can significantly reduce the incidence of RNMB. This method was non-inferior to the use of AMG during the entire perioperative period.

PD-L1/PD-1 pathway: a potential neuroimmune target for pain relief.

Pain is a common symptom of many diseases with a high incidence rate. Clinically, drug treatment, as the main method to relieve pain at present, is often accompanied by different degrees of adverse reactions. Therefore, it is urgent to gain a profound understanding of the pain mechanisms in order to develop advantageous analgesic targets. The PD-L1/PD-1 pathway, an important inhibitory molecule in the immune system, has taken part in regulating neuroinflammation and immune response. Accumulating evidence indicates that the PD-L1/PD-1 pathway is aberrantly activated in various pain models. And blocking PD-L1/PD-1 pathway will aggravate pain behaviors. This review aims to summarize the emerging evidence on the role of the PD-L1/PD-1 pathway in alleviating pain and provide an overview of the mechanisms involved in pain resolution, including the regulation of macrophages, microglia, T cells, as well as nociceptor neurons. However, its underlying mechanism still needs to be further elucidated in the future. In conclusion, despite more deep researches are needed, these pioneering studies indicate that PD-L1/PD-1 may be a potential neuroimmune target for pain relief.

The neurobiological mechanisms and therapeutic prospect of extracellular ATP in depression.

BACKGROUND: Depression is a prevalent psychiatric disorder with high long-term morbidities, recurrences, and mortalities. Despite extensive research efforts spanning decades, the cellular and molecular mechanisms of depression remain largely unknown. What's more, about one third of patients do not have effective anti-depressant therapies, so there is an urgent need to uncover more mechanisms to guide the development of novel therapeutic strategies. Adenosine triphosphate (ATP) plays an important role in maintaining ion gradients essential for neuronal activities, as well as in the transport and release of neurotransmitters. Additionally, ATP could also participate in signaling pathways following the activation of postsynaptic receptors. By searching the website PubMed for articles about "ATP and depression" especially focusing on the role of extracellular ATP (eATP) in depression in the last 5 years, we found that numerous studies have implied that the insufficient ATP release from astrocytes could lead to depression and exogenous supply of eATP or endogenously stimulating the release of ATP from astrocytes could alleviate depression, highlighting the potential therapeutic role of eATP in alleviating depression. AIM: Currently, there are few reviews discussing the relationship between eATP and depression. Therefore, the aim of our review is to conclude the role of eATP in depression, especially focusing on the evidence and mechanisms of eATP in alleviating depression. CONCLUSION: We will provide insights into the prospects of leveraging eATP as a novel avenue for the treatment of depression.

Mining the Micro-Trajectory of Two-Wheeled Non-Motorized Vehicles Based on the Improved YOLOx.

Two-wheeled non-motorized vehicles (TNVs) have become the primary mode of transportation for short-distance travel among residents in many underdeveloped cities in China due to their convenience and low cost. However, this trend also brings corresponding risks of traffic accidents. Therefore, it is necessary to analyze the driving behavior characteristics of TNVs through their trajectory data in order to provide guidance for traffic safety. Nevertheless, the compact size, agile steering, and high maneuverability of these TNVs pose substantial challenges in acquiring high-precision trajectories. These characteristics complicate the tracking and analysis processes essential for understanding their movement patterns. To tackle this challenge, we propose an enhanced You Only Look Once Version X (YOLOx) model, which incorporates a median pooling-Convolutional Block Attention Mechanism (M-CBAM). This model is specifically designed for the detection of TNVs, and aims to improve accuracy and efficiency in trajectory tracking. Furthermore, based on this enhanced YOLOx model, we have developed a micro-trajectory data mining framework specifically for TNVs. Initially, the paper establishes an aerial dataset dedicated to the detection of TNVs, which then serves as a foundational resource for training the detection model. Subsequently, an augmentation of the Convolutional Block Attention Mechanism (CBAM) is introduced, integrating median pooling to amplify the model's feature extraction capabilities. Subsequently, additional detection heads are integrated into the YOLOx model to elevate the detection rate of small-scale targets, particularly focusing on TNVs. Concurrently, the Deep Sort algorithm is utilized for the precise tracking of vehicle targets. The process culminates with the reconstruction of trajectories, which is achieved through a combination of video stabilization, coordinate mapping, and filtering denoising techniques. The experimental results derived from our self-constructed dataset reveal that the enhanced YOLOx model demonstrates superior detection performance in comparison to other analogous methods. The comprehensive framework accomplishes an average trajectory recall rate of 85% across three test videos. This significant achievement provides a reliable method for data acquisition, which is essential for investigating the micro-level operational mechanisms of TNVs. The results of this study can further contribute to the understanding and improvement of traffic safety on mixed-use roads.

