ObjectiveTo investigate the mechanism of Xiezhuo Jiedu prescription in the treatment of ulcerative colitis （UC） by inhibiting ferroptosis and alleviating intestinal mucosal injury based on the nuclear factor E₂ related factor 2/solute carrier family 7 member/glutathione peroxidase 4 （Nrf2/SLC7A11/GPX4） signaling pathway. MethodsA total of 60 male SD rats were divided into a normal group， a model group， high- and low-dose Xiezhuo Jiedu prescription groups （26.64 and 13.32 g·kg^-1， respectively）， a ferroptosis inhibitor group （Ferrostatin-1， 0.005 g·kg^-1）， and a mesalazine group （0.27 g·kg^-1）， with 10 rats in each group. A UC rat model was established by intrarectal administration of trinitrobenzene sulfonic acid （TNBS）-ethanol. The normal group and the model group were intragastrically administered normal saline. The other groups were given intragastric administration according to the corresponding dosage for 7 d. The general condition， disease activity index （DAI） score， colon length， and mucosal injury index （CDMI） score were observed in each group. The pathological changes of colon tissue in each group were observed by hematoxylin-eosin （HE） staining. The intestinal mucosa and mitochondrial morphology in each group were observed by transmission electron microscopy. The expression levels of Occludin， Claudin-1， mucin 2 （MUC2）， and E-cadherin in intestinal tissue were detected by immunofluorescence （IF）. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression levels of serum tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） in each group， and a lactic acid assay kit or ELISA was employed to detect the expression levels of reactive oxygen species （ROS）， ferrous ions （Fe²⁺）， glutathione （GSH）， malondialdehyde （MDA）， 4-hydroxynonenal （4-HNE）， diamine oxidase （DAO）， and D-lactate （D-LA）. Real-time quantitative polymerase chain reaction （Real-time PCR） was applied to detect the mRNA expression levels of Nrf2， SLC7A11， GPX4， Occludin， Claudin-1， MUC2， and E-cadherin in each group， and Western blot was adopted to detect the protein expression levels of Nrf2， p-Nrf2， SLC7A11， and GPX4 in each group. ResultsCompared with the normal group， rats in the model group exhibited listlessness， sluggish response， and mucopurulent and bloody stools. The model group also showed significantly increased DAI score， colon length， CDMI score， and expression levels of TNF-α， IL-6， ROS， Fe²⁺， MDA， 4-HNE， DAO， and D-LA （P<0.01）. In addition， it presented significantly decreased IF values of Occludin， Claudin-1， MUC2， and E-cadherin and mRNA and protein expression levels of IL-10， GSH， Nrf2， p-Nrf2， SLC7A11， and GPX4 （P<0.01）. There were different degrees of improvement in each administration group after treatment， and the improvement was the most significant in the high-dose Xiezhuo Jiedu prescription group （P<0.01）. ConclusionXiezhuo Jiedu prescription may alleviate intestinal mucosal injury by inhibiting ferroptosis of intestinal epithelial cells via regulating the Nrf2/SLC7A11/GPX4 signaling pathway， thereby exhibiting efficacy in the treatment of UC.

[This corrects the article DOI: 10.1016/j.apsb.2019.01.013.].

