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 investigate factors influencing perioperative blood transfusion in patients with scarred uterus during pregnancy undergoing cesarean section, construct and validate a transfusion risk prediction model, and provide evidence for preoperative assessment and blood management. Methods: Clinical data of 405 patients undergoing cesarean section for scarred uterus during pregnancy at the First Affiliated Hospital of Xi'an Jiaotong University from January 2020 to December 2024 were retrospectively collected. The dataset was randomly divided into a training set (n=284) and a validation set (n=121) at a 7∶3 ratio. Within the training set, Firth-penalized logistic regression was employed for multivariate analysis to identify independent factors influencing perioperative blood transfusion and construct a predictive model. Model performance was evaluated in the validation set. Results: Multivariate Firth regression analysis showed that severe placenta previa (OR=75.566, 95%CI: 8.603-9979.174) and placenta accreta (OR=4.591, 95%CI: 1.120-19.416) were independent risk factors for perioperative blood transfusion, while preoperative red blood cell count (OR=0.189, 95%CI: 0.083-0.405) and fibrinogen levels (OR=0.588, 95%CI: 0.395-0.855) were protective factors. The predictive model constructed based on these four variables demonstrated good discriminatory performance, with areas under the receiver operating characteristic curves of 0.803 (95%CI: 0.740-0.867) and 0.753 (95%CI: 0.644-0.862) in the training and validation sets, respectively. Conclusion: For patients with scarred uterus during pregnancy undergoing cesarean section, severe placenta previa and placenta accreta significantly increase the risk of transfusion, while higher preoperative red blood cell count and fibrinogen levels exert a protective effect. The predictive model established in this study facilitates the identification of patients requiring transfusion, thereby enabling preoperative blood preparation and optimized blood management.

Objective We reviewed and analyzed the epidemiological data of 83 imported dengue fever cases reported in Fengtai District, Beijing, from 2007 to 2025, to delineate their epidemiological characteristics and guide the dengue fever prevention and control strategy in the future. Methods Data on dengue fever cases in Fengtai District from 2007 to 2025 were collected to identify the epidemic factors and characteristics using descriptive epidemiological method. Results All 83 dengue fever cases reported in this region over the past two decades have been imported from abroad or other domestic areas, with Southeast Asian countries being identified as the primary source of imported infections, accounting for 42 cases (50.60%), followed by 15 cases (18.07%) from Chinese provinces other than Beijing. The remaining import sources included 13 cases from South Asia,8 from African countries, and each from Oceania, South America, and Europe. Disease onset was found concentrated between May and November. The sex ratio (male-to-female) is 1.59:1. The age of onset ranged from 14 to 61 years old, with a median age of 36. The largest proportion of cases was observed among cadres and office workers (31 cases, 37.35%), followed by businessmen (13 cases, 15.67%), and householders or the unemployed (10 cases,12.05%). Travel visit was identified as the primary reason for their exposure history. Conclusions All dengue fever cases reported in Fengtai from 2007 to 2025 were imported, with an increasing trend of imported cases in Beijing originating from other Chinese provinces. It is essential to strengthen health education for foreign travelers and returning residents, enhance clinical diagnosis and treatment training for medical personnel, eliminate mosquito breeding sites, and reduce mosquito density through active patriotic health campaigns.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

