ObjectiveTo investigate the demyelination induced by Angiostrongylus cantonensis （AC） infection in the brain of Balb/c mice and analyze the untargeted metabolomic changes in the corpus callosum， aiming to elucidate the underlying mechanisms. MethodsBalb/c mice were randomly assigned to a control group （n=6） and an infection group （n=6）. The infection group was orally administered 30 third-stage larvae of AC， while the control group received an equal volume of saline. Body weight， visual function， and behavioral scores were measured on post-infection 3， 6， 9， 12， 15， 18， and 21 days to assess neurological alterations. After 21 days， brain tissues were harvested for immunofluorescence staining， hematoxylin-eosin （HE） staining， and transmission electron microscopy to examine morphological changes in brain myelin and retina. Metabolomics analysis was performed， and differential metabolites were identified using volcano plots and heatmaps. The distribution of fold changes and bar charts were used to profile the key metabolites. These differential metabolites were then subjected to Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and regulatory network analysis. ResultsOn the 9th day after AC infection， Balb/c mice showed a decline in neurological behavioral scores （P<0.05）. By day 15， visual scores decreased （P<0.05）， and by day 21， significant weight loss （P＜0.001） and mortality were observed. Concurrently， transmission electron microscopy and immunofluorescence staining revealed significant myelin damage in the corpus callosum and a marked reduction in oligodendrocytes （P<0.001）. HE staining showed severe retinal ganglion cell damage. Metabolomic analysis revealed that glycerophospholipids were the most abundant differential metabolites， with steroids and sphingolipids being relatively less abundant. Cholesteryl ester CE （20：2） was significantly upregulated （P<0.001）， while phosphatidylmethanol （18：0_18：1） was significantly downregulated （P<0.01）. KEGG enrichment and regulatory network analyses demonstrated that the differential metabolites were mainly enriched in metabolic pathways like steroid biosynthesis， bile secretion， and cholesterol metabolism， and were involved in key metabolic pathways such as sphingolipid metabolism， neural signal regulation， and glycerophospholipid metabolism. ConclusionsAC infection affects the metabolic state of mice via multiple pathways， modifying the levels of metabolites crucial for myelination and myelin stability. Demyelination may be closely linked to the disruption of these key metabolic pathways， particularly the dysregulation of cholesterol and sphingolipid metabolism， potentially playing a central role in demyelination onset. Furthermore， alterations in phospholipid metabolism and abnormal nerve signaling regulation may exacerbate myelin damage.

Objective To identify long non-coding RNA (lncRNA) associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and investigate their mechanisms. Methods Peripheral blood samples were collected from RA-ILD patients (n＝3), RA patients without lung involvement (n＝3), and healthy controls (n＝3). Next-generation sequencing was performed to screen differentially expressed lncRNA. A human fibrotic lung cell model was established by inducing the MRC-5 cell line with transforming growth factor-β (TGF-β). Following siRNA-mediated knockdown of target genes, changes in inflammatory and oxidative stress-related genes were analyzed via real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting and dual-luciferase reporter (DLR) assays were used to validate protein expression, ubiquitination levels, and nuclear translocation of oxidative stress regulators, and antioxidant response element (ARE) transcriptional activity. Rescue experiments were conducted to confirm the role of target lncRNA in oxidative stress and inflammation in fibrotic lung cells. Results High-throughput sequencing revealed significant downregulation of LINC00638 in RA-ILD patients. Knockdown of LINC00638 markedly reduced transcriptional levels of interleukin (IL)-4, nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase 2 (SOD2), while increasing IL-6, IL-1β, interferon-γ (IFN-γ), and reactive oxygen species (ROS) levels. Furthermore, LINC00638 knockdown decreased Nrf2 protein expression, increased its ubiquitination, reduced nuclear translocation, and suppressed ARE transcriptional activity. In MRC-5 cells, LINC00638 knockdown combined with N-acetylcysteine treatment restored Nrf2 and HO-1 levels while reducing IL-6 expression. Conclusions LINC00638 suppresses inflammatory responses in RA-ILD by activating the Nrf2/ARE antioxidant signaling pathway, suggesting its potential as a therapeutic target for diagnosis and treatment.

