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 analyze the prototype components absorbed into blood and brain of Lithocarpus litseifolius leaves， so as to provide a reference for clarifying the pharmacological material basis of its prevention and treatment of central nervous system dis eases. METHODS The ethanol extract of L. litseifolius leaves， as well as the gastric lavage fluid and perfusion solution were prepared. Using rats as subjects， plasma samples of intestinal wall metabolism， intestinal flora metabolism and hepatic metabolism were prepared via in situ intestinal perfusion and closed intestinal loop method； while comprehensive metabolic plasma samples， brain tissue samples， and cerebrospinal fluid samples were collected after intragastric administration. UPLC-HRMS technology was utilized to analyze and identify chemical components and prototype components absorbed into blood and brain of L. litseifolius leaves. RESULTS A total of 66 chemical constituents were identified in L. litseifolius leaves， primarily consisting of flavonoids， organic acids， and others. A total of 16， 13， 11， and 5 prototype components were identified in intestinal wall metabolism， intestinal flora metabolism， hepatic metabolism， and comprehensive metabolic plasma samples， respectively. Additionally， 4 prototype components were detected in brain tissue and 9 in cerebrospinal fluid. Phloridzin， trilobatin， phloretin-2- O -malonyl hexoside， and phloretin were identified as common components across all sample types. CONCLUSIONS Prototype components absorbed into blood and brain of L. litseifolius leaves， such as phloridzin， trilobatin， phloretin， and other components may serve as the pharmacological material basis for their therapeutic effects on central nervous system diseases.

Collagen is a major structural protein in the matrix of animal cells and the most widely distributed and abundant functional protein in mammals. Collagen’s good biocompatibility, biodegradability and biological activity make it a very valuable biomaterial. According to the source of collagen, it can be broadly categorized into two types: one is animal collagen; the other is recombinant collagen. Animal collagen is mainly extracted and purified from animal connective tissues by chemical methods, such as acid, alkali and enzyme methods, etc. Recombinant collagen refers to collagen produced by gene splicing technology, where the amino acid sequence is first designed and improved according to one’s own needs, and the gene sequence of improved recombinant collagen is highly consistent with that of human beings, and then the designed gene sequence is cloned into the appropriate vector, and then transferred to the appropriate expression vector. The designed gene sequence is cloned into a suitable vector, and then transferred to a suitable expression system for full expression, and finally the target protein is obtained by extraction and purification technology. Recombinant collagen has excellent histocompatibility and water solubility, can be directly absorbed by the human body and participate in the construction of collagen, remodeling of the extracellular matrix, cell growth, wound healing and site filling, etc., which has demonstrated significant effects, and has become the focus of the development of modern biomedical materials. This paper firstly elaborates the structure, type, and tissue distribution of human collagen, as well as the associated genetic diseases of different types of collagen, then introduces the specific process of producing animal source collagen and recombinant collagen, explains the advantages of recombinant collagen production method, and then introduces the various systems of expressing recombinant collagen, as well as their advantages and disadvantages, and finally briefly introduces the application of animal collagen, focusing on the use of animal collagen in the development of biopharmaceutical materials. In terms of application, it focuses on the use of animal disease models exploring the application effects of recombinant collagen in wound hemostasis, wound repair, corneal therapy, female pelvic floor dysfunction (FPFD), vaginal atrophy (VA) and vaginal dryness, thin endometritis (TE), chronic endometritis (CE), bone tissue regeneration in vivo, cardiovascular diseases, breast cancer (BC) and anti-aging. The mechanism of action of recombinant collagen in the treatment of FPFD and CE was introduced, and the clinical application and curative effect of recombinant collagen in skin burn, skin wound, dermatitis, acne and menopausal urogenital syndrome (GSM) were summarized. From the exploratory studies and clinical applications, it is evident that recombinant collagen has demonstrated surprising effects in the treatment of all types of diseases, such as reducing inflammation, promoting cell proliferation, migration and adhesion, increasing collagen deposition, and remodeling the extracellular matrix. At the end of the review, the challenges faced by recombinant collagen are summarized: to develop new recombinant collagen types and dosage forms, to explore the mechanism of action of recombinant collagen, and to provide an outlook for the future development and application of recombinant collagen.

