Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.

Objective To investigate the role of the endothelin-1/nitric oxide （ET-1/NO） system in neurological function and cerebral hemodynamics after interventional surgery for cerebral infarction， as well as the association of the levels of ET-1 and NO with neurological recovery and cerebral blood flow after surgery. Methods A total of 108 patients with cerebral infarction who were treated in our hospital from January 2022 to June 2023 were enrolled， and serum samples were collected before surgery and on day 30 after surgery. ELISA was used to measure the levels of ET-1 and NO；National Institutes of Health Stroke Scale（NIHSS） was used to assess neurological function； transcranial Doppler was used to measure cerebral hemodynamic parameters， including mean blood flow velocity， peak systolic velocity， and pulsatility index. A Spearman correlation analysis was used to investigate the correlation of ET-1 and NO with neurological function and cerebral hemodynamics，and the receiver operating characteristic （ROC） curve was used to assess the value of ET-1 and NO in predicting poor neurological function. Results After interventional surgery， there was a significant reduction in the level of ET-1 and a significant increase in the level of NO（both P<0.001）. The patients were divided into good recovery group （NIHSS≤5） and poor recovery group.Compared with the poor recovery group， the good recovery group had a significant reduction in serum ET-1 and a significant increase in serum NO （both P<0.001）. The Spearman correlation analysis showed that the serum level of ET-1 was negatively correlated with neurological recovery and the improvement in cerebral hemodynamics， while the level of NO was positively correlated with these two indicators. The ROC curve analysis showed that ET-1 and NO could effectively predict poor neurological recovery after interventional surgery， with an area under the ROC curve of 0.881 and 0.981，respectively. Conclusion The ET-1/NO system plays an important role in neurological function and cerebral hemodynamics after interventional surgery for cerebral infarction. Reducing ET-1 and increasing NO can facilitate the recovery of neurological function and cerebral blood flow after surgery. The levels of ET-1 and NO can be used as biomarkers for predicting poor postoperative neurological function and provide a scientific basis for optimizing postoperative treatment strategies.
Endothelin-1

ObjectiveCerebrospinal fluid (CSF) plays a crucial role in maintaining the homeostasis of the central nervous system (CNS). CSF rapidly exchanges with interstitial fluid (ISF) via the glymphatic system within the brain parenchyma. CSF-ISF circulation and its associated mechanisms are often referred to as the brain lymphatic system. This system is connected directly to meningeal lymphatic vessels (mLVs), jointly performing the function of clearing metabolic waste from the CNS. Emerging evidence indicates that this system is closely associated with the onset and progression of neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD). Importantly, abnormal CSF circulation is not only a downstream consequence of AD pathology, but also a risk factor. In AD, the dynamics of CSF flow within the CNS are diminished, immune dysregulation occurs, and this may increase the risk of AD by exacerbating the burden of amyloid β-protein (Aβ). In the mouse model of AD, impaired CSF flow compromises this clearance function, leading to cognitive deficits. Clinically, acupuncture at cognition-related acupoints is commonly used for the prevention and treatment of AD. However, whether its therapeutic effects are mediated through the modulation of CSF dynamics remains unclear. This study aimed to evaluate the impact of acupuncture on CSF flow and investigate its acupoint specificity. MethodsMice were randomly assigned to experimental groups for the different electroacupuncture groups with the following acupoints: Baihui point (GV 20), Ear point, Neiguan point (PC 6), and Tianshu point (ST 25). Wild-type mice on a C57BL/6J background were used as controls. Fluorescent tracer was injected into the cisterna magna to label CSF flow. Fluorescence imaging was employed to assess the distribution of CSF within the brain before and after acupuncture stimulation. ResultsFollowing tracer injection into the cisterna magna, fluorescence signals rapidly reached the cerebellum and medulla—the regions closest to the injection site. Fluorescence intensity was higher in ventral brain regions compared to dorsal regions, likely due to greater vascular density in ventral areas facilitating CSF-ISF exchange. Electroacupuncture at the GV 20 produced the most pronounced enhancement of CSF across the whole brain, while stimulation at the ST 25 primarily augmented flow within subcortical regions. In contrast, electroacupuncture at the Ear point or the PC 6 had no observable effect on CSF in mice. ConclusionElectroacupuncture promotes CSF flow into the brain parenchyma in an acupoint-specific manner, with GV 20 exhibiting the most pronounced enhancement of CSF dynamics. These findings suggest that acupuncture-mediated facilitation of CSF flow may represent a potential therapeutic strategy for preventing or delaying age-related cognitive decline.

