ObjectiveMultiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS); however, its underlying neurological pathogenic mechanisms remain incompletely understood. Endogenous formaldehyde (FA), a metabolic byproduct of methylation-demethylation cycles, has recently been implicated in neurotoxicity, oxidative damage, and cognitive impairment. This study aimed to investigate whether excessive FA contributes to myelin sheath demyelination in mice and to evaluate the protective effects and mechanisms of two FA-elimination strategies: sodium bisulfite (NaHSO₃), a classical FA scavenger, and polyethylene glycol-modified astaxanthin nanoparticles (PEG-ATX@NPs), a brain-targeted nano-antioxidant formulation. MethodsA chronic demyelination model was established by feeding female C57BL/6J mice a diet containing 0.2% cuprizone (CPZ) for four weeks, followed by a two-week intervention period. Eighty mice were randomly assigned to four groups: NS (normal saline), CPZ+NS, CPZ+NaHSO₃, and CPZ+PEG-ATX@NPs. Behavioral tests, including open-field, Y-maze, and pole-climbing assays, were conducted to assess locomotor activity, motor coordination, and working memory. FA levels in serum, corpus callosum, and spinal cord were measured using an Na-FA fluorescent probe and quantified via in vivo and ex vivo fluorescence imaging. Neuroinflammatory responses were evaluated by measuring TNF-α, IL-1β, and IL-6 levels using ELISA, while oxidative stress was assessed by reactive oxygen species (ROS) fluorescence intensity. Demyelination was examined via Luxol fast blue staining, and microglial activation was analyzed by Iba1 immunofluorescence. Correlation analyses were performed to explore relationships among FA levels, inflammatory cytokines, ROS intensity, and behavioral parameters. ResultsCompared with the NS group, mice in the CPZ+NS group exhibited significant weight loss, impaired motor coordination and memory, and markedly reduced myelin regeneration (P<0.05). FA levels and pro-inflammatory cytokines were significantly elevated in serum, corpus callosum, and spinal cord (P<0.05). FA-associated fluorescence in brain and spinal tissues, as well as ROS intensity across all tissues examined, also increased substantially (P<0.05). CPZ treatment induced pronounced microglial activation and severe demyelination in the corpus callosum (P<0.01). Both NaHSO₃ and PEG-ATX@NPs effectively reduced FA accumulation in the brain and spinal cord, attenuated demyelination, suppressed microglial activation, decreased inflammatory cytokine levels, and improved motor and cognitive performance. These results confirm that CPZ induced severe demyelination accompanied by oxidative stress, neuroinflammation, and abnormal FA accumulation. Following intervention with either NaHSO₃ or PEG-ATX@NPs, endogenous FA levels in the CNS were substantially reduced. Both treatments alleviated demyelination and significantly decreased the number of activated microglia. Levels of TNF-α, IL-1β, and IL-6 in serum, corpus callosum, and spinal cord were downregulated. Behavioral performance improved significantly, as evidenced by enhanced locomotor activity, better coordination, and improved memory function. These findings indicate that both FA-scavenging agents mitigate CPZ-induced biochemical and behavioral abnormalities. ConclusionThis study demonstrates that excessive endogenous FA is closely associated with cognitive impairment, inflammatory dysregulation, and demyelination in a CPZ-induced chronic demyelination mouse model. Clearing abnormally elevated FA effectively reduces neuroinflammation, suppresses microglial overactivation, decreases oxidative stress, and alleviates demyelination, ultimately improving motor and cognitive outcomes in mice. These results suggest that targeting endogenous FA represents a promising therapeutic strategy for MS and other demyelinating disorders. Further investigations are warranted to explore the long-term safety, dosage optimization, and molecular pathways involved in FA-mediated neurotoxicity.

ObjectiveMultiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS); however, its underlying neurological pathogenic mechanisms remain incompletely understood. Endogenous formaldehyde (FA), a metabolic byproduct of methylation-demethylation cycles, has recently been implicated in neurotoxicity, oxidative damage, and cognitive impairment. This study aimed to investigate whether excessive FA contributes to myelin sheath demyelination in mice and to evaluate the protective effects and mechanisms of two FA-elimination strategies: sodium bisulfite (NaHSO₃), a classical FA scavenger, and polyethylene glycol-modified astaxanthin nanoparticles (PEG-ATX@NPs), a brain-targeted nano-antioxidant formulation. MethodsA chronic demyelination model was established by feeding female C57BL/6J mice a diet containing 0.2% cuprizone (CPZ) for four weeks, followed by a two-week intervention period. Eighty mice were randomly assigned to four groups: NS (normal saline), CPZ+NS, CPZ+NaHSO₃, and CPZ+PEG-ATX@NPs. Behavioral tests, including open-field, Y-maze, and pole-climbing assays, were conducted to assess locomotor activity, motor coordination, and working memory. FA levels in serum, corpus callosum, and spinal cord were measured using an Na-FA fluorescent probe and quantified via in vivo and ex vivo fluorescence imaging. Neuroinflammatory responses were evaluated by measuring TNF-α, IL-1β, and IL-6 levels using ELISA, while oxidative stress was assessed by reactive oxygen species (ROS) fluorescence intensity. Demyelination was examined via Luxol fast blue staining, and microglial activation was analyzed by Iba1 immunofluorescence. Correlation analyses were performed to explore relationships among FA levels, inflammatory cytokines, ROS intensity, and behavioral parameters. ResultsCompared with the NS group, mice in the CPZ+NS group exhibited significant weight loss, impaired motor coordination and memory, and markedly reduced myelin regeneration (P<0.05). FA levels and pro-inflammatory cytokines were significantly elevated in serum, corpus callosum, and spinal cord (P<0.05). FA-associated fluorescence in brain and spinal tissues, as well as ROS intensity across all tissues examined, also increased substantially (P<0.05). CPZ treatment induced pronounced microglial activation and severe demyelination in the corpus callosum (P<0.01). Both NaHSO₃ and PEG-ATX@NPs effectively reduced FA accumulation in the brain and spinal cord, attenuated demyelination, suppressed microglial activation, decreased inflammatory cytokine levels, and improved motor and cognitive performance. These results confirm that CPZ induced severe demyelination accompanied by oxidative stress, neuroinflammation, and abnormal FA accumulation. Following intervention with either NaHSO₃ or PEG-ATX@NPs, endogenous FA levels in the CNS were substantially reduced. Both treatments alleviated demyelination and significantly decreased the number of activated microglia. Levels of TNF-α, IL-1β, and IL-6 in serum, corpus callosum, and spinal cord were downregulated. Behavioral performance improved significantly, as evidenced by enhanced locomotor activity, better coordination, and improved memory function. These findings indicate that both FA-scavenging agents mitigate CPZ-induced biochemical and behavioral abnormalities. ConclusionThis study demonstrates that excessive endogenous FA is closely associated with cognitive impairment, inflammatory dysregulation, and demyelination in a CPZ-induced chronic demyelination mouse model. Clearing abnormally elevated FA effectively reduces neuroinflammation, suppresses microglial overactivation, decreases oxidative stress, and alleviates demyelination, ultimately improving motor and cognitive outcomes in mice. These results suggest that targeting endogenous FA represents a promising therapeutic strategy for MS and other demyelinating disorders. Further investigations are warranted to explore the long-term safety, dosage optimization, and molecular pathways involved in FA-mediated neurotoxicity.

