BACKGROUND:Macrophage polarization plays a key role in chronic inflammatory joint diseases such as rheumatoid arthritis.Cerium dioxide(CeO2)nanoparticles have a wide range of biomedical applications such as modulating the local inflammatory microenvironment of tissues.OBJECTIVE:To investigate the role of CeO2 nanoparticles on macrophage polarization and inflammatory factor expression,as well as inflammatory modulation in a co-culture system of macrophages and fibroblasts.METHODS:(1)CeO2 nanoparticles were dispersed and observed morphologically by transmission electron microscopy.(2)Human leukemia monocytes(THP-1)were induced to differentiate and establish the M1 macrophage pro-inflammatory cell model of rheumatoid arthritis.The cells were divided into M0 group(undifferentiated macrophages),M1 group(successful macrophage modeling),CeO2 nanoparticle treatment group(M1 group with CeO2 nanoparticle treatment),and dexamethasone control group(M1 group with dexamethasone treatment)and incubated for 48 hours.The effects of CeO2 nanoparticles on the expression of inflammatory factors(endogenous nitric oxide synthase,CD86,CD80)in M1 macrophages and M1 macrophage phenotype(CD80,CD206)were detected by RT-qPCR,western blot assay,and flow cytometry.(3)A co-culture system of macrophages and fibroblasts was established,and CeO2 nanoparticles acted on the upper macrophages.The regulation of CeO2 nanoparticles on the expression of inflammatory factors(interleukin-6,tumor necrosis factor-α,cyclooxygenase-2,and endogenous nitric oxide synthase)of fibroblasts in the co-culture system was observed at the mRNA and protein levels.RESULTS AND CONCLUSION:(1)Transmission electron microscopy showed that the diameter of CeO2 nanoparticles was(19.5±2.0)nm.(2)Compared with the M0 group,the mRNA of endogenous nitric oxide synthase and CD86,and the protein expression of endogenous nitric oxide synthase and CD80 in the M1 group were upregulated.Compared with the M1 group,the mRNA expression of endogenous nitric oxide synthase and CD86,and the protein expression of endogenous nitric oxide synthase and CD80 in the CeO2 nanoparticle treatment group were downregulated.Flow cytometry showed that 20 nm CeO2 nanoparticles downregulated the number of M1 macrophages.(3)Compared with the M1 group,20 nm CeO2 nanoparticles downregulated the mRNA and protein expression of inflammatory factors(tumor necrosis factor α,interleukin 6,cyclooxygenase 2,and endogenous nitric oxide synthase)in the co-culture system HFL1 cells.(4)The results showed that 20 nm CeO2 nanoparticles can alleviate inflammation in the co-culture system by inhibiting the expression of pro-inflammatory factors in M1 macrophages,providing a new idea for the treatment of inflammatory diseases such as rheumatoid arthritis.

This article provides a systematic interpretation and review of the Society of Critical Care Medicine 2024 Guidelines on Adult ICU Design. Developed based on the Grading of Recommendations Assessment, Development and Evaluation methodology, the guideline address five core themes: ICU layout, room design, infection control, infrastructure, and staff spaces, and put forward 17 evidence-based recommendations, including 5 good practice statements. This article briefly introduces the guideline development methods and evidence characteristics, and focuses on summarizing key recommendations, including high-visibility layouts, single-bed ward settings, natural lighting and noise reduction strategies, integrated infection prevention and control design, remote monitoring, and flexible capacity expansion capabilities. Furthermore, it delves into the applicability and localized implementation pathways within China's healthcare environment, analyzing limitations in terms of evidence quality, specialty applicability, and cost-effectiveness. Furthermore, by integrating the Chinese Guidelines for the Construction and Development of Critical Care Medicine (2025 Edition) and current domestic practices, the article proposes tiered and phased implementation recommendations. This article aims to provide domestic healthcare institutions with a scientific reference that balances international cutting-edge concepts with China's real-world conditions for the construction and renovation of ICUs, thereby promoting the development of intensive care environments centered on patient safety, healthcare worker well-being, and infection control.

