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.

The Type III Secretion System (T3SS) serves as a pivotal virulence apparatus for numerous Gram-negative bacterial pathogens, enabling them to infect both animal and plant hosts. Functioning as a molecular syringe, the T3SS directly translocates bacterial effector proteins from the bacterial cytoplasm into the interior of eukaryotic host cells. These effectors are central weapons that precisely manipulate a wide spectrum of host cellular physiological processes, ranging from cytoskeletal dynamics to immune signaling, to establish a favorable niche for bacterial survival and proliferation. Among the diverse arsenal of T3SS effectors, the YopJ family constitutes a critical group of virulence factors. Members of this family are characterized by a conserved catalytic triad structure—a hallmark of the CE clan of cysteine proteases that has been evolutionarily repurposed to confer acetyltransferase activity. A defining and intriguing feature of these enzymes is their stringent dependence on a host-derived eukaryotic cofactor, inositol hexakisphosphate (IP₆), for allosteric activation. This requirement acts as a sophisticated molecular safeguard, ensuring enzymatic activity only within the appropriate host environment, thereby preventing detrimental effects on the bacterium itself. While seminal studies on individual members such as Yersinia’s YopJ and Salmonella’s AvrA have provided deep mechanistic insights, a systematic and integrative understanding of the structure-function relationships across the entire family remains fragmented. Key questions persist regarding how a conserved catalytic core has diverged to recognize distinct host substrates in different kingdoms of life. To address this gap, this article provides a systematic review of the YopJ family, focusing on three interconnected aspects: their structural features, their catalytic mechanism, and their divergent immunosuppressive strategies in animal versus plant hosts. By conducting a comparative analysis of the sequences and resolved three-dimensional structures of three representative members (e.g., HopZ1a, PopP2, AvrA), we elucidate regions of significant variation embedded within the conserved core catalytic architecture. These variable regions, often involving surface loops and substrate-binding interfaces, are crucial determinants of target specificity and functional specialization. The functional divergence of this effector family is most apparent when comparing their modes of action in different hosts. In animal hosts, YopJ-family effectors primarily sabotage innate immune signaling pathways. They achieve this by acetylating key serine and threonine residues within the activation loops of critical kinases in the MAPK and NF‑κB pathways. This post-translational modification blocks the phosphorylation and subsequent activation of these kinases, leading to potent suppression of inflammatory cytokine production. Conversely, in plant hosts, the strategy broadens to dismantle the two-tiered plant immune system. YopJ homologs target a more diverse set of substrates, including immune-associated receptor-like cytoplasmic kinases (RLCKs), microtubule networks via tubulin acetylation (which disrupts cellular trafficking and signaling), and transcription factors central to defense gene regulation. This multi-target approach effectively suppresses both Pattern-Triggered Immunity (PTI) and Effector-Triggered Immunity (ETI). In conclusion, this synthesis aims to deepen the mechanistic understanding of YopJ family-mediated pathogenesis by integrating structural biology with cellular function across host kingdoms. Elucidating the precise molecular basis for substrate selection—how conserved platforms achieve target diversity—is a major frontier. Furthermore, this knowledge provides a vital theoretical foundation for developing novel anti-virulence strategies. Targeting the conserved IP₆-binding pocket or the catalytic acetyltransferase activity itself represents a promising avenue for designing broad-spectrum inhibitors that could disarm this critical family of bacterial effectors, potentially offering new therapeutic approaches against a range of pathogenic bacteria.

