ObjectiveTo explore the effects and mechanism of the modified Danggui Yinzi on "itch-anxiety" model rats of chronic urticaria （CU）. MethodsThe 36 SPF-grade 6-8-week-old female SD rats were randomly divided into a blank control group，a model group，a positive control group，a low-dose modified Danggui Yinzi group，a medium-dose modified Danggui Yinzi group，and a high-dose modified Danggui Yinzi group. A "itch-anxiety" model was established by intraperitoneal injection of a suspension of sodium chloride and aluminum hydroxide and ovalbumin，combined with chronic unpredictable emotional stress stimulation. After successful modeling，rats in each group were administered drugs by gavage. The positive control group was given intragastric administration of the drug solutions of cetirizine and fluoxetine （2.08 mg·kg^-1·d^-1 fluoxetine， 2 mg·kg^-1·d^-1 cetirizine）， the low-，medium-，and high-dose modified Danggui Yinzi groups were administered traditional Chinese medicine at 1.44，2.88， 5.76 g·kg^-1， respectively，while the blank control group and model group were given an equal volume of normal saline. All interventions lasted for 15 days. Behavioral changes were evaluated by the elevated plus-maze test （detecting the percentage of entries into the open arms （OE%），the percentage of time spent in the open arms （OT%），and the total number of entries into the open and closed arms （TNE）），the open-field test （detecting total activity，average movement speed，and latency to enter the central area），and scratching behavior observation. Pathological changes of skin tissues were observed by hematoxylin-eosin （HE） staining and toluidine blue staining，while those of amygdala tissues were observed by HE staining，Nissl staining，and immunofluorescence detection of ionized calcium-binding adapter molecule-1 （Iba-1）. The content of immunoglobulin E （IgE），interleukin-33 （IL-33），histamine in serum and glutamate in the amygdala was detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the protein expression of striatal-enriched protein tyrosine phosphatase （STEP），N-methyl-D-aspartate receptor subunit 2B （NR2B）， calmodulin-dependent protein kinase Ⅱ （CaMKⅡ），phosphorylated CaMKⅡ （p-CaMKⅡ），mitogen-activated protein kinase （MAPK），phosphorylated MAPK （p-MAPK），nuclear factor kappa-light-chain-enhancer of activated B cells （NF-κB），phosphorylated NF-κB （p-NF-κB），and postsynaptic density protein-95 （PSD-95） in the amygdala. ResultsCompared with the blank control group，the model group rats showed obvious anxiety-like behaviors （decreased OE%，OT%，and TNE，reduced total activity，slower average movement speed，and prolonged latency to enter the central area），increased scratching times，obvious skin inflammation and mast cell degranulation，severe amygdala tissue damage，increased glutamate content in the amygdala，and elevated levels of IgE and IL-33 in serum. The expression of STEP，NF-κB，p-NF-κB，NR2B，MAPK，p-MAPK，CaMKⅡ，and p-CaMKⅡ proteins in the amygdala increased，while the expression of PSD-95 protein decreased （P<0.05）. Compared with the model group，the modified Danggui Yinzi group of each dose had increased OE%，OT%，TNE，total activity，and average movement speed，shortened latency to enter the central area， reduced scratching times，alleviated skin inflammation and mast cell degranulation，relieved amygdala tissue damage，decreased glutamate content in the amygdala，and reduced levels of IgE and IL-33 in serum. Moreover，compared with the model group，the low -，medium-，and high-dose modified Danggui Yinzi groups showed decreased expression levels of STEP，NF-κB，p-NF-κB，NR2B，MAPK，p-MAPK，CaMKⅡ，and p-CaMKⅡ proteins in the amygdala，and increased expression of PSD-95 protein. There was a significant dose-effect relationship，with the high-dose group showing the most significant regulatory effect （P<0.05）. ConclusionThe modified Danggui Yinzi has a therapeutic effect on "itch-anxiety" model rats of CU. Its mechanism may be related to regulating glutamate metabolism in the amygdala，modulating the STEP/NR2B/CaMKⅡ/MAPK/NF-κB pathway，and regulating the expression of PSD-95.

OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

Background: In Mongolia, cervical cancer accounted for 11.9% of all cancers diagnosed in women and 7.3% of cancer-related deaths in 2017, ranking as the third most common cancer among women. The American Society for Radiation Oncology (ASTRO) guidelines recommend concurrent chemo-radiotherapy (CCRT) as a standard and effective treatment for patients with FIGO stage IB3–IVA cervical cancer. Accurate assessment of tumor response following CCRT is essential for evaluating treatment efficacy, identifying residual disease, and estimating the risk of recurrence. Magnetic resonance imaging (MRI) is widely used to assess tumor size, local extent, parametric involvement, and post-treatment morphological changes. In contrast, 18F-FDG PET/CT provides both anatomical and functional information and enables quantitative assessment of tumor metabolic activity using the standardized uptake value (SUV). Aim: To estimate the relationship between treatment response to concurrent chemo-radiotherapy and radiological parameters obtained from MRI and 18F-FDG PET/CT in patients with cervical cancer. Materials and Methods: This retrospective study included 35 patients with histo-pathologically confirmed cervical carcinoma who received concurrent chemo-radiotherapy at the Department of Radiation Oncology, National Cancer Center, between 2024 and 2025. Pelvic MRI examinations were performed using a 1.5-T Siemens MRI system to evaluate tumor dimensions and local tumor characteristics before and after treatment. 18F-FDG PET/CT was performed to assess the metabolic activity of the primary tumor, and the maximum SUV was measured. Tumor response following CCRT was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The relationships between tumor response, changes in tumor size, and pre-treatment SUV were statistically analyzed. Result: A total of 35 patients aged 32–73 years were included in the study, with a mean age of 51.2±12.6 years. The mean baseline longitudinal tumor diameter measured by MRI was 54.3±15.8 mm. Twenty-eight patients (80.0%) had tumors larger than 4 cm, whereas 7 (20.0%) had tumors smaller than 4 cm. According to the FIGO staging system, 22 patients (62.9%) had stage IIIC1 disease, 7 (20.0%) had stage IIIC2, 3 (8.6%) had stage IIIB, 2 (5.7%) had stage IIB, and 1 (2.9%) had stage IVA disease. Histopathologically, 31 patients (88.6%) had squamous cell carcinoma, 3 (8.6%) had adenocarcinoma, and 1 (2.9%) had clear cell carcinoma. Of the 35 patients, 23 (65.7%) had reached the scheduled post-treatment follow-up time and were evaluable for treatment response according to RECIST 1.1, whereas 12 patients (34.3%) had not yet reached the scheduled time for post-treatment assessment. Among the 23 evaluable patients, 15 (65.2%) achieved a complete response (CR), while 8 (34.8%) achieved a partial response (PR). Following CCRT, the longest tumor diameter measured by MRI decreased by a mean of 94.8% in the CR group and 65.3% in the PR group. The reduction in tumor diameter was significantly greater in the CR group than in the PR group (p=0.0016). The mean baseline primary tumor SUVmax on 18F-FDG PET/CT was 16.0±9.8 in the CR group and 24.3±14.5 in the PR group. Although the baseline SUVmax tended to be lower in the CR group, the difference did not reach statistical significance (Mann–Whitney U test, p=0.059). A higher baseline SUVmax tended to be associated with a smaller reduction in tumor diameter following CCRT. Conclusion CCRT resulted in a significant reduction in primary tumor size in patients with cervical cancer. The reduction in tumor size was significantly greater among patients who achieved a complete response than among those who achieved a partial response. Although pre-treatment 18F-FDG PET/CT findings suggest that MRI-based tumor size assessment combined with metabolic information from 18F-FDG PET/CT may provide complementary information for evaluating treatment response following CCRT.

Using surface-enhanced infrared absorption spectroscopy in conjunction with electrochemical techniques,this study investigates the origins of variations in electrocatalytic activity of 4-nitrothiophenol(4-NTP)under the influence of three cations:Li+,Na+,and tetramethylammonium(TMA+).The findings highlight the significant impact of specific interactions between cations and the electrode surface on electrocatalytic activity.By constructing vibrational Stark spectra,the study reveals the impact of cations on the structure of the electric double layer and the interfacial electric field.Further spectroscopic and electrochemical characterizations demonstrate that differences in the hydrophilic and hydrophobic properties of cations influence their specific interactions with the interface.Notably,TMA+,through specific interactions,acts as a mediator for charge transfer,effectively reducing the charge transfer resistance of the system and thereby enhancing electrocatalytic activity to some extent.These results elucidate the influence of specific cation/interface interactions and cation properties on electrocatalytic reactions,contributing to a deeper understanding of cation effects at electrochemical charged interfaces.

