Chronic pain can cause both hyperalgesia and cognitive impairment symptoms and involves long-term alterations in the neural circuits, leading to abnormal cortical activity. GABAergic signaling are particularly emerging as relevant components of pain processing within the prefrontal cortex. The mechanism through which cortical circuits change and cause chronic pain and memory impairment remains unclear to date. We modeled chronic neuropathic pain in mice using chronic constrictive injury (CCI), an open field test, a Y maze spontaneous alternation experiment, a novel object recognition test and barnes maze were used to assess neurobehavioral changes in the mice. Whole-cell patch-clamp technique was used to assess the intrinsic activity of neurons, and fiber photometry recording was used to measure the calcium activity of GABAergic neurons. In vivo multi-channel technique was employed to assess alterations in cortical excitability. Western blot and immunofluorescence were used to measure the expression of activating transcription factor 4 (ATF4) and Neuronal excitability. In this study, persistent elevation of GABAergic neuronal activity in prelimbic cortex layer 5 (PrL-L5) was demonstrated to regulate the chronic pain and memory impairment. This elevated GABAergic neuronal activity affects the excitatory/inhibitory (E/I) imbalance by influencing the excitability of pyramidal neurons. The inhibition of PrL-L5 GABAergic neuronal activity reversed the hypersensitivity and memory deficits. In contrast, the optogenetic activation of PrL-L5 GABAergic neurons induced hypersensitivity and memory impairment in naive mice. Furthermore, ATF4 regulates hyperpathia and memory impairment through impact GABAergic neuronal activity. We revealed a cortical GABAergic neural microcircuit that involved chronic pain and memory impairment through modulating E/I imbalance by influencing the excitability of pyramidal neurons. These findings provide novel insights for targeted interventions in patients with comorbid chronic pain and memory impairment. Not applicable.

Extracellular vesicles (EVs) circulating in body fluids offer immense potential for diagnostic applications; however, their clinical utility has been hindered by the lack of efficient isolation methods for complex biological samples (e.g., plasma). To address these limitations, we develop a reusable magnetic bead (MB)-based (ReMag)-EV platform for efficient isolation of high-purity EVs. This platform utilizes Wulff-type boronic acids (WBA), which reversibly bind to carbohydrates on EV membranes under neutral pH, allowing selective EV capture without affecting the integrity due to harsh conditions. Compared to traditional methods, this platform demonstrates significant improvements, yielding 1.3 times more EVs than ultracentrifugation (UC) and 3.1 times more EVs than size-exclusion chromatography (SEC), while achieving higher purity (79.7% lipid particles) that surpasses UC (38.4% lipid particles) and SEC (47.2% lipid particles). Proteomics studies using plasma samples from healthy donors and breast cancer (BC) patients indicate that the ReMag-EV platform isolates 1.88 times more unique proteins than that of UC and captures a much higher proportion (87.56%, vs 78.71% for UC) of database-reported EV proteins (ExoCarta and Vesiclepedia). Comparative analysis of EV protein profiles between healthy donors and BC patients revealed significant differences in protein expression, further highlighting the platform's ability to isolate high-purity EVs for cancer diagnosis.

As innate immune cells, natural killer (NK) cells play a vital role in combating tumors and infections, making them a promising tool for cancer immunotherapy. Although NK cell has achieved impressive results in treating of hematologic malignancies, the therapeutic efficiency of NK cells on solid tumors remains unsatisfactory. By enhancing the sensitivity of NK cells to specific target cells, it is possible to boost their cytotoxicity and therapeutic effect against solid tumors. Tumor derived exosomes (TEXs) have immunostimulatory effects on NK cells, however, the TEXs carried immune checkpoints ligand also impair NK cells activity. In the present study, PD-L1 was knocked out from lung cancer cell line A549, and the exosomes derived from wild-type A549 cells (WT-EXO) and PD-L1 knocked-out A549 cell (KO-EXO) were used to pre-immunize NK cells. Results showed that, PD-L1 knocking out can reduce the inhibitory effect of WT-EXO on NK cells viability. Meanwhile, A549 cells derived exosomes (WT-EXO and KO-EXO) both boost the cytotoxicity of NK cells, with KO-EXO exhibited better stimulated effect than the other one. The enhanced killing rates of NK cells can be partially attributed to increased IFN-γ secretion following exosomes pre-immunization. Western blot results indicated that the signaling proteins pSTAT1, along with their associated pathways, play important roles in exosomes-induced enhancement of NK cell cytotoxicity. Simultaneously, it was observed that exosomes-preimmunized NK cells exhibited an upregulation of immunological memory markers CD25 and CD159c. Moreover, KO-EXO pre-immunized NK cells showed better infiltration and anti-tumor effects compared to the untreated NK cells in A549 cell bearing mice model. These results highlight the therapeutic potential of engineered TEXs in boosting NK cell based anti-lung cancer immunotherapy.