Objective To describe the clinical characteristics and nutritional management status of hospitalized elderly patients with multimorbidity in a tertiary hospital's geriatric center in 2024, and to analyze the correlation between nutritional status and hospitalization outcomes, thereby providing a basis for optimizing nutritional management pathways for this population. Methods A retrospective study was conducted, including 2 937 elderly patients with multimorbidity. Data on general information, clinical indicators, nutritional risk screening and assessment, nutritional therapy, and costs were collected for descriptive analysis. The relationship between nutritional status (based on BMI and serum albumin levels) and hospitalization outcomes was explored. Results The average age of the patients was (77.45±10.70) years, with 57.17% being male. The average number of chronic diseases diagnosed was (11.56±5.08) per patient, and 26.01% were critically ill. The nutritional risk screening rate was 80.40%, with a screening positivity rate of 33.44%. The nutritional assessment rate was 31.63%, and the malnutrition prevalence was 23.08%. The low BMI group had the longest median hospital stay [15 (9.75, 22) days] and the highest hospitalization costs [15 057.2 (8 980.48, 28 160.46) CNY]. Serum albumin levels were negatively correlated with hospital stay duration (rs=-0.276, P< 0.01) and hospitalization costs (rs=-0.276, P<0.01). Conclusion Hospitalized elderly patients with multimorbidity are characterized by multiple comorbidities and high healthcare resource consumption. While the nutritional risk screening rate is relatively high, there remains room for improvement in nutritional assessment and therapy. It is necessary to strengthen standardized management throughout the entire process. Nutritional status is a significant variable affecting hospital stay duration and costs, with poorer nutritional status significantly associated with prolonged hospitalization and higher costs, suggesting that it may be an important factor influencing hospitalization outcomes.

Background The Inner Mongolia Autonomous Region is a vast area with a wide array of ecological environments, resulting in considerable regional variations in air pollution characteristics. Current research is limited by a scarcity of systematic, region-wide studies and risk assessments. Objective To assess the health risks associated with inhalation exposure to nine heavy metal and metalloid elements in atmospheric fine particulate matter (PM_2.5) for the population of the Inner Mongolia Autonomous Region. Methods From the 10th to the 16th of each month throughout 2023, atmospheric PM_2.5 samples were collected at designated monitoring sites in 12 leagues (cities) across the Inner Mongolia Autonomous Region to analyze the characteristics and trends in concentration. The health risk assessment model developed by the United States Environmental Protection Agency was employed to evaluate both the non-carcinogenic and carcinogenic risks associated with the heavy metal elements beryllium (Be), cadmium (Cd), chromium (Cr), hydrargyrum (Hg), plumbum (Pb), manganese (Mn), and nickel (Ni) and the metalloid elements stibium (Sb) and arsenic (As). Results In 2023, a total of 1206 valid PM_2.5 samples were analyzed from the Inner Mongolia Autonomous Region. The annual average PM_2.5 concentrations in Inner Mongolia, as well as in the cities of Ordos, Wuhai, and the Alxa League, all exceeded the national limit of 35 μg·m⁻³. The PM_2.5 concentrations across the leagues (cities) exhibited a clear seasonal variation, peaking in winter, followed by spring, and reaching a minimum in summer and autumn. The median PM_2.5 concentration in Ordos throughout the year was higher than that in the other leagues (cities) of the region. Concerning health risks, the non-carcinogenic risks associated with the 9 elements detected in each league (city) were all below 1, indicating acceptable levels. However, the non-carcinogenic risk values for Mn, Cr, and As were relatively high; specifically, Ordos City displayed the highest non-carcinogenic risk values for Mn (7.74×10⁻¹) and Cr (2.97×10⁻²), while Chifeng City recorded the highest value for As (2.34×10⁻³). The carcinogenic risk values for As, Cd, Cr, and Ni fell within the range of 1×10⁻⁹ to 1×10⁻⁵, representing an acceptable level. The health risks varied with age, and the elderly residents faced the highest non-carcinogenic and carcinogenic health risks. Conclusion While the carcinogenic and non-carcinogenic risks from heavy metals and metalloids within atmospheric PM_2.5 in the Inner Mongolia Autonomous Region are generally within acceptable limits, the potential risks that Mn, As, and Cr pose to the health of elderly people warrants particular attention, and Ordos and Chifeng cities exhibit notably higher health risks among other areas. It is recommended that regular, long-term monitoring be conducted, taking into account the specific conditions at monitoring sites across each league (city), and that targeted air quality management strategies be implemented to protect public health.

