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.

AIM To evaluate the chemical constituent consistency in formula granules and traditional decoctions of Gouteng Jiangya Formula.METHODS HPLC characteristic chromatograms were established,the analysis was performed on a 30 ℃ thermostatic YMC-Triart C18 column(4.6 mm× 250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.2％phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 240 nm.Puerarin was used as an internal standard to calculate the relative correction factors of 3'-methoxy puerarin,puerarin apioside,magnolflorine,paeoniflora,daidzin,baicalin,palmatine,berberine,wogonoside and benzoylpaeoniflorin,after which the content detemination was made by quantitative analysis of multi-components by single-marker(QAMS).RESULTS The characteristic chromatograms of 9 batches of formula granules and 15 bacthes of traditional decoctions demonstrated the similarities of more than 0.90 at the detection wavelengths of 192,210,240,260,280,300,320,360 nm,along with similar total peak areas.Eleven constituents showed good linear relationships within their own ranges(r＞0.999 0),whose average recoveries were 97.27％-101.64％with the RSDs of 0.36％-1.11％,the result obtained by QAMS and external standard method demonstrated no significant differences(P＞0.05).The contents of various constituents in the formula granules approximated those in the traditional decoctions.CONCLUSION The consistent kinds and contents of various constituents are obversable in formula granules and traditional decoctions of Gouteng Jiangya Formula,which can provide a reference for the reasonable clinical application of this formula.

Objective To evaluate the efficacy of the manual cyclotorsion compensation method based on the obser-vation screen in the correction of with-the-rule astigmatism during small incision lenticule extraction(SMILE).Methods This prospective study enrolled 40 patients who underwent SMILE and another 40 patients who underwent Q-value-guided femtosecond laser-assisted laser in situ keratomileusis(FS-LASIK)at the Ophthalmology Center of the Second Affiliated Hospital of Nanchang University from April to September 2024.Through the random number method,one eye of each pa-tient who underwent SMILE was assigned to the manual cyclotorsion compensation group(the cyclotorsion group,40 eyes),while the contralateral eye was assigned to the non-cyclotorsion group(the non-cyclotorsion group,40 eyes).Meanwhile,one eye of each patient who underwent FS-LASIK was randomly selected for the FS-LASIK group(40 eyes).The age,uncorrected distance visual acuity(UDVA),spherical power,cylindrical power,spherical equivalent(SE),and corrected distance visual acuity(CDVA)were recorded before surgery and 3 months after surgery,respectively.Astigma-tism was subjected to Alpins vector analysis,and the indicators for assessing astigmatism included target-induced astigma-tism(TIA),surgically-induced astigmatism(SIA),difference vector(DV),correction index(CI),success index(IOS),angle of error(AE),and absolute value of angle of error(|AE|).Results Before surgery,there was no significant difference in age,spherical power,cylindrical power,SE,and CDVA among the cyclotorsion group,the non-cyclotorsion group,and the FS-LASIK group(all P＞0.05).At 3 months after surgery,the cyclotorsion group showed better UDVA and lower cylindrical power than the non-cyclotorsion group,with statistically significant differences(both P＜0.05);howev-er,there was no significant difference in CDVA,spherical power,and SE between the two groups(all P＞0.05).Besides,there was no significant difference in UDVA,CDVA,or refractive parameters between the cyclotorsion and FS-LASIK groups(all P＞0.05).The Alpins vector analysis of astigmatism 3 months after surgery revealed better SIA,CI,IOS,and|AE|in the cyclotorsion group compared with the non-cyclotorsion group,with statistically significant differences(all P＜0.05);however,there was no significant difference in TIA,DV,and AE between the two groups(all P＞0.05).No signifi-cant differences were found between the cyclotorsion and FS-LASIK groups in any astigmatism vector parameter(all P＞0.05).The linear regression analysis results indicated a high linear correlation between TIA and SIA in all groups.Conclu-sion The manual cyclotorsion compensation method based on the observation screen in the correction of with-the-rule astigmatism during SMILE is comparable to Q-value-guided FS-LASIK and superior to the conventional central tear film marking method in SMILE.

Aim To examine the pathogenesis of disul-fide death gene in vascular dementia(VD)by bioin-formatics analysis of disulfide death differentially ex-pressed genes(DEGs)combined with experimental verification.Methods The death DEGs of disulfide were screened and their correlation was analyzed.The VD patients data in the data set were analyzed by clus-tering and typing and gene set variation.The clustering risk of DEGs was tested with a nomogram model,and the optimal learning model was predicted.After the es-tablishment of VD rat model,water maze test,HE stai-ning and RT-qPCR detection were performed to verify the results of health information.Results Four DEGs including SLC7A11 were obtained,which had antago-nistic or synergistic interaction with each other.The genetic data could be divided into two subtypes with significant differences.After typing,VD disulfide DEGs were mainly concentrated in GnRH signaling pathways.The accuracy of the nomogram prediction model was high.Generalized linear was the best ma-chine learning model.Compared with the sham opera-tion group,the escape latency of rats in the model group was prolonged,the number of crossing platforms decreased,the relative mRNA expression levels of Slc3a2 and Slc7a11 decreased,and LRPPRC in-creased.Conclusions SLC7A11 and other disulfide death DEGs and its related GnRH signaling pathway may be an important part of the pathogenesis of VD di-sulfide death.SLC3A2,LRPPRC and SLC7A11 can be used as characteristic genes in the regulation of VD by disulfide death,which may affect VD progression through the regulation of disulfide death.

