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.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

BACKGROUND: The potential impact of pre-existing coronary artery stenosis (CAS) on right ventricular (RV) function during acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and RV dysfunction in patients with acute PE. METHODS: In this multicenter, case-control study, 89 cases and 176 controls matched for age were enrolled at three study centers (Peking Union Medical College Hospital, Fuwai Hospital, and the Second Affiliated Hospital of Harbin Medical University) from January 2016 to December 2020. The cases were patients with acute PE with CAS, and the controls were patients with acute PE without CAS. Coronary artery assessment was performed using coronary computed tomographic angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression analysis was used to evaluate the association between CAS and RV dysfunction. RESULTS: The percentages of RV dysfunction (19.1% [17/89] vs. 44.6% [78/176], P <0.001) and elevated systolic pulmonary artery pressure (sPAP) (19.3% [17/89] vs. 39.5% [68/176], P = 0.001) were significantly lower in the case group than those in the control group. In the multivariable logistic regression model, CAS was independently and negatively associated with RV dysfunction (adjusted odds ratio [OR]: 0.367; 95% confidence interval [CI]: 0.185-0.728; P = 0.004), and elevated sPAP (OR: 0.490; 95% CI: 0.252-0.980; P = 0.035), respectively. CONCLUSIONS Pre-existing CAS was significantly and negatively associated with RV dysfunction and elevated sPAP in patients with acute PE. This finding provides new insights into RV dysfunction in patients with acute PE with pre-existing CAS.
Humans ; Pulmonary Embolism/complications* ; Case-Control Studies ; Male ; Ventricular Dysfunction, Right/physiopathology* ; Female ; Middle Aged ; Aged ; Coronary Stenosis/complications* ; Logistic Models ; Adult

A primary hallmark of pathological cardiac hypertrophy is excess protein synthesis due to enhanced translational activity. However, regulatory mechanisms at the translational level under cardiac stress remain poorly understood. Here we examined the translational regulations in a mouse cardiac hypertrophy model induced by transaortic constriction (TAC) and explored the conservative networks versus the translatome pattern in human dilated cardiomyopathy (DCM). The results showed that the heart weight to body weight ratio was significantly elevated, and the ejection fraction and fractional shortening significantly decreased 8 weeks after TAC. Puromycin incorporation assay showed that TAC significantly increased protein synthesis rate in the left ventricle. RNA-seq revealed 1,632 differentially expressed genes showing functional enrichment in pathways including extracellular matrix remodeling, metabolic processes, and signaling cascades associated with pathological cardiomyocyte growth. When combined with ribosome profiling analysis, we revealed that translation efficiency (TE) of 1,495 genes was enhanced, while the TE of 933 genes was inhibited following TAC. In DCM patients, 1,354 genes were upregulated versus 1,213 genes were downregulated at the translation level. Although the majority of the genes were not shared between mouse and human, we identified 93 genes, including Nos3, Kcnj8, Adcy4, Itpr1, Fasn, Scd1, etc., with highly conserved translational regulations. These genes were remarkably associated with myocardial function, signal transduction, and energy metabolism, particularly related to cGMP-PKG signaling and fatty acid metabolism. Motif analysis revealed enriched regulatory elements in the 5' untranslated regions (5'UTRs) of transcripts with differential TE, which exhibited strong cross-species sequence conservation. Our study revealed novel regulatory mechanisms at the translational level in cardiac hypertrophy and identified conserved translation-sensitive targets with potential applications to treat cardiac hypertrophy and heart failure in the clinic.
Animals ; Humans ; Cardiomegaly/physiopathology* ; Ribosomes/physiology* ; Protein Biosynthesis/physiology* ; Mice ; Cardiomyopathy, Dilated/genetics* ; Ribosome Profiling