BACKGROUND:Macrophage polarization plays a key role in chronic inflammatory joint diseases such as rheumatoid arthritis.Cerium dioxide(CeO2)nanoparticles have a wide range of biomedical applications such as modulating the local inflammatory microenvironment of tissues.OBJECTIVE:To investigate the role of CeO2 nanoparticles on macrophage polarization and inflammatory factor expression,as well as inflammatory modulation in a co-culture system of macrophages and fibroblasts.METHODS:(1)CeO2 nanoparticles were dispersed and observed morphologically by transmission electron microscopy.(2)Human leukemia monocytes(THP-1)were induced to differentiate and establish the M1 macrophage pro-inflammatory cell model of rheumatoid arthritis.The cells were divided into M0 group(undifferentiated macrophages),M1 group(successful macrophage modeling),CeO2 nanoparticle treatment group(M1 group with CeO2 nanoparticle treatment),and dexamethasone control group(M1 group with dexamethasone treatment)and incubated for 48 hours.The effects of CeO2 nanoparticles on the expression of inflammatory factors(endogenous nitric oxide synthase,CD86,CD80)in M1 macrophages and M1 macrophage phenotype(CD80,CD206)were detected by RT-qPCR,western blot assay,and flow cytometry.(3)A co-culture system of macrophages and fibroblasts was established,and CeO2 nanoparticles acted on the upper macrophages.The regulation of CeO2 nanoparticles on the expression of inflammatory factors(interleukin-6,tumor necrosis factor-α,cyclooxygenase-2,and endogenous nitric oxide synthase)of fibroblasts in the co-culture system was observed at the mRNA and protein levels.RESULTS AND CONCLUSION:(1)Transmission electron microscopy showed that the diameter of CeO2 nanoparticles was(19.5±2.0)nm.(2)Compared with the M0 group,the mRNA of endogenous nitric oxide synthase and CD86,and the protein expression of endogenous nitric oxide synthase and CD80 in the M1 group were upregulated.Compared with the M1 group,the mRNA expression of endogenous nitric oxide synthase and CD86,and the protein expression of endogenous nitric oxide synthase and CD80 in the CeO2 nanoparticle treatment group were downregulated.Flow cytometry showed that 20 nm CeO2 nanoparticles downregulated the number of M1 macrophages.(3)Compared with the M1 group,20 nm CeO2 nanoparticles downregulated the mRNA and protein expression of inflammatory factors(tumor necrosis factor α,interleukin 6,cyclooxygenase 2,and endogenous nitric oxide synthase)in the co-culture system HFL1 cells.(4)The results showed that 20 nm CeO2 nanoparticles can alleviate inflammation in the co-culture system by inhibiting the expression of pro-inflammatory factors in M1 macrophages,providing a new idea for the treatment of inflammatory diseases such as rheumatoid arthritis.

Cardiovascular diseases （CVD）， particularly atherosclerosis， represent a major global health burden. Recent studies have revealed that innate immune cells such as monocytes and macrophages can develop immune memory after an initial stimulus， a phenomenon termed “trained immunity”. Growing evidence indicates that trained immunity serves as an underlying mechanism of chronic inflammation in atherosclerotic cardiovascular diseases. This review focuses on outlining the key effector cells involved in trained immunity and their mechanisms of formation， including processes such as metabolic reprogramming and epigenetic modifications， which collectively lead to a heightened immune response upon secondary stimulation. Furthermore， this review systematically summarizes the role of trained immunity in the initiation and progression of atherosclerosis， and elaborates on various therapeutic strategies targeting trained immunity along with their application prospects.

Background/Aims: Biliary tract cancer (BTC) frequently harbors KRAS mutations, which are associated with resistance to traditional treatment and a poor prognosis. Synthetic lethality (SL) strategy may provide other targets of KRAS. Therefore, we aim to identify and validate potential therapeutic targets of KRAS for the treatment of BTC via SL. Methods: The dependency (DepMap) projects were used to predict the synthetic lethal gene of KRAS. FDA-approved anticancer drug library was applied to screen potential drugs effective against KRAS-mutant BTC. Furthermore, the synthetic lethal effects or corresponding mechanisms of potential genes and drugs on BTC were investigated using KRAS-mutant and KRAS-wild type BTC cell lines, patient-derived xenografts (PDX), and KRAS oncogene-driven tumor models, as well as other KRAS-mutant cancer cell lines. Results: Initially, we discovered that the loss of GATA2 reduced the viability of KRAS-mutant but not KRAS-wild-type BTC. Subsequently, the drug library screened out disulfiram, which primarily exerts a synthetic lethal effect by inhibiting interleukin-1β (IL-1β) in KRAS-mutant BTC. Mechanistically, GATA2 specifically enhanced the transcription of IL-1β to promote NF-κB signaling in KRAS-mutant BTC. IL-1β inhibition phenocopied GATA2 deficiency, leading to reduced KRAS-mutant BTC viability. These synthetically lethal effects were confirmed using PDX, a KRAS oncogene-driven tumor model, as well as in other KRAS-mutant cancer cell lines. Conclusions In summary, these results indicate that inhibiting GATA2/IL1β could be a therapeutic strategy in KRAS-mutant BTC and potentially other cancers.

Effective symptom management can alleviate the physical and psychological distress experienced by patients with cancer, improve quality of life, and contribute to treatment adherence and improve clinical outcomes. However, most existing guidelines are developed for healthcare professionals, and patients and the public have limited access to standardized and comprehensible guidance on symptom management. To address this gap and to facilitate effective communication and shared decision-making, this study proposes the development of a patient version of the cancer symptom management guideline. The development process will adhere to the methodological framework recommended by the Guidelines International Network and the World Health Organization. The GRADE approach will be employed to assess the certainty of evidence and to formulate recommendations. In addition, the process will be informed by the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) instrument and the Reporting Items for Practice Guidelines in Healthcare-Public or Patient Versions of Guidelines (RIGHT-PVG). This protocol outlines the establishment of the guideline working group, the identification and prioritization of key questions, evidence retrieval and appraisal, and the formulation of recommendations, with the aim of ensuring methodological rigor and transparency in the development of the patient guideline and providing methodological reference for similar guideline initiatives.