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

The rapid development of artificial intelligence (AI), especially generative AI (GenAI), has already brought, and will continue to bring, revolutionary changes to our daily production and life, as well as create new opportunities and challenges for diagnostic and therapeutic practices in the medical field. Haihe Hospital of Tianjin University collaborates with the National Supercomputer Center in Tianjin, Tianjin University, and other institutions to carry out research in areas such as smart healthcare, smart services, and smart management. We have conducted research and development of a full-process disease diagnosis and treatment assistance system based on GenAI in the field of smart healthcare. The development of this project is of great significance. The first goal is to upgrade and transform the hospital's information center, organically integrate it with existing information systems, and provide the necessary computing power storage support for intelligent services within the hospital. We have implemented the localized deployment of three models: Tianhe "Tianyuan", WiNGPT, and DeepSeek. The second is to create a digital avatar of the chief physician/chief physician's voice and image by integrating multimodal intelligent interaction technology. With generative intelligence as the core, this solution provides patients with a visual medical interaction solution. The third is to achieve deep adaptation between generative intelligence and the entire process of patient medical treatment. In this project, we have developed assistant tools such as intelligent inquiry, intelligent diagnosis and recognition, intelligent treatment plan generation, and intelligent assisted medical record generation to improve the safety, quality, and efficiency of the diagnosis and treatment process. This study introduces the content of a full-process disease diagnosis and treatment assistance system, aiming to provide references and insights for the digital transformation of the healthcare industry.
Artificial Intelligence ; Humans ; Delivery of Health Care ; Generative Artificial Intelligence

AIM:To explore the clinical significance of stearoyl-CoA desaturase 1(SCD1)in colorectal can-cer and to evaluate the effects and mechanisms of diosgenin glucoside on the proliferation of colorectal cancer cells.METHODS:The expression of SCD1 in colorectal cancer tissues was assessed using qPCR and Western blot,and its cor-relation with clinical features was analyzed.The impact of diosgenin glucoside on the viability of SW620 and HCT116 cells was measured using the CCK-8 assay,and the proliferation was further investigated through cell cloning experiments.Ad-ditionally,the effects of diosgenin glucoside on apoptosis-related genes and SCD1 were evaluated by qPCR and Western blot.Molecular docking was employed to analyze the binding site and binding energy between diosgenin glucoside and SCD1.RESULTS:(1)Both SCD1 mRNA and protein were highly expressed in colorectal cancer tissues,with an 88%positive rate.And SCD1 mRNA expression correlated with cancer type and clinical stage.(2)Diosgenin glucoside de-creased the viability and cloning ability of SW620 and HCT116 cells in a dose-dependent manner.(3)Diosgenin gluco-side upregulated the mRNA and protein expression of pro-apoptotic proteins caspase-3 and Bax in a dose-dependent man-ner,while it downregulated the mRNA and protein expression of the anti-apoptotic protein Bcl-2.(4)Diosgenin glucoside reduced the mRNA and protein expression of SCD1 in a dose-dependent manner and bound to SCD1 via hydrogen and con-jugated bonds with a binding energy of-7.7 kcal/mol.CONCLUSION:(1)SCD1 is closely associated with the type and clinical stage of colorectal cancer.(2)The reduction in viability and proliferation of colorectal cancer cells by diosgenin glucoside may be attributed to its binding to SCD1,which lowers its expression and promotes apoptosis.

Objective:To analyze the synergistic relationship between financing and payment systems in China's urban employee basic medical insurance under the background of aging,providing decision-making basis for promoting coordinated development of these two systems.Methods:Based on statistical yearbook data from medical security systems,the Delphi method was employed to identify collaborative analysis indicators for urban employee medical insurance financing and payment under the aging population context.A collaborative theory-based model was constructed to measure the coordination degree of China's urban employee medical insurance financing and payment composite system,while simultaneously assessing the orderliness of the financing and payment system and the coordination degree of the composite system.Results:The order degree of the financing system ranged from 0.324 in 2019 to 0.517 in 2023;the order degree of the payment system ranged from 0.454 in 2019 to 0.517 in 2023;the synergy degree of both systems reached-0.084 in 2023.Conclusions:Influenced by aging,the development speed and scale of China's urban employee basic medical insurance financing system and payment system are asynchronous,with the payment system being more affected than the financing system,resulting in a non-coordinated and disordered development state of the composite financing-payment system.

