Background: Disorders of the blood-brain barrier (BBB) arising from diabetes mellitus are closely related to diabetic encephalopathy. Previous research has suggested that neuron-glia antigen 2 (NG2)-glia plays a key role in maintaining the integrity of the BBB. However, the mechanism by which NG2-glia regulates the diabetic BBB remains unclear. Methods: Type 2 diabetes mellitus (T2DM) db/db mice and db/m mice were used. Evans-Blue BBB permeability tests and transmission electron microscopy techniques were applied. Tight junction proteins were assessed by immunofluorescence and transmission electron microscopy. NG2-glia number and signaling pathways were evaluated by immunofluorescence. Detection of matrix metalloproteinase-9 (MMP-9) in serum was performed using enzyme-linked immunosorbent assay (ELISA). Results: In T2DM db/db mice, BBB permeability in the hippocampus significantly increased from 16 weeks of age, and the structure of tight junction proteins changed. The number of NG2-glia in the hippocampus of db/db mice increased around microvessels from 12 weeks of age. Concurrently, the expression of MMP-9 increased in the hippocampus with no change in serum. Sixteen- week-old db/db mice showed activation of the Wnt/β-catenin signaling in hippocampal NG2-glia. Treatment with XAV-939 improved structural and functional changes in the hippocampal BBB and reduced MMP-9 secretion by hippocampal NG2-glia in db/db mice. It was also found that the upregulation of β-catenin protein in NG2-glia in the hippocampus of 16-week-old db/db mice was significantly alleviated by treatment with XAV-939. Conclusion The results indicate that NG2-glia can lead to structural and functional disruption of the diabetic BBB by activating Wnt/β-catenin signaling, upregulating MMP-9, and degrading tight junction proteins.

Background: and Purpose Live cell-based assays (LCBA) are increasingly used for serological antibody detection due to their ability to preserve antigen conformation, offering moderately higher sensitivity than fixed cell-based assays. However, the clinical necessity of prioritizing LCBA for the detection of aquaporin-4 immunoglobulin G (AQP4-IgG) in neuromyelitis optica spectrum disorder (NMOSD) remains unclear, especially when compared to its established role in diagnosing myelin oligodendrocyte glycoprotein antibody-associated disease. Methods: We compared the performance of live cell-based assays using immunofluorescence (LCBA-IF) and fixed cell-based assays using immunofluorescence (FCBA-IF) in detecting AQP4-IgG in 90 cases of NMOSD meeting 2015 International Panel for Neuromyelitis Optica Diagnosis criteria, alongside 40 controls. Additionally, we further investigated the relationship between AQP4-IgG titers as measured by LCBA-IF and FCBA-IF and clinical parameters in NMOSD patients. Results: Results showed 96.9% agreement between LCBA-IF and FCBA-IF (Cohen’s κ=0.935), with a strong Spearman correlation (0.977, p<0.001). Both methods demonstrated 100% specificity, with LCBA-IF showing slightly higher sensitivity compared to FCBA-IF. Within LCBAIF-tested groups, statistically significant differences in annualized relapse rates were observed across all pairwise comparisons (low-titer vs. moderate-titer, low-titer vs. high-titer, and moderate-titer vs. high-titer; all p<0.050). However, this association reached statistical significance in some FCBA-IF-tested groups. Conclusions Overall, there is a strong concordance between LCBA-IF and FCBA-IF in detecting AQP4-IgG, where LCBA-IF shows slightly higher sensitivity. Furthermore, there is a potential link between elevated AQP4-IgG titers and an increased risk of relapse, and this correlation may appear more pronounced when using LCBA-IF.

Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

BACKGROUND:Pulmonary arterial hypertension is a destructive cardiopulmonary disease for which there is no cure.An association between plasma proteins and pulmonary arterial hypertension has been suggested,but the causal relationship has not been specifically elucidated.OBJECTIVE:To elucidate the causal relationship between plasma proteome and pulmonary arterial hypertension using a two-sample Mendelian randomization method,thereby searching for potential therapeutic targets for pulmonary arterial hypertension.METHODS:Plasma Protein Gene-Wide Association Analysis Statistics for 4 907 Aptamer Measurements in 35 559 Icelanders from the Icelandic Database;Genome-wide association analysis statistics for pulmonary arterial hypertension were obtained from the Finn Gen database,version R9,including 234 cases and 265 626 controls.Analyses were performed using Mendelian randomization and Bayesian co-localization analysis,the findings were examined using sensitivity analyses,and protein-protein interaction network maps were constructed to explore the causal relationship between plasma proteins and pulmonary arterial hypertension.RESULTS AND CONCLUSION:(1)The results of inverse variance weighting,maximum likelihood and Wald ratio methods showed 19 proteins causally associated with pulmonary arterial hypertension(P＜0.05).Among them,10 plasma proteins,including Beta-1,3-N-acetylglucosaminyltransferase manic fringe(odds ratio[OR]=0.12,95％confidence interval[CI]0.02-0.61,P=0.01)and interferon alpha/beta receptor 1(OR=0.45,95％CI 0.24-0.84,P=0.012),might be associated with a reduced risk of pulmonary arterial hypertension.In contrast,nine plasma proteins,such as glucoside xylosyltransferase 1(OR=3.48,95％CI 1.51-8.00,P=0.003)and plasminogen(OR=42.78,95％CI 2.49-734.31,P=0.01),might be associated with an increased risk of pulmonary arterial hypertension.After the false discovery rate was corrected,19 proteins remained significantly associated with pulmonary arterial hypertension.(2)Multiple sensitivity analyses such as the MR-Egger intercept test and leave-one-out method showed no horizontal multiplicity or heterogeneity in the results of the study,indicating the stability of the study's results.(3)Bayesian co-localization analysis showed that six plasma proteins,including plasminogen(PPH4=1.0)and glucoside xylosyltransferase 1(PPH4=0.94),had PPH4＞0.8,suggesting that plasma proteins and the genome-wide association study of pulmonary arterial hypertension had similar causal variance in terms of genetic association.(4)By constructing a protein-protein interaction network map,plasminogen,Annexin A1,fibrinogen gamma chain and matrix metalloproteinase 7 were found to be core proteins.(5)The article used Mendelian randomization analysis to reveal a potential causal association between 4 907 plasma proteins and pulmonary arterial hypertension,suggesting that plasma proteins may be potential therapeutic targets for pulmonary arterial hypertension.The core proteins identified in the study also provide a theoretical basis for further in-depth study of the pathophysiological mechanisms of pulmonary arterial hypertension.Secondly,analyses using the large-scale international databases of Iceland and FinnGen provide new research directions and treatment ideas for pulmonary arterial hypertension in specific populations and environments,as well as ideas and methods that can be used to prevent and treat pulmonary arterial hypertension in China.

BACKGROUND:Pulmonary arterial hypertension is a destructive cardiopulmonary disease for which there is no cure.An association between plasma proteins and pulmonary arterial hypertension has been suggested,but the causal relationship has not been specifically elucidated.OBJECTIVE:To elucidate the causal relationship between plasma proteome and pulmonary arterial hypertension using a two-sample Mendelian randomization method,thereby searching for potential therapeutic targets for pulmonary arterial hypertension.METHODS:Plasma Protein Gene-Wide Association Analysis Statistics for 4 907 Aptamer Measurements in 35 559 Icelanders from the Icelandic Database;Genome-wide association analysis statistics for pulmonary arterial hypertension were obtained from the Finn Gen database,version R9,including 234 cases and 265 626 controls.Analyses were performed using Mendelian randomization and Bayesian co-localization analysis,the findings were examined using sensitivity analyses,and protein-protein interaction network maps were constructed to explore the causal relationship between plasma proteins and pulmonary arterial hypertension.RESULTS AND CONCLUSION:(1)The results of inverse variance weighting,maximum likelihood and Wald ratio methods showed 19 proteins causally associated with pulmonary arterial hypertension(P＜0.05).Among them,10 plasma proteins,including Beta-1,3-N-acetylglucosaminyltransferase manic fringe(odds ratio[OR]=0.12,95％confidence interval[CI]0.02-0.61,P=0.01)and interferon alpha/beta receptor 1(OR=0.45,95％CI 0.24-0.84,P=0.012),might be associated with a reduced risk of pulmonary arterial hypertension.In contrast,nine plasma proteins,such as glucoside xylosyltransferase 1(OR=3.48,95％CI 1.51-8.00,P=0.003)and plasminogen(OR=42.78,95％CI 2.49-734.31,P=0.01),might be associated with an increased risk of pulmonary arterial hypertension.After the false discovery rate was corrected,19 proteins remained significantly associated with pulmonary arterial hypertension.(2)Multiple sensitivity analyses such as the MR-Egger intercept test and leave-one-out method showed no horizontal multiplicity or heterogeneity in the results of the study,indicating the stability of the study's results.(3)Bayesian co-localization analysis showed that six plasma proteins,including plasminogen(PPH4=1.0)and glucoside xylosyltransferase 1(PPH4=0.94),had PPH4＞0.8,suggesting that plasma proteins and the genome-wide association study of pulmonary arterial hypertension had similar causal variance in terms of genetic association.(4)By constructing a protein-protein interaction network map,plasminogen,Annexin A1,fibrinogen gamma chain and matrix metalloproteinase 7 were found to be core proteins.(5)The article used Mendelian randomization analysis to reveal a potential causal association between 4 907 plasma proteins and pulmonary arterial hypertension,suggesting that plasma proteins may be potential therapeutic targets for pulmonary arterial hypertension.The core proteins identified in the study also provide a theoretical basis for further in-depth study of the pathophysiological mechanisms of pulmonary arterial hypertension.Secondly,analyses using the large-scale international databases of Iceland and FinnGen provide new research directions and treatment ideas for pulmonary arterial hypertension in specific populations and environments,as well as ideas and methods that can be used to prevent and treat pulmonary arterial hypertension in China.