ObjectiveThis study aims to explore the potential mechanism of the Xiezhuo Jiedu formula in regulating pyroptosis for the treatment of ulcerative colitis （UC） using bioinformatics and in vivo animal experiments. MethodsDifferentially expressed genes （DEGs） in colon tissues of UC patients were retrieved from the Gene Expression Omnibus （GEO） database. Pyroptosis-related genes were obtained from the GEO and GeneCards databases. The intersection of these datasets yielded pyroptosis-related DEGs （Pyro-DEGs）. Pyro-DEGs were subjected to Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis using the Metascape database. A protein-protein interaction （PPI） network was constructed using the STRING database. Least absolute shrinkage and selection operator （LASSO） prediction model and receiver operating characteristic （ROC） analysis were conducted to identify core Pyro-DEGs with diagnostic and therapeutic potential. Immune infiltration analysis of the UC datasets was performed using the deconvolution method （CIBERSORT）， along with correlation analysis with core Pyro-DEGs. Sixty male Sprague-Dawley （SD） rats were randomly divided into a control group， a model group， high-， medium-， and low-dose groups of Xiezhuo Jiedu formula （26.64， 13.32， 6.66 g·kg^-1）， and a mesalazine group （0.27 g·kg^-1）， with 10 rats in each group. UC was established by intrarectal administration of 3，5-trinitrobenzenesulfonic acid （TNBS） dissolved in ethanol. The control and model groups were given distilled water by gavage， while the treatment groups were administered the corresponding drugs for 7 consecutive days. Hematoxylin-eosin （HE） staining was used to observe the colon histopathology. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of inflammatory factors such as interleukin-1β （IL-1β）， IL-10， IL-18， and transforming growth factor-β （TGF-β）. Immunohistochemistry （IHC） and Western blot were applied to detect the expression of Caspase-1， gap junction alpha-1 protein （GJA1）， peroxisome proliferator-activated receptor gamma （PPARG）， and S100 calcium-binding protein A8 （S100A8）. Real-time quantitative polymerase chain reaction （Real-time PCR） was utilized to measure mRNA expression of Caspase-1， GJA1， PPARG， and S100A8. Western blot was performed to assess protein expression levels of Caspase-1， GJA1， PPARG， and S100A8. ResultsGEO datasets GSE87466 and GSE87473 yielded 64 Pyro-DEGs. KEGG analysis indicated that these genes were enriched in the NOD-like receptor signaling pathway， tumor necrosis factor （TNF） signaling pathway， and hypoxia-inducible factor 1 （HIF-1） signaling pathway. Four core Pyro-DEGs （Caspase-1， GJA1， PPARG， and S100A8） were identified. Immune infiltration analysis showed that expression of these genes was positively correlated with mast cells， neutrophils， M0 macrophages， M1 macrophages， and dendritic cells. Animal experimental results indicated that compared with the control group， the model group had significantly increased levels of IL-1β and IL-18， significantly decreased levels of IL-10 and TGF-β. The model group showed enhanced Caspase-1， GJA1， and S100A8 staining， and significantly increased mRNA and protein expression of Caspase-1， GJA1， and S100A8 （P<0.01）. In contrast， the expression of PPARG was reduced in the model group （P<0.01）. After treatment， all dosage groups showed varying degrees of improvement （P<0.05， P<0.01）， with the high-dose group showing the most significant improvement （P<0.01）. ConclusionCaspase-1， GJA1， PPARG， and S100A8 are core Pyro-DEGs closely associated with the pathogenesis of UC. These genes may collaborate with immune cells such as mast cells， neutrophils， and M0 macrophages to mediate disease development. The Xiezhuo Jiedu formula may regulate the expression of core Pyro-DEGs through the NOD-like receptor， TNF， and HIF-1 core signaling pathways， thereby modulating immune homeostasis in UC rats and effectively alleviating UC.

Objective To investigate the diagnostic value of color Doppler ultrasound of neck vessels combined with head and neck CT angiography (CTA) in detecting carotid artery stenosis among patients with stroke. Methods A total of 104 patients with stroke admitted to the hospital between January 2023 and November 2024 were enrolled. All patients underwent color Doppler ultrasound of neck vessels and head and neck CTA, with digital subtraction angiography (DSA) used as the gold standard. Receiver operating characteristic (ROC) curves were plotted to analyze the diagnostic performance of each modality alone and in combination for detecting carotid artery stenosis in patients with stroke. Results According to the DSA results, among the 104 patients, 7 were normal, while 47, 16, 25, and 9 cases showed mild, moderate, and severe stenosis and occlusion, respectively. Color Doppler ultrasound results showed 6 normal cases, and 45, 20, 23, and 10 cases of mild, moderate, and severe stenosis and occlusion, respectively. Using DSA as the gold standard, the sensitivity, specificity and kappa value for diagnosing carotid artery stenosis were 98.97%, 85.71% and 0.848, respectively. Head and neck CTA results showed 5 normal cases, and 47, 19, 22, and 9 cases of mild, moderate, and severe stenosis and occlusion, respectively. The sensitivity, specificity and kappa value of head and neck CTA for diagnosing carotid artery stenosis were 100.00%, 71.43% and 0.823, respectively. The combined examination results showed that among the 104 patients, there were 7 normal cases, and 46, 18, 24, and 9 cases of mild, moderate, and severe stenosis and occlusion, respectively. The sensitivity, specificity and kappa value of the combined diagnosis were 100.00%, 100.00% and 1.000, respectively. In the ROC analysis, the areas under the curves of color Doppler ultrasound, head and neck CTA, and the combined method were 0.968, 0.934, and 1.000, respectively, with no significant difference among the three ROC curves (Z = 1.017, 0.994, 1.527, respectively, P = 0.309, 0.320, 0.167, respectively). Conclusion Color Doppler ultrasound of neck vessels combined with head and neck CTA shows good consistency with DSA in diagnosing carotid artery stenosis and its severity among patients with stroke. This combined method demonstrates high diagnostic performance, making it worthy of clinical application and promotion.