It is proposed that cold qi-induced accumulation encapsulates the core pathogenesis of the inflammation-cancer transformation in inflammatory bowel disease （IBD）. Cold pathogens may serve as the initiating factor. When first invading the intestines， cold pathogens obstruct the flow of qi； over time， the lingering cold impairs the middle jiao （焦）， eventually leading to the accumulation of cold-phlegm and blood stasis. Based on the progressive nature of this transformation， the process can be divided into three stages， active stage， remission stage， and carcinogenic stage. In the active stage， the main pathogenesis involves stagnation of cold qi and accumulation of damp-heat in the intestines； in the remission stage， cold qi impairs the spleen， disrupting its transport and transformation functions； and in the carcinogenic stage， the mechanisms include cold-induced accumulation， phlegm accumulation from cold， and stagnation of cold and blood stasis. Accordingly， the treatment strategies are proposed.In the active stage， regulating qi， relieving stagnation， and harmonizing cold and heat； in the remission stage， warming yang， dispersing cold， tonifying qi， and strengthening the spleen； and in the carcinogenic stage， promoting qi circulation， dispersing cold， resolving phlegm， activating yang， and eliminating stasis to remove accumulation. These approaches aim to interrupt the transformation of IBD into colorectal cancer.

Objective To investigate the risk factors for early neurological deterioration in mild acute ischemic stroke，to construct a clinical predictive model，and to perform internal validation of this model. Methods A retrospective analysis was performed for 739 patients with mild acute ischemic stroke who were admitted to Department of Neurology，Kuntong Hospital of Zunhua，from October 2020 to December 2023，and they were randomly divided into a training set with 534 patients （72.3%） and a validation set with 205 patients （27.7%） at a ratio of 7∶3. Univariate and multivariate logistic regression analyses were performed for the training set to determine the risk factors for early neurological deterioration in mild acute ischemic stroke. A clinical predictive model was constructed，and internal validation was performed in terms of discriminatory ability，calibration，and clinical decision making. A nomogram was plotted. Results The multivariate logistic regression analysis showed that female sex （OR=1.87，95% CI 1.14~3.09，P=0.014），time window ≤6 hours （OR=3.10，95%CI 1.56~6.19，P=0.001），a baseline NIHSS score of 2 points （OR=3.72，95%CI 1.30~10.61，P=0.014），a baseline NIHSS score of 3 points （OR=4.24，95%CI 1.45~12.35，P=0.008），a TOAST classification of large artery atherosclerosis （OR=3.88，95%CI 2.20~6.83，P<0.001），and the responsible arteries of the basilar artery，the middle cerebral artery，and the internal carotid artery （OR=8.39，95%CI 2.28~30.85，P=0.001； OR=6.22，95%CI 1.78~21.71，P=0.004； OR=5.38，95%CI 1.15~25.13，P=0.032） were independent risk factors for early neurological deterioration in mild acute ischemic stroke. The clinical predictive model constructed showed a moderate discriminatory ability （AUC>0.7），good calibration （P>0.05） in the Hosmer-Lemeshow goodness-of-fit test），and good clinical benefits in both the training set and the validation set. Conclusion This clinical predictive model can effectively predict the onset of early neurological deterioration in mild acute ischemic stroke and guide clinicians to make decisions，and therefore，it holds promise for clinical application.
Nomograms

Objective To use direct dilution method to pretreat human urine, and to determine 19 elements in human urine using inductively coupled plasma mass spectrometry, and to evaluate the uncertainty of the entire experimental process. Methods The relevant mathematical models were established according to JJF 10591-2012 ^“Evaluation and Expression of Measurement Uncertainty^” and CNAS-GL006 ^“Guidance for Evaluation of Uncertainty in Chemical Analysis^”. Taking molybdenum as an example, the uncertainty sources in the determination of 19 elements in human urine by inductively coupled plasma method were analyzed and evaluated, including sample pretreatment, sample repeated measurement, standard solution preparation and standard curve fitting. Results The extended uncertainty of molybdenum in human urine is 2.12μg/L, and the measurement result of molybdenum is (44.8±2.12)μg/L. The measurement result of 19 elements in human urine ranges from less than the detection limit to 601μg/L, and the extended uncertainty range is 0.38~33.6μg/L.Conclusion It was found from the calculation that the uncertainty of the determination result was mainly affected by the uncertainty of the sample repeated measurement and the standard curve fitting. By adjusting the range of standard curve and increasing the number of parallel sample measurement, the uncertainty was reduced and the quality of detection was improved.