ObjectiveCerebrospinal fluid (CSF) plays a crucial role in maintaining the homeostasis of the central nervous system (CNS). CSF rapidly exchanges with interstitial fluid (ISF) via the glymphatic system within the brain parenchyma. CSF-ISF circulation and its associated mechanisms are often referred to as the brain lymphatic system. This system is connected directly to meningeal lymphatic vessels (mLVs), jointly performing the function of clearing metabolic waste from the CNS. Emerging evidence indicates that this system is closely associated with the onset and progression of neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD). Importantly, abnormal CSF circulation is not only a downstream consequence of AD pathology, but also a risk factor. In AD, the dynamics of CSF flow within the CNS are diminished, immune dysregulation occurs, and this may increase the risk of AD by exacerbating the burden of amyloid β-protein (Aβ). In the mouse model of AD, impaired CSF flow compromises this clearance function, leading to cognitive deficits. Clinically, acupuncture at cognition-related acupoints is commonly used for the prevention and treatment of AD. However, whether its therapeutic effects are mediated through the modulation of CSF dynamics remains unclear. This study aimed to evaluate the impact of acupuncture on CSF flow and investigate its acupoint specificity. MethodsMice were randomly assigned to experimental groups for the different electroacupuncture groups with the following acupoints: Baihui point (GV 20), Ear point, Neiguan point (PC 6), and Tianshu point (ST 25). Wild-type mice on a C57BL/6J background were used as controls. Fluorescent tracer was injected into the cisterna magna to label CSF flow. Fluorescence imaging was employed to assess the distribution of CSF within the brain before and after acupuncture stimulation. ResultsFollowing tracer injection into the cisterna magna, fluorescence signals rapidly reached the cerebellum and medulla—the regions closest to the injection site. Fluorescence intensity was higher in ventral brain regions compared to dorsal regions, likely due to greater vascular density in ventral areas facilitating CSF-ISF exchange. Electroacupuncture at the GV 20 produced the most pronounced enhancement of CSF across the whole brain, while stimulation at the ST 25 primarily augmented flow within subcortical regions. In contrast, electroacupuncture at the Ear point or the PC 6 had no observable effect on CSF in mice. ConclusionElectroacupuncture promotes CSF flow into the brain parenchyma in an acupoint-specific manner, with GV 20 exhibiting the most pronounced enhancement of CSF dynamics. These findings suggest that acupuncture-mediated facilitation of CSF flow may represent a potential therapeutic strategy for preventing or delaying age-related cognitive decline.

Objective: Spinal stenosis and degenerative spinal disorders are increasingly prevalent and have a substantial impact on quality of life. Surgical decompression, performed using either open microscopic or endoscopic approaches, remains a cornerstone of management for these conditions. This study examines evolving trends in single-level lumbar spinal decompression procedures performed at a tertiary academic hospital in Singapore. Methods: A retrospective observational study was conducted involving 588 patients who underwent single-level spinal decompression between 2021 and 2024, including endoscopic spine surgery (ESS; n=364) and microdecompression (n=224). Primary outcome measures were changes in 36-Item Short Form Health Survey (SF-36) and visual analogue scale (VAS) scores at 3 months, 6 months, and 2 years postoperatively. Secondary outcomes included length of hospital stay, reoperation rates, and operative time. Patient demographics, spinal level and pathology characteristics, surgical techniques, and postoperative outcomes were analyzed. Difference-in-differences (DID) analysis was used to compare outcomes between the 2 groups. Results: Both groups demonstrated significant postoperative improvements in SF-36 and VAS scores. At 2 years, Short Form Health Survey physical function (SFPF) scores improved in the endoscopic group (mean difference [MD], 18.6; standard deviation [SD], 21.7; p=0.064) and in the open microscopic group (MD, 36.7; SD, 20.9; p=0.007), with a non-significant DID of -18.1 (p=0.155). No DID comparisons across SF-36 domains reached statistical significance. Mean operative time for endoscopic procedures decreased from 249 minutes in 2022 to 145 minutes in 2024, reflecting a procedural learning curve. Surgeons with higher endoscopic caseloads exhibited greater improvements in functional outcomes. Conclusion Both endoscopic and open microscopic decompression achieve comparable short- and long-term clinical outcomes. ESS provides similar effectiveness while being associated with shorter recovery periods and reduced hospital stay. Further research is warranted to identify factors contributing to incomplete symptom resolution or the need for revision surgery.

