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.

ObjectiveHistorically documented Zhejiang Atractylodis Macrocephalae Rhizoma（Baizhu） possesses premium characteristics such as phoenix-like head and crane-like neck， pronounced sweetness， and fragrant aroma. However， its current market circulation is low， and the processed products with Zhejiang-style characteristics are at the risk of being lost. This study aims to preserve the ancient Zhejiang-style processing techniques and evaluate them using modern scientific methods. MethodsMultidimensional intelligent sensory evaluation was used to digitally characterize the "quality-structure" of the external appearance of nine-steamed and nine-processed Baizhu medicinal materials（intermediate processed products） and the "odor-taste" of the internal quality of its decoction pieces（slices）， and the appearance parameters were digitally characterized by colorimeter， texture analyzer， electronic nose and electronic tongue， the chemical composition was analyzed via ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）. Then， cluster analysis on the differences in odor between the medicinal materials（intermediate processed products） and decoction pieces（slices） of nine-steamed and nine-processed Baizhu was conducted， as well as the differences in taste between water-soluble and alcohol-soluble extracts of the decoction pieces（slices）， and the correlation analysis of chroma value-alcohol-soluble extract content-component response value. ResultsThe nine-steamed and nine-processed Baizhu had a dark brown to black epidermis， a brownish-yellow to brownish-gray cross-section， a slightly tough texture， a faint odor， and a slightly sweet， bitter and pungent taste. Texture analyzer measurements revealed minimal adhesion and maximum recovery in the middle section of the characteristic processed Baizhu， consistent with the processing endpoint of thorough steaming and cooking. The head section showed the highest internal hardness， elasticity and chewiness， indicating a denser texture in this area. The electronic nose sensor could clearly distinguish the difference between the medicinal materials and its decoction pieces， with a more significant clustering effect at 60 ℃ for 30 minutes compared to ambient temperature headspace for 2 hours， highlighting the significant impact of the baking degree before slicing on the quality. The electronic tongue taste signal map clearly distinguished the differences between water-soluble and alcohol-soluble extracts of nine-steamed and nine-processed Baizhu decoction pieces， and the addition of auxiliary materials during processing could enhance its alcohol-soluble extract content. A total of 82 chemical components were identified in the characteristic processed Baizhu. After processing， the contents of 58 components increased， while 24 components decreased. Correlation analysis revealed significant negative correlations（P<0.01） between ethanol-soluble extract content and colorimetric values of brightness（L^*）， yellow-bule value（b^*）， and total color difference（E^*_ab）. E^*_ab showed marked negative correlations（P<0.05） with the response values of isochlorogenic acid A and C. ConclusionThis study establishes a modern intelligent sensory evaluation model for multidimensional holographic characterization of nine-steamed and nine-processed Baizhu， clarifying the correlation between increased isochlorogenic acid content and the visual color appearance after different steaming cycles， as well as its intrinsic alcohol-soluble extracts. This provides a reference for quality evaluation and processing standards of the Zhejiang-style characteristic processed products.

GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.

Objective:To explore the effect of CO2 fractional laser combined with glucocorticoid(GC)on T follicular helper cell(Tfh)and B cell subsets in patients with advanced vitiligo(VL).Methods:Patients with advanced VL(128 cases)who were treated in Affiliated Hospital of Hebei University of Engineering from August 2019 to March 2022 were selected as research objects,and divided into group A(64 cases,CO2 fractional laser combined with GC)and group B(64 cases,CO2 fractional laser)according to different treatment methods,clinical efficacy and safety of the two groups were compared.Another healthy subjects(64 cases)were selected as control group.Collected clinical data of the three groups of subjects for comparative analysis.Randomized walking model was used to evaluate the effect of CO2 fractional laser combined with GC on immune function and inflammatory response in patients with advanced VL.Results:Compared with group B,group A had a higher clinical total effective rate(P<0.05)and a lower probability of adverse reactions(P<0.05).After treatment,compared with control group,proportion of Tfh2 and Tfh17 in group A had no significant difference(P>0.05),while proportion of Tfh2 and Tfh17 in group B still had significant difference(P<0.05);compared with group B,proportion of Tfh2 in group A after treatment was higher(P<0.05),while proportion of Tfh17 type was lower(P<0.05).After treat-ment,compared with control group,proportion of memory transformed B cell in group B was still significantly different(P<0.05).After treatment,compared with control group,levels of IgA,IgE and IgM in group B were still significantly different(P<0.05);compared with group B,level of IgM in group A was higher after treatment(P<0.05).After treatment,compared with control group,levels of IL-21 and IL-1β in group B were still significantly different(P<0.05);compared with group B,level of IL-10 in group A after treatment was higher(P<0.05),while levels of IL-21 and IL-1β were lower(P<0.05).Evaluation results of random walking model showed that the improvement of immune function and inflammatory reaction in group A was better than that in group B.Conclusion:CO2 fractional laser combined with GC can improve the immune function and inflammatory reaction of patients with advanced VL better after treatment,and the probability of adverse reactions is lower.

