INTRODUCTION:Intensive care unit-acquired weakness (ICUAW) is one of the most common neuromuscular impairments featuring symmetric and generalized weakness, and typically occurs in critically ill patients, particularly those with sepsis. Mechanistically, ICUAW shares overlapping immunological networks with respiratory viruses. While accumulating evidence supports an association between Guillain-Barré syndrome (GBS) and respiratory viruses, the causal relationship between ICUAW and these pathogens has not been sufficiently documented. AREAS COVERED:This review summarizes current knowledge on the classification, diagnosis, and management of ICUAW, with a focus on its potential association with respiratory viruses. Relevant literature was collected from PubMed, Web of Science, Cochrane Library, and Google Scholar, focusing on English-language studies published between January 2019 and March 2026. This review addressed differential diagnostic challenges, potential pathogenic mechanisms, therapeutic interventions, and preventive strategies of ICUAW. EXPERT OPINION:Emerging evidence suggests that respiratory viruses may exacerbate ICUAW, highlighting timely interventions combining biomarkers such as Interleukin (IL)-6 and Growth Differentiation Factor (GDF)-15 as promising therapeutic targets. Standardization of diagnostic criteria, refinement of animal models, and individualized rehabilitation strategies are warranted. Future studies on ICUAW should emphasize early assessment of muscle strength, evaluation of nutritional therapy efficacy, and prevention of complications.

Acute kidney injury (AKI) is frequent among intensive care unit (ICU) patients and is linked with high morbidity and mortality. In the absence of specific pharmacological treatments for AKI, continuous renal replacement therapy (CRRT) is a primary treatment option. This study aimed to develop and validate a predictive model for 90-day mortality in critically ill patients with AKI undergoing CRRT. Clinical data from DATADRYAD were used. We randomly divided 1121 adult patients receiving CRRT for AKI into training (80%, n = 897) and validation (20%, n = 224) cohorts. A nomogram prediction model was developed using Cox proportional hazards regression with the training set, and was validated internally. Model performance was evaluated based on calibration, discrimination, and clinical utility. The model, incorporating seven predictors-SOFA score, serum creatinine, blood urea nitrogen, albumin levels, Charlson comorbidity index, mean arterial pressure at CRRT initiation, and phosphate levels 24 h after CRRT initiation-demonstrated robust performance. It achieved a C-index of 0.810 in the training set and 0.794 in the validation set. We developed and validated a predictive model based on seven key clinical predictors, showing excellent performance in identifying high-risk patients for 90-day mortality in AKI patients undergoing CRRT.

ObjectiveOur aim is to review the safety and efficacy of hydroxyurea (HU) on β-thalassemia patients.MethodsStudies that evaluated the safety and efficacy of HU on β-thalassemia patients were searched in Pub-Med, Cochrane Databases, Web of Science, China-Biology-Medicine, CNKI, Embase, VIP, and WanFang data. The proportions of response rate (RR) (50% fall in transfusion need in transfusion-dependent β-thalassemia patients, or 1 g/dL elevate in hemoglobin (Hb) levels in transfusion-independent β-thalassemia patients) and good RR (transfusion-free in transfusion-dependent β-thalassemia patients or 2 g/dL elevate in Hb levels in transfusion-independent β-thalassemia patients) were utilized to evaluate the effect size (ES). The secondary outcomes were the adverse events incidence rates of HU in β-thalassemia patients.ResultsTwo randomized controlled trials (RCTs) and 25 single-armed observational studies with typically 1,748 individuals were involved in our analysis. All 27 clinical trials were reported with fair quality. HU, in transfusion-dependent β-thalassemia patients, was related to a significant decrease in transfusion requirements [a pooled RR of 0.37 and a pooled good RR of 0.65 (95% CI, 0.53–0.76)]; in transfusion-independent β-thalassemia patients, it was correlated to an excellent raise in Hb levels [a pooled RR of 0.20 (95% CI, 0.08–0.35) and a pooled good RR of 0.53 (95% CI, 0.41–0.65)]. Neutropenia and leucopenia were the most prevalent adverse events in β-thalassemia patients treated with HU, while the incidence rates of other side effects were relatively lower.ConclusionOur findings demonstrated that β-thalassemia patients tolerated and responded well to HU. Due to the control arms absence in the involved studies, more double-masked RCTs are essential for proving the safety and efficacy of HU in β-thalassemia patients.

