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.

Guided by the concept of quality by design(QbD), this study optimizes the calcination and quenching process of calcined Magnetitum and establishes the XRD characteristic spectra of calcined Magnetitum, providing a scientific basis for the formulation of quality standards. Based on the processing methods and quality requirements of Magnetitum in the Chinese Pharmacopoeia, the critical process parameters(CPPs) identified were calcination temperature, calcination time, particle size, laying thickness, and the number of vinegar quenching cycles. The critical quality attributes(CQAs) included Fe mass fraction, Fe~(2+) dissolution, and surface color. The weight coefficients were determined by combining Analytic Hierarchy Process(AHP) and the criteria importance though intercrieria correlation(CRITIC) method, and the calcination process was optimized using orthogonal experimentation. Surface color was selected as a CQA, and based on the principle of color value, the surface color of calcined Magnetitum was objectively quantified. The vinegar quenching process was then optimized to determine the best processing conditions. X-ray diffraction(XRD) was used to establish the characteristic spectra of calcined Magnetitum, and methods such as similarity evaluation, cluster analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to evaluate the quality of the spectra. The optimized calcined Magnetitum preparation process was found to be calcination at 750 ℃ for 1 h, with a laying thickness of 4 cm, a particle size of 0.4-0.8 cm, and one vinegar quenching cycle(Magnetitum-vinegar ratio 10∶3), which was stable and feasible. The XRD characteristic spectra analysis method, featuring 9 common peaks as fingerprint information, was established. The average correlation coefficient ranged from 0.839 5-0.988 1, and the average angle cosine ranged from 0.914 4 to 0.995 6, indicating good similarity. Cluster analysis results showed that Magnetitum and calcined Magnetitum could be grouped together, with similar compositions. OPLS-DA discriminant analysis identified three key characteristic peaks, with Fe_2O_3 being the distinguishing component between the two. The final optimized processing method is stable and feasible, and the XRD characteristic spectra of calcined Magnetitum was initially established, providing a reference for subsequent quality control and the formulation of quality standards for calcined Magnetitum.
X-Ray Diffraction/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Particle Size

As a new type of production factor that can empower the development of new quality productivity, the data element is an important engine to promote the high quality development of the industry. Traditional Chinese medicine(TCM) dispensing is the most basic work of TCM clinical pharmacy, and its quality directly affects the clinical efficacy of TCM. The integration of data elements and TCM dispensing can stimulate the innovation and vitality of the TCM dispensing industry and promote the high-quality and sustainable development of the industry. A large-scale, detailed, and systematic study on TCM dispensing was conducted. The innovative practice path of data fusion construction in the whole process of TCM dispensing was investigated by integrating the digital resources "nine full activities" of TCM dispensing, creating the digital dictionary of "TCM clinical information data elements", and exploring innovative applications of TCM dispensing driven by data and technology, so as to promote the standardized, digital, and intelligent development of TCM dispensing in medical health services. The research content of this project was successfully selected as the second batch of "Data element×" typical cases of National Data Administration in 2024, which is the only selected case in the field of TCM.
Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal ; Humans

