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.

ObjectivePost-ischemic acute inflammation and the subsequent persistent dysregulation of the immune microenvironment represent major pathological drivers that aggravate neuronal injury and severely restrict functional recovery following ischemic stroke. Although current reperfusion therapies partially restore blood flow, they fail to effectively modulate the secondary inflammatory cascade and oxidative stress, which remain critical barriers to neurological restoration. To address this challenge, this study aimed to engineer and systematically evaluate a biomimetic nanosystem composed of transforming growth factor-β1 (TGF-β1)-loaded platelet membrane-camouflaged lipid nanoparticles (PLP). This nanosystem was designed to achieve dual lesion-targeted delivery and immune microenvironment remodeling. By verifying its spatiotemporal accumulation, anti-inflammatory activity, and neuroprotective efficacy, we sought to establish an integrated therapeutic strategy that simultaneously enables lesion targeting, immune regulation, and functional recovery after ischemic injury. MethodsThe physicochemical properties of PLP, including hydrodynamic particle size, zeta potential, structural stability, and morphology, were characterized using dynamic light scattering, zeta potential analysis, and transmission electron microscopy. The preservation of platelet membrane-derived adhesion and immunoregulatory proteins was confirmed by SDS-PAGE through comparative analysis of protein band profiles between PLP and native platelet membranes. The in vitro biological activities of PLP were evaluated using two complementary cellular models. LPS-induced M1-polarized RAW264.7 macrophages were employed to assess inflammatory modulation, while oxygen glucose deprivation/reperfusion (OGD/R)-induced BV2 microglial cells and SH-SY5Y neuronal cells were utilized to investigate neuroinflammatory regulation and neuronal protection. For in vivo validation, a transient middle cerebral artery occlusion (tMCAO) mouse model was established to mimic ischemia-reperfusion injury. The spatiotemporal biodistribution and lesion-targeting capability of the PLP were monitored through live fluorescence imaging. Therapeutic efficacy was comprehensively evaluated by triphenyltetrazolium chloride (TTC) staining, glial fibrillary acidic protein (GFAP) immunofluorescence analysis, body weight monitoring, and neurological severity score (NSS) assessment. ResultsPLP nanoparticles displayed a uniform spherical morphology, nanoscale particle size distribution, and stable negative surface charge, indicating favorable colloidal stability and circulation potential. SDS-PAGE results confirmed the effective retention of key platelet membrane proteins associated with endothelial adhesion, immune evasion, and inflammatory regulation, demonstrating the successful biomimetic construction. Optimal therapeutic concentrations were determined in OGD/R-induced BV2 cells, where PLP exhibited excellent cytocompatibility and anti-inflammatory activity.In vitro experiments demonstrated that PLP significantly inhibited the polarization of RAW264.7 macrophages toward the pro-inflammatory M1 phenotype and markedly reduced neuronal apoptosis under ischemia-reperfusion conditions. In vivo fluorescence imaging revealed that PLP rapidly accumulated in the ischemic brain hemisphere and maintained prolonged retention for up to 7 d, suggesting enhanced lesion-specific targeting and sustained drug release. Compared with control group, PLP treatment significantly reduced cerebral infarct volume, attenuated reactive astrogliosis, improved weight recovery, and accelerated neurological functional restoration, as reflected by significantly improved NSS scores. ConclusionThis study establishes a multifunctional biomimetic nanoplatform that integrates platelet membrane-mediated active targeting with the anti-inflammatory, antioxidative, and neuroprotective properties of TGF-β1. The PLP system enables rapid lesion homing and long-term retention while synergistically regulating the post-stroke inflammatory microenvironment by suppressing pro-inflammatory immune activation, reducing neuronal apoptosis, and limiting excessive astrocyte reactivity. Importantly, this study proposes a conceptually therapeutic paradigm that combines targeted delivery with immune microenvironment remodeling to achieve comprehensive neurovascular protection. These findings provide strong experimental evidence supporting the translational potential of biomimetic nanotherapeutics as next-generation precision interventions for ischemic stroke.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