Objective:To determine the prevalence, risk factors, and longitudinal associations of loneliness during mid- to late pregnancy with anxiety and depressive symptoms in late pregnancy.Methods:In this prospective cohort study, 1 107 pregnant women at 24-28 weeks' gestation were enrolled between June 2021 and December 2022. Psychological status was assessed during mid-pregnancy (24-28 weeks) and late pregnancy (≥32 weeks) using standardized electronic questionnaires, including the Revised University of California Los Angeles Loneliness Scale (UCLA) Loneliness Scale-Short Form (Cronbach's α=0.82), Patient Health Questionnaire-9 ( α=0.86), and Generalized Anxiety Disorder-7 ( α=0.88). Multivariate logistic regression identified independent risk factors for loneliness. Cross-lagged path models analyzed the longitudinal predictions between loneliness and anxiety/depressive symptoms. Results:The prevalence of loneliness decreased significantly from 10.8% (120/1 107) in mid-pregnancy to 4.8% (37/777) in late pregnancy ( χ2=21.81, P<0.001). Multivariate analysis identified independent risk factors for loneliness: age <30 years ( OR=1.70, 95% CI: 1.15-2.50), annual household income <50 000 CNY ( OR=2.53, 95% CI: 1.28-5.02), unemployment during pregnancy ( OR=1.57, 95% CI: 1.03-2.39), history of alcohol consumption ( OR=1.63, 95% CI: 1.03-2.56), and the presence of mid-pregnancy depressive ( OR=2.76, 95% CI: 1.51-5.04) and anxiety symptoms ( OR=1.65, 95% CI: 1.01-2.71) (all P<0.05). Cross-lagged path models indicated bidirectional associations between loneliness and both anxiety ( β=0.32, P<0.01) and depressive symptoms ( β=0.28, P<0.01). However, the predictive effect of loneliness on subsequent depressive and anxiety symptoms ( β=0.28-0.32) was substantially stronger than the reverse prediction (mid-pregnancy anxiety on late-pregnancy loneliness: β=0.12; mid-pregnancy depression on late-pregnancy loneliness: β=0.11). Loneliness demonstrated high temporal stability (autoregressive effects β=0.29-0.32). Conclusion:Loneliness in mid-pregnancy exhibits a symmetric bidirectional association with anxiety and depressive symptoms in late pregnancy, suggesting it may be a core driver in the development of these emotional symptoms. Younger maternal age (<30 years), low household income (<50 000 CNY/year), unemployment during pregnancy, and a history of alcohol consumption were associated with a higher risk of loneliness and should be prioritized for psychological screening and intervention.

Objective To study NF1 gene variations in 10 suspected cases of neurofibromatosis type I(NF1)and their parents,thereby providing a basis for genetic counselling,clinical diagnosis,and treatment of this disease.Methods A total of 10 patients diagnosed with,or suspected of having NF1 at Northwest Women's and Children's Hospital from March to December 2023 were selected as study subjects.Whole exome sequencing(WES)was performed to analyse NF1 gene mutations in the patients and their parents,with the findings validated by Sanger sequencing.Results Pathogenic mutations were identified in 6 of the 10 families,with the remaining 4 cases showing no pathogenic gene mutations.In Family 1,a de novo mutation,c.6505A>T,was detected in the NF1 gene.In Family 2,a de novo mutation,c.6705-3C>A,was identified in the NF1 gene.In Family 3,a de novo mutation,c.6853delT,was detected in the NF1 gene.In Family 4,a de novo mutation,c.2446C>T,was found in the NF1 gene.In Family 5,a paternal mutation,c.6067T>A,was identified in the NF1 gene.In Family 6,a paternal mutation,c.2991_2993dup,was detected in the NF1 gene.Conclusion The identification of new mutation sites enriches the mutation spectrum of the NF1 gene.This study provides important guidance for genetic counselling and prenatal diagnosis,offering crucial information for families with reproductive needs.

Objective To study NF1 gene variations in 10 suspected cases of neurofibromatosis type I(NF1)and their parents,thereby providing a basis for genetic counselling,clinical diagnosis,and treatment of this disease.Methods A total of 10 patients diagnosed with,or suspected of having NF1 at Northwest Women's and Children's Hospital from March to December 2023 were selected as study subjects.Whole exome sequencing(WES)was performed to analyse NF1 gene mutations in the patients and their parents,with the findings validated by Sanger sequencing.Results Pathogenic mutations were identified in 6 of the 10 families,with the remaining 4 cases showing no pathogenic gene mutations.In Family 1,a de novo mutation,c.6505A>T,was detected in the NF1 gene.In Family 2,a de novo mutation,c.6705-3C>A,was identified in the NF1 gene.In Family 3,a de novo mutation,c.6853delT,was detected in the NF1 gene.In Family 4,a de novo mutation,c.2446C>T,was found in the NF1 gene.In Family 5,a paternal mutation,c.6067T>A,was identified in the NF1 gene.In Family 6,a paternal mutation,c.2991_2993dup,was detected in the NF1 gene.Conclusion The identification of new mutation sites enriches the mutation spectrum of the NF1 gene.This study provides important guidance for genetic counselling and prenatal diagnosis,offering crucial information for families with reproductive needs.

