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 systematically compare mature experiences of comprehensive drug value assessment in typical countries/regions and to provide decision-making references for China to establish a scientific and standardized comprehensive drug value assessment system for medical-insured drugs. METHODS The literature analysis was used to systematically review drug value assessment frameworks in 11 representative countries/regions， namely the UK， Canada， Italy， Australia， Germany， France， South Korea， Japan， the United States， as well as Taiwan （China） and Hong Kong （China）. Comparisons were made across three dimensions： assessment entities， value dimension， and application of results. RESULTS &CONCLUSIONS In most countries/regions， independent technical assessment institutions have been established as part of the drug value evaluation system， with the involvement of multiple stakeholders （e.g.， the UK， Canada）. The mainstream drug value assessment frameworks have generally transcended the traditional core dimensions of safety， efficacy， and cost-effectiveness， exhibiting two major trends： the continuous expansion of assessment dimensions and stricter evidence requirements. Assessment outcomes are closely integrated with payment policies， ranging from providing technical advice for decision-making （e.g.， Italy， France） to directly determining reimbursement eligibility （e.g.， the UK， Germany）. The following recommendations are proposed for China： first， establish an evaluation mechanism featuring multi-stakeholder participation and separation of evaluation from decision-making. Second， develop a comprehensive evaluation framework integrating clinical， economic， patient， and societal value， emphasizing quantitative indicator exploration and real-world evidence application. Third， promote direct linkage between value-based tiering outcomes and medical insurance reimbursement decisions or access negotiations to balance patient benefits， fund sustainability， and industrial innovation.

ObjectiveTo investigate the effects of metformin on the immune functions of immature dendritic cells （imDCs） and the underlying mechanisms. MethodsMouse bone marrow-derived imDCs were treated with different concentrations of metformin. The working concentration and treatment time of metformin in this study were determined based on the results of cell apoptosis and cell viability assays. The effects of metformin on the phagocytic capacity of imDCs was evaluated using an antigen endocytosis assay. The expression of cluster of differentiation 205 （CD205）， the polymerization of filamentous actin （F-actin）， and the underlying regulatory mechanisms were investigated through flow cytometry， laser confocal fluorescence microscopy， and Western blot. ResultsThe working concentrations of metformin were 1， 2， 4 mmol/L for 24 h determined by the apoptosis and cell viability assays.Metformin significantly suppressed the phagocytic capacity of imDCs， down-regulated the expression of the mannose receptor CD205 on the cell surface， which was closely associated with phagocytic function； metformin inhibited the RhoA-ROCK1-LIMK1-Cofilin signaling pathway， which inhibited the polymerization of F-actin and disturbed its dynamic remodeling of imDCs. ConclusionMetformin can inhibit the expression of CD205 and disrupt the remodeling of F-actin， thereby suppressing the antigen-capturing capacity of imDCs.

ObjectiveTo investigate the efficacy of selective internal radiation therapy （SIRT） in patients with unresectable hepatocellular carcinoma， and to provide a reference for the selection of clinical treatment regimens. MethodsA retrospective analysis was performed for the clinical data of 73 patients with unresectable hepatocellular carcinoma who received yttrium-90 microsphere SIRT in Eastern Hepatobiliary Surgery Hospital from May 1， 2023 to September 1， 2024. According to tumor characteristics， physical status， liver reserve function， laboratory tests， and SIRT treatment strategy， the patients were divided into radiation segmentectomy group with 9 patients， conversion therapy group with 47 patients， and palliative treatment group with 17 patients. Based on the results of postoperative follow-up， modified Response Evaluation Criteria in Solid Tumors were used to assess radiographic images. A one-way analysis of variance was used for comparison of normally distributed continuous data between three groups， and the chi-square test was used for comparison of categorical data between three groups； the Logistic regression model was used to perform the multivariate analysis. ResultsThere was a significant difference in postoperative outcome between the radiation segmentectomy group， the conversion therapy group， and the palliative treatment group （χ²=30.060， P<0.001）. The disease control rate was 100.0% （9/9） in the radiation segmentectomy group， 83.0% （39/47） in the conversion therapy group， and 29.4% （5/17） in the palliative treatment group， with a significant difference between the three groups （χ²=19.575， P<0.001）， and there was also a significant difference in objective response rate between the three groups （χ²=17.749， P<0.001）. The multivariate Logistic regression analysis showed that the number of tumors （odds ratio ［OR］=0.085， 95% confidence interval ［CI］： 0.008 — 0.906， P=0.041） and combined targeted immunotherapy （OR=18.808， 95%CI： 1.704 — 207.616， P=0.017） were independent influencing factors for achieving complete response. ConclusionThe number of tumors is an independent influencing factor for the efficacy of SIRT and is an important basis for selecting different treatment goals. SIRT combined with targeted immunotherapy may achieve better efficacy.

