ObjectiveTo assess the efficiency of a Sophora flavescens Ait (S. flavescens, Ku Shen)-soluble microneedle (SFA-MN) for improving skin lesion symptoms in mice with psoriasis.MethodsSFA-MNs were prepared using a two-mold molding process with 20% w/v polyvinylpyrrolidone and 15% w/v polyvinyl alcohol. The SFA-MNs were assessed for morphology, mechanical properties, in vitro dissolution, identification of components, and skin lesion improvement in imiquimod-induced psoriasis mice.ResultsThe SFA-MNs demonstrated good mechanical properties for efficiently penetrating the dermis, facilitating efficient drug delivery. Furthermore, they effectively inhibited mast cell levels in the dorsal lesion area of psoriasis mice and reduced the expression of the T-lymphocyte factor cluster of differentiation 3 and tumor necrosis factor-α. In addition, this system alleviated skin inflammation, splenic swelling, and thymic atrophy in the psoriasis-like mouse model. Seven major components were detected from SFA-MNs by comparison of the mass-to-nucleus ratios (m/z) of the secondary fragments N-methylcytisine, 5α, 9α-dihydroxymatrine, sophoramine, matrine, oxysophocarpine, oxymatrine, and kushenol O.ConclusionThe drug delivery strategy combining traditional herbal S. flavescens with soluble microneedle technology provides more targeted and effective immune regulation for treating psoriasis-like mice models, enabling enhanced therapeutic effects compared with the control group.

Objective:To explore the association between circadian syndrome (CircS), metabolic syndrome (MetS) and mild cognitive impairment (MCI) in elderly rural adults in China.Methods:From March to September 2018, totally 5 765 participants aged 60 years or older from 52 villages in Yanlou Town, Yanggu County, Shandong Province were selected. The data included demographic, underlying disease and neuropsychological data were collected by questionaire survey. Having ≥3 of the following components was defined as MetS: elevated waist circumference, high triglycerides, low high-density lipoprotein cholesterol, elevated blood pressure and elevated fasting glucose. Having ≥4 of the following components was defined as CircS: short sleep (<6 h/d), depression and five other components which were used to define MetS, with elevated waist circumference as a mandatory item. MCI was diagnosed according to Petersen's criteria and further classified into amnestic MCI (aMCI) and non-amnestic MCI (naMCI) based on whether the memory domains impaired.Data were analyzed using multivariable Logistic regression and general linear regression models by R statistical software.Results:In the total sample ( n=4 898), 1 280 participants were diagnosed with MCI, of which 1 075 were aMCI and 205 were naMCI.Compared to the normal group, CircS alone was significantly associated with increased risks of MCI ( B=0.695, P=0.039) and aMCI ( B=0.782, P=0.024), as well as lower verbal fluency scores ( B=-0.244, P=0.045). No significant associations were found between MetS alone or both MetS and CircS and cognitive impairment( P>0.05). At the component level, short sleep and depression were associated with increased risks of MCI ( B=0.167, P=0.025; B=0.605, P<0.001) and aMCI ( B=0.185, P=0.020; B=0.600, P<0.001). Conclusion:Individuals with CircS are at a higher risk of cognitive impairment, CircS is more strongly associated with cognitive impairment than MetS, with short sleep duration and depressive symptoms potentially playing key roles.

