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.

This study employed the drug affinity responsive target stability (DARTS) technique to investigate the molecular mechanism of the antipsychotic drug penfluridol against melanoma, revealing the biological pathway to exert its effect on the HSPA6/p53/p21 signaling axis. Experiments such as the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and cell colony formation ability assay confirmed that penfluridol could significantly downregulate the expression of cyclin D1 and cyclin-dependent kinase 4 (CDK4) in melanoma A375 and B16 cells, induce cell cycle arrest in the G1 phase, and thus inhibit the proliferation of melanoma cells. Meanwhile, the results of Western blot, Hoechst 33342 staining and Annexin V-FITC/PI double staining experiments showed that penfluridol could significantly downregulate the expression of Bcl-2 and upregulate the expression of Bax and cleaved caspase-3, inducing cell apoptosis. Further, the DARTS technique was used to identify heat shock 70 kD protein 6 (HSPA6) as the key target bound by penfluridol. Penfluridol activates the p53/p21 pathway by upregulating HSPA6. Knocking down HSPA6 reverses not only the activation of the p53/p21 pathway mediated by penfluridol but also the associated cell cycle arrest and apoptosis. Animal experiments on tumor-bearing mice also confirmed that knocking down HSPA6 could reverse the in vivo anti-tumor activity of penfluridol. This study clarified that penfluridol can inhibit the progression of melanoma by targeting HSPA6 to activate the p53/p21 signaling axis, providing a new perspective for the repositioning of antipsychotic drugs in cancer treatment.

ObjectiveTo investigate the mechanism of Yijing decoction to inhibit oxidative stress induced by chronic iron overload and improve ovarian reserve hypofunction in mice. MethodsSeventy-two female C57BL/6J mice with normal estrous cycles were randomly divided into six groups （n=12 per group）：blank group，model group，Yijing decoction（YJD） low-dose group，medium-dose group，high-dose group，and dehydroepiandrosterone （DHEA） group. Mice in the blank group received intraperitoneal injections of normal saline，while those in all other groups were administered iron dextran （Sigma-Aldrich） at a dose of 0.5 g·kg^-1 once weekly for 8 weeks to establish a chronic iron overload model. Following the final injection，interventions were initiated and continued for 4 weeks. The low，medium，and high dose groups of YJD received oral gavage of Yijing decoction aqueous solution at doses of 18.165， 36.33，and 72.66 g·kg^-1·d^-1，respectively. The DHEA group received DHEA aqueous solution at 10.812 5 mg·kg^-1·d^-1. The blank and model groups received an equivalent volume of distilled water by gavage once daily. Body weight was recorded weekly，and food intake was monitored throughout the treatment period. Vaginal smears were collected daily and stained with hematoxylin-eosin （HE） to assess estrous cycle regularity. At the end of the experiment，mice were euthanized，and bilateral ovaries and uteri were rapidly excised and weighed to calculate ovarian and uterine indices （mg·g^-1）. Ovarian tissues were fixed，embedded，and sectioned for hematoxylin and eosin （HE） staining to evaluate histopathological changes. Iron deposition in ovarian tissue was visualized using Prussian blue staining. Serum levels of follicle-stimulating hormone （FSH），luteinizing hormone （LH），estradiol （E₂），and anti-Müllerian hormone （AMH） were measured by enzyme-linked immunosorbent assay （ELISA）. Malondialdehyde （MDA） content and superoxide dismutase （SOD） activity in ovarian homogenates were determined using commercial biochemical assay kits. Reactive oxygen species （ROS） levels in ovarian tissue were assessed by ROS fluorescence staining on frozen sections. Mitochondrial ultrastructure in ovarian tissue was examined by transmission electron microscopy （TEM）. Total RNA was extracted from ovarian tissue for real-time quantitative polymerase chain reaction （Real-time PCR） to quantify mRNA expression of ferritin heavy chain 1 （Fth1），ferritin light chain （Ftl），transferrin （Tf），transferrin receptor 1 （Tfr1），catalase （Cat），and glutathione peroxidase 1 （GPX1）. Protein expression levels of Fth1，Ftl，Tf，Tfr1，and glutathione peroxidase 4 （GPX4） were analyzed by Western blot. ResultsCompared with the blank group，mice in the model group exhibited significantly reduced body weight and severe estrous cycle disruption （P<0.01），a markedly increased uterine index （P<0.01），and a significantly decreased ovarian index （P<0.01）. The number of antral follicles was significantly reduced，while atretic follicles were markedly increased，accompanied by pronounced iron deposition in the ovarian stroma. Serum levels of AMH and E₂，as well as ovarian SOD activity，protein and mRNA expression of Tf and Tfr1，and mRNA levels of GPX1 and Cat were all significantly downregulated （P<0.05，P<0.01）. Conversely，serum FSH and LH levels，MDA content，protein and mRNA expression of Fth1 and Ftl，and ROS fluorescence intensity were significantly elevated （P<0.05，P<0.01），along with a marked decrease in GPX4 protein expression （P<0.01）. TEM revealed an increased number of damaged mitochondria in ovarian tissue，characterized by loss or disappearance of mitochondrial cristae. Compared with the model group，treatment with low，medium，and high doses of YJD and DHEA significantly improved body weight and ameliorated estrous cycle irregularities （P<0.05，P<0.01），decreased the uterine index （P<0.05），and increased the ovarian index （P<0.05，P<0.01）. These groups also showed increased numbers of antral follicles，reduced atretic follicles，and significantly diminished iron deposition in the ovarian stroma. Serum AMH and E₂ levels，ovarian SOD activity，protein and mRNA expression of Tf and Tfr1，and mRNA levels of GPX1 and Cat were all significantly upregulated （P<0.05，P<0.01）. In contrast，serum FSH and LH levels，MDA content，protein and mRNA expression of Fth1 and Ftl，and ROS fluorescence intensity were significantly reduced （P<0.05，P<0.01），while GPX4 protein expression was markedly increased （P<0.01）. Moreover，mitochondrial damage was alleviated，and mitochondrial ultrastructure was notably restored in ovarian tissue. ConclusionYijing decoction ameliorates ovarian reserve function in mice with chronic iron overload by upregulating the expression of Tf，Tfr1，and GPX4，downregulating the expression of Ft，Fth1，and Ftl，thereby alleviating systemic iron metabolism disorders，reducing oxidative stress in ovarian tissue，and restoring mitochondrial morphology and structure.

