BACKGROUND:Chronic pain is characterized by persistent and often debilitating symptoms, yet its underlying neural mechanisms remain poorly understood. This study investigates alterations in brain oscillations and connectivity in chronic pain patients using electroencephalography (EEG), aiming to identify potential neural signatures of chronic pain. METHODS:This cross-sectional study analyzed EEG data from 42 chronic pain patients and 42 healthy controls to identify differences in oscillatory activity and network connectivity. Connectivity analyses were corrected for multiple comparisons using network-based statistics. Machine learning techniques were employed to evaluate the potential of these neural signatures as biomarkers for chronic pain. RESULTS:Chronic pain patients exhibited decreased power in high-frequency bands. Conversely, functional connectivity analysis revealed widespread enhancements in gamma synchronization in chronic pain patients. Dynamic connectivity analysis demonstrated that chronic pain patients had significantly increased gamma synchronization within the default mode network (DMN), particularly in a dominant state characterized by stronger intra-cingulate connections. A machine learning model effectively differentiated patients from controls, achieving robust accuracy of 75.5% ± 6.9%, with sensitivity of 75.3% ± 12.6% and specificity of 80.0% ± 10.5%, primarily driven by the DMN connectivity features. Correlation analysis indicated that the connection between the left posterior cingulate and caudal anterior cingulate within the DMN was positively correlated with pain duration (p = 0.021, r = 0.354). CONCLUSION:Enhanced gamma synchronization within the DMN plays a critical role in the pathophysiology of chronic pain. DMN gamma synchronization may serve as a valuable neural marker for chronic pain, providing new insights into its underlying mechanisms.

Neuroinflammation driven by oxidative stress remains a therapeutic challenge due to the instability and low bioavailability of conventional antioxidants. Here, we developed CeO2@MOF-LF, a self-fluorescent nanozyme integrating cerium dioxide (CeO2) nanoparticles within a TCPP-Fe metal-organic framework (MOF), surface-modified with lactoferrin (LF) for nasal-to-brain delivery. 1) Cascade antioxidant catalysis: Synergizing CeO2 ' s redox cycling (Ce3+/Ce4+) with MOF's ROS scavenging, decomposing H2O2/center dot OH into H2O/O2, achieving 83.7 % ROS clearance in BV2 cells (vs. 41.6 % for free CeO2); 2) Real-time biodistribution tracking: Utilizing MOF's intrinsic fluorescence for quantitative pharmacokinetic analysis, revealing 2.5-fold higher brain accumulation than intravenous injection at 12 h post-nasal administration; 3) Targeted neuroprotection: LF-mediated mucoadhesion prolonged nasal retention, facilitating transport via olfactory pathway. In LPS-induced neuroinflammatory mice, CeO2@MOF-LF suppressed microglial activation, rescuing cognitive deficits in Morris water maze tests (escape latency decreased by 38.9 %). RNA sequencing results from brain tissue also confirm the cascade antioxidant capacity of the nanozyme CeO2@MOF-LF. The nanozyme's self-fluorescence allowed precise in vivo localization, while exhibiting complete clearance within 7 days. This multifunctional platform provides a paradigm for spatiotemporally controlled neuroinflammation therapy.

Sepsis-associated encephalopathy (SAE) occurs in 70% of severely infected patients and the incidence rate of 17.7%. Previous studies have shown that Nicotinamide adenine dinucleotide (NADH) may treat nerve damage, but its inability to directly penetrate cell membranes limits its application. In this study, a nanoparticle (NADH@HMONs-AAL) with one modification of triple-role nano-therapy is creatively prepared to treat SAE, and it is delivered to the brain through intranasal administration. There are three-fold to introduce aleuria aurantia lectin (AAL) to modify the surface of NADH@HMONs. First, AAL adhered to HMONs as a mesoporous blocker to prevent drug leakage. Then, AAL increases the hydrophilic and hydrophobic properties of the nanoparticles, making NADH@HMONs more easily enter cells. Third, AAL allowed NADH@HMONs to bind to L-fucose residues expressed on the olfactory epithelium, reducing clearance by cilia and effectively transporting NADH@HMONs-AAL to the brain. This research indicates that NADH@HMONs-AAL can directly enter the brain through intranasal administration and rapidly release NADH within cells. It repairs neuronal damage in the hippocampus and improves cognitive dysfunction in SAE-induced cognitive neuroinflammatory mice. In conclusion, the nanoparticle prepared in this study using precision can alleviate the cognitive dysfunction caused by SAE, and provide a promising delivery route and method for treating neurological diseases. A nanoparticle (NADH@HMONs-AAL) with one modification of triple-role nano-therapy is creatively prepared to treat cognitive dysfuction of neuroinflammatory. NADH@HMONs-AAL is administered through nasal drops, entering the brain via the nose-brain pathway. Aleuria aurantia lectin (AAL) can prevent drug leakage, making NADH@HMONs more easily enter cells and specifically bind to the olfactory epithelium. NADH@HMONs-AAL improves cognitive dysfunction in neuroinflammatory mice. image

