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.

Objective To investigate the role and potential mechanism of secreted phosphoprotein 1 (SPP1)⁺ macrophages in the formation of chronic renal allograft fibrosis. Methods The expression features of SPP1⁺ macrophages in renal allografts of chronic allograft dysfunction (CAD) patients were analyzed based on single-cell transcriptome data of renal tissues from patients with CAD. Transcription factor VIPER analysis and DoRothEA transcription factor activity analysis were performed on the single-cell transcriptome data. Renal tissue samples were collected from kidney transplant recipients, including the CAD group (n=5) and the non-renal allograft fibrosis group (CTL group, n=5). A mouse model of chronic allograft rejection was established and divided into the allogeneic kidney transplantation group (CAD group, n=3) and the syngeneic kidney transplantation group (SYN group, n=3). Hematoxylin-eosin staining was used to detect renal tissue injury in mice, and Masson staining was used to detect renal tissue fibrosis. Immunofluorescence staining was performed to detect SPP1 expression in renal tissues of transplant recipients and mouse renal allografts. Bone marrow-derived macrophages (BMDMs) were extracted from mice and subjected to hypoxia stimulation. The expression of hypoxia-inducible factor (HIF)-1α and SPP1 was detected by Western blot, and SPP1 expression was detected by flow cytometry. BMDMs were transfected with HIF-1α overexpression plasmid and HIF-1α small interfering RNA (siRNA) followed by hypoxia intervention, and the expression of HIF-1α and SPP1 was detected by Western blot. Mouse aortic endothelial cells (MAECs) were co-cultured with the supernatant of BMDMs, and the expression of endothelial-mesenchymal transition (EndMT)-related markers was detected by Western blot and immunofluorescence. Results Single-cell transcriptome analysis showed that the proportion of SPP1⁺ macrophages in renal allograft tissues was significantly higher in the CAD group than in the CTL group (P<0.05). The renal injury score and the percentage of interstitial fibrotic area in the CAD group were significantly higher than those in the SYN group (both P<0.05). Immunofluorescence staining showed that the proportion of SPP1⁺ macrophages was increased in the CAD group compared with the CTL group, and also increased in the CAD group compared with the SYN group (both P<0.05). VIPER analysis and DoRothEA transcription factor activity analysis revealed activation of the hypoxia pathway and upregulated expression of transcription factors such as HIF-1α in SPP1⁺ macrophages. SPP1 expression was elevated in BMDMs under hypoxic conditions. Knockdown of HIF-1α inhibited hypoxia-induced SPP1 protein expression, whereas overexpression of HIF-1α upregulated SPP1 protein levels. After co-culture of hypoxia-induced BMDMs with MAECs, the expression levels of EndMT-related markers were increased. Conclusions SPP1⁺ macrophages differentiated under hypoxia are significantly infiltrated in the formation of chronic renal allograft fibrosis, and may promote renal allograft fibrosis by inducing EndMT in renal vascular endothelial cells.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

Objective To establish a molecular method for the identification of Aucklandia lappa Decne.and its common adulterants,Inula helenium L.,based on tetra-primer amplification refractory mutation system(ARMS).Methods After the analysis and comparison of internal transcribed spacer 2(ITS2)sequence differences between Aucklandia lappa Decne.and Inula helenium L.,single-nucleotide polymorphism(SNP)sites were found to design specific primers for identification,the ARMS method was established to specifically amplify samples from different sources,and identification was carried out according to the size of specific amplification bands.Results The results showed that 170 bp and 271 bp specific bands could be amplified by Aucklandia lappa Decne.and Inula helenium L.,respectively,under the following conditions:annealing temperature 56℃,cycle number 25,primer concentration ratio of internal and external primers 1∶4,agarose gel concentration 1.5%and using 2×TSINGKE Master Mix(blue),the detection limit of adulterates in Aucklandia lappa Decne.and Inula helenium L.mixture sample was 5%.The 23 samples collected from the market were identified,results comparison was the same among ARMS detection,DNA barcoding,and plant classification.Conclusion The ARMS method established in this study can accurately identify Aucklandia lappa Decne.and Inula helenium L.,which has the characteristics of strong specificity and high sensitivity and simple operation,can provide basic research for solving the problem of admixture identification and technical support for the quality control of Aucklandia lappa Decne.medicinal materials.

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.

