Triple-negative breast cancer (TNBC) remains a refractory subtype of breast cancer due to its resistance to various therapeutic strategies. In this study, we introduce a "brake-release and accelerator-pressing" approach to engineer a microneedle patch embedded with copper-doped Prussian blue nanoparticles (Cu-PB) and the ferroptosis inducer sorafenib (SRF) for raised chemodynamic (CDT)/photothermal (PTT) combination therapy against TNBC. Upon transdermal insertion, the dissolving microneedles swiftly disintegrate and facilitate the release of SRF. Under gentle external light exposure, copper ions (Cu²⁺) and iron ions (Fe³⁺) were liberated from Cu-PB. The direct chelation of Cu²⁺ and the indirect suppression by SRF, collectively attenuate glutathione peroxidase 4 (GPX4) enzymatic function, destabilizing the cellular redox equilibrium (referred to as the "brake-release" strategy). The release of Cu²⁺ and Fe³⁺ ions instigates a Fenton/Fenton-like reaction within tumor cells, further yielding hydroxyl radicals and elevating reactive oxygen species (ROS) concentrations (referred to as the "accelerator-pressing" strategy). This overwhelming ROS accumulation, coupled with the impaired clearance of resultant lipid peroxides (LPO), ultimately triggers a robust ferroptosis cell death response. In summary, this study presents an innovative combinatorial therapeutic strategy based on dual-ferroptosis induction for TNBC, implying a promising therapeutic platform for developing ferroptosis-centered treatments for this aggressive breast cancer subtype.

Objective:To investigate the diagnostic value of repeated endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in patients with suspected neoplastic lesions.Methods:Patients with clinically suspected neoplastic lesions, who did not receive a definitive diagnosis following the initial EUS-FNA and subsequently underwent repeated EUS-FNA, were collected from the gastrointestinal endoscopy center of Qilu Hospital of Shandong University from January 2018 to October 2023. The ultrasonographic endoscopic images, pathology, and follow-up data were reviewed. Patients with confirmed diagnoses following repeated EUS-FNA were analyzed to determine the diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of repeat EUS-FNA for tumor and non-neoplastic lesions.Results:A total of 36 patients with space-occupying lesions in different parts were included in the study, and the final diagnosis was 80.6% (29/36) of tumor lesions and 19.4% (7/36) of non-tumor lesions. Among these, 34 patients received definitive diagnoses. The diagnostic sensitivity of repeated EUS-FNA for tumor was 82.8% (24/29), the specificity was 100.0% (7/7), the positive predictive value was 100.0% (24/24), the negative predictive value was 58.3% (7/12), and the accuracy was 86.1% (31/36).Conclusion:Repeated EUS-FNA proves to be an effective and practical approach for cases where is suspicion of neoplastic lesions and the initial EUS-FNA pathology findings remain inconclusive.

Neurodegenerative diseases are a group of chronic progressive diseases characterized by inflammation,degenera-tion and apoptosis.Chronic neuroinflammation is gradually becoming a potential pathogenic and predisposing factor.As a widely expressed non-histone nucleoprotein,HMGB1 participates in inflammatory process of human body through receptors of advanced glycation end products and Toll-like receptors while maintaining chromosome homeostasis.As a key factor of neuroinflammation,HMGB1 is widely involved in development of neurodegenerative diseases and may become a biomarker and a potential therapeutic target of neurodegenerative diseases.This article reviews the role of HMGB1 in neurodegenerative diseases and tries to provide ground-work for basic research and clinical application for targeting HMGB1 in the treatment of neurodegenerative diseases.