AIM:To investigate the effects of high-altitude hypoxic exposure on retinal injury and the associated changes in oxidative stress-related indicators in rats. METHODS: Twenty-four healthy male Sprague-Dawley(SD)rats were randomly divided into a plain group and a high-altitude group, with 12 rats(24 eyes)in each group. Rats in the plain group were housed under normoxic conditions in an SPF-grade animal facility, whereas rats in the high-altitude group were placed in a special environmental chamber simulating an altitude of 6 000 m for 7 d. Optical coherence tomography(OCT)was used to assess retinal layer architecture and quantify retinal thickness. Hematoxylin-eosin(HE)staining was performed to observe retinal histopathological changes. Immunofluorescence(IF)was used to detect the expression of hypoxia-inducible factor-1α(HIF-1α)in retinal tissue. Transmission electron microscopy(TEM)was applied to examine the ultrastructure of retinal ganglion cells(RGCs). Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of malondialdehyde(MDA), total superoxide dismutase(T-SOD), and reduced glutathione(GSH)in retinal tissue. In addition, intracellular reactive oxygen species(ROS)levels in retinal tissue were assessed using the 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe. RESULTS: OCT examination revealed disorganized retinal architecture in the high-altitude group, with increased inner and middle ring thickness and decreased outer ring thickness compared with the plain group(all P<0.05). HE staining showed varying degrees of retinal layer damage, blurred layer boundaries, loosely arranged RGCs, and partial cellular necrosis in the high-altitude group. IF analysis demonstrated significantly increased HIF-1α expression in the inner nuclear layer of the high-altitude group(P<0.01). TEM revealed mitochondrial swelling, disrupted cristae, and reduced matrix electron density in RGCs of the high-altitude group. ELISA and fluorescence probe assays showed significantly elevated MDA levels and ROS fluorescence intensity, accompanied by decreased T-SOD and GSH levels in the retinal tissue of the high-altitude group(all P<0.05). CONCLUSION: Exposure to a high-altitude hypoxic environment induces marked morphological and ultrastructural damage in the rat retina and significantly enhances oxidative stress, suggesting that oxidative stress may play a critical role in retinal injury induced by high-altitude hypoxia.

ObjectiveTo investigate the expression level of mammalian sterile 20-like kinase 1 （MST1） in prostate cancer （PCa） tissues， its biological functions， and its regulatory effects on androgen receptor （AR） and vascular endothelial growth factor （VEGF） expression. MethodsImmunohistochemistry was performed to detect MST1 expression in 77 prostate cancer tissues and 34 benign prostatic hyperplasia （BPH） tissues， and the relationship between MST1 expression and clinicopathological parameters was analyzed. MST1-overexpressing C4-2 and LNCaP cell lines were constructed. CCK-8 assay， Transwell migration assay， and angiogenesis assay were conducted to evaluate the effects of MST1 on cell proliferation， migration， and angiogenesis. The expression changes of AR and VEGF were detected by qRT-PCR and Western blot. ResultsMST1 expression was significantly lower in PCa tissues compared with BPH tissues （P=0.012）. Low MST1 expression was significantly associated with tumor metastasis （P=0.033）. MST1 overexpression inhibited C4-2 cell proliferation and migration， with transmembrane migrated cells reduced by 53.6% （P<0.01）. MST1 overexpression decreased the mRNA and protein expression levels of AR and VEGF （P<0.05）. Angiogenesis assay demonstrated that the length of new vessel structure was significantly reduced （P<0.05）. ConclusionMST1 shows a low expression level in PCa tissues and is associated with tumor metastasis. MST1 exerts tumor-suppressive effects in prostate cancer by inhibiting cell proliferation， migration， and angiogenesis， as well as downregulating the expression of AR and VEGF， indicating its potential as a therapeutic target for prostate cancer.