Small extracellular vesicles (sEVs) are nanosized membrane‐bound particles facilitating intercellular communication in the nervous system. Although previous studies investigated sEVs released from various neural cell lines, a comprehensive comparison among various immortalized neural lineages has not yet been performed. Herein, we isolated sEVs from four representative immortalized neural cell lines, including SH‐SY5Y (neuroblastoma), differentiated SH‐SY5Y neurons, 1321N1 (astrocytes), and BV2 (microglia), in order to elucidate cell‐type‐specific characteristics under controlled in vitro conditions. The results reveal that all isolated sEVs exhibited characteristic morphology under transmission electron microscopy, while the particle diameters were also within the expected range of 30–200 nm as determined by nano‐flow cytometry. A significant variation in size was observed between the different cell‐line‐derived sEVs where neuron‐derived sEVs exhibited the smallest size and the surface charge was less negative than other sEVs. Microglia‐derived sEVs, on the other hand, were largest in size and presented the most negative surface charge and highest RNA content. Such variations in the different types of sEV suggest the variability in the composition of the different types of neural cell types. The presence of sEV markers like CD9, CD63, CD81, and Alix was confirmed by Western blot analysis. Additional proteomic analysis helped in identifying the composition of the sEVs, revealing the characteristic protein fingerprinting of the neural origin of the sEVs. Neuron‐derived sEVs were enriched in proteins linked to synaptic activity and neurogenesis, whereas astrocyte‐derived sEVs expressed proteins involved in metabolic and antioxidant pathways. Microglial sEVs expressed proteins linked with immune regulatory mechanisms. Interestingly, sEVs originating from differentiated neurons expressed a distinctive proteomic profile that was different from their undifferentiated SH‐SY5Y counterparts. Collectively, this study provides for the first time an in‐depth characterization profile for sEVs derived from neurons, which were differentiated from SH‐SY5Y cells, and, furthermore, provides a comparative framework of immortalized neural cell‐derived sEVs, allowing for the provision of a reproducible and physiologically relevant reference model to further neurodegenerative disease research.

The precise separation of enantiomers is essential for developing effective chiral drugs, yet conventional membranes are constrained by the ubiquitous selectivity-permeability trade-off and low flux, limiting scalable production of single-enantiomer drugs. Herein, we present a cascade reaction strategy integrating Sonogashira-Hagihara coupling and Friedel-Crafts alkylation to fabricate porous conjugated microporous polymer membranes (CCMP-MP1−4/SiO2). This approach enhances specific surface area by 400-fold compared to the product from the Sonogashira-Hagihara coupling reaction alone, creating interconnected porous networks that facilitate mass transport. This hypothesis was confirmed by pore-size gradient experiments, which revealed a critical size-matching effect: matched molecular dimensions enable high-speed mass transfer with 97

Small extracellular vesicles (sEVs) have emerged as crucial mediator of intercellular communication, playing key roles in various physiological and pathological processes. Comprehensive sEV analysis has become increasingly important for understanding its molecular composition, biological functions, and potential applications in disease diagnosis, prognosis, and therapy. This chapter provides an overview of recent advances in sEV analysis, focusing on biomolecules including proteins, nucleic acids, lipids, and glycans. Furthermore, the application of various omics technologies (including proteomics, genomics, transcriptomics, lipidomics, and glycomics) is discussed. These technologies have significantly expanded the understanding of sEV biology and function. By highlighting these latest developments in sEV analysis, this chapter aims to provide a comprehensive review of the current state of this field.