The hippocampus, a major component of the limbic system, is the most important region related to emotion regulation and memory processing. Cognitive impairment and depressive symptoms observed in Alzheimer's disease (AD) patients may be attributed to hippocampal damage caused by amyloid β-protein (Aβ). Our previous studies have demonstrated that a steroid sulfatase inhibitor DU-14 can enhance hippocampal synaptic plasticity and spatial memory abilities in a chronic AD murine model by counteracting the toxic effects of Aβ. However, limited experimental evidence exists regarding the efficacy of steroid sulfatase inhibitor on depressive symptoms in AD animal models. In this study, we investigated the effects of DU-14 on depressive symptoms and theta-band neuronal oscillations in rats with intrahippocampal injection of Aβ_1-42 using various behavioral tests such as sucrose preference test, tail suspension test, forced swimming test, and in vivo hippocampal local field potential (LFP) recording. The results demonstrated that, in comparison to the control group: (1) rats in the Aβ group exhibited a decrease in sucrose preference, indicating a loss of interest in pleasurable activities; (2) rats in the Aβ group displayed aggravated depressive-like behavior characterized by prolonged immobility time during tail suspension and forced swimming tests; (3) Aβ disrupted the induction of theta rhythm via tail pinch stimulation, and resulted in a significant reduction in peak power of theta rhythm. In contrast to the Aβ group, pretreatment with DU-14 resulted in: (1) a significant improvement in Aβ-induced anhedonia, as evidenced by increased sucrose preference; (2) significant alleviation of Aβ-induced despair and depressive-like behaviors, reflected by reduced immobility time during tail suspension and forced swimming tests; (3) successful mitigation of Aβ-mediated inhibition on bilateral hippocampal theta rhythm. These findings indicate that steroid sulfatase inhibitor DU-14 can counteract neurotoxicity induced by Aβ, and prevent Aβ-induced depressive-like behavior and suppression of theta rhythm.
Animals ; Amyloid beta-Peptides/toxicity* ; Rats ; Depression/physiopathology* ; Theta Rhythm/drug effects* ; Hippocampus/physiopathology* ; Male ; Rats, Sprague-Dawley ; Alzheimer Disease/physiopathology* ; Steryl-Sulfatase/antagonists & inhibitors* ; Peptide Fragments ; Behavior, Animal/drug effects*

The medicinal materials of Bawei Chenxiang Pills(BCPs) were extracted via three methods: reflux extraction by water, reflux extraction by 70% ethanol, and extraction by pure water following reflux extraction by 70% ethanol, yielding three extracts of ST, CT, and CST. The efficacy of ST(760 mg·kg~(-1)), CT(620 mg·kg~(-1)), and CST(1 040 mg·kg~(-1)) were evaluated by acute myocardial ischemia(AMI) and p-chlorophenylalanine(PCPA)-induced insomnia in mice, respectively. Western blot was further utilized to investigate their hypnosis mechanisms. The main chemical components of different extracts were identified by the UPLC-Q-Exactive-MS technique. The results showed that CT and CST significantly increased the ejection fraction(EF) and fractional shortening(FS) of myocardial infarction mice, reduced left ventricular internal dimension at end-diastole(LVIDd) and left ventricular internal dimension at end-systole(LVIDs). In contrast, ST did not exhibit significant effects on these parameters. In the insomnia model, CT significantly reduced sleep latency and prolonged sleep duration, whereas ST only prolonged sleep duration without shortening sleep latency. CST showed no significant effects on either sleep latency or sleep duration. Additionally, both CT and ST upregulated glutamic acid decarboxylase 67(GAD67) protein expression in brain tissue. A total of 15 main chemical components were identified from CT, including 2-(2-phenylethyl) chromone and 6-methoxy-2-(2-phenylethyl) chromone. Six chemical components including chebulidic acid were identified from ST. The results suggested that chromones and terpenes were potential anti-myocardial ischemia drugs of BCPs, and tannin and phenolic acids were potential hypnosis drugs. This study enriches the pharmacological and chemical research of BCPs, providing a basis and reference for their secondary development, quality standard improvement, and clinical application.
Animals ; Drugs, Chinese Herbal/isolation & purification* ; Mice ; Male ; Sleep Initiation and Maintenance Disorders/physiopathology* ; Humans ; Myocardial Infarction/drug therapy* ; Myocardial Ischemia/drug therapy*