Objective:This study aims to investigate the expression of uridine diphosphate-glucose[]pyrophos-phorylase 2(UGP2)in breast cancer(BC)tissues and its oncogenic mechanism,assessing its potential value as a diag-nostic and prognostic biomarker for breast cancer.Methods:(1)Online database analysis was conducted to assess UGP2 mRNA and protein expression levels in breast cancer and explore their correlation with clinical characteristics.Im-munohistochemistry(IHC)was used to verify UGP2 expression in human breast cancer tumor tissues and evaluate its relationship with clinicopathological features.(2)Kaplan-Meier survival analysis and COX regression models were used to analyze the impact of UGP2 expression on breast cancer patient prognosis.(3)Bioinformatics methods were em-ployed to investigate the correlation between UGP2 and tumor immune cell infiltration,and to predict the biological func-tions and associated signaling pathways of UGP2 in breast cancer.Results:(1)The mRNA and protein expression levels of UGP2 were upregulated in breast cancer tissues(both P<0.05),and were negatively correlated with ER-positive and PR-positive status(OR<1,P<0.05),while positively correlated with Ki-67 levels and the triple-negative breast cancer(TNBC)subtype(OR>1,P<0.05).(2)Elevated expression levels of UGP2 were associated with poorer survival rates in breast cancer patients(both P<0.05)and were identified as an independent adverse prognostic factor for breast cancer(HR=1.40,P<0.05).(3)Functional analysis results suggested that UGP2 may promote tumor progression by regulating metabolism,hormone signaling,and the immune microenvironment.Additionally,UGP2 expression was negatively cor-related with NK cell activation status and positively correlated with the inhibitory state.Conclusion:UGP2 expression is elevated in breast cancer tissues and is closely associated with poor patient prognosis.It may promote cancer pro-gression through mechanisms such as metabolic reprogramming and immune suppression.UGP2 shows promise as a potential biomarker and therapeutic target in breast cancer,providing a basis for personalized treatment.

This study was aimed at investigating the effects of demethylase fat mass and obesity-associated protein(FTO)and methyltransferase methyltransferase like protein 3(METTL3),key molecules in N6-methyladenosine(m6A)modification,on the replication and proliferation of Japanese encephalitis virus(JEV).Recombinant lentiviruses were generated by packaging the FTO and green fluorescent protein into lentiviral vectors.Neuro2a cells,a mouse neuroblastoma cell line,were infected with the lentivirus,and stable FTO-expressing cell lines were obtained through puromycin selection.Successful overexpression of FTO was confirmed through fluorescence microscopy,real-time quantitative PCR,and western blot analysis.When Neuro2a cells overexpressing FTO were infected with JEV,the overexpression of FTO decreased JEV replication in the cells,and increased the expression of interferon(IFN)and related molecules.Additionally,treatment of JEV-infected Neuro2a cells with the METTL3-specific inhibitor STM2457 resulted in a dose-dependent decrease in JEV replication and viral protein expression.These findings suggested that lowering m6A methylation levels inhibits JEV replication,thus shedding light on the regulatory role of methylation modification in JEV replication.