INTRODUCTION:Given the increased incidence of renal anemia and cognitive dysfunction in patients with chronic kidney disease (CKD), the association between hemoglobin levels and cognitive function in these patients remains elucidated. An optimal level of hemoglobin for the best cognitive performance in CKD has yet to be determined. METHODS:A retrospective cross-sectional study was conducted using data from 2011-2014 of the National Health and Nutrition Examination Survey (NHANES). Enrolled subjects for analysis were divided into the CKD and the non-CKD groups. The Animal Fluency Test (AF), Digit Symbol Substitution Test (DSST), Consortium to Establish a Registry for Alzheimer's Disease Word Learning Test (CERAD-WL) and Word List Recall Test (CERAD-DR) were used to evaluate cognitive performances. We quantified the association between hemoglobin levels and cognitive function in patients with CKD and non-CKD subjects by using the logistic regression analysis. Plotted curves and inflection points were calculated by a recursive algorithm. RESULTS:The ratio of cognitive impairment was higher in the CKD group than in the non-CKD group. Hemoglobin levels were correlated with CERAD-DR and DSST in patients with CKD. For non-CKD subjects, the hemoglobin level was not correlated with any test results. The potential range of the hemoglobin level was 11.0 - 12.7 mg/dL for keeping better cognitive performance of patients with CKD. CONCLUSION:Hemoglobin levels are associated with cognitive performance in patients with CKD. The treatment of renal anemia would be meaningful to reduce cognitive impairment in CKD.

As a result of evolution,our body has evolved into a sophisticated system in which various tissues and organs cooperate in a highly or-chestrated manner.Few tissues or organs operate in isolation.The brain serves as the command center of our body and is relatively isolated from the peripheral system due to the presence of the blood-brain barrier(BBB).This barrier prevents direct and extensive interaction between blood cells,plasma molecules,and brain cells,contributing to the long-standing perception of the brain as an"immune-privileged"area.Conse-quently,neuroscientists and immunologists historically conducted sepa-rate research with minimal overlap between these two disciplines.How-ever,this perspective has undergone reconsideration over the past few decades.

BackgroundRespiratory failure requiring mechanical ventilation (MV) is a common and severe complication of Guillain-Barré syndrome (GBS) with a reported incidence ranging from 20% to 30%. Thus, we aim to develop a nomogram to evaluate the risk of MV in patients with GBS at admission and tailor individualized care and treatment.MethodsA total of 633 patients with GBS (434 in the training set, and 199 in the validation set) admitted to the First Hospital of Jilin University, Changchun, China from January 2010 to January 2021 were retrospectively enrolled. Subjects (n=71) from the same institution from January 2021 to May 2022 were prospectively collected and allocated to the testing set. Multivariable logistic regression analysis was applied to build a predictive model incorporating the optimal features selected in the least absolute shrinkage and selection operator (LASSO) in the training set. The predictive model was validated using internal bootstrap resampling, an external validation set, and a prospective testing set, and the model's performance was assessed by using the concordance index (C-index), calibration curves, and decision curve analysis (DCA). Finally, we established a multivariable logistic model by using variables of the Erasmus GBS Respiratory Insufficiency Score (EGRIS) and did the same analysis to compare the performance of our predictive model with the EGRIS model.ResultsVariables in the final model selected by LASSO included time from onset to admission, facial and/or bulbar weakness, Medical Research Council sum score at admission, neutrophil-to-lymphocyte ratio, and platelet-lymphocyte ratio. The model presented as a nomogram displaying favorable discriminative ability with a C-index of 0.914 in the training set, 0.903 in the internal validation set, 0.953 in the external validation set, and 0.929 in the testing set. The model was well-calibrated and clinically useful as assessed by the calibration curve and DCA. As compared with the EGRIS model, our predictive model displayed satisfactory performance.ConclusionsWe constructed a nomogram for early prediction of the risk of MV in patients with GBS. This model had satisfactory performance and appeared more efficient than the EGRIS model in Chinese patients with GBS.