AIM To investigate the effects of Huazhuo Jiedu Shugan Formula(HJSGF)on improving learning and memory impairment in a rat model of vascular dementia(VD)via SIRT1/PGC-1α/PPARγ pathway.METHODS The SD rats were randomly divided into the sham control group,the model group,the donepezil group(0.5 mg/kg),and the low-,medium-and high-dose HJSGF groups(2.7,5.4,10.8 g/kg),with 10 rats in each group.The VD rat models established by bilateral common carotid artery permanent ligation(2-VO)had their neurological behavior assessment using the Longa5-point scale,and their modeling success confirmed by the Morris water maze test and their 3-week corresponding dosing of drugs by gavage afterward.After the drug administration,the rats had their spatial memory ability tested through behavioral experiments;their serum levels of IL-18 and IL-1β measured by ELISA;their histopathological changes and neuronal morphology in the hippocampal CA1 region observed by HE staining and Nissl staining;and their hippocampal protein expressions of SIRT1,PGC-1α and PPARγ detected by immunohistochemistry and Western blot.RESULTS Compared with the sham control group,the model group showed prolonged escape latency(P＜0.01);decreased platform crossing times and target quadrant residence time(P＜0.01);disorganized arrangement of hippocampal CA1 neurons,nuclear condensation,reduced Nissl bodies,increased secretion and protein expressions of IL-1β and IL-18(P＜0.01);and reduced hippocampal protein expressions of SIRT1,PGC-1α and PPARγ(P＜0.01).Compared with the model group,the groups intervened with donepezil or HJSGF showed shortened escape latency(P＜0.05,P＜0.01);increased platform crossing times and target quadrant residence time(P＜0.05,P＜0.01);alleviated damage of the hippocampal CA1 region,reduced secretion and protein expressions of IL-1β and IL-18(P＜0.05,P＜0.01);and elevated hippocampal protein expressions of SIRT1,PGC-1α and PPARγ(P＜0.05,P＜0.01).CONCLUSION HJSGF may alleviate the inflammatory responses in VD rats and therefore improve their learning and memory impairment by activating the SIRT1/PGC-1α/PPARγ signaling pathway.

In this study,a sensitive lateral flow immunoassay(LFIA)platform based on carbon dots-mesoporous silica nanocomposite(CD-MSNs)fluorescent probes was constructed for high-performance detection of inflammatory marker interleukin-6(IL-6).Green fluorescent carbon dots(CDs)were prepared by hydrothermal method with 3,9-perylenic acid and 3-aminopropyltriethoxysilane(APTES)as raw materials,and highly fluorescent CD-MSNs composites were then constructed by encapsulating the prepared CDs in mesoporous silica nanoparticles(MSNs).Fluorescent probes were prepared by covalent coupling of CD-MSNs with IL-6 antibody.Fluorescent immunochromatographic test strips were constructed by spraying IL-6 capture antibody and goat anti-mouse IgG on nitrocellulose membrane as detection line(T-line)and quality control line(C-line),respectively.The fluorescence immunoassay analyzer was used to quantitatively detect the fluorescence intensity of T-line,and the experimental results showed that the LFIA platform based on this probe had a good linear relationship in IL-6 concentration range of 102-106 pg/mL,and the detection limit was 64 pg/mL,which was two orders of magnitude more sensitive than that of the traditional colloidal gold test strips.This method effectively solved the issue of insufficient sensitivity of traditional LFIA technique,and provided a rapid and highly sensitive detection method for early diagnosis of inflammatory diseases.

Objective:To analysis of the latent profiles and influencing factors of body image in patients with postoperative oral cancer.Methods:From July 2024 to March 2025, a total of 332 patients with primary oral cancer confirmed by pathology, aged ≥18 years, and undergoing oral cancer surgery at Hunan Cancer Hospital were selected using simple random sampling and cluster sampling. Among them, 25 were female and 307 were male. The body image scale and the Rosenberg self-esteem scale were used to investigate the patients. The main indicators included the total scale scores and scores on various dimensions of body image, such as appearance evaluation and health focus, with particular attention to satisfaction with facial appearance and oral function.The correlation between self-esteem and body image was analyzed, and differences in scores were compared based on gender, age, self-esteem level, and surgical procedure.Results:Among the 332 patients, 93.4% (310/332) were married, and 6.6% (22/332) were unmarried, divorced, or widowed. A total of 84.3% (280/332) underwent flap transplantation surgery, while 15.7% (52/332) did not. The body image distress in the 332 patients could be categorized into a body image adaptation group [80.12% (266/332)] and a body image disorder group [19.88% (66/332)]. Unmarried/divorced/widowed status ( P=0.020), undergoing flap transplantation ( P=0.006), and self-esteem level ( P<0.001) were identified as influencing factors for postoperative body image disorder in oral cancer patients. Conclusions:Given the varying levels of body image concerns among oral cancer patients, healthcare providers can implement targeted, personalized nursing interventions based on their distinct categories and influencing factors.