Objective To explore the method for establishing a pig left lung orthotopic transplantation model. Methods A total of 4 male Yorkshire pigs weighing (40.0±2.5) kg underwent surgical procedures, including anesthesia, tracheal intubation, donor lung procurement, and recipient lung transplantation. Histological morphology and blood gas analysis of the transplanted lungs were assessed 2 hours after reperfusion to evaluate the histological changes and function of the transplanted lungs. Results The pigs underwent left lung in situ transplantation, effectively simulating conditions relevant to human lung transplantation. Two hours after the transplantation, arterial blood gas analysis showed that arterial partial pressure of oxygen was 155.4-178.6 mm Hg, arterial partial pressure of carbon dioxide was 53.1-62.4 mm Hg, and the oxygenation index was 310.8-357.2 mm Hg. Hematoxylin and eosin staining indicated a low degree of pulmonary edema and minimal cellular infiltration. Conclusion The pig left lung orthotopic transplantation model possesses strong operability and stability. Researchers can replicate this model according to the described methods and further conduct basic research and explore clinical translational applications.

Mild cognitive impairment （MCI） is a critical precursor stage of Alzheimer’s disease， and the development of MCI is closely associated with liver function. As a core metabolic organ， the liver regulates cognitive function through the liver-brain axis. Epidemiological studies have shown the association between liver function parameters and MCI. The liver affects cognitive function by clearing peripheral β-amyloid （mainly via the PPARα-LRP-1 pathway）， secreting hepatic factors such as FGF21 and sEH to modulate neuronal energy metabolism， and mediating oxidative stress and systemic inflammatory responses. Anti-inflammatory/antioxidant measures， dietary pattern adjustments， and aerobic exercise are currently effective strategies for regulating liver function and mitigating mild cognitive impairment. This article systematically reviews the role and mechanism of the liver-brain axis in MCI， in order to provide new perspectives for developing liver-targeted therapies for cognitive impairment.

Objective:To observe the effects of Bushen Antai Mixture on nuclear transcription factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/nuclear transcription factor-κB (NF-κB) in placental tissue of recurrent spontaneous abortion (RSA) mice.Methods:The CBA/J mice (female) and DBA/2 (male), CBA/J mice (female) and BALB/c (male) were caged at a ratio of 2 : 1 to establish RSA and normal pregnant mice, respectively. The next morning, the vaginal plug was found or the sperm was seen under the microscope as the successful modeling, which was counted as the first day of pregnancy. CBA/J×BALB/c mice were set as normal group, and the RSA model pregnant mice were divided into model group, progesterone group, and Bushen Antai Mixture low-, medium-, and high-dosage groups using a random number table method, with 6 mice in each group. The normal group and the model group were given distilled water by gavage. Bushen Antai Mixture low-, medium-, and high-dosage groups were given 3.9 g/kg, 11.7 g/kg and 23.4 g/kg Bushen Antai Mixture by gavage. The progesterone group was given progesterone capsule aqueous solution 26 mg/kg by gavage for 14 consecutive days. The embryo loss rate of mice was calculated. The pathological changes of placental tissues were observed by HE staining. The expressions of Nrf2, HO-1 and NF-κB protein and mRNA in placental tissues were detected by Western blot and RT-qPCR.Results:Compared with the model group, the embryo loss rate of mice in the Bushen Antai Mixture low-, medium-, and high-dosage groups and the progesterone group significantly decreased ( P<0.05, P<0.01); the pathological morphology of placental tissue improved; the expressions of Nrf2, HO-1 protein and mRNA in placental tissue significantly increased ( P<0.05, P<0.01), and the expression of NF-κB protein and mRNA significantly decreased ( P<0.05, P<0.01). Conclusion:Bushen Antai Mixture may may treat RSA by activating the Nrf2/HO-1 pathway, inhibiting NF - κB expression, and improving oxidative stress and inflammatory response in the placental tissue of RSA pregnant mice.