Objective:To investigate the effect of FOXQ1 expression on chemoresistance in colorectal cancer and analyze its regulatory role in SIRT1 expression and p53 deacetylation under DNA damage response(DDR)condi-tions.Methods:qRT-PCR was used to detect FOXQ1 mRNA expression levels in SW620 cells and SW620 cells stimulated with cisplatin(CDDP).Lentiviral vectors were constructed for FOXQ1 overexpression and RNA interference.The cells were divided into three groups:FOXQ1 overexpression group(oe-FOXQ1),FOXQ1 RNA interference group(sh-FOXQ1),and a control group transfected with an empty vector(NC).The half-maximal inhibitory concentration(IC50)of CDDP in each group was determined using the CCK-8 assay.Apoptosis level and cell viability were assessed using the Annexin V-APC/7-ADD apoptosis detection kit and Calcein/PI staining.Western blot analysis was performed to evaluate the effect of FOXQ1 on SIRT1 expression and acetylated p53 levels.The SIRT1 pathway inhibitor(S)-Selisi-stat was introduced to observe changes in p53 acetylation levels.Results:Compared to normal colon tissues,FOXQ1 expression was significantly upregulated in SW620 cells(P＜0.05),and low-dose CDDP stimulation further en-hanced its expression(P＜0.05).After 24 hours of CDDP treatment,the IC50 values for the oe-FOXQ1,sh-FOXQ1,and NC groups were 58.3 μmol/L,36.4 μmol/L,and 43.7 μmol/L,respectively,with statistically significant differences among the groups(P＜0.05).Compared to the NC group,the oe-FOXQ1 group showed a decrease in late apoptotic cell count(P＜0.05),while the sh-FOXQ1 group exhibited an increase(P＜0.05).Cytotoxic fluorescence staining re-vealed that the proportion of cell death was lower in the oe-FOXQ1 group and higher in the sh-FOXQ1 group com-pared to the NC group(P＜0.05).Protein expression analysis showed that FOXQ1 and SIRT1 levels were higher in the oe-FOXQ1 group and lower in the sh-FOXQ1 group compared to the NC group(P＜0.05).FOXQ1 overexpression pro-moted p53 deacetylation,while the addition of the SIRT1 pathway inhibitor(S)-Selisistat restored p53 acetylation levels(P＜0.05).Conclusion:FOXQ1 promotes p53 deacetylation by upregulating SIRT1 expression,thereby inhibiting DDR-induced apoptosis.

Background and Aims:Papillary thyroid carcinoma(PTC)is the most common endocrine malignancy,yet the molecular mechanisms underlying its invasion and metastasis remain unclear.This study aimed to investigate the role of the transcription factor ETV4 in PTC and its regulatory relationship with cadherin-3(CDHP/CDH3).Methods:Expression levels of ETV4 and CDHP were analyzed using TCGA and GTEx databases,and further validated in normal thyroid cells and multiple PTC cell lines by qRT-PCR and Western blot analysis.ETV4-knockdown models were established using siRNA,and changes in CDHP expression and cellular behaviors were assessed by qRT-PCR,Western blot,CCK-8,wound healing,and Transwell assays.Results:Bioinformatics analysis revealed significantly higher expression of ETV4 and CDHP in PTC tissues compared to normal thyroid tissues(P<0.001).Correlation analysis demonstrated a strong positive association between ETV4 and CDHP expression(R2>0.5,P<0.01).In vitro assays confirmed that both ETV4 and CDHP were upregulated in all tested PTC cell lines at the mRNA and protein levels(all P<0.05).Knockdown of ETV4 led to marked reduction of CDHP expression(P<0.05),accompanied by decreased cell proliferation,migration,and invasion as demonstrated by CCK-8,wound healing,and Transwell assays(all P<0.05).Conclusion:ETV4 may transcriptionally upregulates CDHP to promote proliferation,migration,and invasion of PTC cells.The ETV4/CDHP axis may serve as a novel biomarker and potential therapeutic target in PTC.