Objective:To explore the diagnostic value of the combined detection of v-Kirsten Ras viral oncogene homolog(KRAS),transmembrane protein 243(TMEM243),cell division cycle protein 42(CDC42)and RAS like family 11 member B(RASL11B)for different types of Hashimoto's thyroiditis(HT).Methods:From January 2023 to December 2024,a total of 185 HT patients who received detection in Hebei Yanda Hospital were selected by using a random number table method,and they were divided into three groups according to HT type,which included the euthyroid HT group(65 cases),the hypothyroid HT group(60 cases)and the hyperthyroidism HT group(60 cases).Another 65 healthy individuals who underwent physical examination during the same period were selected as the healthy control group.An analyzer of enzyme-linked immunosorbent assay(ELISA)was used to measure and analyze the levels of KRAS,TMEM243,CDC42 and RASL11B in the four groups.Differences in autoantibody levels among different HT patients were compared.Logistic regression analysis was conducted to assess influence factors for HT.A nomogram model was constructed to realize visual presentation on the basis of the influence factors.Receiver operating characteristic(ROC)curves were adopted to assess the diagnostic efficacy of antibodies for subjects in the four groups.Results:The KRAS,TMEM243,CDC42 and RASL11B levels in the three HT groups were significantly higher than those in the healthy control group(F=906.962,840.078,830.290,846.182,P<0.05),respectively.Multivariate logistic regression analysis showed that KRAS,TMEM243,CDC42 and RASL11B were risk factors for HT(OR=4.071,1.424,1.026,1.031,P<0.05).The area under curve(AUC)of the ROC curve of the combined detection of four indicators of autoantibodies was 0.975,which sensitivity and specificity were respectively 94.05%and 92.31%.Conclusion:There were overexpression of KRAS,TMEM243,CDC42 and RASL11B in HT patients,especially,the overexpression of hyperthyroidism HT patients is more significant.The combined detection of the four indicators of autoantibody has favorable performance and clinical reference value in diagnosing HT.

Objective:To explore the diagnostic value of the combined detection of v-Kirsten Ras viral oncogene homolog(KRAS),transmembrane protein 243(TMEM243),cell division cycle protein 42(CDC42)and RAS like family 11 member B(RASL11B)for different types of Hashimoto's thyroiditis(HT).Methods:From January 2023 to December 2024,a total of 185 HT patients who received detection in Hebei Yanda Hospital were selected by using a random number table method,and they were divided into three groups according to HT type,which included the euthyroid HT group(65 cases),the hypothyroid HT group(60 cases)and the hyperthyroidism HT group(60 cases).Another 65 healthy individuals who underwent physical examination during the same period were selected as the healthy control group.An analyzer of enzyme-linked immunosorbent assay(ELISA)was used to measure and analyze the levels of KRAS,TMEM243,CDC42 and RASL11B in the four groups.Differences in autoantibody levels among different HT patients were compared.Logistic regression analysis was conducted to assess influence factors for HT.A nomogram model was constructed to realize visual presentation on the basis of the influence factors.Receiver operating characteristic(ROC)curves were adopted to assess the diagnostic efficacy of antibodies for subjects in the four groups.Results:The KRAS,TMEM243,CDC42 and RASL11B levels in the three HT groups were significantly higher than those in the healthy control group(F=906.962,840.078,830.290,846.182,P<0.05),respectively.Multivariate logistic regression analysis showed that KRAS,TMEM243,CDC42 and RASL11B were risk factors for HT(OR=4.071,1.424,1.026,1.031,P<0.05).The area under curve(AUC)of the ROC curve of the combined detection of four indicators of autoantibodies was 0.975,which sensitivity and specificity were respectively 94.05%and 92.31%.Conclusion:There were overexpression of KRAS,TMEM243,CDC42 and RASL11B in HT patients,especially,the overexpression of hyperthyroidism HT patients is more significant.The combined detection of the four indicators of autoantibody has favorable performance and clinical reference value in diagnosing HT.

Neurodegenerative diseases are a group of chronic progressive diseases characterized by inflammation,degenera-tion and apoptosis.Chronic neuroinflammation is gradually becoming a potential pathogenic and predisposing factor.As a widely expressed non-histone nucleoprotein,HMGB1 participates in inflammatory process of human body through receptors of advanced glycation end products and Toll-like receptors while maintaining chromosome homeostasis.As a key factor of neuroinflammation,HMGB1 is widely involved in development of neurodegenerative diseases and may become a biomarker and a potential therapeutic target of neurodegenerative diseases.This article reviews the role of HMGB1 in neurodegenerative diseases and tries to provide ground-work for basic research and clinical application for targeting HMGB1 in the treatment of neurodegenerative diseases.

