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/Aims: Natural killer (NK) cell function is generally considered dampened in chronic hepatitis B virus (HBV) infection; however, the NK cell pool exhibits phenotypic and functional heterogeneity, and the antibody--mediated effect of NK cells remains less characterized. This study evaluated the dynamic changes in antibody-mediated NK cell responses and the involvement of distinct NK subsets across disease stages and during antiviral treatment. Methods: A T-cell receptor-like antibody specific for the HBV core 18–27 peptide (cTCRL-Ab) was used to determine the antibody-mediated effect of NK cells, and an array of NK cell surface markers were analyzed in cross-sectional and longitudinal cohorts of patients with chronic HBV infection. Single-cell RNA sequencing (scRNA-seq) was performed to identify the heterogeneity of NK subsets. Results: The cTCRL-Ab enabled the detection of NK cell cytolytic activity and IFNγ production. Notably, cTCRL-Ab-mediated NK cell responses were compromised in chronically HBV-infected patients, particularly in those receiving pegylated interferon-α (Peg-IFNα), which was associated with the downregulation of CD16 expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated NK cell function by reducing CD16 expression in vitro. scRNA-seq revealed that CD16 downregulation occurred mainly within a dysfunctional CD16hi NK subset exhibiting exhaustion properties. In contrast, an activated CD16hiNK subpopulation (CX3CR1⁺KLRC2–CD16hi) with high cytotoxicity was enriched in patients who experienced favorable treatment responses. Furthermore, the intrahepatic CX3CR1+KLRC2–CD16hi subset tended to exhibit functional restoration in HBsAg-loss individuals. Conclusions Our data contribute to the understanding of antibody-mediated responses of NK cells in chronic HBV infection, and highlight a previously unappreciated functional CX3CR1+KLRC2–CD16hiNK subset as a potential therapeutic target.

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.

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

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.

Objective To explore the mediating role of activities of daily living (ADL) in pain and depressive symptoms in the elderly in China. Methods Utilizing the data from 2020 China Health and Retirement Longitudinal Study, 4403 Chinese elderly individuals aged ≥ 60 years old were selected as the research subjects. Depression Scale (CES-D 10) of the Center for Epidemiological Survey and ADL scale were used in the study. The PROCESS4.1 macro was used to test the mediating effect of daily living activities between pain and depressive symptoms, and the Bootstrap method was applied for verification of the mediating variables. Results A total of 2368 cases of depressive symptoms were detected in the elderly in China, with a detection rate of 53.78%. Pain was positively correlated with depressive symptoms (r=0.27, P<0.01), and activities of daily living were negatively correlated with pain and depressive symptoms (r=-0.27, -0.337, P<0.01). The results showed that the total effect value of pain on depressive symptoms was 0.33, the direct effect value was 0.24, and the mediating effect value of daily living activities was 0.09, accounting for 27.27%. Conclusion Pain and activities of daily living are important factors influencing depressive symptoms in the elderly, and activities of daily living play a partial mediating role in the relationship between pain and depressive symptoms in the elderly.

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.

The microbial limit standards in the Chinese Pharmacopoeia 2020 edition primarily focus on total aerobic microbial count and specified objectionable microorganisms,which are insufficient for comprehensively assessing the potential risks posed by microbial contamination to drug efficacy and patient safety.With the increasing com-plexity of rising regulatory requirements,there is an urgent need to establish a scientific and systematic microbial risk assessment and control framework.In response,the Chinese Pharmacopoeia 2025 edition,introduces a new general guideline 9212 Risk Assessment and Control of Unacceptable Microorganisms for Non-sterile Products.This chapter systematically constructs a framework for the identification and control of risks associated with unacceptable microorganisms,filling a gap in the relevant field within international pharmacopoeias.This article systematically elaborates on its key elements based on its core framework and content.It covers the development background,core concepts,testing and identification strategies,evaluation of risk characterization factors,formulation of risk control measures,and implementation pathways.The aim is to provide pharmaceutical enterprises and regulatory agencies with systematic and clear practical guidance.

Whole Genome Sequencing(WGS)technology,leveraging its significant advantages in precise microbial identification and traceability analysis,has become a core tool in international pharmaceutical microbial quality control.The release and implementation of the Guideline 9110 for Microbial Whole Genome Sequencing Technology in the Chinese Pharmacopoeia 2025 Edition marks the official entry of China's pharmaceutical microbial quality con-trol into the genomic era.Guideline 9110 establishes universal technical specifications for the application of WGS technology in pharmaceutical microbial quality control,covering laboratory general requirements,key technical parameters,technical workflow,major factors affecting sequencing results,method validation,and application guidance.This article focuses on the background of the standard's development and its technical rationale,provi-ding a systematic interpretation of key technical indicators,the scope of application,and essential points for techni-cal implementation.It aims to offer theoretical guidance and practical references for the industry in applying WGS technology.