OBJECTIVES:This study aims to evaluate the immunomodulatory effects of an 808 nm laser therapy on human primary natural killer (NK) cells. METHODS:We assessed NK cell viability, apoptosis, ATP and ROS production, cytotoxicity against target cells, and the expression of functional receptors and cytokines following irradiation with an 808 nm laser in vitro. Furthermore, a laser-irradiated mouse model was used for in vivo studies. For the cell experiments, the irradiation parameters were set at 200 mW and 21 mW/cm2. In the mouse model, cells were irradiated at 10 J/cm2 for 60 s every other day over a 2-week period. RESULTS:The results showed that 808 nm laser photobiomodulation did not induce significant apoptosis in human NK cells after continuous irradiation. Laser irradiation increased intracellular ROS and ATP levels in human NK cells and altered ROS levels in mouse peripheral blood cells. In vitro experiments further demonstrated increased NK cell-associated cytotoxic responses, accompanied by elevated expression of NKG2D and enhanced degranulation-related signals. In vivo analyses revealed altered proportions of lymphocytes, neutrophils, and NK cell-associated populations in mouse peripheral blood following laser irradiation. In addition, serum CXCL1 and IL-12p40 levels were decreased in mice after laser treatment, suggesting potential modulation of systemic inflammatory responses. Furthermore, altered expression of JNK, PI3K, and p38 signaling proteins was observed in mouse peripheral blood leukocytes following laser irradiation. CONCLUSIONS:This study demonstrated that 808 nm laser photobiomodulation was associated with immunomodulatory alterations in human NK cells in vitro and systemic immune-related responses in vivo. These findings provide preliminary experimental evidence supporting the potential immunomodulatory application value of 808 nm laser photobiomodulation.

Sex differences in pain perception and analgesic response have become increasingly recognized; however, their impact on moderate-to-severe postoperative pain following elective thoracic surgery remains poorly characterized. Adult patients who underwent elective thoracic surgery were enrolled and stratified into two groups by sex. The primary outcome was the incidence of moderate-to-severe pain in the Post-Anesthesia Care Unit (PACU). Secondary outcomes included the incidence and severity of moderate and severe pain in the PACU, postoperative hospital length of stay, time to first ambulation, and time to chest tube removal. Following propensity score matching (PSM), univariate logistic regression was performed to assess the association between sex and the incidence of moderate-to-severe pain in the PACU. Sensitivity analyses were conducted using three distinct models. Subgroup analyses using multivariable logistic regression were carried out to validate the effect of sex on moderate-to-severe pain in the PACU across different patient populations. A multivariate logistic regression model was employed to identify risk factors for moderate-to-severe pain in the PACU, and a receiver operating characteristic (ROC) curve was generated. An exploratory mediation analysis was conducted to examine potential mediating effects of moderate-to-severe pain in the PACU. A total of 12,075 patients were initially enrolled, with 2,974 patients included in the final analysis after PSM. The incidence of moderate-to-severe pain in the PACU was significantly higher in males than in females (4.17

Small extracellular vesicles (sEVs) have emerged as central mediators of intercellular communication in the central nervous system (CNS) and are increasingly recognized for their dual roles in the pathogenesis and treatment of neurodegenerative diseases (NDDs). In disease contexts, sEVs facilitate the intercellular dissemination of pathogenic proteins and nucleic acids, thereby contributing to the propagation of Alzheimer's disease (AD) and Parkinson's disease (PD) pathology. Conversely, their intrinsic biocompatibility, capacity to traverse brain barriers, and inherent organotropic properties position sEVs as highly promising nanocarriers for CNS drug delivery. While mesenchymal stem cell-derived sEVs have been widely investigated in preclinical NDD models, accumulating evidence suggests that sEVs derived from neural cells, including neural stem cells, neurons, astrocytes, microglia, oligodendrocytes, and brain endothelial cells may offer superior brain targeting, disease relevance, and functional efficacy. This review provides a comprehensive and critical analysis of current knowledge on neural cell-derived sEVs, encompassing their physiological roles in brain homeostasis, their involvement in AD and PD pathogenesis, and their emerging therapeutic applications. We discuss cell-type-specific sEV cargo profiles, mechanisms underlying blood-brain and blood-cerebrospinal fluid barrier traversal, and recent advances in endogenous and exogenous engineering strategies that enhance cargo loading, targeting precision, and therapeutic performance. Importantly, we address key translational challenges that currently limit clinical implementation. By integrating mechanistic insights with therapeutic and engineering perspectives, this review highlights neural cell-derived sEVs as a biologically informed and versatile platform, underscoring their potential to advance next-generation neuro-nanomedicine for NDDs.