Objective:To investigate the diagnostic value of repeated endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in patients with suspected neoplastic lesions.Methods:Patients with clinically suspected neoplastic lesions, who did not receive a definitive diagnosis following the initial EUS-FNA and subsequently underwent repeated EUS-FNA, were collected from the gastrointestinal endoscopy center of Qilu Hospital of Shandong University from January 2018 to October 2023. The ultrasonographic endoscopic images, pathology, and follow-up data were reviewed. Patients with confirmed diagnoses following repeated EUS-FNA were analyzed to determine the diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of repeat EUS-FNA for tumor and non-neoplastic lesions.Results:A total of 36 patients with space-occupying lesions in different parts were included in the study, and the final diagnosis was 80.6% (29/36) of tumor lesions and 19.4% (7/36) of non-tumor lesions. Among these, 34 patients received definitive diagnoses. The diagnostic sensitivity of repeated EUS-FNA for tumor was 82.8% (24/29), the specificity was 100.0% (7/7), the positive predictive value was 100.0% (24/24), the negative predictive value was 58.3% (7/12), and the accuracy was 86.1% (31/36).Conclusion:Repeated EUS-FNA proves to be an effective and practical approach for cases where is suspicion of neoplastic lesions and the initial EUS-FNA pathology findings remain inconclusive.

Objective:To evaluate the efficacy of omalizumab in the treatment of chronic spontaneous urticaria (CSU), and to analyze its influencing factors.Methods:CSU patients treated with omalizumab were prospectively enrolled from the Department of Dermatology, General Hospital of Ningxia Medical University from October 2021 to October 2023. These patients received subcutaneous injections of omalizumab at a dose of 300 mg every 4 weeks (150 mg for patients aged under 12 years) for at least 3 consecutive sessions. Data on general information, blood routine test, and serum total IgE levels were collected, and the 7-day Urticaria Activity Score (UAS7), Urticaria Control Test (UCT), Dermatology Life Quality Index (DLQI), Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL), and the Beck Anxiety Inventory (BAI) were evaluated by dermatologists at baseline, and after 4, 8, and 12 weeks of treatment. A decrease in UAS7 score of ≥ 11 points was defined as good disease control, while a decrease in UAS7 score of < 11 points was defined as poor control. Univariate binary logistic regression and multivariate logistic regression models were used to identify factors influencing the efficacy.Results:A total of 81 CSU patients were enrolled, including 34 males (42.0%) and 47 females (58.0%) ; their ages ranged from 6 to 66 years (39.2 ± 17.9 years), and the disease duration was 42.3 ± 6.9 months; the serum total IgE levels were 249.5 ± 216.3 IU/ml, with 54 patients (66.7%) showing elevated IgE levels (> 100 IU/ml). Compared with baseline levels, the UAS7, DLQI, and CU-Q2oL scores all significantly decreased at weeks 4, 8, and 12, while the UCT scores significantly increased (all P < 0.05). According to the UAS7 change values, 68 patients (83.9%) were well controlled, and 13 (16.1%) were poorly controlled. Univariate logistic regression analysis showed that higher total IgE levels and higher mean platelet volume (MPV) were associated with better efficacy, while higher body mass index (BMI), higher BAI, and the complication of other allergic diseases were associated with poorer efficacy (all P < 0.05). Multivariate logistic regression analysis indicated that BMI, BAI, and MPV significantly affected efficacy: higher MPV was associated with better efficacy ( OR = 3.36, 95% CI: 1.196 - 9.465, P = 0.020), while higher BMI ( OR = 0.76, 95% CI: 0.599 - 0.957, P = 0.016) and higher BAI ( OR = 0.92, 95% CI: 0.870 - 0.985, P = 0.021) were associated with poorer efficacy. During the whole study, only 4 patients (5%) experienced drowsiness, low fever, redness or discomfort at the injection sites, and no serious adverse events were reported. Conclusion:Omalizumab exhibited significant efficacy and high safety in the 12-week treatment of CSU, and BMI and BAI appeared to be risk factors for efficacy, while MPV seemed to be a protective factor affecting efficacy.