The therapeutic effects of Yueju Pills on depression and cardiovascular diseases have been widely recognized. Previous studies have shown that the drug can significantly improve depressive-like behaviors induced by chronic unpredictable mild stress(CUMS) combined with atherosclerosis(AS). Given the complex pathogenesis of psychocardiac diseases, this study integrated metabolomics and network pharmacology to systematically elucidate the mechanism of Yueju Pills in alleviating depressive symptoms in psychocardiac diseases. The results demonstrate that, after Yueju Pill intervention, the levels of 9 abnormal metabolites in the hippocampus restore to normal ranges, primarily involving key pathways or signaling pathways, including the cyclic adenosine monophosphate(cAMP), mammalian target of rapamycin(mTOR), glycine/serine/threonine metabolism, and aminoacyl-tRNA biosynthesis. In a high-fat diet-induced CUMS ApoE~(-/-) mouse model, Yueju Pills significantly increases adenosine monophosphate(AMP) levels and decreases L-alanine and D-glyceric acid levels in the hippocampus. In conclusion, Yueju Pills exert antidepressant effects by regulating multiple metabolic axes, including glycine/serine/threonine metabolism and the cAMP, mTOR signaling pathways. Network pharmacology predictions reveal that the treatment of CUMS combined with AS by its core active components may be realized through modulating pathways concerning neuroinflammation and synaptic plasticity, including serine/threonine-protein kinase 1(AKT1), mitogen-activated protein kinase 1(MAPK1), and prostaglandin-endoperoxide synthase 2(PTGS2). This study provides a theoretical reference for the clinical application of Yueju Pills in alleviating the depressive symptoms of psychocardiac diseases.
Animals ; Network Pharmacology ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Metabolomics ; Male ; Depression/genetics* ; Humans ; Hippocampus/drug effects* ; Mice, Inbred C57BL ; Signal Transduction/drug effects*

This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2 , and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.
Humans ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Disorder of Sex Development, 46,XY/blood* ; Male ; Membrane Proteins/genetics* ; Child, Preschool ; Child ; Retrospective Studies ; Adolescent ; Female ; Mutation ; Testosterone/blood* ; Infant ; Dihydrotestosterone/blood*

OBJECTIVES: To study the differences in clinical characteristics of term and preterm neonates with necrotizing enterocolitis (NEC) undergoing surgical treatment. METHODS: A retrospective analysis was conducted on the clinical data of 142 NEC neonates who underwent surgery at the Children's Hospital of Chongqing Medical University from June 2017 to August 2023. The neonates were categorized into a preterm group (gestational age <37 weeks; 95 cases) and a term group (gestational age 37-42 weeks; 47 cases) to compare clinical characteristics. RESULTS: The preterm group had a higher postnatal age at both diagnosis and surgery compared to the term group (P<0.05). The preterm group also had a higher incidence of preoperative bloody stools, lower preoperative platelet counts, and higher rates of preoperative respiratory distress, apnea, reduced/absent bowel sounds, and mechanical ventilation compared to the term group (P<0.05). Postoperatively, the preterm group had higher rates of purulent meningitis, sepsis, and coagulation dysfunction, lower postoperative platelet counts, and lower intraoperative minimum body temperature than the term group (P<0.05). CONCLUSIONS There are significant differences in the clinical characteristics of preterm and term neonates with NEC undergoing surgery, suggesting the need for tailored perioperative management strategies based on these characteristics.
Humans ; Enterocolitis, Necrotizing/surgery* ; Infant, Newborn ; Retrospective Studies ; Male ; Female ; Infant, Premature ; Gestational Age