Healthy dental pulp is essential for preserving teeth and maintaining their normal function. Vital pulp therapy (VPT) is widely used in clinical applications because it aims to preserve vital pulp and enhance the long-term survival of teeth. An accurate diagnosis of pulp vitality is a prerequisite for successful VPT. However, accurately assessing pulp viability remains challenging in clinical practice. Pulp viability is influenced by various factors, including the type of pulp exposure, caries status, periodontitis, trauma, treatment factors, patient age, and individual differences. Assessing pulp viability requires a comprehensive consideration of medical history and clinical manifestations, along with a combination of various auxiliary methods, such as pulp sensibility tests, pulp blood flow tests, imaging techniques and molecular diagnostics. In the future, the technology for assessing pulp vitality should evolve toward chairside, visualization, and precision techniques, to achieve consistency between clinical and histological diagnoses, thereby providing patients with the most effective treatment.

Ulcerative colitis （UC） is a refractory disease of the digestive system characterized by diverse etiologies， complex pathogenesis， a prolonged course， and frequent relapses. In recent years， the incidence of UC has been increasing annually， severely impairing patients' quality of life， posing a risk of malignant transformation that may threaten patients' lives， and resulting in a substantial medical burden. Traditional Chinese medicine （TCM） compound formulas， with their advantages of multi-component and multi-target actions， have become a new therapeutic option for UC. The NOD-like receptor pyrin domain-containing 3 （NLRP3） inflammasome is a core component of innate immunity， and its aberrant activation is closely associated with the onset and progression of UC， involving multiple processes such as inflammation and oxidative stress， and exhibiting crosstalk with pathways including nuclear factor-κB （NF-κB）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and thioredoxin-interacting protein （TXNIP）. At present， NLRP3 has become one of the most intensely studied hotspots in UC-related research. Although increasing studies have focused on the regulation of the NLRP3 inflammasome by TCM compound formulas for UC treatment， challenges remain due to the complex pathogenesis of UC and the compositional diversity of TCM， hindering the realization of precision therapy. In this context， by reviewing literature from the past decade， this paper summarizes the activation process of NLRP3 and its relationship with UC， and elucidates the roles and mechanisms by which TCM compound formulas regulate the NLRP3 inflammasome and related signaling pathways， with a view to providing a reference for further research into the pathogenesis of UC， TCM treatment strategies， and their mechanisms of action.

Ulcerative colitis （UC） is a refractory disease of the digestive system characterized by diverse etiologies， complex pathogenesis， a prolonged course， and frequent relapses. In recent years， the incidence of UC has been increasing annually， severely impairing patients' quality of life， posing a risk of malignant transformation that may threaten patients' lives， and resulting in a substantial medical burden. Traditional Chinese medicine （TCM） compound formulas， with their advantages of multi-component and multi-target actions， have become a new therapeutic option for UC. The NOD-like receptor pyrin domain-containing 3 （NLRP3） inflammasome is a core component of innate immunity， and its aberrant activation is closely associated with the onset and progression of UC， involving multiple processes such as inflammation and oxidative stress， and exhibiting crosstalk with pathways including nuclear factor-κB （NF-κB）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and thioredoxin-interacting protein （TXNIP）. At present， NLRP3 has become one of the most intensely studied hotspots in UC-related research. Although increasing studies have focused on the regulation of the NLRP3 inflammasome by TCM compound formulas for UC treatment， challenges remain due to the complex pathogenesis of UC and the compositional diversity of TCM， hindering the realization of precision therapy. In this context， by reviewing literature from the past decade， this paper summarizes the activation process of NLRP3 and its relationship with UC， and elucidates the roles and mechanisms by which TCM compound formulas regulate the NLRP3 inflammasome and related signaling pathways， with a view to providing a reference for further research into the pathogenesis of UC， TCM treatment strategies， and their mechanisms of action.