Sj?gren's syndrome(SS)is one of the common rheumatic diseases in clinical practice.Modern medicine commonly uses drugs such as artificial tears,saliva,glucocorticoids,immunosuppressants,and biologics to control the condition.Clinical practice has shown that in addition to modern medical basic treatment,the use of traditional Chinese medicine(TCM)can help improve the clinical efficacy of SS.According to the symptoms and signs of Sj?gren's syndrome in TCM,it is classified as"dryness and obstruction",and the core pathogenesis of the disease is spleen deficiency and deficiency of body fluids.Subsequently,toxic and pathogenic factors gather,leading to the decline of internal organs.The initial causes are spleen damage,unstable barrier,and invasion of pathogenic factors.The core link is spleen dysfunction,insufficient body fluid,and dryness arising from it.Spleen deficiency generates evil,obstruction of qi,and lack of body fluids are the root causes of illness.The main treatment method is the"spleen strengthening method",which treats spleen deficiency,dampness and stagnation,and the body fluid is not distributed.The treatment focuses on strengthening the spleen and qi,supplementing the lungs and generating fluids.Spleen deficiency leads to loss of vitality,blood stasis obstructs blood vessels,and the treatment is to strengthen the spleen,soothe the liver,remove blood stasis,and unblock the orifices.The spleen yang is not vigorous,and qi transformation is impaired.The treatment is to invigorate the spleen and warm the stomach,promote yang circulation,and promote diuresis.

Objective To examine the expression pattern of apoptosis signal-regulating kinase 1(ASK1)in the intestinal tissues of patients with Crohn's disease(CD),and analyze its mechanistic impact on intestinal epithelial barrier function and inflammatory responses.Methods Ileal tissue samples from Crohn's disease patients and healthy controls were collected.ASK1 protein level was assessed by immunohistochemistry,and its relationship with the Crohn's disease activity index(CDAI)was analyzed.A mouse model of acute colitis was constructed using TNBS,and subjected to qRT-PCR,Western blotting and immunohistochemistry for ASK1 expression,and the association between ASK1 expression and the disease activity index was examined.Lentivirus transfection was employed to create stable Caco-2 cell lines with altered ASK1 expression,and the intestinal barrier integrity and inflammation were assessed by measuring transepithelial electrical resistance(TEER),FITC-dextran leakage,and IL-6,IL-1β levels.Furthermore,the effects of ASK1 expression on Krüppel-like factor 4(KLF4)levels was examined using qRT-PCR and Western blotting.Results ASK1 was highly expressed in the ileum of CD patients and positively correlated with CDAI.In a TNBS-induced mouse model of acute colitis,ASK1 expression was up-regulated and positively correlated with DAI.Inflammation-induced ASK1 overexpression weakened the Caco-2 cell intestinal barrier,whereas ASK1 knockdown strengthened it.Moreover,ASK1 had the capability to enhance the expression of inflammatory factors.Additionally,ASK1 knockdown increased KLF4 expression,while overexpression decreased it,indicating a negative correlation between ASK1 and KLF4.Conclusion ASK1 expression is notably higher in CD and positively correlates with disease activity.ASK1 can influence intestinal barrier integrity and inflammatory factor expression,possibly through its impact on KLF4 expression.