Water-soluble silver nanoclusters(DHLA-AgNCs)with red fluorescence emission were synthesized using silver nitrate(AgNO3)as silver source,dihydrolipoic acid(DHLA)as ligand and sodium borohydride(NaBH4)as reducing agent by one-pot method.Based on the selective quenching of DHLA-AgNCs by tetracycline(TC),a rapid and selective fluorescence analysis method for detection of TC was constructed by monitoring the fluorescence intensity change at 650 nm.Under the optimal detection conditions,the fluorescence quenching efficiency of DHLA-AgNCs showed good linear relationship with concentration of TC within the range of 10.0-120.0 μmol/L,and the limit of detection(LOD)was 0.39 μmol/L.This method was successfully applied to detection of TC in milk samples,with spiked recoveries ranging from 99.5%to 102.5%,and relative standard deviations(RSDs)less than 5%.This method had the advantages of simplicity,rapidity,strong specificity and low cost,and thus provided a simple and feasible strategy for selective detection of TC.

Objective:To investigate the changes in brain functional network and structural-functional network coupling in children with drug-resistant epilepsy (DRE), and to analyze their correlation with cognitive function, disease duration, and age of onset.Methods:This study was a cross-sectional study. Clinical and imaging data of 19 children with DRE who received consultation and treatment at the Affiliated Hospital of Zunyi Medical University from August 2021 to August 2023 (DRE group) were prospectively included. Another 27 age-and sex-matched healthy children were collected as the healthy control group. All subjects had 3D-T 1WI, T 2 fluid-attenuated inversion recovery, diffusion tensor imaging (DTI), resting-state functional magnetic resonance imaging (rs-fMRI) scans and Wechsler Intelligence Scale assessments. Independent sample t-test and Mann-Whitney U test were used to analyze the global and local topological attributes, as well as the structural-functional coupling (SFC) values at the whole brain and modular levels in two groups. Correlations between abnormal resting state brain functional network indicators and the Wechsler Intelligence Scale score [verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), processing speed index (PSI), full scale intelligence quotient (FSIQ)], disease duration and age of onset was evaluated using a Spearman or Pearson correlation analysis. Results:Compared to the healthy control group, DRE group exhibited decreased VCI, PRI, WMI, PSI, FSIQ and the differences were all statistically significant (all P<0.05). Both brain functional networks had small world attributes. There was a statistically significant difference in the area under the curve of sparsity of degree centrality (DC) in the left pallidum between the DRE group and healthy control group (2.998±0.942, 4.992±1.945, t=-4.07, FDR corrected P<0.05). Compared with the control group, the DRE group had decreased SFC within the limbic network (LN) ( P<0.05), increased SFC within the sensorimotor (SMN) ( P<0.05), decreased SFC between the default mode network-LN ( P<0.05), and increased SFC between the SMN-attentional network (AN) ( P<0.05). There was no statistically significant difference in SFC at the whole brain level between the two groups. Correlation analysis indicated that DC in left pallidum in DRE group negatively correlated with the PSI ( r=-0.537, P=0.018), and SFC between the SMN and AN demonstrated a negative correlation with age of onset ( r=-0.537, P=0.018). Conclusion:The altered DC in left pallidum may be related to cognitive impairment in children with DRE, providing biomarker information for the study of neural mechanisms in children with DRE.