With the increasing demand for dynamic,real-time and rapid qualitative analysis of chemical composition in areas such as emergency response and space exploration,chip-scale mass spectrometers have attracted significant attention.These devices are expected to drive the integration of mass spectrometry with micro/nano-fabrication and intelligent sensing technologies,fostering profound innovation and breakthroughs in analytical chemistry.As an excellent mass analyzer,the ion trap exhibits numerous advantages,and its miniaturization creates favorable conditions for the high-density integration of miniature mass spectrometers.However,the reduction in ion storage capacity may compromise its sensitivity and dynamic range,rendering the study of ion unidirectional ejection in highly miniaturized ion traps of significant practical importance.In this work,a research was conducted on achieving efficient ion unidirectional ejection while maintaining high mass resolution in the extremely miniature hyperbolic linear ion trap(M-HLIT)with a field radius of 1 mm,and an electric field compensation method was proposed,which combined asymmetric electrode stretching and unbalanced RF voltage to achieve high-precision optimization of the electric field composition.Simulations showed that in an ideal structure,this method achieved 100％unidirectional ejection efficiency with the mass resolution of 518,significantly outperforming traditional asymmetric structure method(365)and unbalanced voltage method(321).Following the introduction of ion ejection slots,further optimization through bidirectional stretching and electrical parameters improved the resolution to 790 while maintaining a unidirectional ejection efficiency of 93％.This method eliminated the requirement for additional excitation voltage,offering an ideal solution for the miniature mass analyzer with high detection performance of chip-level mass spectrometers.

A novel analytical method was developed in this study by combining online solid phase extraction with ultra performance liquid chromatography-tandem mass spectrometry(Online SPE-UPLC-MS/MS)for simultaneous determination of 50 kinds of steroid hormones in surface water.Specifically,after high-speed centrifugation of 4 mL water samples,the supernatant was directly injected into an Oasis HLB online SPE column for enrichment and purification.Subsequently,the target compounds were transferred to the analytical column via valve switching for separation and analysis.The chromatographic separation was performed on a Thermo Acclaim RSLC C18 column(100 mm×2.1 mm,2.2 μm),using a mobile phase composed of 5 mmol/L ammonium fluoride aqueous solution and acetonitrile.Mass spectrometric detection was conducted in positive ion mode,utilizing multiple reaction monitoring(MRM)with quantification achieved by the internal standard method.The method validation demonstrated that the limits of detection(LOD)for the 50 kinds of steroid hormones ranged from 0.02 to 0.50 ng/L,while the limits of quantification(LOQ)were between 0.08 and 1.67 ng/L.The average recoveries in surface water samples at spiked concentrations of 5,20 and 200 ng/L were between 74.1％and 119％,with relative standard deviations(RSDs)of 0.2％to 9.9％.This method was applied to analyze 11 surface water samples collected from sites surrounding a pharmaceutical and chemical industrial park.A total of 44 kinds of steroid hormones were detected,with concentrations ranging from 0.11 to 88.6 ng/L,revealing the presence of hormone contamination in the environmental waters surrounding industrial areas.Compared with the traditional offline SPE methods,the proposed online SPE technique significantly reduced sample volume requirements and pretreatment time,while minimizing the loss of target compounds during the pretreatment process.Moreover,compared to reported online SPE techniques,this method achieved high-throughput analysis of multiple classes of steroid hormones,with lower detection limits and higher recoveries.Overall,this method provided rapid sample preparation,high sensitivity,and excellent stability,making it suitable for the direct analysis of trace steroid hormones in surface water.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Aim To examine the pathogenesis of disul-fide death gene in vascular dementia(VD)by bioin-formatics analysis of disulfide death differentially ex-pressed genes(DEGs)combined with experimental verification.Methods The death DEGs of disulfide were screened and their correlation was analyzed.The VD patients data in the data set were analyzed by clus-tering and typing and gene set variation.The clustering risk of DEGs was tested with a nomogram model,and the optimal learning model was predicted.After the es-tablishment of VD rat model,water maze test,HE stai-ning and RT-qPCR detection were performed to verify the results of health information.Results Four DEGs including SLC7A11 were obtained,which had antago-nistic or synergistic interaction with each other.The genetic data could be divided into two subtypes with significant differences.After typing,VD disulfide DEGs were mainly concentrated in GnRH signaling pathways.The accuracy of the nomogram prediction model was high.Generalized linear was the best ma-chine learning model.Compared with the sham opera-tion group,the escape latency of rats in the model group was prolonged,the number of crossing platforms decreased,the relative mRNA expression levels of Slc3a2 and Slc7a11 decreased,and LRPPRC in-creased.Conclusions SLC7A11 and other disulfide death DEGs and its related GnRH signaling pathway may be an important part of the pathogenesis of VD di-sulfide death.SLC3A2,LRPPRC and SLC7A11 can be used as characteristic genes in the regulation of VD by disulfide death,which may affect VD progression through the regulation of disulfide death.