Background and aims As a ferroptosis inducer, sorafenib, a first-line treatment for hepatocellular carcinoma (HCC), has a significant antitumor effect. Nonetheless, HCC patients frequently develop sorafenib resistance. Here, we investigated the impacts of progestagen-associated endometrial protein (PAEP), which controls sorafenib resistance and tumorigenesis in HCC. Furthermore, we investigated the function of PAEP and the underlying molecular mechanisms that cause HCC ferroptosis when sorafenib is applied. Methods Western blot analysis, cell proliferation, colony formation and animal experiments were performed to investigate the function of PAEP in sorafenib resistance and tumorigenesis in HCC. We detected the levels of reactive oxygen species, iron, and malondialdehyde and preformed transmission electron microscopy to investigate the relationship between PAEP and ferroptosis. Co-immunoprecipitation (co-IP) assay was performed to investigate the underlying molecular mechanisms of PAEP that cause HCC ferroptosis. Results PAEP was significantly overexpressed in HCC tissues, and this was associated with a poor clinical prognosis. PAEP silencing dramatically reduced HCC cells’ malignant phenotype. We found that sorafenib-induced ferroptosis was more sensitive to HCC cells with PAEP knockdown. Furthermore, the orthotopic cell line-derived xenograft mouse model results showed that sorafenib sensitivity can be effectively increased in vivo by PAEP knockdown. We determined that transferrin (TF) was a PAEP target using the String database, and we further supported this finding with Co-IP analysis. Additionally, on sorafenib-induced ferroptosis in HCC cells, TF partially reversed the effects of PAEP knockdown. Conclusions Our research indicates that PAEP may be a potential biomarker for predicting sorafenib resistance in HCC and disruption of PAEP expression may be a potential cancer-directed therapeutic option for HCC.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

Objective:To screen the risk factors of acute kidney injury (AKI) in patients with multiple trauma, construct a prediction model accordingly, and evaluate its predictive value.Methods:A retrospective cohort study was performed to analyze the clinical data of 560 multiple trauma patients who were admitted to while Affiliated Hospital of Jiangsu University from January 2017 to June 2023, including 424 males and 136 females, aged 18-91 years [(55.5±15.0)years]. The patients were randomly divided into a training set ( n=392) and validation set ( n=168) with a ratio of 7∶3. Of all, 77 patients were combined with AKI in the training set, while 33 patients combined with AKI in the validation set. The AKI group and non-AKI group in the training set were compared in terms of gender, age, hypertension, diabetes, cause of injury, abbreviated injury scale (AIS) score of head and neck injury, AIS score of maxillofacial injury, AIS score of chest injury, AIS score of abdominal injury, AIS score of extremities and pelvic injury, AIS score of body surface injury, systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate, body temperature, red blood cell and plasma transfusion volume within 24 hours following admission, emergency surgery, mechanical ventilation, vasoactive drug therapy, Glasgow coma score (GCS) on admission, revised trauma score (RTS) on admission, acute physiology and chronic health assessment II (APACHE II) on admission, injury severity score (ISS) on admission, and laboratory test results on admission including white blood cell count, neutrophil count, lymphocyte count, C-reactive protein, hemoglobin, platelet count, activated partial thromboplastin time (APTT), prothrombin (PT), fibrinogen (FIB), thrombin time (TT), international normalized ratio (INR), D-dimer, blood lactate, base excess, total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, globulin, urea nitrogen, serum creatinine, blood glucose, potassium, sodium and chloronium. In the training set, univariate analysis and Lasso regression analysis were used to screen the risk factors of AKI in patients with multiple trauma, which were then included into multivariate logistic regression analysis to identify the independent risk factors. A nomogram prediction model was constructed using the R software based on the above independent risk factors. Hosmer-Lemeshow (H-L) goodness-of-fit test was performed to evaluate the fitting degree of the prediction model in the training set and the validation set, and the receiver operating characteristic (ROC) curve, calibration curve and clinical decision curve (DCA) were plotted in the training set and the validation set to evaluate the predictive performance of the prediction model. Results:There were statistically significant differences in AIS score of abdominal injury, heart rate, body temperature, red blood cell and plasma transfusion volume within 24 hours following admission, emergency surgery, mechanical ventilation, vasoactive drug therapy, GCS on admission, RTS on admission, APACHE II on admission, ISS on admission as well as hemoglobin, platelet count, APTT, PT, FIB, TT, INR, blood lactate, base excess, AST, albumin, globulin, urea nitrogen, serum creatinine, blood glucose and sodium on admission between the AKI group and the non-AKI group ( P<0.05 or 0.01). The characteristic variables screened by Lasso regression analysis included AIS score of abdominal injury, red blood cell transfusion volume within 24 hours following admission, mechanical ventilation, vasoactive drugs therapy, blood lactate on admission, blood creatinine on admission, AST on admission, and blood sodium on admission. Multivariate logistic regression analysis showed that red blood cell transfusion volume within 24 hour following admission ( OR=1.09, 95% CI 1.01, 1.18), mechanical ventilation ( OR=2.49, 95% CI 1.06, 5.85), vasoactive drug therapy ( OR=2.04, 95% CI 1.03, 4.03), blood lactate on admission ( OR=1.10, 95% CI 1.01, 1.21) and serum creatinine on admission ( OR=1.02, 95% CI 1.01, 1.03) were independent risk factors for AKI in patients with multiple trauma ( P<0.05). The regression equation was constructed: Logit[ P/(1- P)]=0.086 2×"red blood cell transfusion volume within 24 hour following admission"+0.912 7×"mechanical ventilation"+0.713 2×"vasoactive drug therapy"+0.098 9×"blood lactate on admission"+0.019 2×"serum creatinine on admission" -4.822 3. H-L goodness-of-fit test showed χ2 value of 9.50 in the training set ( P>0.05) and 6.43 in the validation set ( P>0.05). The results of the ROC curve indicated that the area under the curve (AUC) was 0.84 (95% CI 0.78, 0.89) in the training set and 0.80 (95% CI 0.72, 0.88) in the validation set. The calibration curves showed good agreement with the actual curves, with the predicted probability consistent with the actual probability in both training set and validation set. DCA analysis showed that the threshold probability ranged from 2% to 70% with the net benefit rate of the prediction model greater than 0 in the training set, while the threshold probability ranged from 3% to 69% with the net benefit rate of the prediction model greater than 0 in the validation set. Conclusions:Red blood cell transfusion volume within 24 hours following admission, mechanical ventilation, vasoactive drug therapy, lactate and serum creatinine on admission are independent risk factors for AKI in patients with multiple trauma. The nomogram prediction model based on the above 5 predictive variables of AKI in patients with multiple trauma shows good predictive efficacy and clinical application value.