Genetic polymorphisms are associated with individual susceptibility to dexmedetomidine.

Introduction: Dexmedetomidine (DXM) is widely used as an adjuvant to anesthesia or a sedative medicine, and differences in individual sensitivity to the drug exist. This study aimed to investigate the effect of genetic polymorphisms on these differences. Methods: A total of 112 patients undergoing hand surgery were recruited. DXM 0.5 µg/kg was administered within 10 min and then continuously injected (0.4 µg/kg/h). Narcotrend index, effective dose and onset time of sedation, MAP, and HR were measured. Forty-five single nucleotide polymorphisms (SNPs) were selected for genotype. Results: We observed individual differences in the sedation and hemodynamics induced by DXM. ABCG2 rs2231142, CYP2D6 rs16947, WBP2NL rs5758550, KATP rs141294036, KCNMB1 rs11739136, KCNMA1 rs16934182, ABCC9 rs11046209, ADRA2A rs1800544, and ADRB2 rs1042713 were shown to cause statistically significant (p < 0.05) influence on the individual variation of DXM on sedation and hemodynamics. Moreover, the multiple linear regression analysis indicated sex, BMI, and ADRA2A rs1800544 are statistically related to the effective dose of DXM sedation. Discussion: The evidence suggests that the nine SNPs involved in transport proteins, metabolic enzymes, and target proteins of DXM could explain the individual variability in the sedative and hemodynamic effects of DXM. Therefore, with SNP genotyping, these results could guide personalized medication and promote clinical and surgical management.

Anaesthesia-related mortality within 24 h following 9,391,669 anaesthetics in 10 cities in Hubei Province, China: a serial cross-sectional study.

Background: The mortality risk related to anaesthesia in China remains poorly characterized. The objective of this study was to evaluate the anaesthesia-related mortality in terms of its incidence, changes, causes and preventability in Hubei, China, between 2017 and 2021 using a series of annual surveys. Methods: We prospectively collected information on patient, surgical, anaesthesia, and hospital characteristics for 9,391,669 anaesthesia procedures performed between 2017 and 2021 in 10 cities within Hubei Province, China. Anaesthesia-related death was defined as death that deemed to be entirely or partially attributable to anaesthesia, occurring within 24 h following anaesthesia administration. All fatalities were scrutinized consecutively to determine their root causes and preventability. The incidence and patterns of anaesthesia-related deaths were analysed from 2017 to 2021. A mixed-effects model with a Poisson link function was fitted to evaluate the city-level annual changes in risk-adjusted incidence of anaesthesia-related deaths. Findings: 600 cases of anaesthetic deaths occurred from 2017 to 2021, yielding an incidence of 6.4 per 100,000 anaesthesia procedures [95% confidence interval (95% CI): 5.9, 6.9], and most were preventable (71.3%). There was a significant decrease from 2017 to 2021, in the incidences of anaesthesia-related death across all patients, those with American Society of Anaesthesiologists physical status (ASAPS) ≥III, and those who had general anaesthesia, with a percentage reduction of 57.6%, 59.1%, and 55.9%, respectively. The risk-adjusted annual changes indicated significant downward trends for the incidence of anaesthetic mortality from 2017 to 2018, 2019, 2020, and 2021. For instance, the risk-adjusted annual changes for the anaesthetic mortality incidence from 2017 to 2021 was -2.5 (95% CI: -1.4, -4.7). Interpretation: In this large, comprehensive database study conducted in Central China, the anaesthesia-related death incidence was 6.4 per 100,000. Notably, the incidence of anaesthesia-related deaths decreased between 2017 and 2021. However, further in-depth analysis is needed to understand the extent to which these trends represent a change in patient safety. Funding: Innovation and optimization of perioperative respiratory system management strategy (Hubei Technological Innovation Special Fund, 2019ACA167).

M2 macrophage polarization: a potential target in pain relief.