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Objective To study the effect of wall thickness on the accuracy(trueness and precision)of 3D printed models.Methods The 3D scanning data of the standard gypsum dental arch model was imported into Exocad software.And four sets of models were de-signed,including horseshoe shaped solid model and horseshoe shaped hollow models with different wall thicknesses(2 mm,3 mm,4 mm).On the first and seventh day after printing,the 3D scanning data of resin models were imported into Geomagic software.Deviation analysis were performed on 3D printed models for the root mean square(root mean square,RMS).Results The trueness range of the four groups of printed models on the first day was(34.63±4.17)μm to(45.26±6.50)μm,there was no statistical difference.The pre-cision range was(30.25±10.18)μm to(47.65±14.77)μm,and the precision of the solid group was lower than the other three groups(P＜0.05).The trueness range of the four groups of printing models on the 7th day was(49.00±9.11)μm to(69.25±9.70)μm.The trueness of the 2 mm wall thickness group was lower than that of the solid group and the 4 mum wall thickness group(P＜0.05).Con-clusion The accuracy of printing models with different wall thicknesses was within the clinical acceptance range.There was no statisti-cally significant difference in the trueness values of the four groups of printing models on the first day.The precision value of the solid group was the lowest.On the 7th day,the trueness of the wall thickness of 2 mm group was lower than that of the solid group and the 4 mum wall thickness group.

Undifferentiated spindle cell sarcoma of the prostate is clinically rare. This article reports a case of a 29-year-old male who presented on February 7，2022，with a two-week history of localized pain in the perineal area and spermatic cord. The diagnosis of prostatic undifferentiated spindle cell sarcoma was confirmed by imaging studies and prostate needle biopsy pathology. After consultation by the urologic oncology multidisciplinary team and considering the patient's preference，a treatment plan of radical radiotherapy combined with chemotherapy，immunotherapy，and targeted therapy was adopted，Partial stereotactic body radiotherapy（P-SBRT）was delivered to the tumor center with a total dose of 74.4 Gy，combined with cisplatin and pembrolizumab. Lung metastasis progression occurred 1.5 months after radiotherapy，and treatment was switched to a combination of pirarubicin，ifosfamide，pembrolizumab，and bevacizumab. After 39 months of follow-up，the disease remained well-controlled with preserved organ function and long-term survival. This case，utilizing a multidisciplinary comprehensive diagnosis and treatment model，provides a reference for organ-preserving non-surgical management in patients with prostate soft tissue sarcoma.

Objective To observe the feasibility of transesophageal echocardiography(TEE)combined with agitated saline contrast echocardiography(ASCE)for identifying morphological characteristics of high-risk patent foramen ovale(PFO)and evaluating the risk of PFO related stroke.Methods Totally 212 PFO patients diagnosed by TEE combined with ASCE were enrolled,including 100 cases with cryptogenic stroke(CS)(CS group)and 112 without CS(non-CS group).Anatomical morphological characteristics of PFO were comparatively analyzed between groups to screen the independent factors of CS.Results In CS group,the left and right atrial opening diameters of PFO were all larger than those in non-CS group in both resting-state and stimulated state.The aortic root diameter in CS group was larger than that in non-CS group,and the incidence of atrial septal aneurysm(ASA),high activity of the atrial septum,inferior vena cava valve or Chiari network,large amount of right-to-left-shunt(RLS)in stimulated state,and multiple outlets of the oval valve in CS group were all higher than those in non-CS group(all P＜0.05).Logistic regression analysis showed that ASA,high atrial septal activity,large amount of RLS and multiple oval valve outlets were all independent factors associated with CS(OR=0.211,0.384,0.999,0.199,all P＜0.05).Conclusion TEE combined with ASCE could identify anatomical characteristics of high-risk PFO and assess the risk of PFO related stroke.