Background: Patients with coarctation of the aorta (CoA) and an interrupted aortic arch (IAA) may present with small mitral valves (MVs) and a reduced left ventricular (LV) volume. Biventricular repair (BVR) in these patients is dependent on adequate size of the left cardiac structures.Purpose: This study evaluated the impact of the hemodynamic characteristics of atrial septal defects (ASDs) on MV growth following surgical repair. Methods: We retrospectively reviewed the data of patients diagnosed with CoA or IAA between 2007 and 2024. The z score for MV size measured 6 months postoperatively (Z2) was compared with the preoperative MV size (Z1). The factors associated with MV growth were also studied. Results: A total of 161 patients with CoA or IAA were included. Transthoracic echocardiography was used to assess the MV and LV dimensions preoperatively and 6 months postoperatively. Of the cohort, 155 (96.3%) underwent initial BVR and 6 underwent single-ventricle palliation. MV z scores significantly increased following BVR (mean change: +0.45±1.35; P<0.001) but decreased after single-ventricle repair (-0.56±0.49, P=0.04). Multivariate analysis identified the initial MV z score and ASD pressure gradient as independent predictors of MV growth (R2=0.39). Conclusion Annular growth of the MV was not observed in patients who underwent single-ventricle palliation. In contrast, among patients who achieved BVR, those with a small preoperative MV annulus and low ASD pressure gradient demonstrated subsequent catch-up MV growth, suggesting that adequate left-sided preload is essential for MV development.

ObjectiveTo explore the mechanism by which Y-box binding protein 1 （YB1） mediates the expression of multidrug resistance gene 1 （MDR1） and regulates cisplatin-induced resistance in intrahepatic cholangiocarcinoma （ICC）. MethodsAfter treating human ICC HCCC-9810 cells with different concentrations of cisplatin， Western blot and immunofluorescence techniques were used to detect the expression of YB1 and phosphorylated YB1 （pYB1） and changes in their cellular localization. In addition， qPCR and Western blot were used to analyze the expression changes of drug resistance-related proteins MDR1， multidrug resistance-associated protein 2 （MRP2）， and major vault protein （MVP）. Chromatin immunoprecipitation （ChIP） assay was performed to examine the binding of YB1 to the MDR1 promoter in HCCC-9810 cells with or without cisplatin treatment. Additionally， bisulfite sequencing （BS-seq） was used to determine the methylation status of cytosine-phosphate-guanine （CpG） islands within the MDR1 promoter in HCCC-9810 cells， before and after cisplatin treatment. ResultsAfter HCCC-9810 cells were treated with cisplatin， the total amount of intracellular YB1 protein did not change， but the level of pYB1 gradually increased， accompanied by the nuclear migration of YB1 and pYB1 protein. After HCCC-9810 cells were induced with cisplatin， the expression of MDR1 significantly increased， and the drug resistance of the cells also increased. If the expression of MDR1 was inhibited beforehand， the increase in drug resistance of the cells can be reversed. Similarly， after knocking down the expression of YB1 in HCCC-9810 cells， the nuclear migration of YB1 and pYB1 significantly decreased， and the expression of MDR1 significantly decreased， resulting in a significant increase in sensitivity to cisplatin chemotherapy. When HCCC-9810 cells were not stimulated by external factors， the CpG island in the promoter region of MDR1 showed a high methylation state， and multiple transcription factors， including YB1， could not bind to it. When HCCC-9810 cells were treated with cisplatin， the CpG island in the promoter region of MDR1 underwent demethylation， and the binding force between YB1 and the MDR1 promoter in the nucleus increased， activating MDR1 expression. ConclusionYB1 is highly expressed in the cytoplasm of ICC cells. Cisplatin chemotherapy induces nuclear translocation of YB1， accompanied by demethylation of the CpG island in the MDR1 promoter. Nuclear YB1 binds to the MDR1 promoter and activates transcription， ultimately leading to chemotherapy resistance.