IntroductionGuillain-Barre syndrome (GBS) is a group of acute immune-mediated disorders in the peripheral nervous system. Both infectious and noninfectious factors are associated with GBS, which may act as triggers of autoimmune responses leading to neural damage and dysfunction.Areas coveredSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its vaccines as well as flaviviruses have been associated with GBS, although a robust conclusion has yet to be reached. Immunomodulatory treatments, including intravenous immunoglobulins (IVIg) and plasma exchange (PE), have long been the first-line therapies for GBS. Depending on GBS subtype and severity at initial presentation, the efficacy of IVIg and PE can be variable. Several new therapies showing benefits to experimental animals merit further investigation before translation into clinical practice. We review the state-of-the-art knowledge on the immunopathogenesis of GBS in the context of coronavirus disease 2019 (COVID-19). Immunomodulatory therapies in GBS, including IVIg, PE, corticosteroids, and potential therapies, are summarized.Expert opinionThe association with SARS-CoV-2 remains uncertain, with geographical differences that are difficult to explain. Evidence and guidelines are lacking for the decision-making of initiating immunomodulatory therapies in mildly affected patients or patients with regional subtypes of GBS.

OPINION article Front. Neurol., 10 January 2024Sec. Neuromuscular Disorders and Peripheral Neuropathies Volume 14 - 2023 | https://doi.org/10.3389/fneur.2023.1336794

Multiple sclerosis is an inflammatory disorder characterized by inflammation, demyelination, and neurodegeneration in the central nervous system. Although current first-line therapies can help manage symptoms and slow down disease progression, there is no cure for multiple sclerosis. The gut-brain axis refers to complex communications between the gut flora and the immune, nervous, and endocrine systems, which bridges the functions of the gut and the brain. Disruptions in the gut flora, termed dysbiosis, can lead to systemic inflammation, leaky gut syndrome, and increased susceptibility to infections. The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors, and gut flora may play a pivotal role in regulating immune responses related to multiple sclerosis. To develop more effective therapies for multiple sclerosis, we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis. This review provides an overview of the role of the gut flora in multiple sclerosis.

Peritoneal dialysis is an efficient renal replacement therapy for patients with end-stage kidney disease. However, continuous exposure of the peritoneal membrane to dialysate frequently leads to peritoneal fibrosis, which alters the function of the peritoneal membrane and results in withdrawal from peritoneal dialysis in patients. Among others, high glucose dialysate is considered as a predisposing factor for peritoneal fibrosis in patients on peritoneal dialysis. Glucose-induced inflammation, metabolism disturbance, activation of the renin–angiotensin–aldosterone system, angiogenesis and noninflammation-induced reactive oxygen species are implicated in the pathogenesis of high glucose dialysate-induced peritoneal fibrosis. Specifically, high glucose causes chronic inflammation and recurrent peritonitis, which could cause migration and polarization of inflammatory cells, as well as release of cytokines and fibrosis. High glucose also interferes with lipid metabolism and glycolysis by activating the sterol-regulatory element-binding protein-2/cleavage-activating protein pathway and increasing hypoxia inducible factor-1α expression, leading to angiogenesis and peritoneal fibrosis. Activation of the renin–angiotensin-aldosterone system and Ras-mitogen activated protein kinase signaling pathway is another contributing factor in high glucose dialysate-induced fibrosis. Ultimately, activation of the transforming growth factor-β1/Smad pathway is involved in mesothelial-mesenchymal transition or epithelial-mesenchymal transition, which leads to the development of fibrosis. Although possible intervention strategies for peritoneal dialysate-induced fibrosis by targeting the transforming growth factor-β1/Smad pathway have occasionally been proposed, lack of laboratory evidence renders clinical decision-making difficult. We therefore aim to revisit the upstream pathways of transforming growth factor-beta1/Smad and propose potential therapeutic targets for high glucose-induced peritoneal fibrosis.