Definitive chemoradiotherapy (dCRT) has become a cornerstone in the treatment of locally advanced esophageal cancer; however, local control remains suboptimal, and persistent lesions or locoregional recurrences after treatment are not uncommon. For patients without distant metastases but with local failure, whether surgical intervention can still offer curative potential remains a major clinical dilemma. Salvage esophagectomy (SE) offers potential long-term survival for selected patients, but this procedure is performed in the context of severe fibrosis, impaired local blood supply, and obscured anatomical planes following chemoradiotherapy, resulting in significantly higher perioperative risk compared to primary esophagectomy. Consequently, controversies exist regarding patient selection, preoperative restaging, choice of surgical approach, extent of lymphadenectomy, gastrointestinal reconstruction, and perioperative management. In recent years, with the refinement of restaging modalities such as PET/CT, the accumulation of experience in high-volume centers, and emerging evidence from clinical studies, the clinical role of SE has gradually shifted from a "high-risk salvage measure" to a "selective curative strategy aimed at achieving long-term survival in carefully selected patients". Nevertheless, standardized guidelines for patient selection, technical approaches, and perioperative management are still lacking. Based on current evidence and clinical experience, experts organized by the Integrated Esophageal Cancer Committee of Chinese Anti-Cancer Association systematically reviewed key issues regarding SE, including its definition, indications, preoperative evaluation, choice of surgical approach, lymphadenectomy, gastrointestinal reconstruction, and perioperative management, and formulated a Chinese expert consensus. This consensus aims to provide guidance for standardized assessment, appropriate referral, individualized surgical decision-making, and optimized perioperative management of patients with locoregional failure after dCRT. Ultimately, this will increase the likelihood of R0 resection, reduce the risk of severe complications, and promote the safer, more judicious, and standardized implementation of SE in high-risk scenarios.

BackgroundObstructive sleep apnea （OSA） represents a prevalent sleep disordered breathing condition characterized by complex pathophysiology. The arousal threshold （ArTH）， a core non-anatomical contributor to OSA pathogenesis， is intimately tied to the disease severity and clinical phenotypes. To date， research regarding factors associated with ArTH has yielded inconsistent findings， and ArTH profiles and disparities across populations with different genetic backgrounds are not fully elucidated. ObjectiveTo explore the differences of ArTH in OSA patients with different genetic backgrounds and analyze the key factors affecting ArTH， thereby providing evidence for understanding OSA pathophysiology and formulating targeted treatment regimens. MethodsA total of 285 patients who met the diagnostic criteria for OSA， as defined by the Multidisciplinary Diagnosis and Treatment Guidelines for Adult Obstructive Sleep Apnea， were retrospectively enrolled in this study. All participants underwent overnight polysomnography （PSG） at the Sleep Medicine Center of Inner Mongolia Mental Health Center from December 2022 to May 2024. Based on the study design， the cohort was stratified into two distinct genetic background subgroups （group A and group B）. Demographic and clinical characteristics， the Epworth Sleepiness Scale （ESS） score， and overnight PSG data were collected. The apnea hypopnea index （AHI）， the lowest pulse oxygen saturation （LSpO₂）， and fraction of hypopneas （F_Hypopneas） were utilized as surrogate indicators to estimate ArTH in OSA patients. The influencing factors of low ArTH were tested by binary Logistic regression analysis. ResultsAmong the 285 OSA patients， there were 227 cases （79.65%） in group A and 58 cases （20.35%） in group B. Comparisons between the two genetic background subgroups revealed no statistically significant differences in the proportion of low ArTH， ESS score， PSG parameters， and the three markers for low ArTH （AHI<30 events/h， LSpO₂>82.5%， F_Hypopneas>58.3%） （P>0.05）. Binary Logistic regression analysis identified sex （OR=2.421， 95% CI： 1.070–5.478）， BMI （OR=0.847， 95% CI： 0.770–0.932）， N1 sleep duration （OR=0.974， 95% CI： 0.963–0.985）， and hypertension （OR=0.348， 95% CI： 0.143–0.848） as independent factors associated with low ArTH in the total cohort. Stratified analysis by genetic backgrounds revealed that sex（OR=3.799， 95% CI： 1.389–10.392）， BMI（OR=0.819， 95% CI：0.723–0.929）， and N1 sleep duration（OR=0.973， 95% CI： 0.961–0.986） were independent factors of low ArTH in group A. In contrast， only N1 sleep duration （OR=0.951， 95% CI： 0.911–0.993） remained a significant factor in group B. ConclusionArthur may have conservative characteristics in patients with OSA with different genetic backgrounds， but the pathophysiological mechanism of OSA may have population heterogeneity. ［Funded by Inner Mongolia Autonomous Region Natural Science Fundation Project （number， 2024QN08050）； Intra-institutional Scientific Research Project of Inner Mongolia Mental Health Center （number， 2022QNWN0010）］

To summarize the applications of data-intelligence technology in diagnosing lysosomal storage disease(LSD), analyze their opportunities and challenges in clinical practice as well as their development trends, and provide insights and recommendations for advancing digitally driven auxiliary diagnostic technologies.