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.

According to the work goals and tasks determined by edition outline of the Chinese Pharmacopoeia 2025 Edition, the standards system of Water for Pharmaceutical Purposes has been perfected. This article focuses on the Work Background, Overall Approach,Work Methodology,Standard Framework,Key Content and Significance on the standards system of Water for Pharmaceutical Purposes in the Chinese Pharmacopoeia 2025, which can contribute to accurately understand and utilize the standards in Chinese Pharmacopoeia.

Objective: To systematically analyze the revisions content and technological development trends of microbiological standards in the Chinese Pharmacopoeia (ChP) 2025 Edition, and explore its novel requirements in risk-based pharmaceutical product lifecycle management.
Methods: A comprehensive review was conducted on 26 microbiological-related standards to summarize the revision directions and scientific implications from perspectives including the revision overview, international harmonization of microbiological standards, risk-based quality management system, and novel tools and methods with Chinese characteristics.
Results: The ChP 2025 edition demonstrates three prominent features in microbiological-related standards: enhanced international harmonization, introduced emerging molecular biological technologies, and established a risk-based microbiological quality control system.
Conclusion: The new edition of the Pharmacopoeia has systematically constructed a microbiological standard system, which significantly improves the scientificity, standardization and applicability of the standards, providing a crucial support for advancing the microbiological quality control in pharmaceutical industries of China.

According to the work goals and tasks determined by edition outline of the Chinese Pharmacopoeia 2025 Edition,the standards system of Water for Pharmaceutical Purposes has been perfected.This article focuses on the Work Background,Overall Approach,Work Methodology,Standard Framework,Key Content and Significance on the standards system of Water for Pharmaceutical Purposes in the Chinese Pharmacopoeia 2025,which can contribute to accurately understand and utilize the standards in Chinese Pharmacopoeia.

Objective:To systematically analyze the revisions content and technological development trends of microbiological standards in the Chinese Pharmacopoeia(ChP)2025 Edition,and explore its novel requirements in risk-based pharmaceutical product lifecycle management.Methods:A comprehensive review was conducted on 26 microbiological-related standards to summarize the revision directions and scientific implications from perspectives including the revision overview,international harmonization of microbiological standards,risk-based quality man-agement system,and novel tools and methods with Chinese characteristics.Results:The ChP 2025 edition demon-strates three prominent features in microbiological-related standards:enhanced international harmonization,intro-duced emerging molecular biological technologies,and established a risk-based microbiological quality control sys-tem.Conclusion:The new edition of the Pharmacopoeia has systematically constructed a microbiological standard system,which significantly improves the scientificity,standardization and applicability of the standards,providing a crucial support for advancing the microbiological quality control in pharmaceutical industries of China.

Osteosarcoma is a primary bone tumor originating from mesenchymal tissues,highly aggressive and metastatic,and is one of the causes of orthopedic disorders in children and adolescents.The establishment of an osteosarcoma model is useful for studying the changes in the physiology and pathology of the organism after the occurrence of osteosarcoma.The establishment methods of osteosarcoma models not only differ in terms of difficulty,tumorigenicity,tumor-formation time,tumor survival time,tumor metastasis,and safety,but also in terms of simulating human osteosarcoma biological characteristics and histological features.In addition,the wide application of tissue engineering in tumor modeling is conducive to better study the role of the osteosarcoma microenvironment in osteosarcoma genesis and development.In this paper,we summarize the roles of different osteosarcoma animal models and their tissue engineering models in different experiments,in order to provide help for the study of osteosarcoma pathogenesis and drug intervention mechanism.

Osteoporosis is a systemic disease characterized by imbalanced bone metabolism and destruction of bone microstructure, with reduced bone density, decreased bone quality, and significantly increased risk of fracture as its hallmarks. At present, osteoporosis is primarily diagnosed through bone density measurement. However, this method has low sensitivity and is challenging for the early diagnosis of osteoporosis. We analyzed osteoporosis-related metabolomics studies based on blood, urine, and fecal samples, as well as the application of multi-omics approaches in elucidating its pathogenesis. Evidence suggests that metabolomics can detect metabolic alterations prior to measurable changes in bone mineral density, offering promising avenues for early osteoporosis detection. Blood-based metabolomics studies indicate that amino acid metabolism dysregulation is a key feature of osteoporosis. Specifically, glycine, glutamine, lysine, and hydroxyproline exhibit negative correlations with bone mineral density, whereas tryptophan, branched-chain amino acids, and arginine show positive associations. Lipid metabolism disturbances are characterized by increased levels of phosphatidylcholine, phosphatidylethanolamine, and triglycerides, alongside decreased levels of sphingomyelin and carnitine. Fecal metabolomics studies highlight the significance of the "gut-bone axis" in osteoporosis, where gut microbiota dysbiosis influences bone metabolism through modulation of arginine and proline metabolism and aminoacyl-tRNA biosynthesis pathways. Multi-omics approaches integrate metabolomics, genomics, proteomics, and other omics data to provide a more comprehensive understanding of osteoporosis' molecular mechanisms, enabling the identification of key biomarkers and therapeutic targets. Metabolomics holds considerable potential for early diagnosis, while multi-omics integration offers novel insights into the complex pathophysiological mechanisms underlying osteoporosis. As detection technologies and analytical methods continue to advance, omics-based strategies are expected to play a pivotal role in the development of precision medicine for osteoporosis.