Pain imposes a significant urden on patients, affecting them physically, psychologically, and economically. Despite numerous studies on the pathogenesis of pain, its clinical management remains suboptimal, leading to the under-treatment of many pain patients. Recently, research on the role of macrophages in pain processes has been increasing, offering potential for novel therapeutic approaches. Macrophages, being indispensable immune cells in the innate immune system, exhibit remarkable diversity and plasticity. However, the majority of research has primarily focused on the contributions of M1 macrophages in promoting pain. During the late stage of tissue damage or inflammatory invasion, M1 macrophages typically transition into M2 macrophages. In recent years, growing evidence has highlighted the role of M2 macrophages in pain relief. In this review, we summarize the mechanisms involved in M2 macrophage polarization and discuss their emerging roles in pain relief. Notably, M2 macrophages appear to be key players in multiple endogenous pathways that promote pain relief. We further analyze potential pathways through which M2 macrophages may alleviate pain.

Early plasma proteomic biomarkers and prediction model of acute respiratory distress syndrome after cardiopulmonary bypass: a prospective nested cohort study.

BACKGROUND: Early recognition of the risk of acute respiratory distress syndrome (ARDS) after cardiopulmonary bypass (CPB) may improve clinical outcomes. The main objective of this study was to identify proteomic biomarkers and develop an early prediction model for CPB-ARDS. METHODS: The authors conducted three prospective nested cohort studies of all consecutive patients undergoing cardiac surgery with CPB at Union Hospital of Tongji Medical College Hospital. Plasma proteomic profiling was performed in ARDS patients and matched controls (Cohort 1, April 2021-July 2021) at multiple timepoints: before CPB (T1), at the end of CPB (T2), and 24 h after CPB (T3). Then, for Cohort 2 (August 2021-July 2022), biomarker expression was measured and verified in the plasma. Furthermore, lung ischemia/reperfusion injury (LIRI) models and sham-operation were established in 50 rats to explore the tissue-level expression of biomarkers identified in the aforementioned clinical cohort. Subsequently, a machine learning-based prediction model incorporating protein and clinical predictors from Cohort 2 for CPB-ARDS was developed and internally validated. Model performance was externally validated on Cohort 3 (January 2023-March 2023). RESULTS: A total of 709 proteins were identified, with 9, 29, and 35 altered proteins between ARDS cases and controls at T1, T2, and T3, respectively, in Cohort 1. Following quantitative verification of several predictive proteins in Cohort 2, higher levels of thioredoxin domain containing 5 (TXNDC5), cathepsin L (CTSL), and NPC intracellular cholesterol transporter 2 (NPC2) at T2 were observed in CPB-ARDS patients. A dynamic online predictive nomogram was developed based on three proteins (TXNDC5, CTSL, and NPC2) and two clinical risk factors (CPB time and massive blood transfusion), with excellent performance (precision: 83.33%, sensitivity: 93.33%, specificity: 61.16%, and F1 score: 85.05%). The mean area under the receiver operating characteristics curve (AUC) of the model after 10-fold cross-validation was 0.839 (95% CI: 0.824-0.855). Model discrimination and calibration were maintained during external validation dataset testing, with an AUC of 0.820 (95% CI: 0.685-0.955) and a Brier Score of 0.177 (95% CI: 0.147-0.206). Moreover, the considerably overexpressed TXNDC5 and CTSL proteins identified in the plasma of patients with CPB-ARDS, exhibited a significant upregulation in the lung tissue of LIRI rats. CONCLUSIONS: This study identified several novel predictive biomarkers, developed and validated a practical prediction tool using biomarker and clinical factor combinations for individual prediction of CPB-ARDS risk. Assessing the plasma TXNDC5, CTSL, and NPC2 levels might identify patients who warrant closer follow-up and intensified therapy for ARDS prevention following major surgery.

Electroacupuncture alleviates postoperative pain through inhibiting neuroinflammation via stimulator of interferon genes/type-1 interferon pathway.