Objective:To investigate the expression of X-box binding protein 1 (XBP1) and programmed death-ligand 1 (PD-L1) in cutaneous malignant melanoma (CMM) and their clinical significance. Methods:Fifty-three patients with CMM and fifty-six patients with pigmented nevus were selected from those admitted to the General Hospital of Ningxia Medical University between January 2017 and July 2023. The expression levels of XBP1 and PD-L1 in malignant melanoma tissues and pigmented nevus tissues were detected using immunohistochemic-al staining. The relationships between the expression levels of XBP1 and PD-L1 and the clinical characteristics of patients with CMM were then analyzed. Spearman's analysis was applied to assess the correlation between XBP1 and PD-L1 expression levels in CMM. Results:The expression levels of XBP1 and PD-L1 were significantly higher in CMM tissues than those in pigmented nevus tissues (P<0.05). Elevated XBP1 expression levels in patients with CMM were associated with clinical stages Ⅱ-Ⅳ and tumor-infiltrating lymphocytes (TILs) grade 2-3 (P<0.05). Similarly,elevated PD-L1 expression levels in patients with CMM were associated with ulceration of the primary foci,clinical stages Ⅱ-Ⅳ,Clark grades Ⅳ-Ⅴ,and TILs grades 2-3 (P<0.05). Spearman's analysis demonstrated a positive correlation between XBP1 and PD-L1 expression in CMM (P<0.05). Conclusions:XBP1 and PD-L1 can be used as molecular markers for the diagnosis and evaluation of CMM. Ad-ditionally,XBP1 may affect the development of CMM by regulating the expression of PD-L1,thereby altering the tumor microenvironment.

Objective To investigate the mechanism of Sanguisorbae Radix(SR)in the treatment of ulcerative colitis(UC).Methods Using the GSE92415 dataset from the Gene Expression Omnibus database,we analyzed differentially expressed genes and carried out weighted gene correlation network analysis and FerrDb analysis.Core genes were identified through protein-protein interaction(PPI)network and correlation analysis.UC mouse model induced by dextran sulfate sodium(DSS)was constructed and treated with SR via intragastric administration for 9 days.Disease activity index(DAI)and colon length were recorded.Pathological changes in colon tissue were observed using the HE staining.Levels of inflammatory cytokines such as tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were detected by enzyme linked immunosorbent assay(ELISA).Lipid peroxidantion factors such as malondialdehyde(MDA)and glutathione(GSH)were detected using biochemical test kits.Protein expression levels of zonula occludens protein-1(ZO-1)tight junction protein,peroxisome proliferator-activated receptor gamma(PPARG),solute carrier family 7 member 11(SCL7A11),and glutathione peroxidase 4(GPX4)were examined by Western blot or immunofluorescence labeling.Results Nine differentially expressed genes associated with ferroptosis were screened and PPARG was identified as a key gene.Correlation analysis showed a strong correlation between PPARG and ferroptosis.Subsequently,the potential mechanism of SR in improving UC in mice was discussed according to the bioinformatics screening results.The experimental results demonstrated that SR significantly reduced the DAI,prevented colon shortening and improved intestinal mucosal barrier function in the colon.SR decreased TNF-α and IL-6 levels,MDA content and GSH levels in colon tissues.SR also enhanced the expression of PPARG,SLC7A11 and GPX4,which reversed the effect of DSS in mice with colitis.Conclusions Ferroptosis is closely related to UC.SR can inhibit ferroptosis by regulating PPARG and SCL7A11/GPX4 expression,thereby improving colon epithelial injury and dysfunction in UC mice.This provides ideas and directions for UC treatment strategies.