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 analyze the epidemiological characteristics of 8 major respiratory pathogens in influenza-like illness (ILI) cases with acute respiratory infections at fever clinics in Huangpu District, Shanghai from 2015 to 2024, and to provide a scientific basis for the prevention and treatment of respiratory diseases. MethodsA retrospective study was conducted in Huangpu District. Individuals meeting the case definition of ILI from 2015 to 2024 was registered. Their nasopharyngeal swabs were collected for pathogen detection. A total of 8 respiratory viruses were tested, including Influenza A virus (Flu A), Influenza B virus (Flu B), adenovirus (ADV), enterovirus/human rhinovirus (EV/HRV), human parainfluenza virus (HPIV), human coronavirus (HCoV), respiratory syncytial virus (RSV), and human metapneumovirus (HMPV). ResultsFrom 2015 to 2019, a total of 344 ILI cases were tested, of which 192 out of 344 cases (55.81%) were tested positive for single respiratory pathogen. From 2023 to 2024, 1 557 ILI cases were tested, with 572 out of 1 557 cases (36.74%) being positive for single pathogen. From 2023 to 2024, the positive rate of single pathogen in ILI cases was significantly lower than that in 2015‒2019 (χ²=42.66, P<0.001). Specifically, the positive rate of Flu A (χ²=74.43, P<0.001) decreased, while that of HPIV (χ²=8.66, P=0.003) increased, both with statistically significant differences. According to the seasonal pattern, the epidemic intensity of Flu A decreased in summer, while that of HPIV increased in summer and autumn. Demographic results showed statistically significant differences in the positive rates of EV/HRV between genders (χ²=22.38, P<0.001), with males exhibiting a higher positive rate than females. No statistically significant differences were identified in the positive rates of single pathogen among different age groups (χ²=4.42, P=0.110). Nevertheless, statistically significant differences were noted when comparing the positive rates of EV/HRV, Flu A, Flu B and HPIV across different age groups (P<0.05). EV/HRV was more commonly detected in the 15‒<25 age group (10.93%), while Flu A and HPIV had the highest positive rates in the ≥60 age group (21.24% and 4.77%). Flu B had the highest positive rate in the 25‒<60 age group (11.26%). 52.63% of cases with co-infections occurred during winter, with the primary pathogens involved being EV/HRV (9 cases) and HCoV (6 cases). The most prevalent combination of co-infection was Flu A with EV/HRV. ConclusionThe prevalence of respiratory pathogens among ILI cases from 2023 to 2024 exhibited notable fluctuations compared to that from 2015 to 2019. Therefore, influenza surveillance should be strengthened, and attention should also be paid to the prevalence of respiratory pathogens such as HPIV. These findings have profound implications for future research, surveillance, vaccine planning, and public health policy making.

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.

Objective: To define the mechanism by which swine TRIM25 restricts vesicular stomatitis virus replication. Methods: Porcine 3D4/21 cells with TRIM25 overexpression or knockdown were infected with vesicular stomatitis virus. Viral replication was quantified by immunoblotting, quantitative reverse transcription polymerase chain reaction, and 50% tissue culture infectious dose assays. Type I interferon signaling was assessed by transcript quantification, interferon-beta and interferon-stimulated response element reporter assays, and co-immunoprecipitation.Viral RNA binding was tested by RNA immunoprecipitation. Results: TRIM25 overexpression reduced viral RNA and infectious titers, whereas TRIM25 knockdown increased replication (p < 0.01). TRIM25 increased interferon-beta and interferon-stimulated gene expression and enhanced interferon-beta and interferonstimulated response element promoter activity (p < 0.01). Mechanistically, TRIM25 promoted Lys63-linked ubiquitination of RIG-I and increased phosphorylation of TANK-binding kinase 1 and interferon regulatory factor 3. TRIM25 also bound vesicular stomatitis virus genomic RNA, and binding required the C-terminal region. Conclusions and Relevance: Porcine TRIM25 restricts vesicular stomatitis virus replication by amplifying type I interferon signaling and directly binding viral RNA.