EDITORIAL article Front. Cell. Neurosci., 06 February 2023Sec. Non-Neuronal Cells Volume 17 - 2023 | https://doi.org/10.3389/fncel.2023.1141622

Introduction The aim was to observe the effect of Toll-like receptor 4 (TLR4) deficiency on clinical severity and expression of Th1/Th2/Th17-associated cytokines in experimental autoimmune neuritis (EAN). Material and methods We selected C57BL/10 wild type (WT) mice and TLR4 knockout (KO) mice with the C57BL/10 background for induction of the EAN model by immunizing mice twice (days 0 and 8) via subcutaneous injection of 180 µg P0 peptide 180–199 emulsion in 25 µl of PBS and 0.5 mg Mycobacterium tuberculosis (Difco, USA) in 25 µl of Freund’s incomplete adjuvant into the back of mice. The concentrations of serum cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ and TNF) were determined using the Ms Th1/Th2/Th17 CBA kit. Results We found that TLR4 deficiency could attenuate the clinical severity and delay the onset of EAN. Moreover, our data showed that the sera levels of IFN-γ, TNF, IL-6 and IL-17A were elevated in the WT mice with EAN when compared with the naive WT mice, but only the production of IL-17A was significantly lower in the TLR4 KO mice with EAN than in their WT counterparts. Conclusions Based on these findings, TLR4 may contribute to the pathogenesis of EAN by regulating Th17 cells and the production of Th17-associated factors. However, the exact mechanism remains unclear and more evidence is needed to elucidate its role in EAN.

Neuroimmunology is an interdisciplinary branch of biomedical science that emerges from the intersection of studies on the nervous system and the immune system. The complex interplay between the two systems has long been recognized. Research efforts directed at the underlying functional interface and associated pathophysiology, however, have garnered attention only in recent decades. In this narrative review, we highlight significant advances in research on neuroimmune interplay and modulation. A particular focus is on early- and middle-career neuroimmunologists in China and their achievements in frontier areas of "neuroimmune interface", "neuro-endocrine-immune network and modulation", "neuroimmune interactions in diseases", "meningeal lymphatic and glymphatic systems in health and disease", and "tools and methodologies in neuroimmunology research". Key scientific questions and future directions for potential breakthroughs in neuroimmunology research are proposed.

Objective Cognitive impairment is a common complication of chronic kidney disease (CKD). Caffeine intake has been reported to improve cognitive performance in several studies. However, whether the benefits of caffeine intake on cognitive function apply to patients with CKD remains unknown. Methods We performed a retrospective cross-sectional study based on the National Health and Nutrition Examination Survey (NHANES). The data of CKD subjects and non-CKD subjects from NHANES 2011−2014 were analyzed. Propensity score matching (PSM) was performed based on age, sex, diabetes, cancer, educational level, energy intake and protein intake to select subjects. The Consortium to Establish a Registry for Alzheimer’s Disease Word Learning Test (CERAD-WL), the CERAD Word List Recall Test (CERAD-DR), the Animal Fluency Test (AF) and the Digit Symbol Substitution Test (DSST) were used, whereby the occurrence of cognitive impairment was identified. Logistic regression models were performed to evaluate the association between caffeine intake and cognitive performance in CKD and non-CKD participants. Stratified analyses according to the stage of CKD and the urinary albumin/creatinine ratio levels were performed. Plot curves were then generalized to present a non-linear relationship, and the inflection point for each non-linear model was obtained by using a recursive algorithm. Results Cognitive impairment was more prevalent in CKD patients than in non-CKD subjects. For CKD patients, caffeine intake was associated with higher CERAD-WL, CERAD-DR, AF and DSST scores. For non-CKD subjects, caffeine intake was associated with higher DSST scores only. Subgroup analysis revealed that caffeine only benefited the cognitive function of patients with CKD stages 2 and 3. The analysis showed non-linear relationships of caffeine intake and cognitive function for both CKD and non-CKD subjects. The inflection point of caffeine intake for CKD patients was 279 mg/day. Conclusion The recommended dose of caffeine intake to improve the cognitive function of CKD patients is ≤279 mg/day.

