ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease （AD） based on network pharmacology， molecular docking， and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and the Encyclopedia of Traditional Chinese Medicine（ETCM） databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards， Online Mendelian Inheritance in Man（OMIM）， TTD， PharmGKB， and DrugBank databases were used to obtain the relevant targets of AD. The intersection （common targets） of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken， and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction（PPI） network. The CytoNCA plugin within Cytoscape was used to screen out the core targets， and the Metascape platform was used to perform gene ontology（GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2， and AutoDock Vina was used for molecular docking. Scopolamine （SCOP） was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control （CON） group （0.9% NaCl， n=8）， model （SCOP） group （3 mg·kg^-1·d^-1， n=8）， positive control group （3 mg·kg^-1·d^-1 of SCOP+3 mg·kg^-1·d^-1 of Donepezil， n=8）， and Kaixinsan group （3 mg·kg^-1·d^-1 of SCOP+6.5 g·kg^-1·d^-1 of Kaixinsan， n=8）. Mice in each group were administered with 0.9% NaCl， Kaixinsan， or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin （HE） staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay（ELISA） was used to determine the serum acetylcholine （ACh） and acetylcholinesterase （AChE） contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3（STAT3） and nuclear transcription factor（NF）-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained， and 578 potential targets （common targets） of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol， gijugliflozin， etc.. Potential core targets were STAT3， NF-κB p65， et al. GO functional enrichment analysis obtained 3 124 biological functions， 254 cellular building blocks， and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways， mainly involving cancer-related pathways， TRP pathway， cyclic adenosine monophosphate（cAMP） pathway， and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65， STAT3， and other targets involved in the NF-κB signaling pathway.

Uveitis is a blinding inflammatory disease that affects multiple structures within the eye, posing significant risks to patients' vision and mental health. Current treatments mainly involve glucocorticoids and immunosuppressants, which are associated with significant side effects, high relapse rates, and substantial costs. Recent research suggests that the gut microbiota may play a role in the development of uveitis through the gut-eye axis, with related metabolites also influencing disease progression. Modulating the gut microbiota or its metabolites could offer new therapeutic avenues for uveitis. This review explores the relationship between gut microbiota and various uveitis-associated diseases, such as systemic sarcoidosis, Vogt-Koyanagi-Harada syndrome, Behcet's disease, multiple sclerosis, and birdshot chorioretinopathy. It also discusses advancements in microbiota-related therapies, including probiotics and prebiotics, antibiotics, immunomodulators, phage therapy, and fecal microbiota transplantation. The aim is to provide a reference for the development of new therapies targeting specific microbial communities and genetic markers associated with uveitis, thereby promoting the realization of precision medicine.

AIM: To explore the diagnostic value of 18 MHz color Doppler ultrasonography for epiretinal membrane.METHODS: A total of 44 cases(80 eyes)of patients with proposed diagnosis of cataract and vitreous opacity by fundus examination in our hospital between January 2020 and January 2022 were collected, and the affected eyes were examined by optical coherence tomography(OCT)and 18 MHz color Doppler ultrasonography, and the differences in the diagnostic sensitivity, specificity, and accuracy were compared between 18 MHz color Doppler ultrasonography and OCT for the diagnosis of epiretinal membrane.RESULTS: In the 80 eyes detected by 18 MHz color Doppler ultrasonography, 62 had epiretinal membrane and 18 had non epiretinal membrane. Totally 54 eyes were confirmed to have epiretinal membrane by OCT, 13 eyes were not diagnosed with epiretinal membrane, 5 eyes were missed diagnosis, and 8 eyes were misdiagnosed. The diagnostic consistency between 18 MHz color Doppler ultrasonography and OCT was high(Kappa=0.892, P<0.05); the 18 MHz color Doppler ultrasonography detection sensitivity of epiretinal membrane was 92%, specificity was 62%, missed diagnosis rate was 8%, misdiagnosis rate was 38%, and accuracy was 84%; compared with OCT detection, 18 MHz color Doppler ultrasonography detected a lower specificity, correct rate, positive prediction accuracy, negative prediction accuracy, and higher misdiagnosis rate(all P<0.05), and the difference in diagnostic sensitivity compared with leakage rate was not statistically significant(all P>0.05).CONCLUSION: 18 MHz color Doppler ultrasonography has some value in identifying epiretinal membrane lesions and is consistent with OCT testing.