OBJECTIVE: This work explores the impact of electroacupuncture (EA) on acute postoperative pain (APP) and the role of stimulator of interferon genes/type-1 interferon (STING/IFN-1) signaling pathway modulation in the analgesic effect of EA in APP rats. METHODS: The APP rat model was initiated through abdominal surgery and the animals received two 30 min sessions of EA at bilateral ST36 (Zusanli) and SP6 (Sanyinjiao) acupoints. Mechanical, thermal and cold sensitivity tests were performed to measure the pain threshold, and electroencephalograms were recorded in the primary somatosensory cortex to identify the effects of EA treatment on APP. Western blotting and immunofluorescence were used to examine the expression and distribution of proteins in the STING/IFN-1 pathway as well as neuroinflammation. A STING inhibitor (C-176) was administered intrathecally to verify its role in EA. RESULTS: APP rats displayed mechanical and thermal hypersensitivities compared to the control group (P < 0.05). APP significantly reduced the amplitude of θ, α and γ oscillations compared to their baseline values (P < 0.05). Interestingly, expression levels of proteins in the STING/IFN-1 pathway were downregulated after inducing APP (P < 0.05). Further, APP increased pro-inflammatory factors, including interleukin-6, tumor necrosis factor-α and inducible nitric oxide synthase, and downregulated anti-inflammatory factors, including interleukin-10 and arginase-1 (P < 0.05). EA effectively attenuated APP-induced painful hypersensitivities (P < 0.05) and restored the θ, α and γ power in APP rats (P < 0.05). Meanwhile, EA distinctly activated the STING/IFN-1 pathway and mitigated the neuroinflammatory response (P < 0.05). Furthermore, STING/IFN-1 was predominantly expressed in isolectin-B4- or calcitonin-gene-related-peptide-labeled dorsal root ganglion neurons and superficial laminae of the spinal dorsal horn. Inhibition of the STING/IFN-1 pathway by intrathecal injection of C-176 weakened the analgesic and anti-inflammatory effects of EA on APP (P < 0.05). CONCLUSION: EA can generate robust analgesic and anti-inflammatory effects on APP, and these effects may be linked to activating the STING/IFN-1 pathway, suggesting that STING/IFN-1 may be a target for relieving APP. Please cite this article as: Ding YY, Xu F, Wang YF, Han LL, Huang SQ, Zhao S, Ma LL, Zhang TH, Zhao WJ, Chen XD. Electroacupuncture alleviates postoperative pain through inhibiting neuroinflammation via stimulator of interferon genes/type-1 interferon pathway. J Integr Med. 2023; 21(5): 496-508.

IGF/IGF-1R signal pathway in pain: a promising therapeutic target.

Pain, one of the most important problems in the field of medicine and public health, has great research significance. Opioids are still the main drugs to relieve pain now. However, its application is limited due to its obvious side effects. Therefore, it is urgent to develop new drugs to relieve pain. Multiple studies have found that IGF/IGF-1R pathway plays an important role in the occurrence and development of pain. The regulation of IGF/IGF-1R pathway has obvious effect on pain. This review summarized and discussed the therapeutic potential of IGF/IGF-1R signal pathway for pain. It also summarized that IGF/IGF-1R regulates pain by acting on neuronal excitability, neuroinflammation, glial cells, apoptosis, etc. However, its mechanisms of occurrence and development in pain still need further study in the future. In conclusion, although more deep researches are needed, these studies indicate that IGF/IGF-1R signal pathway is a promising therapeutic target for pain.

STING-IFN-I pathway relieves incision induced acute postoperative pain via inhibiting the neuroinflammation in dorsal root ganglion of rats.

BACKGROUND: The purpose of this study was to study the effect of STING-IFN-I pathway on incision induced postoperative pain in rats and its possible mechanisms. METHODS: The pain thresholds were evaluated by measuring the mechanical withdrawal threshold and the thermal withdrawal latency. The satellite glial cell and macrophage of DRG were analyzed. The expression of STING, IFN-a, P-P65, iNOS, TNF-α, IL-1ß and IL-6 in DRG was evaluated. RESULTS: The activation of STING-IFN-I pathway can reduce the mechanical hyperalgesia, thermal hyperalgesia, down-regulate the expression of P-P65, iNOS, TNF-α, IL-1ß and IL-6, and inhibit the activation of satellite glial cell and macrophage in DRG. CONCLUSIONS: The activation of STING-IFN-I pathway can alleviate incision induced acute postoperative pain by inhibiting the activation of satellite glial cell and macrophage, which reducing the corresponding neuroinflammation in DRG.

Combining High-Z Sensitized Radiotherapy with CD73 Blockade to Boost Tumor Immunotherapy.