Advances in nanotechnology have paved the way for innovative drug delivery systems that enhance the effectiveness of cancer treatment. Cancer cell membrane‐based nanoparticles (CCM‐NPs) and cancer cell‐derived small extracellular vesicles (CsEVs) are emerging as promising drug delivery systems for cancer treatment due to their inherent properties such as low immunogenicity and natural targeting capabilities to cancer cells. However, a comprehensive comparison of the advantages, disadvantages, and similarities of these two platforms is lacking. This review summarizes the natural, engineered, and hybrid forms of CCM‐NPs and CsEVs‐based drug delivery platforms with a focus on comparison of these two platforms, considering key aspects including preparation methods, drug encapsulation strategies, delivery pathways, immune evasion, targeting ability, and their potential for clinical applications. By understanding the strengths and weaknesses of each approach, the aim is to pave the way for next‐generation nanoscale drug delivery platforms and contribute to the development of more effective and personalized cancer therapies.

Objective This multicentre study aimed to develop and validate a machine learning (ML) model to predict postoperative nausea and vomiting (PONV) in patients undergoing sedated gastrointestinal endoscopy. We compared multiple algorithms, applied SHAP for feature interpretability, and translated the optimized model into a web-based tool. Methods A total of 745 patients were prospectively enrolled from four tertiary hospitals in China, including a development cohort of 428 patients from the First Affiliated Hospital of Zhengzhou University (July-December 2023) and an external validation cohort of 317 patients from three institutions (June-August 2024). Eligible patients were aged 18-80 years with ASA I-III. Exclusions included severe cardiopulmonary comorbidities, >30% missing data, complications or withdrawal. Eleven ML algorithms were trained using demographic, clinical and procedural variables. Model performance was assessed via AUC, accuracy, precision, recall, F1-score, specificity and Cohen's kappa score. Calibration and SHAP analysis were conducted, and the final model was deployed as a Streamlit-based tool. Results This study enrolled 745 patients (428 in internal training and 317 in external validation cohorts). While the incidence of PONV showed no significant inter-cohort difference (29.0% vs. 29.6%, p = .85), notable disparities existed in weight, opioid use, examination type, anaesthesia duration, smoking history and diastolic blood pressure parameters (p < .05). Among 11 ML models evaluated, linear discriminant analysis (LDA) demonstrated superior generalizability in external validation (AUC: 0.834 [95%CI, 0.761-0.927]), outperforming logistic regression and support vector machines that achieved AUC > 0.800 in internal testing. The optimally calibrated LDA model facilitated development of a real-time risk prediction (https://p9xjczqdwwf7obxf6u7jeo.streamlit.app/), with SHAP interpretability analysis identifying prior PONV history, height, examination type and opioid usage as primary predictive determinants. Conclusions LDA demonstrated superior generalizability and was implemented as a web-based risk prediction tool, enabling real-time PONV assessment and supporting individualized perioperative management.

BACKGROUND:The progression of atherosclerosis (AS) is closely associated with neutrophil extracellular trap (NET) formation, yet the regulatory mechanisms between macrophages and neutrophils remain unclear. METHODS:In this study, we established an AS model using ApoE-/- mice and isolated exosomes from macrophages stimulated with oxidized low-density lipoprotein (ox-LDL). Multiple techniques, including qRT-PCR, Western blot, co-immunoprecipitation, RIP, and dual-luciferase reporter assays, were employed to analyze the regulatory role of miR-146a-5p on the PNKP/DDOST/JAGN1 complex. RESULTS:Exosomes derived from ox-LDL-stimulated macrophages exhibited elevated miR-146a-5p expression, which targeted and suppressed polynucleotide kinase 3'-phosphatase (PNKP) expression, thereby reducing PNKP-dolichyl-diphosphooligosaccharide-protein glycosyltransferase non-catalytic subunit (DDOST) interaction and enhancing DDOST phosphorylation. This process activated junctional adhesion molecule-like protein (JAGN1)-dependent NET formation. Inhibition of miR-146a-5p significantly decreased neutrophil reactive oxygen species (ROS) levels, reduced NETs generation, and markedly improved plaque burden and attenuated inflammatory responses in AS mice. CONCLUSION:Our study reveals a novel mechanism by which macrophage-derived exosome miR-146a-5p regulates NETs formation through the PNKP/DDOST/JAGN1 axis, providing potential therapeutic strategies for targeted AS treatment.