Ischemic stroke is a devastating neuro-logical disease worldwide,with high global burden.The microglial activation-driven neuroinflammation plays a critical role in pathophysiology of ischemic stroke.After the ictus of brain ischemic attack,cy-tosolic double-stranded DNA(dsDNA)released by necrotic neuronal cells is a potential damage-asso-ciated molecular pattern(DAMP)to activate cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway.cGAS-STING sig-naling pathway has emerged as a key player in mi-croglial activation,sterile neuroinflammation,and cell death following ischemic stroke.Targeting this pathway holds promise for developing novel thera-peutics that effectively mitigate neuroinflamma-tion,prevent cell death,and enhance patient out-comes.In this review,we first outline the principal elements of the cGAS-STING signaling cascade,then discusses the pivotal role of the cGAS-STING pathway in ischemic stroke.Then,we outline selec-tive small-molecules modulators that function as cGAS-STING inhibitors and summarize their mecha-nisms to treat Ischemic stroke.Finally,we discuss key limitations of the current therapeutic paradigm and generate possible strategies to overcome them.

Ischemic stroke is a devastating neuro-logical disease worldwide,with high global burden.The microglial activation-driven neuroinflammation plays a critical role in pathophysiology of ischemic stroke.After the ictus of brain ischemic attack,cy-tosolic double-stranded DNA(dsDNA)released by necrotic neuronal cells is a potential damage-asso-ciated molecular pattern(DAMP)to activate cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway.cGAS-STING sig-naling pathway has emerged as a key player in mi-croglial activation,sterile neuroinflammation,and cell death following ischemic stroke.Targeting this pathway holds promise for developing novel thera-peutics that effectively mitigate neuroinflamma-tion,prevent cell death,and enhance patient out-comes.In this review,we first outline the principal elements of the cGAS-STING signaling cascade,then discusses the pivotal role of the cGAS-STING pathway in ischemic stroke.Then,we outline selec-tive small-molecules modulators that function as cGAS-STING inhibitors and summarize their mecha-nisms to treat Ischemic stroke.Finally,we discuss key limitations of the current therapeutic paradigm and generate possible strategies to overcome them.

Objective:To determine the prevalence, risk factors, and longitudinal associations of loneliness during mid- to late pregnancy with anxiety and depressive symptoms in late pregnancy.Methods:In this prospective cohort study, 1 107 pregnant women at 24-28 weeks' gestation were enrolled between June 2021 and December 2022. Psychological status was assessed during mid-pregnancy (24-28 weeks) and late pregnancy (≥32 weeks) using standardized electronic questionnaires, including the Revised University of California Los Angeles Loneliness Scale (UCLA) Loneliness Scale-Short Form (Cronbach's α=0.82), Patient Health Questionnaire-9 ( α=0.86), and Generalized Anxiety Disorder-7 ( α=0.88). Multivariate logistic regression identified independent risk factors for loneliness. Cross-lagged path models analyzed the longitudinal predictions between loneliness and anxiety/depressive symptoms. Results:The prevalence of loneliness decreased significantly from 10.8% (120/1 107) in mid-pregnancy to 4.8% (37/777) in late pregnancy ( χ2=21.81, P<0.001). Multivariate analysis identified independent risk factors for loneliness: age <30 years ( OR=1.70, 95% CI: 1.15-2.50), annual household income <50 000 CNY ( OR=2.53, 95% CI: 1.28-5.02), unemployment during pregnancy ( OR=1.57, 95% CI: 1.03-2.39), history of alcohol consumption ( OR=1.63, 95% CI: 1.03-2.56), and the presence of mid-pregnancy depressive ( OR=2.76, 95% CI: 1.51-5.04) and anxiety symptoms ( OR=1.65, 95% CI: 1.01-2.71) (all P<0.05). Cross-lagged path models indicated bidirectional associations between loneliness and both anxiety ( β=0.32, P<0.01) and depressive symptoms ( β=0.28, P<0.01). However, the predictive effect of loneliness on subsequent depressive and anxiety symptoms ( β=0.28-0.32) was substantially stronger than the reverse prediction (mid-pregnancy anxiety on late-pregnancy loneliness: β=0.12; mid-pregnancy depression on late-pregnancy loneliness: β=0.11). Loneliness demonstrated high temporal stability (autoregressive effects β=0.29-0.32). Conclusion:Loneliness in mid-pregnancy exhibits a symmetric bidirectional association with anxiety and depressive symptoms in late pregnancy, suggesting it may be a core driver in the development of these emotional symptoms. Younger maternal age (<30 years), low household income (<50 000 CNY/year), unemployment during pregnancy, and a history of alcohol consumption were associated with a higher risk of loneliness and should be prioritized for psychological screening and intervention.