Radiation therapy (RT) has the capacity to induce immunogenic death in tumor cells, thereby potentially inducing in situ vaccination (ISV) to prime systemic antitumor immune responses. However, RT alone is often faced with various limitations during ISV induction, such as insufficient X-ray deposition and an immunosuppressive microenvironment. To overcome these limitations, we constructed nanoscale coordination particles AmGd-NPs by self-assembling high-Z metal gadolinium (Gd) and small molecular CD73 inhibitor AmPCP. Then, AmGd-NPs could synergize with RT to enhance immunogenic cell death, improve phagocytosis, and promote antigen presentation. Additionally, AmGd-NPs could also gradually release AmPCP to inhibit CD73's enzymatic activity and prevent the conversion of extracellular ATP to adenosine (Ado), thereby driving a proinflammatory tumor microenvironment that promotes DC maturation. As a result, AmGd-NPs sensitized RT induced potent in situ vaccination and boosted CD8+ T cell-dependent antitumor immune responses against both primary and metastatic tumors, which could also be potentiated by immune checkpoint inhibitory therapy.

A retrospect and outlook on the neuroprotective effects of anesthetics in the era of endovascular therapy.

Studies on the neuroprotective effects of anesthetics were carried out more than half a century ago. Subsequently, many cell and animal experiments attempted to verify the findings. However, in clinical trials, the neuroprotective effects of anesthetics were not observed. These contradictory results suggest a mismatch between basic research and clinical trials. The Stroke Therapy Academic Industry Roundtable X (STAIR) proposed that the emergence of endovascular thrombectomy (EVT) would provide a proper platform to verify the neuroprotective effects of anesthetics because the haemodynamics of patients undergoing EVT is very close to the ischaemia-reperfusion model in basic research. With the widespread use of EVT, it is necessary for us to re-examine the neuroprotective effects of anesthetics to guide the use of anesthetics during EVT because the choice of anesthesia is still based on team experience without definite guidelines. In this paper, we describe the research status of anesthesia in EVT and summarize the neuroprotective mechanisms of some anesthetics. Then, we focus on the contradictory results between clinical trials and basic research and discuss the causes. Finally, we provide an outlook on the neuroprotective effects of anesthetics in the era of endovascular therapy.

Daytime variation in non-cardiac surgery impacts the recovery after general anesthesia.

BACKGROUND: Circadian rhythm involved with physiology has been reported to affect pharmacokinetics or pharmacodynamics. We hypothesized that circadian variations in physiology disturb anesthesia and eventually affect recovery after anesthesia. METHODS: A retrospective cohort study initially included 107,406 patients (1 June 2016-6 June 2021). Patients were classified into morning or afternoon surgery groups. The primary outcome was daytime variation in PACU (post-anesthesia care unit) recovery time and Steward score. Inverse probability weighting (IPW) approach based on propensity score and univariable/multivariable linear regression were used to estimate this outcome. RESULTS: Of 28,074 patients, 13,418 (48%) patients underwent morning surgeries, and 14,656 (52%) patients underwent afternoon surgeries. LOWESS curves and IPW illustrated daytime variation in PACU recovery time and Steward score. Before adjustment, compared to morning surgery group, afternoon surgery group had less PACU recovery time (median [interquartile range], 57 [46, 70] vs. 54 [43, 66], p < 0.001) and a higher Steward score (5.62 [5.61, 5.63] vs. 5.66 [5.65, 5.67], p < 0.001). After adjustment, compared to morning surgery group, afternoon surgery group had less PACU recovery time (58 [46, 70] vs. 54 [43, 66], p < 0.001). In multivariable linear regression, morning surgery is statistically associated with an increased PACU recovery time (coefficient, -3.20; 95% confidence interval, -3.55 to -2.86).Among non-cardiac surgeries, daytime variation might affect recovery after general anesthesia. These findings indicate that the timing of surgery improves recovery after general anesthesia, with afternoon surgery providing protection.KEY MESSAGESIn this retrospective cohort study of 28,074 participants, the afternoon surgery group has a higher Steward score than the morning surgery group.In multivariable linear regression, morning surgery is statistically associated with an increased PACU recovery time.Among non-cardiac surgeries, daytime variation affects the recovery after general anesthesia, with afternoon surgery providing protection.

Electroacupuncture Alleviates CFA-Induced Inflammatory Pain via PD-L1/PD-1-SHP-1 Pathway.