The immune system of patients undergoing major surgery usually has obvious immune responses during the perioperative period, and the patient’s immune status would affect the patient’s prognosis. In this study single-cell sequencing technology was used to investigate the effect of surgery/anesthesia on peripheral blood mononuclear cells (PBMCs) in depth during the perioperative period. We performed an in-depth analysis of our previously published data, which included a total of 4 patients were recruited in this study. Their peripheral blood samples were collected pre operation, 0, 24, and 48 h post operation, and then PBMCs were extracted, followed by single cell sequencing. The results of sequencing were analyzed with R packages seurat and scSTAR. Finally, RT-PCR technology was used to verify the expression of key genes in monocyte. The ratio of CD4+ and CD8+ T cells and Tregs showed little change, and the function of CD4+ and CD8+ T cells recovered soon. The function of Treg had not been restored 48 h post operation. Non-classical monocyte was impressed after surgery and showed no recovery trend within 48 h. Similar to scRNA-seq, the expression levels of MDM2 and SESN1 in patients with tumor increased significantly after surgery. Surgery/anesthesia had little effect on CD4+ and CD8+ T cells, and continued to affect the functional changes of Treg. It had more impact on monocytes, which may cause them to promote tumor development to a certain extent.

Exosomes carry various biological information and are abundant in body fluids, making them a promising noninvasive biomarker for disease diagnosis and prognosis. However, current detection methods have limitations in sensitivity, specificity, and cost effectiveness, hindering their clinical application. To address these challenges, we have developed a fast, accurate, and cost-effective method for detecting exosomes with high sensitivity and specificity, making it ideal for clinical applications. Clusters of differentiation 63 (CD63) aptamer with its complementary DNA (CD63 aptamer/cDNA) linked to streptavidin-coated magnetic beads (SA-MBs) are used as a capture probe. Exosomes with CD63 proteins can bind to the aptamer and release the cDNA, which initiates rolling circle amplification (RCA) to magnify the cDNA copies. The negatively charged RCA products induce the aggregation of positively charged spermine-modified silver nanoparticles (AgNPs) through electrostatic attraction. The aggregation of AgNPs can be observed visually with the naked eye or quantitatively analyzed using ultraviolet-visible (UV-vis) spectroscopy to determine the concentration of exosomes, with limits of detection of 4.0 × 104 particles/mL for visual observation and 800 particles/mL for UV-vis spectroscopy, respectively. The method has also been demonstrated for detecting the exosomes in serum samples, indicating its potential for clinical use in liquid biopsy.

The role of the intestinal microbiota in hyperalgesia in ovariectomized mice remains unclear. This study aimed to investigate pain behavior and dynamic changes in the intestinal microbiota and the levels of related metabolites in a model of surgical menopause and to verify the hypothesis that the intestinal microbiota mediates the occurrence and persistence of hyperalgesia through neuroinflammation. An ovariectomy (OVX) model was constructed to assess the intestinal microbiota composition, the levels of related metabolites, and inflammation levels in the spinal dorsal root ganglion (DRG). Fecal microbiota transplantation (FMT) was used to alter the intestinal microbiota, and its impact on pain-related behaviors and the level of inflammation in the DRG was evaluated. The mechanical pain threshold was significantly lower in the OVX group compared with the sham group at 4-8 w after surgery, and the thermal pain threshold was greater at 5 and 8 w after surgery. A decrease in the mechanical pain threshold was observed in the OVX group 5, and 7-9 weeks after FMT, indicating hyperalgesia. PCoA and OPLS-DA revealed differences in the composition of the microbiota and the abundance of related metabolites between the OVX and sham groups. Correlation analysis revealed an association between pain thresholds and the levels and metabolites of certain bacterial genera. The expression of C/EBPβ and IL-1β in the OVX group was greater than that in the sham group, and the expression of IL-6, IL-1β, and TRPV1 in the sham group was greater than that in the OVX group after FMT. In conclusion, the dynamic changes in the intestinal microbiota in female mice induced by surgical menopause result in hyperalgesia, possibly due to an increase in the severity of inflammation in the spinal DRG.