神经科学是研究神经系统的结构、功能与疾病,探讨认知和行为的本质与规律的学科.神经科学兼具生物学、医学和交叉科学的属性.作为生物学的一门分支,神经科学解析包括初级神经系统功能如感知觉和本能行为,中级神经系统功能如情感、学习、记忆、注意、思维、决策等,及高级认知功能如人类智慧起源、自我意识、语言等在微观、介观、宏观不同层次的工作原理.作为现代医学的一个分支,神经科学是理解神经精神疾病的根本基础,也是发展临床诊疗新技术和新手段的重要途径.作为一门交叉学科,神经科学与心理学、免疫学、遗传学、药学、数学、物理学、化学、信息科学、计算科学和工程材料科学等学科存在广泛的交叉融合.神经科学学科的发展在我国社会经济发展中具有极其重要的地位.神经科学界已经认识到生物—心理学—社会医学模式在人口健康和疾病领域中的重要价值,因此神经科学家近年来在心理—行为—神经—内分泌 免疫的总体框架下积极开展研究,以期系统理解人类大脑的基本工作原理以及神经精神疾病.基于大脑工作原理的人工智能技术正成为新一轮科技革命的目标,有望开发低功耗、高效率、强"鲁棒"性的类脑智能产品.当前我国神经科学的发展面临着激烈的国际竞争.进一步加大对神经科学的投入、鼓励原创性的科学探索、加强科研队伍建设、努力满足经济社会发展需求、重视新研究技术和新实验范式的开发,以及多学科的交叉融合等,是应对挑战的重要策略.本文基于国家自然科学基金委员会关于神经科学学科发展战略调研的成果,回顾国家自然科学基金资助情况,归纳学科的前沿科学问题和优先发展领域,尤其从国家自然科学基金的视角提出我国神经科学学科发展的机遇、挑战和建议.

Bromadiolone, a widely-used rodent control drug, could act as a long-acting anticoagulant. Patients of bromadiolone poisoning often present with multiorgan hemorrhage. However, neurological symptoms of bromadiolone poisoning are seldom reported. We report a rare case with convulsive status epilepticus as the initial presentation of bromadiolone poisoning. A previously healthy 18-year-old man presented with persistent unconsciousness and repeated convulsive seizures. Magnetic resonance imaging revealed lesions in the corpus callosum. Laboratory test revealed the microscopic hematuria, prolonged prothrombin time, prolonged activated partial thromboplastin time and the presence of bromadiolone. The patient was diagnosed as the bromadiolone poisoning and treated with hemofiltration, vitamin K and prothrombin complex. Consciousness of the patient was regained and all neurological symptoms diminished after 7 days. Coagulopathy was totally corrected after 3 weeks, and a 2-month regimen of vitamin K supplementation was prescribed after discharge. Our case suggests that bromadiolone poisoning may involve the central nervous system. The atypical and initial symptoms of neurological disorders might lead to misdiagnosis of bromadiolone poisoning. Poisoning should be considered when acute neurological symptoms are combined with bleeding tendency. The vitamin K treatment is effective for both coagulopathy and central nervous system disorders in bromadiolone poisoning.