Objective:To explore the value of ultrasound imaging characteristics combined with clinical indicators in assessing the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC).Methods:A retrospective analysis was conducted for patients who underwent pancreatic contrast-enhanced ultrasound (CEUS) from September 2017 to October 2023 at Peking Union Medical College Hospital and were diagnosed with PDAC based on pathological findings. Various parameters were recorded, including CA19-9 levels, tumor size, location, morphologic features, echogenicity, presence of internal cystic components, dilatation of the main pancreatic duct, peripheral vascular invasion, CEUS characteristics, presence or absence of liver metastasis, and treatment methods. In April 2024, patient survival information was obtained through telephone follow-up or review of medical records. Based on the results of the cox regression model analysis, a nomogram model of the risk of death was developed. The receiver operating characteristic (ROC) curves were applied to evaluate the predictive efficacy of the model. The calibration curves were plotted to evaluate the accuracy of the model, and clinical decision curves were used to evaluate the clinical benefit of the model.Results:This study included a total of 207 patients with PDAC. As of April 2024, 71 patients were alive and 136 died, with a median survival time of 14 months (95% CI: 12 -17). Multivariate analysis confirmed that the elevated CA19-9 ( HR=1.689, 95% CI: 1.102-2.588), tumor size >4 cm ( HR=1.641, 95% CI: 1.159-2.322), taller-than-wide shapes ( HR=1.450, 95% CI: 1.019-2.065), incomplete hypo-enhancement ( HR=1.618, 95% CI: 1.100-2.380), and liver metastasis ( HR=1.687, 95% CI: 1.175-2.423) were independent risk factors for survival in patients with PDAC. A nomogram model was further constructed for 6-month, 12-month and 3-year survival of patients with PDAC. The areas under the ROC curve were 0.679, 0.705 and 0.815, respectively. The calibration curves suggested that the model was more accurate, and the clinical decision curves showed that the model had a better clinical benefit. Conclusion:The combined use of ultrasound imaging characteristics and clinical indicators could effectively predict the prognosis of PDAC patients. Specifically, tumor size >4 cm, taller-than-wide shapes, incomplete hypo-enhancement, elevated CA19-9, and the presence of liver metastasis are correlated with poorer survival outcomes. The nomogram model constructed on the basis of these factors can be used to assess the survival of patients with PDAC.

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.

Objective:To explore the value of using computed tomography(CT)values to distinguish fresh and old fractures vertebral bodies in osteoporotic vertebral compression fractures(OVCF).Methods:Retrospective analysis of clinical data of 101 OVCF patients in our hospital from September 2022 to September 2023.Kappa test for consistency between magnetic resonance imaging(MRI)and vertebral CT values in distinguished fresh or old OVCF.The difference of CT values between fresh,old fractures and adjacent normal vertebral bodies were compared.The diagnostic efficiency was analyed by receiver operating characteristic(ROC)curve.Results:There was a high consistency between vertebral CT values and MRI in the diagnosis of OVCF in fresh and old fractures(Kappa value=0.934).There was a difference in difference of CT values between adjacent normal vertebral bodies and fresh fractures vertebral bodies(P＜0.05).There was a difference in difference of CT values of fresh fractures vertebral bodies and old fractures vertebral bodies(P＜0.05).The ROC curve analysis results showed that,the combined measurement of CT values of fresh and old fractured vertebral bodies has an area under the curve(AUC)of 0.723,which was higher than alone measurement of the CT values of fresh fractured vertebral bodies and old fractured vertebral bodies of 0.536 and 0.610(Z=2.548,2.605,2.841,P＜0.05).Conclusion:CT values of vertebral bodies show high consistency in distinguish fresh and old fractures of OVCF compared to MRI findings,and the diagnostic efficiency of combine detection is relatively high.

Objective:To explore the diagnostic value of conventional computed tomography(CT)combined with enhanced CT scan in bone metastases.Methods:This study was a retrospective observational study,84 suspected bone metastases patients admitted to our hospital from January 2022 to August 2024 were selected,All patients underwent conventional CT and enhanced CT scan and pathological examination,Using pathological examination results as the"gold standard"for diagnosis.The imaging manifestations of bone metastases using conventional CT combined with enhanced CT scan examination were observed;The detection rate and bone metastases types of conventional CT and enhanced CT scan were analyzed;The bone metastases location in different types of malignant tumors were analyzed;The detection results of bone metastases between conventional CT and enhanced CT scan were compared;the diagnostic efficacy of conventional CT and enhanced CT scan alone and in combination for bone metastases were analyzed by Receiver operating characteristic(ROC)curve.Results:The detection rate of osteogenic,osteolytic,cystic and mixed bone metastases by conventional CT combined with enhanced CT scan was supered to that of conventional CT and enhanced CT scan alone(P＜0.05).Bone metastases from lung cancer,breast cancer and other tumors mainly occur in the spine,limbs and ribs,while esophageal cancer,gastric cancer,liver cancer,prostate cancer,thyroid cancer,renal cancer,and nasopharyngeal cancer had relatively fewer bone metastases.The positive detection cases of bone metastases used conventional CT combined with enhanced CT scan were supered to those used conventional CT and enhanced CT scan alone.The sensitivity,specificity and accuracy of conventional CT combined with enhanced CT scan for the diagnosis of bone metastases were 94.00％,94.11％and 94.04％,respectively,and the positive/negative predictive values were 95.91％and 91.42％,respectively.The sensitivity,specificity and accuracy of conventional CT scan were 84.00％,78.78％and 80.95％,respectively,and the positive/negative predictive values were 85.71％and 74.28％,respectively.The sensitivity,specificity and accuracy of enhanced CT were 89.79％,85.71％and 88.09％,respectively.and the positive and negative predictive values were 89.79％and 85.71％,respectively.The diagnostic efficacy of conventional CT combined with enhanced CT scan for bone metastases was significantly better than that of conventional CT and enhanced CT scan alone.Conclusions:Conventional CT combined with enhanced CT scan can significantly improve the diagnostic efficiency of bone metastases,and provide an important basis for clinical treatment.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.