Small extracellular vesicles (sEVs) are membrane-bound nanoparticles (<200 nm) released into bodily fluids, carrying proteins, lipids, and nucleic acids that reflect the state of their parent cells. In lung cancer, bacterial infections can worsen disease progression by altering sEV composition, influencing immune responses, metastasis, and therapy resistance. However, current tools are limited in profiling host-derived sEVs during host-pathogen interactions. Here, we present an integrated microfluidic platform for on-chip analysis of sEVs from A549 lung epithelial cells infected with Pseudomonas aeruginosa strain PAO1. This platform integrates host-pathogen coculture with on-chip sEV capture and multiplexed molecular profiling of host cell-derived sEVs. A two-layer modular design enables stepwise cell loading, controlled coculture, and efficient sEV capture through hydrophobic interactions between the sEV membrane and silane-modified polymer that modified on the chip. Multiplexed surface-enhanced Raman scattering (SERS) nanotags allow simultaneous detection of key sEV biomarkers from A549 cells (CD81, EGFR, EpCAM), and PAO1 (oprF). Through SERS mapping, molecular signatures across sEVs are spatially resolved, providing insights into compositional changes in sEVs following PAO1 exposure. By minimizing direct bacterial contact and relying on diffusion-driven capture, the system more closely mimics physiological infection processes.

Objective To investigate the risk factors for chronic postsurgical pain (CPSP) following modified radical mastectomy (MRM) for breast cancer and to establish a clinical prediction model.Methods A prospective cohort study was conducted, enrolling patients who underwent MRM for breast cancer. Comprehensive data were systematically collected at three time points: preoperatively, intraoperatively, and postoperatively. Follow-up assessments were performed at 3 and 6 months postoperatively. Separate prediction models were constructed for CPSP at 3 months and 6 months postoperatively. A comprehensive clinical prediction model was developed through a systematic approach.Results A total of 235 patients were enrolled in this study. Postoperative insomnia and follicle-stimulating hormone (FSH) levels were independent risk factors for CPSP at both 3 and 6-month postoperatively, while a higher body mass index (BMI) was a protective factor for CPSP at 3-month postoperatively. The AUC values of the model at 3 and 6-month postoperatively were 0.767 (0.706-0.829) and 0.733 (0.666-0.799), respectively. Model performance and stability were further confirmed by receiver operating characteristic (ROC) curves, decision curve analysis (DCA), calibration curves, and a nomogram, indicating good discrimination and clinical applicability.Conclusion Postoperative insomnia and FSH levels are independent risk factors for CPSP at 3 and 6-month postoperatively, and a higher BMI is a protective factor for CPSP at 3-month postoperatively. Early identification and management of postoperative insomnia, as well as preoperative screening of FSH levels, may help reduce the risk of CPSP.