ObjectiveTo explore the factors influencing home-based rehabilitation exercise and the needs for digital interventions among patients with spinal muscular atrophy (SMA), based on the behavior change wheel (BCW), and to provide evidence for the development of digital home-based rehabilitation interventions. MethodsA two-phase qualitative study was conducted from December, 2024 to March, 2025. Using convenience sampling, 14 participants were recruited, including patients with SMA, primary caregivers, rehabilitation professionals, clinicians, a patient organization representative and a health policy expert. In phase 1, semi-structured individual interviews were conducted with seven participants, including patients, caregivers and a patient organization representative, to identify factors influencing home-based rehabilitation exercise and unmet needs. In phase 2, a focus group involving 12 stakeholders was conducted, including five participants who had participated in phase 1, to explore requirements for the functions, knowledge content and interface design of a digital intervention, five of them had participated in phase 1. Overall, the two phases involved 14 individual participants, accounting for 19 participant-instances. Thematic analysis was performed using both deductive and inductive approaches, guided by the capability-opportunity-motivation-behavior (COM-B) model. ResultsSix themes were identified. phase 1 showed that patients with SMA experienced inadequate continuity of rehabilitation services and limited access to professional rehabilitation resources, with interruptions in institution-based rehabilitation coexisting with declining adherence to home-based exercise. Home-based rehabilitation exercise was jointly influenced by capability-, opportunity- and motivation-related factors, including limited capabilities of patients and caregivers, constraints in time and supportive conditions and insufficient goals, feedback, and incentives. Individualized rehabilitation plans and professional guidance were the major unmet needs. phase 2 showed that the core functions of a digital intervention should include individualized exercise plans, professional guidance and feedback, reminders and incentives, safety monitoring, remote assessment, and privacy and permission management. Core knowledge content should include stratified exercise guidance, caregiving skills, recognition of abnormal conditions, and information on when and how to seek help. The interface should be simple, impose a low user burden and accommodate different types of users. ConclusionHome-based rehabilitation exercise among patients with SMA is jointly influenced by multiple capability-, opportunity- and motivation-related factors. Digital interventions should prioritize individualized rehabilitation plans, professional guidance and sustained behavioral support. These findings may inform the development of a digital home-based rehabilitation intervention prototype for patients with SMA; its feasibility, safety, clinical effectiveness and economic value require further evaluation.

Pheochromocytoma is a neuroendocrine tumor that produces catecholamines, leading to elevated blood pressure and metabolic changes in patients. It can result in serious complications affecting the heart, brain, kidneys, and blood vessels, potentially becoming a primary cause of death. Most pheochromocytoma patients present with atypical symptoms, making misdiagnosis or missed diagnosis common. This article reports a case of pheochromocytoma crisis misdiagnosed as severe viral myocarditis and includes a review of the relevant literature.