Objective:To systematically evaluate the current financing status of Beijing's urban and rural residents'basic medical insurance,analyze equity disparities among different groups under the existing flat-rate financing policy.By simulating the equity changes of various financing schemes with different contribution rates,this study aims to provide foundations for advancing medical insurance financing system reform.Methods:Based on the per capita disposable income and number of insured residents in Beijing's 16 districts from 2018 to 2023,we separately calculated the Gini coefficient,concentration index,and Kakwani index,along with their changes before and after financing adjustments,to assess the funding burden among different insured groups.Using the geometric mean method,we projected per capita disposable income and insured populations for each district in Beijing from 2024 to 2035,simulating various financing schemes under different premium rate systems.Results:From 2018 to 2023,the Gini coefficient of net income after financing consistently exceeded that of original income before financing.The concentration index remained positive and showed an upward trend,while the Kakwani index was negative for all periods.The Gini coefficient after financing slightly decreased for the elderly and working populations with fiscal subsidy support,whereas it remained higher than that for students and children.Under the simulated differentiated rate system,the post-funding Gini coefficient for 2024-2035 was lower than the original value,and the Kakwani index was positive.Conclusions:The current fixed-amount financing mechanism for urban and rural residents'basic medical insurance exhibits regressive characteristics and insufficient fairness,with disparities in equity among different insured groups.It is necessary to establish differentiated financing standards based on differential rates,particularly implementing a financing mechanism with dynamic adjustments according to regional and group income levels,to enhance the fairness of financing for urban and rural residents'basic medical insurance.

Aim To investigate the effect of neogam-bogic acid(NGA)on inducing ferroptosis in osteosar-coma K7M2 cells and subcutaneous transplanted tumor mice and explore the underlying mechanism.Methods MTT assay was employed to detect the effect of NGA(1,2,4,8,16,32,64,128 μmol·L-1)on cell prolif-eration,and the IC50 value was calculated.Calcein AM assay was used to detect cell viability.Transwell was applied to detect cell invasion.TEM was utilized to ob-serve the mitochondria morphology.K7M2 cells were subjected to treat with ferroptosis inducers erastin(Era)and inhibitors ferrostatin-1(Fer-1)to assess the levels of MDA,GSH,Fe2+,and LDH.RT-qPCR and Western blot were used to detect the mRNA and protein expression of STAT3,GPX4,and SLC7A11.A transplanted tumor model was established and treated with NGA to assess the impact of it on tumor growth and ferroptosis in vivo.HE staining was applied to ana-lyze the pathological status of tumor tissues.Nile red fluorescence staining was applied to detect the level of lipid components in tumor tissues.Results The pro-liferation,viability and invasion ability of K7M2 cells were significantly reduced after treatment with NGA at different concentrations(P＜0.05),and typical fea-tures of ferroptosis such as decreased mitochondrial vol-ume and reduced mitochondrial spine were observed.Compared to the control,the expression of MDA,Fe2+and LDH significantly increased(P＜0.01),while the content of GSH significantly decreased(P＜0.01).The ferroptosis in osteosarcoma was enhanced by the erastin,while inhibited by ferrostatin-1.In terms of mechanism,NGA inhibited the mRNA and protein ex-pression levels of STAT3,GPX4 and SLC7A11(P＜0.05).In vivo experiments confirmed that NGA signif-icantly improved the pathological state of tumor tissues,inhibited tumor growth,and induced ferroptosis in os-teosarcoma tissue cells.Conclusion NGA induces ferroptosis in osteosarcoma cells both in vitro and in vi-vo by inhibiting the STAT3/GPX4/SLC7A11 signaling axis,thereby exerting an anti-osteosarcoma effect.