Atherosclerosis is a complex pathological condition resulting from lipid deposition， chronic inflammatory responses， and fibrosis， with a prolonged disease course and multifactorial etiology. Based on the traditional Chinese medicine （TCM） theory of accumulation syndrome， atherosclerosis can be classified under this category， with its pathogenesis involving phlegm， blood stasis， deficiency， and accumulation. This paper proposed a stage-based intervention strategy using the four therapeutic principles of "attacking， supplementing， dispersing， dissipating"， and divided into six stages based on the pathological progression， including the stage of accumulation before formation， the stage of accumulation already formed， the stage of nucleus accumulation， the stage of nucleus accumulation decay， the stage of nucleus accumulation consolidation， and the stage of severe stenosis of nucleus. At different stages， the intervention focuses on reinforcing healthy qi and consolidating the root， tonifying the kidneys and spleen， dispersing and removing turbidity， removing phlegm stagnation， promoting qi circulation， dispersing accumulations and removing stasis， attacking accumulation and expelling stasis， directing the turbid downward and dispersing accumulation， and treatment would be adjusted based on specific symptoms， which provides a theoretical framework for the prevention and treatment of atherosclerosis with TCM.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

BackgroundMigraine is a common chronic neurological disease， and patent foramen ovale （PFO） has been closely associated with migraine. Current research primarily focuses on the pathological mechanism and the therapeutic effects of interventional closure， with limited attention paid to the impact of PFO on sleep quality in migraine patients. ObjectiveTo compare the difference in sleep quality between PFO-positive and PFO-negative migraine patients， and to analyzes influencing factors of sleep quality in PFO-positive migraine patients， so as to provide references for clinical interventions to improve sleep quality in PFO-positive migraine patients. MethodsA total of 673 migraine patients who met the diagnostic criteria of migraine in the International Classification of Headache Disorders， third edition （ICHD-3）， and all patients underwent contrast-enhanced transcranial Doppler （c-TCD） and transthoracic echocardiographic right heart contrast echocardiography （cTTE） in the Third Hospital of Mianyang from January 2020 to October 2024. Basic demographic data were collected using a self-designed questionnaire， headache severity was assessed with the Visual Analogue Scale （VAS）， and sleep quality was invaluated using the Pittsburgh Sleep Quality Index （PSQI）. PFO patients was diagnosed through c-TCD combined with c-TTE. Binary logistic regression analysis was employed to examine the influencing factors of sleep quality in PFO-positive migraine patients. ResultsA total of 673 （100.00%） migraine patients were enrolled， including 223 PFO-positive cases （33.14%） and 450 PFO-negative cases（66.86%）. The PFO-positive group showed significantly more severe headache severity （χ²=15.799， P<0.01） and poorer sleep quality （χ²=14.377， P<0.01） compared with PFO-negative group. PFO-positive patients demonstrated significantly higher barrier factor scores of sleep quality， sleep latency， sleep efficiency， sleep disturbance， hypnotic medication use， and daytime dysfunction compared with PFO-negative counterparts （t=3.634， 3.269， 2.785， 3.428， 2.907， 3.637， Bonferroni adjust P<0.05/7=0.007）.By contrast， no significant difference was noted in sleep duration scores between the two groups（t=2.349， Bonferroni adjust P>0.05/7=0.007）.The Binary Logistic regression analysis revealed that age （OR=1.021， 95% CI： 1.001~1.041）， headache severity （OR=6.030， 95% CI： 4.085~8.901）， and PFO grade （OR=1.893，95% CI： 1.288~2.784）were significant influencing factors for sleep quality in migraine patients with PFO. ConclusionMigraine patients with PFO-positive exhibited poorer sleep quality compared wtih PFO-negative patients. Older age， higher headache servity， and more severe PFO grade are identified as risk factors for impaired sleep quality in PFO-positive migraine patients.

Objective To investigate the mechanism of kaempferol(KPF)in the treatment of macular edema sec-ondary to retinal vein occlusion(RVO-ME).Methods RVO model was established in SD rats using photocoagulation.Twenty SD rats were randomly divided into:Control group(normal rats,saline injection),Model group(RVO model rats,saline injection),Low KPF group[RVO model rats,KPF injection(8 mg·kg-1·d-1)],High KPF group[RVO model rats,KPF injection(16 mg·kg-1·d-1)],with 5 rats per group for 14 days.Fundus photography observed retinal vessels;HE staining evaluated retinal structural changes.HRMECs were randomly divided into:control group(no intervention),CoCl2 group(300 μmol·L-1 CoCl2),Low-dose KPF group(300 μmol·L-1 CoCl2+20 μmol·L-1 KPF),High-dose KPF group(300 μmol·L-1 CoCl2+30 μmol·L-1 KPF)and pathway inhibitor group(DAPT group)(300 μmol·L-1 CoCl2+20 μmol·L-1 DAPT),with 24-hour intervention.CCK-8 assay detected cell viability;Scratch test measured cell migration rate;ELISA quantified inflammatory factors[interleukin(IL)-6,tumor necrosis factor(TNF)-α];FITC-dextran assay evalu-ated endothelial monolayer permeability;Immunofluorescence detected zonula occludens(ZO)-1 expression;Western blot and RT-PCR measured protein and mRNA levels of ZO-1,Occludin,Notch1,and Hes1.Results Fundus photography showed interrupted venous blood flow and retinal edema in Model group,alleviated by KPF.HE staining revealed disorder-ed retinal arrangement and severe edema in the Model group,improved by KPF.Compared with CoCl2 group,Low-and High-dose KPF groups showed reduced cell migration rate,increased cell vitality(both P＜0.05),IL-6 and TNF-α levels de-creased in Low-and High-dose KPF groups and DAPT group(all P＜0.05),permeability coefficient decreased in Low-and High-dose KPF groups and DAPT group(all P＜0.05),ZO-1 expression increased in Low-and High-dose KPF groups and DAPT group(all P＜0.05),ZO-1 and Occludin protein/mRNA levels increased;Notch1 and Hes1 protein/mRNA levels de-creased in Low-and High-dose KPF groups and DAPT group(all P＜0.05).Conclusion KPF treat RVO-ME by inhibiting the Notch1/Hes1 pathway,exerting anti-inflammatory effects and improving intercellular tight junctions.