ObjectiveTo optimize the technical parameters of mouse embryo transfer (including oviduct opening method, pseudopregnant recipient body weight, number of embryos transferred per recipient, and unilateral vs. bilateral oviduct transfer), improve the efficiency of embryo transfer (the pregnancy rate of recipient female mice after embryo transfer is used as the evaluation index), and improve the utilization rate of high-quality embryo germplasm resources (the birth rate of mice after embryo transfer is used as the evaluation index). Methods560 SPF-grade ICR mice and 440 C57BL/6J mice were used as experimental animals. 2-cell embryos were obtained through in vitro fertilization. A single-factor controlled variable method was used to systematically investigate the effects of four factors, including oviduct opening method, pseudopregnant recipient body weight, number of embryos transferred per recipient, and unilateral vs. bilateral oviduct transfer, on the pregnancy rate and birth rate of mouse embryo transfer. ResultsThe pregnancy rate of recipients with an opening made in the oviduct using a 26G syringe needle reached 90%, which was significantly higher than the 43% in the group with oviduct openings cut by Vannas scissors (P<0.05). Pseudopregnant recipients weighing 29-35 g exhibited optimal embryo transfer outcomes, with a pregnancy rate of 90% and a birth rate of 44%, and no pups were crushed by the recipient mothers. The highest birth rate of 42% was observed in the group receiving 16-25 embryos per recipient. Transferring 26-35 embryos per recipient achieved a 90% pregnancy rate and maximized embryo utilization efficiency. However, transfer efficiency decreased significantly when more than 35 embryos were transferred. Transfer of 24-26 embryos per recipient balanced relatively high pregnancy and birth rates. Bilateral oviduct transfer of mouse embryos yielded slightly higher pregnancy and birth rates than unilateral transfer, but the difference was not statistically significant (P>0.05). ConclusionSelecting pseudopregnant recipient female mice weighing 29-35 g, using a 26G syringe needle to make an opening in the oviduct, and controlling the number of transferred embryos at 24-26 per recipient can effectively improve the success rate of embryo transfer and achieve efficient utilization of high-quality embryo germplasm resources.

ObjectiveTo compare the application value of two endoscopic ultrasound （EUS）-guided targeted vascular embolization techniques in secondary prevention of esophagogastric variceal bleeding （EGVB）， and to clarify the clinical advantages of targeted main trunk embolization. MethodsA retrospective analysis was performed for 59 patients who were admitted to Beijing Ditan Hospital， Capital Medical University， from April 2023 to July 2024 and received secondary prevention of gastroesophageal varices （GOV）-type EGVB， and according to the surgical procedure， they were divided into EUS-PCSS targeting the distal segment of the source vessel or perforating branch vessels （EUS-PCSS-D/P） group with 29 patients and EUS-PCSS targeting the source vascular trunk （EUS-PCSS-T） group with 30 patients. The two groups were observed in terms of rebleeding rate， variceal eradication efficiency， and the incidence rate of adverse events. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups； the Mann-Whitney U test was used for subgroup analysis， and ordinal Logistic regression was used for multivariate analysis. ResultsThere were no significant differences in baseline data between the two groups （all P>0.05）. Compared with the EUS-PCSS-D/P group， the EUS-PCSS-T group had a significantly smaller diameter of punctured vessels （5.39±2.03 mm vs 7.00±2.21 mm， t=3.012， P=0.005）， a significantly lower treatment rate of supplementary endoscopic injection sclerotherapy （EIS） （40.00% vs 79.31%， χ²=7.521， P=0.006）， and a significantly lower amount of lauromacrogol used （16.08±7.25 mL vs 22.17±6.83 mL， t=2.518， P=0.015）， and there were no significant differences between the two groups in the amount of tissue adhesive used， the number of puncture sites， and treatment costs （all P>0.05）. There were no significant differences between the two groups in rates of GOV-related and all-cause gastrointestinal rebleeding （all P>0.05）. Compared with the EUS-PCSS-D/P group， the EUS-PCSS-T group had a significantly lower number of treatment sessions required for GOV eradication （2.00 ［1.25 — 2.00］ vs 3.00 ［2.00 — 4.00］， Z=3.872， P<0.001）， with a higher two-session eradication rate （50.00% vs 17.86%， χ²=7.102， P=0.008） and a lower eradication rate for three or more sessions （23.33% vs 71.43%， χ²=15.326， P<0.001）. The subgroup analysis showed that history of endoscopic treatment and supplementary EIS did not affect the number of treatment sessions required for GOV regression （all P>0.05）， and the ordinal Logistic regression analysis showed that treatment grouping was an independent influencing factor for the number of treatment sessions required for GOV regression （odds ratio=0.32， 95% confidence interval： 0.15 — 0.68， P=0.007）. There was no significant difference in the incidence rate of adverse events between the two groups （P>0.05）， and no ectopic embolism was observed in the EUS-PCSS-T group. ConclusionThe EUS-PCSS-T procedure can significantly improve the eradication efficiency of GOV and reduce the number of treatment sessions； its efficacy is not affected by history of endoscopic treatment or supplementary EIS therapy， and it has a favorable safety profile.