Objective To explore the role of miR-429 in synovial mesenchymal stem cell-derived exosomes(SMSC-Exos)in repairing cartilage damage in temporomandibular joint osteoarthritis(TMJ OA)by extracting SMSC-Exos from human synovial tissue and screening differentially expressed microRNA(miRNA)through transcriptome sequencing.Methods Human synovial tissues were obtained from 6 patients who underwent surgery at the First Medical Center of the Chinese PLA General Hospital from June to December 2023,including 3 patients with osteoarthritis(OA group)and 3 control patients(control group),all of whom were male.SMSC-Exos were extracted from the synovial tissues for miRNA sequencing and differential expression analysis.Further,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed on the target genes of differentially expressed miRNA to identify key functional miRNA and construct miRNA-target gene regulatory networks and protein-protein interaction(PPI)networks of target genes.An in vitro model of rabbit condylar cartilage cell inflammatory microenvironment induced by interleukin-1β(IL-1β)was established,with the control group cultured in DMEM/F12 basic medium and the inflammation-induced group cultured in DMEM/F12 basic medium containing 10 ng/ml IL-1β.RT-qPCR was used to detect the effects of overexpressed target miRNA on the mRNA expression levels of cartilage phenotype factors such as type Ⅱ collagen α1 chain(Col2a1),aggrecan(Acan),as well as inflammatory factors including a disintegrin and metalloproteinase with thrombospondin motifs 5(Adamts5)and cyclooxygenase-2(Cox-2).Results(1)SMSC-Exos were successfully isolated,cultured,and identified.(2)miRNA sequencing of SMSC-Exos from OA and control groups revealed 16 differentially expressed miRNAs(|log2FC|>2,P<0.05).Compared with control group,7 miRNAs were up-regulated and 9 were down-regulated in OA group.GO and KEGG analysis indicated that the target genes of miR-429 were mainly involved in development process,anatomical structure development,system development,cell development and differentiation,and were enriched in inflammation-related pathways such as mitogen-activated protein kinase(MAPK)and phosphatidylinositol 3-kinase-protein kinase B(PI3K-Akt).(3)Functional validation of miR-429 in the rabbit condylar cartilage cell inflammatory model showed that overexpression of miR-429 increased the mRNA expression levels of Col2a1 and Acan(P<0.05)and decreased the mRNA expression levels of Adamts5 and Cox-2(P<0.05)in the inflammation-induced group.Conclusions miRNA sequencing of SMSC-Exos isolated and identified from human synovial tissues reveals a specific miRNA expression profile in OA patients,with miR-429 significantly down-regulated.Functional validation demonstrates that overexpression of miR-429 has reparative and anti-inflammatory effects on condylar cartilage cells in an inflammatory microenvironment.

Objective To investigate the differences of perineuronal net(PNN)and parvalbumin(PV)-positive neuron distribution across specific brain regions between young and aged mice.Methods Brains from young(45 days)and aged(350 days)mice(n=4 per group)were fixed with 4％paraformaldehyde,sectioned(50 μm)using a vibratome,and stained with Wisteria floribunda agglutinin(WFA)and PV immunofluorescence.Quantitative analyses of PNN-positive and PV-positive neurons,along with PNN encapsulation of PV-positive neurons,were performed in the anterior cingulate cortex(ACC),somatosensory cortex barrel field layer 4(S1BF L4),striatum(STR),and hippocampal CA2 region.Results Aged mice exhibited no significant changes in PNN-positive or PV-positive neuron counts in ACC,S1BF L4,or STR compared to young mice,but showed significantly increased PNN encapsulation of PV-positive neurons.In hippocampal CA2,PNN-positive neurons increased significantly without PV-positive neuron alterations.Conclusion The differences in PNN-PV neuron interactions and PNN density exist in specific brain regions of young and aged mice.

Objective To develop a method of combining electroencephalogram(EEG)/electromyography(EMG)with multi-regional fiber photometry recording to simultaneously capture the changes of neuronal activity in the whole brain and specific brain regions during epileptic seizures.Methods The mouse head was divided into left and right regions based on the middle suture of the skull.EEG electrodes(EEG/EMG)were implanted in one side,while optical fibers were implanted in the striatum,hippocampus,entorhinal cortex,and thalamus on the contralateral side to simultaneously monitor EEG,EMG,and calcium signal dynamics.Results By combining EEG/EMG with multi-regional fiber photometry recording,differences in neuronal activity across brain regions,alongside EEG and EMG,were observed during different behavioral states.In a kainic acid(KA)-induced epilepsy model,abnormal synchronous neuronal discharges in the mouse brain were accompanied by calcium signal changes in the striatum,hippocampus,entorhinal cortex,and thalamus,with the earliest changes occurring in the hippocampus.Conclusion The combined use of EEG/EMG and multi-brain-region fiber photometry is successfully implemented in mice.This method synchronously recordes abnormal calcium signal changes across multiple brain regions,along with EEG and EMG,in the KA-induced epilepsy model.