This study investigated the therapeutic effects and mechanisms of Modified Yiyi Fuzi Baijiang Powder on ulcerative colitis(UC) in rats from the perspective of dampness. SD rats were randomly allocated into six groups(n=10): control, model, mesalazine, and Modified Yiyi Fuzi Baijiang Powder at low(3.96 g·kg~(-1)·d~(-1)), medium(7.92 g·kg~(-1)·d~(-1)), and high(15.84 g·kg~(-1)·d~(-1)) doses. UC was induced in all groups except the control by administration with 3% dextran sulfate sodium(DSS) solution for 7 days. The disease activity index(DAI) was recorded, and the colon tissue was collected for analysis. Histopathological changes were assessed by hematoxylin-eosin staining. Serum levels of D-lactic acid(D-LA) and diamine oxidase(DAO) were measured by ELISA. Immunohistochemistry and PCR were employed to evaluate the expression of aquaporins(AQP3, AQP4) and tight junction proteins [zonula occludens-1(ZO-1) and occludin] at both protein and mRNA levels. Compared with the control group, the model group showed an increased DAI scores(P<0.05), intestinal mucosal damage, elevated serum levels of DAO and D-LA(P<0.05), and decreased expression of AQP3, AQP4, ZO-1, and occludin(P<0.05). Treatment with Modified Yiyi Fuzi Baijiang Powder reduced the DAI scores(P<0.05), lowered the serum levels of D-LA and DAO(P<0.05), and upregulated the expression of AQP3, AQP4, ZO-1, and occludin at both protein and mRNA levels compared with the model group. These findings suggest that Modified Yiyi Fuzi Baijiang Powder exerts therapeutic effects on UC by reducing the intestinal mucosal permeability, promoting colonic mucosal repair, and regulating abnormal intestinal water metabolism, which may involve the upregulation of AQP3 and AQP4 expression.
Animals ; Colitis, Ulcerative/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Intestinal Mucosa/metabolism* ; Male ; Aquaporin 3/metabolism* ; Aquaporin 4/metabolism* ; Permeability/drug effects* ; Humans ; Powders ; Intestinal Barrier Function

Objective:To investigate the effects of brief mindfulness-based stress reduction(MBSR)on preoperative anxiety in pa-tients undergoing painless gastrointestinal endoscopy.Methods:We enrolled 100 patients scheduled to undergo elective painless gas-trointestinal endoscopy at The First Affiliated Hospital of Zhengzhou University from September 2024 to April 2025.The inclusion cri-teria were:age,18-60 years;body mass index,18.0-28.0 kg/m2;American Society of Anesthesiologists physical status,class Ⅰ orⅡ;and no gender restriction.The patients were assigned to experimental group(n=50)or control group(n=50)using a random num-ber table.A dedicated nursing team implemented the brief MBSR protocol.At 30 minutes before endoscopy,both groups underwent anxiety assessment using the Amsterdam Preoperative Anxiety and Information Scale(APAIS).All the patients received routine preop-erative education.Guided by the nurses,the experimental group received the brief MBSR intervention consisting of mindful body scan-ning,mindful breathing,and mindful music listening,for 12 minutes each at 30 and 15 minutes before the procedure.We recorded the APAIS score,bispectral index(BIS),heart rate(HR),systolic blood pressure(SBP),diastolic blood pressure(DBP),and mean arterial pressure(MAP)at 30 minutes before the procedure(T0),after brief MBSR(T1),and immediately before anesthesia induction(T2);the length of stay in the post-anesthesia care unit(PACU)and postoperative adverse reactions;and the APAIS score and degree of sat-isfaction of patients at discharge from the PACU(T3).Results:Com-(all P<0.05).However,no significant differences were observed be-pared with the control group,the experimental group exhibited sig-nificantly lower APAIS scores,significantly reduced BIS values,and significantly lower HR values at T1 and T2 and a significantly lower APAIS score and a significantly higher degree of satisfaction at T3 tween the groups in SBP,DBP,MAP,postoperative adverse events,or PACU length of stay at any time point(all P>0.05).Conclusion:Brief MBSR is an effective non-pharmacological intervention to cope with perioperative negative emotions in patients undergoing pain-less gastrointestinal endoscopy,which can alleviate preoperative anxiety,reduce electroencephalographic arousal,and improve patient satisfaction.