Objective:To investigate the utility of a computational pathology-based tumor microenvironment(TME)score derived from whole slide images(WSIs)in predicting the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)in patients with EGFR mutation-positive non-small cell lung cancer(NSCLC).Methods:This retrospective study collected 240 EGFR-mutant NSCLC pa-tients treated with EGFR-TKIs at The First Affiliated Hospital of Wannan Medical College and analyzed hematoxylin-eosin(H&E)-stained WSIs of biopsy specimens,along with clinical and imaging data.The patients were randomly assigned into a training cohort(n=160)and an inde-pendent validation cohort(n=80)in a 2:1 ratio.Treatment response was assessed based on CT findings at 3 months after EGFR-TKIs initi-ation.Computational pathology was employed to automatically quantify the proportions of four TME components(tumor epithelium,stroma,lymphocytes,and vasculature)within the tumor regions of WSIs.Multivariate Logistic regression in the training cohort identified TME components independently predictive of treatment response(P<0.05),which were then integrated into a TME-score.The predictive performance was evaluated using receiver operating characteristic(ROC)curve analysis and area under the curve(AUC).The TME-score model was compared with a clinical-feature-based model and a combined model(TME-score+clinical features).Finally,the models were val-idated in the independent cohort.Results:In the training cohort,the TME-score,incorporating epithelial and stromal proportions,achieved an AUC of 0.827(95%CI:0.749-0.892)for predicting treatment response,while the validation cohort yielded an AUC of 0.845(95%CI:0.735-0.937).Both outperformed the clinical model(AUCs=0.730[95%CI:0.645-0.804]and 0.712[95%CI:0.586-0.824],respectively).The combined model(TME-score+clinical features,including cytokeratin 19 fragment and non-contrast CT values)further improved predictive performance(AUCs=0.884[95%CI:0.827-0.932]and 0.882[95%CI:0.798-0.950],respectively).Delong's test for pairwise model comparis-ons showed significant differences(all P<0.05)except TME-score and the combined model in the validation cohort(P=0.289).Conclusions:TME-score outperformed clinical models in predicting EGFR-TKIs efficacy in EGFR mutation-positive NSCLC patients and may serve as a novel tool for identifying patients likely to benefit from targeted therapy.