Objective:To explore the stratified treatment plan process for neonatal congenital chylothorax by summarizing its clinical treatment characteristics.Methods:A retrospective analysis was conducted on the clinical data of 36 neonates with congenital chylothorax treated at the Department of Neonatology of Beijing Children's Hospital, Capital Medical University, from January 1, 2010, to December 31, 2021. Based on different treatment methods and initial drainage volumes, the cases were divided into the conservative treatment group [initial drainage volume<20 ml/(kg·d), n=20], octreotide group [initial drainage volume ≥20-<30 ml/(kg·d), n=4], erythromycin group [initial drainage volume ≥30-<50 ml/(kg·d), n=6], and octreotide plus erythromycin group [initial drainage volume≥50 ml/(kg·d), n=6]. The clinical characteristics and treatment effects of the children in different treatment groups, as well as the choice of further treatment plans, were summarized to determine the timing of different treatment methods. A more standardized stratified treatment plan was formulated by combining the literature. Results:Among the 36 cases of congenital chylothorax, 18 cases (50.0%) were diagnosed in utero, with no intrauterine intervention. In the conservative treatment group, 20 cases were treated with respiratory support, thoracic drainage, and nutritional therapy. Except for one case who was discharged after abandoning treatment, the remaining 19 cases were cured. In the octreotide group, four children received continuous intravenous infusion of octreotide at doses ranging from 1 to 10 μg/(kg·h), with three cases improving and one case being cured. No adverse effects such as hypoglycemia, thyroid dysfunction, or neonatal necrotizing enterocolitis occurred. In the group of six children who received intrapleural erythromycin injections, the dosage of erythromycin was 25-30 mg/kg, and the median thoracic drainage volume was reduced to approximately 50% of the pre-treatment volume after 3-5 injections, with four cases improving and two cases being cured. In the group of six children who received octreotide combined with erythromycin, treatment involved the intravenous infusion of octreotide along with intrapleural erythromycin injections. Four cases showed improvement, and two cases were cured. Based on previous treatments and a comprehensive review of the literature, a stratified treatment flowchart with invasiveness ranging from low to high was finally formed. Conclusions:For congenital chylothorax, a stratified treatment approach is recommended based on initial drainage volume and the response to treatment. This approach ranges from conservative treatment to pharmacological treatment (intravenous infusion of octreotide). For children with poor outcomes, surgical treatment (intrapleural erythromycin injection or other surgical interventions) can be added.

Objective To investigate the associations between unilateral or bilateral hearing loss and 12 chronic diseases as well as multimorbidity among the oldest old in China,and to identify disparities in these associations of left-and right-side hearing loss with chronic diseases.Methods Totally 7 437 people aged ≥80 years old were selected from the Chinese Longitudinal Health and Longevity Survey(CLHLS)2018 cross-sectional data.With 12 chronic diseases and multimorbidity as outcome variables,the hearing loss as explanatory variable,socio-demographic characteristics,family factors,and lifestyle as covariates,the correlations of unilateral(left-or right-side)and bilateral hearing loss with chronic diseases and multimorbidity were analyzed using multivariate logistic regression model,and the trend analyses were carried out.Results There were 205(2.76％),227(3.05％)and 3 598(48.38％)old people with left-side,right-side and bilateral hearing loss,respectively.After adjusting for confounders,the oldest old with left-sided or bilateral hearing loss had a greater risk of multimorbidity compared with those with normal hearing function,with odds ratio(95％confidence interval)of 2.14(1.58-2.90)and 1.27(1.13-1.43),respectively,while no association between right-sided hearing loss and multimorbidity was observed(P＞0.05).Trend analysis showed that the risk of multimorbidity increased with hearing loss from none to unilateral and then to bilateral(P＜0.001).Conclusion Hearing loss may be related to the increased risk of multimorbidity in the oldest old,and the risk of those with bilateral hearing loss is higher.More attention should be paid to the prevention and treatment of hearing loss in the oldest old.