OBJECTIVE To investigate the deglycosylation metabolism of dioscin in vivo and the changes of its anti-tumor activi-ty of its deglycosylated metabolites.METHODS An LC-MS/MS analysis method for simultaneous determination of dioscin and its deglycosylation metabolites was established to study the cumulative excretion amount of dioscin and its deglycosylated metabolites in rat feces after oral administration.To mimic its deglycosylation metabolism,HPLC method was applied to investigate the time-dependent changes in the prototype components and metabolites of dioscin after incubation in artificial gastric juice.Solid-phase extraction tech-nology was employed to isolate the product of dioscin following hydrolysis by artificial gastric juice.The cytotoxic effects of this product on human colon cancer cells HCT-116 were assessed using the CCK-8 assay across different hydrolysis time periods.Concurrently,the enzymatic activities of caspase-3 and caspase-9,along with the expression levels of cytochrome C,were measured to elucidate the impact of dioscin post-hydrolysis on the cytotoxicity against HCT-116 cells.RESULTS Dioscin and its series of deglycosylated me-tabolites were detected in rat feces,revealing no significant differences in the cumulative excretion amounts of Polyphyllin Ⅴ and Pro-genin Ⅱ.Dioscin was shown to generate a range of deglycosylated metabolites in artificial gastric juice.Furthermore,dioscin and its deglycosylated metabolites inhibited the proliferation of HCT-116 cells,induced morphological changes,and increased the enzymatic activities of caspase-3 and caspase-9,as well as cytochrome C expression.However,it was observed that the antitumor activity of the deglycosylated metabolites diminished with prolonged hydrolysis time.CONCLUSION The deglycosylation metabolism of dioscin sig-nificantly attenuates its inhibitory effect on the proliferation of HCT-116 cells.Suppressing the acid-mediated or gut microbiota-medi-ated deglycosylation metabolism may be a promising strategy to preserve its antitumor activity.

Ulcerative colitis(UC)is a chronic inflammatory bowel disease affecting the colon(particularly the descending colon and sigmoid)and rectum.UC primarily presents with persistent or recurrent diarrhea,abdominal pain,bloody stools,and other symptoms.The primary pathological mechanism of UC involves intestinal barrier injury.When the intestinal barrier function is compromised,characterized by loss of epithelial layer integrity,thinning of the mucus layer,and microbiota dysregulation,pathogenic microorganisms can infiltrate the lamina propria from the intestinal lumen through the damaged barrier,triggering and exacerbating the intestinal inflammatory response.Current treatments for UC are limited by high costs,numerous adverse reactions,and a high likelihood of relapse.Consequently,there is an urgent need for the development of new drugs that can effectively and safely treat UC.Natural products have become significant research targets in treating various diseases due to their broad biological activity,multiple action targets,low toxicity,and easy availability.They play a crucial role in the targeted repair of the intestinal barrier,with potential mechanisms including enhancing intes-tinal epithelial cells and their secreted proteins,regulating gut microbiota and its metabolism,and balancing immune cell subsets.Additionally,it is essential to consider the synergistic effects,bioavailability,and safety of natural products.This paper summarizes the natural products reported in the past five years for their anti-UC properties by repairing the intestinal barrier,providing a theoretical basis for the development and application of natural products in anti-UC drugs.

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of toripalimab （Tor） combined with chemotherapy （CT） in the treatment of locally advanced or metastatic non-small cell lung cancer （NSCLC）. METHODS PubMed， the Cochrane Library， Embase， Web of Science， CBM， CNKI， Wanfang Data， and Health Technology Assessment （HTA） related websites were searched to collect the HTA reports， systematic reviews/meta-analyses and pharmacoeconomic studies of Tor+CT in the treatment of locally advanced or metastatic NSCLC from database/website inception to March 31， 2025. After data extraction and quality evaluation， the results of the included studies were analyzed descriptively. RESULTS A total of eleven studies were included， involving five systematic reviews/meta-analyses， and six pharmacoeconomic studies. Among the five systematic reviews/ meta-analyses， two were of high quality， while there was one each of moderate， low， and very low quality. All six pharmacoeconomic studies were of good quality. In terms of efficacy， compared with CT， Tor+CT significantly improved patients’ progression-free survival （PFS） and overall survival （P＜0.05）. In addition， compared with ipilimumab+CT， durvalumab， durvalumab+tremelimumab and sugemalimab+CT， Tor+CT could also improve the PFS （P＜0.05）. In terms of safety， there was no significant difference in the incidence of grade≥3 adverse events between patients receiving Tor+CT and CT （P＞0.05）； while Tor+CT had a lower incidence of grade≥3 adverse E-mail： events， compared with camrelizumab+CT， pembrolizumab+ 3233255290@qq.com ipilimumab， nivolumab+CT and atezolizumab+CT （P＜0.05）.In terms of cost-effectiveness， Tor+CT treatment had certain cost-effectiveness advantages， compared with CT. CONCLUSIONS Compared with CT， other programmed death-1/programmed death-ligand 1 inhibitors alone， or their combination with CT， Tor+CT for the treatment of locally advanced or metastatic NSCLC has good efficacy， safety and cost-effectiveness.