OBJECTIVE: To explore the mechanism of Dihuang Yinzi (DHYZ) in the treatment of Alzheimer's disease (AD) by integrating metabolomics and experimental verification. METHODS: Forty-eight male APP/PS1 mice were divided into model, high- (DHYZ-H), medium- (DHYZ-M), and low-dose DHYZ (DHYZ-L) groups (12 mice per group) according to a random number table. Mice in DHYZ groups were gavaged with DHYZ 6.34, 12.68, and 25.35 g/(kg·d), respectively. Twelve C57BL/6 mice were gavaged with distilled water as the blank group. Metabolomics was used to analyze differential metabolites in the brains of mice. Morris water maze test was used to detect the memory abilities of mice. The hematoxylin-eosin staining and transmission electron microscopy were used to observe the general morphology and ultrastructure of neurons. The enzyme-linked immunosorbent assay was used to detect the levels of superoxide dismutase (SOD), reactive oxygen species (ROS), and amyloid β -protein 1-42 (A β_1-42). The real-time quantitative polymerase chain reaction was used to detect the mRNA expressions of density-regulated protein 1 (DRP1), fission 1 (FIS1), mitofusin-1 (MFN1), and optic atrophy protein 1 (OPA1). Western blot was used to detect the protein expressions of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP response binding protein (CREB), brain-derived neurotrophic factor (BDNF), synapsin 1 (SYN1), synaptophysin (SYP), and postsynaptic density protein 95 (PSD95). RESULTS: A total of 82 differential metabolites were identified in the brains of APP/PS1 mice, among which 7 differential metabolites could be regulated by DHYZ. After DHYZ intervention, the memory abilities of mice significantly increased (P<0.05 or P<0.01), the number of synapses and neurons in the hippocampus increased, and the mitochondrial morphology and structure were relatively intact. The DHYZ groups exhibited a significant reduction in hippocampal ROS and A β_1-42 levels, along with a significant elevation in SOD level (P<0.05 or P<0.01). The mRNA expressions of DRP1 and FIS1 were reduced, while the mRNA expressions of MFN1 and OPA1 were increased after DHYZ treatment (P<0.05 or P<0.01). The cAMP/PKA/CREB-BDNF pathway was activated, and the expressions of SYN1, SYP and PSD95 proteins were significantly increased in the DHYZ-H group (P<0.05 or P<0.01). CONCLUSIONS DHYZ could improve mitochondrial dynamics and synaptic plasticity in APP/PS1 mice, inhibit oxidative stress, and thereby enhancing learning and memory abilities in APP/PS1 mice. Its mechanism might be related to activation of the cAMP/PKA/CREB-BDNF signaling pathway.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; Male ; Cyclic AMP Response Element-Binding Protein/metabolism* ; Brain/drug effects* ; Metabolomics ; Mice, Inbred C57BL ; Neuronal Plasticity/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Cyclic AMP-Dependent Protein Kinases/metabolism* ; Cyclic AMP/metabolism* ; Reactive Oxygen Species/metabolism* ; Amyloid beta-Protein Precursor/metabolism* ; Mice, Transgenic ; Mice ; Amyloid beta-Peptides/metabolism* ; Signal Transduction/drug effects* ; Alzheimer Disease/drug therapy* ; Superoxide Dismutase/metabolism*

OBJECTIVE: To elucidate the modulation mechanism of Suanzaoren Decoction (SZRD) on basolateral amygdala (BLA) neuronal activity to alleviate chronic restraint stress (CRS)-related behavioral deficits. METHODS: The male C57BL/6J mice were assigned to 4 groups using the complete randomization method, including control (CON, n=19), CRS (n=19), SZRD (n=21), and fluoxetine (Flu, n=22) groups. Mice were restrained for 6 h per day, over a 21-d period to establish CRS models. The CON group remained in their cages without food or water during the 6-h matching period. SZRD and Flu groups received intragastric administration of SZRD (4.68 g/kg) and Flu (20 mg/kg) daily, respectively, 30 min before restraint for 21 consecutive days. The therapeutic effects of SZRD were evaluated using behavioral tests including the tail suspension test, elevated plus maze test, and forced swimming test. The cellular Fletcher B. Judson murine osteosarcoma proto-oncogene (c-Fos) expression in the BLA was measured using immunofluorescence, while action potential (AP) firing and synaptic transmission in BLA pyramidal neurons were evaluated using whole-cell patch-clamp recordings. RESULTS: SZRD administration significantly increased time spent in the open arms and open-arm entries while reducing immobility time (P<0.05 or P<0.01). It downregulated CRS-induced c-Fos expression and AP firing of pyramidal neurons in the BLA (P<0.01). Additionally, SZRD selectively attenuated excitatory (P<0.01), but not inhibitory, synaptic transmission onto BLA pyramidal neurons. CONCLUSION SZRD alleviated CRS-induced anxiety- and depression-like behaviors in mice by modulating the excitability and synaptic transmission of BLA pyramidal neurons.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Depression/complications* ; Pyramidal Cells/pathology* ; Male ; Mice, Inbred C57BL ; Basolateral Nuclear Complex/pathology* ; Restraint, Physical ; Anxiety/complications* ; Behavior, Animal/drug effects* ; Stress, Psychological/physiopathology* ; Mice ; Proto-Oncogene Proteins c-fos/metabolism* ; Action Potentials/drug effects* ; Synaptic Transmission/drug effects*

OBJECTIVE To establish a combined pharmacokinetic(PK)-pharmacodynamic(PD)model for knee osteoarthritis(KOA)of crossbow drug microemulsion multi-components(benzoylmesaconine,benzoylhypacoitine,mesaconitine,periplocin,neo-chlorogenic acid,vanillic acid,chlorogenic acid),and elucidate the dynamic changes in the KOA rats and the interrelation with the e-lapsed efficacy of the drug.METHODS A KOA rat model was induced by 4%papain;the PK process of crossbow medicine microe-mulsion components in rat synovial fluid was analyzed by UPLC to establish a PK model;the contents of MMP-3,MMP-13,TNF-α and IL-1β in KOA rats at different time points after administration were determined by ELISA analysis to establish a PD model;Phoe-nix WinNonlin software was used to fit the PK and PD data to obtain a PK-PD model.RESULTS PK results showed that the multi-components of the microemulsion were slowly absorbed in the joint cavity and gradually reached the peak value within 3-5 h.The Cmax of benzoylmesaconine,benzoylhypacoitine mesaconitine,periplocoside,neochlorogenic acid,vanillic acid and chlorogenic acid were 1.23,1.48,1.62,4.67,0.93,1.25 and 2.35 μg·mL-1,respectively;the area under the drug-time curve(AUC0-11)was 2.58,4.04,3.54,12.15,2.51,2.41 and 4.11 h·μg·mL-1,respectively.PD results showed that at different time points after adminis-tration,the contents of MMP-3,IL-1β,TNF-α,and MMP-13 decreased to varying degrees,among which MMP-3 decreased insig-nificantly,with significant differences only at 6 h;the contents of the remaining IL-1β,TNF-α,and MMP-13 decreased significantly(P<0.05,P<0.01),and showed the phenomenon of lagged efficacy;the PK-PD binding model showed that the drug concentration of the multi-component drug in the crossbow medicine microemulsion could be well fitted with its drug efficacy data.CONCLUSION The established PK-PD binding model can predict the drug efficacy changes after administration,and provides a corresponding refer-ence for the crossbow medicine microemulsion treatment of KOA.

This study assessed the role and mechanism of the recombinant Bacillus Calmette-Gue?rin vaccine(rBCG)with c-di-AMP adjuvant in regulating metabolism and immunity in epididymal white adipose(eWAT)in mice.Male C57BL/6 mice were intravenously immunized with BCG and rBCG,and their body weights were monitored.eWAT was isolated from the mice,and the stromal vascular fractions(SVFs)cell number was counted with a hemocytometer.Sections of mouse adipose tissue were prepared,and the size,number,and morphology of eWAT adipocytes and crown-like structure(CLS)formation were compared under a microscope after HE staining.The transcription levels of lipid metabolism-associated factors,cytokines and aging-associated genes in each group were determined with qRT-PCR.The body weights of mice gradually increased after immunization with BCG and rBCG.The proportions of eWAT increased,and the SVFs cell number decreased,in rBCG immunized mice.HE staining indicated that BCG immunization promoted hyperplasia,whereas rBCG immunization promoted hypertrophy of eWAT adipocytes;moreover,both BCG and rBCG immunization induced CLS formation in eWAT.The qRT-PCR results indicated that rBCG immunization inhibited the expression of genes associated with lipolysis and energy expenditure in eWAT.BCG immunization had little effect on cytokine transcription,whereas rBCG significantly induced the transcription of IFN-γ and IL-1Ra,and inhibited that of IL-15 and IL-2,but did not induce the expression of aging-associated genes.Thus,rBCG immunization induced eWAT adipocyte hypertrophy,which was associated with the inhibition of eWAT lipolysis and the regulation of cytokine expression.