Objective:To explore the effect of CO2 fractional laser combined with glucocorticoid(GC)on T follicular helper cell(Tfh)and B cell subsets in patients with advanced vitiligo(VL).Methods:Patients with advanced VL(128 cases)who were treated in Affiliated Hospital of Hebei University of Engineering from August 2019 to March 2022 were selected as research objects,and divided into group A(64 cases,CO2 fractional laser combined with GC)and group B(64 cases,CO2 fractional laser)according to different treatment methods,clinical efficacy and safety of the two groups were compared.Another healthy subjects(64 cases)were selected as control group.Collected clinical data of the three groups of subjects for comparative analysis.Randomized walking model was used to evaluate the effect of CO2 fractional laser combined with GC on immune function and inflammatory response in patients with advanced VL.Results:Compared with group B,group A had a higher clinical total effective rate(P<0.05)and a lower probability of adverse reactions(P<0.05).After treatment,compared with control group,proportion of Tfh2 and Tfh17 in group A had no significant difference(P>0.05),while proportion of Tfh2 and Tfh17 in group B still had significant difference(P<0.05);compared with group B,proportion of Tfh2 in group A after treatment was higher(P<0.05),while proportion of Tfh17 type was lower(P<0.05).After treat-ment,compared with control group,proportion of memory transformed B cell in group B was still significantly different(P<0.05).After treatment,compared with control group,levels of IgA,IgE and IgM in group B were still significantly different(P<0.05);compared with group B,level of IgM in group A was higher after treatment(P<0.05).After treatment,compared with control group,levels of IL-21 and IL-1β in group B were still significantly different(P<0.05);compared with group B,level of IL-10 in group A after treatment was higher(P<0.05),while levels of IL-21 and IL-1β were lower(P<0.05).Evaluation results of random walking model showed that the improvement of immune function and inflammatory reaction in group A was better than that in group B.Conclusion:CO2 fractional laser combined with GC can improve the immune function and inflammatory reaction of patients with advanced VL better after treatment,and the probability of adverse reactions is lower.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Aim To investigate the effects of rutae-carpine(RUT)on lung inflammation in septic mice and the underlying mechanisms.Methods The sepsis mouse model was generated by intraperitoneal injection of lipopolysaccharide(LPS)at 5 mg·kg-1.The mice were randomly divided into the Control group,Model group,Low-dose,Medium-dose,High-dose RUT(5,10,20 mg·kg-1)treatment group and dexamethasone(DEX,2 mg·kg-1),with 10 mice in each group.The mice were intraperitoneally injected with RUT 30 min before LPS injection.HE staining was used to observe the morphology of lung tissues,and activity of my-eloperoxidase was determined to assess the neutrophil infiltration.Wet/dry weight ratio and Evan's blue ex-travasation of lung tissues were examined to assess lung edema.Survival analysis was performed to determine the in vivo protective effects of RUT.ELISA and quan-titative RT-PCR analysis were employed to determine the contents and gene expression of pro-inflammatory mediators,including tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1 β),IL-6,and IL-18 in lung tis-sues.Western blot was used to detect the protein levels of p38 MAPK,NF-κB,Caspase-1,NOD-like receptor family pyrin domain containing 3(NLRP3)and IL-18.Results RUT at 10-20 mg·kg-1 could dose-de-pendently inhibit leukocyte infiltration,reduce pro-in-flammatory mediator production,vascular permeability and wet/dry weight ratio in lungs,similar to the effects induced by DEX.The mice treated with RUT exhibited increased survival,down-regulated expressions of p-p38 MAPK,p-NF-κB,Caspase-1,NLRP3,and IL-18 pro-teins in lungs,with decreased IL-18 mRNA level.Conclusions RUT exhibits protective effects on sep-sis-induced lung injury,manifested by reduced inflam-mation and edema,potentially via inhibition of p38 MAPK signaling pathway and inflammasome formation.

Objective To summarize the clinical features and prognosis of children suffered from malignant solid tumors of head and neck.Methods The clinical data of children with primary malignant solid tumors located in the head and neck was retrospectively analyzed from January 2007 to December 2021 in the Department of Oncology,Beijing Children's Hospital,Capital Medical University,and the clinical features,prognostic factors were summarized.Results A total of 234 children with malignant solid tumors of head and neck were included,with a male to female ratio of 1∶0.7,aged from 3 months to 17 years and 6 months(median age 51 months).173 cases(73.9％)were treated with local painless masses.Other symptoms included snoring and facial paralysis.The proportion of rhabdomyosarcoma(RMS)was the highest(145 cases,62.0％),followed by neuroblastoma(NB)(25 cases,10.7％),Ewing sarcoma(19 cases,8.1％),etc.A total of 47 cases(20.1％)had distant metastasis.The patients received surgery,chemotherapy and radiotherapy under the mode of multidisciplinary treatment(MDT).The 3-year and 5-year overall survival(OS)were 80.8％and 75.8％,respectively,and the 3-year and 5-year progression free survival(PFS)were 64.0％and 58.9％,respectively.Tumor survivors had abnormal appearance or facial motor function(49 cases,41.2％),developmental problems or abnormal tooth loss(18 cases,15.1％),and other long-term complications that may be related to the tumor or treatment.Conclusion There are various pathologic types of pediatric head and neck malignant solid tumors,RMS and NB are the most common.Local painless mass was the most common complaint.Distant metastasis is an independent risk factor for the prognosis of head and neck malignant solid tumors.Under the MDT model,the prognosis of malignant solid tumors of the head and neck in our center was generally good.In the treatment of the tumors,the side effects and sequelae should be controlled as small as possible under the premise of long-term survival.