Objective:To evaluate the clinical efficacy of methylation sensitive-high resolution melting curve (MS-HRM) detection of IFN-induced protein 44-like (IFI44L) gene methylation in the diagnosis of systemic lupus erythematosus (SLE), as well as the relationship between IFI44L gene markers and the early onset of SLE.Methods:From February 2020 to September 2022, the MS-HRM was used to detect the methylation level of the IFI44L gene in peripheral blood mononuclear cells of 602 SLE patients and 524 other autoimmune disease patients (excluding SLE) from Beijing Peking Union Medical College Hospital, Guangdong Provincial People′s Hospital, and Shenzhen People′s Hospital, totaling 1 126 patients. Compared with the 2012 SLICC criteria, the suspected cases were followed up for 6 months until the onset and clinical diagnosis of SLE were confirmed. The measurement data of normal distribution were expressed as mean±SD, and the consistency analysis was performed using the Kappa consistency test. The clinical diagnostic efficacy indicators were calculated using the receiver operating characteristic (ROC) curve. Results:RR (95% CI) of early suspected cases was 17.06 (9.43, 30.82). The results of IFI44L gene methylation level were in good agreement with the 2012 SLICC criteria, and the sensitivity, specificity and total coincidence rate were 90.53%, 92.56% and 91.47%, respectively. The Kappa value (95% CI) was 0.829(0.796, 0.862) ( P<0.001). The diagnostic efficiency of IFI44L gene methylation level ( Kappa value 0.817) was superior to anti-nuclear antibody, anti-SM antibody and anti-dsDNA antibody ( Kappa value 0.418, 0.216 and 0.440, respectively). The Kappa values (95% CI) of methylation between MS-HRM and pyrosequencing was 0.861(0.806, 0.916), P<0.001. Conclusion:The hypomethylation of IFI44L gene methylation level detected by MS-HRM is closely related to the occurrence and development of SLE, and its diagnostic performance is better than that of three autoantibodies in SLE diagnosis, which can be used for the early diagnosis of SLE.

Objective To observe the dynamic changes in serum levels of IL-6,IL-8,TREM-1,uPAR,and presepsin in patients with septic shock and to analyze the diagnostic significance of these biomarkers.Methods A total of 150 sepsis patients admitted to the hospital between February 2023 and February 2025 were prospectively enrolled as study subjects.According to their clinical conditions,the participants were categorized into a sepsis group(non-shock,n=44)and a septic shock group(n=106).Additionally,30 healthy individuals with normal clinical indicators during the same period were selected as the control group.The serum levels of IL-6,IL-8,TREM-1,uPAR,and presepsin were measured and compared across the different groups.Spearman correlation analysis and logistic regression analysis were conducted to assess the association between these biomarkers and the severity of sepsis.The diagnostic performance of these biomarkers for septic shock was evaluated using receiver operating characteristic(ROC)curve analysis.Results There were statistically significant differences in serum levels of IL-6,IL-8,TREM1,uPAR,and presepsin among the different groups(P<0.05),with the highest values observed in the septic shock group,followed by the sepsis group and the control group(P<0.05).The APACHE Ⅱ and SOFA scores of patients with septic shock were significantly higher than those of patients with sepsis(P<0.05).Spearman correlation analysis revealed that serum concentrations of IL-6,IL-8,TREM1,uPAR,and presepsin were positively correlated with both APACHE Ⅱ and SOFA scores,with correlation coeffi-cients(rs)of 0.758,0.880,0.837,0.832,and 0.846 for APACHE Ⅱ score,and 0.487,0.549,0.557,0.626,and 0.664 for SOFA score,respectively(P<0.05).Logistic regression analysis indicated that serum levels of IL-6(OR=1.055),IL-8(OR=1.054),TREM1(OR=1.038),uPAR(OR=1.010),and presepsin(OR=2.103)were significantly associated with the development of septic shock(P<0.05).ROC curve analysis demonstrated that the AUC values for serum IL-6,IL-8,TREM1,uPAR,and presepsin in diagnosing septic shock were 0.608,0.724,0.887,0.848,and 0.885,with corresponding sensitivities of 0.432,0.909,0.795,0.909,and 0.591,and specificities of 0.880,0.481,0.915,0.736,and 0.977,respectively.When these biomarkers were combined,the AUC increased to 0.973,with a sensitivity of 0.943 and a specificity of 0.953.Furthermore,the AUC for prese-psin alone was significantly higher than that for IL-6 and IL-8 alone(P<0.05).Additionally,the AUC for the combined biomarkers was significantly greater than that for each biomarker individually(P<0.05).Conclusions Serum levels of IL-6,IL-8,TREM1,uPAR,and presepsin are significantly elevated in patients with septic shock,which may aid in the clinical diagnosis of the condition.The combined use of these five biomarkers en-hances the accuracy of diagnosing septic shock.