BackgroundPerioperative stroke is a serious and potentially fatal complication following non-cardiac surgery. Thus, it is important to identify the risk factors and develop an effective prognostic model to predict the incidence of perioperative stroke following non-cardiac surgery.Methods and findingsWe identified potential risk factors and built a model to predict the incidence of perioperative stroke using logistic regression derived from hospital registry data of adult patients that underwent non-cardiac surgery from 2008 to 2019 at The First Medical Center of Chinese PLA General Hospital. Our model was then validated using the records of two additional hospitals to demonstrate its clinical applicability. In our hospital cohorts, 223,415 patients undergoing non-cardiac surgery were included in this study with 525 (0.23%) patients experiencing a perioperative stroke. Thirty-three indicators including several intraoperative variables had been identified as potential risk factors. After multi-variate analysis and stepwise elimination (P < 0.05), 13 variables including age, American Society of Anesthesiologists (ASA) classification, hypertension, previous stroke, valvular heart disease, preoperative steroid hormones, preoperative β-blockers, preoperative mean arterial pressure, preoperative fibrinogen to albumin ratio, preoperative fasting plasma glucose, emergency surgery, surgery type and surgery length were screened as independent risk factors and incorporated to construct the final prediction model. Areas under the curve were 0.893 (95% confidence interval (CI) [0.879, 0.908]; P < 0.001) and 0.878 (95% CI [0.848, 0.909]; P < 0.001) in the development and internal validation cohorts. In the external validation cohorts derived from two other independent hospitals, the areas under the curve were 0.897 and 0.895. In addition, our model outperformed currently available prediction tools in discriminative power and positive net benefits. To increase the accessibility of our predictive model to doctors and patients evaluating perioperative stroke, we published an online prognostic software platform, 301 Perioperative Stroke Risk Calculator (301PSRC). The main limitations of this study included that we excluded surgical patients with an operation duration of less than one hour and that the construction and external validation of our model were from three independent retrospective databases without validation from prospective databases and non-Chinese databases.ConclusionsIn this work, we identified 13 independent risk factors for perioperative stroke and constructed an effective prediction model with well-supported external validation in Chinese patients undergoing non-cardiac surgery. The model may provide potential intervention targets and help to screen high-risk patients for perioperative stroke prevention.

Purpose:This study aimed to investigate the effect of nebulized dexmedetomidine on postoperative nausea and vomiting (PONV) in female patients undergoing radical thoracoscopic lung cancer resection. Patients and Methods:Patients were enrolled and randomized into the nebulized dexmedetomidine group (Dex group) and the normal saline group (NS group). The primary outcome was the overall incidence of PONV within 48 hours postoperatively. Secondary outcomes included the incidence and grade of PONV at multiple postoperative time points (T1: during PACU stay; T2: from PACU discharge to 8 hours postoperatively; T3: 8-16 hours postoperatively; T4: 16-24 hours postoperatively; T5: 24-32 hours postoperatively; T6: 32-40 hours postoperatively; T7: 40-48 hours postoperatively), postoperative sore throat (POST), Visual Analogue Scale (VAS) scores at the above time points, use of rescue analgesics and antiemetics, Quality of Recovery 15-item scale (QoR-15) scores et al. Results:A total of 64 eligible patients were enrolled, with 57 completing the study. There was no statistically significant difference in the overall incidence of PONV within 48 hours postoperatively between two groups. However, the incidence of PONV and POST in the Dex group was significantly lower than that in the NS group at T2. The area under the curve of VAS in the Dex group was significantly lower than that in the NS group within 24 hours and 48 hours postoperatively. The Dex group had a significantly lower rate of rescue analgesic use and higher postoperative QoR-15 scores within 48 hours postoperatively compared with the NS group. Conclusion:Nebulized inhalation of 1 μg/kg dexmedetomidine preoperatively can reduce the incidence of early postoperative PONV, enhance postoperative analgesia, alleviate postoperative sore throat, and improve postoperative recovery quality in female patients undergoing radical lung cancer surgery. Trial Number and Registry Url:Registration number, ChiCTR2400086070; https://www.chictr.org.cn/bin/project/edit?pid=235076.

Small extracellular vesicles (sEVs) are nanoscale vesicles carrying biomolecules reflective of their cellular origin, making them attractive biomarkers for cancer diagnosis. In this study, we present a high-throughput strategy integrating amphiphile-dendrimer supramolecular probe (ADSP)-based sEV capture with surface-enhanced Raman scattering (SERS) for sensitive, multiplexed detection of breast cancer (BC)-related surface proteins. Plasma-derived sEVs from BC patients at different clinical stages were analyzed, focusing on CD9, EpCAM, and HER2 as key proteins linked to vesicle identity and tumor progression. Gold nanoparticle-based SERS nanotags conjugated with specific antibodies enabled precise detection. Statistical and machine learning analyses of protein profiles allowed accurate discrimination among healthy donors, ductal carcinoma in situ (Stage 0), early stage BC (Stage I-II), and metastatic-stage BC (Stage IV). This integrated platform provides a powerful tool for BC diagnosis and highlights the potential of sEV-based liquid biopsy strategies for clinical application.