Bioassay-guided fractionation of the methanolic extract of Artemisia iwayomogi Kitamura led to the isolation of 12 known compounds (1‒12). Notably, this study marks the first report of 3-epimeridinol (1) being isolated and structurally characterized from a natural source. Additionally, compounds 3, 4, and 7 were isolated from the Asteraceae family for the first time. The structural elucidation of the isolated compound was achieved through analysis of 1D, 2D NMR, and MS data. Upon evaluation of their inhibitory effects against lipopolysaccharideinduced nitric oxide production, compound 12 demonstrated significant inhibitory activity with greater potency than the reference compound quercetin. These results established A. iwayomogi as a promising source of antiinflammatory agents.

The roots of Astragalus membranaceus Bunge have long been used in herbal medicine for their diversebiological activities. Notably, its potential anti-diabetic properties have been extensively studied, highlighting promising therapeutic prospects. In this study, we conducted a comprehensive investigation focusing on flavonoid components from the roots of A. membranaceus and their PTP1B inhibitory activity. As a result, we isolated a total of 24 flavonoids, among which formonentin (1), pratensein (3), and vesticarpan (19) emerged as the most potent inhibitors against PTP1B with IC50 value of 10.9 ± 1.09 μM, 10.0 ± 1.71 μM, and 10.3 ± 1.31 μM, respectively.Additionally, through the enzyme kinetic analysis, the inhibition mode of compound 19 was determined as a competitive inhibitor, with Ki value of 7.6 ± 1.17 μM. Furthermore, the molecular docking simulation elucidated the binding mechanism of compound 19 with PTP1B, mainly through van der Waals forces and hydrogen bonds.This study highlights the PTP1B inhibitory potential of the flavonoid constituents derived from the roots of A. membranaceus. Moreover, discovering vesticarpan (19) as a novel PTP1B inhibitor provides a significant foundation for further investigations to develop innovative therapeutic strategies for diabetes treatment.

Damage to barrier function due to a loss of moisture in the skin can lead to skin diseases, such as atopy and psoriasis. Hyaluronic acid (HA) has the ability to retain large amounts of moisture and thereby protects the skin against moisture loss. In addition, tight junctions prevent water loss and maintain barrier functions by restricting molecular movement through cell-to-cell connections. In this study, the effects of Prunus yedoensis bark water extract (PYBWE) on HA synthesis and tight junction protein expression in HaCaT cells were evaluated.In HaCaT cells, PYBWE had effects on the MAPKs, CREB, AKT, NF-κB, and CLDN-4 signaling pathways, at 25, 50, and 100 µg/mL concentrations increasing the amount of HA produced via HAS-2 and effectively improving skin barrier function.

Purpose: This study aimed to characterize the clinical patterns and severity of brain injury in neonates who survived extracorporeal membrane oxygenation (ECMO) therapy for acute respiratory failure during the neonatal period, to evaluate their short-term neurodevelopmental outcomes, and to identify the factors associated with these outcomes. Methods: We retrospectively reviewed the medical records of neonates who survived ECMO between 2018 and 2024. Based on brain magnetic resonance imaging (MRI) findings, the patients were classified into two groups: no/mild and moderate/severe brain injury. Neurodevelopmental outcomes were assessed at 12–40 months of age using the Bayley Scale of Infant Development II/III and/or the Korean Developmental Screening Test. Results: Among the 19 neonates included in the study, 18 (94.7%) showed varying degrees of brain injury on MRI (mild: 12, moderate: 1, severe: 5). Neonates with moderate/severe brain injury had significantly longer durations of ECMO support and extended durations of mechanical ventilation and were more likely to receive continuous renal replacement therapy than those with no or mild injury. Developmental delay was identified in 36.8% of survivors and was significantly associated with prolonged mechanical ventilation, longer neonatal intensive care unit stays, and a higher incidence of seizures. Conclusion Brain injury is frequently observed on MRI in neonates treated with ECMO. However, its direct association with adverse neurodevelopmental outcomes is not definitive. Since MRI findings alone cannot predict developmental outcomes, clinical and environmental factors should be integrated into prognostic assessments.