Psoriasis arthritis (PsA) is a chronic inflammatory musculoskeletal disease intricately linked to psoriasis (PsO), with a multifaceted etiology encompassing genetic, environmental, and immunological factors. Characterized by complex clinical manifestations, PsA often follows a protracted course with a propensity for relapses, potentially culminating in joint deformity and disability. The condition is further complicated by associated comorbidities such as inflammatory bowel disease, uveitis, cardiovascular disease, and metabolic syndrome, which significantly diminish patients′ quality of life. Early detection and screening of PsA are crucial for its management and prevention of adverse outcomes. However, in China, there is a notable deficiency in the recognition and early diagnosis of PsA, with missed or incorrect diagnoses being relatively common. The consensus comprises four overarching statements and sixteen detailed recommendations, with the overarching goal of enhancing the early diagnosis and treatment of PsA by clinical physicians, thereby improving patient outcomes.

Objective:To screen high risk children for lysosomal storage diseases (LSD) in southern China and analyze the spectrum characteristics of LSD in this region.Methods:A cross-sectional study was conducted. A total of 7 435 children at high risk of LSD were screened at Guangzhou Women and Children′s Medical Center, Guangzhou Medical University from January 2009 to December 2024. The activities of 22 lysosomal enzymes from peripheral blood leukocytes or plasma were measured by fluorescence or colorimetric assays with synthetic substrates to screen for 24 LSD subtypes.Results:Among the 7 435 high risk children, 759 children were diagnosed with LSD (10.2%). The diagnosed cases included 506 males and 253 females, with an age at diagnosis of 3.0 (2.5, 5.5) years. The common disease types were mucopolysaccharidosis (MPS) (390 cases (51.4%)), sphingolipidoses (269 cases (35.4%)), glycogen storage disease (62 cases (8.2%)), and mucolipidosis types Ⅱ and Ⅲ (29 cases (3.8%)). Among the positive cases, 21 disease subtypes were identified. The 5 frequent subtypes, in descending order, were MPS type Ⅱ (197 cases (26.0%)), Gaucher disease (111 cases (14.6%)), MPS type ⅣA (87 cases (11.5%)), glycogen storage disease type Ⅱ (62 cases (8.2%)), and metachromatic leukodystrophy (MLD) (49 cases (6.5%)). The rarest subtypes were mannosidosis, multiple sulfatase deficiency and Wolman disease, each with 1 case (0.1%).Conclusions:Enzyme activity screening is essential for diagnosing high risk children with LSD. In Southern China, the most common LSD subtypes are MPS Ⅱ, Gaucher disease, MPS ⅣA, glycogen storage disease type Ⅱ, and MLD, while mannosidosis, multiple sulfatase deficiency and Wolman disease are the rarest.