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.

Objective:To construct an evaluation indicator system for accessories of patient monitor,so as to provide a basis for clinical management,equipment procurement,and technical improvement for accessories of medical monitor.Methods:The initial selection indicators of corresponding accessories of three types of monitoring of medical monitors,including electrocardiogram(ECG),blood oxygen saturation(SpO2)and non-invasive blood pressure(NIBP),were determined through literature research,expert consultation,and actual investigation.The Delphi method was adopted to conduct two rounds of questionnaire consultation for experts from clinical medicine,biomedical engineering and other fields in medical institutions included Sichuan Provincial People's Hospital,The Affiliated Hospital of Southwest Medical University and Medical Institute of Chengdu Institute of Metrology Verification and Testing.The evaluation indicators were screened and optimized,and the Analytic Hierarchy Process(AHP)was used to calculate the weights of each indicator.The consistency test was conducted to verify the rationality of the evaluation indicator system.Results:The evaluation indicator system for accessories of medical monitor included three first-level indicators:clinical value,cost value,and management value.The number of second-level indicators about ECG,SpO2 and NIBP of evaluation indicator system were respectively 10,9 and 8,and the number of third-level indicators of that were respectively 20,19,and 14.In the first-level indicators,the clinical value had the highest weight,with 72.49%for ECG,70.88%for SpO2 and 70.32%for NIBP.In the second-level indicators,the accuracy(28.70%for ECG,38.13%for SpO2 and 43.03%for NIBP)and safety(27.47%for ECG,26.48%for SpO2 and 23.06%for NIBP)were the core indicators.The weights of cost value and management value were between 14.62%and 17.41%,and between 12.27%and 12.89%,respectively.Conclusion:The evaluation indicator system for accessories of medical monitor integrates multi-dimensional expert opinions and quantitative analysis,highlights the priority principle for clinical performance.It can provide theoretical support for optimizing selection about accessory for medical institutions,and improving quality of monitoring,and promoting standardized management in the industry.

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.

Objective:To explore the association between mouth breathing (MB) and functional speech sound disorders (FSSDs) in children, aiming to establish a novel theoretical basis for FSSD interventions.Methods:Eighty-nine children with an FSSD aged 4-12 years formed the FSSD group, while eighty-five age-matched healthy children served as controls. Their clinical data were processed using independent sample t-tests and chi-square tests to test for any significant differences between the two groups in terms of gender, age, mouth breathing status, post-frenotomy condition, Mandarin exposure before age 4, and delayed speech onset. Multivariate logistic regressions were evaluated to identify risk factors for FSSD in such children and to seek any association between mouth brea-thing and FSSD.Results:The regression analysis identified the following risk factors for childhood FSSD, ranked by odds ratio ( OR) magnitude: mouth breathing (adjusted OR=22.168, 95% CI=7.849-62.608, P≤0.01), delayed speech onset (adjusted OR=20.091, 95% CI=4.812-83.878, P≤0.01), age (a protective effect) (adjusted OR=0.979, 95% CI=0.962-0.997, P≤0.05). Univariate analysis of mouth breathing and associated factors revealed significant associations of FSSD with mouth breathing (χ 2=52.15, P≤0.01) and delayed speech onset (χ 2=25.873, P≤0.01). Conclusions:The significant risk factors for childhood functional speech sound disorders are mouth breathing (showing the highest adjusted OR), delayed speech onset and age. These findings suggest that early screening and therapeutic interventions for mouth breathing should be clinically prioritized to minimize FSSD risk.

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.