Objective:To explore the expression changes of nerve growth factor (NGF)/tropomyosin receptor kinase A (TrkA) signaling pathway of dorsal root ganglia (DRG) in incisional rat remifentanil-induced hyperalgesia and its effect on the expression of membrane delta opioid receptor (DOR).Methods:A total of 48 SPF male SD rats were randomly divided into 6 groups based on body weight matching, with 8 in each group, which were control group (infusion of 0.9% NaCl solution via the tail vein), incision pain group (incision pain model established using the Brennan method), remifentanil group (infusion of remifentanil via the tail vein), incision pain+ remifentanil model group (incision pain model established using the Brennan method, followed by infusion of remifentanil via the tail vein), NGF group and TrkA inhibitor group(established incision pain+ remifentanil model after intrathecal injection of NGF (0.06 μg/g) or K252a (0.3 μg/g, TrkA inhibitor)). Mechanical paw withdrawal threshold (PWT) was used to assess pain sensitivity in rats. Western blot was employed to measure the expression of NGF, TrkA, and the total DOR(tDOR) and the membrane DOR(mDOR) in DRG tissues. Immunoelectron microscopy was used to detect subcellular DOR expression in DRG. Data were processed using SPSS 24.0 software. Multiple comparisons among groups were conducted by repeated measures ANOVA or one-way ANOVA, and post-hoc comparisons were performed using the Bonferroni test.Results:(1) The results of pain behavior showed that there was a significant interaction effect between time and group in the comparison of PWT among the six groups of rats before and after intervention ( F=345.817, P<0.001). At each time point after intervention, the PWTs of the incision pain+ remifentanil group were lower than those of the incision pain group and remifentanil group, the PWTs of the NGF group were lower than those of the incision pain+ remifentanil group, and the PWTs of the TrkA inhibitor group were higher than those of the incision pain+ remifentanil group and NGF group (all P<0.05). (2)The Western blot results showed that there were statistically significant differences in the relative levels of NGF, TrkA, and mDOR in the DRG tissues of the six groups of rats ( F=156.2, 163.8, 421.2, all P<0.001). The levels of NGF, TrkA, and mDOR proteins in the incision pain+ remifentanil group (1.45±0.07, 1.46±0.04, 3.01±0.20) were higher than those in the incision pain group (1.25±0.05, 1.24±0.04, 1.84±0.05) and remifentanil group (1.24±0.04, 1.26±0.03, 1.84±0.04) (all P<0.05). The levels of NGF, TrkA, and mDOR in the NGF group (1.57±0.03, 1.58±0.07, 3.74±0.25) were higher than those in the incision pain+ remifentanil group (all P<0.05). The relative expression levels of TrkA, and mDOR in the TrkA inhibitor group (1.25±0.04, 1.68±0.07) were lower than those in the incision pain+ remifentanil group and the NGF group (all P<0.05). (3)The results of immunoelectron microscopy showed that there were statistically significant differences in the localization of DOR in the cell membrane, subcellular sites of synthesis pathways, and subcellular localization of degradation pathways among the six groups of rat DRG tissues ( F=140.3, 60.63, 60.28, all P<0.01). The DOR of the synthesis pathway of incision pain+ remifentanil group was higher than that of the incision pain group and remifentanil group, while the DOR of the synthesis pathway of NGF was higher than that of the incision pain+ remifentanil group.The DOR of the synthesis pathway of TrkA inhibitor group was lower than that of the incision pain+ remifentanil group and NGF group (both P<0.05). The DOR of the degradation pathway in the incision pain+ remifentanil group was lower than that in the incision pain group and remifentanil group, the DOR of the degradation pathway in the NGF group was lower than that in the incision pain+ remifentanil group, and the DOR of the degradation pathway in the TrkA inhibitor group was higher than that in the incision pain+ remifentanil group and NGF group (both P<0.05). Conclusion:The NGF/TrkA signaling pathway is involved in rat incisional pain-remifentanil hyperalgesia by upregulating the delta opioid receptor of the dorsal root ganglia.

BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia

Osteosarcoma is a highly aggressive malignant bone tumor whose immuno evasion mechanisms play a pivotal role in tumor progression and therapeutic resistance. Recent studies have identified mitochondrial transfer as a novel mode of intercellular communication that significantly influences metabolic reprogramming and immune evasion in osteosarcoma cells. This mechanism operates through three principal pathways: (1) enhancing energy metabolic efficiency in tumor cells; (2) mitigating intracellular oxidative stress; and (3) modulating immune checkpoint molecule expression. Collectively, these alterations impair host immune surveillance while promoting tumor proliferation, invasion, and distant metastasis through metabolic remodeling, immune tolerance induction, and tumor microenvironment reconstruction. This review systematically elucidates the molecular mechanisms by which mitochondrial transfer regulates immune evasion in osteosarcoma and its dynamic impact on the tumor microenvironment. Furthermore, we discuss the translational potential of targeting this pathway for precision therapy and outline future research directions in this emerging field.