As the population is aging rapidly,the incidence of Alzheimer's disease(AD)is increasing year by year.The World Health Organization stresses that early prevention plays a key role in reducing the incidence of AD.Subjective cognitive decline(SCD)is an early window of AD development,and timely intervention can effectively slow down the progression of the disease or prevent it from developing into dementia,thus reducing the burden on the society.White matter hyperintensity(WMH)can effectively reflect white matter changes and provide strong evidence to identify SCD.In this paper,we review the recent research progress in WMH and SCD,reveal the problems in the current research on WMH,explain the correlation between WMH and SCD in terms of physiopathology and cognitive function,and put forward several suggestions for the future research.
Humans ; White Matter/pathology* ; Cognitive Dysfunction/pathology* ; Alzheimer Disease/pathology* ; Magnetic Resonance Imaging

Acute urinary retention(AUR)occurs frequently among astronauts on orbit.The current treatment is complex and easy to damage the urethra,which seriously affects the life and work of astronauts.In contrast,acupuncture,a traditional Chinese remedy,has shown promising results in managing urinary retention.However,the specific acupoints that could potentially prevent AUR remain uncertain due to the unique physiological conditions experienced by individuals in space compared to those on Earth.To address this gap,our research delved into the mechanisms of AUR and acupuncture within both traditional Chinese medicine and modern medical practices.We conducted a thorough literature review from Pubmed,Web of Science,CNKI,Wanfang database,VIP database and Chinese Medical Code database.A hierarchical evidence-scoring approach was utilized to analyze the included literatures,thus devised acupuncture protocols for the treatment of AUR.The outcomes of our study aim to establish a foundation for the application of acupuncture in managing AUR.

Objective To explore whether creatine therapy regulates neuronal ferroptosis by inhibiting the activation of STAT1 signaling pathway associated with suppressor of cytokine signaling 1(SOCS1)in Alzheimer's disease.Methods Immunohistochemical staining and counting of positive results using paraffin sections of human brain frontal lobes were employed to determine the trend of changes in the target proteins.Further validation was performed by immunofluorescence and Western blotting.STAT1 phosphorylation was inhibited by creatine injection using eleven FAD4T mice and by cerebellar medullary pool puncture,and the expression of target proteins was examined by immunohistochemistry and immunofluorescence after postmortem sampling.Results Compared with the age controls,interferon-γ(IFN-γ),an activating cytokine of the STAT1 signaling pathway,and SOCS1,a negative regulator of STAT1 activation,were both significantly up-regulated,STAT1 phosphorylation was enhanced,and the ferroptosis markers ferritin light chain(FTL)and cystine/glutamate transporter(xCT)increased markedly in the cortex of AD human brains;Creatine treatment of FAD4T mice resulted in a reduction of both IFN-γ and SOCS1,and a significant decrease in the ferroptosis markers FTL and xCT(SLC7A11).Conclusion Creatine ameliorates neuronal ferroptosis in AD model mice by reducing neuronal STAT1-SOCS1 signalling activation.

Objective:To analyze the applied effect of artificial intelligence(AI)rehabilitation system combined with telemedicine platform in individualized rehabilitation treatment for patients with long-term coma,so as to realize individual management for them.Methods:An AI rehabilitation system that aimed to patients with long-term coma was designed by integrating data of multimodal sensors included inertial sensor,image sensor and bioelectric sensor.A telemedicine platform,which included seven modules(patient management,consultation management,video communication,data transmission,electronic medical records,cost management and system maintenance),was designed by using a browser/server(B/S)architecture.The changes of patients'condition were followed up,and the full process of the management for rehabilitation treatment and the individualization of treatment plan were realized.A total of 60 inpatients whose coma duration exceeded 28 days were selected from the Coma Awakening Center of Dongguan Shipai Hospital between October 1,2021 and September 30,2022.They were randomly divided into control group(n=30)and observation group(n=30)by random number table.The control group received physical therapy and rehabilitation training based on evaluation results of rehabilitation,while the observation group adopted AI rehabilitation system combined with the telemedicine platform to conduct intervention.The consciousness levels,quality of life,hospital stay duration and treatment costs of two group were compared after intervention.Results:The Glasgow Coma Scale(GCS)scores,Coma Recovery Scale-Revised(CRS-R)scores,and Persistent Vegetative State(PVS)scores of two groups after intervention were significantly higher than those before intervention,and these indicators of observation group were significantly higher than them of control group after intervention,and the differences were significant(t=7.187,15.586,9.293,P<0.05),respectively.There were not significant differences in Glasgow Outcome Scale(GOS)scores and Activities of Daily Living(ADL)scores between two groups before intervention(P>0.05),and these scores of two groups were significantly increased after intervention,and these scores of observation group were significantly higher than them of control group after intervention,and the differences were significant(t=7.584,6.755,P<0.05).Additionally,the hospital stay duration and treatment costs of observation group were significantly less than those of control group,and the differences were significant(t=20.965,9.503,P<0.05).Conclusion:The intervention of AI rehabilitation system combines with a telemedicine platform on patients with long-term coma can enhance GCS,CRS-R,PVS,GOS and ADL scores,and reduce hospital stay duration and treatment cost.