Objective:To develop an early exercise rehabilitation nursing for elderly patients undergoing total hip arthroplasty (THA) based on the best evidence, and explore its clinical effects.Methods:This study was a randomized controlled trial. From August to December 2022, convenience sampling was used to select 126 elderly THA patients admitted to the Department of Orthopedics of the First Affiliated Hospital of Naval Medical University as participants. Patients were divided into observation group and control group using a random number table method, with 63 cases in each group. Control group was treated with a usual exercise rehabilitation nursing, while observation group was treated with an early exercise rehabilitation nursing for elderly THA patients based on the best evidence. Changhai Pain Rating Scale, Harris Hip Score, and Barthel Index were used to evaluate pain, hip function, and activities of daily living in two groups of patients. The first time off the bed, hospital stay, and incidence of complications were recorded and compared between the two groups.Results:The Harris Hip scores of observation group patients three days after surgery and on the day of discharge were (61.13±4.82) and (77.84±4.43), respectively, which were higher than those of control group (50.75±6.19) and (70.25±7.47), and the differences were statistically significant ( t=10.502, 6.937; both P<0.01). Barthel Index scores of observation group patients were higher than those of control group on the day of surgery, three days after surgery, and the day of discharge, and the differences were statistically significant ( t=3.531, 4.609, 10.112; all P<0.01). The incidence of postoperative complications in observation group was 11.11% (7/63), while in control group it was 42.86% (27/63), with a statistically significant difference (χ 2=16.113, P<0.01). There were no statistically significant differences in the resting pain score and exercise pain score between the two groups of patients on the day after surgery ( t=-1.693, -1.354; both P>0.05). The resting pain score and exercise pain score of observation group were lower than those of control group three days after surgery and on the day of discharge, and the differences were statistically significant (all P<0.05). Observation group had a shorter first time off the bed and hospital stay (1.34±0.37) and (5.48±0.66) days compared to control group (2.13±0.48) and (6.29±0.83) days, with statistically significant differences ( t=-10.346, -6.063; both P<0.01) . Conclusions:An evidence-based early exercise rehabilitation nursing for elderly THA patients can reduce the degree of pain, minimize the occurrence of complications, shorten the first time off the bed and hospital stay, and promote recovery of elderly patient.

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Objective:To systematically evaluate the effect of virtual reality exercise training on gait performance in older adults.Methods:Randomized controlled trials on the rehabilitation effects of virtual reality exercise training on gait performance in older adults were electronically searched in PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Data, VIP, and China Biology Medicine disc. The search period was from establishing of the database to January 10, 2025. Version 2 of the Cochrane risk of bias tool for randomized trials (RoB 2) was used to evaluate the methodological quality of the included literature. Meta-analysis was performed using RevMan 5.4.Results:A total of 27 articles were included. Meta-analysis showed that the effect of virtual reality exercise on improving the functional walking ability of older adults was better than traditional exercise [ WMD=-0.83, 95% CI (-1.31, -0.36) , P<0.01]. However, virtual reality exercise did not improve step speed, stride length, step frequency, and dynamic gait indices in older adults ( P>0.05) . Subgroup analysis showed that virtual reality exercise was more effective than traditional exercise in improving step speed in older adults when the length of the weekly intervention was≥120 min [ SMD=0.48, 95% CI (0.04, 0.92) , P=0.03]. Conclusions:Virtual reality exercise training effectively improves walking ability in older adults but has no advantage in improving refined gait-related indicators. Future interventions in the form of virtual reality exercise training combined with traditional exercise rehabilitation are recommended for older adults.

Objective:To verify the efficacy of VELscope autofluorescence examination technology in the early warning of potential oral malignant diseases.Methods:80 patients with suspected dysplasia were included and underwent oral examination,visually en-hanced lesion scope(VELscope)autofluorescence examination and histopathology examination respectively,the fluorescence imaging results were compared with the histopathological results.Results:Pathological reports showed 64 cases with mild or no dysplasia,9 cases with moderate or severe dysplasia,1 case with moderate dysplasia without malignant transformation and 6 cases with cancer.The results of VELscope showed that there were 73 positive cases and negative 7 cases of fluorescence deletion.The sensitivity and specificity of VELscope were 93.75％and 9.37％respectively,and the sensitivity could reach 100％in the cancerous tissue.Con-clusion:As a non-invasive examination method,VELscope is highly sensitive but lowly specific.