OBJECTIVE To investigate the intervention effect and its potential mechanism of Yifei xuanfei jiangzhuo formula by inhibiting mitochondrial fission in a vascular dementia （VaD） model rats. METHODS VaD rat model was established by bilateral common carotid artery ligation. The experimental animals were randomly divided into sham operation group （SHAM）， model group （MOD），Yifei xuanfei jiangzhuo formula low-dose group （YFXF-L）， Yifei xuanfei jiangzhuo formula high-dose group （YFXF-H）， and Donepezil hydrochloride group （positive control）， with 9 animals in each group. After 30 days of intervention， the spatial learning memory ability was assessed by Morris water maze experiment； HE staining was used to observe histopathological changes in CA1 area of hippocampus； ELISA was used to detect the levels of serum inflammatory factors [interleukin-1β （IL-1β） and IL-4]； Western blot was used to detect the expressions of heat shock protein 90 （HSP90）/mixed lineage kinase domain-like protein （MLKL）/dynamin-related protein 1 （Drp1） pathway-related proteins， mitochondrial fusion proteins （MFN1， MFN2）， and adenosine triphosphate synthase 5A （ATP5A） in hippocampal tissues. The immunohistochemistry was used to detect the level of phosphorylated MLKL （p-MLKL）； real-time fluorescence quantitative PCR was adopted to detect mRNA expressions ofHSP90， MFN1， MFN2 and ATP5A. RESULTS Compared with SHAM group， the escape latency of rats in the MOD group was significantly prolonged， the number of crossing the platform was significantly reduced， and the hippocampal tissues showed typical neuronal damage characteristics， the positive expression level of p-MLKL and the serum level of IL-1β significantly increased， while the serum level of IL-4 significantly decreased， the protein and mRNA expression of HSP90， as well as the protein expressions of p-MLKL/MLKL and p-Drp1（Ser616）/Drp1 were all significantly increased in hippocampal tissue， the protein and mRNA expressions of MFN1， MFN2 and ATP5A， and protein expression of p-Drp1（Ser637）/Drp1 were all significantly decreased （P＜0.05）. After the intervention of Yifei xuanfei jiangzhuo formula， above indicators in each treatment group were all significantly reversed （P＜0.05）. CONCLUSIONS Yifei xuanfei jiangzhuo formula may alleviate neuronal damage and neuroinflammatory responses in VaD rats by regulating the HSP90/MLKL/Drp1 signaling pathway， inhibiting mitochondrial fission， thereby maintaining mitochondrial dynamic balance and improving mitochondrial function.

BackgroundExecutive function deficits constitute a core problem in attention-deficit/hyperactivity disorder （ADHD）. Previous assessments of executive function in children with ADHD have predominantly relied on performance-based neuropsychological tests conducted in laboratory settings， though their predictive validity for real-world functional outcomes remains limited. In contrast， ecological executive function emphasizes the evaluation of complex task management in naturalistic contexts， demonstrating a stronger predictive power for functional adaptation in daily living among children with ADHD， such as multitasking performance， social interactions and so on. However， current empirical evidence regarding ecological executive function in this population remains insufficient. ObjectiveTo investigate the executive function characteristics of children with ADHD from an ecological perspective， thereby providing references for developing targeted interventions. MethodsA case control study was conducted， including 277 ADHD children who met the Diagnostic and Statistical Manual of Mental Disorders， fourth edition （DSM-IV） criteria and were selected at the Child Health Care and Mental Health Center of Shenzhen Children's Hospital from June 2017 to December 2020， as well as 98 healthy controls were recruited from primary and secondary schools in Shenzhen. All participants were assessed using Wechsler Intelligence Scale for Children， fourth edition （WISC-IV） and Behavior Rating Inventory of Executive Function （BRIEF）. Differences in WISC-IV and BRIEF scores were compared between ADHD group and control groups， followed by the comparison of BRIEF scores by gender and ADHD subtypes. ResultsAmong the 277 children with ADHD， 136 cases （49.10%） had predominantly inattentive type （ADHD-I）， 6 cases （2.17%） had predominantly hyperactive-impulsive type （ADHD-HI）， and 135 cases （48.73%） had combined type （ADHD-C）. ADHD group demonstrated significantly lower scores on both the WISC-IV total IQ and four index scores （verbal comprehension， perceptual reasoning， working memory and processing speed） than control group （t=3.698~9.335， P<0.01）. After controlling for WISC-IV total IQ as a covariate， the scores of each factor in the dimensions of behavioral regulation index （inhibition， shifting， emotional control） and metacognition index （task initiation， working memory， planning， monitoring and organization） were all higher in ADHD group than in control group， and the differences were statistically significant （F=46.563~290.475， P<0.01）. In terms of gender， no statistically significant difference was found in BRIEF composite scores （behavioral regulation index or metacognition index） of children with ADHD （t=0.105~1.190， P>0.05）. In terms of ADHD subtypes， children with ADHD-C reported significantly higher scores than those with ADHD-I on the scores of inhibition， emotional control， organization and monitoring in BRIEF （t=2.481~7.343， P<0.05 or 0.01）. ConclusionChildren with ADHD have multidimensional deficits in ecological executive function， which vary across different subtypes. ［Funded by Shenzhen Excellent Science and Technology Innovation Talent Training Project （number， RCYX20221008092849069）； the Sanming Project of Medicine in Shenzhen］