Aim To investigate the protective effect of liraglutide(LIRA)on acetaminophen(APAP)-in-duced hepatotoxicity at the in vivo level and to reveal the underlying mechanism.Methods Forty SPF grade male C57BL/6J mice were randomly divided into the Control,LIRA(200 μg·kg-1),APAP(500 mg·kg-1),LIRA+APAP,LIRA+APAP+3-methylade-nine(3-MA,30 mg·kg-1)groups,with eight mice in each group.The mice were administered for three con-secutive days,and the materials were taken after 24 h.The general condition and body weight of mice in each group were recorded,and liver morphology was ob-served.Serum ALT and AST levels,as well as SOD ac-tivity,MDA,and GSH content in liver homogenates,were measured using biochemical assay kits.The levels of inflammatory cytokines IL-6,TNF-α,and IL-1β in serum were detected by ELISA.Liver pathological changes were assessed by HE staining,while mitochon-drial and autophagosome structures in liver tissues were observed using transmission electron microscopy.The number of PCNA-positive cells in liver tissues was e-valuated using immunohistochemical staining.The pro-tein expression levels of LC3Ⅱ,p62,Bax,Bcl-2,PC-NA,and CyclinD1 in liver tissues were determined by Western blot.Results LIRA pretreatment can im-prove the general condition of mice with acetamino-phen-induced liver injury(AILI),reduce serum ALT and AST levels,and effectively ameliorate the appear-ance and morphology of the liver as well as the patho-logical damage to liver tissue.Simultaneously,the lev-els of inflammatory cytokines IL-6,TNF-α,and IL-1βare significantly decreased;SOD activity and GSH con-tent are significantly increased,while MDA content is significantly reduced.Transmission electron microsco-py observations reveal the presence of numerous auto-phagosomes in the cytoplasm of liver tissue.Immuno-histochemical staining results indicate a significant in-crease in the number of PCNA-positive cells.Further-more,the expression of LC3Ⅱ,Bcl-2,PCNA,and Cy-clinD1 proteins in liver tissue is significantly upregulat-ed,while the expression of p62 and Bax proteins is significantly downregulated.However,after interven-tion with the autophagy inhibitor 3-MA,the aforemen-tioned protective effects of LIRA are significantly.Conclusions LIRA pretreatment can significantly im-prove liver injury in AILI mice.Its protective mecha-nism may be related to enhancing autophagy in hepato-cytes,thereby reducing oxidative stress,inflammatory response and apoptosis in liver of AILI mice.

Chronic urticaria (CU) is a persistent immune-mediated skin disease with an incompletely understood pathogenesis. As the largest micro-ecosystem in the human body, the gut microbiota participates in complex metabolic processes and produces a wide range of metabolites. The gut microbiota-metabolism axis plays a crucial role in the onset and progression of CU. Patients with CU commonly exhibit gut dysbiosis, characterized by a reduction in beneficial bacteria and an increase in opportunistic pathogens, accompanied by alterations in key metabolites. These changes may disrupt the intestinal barrier and modulate the function of immune cells such as mast cells and T cells, thereby triggering or aggravating distal cutaneous inflammation and contributing to CU pathophysiology. Certain bacterial taxa and metabolites hold promise as potential biomarkers for CU diagnosis, therapeutic response, and prognosis, while interventions targeting gut microbiota have demonstrated potential in ameliorating CU symptoms. Elucidating the characteristics and mechanistic roles of gut microbiota and metabolism in CU could provide a theoretical basis for developing novel individualized diagnostic and therapeutic strategies.
Humans ; Gastrointestinal Microbiome/physiology* ; Chronic Urticaria/etiology* ; Dysbiosis/complications* ; Mast Cells

Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

Objective:To investigate the effects of Feilike mixture combined with Montelukast sodium on pulmonary function and inflammatory immune response in patients with Acute exacerbation of Chronic obstructive Pulmonary Disease(AECOPD).Methods:82 patients with AECOPD were divided into control group and observation group,with 41 cases in each group by random number table method.The control group was treated with conventional treatment+Montelukast sodium,and the observation group was treated with Feilike mixture+conventional treatment+montelukast sodium.After two weeks,the clinical efficacy,pulmonary function,immune function,inflammatory factors,and treatment safety of the two groups were evaluated.Results:The total effective rate in observation group was higher than that in control group(P＜0.05).Ratio of Forced expiratory volume in the first second(FEV1)to forced vital capacity(FVC)(FEV1/FVC),FEV1,FEV1 percentage of estimated value(FEV1％pred)in observa tion group after treatment were higher than those in control group(P＜0.05).CD3+,CD4+,CD4+/CD8+in observation group after treatment were higher than those in control group,and CD8+was lower than that in control group(P＜0.05).The levels of pulmonary surfactant protein-A(SP-A),interleukin-17(IL-17)and Granulocyte colony-stimulating factor(G-CSF)in observation group after treatment were lower than those in control group(P＜0.05).There was no difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion:Feilike Mixture combined with Montelukast sodium can effectively improve pulmonary function and regulate inflammatory immune response in patients with AECOPD,with no obvious adverse reactions during the treatment.