AIM:To investigate the effects of the Qingfei-Jiedu-Huatan formula(QJHF)on damage to the lung vascular endothelial barrier induced by Klebsiella pneumoniae in mice with severe pneumonia,as well as to elucidate its underlying mechanisms.METHODS:Fifty-one C57BL/6J mice were randomly divided into control group(n=6),model group(n=15),QJHF group(n=15),and ceftriaxone sodium(CRO)group(n=15).Severe pneumonia was in-duced in the mice by a single tracheal intubation with 50 μL of 1×1011 CFU/mL Klebsiella pneumoniae on day 0.Six hours after modeling,the mice in QJHF and CRO groups received their respective treatments,while those in control and model groups were administered an equal volume of saline.All mice were sacrificed on day 3 after the end of gavage.Lung histo-pathological changes were assessed using hematoxylin-eosin(HE)staining.Levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and IL-6 in lung tissues were measured by enzyme-linked immunosorbent assay(ELISA).Flow cytometry was used to detect CD11b+Ly6g+cells in bronchoalveolar lavage fluid(BALF).Proteomics and network pharma-cology analyses were conducted to elucidate the mechanisms of drug action.Western blot was conducted to assess the ex-pression levels of vascular endothelial cadherin(VE-cadherin),zonula occludens-1(ZO-1),occludin,vascular endothe-lial growth factor(VEGF),P38 mitogen-activated protein kinase(P38),and phosphorylated P38(p-P38)in lung tis-sues.RESULTS:Treatment with QJHF significantly attenuated the symptoms such as mental status and respiratory dis-tress,reduced mortality,mitigated lung tissue lesions,and decreased levels of IL-6,TNF-α,IL-1β,as well as BALF to-tal protein concentration,total cell count and neutrophil content in a mouse model of severe pneumonia(P＜0.05 or P＜0.01).Additionally,QJHF increased the expression of VE-cadherin,ZO-1 and occludin proteins in lung tissues.Pro-teomic analysis demonstrated that QJHF modulated the expression of 129 proteins in the lung tissues of mice suffering from severe pneumonia.Network pharmacology identified 328 potential targets associated with 14 major bioactive components of QJHF and 1 665 genes related to severe pneumonia,with 125 overlapping genes between the two datasets.The construc-tion of a protein-protein interaction(PPI)network,along with Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of the regulated proteins and overlapping genes,indicated that QJHF primarily in-fluenced the PI3K-Akt,MAPK and Rap1 signaling pathways,as well as VEGFR.Western blot analysis showed that QJHF significantly inhibited the expression of VEGF and P38 in lung tissues(P＜0.05 or P＜0.01).CONCLUSION:Treatment with QJHF attenuates severe pneumonia in mice,potentially by inhibiting VEGF/P38 signaling to protect the vascular endothelial barrier.

Objective:To explore the value of a model based on 18F-FDG PET/CT radiomics features in assessing the prognosis of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer undergoing neoadjuvant targeted chemotherapy. Methods:This retrospective analysis included 132 female patients (age (50±11) years) diagnosed with HER2-positive breast cancer who underwent 18F-FDG PET/CT prior to treatment between January 2016 and August 2022 in Tianjin Medical University Cancer Institute and Hospital. Data were split into training (105 cases) and validation (27 cases) cohorts using stratified sampling (8∶2). Clinical pathological data and progression-free survival (PFS) were recorded. PET and CT images were annotated for lesion delineation and radiomics features extraction. The least absolute shrinkage and selection operator (LASSO) algorithm was used to select features in the training cohort, and the radiomics score (Rad-score) was calculated. Cox proportional hazards regression analysis was performed to identify risk factors for PFS. A nomogram model was constructed, and the concordance index (C-index) was calculated to assess predictive performance. Results:Univariate Cox regression showed that N stage (hazard ratio ( HR)=2.36, 95% CI: 1.04-5.37, P=0.040) and Rad-score ( HR=14.50, 95% CI: 3.39-62.13, P<0.001) were related to PFS in patients with HER2-positive breast cancer after neoadjuvant therapy. Multivariate analysis indicated the Rad-score as an independent risk factor for PFS ( HR=13.32, 95% CI: 3.10-57.20, P<0.001). The nomogram model combining N stage and Rad-score predicted PFS more accurately than the Rad-score model alone, with C-indexes of 0.80 vs 0.74 in the training cohort, and 0.77 vs 0.71 in the validation cohort. Conclusions:Radiomics based on pre-treatment 18F-FDG PET/CT can predict PFS in patients with HER2-positive breast cancer undergoing neoadjuvant targeted chemotherapy. The nomogram model combining radiomics features and clinical risk factor improves prognostic prediction.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.