Objective This study aims to investigate the expression, phenotypic changes, and mechanisms of action of guanylate-binding protein 2 (GBP2) in the process of silica-induced pulmonary fibrosis. Methods The expression and localization of GBP2 in silicotic lung tissue were detected by immunohistochemical staining and immunofluorescence. An in vitro cell model was constructed, and methods such as Western blot and real-time quantitative reverse transcription polymerasechain reaction were utilized to investigate the function of GBP2 in different cell lines following silica stimulation. The mechanism of action of GBP2 in various cell lines was elucidated using Western blot analysis. Results GBP2 was highly expressed in the lung tissue of patients with silicosis. Immunohistochemical staining and immunofluorescence have revealed that GBP2 was localized in macrophages and epithelial cells. In vitro cell experiments demonstrated that silicon dioxide stimulated THP-1 cells to activate the c-Jun pathway through GBP2, promoting the secretion of inflammatory factors and facilitating the occurrence of M2 macrophage polarization. In epithelial cells, GBP2 promoted the occurrence of epithelial to mesenchymal transition (EMT) by upregulating Krueppel-like factor 8 (KLF8). Conclusion GBP2 not only activates c-Jun in macrophages to promote the production of inflammatory factors and the occurrence of M2 macrophage polarization, but also activates the transcription factor KLF8 in epithelial cells to induce EMT, collectively promoting the progression of silicosis.
Humans ; Silicosis/genetics* ; Macrophages/cytology* ; Epithelial Cells/pathology* ; GTP-Binding Proteins/physiology* ; Epithelial-Mesenchymal Transition ; Disease Progression ; Cell Line ; Male

Objectives To investigate interleukin 36γ (IL-36γ) expression, and analyze the influence of IL-36γ to CD8⁺ T cell activity in chronic obstructive pulmonary diseases (COPD) patients with secondary fungal pneumonia. Methods Peripheral blood was collected from 47 COPD patients, 39 COPD patients with secondary fungal pneumonia, and 20 controls. Bronchial alveolar lavage fluid (BALF) was isolated from 27 COPD patients with secondary fungal pneumonia. CD8⁺ T cells were purified. The levels of four IL-36 isoforms in plasma and BALF were measured by enzyme linked immunosorbent assay (ELISA). CD8⁺ T cells were stimulated with recombinant human IL-36γ. The levels of interferon γ(IFN-γ), tumor necrosis factor α(TNF-α), perforin and granzyme B in the cultured supernatants were measured by ELISA. Recombinant human IL-36γ-stimulated CD8⁺ T cells were co-cultured with NCI-H1882 cells in either direct cell-to-cell contact or Transwell^TM manner. The levels of IFN-γ, TNF-α, and lactate dehydrogenase in the cultured supernatants were assessed. The percentage of target cell death was calculated. Results Plasma IL-36α, IL-36β, and IL-36γ levels were significantly elevated in both COPD group and COPD with secondary fungal pneumonia group compared with those in control group. However, only plasma IL-36γ level was higher in COPD with secondary fungal pneumonia group than that in COPD group [(200.11±99.95)pg/mL vs (53.03±87.18)pg/mL, P=0.023]. There was no remarkable difference in plasma IL-36 receptor antagonist level among three groups. IL-36γ level in BALF from infectious site was higher than that from non-infectious site in COPD with secondary fungal pneumonia group [(305.82±59.60)pg/mL vs (251.93±76.01)pg/mL, P=0.011]. IL-36γ stimulation enhanced IFN-γ, TNF-α, perforin and granzyme B secreted by CD8⁺ T cells. When IL-36γ-stimulated CD8⁺ T cells were directly mixed with NCI-H1882 cells for co-culture, the percentage of cell death was increased [(16.06±3.67)% vs (11.47±2.36)%, P=0.002]. When using Transwell^TM plate for non-contact co-culture, IL-36γ-stimulated CD8⁺ T cell-mediated death of NCI-H1882 cells showed no significant difference compared to that without stimulation [(4.77±0.78)% vs (4.99±0.92)%, P=0.554]. Conclusion IL-36γ level in plasma and infectious site is elevated in COPD patients with secondary fungal pneumonia, which enhances the cytotoxicity of CD8⁺ T cells in peripheral blood and infectious microenviroment.
Humans ; Pulmonary Disease, Chronic Obstructive/complications* ; CD8-Positive T-Lymphocytes/metabolism* ; Male ; Female ; Aged ; Middle Aged ; Interferon-gamma/metabolism* ; Interleukin-1/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Lung Diseases, Fungal/complications* ; Bronchoalveolar Lavage Fluid/chemistry* ; Perforin/metabolism* ; Pneumonia/immunology* ; Granzymes/metabolism*