Objective To investigate the structural changes and influencing factors of the average inpatient cost per admis-sion in public hospitals in Guangdong Province.Methods Grey relational analysis and structural variation degree analysis were used to analyze the correlation and changes between the average inpatient cost per admission and various cost components in public hospitals of Guangdong Province from 2017 to 2023.Results The average inpatient cost per admission in public hospitals of Guangdong Province showed an overall upward trend from 2017 to 2023,with an average annual growth rate of 3.84％.Among the components,laboratory test fees and examination fees grew at average annual rates of 6.17％and 6.68％,respectively.The top four cost components with the highest grey relational degree with the average inpatient cost were laboratory test fees(0.867),exam-ination fees(0.835),nursing fees(0.784),and treatment fees(0.728).The top four components with the largest structural vari-ation values were surgery fees(2.57％),medical material fees(1.77％),laboratory test fees(1.56％),and examination fees(1.45％).Conclusion The growth of the average inpatient cost per admission has slowed,and the cost structure has been opti-mized to some extent.However,the relatively rapid increase in laboratory test and examination fees has a significant impact on the cost structure.It is necessary to deepen the coordinated governance of healthcare,medical insurance,and medicine,strengthen the leveraging role of medical insurance payment,improve the external governance system and scientific compensation mechanism,and combine these with refined hospital management to promote reasonable cost control and high-quality development in public hospitals.

Objective:To develop an artificial intelligence (AI)-based platelet review strategy to identify abnormal platelet histograms with no significant difference between initial impedance platelet count (PLT-I) and PLT-F results.Methods:This study included 5 119 routine blood analysis in Nanfang Hospital of Southern Medical University and its Ganzhou branch from July 2023 and March 2024. Specimens exhibiting abnormal platelet histograms and an initial platelet count >40×10?/L underwent review using the fluorescent platelet count (PLT-F) channel. Consistency of the results was defined as a difference between impedance platelet count (PLT-I) and PLT-F less than ±20% of the PLT-F results. A deep learning model was developed using platelet and red blood cell histogram data from a training set of 3 807 specimens. The model′s diagnostic performance was evaluated on an independent external validation set ( n=805) using receiver operating characteristic (ROC) curve analysis. Changes in the number of reviewed samples and sample turnaround time were analyzed to assess its clinical utility. Results:The deep learning model based on platelet and red blood cell histograms achieved an area under the ROC curve (AUC) of 0.854 in the training set. At a cutoff value of 0.1, the sensitivity was 0.954 and specificity was 0.358. The model could reduce review by 16.80% (190/1 131). In the validation set, the AUC was 0.805, with a sensitivity of 0.955 and specificity of 0.307, corresponding to a reduction of 17.41% (47/270) in reviewed specimens.Conclusion:The platelet review prediction model developed based on deep learning technology can efficiently identify samples with consistent results before and after review, reducing unnecessary reviews and shortening specimen testing time, thereby improving the efficiency of platelet test.