Background According to the Chinese Society of Anesthesiology, it is recommended that patients with difficult airways be documented and notified, which will provide healthcare professionals with a direct reference when managing airways. However, compliance with this initiative remains unclear. This study was conducted to investigate the current status and need for difficult airway notification at Plastic Surgery Hospital and to explore the factors contributing to noncompliance. Methods Anesthesiologists, surgeons, and patients in Plastic Surgery Hospital were administered separate questionnaires regarding notification of difficult airway management. Participants were surveyed regarding their attitudes and current practices regarding difficult airway notification. In addition, questions were asked regarding the barriers that contribute to noncompliance. Results A total of 632 valid responses were obtained and analyzed, giving a response rate of 99.21%. 399 patients (89.46%) felt it was very important for anesthesiologists to inform them about their difficult airway, and 91.03% felt it was very important for them to receive a letter of their airway assessment. However, twenty-two anesthesiologists (64.7%) reported verbally informing less than 50% of patients about their difficult airway after surgery, and only four anesthesiologists informed all patients they encountered. Most surgeons (91.22%) and anesthesiologists (91.18%) believe that it is vital to inform patients verbally, while 114 surgeons (77.03%) and 31 anesthesiologists (91.18%) believe that it is essential to complete a difficult airway notification alert. Among the factors causing noncompliance, 17 (34.69%) believed that absence of mandatory rules, 9 (18.37%) believed that increased workload, and 8 (16.33%) believed that notification methods were lacking. Conclusions The compliance to difficult airway notification remains low in Plastic Surgery Hospital despite the high incidence of difficult airways. Although anesthesiologists, surgeons, and patients are strongly in favor of it. Among the barriers to compliance were the absence of a well-developed notification system and a means of notification such as an alert form for difficult airways. This may spur the anesthesiology society to publish the notification system.

Adequate drug delivery across the blood-brain barrier(BBB)is a critical factor in treating central nervous system(CNS)disorders.Inspired by swimming fish and the microstructure of the nasal cavity,this study is the first to develop swimming short fibrous nasal drops that can directly target the nasal mucosa and swim in the nasal cavity,which can effectively deliver drugs to the brain.Briefly,swimming short fibrous nasal drops with charged controlled drug release were fabricated by electrospinning,homogenization,the π-π conjugation between indole group of fibers,the benzene ring of leucine-rich repeat kinase 2(LRRK2)inhibitor along with charge-dipole interaction between positively charged poly-lysine(PLL)and negatively charged surface of fibers;this enabled these fibers to stick to nasal mucosa,prolonged the residence time on mucosa,and prevented rapid mucociliary clearance.In vitro,swimming short fibrous nasal drops were biocompatible and inhibited microglial activation by releasing an LRRK2 inhibi-tor.In vivo,luciferase-labelled swimming short fibrous nasal drops delivered an LRRK2 inhibitor to the brain through the nasal mucosa,alleviating cognitive dysfunction caused by sepsis-associated encephalopathy by inhibiting microglial inflammation and improving synaptic plasticity.Thus,swim-ming short fibrous nasal drops is a promising strategy for the treatment of CNS diseases.