Objective:To evaluate the efficacy and feasibility of a domestically developed robotic surgical system based on fiber-optic dedicated line communication in cross-regional urological telesurgery.Methods:This was multicenter，single-arm，retrospective case series study. The data of patients who underwent urological telesurgeries using the telesurgical system between January 2023 and December 2024 were analyzed. The cohort included 59 patients from seven hospitals across China. Among the patients，47 were male（79.7%）and 12 were female（20.3%），with a median age of 63.0（56.0，68.0）years and a body mass index of（24.7 ± 3.0）kg/m 2. Surgical procedures included 32 radical prostatectomies，24 partial nephrectomies，one radical nephrectomy，one adrenalectomy，and one ureteral reconstruction. The perioperative indicators，pathological results and postoperative complications were analyzed. The network monitoring data were collected，and the perioperative data of patients，remote system monitoring data and costs were compared between the two communication modes of optical transport network（OTN）and cloud-connect network（CCN）. Results:All 59 remote surgeries were successfully completed，with a mean operative time of（138.0 ± 54.0）minutes，median intraoperative blood loss of 50.0（30.0，100.0）ml and a postoperative hospital stay of 5.0（4.0，6.0）days. No cases required reoperation，Clavien-Dindo grade ≥3 complications，or readmission. The geographical distance between the primary and remote surgical sites ranged from 450 to 2 800 km. Network monitoring revealed increased bidirectional latency with distance increasing：the shortest latency time（Hefei-Hangzhou，450 km）was（16.59 ± 0.80）ms，while the longest（Harbin-Hangzhou，2 200 km）latency time was（53.31 ± 0.31）ms. Average frame loss per procedure was 0?1.27 frames. The results of subgroup analysis comparing OTN and CCN communication modes showed no significant differences in operative time［（130.7 ± 70.5）minutes vs.（142.1 ± 42.9）minutes， P = 0.442］，postoperative hospitalization［6.0（4.0，8.0）d vs. 5.0（4.0，6.0）d， P = 0.581］，or readmission rates（0 vs. 0）. However，CCN demonstrated significant cost advantages with 500 RMB per operation vs. 3 000 RMB per operation for OTN. Conclusions:Urological telesurgery using fiber-optic communication is feasible. The CCN mode，with its cost-effectiveness，excellent usability，and multi-point interconnection flexibility，is currently the preferred communication model for telesurgical applications.

Standardised emergency management protocols for hand injury in microsurgery is critical, as it directly determines ultimate clinical outcomes. This consensus consolidates expert insights regarding diagnostic and treatment procedure for hand injury in microsurgery, emergency support protocols and key points of emergency workflow optimisation. It summarises the opinions of experts and puts forward standardised recommendations to guide clinical practice in microsurgical treatment process, so as to further improve the quality of treatment for hand injury in microsurgery and maximise the protection of limb function and quality of life of patients.

Objective To investigate the status of management of iodinated contrast media(ICM)extravasation in Henan Province,as well as nurses' knowledge and influencing factors,in order to provide a basis for optimizing management strategies.Methods A self-designed questionnaire was applied,employing convenience sampling,to survey nursing administrators and nurses in the radiology departments of 55 tertiary hospitals across 16 regions of Henan Province,from December 2024 to January 2025.Multiple linear regression analysis was conducted to explore the factors influencing nurses' knowledge.Results A total of 55 nursing administrators and 64 nurses participated,with a valid questionnaire response rate of 100％.The survey results reveal that only 5.45％of radiology depart-ments utilized high-pressure central venous catheters,and 32.73％employed vascular visualization techniques.When setting the high-pressure injection speed for ICM,only 54.55％of radiology departments required an assessment of the type and model of intravenous access.Additionally,only 9.09％of radiology departments mandated an observa-tion for 2 to 4 hours following ICM extravasation.Furthermore,only 50.91％of radiology departments had estab-lished an information system for ICM use.The nurses' knowledge score regarding the prevention and management of ICM extravasation was(90.00±17.59),influenced by years of experience in radiology and professional titles(P＜0.05).Conclusion The prevention and management measures for ICM in radiology departments in Henan Province need further improvement.Nursing administrators should optimize management strategies,improve relevant training systems,and continuously enhance nurses' knowledge and practical abilities.