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.

OBJECTIVES: To investigate the effect of Haematococcus pluvialis (HP) on bleomycin (BLM)-induced pulmonary fibrosis in mice and on TGF-β1-induced human fetal lung fibroblasts (HFL1). METHODS: Thirty male C57BL/6 mice were randomly divided into control group, BLM-induced pulmonary fibrosis model group, low- and high-dose HP treatment groups (3 and 21 mg/kg, respectively), and 300 mg/kg pirfenidone (positive control) group. The effects of drug treatment for 21 days were assessed by examining respiratory function, lung histopathology, and expression of fibrosis markers in the lung tissues of the mouse models. In TGF-β1-induced HFL1 cell cultures, the effects of treatment with 120, 180 and 240 μg/mL HP or 1.85 μg/mL pirfenidone for 48 h on expression levels of fibrosis markers were evaluated. Transcriptome analysis was carried out using the control cells and cells treated with TGF-β1 and 240 μg/mL HP. RESULTS: HP obviously alleviated BLM-induced lung function damage and fibrotic changes in mice, evidenced by improved respiratory function, lung tissue morphology and structure, inflammatory infiltration, and collagen deposition and reduced expressions of fibrotic proteins. HP at the high dose produced similar effect to PFD. In TGF-β1-induced HFL1 cells, treatment with 240 μg/mL HP significantly reduced the mRNA and protein expression levels of α-SMA and FN. Transcriptome analysis revealed that multiple key genes and pathways mediated the protective effect of HP against pulmonary fibrosis. CONCLUSIONS HP alleviates pulmonary fibrosis in both the mouse model and cell model, possibly as the result of the synergistic effects of its multiple active components.
Animals ; Pulmonary Fibrosis/chemically induced* ; Bleomycin/adverse effects* ; Mice, Inbred C57BL ; Male ; Mice ; Fibroblasts/drug effects* ; Lung/pathology* ; Transforming Growth Factor beta1/pharmacology* ; Myofibroblasts/drug effects* ; Humans ; Pyridones

The ambiguity of etiology makes temporomandibular joint osteoarthritis (TMJOA) "difficult-to-treat". Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management. Nonetheless, challenges such as low yields and insignificant efficacy of current exosome therapies necessitate significant advances. Addressing lower strontium (Sr) levels in arthritic synovial microenvironment, we studied the effect of Sr element on exosomes and miRNA selectively loading in synovial mesenchymal stem cells (SMSCs). Here, we developed an optimized system that boosts the yield of SMSC-derived exosomes (SMSC-EXOs) and improves their miRNA profiles with an elevated proportion of beneficial miRNAs, while reducing harmful ones by pretreating SMSCs with Sr. Compared to untreated SMSC-EXOs, Sr-pretreated SMSC-derived exosomes (Sr-SMSC-EXOs) demonstrated superior therapeutic efficacy by mitigating chondrocyte ferroptosis and reducing osteoclast-mediated joint pain in TMJOA. Our results illustrate Alix's crucial role in Sr-triggered miRNA loading, identifying miR-143-3p as a key anti-TMJOA exosomal component. Interestingly, this system is specifically oriented towards synovium-derived stem cells. The insight into trace element-driven, site-specific miRNA selectively loading in SMSC-EXOs proposes a promising therapeutic enhancement strategy for TMJOA.
MicroRNAs/metabolism* ; Mesenchymal Stem Cells/drug effects* ; Osteoarthritis/drug therapy* ; Exosomes/drug effects* ; Strontium/pharmacology* ; Synovial Membrane/cytology* ; Humans ; Animals ; Temporomandibular Joint Disorders/therapy* ; Temporomandibular Joint