Purpose: This study aimed to investigate the effects of postnatal systemic corticosteroids on neurodevelopment in very low birth weight (VLBW) preterm infants. Methods: This was a population-based study of the Korean Neonatal Network of VLBW infant born at 23+0 and 31+6 weeks of gestation between 2013 and 2020. VLBW preterm infants assessed using the Bayley Scales of Infant and Toddler Development, third edition (BSID-III) at 18–24 months of corrected age and 3 years of age were enrolled. The primary outcomes were BSID-III scores and neurodevelopmental delays, with scores of <85. Socioeconomic status and clinical variables were adjusted for using multivariate regression analyses. Results: In total, 517 infants were enrolled in this study. Among the 216 (41.8%) infants who received postnatal systemic corticosteroids, the rate of cognitive delay was significantly higher at 18–24 months of corrected age than at 3 years of age. The rates of language and motor delays were significantly higher both at 18–24 months of corrected age and at 3 years of age. When multivariate logistic regression was performed, postnatal systemic corticosteroid use was significantly associated with cognitive delay at 18–24 months of corrected age, but not at 3 years of age. There was no significant association between postnatal systemic corticosteroid use and language or motor delay at 18-24 months of corrected age or at 3 years of age after multivariate logistic regression. Conclusion Postnatal systemic corticosteroid use in VLBW preterm infants increased the risk of cognitive delay at 18–24 months of corrected age, but not at 3 years.

Objective: Based on spinopelvic parameters and biomechanical principles, the pedicle-facet joint (PFJ) morphological characteristics of isthmic and degenerative spondylolisthesis were analyzed, and the mechanism of their onset and progression was discussed. Methods: This retrospective cross-sectional study included 194 patients with L5 spondylolysis or L5–S1 low-grade isthmic spondylolisthesis (IS group), 172 patients with L4–5 degenerative spondylolisthesis (DS group), and 366 patients with nonlumbar spondylolysis (NL group). The spinopelvic parameters and PFJ morphological parameters of the patients were measured, the differences in these parameters among and within the 3 groups were compared, and the correlations were analyzed. Results: Sacral slope (SS) and lumbar lordosis (LL) were the highest in the IS group, the second highest in the DS group, and the lowest in the NL group. Among the 3 groups, the L4 facet joint angle (FJA) was the largest in the IS group, the second largest in the NL group, and the smallest in the DS group. The L4 pedicle-facet joint angle (PFA) was the largest in the DS group, the second largest in the IS group, and the smallest in the NL group. Pearson correlation analysis showed that within each group, SS and LL were negatively correlated with FJA and positively correlated with PFA. Conclusion This study found a correlation between the PFJ morphological characteristics of patients with lumbar spondylolisthesis and spinopelvic parameters, suggesting that the morphological characteristics of PFJs may be caused by varying stresses under different spinopelvic morphologies.

BACKGROUND/OBJECTIVES: This study aimed to use plasma metabolites to identify clusters of breast cancer survivors and to compare their dietary characteristics and health-related factors across the clusters using unsupervised machine learning. SUBJECTS/METHODS: A total of 419 breast cancer survivors were included in this crosssectional study. We considered 30 plasma metabolites, quantified by high-throughput nuclear magnetic resonance metabolomics. Clusters were obtained based on metabolites using 4 different unsupervised clustering methods: k-means (KM), partitioning around medoids (PAM), self-organizing maps (SOM), and hierarchical agglomerative clustering (HAC). The t-test, χ2 test, and Fisher’s exact test were used to compare sociodemographic, lifestyle, clinical, and dietary characteristics across the clusters. P-values were adjusted through a false discovery rate (FDR). RESULTS: Two clusters were identified using the 4 methods. Participants in cluster 2 had lower concentrations of apolipoprotein A1 and large high-density lipoprotein (HDL) particles and smaller HDL particle sizes, but higher concentrations of chylomicrons and extremely large very-low-density-lipoprotein (VLDL) particles and glycoprotein acetyls, a higher ratio of monounsaturated fatty acids to total fatty acids, and larger VLDL particle sizes compared with cluster 1. Body mass index was significantly higher in cluster 2 compared with cluster 1 (FDR adjusted-PKM < 0.001; PPAM = 0.001; PSOM < 0.001; and PHAC = 0.043). CONCLUSION The breast cancer survivors clustered on the basis of plasma metabolites had distinct characteristics. Further prospective studies are needed to investigate the associations between metabolites, obesity, dietary factors, and breast cancer prognosis.