Nasal administration can bypass the blood-brain barrier and directly deliver drugs to the brain, providing a non-invasive route for central nervous system (CNS) diseases. Inspired by the appearance that a gate can block the outside world and the characteristics of the sol-gel transition can form a "gate" in the nasal cavity, a Drop to Gate nasal drop (DGND) is designed to set a gate in nose, which achieves protecting role from the influence of nasal environment. The DGND demonstrates the efficiency and application prospect of delivering drugs to the brain through the N-to-B. The effective concentration of single administration is increased through the hydrophobic interaction between C8-GelMA and SRT1720 (SA), and then cross-linked under UV to form nanogel, which can respond to MMP in the inflammatory microenvironment of sepsis-induced cognitive dysfunction. Finally, the SA/nanogel is compounded into the thermogel, which can respond to the nasal cavity temperature to form DGND in situ, increasing the residence time and delivery efficiency of drugs in the nasal cavity. In vitro, the DGND alleviates lipopolysaccharides (LPS)-induced BV2 inflammation. In vivo, DGND effectively targets the nasal mucosa and deliver drugs to the brain, which activate Sirt1 to alleviate inflammation mediated by microglia and improve cognitive dysfunction in sepsis mice. A Drop to Gate nasal drops (DGND) inspired by the appearance that a gate can block the outside world and the characteristic of the sol-gel transition can form a "gate" structure in the nasal cavity is developed in this article. It demonstrates the effectiveness and application prospects of delivering drugs to the brain through the N-to-B pathway to attenuate sepsis-induced cognitive dysfunction. image

Asthma is a common respiratory disease characterized by chronic airway inflammation. Dexmedetomidine (DEX), a highly selective α2 adrenergic receptor agonist, has been shown to participate in regulating inflammatory states and thus exert organ protective actions. However, the potential of DEX in asthma is still unknown. This study is aimed at investigating the role of DEX in a mouse model of house dust mite- (HDM-) induced asthma and exploring its underlying mechanism. Here, we found that DEX treatment significantly ameliorated airway hyperresponsiveness, airway inflammation, and airway remodeling in the asthmatic mice, which were similar to the efficacy of the reference anti-inflammatory drug dexamethasone. In addition, DEX reversed the increased expression of toll-like receptor 4 (TLR4) and its downstream signaling adaptor molecule nuclear factor-κB (NF-κB) in the lung tissue of asthmatic mice. Furthermore, these protective effects of DEX were abolished by yohimbine, an α2 adrenergic receptor antagonist. These results indicate that DEX is capable of ameliorating airway inflammation and remodeling in asthmatic mice, and this protective effect is associated with the inhibition of the TLR4/NF-κB signaling pathway.

Background: Asthma is a disease that affects health worldwide. It is characterised by inflammation and airway hyperreactivity. Because airway hyperreactivity can occur in other diseases, perioperative airway hyperreactivity is more insidious and widespread than in asthma and has serious implications that need to be addressed urgently. The use of dexmedetomidine in acute asthma and lung protection has been reported, but the exact mechanism is unclear. Objective: To investigate the effectiveness and mechanisms associated with dexmedetomidine in airway hyperresponsiveness. Methods: Forty BALB/c female mice were randomly divided into five groups: group K (blank group), group A (asthma group), group HD (asthma + dexmedetomidine treatment group), group TH (asthma + yohimbine group) and group HT (asthma + dexmedetomidine + yohimbine group), and the airway resistance of group K, group A and group HD were analysed by invasive airway resistance assay, ELISA assay, immunohistochemistry and q-PCR, respectively. Airway resistance; IL-4 and IgE levels in serum and BLAF; and IL-4, IL-13, Muc5AC, NFκB, TLR2, TLR4 and TSLP1 protein levels in lung tissues of the 5 groups were analysed by invasive airway resistance assay, ELISA, immunohistochemistry and qPCR. Results: Compared with group A, there were statistical differences in airway resistance ( P < 0.05); LIL-4 and IgE ( P < 0.05) in serum and BLAF; and Muc5AC, TLR4 and NFκB protein contents ( P < 0.05) in lung tissues in the HD group. Conclusion: 1. Dexmedetomidine can attenuate airway hyperresponsiveness in the OVA asthma model; 2. Dexmedetomidine reduced the production of IL-4 and IgE by down-regulating the TLR4/NF-κB signaling pathway, thereby reducing the lung inflammatory response and airway hyperresponsiveness in the OVA-induced asthma model.