Objective:To explore the effects of Qingre Qudu Decoction for fumigation combined with three-gap drainage on wound healing and serum inflammatory factors in patients with acute perianal abscess.Methods:Randomized controlled trial was conducted. A total of 117 patients with acute perianal abscess in the hospital were enrolled as the observation objects between August 2022 and May 2024. According to random number table method, they were divided into observation group (59 cases) and control group (58 cases). Both groups received three-gap drainage therapy. On basis of three-gap drainage, control group was given potassium permanganate, while observation group was given Qingre Qudu Decoction for fumigation. All patients were treated for 14 d. The growth of granulation tissue and wound secretions before and after treatment was evaluated. VAS scale was used to evaluate the degree of incision pain, and Wexner score was used to assess incontinence; ELISA was used to detect serum activator A (ACTA), immunoturbidimetry was used to detect serum CRP, and radioimmunoassay was used to detect serum IL-6 levels. The occurrence of complications and abscess recurrence during treatment was recorded, and clinical efficacy was evaluated.Results:The total effective rate of the observation group was 96.61% (57/59), while that of the control group was 82.76% (48/58), with statistical significance ( χ2=6.10, P=0.014). After treatment, scores of granulation tissue growth and wound secretions in observation group, and scores of VAS and Wexner incontinence in observation group were lower than those in the control group ( t=9.66, 5.00, 7.98, 3.65, P<0.001), and wound healing time was shorter than that in control group ( t=8.41, P<0.001). After treatment, levels of serum ACTA, CRP and IL-6 in observation group were lower than those in control group ( t=15.30, 2.08, 19.34, P<0.01 or P<0.05). The incidence of postoperative complications in the observation group was 6.78% (4/59), while in the control group it was 27.59% (16/58), with statistical significance ( χ2=8.93, P=0.003). Conclusion:Qingre Qudu Decoction for fumigation combined with three-gap drainage can relieve postoperative incision pain, inhibit inflammatory response, accelerate the recovery of wound and promote the recovery of anal function and improve clinical efficacy.

Objective To explore the role of miR-429 in synovial mesenchymal stem cell-derived exosomes(SMSC-Exos)in repairing cartilage damage in temporomandibular joint osteoarthritis(TMJ OA)by extracting SMSC-Exos from human synovial tissue and screening differentially expressed microRNA(miRNA)through transcriptome sequencing.Methods Human synovial tissues were obtained from 6 patients who underwent surgery at the First Medical Center of the Chinese PLA General Hospital from June to December 2023,including 3 patients with osteoarthritis(OA group)and 3 control patients(control group),all of whom were male.SMSC-Exos were extracted from the synovial tissues for miRNA sequencing and differential expression analysis.Further,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed on the target genes of differentially expressed miRNA to identify key functional miRNA and construct miRNA-target gene regulatory networks and protein-protein interaction(PPI)networks of target genes.An in vitro model of rabbit condylar cartilage cell inflammatory microenvironment induced by interleukin-1β(IL-1β)was established,with the control group cultured in DMEM/F12 basic medium and the inflammation-induced group cultured in DMEM/F12 basic medium containing 10 ng/ml IL-1β.RT-qPCR was used to detect the effects of overexpressed target miRNA on the mRNA expression levels of cartilage phenotype factors such as type Ⅱ collagen α1 chain(Col2a1),aggrecan(Acan),as well as inflammatory factors including a disintegrin and metalloproteinase with thrombospondin motifs 5(Adamts5)and cyclooxygenase-2(Cox-2).Results(1)SMSC-Exos were successfully isolated,cultured,and identified.(2)miRNA sequencing of SMSC-Exos from OA and control groups revealed 16 differentially expressed miRNAs(|log2FC|>2,P<0.05).Compared with control group,7 miRNAs were up-regulated and 9 were down-regulated in OA group.GO and KEGG analysis indicated that the target genes of miR-429 were mainly involved in development process,anatomical structure development,system development,cell development and differentiation,and were enriched in inflammation-related pathways such as mitogen-activated protein kinase(MAPK)and phosphatidylinositol 3-kinase-protein kinase B(PI3K-Akt).(3)Functional validation of miR-429 in the rabbit condylar cartilage cell inflammatory model showed that overexpression of miR-429 increased the mRNA expression levels of Col2a1 and Acan(P<0.05)and decreased the mRNA expression levels of Adamts5 and Cox-2(P<0.05)in the inflammation-induced group.Conclusions miRNA sequencing of SMSC-Exos isolated and identified from human synovial tissues reveals a specific miRNA expression profile in OA patients,with miR-429 significantly down-regulated.Functional validation demonstrates that overexpression of miR-429 has reparative and anti-inflammatory effects on condylar cartilage cells in an inflammatory microenvironment.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.