Inflammatory pain is difficult to treat clinically, but electroacupuncture (EA) has been demonstrated to be effective in alleviating inflammatory pain. Programmed cell death ligand-1 (PD-L1) and its downstream signal, Src homology region two domain-containing phosphatase-1 (SHP-1) have a critical role in relieving inflammatory pain. However, whether the PD-L1/PD-1-SHP-1 pathway mediates the analgesic and anti-inflammatory effects of EA in inflammatory pain remains unclear. Here, we observed that EA reversed the complete Freund's adjuvant (CFA)-induced hyperalgesia. EA reduced the expression of IL-6, iNOS, and NF-κB pathway in dorsal root ganglia (DRG) on day 7 after CFA injection but had no effect on the expression of IL-6, iNOS, and NF-κB PP65 on day 21 after CFA injection. Moreover, EA upregulated the protein levels of the PD-L1/PD-1-SHP-1 pathway on day 7 and day 21 after CFA injection. Furthermore, EA upregulated PD-L1 expression in calcitonin gene-related peptide (CGRP)+ but not in isohaemagglutinin B4 (IB4)+ and NF200+ neurons on day 7 and day 21 after CFA injection. Intrathecal injection of the PD-L1/PD-1 inhibitor BMS-1 (50 or 100 µg) blocked the EA-induced analgesic effect, significantly increased IL-6 and iNOS levels, and reduced the levels of PD-L1/PD-1-SHP-1. BMS-1 (50 or 100 µg) significantly reduced the expression of PD-L1 in IB4+, CGRP+, and NF200+ neurons. Our results show that EA's anti-inflammatory and analgesic effects are associated with activating the PD-L1/PD-1-SHP-1 pathway and suppressing its regulated neuroinflammation. This study provides a new potential therapeutic target for treating inflammatory pain.

Study of the Association of Single Nucleotide Polymorphisms in Candidate Genes With Sevoflurane.

The susceptibility of different individuals to anesthetics varies widely, and sevoflurane is no exception. We hypothesized that polymorphisms in genes involved in pharmacokinetics and pharmacodynamics may explain this variation. A total of 151 individuals undergoing otorhinolaryngology surgery were included. The influence of genetic polymorphisms on sevoflurane sensitivity were investigated through SNaPshot technology. Individuals carrying KCNK2 rs6686529 G > C, MTRR rs3733784 TT, rs2307116 GG, or rs1801394 AA polymorphisms had a higher sensitivity to the sedative effect of sevoflurane than those without those polymorphisms. The univariate linear regression analysis indicated that MTRR rs3733784 TT, rs2307116 GG, and rs1801394 AA were potentially significant predictors of higher sensitivity to the sedative effect of sevoflurane. Moreover, CYP2E1 rs3813867 G > C and rs2031920 C > T, GABRG1 rs279858 T > C, KCNK3 rs1275988 CC, GRIN2B rs1806201 GG, MTRR rs2307116 G > A, and rs1801394 A > G were associated with a higher sensitivity to the cardiovascular effect of sevoflurane. Our results suggested that 9 single nucleotide polymorphisms in genes involved in metabolizing enzymes, transport proteins, target proteins of sevoflurane and folate metabolism may help to explain individual differences in the susceptibility to the sedative or cardiovascular effect of sevoflurane.

Influence of genetic variants on remifentanil sensitivity in Chinese women.

WHAT IS KNOWN AND OBJECTIVE: Significant individual differences have been observed in pain sensitivity and analgesic effect of opioids. Previous studies have shown that genetic factors contributed to analgesics requirement obviously. Therefore, we investigated the role of genetic polymorphisms in the sensitivity to the analgesic effect of remifentanil in this study. METHODS: One hundred thirty-seven patients undergoing gynaecological surgery were observed. Before procedures, we measured the basal pain threshold of each patient, including the pressure pain threshold and pressure pain tolerance threshold. Subsequently, patients received a continuous remifentanil infusion for 15 min at a constant rate of 0.2 µg/(kg min). The pain thresholds were measured again after the remifentanil infusion. Moreover, respiratory depression was estimated using oxygen saturation during infusion. DNA was extracted from peripheral venous blood and genotyped using SNaPshot technology. RESULTS AND DISCUSSION: Polymorphisms were found in genes associated with the individual variation in analgesia. Participants carrying OPRM1 rs9397685 AA, ADRB1 rs1801253 CC, and GCH1 rs8007267 CC polymorphisms showed higher sensitivity to analgesic effect induced by remifentanil, and the participants carrying the OPRD1 rs2234918 TT showed lower sensitivity to remifentanil-related respiratory depression. Moreover, individual susceptibility to remifentanil increases with age. WHAT IS NEW AND CONCLUSION: Gene variation in OPRM1 rs9397685 AA, ADRB1 rs1801253 CC, GCH1 rs8007267 CC, and OPRD1 rs2234918 TT were related to the conspicuous interindividual differences in the analgesia and respiratory depression of remifentanil, mainly by affecting the target protein receptors and relative metabolic enzymes.