小颌畸形患者因口咽腔容积小、舌体相对肥大,易出现鼾症、阻塞性睡眠呼吸暂停低通气综合征等,是困难气道高发人群.除气道结构异常外,小颌畸形患者还可合并中枢性呼吸暂停、神经系统异常以及心血管畸形等情况,因此,这类患者围术期气道管理存在巨大挑战.本文通过回顾近5年小颌畸形相关文献,以此类患者气道解剖结构特点为基础,对小颌畸形患者围手术期气道管理的研究进展进行综述.

lntracellular calcium ion is the key secondary messenger system of the cellular processes in airway smooth muscle cells(ASMc). The treatment and regulation of Ca(2+)in airway smooth muscle (ASM) is, in part, to associated with many airway diseases such as asthma, COPD and pulmonary fibrosis. The mechanism of contraction and relaxation of ASM is a concerned aspect in airway diseases. This review emphasizes established and recent discoveries whice show the research progress of Ca(2+)on cell contraction and relaxation in ASM in recent years, to provide theoretical support and new targets for clinical prevention and treatment of perioperative bronchospasm and variousrespiratory related diseases.

近年来,随着困难气道管理工具的研发和推广应用,困难气道管理指南的制定以及对气道管理培训的重视和积极开展,困难气道的发生率显著降低[1-10].尽管如此,由于迄今仍缺乏公认的、健全的能够准确预测困难气道的评估体系,未预料的困难气道时有发生,如果未及时给予恰当处理,将导致患者缺氧性脑损伤,甚至死亡[3,11].此外,众多文献明确指出,气道评估不完善以及预防体系不健全是导致气道管理失败和气道相关不良事件增加的主要原因[10,12-14].

Abstract lntracellular calcium ion is the key secondary messenger system of the cellular processes in airway smooth muscle cells(ASMc). The treatment and regulation of Ca2+ in airway smooth muscle (ASM) is, in part, to associated with many airway diseases such as asthma, COPD and pulmonary fibrosis. The mechanism of contraction and relaxation of ASM is a concerned aspect in airway diseases. This review emphasizes established and recent discoveries whice show the research progress of Ca2+ on cell contraction and relaxation in ASM in recent years, to provide theoretical support and new targets for clinical prevention and treatment of perioperative bronchospasm and variousrespiratory related diseases.

近年来,随着多种困难气道管理工具的研发、推广应用以及对气道管理培训的重视和完善,困难气管插管发生率显著降低[1]. 然而,导致气道管理失败和气道相关不良事件发生的主要原因仍然是气道评估不完善和预防体系不健全[1-3]. 为了完善术前气道评估,并保证困难气道患者再次手术安全,除了相关病史、体格检查以及影像学等辅助检查之外,记录了既往困难气道管理相关情况的困难气道告知书将会给气道管理相关医护人员提供直接、有价值的参考[4].2017年中华医学会麻醉学分会发布的困难气道管理指南指出,术后应将困难气道处理情况记录并告知患者[5]. 目前,美国、加拿大已经建立了规范的困难气道告知体系,并且困难气道告知书已经得到广泛应用. 本文总结归纳了美国、加拿大困难气道告知书的书写内容[6] ,以及困难气道告知书在困难气道管理中的具体应用,旨在为探索创建国内困难气道告知书的书写模式和建立困难气道告知体系提供借鉴.

喉罩通气道是临床较为常用的一种声门上通气工具.其置入操作简单、便捷,对咽喉部刺激小,血流动力学平稳,通气效果良好.随着喉罩种类和型号的丰富,喉罩在小儿和成人患者的通气维持、困难气道引导插管和紧急气道处理中占重要地位,且在重症患者气道维持和处理中的应用也日益广泛.在喉罩使用过程中,应严格掌握其适应证和禁忌证,避免对患者不必要的损伤.同时,还应加强喉罩置入技术和喉罩气道管理的相关培训.未来,可联合应用超声技术,以拓展喉罩在小儿气道管理中的应用.